361 research outputs found
Epidemic curves made easy using the R package incidence.
The epidemiological curve (epicurve) is one of the simplest yet most useful tools used by field epidemiologists, modellers, and decision makers for assessing the dynamics of infectious disease epidemics. Here, we present the free, open-source package incidence for the R programming language, which allows users to easily compute, handle, and visualise epicurves from unaggregated linelist data. This package was built in accordance with the development guidelines of the R Epidemics Consortium (RECON), which aim to ensure robustness and reliability through extensive automated testing, documentation, and good coding practices. As such, it fills an important gap in the toolbox for outbreak analytics using the R software, and provides a solid building block for further developments in infectious disease modelling. incidence is available from https://www.repidemicsconsortium.org/incidence
Suppression of the spin waves nonreciprocity due to interfacial Dzyaloshinskii Moriya interaction by lateral confinement in magnetic nanostructures
Despite the huge recent interest towards chiral magnetism related to the
interfacial Dzyaloshinskii Moriya interaction (iDMI) in layered systems, there
is a lack of experimental data on the effect of iDMI on the spin waves
eigenmodes of laterally confined nanostructures. Here we exploit Brillouin
Light Scattering (BLS) to analyze the spin wave eigenmodes of non-interacting
circular and elliptical dots, as well as of long stripes, patterned starting
from a Pt(3.4 nm)/CoFeB(0.8 nm) bilayer, with lateral dimensions ranging from
100 nm to 400 nm. Our experimental results, corroborated by micromagnetic
simulations based on the GPU-accelerated MuMax3 software package, provide
evidence for a strong suppression of the frequency asymmetry between
counter-propagating spin waves (corresponding to either Stokes or anti-Stokes
peaks in BLS spectra), when the lateral confinement is reduced from 400 nm to
100 nm, i.e. when it becomes lower than the light wavelength. Such an evolution
reflects the modification of the spin wave character from propagating to
stationary and indicates that the BLS based method of quantifying the i-DMI
strength from the frequency difference of counter propagating spin waves is not
applicable in the case of magnetic elements with lateral dimension below about
400 nm.Comment: Accepted for pubblication by: Physical Review
Exclusive Photoproduction of Large Momentum-Transfer K and K* Mesons
The reactions gamma p -> K+ Lambda and gamma p -> K* Lambda are analyzed
within perturbative QCD, allowing for diquarks as quasi-elementary constituents
of baryons. The diquark-model parameters and the quark-diquark distribution
amplitudes of proton and Lambda are taken from previous investigations of
electromagnetic baryon form factors and Compton-scattering off protons.
Unpolarized differential cross sections and polarization observables are
computed for different choices of the K and K* distribution amplitudes. The
asymptotic form of the K distribution amplitude (proportional to x1 x2) is
found to provide a satisfactory description of the K photoproduction data.Comment: 32 pages, 7 figures available as tared, compressed and uuencoded
PS-file
Estimating the global burden of endemic canine rabies
Background: Rabies is a notoriously underreported and neglected disease of lowincome
countries. This study aims to estimate the public health and economic burden
of rabies circulating in domestic dog populations, globally and on a country-by-country
basis, allowing an objective assessment of how much this preventable disease costs
endemic countries.<p></p>
Methodology/Principal Findings: We established relationships between rabies mortality
and rabies prevention and control measures, which we incorporated into a model
framework. We used data derived from extensive literature searches and
questionnaires on disease incidence, control interventions and preventative measures
within this framework to estimate the disease burden. The burden of rabies impacts on
public health sector budgets, local communities and livestock economies, with the
highest risk of rabies in the poorest regions of the world. This study estimates that
globally canine rabies causes approximately 59,000 (95% Confidence Intervals: 25-
159,000) human deaths, over 3.7 million (95% CIs: 1.6-10.4 million) disability-adjusted
life years (DALYs) and 8.6 billion USD (95% CIs: 2.9-21.5 billion) economic losses
annually. The largest component of the economic burden is due to premature death
(55%), followed by direct costs of post-exposure prophylaxis (PEP, 20%) and lost
income whilst seeking PEP (15.5%), with only limited costs to the veterinary sector due
to dog vaccination (1.5%), and additional costs to communities from livestock losses
(6%).<p></p>
Conclusions/Significance: This study demonstrates that investment in dog vaccination,
the single most effective way of reducing the disease burden, has been inadequate
and that the availability and affordability of PEP needs improving. Collaborative
investments by medical and veterinary sectors could dramatically reduce the current
large, and unnecessary, burden of rabies on affected communities. Improved
surveillance is needed to reduce uncertainty in burden estimates and to monitor the
impacts of control efforts.<p></p>
TGF-Beta Modulates the Integrity of the Blood Brain Barrier In Vitro, and Is Associated with Metabolic Alterations in Pericytes
The blood–brain barrier (BBB) is a selectively permeable boundary that separates the
circulating blood from the extracellular fluid of the brain and is an essential component for brain
homeostasis. In glioblastoma (GBM), the BBB of peritumoral vessels is often disrupted. Pericytes,
being important to maintaining BBB integrity, can be functionally modified by GBM cells which
induce proliferation and cell motility via the TGF-β-mediated induction of central epithelial to
mesenchymal transition (EMT) factors. We demonstrate that pericytes strengthen the integrity of
the BBB in primary endothelial cell/pericyte co-cultures as an in vitro BBB model, using TEER
measurement of the barrier integrity. In contrast, this effect was abrogated by TGF-β or conditioned
medium from TGF-β secreting GBM cells, leading to the disruption of a so far intact and tight BBB.
TGF-β notably changed the metabolic behavior of pericytes, by shutting down the TCA cycle, driving
energy generation from oxidative phosphorylation towards glycolysis, and by modulating pathways
that are necessary for the biosynthesis of molecules used for proliferation and cell division. Combined
metabolomic and transcriptomic analyses further underscored that the observed functional and
metabolic changes of TGF-β-treated pericytes are closely connected with their role as important
supporting cells during angiogenic processes
COVID-19-Pandemie: Surveillance und Studien des Robert Koch-Instituts zur Lage- und Maßnahmenbewertung
Als nationales Public-Health-Institut überwacht und analysiert das RKI die Verbreitung übertragbarer und nicht übertragbarer Krankheiten in Deutschland. Im Rahmen der COVID-19-Pandemie wurden die bestehenden Surveillance-Systeme zur Überwachung akuter respiratorischer Atemwegserkrankungen angepasst und erweitert und durch wissenschaftliche Studien ergänzt. Der im Epidemiologischen Bulletin 29/2022 veröffentlichte Beitrag gibt eine Übersicht über die in der COVID-19-Pandemie besonders relevanten Informations- und Datenquellen, die der epidemiologischen Lagebewertung sowie der Planung, Durchführung und Bewertung von Präventions- und Bekämpfungsmaßnahmen dienen
HLA-DP on Epithelial Cells Enables Tissue Damage by NKp44+ Natural Killer Cells in Ulcerative Colitis
Background & aims: Ulcerative colitis (UC) is characterized by severe inflammation and destruction of the intestinal epithelium, and is associated with specific risk single nucleotide polymorphisms in HLA class II. Given the recently discovered interactions between subsets of HLA-DP molecules and the activating natural killer (NK) cell receptor NKp44, genetic associations of UC and HLA-DP haplotypes and their functional implications were investigated.Methods: HLA-DP haplotype and UC risk association analyses were performed (UC: n = 13,927; control: n = 26,764). Expression levels of HLA-DP on intestinal epithelial cells (IECs) in individuals with and without UC were quantified. Human intestinal 3-dimensional (3D) organoid cocultures with human NK cells were used to determine functional consequences of interactions between HLA-DP and NKp44.Results: These studies identified HLA-DPA1∗01:03-DPB1∗04:01 (HLA-DP401) as a risk haplotype and HLA-DPA1∗01:03-DPB1∗03:01 (HLA-DP301) as a protective haplotype for UC in European populations. HLA-DP expression was significantly higher on IECs of individuals with UC compared with controls. IECs in human intestinal 3D organoids derived from HLA-DP401pos individuals showed significantly stronger binding of NKp44 compared with HLA-DP301pos IECs. HLA-DP401pos IECs in organoids triggered increased degranulation and tumor necrosis factor production by NKp44+ NK cells in cocultures, resulting in enhanced epithelial cell death compared with HLA-DP301pos organoids. Blocking of HLA-DP401-NKp44 interactions (anti-NKp44) abrogated NK cell activity in cocultures.Conclusions: We identified an UC risk HLA-DP haplotype that engages NKp44 and activates NKp44+ NK cells, mediating damage to intestinal epithelial cells in an HLA-DP haplotype-dependent manner. The molecular interaction between NKp44 and HLA-DP401 in UC can be targeted by therapeutic interventions to reduce NKp44+ NK cell-mediated destruction of the intestinal epithelium in UC
Establishment and characterization of a new human pancreatic adenocarcinoma cell line with high metastatic potential to the lung
<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer is still associated with devastating prognosis. Real progress in treatment options has still not been achieved. Therefore new models are urgently needed to investigate this deadly disease. As a part of this process we have established and characterized a new human pancreatic cancer cell line.</p> <p>Methods</p> <p>The newly established pancreatic cancer cell line PaCa 5061 was characterized for its morphology, growth rate, chromosomal analysis and mutational analysis of the K-<it>ras</it>, EGFR and p53 genes. Gene-amplification and RNA expression profiles were obtained using an Affymetrix microarray, and overexpression was validated by IHC analysis. Tumorigenicity and spontaneous metastasis formation of PaCa 5061 cells were analyzed in pfp<sup>-/-</sup>/rag2<sup>-/- </sup>mice. Sensitivity towards chemotherapy was analysed by MTT assay.</p> <p>Results</p> <p>PaCa 5061 cells grew as an adhering monolayer with a doubling time ranging from 30 to 48 hours. M-FISH analyses showed a hypertriploid complex karyotype with multiple numerical and unbalanced structural aberrations. Numerous genes were overexpressed, some of which have previously been implicated in pancreatic adenocarcinoma (GATA6, IGFBP3, IGFBP6), while others were detected for the first time (MEMO1, RIOK3). Specifically highly overexpressed genes (fold change > 10) were identified as EGFR, MUC4, CEACAM1, CEACAM5 and CEACAM6. Subcutaneous transplantation of PaCa 5061 into pfp<sup>-/-</sup>/rag2<sup>-/- </sup>mice resulted in formation of primary tumors and spontaneous lung metastasis.</p> <p>Conclusion</p> <p>The established PaCa 5061 cell line and its injection into pfp<sup>-/-</sup>/rag2<sup>-/- </sup>mice can be used as a new model for studying various aspects of the biology of human pancreatic cancer and potential treatment approaches for the disease.</p
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