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Richard Kuhn

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https://www.readbyqxmd.com/read/28678784/personalized-rna-mutanome-vaccines-mobilize-poly-specific-therapeutic-immunity-against-cancer
#1
Ugur Sahin, Evelyna Derhovanessian, Matthias Miller, Björn-Philipp Kloke, Petra Simon, Martin Löwer, Valesca Bukur, Arbel D Tadmor, Ulrich Luxemburger, Barbara Schrörs, Tana Omokoko, Mathias Vormehr, Christian Albrecht, Anna Paruzynski, Andreas N Kuhn, Janina Buck, Sandra Heesch, Katharina H Schreeb, Felicitas Müller, Inga Ortseifer, Isabel Vogler, Eva Godehardt, Sebastian Attig, Richard Rae, Andrea Breitkreuz, Claudia Tolliver, Martin Suchan, Goran Martic, Alexander Hohberger, Patrick Sorn, Jan Diekmann, Janko Ciesla, Olga Waksmann, Alexandra-Kemmer Brück, Meike Witt, Martina Zillgen, Andree Rothermel, Barbara Kasemann, David Langer, Stefanie Bolte, Mustafa Diken, Sebastian Kreiter, Romina Nemecek, Christoffer Gebhardt, Stephan Grabbe, Christoph Höller, Jochen Utikal, Christoph Huber, Carmen Loquai, Özlem Türeci
T cells directed against mutant neo-epitopes drive cancer immunity. However, spontaneous immune recognition of mutations is inefficient. We recently introduced the concept of individualized mutanome vaccines and implemented an RNA-based poly-neo-epitope approach to mobilize immunity against a spectrum of cancer mutations. Here we report the first-in-human application of this concept in melanoma. We set up a process comprising comprehensive identification of individual mutations, computational prediction of neo-epitopes, and design and manufacturing of a vaccine unique for each patient...
July 13, 2017: Nature
https://www.readbyqxmd.com/read/28655823/can-an-fda-approved-alzheimer-s-drug-be-repurposed-for-alleviating-neuronal-symptoms-of-zika-virus
#2
Devika Sirohi, Richard J Kuhn
Zika virus caught the world by surprise by its rapid spread and frightening disease outcomes. This major epidemic motivated many scientists to focus their attention on controlling this emerging pathogen. As many as 45 vaccine candidates are being developed, but progress in the antiviral arena has been slower. In a recent article (mBio 8:e00350-17, 2017, https://doi.org/10.1128/mBio.00350-17), Costa and colleagues showed that an FDA-approved drug used to treat Alzheimer's disease may moderate Zika virus-induced neuronal damage...
June 27, 2017: MBio
https://www.readbyqxmd.com/read/28582774/a-giant-planet-undergoing-extreme-ultraviolet-irradiation-by-its-hot-massive-star-host
#3
B Scott Gaudi, Keivan G Stassun, Karen A Collins, Thomas G Beatty, George Zhou, David W Latham, Allyson Bieryla, Jason D Eastman, Robert J Siverd, Justin R Crepp, Erica J Gonzales, Daniel J Stevens, Lars A Buchhave, Joshua Pepper, Marshall C Johnson, Knicole D Colon, Eric L N Jensen, Joseph E Rodriguez, Valerio Bozza, Sebastiano Calchi Novati, Giuseppe D'Ago, Mary T Dumont, Tyler Ellis, Clement Gaillard, Hannah Jang-Condell, David H Kasper, Akihiko Fukui, Joao Gregorio, Ayaka Ito, John F Kielkopf, Mark Manner, Kyle Matt, Norio Narita, Thomas E Oberst, Phillip A Reed, Gaetano Scarpetta, Denice C Stephens, Rex R Yeigh, Roberto Zambelli, B J Fulton, Andrew W Howard, David J James, Matthew Penny, Daniel Bayliss, Ivan A Curtis, D L DePoy, Gilbert A Esquerdo, Andrew Gould, Michael D Joner, Rudolf B Kuhn, Jonathan Labadie-Bartz, Michael B Lund, Jennifer L Marshall, Kim K McLeod, Richard W Pogge, Howard Relles, Christopher Stockdale, T G Tan, Mark Trueblood, Patricia Trueblood
The amount of ultraviolet irradiation and ablation experienced by a planet depends strongly on the temperature of its host star. Of the thousands of extrasolar planets now known, only six have been found that transit hot, A-type stars (with temperatures of 7,300-10,000 kelvin), and no planets are known to transit the even hotter B-type stars. For example, WASP-33 is an A-type star with a temperature of about 7,430 kelvin, which hosts the hottest known transiting planet, WASP-33b (ref. 1); the planet is itself as hot as a red dwarf star of type M (ref...
June 22, 2017: Nature
https://www.readbyqxmd.com/read/28532404/use-of-the-qiagen-genereader-ngs-system-for-detection-of-kras-mutations-validated-by-the-qiagen-therascreen-pcr-kit-and-alternative-ngs-platform
#4
Agus Darwanto, Anne-Mette Hein, Sascha Strauss, Yi Kong, Andrew Sheridan, Dan Richards, Eric Lader, Monika Ngowe, Timothy Pelletier, Danielle Adams, Austin Ricker, Nishit Patel, Andreas Kühne, Simon Hughes, Dan Shiffman, Dirk Zimmermann, Kai Te Kaat, Thomas Rothmann
BACKGROUND: The detection of somatic mutations in primary tumors is critical for the understanding of cancer evolution and targeting therapy. Multiple technologies have been developed to enable the detection of such mutations. Next generation sequencing (NGS) is a new platform that is gradually becoming the technology of choice for genotyping cancer samples, owing to its ability to simultaneously interrogate many genomic loci at massively high efficiency and increasingly lower cost. However, multiple barriers still exist for its broader adoption in clinical research practice, such as fragmented workflow and complex bioinformatics analysis and interpretation...
May 22, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28520460/the-influence-of-body-mass-index-on-outcomes-after-hip-arthroscopic-surgery-with-capsular-plication-for-the-treatment-of-femoroacetabular-impingement
#5
Bryan M Saltzman, Benjamin D Kuhns, Bryce Basques, Timothy Leroux, Jennifer Alter, Richard C Mather, Michael J Salata, Shane J Nho
BACKGROUND: It remains unknown how variations in body mass index (BMI) influence outcomes after primary hip arthroscopic surgery with capsular plication for femoroacetabular impingement (FAI). PURPOSE: To evaluate the effect that abnormal BMI (namely, overweight, obese, morbidly obese, and underweight) versus normal weight has on patient-reported clinical outcomes more than 2 years postoperatively from primary hip arthroscopic surgery with capsular plication by a single surgeon...
May 1, 2017: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/28441511/do-patients-with-borderline-dysplasia-have-inferior-outcomes-after-hip-arthroscopic-surgery-for-femoroacetabular-impingement-compared-with-patients-with-normal-acetabular-coverage
#6
Gregory L Cvetanovich, David M Levy, Alexander E Weber, Benjamin D Kuhns, Richard C Mather, Michael J Salata, Shane J Nho
BACKGROUND: The literature contains conflicting reports regarding whether outcomes of hip arthroscopic surgery for patients with borderline dysplasia are inferior to outcomes in patients with normal acetabular coverage. PURPOSE: To assess differences in the outcomes of hip arthroscopic surgery for femoroacetabular impingement (FAI) in groups of patients with borderline dysplasia and normal coverage. STUDY DESIGN: Cohort study; Level of evidence, 3...
April 1, 2017: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/28380995/wavelength-calibration-of-a-high-resolution-spectrograph-with-a-partially-stabilized-15-ghz-astrocomb-from-550-to-890-nm
#7
Richard A McCracken, Éric Depagne, Rudolf B Kuhn, Nicolas Erasmus, Lisa A Crause, Derryck T Reid
A visible astrocomb spanning 555-890 nm has been implemented on the 10-m Southern African Large Telescope, delivering complete calibration of one channel of its high-resolution spectrograph and an accurate determination of its resolving power. A novel co-coupling method allowed simultaneous observation of on-sky, Th-Ar lamp and astrocomb channels, reducing the wavelength calibration uncertainty by a factor of two compared to that obtained using only Th-Ar lines. The excellent passive stability of the master frequency comb laser enabled broadband astrocomb generation without the need for carrier-envelope offset frequency locking, and an atomically referenced narrow linewidth diode laser provided an absolute fiducial marker for wavelength calibration...
March 20, 2017: Optics Express
https://www.readbyqxmd.com/read/28300075/a-human-antibody-against-zika-virus-crosslinks-the-e-protein-to-prevent-infection
#8
S Saif Hasan, Andrew Miller, Gopal Sapparapu, Estefania Fernandez, Thomas Klose, Feng Long, Andrei Fokine, Jason C Porta, Wen Jiang, Michael S Diamond, James E Crowe, Richard J Kuhn, Michael G Rossmann
The recent Zika virus (ZIKV) epidemic has been linked to unusual and severe clinical manifestations including microcephaly in fetuses of infected pregnant women and Guillian-Barré syndrome in adults. Neutralizing antibodies present a possible therapeutic approach to prevent and control ZIKV infection. Here we present a 6.2 Å resolution three-dimensional cryo-electron microscopy (cryoEM) structure of an infectious ZIKV (strain H/PF/2013, French Polynesia) in complex with the Fab fragment of a highly therapeutic and neutralizing human monoclonal antibody, ZIKV-117...
March 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28196962/spatial-and-temporal-analysis-of-alphavirus-replication-and-assembly-in-mammalian-and-mosquito-cells
#9
Joyce Jose, Aaron B Taylor, Richard J Kuhn
Sindbis virus (SINV [genus Alphavirus, family Togaviridae]) is an enveloped, mosquito-borne virus. Alphaviruses cause cytolytic infections in mammalian cells while establishing noncytopathic, persistent infections in mosquito cells. Mosquito vector adaptation of alphaviruses is a major factor in the transmission of epidemic strains of alphaviruses. Though extensive studies have been performed on infected mammalian cells, the morphological and structural elements of alphavirus replication and assembly remain poorly understood in mosquito cells...
February 14, 2017: MBio
https://www.readbyqxmd.com/read/28134265/consensus-statement-virus-taxonomy-in-the-age-of-metagenomics
#10
Peter Simmonds, Mike J Adams, Mária Benkő, Mya Breitbart, J Rodney Brister, Eric B Carstens, Andrew J Davison, Eric Delwart, Alexander E Gorbalenya, Balázs Harrach, Roger Hull, Andrew M Q King, Eugene V Koonin, Mart Krupovic, Jens H Kuhn, Elliot J Lefkowitz, Max L Nibert, Richard Orton, Marilyn J Roossinck, Sead Sabanadzovic, Matthew B Sullivan, Curtis A Suttle, Robert B Tesh, René A van der Vlugt, Arvind Varsani, F Murilo Zerbini
The number and diversity of viral sequences that are identified in metagenomic data far exceeds that of experimentally characterized virus isolates. In a recent workshop, a panel of experts discussed the proposal that, with appropriate quality control, viruses that are known only from metagenomic data can, and should be, incorporated into the official classification scheme of the International Committee on Taxonomy of Viruses (ICTV). Although a taxonomy that is based on metagenomic sequence data alone represents a substantial departure from the traditional reliance on phenotypic properties, the development of a robust framework for sequence-based virus taxonomy is indispensable for the comprehensive characterization of the global virome...
March 2017: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/28133442/measuring-and-specifying-combinatorial-coverage-of-test-input-configurations
#11
D Richard Kuhn, Raghu N Kacker, Yu Lei
A key issue in testing is how many tests are needed for a required level of coverage or fault detection. Estimates are often based on error rates in initial testing, or on code coverage. For example, tests may be run until a desired level of statement or branch coverage is achieved. Combinatorial methods present an opportunity for a different approach to estimating required test set size, using characteristics of the test set. This paper describes methods for estimating the coverage of, and ability to detect, t-way interaction faults of a test set based on a covering array...
December 2016: Innovations in Systems and Software Engineering
https://www.readbyqxmd.com/read/28107887/associations-between-positive-emotional-well-being-and-stress-induced-myocardial-ischemia-well-being-scores-predict-exercise-induced-ischemia
#12
Jacob P Feigal, Stephen H Boyle, Zainab Samad, Eric J Velazquez, Jennifer L Wilson, Richard C Becker, Redford B Williams, Cynthia M Kuhn, Thomas L Ortel, Joseph G Rogers, Christopher M O'Connor, Wei Jiang
OBJECTIVE: Depressive symptoms have been associated with myocardial ischemia induced by mental (MSIMI) and exercise (ESIMI) stress in clinically stable ischemic heart disease (IHD) patients, but the association between positive emotions and inducible ischemia is less well characterized. The objective of this study was to examine the associations between ratings of well-being and stress-induced ischemia. METHODS: Subjects were adult patients with documented IHD underwent mental and exercise stress testing for the Responses of Myocardial Ischemia to Escitalopram Treatment (REMIT) trial...
February 2017: Journal of Psychosomatic Research
https://www.readbyqxmd.com/read/28086865/rnai-reveals-proteins-for-metabolism-and-protein-processing-associated-with-langat-virus-infection-in-ixodes-scapularis-black-legged-tick-ise6-cells
#13
Jeffrey M Grabowski, Monika Gulia-Nuss, Richard J Kuhn, Catherine A Hill
BACKGROUND: Tick-borne flaviviruses (TBFs) cause thousands of human cases of encephalitis worldwide each year, with some TBF infections progressing to hemorrhagic fever. TBFs are of medical and veterinary importance and strategies to reduce flavivirus transmission by the tick vector may have significant application. Analyses of the proteome of ISE6 cells derived from the black legged tick, Ixodes scapularis infected with the TBF, Langat virus (LGTV), have provided insights into proteins and cellular processes involved with LGTV infection...
January 13, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28078475/50-years-of-the-international-committee-on-taxonomy-of-viruses-progress-and-prospects
#14
Michael J Adams, Elliot J Lefkowitz, Andrew M Q King, Balázs Harrach, Robert L Harrison, Nick J Knowles, Andrew M Kropinski, Mart Krupovic, Jens H Kuhn, Arcady R Mushegian, Max L Nibert, Sead Sabanadzovic, Hélène Sanfaçon, Stuart G Siddell, Peter Simmonds, Arvind Varsani, Francisco Murilo Zerbini, Richard J Orton, Donald B Smith, Alexander E Gorbalenya, Andrew J Davison
We mark the 50th anniversary of the International Committee on Taxonomy of Viruses (ICTV) by presenting a brief history of the organization since its foundation, showing how it has adapted to advancements in our knowledge of virus diversity and the methods used to characterize it. We also outline recent developments, supported by a grant from the Wellcome Trust (UK), that are facilitating substantial changes in the operations of the ICTV and promoting dialogue with the virology community. These developments will generate improved online resources, including a freely available and regularly updated ICTV Virus Taxonomy Report...
May 2017: Archives of Virology
https://www.readbyqxmd.com/read/28078102/repeated-mild-traumatic-brain-injury-causes-focal-response-in-lateral-septum-and-hippocampus
#15
Rebecca Acabchuk, Denise I Briggs, Mariana Angoa-Pérez, Meghan Powers, Richard Wolferz, Melanie Soloway, Mai Stern, Lillian R Talbot, Donald M Kuhn, Joanne C Conover
AIM: To advance our understanding of regional and temporal cellular responses to repeated mild traumatic brain injury (rmTBI), we used a mouse model of rmTBI that incorporated acceleration, deceleration and rotational forces. MATERIALS & METHODS: A modified weight-drop method was used to compare two inter-injury intervals, rmTBI-short (five hits delivered over 3 days) and rmTBI-long (five hits delivered over 15 days). Regional investigations of forebrain and midbrain histological alterations were performed at three post-injury time points (immediate, 2 weeks and 6 weeks)...
December 2016: Concussion
https://www.readbyqxmd.com/read/28067914/structure-of-the-immature-zika-virus-at-9-%C3%A3-resolution
#16
Vidya Mangala Prasad, Andrew S Miller, Thomas Klose, Devika Sirohi, Geeta Buda, Wen Jiang, Richard J Kuhn, Michael G Rossmann
The current Zika virus (ZIKV) epidemic is characterized by severe pathogenicity in both children and adults. Sequence changes in ZIKV since its first isolation are apparent when pre-epidemic strains are compared with those causing the current epidemic. However, the residues that are responsible for ZIKV pathogenicity are largely unknown. Here we report the cryo-electron microscopy (cryo-EM) structure of the immature ZIKV at 9-Å resolution. The cryo-EM map was fitted with the crystal structures of the precursor membrane and envelope glycoproteins and was shown to be similar to the structures of other known immature flaviviruses...
February 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28067532/mental-stress-induced-left-ventricular-dysfunction-and-adverse-outcome-in-ischemic-heart-disease-patients
#17
Julia L Sun, Stephen H Boyle, Zainab Samad, Michael A Babyak, Jennifer L Wilson, Cynthia Kuhn, Richard C Becker, Thomas L Ortel, Redford B Williams, Joseph G Rogers, Christopher M O'Connor, Eric J Velazquez, Wei Jiang
Aims Mental stress-induced myocardial ischemia (MSIMI) occurs in up to 70% of patients with clinically stable ischemic heart disease and is associated with increased risk of adverse prognosis. We aimed to examine the prognostic value of indices of MSIMI and exercise stress-induced myocardial ischemia (ESIMI) in a population of ischemic heart disease patients that was not confined by having a recent positive physical stress test. Methods and results The Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment (REMIT) study enrolled 310 subjects who underwent mental and exercise stress testing and were followed annually for a median of four years...
January 1, 2017: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/27974654/water-relations-in-tree-physiology-where-to-from-here
#18
REVIEW
Joe Landsberg, Richard Waring
We look back over 50 years of research into the water relations of trees, with the objective of assessing the maturity of the topic in terms of the idea of a paradigm, put forward by Kuhn in 1962. Our brief review indicates that the physical processes underlying the calculation of transpiration are well understood and accepted, and knowledge of those processes can be applied if information about the leaf area of trees, and stomatal conductance, is available. Considerable progress has been made in understanding the factors governing stomatal responses to environment, with insights into how the hydraulic conducting system of trees determines the maximum aperture of stomata...
December 14, 2016: Tree Physiology
https://www.readbyqxmd.com/read/27896659/the-relationship-between-pulsatile-flow-impingement-and-intraluminal-thrombus-deposition-in-abdominal-aortic-aneurysms
#19
Richard J Lozowy, David C S Kuhn, Annie A Ducas, April J Boyd
Direct numerical simulations were performed on four patient-specific abdominal aortic aneurysm (AAA) geometries and the resulting pulsatile blood flow dynamics were compared to aneurysm shape and correlated with intraluminal thrombus (ILT) deposition. For three of the cases, turbulent vortex structures impinged/sheared along the anterior wall and along the posterior wall a zone of recirculating blood formed. Within the impingement region the AAA wall was devoid of ILT and remote to this region there was an accumulation of ILT...
November 28, 2016: Cardiovascular Engineering and Technology
https://www.readbyqxmd.com/read/27832824/genome-of-the-asian-longhorned-beetle-anoplophora-glabripennis-a-globally-significant-invasive-species-reveals-key-functional-and-evolutionary-innovations-at-the-beetle-plant-interface
#20
Duane D McKenna, Erin D Scully, Yannick Pauchet, Kelli Hoover, Roy Kirsch, Scott M Geib, Robert F Mitchell, Robert M Waterhouse, Seung-Joon Ahn, Deanna Arsala, Joshua B Benoit, Heath Blackmon, Tiffany Bledsoe, Julia H Bowsher, André Busch, Bernarda Calla, Hsu Chao, Anna K Childers, Christopher Childers, Dave J Clarke, Lorna Cohen, Jeffery P Demuth, Huyen Dinh, HarshaVardhan Doddapaneni, Amanda Dolan, Jian J Duan, Shannon Dugan, Markus Friedrich, Karl M Glastad, Michael A D Goodisman, Stephanie Haddad, Yi Han, Daniel S T Hughes, Panagiotis Ioannidis, J Spencer Johnston, Jeffery W Jones, Leslie A Kuhn, David R Lance, Chien-Yueh Lee, Sandra L Lee, Han Lin, Jeremy A Lynch, Armin P Moczek, Shwetha C Murali, Donna M Muzny, David R Nelson, Subba R Palli, Kristen A Panfilio, Dan Pers, Monica F Poelchau, Honghu Quan, Jiaxin Qu, Ann M Ray, Joseph P Rinehart, Hugh M Robertson, Richard Roehrdanz, Andrew J Rosendale, Seunggwan Shin, Christian Silva, Alex S Torson, Iris M Vargas Jentzsch, John H Werren, Kim C Worley, George Yocum, Evgeny M Zdobnov, Richard A Gibbs, Stephen Richards
BACKGROUND: Relatively little is known about the genomic basis and evolution of wood-feeding in beetles. We undertook genome sequencing and annotation, gene expression assays, studies of plant cell wall degrading enzymes, and other functional and comparative studies of the Asian longhorned beetle, Anoplophora glabripennis, a globally significant invasive species capable of inflicting severe feeding damage on many important tree species. Complementary studies of genes encoding enzymes involved in digestion of woody plant tissues or detoxification of plant allelochemicals were undertaken with the genomes of 14 additional insects, including the newly sequenced emerald ash borer and bull-headed dung beetle...
November 11, 2016: Genome Biology
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