Linear Air Trough

The construction and operation of a linear air trough, a device for floating small rectangular blocks (called gliders) on an air film, is described. The apparatus is useful for demonstrations and laboratory study of one-dimensional particle mechanics. The very small friction that is present is due to the viscosity of the air film, and causes the speed of a glider to decay with a time constant of the order of a few hundred seconds. A type of bumper has been designed which yields a coefficient of restitution greater than 0.99. Ten of these air troughs have been used in a student laboratory for a year, and have proved quite successful in experiments involving Newton's laws, collisions, damped harmonic motion, and motion on an incline

Nextclade: clade assignment, mutation calling and quality control for viral genomes

The variants of concern (VoCs) of SARS-CoV-2 have highlighted the need for a global molecular surveillance of pathogens via whole genome sequencing. Such sequencing, for SARS-CoV-2 and other pathogens, is performed by an ever increasing number of labs across the globe, resulting in an increased need for an easy, fast, and decentralized analysis of initial data. Nextclade aligns viral genomes to a reference sequence, calculates several quality control (QC) metrics, assigns sequences to a clade or variant, and identifies changes in the viral proteins relative to the reference sequence. Nextclade is available as a command-line tool and as a web application with completely client based processing, meaning that sequence data doesn't leave the user's browser

Examining Synaptotagmin 1 Function in Dense Core Vesicle Exocytosis under Direct Control of Ca2+

We tested the long-standing hypothesis that synaptotagmin 1 is the Ca2+ sensor for fast neurosecretion by analyzing the intracellular Ca2+ dependence of large dense-core vesicle exocytosis in a mouse strain carrying a mutated synaptotagmin C2A domain. The mutation (R233Q) causes a twofold increase in the KD of Ca2+-dependent phospholipid binding to the double C2A-C2B domain of synaptotagmin. Using photolysis of caged calcium and capacitance measurements we found that secretion from mutant cells had lower secretory rates, longer secretory delays, and a higher intracellular Ca2+-threshold for secretion due to a twofold increase in the apparent KD of the Ca2+ sensor for fast exocytosis. Single amperometric fusion events were unchanged. We conclude that Ca2+-dependent phospholipid binding to synaptotagmin 1 mirrors the intracellular Ca2+ dependence of exocytosis

Poisson transition rates from time-domain measurements with finite bandwidth

In time-domain measurements of a Poisson two-level system, the observed transition rates are always smaller than those of the actual system, a general consequence of finite measurement bandwidth in an experiment. This underestimation of the rates is significant even when the measurement and detection apparatus is ten times faster than the process under study. We derive here a quantitative form for this correction using a straightforward state-transition model that includes the detection apparatus, and provide a method for determining a system's actual transition rates from bandwidth-limited measurements. We support our results with computer simulations and experimental data from time-domain measurements of quasiparticle tunneling in a single-Cooper-pair transistor.Comment: 4 pages, 5 figure

Potential impact of seasonal forcing on a SARS-CoV-2 pandemic

A novel coronavirus (SARS-CoV-2) first detected in Wuhan, China, has spread rapidly since December 2019, causing more than 100,000 confirmed infections and 4000 fatalities (as of 10 March 2020). The outbreak has been declared a pandemic by the WHO on Mar 11, 2020. Here, we explore how seasonal variation in transmissibility could modulate a SARS-CoV-2 pandemic. Data from routine diagnostics show a strong and consistent seasonal variation of the four endemic coronaviruses (229E, HKU1, NL63, OC43) and we parameterise our model for SARS-CoV-2 using these data. The model allows for many subpopulations of different size with variable parameters. Simulations of different scenarios show that plausible parameters result in a small peak in early 2020 in temperate regions of the Northern Hemisphere and a larger peak in winter 2020/2021. Variation in transmission and migration rates can result in substantial variation in prevalence between regions. While the uncertainty in parameters is large, the scenarios we explore show that transient reductions in the incidence rate might be due to a combination of seasonal variation and infection control efforts but do not necessarily mean the epidemic is contained. Seasonal forcing on SARS-CoV-2 should thus be taken into account in the further monitoring of the global transmission. The likely aggregated effect of seasonal variation, infection control measures, and transmission rate variation is a prolonged pandemic wave with lower prevalence at any given time, thereby providing a window of opportunity for better preparation of health care systems

Interactions between seasonal human coronaviruses and implications for the SARS-CoV-2 pandemic: A retrospective study in Stockholm, Sweden, 2009-2020

The four seasonal coronaviruses 229E, NL63, OC43, and HKU1 are frequent causes of respiratory infections and show annual and seasonal variation. Increased understanding about these patterns could be informative about the epidemiology of SARS-CoV-2.; Results from PCR diagnostics for the seasonal coronaviruses, and other respiratory viruses, were obtained for 55,190 clinical samples analyzed at the Karolinska University Hospital, Stockholm, Sweden, between 14 September 2009 and 2 April 2020.; Seasonal coronaviruses were detected in 2130 samples (3.9 %) and constituted 8.1 % of all virus detections. OC43 was most commonly detected (28.4 % of detections), followed by NL63 (24.0 %), HKU1 (17.6 %), and 229E (15.3 %). The overall fraction of positive samples was similar between seasons, but at species level there were distinct biennial alternating peak seasons for the Alphacoronaviruses, 229E and NL63, and the Betacoronaviruses, OC43 and HKU1, respectively. The Betacoronaviruses peaked earlier in the winter season (Dec-Jan) than the Alphacoronaviruses (Feb-Mar). Coronaviruses were detected across all ages, but diagnostics were more frequently requested for paediatric patients than adults and the elderly. OC43 and 229E incidence was relatively constant across age strata, while that of NL63 and HKU1 decreased with age.; Both the Alphacoronaviruses and Betacoronaviruses showed alternating biennial winter incidence peaks, which suggests some type of immune mediated interaction. Symptomatic reinfections in adults and the elderly appear relatively common. Both findings may be of relevance for the epidemiology of SARS-CoV-2

The role of ClpXP-mediated proteolysis in resculpting the proteome after DNA damage

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2005.Includes bibliographical references (p. 120-136).When faced with environmental assaults, E. coli can take extreme measures to survive. For example, starving bacteria consume their own proteins, and bacteria with severe DNA damage introduce mutations into their genomes. These survival tactics require restructuring of the bacterial proteomic landscape. To reshape the proteome, bacteria alter both protein synthesis and protein degradation. For important regulatory proteins and proteins potentially harmful to the cell under non-stress conditions, these changes must be environmentally responsive and specific. This thesis explores the role of the ClpXP protease in the response to DNA damage. First, we determine how DNA damage affects substrate selection by ClpXP. These experiments combine quantitative proteomics and use of an inactive variant of ClpP to "trap" cellular ClpXP substrates and compare their relative levels with and without DNA damage. Analysis of trapped substrates reveals that cellular stress can result in dramatic changes in protease substrate selection. Next, we explore a specific mechanism that allows coupling of an environmental signal to a change in proteolysis. When the cell senses DNA damage, it triggers autocleavage of the LexA repressor. Autocleavage creates new signals for ClpXP recognition, ensuring the timely degradation of the LexA cleavage products. The mechanism of LexA recognition became a model for cleavage-dependent recognition of other substrates. Finally, we determined the mechanism of ClpX recognition of a known, damage-inducible substrate, UmuD'. We find that UmuD directs UmuD' degradation in an SspB-like manner. These experiments show how, with the right sequence motif, an interacting partner can become a ClpXP delivery factor.(cont.) This thesis work contributes to the idea that the bacterial cell has an imperative to degrade certain stress response proteins. Substrate priorities may change throughout the stress response and cellular proteases have devised a variety of strategies to ensure selection of the right substrate at the right time with respect to cellular conditions. This allows the cell to put its best proteome forward as it meets repeated cycles of environmental stress.by Saskia B. Neher.Ph.D

Effect of anisotropy and destructuration on behavior of Haarajoki test embankment

This paper investigates the influence of anisotropy and destructuration on the behavior of Haarajoki test embankment, which was built by the Finnish National Road Administration as a noise barrier in 1997 on a soft clay deposit. Half of the embankment is constructed on an area improved with prefabricated vertical drains, while the other half is constructed on the natural deposit without any ground improvement. The construction and consolidation of the embankment is analyzed with the finite-element method using three different constitutive models to represent the soft clay. Two recently proposed constitutive models, namely S-CLAY1 which accounts for initial and plastic strain induced anisotropy, and its extension, called S-CLAY1S which accounts, additionally, for interparticle bonding and degradation of bonds, were used in the analysis. For comparison, the problem is also analyzed with the isotropic modified cam clay model. The results of the numerical analyses are compared with the field measurements. The simulations reveal the influence that anisotropy and destructuration have on the behavior of an embankment on soft clay

Impact of cross-border-associated cases on the SARS-CoV-2 epidemic in Switzerland during summer 2020 and 2021

During the summers of 2020 and 2021, the number of confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Switzerland remained at relatively low levels, but grew steadily over time. It remains unclear to what extent epidemic growth during these periods was a result of the relaxation of local control measures or increased traveling and subsequent importation of cases. A better understanding of the role of cross-border-associated cases (imports) on the local epidemic dynamics will help to inform future surveillance strategies. We analyzed routine surveillance data of confirmed cases of SARS-CoV-2 in Switzerland from 1 June to 30 September 2020 and 2021. We used a stochastic branching process model that accounts for superspreading of SARS-CoV-2 to simulate epidemic trajectories in absence and in presence of imports during summer 2020 and 2021. The Swiss Federal Office of Public Health reported 22,919 and 145,840 confirmed cases of SARS-CoV-2 from 1 June to 30 September 2020 and 2021, respectively. Among cases with known place of exposure, 27% (3,276 of 12,088) and 25% (1,110 of 4,368) reported an exposure abroad in 2020 and 2021, respectively. Without considering the impact of imported cases, the steady growth of confirmed cases during summer periods would be consistent with a value of that is significantly above the critical threshold of 1. In contrast, we estimated at 0.84 (95% credible interval, CrI: 0.78–0.90) in 2020 and 0.82 (95% CrI: 0.74–0.90) in 2021 when imported cases were taken into account, indicating that the local was below the critical threshold of 1 during summer. In Switzerland, cross-border-associated SARS-CoV-2 cases had a considerable impact on the local transmission dynamics and can explain the steady growth of the epidemic during the summers of 2020 and 2021

Development of Readout Interconnections for the Si-W Calorimeter of SiD

The SiD collaboration is developing a Si-W sampling electromagnetic calorimeter, with anticipated application for the International Linear Collider. Assembling the modules for such a detector will involve special bonding technologies for the interconnections, especially for attaching a silicon detector wafer to a flex cable readout bus. We review the interconnect technologies involved, including oxidation removal processes, pad surface preparation, solder ball selection and placement, and bond quality assurance. Our results show that solder ball bonding is a promising technique for the Si-W ECAL, and unresolved issues are being addressed.Comment: 8 pages + title, 6 figure