A dual function for Pex3p in peroxisome formation and inheritance

Saccharomyces cerevisiae Pex3p has been shown to act at the ER during de novo peroxisome formation. However, its steady state is at the peroxisomal membrane, where its role is debated. Here we show that Pex3p has a dual function: one in peroxisome formation and one in peroxisome segregation. We show that the peroxisome retention factor Inp1p interacts physically with Pex3p in vitro and in vivo, and split-GFP analysis shows that the site of interaction is the peroxisomal membrane. Furthermore, we have generated PEX3 alleles that support peroxisome formation but fail to support recruitment of Inp1p to peroxisomes, and as a consequence are affected in peroxisome segregation. We conclude that Pex3p functions as an anchor for Inp1p at the peroxisomal membrane, and that this function is independent of its role at the ER in peroxisome biogenesis

Accelerated Bayesian Inference for Molecular Simulations using Local Gaussian Process Surrogate Models

While Bayesian inference is the gold standard for uncertainty quantification and propagation, its use within physical chemistry encounters formidable computational barriers. These bottlenecks are magnified for modeling data with many independent variables, such as X-ray/neutron scattering patterns and electromagnetic spectra. To address this challenge, we apply a Bayesian framework accelerated via local Gaussian process (LGP) surrogate models. We show that the time-complexity of LGPs scales linearly in the number of independent variables, in stark contrast to the computationally expensive cubic scaling of conventional Gaussian processes. To illustrate the method, we trained a LGP surrogate model on the experimental radial distribution function of liquid neon, and observed a remarkable 288,000-fold speed-up compared to molecular dynamics with insignificant loss in predictive accuracy. We conclude that LGPs are robust and efficient surrogate models, poised to expand the application of Bayesian inference in molecular simulations to a broad spectrum of ever-advancing experimental data

Strain induced power enhancement of far-UVC LEDs on high temperature annealed AlN templates

High temperature annealed AlN/sapphire templates exhibit a reduced in-plane lattice constant compared to conventional non-annealed AlN/sapphire grown by metalorganic vapor phase epitaxy (MOVPE). This leads to additional lattice mismatch between the template and the AlGaN-based ultraviolet-C light emitting diode (UVC LED) heterostructure grown on these templates. This mismatch introduces additional compressive strain in AlGaN quantum wells resulting in enhanced transverse electric polarization of the quantum well emission at wavelengths below 235 nm compared to layer structures deposited on conventional MOVPE-grown AlN templates, which exhibit mainly transverse magnetic polarized emission. In addition, high temperature annealed AlN/sapphire templates also feature reduced defect densities leading to reduced non-radiative recombination. Based on these two factors, i.e., better outcoupling efficiency of the transverse electric polarized light and an enhanced internal quantum efficiency, the performance characteristic of far-UVC LEDs emitting at 231 nm was further improved with a cw optical output power of 3.5 mW at 150 mA

Rosacea and perioral dermatitis: a single‐center retrospective analysis of the clinical presentation of 1032 patients

Background Rosacea is a common chronic inflammatory cutaneous disorder affecting nearly 5.5 % of the adult population. Our aim was to evaluate the prevalence and epidemiology of rosacea and perioral dermatitis (POD) in an ambulatory care setting. Methods We retrospectively analyzed medical data of patients with a confirmed diagnosis of rosacea or perioral dermatitis (POD) presenting at our university hospital outpatient clinic during a 3‐year period. Results Out of 1032 patients, 81.5 % were diagnosed with rosacea and 18.5 % with POD. Overall prevalence was 1.4 % for rosacea and 0.3 % for POD. 69.3 % of the analyzed patients were female. Overall mean age was 49.3 ± 7.7 (1–92) years; the women’s average age was less than the men’s. Patients with POD were younger and predominantly female, whereas patients with phymatous rosacea were older and predominantly male. The most common phenotypes were papulopustular rosacea (68.4 %), erythematotelangiectatic rosacea (22.5 %), and phymatous rosacea (8.0 %). Special forms of rosacea were diagnosed in 15.8 % of the patients; the most frequent were ocular rosacea (6.9 %) and steroid‐induced rosacea (5.4 %). Conclusions The large patient cohort analyzed in our study provides a good estimate of the frequency of the rosacea subtypes, special forms and of perioral dermatitis in a hospital‐based outpatient care setting

From the cell membrane to the nucleus: unearthing transport mechanisms for Dynein

Mutations in the motor protein cytoplasmic dynein have been found to cause Charcot-Marie-Tooth disease, spinal muscular atrophy, and severe intellectual disabilities in humans. In mouse models, neurodegeneration is observed. We sought to develop a novel model which could incorporate the effects of mutations on distance travelled and velocity. A mechanical model for the dynein mediated transport of endosomes is derived from first principles and solved numerically. The effects of variations in model parameter values are analysed to find those that have a significant impact on velocity and distance travelled. The model successfully describes the processivity of dynein and matches qualitatively the velocity profiles observed in experiments

Observation of NO(x) Enhancement and Ozone Depletion in the Northern and Southern hemispheres after the October-November 2003 Solar Proton Events

The large solar storms in October-November 2003 produced enormous solar proton events (SPEs) where high energetic particles reached the Earth and penetrated into the middle atmosphere in the polar regions. At this time, the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) was observing the atmosphere in the 6-68 km altitude range. MIPAS observations of NO(x) (NO+NO2) and O3 of the period from 25 October to 14 November 2003 are the first global measurements of NO(x) species, covering both the summer (daylight) and winter (dark) polar regions during an SPE. Very large values of NO(x) in the upper stratosphere of 180 ppbv (parts per billion by volume) have been measured, and a large asymmetry in Northern and Southern polar cap NO(x) enhancements was found. Arctic mean polar cap (>60 deg) NO(x) enhancements of 20 to 70 ppbv between 40 to 60 km lasted for at least two weeks, while the Antarctic mean NO(x) enhancement was between 10 and 35 ppbv and was halved after two weeks. Ozone shows depletion signatures associated with both HO(x) (H+OH+HO2) and NO(x) enhancements but at different time scales. Arctic lower mesospheric (upper stratospheric) ozone is reduced by 50-70% (30-40%) for about two weeks The large solar storms in October-November 2003 produced after the SPEs. A smaller ozone depletion signal was observed in the Antarctic atmosphere. After the locally produced Arctic middle and upper stratospheric as well as mesospheric NO(x) enhancement, large amounts of NO(x) were observed until the end of December. These are explained by downward transport processes

Kendomycin Cytotoxicity against Bacterial, Fungal, and Mammalian Cells Is Due to Cation Chelation

Kendomycin is a small-molecule natural product that has gained significant attention due to reported cytotoxicity against pathogenic bacteria and fungi as well as a number of cancer cell lines. Despite significant biomedical interest and attempts to reveal its mechanism of action, the cellular target of kendomycin remains disputed. Herein it is shown that kendomycin induces cellular responses indicative of cation stress comparable to the effects of established iron chelators. Furthermore, addition of excess iron and copper attenuated kendomycin cytotoxicity in bacteria, yeast, and mammalian cells. Finally, NMR analysis demonstrated a direct interaction with cations, corroborating a close link between the observed kendomycin polypharmacology across different species and modulation of iron and/or copper levels.Peer reviewe

Aging Studies for the Large Honeycomb Drift Tube System of the Outer Tracker of HERA-B

The HERA-B Outer Tracker consists of drift tubes folded from polycarbonate foil and is operated with Ar/CF4/CO2 as drift gas. The detector has to stand radiation levels which are similar to LHC conditions. The first prototypes exposed to radiation in HERA-B suffered severe radiation damage due to the development of self-sustaining currents (Malter effect). In a subsequent extended R&D program major changes to the original concept for the drift tubes (surface conductivity, drift gas, production materials) have been developed and validated for use in harsh radiation environments. In the test program various aging effects (like Malter currents, gain loss due to anode aging and etching of the anode gold surface) have been observed and cures by tuning of operation parameters have been developed.Comment: 14 pages, 6 figures, to be published in the Proceedings of the International Workshop On Aging Phenomena In Gaseous Detectors, 2-5 Oct 2001, Hamburg, German

Performance of a Large-Area GEM Detector Prototype for the Upgrade of the CMS Muon Endcap System

Gas Electron Multiplier (GEM) technology is being considered for the forward muon upgrade of the CMS experiment in Phase 2 of the CERN LHC. Its first implementation is planned for the GE1/1 system in the $1.5 < \mid\eta\mid < 2.2$ region of the muon endcap mainly to control muon level-1 trigger rates after the second long LHC shutdown. A GE1/1 triple-GEM detector is read out by 3,072 radial strips with 455 $\mu$rad pitch arranged in eight $\eta$-sectors. We assembled a full-size GE1/1 prototype of 1m length at Florida Tech and tested it in 20-120 GeV hadron beams at Fermilab using Ar/CO$_{2}$ 70:30 and the RD51 scalable readout system. Four small GEM detectors with 2-D readout and an average measured azimuthal resolution of 36 $\mu$rad provided precise reference tracks. Construction of this largest GEM detector built to-date is described. Strip cluster parameters, detection efficiency, and spatial resolution are studied with position and high voltage scans. The plateau detection efficiency is [97.1 $\pm$ 0.2 (stat)]\%. The azimuthal resolution is found to be [123.5 $\pm$ 1.6 (stat)] $\mu$rad when operating in the center of the efficiency plateau and using full pulse height information. The resolution can be slightly improved by $\sim$ 10 $\mu$rad when correcting for the bias due to discrete readout strips. The CMS upgrade design calls for readout electronics with binary hit output. When strip clusters are formed correspondingly without charge-weighting and with fixed hit thresholds, a position resolution of [136.8 $\pm$ 2.5 stat] $\mu$rad is measured, consistent with the expected resolution of strip-pitch/$\sqrt{12}$ = 131.3 $\mu$rad. Other $\eta$-sectors of the detector show similar response and performance.Comment: 8 pages, 32 figures, submitted to Proc. 2014 IEEE Nucl. Sci. Symposium, Seattle, WA, reference adde

Overview of large area triple-GEM detectors for the CMS forward muon upgrade

In order to cope with the harsh environment expected from the high luminosity LHC, the CMS forward muon system requires an upgrade. The two main challenges expected in this environment are an increase in the trigger rate and increased background radiation leading to a potential degradation of the particle ID performance. Additionally, upgrades to other subdetectors of CMS allow for extended coverage for particle tracking, and adding muon system coverage to this region will further enhance the performance of CMS