Human Behavior

Haunted by a will | – theberkshireedge.com

I recently read a 2015 novel called Orhans Inheritance by Californian Aline Ohanesian. Its such a fine first book that Ohanesian won the PEN/Bellwether Prize for Socially Engaged Fiction that year. When a Turkish grandfather in Anatolia dies and leaves the family home to a woman nobody knows, his grandson Orhan is dispatched to find her and winds up in an Armenian-run nursing home in California. Unable to set the book aside, I found myself dragged backward into 1914 and historic wounds I knew little about. After waves of massacres of Armenians from 1894 to 1896 and again in 1909, the Ottoman Turkish government murdered or removed its entire Armenian population, beginning with intellectuals and members of its liberation movement under cover of the chaos of World War I. The final estimated death toll is 1.5 million people. To this day, Turkey refuses to call it genocide. At the time, the government branded Armenians as subversives, shrugged, and said, terrible things happen in wars, as if a million and a half people were just collateral damage. It led me to a months-long investigation of how these sorts of inhumane and illegal horrors keep happening.

A Display in Armenian Library and Museum of America in Watertown. Photo courtesy Armenian Library and Museum of America

Before Americans retreated from assuming unsupervised play in the fresh air was a norm for children, we could pass bullying, factional struggle and the falling apart and reforming of friendly groups several times a day in any street or backyard. Because human behavior tends to remain recognizable in all times and places, we continue to bump into them in school yards, playgrounds, and prototypically even in our preschools as well as in offices and other adult institutions. Three thousand years ago, the Middle East was inhabited by ancestors of people continuing to struggle with each other today. Among them were Armenians, who lived mainly on the Anatolian plain in the shadow of Mount Ararat, and claim to be descendants of Noah. They had their own kingdom among the Greeks and the Persians before the birth of Christ.

In 1 A.D., Armenia came under full Roman control, and began leaning toward Western philosophical, religious and political ideas. It became the first nation to adopt Christianity as its state religion. In the fifth century, Armenians resented re-imposition of Zoroastrianism, endured a major military defeat by the Persians immortals and elephants, followed that with their own lengthy guerilla wars of independence, and finally signed the Treaty of Nvarsak in 484 A.D. to guarantee all Armenians religious freedom.

Catalog From the Metropolitan Museum of Arts Armenia: Art, Religion and Trade in the Middle Ages exhibit. Image courtesy Metropolitan Museum of Art

The Middle Ages were volatile for everyone in the region. Muslims conquered Persia, including its Armenians, and Byzantines took much of the remaining territory of Armenia, but Emperor Heraclius and the rulers who followed there were of Armenian descent. The state they administered was often called the Armenian Dynasty, and produced a Golden Age that had a great influence on the Byzantine Empire. It was overlapped by the Kingdom of Cilician Armenia. Cilicia sometimes supported Europes Crusades against Islam, and sometimes didnt. While successful enough to be courted by surrounding powers, Cilicia was internally torn between pro-Catholic and anti-Catholic factions that weakened it so that the Mamalukes of Egypt eventually destroyed it. In the 1600s, there was one mass deportation accompanied by a scorched earth policy during a war between Persians and Ottomans that left at least 150,000 Armenians dead and their towns and farms laid waste, beginning a dubious pattern of making Armenians the previously mentioned collateral damage.

This khachkar (a carved, memorial stele bearing a cross) was carved at Goshavnk in 1291 by the artist Poghos. Photo courtesy Wikipedia

An exhibition at the Metropolitan Museum of Art in New York, on view from Sept. 22, 2018, through Jan. 13, 2019, was called Armenia: Art, Religion and Trade in the Middle Ages. It featured room after room of glorious illuminated manuscripts, sculptures, maps, paintings, site photographs of distinctive Armenian architecture, and khachkars (stelae of crosses carved in stone). Although its distinct Christianity continued to face eastward, Armenia had a strong presence along the Silk Road, so Eastern and Western images tended to meld in the show. One saw the art of a confident, adaptable, cosmopolitan people.

Wherever we look, past and present, competition is a constant among human beings. Like individuals, countries want to stretch and develop, yet its not to the advantage of autocratic governments to encourage ambition and education among their people. By the 1900s, life in the dictatorial Ottoman Turkish Empire became tenuous for Armenians because generations of them had studied, traveled, joined the professions and the arts, and grown to be owners of successful businesses. By the late 1800s, they had even become ubiquitous in the government at Constantinople. Their successes embarrassed Muslim fellow citizens, compounding resentment based on the viewpoint of Islam that Armenians were infidels. Jealousy and fear of the other led to the terrible troubles that occurred in the late 19th and early 20th centuries.

Exterior of Armenian Library and Museum of America in Watertown. It holds the largest collection of Armenian artifacts and information outside of Armenia. Photo courtesy Armenian Library and Museum of America

Today, many Armenians continue to flee socio-economic problems from Russia to the Middle East, still going into diaspora all over the world. Their largest population in the U.S. is in California, but its well known that among the many Armenians in the Northeast (its estimated that there are between 50,000 and 70,000 Armenians in the Boston area alone, and New York boasts thousands more.), theres a large and prominent population in Watertown, Massachusetts. Watertown is proud of its Armenian Library and Museum of America, a handsome, four-story building that was once a bank, which houses the largest collection of Armenian artifacts outside of Armenia.

An elegant, inspirational Armenian Heritage Park was opened in downtown Boston in 2012. The inscription on the monument reads:

Abstract sculpture at the Armenian Heritage Park at the Rose Fitzgerald Kennedy Greenway in Boston commemorates the welcoming of Armenian refugees to Boston after the Armenian Genocide from 1915-23 and beyond. It is taken apart and reconfigured each spring to symbolize the dispersion and coming together of immigrants from different shores. There are 24-26 different configurations. Photo courtesy Trip Advisor

Boston and the Commonwealth of Massachusetts have offered hope and refuge for immigrants seeking to begin new lives. This park is a gift to the people of the Commonwealth and the City of Boston from the Armenian-American community of Massachusetts. This sculpture is offered in honor of the one and one half million victims of the Armenian Genocide of 1915-1923. May it stand in remembrance of all genocides that have followed, and celebrate the diversity of the communities that have re-formed in the safety of these shores.

Once again, a fascinating book has made me aware of another corner of my own ignorance; and this time it has introduced me to the centuries long backstories of friends and neighbors. The continuing inclination of people to abuse each other is confounding. Yet Im reminded of the miracle of America, however flawed, which stumbled into being a refuge from the worlds consistent cruelties not out of altruism, but by virtue of needing immigrants to fill and develop a vast land. Whats most amazing is that despite modern struggles, it persists.

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Haunted by a will | - theberkshireedge.com

Human Behavior

An Old and Contested Solution to Boost Reading Scores: Phonics – The New York Times

WASHINGTON Bit! Ayana Smith called out as she paced the alphabet rug in front of her kindergarten students at Garrison Elementary School.

Buh! Ih! Tuh! the class responded in unison, making karate chop motions as they enunciated the sound of each letter. In a 10-minute lesson, the students chopped up and correctly spelled a string of words:

Top. Tuh! Ah! Puh!

Wig. Wuh! Ih! Guh!

Ship. Shuh! Ih! Puh!

Ms. Smiths sounding-out exercises might seem like a common-sense way to teach reading. But for decades, many teachers have embraced a different approach, convinced that exposing students to the likes of Dr. Seuss and Maya Angelou is more important than drilling them on phonics.

Lagging student performance and newly relevant research, though, have prompted some educators to reconsider the ABCs of reading instruction. Their effort gained new urgency after national test scores last year showed that only a third of American students were proficient in reading, with widening gaps between good readers and bad ones.

Now members of this vocal minority, proponents of what they call the science of reading, congregate on social media and swap lesson plans intended to avoid creating curriculum casualties students who have not been effectively taught to read and who will continue to struggle into adulthood, unable to comprehend medical forms, news stories or job listings.

The bible for these educators is a body of research produced by linguists, psychologists and cognitive scientists. Their findings have pushed some states and school districts to make big changes in how teachers are trained and students are taught.

The science of reading stands in contrast to the balanced literacy theory that many teachers are exposed to in schools of education. That theory holds that students can learn to read through exposure to a wide range of books that appeal to them, without too much emphasis on technically complex texts or sounding out words.

Eye-tracking studies and brain scans now show that the opposite is true, according to many scientists. Learning to read, they say, is the work of deliberately practicing how to quickly connect the letters on the page to the sounds we hear each day.

The evidence is about as close to conclusive as research on complex human behavior can get, writes Mark Seidenberg, a cognitive neuroscientist and reading expert at the University of Wisconsin, Madison.

Phonics has gone in and out of style for decades, and the current conflict over how to teach reading is only the latest in a tug-of-war that dates to the 19th century. A major push for phonics instruction under President George W. Bush, through a federal program called Reading First, did not produce widespread achievement gains, raising questions about whether the current efforts can succeed.

Phonics boosters say they now know more about what works, and that phonics alone isnt the answer. Alongside bigger doses of sounding out, they want struggling students to grapple with more advanced books, so they wont get stuck in a cycle of low expectations and boredom. Some schools are devoting more time to social studies and science, subjects that help build vocabulary and knowledge in ways that can make students stronger readers.

States have passed laws requiring that schools use phonics-centric curriculums and screen students more aggressively for reading problems or even hold back those who struggle most. In January, Education Secretary Betsy DeVos castigated colleges of education for teaching what she described as junk science about reading.

But the education establishment is pushing back, worried that too many lessons like Ms. Smiths could be stultifying a poor substitute for a teacher reading aloud from a book of Shel Silverstein poems, or guiding children through lushly illustrated stories by Ezra Jack Keats. They blame low student performance on such factors as inexperienced teachers, school funding inequities and homes that lack books or time for parents to read to their children.

The guardians of balanced literacy acknowledge that phonics has a place. But they trust their own classroom experience over brain scans or laboratory experiments, and say they have seen many children overcome reading problems without sound-it-out drills. They value children picking books that interest them and worry that pushing students into harder texts could turn them off reading entirely.

Karen K. Wixson, an author of a recent report warning that too much phonics can harm children, called the new push incredibly, scarily nave.

In Ms. Smiths classroom in Washington, Madisyn Hall-Jones, 5, demonstrated her progress by reading aloud a short story about picking apples that she had written and illustrated herself.

Its not rote, the schools principal, Brigham Kiplinger, said of the phonics-driven curriculum. Its joyful.

Washington is one of only two jurisdictions, along with Mississippi, to increase average reading scores on National Assessment of Educational Progress tests between 2017 and 2019. Both did so despite high-poverty student populations, and both are requiring more phonics.

For us, this is social justice work, Mr. Kiplinger said. The majority of students at Garrison Elementary come from low-income families. If parents express concerns about the new curriculum, he invites them to visit a classroom like Ms. Smiths and see the difference.

Parents in suburban St. Louis are looking for similar results. More than a third of kindergarten to third-grade students in the highly regarded Lindbergh school district tested as at risk for dyslexia last spring, after Missouri instituted mandatory screening. Angry district residents sent an open letter to the school board in November, demanding that the district embrace the science of reading.

The district said it had added a new phonics sequence in the early elementary grades and retrained some teachers. But it stands by its broader balanced literacy approach, which it said gives teachers the autonomy to tailor instruction to students at all levels.

Thats not enough for parents like Diane Dragan. An attorney who has three children with dyslexia, Ms. Dragan noted that well-off parents in her area regularly pay thousands of dollars to have their children taught intensive phonics at private tutoring centers.

The irony to me is that the public-school teacher who teaches balanced literacy during the day moonlights to do science-based tutoring for kids who fail to learn to read, Ms. Dragan said.

In Mississippi, all prospective elementary schoolteachers are now required to pass a test in the foundations of reading, including phonics. The state has also dispatched literacy coaches to struggling schools.

More controversially, it passed a law in 2013 requiring third graders to be held back if they score poorly on an end-of-year reading exam; last year, about 10 percent of them were retained, for reading difficulties or other reasons.

Some reading experts have called Mississippis recent gains into question, arguing that by retaining so many of the lowest-scoring third graders, the state had stigmatized students and manufactured a higher-performing pool of test takers. But Shannon D. Whitehead, the principal of McNeal Elementary School in Canton, Miss., supported the states decision to get tough.

Her school put in place a phonics sequence that continues through fifth grade, and started assigning more challenging literature, including Langston Hughes poems. It hosts early-morning, after-school and Saturday tutoring sessions for students at risk of failing state tests. Scores have improved modestly.

As painful as it can be to tell a child they have to repeat a year, Dr. Whitehead said, in order for us to ensure that our students are able to compete globally, we have to have an accountability system.

One of the most popular reading curriculums in the country used in about 20 percent of schools, including the Lindbergh district near St. Louis was developed by Lucy Calkins, a professor at Teachers College, Columbia University. She is widely admired for her emphasis on helping students develop a love of reading and writing.

But her curriculum, which follows the balanced literacy model, has come under increasing fire from critics who say it devotes too little time to phonics practice and gives teachers and students too much choice over what books to read, allowing them to avoid more challenging texts. Earlier this month, the public schools in Oakland, Calif., told staff members that the district would move away from Professor Calkinss materials after the citys N.A.A.C.P. chapter and parent activists demanded the use of research-proven strategies.

In an interview, Professor Calkins decried what she called a feeling of animosity and mistrust between the camps in the reading wars. She acknowledged that many teachers needed more training on how to teach phonics effectively, and said she was working with schools in her network to provide that.

But she pushed back against a key argument of many phonics activists that there is no downside to all of the children in a classroom getting the type of repetitive practice in letter-sound relationships that struggling readers need.

Theres not a chance were going to want to hold an entire class to the pace of the 5 percent that have dyslexia, she said. Other children need opportunities for comprehension, for writing instruction and for analytic thinking.

Wiley Blevins, a phonics expert who considers himself to be in the center of the reading wars, acknowledged that phonics instruction is often implemented badly. Texts created to help students practice sound-letter combinations can be boring and even nonsensical, he said.

Ideally, students in early elementary school would spend about half of their reading and writing time on phonics, he said, using quality materials. If this happened consistently, by third grade, most students would not need explicit phonics anymore.

Even some leading researchers in the science of reading, including Professor Seidenberg, acknowledge that studies do not yet point toward specific curriculum materials that will be most effective at teaching phonics.

The science that you need to know it is good, he said. The science on how to teach it effectively is not.

Ms. Smith, the Washington kindergarten teacher, has embraced her schools new focus on phonics, which she said had engaged both low-achieving and high-achieving students.

She reads to her class each day from beloved childrens literature, like the Elephant and Piggie series by Mo Willems. But it is the simple phonics texts, she said, that have done the most to build the students confidence, because over time, they are able to accurately read them aloud to their classmates.

They will get to the end of the sentence and see a period, she said, and their face will light up.

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An Old and Contested Solution to Boost Reading Scores: Phonics - The New York Times

Human Behavior

Study shows how a tiny and strange marine animal produces unlimited eggs and sperm over its lifetime – National Human Genome Research Institute

A little-known ocean-dwelling creature most commonly found growing on dead hermit crab shells may sound like an unlikely study subject for researchers, but this animal has a rare ability it can make eggs and sperm for the duration of its lifetime. This animal, called Hydractinia, does so because it produces germ cells, which are precursors to eggs and sperm, nonstop throughout its life. Studying this unique ability could provide insight into the development of human reproductive system and the formation of reproductive-based conditions and diseases in humans.

By sequencing and studying the genomes of simpler organisms that are easier to manipulate in the lab, we have been able to tease out important insights regarding the biology underlying germ cell fate determination knowledge that may ultimately help us better understand the processes underlying reproductive disorders in humans, Dr. Andy Baxevanis, director of the National Human Genome Research Institutes (NHGRI) Computational Genomics Unit and co-author of the paper. NHGRI is part of the National Institutes of Health.

In a study published in the journal Science, collaborators at NHGRI, the National University of Ireland, Galway, and the Whitney Laboratory for Marine Bioscience at the University of Florida, Augustine, reported that activation of the gene Tfap2 in adult stem cells in Hydractinia can turn those cells into germ cells in a cycle that can repeat endlessly.

In comparison, humans and most other mammals generate a specific number of germ cells only once in their lifetime. Therefore, for such species, eggs and sperm from the predetermined number of germ cells may be formed over a long period of time, but their amount is restricted. An international team of researchers have been studying Hydractinias genome to understand how it comes by this special reproductive ability.

Hydractinia lives in colonies and is closely related to jellyfish and corals. Although Hydractinia is dissimilar to humans physiologically, its genome contains a surprisingly large number of genes that are like human disease genes, making it a useful animal model for studying questions related to human biology and health.

Hydractinia colonies possess feeding polyps and sexual polyps as a part of their anatomy. The specialized sexual polyps produce eggs and sperm, making them functionally similar to gonads in species like humans.

During human embryonic development, a small pool of germ cells that will eventually become gametes is set aside, and all sperm or eggs that humans produce during their lives are the descendants of those original few germ cells. Loss of these germ cells for any reason results in sterility, as humans do not have the ability to replenish their original pool of germ cells.

In a separate study, Dr. Baxevanis at NHGRI and Dr. Christine Schnitzler at the Whitney Lab have completed the first-ever sequencing of the Hydractinia genome. In this study, researchers used this information to scrutinize the organisms genome for clues as to why there are such marked differences in reproductive capacity between one of our most distant animal relatives and ourselves.

Having this kind of high-quality, whole-genome sequence data in hand allowed us to quickly narrow down the search for the specific gene or genes that tell Hydractinias stem cells to become germ cells, said Dr. Baxevanis.

The researchers compared the behavior of genes in the feeding and sexual structures of Hydractinia. They found that the Tfap2 gene was much more active in the sexual polyps than in the feeding polyps in both males and females. This was a clue that the gene might be important in generating germ cells.

The scientists next confirmed that Tfap2 was indeed the switch that controls the process of perpetual germ cell production. The researchers used the CRISPR-Cas9 gene-editing technique to remove Tfap2 from Hydractinia and measured the resulting effects on germ cell production. They found that removing Tfap2 from Hydractinia stops germ cells from forming, bolstering the theory that Tfap2 controls the process.

The researchers also wanted to know if Tfap2 was influencing specific cells to turn into germ cells. Their analysis revealed that Tfap2 only causes adult stem cells in Hydractinia to turn into germ cells.

Interestingly, the Tfap2 gene also regulates germ cell production in humans, in addition to its involvement in myriad other processes. However, in humans, the germ cells are separated from non-germ cells early in development. Still, despite the vast evolutionary distance between Hydractinia and humans, both share a key gene that changes stem cells into germ cells.

This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose and treat disease. Science is an unpredictable and incremental process each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.

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Study shows how a tiny and strange marine animal produces unlimited eggs and sperm over its lifetime - National Human Genome Research Institute

Genetics

Parkinson’s driven by inflammation, genetics and the environment – UAB News

Written by Jesse Saffron, Ph.D., National Institute of Environmental Health Sciences. Used by permission

The reality is that today, we still dont have a treatment that slows or alters the progression ofParkinsons disease, saidDavid Standaert, M.D., Ph.D.

In 1817, James Parkinson published An Essay on the Shaking Palsy, describing the disease that now bears his surname. The British surgeons proposed treatment bloodletting proved ineffective, and the intervening two centuries led to no breakthroughs for patients.

The reality is that today, we still dont have a treatment that slows or alters the progression ofParkinsons disease, saidDavid Standaert, M.D., Ph.D., during a Jan. 8 talk at the National Institute of Environmental Health Sciences. He is chair of the Department of Neurology at the University of Alabama at Birmingham. We can help patients function better, but were not changing the underlying nature of the disease.

Parkinsons disease is complex, involvinggenetic and environmental factors, and their interaction.Guohong Cui, M.D., Ph.D., head of the NIEHS In Vivo Neurobiology Group, invited Standaert to discuss the role immunity plays in the disorder. Both researchers seek to discover ways to slow advancement of the condition and make it less severe.

Dr. Standaert is an established researcher in the Parkinsons field, which is one of the major areas my lab works in, Cui said. His team examines how pesticides interact with genetic factors associated with the disease and ways to slow dopamine loss, which is a hallmark of the disorder.

At UAB, Standaert directs the Morris K. Udall Center of Excellence in Parkinsons Disease Research, one of eight such centers funded by theNational Institute of Neurological Disorders and Stroke. One of his research questions is whether immune system responses to a protein called alpha-synuclein trigger neurodegeneration.

Alpha-synuclein is a cornerstone of research in Parkinsons disease, Standaert told the audience. It is a small protein present in high levels in neurons throughout the brain. It participates in virtually every form of the disease, whether through mutation, overexpression or aggregation, which is probably the most common mechanism.

Abnormal forms of alpha-synuclein may activate immune cells in the brain, leading to inflammation that drives progression of the disorder.

For many years, it was said that this is a degenerative disease and cells are dying, so, of course, theres inflammation, he said. I think in the last few years, weve turned this around and realized that the inflammation may come first, as part of a process that leads to degeneration.

When mutated, the LRRK2 protein can worsen problems caused by alpha-synuclein. It is one of the most common genetic causes of Parkinsons. In our clinic, about 2 to 3 percent of patients have LRRK2 mutations, he noted. Those mutations may cause Parkinsons by cranking up sensitivity of the immune system they may increase the magnitude of the response to alpha-synuclein.

But other factors bear consideration. To study the mechanisms responsible for Parkinsons disease, there is a need for model systems that replicate the effects of environmental toxins, Standaert said. He highlighted research by NIEHS grantee Briana De Miranda, Ph.D., of the University of Pittsburgh. She studies, among other things, how organic solvents may boost susceptibility to Parkinsons disease in individuals with LRRK2 mutations.

Standaert says the fact that inflammation may cause the disorder to advance more than it otherwise would means that anti-inflammatory drugs could hold promise. We have immunologic treatments for a lot of other diseases, such as inflammatory bowel disease, psoriasis and multiple sclerosis, Standaert said in an interview. Could we use one of those or something similar in Parkinsons disease to slow its progression?

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Parkinson's driven by inflammation, genetics and the environment - UAB News

Genetics

Meet the British genetics boss on the frontline of the coronavirus epidemic – Telegraph.co.uk

Zika, Ebola, Yellow Fever, H1N1 Swine Flu and now coronavirus: for one rapidly growing British company, outbreaks of the worlds deadliest pathogens represent an extraordinary call to arms.

While the rest of us cower and don surgical masks, Oxford Nanopore dispatches its handheld devices into the epicentre of epidemics, helping decode the DNA of deadly viruses and track their mutation and spread.

Chinas Centre for Disease Control and Prevention, in Beijing, is the latest to deploy Nanopore technologyputting 200 of the companys Minion devices, which are the size and shape of old clamshell mobile telephones, on the frontline of efforts to roll back the coronavirus.

The advantage of the Minion over gene sequencing rivals, says Oxford Nanopores CEO Gordon Sanghera, is that they are both portable and rapid. We are the only platform in the world that can give you live real-time genomic information, he says. The ability to look at it [the virus genome] in real time and contain or control it, all of that will evolve from data generation that no-one else can do.

The deployment of Minion devices will allow global health authorities to track the virus in unprecedented ways, says Nick Loman, professor of Microbial Genomics and Bioinformatics at the University of Birmingham: You can see the evolution of the virus, how its spreading, the rate of growth. With Nanopore you have the ability to get instrumentation in lots of different places, with lots of different groups sharing virus genome sequences.

Such information, when collated, could reveal infections with DNA sequences that are very similar, for example, allowing them to be traced back to so-called super-spreaders. Detailed genomic information could also help British authorities work out whether local cases of the disease have been picked up in Asia, or have been passed from person to person in the UK.

For that we need to see as much genomic data published as possible, says Loman. You want a representative sample from genomes from each site of infection, across time ,and published on the internet. Nanopores devices, he says, facilitate that because they are portable, rapid and cheap.

The coronavirus represents a particularly dramatic use case of the DNA decoding devices manufactured by Nanopore a spinout from Oxford University whose latest funding round of 109m six weeks ago valued it at 1.6bn.

A quarter of that raise was primary investment, made directly to the company. But three-quarters was secondary investment, with existing shareholders selling their stakes to new investors, with the price at 58 a share. Those sales included stakes in the company held by Neil Woodford the fund manager whose suspended Equity Income Fund and Woodford Patient Capital Trust (WPCT) once owned a combined 12.4pcof Oxford Nanopore.

WPCT is now managed by Schroders as the UK Public Private Trust, where Oxford Nanopore, at almost 15pc, is one of the top holdings.

Its unfortunate the Woodford Fund is where it is, says Sanghera. From a personal perspective, it's distressing for me because Neil is a friend of mine, but from a business perspective we've often refreshed our shareholder base in the 15 years weve been going. It is distressing when its such a fantastic and enthusiastic shareholder who is no longer available to us, but thats business, we have a plan and a strategy and we're executing on that.

That strategy includes the opening last year of a factory to produce various devices which, as well as the portable, small capacity Minion, include a bigger capacity device known as the Promethion. The factory will eventually be largely automated, says Sanghera, with robotic handling and silent running which will have a direct impact on efficiencies and thus on yields and margins.

The factory, he says, will allow the company to produce enough devices to hit one billion dollars in revenues in sales in five years time. Its 2018 revenues were $43m (33m).

It is still not breaking even. We anticipate break even in the next couple of years, says Sanghera. But the balance is growth versus revenue. We could reduce growth and hit profitability in 2021, but thats not necessarilythe right thing to do. The right thing for the business to do will be rapid expansion into new markets new territories, new projects.

Somewhere in the same timeline, perhaps one to three years away, is a stock market floatation which, he says, will value the company at anywhere between three and 10 billion dollars. The genomics space is very hot, he says.

To achieve that valuation, though, Sanghera thinks that the company will have to clear several hurdles. It will have to carve out a reputation for delivering steady revenues (DNA decoding, he says, makes Oxford Nanopore just too complex as a tech story). Revenue is why the new factory, and regular sales of its kit, is so important.

He also wants to demonstrate a couple of end-user applications he plucks shrimp farming from the air as an example where DNA sequencing can help productivity in previously unthought of ways. The third hurdle before flotation, is to take some market share from BGI and Illumina.

Those two companies Chinese and American respectively are Oxford Nanopores major competitors in the DNA decoding world. And while Nanopore has made its name with the handheld Minion device pictured below, Promethion is helping it edge into rival territory, dominated by Illumina, involving mass sequencing of hundreds of thousands of people in a general population.

On December 10th, just weeks beforeChina reported the coronavirus to the World Health Organisation, Oxford Nanopore signed a multi-million pound deal (it refuses to reveal the exact sum) with the United Arab Emirates, to sequence the genome of up to a million of its residents.

Such pop-gen (population-genetic) studies such as the UKs 100,000 genomes project allow mass DNA analysis across entire countries to help identify rare diseases, and initiate the delivery of personalised treatments.

Its the first time we competed head to head with Illumina and it's the first pop-gen order thats gone to us, says Sanghera. Thats a significant milestone for us.

The competition with Illumina is particularly intense because the two companies use different methods to decode DNA. Nanopore technology uses electric currents to detect the four different chemical bases on a strand of DNA as it is fed through a miniscule hole. Illumina marks the same bases with dyes then uses a machine to read the dye markers. Illuminas advocates say its technology is more accurate. Nanopore says it can read longer strands of DNA.

We believe we can compete on accuracy, says Sanghera, adding that the UAE dataset will put that debate to bed. In the hands of our customers the accuracy question doesnt really come up.

Which is just as well because currently their most urgent customers are the staff of Chinas CDC. When we launched the Minion, the idea was that when you have an outbreak, it will be possible to do real time genomic surveillance. That is fundamentally game changing, says Sanghera.

Its humbling that something we started 15 years ago is actually useful. We spent a lot of time wondering if anyone was going to buy it. Does anybody care? Are we deluded? I want the Coronavirus to go away. If theres any way we can help with that, good.

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Meet the British genetics boss on the frontline of the coronavirus epidemic - Telegraph.co.uk

Genetics

How to turn racists genetic arguments against them – The Irish Times

It was funny once. The perfectly square bit of dirt on the window. The shocked reactions of Craggy Islands Chinese community. The local farmer who doesnt have much time to be a racist, because he just likes to have a cup of tea in the evening. The feckin Greeks

Dermot Morgans finest televisual moment that evocation of Nazi speech-making in front of the greatest window in comedy is perhaps a little less funny now that prime minsters or presidents of Hungary, Turkey, the United Kingdom and the United States are happy and comfortable to spout racist statements, and not merely get away with it but be applauded for it by their supporters.

How have we reached this point? Its the very question asked by geneticist and broadcaster Dr Adam Rutherford. Hes the Rutherford in the BBCs popular radio programme The Curious Cases of Rutherford and Fry, in which he and Dr Hannah Fry try to solve listeners scientific queries.

In the case of the resurgence of publicly acceptable racism, Rutherford decided that a radio show was insufficient and that a book would be needed. How to Argue with a Racist is published this week, and Rutherford will be delivering a lecture on the subject during the Northern Ireland Science Festival.

So, how did we get back here? I find myself asking the same question, Rutherford says. I find myself in lectures thinking how strange it is that Im now talking about this, because these are mostly questions that were parked, in my field genetics years ago. Maybe decades ago. And we keep discovering interesting things about evolution and population differences, and migration, and so on, but the question of how race as a concept relates to biological diversity, that ended a while back.

Having these conversations in the academy is one thing, but as someone who tries to communicate science, to talk about it, as a broadcaster and as a writer, I found I was suddenly having very different conversations. Conversations about race, when we were talking about ancestry In some ways, science has failed to convey to the public what is correct, and so I want to equip people with what current scientific thinking is, so that when the question comes up, they have the tools to respond. To say, Yes, there hasnt been a white man in the Olympic 100m final since 1980, but no thats not because of any lack of African-American ancestry.

Its precisely that sort of casual, inauspicious racism that Rutherford looks to quash with his book. The idea that Olympic athletes with African heritage are somehow better because their genes are imbued with extra strength is rubbish, he says. For a kick-off, using athletes as a test sample is a daft idea because anyone with the sort of genetic gifts that allow them to perform at the highest level is a poor sample of what a broader population is like. Beyond that, theres a simpler rebuttal if those with African heritage are inherently genetically better at running very quickly than others, then where are the Olympic 100m champions from South America, Europe or elsewhere with populations that can trace heritage to Africa?

Besides, tracing your genetic lineage in that manner, looking for secrets and answers to why you are so underprivileged compared with others, is a nonsense, says Rutherford. I do think that part of the change in culture which means I kind of had to write this book is to do with the rise of nationalism and the more open discussion of race. Certainly there are more open discussions of public racism than at any point I can remember in my lifetime. There are other factors, though, such as the rise in genetic ancestry testing kits. Now, theyre not pernicious in themselves, but I argue that they have fostered a misunderstanding of what genetics means, and specifically in the form of a sort of reversion to essentialism. So a notion that were determined by our genes and our ancestry, which as a geneticist I just dont think are scientifically valid nor verifiable to the extent that people adopt them.

So, when you take one of these tests and it comes back saying that youre 10 per cent Swedish, or 15 per cent Irish, these are very broad strokes, that are not scientifically meaningless, but they are of only trivial relevance. But people attribute very great significance to them. For instance, I sometimes talk about the fact that, genetically speaking, there is no such coherent ancestral group as Celts. But try telling that to an audience in Glasgow and see what happens.

Over in Ireland youve got some of the best genetic genealogists in the world, people like Dan Bradley [head of the school of genetics at Trinity College Dublin] who has been tracking the story of the Irish for years, and thats really important work, its important to understand the movement of peoples and the migration of peoples. But theyre always complex. Ancestry is a matted web, not linear family trees.

For example, I have a friend who told me that hes descended from Niall of the Nine Hostages, and they can trace their ancestry back to him. Well, theres two things about that. One, no one is actually really sure if Niall of the Nine Hostages existed, which is problematic for a starter.

The second thing, though, is that if he did exist, he lived in the fourth or fifth century, and thats a date which comes before the isopoint, which is the time at which everyone in Europe is descended from everyone else. So if Niall did exist, and if my friend Bill is directly descended from him, then so too am I. And so are you. And so is a guy in southern Italy, and in Turkey, and literally everyone else in Europe. So if you can attach some kind of tribal identity to that, that idea that youre descended from some fifth-century Irish king, well everyone else is too.

This is a relatively recent revelation. One that has the power to stun those who claim kinship with any royal lineage, or who might have notions of racial purity. The simple, genetic, fact is that your family tree isnt a neat family tree at all. Its more like an overgrown shrub, especially the farther back you go. And because everyone elses is, too, it means that the family shrubs intertwine and merge until, once you go back a surprisingly few generations, were all related to everyone else.

Thus the late actor Christopher Lees claim to be directly descended from Charlemagne is accurate, but also meaningless. Not everyone can prove it using family trees. Christopher Lee could, because he was the descendent of an Italian contessa, so they had the paper trail of her family going back. The whole Danny Dyer story, which showed that he was a direct descendent of Edward III, they were able to paper-trail that too, and very few people can actually do that, but I calculated out a mathematical proof that anyone with long-standing English heritage is also 100 per cent descended from Edward III.

At which point I suggest that we should use our now undisputed and mathematically proven royal lineage to, shall we say, take back control, but Rutherford politely declines my invitation to insurrection. The point is, of course, more profound than working out where you stand in line for a throne. Its the fact that every white supremacist has, if you trace their genetic code back, African ancestry. Every Nazi has Jewish heritage. Every Briton is a mish-mash of European bloodlines.

The problem, of course, is that while all of this science is correct and provable, its also useless in the face of racism. As someone once said: You can argue with a racist; you can argue with a Labrador retriever, too, for all the good it will do you.

Rutherford agrees, but says theres a more important battle, on two fronts, to be fought. Part of the book discusses actual neo-Nazis and white supremacists, because they are obsessed with genetics. And their misunderstanding of genetics makes them think that they can prove some sort of racial purity, which is a nonsense. Arguing with those guys using science is a demonstration of the old Jonathan Swift maxim that you cant reason someone out of a position that they didnt reason themselves into, he says.

Who Im really interested in reaching, though, are those who arent racists, and who dont think like that. But because of relying on stereotypes, or myths, or the cultural sphere that says that race is real, or that some factors are biologically encoded and that those factors segregate by race, I want those discussions to be the ones that are informed by science. Because those people arent fundamentally racist, so when youre armed with facts, and youre armed with a knowledge of history, then I think that is your best route to change. Science is a powerful ally, its the best ally we have, I think. But whats the Bob Dylan line? I know my song well before I start singing.

One of the ideas I explore is that scientists need to get more involved. Its no longer good enough to simply say: Heres the data and let society decide. Racists have no such compunctions, and will use every tool at their disposal to spread their message. So if we. as scientists, sit back and say, Hey, its just the data and I dont know what the political ramifications are, thats for others to discuss, then were volunteering ourselves to defeat, and for our voices to be silenced in favour of populist, emotive arguments, and thats the political landscape in which we now live.

Racism isnt wrong because its drawn from and based on a misunderstanding, or specious scientific ideas. Racism is wrong because its an affront to basic human dignity. What Im saying is, if you want to be a racist, fine, fill your boots, go ahead, but you cant have my scientific tools, my weapons, to justify your position.

How to Argue with a Racist by Adam Rutherford is published by Orion. Northern Ireland Science Festival runs February 13th-23rd. nisciencefestival.com

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How to turn racists genetic arguments against them - The Irish Times

Genetics

Remote collaborative research drives new insights on a rare genetic disorder linked to schizophrenia – USC News

The key to a better understanding of schizophrenia may exist in a genetic disorder so rare that researchers havent been able to conduct an adequate study until now.

The genetic disorder 22q11.2 deletion syndrome (22q11DS), caused by a small segment of missing DNA on chromosome 22, is the strongest known genetic risk factor for developing schizophrenia. About a quarter of people with the disorder develop schizophrenia or experience psychotic symptoms, so studying it provides a unique window into how such psychiatric problems develop over time.

But theres one problem: Only about one in 4,000 people have it. Even a large city like Los Angeles may hold just a few hundred people with the condition.

Fortunately, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) consortium, led by Paul M. Thompson, PhD, associate director of the Mark and Mary Stevens Neuroimaging and Informatics Institute (INI) at the Keck School of Medicine of USC, has spent the past 10 years uniting researchers around the world to pool data and insights on rare diseases. Now, ENIGMA has launched a new working group to study 22q11DS using data collected by researchers across the U.S., Canada, Europe, Australia and South America.

Weve pieced together many of the major research centers studying 22q11DS around the world to create the largest-ever neuroimaging study of the disorder, said Christopher Ching, PhD, a postdoctoral researcher at the INI and lead author of the working groups latest study.

Thompson, Ching and the ENIGMA 22q11.2 Deletion Syndrome Working Group published their results in the American Journal of Psychiatry on Feb. 12.

Correlations become clear with advanced neuroimaging

To get a clear picture of the brain abnormalities associated with schizophrenia in individuals with 22q11DS, the studys authors examined magnetic resonance imaging (MRI) scans from 533 people with the disorder and 330 healthy control subjects. Using advanced analytic techniques developed at the USC INI, the authors measured and mapped structural differences between the brains of the two groups.

Overall, individuals with 22q11DS had significantly lower brain volumes, as well as lower volumes in specific structures including the thalamus, hippocampus and amygdala, compared with the control group. They also had higher volumes in several brain structures. The magnitude of these abnormalities, especially in those 22q11DS individuals that had psychosis, was larger than is typical in many other common psychiatric conditions.

Notably, the brain changes seen in people with 22q11DS and psychosis significantly overlapped with the brain changes observed in the largest-ever neuroimaging studies of schizophrenia and other serious mental illnesses including bipolar disorder, major depression and obsessive-compulsive disorder.

Thats important because these overlapping brain signatures add evidence to support 22q11DS as a good model for understanding schizophrenia in the wider population, Ching said. And thanks to these large ENIGMA studies, we now have a way to directly compare standardized brain markers across major psychiatric illnesses on an unprecedented scale.

This powerful connection means that studying 22q11DS may provide a clear path toward finding a biomarker, or a reliable biological indicator, of schizophrenia. Because of the large sample size used in the analysis, the researchers also found that larger segments of missing DNA in 22q11DS are linked to more extensive brain abnormalities.

Next steps in research

Looking forward, the studys authors aim to explore the similarities between brain abnormalities in individuals with 22q11DS and those with schizophrenia, bipolar disorder, major depressive disorder and obsessive-compulsive disorder, drawing on data from other ENIGMA groups to better understand whether various psychiatric illnesses may share common origins and affect similar or distinct brain circuits.

The group also plans to use these new analytic tools to explore 22q11DS in animal models, where they can conduct more controlled experiments to better understand the effects of the missing DNA segments across development.

We can even experimentally manipulate specific genes within the locus to better understand how and when they are affecting the development of these brain structures, said Carrie Bearden, PhD, professor of psychiatry and biobehavioral science and psychology at the University of California, Los Angeles, chair of the working group and corresponding author of the study.

Zara Greenbaum

The study was funded by NIHgrantU54EB020403 from the Big Data to Knowledge (BD2K) Program, NIMH Grant RO1 MH085953, and NIA T32AG058507.

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Remote collaborative research drives new insights on a rare genetic disorder linked to schizophrenia - USC News

Genetics

Has Signal Genetics (MGEN) Outpaced Other Medical Stocks This Year? – Yahoo Finance

Investors focused on the Medical space have likely heard of Signal Genetics (MGEN), but is the stock performing well in comparison to the rest of its sector peers? A quick glance at the company's year-to-date performance in comparison to the rest of the Medical sector should help us answer this question.

Signal Genetics is one of 901 companies in the Medical group. The Medical group currently sits at #1 within the Zacks Sector Rank. The Zacks Sector Rank gauges the strength of our 16 individual sector groups by measuring the average Zacks Rank of the individual stocks within the groups.

The Zacks Rank is a proven model that highlights a variety of stocks with the right characteristics to outperform the market over the next one to three months. The system emphasizes earnings estimate revisions and favors companies with improving earnings outlooks. MGEN is currently sporting a Zacks Rank of #2 (Buy).

Within the past quarter, the Zacks Consensus Estimate for MGEN's full-year earnings has moved 26.19% higher. This shows that analyst sentiment has improved and the company's earnings outlook is stronger.

Based on the latest available data, MGEN has gained about 56.28% so far this year. Meanwhile, stocks in the Medical group have gained about 2.09% on average. This shows that Signal Genetics is outperforming its peers so far this year.

To break things down more, MGEN belongs to the Medical - Biomedical and Genetics industry, a group that includes 385 individual companies and currently sits at #73 in the Zacks Industry Rank. This group has gained an average of 0.20% so far this year, so MGEN is performing better in this area.

Investors with an interest in Medical stocks should continue to track MGEN. The stock will be looking to continue its solid performance.

Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free reportTo read this article on Zacks.com click here.Zacks Investment Research

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Has Signal Genetics (MGEN) Outpaced Other Medical Stocks This Year? - Yahoo Finance

Genetics

Seattle Genetics gets another drug close to the finish line – Endpoints News

Seattle Genetics productive streak continues.

After closing out 2019 with its second approved drug a potential blockbuster in Padcev the ADC biotech then presented data showing that Padcev combined with Keytruda may be more effective than Keytruda alone for bladder cancer patients.

And on Thursday, the company announced another drug has been accepted for FDA review and has been given priority status. The drug, tucatinib, is being assessed as part of a combination treatment for locally advanced or metastatic HER2-positive breast cancer. A PDUFA date has been set for August 20, 2020.

The application to market the drug is based on positive progression-free survival and overall survival data from a Phase II trial unveiled in December: Patients given tucatinib lived about 2 months longer without their cancer returning.

Unlike the rest of Seattles pipeline, tucatinib is not anADC, or an antibody-drug conjugate. Once a trendy idea, the concept fell mostly out of the news for years before Seattle Genetics recent success revived interest. The technology essentially uses an antibody as a kind of homing system to guide a cytotoxic drug to the tumor site.

Rather, the drug is a selective tyrosine kinase inhibitor for HER2. It did not come from in-house, but was originally developed by Array BioPharma, who licensed it to Cascadian Therapeutics. Seattle Genetics bought Cascadian for $614 million in 2018.

In addition to tucatinib and Padcev, known chemically as enfortumab vedotin, Seattle Genetics also has a Phase II ADC in collaboration with Genmab and a Phase II ADC in collaboration with Takeda.

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Seattle Genetics gets another drug close to the finish line - Endpoints News

Anatomy

‘Birds of Prey’ | Anatomy of a Scene – The New York Times

Hi, Im Cathy Yan, the director of Birds of Prey. So were near the end of the movie. And this is the culminating, the final fight scene between the women and the gangs that Roman Sionis, played by Ewan McGregor, sends in to the funhouse, which is called the Booby Trap. Well, originally, it wasnt a funhouse, actually. I believe, originally, it was a hotel. And they were supposed to fight their way down. But then, when I got together with our amazing production designer, KK Barrett, and our DP, Matthew Libatique, we kind of thought, wouldnt it be more interesting to convey a location that felt like Harley Quinns mind on acid? Our actresses, theyre actually doing the majority of the stunts themselves. That was four to five months of brutal training. When we were in prep, the actors were training pretty much every day with our stunt team. Come on! Margot learned to roller skate for this movie because she ends up roller skating in a good portion of the movie. She learned to roller skate on a bank track for the derby scene. And then, obviously, shes roller skating here. And for this moment, she is actually just roller skating. And she was so she became so good that she was able to stop herself, which is actually the most difficult thing to do, while on a rotating carousel, which is infinitely harder than when youre not on a rotating carousel. What was another big challenge that we only sort of realized on the day, too, was that because the background was so different, for continuity, whenever we started a take, we had to make sure that we started and ended at the same point. So the carousel became a sort of clock. And we had a number for each of the hands. And then each hand had to directly correlate with a point outside in the funhouse so that we were able to actually match up the backgrounds. If we didnt do that, then it would have been a complete nightmare. [MUSIC PLAYING] [SHOUTS] Ah. Wait.

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'Birds of Prey' | Anatomy of a Scene - The New York Times