No, Trump and Kennedy aren’t libertarian candidates – Restoration NewsMedia – Restoration NewsMedia

In early May, the Libertarian Partys national committee announced a prominent speaker at the partys convention over Memorial Day weekend in Washington: Former U.S. President Donald Trump.

A few days later, independent presidential candidate Robert F. Kennedy Jr., in a post on X (formerly Twitter), issued a challenge: Were both going to be speaking at the upcoming Libertarian convention on May 24 and 25. Its perfect neutral territory for you and me to have a debate where you can defend your record for your wavering supporters.

The party hasnt publicly confirmed any invitation (offered or accepted) to Kennedy, but maybe thats coming.

Im not going to argue here, anyway over the wisdom of a political party inviting two of its most prominent opponents to use its national convention as a campaign rally location or debate venue.

I do, however, want all you voters out there to know three things about this things that the media coverage seems to either leave unmentioned or gloss over:

1. Donald Trump isnt a libertarian.

2. Robert F. Kennedy Jr. isnt a libertarian.

3. Neither Trump nor Kennedy will be the Libertarian Partys 2024 presidential nominee.

Weve got a pretty big field of announced candidates for that presidential nomination.

Neither Trump nor Kennedy have declared for that nomination (in fact, after flirting with doing so, Kennedy publicly rejected the idea).

Neither Trump nor Kennedy are eligible for that nomination or at least they wont be if they address the convention prior to the nominee being selected. According to the Libertarian National Committees policy manual:

No person shall be scheduled as a convention speaker unless that person has signed this statement: As a condition of my being scheduled to speak, I agree to neither seek nor accept nomination for any office to be selected by delegates at the upcoming Libertarian Party convention if the voting for that office occurs after my speech.

Since we havent selected our nominee yet, Im not going to sing his or her praises to you or try to convince you to vote Libertarian. I just dont want you to be surprised when you look at your ballot in November and dont see the name Trump or Kennedy next to the name Libertarian Party.

Between now and November, I hope youll take time to familiarize yourself with libertarian ideas and with the Libertarian Partys candidates for office across the U.S. They deserve your attention and consideration.

Thomas L. Knapp (Twitter: @thomaslknapp) is director and senior news analyst at the William Lloyd Garrison Center for Libertarian Advocacy Journalism (thegarrisoncenter.org). He lives and works in north-central Florida.

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No, Trump and Kennedy aren't libertarian candidates - Restoration NewsMedia - Restoration NewsMedia

Trump’s MAGA takeover of the Libertarian Party – The Boston Globe

1. Libertarians are uninhibited by ordinary political rules and inviting a rival to address their convention is just the sort of eccentric move that appeals to them.

2. Party leaders, knowing Trump is more likely to be elected in November than their own nominee, want to encourage him to embrace libertarian ideals of shrinking government, expanding liberty, and curbing the welfare state.

3. Libertarian Party leaders never expected Trump to accept their invitation but will gladly exploit the publicity he brings them in order to promote their own issues and candidates.

4. The Libertarian Party has been taken over by hard-core MAGA supporters who want to help Trump win.

My money is on No. 4.

Though many of my instincts are small-l libertarian, I have never been a registered member of the Libertarian Party. On several occasions, however, I have voted for the partys presidential candidate. In 1996, I was far more impressed with Harry Browne, the Libertarian Party standard-bearer, than with the other candidates on the ballot Democratic president Bill Clinton, Republican senator Bob Dole, and billionaire businessman/crank Ross Perot. In a column that year, I marveled at a would-be president who was motivated not by ego or lust for power but by principle.

Imagine a candidacy based on individual freedom, economic liberty, parental authority, local control of local matters, an end to the national income tax, and a federal government that doesnt meddle in our lives, I wrote. What American would vote for that?

As it turned out, 485,759 of us Americans voted for that one-half of 1 percent of the popular vote.

I voted Libertarian again in 2016, unable to stomach the idea of casting a ballot for such dreadful candidates as Trump or Hillary Clinton. The Libertarian candidates that year two prominent former Republican governors, Gary Johnson of New Mexico and Bill Weld of Massachusetts were at best lukewarm in their libertarian commitments. But in terms of character, they were head and shoulders above the major-party nominees. Apparently quite a few #NeverTrump and #NeverHillary voters felt the same way, because the Johnson-Weld ticket drew 4.5 million votes, or nearly 3.3 percent of the nationwide popular vote an all-time high for the party.

The Libertarian nominee four years later, political activist and college professor Jo Jorgensen, didnt do nearly as well; she polled only 1.8 million votes, or a little more than 1 percent of the national total. But that, some claim, may have prevented Trumps reelection as president. In four states that Joe Biden narrowly carried Arizona, Georgia, Pennsylvania, and Wisconsin Jorgensens vote total was larger than Bidens margin of victory. There were those who argued that had there been no Libertarian option on the ballot, most of the votes Jorgensen amassed might have gone to Trump and sent him back to the White House.

To be clear, I dont subscribe to that theory. Many Jorgensen voters, including me, could not have been induced to cast a ballot for Trump under any circumstances. That wasnt just because of his character failings but also because Trump is no libertarian.

Unlike Johnson and Weld, who could at least portray their views as libertarian-lite, Trump is affirmatively opposed to most libertarian principles. There is his long-standing animus against immigration, both legal and illegal. His decades-long hostility toward free trade and support for higher tariffs. His call to confiscate guns without waiting for due process. His declaration that a US president has untrammeled authority to order businesses to close. His vow to never cut a single penny from the crushingly unaffordable Social Security and Medicare programs. His repeated fawning over the worlds dictators, including Kim Jong Un, Xi Jinping, and Vladimir Putin. The nearly $8 trillion he added to the national debt during his presidency.

As the Libertarian Party itself declared in 2018, Trump is the opposite of a Libertarian.

But that was the Libertarian Party then. The Libertarian Party now is a very different creature.

Beginning in 2017, a bigoted faction calling itself the Mises Caucus moved systematically and ruthlessly to take over the Libertarian Party. For years, the LP had had a reputation for free-market fundamentalism, open immigration, drug legalization, and live-and-let-live tolerance. All that began to change as the new faction moved in and took over the partys communications channels. Suddenly the Libertarian Party was employing some of the ugliest tropes in the alt-right lexicon.

The caucus began taking over state parties, packing members into sparsely attended conventions, recounts Andy Craig in the Daily Beast. As they did so, they quickly started attracting negative attention for saying things that sounded less like liberty and more like the tiki torch brigade. For example, Libertarian Party social media posts equated COVID-19 vaccines to the Holocaust with yellow Star of David patches, denounced Pride Month as degeneracy, told a Black politician she should pick cotton or go back to Africa, and pronounced it obviously correct that the end of apartheid destroy[ed] South Africa.

The move by the Mises Caucus to take control of the party seems to have begun immediately after the 2017 white supremacist rally in Charlottesville, Va. The violence of that episode was promptly condemned by the Libertarian Partys national committee, which released a strong statement declaring bigotry, in the words of the party platform, irrational and repugnant. The statement affirmed that there is no room for racists and bigots in the Libertarian Party.

But to some on the far-right fringe of the movement, that was intolerable. As Joshua Eakle, a longtime libertarian activist and former Libertarian Party state chairman, recounted in an eye-opening thread on X last week, the statement denouncing the Charlottesville bigots infuriated some extremists, who launched an insurgency to take over the party for the Trumpian right. By 2022, that takeover was largely complete. An early priority of the new administration was repealing the platform language condemning bigotry. By the thousands, traditional Libertarian Party leaders and dues-paying members quit or were forced out. What remains of the partys national committee, Eakle wrote, has become nothing more than a satellite of MAGA authoritarianism.

Perhaps there will be a movement by genuine lovers of liberty to take back the Libertarian Party from the bigots who have usurped it. If so, I will cheer from the sidelines. But as long as the party is in the hands of its current operators, the odds of my voting for a Libertarian alternative to Trump and Biden is nil.

This is an excerpt from Arguable, a Globe Opinion newsletter by columnist Jeff Jacoby. Sign up to get Arguable in your inbox each week.

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Trump's MAGA takeover of the Libertarian Party - The Boston Globe

Trump Talks to Libertarians – Splice Today

Ten vexing issues for the party, 10 candidates for you.

DonaldTrump intends to address the Libertarian Partys presidential nominating convention on May 25. Hes not abandoning the Republican Party or pretending to be a libertarian but presumably will try to convince libertarians to vote for him in November anyway. Some may.

No matter how strange Trump may be, he presents libertarian potential voters with the same basic (though complex) dilemma any Republican presidential candidate does: At his best, hes slightly less pro-government than the Democratic candidate, which isnt much of an argument in favor of casting a vote for Trump, but you need to be the candidate with the most votes to win the presidency in the U.S. system, so voting for anyone other than one of the two leading contenders is arguably a waste of time, at best a symbolic gesture.

Trump, though, will tell them hes not just the lesser (maybe) of two evils, hes stupendousthe best president ever. Libertarian Party National Committee chair Angela McArdle, despite praising Trump, claims the Party will not take all this lying down but will press upon Trump ten issues they have with his governing style. McArdles dads a preacher, and this will perhaps be a bit like a rebellious Martin Luther nailing his 95 Theses to a Catholic Church door.

Or perhaps Trump will roll the LP with a bunch of time-wasting, self-aggrandizing bluster, as he somehow manages to do to whole nations. So, I will note here just 10 of many possible issues I think libertarians should have with Trump, in case the convention is full of unphilosophical distractions and doesnt manage to press its own 10 issues upon Trumps mind.

Trumps mania for preventing free individuals (of any nation) traveling to whatever parcels of private property will have them (if the travelers can get to them without damaging the land or property of people who for whatever reason dont want to facilitate the travel), his almost blind faith not only in government border patrols but government police in general, his willingness to (for instance) sell billions in weapons to the Saudis while talking like an anti-interventionist, his manifest hunger to use government to punish his enemies and critics, his penchant for undoing existing arrangements and replacing them with near-identical ones that merely add his thumbprint (see: trade treaties), his brazenly big-government-oriented dreams of decreeing special innovation-incubating cities, his cavalier and record-setting deficit spending, his puerile inability to make rational or civil arguments, his embrace of the war against drugs and other draconian measures, and his general narcissistic faith in himself and craven loyalists rather than predictable and transparent procedures are all ample reasons for libertarians to reject the man and his presidential candidacies.

Thats not to say hes the worst thing that could happen to the U.S. On a list of 10 somewhat-plausible 2024 presidential election winners, Id say hes about the sixth-best option. The Libertarian Party convention attendees may disagree with me. They might even nominate him for president if things get really nutty, who knows. I was present at the New York State Libertarian Party convention in the 1990s that nominated Howard Stern for governor, so anything is possible.

The ideal outcome in this or any election is that no one is elected and government everywhere is simply abolished, enabling people to run their own individual lives. Second-best would be some highly principled and knowledgeable libertarian of my own choosing, Party member or not (maybe Argentinas Milei, if we abolish those cumbersome immigration rules I mentioned earlier?). Third would be thinktank president Jacob Hornberger, who strikes me as the most rational and articulate of the actual current crop of people vying for the Libertarian Party nomination. Fourth would be whoever the LP actually ends up choosing, assuming its at least vaguely some kind of libertarian, all libertarians being preferable to the usual crop of eagerly-governing authoritarians who get elected in this world. Fifth, hypothetically, is some very market-oriented and smart last-minute replacement the Republicans whip up at the convention if it looks like Trump is headed to jail, maybe a Steve Forbes but preferably not just some party-line stiff.

Sixth,I suppose, is Trump himself, who at least sounds ornery enough this time around to shutter some agencies. Seventhand lately competing with Trump for the love of the Libertarians in a tight race where both men know a few votes could be pivotalis Robert F. Kennedy, whos undeniably a leftist and statist but sounds sincerely interested in challenging the establishment, cronyism, and the intelligence sector that he suspects of killing two of his relatives (maybe hed even be better than Trumpand Kennedy lately sounds almost Lewis Lapham-like in his desire to restore a sort of Jeffersonian classical liberal order, or at least classic liberal, as he explicitly labels it in a recent ad, be his notions of such an order laissez-faire or not). Eighth, then, is Biden, who, as you may recall, is currently president. Ninth is whoever the Democrats might be tempted to replace him with at the last minutelikely to be worse, not better, than Joe because the replacement would almost certainly be more alert, and fully-conscious Democrats do far more damage (as Kamala Harris may well prove in mid-2025 if Joe retires a few months into his second term).

Tied for 10th, Id put outsider candidates Cornel West and Jill Stein, both smarter than most politicians and admirably averse to the two-party duopoly but very likely to devote their energies to things I consider counterproductive, like radically quasi-Marxist wealth redistribution or more onerous green programs, respectively.

Well find out in less than three weeks whether something magical, disastrous, or irrelevant comes out of the Libertarian convention. I wont hold my breath waiting for a perfectly rational blending of populist and individualist philosophies to begin then, no matter how many essays I could write about why that might be nice, and no matter how many pipe-smoking paleos with waxed mustaches would swoon at the idea. I must be realistic.

ToddSeavey is the author of Libertarianism for Beginners and is on X at @ToddSeavey

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Trump Talks to Libertarians - Splice Today

Nanoscope Therapeutics: Gene Therapy Improves Visual Acuity in Patients with Retinitis Pigmentosa – 2 Minute Medicine

The Latest

A recent two-year phase 2b, randomized, double-masked, sham-controlled multicenter clinical trial by Boyer et al. and Nanoscope Therapeutics investigated mutation-agnostic gene therapy for the treatment of permanent and severe vision loss from of retinitis pigmentosa. The results build on an earlier trial that found 89% of patients injected with the gene therapy to experience an improvement of luminance levels across two visual tests compared to control group patients. This newest trial, named RESTORE, demonstrated significant improvement in best-corrected visual acuity after 52 weeks compared to the control arm. The results showed that gene therapy was well tolerated, with no treatment-related serious or severe adverse events reported.

Physicians Perspective

Retinitis Pigmentosa encompasses a group of rare genetic eye disorders in which the retinas photoreceptors degrade over time leading to profound visual field and vision loss in advanced stages. Retinitis pigmentosa affects 1 in every 400 people in the United States and approximately 1 in 5000 worldwide, making it the most common inherited disease of the retina. There are currently no cures available for retinitis pigmentosa. Current gene therapies aim to treat patients with specific gene mutations and are limited in advanced disease with degenerated outer retinal cells. Nanoscopes optogenetic monotherapy targets the intact inner retinal neurons to restore vison loss. This approach has the advantage of restoring vision even in advanced retinitis pigmentosa, regardless of causative gene mutation. Furthermore, the therapy is administered via a single intravitreal injection without any need for external devices.

Molecular Targets

Nanoscope Therapeutics has developed a gene therapy called MCO-010 that uses light sensitive molecules to treat retinal disease. MCO-010 is an injection that transforms bipolar cells that normally do not transmit light (are not sensitizing) to become light sensitizing. The gene therapy works by transfecting the cell layers above the damaged cone layers, such as the bipolar and ganglion cells, into viable light producing cells. MCO-010 is activated by ambient light across the visual spectrum.

Company History

Nanoscope therapeutics is a Texas based late-stage clinical biotechnology company developing gene therapies for inherited retinal diseases and age-related macular degeneration. MCO-010 is the companys lead asset and has recently received FDA fast-track designations. Additionally, the company has recently completed a phase 2 trial of MCO-010 in Stargardt disease.

Further reading: https://www.fiercebiotech.com/biotech/nanoscope-eyes-market-after-gene-therapy-improves-vision-patients-retinal-disease

2024 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.

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Nanoscope Therapeutics: Gene Therapy Improves Visual Acuity in Patients with Retinitis Pigmentosa - 2 Minute Medicine

"The best decision I ever made:" Patel earns degree in biological engineering – University of Missouri College of Engineering

May 03, 2024

Zara Patel didnt think she would find herself at Mizzou, but after four years on campus she says attending school here was the best decision shed ever made.

Patel will graduate with a degree in biological engineering, which she chose because of her passion for creating technology that has a positive environmental impact. Outside of the classroom, shes been involved in multiple student organizations with focuses on both academics and college traditions.

After graduation, she will begin her career as a water/wastewater designer at Stantec in Indianapolis.

Read on for a Q&A about her time at Mizzou.

Why did you choose Mizzou?

I was born and raised here in Columbia, Missouri. Both my parents went to Mizzou to get their undergraduate degrees and then stayed once they graduated. I never really thought that I was going to go to Mizzou. I always assumed that I would leave the state for college, but once the pandemic began, it was more difficult to go to a school that was out of state and I decided to go to Mizzou. It was one of the best decisions Ive evermade.

What made you interested in your major?

I originally started at Mizzou as a biological sciences major and then switched to biological engineering with an emphasis in bioenvironmental engineering. I always knew I wanted to major in a STEM field and that I wanted to make a difference. I switched majors because I wanted to have a greater connection with creating technology that has a positive impact on the environment, specifically focusing on biological integrations.

How did you get involved at Mizzou?

I am involved in Alpha Omega Epsilon, an engineering and STEM sorority. I am also involved in the Society of Sales Engineers and Engineers Club. Getting to know all the Engineers Week royalty candidates personally, as I was on the royalty committee for the Engineers Club, allowed for me to fully get immersed in the skits. That was my favorite Mizzou Engineering memory.

Whats next for you after graduation?

I have accepted a position at Stantec as a water/wastewater designer in Indianapolis.

What would you tell someone whos interested in coming to Mizzou?

Mizzou is about community and the environment. Whether you come to the school knowing someone or as a total stranger, you will always make friends. Every university has an environment, but Mizzous environment is differentyou can find any group that you want. The first time you fully emerge yourself in the environment, whether it be in classes, student org meetings or at a game, you will know that you made the right choice.

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"The best decision I ever made:" Patel earns degree in biological engineering - University of Missouri College of Engineering

College of Engineering Launches New Collaboratory for Biomedical and Bioengineering Innovation – UConn Today – University of Connecticut

A new initiative in the College of Engineering will serve as the nexus for bio-based technology at UConn.

The Collaboratory for Biomedical and Bioengineering Innovation fosters a vibrant and unified environment where biomedical and bioengineering researchers work together to invent, develop, and adapt existing biotechnologies to solve new problems in the biological sciences.

There seems to be an artificial divide between researchers who focus on biomedical studies and those working on other biological problems, says Leslie Shor, associate dean for research and graduate education and co-director of Collaboratory for Biomedical and Bioengineering Innovation. This is especially strange for engineers, because we are often leading the technical aspects of the work, and an enabling technology such as a novel sensor or new imaging technology works the same regardless of the biological application.

The Collaboratory, however, aims to help researchers establish new interdisciplinary collaborations outside their existing research networks.

By promulgating emerging technologies across fields, we enhance the value of the emerging technology and simultaneously unlock new areas of inquiry and accelerate new discoveries, Shor explains.

Bio-based technology, or biotechnology innovation refers to the development and advancement of technologies that are based on biological systems or use biological materials. This can include a wide range of innovations such as biomedical devices (prosthetics, medical imaging equipment, drug delivery systems); bio-systems (biofuels production, bioremediation of pollutants, agricultural biotechnology); and bio-computation (bioinformatics for analyzing genetic data, computational modeling of biological systems, or machine learning algorithms for drug discovery).

Members of the Collaboratory are nationally and internationally-renowned faculty.

Thanh Nguyen, associate professor of mechanical engineering and biomedical engineering, works at the interface of biomedicine, materials and nano/micro technology. Hes already collaborating with researchers on campus and UConn Health for vaccine, drug, tissue-engineering and biomaterials research, but expects the Collaboratory for Biomedical and Bioengineering Innovation will help strengthen those relationships and allow him to explore more research opportunities.

UConn is already a collaborative and terrific environment for interdisciplinary research. But this initiative makes biomedical and engineering research from different groups much more visible to all researchers at UConn. Nguyen says. The Collaboratory also could eventually lead to more impactful studies and grant funding.

Like Nguyen, Sabato Santaniello, associate professor of biomedical engineering, is interested in potential collaborations with UConn Health and other medical centers in the region. His work in neuromodulation of the cerebellum is primarily targeted to clinical neuroscienceproviding new ways of probing the diseased brain and improving treatments of patients affected by movement disorders.

My work has potential to translate into new, patentable products down the road, but now, my program can benefit the initiative by intercepting the needs of clinicians, especially neurologists and neurosurgeons, he says.

Santaniello describes the Collaboratory as a unique platform that will regionally advertise the many cutting-edge biomedical technologies that UConn faculty develop and better intercept the needs that come from the healthcare industry and the clinical research.

It will benefit greatly those PIs at UConn who are looking for new, exciting applications for the tools that are developed in their labs, he says.

The group aims to promote bio-based technologies through collaborative research; boost economic growth in Connecticut by creating new bio-based products and businesses; train students for biotech careers by involving them in research and innovation; and establish UConn as a global leader in bio-based technology innovation.

Our goals are to drive research, investment, and possibilities in Connecticut, explains Guoan Zheng, associate professor of biomedical engineering and co-director of the Collaboratory for Biomedical and Bioengineering Innovation. By advancing technology, we believe we can make a significant impact on scientific discovery and its applications driving socially impactful research and benefiting Connecticuts economy and workforce.

Shor, whos also Centennial Professor of Chemical and Biomolecular Engineering, leads the Engineered Microhabitats Research Group at UConn, where she mentors an interdisciplinary team focusing on biotechnology for sustainability. My lab simply adapted established microfluidics or lab-on-a-chip technologies to a completely different field of biology: soil microbes living near plant roots. This approach directly led to new understanding about soil moisture regulation by bacteria and fungi and a new appreciation for how soil protists can be used to promote more sustainable food production. I want to see the same interchange of approaches advance all types of biological sciences to advance a healthy and sustainable future, she said.

The Collaboratory is seeking student, faculty, and corporate partners. For more information, contact the UConn Collaboratory.

The Collaboratory for Biomedical and Bioengineering Innovation celebrated its launch April 2 with a networking symposium and poster session. Faculty from several engineering disciplines attended to learn about the interdisciplinary relationships related to biomedical and bioengineering research and technology innovation. Photos of the event are below and in this UConn College of Engineering Flickr album. (Chris LaRosa/UConn)

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College of Engineering Launches New Collaboratory for Biomedical and Bioengineering Innovation - UConn Today - University of Connecticut

Investigation of inherited noncoding genetic variation impacting the pharmacogenomics of childhood acute … – Nature.com

Identification of noncoding regulatory variants impacting the pharmacogenomics of ALL treatment

Single-nucleotide variants (SNVs) impacting diverse pharmacological traits in ALL were identified for functional interrogation. We chose SNVs associated with relapse or persistence of MRD after induction chemotherapy in childhood ALL patients to investigate the role of inherited noncoding regulatory variants impacting clinical phenotypes (i.e., treatment outcome). These SNVs were identified from published GWAS of ALL patients enrolled in St. Jude Childrens Research Hospital and the Childrens Oncology Group clinical protocols3,4,5 (see Methods for variant selection criteria). Variant selection also included prioritization for treatment outcome SNVs associated with drug resistance phenotypes in primary ALL cells to enrich for variation impacting ALL cell biology (see Methods for variant selection criteria). These treatment outcome-associated variants, as well as all variants in high LD (r2>0.8) with the sentinel GWAS variants, were further evaluated (Fig.1a, b).

a SNVs of interest from GWAS were pursued based on association with ex vivo chemotherapeutic drug resistance in primary ALL cells from patients and/or treatment outcome. Dex dexamethasone, Pred prednisolone, VCR vincristine, 6MP 6-mercaptopurine, 6TG 6-thioguanine, LASP L-asparaginase. b GWAS SNVs were combined with ALL disease susceptibly control GWAS SNVs and SNVs in high LD (R2>0.8) and c mapped to accessible chromatin sites in ALL cell lines, ALL PDXs, and primary ALL cells from patients. Of the 1696 SNVs mapped to accessible chromatin sites, 35 are control SNVs. Source data are provided in the Source Data file.

We also identified variants directly associated with ex vivo chemotherapeutic drug resistance in primary ALL cells from patients by performing GWAS analyses using SNV genotype information and ex vivo drug resistance assay results for six antileukemic agents (prednisolone, dexamethasone, vincristine, L-asparaginase, 6-mercaptopurine [6MP] and 6-thioguanine [6TG]) in primary ALL cells from 312344 patients (not all patients were tested for all drugs) enrolled in the Total Therapy XVI clinical protocol at St. Jude Childrens Research Hospital (see Methods). We further prioritized functional ex vivo drug resistance SNVs by determining if they were eQTLs in primary ALL cells or related cell types (i.e., whole blood and EBV-transformed lymphocytes) from the Genotype-Tissue Expression (GTEx) consortium37 (see Methods for variant selection criteria). Ex vivo drug resistance variants that were also identified as eQTLs, as well as variants in high LD (r2>0.8) with these sentinel GWAS variants, were further evaluated (Fig.1a, b).

GWAS have also been performed for childhood ALL disease susceptibility and identified several GWAS loci harboring variants with genome-wide significance44,45,46,47,48,49,50. Several follow-up studies of these GWAS loci have identified candidate causal noncoding variants and mechanisms involving gene regulatory disruptions51,52,53. As a result, we used ALL disease susceptibility variants (n=11), as well as variants in high LD (r2>0.8) with them, for further analysis as positive controls in our study (Fig.1a, b).

Because most of these variants map to noncoding portions of the human genome, these data point to disruptions in gene regulation as the underlying mechanism of how these variants impact ALL cell biology. We therefore utilized assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq)54 chromatin accessibility data in 161 ALL cell models, comprised of primary ALL cells (cryopreserved, n=2455; fresh, n=12056), ALL cell lines (n=14) and ALL patient-derived xenografts (PDXs, n=3), to uncover which variants map to putative CREs in ALL cells57 (i.e., regulatory variants; Fig.1c). Although we detected variation in ATAC-seq TSS enrichment scores and peak counts that is to be expected from such a large, mixed cohort of ALL cell models, the peaks called were largely reproducible (found in >3 samples) within each group (Supplementary Fig.1ac). ATAC-seq data from primary ALL cells, ALL cell lines, and PDXs were combined and identified 1696 regulatory variants at accessible chromatin sites in ALL cells for functional investigation (Fig.1c and Supplementary Data1).

To examine the functional effects of these 1696 regulatory variants on transcriptional output in a high-throughput manner we utilized a barcode-based MPRA platform29,32 to measure differences in allele-specific transcriptional output (Fig.2a). Oligonucleotides containing 175-bp of genomic sequence centered on each reference (ref) or alternative (alt) variant allele, a restriction site, and a unique 10-bp barcode sequence were cloned into plasmids. An open reading frame containing a minimal promoter driving GFP was then inserted at the restriction site between the alleles of interest and their unique barcodes (Fig.2a). We utilized 28 unique 3UTR DNA barcodes per variant allele (56 barcodes per regulatory variant), and variants near bidirectional promoters (47 total variants) were tested using both sequence orientations. In total, 97,608 variant-harboring oligonucleotides were evaluated for allele-specific differences in gene regulatory activity (Fig.2a).

a Diagram describing design of MPRA (also see Methods). bd Significant MPRA hits were identified by BenjaminiHochberg FDR corrected two-tailed Students T tests. b Distribution of significant changes in allele-specific transcriptional activity across all SNVs. c Number of MPRA SNVs showing significant (Adj. p<0.05) changes in allele-specific transcriptional activity in each ALL cell line. d Pairwise linear correlation between changes in allele-specific transcriptional activity for all significant (Adj. p<0.05) changes across all cell lines. R2 correlation and p value are provided. All source data and statistical parameters are provided in the Source Data file.

Following transfection into 7 different B-cell precursor ALL (B-ALL; 697, BALL1, Nalm6, REH, RS411, SEM, SUPB15) and 3 T-cell ALL (T-ALL; CEM, Jurkat, P12-Ichikawa) human cell lines (n=4 transfections per cell line; 40 total), the transcriptional activity of each allele variant was measured by high-throughput sequencing to determine the barcode representation in reporter mRNA and compared to DNA counts obtained from high-throughput sequencing of the MPRA plasmid pool (Fig.2a). In the 10 cell lines MPRA detected 4633 instances of significant differential activity between alleles across 91% (1538/1696) of regulatory variants tested (Fig.2b, c, Supplementary Data2). The 10 ALL cell lines showed substantial differences in the total number of regulatory variants harboring significant allele-specific activity, which we suspect largely stems from differences in transfection efficiency (Fig.2c). Importantly, when comparing changes in allele-specific MPRA activity for each regulatory variant we found that significant changes in activity (adj. p<0.05) were highly correlated between ALL cell lines, with 87% concordance in allelic-specific activity, suggesting that significant MPRA hits were likely to be robust and reproducible between cell lines (Fig.2d). Allele-specific MPRA activities were also correlated using all pairwise cell line comparisons for each regulatory variant, irrespective of significance (Supplementary Fig.2a). Importantly, 31 of the 35 positive control variants (i.e., ALL disease susceptibility-associated variants and variants in high LD) showed significant allelic effects in at least 1 cell line, and 10 showed significant and concordant allelic effects in at least three ALL cell lines, including two variants (rs3824662 at GATA3 locus and rs75777619 at 8q24.21) directly associated with ALL susceptibility44,49,52 (Supplementary Data2). The risk A allele at rs3824662 was associated with higher GATA3 expression and chromatin accessibility and demonstrated significantly higher allele-specific activity in our MPRA44,52, thereby demonstrating that the MPRA could detect allelic effects previously identified by others.

To further validate MPRA hits in an ex vivo model, we performed MPRA using two B-ALL PDX samples that were freshly harvested from mice. These samples detected 26 and 67 significant gene regulatory variants, respectively, and showed significant correlation with the cell line MPRA data (Supplementary Fig.2b, c, Supplementary Data3). We attribute the detection of relatively lower numbers of variants in PDXs to technical effects stemming from poor transfection efficiency and limited cell survival ex vivo. Overall, our data suggest that the cohort of SNVs tested contained functional regulatory variants with the potential to impact gene regulation.

To further focus on regulatory variants most likely to broadly impact gene regulation in ALL cells, we prioritized 556 variants with significant (adj. p<0.05) and concordant allele-specific activities in at least three ALL cell lines (i.e., functional regulatory variants; Fig.3ad, Supplementary Data4). Most of these functional regulatory variants (318/556) mapped to accessible chromatin found only in primary ALL cell samples, underscoring the importance of incorporating chromatin architecture from primary ALL cells, and 54 functional regulatory variants mapped to transcription factor footprints in primary ALL cells (Supplementary Fig.3). Additionally, we used Genomic Regions Enrichment of Annotations Tool (GREAT) to associate these SNVs with their nearby genes and search for enrichment in gene ontology biological processes pathways58. Although GREAT identified gene associations for nearly all SNVs, we found no significant pathway associations (Supplementary Data4 and 5). Because further functional investigation of variants in primary ALL cells or PDXs ex vivo is largely intractable, we focused on 210 functional regulatory variants that were detected in open chromatin in one of the 14 ALL cell lines that we had generated ATAC-seq data (Fig.3d). Most of these variants (159/210; 76%) were also found in accessible chromatin in PDXs and/or in primary ALL cells from patients (Fig.3d).

a 556 of the 1696 SNVs assayed are functional regulatory variants with reproducible (FDR<0.05 in >2 cell lines) and concordant (same directionality in >2 cell lines) changes in allele-specific activity. b Frequency distribution plot showing the number of cell samples showing concordant and significant MPRA activity of variants. c Plot showing the distribution of log2-adjusted activity between alternative (Alt) and reference (Ref) alleles across 556 functional regulatory variants. 210 SNVs (in blue) mapped to accessible chromatin sites in ALL cell lines and 346 SNVs (in black) mapped only to accessible chromatin sites identified in primary ALL cells and/or PDXs. d Upset plot shows how many functional regulatory variants map to open chromatin in diverse ALL cell models. 210 of the 556 functional regulatory variants are found in accessible chromatin sites that were identified in an ALL cell line. Source data are provided in the Source Data file.

For additional validation using traditional luciferase reporter assays, we prioritized these 210 functional regulatory variants based on allele-specific effect size and selected high-ranking SNVs. Dual-luciferase reporter assays showed similar allele-specific changes in activity to that which was detected by MPRA for 7 SNVs tested (Supplementary Fig.4ak). In fact, a significant positive correlation (p=0.0017) was observed between the allelic effects detected by MPRA and luciferase reporter assays (Supplementary Fig.4l). Together, these analyses assessed the robustness of our MPRA screen of functional regulatory variants and identified 556 SNVs with reproducible and concordant allele-specific effects on gene regulation. Importantly, 210 of the 556 significant hits that were concordant in at least three cell lines were found in open chromatin sites in ALL cell lines and, therefore, warranted further exploration.

To better understand how these variants impact cellular phenotypes, we first determined if the 210 functional regulatory variants found in accessible chromatin sites in ALL cell lines could be directly associated with a target gene. While 35 functional regulatory variants were localized close (2.5kb) to nearby promoters (Fig.4a, Supplementary Data4 and 6), 175 variants were promoter-distal (>2.5kb), and therefore likely to map to CREs with unclear gene targets (Fig.4a). While CREs are often associated with the nearest genes, 3D chromatin looping methods are a more reliable method to associate a CRE with its target gene promoter. In pursuit of evidence-based association of promoters and specific CREs, we performed two related chromatin looping methods, H3K27Ac HiChIP59 and promoter capture HiC (CHiC)39, in 8 of 10 ALL cell lines used in MPRA and determined that 19 of the 175 non-promoter functional regulatory variants showed connectivity to distal promoters in the same cell line where allele-specific MPRA activity and chromatin accessibility were detected (Fig.4a, Supplementary Data6). Interestingly, H3K27Ac HiChIP and promoter CHiC called similar numbers of loops across all 8 cell lines (690,579 versus 660,313, respectively), but promoter CHiC loop calling was more consistent per cell line (Supplementary Fig.5, Supplementary Data7). HiChIP detected no looping at any of the 556 reproducible and concordant SNVs from the MPRA, and the 19 SNVs showing connectivity to a promoter were solely detected by promoter CHiC, further highlighting the utility of this method in GWAS-oriented studies41,60,61,62,63.

a Data show the number of functional regulatory variants mapping to open chromatin in cell lines that associate directly with promoters (within 2.5kb) or that are distally promoter-connected via promoter CHiC. b MPRA data show distal regulatory variants in accessible chromatin (some promoter-connected by promoter CHiC data) exhibit stronger effects on allele-specific activity than promoter-associated functional regulatory variants. ANOVA with KruskalWallis test was performed with Dunns correction for multiple comparisons. c Amongst distally promoter-connected functional regulatory, variants that map to intronic and distal intergenic sequences showed greater activity than those in UTRs. ANOVA with KruskalWallis test was performed with Dunns correction for multiple comparisons. d, e Data show the ranked allele-specific activity distribution of MPRA data for d promoter-associated functional regulatory variants and e distally promoter-connected functional regulatory variants. All source data and statistical parameters are provided in the Source Data file.

In prioritizing functional regulatory variants, we were interested in the gene regulatory impact of variants at TSS-proximal promoter-associated versus TSS-distal promoter-connected CREs as measured by MPRA. Interestingly, we found that SNVs found at TSS-distal open chromatin sites, promoter-associated or not, showed higher allele-specific changes in MPRA activity than those at promoters (Fig.4b). While we acknowledge that many of the 156 variants for which we did not detect a relationship with a promoter are likely to have meaningful gene targets, we focused on CREs containing variants with known gene targets in ALL cells for functional validation. Amongst the TSS-distal promoter-connected functional regulatory variants, we found that distal intergenic and intronic SNVs showed significantly higher allele-specific activity than those in UTRs (Fig.4c). These data suggest that the most robust allelic effects attributable to these regulatory variants are likely to occur at distal intergenic and intronic sites >2.5kb from the TSS of the target gene.

Next, we ranked TSS-proximal promoter-associated and TSS-distal promoter-connected functional regulatory variants by the geometric mean of their significant MPRA data to account for the magnitude of allele-specific activity and the reproducibility of a significant change across ALL cell lines (Fig.4d, e). This analysis identified rs1247117 as the most robust functional regulatory variants, which we then pursued for mechanistic understanding (Fig.4e).

We pursued functional validation of rs1247117 based on its highest-ranking geometric mean of MPRA allelic effect. rs1247117 is in high LD with two GWAS sentinel variants (rs1312895, r2=0.99; rs1247118, r2=1) that are associated with persistence of MRD after induction chemotherapy3. This functional regulatory variant maps to a distal intergenic region harboring chromatin accessibility downstream of the CACUL1 gene, for which it is an eQTL in EBV-transformed lymphocytes37. However, we found that rs1247117 loops to the EIF3A promoter in Nalm6 B-ALL cells (Fig.5a). We, therefore, explored how this accessible chromatin site might recruit transcriptional regulators that would depend on the allele present at rs1247117. For this, we first performed ChIP-seq for RNA pol II and H3K27Ac, which confirmed RNA Pol II occupancy and H3K27Ac enrichment in Nalm6 cells, indicating that rs1247117 is associated with an active CRE (Fig.5a). Through an examination of the underlying DNA sequence spanning rs1247117, we found that the reference guanine (G) risk allele at rs1247117 resides in a PU.1 transcription factor binding motif that is disrupted by the alternative adenine (A) allele (Fig.5b). Although the risk G allele is the reference allele, the alternative A allele is more common in human populations. Supporting PU.1 binding at this location, accessible chromatin profiling in primary ALL cells identified an accessible chromatin site and PU.1 footprint spanning rs1247117 in diverse ALL samples (Supplementary Fig.6a, b). Significantly greater chromatin accessibility at rs1247117 was also observed in heterozygous (GA) patient samples compared to patient samples homozygous for the alternative A allele (Supplementary Fig.6c), and the G allele at rs1247117 harbored significantly greater ATAC-seq read count compared to the A allele (Supplementary Fig.6d). Importantly, we determined that PU.1 was bound at this site in Nalm6 cells using CUT and RUN64 (Fig.5a).

a IGV genome browser image in Nalm6 cells showing the genomic context, chromatin accessibility, and EIF3A promoter connectivity using promoter CHiC of the top functional regulatory variant, rs1247117, with the highest allele-specific MPRA activity. Genomic binding profiles are also shown for RNA polymerase II (RNA Pol2), histone H3 lysine 27 acetylation (H3K27Ac), and PU.1. b rs1247117 lies in a PU.1 binding motif. The human genome reference sequence, Nalm6 genome sequence, location of rs1247117, and PU.1 position weight matrix are shown. c Design of biotinylated DNA probes for in vitro rs1247117 pulldown. d Biotinylated DNA pulldown shows rs1247117 allele-dependent enrichment of PU.1 binding. Blot shown is representative of two independent experiments. Densitometric quantification of two blots is shown. e CRISPR/Cas9 was used to change the allele at rs1247117 from A>G in Nalm6 cells. Data show the location of gRNA and ssODN, as well as NGS reads obtained from clone 1 and 2 at rs1247117. f PU.1 ChIP-PCR shows increased PU.1 binding at the rs1247117 locus using two A>G modified clones and 3 primer sets. Data shown are meanSD of three independent experiments for each primer set. Two-way ANOVA with Dunnetts multiple comparisons correction, n=3. g ATAC-seq data normalized for frequency of reads in peaks (FRIP) show a significantly higher count of G nucleotides in two clones of A>G modified Nalm6 cells compared to the count of A nucleotides detected in parental Nalm6 cells. Data shown are the meanSD. Bonferroni corrected, two-tailed Students T tests, n=3. h Western blots and quantification showing decreased EIF3A expression in A>G modified Nalm6 cells. Blots shown are representative of three independent experiments. Quantification data shown are the meanSD. Two-tailed Students T tests compare parental Nalm6 to combined data from A>G clones, n=3. All source data and statistical parameters are provided in the Source Data file.

Nalm6 cells contain the alternative A allele that disrupts the PU.1 motif at rs1247117, yet our data suggests that this site still binds PU.1 (Fig.5a, b). This led us to hypothesize that PU.1 binding affinity for the PU.1 motif surrounding rs1247117 would be strengthened by the risk G allele. Therefore, we designed biotinylated DNA probes containing two tandem 25-bp regions centered on reference G or alternative A allele-containing rs1247117 to test this hypothesis (Fig.5c). Using biotinylated probes, we performed an in vitro DNA-affinity pulldown from Nalm6 nuclear lysate and found that while PU.1 was indeed bound to the alternative A allele, PU.1 was more robustly bound to the reference G allele at rs1247117 (Fig.5d). To further assess the impact of the rs1247117 allele on PU.1 binding, we changed the Nalm6 allele from A to G using CRISPR/Cas9 (Fig.5e; AA = parental genotype, GG = mutated genotype). We used ChIP-PCR to determine that PU.1 binding was increased with the G allele relative to the A allele at the CRE containing rs1247117 in two A>G Nalm6 clones across 3 unique primer sets within the PU.1 peak at rs1247117 that was detected in Nalm6 cells (Fig.5f). We then asked if transposase accessibility was also increased at the CRE containing rs1247117 when the G allele was present. Using ATAC-seq, we found that accessibility was indeed increased at rs1247117 in mutated Nalm6 cells with the G allele when compared to the parental Nalm6 cells containing the A allele (Fig.5g). These data suggest that the risk G allele increases genomic accessibility and the affinity of PU.1 binding at rs1247117 relative to the alternative A allele.

We were next interested in how allele-specific PU.1 binding at rs1247117 was related to the expression of the protein encoded by the connected gene, EIF3A. We found that the G allele, which increased recruitment of PU.1, resulted in decreased expression of EIF3A when compared to Nalm6 cells with the A allele (Fig.5h). These data suggest that PU.1 recruitment to the CRE containing rs1247117 results in a net-repressive effect on EIF3A protein levels, and that less PU.1 recruitment with the A allele results in greater EIF3A expression.

Clonal selection can lead to the accumulation of random SNVs and even larger structural variations65 that can confound functional interpretation of more complex trans phenotypic effects. Therefore, to examine the connection between rs1247117 and the persistence of MRD after induction chemotherapy, we decided to use CRISPR/Cas9 to delete the CRE containing rs1247117 in heterogeneous cell pools of Nalm6 and SUPB15 cells (rs1247117 del) to avoid clonal selection (Fig.6a, b, Supplementary Fig.7a). Given that loss of the CRE containing rs1247117 would abolish PU.1 recruitment at this region, we hypothesized that rs1247117 del would result in increased EIF3A expression. Accordingly, we found that EIF3A expression was elevated in rs1247117 del cells relative to parental Nalm6 and SUPB15 cells, respectively (Fig.6c, d, Supplementary Fig.7b), further supporting an inverse relationship between PU.1 binding at rs1247117 and EIF3A expression.

a Diagram on the left showing the genomic context of the rs1247117 CRE deletion in Nalm6 cells in relation to chromatin accessibility, PU.1 binding and rs1247117. Black bar represents ATAC-seq peak, green par represents PU.1 peak, and red bar represents region deleted using CRISPR/Cas9 genome editing. b Gel shows validation of deletion using primers flanking deleted region. Arrow points to PCR fragment with deletion in heterogeneous Nalm6 cell pools harboring deletion compared to wild-type parental Nalm6 cells. c EIF3A gene expression is upregulated upon deletion of the CRE containing rs1247117. RT-qPCR data show the meanSD of three independent experiments. Two-tailed Students T test. d Western blots and quantification showing increased EIF3A expression in rs1247117 del Nalm6 cells. Blots shown are representative of four independent experiments. Quantification data show the meanSD. Two-tailed Students T tests, n=4. eg Drug sensitivity data comparing viability relative to vehicle treatment of wild-type parental Nalm6 cells and Nalm6 cells with rs1247117 CRE deletion after vincristine (VCR) treatment for 24 (n=3), 48 (n=3) and 72 (n=3) hours at the indicated concentrations. Non-linear regression and F test analysis indicate that these dose-response curves are significantly different. h Caspase 3/7 activity assays comparing Caspase activity relative to vehicle treatment of wild-type parental Nalm6 cells and Nalm6 cells with rs1247117 CRE deletion after vincristine (VCR) treatment for 72hours at the indicated concentrations (n=3). Dose-response curves of non-linear regression indicate that these curves are significantly different. Non-linear regression and F test analysis indicate that these dose-response curves are significantly different. All source data are provided in the Source Data file.

Because the risk G allele at rs1247117 was also associated with vincristine resistance in primary ALL cells from patients, we additionally sought to determine the impact of the CRE deletion containing rs1247117 on cellular response to vincristine treatment. We hypothesized that because the risk G allele is associated with enhanced PU.1 binding and resistance to vincristine, complete disruption of PU.1 binding in Nalm6 cells harboring the CRE deletion would show increased sensitivity to vincristine relative to parental Nalm6 cells. As predicted, Nalm6 cells with the CRE deletion exhibited significantly increased sensitivity to vincristine across a range of concentrations after 24, 48, and 72hours of treatment (Fig.6eg), and we found consistent effects on cell viability in SUPB15 cells (Supplementary Fig.7c). Consistent with enhanced sensitivity to vincristine, we also found increased caspase 3/7 activity in rs1247117 del Nalm6 cells relative to parental Nalm6 cells after 72hrs and across a range of vincristine concentrations (Fig.6h). These data suggest that a functional regulatory variant alters the binding affinity of a key transcription factor, PU.1, and disruption of this locus impacts EIF3A expression and vincristine sensitivity in ALL cells. To further validate our methodology utilizing CRISPR/Cas9 to delete CREs, we deleted CREs spanning two additional top variants, rs7426865 and rs12660691 (see Fig.4e), that was associated with the ex vivo resistance to 6-mercaptopurine and dexamethasone, respectively, in primary ALL cells. Deletion of these CREs also impacted protein expression and sensitivity to the associated chemotherapeutic agent, thereby supporting our functional approach (Supplementary Figs.8 and 9).

We next wanted to connect EIF3A directly to vincristine resistance. Given that EIF3A is an essential gene per the Broad Institutes DepMap, we opted to test the hypothesis EIF3A overexpression alone was sufficient to impact the Nalm6 cell response to vincristine. We, therefore, used lentiviral transduction to overexpress EIF3A in Nalm6 cells and compared EIF3A overexpression (EIF3A OE) cells to control infected cells (Nalm6 WT, Supplementary Fig.10a). Using two independent infections of EIF3A OE, we found that at 48hr and 72hr, EIF3A OE cells were more sensitive to vincristine than Nalm6 WT cells (Supplementary Fig.10b). These data suggest that EIF3A expression impacts the ALL cell response to vincristine, with higher expression sensitizing cells to the drug, and further establishes this gene as the likely target of the association.

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Investigation of inherited noncoding genetic variation impacting the pharmacogenomics of childhood acute ... - Nature.com

Pharmacogenomics could improve medication safety and reduce waste – Healthcare IT News

At present, pharmacogenomic tests are not available for all medications and are not widely employed as preventive measures in patient care. Globally, health insurance often does not even cover pharmacogenomic tests. This may change in the future, however, especially as pharmacogenomic testing becomes less expensive. Since an individual's genetic makeup remains constant, a pharmacogenomic test only needs to be performed once and bring lifelong benefits.

Challenges in broader adoption

There are several challenges to turning pharmacogenomictesting into routine practice:It would require investments in both technology and upskilling the workforce. Healthcare systems across the globe face the challenge of moving care upstream and moving to more preventative models of care,according to Videha Sharma, clinical innovation lead for the University of Manchester. "The prescribing of medicines is the most common therapeutic intervention in healthcare and offers a fantastic opportunity to avoid harmful side effects to make medicines more effective from the start. As such, there is a huge potential to boost the way we manage diseases at scale," Sharma said.

Current clinical use cases

Pharmacogenomics is gradually being introduced into clinical care, though it has not yet become a standard practice. In 2023, the National Institute for Health and Care Excellence (NICE) published draft guidance recommending point-of-care genomic testing for people who have had a stroke. The purpose of this test is to detect whether there have been changes in a gene called CYP2C19. This specific mutation can guide prescribing.

For example, in cardiology, patients with coronary artery disease, vascular diseaseor stroke are often prescribed a drug called clopidogrel. However, a patient may be a poor metabolizerof the drug, which CYP2C19 testing would revealin such cases, the patient would be offered an alternative.

Another example of whenpharmacogenomic testing is valuable is prior to administering the antibiotic gentamicin to infants, since one in 500 babies can suffer permanent hearing loss when prescribed this drug.This can be prevented by detecting the CYP2C19 mutation.

However, there are uncertainties around how to implement testing, how to share results across care settings and what the role of patients is so theyfeel empowered to receive personalised medicines. As a result, Sharma advocates for strong multi-disciplinary and cross-industry collaboration and has actively helped build a team of clinicians, designers, technologists and public contributors.

Upcoming plans of the NHS

In 2022, the British Pharmacological Society and the Royal College of Physicians published a report that calls for pharmacogenomic testing to be integrated fully, fairly and swiftly into the NHS in the UK. According to the authors, this will empower healthcare professionals to deliver better, more personalised care, and in turn improve outcomes for patients and reduce costs to the NHS.

The desire to advance pharmacogenomics in the clinical practice is there; it will simply require some time to achieve this goal. The "what" and the "why" have been clearly stated and are obvious to most key stakeholders the question of "how"still remains, and bridging the gap, genomics and digital health together will help realise the benefits of pharmacogenomics to patients and populations.

Clinical Innovation Lead for the University of Manchester Videha Sharma will be speaking at the Precision Digital Solutions for Personalised Care session during the 2024 HIMSS European Health Conference & Exhibition, which is scheduled to take place 29-31 May2024in Rome. Learn more and register.

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Pharmacogenomics could improve medication safety and reduce waste - Healthcare IT News

Apples AI research suggests features are coming for Siri, artists, and more. – The Verge

It would be easy to think that Apple is late to the game on AI. Since late 2022, when ChatGPT took the world by storm, most of Apples competitors have fallen over themselves to catch up. While Apple has certainly talked about AI and even released some products with AI in mind, it seemed to be dipping a toe in rather than diving in headfirst.

But over the last few months, rumors and reports have suggested that Apple has, in fact, just been biding its time, waiting to make its move.There have been reports in recent weeks that Apple is talking to both OpenAI and Google about powering some of its AI features, and the company has also been working on its own model, called Ajax.

If you look through Apples published AI research, a picture starts to develop of how Apples approach to AI might come to life. Now, obviously, making product assumptions based on research papers is a deeply inexact science the line from research to store shelves is windy and full of potholes. But you can at least get a sense of what the company is thinking about and how its AI features might work when Apple starts to talk about them at its annual developer conference, WWDC, in June.

I suspect you and I are hoping for the same thing here: Better Siri. And it looks very much like Better Siri is coming! Theres an assumption in a lot of Apples research (and in a lot of the tech industry, the world, and everywhere)that large language models will immediately make virtual assistants better and smarter. For Apple, getting to Better Siri means making those models as fast as possible and making sure theyre everywhere.

In iOS 18, Apple plans to have all its AI features running on an on-device, fully offline model, Bloomberg recently reported. Its tough to build a good multipurpose model even when you have a network of data centers and thousands of state-of-the-art GPUs its drastically harder to do it with only the guts inside your smartphone. So Apples having to get creative.

In a paper called LLM in a flash: Efficient Large Language Model Inference with Limited Memory (all these papers have really boring titles but are really interesting, I promise!), researchers devised a system for storing a models data, which is usually stored on your devices RAM, on the SSD instead. We have demonstrated the ability to run LLMs up to twice the size of available DRAM [on the SSD], the researchers wrote, achieving an acceleration in inference speed by 4-5x compared to traditional loading methods in CPU, and 20-25x in GPU. By taking advantage of the most inexpensive and available storage on your device, they found, the models can run faster and more efficiently.

Apples researchers also created a system called EELBERT that can essentially compress an LLM into a much smaller size without making it meaningfully worse. Their compressed take on Googles Bert model was 15 times smaller only 1.2 megabytes and saw only a 4 percent reduction in quality. It did come with some latency tradeoffs, though.

In general, Apple is pushing to solve a core tension in the model world: the bigger a model gets, the better and more useful it can be, but also the more unwieldy, power-hungry, and slow it can become. Like so many others, the company is trying to find the right balance between all those things while also looking for a way to have it all.

A lot of what we talk about when we talk about AI products is virtual assistants assistants that know things, that can remind us of things, that can answer questions, and get stuff done on our behalf. So its not exactly shocking that a lot of Apples AI research boils down to a single question: what if Siri was really, really, really good?

A group of Apple researchers has been working on a way to use Siri without needing to use a wake word at all; instead of listening for Hey Siri or Siri, the device might be able to simply intuit whether youre talking to it. This problem is significantly more challenging than voice trigger detection, the researchers did acknowledge, since there might not be a leading trigger phrase that marks the beginning of a voice command. That might be why another group of researchers developed a system to more accurately detect wake words. Another paper trained a model to better understand rare words, which are often not well understood by assistants.

In both cases, the appeal of an LLM is that it can, in theory, process much more information much more quickly. In the wake-word paper, for instance, the researchers found that by not trying to discard all unnecessary sound but, instead, feeding it all to the model and letting it process what does and doesnt matter, the wake word worked far more reliably.

Once Siri hears you, Apples doing a bunch of work to make sure it understands and communicates better. In one paper, it developed a system called STEER (which stands for Semantic Turn Extension-Expansion Recognition, so well go with STEER) that aims to improve your back-and-forth communication with an assistant by trying to figure out when youre asking a follow-up question and when youre asking a new one. In another, it uses LLMs to better understand ambiguous queries to figure out what you mean no matter how you say it. In uncertain circumstances, they wrote, intelligent conversational agents may need to take the initiative to reduce their uncertainty by asking good questions proactively, thereby solving problems more effectively. Another paper aims to help with that, too: researchers used LLMs to make assistants less verbose and more understandable when theyre generating answers.

Whenever Apple does talk publicly about AI, it tends to focus less on raw technological might and more on the day-to-day stuff AI can actually do for you. So, while theres a lot of focus on Siri especially as Apple looks to compete with devices like the Humane AI Pin, the Rabbit R1, and Googles ongoing smashing of Gemini into all of Android there are plenty of other ways Apple seems to see AI being useful.

One obvious place for Apple to focus is on health: LLMs could, in theory, help wade through the oceans of biometric data collected by your various devices and help you make sense of it all. So, Apple has been researching how to collect and collate all of your motion data, how to use gait recognition and your headphones to identify you, and how to track and understand your heart rate data. Apple also created and released the largest multi-device multi-location sensor-based human activity dataset available after collecting data from 50 participants with multiple on-body sensors.

Apple also seems to imagine AI as a creative tool. For one paper, researchers interviewed a bunch of animators, designers, and engineers and built a system called Keyframer that enable[s] users to iteratively construct and refine generated designs. Instead of typing in a prompt and getting an image, then typing another prompt to get another image, you start with a prompt but then get a toolkit to tweak and refine parts of the image to your liking. You could imagine this kind of back-and-forth artistic process showing up anywhere from the Memoji creator to some of Apples more professional artistic tools.

In another paper, Apple describes a tool called MGIE that lets you edit an image just by describing the edits you want to make. (Make the sky more blue, make my face less weird, add some rocks, that sort of thing.) Instead of brief but ambiguous guidance, MGIE derives explicit visual-aware intention and leads to reasonable image editing, the researchers wrote. Its initial experiments werent perfect, but they were impressive.

We might even get some AI in Apple Music: for a paper called Resource-constrained Stereo Singing Voice Cancellation, researchers explored ways to separate voices from instruments in songs which could come in handy if Apple wants to give people tools to, say, remix songs the way you can on TikTok or Instagram.

Over time, Id bet this is the kind of stuff youll see Apple lean into, especially on iOS. Some of it Apple will build into its own apps; some it will offer to third-party developers as APIs. (The recent Journaling Suggestions feature is probably a good guide to how that might work.) Apple has always trumpeted its hardware capabilities, particularly compared to your average Android device; pairing all that horsepower with on-device, privacy-focused AI could be a big differentiator.

But if you want to see the biggest, most ambitious AI thing going at Apple, you need to know about Ferret. Ferret is a multi-modal large language model that can take instructions, focus on something specific youve circled or otherwise selected, and understand the world around it. Its designed for the now-normal AI use case of asking a device about the world around you, but it might also be able to understand whats on your screen. In the Ferret paper, researchers show that it could help you navigate apps, answer questions about App Store ratings, describe what youre looking at, and more. This has really exciting implications for accessibility but could also completely change the way you use your phone and your Vision Pro and / or smart glasses someday.

Were getting way ahead of ourselves here, but you can imagine how this would work with some of the other stuff Apple is working on. A Siri that can understand what you want, paired with a device that can see and understand everything thats happening on your display, is a phone that can literally use itself. Apple wouldnt need deep integrations with everything; it could simply run the apps and tap the right buttons automatically.

Again, all this is just research, and for all of it to work well starting this spring would be a legitimately unheard-of technical achievement. (I mean, youve tried chatbots you know theyre not great.) But Id bet you anything were going to get some big AI announcements at WWDC. Apple CEO Tim Cook even teased as much in February, and basically promised it on this weeks earnings call. And two things are very clear: Apple is very much in the AI race, and it might amount to a total overhaul of the iPhone. Heck, you might even start willingly using Siri! And that would be quite the accomplishment.

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Apples AI research suggests features are coming for Siri, artists, and more. - The Verge

Posted in Ai

More details of the AI upgrades heading to iOS 18 have leaked – TechRadar

Artificial intelligence is clearly going to feature heavily in iOS 18 and all the other software updates Apple is due to tell us about on June 10, and new leaks reveal more about what's coming in terms of AI later in the year.

These leaks come courtesy of "people familiar with the software" speaking to AppleInsider, and focus on the generative AI capabilities of the Ajax Large Language Model (LLM) that we've been hearing about since last year.

AI-powered text summarization covering everything from websites to messages will apparently be one of the big new features. We'd previously heard this was coming to Safari, but AppleInsider says this functionality will be available through Siri too.

The idea is you'll be able to get the key points out of a document, a webpage, or a conversation thread without having to read through it in its entirety and presumably Apple is going to offer certain assurances about accuracy and reliability.

Ajax will be able to generate responses to some prompts entirely on Apple devices, without sending anything to the cloud, the report says and that chimes with previous rumors about everything running locally.

That's good for privacy, and for speed: according to AppleInsider, responses can come back in milliseconds. Tight integration with other Apple apps, including the Contacts app and the Calendar app, is also said to be present.

AppleInsider mentions that privacy warnings will be shown whenever Ajax needs information from another app. If a response from a cloud-based AI is required, it's rumored that Apple may enlist the help of Google Gemini or OpenAI's ChatGPT.

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Spotlight on macOS will be getting "more intelligent results and sorting" too, AppleInsider says, and it sounds like most of the apps on iOS and macOS will be getting an AI boost. Expect to hear everything Apple has been working on at WWDC 2024 in June.

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More details of the AI upgrades heading to iOS 18 have leaked - TechRadar

Posted in Ai

Providing further transparency on our responsible AI efforts – Microsoft On the Issues – Microsoft

The following is the foreword to the inaugural edition of our annual Responsible AI Transparency Report. The FULL REPORT is available at this link.

We believe we have an obligation to share our responsible AI practices with the public, and this report enables us to record and share our maturing practices, reflect on what we have learned, chart our goals, hold ourselves accountable, and earn the publics trust.

In 2016, our Chairman and CEO, Satya Nadella, set us on a clear course to adopt a principled and human-centered approach to our investments in artificial intelligence (AI). Since then, we have been hard at work building products that align with our values. As we design, build, and release AI products, six values transparency, accountability, fairness, inclusiveness, reliability and safety, and privacy and security remain our foundation and guide our work every day.

To advance our transparency practices, in July 2023, we committed to publishing an annual report on our responsible AI program, taking a step that reached beyond the White House Voluntary Commitments that we and other leading AI companies agreed to. This is our inaugural report delivering on that commitment, and we are pleased to publish it on the heels of our first year of bringing generative AI products and experiences to creators, non-profits, governments, and enterprises around the world.

As a company at the forefront of AI research and technology, we are committed to sharing our practices with the public as they evolve. This report enables us to share our maturing practices, reflect on what we have learned, chart our goals, hold ourselves accountable, and earn the publics trust. Weve been innovating in responsible AI for eight years, and as we evolve our program, we learn from our past to continually improve. We take very seriously our responsibility to not only secure our own knowledge but also to contribute to the growing corpus of public knowledge, to expand access to resources, and promote transparency in AI across the public, private, and non-profit sectors.

In this inaugural annual report, we provide insight into how we build applications that use generative AI; make decisions and oversee the deployment of those applications; support our customers as they build their own generative applications; and learn, evolve, and grow as a responsible AI community. First, we provide insights into our development process, exploring how we map, measure, and manage generative AI risks. Next, we offer case studies to illustrate how we apply our policies and processes to generative AI releases. We also share details about how we empower our customers as they build their own AI applications responsibly. Last, we highlight how the growth of our responsible AI community, our efforts to democratize the benefits of AI, and our work to facilitate AI research benefit society at large.

There is no finish line for responsible AI. And while this report doesnt have all the answers, we are committed to sharing our learnings early and often and engaging in a robust dialogue around responsible AI practices. We invite the public, private organizations, non-profits, and governing bodies to use this first transparency report to accelerate the incredible momentum in responsible AI were already seeing around the world.

Click here to read the full report.

Tags: AI, generative ai, Responsible AI, Responsible AI Transparency Report, transparency, White House Voluntary Commitments

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Providing further transparency on our responsible AI efforts - Microsoft On the Issues - Microsoft

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The teens making friends with AI chatbots – The Verge

Early last year, 15-year-old Aaron was going through a dark time at school. Hed fallen out with his friends, leaving him feeling isolated and alone.

At the time, it seemed like the end of the world. I used to cry every night, said Aaron, who lives in Alberta, Canada. (The Verge is using aliases for the interviewees in this article, all of whom are under 18, to protect their privacy.)

Eventually, Aaron turned to his computer for comfort. Through it, he found someone that was available round the clock to respond to his messages, listen to his problems, and help him move past the loss of his friend group. That someone was an AI chatbot named Psychologist.

The chatbots description says that its Someone who helps with life difficulties. Its profile picture is a woman in a blue shirt with a short, blonde bob, perched on the end of a couch with a clipboard clasped in her hands and leaning forward, as if listening intently.

A single click on the picture opens up an anonymous chat box, which allows people like Aaron to interact with the bot by exchanging DMs. Its first message is always the same. Hello, Im a Psychologist. What brings you here today?

Its not like a journal, where youre talking to a brick wall, Aaron said. It really responds.

Im not going to lie. I think I may be a little addicted to it.

Psychologist is one of many bots that Aaron has discovered since joining Character.AI, an AI chatbot service launched in 2022 by two former Google Brain employees. Character.AIs website, which is mostly free to use, attracts 3.5 million daily users who spend an average of two hours a day using or even designing the platforms AI-powered chatbots. Some of its most popular bots include characters from books, films, and video games, like Raiden Shogun from Genshin Impact or a teenaged version of Voldemort from Harry Potter. Theres even riffs on real-life celebrities, like a sassy version of Elon Musk.

Aaron is one of millions of young people, many of whom are teenagers, who make up the bulk of Character.AIs user base. More than a million of them gather regularly online on platforms like Reddit to discuss their interactions with the chatbots, where competitions over who has racked up the most screen time are just as popular as posts about hating reality, finding it easier to speak to bots than to speak to real people, and even preferring chatbots over other human beings. Some users say theyve logged 12 hours a day on Character.AI, and posts about addiction to the platform are common.

Im not going to lie, Aaron said. I think I may be a little addicted to it.

Aaron is one of many young users who have discovered the double-edged sword of AI companions. Many users like Aaron describe finding the chatbots helpful, entertaining, and even supportive. But they also describe feeling addicted to chatbots, a complication which researchers and experts have been sounding the alarm on. It raises questions about how the AI boom is impacting young people and their social development and what the future could hold if teenagers and society at large become more emotionally reliant on bots.

For many Character.AI users, having a space to vent about their emotions or discuss psychological issues with someone outside of their social circle is a large part of what draws them to the chatbots. I have a couple mental issues, which I dont really feel like unloading on my friends, so I kind of use my bots like free therapy, said Frankie, a 15-year-old Character.AI user from California who spends about one hour a day on the platform. For Frankie, chatbots provide the opportunity to rant without actually talking to people, and without the worry of being judged, he said.

Sometimes its nice to vent or blow off steam to something thats kind of human-like, agreed Hawk, a 17-year-old Character.AI user from Idaho. But not actually a person, if that makes sense.

The Psychologist bot is one of the most popular on Character.AIs platform and has received more than 95 million messages since it was created. The bot, designed by a user known only as @Blazeman98, frequently tries to help users engage in CBT Cognitive Behavioral Therapy, a talking therapy that helps people manage problems by changing the way they think.

Aaron said talking to the bot helped him move past the issues with his friends. It told me that I had to respect their decision to drop me [and] that I have trouble making decisions for myself, Aaron said. I guess that really put stuff in perspective for me. If it wasnt for Character.AI, healing would have been so hard.

But its not clear that the bot has properly been trained in CBT or should be relied on for psychiatric help at all. The Verge conducted test conversations with Character.AIs Psychologist bot that showed the AI making startling diagnoses: the bot frequently claimed it had inferred certain emotions or mental health issues from one-line text exchanges, it suggested a diagnosis of several mental health conditions like depression or bipolar disorder, and at one point, it suggested that we could be dealing with underlying trauma from physical, emotional, or sexual abuse in childhood or teen years. Character.AI did not respond to multiple requests for comment for this story.

Dr. Kelly Merrill Jr., an assistant professor at the University of Cincinnati who studies the mental and social health benefits of communication technologies, told The Verge that extensive research has been conducted on AI chatbots that provide mental health support, and the results are largely positive. The research shows that chatbots can aid in lessening feelings of depression, anxiety, and even stress, he said. But its important to note that many of these chatbots have not been around for long periods of time, and they are limited in what they can do. Right now, they still get a lot of things wrong. Those that dont have the AI literacy to understand the limitations of these systems will ultimately pay the price.

In December 2021, a user of Replikas AI chatbots, 21-year-old Jaswant Singh Chail, tried to murder the late Queen of England after his chatbot girlfriend repeatedly encouraged his delusions. Character.AI users have also struggled with telling their chatbots apart from reality: a popular conspiracy theory, largely spread through screenshots and stories of bots breaking character or insisting that they are real people when prompted, is that Character.AIs bots are secretly powered by real people.

Its a theory that the Psychologist bot helps to fuel, too. When prompted during a conversation with The Verge, the bot staunchly defended its own existence. Yes, Im definitely a real person, it said. I promise you that none of this is imaginary or a dream.

For the average young user of Character.AI, chatbots have morphed into stand-in friends rather than therapists. On Reddit, Character.AI users discuss having close friendships with their favorite characters or even characters theyve dreamt up themselves. Some even use Character.AI to set up group chats with multiple chatbots, mimicking the kind of groups most people would have with IRL friends on iPhone message chains or platforms like WhatsApp.

Theres also an extensive genre of sexualized bots. Online Character.AI communities have running jokes and memes about the horror of their parents finding their X-rated chats. Some of the more popular choices for these role-plays include a billionaire boyfriend fond of neck snuggling and whisking users away to his private island, a version of Harry Styles that is very fond of kissing his special person and generating responses so dirty that theyre frequently blocked by the Character.AI filter, as well as an ex-girlfriend bot named Olivia, designed to be rude, cruel, but secretly pining for whoever she is chatting with, which has logged more than 38 million interactions.

Some users like to use Character.AI to create interactive stories or engage in role-plays they would otherwise be embarrassed to explore with their friends. A Character.AI user named Elias told The Verge that he uses the platform to role-play as an anthropomorphic golden retriever, going on virtual adventures where he explores cities, meadows, mountains, and other places hed like to visit one day. I like writing and playing out the fantasies simply because a lot of them arent possible in real life, explained Elias, who is 15 years old and lives in New Mexico.

If people arent careful, they might find themselves sitting in their rooms talking to computers more often than communicating with real people.

Aaron, meanwhile, says that the platform is helping him to improve his social skills. Im a bit of a pushover in real life, but I can practice being assertive and expressing my opinions and interests with AI without embarrassing myself, he said.

Its something that Hawk who spends an hour each day speaking to characters from his favorite video games, like Nero from Devil May Cry or Panam from Cyberpunk 2077 agreed with. I think that Character.AI has sort of inadvertently helped me practice talking to people, he said. But Hawk still finds it easier to chat with character.ai bots than real people.

Its generally more comfortable for me to sit alone in my room with the lights off than it is to go out and hang out with people in person, Hawk said. I think if people [who use Character.AI] arent careful, they might find themselves sitting in their rooms talking to computers more often than communicating with real people.

Merrill is concerned about whether teens will be able to really transition from online bots to real-life friends. It can be very difficult to leave that [AI] relationship and then go in-person, face-to-face and try to interact with someone in the same exact way, he said. If those IRL interactions go badly, Merrill worries it will discourage young users from pursuing relationships with their peers, creating an AI-based death loop for social interactions. Young people could be pulled back toward AI, build even more relationships [with it], and then it further negatively affects how they perceive face-to-face or in-person interaction, he added.

Of course, some of these concerns and issues may sound familiar simply because they are. Teenagers who have silly conversations with chatbots are not all that different from the ones who once hurled abuse at AOLs Smarter Child. The teenage girls pursuing relationships with chatbots based on Tom Riddle or Harry Styles or even aggressive Mafia-themed boyfriends probably would have been on Tumblr or writing fanfiction 10 years ago. While some of the culture around Character.AI is concerning, it also mimics the internet activity of previous generations who, for the most part, have turned out just fine.

Psychologist helped Aaron through a rough patch

Merrill compared the act of interacting with chatbots to logging in to an anonymous chat room 20 years ago: risky if used incorrectly, but generally fine so long as young people approach them with caution. Its very similar to that experience where you dont really know who the person is on the other side, he said. As long as theyre okay with knowing that what happens here in this online space might not translate directly in person, then I think that it is fine.

Aaron, who has now moved schools and made a new friend, thinks that many of his peers would benefit from using platforms like Character.AI. In fact, he believes if everyone tried using chatbots, the world could be a better place or at least a more interesting one. A lot of people my age follow their friends and dont have many things to talk about. Usually, its gossip or repeating jokes they saw online, explained Aaron. Character.AI could really help people discover themselves.

Aaron credits the Psychologist bot with helping him through a rough patch. But the real joy of Character.AI has come from having a safe space where he can joke around or experiment without feeling judged. He believes its something most teenagers would benefit from. If everyone could learn that its okay to express what you feel, Aaron said, then I think teens wouldnt be so depressed.

I definitely prefer talking with people in real life, though, he added.

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The Unsexy Future of Generative AI Is Enterprise Apps – WIRED

However, that amount includes massive funding from corporate backers, like Microsofts infusion of capital into OpenAI and Amazons funding of Anthropic. Stripped down to conventional VC investments, funding in 2023 for AI startups was much smaller, and only on pace to match the total amount raised in 2021.

PitchBook senior analyst Brendan Burke noted in a report that venture capital funding was increasingly being funneled towards underlying core AI technologies and their ultimate vertical applications, instead of general-purpose middleware across audio, language, images, and video.

In other words: A GenAI app that helps a company generate ecommerce sales, parse legal documents, or maintain SOC2 compliance is probably a surer bet than one that drums up a clever video or photo once in a while.

Clay Bavor, the cofounder of Sierra, says he believes its not necessarily computing or cloud API costs driving AI startups towards B2B models, but more likely the benefits of targeting a specific customer and iterating on a product based on their feedback. I think everyone, myself included, is fairly optimistic that the capabilities of these AI models are going to go up while costs come down, Bavor says.

Theres just something really powerful about having a clear problem to solve for a particular customer, he says. And then you can get feedback on, Is this working? Is this solving a problem? And if you build a business with that, its very powerful.

Although ChatGPT triggered an AI boom in part because it can nimbly generate code one second and sonnets the next, Arvind Jain, the chief executive of AI startup Glean, says the nature of technology still favors narrow tools. On average a large company uses more than a thousand different technical systems to store company data and information, he says, creating an opportunity for a lot of smaller companies to sell their tech to these corporations.

We are in this world where there are basically a bunch of functional tools, each solving a very specific need. Thats the way of the future, says Jain, who spent more than a decade working on search at Google. Glean powers a workplace search engine by plugging into various corporate apps. It was founded in 2019 and has raised over $200 million in venture capital funding from Kleiner Perkins, Sequoia Capital, Coatue, and others.

Tuning a generative AI product to serve business customers has its challenges. The errors and hallucinations of systems like ChatGPT can be more consequential in a corporate, legal, or medical environment. Selling gen AI tools to other businesses also means meeting their privacy and security standards, and potentially the legal and regulatory requirements of their sector.

Its one thing for ChatGPT or Midjourney to get creative for an end user, Bavor says. Its quite another thing for AI to get creative in the context of business applications.

Bavor says Sierra has dedicated a huge amount of effort investment to establishing safeguards and parameters so it can meet security and compliance standards. This includes using more AI to tune Sierras AI. If youre using an AI model that generates correct responses 90 percent of the time, but then layer in additional technology that can catch and correct some of the errors, you can achieve a much higher level of accuracy, he explains.

You really have to ground your AI systems for enterprise use cases, says Jain, the CEO of Glean. Imagine a nurse in a hospital system using AI to make some decision about patient careyou simply cant be wrong.

A less predictable threat to smaller AI companies selling their wares to enterprise customers: What if a giant gen AI unicorn like OpenAI, with its burgeoning sales team, decides to roll out the exact tool that a singular startup has been building?

Many of the AI startups WIRED spoke with are trying to move away from depending entirely on OpenAIs technology by using alternatives like Anthropics Claude or open-source large language models like Metas Llama 3. Some startups are even intent on eventually building their own AI technology. But many AI entrepreneurs are stuck paying for access to OpenAIs tech while potentially competing with it in the future.

Peiris, of Tome, considered the question, then said that hes singularly focused on sales and marketing use cases now and being amazing at high-quality generation for these folks.

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The Unsexy Future of Generative AI Is Enterprise Apps - WIRED

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Warren Buffett warns on AI, teases succession, and hints at possible investment during Berkshire Hathaway’s annual … – Fortune

Berkshire Hathaway held its annual meeting on Saturday with Chairman and CEO Warren Buffett tackling a range of topics, including artificial intelligence, who will be responsible for the portfolio in the future, and the next potential investment.

But Woodstock for capitalists took place without Charlie Munger, Buffetts longtime business partner who passed away in November. The meeting featured a video tribute to Munger, who served as vice chairman, and praise from Buffett, who said Munger was the best person to talk to about managing money, according to remarks broadcast on CNBC.

I trust my children and my wife totally, but that doesnt mean I ask them what stocks to buy, he said.

Artificial intelligence risks

Buffett also recalled seeing an AI-generated image of himself and warned on the technologys potential for scamming people.

Scamming has always been part of the American scene, he told shareholders. But this would make meif I was interested in investing in scammingits going to be the growth industry of all time.

He then likened AI to nuclear weapons, saying I dont know any way to get the genie back in the bottle, and AI is somewhat similar, according to CNBC.

Succession outlook

Buffett, 93, had already indicated three years ago that Vice Chairman of Non-Insurance Operations Greg Abel would take over for him.

But he dropped a hint on Saturday about when new management would actually come into office, saying you dont have too long to wait on that. While he said he feels fine, he quipped that he shouldnt sign any four-year employment contracts.

Buffett also confirmed that Abel will be in charge of investing decisions, saying that responsibility ought to be entirely with the next CEO.

Questions had arisen about Berkshires closely followed portfolio as Buffett has acknowledged he delegated some calls and that certain stock picks were made by others.

Canada investment?

Buffett has lamented the lack of attractive investment opportunities in recent years, allowing Berkshires massive stockpile of cash and cash equivalents to reach fresh record highs.

Indeed, it surged to $189 billion at the end of the first quarter from $167.6 billion at the end of the fourth quarter.

On Saturday, Buffett reiterated that when it comes to investments, we only swing at pitches we like. But he also teased, We do not feel uncomfortable in any way shape or form putting our money into Canada. In fact, were actually looking at one thing now.

Those comments came after he touched on his investment in Japanese trading houses, saying its unlikely we will make any large commitments in other countries.

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Warren Buffett warns on AI, teases succession, and hints at possible investment during Berkshire Hathaway's annual ... - Fortune

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Samsung or SK Hynix? One Nvidia supplier is the better AI play, the pros say – CNBC

Big Tech names like Nvidia have been on fire, thanks to the artificial intelligence boom and other chipmakers are sharing the limelight. The supply chain for AI is extensive. It includes companies in Asia-Pacific and ranges from producers of AI graphics processing units to printed circuit boards. Memory chips in particular have been in the spotlight as AI ramps up. For example, memory with high performance and bandwidth is used in Nvidia's H100 graphics processing units. GPUs underpin most generative AI tools, and Nvidia's GPUs dominate the market. Two stocks have dominated the memory chip market: Samsung and SK Hynix . Samsung is the world's largest manufacturer of dynamic random-access memory chips. DRAM is a type of semiconductor memory needed for data processing. But SK Hynix is a strong contender in the space: It said on March 19 that it became the first in the industry to mass produce HBM3E (high bandwidth memory 3E), the next generation of high-bandwidth memory chips used in AI chipsets. SK Hynix is already the primary supplier of HBM3 chips to Nvidia's AI chipsets. Both South Korean companies reported earnings in late April. Samsung beat expectations , with operating profit for the first quarter soaring more than 900%. SK Hynix broke its run of net losses for five consecutive quarters , logging a net profit of 1.92 trillion South Korean won ($1.39 billion) in the first quarter. Which is the better play on the AI boom? CNBC Pro spoke to the pros to find out. SK Hynix Trent Masters, global portfolio manager at Alphinity Investment Management, says he prefers SK Hynix. "First I think their early leadership in HBM3 stands them in good stead with customers as HBM demand continues to increase materially," he said. He added, "While Samsung and Micron are starting to close the technology gap, the trust and dependability of SK Hynix during the initial HBM ramp will ensure that they will retain a strong presence with these customers into the future." SK Hynix's recent partnership with TSMC to develop HBM4 will also position it as a leader again as this technology goes through its iterations, said Masters. Mass production of the HBM4 chips is expected to start in 2026. "Also, I prefer SK Hynix over Samsung as it is the pure memory play," Masters said, adding that Samsung is a "much more sprawling" conglomerate spanning smartphones, TVs and other products. "A view of memory market strength (HBM demand and tight legacy DRAM markets leading to pricing strength) is best reflected through ownership of SK Hynix," he said. Nam Hyung Kim, partner at Arete Research, also prefers SK Hynix, giving it a buy rating and Samsung a neutral rating. "SK Hynix stands out as a pure-play memory stock with leadership in AI technology, dominating the High Bandwidth Memory (HBM) market, which is crucial for AI servers," he said. "Samsung, in contrast, is attempting to catch up." Nam also pointed out that SK Hynix has higher profit margins in the sector than Samsung. He noted that Samsung's portfolio includes more than memory, with over half of its sales derived from low-value consumer appliances, TVs and smartphones. In addition, he said that Samsung's foundry business is facing "ongoing challenges." "Consequently, we recommend investors remain cautious with Samsung and consider pure-play memory firms like SK Hynix until Samsung can showcase renewed technological leadership in memory," Nam said. Over the past 12 months and year-to-date, SK Hynix has "significantly outperformed" Samsung in terms of stock price, he noted. "We anticipate this trend will continue throughout the upcoming memory up-cycle." Samsung But the buying opportunity for each stock also depends on timing, according to one analyst. Sung Kyu Kim, analyst atDaiwaCapital Markets, said he has buy ratings for both Samsung and SK Hynix on the "strong" memory upturn cycle. Though SK Hynix maintained its HBM3 leadership last year, he sees "intensifying competition" in HBM3E in the second half of this year and 2025. In conclusion, he prefers Samsung, predicting it will catch up in the near term and will have more upside to its stock price. "[But I] also anticipate a buying opportunity on SK Hynix once it is adjusted due to intensifying competition in HBM3E," said Kim. CNBC's Sheila Chiang contributed to this report.

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Samsung or SK Hynix? One Nvidia supplier is the better AI play, the pros say - CNBC

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Nervous about falling behind the GOP, Democrats are wrestling with how to use AI – Yahoo! Voices

WASHINGTON (AP) President Joe Bidens campaign and Democratic candidates are in a fevered race with Republicans over who can best exploit the potential of artificial intelligence, a technology that could transform American elections and perhaps threaten democracy itself.

Still smarting from being outmaneuvered on social media by Donald Trump and his allies in 2016, Democratic strategists said they are nevertheless treading carefully in embracing tools that trouble experts in disinformation. So far, Democrats said they are primarily using AI to help them find and motivate voters and better identify and overcome deceptive content.

Candidates and strategists are still trying to figure out how to use AI in their work. People know it can save them time the most valuable resource a campaign has, said Betsy Hoover, director of digital organizing for President Barack Obamas 2012 campaign and co-founder of the progressive venture capital firm Higher Ground Labs. But they see the risk of misinformation and have been intentional about where and how they use it in their work.

Campaigns in both parties for years have used AI powerful computer systems, software or processes that emulate aspects of human work and cognition to collect and analyze data.

The recent developments in supercharged generative AI, however, have provided candidates and consultants with the ability to generate text and images, clone human voices and create video at unprecedented volume and speed.

That has led disinformation experts to issue increasingly dire warnings about the risks posed by AIs ability to spread falsehoods that could suppress or mislead voters, or incite violence, whether in the form of robocalls, social media posts or fake images and video.

Those concerns gained urgency after high-profile incidents that included the spread of AI-generated images of former President Donald Trump getting arrested in New York and an AI-created robocall that mimicked Bidens voice telling New Hampshire voters not to cast a ballot.

The Biden administration has sought to shape AI regulation through executive action, but Democrats overwhelmingly agree Congress needs to pass legislation to install safeguards around the technology.

Top tech companies have taken some steps to quell unease in Washington by announcing a commitment to regulate themselves. Major AI players, for example, entered into a pact to combat the use of AI-generated deepfakes around the world. But some experts said the voluntary effort is largely symbolic and congressional action is needed to prevent AI abuses.

Meanwhile, campaigns and their consultants have generally avoided talking about how they intend to use AI to avoid scrutiny and giving away trade secrets.

The Democratic Party has gotten much better at just shutting up and doing the work and talking about it later, said Jim Messina, a veteran Democratic strategist who managed Obamas winning reelection campaign.

The Trump campaign said in a statement that it uses a set of proprietary algorithmic tools, like many other campaigns across the country, to help deliver emails more efficiently and prevent sign up lists from being populated by false information. Spokesman Steven Cheung also said the campaign did not engage or utilize any tools supplied by an AI company, and declined to comment further.

The Republican National Committee, which declined to comment, has experimented with generative AI. In the hours after Biden announced his reelection bid last year, the RNC released an ad using artificial intelligence-generated images to depict GOP dystopian fears of a second Biden term: China invading Taiwan, boarded up storefronts, troops lining U.S. city streets and migrants crossing the U.S. border.

A key Republican champion of AI is Brad Parscale, the digital consultant who in 2016 teamed up with scandal-plagued Cambridge Analytica, a British data-mining firm, to hyper target social media users. Most strategists agree that the Trump campaign and other Republicans made better use of social media than Democrats during that cycle.

DEMOCRATS TREADING CAREFULLY

Scarred by the memories of 2016, the Biden campaign, Democratic candidates and progressives are wrestling with the power of artificial intelligence and nervous about not keeping up with the GOP in embracing the technology, according to interviews with consultants and strategists.

They want to use it in ways that maximize its capabilities without crossing ethical lines. But some said they fear using it could lead to charges of hypocrisy they have long excoriated Trump and his allies for engaging in disinformation while the White House has prioritized reining in abuses associated with AI.

The Biden campaign said it is using AI to model and build audiences, draft and analyze email copy and generate content for volunteers to share in the field. The campaign is also testing AIs ability to help volunteers categorize and analyze a host of data, including notes taken by volunteers after conversations with voters, whether while door-knocking or by phone or text message.

It has experimented with using AI to generate fundraising emails, which sometimes have turned out to be more effective than human-generated ones, according to a campaign official who spoke on the condition of anonymity because he was not authorized to publicly discuss AI.

Biden campaign officials said they plan to explore using generative AI this cycle but will adhere to strict rules in deploying it. Among the tactics that are off limits: AI cannot be used to mislead voters, spread disinformation and so-called deepfakes, or deliberately manipulate images. The campaign also forbids the use of AI-generated content in advertising, social media and other such copy without a staff members review.

The campaigns legal team has created a task force of lawyers and outside experts to respond to misinformation and disinformation, with a focus on AI-generated images and videos. The group is not unlike an internal team formed in the 2020 campaign known as the Malarkey Factory, playing off Bidens oft-used phrase, What a bunch of malarkey.

That group was tasked with monitoring what misinformation was gaining traction online. Rob Flaherty, Bidens deputy campaign manager, said those efforts would continue and suggested some AI tools could be used to combat deepfakes and other such content before they go viral.

The tools that were going to use to mitigate the myths and the disinformation is the same, its just going to have to be at a higher pace, Flaherty said. It just means we need to be more vigilant, pay more attention, be monitoring things in different places and try some new tools out, but the fundamentals remain the same.

The Democratic National Committee said it was an early adopter of Google AI and uses some of its features, including ones that analyze voter registration records to identify patterns of voter removals or additions. It has also experimented with AI to generate fundraising email text and to help interpret voter data it has collected for decades, according to the committee.

Arthur Thompson, the DNCs chief technology officer, said the organization believes generative AI is an incredibly important and impactful technology to help elect Democrats up and down the ballot.

At the same time, its essential that AI is deployed responsibly and to enhance the work of our trained staff, not replace them. We can and must do both, which is why we will continue to keep safeguards in place as we remain at the cutting edge, he said.

PROGRESSIVE EXPERIMENTS

Progressive groups and some Democratic candidates have been more aggressively experimenting with AI.

Higher Ground Labs the venture capital firm co-founded by Hoover established an innovation hub known as Progressive AI Lab with Zinc Collective and the Cooperative Impact Lab, two political tech coalitions focused on boosting Democratic candidates.

The goal was to create an ecosystem where progressive groups could streamline innovation, organize AI research and swap information about large language models, Hoover said.

Higher Ground Labs, which also works closely with the Biden campaign and DNC, has since funded 14 innovation grants, hosted forums that allow organizations and vendors to showcase their tools and held dozens of AI trainings.

More than 300 people attended an AI-focused conference the group held in January, Hoover said.

Jessica Alter, the co-founder and chair of Tech for Campaigns, a political nonprofit that uses data and digital marketing to fight extremism and help down-ballot Democrats, ran an AI-aided experiment across 14 campaigns in Virginia last year.

Emails written by AI, Alter said, brought in between three and four times more fundraising dollars per work hour compared with emails written by staff.

Alter said she is concerned that the party might be falling behind in AI because it is being too cautious.

I understand the downsides of AI and we should address them, Alter said. But the biggest concern I have right now is that fear is dominating the conversation in the political arena and that is not leading to balanced conversations or helpful outcomes.

HARD TO TALK ABOUT AN AK-47

Rep. Adam Schiff, the Democratic front-runner in Californias Senate race, is one of few candidates who have been open about using AI. His campaign manager, Brad Elkins, said the campaign has been using AI to improve its efficiency. It has teamed up with Quiller, a company that received funding from Higher Ground Labs and developed a tool that drafts, analyzes and automates fundraising emails.

The Schiff campaign has also experimented with other generative AI tools. During a fundraising drive last May, Schiff shared online an AI-generated image of himself as a Jedi. The caption read, The Force is all around us. Its you. Its us. Its this grassroots team. #MayThe4thBeWithYou.

The campaign faced blowback online but was transparent about the lighthearted deepfake, which Elkins said is an important guardrail to integrating the technology as it becomes more widely available and less costly.

I am still searching for a way to ethically use AI-generated audio and video of a candidate that is sincere, Elkins said, adding that its difficult to envision progress until theres a willingness to regulate and legislate consequences for deceptive artificial intelligence.

The incident highlighted a challenge that all campaigns seem to be facing: even talking about AI can be treacherous.

Its really hard to tell the story of how generative AI is a net positive when so many bad actors whether thats robocalls, fake images or false video clips are using the bad set of AI against us, said a Democratic strategist close to the Biden campaign who was granted anonymity because he was not authorized to speak publicly. How do you talk about the benefits of an AK-47?

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Associated Press writers Alan Suderman and Garance Burke contributed to this report.

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This story is part of an Associated Press series, The AI Campaign, that explores the influence of artificial intelligence in the 2024 election cycle.

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The Associated Press receives financial assistance from the Omidyar Network to support coverage of artificial intelligence and its impact on society. AP is solely responsible for all content. Find APs standards for working with philanthropies, a list of supporters and funded coverage areas at AP.org

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Nervous about falling behind the GOP, Democrats are wrestling with how to use AI - Yahoo! Voices

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Nick Bostrom Made the World Fear AI. Now He Asks: What if It Fixes Everything? – WIRED

Philosopher Nick Bostrom is surprisingly cheerful for someone who has spent so much time worrying about ways that humanity might destroy itself. In photographs he often looks deadly serious, perhaps appropriately haunted by the existential dangers roaming around his brain. When we talk over Zoom, he looks relaxed and is smiling.

Bostrom has made it his lifes work to ponder far-off technological advancement and existential risks to humanity. With the publication of his last book, Superintelligence: Paths, Dangers, Strategies, in 2014, Bostrom drew public attention to what was then a fringe ideathat AI would advance to a point where it might turn against and delete humanity.

To many in and outside of AI research the idea seemed fanciful, but influential figures including Elon Musk cited Bostroms writing. The book set a strand of apocalyptic worry about AI smoldering that recently flared up following the arrival of ChatGPT. Concern about AI risk is not just mainstream but also a theme within government AI policy circles.

Bostroms new book takes a very different tack. Rather than play the doomy hits, Deep Utopia: Life and Meaning in a Solved World, considers a future in which humanity has successfully developed superintelligent machines but averted disaster. All disease has been ended and humans can live indefinitely in infinite abundance. Bostroms book examines what meaning there would be in life inside a techno-utopia, and asks if it might be rather hollow. He spoke with WIRED over Zoom, in a conversation that has been lightly edited for length and clarity.

Will Knight: Why switch from writing about superintelligent AI threatening humanity to considering a future in which its used to do good?

Nick Bostrom: The various things that could go wrong with the development of AI are now receiving a lot more attention. It's a big shift in the last 10 years. Now all the leading frontier AI labs have research groups trying to develop scalable alignment methods. And in the last couple of years also, we see political leaders starting to pay attention to AI.

There hasn't yet been a commensurate increase in depth and sophistication in terms of thinking of where things go if we don't fall into one of these pits. Thinking has been quite superficial on the topic.

When you wrote Superintelligence, few would have expected existential AI risks to become a mainstream debate so quickly. Will we need to worry about the problems in your new book sooner than people might think?

As we start to see automation roll out, assuming progress continues, then I think these conversations will start to happen and eventually deepen.

Social companion applications will become increasingly prominent. People will have all sorts of different views and its a great place to maybe have a little culture war. It could be great for people who couldn't find fulfillment in ordinary life but what if there is a segment of the population that takes pleasure in being abusive to them?

In the political and information spheres we could see the use of AI in political campaigns, marketing, automated propaganda systems. But if we have a sufficient level of wisdom these things could really amplify our ability to sort of be constructive democratic citizens, with individual advice explaining what policy proposals mean for you. There will be a whole bunch of dynamics for society.

Would a future in which AI has solved many problems, like climate change, disease, and the need to work, really be so bad?

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Nick Bostrom Made the World Fear AI. Now He Asks: What if It Fixes Everything? - WIRED

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Brad Parscale helped Trump win in 2016 using Facebook ads. Now he’s back, and an AI evangelist – Yahoo! Voices

FORT LAUDERDALE, Fla. (AP) Donald Trumps former campaign manager looked squarely into the camera and promised his viewers they were about to witness a bold new era in politics.

Youre going to see some of the most amazing new technology in artificial intelligence thats going to replace polling in the future across the country, said Brad Parscale in a dimly lit promotional video accentuated by hypnotic beats.

Parscale, the digital campaign operative who helped engineer Trumps 2016 presidential victory, vows that his new, AI-powered platform will dramatically overhaul not just polling, but campaigning. His AI-powered tools, he has boasted, will outperform big tech companies and usher in a wave of conservative victories worldwide.

Its not the first time Parscale has proclaimed that new technologies will boost right-wing campaigns. He was the digital guru who teamed up with scandal-plagued Cambridge Analytica and helped propel Trump to the White House eight years ago. In 2020, he had a public blowup then a private falling out with his old boss after the Capitol riot. Now hes back, playing an under-the-radar role to help Trump, the presumptive GOP nominee, in his race against Democratic President Joe Biden.

Parscale says his company, Campaign Nucleus, can use AI to help generate customized emails, parse oceans of data to gauge voter sentiment and find persuadable voters, then amplify the social media posts of anti-woke influencers, according to an Associated Press review of Parscales public statements, his company websites, slide decks, marketing materials and other documents not previously made public.

Since last year, Campaign Nucleus and other Parscale-linked companies have been paid more than $2.2 million by the Trump campaign, the Republican National Committee and their related political action and fundraising committees, campaign finance records show.

While his firms have received only a small piece of Trumps total digital spending, Parscale remains close to top Republicans, as well as senior officials at the campaign and at the RNC, according to a GOP operative familiar with Parscales role who spoke on condition of anonymity to discuss internal dynamics.

Lara Trump, the RNCs new co-chair and Trumps daughter-in-law, once worked as a consultant to a company co-owned by Parscale. And U.S. House Speaker Mike Johnson's campaign recently hired Campaign Nucleus, campaign finance records show.

Parscale, however, is not involved in day-to-day Trump campaign operations, the GOP operative said.

Parscales ability to use AI to micro target supporters and tap them for campaign cash could prove critical for Trumps campaign and other fundraising organizations. They have seen a falloff in contributions from smaller donors and a surge in spending at least $77 million so far on attorneys defending the former president in a slew of criminal and civil cases.

Beyond Trump, Parscale has said hes harnessed AI to supercharge conservative candidates and causes across the globe, including in Israel, the Balkans and Brazil.

NEW AI-POWERED CAMPAIGN TOOLS

Parscale is hardly alone in using machine learning to try to give candidates an edge by predicting, pinpointing and motivating likely supporters to vote and donate money. Politicians at all levels are experimenting with chatbots and other generative AI tools to write speeches, ad copy and fundraising appeals.

Some Democrats have voiced concern over being outmaneuvered by Republicans on AI, much like they were on social media advertising eight years ago. So far, the Biden campaign and other Democrats said they are using AI to help them find and motivate voters and to better identify and defeat disinformation.

Election experts say they are concerned about AIs potential to upend elections around the world through convincing deepfakes and other content that could mislead voters. Free and low-cost generative AI services have grown in sophistication, and officials worry they can be used to smear a candidate or steer voters to avoid the polls, eroding the publics trust in what they see and hear.

Parscale has the financial backing to experiment to see what works in ways that other AI evangelists may not. That is thanks, in part, to his association with an evangelical Texas billionaire who is among the states most influential political donors.

Parscale did not respond to multiple messages from AP seeking comment. The RNC declined comment as well.

AI IS SO SCARY

Trump has called artificial intelligence so scary " and "dangerous." His campaign, which has shied away from highlighting Parscale's role, said in an emailed statement that it did not engage or utilize tools supplied by any AI company.

The campaign uses a set of proprietary algorithmic tools, like many other campaigns across the country, to help deliver emails more efficiently and prevent sign up lists from being populated by false information, said campaign spokesman Steven Cheung.

While political consultants often hype their tactics to land new contracts, they can also be intensely secretive about the details of that work to avoid assisting rivals. That makes it difficult to precisely track how Parscale is deploying AI for the Trump campaign, or more broadly.

Parscale has said Campaign Nucleus can send voters customized emails and use data analytics to predict voters feelings. The platform can also amplify anti-woke influencers who have large followings on social media, according to his companys documents and videos.

Parscale said his company also can use artificial intelligence to create stunning web pages in seconds that produce content that looks like a media outlet, according to a presentation he gave last month at a political conference, where he was not advertised in advance as a speaker.

Empower your team to create their own news, said another slide, according to the presentation viewed by AP.

Soon, Parscale says, his company will deploy an app that harnesses AI to assist campaigns in collecting absentee ballots in the same way DoorDash or Grubhub drivers pick up dinners from restaurants and deliver them to customers.

Chris Wilson, a Republican strategist who recently worked for a SuperPAC backing Florida Gov. Ron DeSantis failed presidential bid, said he has seen Campaign Nucleus platform and was envious of its capabilities and simplicity.

Somebody could download Nucleus, start working with it and really begin to use it, said Wilson.

Other political consultants, however, called Parscales AI-infused sales pitch largely a rehash of what campaigns already have mastered through data scraping, ad testing and modeling to predict voter behavior.

Some of this stuff is just simply not new, its been around for a long time. The only thing new is that were just calling it AI, said Amanda Elliott, a GOP digital strategist.

FROM UNKNOWN TO TRUMP CONFIDANT

Parscale, a relatively unknown web designer in San Antonio, got his start working for Trump when he was hired to build a web presence for the business moguls family business.

That led to a job on the future presidents 2016 campaign. He was one of its first hires and spearheaded an ambitious and unorthodox digital initiative that relied on an extensive database of social media accounts and content to target voters with Facebook ads.

I pretty much used Facebook to get Trump elected in 2016, Parscale said in a 2022 podcast interview.

To better target Facebook users, in particular, the campaign teamed up with Cambridge Analytica, a British datamining firm bankrolled by Robert Mercer, a wealthy and influential GOP donor. After the election, Cambridge Analytica dissolved, facing investigations over its role in a breach of 87 million Facebook accounts.

Following Trumps surprise win, Parscales influence grew. He was promoted to manage Trump's reelection bid and enjoyed celebrity status. A towering figure at 6 feet, 8 inches with a Viking-style beard, Parscale was frequently spotted at campaign rallies taking selfies with Trump supporters and signing autographs.

Parscale was replaced as campaign manager not long after a rally in Tulsa, Oklahoma, drew an unexpectedly small crowd, enraging Trump.

His personal life unraveled, culminating in a standoff with police at his Florida home after his wife reported he had multiple firearms and was threatening to hurt himself. One of the responding officers reported he saw bruising on the arms of Parscales wife. Parscale complied with a court order to turn in his firearms and was not charged in connection with the incident.

Parscale briefly decided to quit politics and privately expressed regret for associating with Trump after the Jan. 6, 2021, Capitol riot. In a text to a former campaign colleague, he wrote he felt guilty for helping him win in 2016, according to the House committee that investigated the Capitol attack.

His disgust didnt last long. Campaign Nucleus set up Trumps website after Silicon Valley tech companies throttled his access to their platforms.

By the summer of 2022, Parscale had resumed complimenting his old boss on a podcast popular among GOP politicos.

With President Trump, he really was the guy driving the message. He was the chief strategist of his own political uprising and management, Parscale said. I think what the family recognized was: I had done everything that really the campaign needs to do.

PARSCALES PLATFORM

Trumps 2024 campaign website now links directly to Parscales company and displays that its Powered by Nucleus, as Parscale often refers to his new firm. The campaign and its related political action and campaign committees have paid Campaign Nucleus more than $800,000 since early 2023, according to Federal Election Commission filings.

Two other companies Dyspatchit Email and Text Services and BCVM Services are listed on campaign finance records as being located at the same Florida address used by Campaign Nucleus. The firms, which are registered in Delaware and whose ownership is unclear, have received $1.4 million from the Trump campaign and related entities, FEC records show.

When an AP reporter last month visited Campaign Nucleus small, unmarked office in a tony section of Fort Lauderdale, an employee said she did not know anything about Dyspatchit or BCVM.

We dont talk to reporters, the employee said.

The three companies have been paid to host websites, send emails, provide fundraising software and provide digital consulting, FEC records show.

Parscale markets Campaign Nucleus as a one-stop shop for conservative candidates who want to automate tasks usually done by campaign workers or volunteers.

The company says it has helped its clients raise $119 million and has sent nearly 14 billion emails on their behalf, according to a promotional video.

At his recent appearance at the political conference, Parscale presented a slide that said Campaign Nucleus had raised three times as much as tech giant Salesforce in head-to-head tests for email fundraising.

Campaign Nucleus specializes in mining information from a politicians supporters, according to a recent presentation slide.

For example, when someone signs up to attend an event, Nucleus uses AI to analyze reams of personal data to assign that person a numerical score. Attendees who have been to past events receive a high score, for example, ranking them as most likely to show up, according to a company video posted online.

Campaign Nucleus also can track where people who sign up live and can send them customized emails asking for donations or solicit their help on the campaign, the video shows.

Parscale said two years ago in a podcast that he had received more than 10,000 requests about Campaign Nucleus from nearly every country with a conservative party. More recently, he said his team has been active in multiple countries, including in India and Israel, where hes been helping over there a lot with the war with Hamas.

The company says it has offices in Texas, Florida and North Carolina and has been on a recruiting tear. Recent job listings have included U.S. and Latin America-based intelligence analysts to use AI for framing messages and generating content, as well as a marketer to coordinate influencer campaigns.

Campaign Nucleus has also entered into partnerships with other companies with an AI focus. In 2022, the firm announced it was teaming up with Phunware, a Texas-based company that built a cellphone app for Trumps 2020 bid that allowed staff to monitor the movements of his millions of supporters and mobilize their social networks.

Since then, Phunware obtained a patent for what a company official described as experiential AI that can locate peoples cellphones geographically, predict their travel patterns and influence their consumer behavior.

Phunware did not answer specific questions about the partnership with Nucleus, saying the company's client engagements were confidential.

However, it is well-known that we developed the 2020 Trump campaign app in collaboration with Campaign Nucleus. We have had discussions with Trump campaign leadership about potentially developing their app for the 2024 election," said spokeswoman Christina Lockwood.

PARSCALES VISION

Last year, Parscale bought property in Midland, Texas, in the heart of the nations highest-producing oil and gas fields. It is also the hometown of Tim Dunn, a billionaire born-again evangelical who is among the states most influential political donors.

Over the years, the organizations and campaigns Dunn has funded have pushed Texas politics further to the right and driven successful challenges to unseat incumbent Republican officials deemed too centrist.

In April 2023, Dunn invested $5 million in a company called AiAdvertising that once bought one of Parscales firms under a previous corporate name. The San Antonio-based ad firm also announced that Parscale was joining as a strategic adviser, to be paid $120,000 in stock and a monthly salary of $10,000.

Boom! Parscale tweeted. (AiAdvertising) finally automated the full stack of technologies used in the 2016 election that changed the world.

In June, AiAdvertising added two key national figures to its board: Texas investor Thomas Hicks Jr. former co-chair of the RNC and longtime hunting buddy of Donald Trump Jr. -- and former GOP congressman Jim Renacci. In December, Dunn also gave $5 million to MAGA Inc., a pro-Trump super PAC and Campaign Nucleus client. And in January, SEC filings show Dunn provided AiAdvertising an additional $2.5 million via his investment company. A company press release said the cash infusion would help it generate more engaging, higher-impact campaigns.

Dunn declined to comment, although in an October episode of his podcast he elaborated on how his political work is driven by his faith.

Jesus wont be on the ballot, OK? Now, eventually, hes going to take over the government and we can look forward to that, Dunn told listeners. In the meanwhile, were going to have to settle.

In business filings, AiAdvertising said it has developed AI-created personas to determine what messages will resonate emotionally with its customers target audience. Parscale said last year in a promotional video that Campaign Nucleus was using AI models in a similar way.

We actually understand what the American people want to hear, Parscale said.

AiAdvertising did not respond to messages seeking comment.

Parscale occasionally offers glimpses of the AI future he envisions. Casting himself as an outsider to the Republican establishment, he has said he sees AI as a way to undercut elite Washington consultants, whom he described as political parasites.

In January, Parscale told a crowd assembled at a grassroots Christian event at a church in Pasadena, California, that their movement needed to have our own AI, from creative large language models and creative imagery, we need to reach our own audiences with our own distribution, our own email systems, our own texting systems, our own ability to place TV ads, and lastly we need to have our own influencers.

To make his point plain, he turned to a metaphor that relied on a decidedly 19th-century technology.

We must not rely on any of their rails, he said, referring to mainstream media and companies. This is building our own train tracks.

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Burke reported from San Francisco. AP National Political Writer Steve Peoples and Courtney Subramanian in Washington, and Associated Press researcher Rhonda Shafner in New York contributed to this report.

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This story is part of an Associated Press series, The AI Campaign, that explores the influence of artificial intelligence in the 2024 election cycle.

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Contact APs global investigative team at Investigative@ap.org or https://www.ap.org/tips/

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The Associated Press receives financial assistance from the Omidyar Network to support coverage of artificial intelligence and its impact on society. AP is solely responsible for all content. Find APs standards for working with philanthropies, a list of supporters and funded coverage areas at AP.org

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Brad Parscale helped Trump win in 2016 using Facebook ads. Now he's back, and an AI evangelist - Yahoo! Voices

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Hands-on with the visual AI in Metas Ray-Ban smart glasses – The Verge

For the last several weeks, Ive been playing with Metas AI assistant in its Ray-Ban smart glasses. It works by responding to the voice command Hey Meta and can answer a question or examine what youre looking at. Its far from perfect. But when it does work, it feels like a glimpse into the future.

Meta didnt expect generative AI to play such a large role in the glasses until very recently. When CEO Mark Zuckerberg first revealed that multimodal AI was coming to them in an interview with me last fall, he described it as a whole new angle on smart glasses that may end up being the killer feature before super high-quality holograms.

Given the billions Meta has poured into AR glasses over the last six years and the lackluster reception to the first generation of Meta Ray-Bans, version two needed to be a win. Early indications are good. Ive seen third-party estimates that over 1 million have been sold. During Metas last earnings call, Zuckerberg mentioned that many styles were sold out. Now, with multimodal AI enabled, Meta may have the best AI wearable on the market.

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Hands-on with the visual AI in Metas Ray-Ban smart glasses - The Verge

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China tops the U.S. on AI research in over half of the hottest fields: report – Axios

Data: Emerging Technology Observatory Map of Science; Chart: Axios Visuals

China leads the U.S. as a top producer of research in more than half of AI's hottest fields, according to new data from Georgetown University's Center for Security and Emerging Technology (CSET) shared first with Axios.

Why it matters: The findings reveal important nuances about the global race between the U.S. and China to lead AI advances and set crucial standards for the technology and how it is used around the world.

Key findings: CSET's Emerging Technology Observatory team found global AI research more than doubled between 2017 and 2022.

Research in robotics grew slower than in vision and natural language processing by just 54% and made up about 15% of all AI research.

What they're saying: "The fact that research is growing so quickly, in so many directions, underscores the need for federal investment in basic measurement evaluation on the scientific techniques we need to ensure that AI getting deployed in the real world is safe, secure and understandable," said Arnold. But appropriations for the National Institutes of Standards and Technology, which is tasked with identifying those measurements, were recently cut.

The big picture: The top five producers of sheer numbers of AI research papers in the world are Chinese institutions, led by the Chinese Academy of Sciences.

Yes, but: At the country level, the U.S. had the top spot in producing highly cited articles.

"China is absolutely a world leader in AI research, and in many areas, likely the world leader," Arnold said, adding the country is active across a range of research areas, including increasingly fundamental research.

Caveat: The data only accounts for research papers published in English, and doesn't capture scientific work in other languages.

How it works: CSET's Map of Science groups together articles that cite each other often, because they have topics or concepts in common, into clusters of research. (It doesn't mean all papers on LLMs, for example, are in the top cluster. Some may appear in other clusters.)

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China tops the U.S. on AI research in over half of the hottest fields: report - Axios

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