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  • richardmitnick 7:12 am on February 8, 2016 Permalink | Reply
    Tags: , ,   

    From New Scientist: “How Do You Find an Exoplanet? An insider account gives top tips” 

    NewScientist

    New Scientist

    3 February 2016
    Lewis Dartnell

    ESO VLT
    Soon, Chile’s giant telescope will search for Earth-like exoplanets ESO/S. Bruner

    ASTRONOMY has changed a lot in the days since you had to go and sit for hours with your eyeball at the focal point of a 5-metre-diameter telescope atop a mountain.

    This is quickly evident in How Do You Find an Exoplanet? by John Asher Johnson, formerly a leading researcher at NASA. In 2012, his team discovered three exoplanets orbiting a red dwarf, including the smallest found to date. Now a professor at Harvard University, Johnson’s enthusiasm for his vibrant field is palpable in this valuable, concise guide for amateur astronomers and anyone else not afraid of a few technicalities.

    Today, telescopes are controlled from a computer in a heated room. We have also lived through a revolution in our understanding of the cosmos. At the time of writing, we have discovered 2042 worlds orbiting other stars. This is one of the hottest areas in current research, with new finds making headlines almost weekly.

    Since these remote planets are vanishingly dim alongside the overwhelming glare of their host stars, how do we find them? Johnson rattles through the astronomers’ main tricks. The two most successful techniques involve measuring the radial velocity, or wobble, of a star as it is tugged by an orbiting planet, and registering the minuscule dimming of starlight as a planet transits across the face of a star.

    We are also getting good at capturing images of exoplanets alongside their stars. And then there is microlensing, where an exoplanet is detected by the way its gravity focuses the light of a distant background star. [Albert] Einstein’s general theory of relativity predicts this effect, but attempts to apply it to astronomy were abandoned in 1936 because of the limits of photographic plate technology at the time.

    The greatest value of reading an “insider” book, though, is the insight the author can give us into what we can expect in the near future. For my money, the most exciting discoveries will come from ESPRESSO – a particularly apt acronym for this nocturnal profession – which stands for Echelle Spectrograph for Rocky Exoplanet and Stable Spectroscopic Observations.

    ESO Espresso
    Espresso in the clean room

    This ultra-high-resolution spectrometer will soon be installed in the [ESO] Very Large Telescope in northern Chile, where it will simultaneously harness the light-gathering capabilities of four huge 8.2- metre telescopes. By measuring the wobble of a targeted star down to a velocity of just 10 centimetres per second, ESPRESSO will be able to detect Earth-like planets in the habitable zone of their star.

    As those headlines about new exoplanets increase, after reading this book, you will be able to say you predicted as much.

    How Do You Find an Exoplanet?
    John Asher Johnson
    Princeton University Press

    See the full article here .

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  • richardmitnick 1:07 am on February 8, 2016 Permalink | Reply
    Tags: , Climate studies,   

    From Nature: “Job cuts in Australia target climate scientists” 

    Nature Mag
    Nature

    05 February 2016
    Myles Gough

    National science agency announces strategic shift away from measuring and modelling climate change.

    Hundreds of climate researchers at Australia’s national science agency are set to lose their jobs after the organization announced that it would shift its strategy away from basic climate science.

    The Commonwealth Scientific and Industrial Research Organisation (CSIRO) employs thousands of scientists across Australia, and has been a leader in climate modelling and ocean observation in the Southern Hemisphere for decades.

    CSIRO bloc

    But in an e-mail sent to CSIRO staff members this week, chief executive Larry Marshall wrote that he expected the agency to shed up to 350 jobs over the next two years, of which the burden would fall on climate-science areas, including research divisions in the Oceans and Atmosphere and Land and Water units.

    Climate models and measurements had now proven the existence of global climate change, Marshall wrote, and the questions for the organization would now be: “What do we do about it” and “how can we find solutions for the climate we will be living with?” A spokesperson for CSIRO said that the cuts from climate-research units were a strategic decision.

    “The CSIRO is effectively saying ‘climate science is done and we’re moving on to adaptation and mitigation’,” says John Church, an expert in sea-level rise in the Ocean and Atmosphere unit who has spent 38 years with the organization. “My view is that there is inaccurate and misleading science in that statement — climate science is not done,” he says.

    Another senior scientist from the unit, who spoke to Nature on the condition of anonymity, says that 220 jobs will be cut from the two units; the 110 cuts from his unit will draw directly from the roughly 130 scientists (of the unit’s 421 staff) who work on climate science-related activities, he says. “More than 80% [of our climate scientists] will be cut. This is not about myself, it’s about my people and the capability we spent 40 years to build. It will be going overnight.”

    Disastrous move

    Other Australian researchers were quick to condemn the announcement. “This is a disastrous move that will decimate ocean and climate sciences in Australia,” Matthew England, co-director of the University of New South Wales’ Climate-Change Research Centre in Sydney, told the Australian Science Media Centre (SMC) in Adelaide.

    Penny Sackett, an astronomer at the Australian National University in Canberra, and a former chief scientist for the country, told the SMC that she was “stunned by reports that CSIRO management no longer thinks measuring and understanding climate change is important, innovative or impactful”.

    Andrew Holmes, president of the Australian Academy of Science in Canberra, said in a statement that the CSIRO job losses followed cuts of more than Aus$20 million (US$19 million) to climate and environmental science in the 2014–15 federal budget, and meant that there was “serious concern” about the country’s ability to conduct research in the area.

    “We call on the government to quickly make alternative arrangements to continue a comprehensive national program of climate research,” he said.

    Australia’s science and innovation minister, Christopher Pyne, did not respond to Nature’s requests for comment.

    The cuts come after a difficult time for CSIRO, which employs more than 5,000 people but dropped 1,300 jobs in the two years up to June 2015, largely because of a 2014 federal budget that cut CSIRO funding by 16%, or roughly Aus$115 million, over four years.

    Despite the most recent job losses, a CSIRO spokesperson said, “we expect that after two years, staff numbers will be at the same levels they are now, or higher.” But Sam Popovski, the secretary of the CSIRO Staff Association, says that there are doubts that, with flat federal funding for the next three years, CSIRO will be able to keep its staffing levels stable.

    Nature doi:10.1038/nature.2016.19313

    See the full article here .

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    Nature is a weekly international journal publishing the finest peer-reviewed research in all fields of science and technology on the basis of its originality, importance, interdisciplinary interest, timeliness, accessibility, elegance and surprising conclusions. Nature also provides rapid, authoritative, insightful and arresting news and interpretation of topical and coming trends affecting science, scientists and the wider public.

     
  • richardmitnick 12:53 am on February 8, 2016 Permalink | Reply
    Tags: , , , Ultracool dwarfs   

    From CAASTRO: “Radio-loud ultracool dwarfs allow analysis of magnetic fields” 

    CAASTRO bloc

    CAASTRO ARC Centre of Excellence for All Sky Astrophysics

    8 February 2016
    No writer credit

    The group of lowest mass stars and brown dwarfs are collectively called ultracool dwarfs. A number of these objects are sources of both burst and quiescent radio emission. The radio bursts are sometimes found to occur periodically on the timescale of the rotation of the ultracool dwarf or as isolated events. They are highly circularly polarised and occur over a timescale of a few minutes. Alternatively, the quiescent emission is observed to have very little variability and low circular polarisation. Both radio emission components are thought to be the result of magnetic processes and imply that ultracool dwarfs are able to generate and sustain strong magnetic fields. This is unexpected though, given their non-solar-like interior and the observed decline in the strength of magnetic activity tracers at other wavelengths.

    Brown dwarf
    Artist’s concept of a T-type brown dwarf

    Radio surveys of ultracool dwarfs have found that about 10% of these systems are radio luminous, with 21 currently known to have radio emission. Correlations between the presence of radio emission and other dwarf properties such as rotation are not well established. Furthermore, little is known about the magnetic environment responsible for the radio emission observed in ultracool dwarfs. To address these issues, CAASTRO members Dr Christene Lynch and Dr Tara Murphy (University of Sydney), together with colleagues from Australia and overseas, carried out a survey of 15 ultracool dwarfs located in the Southern hemisphere using the Australia Telescope Compact Array [ATCA].

    CSIRO Australia Compact Array
    CSIRO ATCA

    ATCA is able to simultaneously observe over a wide range of frequencies, providing detailed information on the time-frequency structure of radio bursts and quiescent emission. Such a characterisation is required if we want to constrain the magnetic properties of ultracool dwarfs.

    The researchers detected radio emission from three of the 15 observed sources, including the detection of a new source, 2MASSW J0004348–404405. The emission from these three sources showed no variability or burst emission and was consistent with emission from a gyrosynchrotron mechanism. To characterise the magnetic conditions responsible for the observed radio emission, the team constructed a simple stellar magnetospheric model consisting of mildly-relativistic electrons that spiralled in a uniform magnetic field. They found the observed quiescent emission to be consistent with radio emission expected from a magnetic environment with a field strength 10 – 230 G and electron density 104 – 108 cm-3. Additionally, they analysed the general trends of the radio emission for this sample of 15 sources and found that the radio activity increased for later spectral types and more rapidly rotating objects.

    Publication details:
    Christene Lynch, Tara Murphy et al. in MNRAS (2016): Radio detections of southern ultracool dwarfs

    See the full article here .

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    Astronomy is entering a golden age, in which we seek to understand the complete evolution of the Universe and its constituents. But the key unsolved questions in astronomy demand entirely new approaches that require enormous data sets covering the entire sky.

    In the last few years, Australia has invested more than $400 million both in innovative wide-field telescopes and in the powerful computers needed to process the resulting torrents of data. Using these new tools, Australia now has the chance to establish itself at the vanguard of the upcoming information revolution centred on all-sky astrophysics.

    CAASTRO has assembled the world-class team who will now lead the flagship scientific experiments on these new wide-field facilities. We will deliver transformational new science by bringing together unique expertise in radio astronomy, optical astronomy, theoretical astrophysics and computation and by coupling all these capabilities to the powerful technology in which Australia has recently invested.

    PARTNER LINKS

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    The University of Western Australia
    The University of Melbourne
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    The Australian National University
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  • richardmitnick 11:41 am on February 7, 2016 Permalink | Reply
    Tags: 5 Things Built at Cornell Tech This Year, ,   

    From Cornell: “5 Things Built at Cornell Tech This Year” 

    Cornell Bloc

    Cornell University

    January 11, 2016 [This just popped up in social media. Cornell is not very good at social media.]

    Cornell Tech students, postdocs and staff are constantly building and innovating whether it’s in the classroom, at work and even during summer break.

    Here are 5 things built at Cornell Tech and demonstrated during Open Studio, our end-of-semester celebration of student, faculty and staff projects:

    Cornell robot car
    1) RoboTC
    Developed by Wilson Pulling, MEng ‘16, RoboTC makes it easier for makers to build robots. Pulling compares the difficulty of building robots today to developing software years ago and wants to make building robots as easy as building an app. RoboTC is a chip which attaches to any robot and allows makers to download functionalities from an “algorithm store” instead of coding them from scratch.

    This enables easy implementation of otherwise difficult tasks such as path planning and object recognition, which Pulling hopes will drastically expand the scope of maker projects and help them to make the leap from robotics tinkerers to robotics entrepreneurs.

    Cornell Spider Eyes
    2) Spider Eyes
    Connective Media student Joanna Zhang ‘16 built an application called Spider Eyes over her summer break. The program crawls Wikipedia and visualizes all the connected Wikipedia articles and their relationship with the searched term. The size of each node on the web of related pages shows the importance of that page to the search.

    Cornell Facepage
    3) Facepage
    As part of her Connective Media specialization project, Zhang is building Facepage. The software generates a timeline of news for a searched term or topic. For example, a search of Barack Obama would return thousands of news articles. Facepage gathers the information, summarizes it and presents it to users in a easy-to-comprehend timeline.

    Demo
    4) Slice
    Jai Chaudhary, developer in residence and MEng ‘15, has built a semantic search system currently being used by radiologists at Weill Cornell Medical College. It searches patient records with more precision than previous systems. What separates Slice from a normal keyword search is its ability to filter out terms in negative context. For example, if a radiologist searches for patients with cancer on other platforms, results for ‘no cancer’ would show up as well. Slice allows for positive searches, saving radiologists valuable time sorting through records.

    Slice is currently being used by about 36 radiologists at Weill and has helped them compile 5,000 reports in just 2 months. The long term vision for Slice is to further understand contextual meaning of terms and combine it with radiologist search intent.

    Cornell City Hive
    5) City Hive
    City Hive is a mobile first e-commerce platform developed by Runway Startup Postdoc Roi Kliper and his team. The platform allows for buy buttons and calls to action to be seamlessly integrated within the content being viewed on webpages, apps and other digital media. City Hive is currently being used by multiple customers and is shifting the power equilibrium of commerce online.

    See the full article here .

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    Once called “the first American university” by educational historian Frederick Rudolph, Cornell University represents a distinctive mix of eminent scholarship and democratic ideals. Adding practical subjects to the classics and admitting qualified students regardless of nationality, race, social circumstance, gender, or religion was quite a departure when Cornell was founded in 1865.

    Today’s Cornell reflects this heritage of egalitarian excellence. It is home to the nation’s first colleges devoted to hotel administration, industrial and labor relations, and veterinary medicine. Both a private university and the land-grant institution of New York State, Cornell University is the most educationally diverse member of the Ivy League.

    On the Ithaca campus alone nearly 20,000 students representing every state and 120 countries choose from among 4,000 courses in 11 undergraduate, graduate, and professional schools. Many undergraduates participate in a wide range of interdisciplinary programs, play meaningful roles in original research, and study in Cornell programs in Washington, New York City, and the world over.

     
  • richardmitnick 3:23 pm on February 6, 2016 Permalink | Reply
    Tags: , , , , New Bedrest Adventure Adds Artificial Gravity   

    From ESA: New Bedrest Adventure Adds Artificial Gravity 

    ESA Space For Europe Banner
    European Space Agency

    2 February 2016
    No writer credit found

    The human body is made for living on Earth – take away the constant pull of gravity and muscles and bones begin to waste away. Living in space is hard on astronauts and ways must be found to keep them fit and safe.

    ESA and NASA are planning to confine human subjects to bed for 60 days in 2017 in Cologne, Germany to probe the effects of spaceflight, with periods in a centrifuge to test if artificial gravity can keep them healthy.

    Bedrest studies offer a way of testing measures to counter some of the negative aspects of living in space. Volunteers are kept in beds with the head end tilted 6° below the horizontal. For 60 days one of the subject’s shoulders must be touching the bed at all times.

    As blood flows to the head and muscle is lost from underuse, researchers can investigate changes and test techniques from diet to physical exercise.

    Human centrifuge for artificial gravity

    The study will be conducted at the DLR German Aerospace Center’s :envihab flagship site in Cologne. Built from the ground up to research the human body under spaceflight conditions, it allows researchers to change almost every aspect of the environment, including humidity, daylight and temperature.

    ESA and DLR have already run their first study – spare a thought for the 12 brave volunteers who finished 60 days in bed last November – but this one will be the first to use the facility’s centrifuge. By spinning the subjects, the blood is encouraged to flow back towards the feet.

    The advantage of artificial gravity is that it has the potential of reducing most of the negative effects of weightlessness on the human body in one go.

    :envihab’s centrifuge can adjust the centre of spin so that subjects can be spun around their heads or chests. Changing the position could have far-reaching consequences for rehabilitation but, as this is a new domain, nobody knows yet.

    Jennifer Ngo-Anh, leading ESA’s human research, says, “I am happy to start this new bedrest study with our friends and colleagues from NASA, our first in 10 years. This study begins a series of bedrest studies focusing on artificial gravity, making use of the ESA-built centrifuges in Cologne and at MEDES in Toulouse, France.

    “This exciting research platform offers scientists around the world a way to collect results and contribute to long-duration missions to the Moon, Mars and even beyond.”

    The results are helping astronaut physicians to design better ways for astronauts to keep fit, but the knowledge is also directly applicable to bedridden people on Earth.

    Scientists are invited to submit research proposals via this link. The letter of intent is due by 15 February, with a workshop at ESA’s technical heart, ESTEC, on 22 February.

    DLR Bloc

    NASA image

    See the full article here .

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    The European Space Agency (ESA), established in 1975, is an intergovernmental organization dedicated to the exploration of space, currently with 19 member states. Headquartered in Paris, ESA has a staff of more than 2,000. ESA’s space flight program includes human spaceflight, mainly through the participation in the International Space Station program, the launch and operations of unmanned exploration missions to other planets and the Moon, Earth observation, science, telecommunication as well as maintaining a major spaceport, the Guiana Space Centre at Kourou, French Guiana, and designing launch vehicles. ESA science missions are based at ESTEC in Noordwijk, Netherlands, Earth Observation missions at ESRIN in Frascati, Italy, ESA Mission Control (ESOC) is in Darmstadt, Germany, the European Astronaut Centre (EAC) that trains astronauts for future missions is situated in Cologne, Germany, and the European Space Astronomy Centre is located in Villanueva de la Cañada, Spain.

    ESA50 Logo large

     
  • richardmitnick 12:46 pm on February 6, 2016 Permalink | Reply
    Tags: , , Pangaea,   

    From livescience: “What If the Supercontinent Pangaea Had Never Broken Up?” 

    Livescience

    Brought forward 2.6.16
    Original date May 13, 2011

    Adam Hadhazy

    Things would be a little different.

    Pangaea and its breakup

    From about 300 million to 200 million years ago, all seven modern continents were mashed together as one landmass, dubbed Pangaea . The continents have since “drifted” apart because of the movements of the Earth’s crust, known as plate tectonics. Some continents have maintained their puzzle piece-like shapes: Look at how eastern South America tucks into western Africa.

    Techtonic plates
    The tectonic plates of the world were mapped in the second half of the 20th century.

    Life would be: Far less diverse. A prime driver of speciation the development of new species from existing ones is geographical isolation, which leads to the evolution of new traits by subjecting creatures to different selective pressures. Consider, for example, the large island of Madagascar, which broke off from Gondwana, Pangaea’s southern half, 160 million years ago. About nine out of 10 of the plant and mammal species that have evolved on the island are not found anywhere else on the planet, according to Conservation International.

    A locked-in Pangaea further constrains life’s possibilities because much of its interior would be arid and hot, said Damian Nance, a professor of geosciences at Ohio University. “Because of Pangaea’s size, moisture-bearing clouds would lose most of their moisture before getting very far inland,” Nance told Life’s Little Mysteries.

    Excess mass on a spinning globe shifts away from the poles, so the supercontinent would also become centered on the equator, the warmest part of the planet. Reptiles could deal with such a climate better than most, which is partly why dinosaurs, which emerged during the time the planet’s surface was one giant chunk, thrived before mammals.

    See the full article here .

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  • richardmitnick 12:29 pm on February 6, 2016 Permalink | Reply
    Tags: , , Nature Genetics   

    From Nature: “The many ways MYB drives cancer” 

    Nature Mag
    Nature

    free association
    free association from Nature Genetics

    Nature Genetics | Free Association

    05 Feb 2016
    Posted by Brooke LaFlamm

    Two papers published online this week in Nature Genetics demonstrate that MYB, long known as a cancer gene, has many different strategies for driving tumorigenesis.

    Fruitfly eye signals about cancer
    Fruitfly eye, evidence of cancer

    Bradley Bernstein, Birgit Knoechel and colleagues studied the role of MYB translocations in adenoid cystic carcinoma (ACC) and found that MYB translocations can reposition the gene to be driven by super-enhancers—which themselves are bound by MYB to drive its own expression even higher. In an interesting twist, they also found that MYB drives different regulatory programs in different ACC cell lineages: MYB’s oncogenic function is mediated by TP63 in myoepithelial cells, while in luminal epithelial cells, MYB appears to act through the Notch signaling pathway.

    In an independent study focused on pediatric angiocentric gliomas, Keith Ligon, Rameen Beroukhim, Adam Resnick and colleagues found that MYB translocations resulting in MYB-QKI fusion genes are the most common MYB alteration in this cancer type. The fusion results in higher expression of MYB and loss of QKI expression, both of which contribute to the development of these gliomas. As in the ACC study, this translocation resulted in repositioning of MYB near enhancers that help drive its expression up. At the same time, the translocation caused loss of some regulatory elements, also leading to aberrant expression of MYB, and loss of function of QKI, a tumor suppressor. Thus, MYB-QKI uses three different mechanisms to drive gliomagenesis.

    Both cancer types are relatively rare but aggressive, and new treatment options are sorely needed. Adenoid cystic carcinoma (ACC) occurs in secretory glands, mainly the salivary glands in the head and neck, and can spread to the nerves as well as metastasizing to distant sites, such as the lungs. The tumors are often resistant to therapy and can recur many years after the primary tumor has been removed surgically. Angiocentric gliomas are very rare brain tumors that generally affect children and young adults. Very little is known about the genetic changes that occur in this tumor type and, prior to this study, there were no known recurrent driver mutations, which are often good candidates for new targeted drug therapies. “The discovery of a recurrent rearrangement in angiocentric glioma provides a clinically relevant diagnostic marker, and insights into the biology that drives these tumors,” said Pratiti Bandopadhayay, one of the lead authors of the study.

    We asked some of the authors from both studies to tell us a little more about the work and why it is important. Yotam Drier and Birgit Knoechel talked to us about the study in ACC. Pratiti Bandopadhayay, Lori Ramkissoon, Guillaume Bergthold and Payal Jain talked to us about the study in angiocentric gliomas.

    How do your findings clarify earlier results showing a role for MYB in ACC? Do you think these findings are relevant for other cancer types?

    Yotam Drier and Birgit Knoechel (Broad Institute):

    Our work identified a unifying mechanism for MYB over-expression in ACC. Persson et al. suggested in 2009 that MYB over-expression occurs where the MYB 3′ untranslated region (UTR) is lost. However, in most cases of ACC the MYB 3′ UTR remains intact, and we now describe that in all cases of detected MYB rearrangements in this cancer–independent of whether the 3′ UTR is retained or lost–MYB is being driven by hijacking MYB bound super-enhancers, thus creating a positive feedback loop. This is complementary to the previous model, and we believe that in those cases where the MYB 3′ UTR is lost, both mechanisms would contribute to increased MYB expression.

    We believe that similar rearrangements involving enhancer translocations may contribute to MYB overexpression in other cancer types. For example, our colleagues at Dana Farber simultaneously report a similar mechanism of MYB activation in angiocentric gliomas.

    How do the mechanisms described in your paper compare to what is described in the related paper by Drier et al.?

    Pratiti Bandopadhayay, Lori Ramkissoon and Guillaume Bergthold (Dana-Farber Cancer Institute) and Payal Jain (Children’s Hospital of Philadelphia):

    We were excited to learn about the findings from the Bernstein group as their findings compliment ours, in a completely different tumor type. We found that angiocentric gliomas harbor rearrangements involving the MYB and QKI genes, while Dr. Bernstein’s team focused on adenoid cystic carcinomas, which frequently have similar MYB rearrangements. Both papers show that MYB rearrangements result in aberrant activation of the MYB promoter to drive expression of the oncogenic fusion proteins, and that these fusion proteins then participate in auto-regulatory feedback loops to drive their own expression.

    From your perspective, what was the most unexpected finding in this study?

    Yotam Drier and Birgit Knoechel:

    We were surprised by our finding that MYB orchestrates 2 opposing epigenetic states—a TP63-dependent program in myoepithelial cells and a NOTCH-dependent program in luminal cells. Thus, overexpression of a single transcription factor can drive distinct epigenetic states that depend on the cellular context in which the overexpression occurs.

    Pratiti Bandopadhayay, Lori Ramkissoon, Guillaume Bergthold and Payal Jain:

    The unexpected result of our study that we find very exciting is that this one single driver rearrangement contributes to tumor growth through multiple mechanisms. MYB-QKI rearrangements simultaneously drive expression of a fusion protein that causes cells to grow faster and form tumors, it changes the regulatory landscape of the gene to promote expression of this protein and it simultaneously disrupts a tumor suppressor gene (QKI) that in turn also makes the cells divide faster. We feel that this finding is likely relevant to a number of other pediatric and adult cancers.

    How does the fusion with QKI impact the function of the translocated MYB and do you think it is necessary for its role in driving gliomagenesis?

    Pratiti Bandopadhayay, Lori Ramkissoon, Guillaume Bergthold and Payal Jain:

    The rearrangement with QKI results in displacement of regulatory elements on QKI towards MYB and these elements help drive expression of MYB-QKI. In addition, it disrupts the function of QKI itself, which is a tumor suppressor gene. We feel that the association with QKI is important in angiocentric glioma since the rearrangement between MYB and QKI occurred with such high frequency in our study.

    What are the additional steps needed before your findings can be implemented in the clinic?

    Yotam Drier and Birgit Knoechel:

    Interestingly, while BET inhibition can slow tumor growth in low grade ACCs, high grade ACCs often show genetic activation of NOTCH and are thus amenable to treatment with gamma secretase inhibitors or other NOTCH targeting therapies. It will be important to evaluate whether combining BET inhibition with NOTCH inhibition may show additional effects over BET inhibition alone. It is conceivable that by adding the NOTCH inhibitor one might preferentially target the luminal epithelial cells which are characterized by a NOTCH driven regulatory program. This will need to be tested further in preclinical models. Moreover, the fact that grade 3 tumors failed to respond to BET inhibition requires further preclinical analyses. Identifying mechanisms of BET inhibitor failure which are just entering clinical trials will be of utmost importance in order to predict which patients may benefit from these.

    Pratiti Bandopadhayay, Lori Ramkissoon, Guillaume Bergthold and Payal Jain:

    We are excited that our results provide us with novel possibilities to treat angiocentric gliomas. As MYB is a transcription factor the likelihood of targeting it or the MYB-QKI fusion is challenging; however we identified several downstream targets that represent potential therapeutic strategies. In addition, the finding of altered regulatory elements represents another exciting therapeutic strategy. Our findings directly impact clinical care for children with angiocentric glioma through development of two diagnostic tests that will be used to support the diagnosis of angiocentric glioma. We also feel our findings are likely relevant to other pediatric and adult cancers that are driven by driver rearrangements.

    Finally we would like to highlight that multiple institutions and funding sources helped facilitate this study. We would also like to acknowledge the families whose children have been afflicted with Pediatric Low-Grade Glioma.

    See the full article here .

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    Nature is a weekly international journal publishing the finest peer-reviewed research in all fields of science and technology on the basis of its originality, importance, interdisciplinary interest, timeliness, accessibility, elegance and surprising conclusions. Nature also provides rapid, authoritative, insightful and arresting news and interpretation of topical and coming trends affecting science, scientists and the wider public.

     
  • richardmitnick 6:50 am on February 6, 2016 Permalink | Reply
    Tags: , , , SPIE   

    From SPIE: “Tracking DNA damage with electrochemical sensing” 

    SPIE

    SPIE

    2.6.16
    Jason D. Slinker
    The University of Texas at Dallas
    Richardson, TX

    DNA, the fundamental biomolecule of life, is constantly subject to damage that threatens the vitality of cells and the integrity of the genome. Without enzymatic intervention, this damage can produce mutations that lead to cancerous tumors. Furthermore, many current and developing treatments of cancer and disease rely on the generation of DNA damage products, which—from a chemical standpoint—are very subtle. For example, 8-oxoguanine, the most prevalent oxidative DNA damage product, involves the addition of a single oxygen bond to a guanine base. Remarkably, enzymes in cells recognize and remove this damage and other products of degradation. Biological assays that follow repair of this subtle DNA damage assist cancer studies by advancing fundamental understanding of DNA-protein interactions, connecting damage to diagnosis, and informing options for treatment.

    We have demonstrated devices that follow DNA damage repair in real time, with a convenient, low-cost package (see Figure 1).1 In this device, DNA is bound to the circular electrodes of multielectrode chips, and a redox probe at the top of the DNA reports charge transfer through it. DNA is the natural recognition element not only for the binding of repair proteins but also for their repair activity, and it can be synthesized with or without damage/lesion sites to establish controls. Furthermore, DNA can also serve as an electrical transducing element when modified with a redox-active probe and self-assembled on a working electrode, as first demonstrated by the Barton group.2 We have combined these features of DNA, using them to form devices capable of selectively detecting oxidative DNA damage repair (see Figure 1) and changes in DNA stability.1 The devices give a direct measure of molecular-level repair, providing a window into intracellular DNA repair by DNA-binding proteins.

    DNA Device
    Figure 1. Top: Schematic of detection of oxidative damage removal. Bottom: Image of the device used to study DNA-damaging drugs. (Photo by Randy Anderson). FPG: Formamidopyrimidine DNA glycosylase. e-: Electron.

    Specifically, we have used our approach to show sensitive and selective electrochemical sensing of 8-oxoguanine and uracil repair glycosylase activity. We produced sensors on electrospun fibers as low-cost devices with improved dynamic range. Our experiments compared electroactive, probe-modified DNA monolayers containing a base defect with the rational control of defect-free monolayers. We found damage-specific limits of detection on the order of femtomoles of proteins, corresponding to mere nanograms of the enzymes. The DNA chips enabled the real-time observation of protein activity, and we observed base excision activity on the order of seconds. We also demonstrated damage-specific detection in a mixture of enzymes and in response to environmental oxidative damage. We showed how nanofibers may behave similarly to conventional gold-on-silicon devices, revealing the potential of these low-cost devices for sensing applications. This device approach enables sensitive, selective, and rapid assay of repair protein activity, allowing biological interrogation of DNA damage repair.

    Given the ability of these devices to follow induced oxidative damage, we are further using them to follow DNA-damaging anticancer drug activity. We are working with the group of David Boothman of the University of Texas Southwestern Medical Center to sense DNA repair activity in conjunction with a novel drug therapy that selectively produces oxidative damage of DNA in cancer cells, bringing about selective cancer cell death. We represent key features of a living system to reproduce DNA damaging and repair activity pathways on the chip. Recent results have shown that we can follow specific drug-induced DNA damage excision and subsequent DNA repair with our devices. Furthermore, the multiple electrodes of the chip allowed us to perform controls of each associated enzyme and to obtain high statistical confidence of results. Given this success, we have launched studies of other DNA damaging drugs to explore the generality of this technique.

    In summary, we have designed and fabricated low-cost devices that are capable of electrochemical sensing of 8-oxoguanine and uracil repair glycosylase activity. Ultimately, in addition to their utility in bioassays of DNA-protein interactions, our devices have potential in a number of applications for public health, and our future work will focus on realizing these. The prevalence of high damage repair sites can be an indication of cancers and disease states, and these devices could provide statistically significant diagnosis. Additionally, as a number of cancer treatments involve DNA-damaging agents, our devices can be used to improve treatment outcomes. These devices could be used to sample the activity of multiple drugs with a small volume patient sample, enabling a tailored treatment based on DNA-damaging effectiveness. Similarly, they may also be used to follow the course of cancer treatment through characteristic measures of enzymatic activity of cancer cells versus healthy cells.

    See the full article here.

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  • richardmitnick 6:35 am on February 6, 2016 Permalink | Reply
    Tags: , CRISPR-Cas,   

    From Rockefeller: “A newly discovered form of immunity helps explain how bacteria fight off viruses” 

    Rockefeller U bloc

    Rockefeller University

    A newly discovered form of immunity helps explain how bacteria fight off viruses

    February 4, 2016
    Eva Kiesler | 212-327-7963

    When seeking to protect themselves from viruses, some bacteria use a seemingly risky strategy: They wait until the invading virus has already begun to replicate. Research at The Rockefeller University shows how the microbes use two newly identified enzymes to fight off an infection even after delaying action.

    “A viral infection can kill a bacterial cell—or in some cases, the viral genetic material can provide benefits, such as protection against other viruses. Harmful viruses immediately begin replicating, but beneficial ones implant themselves into the bacterial genome,” says Luciano Marraffini, assistant professor and head of the Laboratory of Bacteriology. “By using a wait-and-see approach, and tolerating the initial phase of the infection, the bacteria are able to make an intelligent choice.”

    The research, published this week in Cell, helps explain how bacteria manage to clear a harmful infection in spite of their slow response. In the future, it might inform the development of new ways to combat infectious disease, among other potential applications.

    A last-minute defense

    The study zeroes-in on two enzymes, Csm3 and Csm6, which are part of a bacterial immune system known as CRISPR-Cas. When these enzymes swing into action during the late phase of infection, they cut up viral RNA.

    The CRISPR (clustered regularly interspersed short palindromic repeats) system is a type of adaptive bacterial immune response that relies on sections of DNA containing sequences matching those in viral genetic code. CRISPR-associated genes use these sequences as guides to target invaders for destruction.

    Typically, CRISPR defense systems attack and destroy the viral DNA within minutes after it has been injected into the bacterial cell, so the invading virus doesn’t get a chance to replicate. However, the specific type of CRISPR investigated in the study—called type III CRISPR-Cas system—waits for the virus to replicate and mounts its attack during a later phase of the infection, after the viral DNA has been copied and is being transcribed into RNA.

    “It appears that type III CRISPR-Cas actually needs the virus to produce RNA before it can target and destroy the viral DNA,” says Wenyan Jiang, a graduate student who is the paper’s first author. “As a result, the system has to deal with hundreds of viral DNA strands instead of one, and can take up to nine hours instead of minutes to clear the infection.”

    An extra safeguard

    There is an inherent peril in waiting until this point, and because of the large number of viral genomes present, the typical DNA-cutting enzymes employed by CRISPR-Cas systems can’t stop the infection alone. So, type III CRISPR-Cas also uses the enzymes Csm3 and Csm6 to target the viral RNA, the researchers found.

    To observe this RNA-focused defense in action, Marraffini, Jiang, and Poulami Samai, a research associate in the lab, generated a mutated form of Staphylococcus epidermidis bacteria that lacked the Csm3 and Csm6 enzymes. When they infected both the mutant and the normal bacteria with a virus, the mutant population succumbed to it.

    The research clarifies how this CRISPR-Cas strategy functions, and also has potential implications for biotechnology and medicine. Because it can make precisely targeted cuts on genomes, CRISPR’s DNA-cleaving abilities have proved useful in developing genetic engineering techniques. Understanding how CRISPR RNA-cutting enzymes work may be useful to manipulate the RNA content of human cells, Marraffini says.

    “The study also advances our knowledge about how bacteria interact with their viruses, which is essential for understanding bacterial pathogenesis,” says Marraffini. “The viral genetic material can increase the virulence of pathogens, and at the same time viruses can be used to kill pathogenic bacteria in the clinic. Understanding the molecular mechanisms at play in the bacteria–virus interactions can help us combat infectious disease.”

    See the full article here .

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    Rockefeller U Campus

    The Rockefeller University is a world-renowned center for research and graduate education in the biomedical sciences, chemistry, bioinformatics and physics. The university’s 76 laboratories conduct both clinical and basic research and study a diverse range of biological and biomedical problems with the mission of improving the understanding of life for the benefit of humanity.

    Founded in 1901 by John D. Rockefeller, the Rockefeller Institute for Medical Research was the country’s first institution devoted exclusively to biomedical research. The Rockefeller University Hospital was founded in 1910 as the first hospital devoted exclusively to clinical research. In the 1950s, the institute expanded its mission to include graduate education and began training new generations of scientists to become research leaders around the world. In 1965, it was renamed The Rockefeller University.

     
  • richardmitnick 6:18 am on February 6, 2016 Permalink | Reply
    Tags: , , , , Water vapor   

    From Eos: “The Forgotten Water Vapor at High Altitudes” 

    Eos news bloc

    Eos

    2.5.16
    Cody Sullivan

    Scientists find that estimations of high-altitude atmospheric water, critical for the greenhouse effect, are not as accurate as previously thought.

    Clouds

    Water vapor is one of the most important greenhouse gases. As it drifts through the atmosphere, the vapor absorbs heat. The warm, moist air rises, leaving the planet’s surface and emitting that heat back out into the upper atmosphere. To determine how well we understand the behavior of water vapor at high altitudes, Jiang et al. compared three different reanalyses—long-term records of changing weather patterns over time—to satellite observations.

    The Microwave Limb Sounder (MLS) is an instrument aboard NASA’s Aura satellite that takes measurements of the atmosphere’s composition, humidity, and temperature at altitudes of roughly 8 kilometers and above.

    NASA JPL Caltech Microwave Limb Sounder
    NASA JPL Caltech Microwave Limb Sounder

    NASA Goddard Aura satellite
    NASA/Goddard Aura satellite

    The researchers used such measurements to examine the accuracy of water vapor calculations from two versions of NASA Modern-Era Retrospective Analysis for Research and Applications (MERRA and MERRA2) reanalysis and the European Centre for Medium-Range Weather Forecasts (ECMWF) Interim Reanalyses—all of which provide climate modelers with estimations of how much water is in the atmosphere. The authors specifically investigated the amounts of water in the upper troposphere and lower stratosphere and how much water was transferred between the two layers. This was the first study of NASA MERRA2 reanalysis since its release in October 2015.

    They found that the reanalyses were fairly inconsistent with the MLS observations. The reanalyses overestimated the average amount of water in the upper troposphere, overshooting the MLS observations by about 150%. The team also found that the MLS measured water vapor traveling between the two layers slower than the reanalyses predicted. Vertical transport within the lower stratosphere in the tropics was 168% faster than the MLS measures according to the ECMWF, whereas MERRA numbers were only 10% faster than the MLS ones. The rate of horizontal water movement was also skewed: MERRA had water moving 106% faster in the Northern Hemisphere and up to 45% slower in the Southern Hemisphere, and ECMWF was 16% faster in both hemispheres.

    These findings highlight our incomplete understanding of water vapor’s distribution and variability in the upper troposphere and lower stratosphere. The researchers call for further study on water vapor behavior at these high altitudes, as the large variance between the reanalyses could hinder the production of accurate climate models. (Journal of Geophysical Research: Atmospheres, doi:10.1002/2015JD023752, 2015)

    —Cody Sullivan, Freelance Writer

    Citation: Sullivan, C. (2016), The forgotten water vapor at high altitudes, Eos, 97, doi:10.1029/2016EO045075. Published on 5 February 2016.

    See the full article here .

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    Eos is the leading source for trustworthy news and perspectives about the Earth and space sciences and their impact. Its namesake is Eos, the Greek goddess of the dawn, who represents the light shed on understanding our planet and its environment in space by the Earth and space sciences.

     
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