Zeitgeist – International – SPIEGEL ONLINE

Zeitgeist - International - SPIEGEL ONLINE

Christine Simon-Noll is active helping refugees in Hamburg's HafenCity neighborhood. She says it is getting much tougher to find volunteers. In an interview, she outlines what needs to happen in order to ensure successful integration. Interview Conducted by Marianne Wellershoff more... [Comment]

Canadian accident investigator Larry Vance claims to have solved the mystery of the disappearance of Malaysia Airlines Flight MH370. In an interview, he explains why he believes the plane's captain deliberately ditched the aircraft. Interview Conducted By Marco Evers more... [Comment]

Arthur Edwards has spent over 40 years photographing the royal family for Britain's Sun newspaper. In an interview, he talks about his experiences and Prince Harry's wedding this weekend. Interview Conducted by Hauke Goos and Jrg Schindler more... [Comment]

The Swedish Academy will not be awarding a Nobel prizein literature this year. And a closer look at the swamp of scandal in Stockholm raises doubts as to whetherit can ever be rehabilitated. By Georg Diez more... [Comment]

The attack on former spy Sergei Skripal thrust the nerve agent Novichok into the spotlight. For many, it was the first time they had heard of the poison, but it has long been a bone of contention between Moscow and the West. By Klaus Wiegrefe more... [Comment]

Each year in Germany, 800 people throw themselves in front of speeding trains, transforming the drivers into involuntary killers. Stephan Kniest has run over four people so far in his career - and fears that a fifth could do him in. By Hauke Goos more... [Comment]

British pop singer Morrissey has accused DER SPIEGEL of falsely quoting him in a recently published interview. The magazine stands behind its reporting and has made the decision to post the audio online in response. more...

An animated reality check of the man who claims to be the greatest U.S. president ever. more... [Video]

How do we want to live in the future? The Social Design Award has selected a shortlist of urban development projects focusing on plants in the city. Now it's your turn to decide which finalist will receive the 2,500-euro audience award. By Marianne Wellershoff more...

Community gardeners and other activists in Berlin are helping the Transition movement to take root in the German capital as part of its worldwide campaign for a sustainable society. By Michael Sontheimer more... [Comment]

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Atheism in Hinduism – Wikipedia

Atheism (Sanskrit: , nir-vara-vda, lit. "statement of no Lord", "doctrine of godlessness") or disbelief in God or gods has been a historically propounded viewpoint in many of the orthodox and heterodox streams of Hindu philosophies.[1] In Indian philosophy, three schools of thought are commonly referred to as nastika for rejecting the doctrine of Vedas: Jainism, Buddhism and Crvka.[2][3]

Hinduism is a religion, but also a philosophy.[4][5] Among the various schools of Hindu philosophy, Samkhya, Yoga and Mimamsa while not rejecting either the Vedas or the Brahman,[6] typically reject a personal God, creator God, or a God with attributes. While Samkhya and Yoga rejected the idea of an eternal, self-caused, creator God, Mimamsa argued that the Vedas could not have been authored by a deity.

Though some schools of thought view the path of the atheist as difficult to follow in matters of spirituality, it is still a valid one.[7] Hindu atheists accept Hinduism more as a "way of life" than a religion.

The Sanskrit term stika ("pious, orthodox") refers to the systems of thought which admit the validity of the Vedas.[8] Sanskrit asti means "there is", and stika (per Pini 4.2.60) derives from the verb, meaning "one who says 'asti'". Technically, in Hindu philosophy the term stika refers only to acceptance of authority of Vedas, not belief in the existence of God.[9] However, though not accepted universally, stika is sometimes translated as "theist" and Nstika as "atheist", assuming the rejection of Vedas to be synonymous to the rejection of God.[10]

Another interpretation by Swami Vivekananda states "As certain religions of the world say that a man who does not believe in a Personal God outside of himself is an atheist, so the Vedanta says, a man who does not believe in himself is an atheist. Not believing in the glory of our own soul is what the Vedanta calls atheism."[11]

The Rig Veda, the oldest of the Vedas, deals with significant skepticism around the fundamental question of a creator God and the creation of the universe. It does not, at many instances, categorically accept the existence of a creator God. Nasadiya Sukta (Creation Hymn) in the tenth chapter of the Rig Veda states:[12][13]

Whence was it produced? Whence is this creation? The gods came afterwards, with the creation of this universe.

The Brihadaranyaka, Isha, Mundaka (in which Brahman is everything and "no-thing") and especially the Chandogya Upanishads have also been interpreted as atheistic because of their stress on the subjective self.[14]

Mimamsa was a realistic, pluralistic school of philosophy which was concerned with the exegesis of the Vedas.[15] The core text of the school was the Purva Mimamsa Sutras of Jaimini (c. 200 BCE200 CE). Mimamsa philosophers believed that the revelation of the Vedas was sacred, authorless (apaurusheyatva) and infallible, and that it was essential to preserve the sanctity of the Vedic ritual to maintain dharma (cosmic order).[16][17]:5253 As a consequence of the belief in sanctity of the ritual, Mimamsas rejected the notion of God in any form.[15] Later commentators of the Mimamsa sutras such as Prabhkara (c. 7th century CE) advanced arguments against the existence of God.[18][19] The early Mimamsa not only did not accept God but said that human action itself was enough to create the necessary circumstances for the enjoyment of its fruits.[20]

Samkhya is an atheistic[21] and strongly dualistic[22][23] orthodox (Astika) school of Indian philosophy. The earliest surviving authoritative text on classical Samkhya philosophy is the Samkhyakarika (c. 350450 CE) of Ivaraka.[17]:63 The Samkhyakarika is silent on the issue of Isvara's existence or nonexistence, although first millennium commentators such as Gaudapada understand the text as compatible with some concept of God. However, the Samkhya Sutra (14th c. CE) and its commentaries explicitly attempt to disprove God's existence through reasoned argument.[24]

Crvka, a materialistic and atheistic school of Indian philosophy, had developed a systematic philosophy by the 6th century CE. Crvkas rejected metaphysical concepts like reincarnation, the afterlife, an extracorporeal soul, the efficacy of religious rites, other worlds (heaven and hell), fate, and accumulation of merit or demerit through the performance of certain actions. Crvkas also refused to ascribe supernatural causes to natural phenomena. Crvka philosophy appears to have died out some time after 1200 CE.[25]

jvikas was a movement (extinct from at least the 13th century CE) whose founder, Makkhali Gosala, was a contemporary of Mahavira and Gautama Buddha (the central figures of Jainism and Buddhism, respectively). Gosala and his followers also denied the existence of a creator god.[26]

Mimamsas argued that there was no need to postulate a maker for the world, just as there was no need for an author to compose the Vedas or a God to validate the rituals.[27] They further thought that the Gods named in the Vedas had no physical existence apart from the mantras that speak their names. In this regard, the power of the mantras was what was seen as the power of Gods.[28] Mimamsas reasoned that an incorporeal God could not author the Vedas, for he would not have the organs of speech to utter words. An embodied God could not author the Vedas either because such a God would be subject to the natural limitations of sensory knowledge and therefore, would not be able to produce supernatural revelations like the Vedas.[29]

Samkhya gave the following arguments against the idea of an eternal, self-caused, creator God:[30]

Therefore, Samkhya maintained not only that the various cosmological, ontological and teleological arguments could not prove God, but that God as normally understood--an omnipotent, omniscient, benevolent creator who is free from suffering--cannot exist.

The Indian Nobel Prize-winner Amartya Sen, in an interview with Pranab Bardhan for the California Magazine published in the JulyAugust 2006 edition by the University of California, Berkeley states:[31]

In some ways people had got used to the idea that India was spiritual and religion-oriented. That gave a leg up to the religious interpretation of India, despite the fact that Sanskrit had a larger atheistic literature than what exists in any other classical language. Madhava Acharya, the remarkable 14th century philosopher, wrote this rather great book called Sarvadarshansamgraha, which discussed all the religious schools of thought within the Hindu structure. The first chapter is "Atheism" a very strong presentation of the argument in favor of atheism and materialism.

According to Markandey Katju, former Chairman of the Press Council of India and former judge of the Supreme Court of India, "...there are six classical systems of Indian philosophy, Nyaya, Vaisheshik, Sankya, Yoga, Purva Mimansa and Uttar Mimansa, and three non-classical systems, Buddhism, Jainism and Charvak. Out of these nine systems eight of them are atheistic as there is no place for God in them. Only the ninth one, that is Uttar Mimansa, which is also called Vedanta, has a place for God in it."[32][33]

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Learn Liberty | What is Libertarian?

Learn Liberty On Demand offers you a series of videos on new and exciting topics in the world of policy and ideas that you can watch any time, anywhere, on your schedule. Have you wondered what distinguishes the ideas of minarchists and anarchists, or the economists of the Austrian and Chicago Schools? If so, this is the place for you.

Youve heard the phrase but what exactly does it mean to be libertarian or classical liberal?Ah, the question of the sages, like Locke and Smith. (Not to mention newer sages like Hayek, Friedman, Rothbard and Nozick!) Now hear it best from one of Learn Libertysown classical liberal sages Dr. Nigel Ashford. Join him in eightengaging videos as he explains the origins, basic tenets and philosophies of classical liberalism like the Austrian School, the Chicago School, Public Choice, Natural Rights, Anarcho-Capitalism and more. Because the more you know what its about the more you can do with it to make the world a better place.

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SparkNotes: Atlas Shrugged: Themes

Themes are the fundamental and often universal ideasexplored in a literary work.The Importance of the Mind

The strike of the mind led by John Galt demonstratesthis central theme of the novel. When the best creative minds aresystematically removed from the world, their importance is laidbare. Without the great thinkers, society spirals quickly downward.The economy collapses, and irrational looters seize power. Randsbelief in the central importance of the mind opposes the prevailingwisdom that labor is responsible for prosperity. As the events ofthe novel show, the mind enables creation and innovation and powersthe engine of the world. Labor alone cannot achieve productivityand prosperity without the guidance of the mind.

Rand sets out to demonstrate through the novels actionwhat happens when governments follow socialist ideas. She arguesthat when men are compelled, through collectivisms forced moralcode, to place the needs of their neighbors above their own rationalself-interest, the result is chaos and evil. Incentive is destroyed,and corruption becomes inevitable. The story of the Twentieth Century MotorCompany illustrates this brilliantly. After the plant adopted amethod in which workers were paid according to perceived needs andordered to work based on perceived ability, the workers became depravedand immoral, each seeking to show himself or herself as most needyand least skilled. The plant failed, and the community was destroyedby mistrust and greed. For Rand, any economic or political planbased on sacrifice of the individual for the group leads to chaosand destruction.

Rand rejects the mind-body dichotomy that is central tomany philosophies and religions. She opposes the idea that the thoughtsand achievements of the mind are pure and noble, but the desiresof the body are base and immoral, and she presents Dagny as a character whoalso rejects the idea. Dagny is proud of her sexuality and sees herphysical desires flowing logically from the evaluations and rationalityof her mind. At first, Rearden accepts the mind-body split. His transformationoccurs when he comes to integrate the two facets of himself intoa rational whole.

Dr. Stadler represents another aspect of this mind-bodydichotomy. He sees the pure science of the mind as removedfrom practical affairs and wonders why the mind that made the motorwould bother with practical applications. For him, the mind is cutoff not just from the body but from practical life. Again, Dagnyrepresents the integrated whole when she concludes that the motorsinventor worked within the reality of practical life because heliked living on earth.

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SparkNotes: Atlas Shrugged: Themes

NASA’s Hubble Telescope captures 15,000 galaxies in one …

NASA, ESA, P. Oesch (University of Geneva), and M. Montes (University of New South Wales)

I honestly almost can't believe this is real and it makes me feel so infinitely small.

Look at this. Just look at it. Take your time with it.

This image of the cosmos comescourtesy of NASA's Hubble Space Telescope, using ultraviolet vision to capture one of the most expansive images of galaxies yet. Combining ultraviolet light with infrared and visible-light data from the Space Telescope has allowed astronomers to build this incredible map of the universe's evolutionary history.

NASA calls it, "one of the largest panoramic views of the fire and fury of star birth in the distant universe." Because light from distant galaxies takes so long to reach us, we are able to see through time. This image lets astronomers look back and track stars being born over the last 11 billion years and features some 15,000 galaxies -- and stars are forming in about 80 percent of them.

This isn't the first time Hubble has provided us with a look back in time either, with the Hubble Ultra Violet Ultra Deep Field's release in 2014. The image above shows an area 14 times larger than its 2014 counterpart.

Space, hey.

Batteries Not Included: The CNET team reminds us why tech is cool.

Culture: Your hub for everything from film and television to music, comics, toys and sports.

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BTCMANAGER | Bitcoin, Blockchain & Cryptocurrency News

Category: Blockchain, Development, News, Tech

The United States government is funding a distributed ledger technology project (DLT), dubbed Open Science Chain (OSC) and its being conducted by researchers at the University of California. According to a statement by the National Science Foundation (NSF) on its official website on August 21, 2018, the OSC is aimed at enhancing scientific research. Subhashini Wins Per the NSF,

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Category: Altcoins, Business, Finance, Investment, News

On August 20, 2018, X Infinity announced that they had successfully raised $20.5 million through a private sale. The Singapore-based fintech firm surpassed their projected target of raising $18 million. The funds will be used to develop a wallet that supports transactions using any digital currency. Faster Transaction Speeds Investors and traders often keep their coins in separate wallets. The

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Category: Altcoins, Bitcoin, Blockchain, Finance, News

According to cryptocurrency analysis website Invest in Blockchain, less than half of the top 100 digital currencies serve a useful purpose by providing real value to the public. According to the website, only 40 cryptocurrency projects were found to have working products. The study was conducted by evaluating each project status, release history and comparing completed features versus features which

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Category: Bitcoin, Blockchain, Development, News, Platform, Tech

The boom in cryptocurrencies last year propelled many to move towards crypto verse. Even people with little or no knowledge jumped on the crypto bandwagon either to make a quick buck or lured by the underpinning technology. Filling the Demand for Blockchain Knowledge But as the investments started pouring in a lot of people started taking an interest in

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Category: Adoption, Altcoins, Blockchain, Development, Ethereum, News

Decentralized apps (Dapps) are seen as the next constellation of utility on the blockchain, but currently, many of them are having problems keeping a user base. The lion share of decentralized apps is focused on platforms for cryptocurrency speculators. It appears the users of Dapps has dropped off after its peak in 2017. While there have been some standouts that

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Category: Altcoins, Business, Finance, Investment, News

On August 19, 2018, Oki Matsumoto, chief executive of Monex group of Japan, voiced his opinion on cryptocurrencies being the future for the finance industry. Matsumotos Is a Visionary With a Futuristic Approach Tokyo-based Monex marked its foray into the cryptocurrency industry via the acquisition of Coincheck, the exchange that was a victim of a recent hack, with the belief

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Category: Altcoins, Bitcoin, Ethereum, Finance, Investment, News

With the total market capitalization of cryptocurrencies reaching beyond $800 billion at the start of 2018, its no wonder that thousands of people have thrown almost their entire life savings into bitcoin and other cryptocurrencies. Now that the value of all outstanding digital tokens has fallen nearly 75 percent, new investors have to deal with the enormous financial loss. Once

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Category: Bitcoin, Blockchain, Mining, News

On August 20, 2018, Bitcoin Mercantile Exchange (BitMEX) published research on a quintessential question bounced around since Bitcoins introduction in 2009: Does Satoshi Nakamoto own a million bitcoins? A Million or not a Million BitMEX based its study on Sergio Demian Lerners 2013 analysis, where the developer uncovered mined Bitcoin blocks can be traced back to their miner, proving the

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Category: Blockchain, News, Regulation, Tech

With national and local authorities in China offering hefty initiatives to tech companies to protect blockchain intellectual property rights, the country has now become a global leader in implementing the technology. Realizing the Potential of Blockchain Technology The Chinese government and tech companies have long surpassed their foreign counterparts in realizing the potential blockchain technology have both for the public

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Category: Altcoins, Bitcoin, Crime, News

Chinese police have recently arrested three men for hacking and stealing 600 million yuan ($87 million) in cryptocurrencies. According to the South China Morning Post, the Xian Police officers stated on Saturday, August 18, 2018, that when it came to cryptocurrency criminal investigations in China, this was the largest number of stolen cryptocurrencies in the nation. First Cryptocurrency-Related Case In

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BTCMANAGER | Bitcoin, Blockchain & Cryptocurrency News

Bahamas Cruises, Bahamas Cruise, Cruise Bahamas, Bahamas …

Find A Bargain

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Are you looking for a Bahamas cruise at an unbelievably low price? Since our opening in 1984, Vacations To Go has helped more than seven million customers find deep discounts on cruises.

The Bahamas are pristine islands off the coast of Florida, known for beautiful, white-sand beaches, crystal-clear water and laid-back style. Bahamas cruises operate year-round and typically range from three to nine nights.

Bahamas cruises depart from the Florida ports of Miami, Fort Lauderdale, Jacksonville and Port Canaveral as well as other ports on the eastern seaboard, as far north as New York. Itineraries may include port calls in Nassau or Freeport or any of the highly popular private islands operated by a number of cruise lines.

Vacations To Go offers the worlds lowest price on every Bahamas cruise.

To scan a complete list of Bahamas cruises for early-bird discounts or last-minute markdowns, use our Find A Bargain search tool.

When you've found the perfect cruise, call us toll-free at 800-338-4962 for a free quote or reservation. We look forward to helping you!

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Bahamas Cruises, Bahamas Cruise, Cruise Bahamas, Bahamas ...

Believer – Transhuman – Amazon.com Music

Reactivated late '80s/early '90s technical-thrash metallers BELIEVER will release their new album, "Transhuman", on April 12 (one day earlier internationally) via Metal Blade Records. The CD was produced by Trauma Team Productions and was mixed by Kevin Gutierrez (RAVEN, PROJECT: FAILING FLESH, DECEASED, DYSRYTHMIA, GARDEN OF SHADOWS) at Assembly Line Studios in Virginia.

Once again, BELIEVER tapped into the artistic genius of Michael Rosner and Eye Level Studio to produce the "Transhuman" artwork and layout.

"We wanted to work with Roz again on 'Transhuman' as our visions of combining art and music truly parallel," the band said. "He just gets it and his artwork is outside the typical box in a way that we strive for musically. It is an amazing collaboration that we have with Roz that continues to evolve. We are excited for everyone to see the final layout!"

The band continued; "Sonically we're extremely happy with this album and can't wait for other people to hear it. We feel like this is a really strong and unique album in the BELIEVER catalog and it's something we're definitely proud of.

"So what will you hear? As we mentioned, we focused more on the overall musicality which included more instrumental layers than we used before. The vocals were also more of a focus as we have had much feedback throughout the years, specifically to get out of the one dimensional realm. Kurt [Bachman] wanted the vocals to be more complimentary to the overall tune feel, so he used many facets of his vocal abilities.

"As with all BELIEVER albums, this one is definitely unique."

Transhumanism: The study of the ramifications, promises, and potential dangers of technologies that will enable us to overcome fundamental human limitations, and the related study of the ethical matters involved in developing and using such technologies.

Fans can pre-order their copy of "Transhuman" at link textthis location where the album is available on its own or bundled with a t-shirt. Also available on the band's pre-order page is a video that shows how the cover art came to be. Below are some images taken from the extraordinary artwork within the CD's packaging.

BELIEVER performed live for the first time in 16 years on September 25, 2009 at Sterling Hotel in Allentown, Pennsylvania.

The band's fourth album, "Gabriel", was released in March 2009 through KILLSWITCH ENGAGE frontman Howard Jones's new imprint label Cesspool Records via Metal Blade. The CD featured guest appearances by Jones, Joe Rico (SACRIFICE), CKY/WORLD UNDER BLOOD guitarist/vocalist Deron Miller and Rocky Gray (EVANESCENCE, SOUL EMBRACED, LIVING SACRIFICE).

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Believer - Transhuman - Amazon.com Music

gene therapy | Encyclopedia.com

Definition

Gene therapy is a rapidly growing field of medicine in which genes are introduced into the body to treat diseases. Genomics is the DNA which is found in an organism's total set of genes and is passed on to the offspring as information necessary for survival. Genetics is the study of the patterns of inheritance of specific traits. Genes control heredity and provide the basic biological code for determining a cell's specific functions. Gene therapy seeks to provide genes that correct or supplant the disease-controlling functions of cells that are not performing in a normal manner.

Somatic gene therapy introduces therapeutic genes at the tissue or cellular level to treat a specific individual. Germ-line gene therapy inserts genes into reproductive cells or possibly into embryos to correct genetic abnormalities that could be passed on to future generations. Initially conceived as an approach for treating inherited diseases such as cystic fibrosis and Huntington's disease, the scope of potential gene therapies has grown to include treatments for cancer, arthritis, and infectious diseases.

In the early 1970s, scientists proposed "gene surgery" for treating inherited diseases caused by abnormally functioning genes. The idea was to take out the disease-causing gene and surgically implant a gene that functioned correctly. Although sound in theory, and after some advances in science, this technique has not yet been successful.

However, in 1983, a group of scientists from Baylor College of Medicine in Houston, Texas, proposed that gene therapy could one day be a viable approach for treating Lesch-Nyhan disease, a rare neurological disorder. The scientists conducted experiments in which an enzyme-producing gene (a specific type of protein) for correcting the disease was injected into a group of cells for replication. The scientists theorized the cells could then be injected into people with Lesch-Nyhan disease, thus correcting the genetic abnormality that caused the disease.

As the science of genetics advanced throughout the 1980s, gene therapy grew in the estimation of medical scientists as a promising approach to treatments for specific diseases. One of the major reasons for the growth of gene therapy was the increasing body of knowledge available to assist in identifying the specific genetic malfunctions that caused inherited diseases. Interest grew as further studies of DNA and chromosomes (where genes reside) showed that specific genetic abnormalities in one or more genes occurred in successive generations of certain family members who experienced diseases like intestinal cancer, manic-depression (bipolar disorder), Alzheimer's disease, heart disease, diabetes, and many more. Although genes may not be the only cause of the disease in all cases, they may make certain individuals more susceptible to developing a particular condition due to environmental influences such as smoking, pollution, and stress. In fact, some scientists theorize that all diseases may have a genetic component.

Gene therapy has grown out of the science of genetics or how heredity functions. Scientists know that life begins in a cell, the basic building block of all multicellular organisms. Humans, for instance, are made up of trillions of cells, each performing a specific function. Within each cell's nucleus (the center part of a cell that regulates its chemical functions) are pairs of chromosomes. These threadlike structures are made up of deoxyribonucleic acid (DNA), which carries the blueprint of life in the form of codes, or genes, that determine dominant or recessive inherited characteristics.

A DNA molecule looks like two ladders with one of the sides taken off both and then twisted around each othera formation known as the double helix. The rungs of these ladders meet (resulting in a spiral staircase-like structure) and are called base pairs. Base pairs are made up of nitrogen-containing molecules and arranged in specific sequences. Millions of these base pairs, or sequences, constitute a single gene, specifically defined as a segment of the chromosome and DNA that contains certain hereditary information. The gene, or combination of genes formed by these base pairs, ultimately directs an organism's growth and characteristics through the production of certain chemicalsprimarily proteins that carry out most of the body's chemical functions and biological reactions.

Scientists have long known that alterations in the genes present within cells may cause inherited diseases such as cystic fibrosis, sickle cell disease, and hemophilia. Similarly, errors in entire chromosomes may cause conditions such as Down syndrome or Turner syndrome. As the study of genetics advanced, however, scientists learned that altered genetic sequences may also make people more susceptible to diseases such as atherosclerosis, cancer, and schizophrenia. These diseases have a genetic component, but are also influenced by environmental factors such as diet and lifestyle. The objective of gene therapy is to treat diseases by introducing functional genes into the body to alter the cells involved in the disease process, either by replacing missing genes or by providing copies of functioning genes to replace nonfunctioning ones. The inserted genes may be naturally occurring genes that produce the desired effect or may be engineered (or altered) genes.

Scientists have known how to manipulate a gene's structure in the laboratory since the early 1970s through a process called gene splicing. The process involves removing a fragment of DNA containing a specific desired genetic sequence and then inserting it into the DNA of another gene. The resultant product is called recombinant DNA, and the process is called genetic engineering. This technique is used in preparing some new therapies (monoclonal antibodies, blood component replacements for hemophilia, anti-inflammatory therapy for collagen diseases).

There are two types of gene therapy. Germ-line gene therapy introduces genes into reproductive cells (sperm and eggs) to participate in germination. Some scientists hope that it may eventually be possible to insert genes into embryos in hopes of correcting genetic abnormalities that can then be passed on to future generations. Most of the current work in applied gene therapy, however, has been in the realm of somatic therapy. In this type of gene therapy, therapeutic genes are inserted into tissue or cells to produce a naturally occurring protein or substance that is lacking or not functioning correctly in an individual.

In both types of therapy, scientists need a mechanism to transport either an entire gene or a recombinant DNA to a cell's nucleus, where the chromosomes and DNA reside. In essence, vectors are molecular delivery trucks. One of the first and most widely used vectors to be developed were viruses, because they invade cells as part of their natural infection process. Viruses have the potential to be excellent vectors because they have a specific relationship with a host in that they colonize certain cell types and tissues in specific organs. As a result, vectors are chosen according to their attraction to certain cells and areas of the body.

One of the first classes of vectors used were retroviruses. Because these viruses are easily cloned (artificially reproduced) in the laboratory, scientists have studied them extensively and learned a great deal about their biologic action. They have also learned how to remove the genetic information that governs viral replication, thus reducing the chances of infection from the host vector.

Retroviruses work best in actively dividing cells, but most cells in a human body are relatively stable and do not often divide. As a result, these cells are used primarily for ex vivo (outside the body) manipulation. First, the cells are removed from a person's body, and the vector, or virus carrying the gene, is inserted into them. Next, the cells are placed into a nutrient culture where they grow and replicate. Once enough cells are gathered, they are returned to the body, usually by injection into the blood stream. Theoretically, as long as these cells survive, they will provide the desired therapy.

Another class of viruses, called adenoviruses, may also prove to be good gene vectors. These viruses effectively infect non-dividing cells in the body, where the desired gene product is then expressed naturally. In addition to being a more efficient approach to the problem of gene transportation, these viruses, which are known to cause respiratory infections, are more easily purified and stabilized than are retroviruses. The result is less liklihood of unintended viral infection. However, these viruses live for several days in the body, and there is some concern about the possibility of infecting other people with the viruses through sneezing or coughing. Other viral vectors include influenza viruses, Sindbis virus, and a herpes virus that infects nerve cells.

Scientists have also studied nonviral vectors. These vectors rely on the natural biologic process in which cells take up (or gather) macromolecules. One approach is to use liposomes, globules of fat produced by the body and taken up by cells. Scientists are also investigating the introduction of raw recombinant DNA by injecting it into the bloodstream or placing it on microscopic beads of gold injected into the skin using air pressure. Another possible vector under development is based on dendrimer molecules. A class of polymers (naturally occurring or artificial substances that have a high molecular weight and are formed by smaller molecules of the same or similar substances) is constructed in a laboratory by combining these smaller molecules. They have been used in manufacturing styrofoam, polyethylene cartons, and Plexiglas. In the laboratory, dendrimers have shown the ability to transport genetic material into human cells. They can also be designed to form an affinity for particular cell membranes by attaching to certain sugars and protein groups. Much additional research must be conducted before dendrimers can be used on a routine basis.

On September 14, 1990, a four-year old girl who had a genetic disorder that prevented her body from producing a crucial enzyme became the first person to undergo gene therapy in the United States. Because her body could not produce adenosine deaminase (ADA), she had a weakened immune system, making her extremely susceptible to severe, life-threatening infections. W. French Anderson and colleagues at the National Institutes of Health's Clinical Center in Bethesda, Maryland, took white blood cells (which are crucial to proper immune system functioning) from the girl, inserted ADA-producing genes into them, and then transfused the cells back into the girl. Although the young girl continued to show an increased ability to produce ADA, debate arose as to whether the improvement resulted from the gene therapy or from an additional drug treatment she received.

Although gene therapy testing in humans has advanced rapidly, many questions surround its use. For example, some scientists are concerned that the therapeutic genes themselves may cause disease. Others fear that germ-line gene therapy may be used to control human development in ways not connected with disease, such as intelligence or physical appearance.

Nevertheless, a new era of gene therapy began as more and more scientists sought to conduct clinical trial (testing in humans) research in this area. In that same year, gene therapy was tested on persons with melanoma (skin cancer). The goal was to help them produce antibodies (disease fighting substances in the immune system) to battle the cancer.

The relative success of these experiments prompted a growing number of attempts at gene therapies designed to perform a variety of functions in the body. For example, a gene therapy for cystic fibrosis aims to supply a gene that alters cells, enabling people with cystic fibrosis to produce a specific protein to battle the disease. Another approach was used for people with brain cancer, in which the inserted gene was designed to make the cancer cells more likely to respond to drug treatment. A third gene therapeutic approach for people experiencing artery blockage, which can lead to strokes, induces the growth of new blood vessels (collateral circulation) near clogged arteries, thus ensuring relatively normal blood circulation.

In the United States, both nucleic acid-based (in vivo) treatments and cell-based (ex vivo) treatments are being investigated. Nucleic acid-based gene therapy uses vectors (such as viruses) to deliver modified genes to target cells. Cell-based gene therapy requires removal of cells from a person, genetically altering the cells and then reintroducing them into the body of the person being treated. Presently, gene therapies for the following diseases are being studied: cystic fibrosis (using adenoviral vector), HIV infection (cell-based), malignant melanoma (cell-based), Duchenne muscular dystrophy (cell-based), hemophilia B (cell-based), kidney cancer (cell-based), Gaucher disease (retroviral vector), breast cancer (retroviral vector), and lung cancer (retroviral vector). When a cell or individual is treated using gene therapy and successful incorporation of engineered genes has occurred, the cell or individual is said to be transgenic.

The medical establishment's contribution to transgenic research has been supported by increased government funding. In 1991, the U.S. government provided $58 million for gene therapy research, with increases in funding of $15-40 million dollars a year over the following four years. With fierce competition over the promise of societal benefits in addition to huge profits, large pharmaceutic corporations have moved to the forefront of transgenic research. In an effort to be first in developing new therapies, and armed with billions of dollars of research funds, such corporations are making impressive progress toward making gene therapy a viable reality in the treatment of once elusive diseases.

Although great strides have been made in gene therapy in a relatively short time, its potential usefulness has been limited by lack of scientific data concerning the multitude of functions that genes control in the human body. For instance, it is now known that much genetic material is contained in non-coding regions. That is, they merely store information that may be used at different times in a cell's life cycle. Some of these large portions of the genome are involved in control and regulation of gene expression. Each individual cell in the body carries thousands of genes that have coding for proteins. Some experts estimate this number to be 150,000 genes. For gene therapy to advance to its full potential, scientists must discover the biologic role for each of these individual genes and identify the location on the DNA helix for each of the base pairs that comprise them.

To address this issue, the National Institutes of Health initiated the Human Genome Project in 1990. Led by Dr. James Watson (one of the co-discoverers of the chemical makeup of DNA) the project's 15-year goal is to map the entire human genome (a combination of the words gene and chromosome). A genome map would clearly identify the location of all genes as well as the more than three billion base pairs that comprise them. With a precise knowledge of gene locations and functions, scientists may one day be able to conquer or control diseases that have plagued humanity for centuries.

Scientists participating in the Human Genome Project have identified an average of one new gene a day, but many expect this rate of discovery to increase. In February of 2001, scientists published a rough draft of the complete human genome; the final complete sequence was published in 2003.

Some of the genes identified through this project include a gene that predisposes people to obesity; one associated with programmed cell death (apoptosis); a gene that guides HIV viral reproduction; and the genes of inherited disorders like Huntington's disease, amyotrophic lateral aclerosis (Lou Gehrig's disease), and some colon and breast cancers.

The potential scope of gene therapy is enormous. More than 4,200 diseases have been identified as resulting directly from non-functioning or abnormal genes, and countless others that may be partially influenced by a person's genetic makeup. Initial research has concentrated on developing gene therapies for diseases whose genetic origins have been established and for other diseases that can be cured or ameliorated by substances genes produce.

The following are examples of potential gene therapies. People with cystic fibrosis lack a gene needed to produce a salt-regulating protein. This protein regulates the flow of chloride into epithelial cells (the cells that line the inner and outer skin layers), that cover the air passages of the nose and lungs. Without this regulation, people with cystic fibrosis have a buildup of thick mucus in their lungs. In turn, this mucus makes these patients prone to lung infections and respiratory problems, and usually leads to death within the first 29 years of life. A gene therapy technique to correct this abnormality might employ an adenovirus to transfer a normal copy of what scientists call the cystic fibrosis transmembrane conductance regulator (CTRF) gene. The gene is introduced into a person by spraying it into the nose or lungs.

Familial hypercholesterolemia (FH) is also an inherited disease, resulting in the inability to process cholesterol properly, which leads to high levels of artery-clogging fat in the bloodstream of even the youngest family members. Persons with FH often suffer heart attacks and strokes because of blocked arteries. A gene therapy approach used to address FH is much more intricate than most gene therapies because it involves partial surgical removal of persons' livers (ex vivo transgene therapy). Corrected copies of a gene that acts to reduce cholesterol buildup are inserted into the liver sections, which are then transplanted back into the people.

Gene therapy has also been tested on persons with acquired immune difficiency syndrome (AIDS ). AIDS is caused by the human immunodeficiency virus (HIV), which weakens the body's immune system to the point that people with the condition are unable to fight off diseases such as pneumonia and cancer. In one approach, genes that produce specific HIV proteins have been altered to stimulate immune system functioning without causing the negative effects that a complete HIV molecule has on the immune system. These genes are then injected in a person's blood stream. Another approach to treating AIDS is to insert, via white blood cells, genes that have been genetically engineered to produce a receptor that would attract HIV and reduce its chances of replicating. These approaches are still primarily experimental.

Several cancers also have the potential to be treated with gene therapy. A therapy tested for melanoma, a progressive, agressive skin cancer, would introduce a gene with an anticancer protein called tumor necrosis factor (TNF) into test tube samples of a person's own cancer cells, which are then reintroduced into the person's body. In brain cancer, the approach is to insert a specific gene that increases the cancer cells' susceptibility to a common drug used in fighting the disease.

Gaucher disease is an inherited disease caused by a mutant gene that inhibits the production of an enzyme called glucocerebrosidase. Persons with Gaucher disease have enlarged livers (hepatomegaly) and spleens (splenomegaly). Clinical gene therapy trials will focus on inserting the gene for producing the missing enzyme.

Gene therapy is also being considered as an approach to solving a problem associated with a surgical procedure known as balloon angioplasty. In this procedure, a stent (a piece of tubular material resembling a straw) is used to open the clogged artery. However, in a "fail-safe" response to the trauma of the stent insertion, the body initiates a natural healing process that produces too many cells in the artery and results in restenosis or reclosing of the artery. The gene therapy approach to preventing this unwanted side effect is to cover the outside surfaces of an inserted stent with a soluble gel containing vectors for genes that may reduce an overactive healing response.

Gene therapy seems elegantly simple in its concept: supply the human body with a gene that can correct a biologic malfunction causing a disease. However, there are many obstacles and some distinct questions concerning the viability of gene therapy. For example, viral vectors must be carefully controlled lest they infect a person with a viral disease. Some vectors, like retroviruses, can also enter normally functioning cells and interfere with natural biologic processes, possibly leading to other diseases. Other viral vectors, such as adenoviruses, are often recognized and destroyed by the immune system so their therapeutic effects are short-lived. Maintaining gene expression so that it performs its role properly after vector delivery is difficult. As a result, some therapies need to be repeated often to provide long-lasting benefits.

One of the most pressing issues, however, is gene regulation. Genes work in concert to regulate their functioning. In other words, several genes may play a part in turning other genes on and off. For example, certain genes work together to stimulate cell division and growth; but if these are not regulated, the inserted genes could cause tumor formation and cancer. Another difficulty is learning how to make the gene go into action only when needed. For the best and safest therapeutic effort, a specific gene should turn on, for example, when certain levels of a protein or enzyme are low and must be replaced. But the gene should also remain dormant when not needed to ensure that it does not oversupply a substance and disturb the body's delicate chemical balance.

One approach to gene regulation is to attach other genes that detect certain biologic activities and then react as a type of automatic off-and-on switch, regulating the activity of other genes according to biologic cues. Although still in the rudimentary stages, researchers are making progress in inhibiting some gene functioning by using a synthetic DNA to block gene transcriptions (the copying of genetic information). This approach may have applications for gene therapy.

While gene therapy holds promise as a revolutionary approach for treating disease, ethical concerns over its use and ramifications have been expressed by scientists and lay people alike. For example, since much needs to be learned about how these genes actually work and their long-term effects, is it ethical to test these therapies on humans, in whom they could have a disastrous result? As with most clinical trials concerning new therapies, including many drugs, the people participating in these studies have usually not responded to more established therapies and are often so ill that the novel therapy is their only hope for long-term survival.

Another questionable outgrowth of gene therapy is that scientists could potentially manipulate genes to control traits in human offspring that are not related to health. For example, perhaps a gene could be inserted to ensure that a child would not be bald, a seemingly harmless goal. However, what if genetic manipulation was used to alter skin color, prevent homosexuality, or ensure good looks? If a gene is found that can enhance intelligence of children who are not yet born, will all members of society have access to the technology, or will it be so expensive that only the elite can afford it?

The Human Genome Project, which plays such an integral role for the future of gene therapy, also has social repercussions. If individual genetic codes can be determined, will such information be used against people? For example, will someone more susceptible to a disease have to pay higher insurance premiums or be denied health insurance altogether? Will employers discriminate between two potential employees, one with a healthy genome and the other with genetic abnormalities?

Cells The smallest living units of the body that carry a full complement of the DNA, and which group together to form tissues and help the body perform specific functions.

Chromosome Threadlike structures in a cell that carry most of the genetic material in the form of DNA and genes.

Clinical trial The testing of a drug or some other type of therapy in a specific human population.

Clone A cell or organism derived through asexual (without sex) reproduction, and which contains the identical genetic information of the parent cell or organism.

DNA (deoxyribonucleic acid) The specific molecules that comprise chromosomes and genes.

Embryo The earliest stage of development of the zygote before the human or animal is considered a fetus (which is usually the point at which the embryo takes on the basic physical form of its species). Embryos are formed in vivo (in utero) or in vitro (in a laboratory) in preparation for implantation.

Enzyme Atypeofmoleculemadebycells that,when released, facilitates chemical reactions in the body.

Eugenics A social movement in which the population of a society, country, or the world is to be improved by selective mating, controlling the passage of hereditary information.

Gene A specific biologic component found in the cell nucleus that carries the instructions for the formation of an organism and its specific traits, such as eye or hair color.

Gene transcription The process by which genetic information is copied from DNA to RNA, resulting in a specific protein formation.

Genetic engineering The manipulation of genetic material to produce specific results in an organism.

Genetics The study of hereditary traits passed on through genes.

Genome The total set of genes carried by an individual or cell.

Genomics The DNA which is found in the organism's total set of genes carried by an individual or cell and is passed on to offspring as information necessary for survival.

Germ-line gene therapy The introduction of genes (natural or engineered) into reproductive cells or embryos to correct inherited genetic abnormalities that can cause disease by replication.

Liposome Fat organelle made up of layers of lipids.

Macromolecule A large molecule composed of thousands of atoms.

Nitrogen An element that is a component of the base pairs in DNA.

Nucleus The central part of a cell that contains most of its genetic material, including chromosomes and DNA.

Protein Macromolecule made up of long sequences of amino acids. Proteins comprise the dry weight of most cells and are involved in structures, hormones, and enzymes in muscle contraction, immunological response, and many other functions essential to life.

Somatic gene therapy The introduction of genes into tissue or cells to treat a genetic disease in an individual.

Vector Something used to transport genetic information to a cell.

Some of these concerns can be traced back to the eugenics movement that was popular in the first half of the twentieth century. This genetic philosophy was a societal movement that encouraged people with so-called positive traits to reproduce while those with less desirable traits were sanctioned from having children. Eugenics was used to pass strict immigration laws in the United States, barring less suitable people from entering the country lest they reduce the quality of the country's collective gene pool. Probably the most notorious example of eugenics in action was the rise of Nazism in Germany, which fostered the Eugenic Sterilization Law of 1933. The law required sterilization for those with certain disabilities and even for some persons who were simply deemed to be unattractive. To ensure that this novel science is not abused, many governments have established organizations specifically for overseeing the development of gene therapy. In the United States, the Food and Drug Administration and the National Institutes of Health require scientists to take a precise series of steps and meet stringent requirements before approving clinical trials.

In fact, gene therapy has been immersed in more controversy and is surrounded by more scrutiny from both the health care and ethics communities than most other technologies (except, perhaps, for cloning) that have the potential to substantially change society. Despite the health and ethical questions surrounding gene therapy, the field will continue to grow and is likely to change medicine more quickly than any previous medical advancement.

Burdette, Walter J. The Basis for Gene Therapy. Springfield, IL, Charles C Thomas, 2001.

Gomez-Navarro, Jesus, Guadalupe Bilbao, and David T. Curiel. "Gene therapy." In Cecil Textbook of Medicine, 21st ed., edited by Goldman, Lee and Bennett, J. Claude. Philadelphia: W.B. Saunders, 2000, 140-143.

Hengge, Ulrich R., and Beatrix Volc-Platzer. The Skin and Gene Therapy. New York: Springer Verlag, 2000.

Huard, Johnny, and Freddie Fu. Gene Therapy and Tissue Engineering in Orthopaedic and Sports Medicine. Boston: Birkhauser, 2000.

Lemoine, Nicholas R., and Richard G. Vile. Understanding Gene Therapy. New York: Springer Verlag, 2000.

Needleman, Robert D. "Fetal growth and development." In Nelson Textbook of Pediatrics, 16th ed. edited by Richard E. Behrman et al., Philadelphia: Saunders, 2000, 27-30.

Valle, David. "Treatment and prevention of genetic disease." In Harrison's Principles of Internal Medicine, 14th ed. edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1998, 403-411.

Walther, Wolfgang, and Ulrike Stein. Gene Therapy of Cancer: Methods and Protocols. Totowa, NJ: Humana Press, 2000.

Gottlieb, S. "Gene therapy shows promise for hemophilia." British Medical Journal 322 no.7300 (2001): 1442A-1443.

Gray, S.G. "Pill-based gene therapy." Trends in Genetics 17 no.7 (2001): 380-384.

McKay, D. "Restoring sight by gene therapy." Trends in Biotechnology, 19 no.7 (2001): 243-246.

Newman, C.M., Lawrie, A., Brisken, A.F., Cumberland, D.C. "Ultrasound gene therapy: on the road from concept to reality." Echocardiography 18 no.4 (2001): 339-347.

Savulescu, J. "Harm, ethics committees and the gene therapy death." Journal of Medical Ethics 27 no.3 (2001): 148-150.

Verma, I.M. "Ombudsman or Hotline for Gene Therapy Clinical Trials?" Molecular Therapeutics 3 no.6 (2001): 817-818.

American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672, (913) 906-6000, http://www.aafp.org.

American Society of Gene Therapy. 611 East Wells Street, Milwaukee, WI 53202, (414) 278-1341, (414) 276-3349. http://www.asgt.org.

World Health Organization. 20 Avenue Appia, 1211 Geneva 27, Switzerland, +41 (22) 791 4140, +41 (22) 791 4268. http://www.who.int/gtb.

American Civil Liberties Union. http://www.aclu.org/issues/aids/docket98.html.

Association of American Medical Colleges. http://www.aamc.org/newsroom/reporter/june2000/view.htm.

Human Genome Project Information. http://www.ornl.gov/hgmis/medicine/genetherapy.html.

National Cancer Institute. http://cancernet.nci.nih.gov/clinpdq/therapy/Questions_and_Answers_About_Gene_Therapy.html.

Public Broadcasting System (animation). http://www.pbs.org/wnet/innovation/show1/html/animation2.html.

University of Pennsylvania. http://www.med.upenn.edu/ihgt/info/whatisgt.html.

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Vanderbilt University. http://www.mc.vanderbilt.edu/gcrc/gene.

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gene therapy | Encyclopedia.com

Gene Therapy The Future of Medicine? | Science Care

Gene therapy is an experimental method of fighting disease that involves correcting or replacing a persons mutated or malfunctioning genes. This promising research is now being used in clinical trials and may lead to improved health outcomes for patients with inherited bleeding and immune disorders as well as some forms of blood cancer and other diseases.

What Is Gene Therapy?

Genes carry the DNA information needed to make proteins that are the building blocks of the human body. Some of these genes can become damaged through mutation, which can lead to disease conditions. Gene therapy is a scientific technique that uses genes to prevent or treat disease in a number of different ways:

Finding the Keys to Alter Body Chemistry

Currently, gene therapy can be used for conditions in which a change in the genetic coding of somatic cells can alter the course of a disease. For example, to correct a disease in which a specific enzyme is missing, the addition of a necessary gene component for production of the enzyme would fix the underlying problem of the disease. In many cases, harmless viruses are employed to serve as packets to carry the new gene to where it is needed. When used this way, the viruses are called vectors, and their own genes may be removed and replaced with the working human gene. Once the gene is correctly placed, it can be switched on to provide the working instructions for correct function.

Conditions Being Treated with Gene Therapy

Although much of this may still sound like the realm of mad scientists tinkering with the human body, gene therapy is an accepted experimental technique that is currently being used to help patients with certain types of cancer to target specific antibodies that can be used to fight the disease. Gene therapy is also being used to correct deficiencies in the production of dopamine, such as in Parkinsons disease, correct some immune system problems, and restore components needed for normal blood cell function in those with certain blood diseases, such hemophilia and beta-Thalassemia. Gene therapy holds promise for treating a wide range of diseases, including cancer, cystic fibrosis, heart disease, diabetes, hemophilia and AIDS.

Potential Risks

Gene therapy does come with some potential risks, all of which, researchers are hoping to overcome. Because the genes have to be delivered using a carrier or vector, the bodys immune system may see the newly introduced viruses as intruders and attack them. Its also possible that the altered viruses may infect additional cells, not just the targeted cells containing mutated genes. There may also be some concern that the viruses may recover their original ability to cause disease, or that the new genes get inserted in the wrong spot in a patients DNA, leading to tumor formation.

Hope for the Future

Gene therapy holds promise as an effective treatment option for a variety of diseases at some point in the near future. An estimated 4,000 medical conditions are a result of gene disorders. If some of these genetic problems can be corrected through gene replacement or manipulation, individuals suffering from these diseases may enjoy longer, healthier lives, free of symptoms and the associated medical expenses.

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Gene Therapy The Future of Medicine? | Science Care

Gene Therapy in Muscular Dystrophy

Gene therapy, the use of genetic material to treat a disease or disorder, is making strides in muscular dystrophy. Although the approach is still considered experimental, studies in animal models have shown promising results and clinical trials in humans are underway.

Gene therapy has the potential to help people with inherited disorders, in which a gene mutation causes cells to produce a defective protein or no protein at all, leading to disease symptoms.

To deliver the genetic material to the cells, scientists use a tool called a vector. This is typically a virus that has been modified so that it doesnt cause disease. It is hoped that the vector will carry the therapeutic gene into the cells nucleus, where it will provide the instructions necessary to make the desired protein.

The most common form of muscular dystrophy, Duchenne muscular dystrophy, is caused by a mutation in the DMD gene, which codes for a protein called dystrophin. Dystrophin is part of a protein complex that strengthens and protects muscle fibers. When the cells dont have functional dystrophin due to the gene mutation, muscles progressively weaken. Scientists think that supplying a gene that codes for a functional form of dystrophin might be an effective treatment for Duchenne muscular dystrophy.

Using gene therapy to deliver a correct form of the dystrophin gene has been challenging because of the size of the DMD gene, which is the largest gene in the human genome so it does not fit into commonly used vectors.

Scientists are having more success with a shortened version of the DMD gene that produces a protein called micro-dystrophin. Even though its a smaller version of dystrophin, micro-dystrophin includes key elements of the protein and is functional.

Administering a gene for micro-dystrophin to golden retriever dogs that naturally develop muscular dystrophy showed promising results in a study published in July 2017. Muscular dystrophy symptoms were reduced for more than two years following the treatment and the dogs muscle strength improved. The gene was delivered using a recombinant adeno-associated virus, or rAAV, as the vector.

A similar therapy is now being tested in people in a Phase 1/2 clinical trial (NCT03375164)at Nationwide Childrens Hospital in Columbus, Ohio. A single dose of the gene therapytreatment containing the gene encoding for micro-dystrophinwill be infused into the blood system of 12 patients in two age groups: 3 months to 3 years, and 4 to 7 years. The first patient in the trial, which is recruiting participants, already has received the treatment, according to a January 2018 press release.

The biopharmaceutical company Sarepta Therapeutics is contributing funding and other support to the project.

Sarepta is developing another potential gene therapy for Duchenne muscular dystrophy where rather than targeting the DMD gene that codes for dystrophin, the therapy will be used to try to increase the expression of a gene called GALGT2. The overproduction of this gene is thought to produce changes in muscle cell proteins that strengthen them and protect them from damage, even in the absence of functional dystrophin.

A Phase 1/2a clinical trial (NCT03333590) was launched in November 2017 at Nationwide Childrens Hospital for the therapy, called rAAVrh74.MCK.GALGT2.

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Muscular Dystrophy Newsis strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

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Gene Therapy in Muscular Dystrophy

Gene & Cell Therapy Defined | ASGCT – American Society of …

Gene therapy is a field of biomedical research with the goal of influencing the course of various genetic and acquired (so-called multi factorial) diseases at the DNA/RNA level. Cell therapy aims at targeting various diseases at the cellular level, i.e. by restoring a certain cell population or using cells as carriers of therapeutic cargo. For many diseases, gene and cell therapy are applied in combination. In addition, these two fields have helped provide reagents, concepts, and techniques that are illuminating the finer points of gene regulation, stem cell lineage, cell-cell interactions, feedback loops, amplification loops, regenerative capacity, and remodeling.

Gene therapy is defined as a set of strategies that modify the expression of an individuals genes or repair abnormal genes. Each strategy involves the administration of a specific nucleic acid (DNA or RNA). Nucleic acids are normally not taken up by cells, thus special carriers, so-called 'vectors' are required. Vectors can be of either viral or non-viral nature.

Cell therapy is defined as the administration of living whole cells for the patient for the treatment of a disease. The origin of the cells can be from the same individual (autologous source) or from another individual (allogeneic source). Cells can be derived from stem cells, such as bone marrow or induced pluripotent stem cells (iPSCs), reprogrammed from skin fibroblasts or adipocytes. Stem cells are applied in the context of bone marrow transplantation directly. Other strategies involve the application of more or less mature cells, differentiated in vitro (in a dish) from stem cells.

Historically, the discovery of recombinant DNA technology in the 1970s provided the tools to efficiently develop gene therapy. Scientists used these techniques to readily manipulate bacterial and viral genomes, isolate genes, identify mutations involved in human diseases, characterize and regulate gene expression and produce human proteins from genes (e.g. production of insulin in bacteria revolutionized medicine). Later, various viral and non-viral vectors were developed along with the development of regulatory elements (e.g. promoters that regulate gene expression), which are necessary to induce and control gene expression. Gene transfer in animal models of disease have been attempted and led to early success. Various routes of administrations have been explored (injection into the bloodstream, into the ventricles of the brain, into muscle etc).

The development of suitable gene therapy treatments for many genetic diseases and some acquired diseases has encountered many challenges, such as immune response against the vector or the inserted gene. Current vectors are considered very safe and recent gene therapy trials documented excellent safety profile of modern gene therapy products. Further development involves uncovering basic scientific knowledge of the affected tissues, cells, and genes, as well as redesigning vectors, formulations, and regulatory cassettes for the genes. While effective long-term treatments for many genetic and inherited diseases are elusive today, some success is being observed in the treatment of several types of immunodeficiency diseases, cancers, and eye disorders.

Historically, blood transfusions were the first type of cell therapy and are now considered routine. Bone marrow transplantation has also become a well-established medical treatment for many diseases, including cancer, immune deficiency and others. Cell therapy is expanding its repertoire of cell types for administration. Cell therapy treatment strategies include: isolation and transfer of specific stem cell populations, induction of mature cells to become pluripotent cells, administration of effector cells and reprogramming of mature cells into iPSCs. Administration of large numbers of effector cells has benefited cancer patients, transplant patients with unresolved infections, and patients with vision problems.

Several diseases benefit most from treatments that combine the technologies of gene and cell therapy. For example, some patients have a severe combined immunodeficiency disease (SCID) but unfortunately, do not have a suitable donor of bone marrow. Scientists have identified that patients with SCID are deficient in adenosine deaminase gene (ADA-SCID), or the common gamma chain located on the X chromosome (X-linked SCID). Several dozen patients have been treated with a combined gene and cell therapy approach. Each individuals hematopoietic stem cells were treated with a viral vector that expressed a copy of the relevant normal gene. After selection and expansion, these corrected stem cells were returned to the patients. Many patients improved and required less exogenous enzymes. However, some serious adverse events did occur and their incidence is prompting development of theoretically safer vectors and protocols. The combined approach also is pursued in several cancer therapies.

Genome editing (gene editing) has recently gained significant attention, due to the discovery and application of the clustered regularly interspaced short palindromic repeats (CRISPR) system. Actually, genome editing dates back several years and earlier generation genome editing systems are currently tested in clinical trials (such as zinc-finger nucleases). The aim of genome editing is to disrupt a disease-causing mutation or correct faulty genes at the chromosomal DNA. Genome editing can be performed in the patients own cells in vitro and edited cells can be administered to the patient (thus genome editing can be combined with cell therapy). However, it is also possible to perform genome editing in vivo by administering the genome editing agent packaged in viral and non-viral vectors.

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Gene & Cell Therapy Defined | ASGCT - American Society of ...

Gene Therapy | Microbiology

Learning Objectives

Many types of genetic engineering have yielded clear benefits with few apparent risks. Few would question, for example, the value of our now abundant supply of human insulin produced by genetically engineered bacteria. However, many emerging applications of genetic engineering are much more controversial, often because their potential benefits are pitted against significant risks, real or perceived. This is certainly the case for gene therapy, a clinical application of genetic engineering that may one day provide a cure for many diseases but is still largely an experimental approach to treatment.

Human diseases that result from genetic mutations are often difficult to treat with drugs or other traditional forms of therapy because the signs and symptoms of disease result from abnormalities in a patients genome. For example, a patient may have a genetic mutation that prevents the expression of a specific protein required for the normal function of a particular cell type. This is the case in patients with Severe Combined Immunodeficiency (SCID), a genetic disease that impairs the function of certain white blood cells essential to the immune system.

Gene therapy attempts to correct genetic abnormalities by introducing a nonmutated, functional gene into the patients genome. The nonmutated gene encodes a functional protein that the patient would otherwise be unable to produce. Viral vectors such as adenovirus are sometimes used to introduce the functional gene; part of the viral genome is removed and replaced with the desired gene (Figure1). More advanced forms of gene therapy attempt to correct the mutation at the original site in the genome, such as is the case with treatment of SCID.

Figure1. Gene therapy using an adenovirus vector can be used to treat or cure certain genetic diseases in which a patient has a defective gene. (credit: modification of work by National Institutes of Health)

So far, gene therapies have proven relatively ineffective, with the possible exceptions of treatments for cystic fibrosis and adenosine deaminase deficiency, a type of SCID. Other trials have shown the clear hazards of attempting genetic manipulation in complex multicellular organisms like humans. In some patients, the use of an adenovirus vector can trigger an unanticipated inflammatory response from the immune system, which may lead to organ failure. Moreover, because viruses can often target multiple cell types, the virus vector may infect cells not targeted for the therapy, damaging these other cells and possibly leading to illnesses such as cancer. Another potential risk is that the modified virus could revert to being infectious and cause disease in the patient. Lastly, there is a risk that the inserted gene could unintentionally inactivate another important gene in the patients genome, disrupting normal cell cycling and possibly leading to tumor formation and cancer. Because gene therapy involves so many risks, candidates for gene therapy need to be fully informed of these risks before providing informed consent to undergo the therapy.

The risks of gene therapy were realized in the 1999 case of Jesse Gelsinger, an 18-year-old patient who received gene therapy as part of a clinical trial at the University of Pennsylvania. Jesse received gene therapy for a condition called ornithine transcarbamylase (OTC) deficiency, which leads to ammonia accumulation in the blood due to deficient ammonia processing. Four days after the treatment, Jesse died after a massive immune response to the adenovirus vector.

Until that point, researchers had not really considered an immune response to the vector to be a legitimate risk, but on investigation, it appears that the researchers had some evidence suggesting that this was a possible outcome. Prior to Jesses treatment, several other human patients had suffered side effects of the treatment, and three monkeys used in a trial had died as a result of inflammation and clotting disorders. Despite this information, it appears that neither Jesse nor his family were made aware of these outcomes when they consented to the therapy. Jesses death was the first patient death due to a gene therapy treatment and resulted in the immediate halting of the clinical trial in which he was involved, the subsequent halting of all other gene therapy trials at the University of Pennsylvania, and the investigation of all other gene therapy trials in the United States. As a result, the regulation and oversight of gene therapy overall was reexamined, resulting in new regulatory protocols that are still in place today.

Presently, there is significant oversight of gene therapy clinical trials. At the federal level, three agencies regulate gene therapy in parallel: the Food and Drug Administration (FDA), the Office of Human Research Protection (OHRP), and the Recombinant DNA Advisory Committee (RAC) at the National Institutes of Health (NIH). Along with several local agencies, these federal agencies interact with the institutional review board to ensure that protocols are in place to protect patient safety during clinical trials. Compliance with these protocols is enforced mostly on the local level in cooperation with the federal agencies. Gene therapies are currently under the most extensive federal and local review compared to other types of therapies, which are more typically only under the review of the FDA. Some researchers believe that these extensive regulations actually inhibit progress in gene therapy research. In 2013, the Institute of Medicine (now the National Academy of Medicine) called upon the NIH to relax its review of gene therapy trials in most cases. However, ensuring patient safety continues to be of utmost concern.

Beyond the health risks of gene therapy, the ability to genetically modify humans poses a number of ethical issues related to the limits of such therapy. While current research is focused on gene therapy for genetic diseases, scientists might one day apply these methods to manipulate other genetic traits not perceived as desirable. This raises questions such as:

The ability to alter reproductive cells using gene therapy could also generate new ethical dilemmas. To date, the various types of gene therapies have been targeted to somatic cells, the non-reproductive cells within the body. Because somatic cell traits are not inherited, any genetic changes accomplished by somatic-cell gene therapy would not be passed on to offspring. However, should scientists successfully introduce new genes to germ cells (eggs or sperm), the resulting traits could be passed on to offspring. This approach, called germ-line gene therapy, could potentially be used to combat heritable diseases, but it could also lead to unintended consequences for future generations. Moreover, there is the question of informed consent, because those impacted by germ-line gene therapy are unborn and therefore unable to choose whether they receive the therapy. For these reasons, the U.S. government does not currently fund research projects investigating germ-line gene therapies in humans.

While there are currently no gene therapies on the market in the United States, many are in the pipeline and it is likely that some will eventually be approved. With recent advances in gene therapies targeting p53, a gene whose somatic cell mutations have been implicated in over 50% of human cancers, cancer treatments through gene therapies could become much more widespread once they reach the commercial market.

Bringing any new therapy to market poses ethical questions that pit the expected benefits against the risks. How quickly should new therapies be brought to the market? How can we ensure that new therapies have been sufficiently tested for safety and effectiveness before they are marketed to the public? The process by which new therapies are developed and approved complicates such questions, as those involved in the approval process are often under significant pressure to get a new therapy approved even in the face of significant risks.

To receive FDA approval for a new therapy, researchers must collect significant laboratory data from animal trials and submit an Investigational New Drug (IND) application to the FDAs Center for Drug Evaluation and Research (CDER). Following a 30-day waiting period during which the FDA reviews the IND, clinical trials involving human subjects may begin. If the FDA perceives a problem prior to or during the clinical trial, the FDA can order a clinical hold until any problems are addressed. During clinical trials, researchers collect and analyze data on the therapys effectiveness and safety, including any side effects observed. Once the therapy meets FDA standards for effectiveness and safety, the developers can submit a New Drug Application (NDA) that details how the therapy will be manufactured, packaged, monitored, and administered.

Because new gene therapies are frequently the result of many years (even decades) of laboratory and clinical research, they require a significant financial investment. By the time a therapy has reached the clinical trials stage, the financial stakes are high for pharmaceutical companies and their shareholders. This creates potential conflicts of interest that can sometimes affect the objective judgment of researchers, their funders, and even trial participants. The Jesse Gelsinger case (see Gene Therapy Gone Wrong above) is a classic example. Faced with a life-threatening disease and no reasonable treatments available, it is easy to see why a patient might be eager to participate in a clinical trial no matter the risks. It is also easy to see how a researcher might view the short-term risks for a small group of study participants as a small price to pay for the potential benefits of a game-changing new treatment.

Gelsingers death led to increased scrutiny of gene therapy, and subsequent negative outcomes of gene therapy have resulted in the temporary halting of clinical trials pending further investigation. For example, when children in France treated with gene therapy for SCID began to develop leukemia several years after treatment, the FDA temporarily stopped clinical trials of similar types of gene therapy occurring in the United States. Cases like these highlight the need for researchers and health professionals not only to value human well-being and patients rights over profitability, but also to maintain scientific objectivity when evaluating the risks and benefits of new therapies.

At what point can the FDA halt the development or use of gene therapy?

Answer d. The FDA halt the development or use of gene therapy at any of the points listed above.

_____________ is a common viral vector used in gene therapy for introducing a new gene into a specifically targeted cell type.

Adenovirus is a common viral vector used in gene therapy for introducing a new gene into a specifically targeted cell type.

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Gene Therapy | Microbiology

Jordan – The New York Times

The Hashemite Kingdom of Jordan is a relatively young, politically liberal Arab state in the Middle East. Once the home of ancient biblical kingdoms and outpost of several powerful foreign empires, Jordan fell under Ottoman Empire control in 1516, where it remained until the British took over governorship at the end of World War I. In 1946, Jordan won its independence, establishing a constitutional monarchy under the rule of King Abdullah I.

From 1953 until 1999, Jordan was governed by Abdullah Is grandson King Hussein, who sought to maintain a political balancing act between the many countries and territories that Jordan borders Israel, Iraq, Saudi Arabia, Syria and the West Bank. During this time, Husseins government often clashed with Jordans large Palestinian population, many of whom resented his annexation of the West Bank in the 1948 Arab-Israeli War and refusal to fight for an independent Palestinian state. Concurrently, Hussein also traded hostilities with Israel, culminating in the 1967 Six-Day War in which Jordan lost its claim to the West Bank. In 1994, Hussein signed a peace treaty with Israel, officially ending the war between the two countries.

Husseins son Abdullah II, who took the throne in 1999 after his fathers death, has pledged to work toward a more open government and to ease restrictions on public expression that were tamped down during Husseins long reign. During the 2010-12 Arab Spring, Abdullah II responded to protesters in capital of Amman and elsewhere by putting into place modest democratic reforms, bypassing the violent upheavals that toppled other rulers in neighboring countries. Abdullah IIs government, following the nations pro-Western foreign policy and international peace efforts, continues to be a key ally to the United States and, in 2013, welcomed news that Jordan was elected a non-permanent member of the United Nations Security Council. Since the start of Syrias civil war in 2011, Abdullahs government has also struggled with massive influx of Syrian refugees, who have strained Jordans already limited resources.

Learn more about Jordan. Scroll below to view our archive of articles and chronology of latest news.

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Jordan - The New York Times

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Astrophysics School of Physics

The Astrophysics group in the School of Physics spans cosmology, extragalactic astronomy, extreme objects, relativistic astrophysics, and knowledge management associated with virtual observatories and software telescopes. Our research programs, comprising theoretical, observational and computational studies, are aligned with the major international facilities such as the Murchison Widefield Array (MWA), Square-Kilometer Array (SKA), Australian Square-Kilometer Array Project (ASKAP), the Hubble space telescope, South Pole Telescope (SPT), POLARBEAR and the Simons Array, Simons Observatory and Laser Interferometer Gravitational Wave Observatory (LIGO). We are also leading Australias first space telescope program, SkyHopper.

The Astrophysics group currently hosts nodes in three ARC Centres of Excellence: OzGrav for gravitational wave astronomy, CAASTRO for all-sky astronomy, and ASTRO-3D to study the Universe in 3 dimensions.

Please contact us to learn more about the research projects and study opportunities available in our group, for undergraduate, Masters, and PhD students. More information can be found on the Study link. We invite applications for our Master of Science (MSc) and Doctorate (PhD) Physics degrees!

View of the Murchison Widefield Array. Credit: MWA

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Astrophysics School of Physics

Satoshi Nakamoto Known to CIA? FBI? Created by NSA? Search …

The request has been rejected, came response from the CIA, with the agency stating that it can neither confirm nor deny the existence of the requested documents. A tech writer petitioned the agency to see what it had on the subject of Satoshi Nakamoto, the name credited with founding Bitcoin, the worlds first decentralized cryptocurrency. There have been legendarily famous attempts to unmask the real person, only to find more paradox, more confusion, more wild theories. At least two online journalists believe a definitive answer just might be had through US intelligence agencies. The evidence borders on compelling and infuriating.

Also read: Star Trek Icon Joins Bitcoin Mining Revolution

Its not often a journalist in the financial technology genre has cause to contact the United States Central Intelligence Agency (CIA), but this week proved reason enough. Keeping normal business hours, the CIAs Office of Public Affairs, Washington, D.C. 20505 (really Vienna, VA) was evidently swamped. Three calls placed to (703) 482-0623, along with one voicemail message on the final attempt, were not returned as of publication.

Inspiration to do so came from Daniel Oberhaus, staff writer at Motherboard. In an effort to follow up on work done by bloggers and investigative journalists on the tantalizing issue of Satoshi Nakamotos identity, Mr. Oberhaus explained, While recently filing some unrelated [Freedom of Information Act] FOIA requests of my own, I figured it couldnt hurt to ask some other three-letter agencies what they know about Nakamoto.

Its a delicate game, FOIA requests. Agencies are keen to dismiss a request out of hand, citing vagueness, ill-prepared request documents, standing, and the perennial go to: national security. The fragility is in having spy agencies at all, for citizens own good is the claim, and the modern movement to make coercive government doings more transparent.

Mr. Oberhaus continued, I decided to start broad and request all internal emails containing Satoshi Nakamotos name from the FBI and CIA. Agencies generally ask for these sorts of requests to be narrowed down with information youre unlikely to have in advance, but sometimes theyll just dump a trove of emails on your plate and say good luck. Instead, the CIA emailed him a response, short and to the point, complete with obnoxious bureaucrat grammar of referring to itself in the third person. The request has been rejected, with the agency stating that it can neither confirm nor deny the existence of the requested documents, the CIA stated flatly.

The CIAs non denial-denial to Mr. Oberhaus is a classic tactic designed to be a true statement without giving away root facts. Its known as the Glomar Response, Glomar being the abbreviation for Global Marine, a company used by the agency to build a ship capable of salvaging downed Soviet-era subs back in the mid 1970s. The now famously canned statement was employed after a journalist filed a FOIA concerning the CIA ship for Soviet subs project.

And that paranoia extends to the present day. Blogger Alexander Muse, a contributor to Medium, wrote a series of posts (3) last year related to his attempt at uncovering Satoshis true identity. Mr. Muse writes about a whole host of subjects, from gourmet cooking to tech startups. His professional experience does involve tech, and he has what seems to be at least a passing interest in bitcoin. He was sucked down the rabbit hole when he learned a contact he had at the Department of Homeland Security (DHS) claimed to have inside information.

According to my source, Mr. Muse explained, the NSA was able to the use the writer invariant method of stylometry to compare Satoshis known writings with trillions of writing samples from people across the globe. By taking Satoshis texts and finding the 50 most common words, the NSA was able to break down his text into 5,000 word chunks and analyse each to find the frequency of those 50 words.This would result in a unique 50-number identifier for each chunk. The NSA then placed each of these numbers into a 50-dimensional space and flatten them into a plane using principal components analysis. The result is a fingerprint for anything written by Satoshi that could easily be compared to any other writing.

His true identity is of utmost importance to the US government precisely because, especially as the price began to rise, so many people were relying on it. The problem, before even the tech could be evaluated on its own merit, was the principal DHS worry: a foreign creator. If bitcoin can do all it claims for itself, disrupting financial markets, a country hostile to the US could quickly start that ball rolling and worse. Why go to so much trouble to identify Satoshi? he asked rhetorically. My source tells me that the Obama administration was concerned that Satoshi was an agent of Russia or Chinathat Bitcoin might be weaponized against us in the future. Knowing the source would help the administration understand their motives. As far as I can tell Satoshi hasnt violated any laws and I have no idea if the NSA determined he was an agent of Russia or China or just a Japanese crypto hacker.

Mr. Muse was ultimately unable to get just who Satoshi is. Instead he was left with the conclusion DHS does know, and that bitcoins first billionaire was probably a collection of folks. For his effort he was personally contacted by DHS and asked to submit to an interview. He did, noting that he was unable to publish just what he discussed with DHS, but he could say their contacting him was due to his Satoshis Medium posts. Ive had to stop taking phone calls or accepting voicemail messages, Mr. Muse concludes. My email is almost unusable with more than 10,000 unread messages at last count. The only way to contact me now is via textand it is likely Im going to have to change my number fairly soon. I still dont know who Satoshi Nakamoto really isbut I believe the NSA does.

Is Satoshis identity known by US intelligence agencies? Let us know in the comments.

Images via the Pixabay.

Verify and track bitcoin cash transactions on ourBCH Block Explorer, the best of its kind anywhere in the world. Also, keep up with your holdings, BCH and other coins, on our market charts atSatoshi Pulse, another original and free service from Bitcoin.com.

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Freedom in the 50 States 2015-2016 | Overall Freedom …

William P. Ruger

William P. Ruger is Vice President of Policy and Research at the Charles Koch Institute and Charles Koch Foundation. Ruger is the author of the biography Milton Friedman and a coauthor of The State of Texas: Government, Politics, and Policy. His work has been published in International Studies Quarterly, State Politics and Policy Quarterly, Armed Forces and Society, and other outlets. Ruger earned an AB from the College of William and Mary and a PhD in politics from Brandeis University. He is a veteran of the war in Afghanistan.

Jason Sorens is Lecturer in the Department of Government at Dartmouth College. His primary research interests include fiscal federalism, public policy in federal systems, secessionism, and ethnic politics. His work has been published in International Studies Quarterly, Comparative Political Studies, Journal of Peace Research, State Politics and Policy Quarterly, and other academic journals, and his book Secessionism: Identity, Interest, and Strategy was published by McGill-Queens University Press in 2012. Sorens received his BA in economics and philosophy, with honors, from Washington and Lee University and his PhD in political science from Yale University.

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Freedom in the 50 States 2015-2016 | Overall Freedom ...

Space Station Casting Studios – The Most Convenient …

Date* Aug 21stAug 22ndAug 23rdAug 24thAug 25thAug 26thAug 27thAug 28thAug 29thAug 30thAug 31stSep 1stSep 2ndSep 3rdSep 4thSep 5thSep 6thSep 7thSep 8thSep 9thSep 10thSep 11thSep 12thSep 13thSep 14thSep 15thSep 16thSep 17thSep 18thAug 21stAug 22ndAug 23rdAug 24thAug 25thAug 26thAug 27thAug 28thAug 29thAug 30thAug 31stSep 1stSep 2ndSep 3rdSep 4thSep 5thSep 6thSep 7thSep 8thSep 9thSep 10thSep 11thSep 12thSep 13thSep 14thSep 15thSep 16thSep 17thSep 18thAug 21stAug 22ndAug 23rdAug 24thAug 25thAug 26thAug 27thAug 28thAug 29thAug 30thAug 31stSep 1stSep 2ndSep 3rdSep 4thSep 5thSep 6thSep 7thSep 8thSep 9thSep 10thSep 11thSep 12thSep 13thSep 14thSep 15thSep 16thSep 17thSep 18thAug 21stAug 22ndAug 23rdAug 24thAug 25thAug 26thAug 27thAug 28thAug 29thAug 30thAug 31stSep 1stSep 2ndSep 3rdSep 4thSep 5thSep 6thSep 7thSep 8thSep 9thSep 10thSep 11thSep 12thSep 13thSep 14thSep 15thSep 16thSep 17thSep 18th

Studio* Studio 1 + 1 Parking Space ($12/hr) Studio 2 + 1 Parking Space ($17/hr) Studio 3 + 1 Parking Space ($25/hr) Studio 4 + 1 Parking Space ($30/hr) Studio 5 + 1 Parking Space ($35/hr) Studio 6 + 1 Parking Space ($38/hr) Conference Room + 1 Parking Space ($20/hr) Acting Studio + 1 Parking Space ($45/hr) Studio 1 + 1 Parking Space ($12/hr) Studio 2 + 1 Parking Space ($17/hr) Studio 3 + 1 Parking Space ($25/hr) Studio 4 + 1 Parking Space ($30/hr) Studio 5 + 1 Parking Space ($35/hr) Studio 6 + 1 Parking Space ($38/hr) Conference Room + 1 Parking Space ($20/hr) Acting Studio + 1 Parking Space ($45/hr) Studio 1 + 1 Parking Space ($12/hr) Studio 2 + 1 Parking Space ($17/hr) Studio 3 + 1 Parking Space ($25/hr) Studio 4 + 1 Parking Space ($30/hr) Studio 5 + 1 Parking Space ($35/hr) Studio 6 + 1 Parking Space ($38/hr) Conference Room + 1 Parking Space ($20/hr) Acting Studio + 1 Parking Space ($45/hr) Studio 1 + 1 Parking Space ($12/hr) Studio 2 + 1 Parking Space ($17/hr) Studio 3 + 1 Parking Space ($25/hr) Studio 4 + 1 Parking Space ($30/hr) Studio 5 + 1 Parking Space ($35/hr) Studio 6 + 1 Parking Space ($38/hr) Conference Room + 1 Parking Space ($20/hr) Acting Studio + 1 Parking Space ($45/hr)

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High seas forecast – Met Office

Issued at: 20:00 on Mon 20 Aug 2018 UTC

For the period 20:00 on Mon 20 Aug 2018 UTC to 20:00 on Tue 21 Aug 2018 UTC

At 201200UTC, low 50 north 34 west 1009 expected 57 north 14 west 1005 by 211200UTC. New low expected 61 north 40 west 1007 by same time. Low 63 north 36 west 1006 expected 65 north 16 west 1006 by that time. at 201200UTC, low 46 north 41 west 1011 expected 44 north 30 west 1017 by 211200UTC. High 57 north 14 west 1020 expected 54 north 12 east 1022 by same time. High 43 north 21 west 1026, slow moving, declining 1022 by that time. at 201200UTC, high 48 north 55 west 1026 expected 47 north 43 west 1031 by 211200UTC. New high expected eastern Greenland 1014 by same time

Sea area Show all areas Sole Shannon Rockall Bailey Faeroes Southeast Iceland East Northern Section West Northern Section East Central Section West Central Section Denmark Strait North Iceland Norwegian Basin

Forecast type High seas forecasts and storm warnings Storm warnings High seas forecasts

There are no storm warnings currently in force for the selected sea area.

Gales expected in Norwegian Basin.

Unscheduled storm warnings are broadcast via Safetynet and in bulletin WONT54 EGRR available via some internet and ftpmail outlets

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High seas forecast - Met Office