2,793 research outputs found
Mechanisms Responsible for omega-Pore Currents in Ca-v Calcium Channel Voltage-Sensing Domains
Mutations of positively charged amino acids in the S4 transmembrane segment of a voltage-gated ion channel form ion-conducting pathways through the voltage-sensing domain, named ω-current. Here, we used structure modeling and MD simulations to predict pathogenic ω-currents in CaV1.1 and CaV1.3 Ca2+ channels bearing several S4 charge mutations. Our modeling predicts that mutations of CaV1.1-R1 (R528H/G, R897S) or CaV1.1-R2 (R900S, R1239H) linked to hypokalemic periodic paralysis type 1 and of CaV1.3-R3 (R990H) identified in aldosterone-producing adenomas conducts ω-currents in resting state, but not during voltage-sensing domain activation. The mechanism responsible for the ω-current and its amplitude depend on the number of charges in S4, the position of the mutated S4 charge and countercharges, and the nature of the replacing amino acid. Functional characterization validates the modeling prediction showing that CaV1.3-R990H channels conduct ω-currents at hyperpolarizing potentials, but not upon membrane depolarization compared with wild-type channels
Prevalence of Antibodies Against Virus-Like Particles of Epidermodysplasia Verruciformis-Associated HPV8 in Patients at Risk of Skin Cancer
There is increasing evidence for widespread occurrences of infection with Epidermodysplasia verruciformis-related human papillomaviruses, both in the general population and in immunosuppressed patients. In order to test for the prevalence of antibodies directed against the native L1 epitopes exposed on the surface of the virions, we have established an IgG-specific enzyme-linked immunosorbent assay with L1 virus-like particles of the Epidermodysplasia verruciformis-specific human papillomavirus 8 as antigen to screen 567 representative serum samples from the general population and immunosuppressed/dermatologic patients. Among healthy European donors (n = 210), 7.6% were found to be seropositive. In a group of renal transplant recipients (n = 185) the antibody prevalence was elevated to 21.1%, irrespective of the presence or absence of skin cancer. High positivity rates could be detected among (i) immunocompetent patients with nonmelanoma skin tumors (45.6%, n = 79) and (ii) Psoralene/UVA treated psoriasis patients (42.9%, n = 42). In contrast, anti-human papillomavirus 8-virus-like particle antibodies were found in only 6.8% of Hodgkin lymphoma patients (n = 44)
Scientific Opportunities with an X-ray Free-Electron Laser Oscillator
An X-ray free-electron laser oscillator (XFELO) is a new type of hard X-ray
source that would produce fully coherent pulses with meV bandwidth and stable
intensity. The XFELO complements existing sources based on self-amplified
spontaneous emission (SASE) from high-gain X-ray free-electron lasers (XFEL)
that produce ultra-short pulses with broad-band chaotic spectra. This report is
based on discussions of scientific opportunities enabled by an XFELO during a
workshop held at SLAC on June 29 - July 1, 2016Comment: 21 pages, 12 figure
Potential migration and subjective well-being in Europe
By examining the preferences over migration destinations of those revealing a desire to permanently leave their country, this paper provides new evidence on the relevance of subjective measures for cross country comparisons. While hard statistics such as GDP per capita and unemployment rates are commonly used to measure a country’s success, this analysis reveals that people’s preferences over alternative migration
destinations are better explained by average levels of life satisfaction in the destination country. Aggregated measures of subjective well-being are, therefore, useful for international comparisons as they better reflect what makes some countries more attractive than others
Magnetic vortex oscillator driven by dc spin-polarized current
Transfer of angular momentum from a spin-polarized current to a ferromagnet
provides an efficient means to control the dynamics of nanomagnets. A peculiar
consequence of this spin-torque, the ability to induce persistent oscillations
of a nanomagnet by applying a dc current, has previously been reported only for
spatially uniform nanomagnets. Here we demonstrate that a quintessentially
nonuniform magnetic structure, a magnetic vortex, isolated within a nanoscale
spin valve structure, can be excited into persistent microwave-frequency
oscillations by a spin-polarized dc current. Comparison to micromagnetic
simulations leads to identification of the oscillations with a precession of
the vortex core. The oscillations, which can be obtained in essentially zero
magnetic field, exhibit linewidths that can be narrower than 300 kHz, making
these highly compact spin-torque vortex oscillator devices potential candidates
for microwave signal-processing applications, and a powerful new tool for
fundamental studies of vortex dynamics in magnetic nanostructures.Comment: 14 pages, 4 figure
Concepts for risk-based surveillance in the field of veterinary medicine and veterinary public health: Review of current approaches
BACKGROUND: Emerging animal and zoonotic diseases and increasing international trade have resulted in an increased demand for veterinary surveillance systems. However, human and financial resources available to support government veterinary services are becoming more and more limited in many countries world-wide. Intuitively, issues that present higher risks merit higher priority for surveillance resources as investments will yield higher benefit-cost ratios. The rapid rate of acceptance of this core concept of risk-based surveillance has outpaced the development of its theoretical and practical bases. DISCUSSION: The principal objectives of risk-based veterinary surveillance are to identify surveillance needs to protect the health of livestock and consumers, to set priorities, and to allocate resources effectively and efficiently. An important goal is to achieve a higher benefit-cost ratio with existing or reduced resources. We propose to define risk-based surveillance systems as those that apply risk assessment methods in different steps of traditional surveillance design for early detection and management of diseases or hazards. In risk-based designs, public health, economic and trade consequences of diseases play an important role in selection of diseases or hazards. Furthermore, certain strata of the population of interest have a higher probability to be sampled for detection of diseases or hazards. Evaluation of risk-based surveillance systems shall prove that the efficacy of risk-based systems is equal or higher than traditional systems; however, the efficiency (benefit-cost ratio) shall be higher in risk-based surveillance systems. SUMMARY: Risk-based surveillance considerations are useful to support both strategic and operational decision making. This article highlights applications of risk-based surveillance systems in the veterinary field including food safety. Examples are provided for risk-based hazard selection, risk-based selection of sampling strata as well as sample size calculation based on risk considerations
The semi-classical expansion and resurgence in gauge theories: new perturbative, instanton, bion, and renormalon effects
We study the dynamics of four dimensional gauge theories with adjoint
fermions for all gauge groups, both in perturbation theory and
non-perturbatively, by using circle compactification with periodic boundary
conditions for the fermions. There are new gauge phenomena. We show that, to
all orders in perturbation theory, many gauge groups are Higgsed by the gauge
holonomy around the circle to a product of both abelian and nonabelian gauge
group factors. Non-perturbatively there are monopole-instantons with fermion
zero modes and two types of monopole-anti-monopole molecules, called bions. One
type are "magnetic bions" which carry net magnetic charge and induce a mass gap
for gauge fluctuations. Another type are "neutral bions" which are magnetically
neutral, and their understanding requires a generalization of multi-instanton
techniques in quantum mechanics - which we refer to as the
Bogomolny-Zinn-Justin (BZJ) prescription - to compactified field theory. The
BZJ prescription applied to bion-anti-bion topological molecules predicts a
singularity on the positive real axis of the Borel plane (i.e., a divergence
from summing large orders in peturbation theory) which is of order N times
closer to the origin than the leading 4-d BPST instanton-anti-instanton
singularity, where N is the rank of the gauge group. The position of the
bion--anti-bion singularity is thus qualitatively similar to that of the 4-d IR
renormalon singularity, and we conjecture that they are continuously related as
the compactification radius is changed. By making use of transseries and
Ecalle's resurgence theory we argue that a non-perturbative continuum
definition of a class of field theories which admit semi-classical expansions
may be possible.Comment: 112 pages, 7 figures; v2: typos corrected, discussion of
supersymmetric models added at the end of section 8.1, reference adde
Set-optimization meets variational inequalities
We study necessary and sufficient conditions to attain solutions of
set-optimization problems in therms of variational inequalities of Stampacchia
and Minty type. The notion of a solution we deal with has been introduced Heyde
and Loehne, for convex set-valued objective functions. To define the set-valued
variational inequality, we introduce a set-valued directional derivative and we
relate it to the Dini derivatives of a family of linearly scalarized problems.
The optimality conditions are given by Stampacchia and Minty type Variational
inequalities, defined both by the set valued directional derivative and by the
Dini derivatives of the scalarizations. The main results allow to obtain known
variational characterizations for vector valued optimization problems
Predicting glioblastoma prognosis networks using weighted gene co-expression network analysis on TCGA data
<p>Abstract</p> <p>Background</p> <p>Using gene co-expression analysis, researchers were able to predict clusters of genes with consistent functions that are relevant to cancer development and prognosis. We applied a weighted gene co-expression network (WGCN) analysis algorithm on glioblastoma multiforme (GBM) data obtained from the TCGA project and predicted a set of gene co-expression networks which are related to GBM prognosis.</p> <p>Methods</p> <p>We modified the Quasi-Clique Merger algorithm (QCM algorithm) into edge-covering Quasi-Clique Merger algorithm (eQCM) for mining weighted sub-network in WGCN. Each sub-network is considered a set of features to separate patients into two groups using K-means algorithm. Survival times of the two groups are compared using log-rank test and Kaplan-Meier curves. Simulations using random sets of genes are carried out to determine the thresholds for log-rank test p-values for network selection. Sub-networks with p-values less than their corresponding thresholds were further merged into clusters based on overlap ratios (>50%). The functions for each cluster are analyzed using gene ontology enrichment analysis.</p> <p>Results</p> <p>Using the eQCM algorithm, we identified 8,124 sub-networks in the WGCN, out of which 170 sub-networks show p-values less than their corresponding thresholds. They were then merged into 16 clusters.</p> <p>Conclusions</p> <p>We identified 16 gene clusters associated with GBM prognosis using the eQCM algorithm. Our results not only confirmed previous findings including the importance of cell cycle and immune response in GBM, but also suggested important epigenetic events in GBM development and prognosis.</p
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