New York City (NYC) has emerged as one of the epicenters of the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. To identify the early transmission events underlying the ...rapid spread of the virus in the NYC metropolitan area, we sequenced the virus that causes coronavirus disease 2019 (COVID-19) in patients seeking care at the Mount Sinai Health System. Phylogenetic analysis of 84 distinct SARS-CoV-2 genomes indicates multiple, independent, but isolated introductions mainly from Europe and other parts of the United States. Moreover, we found evidence for community transmission of SARS-CoV-2 as suggested by clusters of related viruses found in patients living in different neighborhoods of the city.
GENESIS 1.3: a fully 3D time-dependent FEL simulation code Reiche, S.
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
06/1999, Letnik:
429, Številka:
1
Journal Article
Recenzirano
Numerical simulation codes are basic tools for designing Free Electron Lasers (FEL). They are used to study the impact of different parameters, e.g. wiggler errors and external focusing, which allow ...FEL users to optimize the performance. For faster execution some simulation codes assume radial symmetry or decompose the radiation field into a few azimuthal modes, although then this treatment does not include the full description of the FEL. This contribution describes the new FEL code GENESIS 1.3 which uses a fully three-dimensional representation of the FEL equations in the paraxial approximation for time-dependent and steady-state simulations of single-pass FEL. In particular this approach is suitable for cases where the radial symmetry is broken by the electron beam distribution as well as by wiggler errors, betatron motion and off axis injection of the electron beam. The results, presented here, are based on the parameters of the TESLA Test Facility FEL at DESY.
Laser-plasma accelerators are prominent candidates for driving next-generation compact light sources, promising high-brightness, few-femtosecond x-ray pulses intrinsically synchronized to an optical ...laser, and thus are ideally suited for pump-probe experiments with femtosecond resolution. So far, the large spectral width of laser-plasma-driven beams has been preventing a successful free-electron laser (FEL) demonstration using such sources. In this paper, we study the application of an optimized undulator design and bunch decompression to large-energy-spread beams in order to permit FEL amplification. Numerically, we show a proof-of-principle scenario to demonstrate FEL gain in the vacuum ultraviolet range with electron beams from laser-plasma accelerators as currently available in experiments.
Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been reported in immune-compromised individuals and people undergoing immune-modulatory treatments. Although ...intrahost evolution has been documented, direct evidence of subsequent transmission and continued stepwise adaptation is lacking. Here we describe sequential persistent SARS-CoV-2 infections in three individuals that led to the emergence, forward transmission, and continued evolution of a new Omicron sublineage, BA.1.23, over an eight-month period. The initially transmitted BA.1.23 variant encoded seven additional amino acid substitutions within the spike protein (E96D, R346T, L455W, K458M, A484V, H681R, A688V), and displayed substantial resistance to neutralization by sera from boosted and/or Omicron BA.1-infected study participants. Subsequent continued BA.1.23 replication resulted in additional substitutions in the spike protein (S254F, N448S, F456L, M458K, F981L, S982L) as well as in five other virus proteins. Our findings demonstrate not only that the Omicron BA.1 lineage can diverge further from its already exceptionally mutated genome but also that patients with persistent infections can transmit these viral variants. Thus, there is, an urgent need to implement strategies to prevent prolonged SARS-CoV-2 replication and to limit the spread of newly emerging, neutralization-resistant variants in vulnerable patients.
We performed phylogenomic analysis of severe acute respiratory syndrome coronavirus‐2 from 88 infected individuals across different regions of Colombia. Eleven different lineages were detected, ...suggesting multiple introduction events. Pangolin lineages B.1 and B.1.5 were the most frequent, with B.1 being associated with prior travel to high‐risk areas.
Highlights
This is the first genomic epidemiology study of SARS‐CoV2 in Colombia.
The existence of submarine fresh groundwater has been recorded at continental shelves worldwide. The dynamic preservation and lifetime of fresh groundwater in the offshore environment remains an open ...hydrogeological problem. The mechanisms and time scales of fresh groundwater preservation are examined using numerical simulations based on a geologically representative model of the New Jersey shelf, USA. Utilizing two-dimensional depth-migrated seismic and well data, a detailed hydrogeological model is built, with a vertical resolution of 10 m. The model captures the highly heterogeneous shelf environment and accounts for porosity compaction trends derived from core data. The results show transient coupled simulations of groundwater flow and heat and salt transport from the late Pleistocene until present day and projected 18,000 years into the future. They reveal freshwater preservation patterns and yield simulated borehole salinity profiles broadly consistent with field observations. The simulations show that freshwater intervals of a thickness of 200–300 m and lateral extent of tens of kilometers may have been preserved from the Last Glacial Maximum until today. It was found that approximately 30–45% of the initial freshwater volume remains preserved after 12,000 years, depending on the recharge boundary condition. The preserved volume ranges between 15 and 30% after 30,000 years. These results improve the understanding of submarine preservation of fresh groundwater through an interdisciplinary approach which integrates seismic imaging, hydrogeological modeling and high-performance numerical simulation.
Influenza A viruses (IAVs) remain a significant public health threat, causing more than 300,000 hospitalizations in the United States during the 2015-2016 season alone. While only a few IAVs of avian ...origin have been associated with human infections, the ability of these viruses to cause zoonotic infections further increases the public health risk of influenza. Of these, H9N2 viruses in Asia are of particular importance as they have contributed internal gene segments to other emerging zoonotic IAVs. Notably, recent H9N2 viruses have acquired molecular markers that allow for a transition from avian-like to human-like terminal sialic acid (SA) receptor recognition via a single amino acid change at position 226 (H3 numbering), from glutamine (Q226) to leucine (L226), within the hemagglutinin (HA) receptor-binding site (RBS). We sought to determine the plasticity of amino acid 226 and the biological effects of alternative amino acids on variant viruses. We created a library of viruses with the potential of having any of the 20 amino acids at position 226 on a prototypic H9 HA subtype IAV. We isolated H9 viruses that carried naturally occurring amino acids, variants found in other subtypes, and variants not found in any subtype at position 226. Fitness studies in quails revealed that some natural amino acids conferred an
replication advantage. This study shows the flexibility of position 226 of the HA of H9 influenza viruses and the resulting effect of single amino acid changes on the phenotype of variants
and
A single amino acid change at position 226 in the hemagglutinin (HA) from glutamine (Q) to leucine (L) has been shown to play a key role in receptor specificity switching in various influenza virus HA subtypes, including H9. We tested the flexibility of amino acid usage and determined the effects of such changes. The results reveal that amino acids other than L226 and Q226 are well tolerated and that some amino acids allow for the recognition of both avian and human influenza virus receptors in the absence of other changes. Our results can inform better avian influenza virus surveillance efforts as well as contribute to rational vaccine design and improve structural molecular dynamics algorithms.
Abstract
Gastrointestinal symptoms are common in COVID-19 patients but the nature of the gut immune response to SARS-CoV-2 remains poorly characterized, partly due to the difficulty of obtaining ...biopsy specimens from infected individuals. In lieu of tissue samples, we measured cytokines, inflammatory markers, viral RNA, microbiome composition, and antibody responses in stool samples from a cohort of 44 hospitalized COVID-19 patients. SARS-CoV-2 RNA was detected in stool of 41% of patients and more frequently in patients with diarrhea. Patients who survived had lower fecal viral RNA than those who died. Strains isolated from stool and nasopharynx of an individual were the same. Compared to uninfected controls, COVID-19 patients had higher fecal levels of IL-8 and lower levels of fecal IL-10. Stool IL-23 was higher in patients with more severe COVID-19 disease, and we found evidence of intestinal virus-specific IgA responses associated with more severe disease. We provide evidence for an ongoing humeral immune response to SARS-CoV-2 in the gastrointestinal tract, but little evidence of overt inflammation.
The coronavirus disease 2019 (COVID‐19) pandemic has sparked the rapid development of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) diagnostics. However, emerging variants pose the ...risk for target dropout and false‐negative results secondary to primer/probe binding site (PBS) mismatches. The Agena MassARRAY® SARS‐CoV‐2 Panel combines reverse‐transcription polymerase chain reaction and matrix‐assisted laser desorption/ionization time‐of‐flight mass‐spectrometry to probe for five targets across N and ORF1ab genes, which provides a robust platform to accommodate PBS mismatches in divergent viruses. Herein, we utilize a deidentified data set of 1262 SARS‐CoV‐2‐positive specimens from Mount Sinai Health System (New York City) from December 2020 to April 2021 to evaluate target results and corresponding sequencing data. Overall, the level of PBS mismatches was greater in specimens with target dropout. Of specimens with N3 target dropout, 57% harbored an A28095T substitution that is highly specific for the Alpha (B.1.1.7) variant of concern. These data highlight the benefit of redundancy in target design and the potential for target performance to illuminate the dynamics of circulating SARS‐CoV‐2 variants.
Highlights
SARS‐CoV‐2 variation introduces mismatches at diagnostic primer/probe sites.
A multi‐target RT‐PCR/MALDI‐TOF assay captures emergent variants in NYC patients.
Paired sequencing data reveals the Alpha‐specific A28095T causes target dropout.
Diagnostic target performance illuminates dynamics of circulating SARS‐CoV‐2.
Craniofacial development depends on formation and maintenance of sutures between bones of the skull. In sutures, growth occurs at osteogenic fronts along the edge of each bone, and suture mesenchyme ...separates adjacent bones. Here, we perform single-cell RNA-seq analysis of the embryonic, wild type murine coronal suture to define its population structure. Seven populations at E16.5 and nine at E18.5 comprise the suture mesenchyme, osteogenic cells, and associated populations. Expression of Hhip, an inhibitor of hedgehog signaling, marks a mesenchymal population distinct from those of other neurocranial sutures. Tracing of the neonatal Hhip-expressing population shows that descendant cells persist in the coronal suture and contribute to calvarial bone growth. In Hhip
coronal sutures at E18.5, the osteogenic fronts are closely apposed and the suture mesenchyme is depleted with increased hedgehog signaling compared to those of the wild type. Collectively, these data demonstrate that Hhip is required for normal coronal suture development.
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