A Reverse Genetics Platform That Spans the Zika Virus Family Tree

ABSTRACT Zika virus (ZIKV), a mosquito-borne flavivirus discovered in 1947, has only recently caused large outbreaks and emerged as a significant human pathogen. In 2015, ZIKV was detected in Brazil, and the resulting epidemic has spread throughout the Western Hemisphere. Severe complications from ZIKV infection include neurological disorders such as Guillain-Barré syndrome in adults and a variety of fetal abnormalities, including microcephaly, blindness, placental insufficiency, and fetal demise. There is an urgent need for tools and reagents to study the pathogenesis of epidemic ZIKV and for testing vaccines and antivirals. Using a reverse genetics platform, we generated six ZIKV infectious clones and derivative viruses representing diverse temporal and geographic origins. These include three versions of MR766, the prototype 1947 strain (with and without a glycosylation site in the envelope protein), and H/PF/2013, a 2013 human isolate from French Polynesia representative of the virus introduced to Brazil. In the course of synthesizing a clone of a circulating Brazilian strain, phylogenetic studies identified two distinct ZIKV clades in Brazil. We reconstructed viable clones of strains SPH2015 and BeH819015, representing ancestral members of each clade. We assessed recombinant virus replication, binding to monoclonal antibodies, and virulence in mice. This panel of molecular clones and recombinant virus isolates will enable targeted studies of viral determinants of pathogenesis, adaptation, and evolution, as well as the rational attenuation of contemporary outbreak strains to facilitate the design of vaccines and therapeutics. IMPORTANCE Viral emergence is a poorly understood process as evidenced by the sudden emergence of Zika virus in Latin America and the Caribbean. Malleable reagents that both predate and span an expanding epidemic are key to understanding the virologic determinants that regulate pathogenesis and transmission. We have generated representative cDNA molecular clones and recombinant viruses that span the known ZIKV family tree, including early Brazilian isolates. Recombinant viruses replicated efficiently in cell culture and were pathogenic in immunodeficient mice, providing a genetic platform for rational vaccine and therapeutic design

Self-directed growth of AlGaAs core-shell nanowires for visible light applications

Al(0.37)Ga(0.63)As nanowires (NWs) were grown in a molecular beam epitaxy system on GaAs(111)B substrates. Micro-photoluminescence measurements and energy dispersive X-ray spectroscopy indicated a core-shell structure and Al composition gradient along the NW axis, producing a potential minimum for carrier confinement. The core-shell structure formed during the growth as a consequence of the different Al and Ga adatom diffusion lengths.Comment: 20 pages, 7 figure

3D Position Sensitive XeTPC for Dark Matter Search

The technique to realize 3D position sensitivity in a two-phase xenon time projection chamber (XeTPC) for dark matter search is described. Results from a prototype detector (XENON3) are presented.Comment: Presented at the 7th UCLA Symposium on "Sources and Detection of Dark Matter and Dark Energy in the Universe

First Results from the XENON10 Dark Matter Experiment at the Gran Sasso National Laboratory

The XENON10 experiment at the Gran Sasso National Laboratory uses a 15 kg xenon dual phase time projection chamber (XeTPC) to search for dark matter weakly interacting massive particles (WIMPs). The detector measures simultaneously the scintillation and the ionization produced by radiation in pure liquid xenon, to discriminate signal from background down to 4.5 keV nuclear recoil energy. A blind analysis of 58.6 live days of data, acquired between October 6, 2006 and February 14, 2007, and using a fiducial mass of 5.4 kg, excludes previously unexplored parameter space, setting a new 90% C.L. upper limit for the WIMP-nucleon spin-independent cross-section of 8.8 x 10^{-44} cm^2 for a WIMP mass of 100 GeV/c^2, and 4.5 x 10^{-44} cm^2 for a WIMP mass of 30 GeV/c^2. This result further constrains predictions of supersymmetric models.Comment: accepted for publication in Phys. Rev. Let

Religious faith and psychosocial adaptation among stroke patients in Kuwait: A mixed method study

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2012 Springer Science+Business Media.Religious faith is central to life for Muslim patients in Kuwait, so it may influence adaptation and rehabilitation. This study explored quantitative associations among religious faith, self-efficacy, and life satisfaction in 40 female stroke patients and explored the influence of religion within stroke rehabilitation through qualitative interviews with 12 health professionals. The quantitative measure of religious faith did not relate to life satisfaction or self-efficacy in stroke patients. However, the health professionals described religious coping as influencing adaptation post-stroke. Fatalistic beliefs were thought to have mixed influences on rehabilitation. Measuring religious faith among Muslims through a standardized scale is debated. The qualitative accounts suggest that religious beliefs need to be acknowledged in stroke rehabilitation in Kuwait

Constraints on inelastic dark matter from XENON10

It has been suggested that dark matter particles which scatter inelastically from detector target nuclei could explain the apparent incompatibility of the DAMA modulation signal (interpreted as evidence for particle dark matter) with the null results from CDMS-II and XENON10. Among the predictions of inelastically interacting dark matter are a suppression of low-energy events, and a population of nuclear recoil events at higher nuclear recoil equivalent energies. This is in stark contrast to the well-known expectation of a falling exponential spectrum for the case of elastic interactions. We present a new analysis of XENON10 dark matter search data extending to E$_{nr}=75$ keV nuclear recoil equivalent energy. Our results exclude a significant region of previously allowed parameter space in the model of inelastically interacting dark matter. In particular, it is found that dark matter particle masses $m_{\chi}\gtrsim150$ GeV are disfavored.Comment: 8 pages, 4 figure

A search for light dark matter in XENON10 data

We report results of a search for light (<10 GeV) particle dark matter with the XENON10 detector. The event trigger was sensitive to a single electron, with the analysis threshold of 5 electrons corresponding to 1.4 keV nuclear recoil energy. Considering spin-independent dark matter-nucleon scattering, we exclude cross sections \sigma_n>3.5x10^{-42} cm^2, for a dark matter particle mass m_{\chi}=8 GeV. We find that our data strongly constrain recent elastic dark matter interpretations of excess low-energy events observed by CoGeNT and CRESST-II, as well as the DAMA annual modulation signal.Comment: Manuscript identical to v2 (published version) but also contains erratum. Note v3==v2 but without \linenumber

Effects of Sleep Deprivation on Brain Bioenergetics, Sleep, and Cognitive Performance in Cocaine-Dependent Individuals

In cocaine-dependent individuals, sleep is disturbed during cocaine use and abstinence, highlighting the importance of examining the behavioral and homeostatic response to acute sleep loss in these individuals. The current study was designed to identify a differential effect of sleep deprivation on brain bioenergetics, cognitive performance, and sleep between cocaine-dependent and healthy control participants. 14 healthy control and 8 cocaine-dependent participants experienced consecutive nights of baseline, total sleep deprivation, and recovery sleep in the research laboratory. Participants underwent [31]P magnetic resonance spectroscopy (MRS) brain imaging, polysomnography, Continuous Performance Task, and Digit Symbol Substitution Task. Following recovery sleep, [31]P MRS scans revealed that cocaine-dependent participants exhibited elevated global brain β-NTP (direct measure of adenosine triphosphate), α-NTP, and total NTP levels compared to those of healthy controls. Cocaine-dependent participants performed worse on the Continuous Performance Task and Digit Symbol Substitution Task at baseline compared to healthy control participants, but sleep deprivation did not worsen cognitive performance in either group. Enhancements of brain ATP levels in cocaine dependent participants following recovery sleep may reflect a greater impact of sleep deprivation on sleep homeostasis, which may highlight the importance of monitoring sleep during abstinence and the potential influence of sleep loss in drug relapse

Evaluation of the low-lying energy levels of two- and three-electron configurations for multi-charged ions

Accurate QED evaluations of the one- and two-photon interelectron interaction for low lying two- and three-electron configurations for ions with nuclear charge numbers $60\le Z \le 93$ are performed. The three-photon interaction is also partly taken into account. The Coulomb gauge is employed. The results are compared with available experimental data and with different calculations. A detailed investigation of the behaviour of the energy levels of the configurations $1s_{1/2}2s_{1/2} {}^1 S_0$, $1s_{1/2}2p_{1/2} {}^3 P_0$ near the crossing points Z=64 and Z=92 is carried out. The crossing points are important for the future experimental search for parity nonconserving (PNC) effects in highly charged ions