A HPMT based set-up to characterize scintillating crystals

We have developed a fully automatic measurement set-up, capable of measuring light yields arising from scintillating crystals in a linear range of about four orders of magnitude. The photodetector is a Hybrid Photomultiplier Tube especially developed to optimize linear range and photon detection. Crystal and photodetector are temperature controlled by a closed water circuit, as this is essential when measuring low light yield scintillating crystals with a marked temperature dependence of their light yield. Gamma sources can be placed either on top or on the side of the crystal. In this latter case, the source can be automatically moved by a computer-controlled step motor to provide a uniformity profile of the light yield along the crystal. Tagged and not-tagged operation modes are possible. The whole set-up is computer-controlled in an effort to provide fast and reliable measurements, to characterize many crystals per day. This is important for the quality control of the Lead Tungstate crystals that will be applied in the electromagnetic calorimeter of the CMS-detector at the LHC at CERN

Novelty Enhances Visual Perception

The effects of novelty on low-level visual perception were investigated in two experiments using a two-alternative forced-choice tilt detection task. A target, consisting of a Gabor patch, was preceded by a cue that was either a novel or a familiar fractal image. Participants had to indicate whether the Gabor stimulus was vertically oriented or slightly tilted. In the first experiment tilt angle was manipulated; in the second contrast of the Gabor patch was varied. In the first, we found that sensitivity was enhanced after a novel compared to a familiar cue, and in the second we found sensitivity to be enhanced for novel cues in later experimental blocks when participants became more and more familiarized with the familiar cue. These effects were not caused by a shift in the response criterion. This shows for the first time that novel stimuli affect low-level characteristics of perception. We suggest that novelty can elicit a transient attentional response, thereby enhancing perception

phenix.model_vs_data: a high-level tool for the calculation of crystallographic model and data statistics

Application of phenix.model_vs_data to the contents of the Protein Data Bank shows that the vast majority of deposited structures can be automatically analyzed to reproduce the reported quality statistics. However, the small fraction of structures that elude automated re-analysis highlight areas where new software developments can help retain valuable information for future analysis

Why and how does shared language affect subsidiary knowledge inflows? A social identity perspective

We draw on social identity theory to conceptualize a moderated mediation model that examines the relationship between shared language among subsidiary and HQ managers, and subsidiaries’ knowledge inflows from HQ. Specifically, we study (1) whether this relationship is mediated by the extent to which subsidiary managers share HQ goals and vision, and the extent to which HR decisions are centralized; and (2) whether subsidiary type moderates these mediated relationships. Building on a sample of 817 subsidiaries in nine countries/regions, we find support for our model. Implications for research on HQ-subsidiary knowledge flows, social identity theory and international HRM are discussed

Towards automated crystallographic structure refinement with phenix.refine

phenix.refine is a program within the PHENIX package that supports crystallographic structure refinement against experimental data with a wide range of upper resolution limits using a large repertoire of model parameterizations. This paper presents an overview of the major phenix.refine features, with extensive literature references for readers interested in more detailed discussions of the methods

Optimal timing of antiretroviral treatment initiation in HIV-positive children and adolescents: a multiregional analysis from Southern Africa, West Africa and Europe

BACKGROUND: There is limited knowledge about the optimal timing of antiretroviral treatment initiation in older children and adolescents. METHODS: A total of 20 576 antiretroviral treatment (ART)-naïve patients, aged 1-16 years at enrolment, from 19 cohorts in Europe, Southern Africa and West Africa, were included. We compared mortality and growth outcomes for different ART initiation criteria, aligned with previous and recent World Health Organization criteria, for 5 years of follow-up, adjusting for all measured baseline and time-dependent confounders using the g-formula. RESULTS: Median (1st;3rd percentile) CD4 count at baseline was 676 cells/mm(3) (394; 1037) (children aged ≥ 1 and 10 years at enrolment we did not find any difference in mortality or growth with immediate ART initiation, with estimated differences of -0.1% (-0.2%; 0.6%) and -0.03 (-0.05; 0.00), respectively. Growth differences in children aged < 10 years persisted for treatment thresholds using higher CD4 values. Regular follow-up led to better height and mortality outcomes. CONCLUSIONS: Immediate ART is associated with lower mortality and better growth for up to 5 years in children < 10 years old. Our results on adolescents were inconclusive

Inhibition of Nipah Virus Infection In Vivo: Targeting an Early Stage of Paramyxovirus Fusion Activation during Viral Entry

In the paramyxovirus cell entry process, receptor binding triggers conformational changes in the fusion protein (F) leading to viral and cellular membrane fusion. Peptides derived from C-terminal heptad repeat (HRC) regions in F have been shown to inhibit fusion by preventing formation of the fusogenic six-helix bundle. We recently showed that the addition of a cholesterol group to HRC peptides active against Nipah virus targets these peptides to the membrane where fusion occurs, dramatically increasing their antiviral effect. In this work, we report that unlike the untagged HRC peptides, which bind to the postulated extended intermediate state bridging the viral and cell membranes, the cholesterol tagged HRC-derived peptides interact with F before the fusion peptide inserts into the target cell membrane, thus capturing an earlier stage in the F-activation process. Furthermore, we show that cholesterol tagging renders these peptides active in vivo: the cholesterol-tagged peptides cross the blood brain barrier, and effectively prevent and treat in an established animal model what would otherwise be fatal Nipah virus encephalitis. The in vivo efficacy of cholesterol-tagged peptides, and in particular their ability to penetrate the CNS, suggests that they are promising candidates for the prevention or therapy of infection by Nipah and other lethal paramyxoviruses

No need for secondary Pneumocystis jirovecii pneumonia prophylaxis in adult people living with HIV from Europe on ART with suppressed viraemia and a CD4 cell count greater than 100 cells/µL.

INTRODUCTION: Since the beginning of the HIV epidemic in resource-rich countries, Pneumocystis jirovecii pneumonia (PjP) is one of the most frequent opportunistic AIDS-defining infections. The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) has shown that primary Pneumocystis jirovecii Pneumonia (PjP) prophylaxis can be safely withdrawn in patients with CD4 counts of 100 to 200 cells/µL if plasma HIV-RNA is suppressed on combination antiretroviral therapy. Whether this holds true for secondary prophylaxis is not known, and this has proved difficult to determine due to the much lower population at risk. METHODS: We estimated the incidence of secondary PjP by including patient data collected from 1998 to 2015 from the COHERE cohort collaboration according to time-updated CD4 counts, HIV-RNA and use of PjP prophylaxis in persons >16 years of age. We fitted a Poisson generalized additive model in which the smoothed effect of CD4 was modelled by a restricted cubic spline, and HIV-RNA was stratified as low (10,000copies/mL). RESULTS: There were 373 recurrences of PjP during 74,295 person-years (py) in 10,476 patients. The PjP incidence in the different plasma HIV-RNA strata differed significantly and was lowest in the low stratum. For patients off prophylaxis with CD4 counts between 100 and 200 cells/µL and HIV-RNA below 400 copies/mL, the incidence of recurrent PjP was 3.9 (95% CI: 2.0 to 5.8) per 1000 py, not significantly different from patients on prophylaxis in the same stratum (1.9, 95% CI: 0.1 to 3.7). CONCLUSIONS: HIV viraemia importantly affects the risk of recurrent PjP. In virologically suppressed patients on ART with CD4 counts of 100 to 200/µL, the incidence of PjP off prophylaxis is below 10/1000 py. Secondary PjP prophylaxis may be safely withheld in such patients. While European guidelines recommend discontinuing secondary PjP prophylaxis only if CD4 counts rise above 200 cells/mL, the latest US Guidelines consider secondary prophylaxis discontinuation even in patients with a CD4 count above 100 cells/µL and suppressed viral load. Our results strengthen and support this US recommendation

Dysregulation of specialized delay/interference-dependent working memory following loss of dysbindin-1A in schizophrenia-related phenotypes

Dysbindin-1, a protein that regulates aspects of early and late brain development, has been implicated in the pathobiology of schizophrenia. As the functional roles of the three major isoforms of dysbindin-1, (A, B, and C) remain unknown, we generated a novel mutant mouse, dys-1A -/-, with selective loss of dysbindin-1A and investigated schizophrenia-related phenotypes in both males and females. Loss of dysbindin-1A resulted in heightened initial exploration and disruption in subsequent habituation to a novel environment, together with heightened anxiety-related behavior in a stressful environment. Loss of dysbindin-1A was not associated with disruption of either long-term (olfactory) memory or spontaneous alternation behavior. However, dys-1A -/-showed enhancement in delay-dependent working memory under high levels of interference relative to controls, ie, impairment in sensitivity to the disruptive effect of such interference. These findings in dys-1A -/-provide the first evidence for differential functional roles for dysbindin-1A vs dysbindin-1C isoforms among phenotypes relevant to the pathobiology of schizophrenia. Future studies should investigate putative sex differences in these phenotypic effects

Host finding and feeding in Hydrotaea irritans (diptera, muscidae):The role of chemical senses

Hydroteae irritans is commonly considered to be the primary vector for the bacteria which cause summer mastitis in cattle. A behavioral physiology approach was used to investigate potential host odours (kairomones) that may be used by the fly in finding its host and to determine which substrates or sites on the host may be utilised in feeding. Attractant odours include CO2 and butyric, propionic and acetic acids: the latter three are also produced by the bacteria causing summer mastitis. When milk, slaver, nasal secretion, mastitis secretion and blood were offered to flies as feeding substrates only the last three produced significant increases in feeding duration in comparison to controls offered distilled water.Hydroteae irritans is commonly considered to be the primary vector for the bacteria which cause summer mastitis in cattle. A behavioral physiology approach was used to investigate potential host odours (kairomones) that may be used by the fly in finding its host and to determine which substrates or sites on the host may be utilised in feeding. Attractant odours include CO2 and butyric, propionic and acetic acids: the latter three are also produced by the bacteria causing summer mastitis. When milk, slaver, nasal secretion, mastitis secretion and blood were offered to flies as feeding substrates only the last three produced significant increases in feeding duration in comparison to controls offered distilled water