Predictors of Disease Course in Patients with Probable Alzheimer's Disease

The presence of extrapyramidal signs or psychosis may indicate greater disability in patients with probable Alzheimer's disease. We evaluated the ability of these signs, noted at a patient's first visit, to predict one of two specific clinical endpoints: (1) a preselected score on the modified Mini-Mental State examination (cognitive endpoint), and (2) a preselected score on the Blessed Dementia Rating Scale (functional endpoint). Sixty-five patients were followed either until they reached the endpoints or to the end of the study period. Survivorship curves were drawn to predict the distribution of time to onset of an endpoint in patients with and without the clinical signs. Time to reach the cognitive endpoint was shorter for patients with extrapyramidal signs or psychosis compared with those without these signs and symptoms. These clinical signs did not predict the functional endpoint. We conclude that extrapyramidal signs and psychosis may be useful predictors of intellectual decline in Alzheimer's disease

Electron multiplication CCD detector technology advancement for the WFIRST-AFTA coronagraph

The WFIRST-AFTA (Wide Field InfraRed Survey Telescope-Astrophysics Focused Telescope Asset) is a NASA space observatory. It will host two major astronomical instruments: a wide-field imager (WFI) to search for dark energy and carry out wide field near infrared (NIR) surveys, and a coronagraph instrument (CGI) to image and spectrally characterize extrasolar planets. In this paper, we discuss the work that has been carried out at JPL in advancing Electron Multiplying CCD (EMCCD) technology to higher flight maturity, with the goal of reaching a NASA technology readiness level of 6 (TRL-6) by early-to-mid 2016. The EMCCD has been baselined for both the coronagraph's imager and integral field spectrograph (IFS) based on its sub-electron noise performance at extremely low flux levels - the regime where the AFTA CGI will operate. We present results from a study that fully characterizes the beginning of life performance of the EMCCD. We also discuss, and present initial results from, a recent radiation test campaign that was designed and carried out to mimic the conditions of the WFIRST-AFTA space environment in an L2 orbit, where we sought to assess the sensor's end of life performance, particularly degradation of its charge transfer efficiency, in addition to other parameters such as dark current, electron multiplication gain, clock induced charge and read noise

WFIRST coronagraph detector trap modeling results and improvements

The WFIRST coronagraph is being designed to detect and characterize mature exoplanets through the starlight reflected from their surfaces and atmospheres. The light incident on the detector from these distant exoplanets is estimated to be on the order of a few photons per pixel per hour. To measure such small signals, the project has baselined the CCD201 detector made by e2v, a low-noise and high-efficiency electron-multiplying charge-coupled device (EMCCD), and has instituted a rigorous test and modeling program to characterize the device prior to flight. An important consideration is detector performance degradation over the proposed mission lifetime due to radiation exposure in space. To quantify this estimated loss in performance, the project has built a detector trap model that takes into account detailed trap interactions at the sub-pixel level, including stochastic trap capture and release, and the deferment of charge into subsequent pixels during parallel and serial clocking of the pseudo-two-phase CCD201 device. This paper describes recent detector trap model improvements and modeling results

Functional diversity of marine ecosystems after the Late Permian mass extinction event

Article can be accessed from http://www.nature.com/ngeo/journal/v7/n3/full/ngeo2079.htmlThe Late Permian mass extinction event was the most severe such crisis of the past 500 million years and occurred during an episode of global warming. It is assumed to have had significant ecological impact, but its effects on marine ecosystem functioning are unknown and the patterns of marine recovery are debated. We analysed the fossil occurrences of all known Permian-Triassic benthic marine genera and assigned each to a functional group based on their inferred life habit. We show that despite the selective extinction of 62-74% of marine genera there was no significant loss of functional diversity at the global scale, and only one novel mode of life originated in the extinction aftermath. Early Triassic marine ecosystems were not as ecologically depauperate as widely assumed, which explains the absence of a Cambrian-style Triassic radiation in higher taxa. Functional diversity was, however, significantly reduced in particular regions and habitats, such as tropical reefs, and at these scales recovery varied spatially and temporally, probably driven by migration of surviving groups. Marine ecosystems did not return to their pre-extinction state, however, and radiation of previously subordinate groups such as motile, epifaunal grazers led to greater functional evenness by the Middle Triassic

Infrared spectroscopy of cationized arginine in the gas phase: direct evidence for the transition from nonzwitterionic to zwitterionic structure

Abstract: The gas-phase structures of protonated and alkali metal cationized arginine (Arg) and arginine methyl ester (ArgOMe) are investigated with infrared spectroscopy and ab initio calculations. Infrared spectra, measured in the hydrogen-stretch region, provide compelling evidence that arginine changes from its nonzwitterionic to zwitterionic form with increasing metal ion size, with the transition in structure occurring between lithium and sodium. For sodiated arginine, evidence for both forms is obtained from spectral deconvolution, although the zwitterionic form is predominant. Comparisons of the photodissociation spectra with spectra calculated for low-energy candidate structures provide additional insights into the detailed structures of these ions. Arg•Li + , ArgOMe•Li + , and ArgOMe•Na + exist in nonzwitterionic forms in which the metal ion is tricoordinated with the amino acid, whereas Arg•Na + and Arg•K + predominately exist in a zwitterionic form where the protonated side chain donates one hydrogen bond to the N terminus of the amino acid and the metal ion is bicoordinated with the carboxylate group. Arg•H + and ArgOMe•H + have protonated side chains that form the same interaction with the N terminus as zwitterionic, alkali metal cationized arginine, yet both are unambiguously determined to be nonzwitterionic. Calculations indicate that for clusters with protonated side chains, structures with two strong hydrogen bonds are lowest in energy, in disagreement with these experimental results. This study provides new detailed structural assignments and interpretations of previously observed fragmentation patterns for these ions

Combined exome and whole-genome sequencing identifies mutations in ARMC4 as a cause of primary ciliary dyskinesia with defects in the outer dynein arm

Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous ciliopathy disorder affecting cilia and sperm motility. A range of ultrastructural defects of the axoneme underlie the disease, which is characterised by chronic respiratory symptoms and obstructive lung disease, infertility and body axis laterality defects. We applied a next-generation sequencing approach to identify the gene responsible for this phenotype in two consanguineous families

Technology advancement of the CCD201-20 EMCCD for the WFIRST coronagraph instrument: sensor characterization and radiation damage

The Wide Field InfraRed Survey Telescope-Astrophysics Focused Telescope Asset (WFIRST-AFTA) mission is a 2.4-m class space telescope that will be used across a swath of astrophysical research domains. JPL will provide a high-contrast imaging coronagraph instrument—one of two major astronomical instruments. In order to achieve the low noise performance required to detect planets under extremely low flux conditions, the electron multiplying charge-coupled device (EMCCD) has been baselined for both of the coronagraph’s sensors—the imaging camera and integral field spectrograph. JPL has established an EMCCD test laboratory in order to advance EMCCD maturity to technology readiness level-6. This plan incorporates full sensor characterization, including read noise, dark current, and clock-induced charge. In addition, by considering the unique challenges of the WFIRST space environment, degradation to the sensor’s charge transfer efficiency will be assessed, as a result of damage from high-energy particles such as protons, electrons, and cosmic rays. Science-grade CCD201-20 EMCCDs have been irradiated to a proton fluence that reflects the projected WFIRST orbit. Performance degradation due to radiation displacement damage is reported, which is the first such study for a CCD201-20 that replicates the WFIRST conditions. In addition, techniques intended to identify and mitigate radiation-induced electron trapping, such as trap pumping, custom clocking, and thermal cycling, are discussed

The Impact of Global Warming and Anoxia on Marine Benthic Community Dynamics: an Example from the Toarcian (Early Jurassic)

The Pliensbachian-Toarcian (Early Jurassic) fossil record is an archive of natural data of benthic community response to global warming and marine long-term hypoxia and anoxia. In the early Toarcian mean temperatures increased by the same order of magnitude as that predicted for the near future; laminated, organic-rich, black shales were deposited in many shallow water epicontinental basins; and a biotic crisis occurred in the marine realm, with the extinction of approximately 5% of families and 26% of genera. High-resolution quantitative abundance data of benthic invertebrates were collected from the Cleveland Basin (North Yorkshire, UK), and analysed with multivariate statistical methods to detect how the fauna responded to environmental changes during the early Toarcian. Twelve biofacies were identified. Their changes through time closely resemble the pattern of faunal degradation and recovery observed in modern habitats affected by anoxia. All four successional stages of community structure recorded in modern studies are recognised in the fossil data (i.e. Stage III: climax; II: transitional; I: pioneer; 0: highly disturbed). Two main faunal turnover events occurred: (i) at the onset of anoxia, with the extinction of most benthic species and the survival of a few adapted to thrive in low-oxygen conditions (Stages I to 0) and (ii) in the recovery, when newly evolved species colonized the re-oxygenated soft sediments and the path of recovery did not retrace of pattern of ecological degradation (Stages I to II). The ordination of samples coupled with sedimentological and palaeotemperature proxy data indicate that the onset of anoxia and the extinction horizon coincide with both a rise in temperature and sea level. Our study of how faunal associations co-vary with long and short term sea level and temperature changes has implications for predicting the long-term effects of “dead zones” in modern oceans

Changing Selective Pressure during Antigenic Changes in Human Influenza H3

The rapid evolution of influenza viruses presents difficulties in maintaining the optimal efficiency of vaccines. Amino acid substitutions result in antigenic drift, a process whereby antisera raised in response to one virus have reduced effectiveness against future viruses. Interestingly, while amino acid substitutions occur at a relatively constant rate, the antigenic properties of H3 move in a discontinuous, step-wise manner. It is not clear why this punctuated evolution occurs, whether this represents simply the fact that some substitutions affect these properties more than others, or if this is indicative of a changing relationship between the virus and the host. In addition, the role of changing glycosylation of the haemagglutinin in these shifts in antigenic properties is unknown. We analysed the antigenic drift of HA1 from human influenza H3 using a model of sequence change that allows for variation in selective pressure at different locations in the sequence, as well as at different parts of the phylogenetic tree. We detect significant changes in selective pressure that occur preferentially during major changes in antigenic properties. Despite the large increase in glycosylation during the past 40 years, changes in glycosylation did not correlate either with changes in antigenic properties or with significantly more rapid changes in selective pressure. The locations that undergo changes in selective pressure are largely in places undergoing adaptive evolution, in antigenic locations, and in locations or near locations undergoing substitutions that characterise the change in antigenicity of the virus. Our results suggest that the relationship of the virus to the host changes with time, with the shifts in antigenic properties representing changes in this relationship. This suggests that the virus and host immune system are evolving different methods to counter each other. While we are able to characterise the rapid increase in glycosylation of the haemagglutinin during time in human influenza H3, an increase not present in influenza in birds, this increase seems unrelated to the observed changes in antigenic properties