Perceived cycling safety during Corona times - Results of a longitudinal study in Germany

With the beginning of the COVID-19 outbreak and the restrictions put in place to prevent an uncontrolled spread of the virus, the circumstances for daily activities changed. A remarkable shift in the modal split distribution was observed. Cycling was seen as a reliable and resilient option in pandemic times as it allowed social distancing and poses a low risk of contagion. There are detailed studies on the effect of the pandemic on cycling traffic all over the globe which used different data sources, like app data. counters or surveys [1] [2]. Apart from the citizens' behavioral responses to the corona pandemic, the municipalities also put up interventions that were meant to support a shift to cycling-based movements in cities. The question to discuss is what changes will be permanent and which changed circumstances, e.g. increased subjective safety, lead to a long-term change of mobility patterns. The changes in mobility during the COVID-19 pandemic bad different impacts on road traffic collisions and road deaths in different countries. While there was a reduction of both indicators in 32 out of 36 countries in April 2020 compared to April 2019, there was an increase in the other four countries [3]. Others also found a reduction of traffic fatalities in 23 out of 24 countries in 2020 compared to a baseline of the previous years (2017-2019), the only exception being Switzerland [4]. The subjective well-being has also changed differently for the different transport modes throughout the pandemic. For example, in April 2020, 9% of respondents said they would feel more comfortable or much more comfortable if they used or would use a bicycle compared to pre-pandemic times; in summer and autumn 2020, this figure was 11 %, in spring 2021, it was 13%. In autumn 2021, 15% of respondents said they would feel more comfortable or much more comfortable if they used or would use a bicycle than before the spread of the coronavirus [ 5]. [From: Introduction

Pharmacological inhibition of TRPV2 attenuates phagocytosis and lipopolysaccharide‐induced migration of primary macrophages

Background and Purpose: In macrophages, transient receptor potential vanilloid 2 (TRPV2) channel contributes to various cellular processes such as cytokine production, differentiation, phagocytosis and migration. Due to a lack of selective pharmacological tools, its function in immunological processes is not well understood and the identification of novel and selective TRPV2 modulators is highly desirable. Experimental Approach: Novel and selective TRPV2 modulators were identified by screening a compound library using Ca2+ influx assays with human embryonic kidney 293 (HEK293) cells heterologously expressing rat TRPV2. Hits were further characterized and validated with Ca2+ influx and electrophysiological assays. Phagocytosis and migration of macrophages were analysed and the contribution of TRPV2 to the generation of Ca2+ microdomains was studied by total internal reflection fluorescence microscopy (TIRFM). Key Results: The compound IV2-1, a dithiolane derivative (1,3-dithiolan-2-ylidene)-4-methyl-5-phenylpentan-2-one), is a potent inhibitor of heterologously expressed TRPV2 channels (IC50 = 6.3 ± 0.7 μM) but does not modify TRPV1, TRPV3 or TRPV4 channels. IV2-1 also inhibits TRPV2-mediated Ca2+ influx in macrophages. IV2-1 inhibits macrophage phagocytosis along with valdecoxib and after siRNA-mediated knockdown. Moreover, TRPV2 inhibition inhibits lipopolysaccharide-induced migration of macrophages whereas TRPV2 activation promotes migration. After activation, TRPV2 shapes Ca2+ microdomains predominantly at the margin of macrophages, which are important cellular regions to promote phagocytosis and migration. Conclusions and Implications: IV2-1 is a novel TRPV2-selective blocker and underline the role of TRPV2 in macrophage-mediated phagocytosis and migration. Furthermore, we provide evidence that TRPV2 activation generates Ca2+ microdomains, which may be involved in phagocytosis and migration of macrophages

Split-ring resonator experiments and data analysis at FLUTE

FLUTE (Ferninfrarot Linac- Und Test-Experiment) is a compact linac-based test facility for accelerator and diagnostics R&D located at the Karlsruher Institute of Technology (KIT). A new accelerator diagnostics tool, called the split-ring resonator (SRR), was tested at FLUTE, which aims at measuring the longitudinal bunch profile of fs-scale electron bunches. Laser-generated THz radiation is used to excite a high frequency oscillating electromagnetic field in the SRR. Electrons passing through the 20 µm x 20 µm SRR gap are time-dependently deflected in the vertical plane, leading to a vertical streaking of the electron bunch. During the commissioning of the SRR at FLUTE, large series of streaking attempts with varying machine parameters and set-ups were investigated in an automatized way. The recorded beam screen images during this experiment have been analyzed and evaluated. This contribution motivates and presents the automatized experiment and discusses the data analysis

Characterization and optimization of laser-generated THz beam for THz based streaking

At the Ferninfrarot Linac- und Test-Experiment (FLUTE) at the Karlsruhe Institute of Technology (KIT) a new and compact method for longitudinal diagnostics of ultrashort electron bunches is being developed. For this technique, which is based on THz streaking, strong electromagnetic pulses with frequencies around 240 GHz are required. Therefore, a setup for laser-generated THz radiation using tilted-pulse-front pumping in lithium niobate was designed, delivering up to 1 µJ of THz pulse energy with a conversion efficiency of up to 0.03 %. In this contribution we study the optimization of the THz beam transport and environment

Prospects for photon science and beam dynamics studies of a THz undulator at FLUTE

n recent years the interest in high intensity, short-pulse coherent THz radiation for non-linear experimental research and applications grew with upcoming high intensity lasers. In contrast to lasers, accelerators provide free electrons for which emission properties can be tailored to the demand at typically much higher repetition rates than high-intensity lasers can provide. Efforts are ongoing to augment short-bunch accelerators such as the European XFEL with THz radiation sources such as undulators. At the far-infrared linac and test experiment (FLUTE) at KIT, we can facil- itate experiments to investigate coherent THz radiation from different sources and provide short electron bunches. As an additional THz source, a superconducting undulator can be inserted and investigated. In this contribution, we evaluate the opportunities of this THz undulator at FLUTE for linear accelerators and FELs in terms of photon science and beam dynamics

Особенности формирования земельных участков под социальные объекты в сельской местности (д. Лоскутово, п. Светлый Томский район)

Процедура формирования земельных участков под объекты социальных нужд имеет важное практическое значение для Томского района. Автором будут рассмотрены основные этапы проектирования и постановки на кадастровый учет таких земельных участков.The procedure for the formation of land for social needs is of great practical importance for the Tomsk region. The author will consider the main stages of designing and setting up cadastral records of such land plots

Expression of a Structural Protein of the Mycovirus FgV-ch9 Negatively Affects the Transcript Level of a Novel Symptom Alleviation Factor and Causes Virus Infection-Like Symptoms in Fusarium graminearum

Infections of fungi by mycoviruses are often symptomless but sometimes also fatal, as they perturb sporulation, growth, and, if applicable, virulence of the fungal host. Hypovirulence-inducing mycoviruses, therefore, represent a powerful means to defeat fungal epidemics on crop plants. Infection with Fusarium graminearum virus China 9 (FgV-ch9), a double-stranded RNA (dsRNA) chrysovirus- like mycovirus, debilitates Fusarium graminearum, the causal agent of fusarium head blight. In search for potential symptom alleviation or aggravation factors in F. graminearum, we consecutively infected a custom-made F. graminearum mutant collection with FgV-ch9 and found a mutant with constantly elevated expression of a gene coding for a putative mRNA-binding protein that did not show any disease symptoms despite harboring large amounts of virus. Deletion of this gene, named virus response 1 (vr1), resulted in phenotypes identical to those observed in the virus-infected wild type with respect to growth, reproduction, and virulence. Similarly, the viral structural protein coded on segment 3 (P3) caused virus infection-like symptoms when expressed in the wild type but not in the vr1 overexpression mutant. Gene expression analysis revealed a drastic downregulation of vr1 in the presence of virus and in mutants expressing P3. We conclude that symptom development and severity correlate with gene expression levels of vr1. This was confirmed by comparative transcriptome analysis, showing a large transcriptional overlap between the virus-infected wild type, the vr1 deletion mutant, and the P3-expressing mutant. Hence, vr1 represents a fundamental host factor for the expression of virus-related symptoms and helps us understand the underlying mechanism of hypovirulence. IMPORTANCE Virus infections of phytopathogenic fungi occasionally impair growth, reproduction, and virulence, a phenomenon referred to as hypovirulence. Hypovirulence-inducing mycoviruses, therefore, represent a powerful means to defeat fungal epidemics on crop plants. However, the poor understanding of the molecular basis of hypovirulence induction limits their application. Using the devastating fungal pathogen on cereal crops, Fusarium graminearum, we identified an mRNA binding protein (named virus response 1, vr1) which is involved in symptom expression. Downregulation of vr1 in the virus-infected fungus and vr1 deletion evoke virus infection-like symptoms, while constitutive expression overrules the cytopathic effects of the virus infection. Intriguingly, the presence of a specific viral structural protein is sufficient to trigger the fungal response, i.e., vr1 downregulation, and symptom development similar to virus infection. The advancements in understanding fungal infection and response may aid biological pest control approaches using mycoviruses or viral proteins to prevent future Fusarium epidemics

Immunoscreening of the extracellular proteome of colorectal cancer cells

<p>Abstract</p> <p>Background</p> <p>The release of proteins from tumors can trigger an immune response in cancer patients involving T lymphocytes and B lymphocytes, which results in the generation of antibodies to tumor-derived proteins. Many studies aim to use humoral immune responses, namely autoantibody profiles, directly, as clinical biomarkers. Alternatively, the antibody immune response as an amplification system for tumor associated alterations may be used to indicate putative protein biomarkers with high sensitivity. Aiming at the latter approach we here have implemented an autoantibody profiling strategy which particularly focuses on proteins released by tumor cells in vitro: the so-called secretome.</p> <p>Methods</p> <p>For immunoscreening, the extracellular proteome of five colorectal cancer cell lines was resolved on 2D gels, immobilized on PVDF membranes and used for serological screening with individual sera from 21 colorectal cancer patients and 24 healthy controls. All of the signals from each blot were assigned to a master map, and autoantigen candidates were defined based of the pattern of immunoreactivities. The corresponding proteins were isolated from preparative gels, identified by MALDI-MS and/or by nano-HPLC/ESI-MS/MS and exemplarily confirmed by duplex Western blotting combining the human serum samples with antibodies directed against the protein(s) of interest.</p> <p>Results</p> <p>From 281 secretome proteins stained with autoantibodies in total we first defined the "background patterns" of frequently immunoreactive extracellular proteins in healthy and diseased people. An assignment of these proteins, among them many nominally intracellular proteins, to the subset of exosomal proteins within the secretomes revealed a large overlap. On this basis we defined and consequently confirmed novel biomarker candidates such as the extreme C-terminus of the extracellular matrix protein agrin within the set of cancer-enriched immunorectivities.</p> <p>Conclusions</p> <p>Our findings suggest, first, that autoantibody responses may be due, in large part, to cross-presentation of antigens to the immune system via exosomes, membrane vesicles released by tumor cells and constituting a significant fraction of the secretome. In addition, this immunosecretomics approach has revealed novel biomarker candidates, some of them secretome-specific, and thus serves as a promising complementary tool to the frequently reported immunoproteomic studies for biomarker discovery.</p

Lifelong Reduction of LDL-Cholesterol Related to a Common Variant in the LDL-Receptor Gene Decreases the Risk of Coronary Artery Disease—A Mendelian Randomisation Study

Rare mutations of the low-density lipoprotein receptor gene (LDLR) cause familial hypercholesterolemia, which increases the risk for coronary artery disease (CAD). Less is known about the implications of common genetic variation in the LDLR gene regarding the variability of cholesterol levels and risk of CAD.Imputed genotype data at the LDLR locus on 1 644 individuals of a population-based sample were explored for association with LDL-C level. Replication of association with LDL-C level was sought for the most significant single nucleotide polymorphism (SNP) within the LDLR gene in three European samples comprising 6 642 adults and 533 children. Association of this SNP with CAD was examined in six case-control studies involving more than 15 000 individuals.Each copy of the minor T allele of SNP rs2228671 within LDLR (frequency 11%) was related to a decrease of LDL-C levels by 0.19 mmol/L (95% confidence interval (CI) [0.13-0.24] mmol/L, p = 1.5x10(-10)). This association with LDL-C was uniformly found in children, men, and women of all samples studied. In parallel, the T allele of rs2228671 was associated with a significantly lower risk of CAD (Odds Ratio per copy of the T allele: 0.82, 95% CI [0.76-0.89], p = 2.1x10(-7)). Adjustment for LDL-C levels by logistic regression or Mendelian Randomisation models abolished the significant association between rs2228671 with CAD completely, indicating a functional link between the genetic variant at the LDLR gene locus, change in LDL-C and risk of CAD.A common variant at the LDLR gene locus affects LDL-C levels and, thereby, the risk for CAD