Optimizing Beam Transport in Rapidly Compressing Beams on the Neutralized Drift Compression Experiment - II

The Neutralized Drift Compression Experiment-II (NDCX-II) is an induction linac that generates intense pulses of 1.2 MeV helium ions for heating matter to extreme conditions. Here, we present recent results on optimizing beam transport. The NDCX-II beamline includes a 1-meter-long drift section downstream of the last transport solenoid, which is filled with charge-neutralizing plasma that enables rapid longitudinal compression of an intense ion beam against space-charge forces. The transport section on NDCX-II consists of 28 solenoids. Finding optimal field settings for a group of solenoids requires knowledge of the envelope parameters of the beam. Imaging the beam on scintillator gives the radius of the beam, but the envelope angle dr/dz is not measured directly. We demonstrate how the parameters of the beam envelope (r, dr/dz, and emittance) can be reconstructed from a series of images taken at varying B-field strengths of a solenoid upstream of the scintillator. We use this technique to evaluate emittance at several points in the NDCX-II beamline and for optimizing the trajectory of the beam at the entry of the plasma-filled drift section

Regulation of Hemolysin Expression and Virulence of Staphylococcus aureus by a Serine/Threonine Kinase and Phosphatase

Exotoxins, including the hemolysins known as the alpha (α) and beta (β) toxins, play an important role in the pathogenesis of Staphylococcus aureus infections. A random transposon library was screened for S. aureus mutants exhibiting altered hemolysin expression compared to wild type. Transposon insertions in 72 genes resulting in increased or decreased hemolysin expression were identified. Mutations inactivating a putative cyclic di-GMP synthetase and a serine/threonine phosphatase (Stp1) were found to reduce hemolysin expression, and mutations in genes encoding a two component regulator PhoR, LysR family transcriptional regulator, purine biosynthetic enzymes and a serine/threonine kinase (Stk1) increased expression. Transcription of the hla gene encoding α toxin was decreased in a Δstp1 mutant strain and increased in a Δstk1 strain. Microarray analysis of a Δstk1 mutant revealed increased transcription of additional exotoxins. A Δstp1 strain is severely attenuated for virulence in mice and elicits less inflammation and IL-6 production than the Δstk1 strain. In vivo phosphopeptide enrichment and mass spectrometric analysis revealed that threonine phosphorylated peptides corresponding to Stk1, DNA binding histone like protein (HU), serine-aspartate rich fibrinogen/bone sialoprotein binding protein (SdrE) and a hypothetical protein (NWMN_1123) were present in the wild type and not in the Δstk1 mutant. Collectively, these studies suggest that Stk1 mediated phosphorylation of HU, SrdE and NWMN_1123 affects S. aureus gene expression and virulence

Cueing listeners to attend to a target talker progressively improves word report as the duration of the cue-target interval lengthens to 2000 ms

Endogenous attention is typically studied by presenting instructive cues in advance of a target stimulus array. For endogenous visual attention, task performance improves as the duration of the cue-target interval increases up to 800 ms. Less is known about how endogenous auditory attention unfolds over time or the mechanisms by which an instructive cue presented in advance of an auditory array improves performance. The current experiment used five cue-target intervals (0, 250, 500, 1000, and 2000 ms) to compare four hypotheses for how preparatory attention develops over time in a multi-talker listening task. Young adults were cued to attend to a target talker who spoke in a mixture of three talkers. Visual cues indicated the target talker’s spatial location or their gender. Participants directed attention to location and gender simultaneously (‘objects’) at all cue-target intervals. Participants were consistently faster and more accurate at reporting words spoken by the target talker when the cue-target interval was 2000 ms than 0 ms. In addition, the latency of correct responses progressively shortened as the duration of the cue-target interval increased from 0 to 2000 ms. These findings suggest that the mechanisms involved in preparatory auditory attention develop gradually over time, taking at least 2000 ms to reach optimal configuration, yet providing cumulative improvements in speech intelligibility as the duration of the cue-target interval increases from 0 to 2000 ms. These results demonstrate an improvement in performance for cue-target intervals longer than those that have been reported previously in the visual or auditory modalities

A community effort in SARS-CoV-2 drug discovery.

peer reviewedThe COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the "Billion molecules against Covid-19 challenge", to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 molecules, which were subsequently ranked to find 'consensus compounds'. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for biological activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (only the Nsp12 domain), and (alpha) spike protein S. Overall, 27 compounds with weak inhibition/binding were experimentally identified by binding-, cleavage-, and/or viral suppression assays and are presented here. Open science approaches such as the one presented here contribute to the knowledge base of future drug discovery efforts in finding better SARS-CoV-2 treatments.R-AGR-3826 - COVID19-14715687-CovScreen (01/06/2020 - 31/01/2021) - GLAAB Enric

Ferrocene/ferrocenium ion as a catalyst for the photodecomposition of chloroform

Irradiation (λ \u3e 320 nm) of ferrocene in chloroform causes decomposition of chloroform and the accumulation of HCl, CCl3OOH, and C2Cl6. This appears to occur initially through a cycle in which (a) ferrocene is oxidized to ferrocenium and tetrachloroferrate ions, (b) FeCl4 − undergoes photodissociation, and (c) ferrocenium reoxidizes the chloroferrate(II) species. On extended photolysis, the concentrations of CCl3OOH and FeCl4 − build up and a competing cycle in which FeCl4 − is restored through oxidation of the chloroferrate(II) species by CCl3OOH accelerates the decomposition rate

Chlorochromate ion as a catalyst for the photodegradation of chloroform by visible light

Exposure of solutions of tetrabutylammonium chlorochromate in chloroform to UV or blue light causes decomposition of the chloroform and the buildup of HCl and peroxides in solution. The CrO3Cl− is converted during irradiation to CrO2Cl2, which forms a suspension in the chloroform, and then to CrOCl4−. CrO2Cl2 does not by itself catalyze photodecomposition. The initial rate of HCl formation shows an apparently linear dependence on the incident light intensity and on the fraction of light absorbed by chlorochromate, but different values for the apparent quantum yield at 435 nm with high and low concentrations imply a nonlinear contribution to the rate. It is proposed that, at least initially, a cycle involving photoreduction of a Cr(VI) species and thermal reoxidation of Cr(V) by CCl3OOH produces radicals that initiate further decomposition

The soil-borne white root rot pathogen Rosellinia necatrix expresses antimicrobial proteins during host colonization.

Rosellinia necatrix is a prevalent soil-borne plant-pathogenic fungus that is the causal agent of white root rot disease in a broad range of host plants. The limited availability of genomic resources for R. necatrix has complicated a thorough understanding of its infection biology. Here, we sequenced nine R. necatrix strains with Oxford Nanopore sequencing technology, and with DNA proximity ligation we generated a gapless assembly of one of the genomes into ten chromosomes. Whereas many filamentous pathogens display a so-called two-speed genome with more dynamic and more conserved compartments, the R. necatrix genome does not display such genome compartmentalization. It has recently been proposed that fungal plant pathogens may employ effectors with antimicrobial activity to manipulate the host microbiota to promote infection. In the predicted secretome of R. necatrix, 26 putative antimicrobial effector proteins were identified, nine of which are expressed during plant colonization. Two of the candidates were tested, both of which were found to possess selective antimicrobial activity. Intriguingly, some of the inhibited bacteria are antagonists of R. necatrix growth in vitro and can alleviate R. necatrix infection on cotton plants. Collectively, our data show that R. necatrix encodes antimicrobials that are expressed during host colonization and that may contribute to modulation of host-associated microbiota to stimulate disease development

<i>R</i>. <i>necatrix</i> effector candidates show weak structural clustering, which is based on sequence conservation.

(A) Ordered by hierarchical clustering based on structural similarity, the heatmap displays the structural similarity of each effector pair in an all-vs-all alignment based on template modelling (TM) scores that range from 0 to 1. Effector clusters were identified based on a similarity threshold > 0.5. The five largest clusters are highlighted with a black square and ordered by size. (B) Example structure for each of the five clusters based on the effector with the highest similarity to other effectors in the cluster. (C) Characteristics of the five largest structural effector clusters.</p