Are Type Ia Supernovae in Rest-frame H Brighter in More Massive Galaxies?

K.A.P., M.W.-V., and L.G. were supported in part by the US National Science Foundation under grant AST-1311862. K.A. P. additionally acknowledges support from PITT PACC. K.A. P. was also supported in part by the Berkeley Center for Cosmological Physics and the Director, Office of Science, Office of High Energy Physics of the U.S. Department of Energy under contract No. DE-AC02-05CH11231 and U.S. Department of Energy Office of Science under contract No. DE-AC02-76SF00515. L.G. was additionally funded in part by the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 839090. We thank the referee, whose comments have improved this paper, and Saurabh Jha, Kyle Boone, and Ravi Gupta for useful conversations. This research has made use of the NASA/IPAC Extragalactic Database (NED), which is funded by the National Aeronautics and Space Administration and operated by the California Institute of Technology. Funding for the Sloan Digital Sky Survey IV has been provided by the Alfred P. Sloan Foundation, the U.S. Department of Energy Office of Science, and the Participating Institutions. SDSS-IV acknowledges support and resources from the Center for High-Performance Computing at the University of Utah. The SDSS website is www.sdss.org. SDSS-IV is managed by the Astrophysical Research Consortium for the Participating Institutions of the SDSS Collaboration, including the Brazilian Participation Group, the Carnegie Institution for Science, Carnegie Mellon University, the Chilean Participation Group, the French Participation Group, Harvard-Smithsonian Center for Astrophysics, Instituto de Astrofisica de Canarias, Johns Hopkins University, Kavli Institute for the Physics and Mathematics of the Universe (IPMU)/University of Tokyo, Lawrence Berkeley National Laboratory, Leibniz Institut fur Astrophysik Potsdam (AIP), Max-Planck-Institut fur Astronomie (MPIA Heidelberg), Max-Planck-Institut fur Astrophysik (MPA Garching), Max-Planck-Institut fur Extraterrestrische Physik (MPE), National Astronomical Observatories of China, New Mexico State University, New York University, University of Notre Dame, Observatario Nacional/MCTI, The Ohio State University, Pennsylvania State University, Shanghai Astronomical Observatory, United Kingdom Participation Group, Universidad Nacional Autonoma de Mexico, University of Arizona, University of Colorado Boulder, University of Oxford, University of Portsmouth, University of Utah, University of Virginia, University of Washington, University of Wisconsin, Vanderbilt University, and Yale University. This research uses services or data provided by the Astro Data Lab at NSF's National Optical-Infrared Astronomy Research Laboratory. NOIRLab is operated by the Association of Universities for Research in Astronomy (AURA), Inc., under a cooperative agreement with the National Science Foundation. The Legacy Surveys consist of three individual and complementary projects: the Dark Energy Camera Legacy Survey (DECaLS; Proposal ID #2014B-0404; PIs: David Schlegel and Arjun Dey), the Beijing-Arizona Sky Survey (BASS; NOAO Prop. ID #2015A-0801; PIs: Zhou Xu and Xiaohui Fan), and the Mayall z-band Legacy Survey (MzLS; Prop. ID #2016A-0453; PI: Arjun Dey). DECaLS, BASS, and MzLS together include data obtained, respectively, at the Blanco telescope, Cerro Tololo Inter-American Observatory, NSF's NOIRLab; the Bok telescope, Steward Observatory, University of Arizona; and the Mayall telescope, Kitt Peak National Observatory, NOIRLab. The Legacy Surveys project is honored to be permitted to conduct astronomical research on Iolkam Du'ag (Kitt Peak), a mountain with particular significance to the Tohono O'odham Nation. This project used data obtained with the Dark Energy Camera (DECam), which was constructed by the Dark Energy Survey (DES) collaboration. Funding for the DES Projects has been provided by the U.S. Department of Energy, the U.S. National Science Foundation, the Ministry of Science and Education of Spain, the Science and Technology Facilities Council of the United Kingdom, the Higher Education Funding Council for England, the National Center for Supercomputing Applications at the University of Illinois at Urbana-Champaign, the Kavli Institute of Cosmological Physics at the University of Chicago, Center for Cosmology and Astro-Particle Physics at The Ohio State University, the Mitchell Institute for Fundamental Physics and Astronomy at Texas A&M University, Financiadora de Estudos e Projetos, Fundacao Carlos Chagas Filho de Amparo, Financiadora de Estudos e Projetos, Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico and the Ministerio da Ciencia, Tecnologia e Inovacao, the Deutsche Forschungsgemeinschaft and the Collaborating Institutions in the Dark Energy Survey. The Collaborating Institutions are Argonne National Laboratory, the University of California at Santa Cruz, the University of Cambridge, Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas-Madrid, the University of Chicago, University College London, the DES-Brazil Consortium, the University of Edinburgh, the Eidgenossische Technische Hochschule (ETH) Zurich, Fermi National Accelerator Laboratory, the University of Illinois at UrbanaChampaign, the Institut de Ciencies de l'Espai (IEEC/CSIC), the Institut de Fisica d'Altes Energies, Lawrence Berkeley National Laboratory, the Ludwig Maximilians Universitat Munchen and the associated Excellence Cluster Universe, the University of Michigan, NSF's NOIRLab, the University of Nottingham, The Ohio State University, the University of Pennsylvania, the University of Portsmouth, SLAC National Accelerator Laboratory, Stanford University, the University of Sussex, and Texas A&M University. The Legacy Survey team makes use of data products from the Near-Earth Object Wide-field Infrared Survey Explorer (NEOWISE), which is a project of the Jet Propulsion Laboratory/California Institute of Technology. NEOWISE is funded by the National Aeronautics and Space Administration. The Legacy Surveys imaging of the DESI footprint is supported by the Director, Office of Science, Office of High Energy Physics of the U.S. Department of Energy under contract No. DE-AC02-05CH1123; by the National Energy Research Scientific Computing Center, a DOE Office of Science User Facility under the same contract; and by the U.S. National Science Foundation, Division of Astronomical Sciences under contract No. AST-0950945 to NOAO. This publication makes use of data products from the Two Micron All Sky Survey, which is a joint project of the University of Massachusetts and the Infrared Processing and Analysis Center/California Institute of Technology, funded by the National Aeronautics and Space Administration and the National Science Foundation. This research has made use of the NASA/IPAC Infrared Science Archive, which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration. Some of the data presented in this paper were obtained from the Mikulski Archive for Space Telescopes (MAST). STScI is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS5-26555. Support for MAST for non-HST data is provided by the NASA Office of Space Science via grant NNX09AF08G and by other grants and contracts.We analyze 143 Type Ia supernovae (SNe Ia) observed in H band (1.6-1.8 mu m) and find that SNe Ia are intrinsically brighter in H band with increasing host galaxy stellar mass. We find that SNe Ia in galaxies more massive than 10(10)(.4)(3) M-circle dot are 0.13 +/- 0.04 mag brighter in H than SNe Ia in less massive galaxies. The same set of SNe Ia observed at optical wavelengths, after width-color-luminosity corrections, exhibit a 0.10 +/- 0.03 mag offset in the Hubble residuals. We observe an outlier population (vertical bar Delta H-max vertical bar > 0.5 mag) in the H band and show that removing the outlier population moves the mass threshold to 10(10.65) M-circle dot and reduces the step in H band to 0.08 +/- 0.04 mag, but the equivalent optical mass step is increased to 0.13 +/- 0.04 mag. We conclude that the outliers do not drive the brightness-host-mass correlation. Less massive galaxies preferentially host more higher-stretch SNe Ia, which are intrinsically brighter and bluer. It is only after correction for width-luminosity and color- luminosity relationships that SNe Ia have brighter optical Hubble residuals in more massive galaxies. Thus, finding that SNe Ia are intrinsically brighter in H in more massive galaxies is an opposite correlation to the intrinsic (prewidth-luminosity correction) optical brightness. If dust and the treatment of intrinsic color variation were the main driver of the host galaxy mass correlation, we would not expect a correlation of brighter H-band SNe Ia in more massive galaxies.National Science Foundation (NSF) AST-1311862PITT PACCBerkeley Center for Cosmological PhysicsUnited States Department of Energy (DOE) DE-AC02-05CH11231 DE-AC02-05CH1123 DE-AC02-76SF00515European Commission 839090National Aeronautics & Space Administration (NASA)Alfred P. Sloan FoundationUnited States Department of Energy (DOE)Participating InstitutionsCenter for High-Performance Computing at the University of UtahSDSS Collaboration, including the Brazilian Participation GroupCarnegie Institution for Science, Carnegie Mellon UniversityChilean Participation GroupFrench Participation GroupSmithsonian InstitutionHarvard-Smithsonian Center for AstrophysicsInstituto de Astrofisica de CanariasJohns Hopkins UniversityKavli Institute for the Physics and Mathematics of the Universe (IPMU)/University of TokyoUnited States Department of Energy (DOE)Leibniz Institut fur Astrophysik Potsdam (AIP)Max-Planck-Institut fur Astronomie (MPIA Heidelberg) Max-Planck-Institut fur Astrophysik (MPA Garching) Max-Planck-Institut fur Extraterrestrische Physik (MPE)National Astronomical Observatories of ChinaNew Mexico State UniversityNew York UniversityUniversity of Notre DameObservatario Nacional/MCTIOhio State UniversityPennsylvania State UniversityShanghai Astronomical ObservatoryUnited Kingdom Participation GroupUniversidad Nacional Autonoma de MexicoUniversity of ArizonaUniversity of Colorado BoulderUniversity of OxfordUniversity of PortsmouthUniversity of UtahUniversity of VirginiaUniversity of WashingtonUniversity of WisconsinVanderbilt UniversityYale UniversityUnited States Department of Energy (DOE)National Science Foundation (NSF)Spanish GovernmentUK Research & Innovation (UKRI)Science & Technology Facilities Council (STFC)UK Research & Innovation (UKRI)Higher Education Funding Council for EnglandNational Center for Supercomputing Applications at the University of Illinois at Urbana-ChampaignKavli Institute of Cosmological Physics at the University of ChicagoOhio State UniversityMitchell Institute for Fundamental Physics and Astronomy at Texas AM UniversityFinanciadora de Inovacao e Pesquisa (Finep)Fundacao Carlos Chagas Filho de Amparo Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio De Janeiro (FAPERJ)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ)Spanish GovernmentGerman Research Foundation (DFG)Collaborating Institutions in the Dark Energy SurveyNational Energy Research Scientific Computing CenterUnited States Department of Energy (DOE)National Science Foundation (NSF) NSF - Directorate for Mathematical & Physical Sciences (MPS) AST-0950945Association of Universities for Research in Astronomy, Inc., under NASA NAS5-26555 National Aeronautics & Space Administration (NASA) NNX09AF08

Long-Term Survival after Gamma Knife Radiosurgery in a Case of Recurrent Glioblastoma Multiforme: A Case Report and Review of the Literature

The management of recurrent glioblastoma is highly challenging, and treatment outcomes remain uniformly poor. Glioblastoma is a highly infiltrative tumor, and complete surgical resection of all microscopic extensions cannot be achieved at the time of initial diagnosis, and hence local recurrence is observed in most patients. Gamma Knife radiosurgery has been used to treat these tumor recurrences for select cases and has been successful in prolonging the median survival by 8–12 months on average for select cases. We present the unique case of a 63-year-old male with multiple sequential recurrences of glioblastoma after initial standard treatment with surgery followed by concomitant external beam radiation therapy and chemotherapy (temozolomide). The patient was followed clinically as well as with surveillance MRI scans at every 2-3-month intervals. The patient underwent Gamma Knife radiosurgery three times for 3 separate tumor recurrences, and the patient survived for seven years following the initial diagnosis with this aggressive treatment. The median survival in patients with recurrent glioblastoma is usually 8–12 months after recurrence, and this unique case illustrates that aggressive local therapy can lead to long-term survivors in select situations. We advocate that each patient treatment at the time of recurrence should be tailored to each clinical situation and desire for quality of life and improved longevity

Multiple HIV-1-specific IgG3 responses decline during acute HIV-1: implications for detection of incident HIV infection

Different HIV-1 antigen specificities appear in sequence after HIV-1 transmission and the immunoglobulin G (IgG) subclass responses to HIV antigens are distinct from each other. The initial predominant IgG subclass response to HIV-1 infection consists of IgG1 and IgG3 antibodies with a noted decline in some IgG3 antibodies during acute HIV-1 infection. Thus, we postulate that multiple antigen-specific IgG3 responses may serve as surrogates for the relative time since HIV-1 acquisition

Genetic Variants Associated With Cancer Therapy-Induced Cardiomyopathy

BACKGROUND: Cancer therapy-induced cardiomyopathy (CCM) is associated with cumulative drug exposures and preexisting cardiovascular disorders. These parameters incompletely account for substantial interindividual susceptibility to CCM. We hypothesized that rare variants in cardiomyopathy genes contribute to CCM. METHODS: We studied 213 patients with CCM from 3 cohorts: retrospectively recruited adults with diverse cancers (n=99), prospectively phenotyped adults with breast cancer (n=73), and prospectively phenotyped children with acute myeloid leukemia (n=41). Cardiomyopathy genes, including 9 prespecified genes, were sequenced. The prevalence of rare variants was compared between CCM cohorts and The Cancer Genome Atlas participants (n=2053), healthy volunteers (n=445), and an ancestry-matched reference population. Clinical characteristics and outcomes were assessed and stratified by genotypes. A prevalent CCM genotype was modeled in anthracycline-treated mice. RESULTS: CCM was diagnosed 0.4 to 9 years after chemotherapy; 90% of these patients received anthracyclines. Adult patients with CCM had cardiovascular risk factors similar to the US population. Among 9 prioritized genes, patients with CCM had more rare protein-altering variants than comparative cohorts ( P≤1.98e-04). Titin-truncating variants (TTNtvs) predominated, occurring in 7.5% of patients with CCM versus 1.1% of The Cancer Genome Atlas participants ( P=7.36e-08), 0.7% of healthy volunteers ( P=3.42e-06), and 0.6% of the reference population ( P=5.87e-14). Adult patients who had CCM with TTNtvs experienced more heart failure and atrial fibrillation ( P=0.003) and impaired myocardial recovery ( P=0.03) than those without. Consistent with human data, anthracycline-treated TTNtv mice and isolated TTNtv cardiomyocytes showed sustained contractile dysfunction unlike wild-type ( P=0.0004 and P<0.002, respectively). CONCLUSIONS: Unrecognized rare variants in cardiomyopathy-associated genes, particularly TTNtvs, increased the risk for CCM in children and adults, and adverse cardiac events in adults. Genotype, along with cumulative chemotherapy dosage and traditional cardiovascular risk factors, improves the identification of patients who have cancer at highest risk for CCM. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01173341; AAML1031; NCT01371981.This work was supported in part by grants from the Instituto de Salud Carlos III (ISCIII) (PI15/01551, PI17/01941 and CB16/11/00432 to P.G-P. and L.A-P.), the Spanish Ministry of Economy and Competitiveness (SAF2015-71863-REDT to P.G-P.), the John S. LaDue Memorial Fellowship at Harvard Medical School (Y.K.), Wellcome Trust (107469/Z/15/Z to J.S.W.), Medical Research Council (intramural awards to S.A.C. and J.S.W; MR/M003191/1 to U.T), National Institute for Health Research Biomedical Research Unit at the Royal Brompton and Harefield National Health Service Foundation Trust and Imperial College London (P.J.B., S.A.C., J.S.W.), National Institute for Health Research Biomedical Research Centre at Imperial College London Healthcare National Health Service Trust and Imperial College London (D.O.R., S.A.C., S.P., J.S.W.), Sir Henry Wellcome Postdoctoral Fellowship (C.N.T.), Rosetrees and Stoneygate Imperial College Research Fellowship (N.W.), Fondation Leducq (S.A.C., C.E.S., J.G.S.), Health Innovation Challenge Fund award from the Wellcome Trust and Department of Health (UK; HICF-R6-373; S.A.C., P.J.B., J.S. W.), the British Heart Foundation (NH/17/1/32725 to D.O.R.; SP/10/10/28431 to S.A.C), Alex’s Lemonade Stand Foundation (K.G.), National Institutes of Health (R.A.: U01CA097452, R01CA133881, and U01CA097452; Z.A.: R01 HL126797; B.K.: R01 HL118018 and K23-HL095661; J.G.S. and C.E.S.: 5R01HL080494, R01HL084553), and the Howard Hughes Medical Institute (C.E.S.). The Universitario Puerta de Hierro and Virgen de la Arrixaca Hospitals are members of the European Reference Network on Rare and Complex Diseases of the Heart (Guard-Heart; http://guard-heart.ern-net.eu). This publication includes independent research commissioned by the Health Innovation Challenge Fund (HICF), a parallel funding partnership between the Department of Health and Wellcome Trust. The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Ministry of Economy, Industry and Competitiveness and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Grants from ISCIII and the Spanish Ministry of Economy and Competitiveness are supported by the Plan Estatal de I+D+I 2013-2016 – European Regional Development Fund (FEDER) “A way of making Europe”.S

Illusions of Visual Motion Elicited by Electrical Stimulation of Human MT Complex

Human cortical area MT+ (hMT+) is known to respond to visual motion stimuli, but its causal role in the conscious experience of motion remains largely unexplored. Studies in non-human primates demonstrate that altering activity in area MT can influence motion perception judgments, but animal studies are inherently limited in assessing subjective conscious experience. In the current study, we use functional magnetic resonance imaging (fMRI), intracranial electrocorticography (ECoG), and electrical brain stimulation (EBS) in three patients implanted with intracranial electrodes to address the role of area hMT+ in conscious visual motion perception. We show that in conscious human subjects, reproducible illusory motion can be elicited by electrical stimulation of hMT+. These visual motion percepts only occurred when the site of stimulation overlapped directly with the region of the brain that had increased fMRI and electrophysiological activity during moving compared to static visual stimuli in the same individual subjects. Electrical stimulation in neighboring regions failed to produce illusory motion. Our study provides evidence for the sufficient causal link between the hMT+ network and the human conscious experience of visual motion. It also suggests a clear spatial relationship between fMRI signal and ECoG activity in the human brain

The Development of Therapeutic Antibodies That Neutralize Homologous and Heterologous Genotypes of Dengue Virus Type 1

Antibody protection against flaviviruses is associated with the development of neutralizing antibodies against the viral envelope (E) protein. Prior studies with West Nile virus (WNV) identified therapeutic mouse and human monoclonal antibodies (MAbs) that recognized epitopes on domain III (DIII) of the E protein. To identify an analogous panel of neutralizing antibodies against DENV type-1 (DENV-1), we immunized mice with a genotype 2 strain of DENV-1 virus and generated 79 new MAbs, 16 of which strongly inhibited infection by the homologous virus and localized to DIII. Surprisingly, only two MAbs, DENV1-E105 and DENV1-E106, retained strong binding and neutralizing activity against all five DENV-1 genotypes. In an immunocompromised mouse model of infection, DENV1-E105 and DENV1-E106 exhibited therapeutic activity even when administered as a single dose four days after inoculation with a heterologous genotype 4 strain of DENV-1. Using epitope mapping and X-ray crystallographic analyses, we localized the neutralizing determinants for the strongly inhibitory MAbs to distinct regions on DIII. Interestingly, sequence variation in DIII alone failed to explain disparities in neutralizing potential of MAbs among different genotypes. Overall, our experiments define a complex structural epitope on DIII of DENV-1 that can be recognized by protective antibodies with therapeutic potential

Computational Identification of Transcriptional Regulators in Human Endotoxemia

One of the great challenges in the post-genomic era is to decipher the underlying principles governing the dynamics of biological responses. As modulating gene expression levels is among the key regulatory responses of an organism to changes in its environment, identifying biologically relevant transcriptional regulators and their putative regulatory interactions with target genes is an essential step towards studying the complex dynamics of transcriptional regulation. We present an analysis that integrates various computational and biological aspects to explore the transcriptional regulation of systemic inflammatory responses through a human endotoxemia model. Given a high-dimensional transcriptional profiling dataset from human blood leukocytes, an elementary set of temporal dynamic responses which capture the essence of a pro-inflammatory phase, a counter-regulatory response and a dysregulation in leukocyte bioenergetics has been extracted. Upon identification of these expression patterns, fourteen inflammation-specific gene batteries that represent groups of hypothetically ‘coregulated’ genes are proposed. Subsequently, statistically significant cis-regulatory modules (CRMs) are identified and decomposed into a list of critical transcription factors (34) that are validated largely on primary literature. Finally, our analysis further allows for the construction of a dynamic representation of the temporal transcriptional regulatory program across the host, deciphering possible combinatorial interactions among factors under which they might be active. Although much remains to be explored, this study has computationally identified key transcription factors and proposed a putative time-dependent transcriptional regulatory program associated with critical transcriptional inflammatory responses. These results provide a solid foundation for future investigations to elucidate the underlying transcriptional regulatory mechanisms under the host inflammatory response. Also, the assumption that coexpressed genes that are functionally relevant are more likely to share some common transcriptional regulatory mechanism seems to be promising, making the proposed framework become essential in unravelling context-specific transcriptional regulatory interactions underlying diverse mammalian biological processes

Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses.

The third variable (V3) loop and the CD4 binding site (CD4bs) of the HIV-1 envelope are frequently targeted by neutralizing antibodies (nAbs) in infected individuals. In chronic infection, HIV-1 escape mutants repopulate the plasma, and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3 and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tier 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses

Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses

The third variable (V3) loop and the CD4 binding site (CD4bs) of the HIV-1 envelope are frequently targeted by neutralizing antibodies (nAbs) in infected individuals. In chronic infection, HIV-1 escape mutants repopulate the plasma, and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize, but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tier 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses