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Monthly Archives: January 2022
Cook Center for Human Connection Partners with American Federation of Teachers’ Share My Lesson Platform to offer Student Mental Health Lessons -…
Posted: January 24, 2022 at 9:50 am
(Salt Lake City) January 20, 2022 The Cook Center for Human Connection today announced a partnership with the American Federation of Teachers (AFT) Share My Lesson platform to make the new teen mental health animated series and extension lessons available for free to 1.9 million educators. My Life is Worth Living is the first animated series about teen mental health and suicide prevention and is produced by the Cook Center, a Utah-based non-profit dedicated to eradicating suicide and advocating for mental health and wellness, in partnership with Wonder Media. The series is available in 5 languages: English, Spanish, Mandarin, Japanese and Portuguese.
Developed with guidance from former President of the American Association of Suicidology Dr James Mazza and a team of doctors and experts on adolescent mental health, My Life is Worth Living features relatable teen characters and each story models positive, research-based mental wellness skills for grades 7-12. The state-of-the-art animation was produced by Wonder Media CEO Terry Thoren, former CEO of Klasky Csupo, the company that incubated the Simpsons and created Rugrats, The Wild Thornberrys, and Rocket Power.
Created and maintained by the AFT, Share My Lesson is a free, award-winning community-based website that brings together educators, parents and caregivers, paraprofessionals, union and non-union members, educational partners, and higher education professionals who have the common goal of finding and sharing the best educational resources available.
The COVID-19 pandemic has intensified social isolation, and this has been felt deeply in the lives of students. The U.S. Surgeon General recently declared youth mental health is an urgent national public health crisis. However, research shows that connections to friends, family, and community can be the difference between life and death. Storytelling is known to create connections and combat loneliness. Stories can break down the stigma of talking about mental health needs and thoughts of suicide. My Life is Worth Living includes five powerful stories told over 20 episodes. In each episode, relatable teen characters wrestle with challenges that are all too familiar for many viewers, such as depression, bullying, addiction, LGBTQ+ rejection, and abuse, and discover strategies to cope and thrive.
The AFTs Share My Lesson platform currently has 1.9 million members across the United States. The My Life is Worth Living episodes and the printable extension lessons for educators, counsellors, and parents are being released on Share My Lesson this month. To learn more about the series, visit http://www.mylifeisworthliving.org.
The Cook Center for Human Connection The mission of the Cook Center is to bring together the best organizations, programs, and products to prevent suicide, provide mental health support, and enhance the human connections vital for people to thrive. The foundations current focus is on supporting children, families, and schools in eradicating suicide, as well as offering resources and support for those with mental health issues and their caregivers. This work is accomplished through various grants to schools, programs for parents, and global resources to bring greater awareness to the support needed for those affected by mental health needs and suicide. Learn more at CookCenterforHumanConnection.org or MyLifeIsWorthLiving.org/joinourcause.
About Wonder Media Wonder Media is a Los Angeles animation studio founded by Terry Thoren. Following his success as CEO of Klasky Csupo, the studio that incubated the Simpsons and created Rugrats and Wild Thornberrys, Thoren left Hollywood on a mission to develop animated series that have social impact. The studio produces animated stories to prevent trauma for children and teens of all ages. Working with such organizations as the Global Institute for Habits of Mind, the Barbara Sinatra Childrens Center Foundation, and the Betty Ford Childrens Center, Wonder Media has connected children and teens at risk with content that addresses hunger, social-emotional learning, critical thinking, the prevention of child sex abuse, and more. Learn more at Wonder.media.
Featured image: Anil Sharma, Pexels.
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Bill extending life of VISIT FLORIDA breezes through House tourism committee – Florida Politics
Posted: at 9:50 am
A bill to extend the sunset date of VISIT FLORIDA, the state-funded nonprofit tourism marketing corporation, breezed through the House Tourism, Infrastructure & Energy Subcommittee Tuesday.
VISIT FLORIDA would cease to exist after Oct. 1, 2023, under current law. The bill, HB 489, sponsored by St. Pete Beach Republican Rep. Linda Chaney, would extend its scheduled repeal date to Oct. 1, 2028.
Chaney said VISIT FLORIDA uses a targeted approach to attract visitors into Florida.
They run their ads and they know where the consumers are that theyre going to convince to come to the state of Florida, she said. By giving them an extended horizon, theyre going to be able to do that more cost effectively. If you are somebody whos engaging a vendor and they think you may only be a customer for a year, youre not going to get the same rate as somebody whos got a longer horizon.
The bill received some pushback. Critics have accused the organization of being a form of corporate welfare and a misuse of taxpayer money.
However well intentioned some government assistance may be, the fact remains that the practice of states picking winners and losers benefits a favorite few and leaves everyone else to pay the price, said Phillip Suderman, policy director for Americans for Prosperity. Too often the winners are special interests who lobby for special favors while those who bear the cost are everyday citizens and small businesses who have to pick up the tab.
Suderman was joined by other members of Americans for Prosperity in Tuesdays meeting. They, in turn, were joined in opposition by a few small business owners. And Rep. Rick Roth said some of the points being brought up were absolutely valid. But those issues, he said, were already addressed about five years ago.
Those things were taken care of by amending Enterprise Florida and VISIT FLORIDA because of people on the board of Enterprise Florida, Roth said. These arguments were targeted mainly at Enterprise Florida because people on the board were getting benefits. So they were picking winners and losers, but thats all been changed.
About five years ago, VISIT FLORIDA saw some massive housecleaning. The organization had been criticized by both Democrats and Republicans for misspending, ineffectiveness, sketchy bonuses and a lack of accountability. The agency was put on a short leash and only given year-by-year renewals. But last year, on the heels of the COVID-19 pandemic virtually shutting down tourism in Florida, the agency reported major returns.
According to data released by Floridas Office of Economic & Demographic Research, for every $1 of taxpayer money spent on the program, it returned $3.27. And the latest projections from the state show an average of $65.4 million invested into the program over the five-year extension. VISIT FLORIDA said it helped bring a record 131.42 million visitors to Florida in 2019 when it had a budget of around $80 million. And while Rep. Randy Fine pointed out about 99% of those people wouldve likely come either way, he also said far less than that extra 1% is needed for the organization to pay for itself.
What percentage of the visitors of Florida, if they come, make that $80 million worth it? Fine asked. It turns out that if less than one-quarter of 1% of the visitors to the state of Florida wouldnt have come anyway, if one out of every 400 people who came to the state only came because we offered the program, the program pays for itself. Thats the right way to think about a program like this.
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Fierce JPM Week: AstraZeneca cancer R&D head marks Imfinzi as ‘core backbone’ of oncology strategy with the right comboincluding treme – FiercePharma
Posted: at 9:50 am
In the increasingly crowded cancer immunotherapy field, AstraZenecas Imfinzi has mostly been used in stage III non-small cell lung cancer. But with the right combination strategy, the PD-L1 inhibitor has promise in other tumor types, AZs oncology R&D head said.
Imfinzi is a core backbone component of AZs overall strategy for oncology, Susan Galbraith, Ph.D., AZs executive vice president of oncology R&D, said during the Fierce JPM Week virtual conference. The drug just hit gold-standard life extension goals in two phase 3 trials when used alongside chemo in newly diagnosed biliary tract cancer and as part of a cocktail with AZs own CTLA4 inhibitor tremelimumab in first-line liver cancer.
Those trial wins fit AZs philosophy of developing treatments that can improve long-term survival and cure more patients by targeting earlier lines of treatment. But that ambition requires different components and mechanisms, such as the approach with Imfinzi and treme, Galbraith said.
In the first-line liver cancer trial dubbed Himalaya, the Imfinzi-treme pairing slashed the risk of death by 22% over Bayers aging standard-of-care Nexavar. That result marked a rare win for treme after multiple failures in non-small cell lung cancer (NSCLC), head and neck cancer and bladder cancer.
By incorporating lessons from previous trials, AZ's scientists homed in on a regimen called Stride, Galbraith said, which involves a single high dose of treme given in tandem with Imfinzi at the beginning of treatment, followed by Imfinzi alone.
That single punch of CTLA4 inhibition functions as priming the immune system. Previous research has found that with the proper priming, the bodys immune response against cancer can be very long-lasting, delivering a durability effect with an improvement particularly in the tail of the survival curve, Galbraith explained.
In the Himalaya trial, 40.5% of patients on the Stride regimen were still alive after two years, compared with 39.6% for the Imfinzi monotherapy group and 32.6% in the Nexavar arm. At three years, the survival rate stood at 30.7% for Stride, while Imfinzi monotherapy dropped faster to 24.7% and Nexavar to 20.2%.
The dose and schedule refinement, particularly with the Stride regimen, really gives us some insight into how we can improve the therapeutic index, Galbraith said.
Separately, by posting a 20% reduction in the risk of death previously untreated unresectable biliary tract cancer, Imfinzis chemo combo was the first immunotherapy regimen to improve survival in those patients.
RELATED:AstraZeneca climbs a Himalaya to find ill-fated treme a place alongside Imfinzi in liver cancer
Meanwhile, following its approach to target earlier lines of treatment with combos, AZ is running the phase 3 Emerald-1 trial to see whether adding Imfinzior Imfinzi and Roches VEGF inhibitor Avastinon top of transarterial chemoembolization could help patients with locoregional liver cancer. That data could read out later this year. A separate Emerald-2 trial is examining Imfinzi alone or the Imfinzi-Avastin pairing as a post-surgery adjuvant therapy in early liver cancer patients at high risk of recurrence.
Roche won an FDA go-ahead in 2020 for its PD-L1 inhibitor Tecentriq alongside Avastin in newly diagnosed liver cancer. Given that success, Galbraith said shes optimistic about the two Emerald trials.
Beyond treme, AZ recently turned in positive phase 2 results for Imfinzis combination with oleclumab, an anti-CD73 antibody, or monalizumab, an anti-NKG2A antibody, over solo Imfinzi in stage III non-small cell lung cancer. Now AZ is moving both new therapies into phase 3 testing.
AZ gained full rights to monalizumab from a collaboration with Innate Pharma originally signed in 2015. Last week, AZ paid Scorpion Therapeutics $75 million upfront to develop drugs against transcription factors, which have historically been hard to drug.
RELATED:AstraZeneca names Galbraith as Baselga successor in cancer R&D
The British pharma is also known for two billion-dollar licensing deals with Daiichi Sankyo featuring antibody-drug conjugates Enhertu and datopotamab deruxtecan. BTK inhibitor Calquence also came to AZ while it was in late-stage development at Acerta Pharma.
While AZ has a productive internal R&D engine, the company doesn't have a monopoly on all innovation, Galbraith said. Moving forward, AZ is very open to deals across the spectrum of drug development stages for products that can deliver value, she said.
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Real life Rapunzel who started going grey at 13 hasn’t had a haircut in 16 years – The Mirror
Posted: at 9:50 am
Anna Shepherd, 30, says she was devastated and self conscious when she started getting grey hair as a teen and was cruelly teased about it - but now she inspires others not to dye their greys
Image: @prettyshepherd/News Dog Media)
A 'real-life Rapunzel' who first started going grey when she was just thirteen years old has learned to embrace her 5ft long silver locks.
Anna Shepherd, 30, says she was devastated and self-conscious when she started getting grey hair as a teen and was cruelly teased about it.
But over the years she has learned to love her grey hair and says she only needs to wash it once a month, making her life as a farmer easier.
Anna, who lives in Hungary, says she sometimes only combs her knee-length hair once a week when shes busy working and explains how low maintenance it is.
She says she feels honoured when she hears others being inspired not to dye their greys after seeing her hair.
Anna proudly shares snaps of her stunning silver locks with her 16,000 followers on Instagram (@prettyshepherd) although she has received some strange requests from men.
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Anna who has over one million views on her haircare video says: It may partly be genetics, but I only wash my hair once a month because thats how it behaves best.
And I dont apply anything to my hair except some oil after I wash it to tame it and keep it manageable.
Its honestly easier having long hair on the farm because you dont have to style it and you can put it up in a bun.
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Sometimes when Im doing a lot of physical work on the farm, I can go for a week without brushing it and its fine.
I used to get picked on or stared at for my grey hair as a teenager but now I only get compliments.
I feel honoured when women write to me saying that theyve found the courage to go grey because of me. It fills my heart with happiness.
Theres definitely a stigma with a young woman having grey hair and I would love to help change that.
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However I will admit that I do get some strange requests from men online. A male follower offered to pay to lick my grey hair! I was lost for words.
Anna says that she was distraught when she started getting grey hair.
She recalls: I begged my mother to let me dye my hair when I began going grey. I was so sad and worried that I would look old.
I felt extremely self-conscious all the time. People would stare at my strands of grey hair and I would get remarks about it.
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I remember this incident when a boy called me Cruella and it did hurt my feelings.
But over time, I learned to love my grey hair and it became an extension of myself.
Anna says she was inspired to grow her locks after reading folklore and she hasnt had a proper haircut since she was 14 years old.
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Anna, who works as a regenerative farmer with her boyfriend, explains: I joined a folk-dance group as a teenager and became inspired by folklore imagery and women of history with beautiful floor-length hair. I wanted to emulate their hair and started growing it.
The last time I had a proper haircut was when I was fourteen years old. I went to the hairdresser and asked for a trim but the hairdresser chopped off far too much.
Since then I have never been back to the hairdresser. If I ever need to, I just ask my mother to give me a trim but thats only once in a few years.
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Storied Canadian science vessel CCGS Hudson has reached the end of the line – CBC.ca
Posted: at 9:50 am
It's the end of the line for one of Canada's most storied ships.
The 59-year old research vessel CCGS Hudson is set to bedecommissioned, according to a statement from the Canadian Coast Guard released Wednesday.
The release stated that the Coast Guard had deemed the ship "beyond economical repair" following a catastrophic mechanical failure last fall.
The 90-metre long oceanographic science ship has been tied up in St. John's since Nov. 5, when a starboard propulsion motor failed as it came into port.
The Coast Guard has determined repairs would be too costly and too time consuming.
Even before the motor failure, it said Hudson was going to be out of service for the first six months of 2022 for other maintenance to meet safety standards.
"We would end up having to take that large electrical motor out of the ship and to rewind it in a lab setting. And that would take the ship out of service all summer as well. So basically, we'd be removing the ship for the next two years out of service to carry out work," said Gary Ivany, assistant commissioner Atlantic region.
"To get the Hudson back in the water in a timely manner, in a reliable manner, it wouldn't happen."
Crew members were told Wednesday.
In the coming weeks, Hudson will return to its base at the Bedford Institute of Oceanography in Halifax.
In announcing the decommissioning Wednesday the Coast Guard also revealed that delivery of Hudson's replacement from the Seaspan Shipyard in Vancouver has been pushed back by another year to 2025.
The Government of Canada Shipbuilding Strategy website still estimates delivery in 2024.
Since 2017, the Department of Fisheries and Oceans has spent over $25 million on "life extension" refits for the Hudson in an effort to keep the workhorse at sea. It has been collecting scientific data on the east coast for decades.
The programs that benefited from those tripsinclude the Atlantic Zone Monitoring Program, which gathers data used to track changing ocean climate information that affects people and marine species.
To carry out that science,DFO is now looking at a variety of solutions:using remote sensor technology like autonomous ocean gliders, reassigning other Coast Guard ships, and leases and charters of private vessels.
"We're working hard to be able to to make sure that we have either a boat or a series of alternative boats available to be able to deliver on those missions," saidDavid Morin, director general of strategic and regulatory science for DFO.
Morin saidany long-term lease will likely include options that will make the ship available beyond 2025 in case a replacement is not ready.
"Certainly that is something that we are serious about, you know going to be part of.any lease that we undertake is the concept to have some option years,'' he said.
Hudson may have been limping at the end but its longevity was remarkable, said Mac Mackay, who has written extensively on east coast shipping news in his Shipfax Blog.
"It's virtually unheard of that a ship in frontline service would last this long. Most ships are built to last 25 or 30 years,government-built ships a little bit longer because they're so well-maintained," said Mackay.
"To last this long was really quite incredible,"
Hudson is considered a storied ship for a reason.
In 1970 it was the first vessel to circumnavigate North and South America in a single voyage.
"Canada was able to do science with that ship that nobody else could," said Mackay. "And because it's a big oceangoing ship that could stand up to any kind of weather conditions, including ice you wanted to offer it. So we were able to do stuff that we'd never been able to do before."
Although the starboard electrical propulsion motor failed, there are two on board one for each propeller .
The ship still has four main diesel engines that are fully functioning.
So the Hudson will return to Halifax under its own power - on one propeller - where the Coast Guard intends to celebrate Hudson's accomplishments rather than its recent equipment failures.
This year the Canadian Coast Guard will observe its 60th anniversary just one year older than Hudson.
"It's not lost on us, the ship that's been in the fleet in Canada, serving Canadians proudly," saidIvany.
"We want to do that justice as mariners."
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From the Extension: If you’re looking for evergreen plants, a Japanese garden can inspire – Yahoo News
Posted: at 9:49 am
After teaching gardening classes to thousands of Florida residents over the years, Ive observed a variety of landscaping wants and needs. Many new to central Florida residents desire long lasting aesthetic traits.
For example, many residents desire evergreen plants that bloom continuously and do not shed leaves. Low maintenance and slow growth rate are other desirable plant features often expressed by homeowners.
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As I strolled through a garden recently, I wondered why people seek permanence in their yards and gardens. Maybe its a human need for certainty or predictability, but I find the things I enjoy the most about my yard are the moments of fleeting beauty.
Japanese gardens often focus on this idea of impermanence as they often feature evergreens as a backdrop for focal plants offering short-term color. To celebrate ephemeralness, Japanese gardens often feature maples in the fall, camellias in the winter, and azaleas in the spring.
With their multi-petaled, sculptural flowers, camellias beckon the cooler months in the coastal states of the Southeast. Sasanqua camellias bloom as early as October and November, while most other camellias bloom between December and February.
These glossy-leaved evergreens flower for about one to two months. My Sweetie Pie camellia begins to flower right around New Years Day and I look forward to those first blooms every year.
A unique feature of sasanqua camellia Shishi-gashiri is that the flowers fall apart as they come to an end, littering the ground with delicate fuchsia petals. Walking through a path of bright pink flowers conjures up the magic of a fairytale.
Trumper plants bloom on the ground.
I recently visited the UF/IFAS Mid-Florida Research and Education Center in Apopka and the pink trumpet tree in the courtyard made me hold my breath. Not only were the blooms on the tree stunning, but it looked as though a lavender-colored snow had fallen along the ground.
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Pink trumpet trees provide their soft color in the winter months on bare silvery grey stems. This deciduous tree retains leaves throughout most of the year but drops its leaves before flowers emerge.
Two different pink trumpet trees grow in central Florida when planted in a protected or warm area of the yard. The tabebuia species of pink trumpet tree reaches heights of twenty to thirty feet while the Handroanthus species serves as a better fit for smaller yards reaching heights of twelve to eighteen feet.
While Florida may not experience the temporary and dramatic fall of hardwood forests, trees such as maples and crape myrtles add color through their striking leaves. Red maples push bright red growth in the spring and offers red leaves in the fall.
Grow red maples along a wetlands area or in moist soils. Depending on the type, crape myrtles drop their red, orange, or sometimes yellow leaves in the late fall and early winter.
A couple of native vines also provide bright colors in their leaves during the winter months. Wild grape, with its yellow leaves, can be found in many natural areas. Virginia creepers leaves develop into an intense red before they drop.
This weedy vine grew up my shed and I left it to enjoy the color during late fall. Both native vines are aggressive in nature and overtake trees and shrubs if not maintained.
A Fallen Trumpet blooms on a Cardboard Palm.
Grow them in a place where they can be managed and be extremely cautious planting them in forested or natural areas. They are not invasive, and both occur throughout natural lands in Florida and throughout most of the U.S.
Take time to enjoy the ephemeral nature of plants in botanical gardens or on a wooded nature path. Plant for fleeting beauty in your own backyard.
Extension programs are open to all persons without regard to race, color, sex, age, disability, religion, or national origin.
Brooke Moffis is the Commercial Horticulture and FL Friendly Landscaping Agent of UF/IFAS Extension Lake County. Email her at burnb48@ufl.edu.
This article originally appeared on Daily Commercial: If you're looking for evergreen plants, a Japanese garden can inspire
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Global Naval Vessel Maintenance, Repair, and Overhaul Market (2022 to 2031) – Growth, Trends, COVID-19 Impact and Forecasts – ResearchAndMarkets.com -…
Posted: at 9:49 am
DUBLIN--(BUSINESS WIRE)--The "Naval Vessel Maintenance, Repair, and Overhaul (MRO) Market - Growth, Trends, COVID-19 Impact, and Forecasts (2022 - 2031)" report has been added to ResearchAndMarkets.com's offering.
The naval vessel maintenance, repair, and overhaul (MRO) market was valued at about USD 54.04 billion in 2021, and it is projected to register a CAGR of about 2% during the forecast period (2022 - 2031).
Companies Mentioned
Key Market Trends
The Destroyers Accounted for a Major Share by Revenue in 2021
Destroyers are fast, maneuverable, long-endurance warships that escort support and larger vessels in a fleet and defend them against the attacks of smaller powerful short-range surface combatants. The current global fleet of destroyers is around 250. Countries such as the United States, China, and Japan account for the highest share of the existing fleet of destroyers in the world. Due to their rather expensive procurement and operating costs, only a select few navies operate destroyers globally. With the global fleet age of destroyers increasing, countries around the world are investing in the modernization of their fleet with advanced equipment and in-service maintenance and overhaul plans.
Also, the growing requirement of equipping the newer destroyers with the latest weapon systems is driving the need for destroyer modernization programs. For instance, in July 2021, MBDA UK was awarded an 11-year contract to integrate the Common Anti-Air Modular Missile, often referred to as Sea Ceptor, into the UK Navy's Type 45 destroyers' Sea Viper weapon systems. The work will also include the upgrade of the Sea Viper command and control (C2) system. Fitting CAMM onto the Type 45s will give the destroyers a 50% increase in the number of its air defense missiles. The first Type 45 destroyer is expected to be overhauled by summer 2026.
Also, as of 2021, the navies of France and Italy were planning to conduct a mid-life upgrade of the Horizon class of air warfare destroyers that have been in service for more than ten years. In 2020, Naviris provided a contract to Naval Group, which was contracted through OCCAR (Organization for Joint Armament Co-operation) to conduct a feasibility study for the upgrade. Countries are also investing in sustaining the existing destroyer fleets by upgrading decades-old ships with newer systems and extending their service life. In 2021, the United States started upgrading the sensors, electronics, and weapons aboard the existing fleet of DDG-51 Arleigh Burke-class Flight IIA destroyers. Such developments are expected to drive the growth of the segment during the forecast period.
The Asia-Pacific Region Held the Highest Market Share in 2021
The Asia-Pacific region currently dominates the market, and it is expected to continue its dominance during the forecast period. Countries like China, India, and Japan are increasing their investment in strengthening their naval capabilities due to the ongoing geopolitical tensions in the region. China is one of the largest navies in the world, with 335 naval vessels (2019), about 55% larger than in 2005, where the majority of the fleet is more than 13 years.
Similarly, other countries (like India and Japan) are also operating a fleet of aging naval vessels. Due to this, the countries are modernizing their fleets of naval vessels through the integration of advanced technologies (modifications) into the vessels. In this regard, the Australian government announced an investment of USD 75 billion over the next decade to enhance its naval capabilities. Out of the total investment, approximately 1/3rd of the investment is expected toward the improvement and sustainment of its naval vessels.
Under this investment, the country plans to upgrade its Hobart Class Destroyers, ANZAC Class Frigates, and the country navy's Amphibious ships and invest in the upgrade and life extension of the Collins Class submarines that are currently in service (average age more than 20 years). Similar investments in the modernization of naval vessels are anticipated to accelerate the demand for naval vessel MRO in the region in the coming years.
Key Topics Covered:
1 INTRODUCTION
2 RESEARCH METHODOLOGY
3 EXECUTIVE SUMMARY
4 MARKET DYNAMICS
4.1 Market Overview
4.2 Market Drivers
4.3 Market Restraints
4.4 Porter's Five Forces Analysis
5 MARKET SEGMENTATION
5.1 Vessel Type
5.2 MRO Type
5.3 Geography
6 COMPETITIVE LANDSCAPE
6.1 Vendor Market Share
6.2 Company Profiles
7 MARKET OPPORTUNITIES AND FUTURE TRENDS
For more information about this report visit https://www.researchandmarkets.com/r/y8ul06
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$12.9 million to breathe life into Surf Life Saving South Australia clubs and protect swimmers – Premier of South Australia
Posted: at 9:49 am
The Marshall Liberal Government is committing $12.9m to Surf Life Saving South Australia (SLSSA), including a whopping 33% operational funding boost the first increase of its kind for the much-loved organisation in more than 15 years.
Premier Steven Marshall said lifesaving activity and first-aid responses in South Australia had increased by more than 77% between 2018 and 2021.
There are approximately 9,000 dedicated SLSSA volunteers who risk their wellbeing to protect South Australians at our beaches during summer and we know their brave actions save lives, the Premier said.
Supporting SLSSA with $12.9m in funding is how we strengthen these incredible lifesaving services well into the future.
Boosting SLSSAs operational funding means they have more resources at their disposal to respond to water emergencies and support their volunteers.
Were also funding critical club redevelopments that will ensure volunteers have modern, fit-for-purpose facilities that allow them to undertake patrols, important training and education programs.
The redevelopments scheduled over the next four years include Normanville (2022-23), Whyalla and Lonsdale (2023-24), Robe (2024-25) and Moana (2025-26).
Minister for Recreation, Sport and Racing, Corey Wingard, said todays announcement builds on the Marshall Governments already strong partnership with SLSSA, and follows an almost $5m investment in the completed redevelopment of Port Elliot Surf Life Saving Club the biggest in SA history.
The pivotal roles our SLSSA volunteers perform cannot be overstated enough, from patrolling our coastlines to teaching children how to swim through the hugely popular VACSWIM program, Minister Wingard said.
The Marshall Government proudly subsidises the VACSWIM program cutting the cost in half so families can afford to enrol their children in swimming lessons. This summer alone more than 10,000 South Australian kids are involved, and the program is growing each year.
Not only does the initiative promote a healthy active lifestyle for children, but more than 800 instructor jobs in the aquatics industry are up for grabs through the program in a win-win for the community.
SLSSA President, Kevin Watkins, said volunteers performed 11,355 preventative actions in 2018 compared to 20,143 last year.
Our volunteers do an incredible job saving lives on our beaches. Last year alone, 154 lives were saved because a Surf Life Saver was on patrol and able to rescue them, Mr Watkins said.
The more than 80,000 volunteer patrol hours that they performed, across the 21 Surf Life Saving Clubs in SA, provide an invaluable service to the public, to help keep them safe.
SLSSA CEO, Damien Marangon, said: This lift in operational funding and the extension of club redevelopment funding, ensures that our dedicated volunteers are able to remain rescue ready, with world leading lifesaving facilities and equipment to support them to protect beachgoers.
We thank the South Australian Government for their commitment to Surf Life Saving, and we know that this funding will save lives, Mr Marangon said.
Weve unfortunately already seen too many drowning tragedies across our coast this summer, so having this additional funding means we can continue to support our clubs and volunteers patrolling our beaches, educate more people in our water safety programs and strive towards our vision of zero preventable deaths in SA waters.
The latest investment follows the delivery of the Marshall Governments 2018 election commitments, including $630,000 over four years to provide $5,000 to each SLSSA club each year for upgrades to key rescue and emergency response equipment and $190,000 for drones to enhance shark surveillance capability.
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Marimaca Copper Announces Exploration Targets for Depth Extensions of the MOD and Near-Pit Oxide Satellites – Junior Mining Network
Posted: at 9:49 am
VANCOUVER, British Columbia, Jan. 20, 2022 (GLOBE NEWSWIRE) -- Marimaca Copper Corp. (Marimaca Copper or the Company)(TSX: MARI) is pleased to announce Exploration Targets for the Marimaca Oxide Deposit (MOD) depth extension zone (the MAMIX target) discovered in 2021 (see announcement dated October 14 2021), as well as for the Mercedes, Cindy and Roble satellite oxide targets discovered during the successful 2021 Marimaca District exploration drilling campaigns (see announcements dated September 15 2021, July 14 2021 and July 1 2021).
Highlights
MAMIX (MOD Depth Extension)
Satellite Oxide Targets and MOD Oxide Extensions
Definitive Feasibility Study
The potential quantity and grade presented in the exploration target ranges are conceptual and have insufficient exploration and drill density to define a Mineral Resource. At this stage, it is uncertain if further exploration will result in the targets being delineated as a Mineral Resource. Estimates of exploration targets are not Mineral Resources and are too speculative to meet the NI 43-101 reporting standards. The detailed methodology for preparing the Exploration Targets and a summary of supporting technical data can be found at the end of this announcement.
Table 1: Summary of Exploration Targets for Further Exploration at Marimaca
*Mixed refers to a combination of oxides + secondary + primary sulphides and Enriched refers to secondary sulphides (predominantly chalcocite and covellite, with minor chalcopyrite)
Sergio Rivera, VP Exploration of Marimaca Copper, commented:
In 2021, drilling beneath the Marimaca Oxide Deposit encountered significant continuations of higher-grade, leachable mineralization in the form of oxide, mixed and secondary enriched sulphide materials, as well as some primary sulphides. This has clear potential to increase the MOD mineral resource beyond the current Preliminary Economic Assessment (PEA) pit shell.
In late 2020, we took the geological model we have developed for Marimaca and applied it to the surrounding district. We identified three satellite targets Cindy, Mercedes and Robles all of which we drill tested, looking for near surface oxide resources to complement the MOD project. In all three targets, we discovered copper oxide mineralization starting from surface, some with potential for significant scale, that had many similarities to Marimaca. Each of the satellite targets have the potential to deliver meaningful open pit tonnages to any eventual development plans for the Marimaca District. Less well-defined mineralization at the Tarso and Sierra targets remains to be followed up.
Hayden Locke, President and CEO of Marimaca Copper, commented:
Sergio and his exploration team had a remarkable year in 2021. Drill testing three exploration targets, all of which delivered potential shallow oxide materials to add to the outstanding MOD deposit was an excellent result and highlights the underexplored nature of our licence area. A thorough review of the technical data from the MOD PEA showed us that, although these targets have lower grade than the MOD, they all had average grades (in drilling) well above the expected economic cut-off grades for copper mines in this region. As a result, all should be seen as potential mine life extensions to be defined with ongoing work.
More exciting was the discovery of the depth extensions of the MOD. Following extensive reviews of sequential copper assays and logging with our metallurgical team, we believe the extensions are predominantly leachable material and will, therefore, be processable through the same heap leach and SX-EW infrastructure as proposed in the PEA for the MOD. The team is running resource projections, and we are planning to drill MAMIX to an Indicated Resource level in parallel with the remaining infill drilling for the MOD. The intention is to release an updated Mineral Resource Estimate towards the end of the first half of 2022.
Metallurgical and Feasibility Study related workstreams and permitting continue to progress rapidly as we move the exciting MOD towards an eventual investment decision and construction.
Overview and Next Steps
The successful MAMIX extensional drilling program intersected broad zones of mineralization of mixed oxide, enriched and some primary sulphide mineralization below the MOD PEA open pit shell. Results indicate the potential for the expansion of the MODs future leachable Mineral Resource Estimate (MRE) (refer to announcement dated October 14, 2021).
At the Marimaca Oxide Deposit itself, preparatory work is underway for a 22,500m infill campaign. The Company plans to extend the drilling program to include the MAMIX zones to potentially expand its mineral resource inventory. Drill pad and access infrastructure construction are progressing on schedule, with drilling expected to begin by the end of January and will an updated Mineral Resource Estimate MRE planned for mid-year.
The 2021 exploration scout drilling campaign tested several near-surface oxide satellite targets proximal to the MOD to identify additional Marimaca type oxide deposits. The Mercedes, Cindy and Robles satellite targets were identified during an extensive grassroots exploration campaign which included; geological mapping, rock geochemistry, chip channel sampling, a high-resolution drone magnetic survey and IP-R line surveys (see announcement dated September 23, 2020). Each of the three targets was then drill tested during 2021, with 12,750m of RC drilling completed and shallow oxide mineralization identified at all targets. Mercedes was a clear standout, having broad zones of green oxide mineralization from surface with grades similar to the MOD, and we plan to conduct follow up drilling later in the year. Cindy hosted broad zones of oxide mineralization from surface with slightly lower grades, but with a significant surface footprint, with the strike extending over 1km. At the same time drilling encountered shallow oxide mineralization over a large area at Robles. Both present interesting, albeit lower priority, targets for follow-up work.
The Company believes that infill drilling the MOD, defining the MAMIX zone, and further drill testing the Mercedes target provides the shortest path to value accretion. It intends to complete over 25,000m of combined diamond and reverse circulation drilling on these activities for 2022.
Marimacas exploration team is also preparing further generative exploration programs to follow up on important regional targets identified through geophysical surveys across Marimacas district-scale land package.
Summary of Information and Analysis Comprising the Exploration Targets
Marimaca Copper has conducted extensive exploration work to delineate the exploration targets contained in this announcement. This work includes surface mapping of mineralized outcrops, geochemical and physical sampling and assaying, sampling of underground workings, extensive geophysical surveying, and finally, over 19,000m of exploration RC drilling.
Table 3: Exploration Target Range Data
Dimensions are conservative estimates based on surface geological mapping and sampling, underground geological sampling and RC drill intercepts. Grade ranges used in the Exploration Target Ranges are derived from RC drill interception grades within the target dimension area and assumes projections of grades across a mineralized zone. MAMIX dimensions and grade ranges presented benefit from internal modelling estimates completed in conjunction with Marimacas mining engineering and metallurgical consultants as part of the 2022 MAMIX infill drilling program planning.
MAMIX Target
The MAMIX target has been a top priority for the 2021 exploration campaign. MAMIX was initially conceived as a high-priority conceptual exploration target following a comprehensive review by the Marimaca exploration team of the key structural controls of the MOD, as well as complementary magnetic susceptibility, resistivity and chargeability studies indicating the potential for extensions at a depth of the MOD associated with key mineralizing structures (see announcements dated February 2, 2021, and September 23, 2020). The conceptual target was substantiated during the 2021 exploration drilling program. A total of 3,120m over 12 re-entry drill holes were completed at MAMIX, with the maiden program targeting a zone in the southern portion of the MOD. Drilling commenced at depths ranging from 200m to 300m downhole to new final depths of 450m to 500m. Drilling results, discussed in detail in the announcement dated October 14, 2021, intersected significant zones of mixed, enriched and primary mineralization below the PEA pit limits.
The initial 12 hole campaign defined a target area with dimensions of 400m along strike, 350m breadth, and an average mineralized extensional column of 100m downhole, with certain drill holes extending mineralization up to 288m downhole. A plan view diagram of the MAMIX drilling program and certain key cross sections can be viewed in the announcement dated October 14, 2021.
Mercedes Target
The Mercedes Target is located approximately 3km to the north of the MOD and was identified as a large-scale magnetic high during the 2020 high-resolution drone geophysical campaign. Follow up field work was completed in late 2020, and H1 2021 and included 50m x 50m rock geochemical sampling, geological and structural mapping, outcrop sampling and extensive sampling of historic underground workings (refer to announcements dated December 9, 2020 and March 3, 2021). In addition, an induced polarization study consisting of a single 3.5km east-west line across the Mercedes target was completed. Resistivity and chargeability sections demonstrated the potential for broad, laterally extensive supergene zones and potential sulphide mineralization (refer to March 3, 2021 announcement). Surface geochemistry and geophysical studies were both used to design, plan and execute the 2021 maiden drill campaign at Mercedes.
The initial drilling campaign at Mercedes consisted of 4,370m over seventeen shallow RC holes covering approximately 700m of north-south strike. The drilling successfully intersected significant oxide copper mineralization from surface, defining an initial area of interest measuring 400m along strike and 300m width.
Cindy Target
The Cindy Target is located approximately 5km to the north of the MOD and 2km to the north of the Mercedes Target (refer to release December 9 2020) and was initially identified, along with Mercedes and Roble, as a large-scale magnetic anomaly during the 2020 drone-mounted geophysics campaign. Cindy lies on a northern extension of the Naguayn Fault System, the main controlling structure across the Marimaca project. Following the magnetic surveys, Marimaca completed an extensive mapping and sampling campaign in early 2021 and line IP across the target area. Like the Mercedes work program, a 50m x 50m rock geochemistry survey was completed over the target area to complement surface and outcrop geological mapping. In addition, an underground channel sampling program of the historic, shallow artisanal underground workings at Cindy was completed. The underground mine workings cover approximately 200 meters of north south strike over four levels giving a vertical extent of 80 meters (see announcement dated February 17, 2021). The underground channel sampling defined broad zones of higher-grade mineralization with copper hosted primarily in copper oxides atacamite, brochantite and chrysocolla with some localized WAD.
The surface geophysical and geological studies defined an initial target area of interest at Cindy of 800m along strike by 300m across strike. The maiden 2021 drill campaign completed nine holes at ~250m north-south spacings across the 800m strike length. Drilling defined a key target area in the north sections of the broader Cindy target. The drilling intersection was significant mineralization in four drill holes north of the historical underground workings (CIR-02, CIR-03, CIR-08, CIR-09) (refer to announcement dated July 14, 2021). Drill holes CIR-03 and CIR-02 intersected broad zones of mixed copper oxide material from near surface, including 40m with an average grade of 0.51% CuT from 48m downhole and 20m with an average grade of 0.33% CuT from 8m downhole, respectively. Intersections in CIR-08 and 09 were deeper and, as expected, contained increased amounts of primary mineralization when considered in the context of east-dipping structures controlling mineralization at Cindy.
Equally important at Cindy is the compelling potential for extensions to the north. An extension of the magnetic survey that originally identified Cindy also indicated a large anomaly directly to the north of Cindy, the Mititus target. It is located less than 500m to the north of Cindy and may represent its northern continuation. Marimaca is investigating the potential for extensions of the mineralized zone and structures into this area. If successful, this could meaningfully increase the strike length of Cindy.
Roble Target
Roble is located less than 3km to the northeast of the MOD, within the northeast trending Roble Fault System. This is a splay off the regional scale Naguayn Fault System, an important control for mineralization at the MOD. Roble was one of several high-priority anomalies identified within the Marimaca District during the 2020 geophysics campaign. Drone-mounted high-resolution geophysical surveys identified a large magnetic anomaly that was subsequently subject to a comprehensive field geology program prior to drilling. Surface exploration work included rock grid geochemical sampling, reconnaissance mapping, outcrop sampling and 5km of IP line survey. Surface geological work defined a large copper-in-rock anomaly and highlighted the significant extent of outcropping copper oxide mineralization at the surface (refer to announcement on July 1 2021). The surface geological programs successfully identified and delineated three discrete areas of consistently sub-cropping copper mineralization, each extending over 600m by 400m, separated by gravel and sand cover Roble, Nepal and Pele (refer to July 1, 2021 announcement).
A maiden scout RC drilling campaign was subsequently completed at Roble. Fourteen shallow discovery holes were drilled totaling 2,770m. Drilling was completed primarily in a northwest orientation, intercepted mineralization largely controlled by the northeast trending Roble Fault and associated splays. As mentioned, the broader Roble area covers 3 distinct 600m x 400m areas of interest identified through reconnaissance work: Roble main, Nepal and Pele trending in a north-sound direction and separated by shallow gravel cover.
Sierra and Tarso Targets
Sierra is located immediately southeast of the MOD and represents a natural extension of the MOD along the Manolo fault controlling structure. The area was explored as part of the 2019 MOD drilling campaign and consisted of 2,350m of drilling across 9 RC holes at approximately 200m spacing. The exploration campaign extended known limits of the Marimaca Oxide Deposit roughly 600m SE with an area of interest of 600m x 400m identified. No follow up drilling has been completed since the 2019 drilling. Copper mineralization is exposed at surface at old mine workings and outcroppings. The target area is partially covered by gravels indicating potential for further extensions undercover.
Tarso is located immediately northeast of the MOD limits and is predominantly covered by gravel. The area was explored as part of the 2019 MOD drilling campaign, with a portion of drilling included in the 2019 MRE (refer to December 2, 2019 announcement). The exploration drilling not included in the 2019 MRE extended known limits of the Marimaca Oxide Deposit roughly 600m SE with an area of interest of 400m x 400m identified. No follow up drilling has been completed since the 2019 drilling, and the target represents an attractive opportunity to extend copper mineralization below cover to the northeast.
Sampling and Assay Protocol
True widths cannot be determined with the information available at this time. RC holes were sampled on a 2m continuous basis, with dry samples riffle split on site and one quarter sent to the Andes Analytical Assay preparation laboratory in Calama and the pulps then sent to the same company laboratory in Santiago for assaying. A second quarter was stored on site for reference. Samples were prepared using the following standard protocol: drying; crushing to better than 85% passing -10#; homogenizing; splitting; pulverizing a 500-700g subsample to 95% passing -150#; and a 125g split of this sent for assaying. All samples were assayed for %CuT (total copper) and %CuS (acid soluble copper) by AAS. A full QA/QC program, involving insertion of appropriate blanks, standards and duplicates was employed with acceptable results. Pulps and sample rejects are stored by Marimaca Copper for future reference.
Qualified Person
The technical information in this news release, including the information that relates to geology, drilling and mineralization was prepared under the supervision of, or has been reviewed by Sergio Rivera, Vice President of Exploration, Marimaca Copper Corp, a geologist with more than 36 years of experience and a member of the Colegio de Gelogos de Chile and of the Institute of Mining Engineers of Chile, and who is the Qualified Person for the purposes of NI 43-101 responsible for the design and execution of the drilling program.
The QP confirms he has visited the project area, has reviewed relevant project information, is responsible for the information contained in this news release, and consents to its publication.
Contact InformationFor further information please visit http://www.marimaca.comor contact:
Tavistock +44 (0) 207 920 3150Jos Simson/Oliver Lamb / Nick ElwesThis email address is being protected from spambots. You need JavaScript enabled to view it.
Cautionary Notice on Exploration Information
This press release contains information regarding potential exploration results of exploration targets on which the Company intends to conduct further exploration in the near term. Thepotential quantity and grade of such exploration targets described in this press release are conceptual in nature and subject to a number of risks and uncertainties, such that they are not an indication of any current or future economic viability, nor do they satisfy applicable disclosure and information requirements applicable to Mineral Resources. Readers are therefore cautioned on placing any reliance on such information and related expectations. In particular,the potential quantity and grade presented in the exploration target ranges contained in this press release are conceptual in nature and have insufficient exploration and drill density to define a Mineral Resource. At this stage it is uncertain if further exploration will result in the targets being delineated as a Mineral Resource. Estimates of exploration targets are not Mineral Resources and are too speculative to meet therequirementsforreportingMineral Resources under NI 43-101 reporting standards. Readers should also refer to the information provided under Forward-Looking Statements below in the context of their review of information presented in this release.
Forward Looking Statements
This news release includes certain forward-looking statements under applicable Canadian securities legislation. There can be no assurance that such statements will prove to be accurate, and actual results and future events could differ materially from those anticipated in such statements. Forward-looking statements reflect the beliefs, opinions and projections on the date the statements are made and are based upon a number of assumptions and estimates that, while considered reasonable by Marimaca Copper, are inherently subject to significant business, economic, competitive, political and social uncertainties and contingencies. Many factors, both known and unknown, could cause actual results, performance or achievements to be materially different from the results, performance or achievements that are or may be expressed or implied by such forward-looking statements and the parties have made assumptions and estimates based on or related to many of these factors. Such factors include, without limitation: risks related to share price and market conditions, the inherent risks involved in the mining, exploration and development of mineral properties, the uncertainties involved in interpreting drilling results and other geological data, fluctuating metal prices, the possibility of project delays or cost overruns or unanticipated excessive operating costs and expenses, uncertainties related to the necessity of financing, the availability of and costs of financing needed in the future as well as those factors disclosed in the annual information form of the Company dated March 29, 2021, the final short form base prospectus and other filings made by the Company with the Canadian securities regulatory authorities (which may be viewed atwww.sedar.com). Accordingly, readers should not place undue reliance on forward-looking statements. Marimaca Copper undertakes no obligation to update publicly or otherwise revise any forward-looking statements contained herein whether as a result of new information or future events or otherwise, except as may be required by law.
Neither the Toronto Stock Exchange nor the Investment Industry Regulatory Organization of Canada accepts responsibilityfor the adequacy or accuracy of this release.
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Landing Therapeutic Genes Safely in the Human Genome Improving Gene and Cell Therapies – SciTechDaily
Posted: at 9:48 am
By Wyss Institute for Biologically Inspired Engineering at HarvardJanuary 24, 2022
A collaborative research team at Harvards Wyss Institute and the ETH Zurich in Switzerland has identified genomic safe harbors (GSHs) in the tumultuous sea of human genome sequence to land therapeutic genes in. As part of their validation, they inserted a fluorescent GFP reporter gene into candidate GSHs and followed its expression over time. The GSHs could enable safer and longer-lasting expression of genes in future gene and cellular therapies. This illustration won the team the cover of the Cell Reports Methods issue the study is published in. Credit: Erik Aznauryan
Researchers at Harvards Wyss Institute, Harvard Medical School, and the ETH Zurich predict and validate genomic safe harbors for therapeutic genes, enabling safer, more efficient, and predictable gene and cell therapies.
Many future gene and cell therapies to treat diseases like cancer, rare genetic and other conditions could be enhanced in their efficacy, persistence, and predictability by so-called genomic safe harbors (GSHs). These are landing sites in the human genome able to safely accommodate new therapeutic genes without causing other, unintended changes in a cells genome that could pose a risk to patients.
However, finding GSHs with potential for clinical translation has been as difficult as finding a lunar landing site for a spacecraft which has to be in smooth and approachable territory, not too steep and surrounded by large hills or cliffs, provide good visibility, and enable a safe return. A GSH, similarly, needs to be accessible by genome editing technologies, free of physical obstacles like genes and other functional sequences, and allow high, stable, and safe expression of a landed therapeutic gene.
Thus far, only few candidate GSHs have been explored and they all come with certain caveats. Either they are located in genomic regions that are relatively dense with genes, which means that one or several of them could be compromised in their function by a therapeutic gene inserted in their vicinity, or they contain genes with roles in cancer development that could be inadvertently activated. In addition, candidate GSHs have not been analyzed for the presence of regulatory elements that, although not being genes themselves, can regulate the expression of genes from afar, nor whether inserted genes change global gene expression patterns in cells across the entire genome.
Now, a collaboration of researchers at Harvards Wyss Institute for Biologically Inspired Engineering, Harvard Medical School (HMS), and the ETH Zurich in Switzerland, has developed a computational approach to identify GSH sites with significantly higher potential for the safe insertion of therapeutic genes and their durable expression across many cell types. For two out of 2,000 predicted GSH sites, the team provided an in-depth validation with adoptive T cell therapies and in vivo gene therapies for skin diseases in mind. By engineering the identified GSH sites to carry a reporter gene in T cells, and a therapeutic gene in skin cells, respectively, they demonstrated safe and long-lasting expression of the newly introduced genes. The study is published in Cell Reports Methods.
While GSHs could be utilized as universal landing platforms for gene targeting, and thus expedite the clinical development of gene and cell therapies, so far no site of the human genome has been fully validated and all of them are only acceptable for research applications, said Wyss Core Faculty member George Church, Ph.D., a senior author on the study. This makes the collaborative approach that we took toward highly-validated GSHs an important step forward. Together with more effective targeted gene integration tools that we develop in the lab, these GSHs could empower a variety of future clinical translation efforts. Church is a leader of the Wyss Institutes Synthetic Biology Platform, and also the Robert Winthrop Professor of Genetics at HMS and Professor of Health Sciences and Technology at Harvard University and the Massachusetts Institute of Technology (MIT).
The researchers first set up a computational pipeline that allowed them to predict regions in the genome with potential for use as GSHs by harnessing the wealth of available sequencing data from human cell lines and tissues. In this step-by-step whole-genome scan we computationally excluded regions encoding proteins, including proteins that have been involved in the formation of tumors, and regions encoding certain types of RNAs with functions in gene expression and other cellular processes. We also eliminated regions that contain so-called enhancer elements, which activate the expression of genes, often from afar, and regions that comprise the centers and ends of chromosomes to avoid mistakes in the replication and segregation of chromosomes during cell division, said first-author Erik Aznauryan, Ph.D. This left us with around 2,000 candidate loci all to be further investigated for clinical and biotechnological purposes.
Aznauryan started the project as a graduate student with other members of Sai Reddys lab at ETH Zurichs Department of Biosystems Science and Engineering before he visited the Church lab as part of his graduate work, where he teamed up with Wyss Technology Development Fellow Denitsa Milanova, Ph.D. He since has joined Churchs group as a Postdoctoral Fellow. Reddy, senior and lead author of the collaborative study, is an Associate Professor of Systems and Synthetic Immunology at ETH Zurich and focuses on developing new methods in systems and synthetic biology to engineer immune cells for diverse research and clinical applications.
Out of the 2,000 identified GSH sites, the team randomly selected five and investigated them in common human cell lines by inserting reporter genes into each of them using a rapid and efficient CRISPR-Cas9-based genome editing strategy. Two of the GSH sites allowed particularly high expression of the inserted reporter gene in fact, significantly higher than expression levels achieved by the team with the same reporter gene engineered into two earlier-generation GSHs. Importantly, the reporter genes harbored by the two GSH sites did not upregulate any cancer-related genes, said Aznauryan. This also can become possible because regions in the genome distant from one another in the linear DNA sequence of chromosomes, but near in the three-dimensional genome, in which different regions of folded chromosomes touch each other, can become jointly affected when an additional gene is inserted.
To evaluate the two most compelling GSH sites in human cell types with interest for cell and gene therapies, the team investigated them in immune T cells and skin cells, respectively. T cells are used in a number of adoptive cell therapies for the treatment of cancer and autoimmune diseases that could be safer if the receptor-encoding gene was stably inserted into a GSH. Also, skin diseases caused by harmful mutations in genes controlling the function of cells in different skin layers could potentially be cured by insertion and long-term expression of a healthy copy of the mutated gene into a GSH of dividing skin cells that replenish those layers.
We introduced a fluorescent reporter gene into two new GSHs in primary human T cells obtained from blood, and a fully functional LAMB3 gene, an extracellular protein in the skin, into the same GSHs in primary human dermal fibroblasts, and observed long-lasting activity, said Milanova. While these GSHs are uniquely positioned to improve on levels and persistence of gene expression in parent and daughter cells for therapeutics, I am particularly excited about emerging gain-of-function cellular enhancements that could augment the normal function of cells and organs. The safety aspect is then of paramount importance. With an entrepreneurial team at the Wyss, Milanova is developing a platform for genetic rejuvenation and enhancements with a focus on skin rejuvenation.
An extensive sequencing analysis that we undertook in GSH-engineered primary human T cells clearly demonstrated that the insertion has minimal potential for causing tumor-promoting effects, which always is a main concern when genetically modifying cells for therapeutic use, said Reddy. The identification of multiple GSH sites, as we have done here, also supports the potential to build more advanced cellular therapies that use multiple transgenes to program sophisticated cellular responses, this is especially relevant in T cell engineering for cancer immunotherapy.
This collaborative interdisciplinary effort demonstrates the power of integrating computational approaches with genome engineering while maintaining a focus on clinical translation. The identification of GSHs in the human genome will greatly augment future developmental therapeutics efforts focused on the engineering of more effective and safer gene and cellular therapies, said Wyss Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and Boston Childrens Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.
Reference: Discovery and validation of human genomic safe harbor sites for gene and cell therapies by Erik Aznauryan, Alexander Yermanos, Elvira Kinzina, Anna Devaux, Edo Kapetanovic, Denitsa Milanova, George M. Church and Sai T.Reddy, 14 January 2022, Cell Reports Methods.DOI: 10.1016/j.crmeth.2021.100154
Additional authors on the study are Alexander Yermanos, Ph.D, and Edo Kapetanovic, members of Reddys group; Anna Devaux at the University of Basel, Switzerland; and, Elvira Kinzina at the McGovern Institute for Brain Research at MIT. The study was supported by ETH Research Grants, the Helmut Horten Stiftung and Aging and Longevity-Related Research Fund at HMS, as well as a Genome Engineer Innovation Grant 2019 from Synthego to Aznauryan.
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Landing Therapeutic Genes Safely in the Human Genome Improving Gene and Cell Therapies - SciTechDaily
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