6,178 research outputs found
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
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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
Fluoridanwendungen bei Kindern und Jugendlichen in Deutschland: Ergebnisse der Ernährungsstudien KiESEL und EsKiMo II als Module von KiGGS Welle 2 (2014-2017)
Hintergrund und Ziel der Arbeit: Bei der Kariesprophylaxe spielt eine wirksame und sichere Fluoridanwendung eine wichtige Rolle. Fluoride machen den Zahnschmelz widerstandsfähiger und schützen vor Karies. Dieser Beitrag gibt einen Überblick über die Fluoridanwendung aus unterschiedlichen Quellen zur Kariesprophylaxe bei Kindern und Jugendlichen in Deutschland. Methoden: Datengrundlage sind die in KiGGS Welle 2 (2014-2017) durchgeführten Ernährungsstudien KiESEL für 0,5- bis 5-Jährige und EsKiMo II für 6- bis 17-Jährige. Die Daten geben Auskunft über die Verwendung von Fluoridsupplementen, fluoridhaltiger Zahnpasta und fluoridiertem Salz. Ausgewiesen werden Prävalenzen und Ergebnisse multivariater binär-logistischer Regressionen. Es werden Unterschiede nach soziodemografischen Merkmalen berichtet. Ergebnisse: Von den 0,5- bis 5-Jährigen hatten 14,6 % ein Fluoridsupplement erhalten. In allen betrachteten Altersgruppen verwendeten über 90 % der Kinder und Jugendlichen üblicherweise fluoridhaltige Zahnpasta, mit Ausnahme der 0,5- bis 2-Jährigen (63,4 %). In etwa der Hälfte der Haushalte (51,3 %) der 0,5- bis 5-Jährigen wurden Mahlzeiten für das Kind überwiegend mit fluoridiertem Salz zubereitet. Bei den 6- bis 17-Jährigen war dies nur bei etwa einem Drittel (29,8 %) der Fall. Diskussion: Die Verwendung fluoridhaltiger Zahnpasta hat im Vergleich zur KiGGS-Basiserhebung (2003-2006) zugenommen. Sie ist bei den 0,5- bis 2-Jährigen gering, was sich teilweise durch die Empfehlungen zur Zeit der Datenerhebung erklären lässt, aber auch damit, dass bei einem Teil dieser Kinder (noch) keine Zahnpasta verwendet wurde. Fluoridiertes Salz wird insbesondere bei Kindern ab 6 Jahren noch zu selten zur Mahlzeitenzubereitung genutzt. Dies spricht für eine verstärkte Kommunikation der Empfehlungen zur Kariesprophylaxe und zur Förderung einer zahngesunden Ernährung.Background and objectives: Effective and safe fluoride application plays an important role in caries prophylaxis. Fluoride makes tooth enamel more resistant and protects from tooth decay. This article provides an overview of fluoride application from different sources in children and adolescents in Germany. Methods: This study is based on data from the nutrition studies KiESEL for 0.5-5 year olds and EsKiMo II for 6-17 year olds, which were carried out in KiGGS wave 2 (2014-2017). The data provide information about the use of fluoride via supplements, toothpaste, and table salt. Prevalences and results of multivariate binary logistic regressions and differences with respect to socio-demographic characteristics are reported. Results: In all, 14.6% of the 0.5- to 5-year-olds have received fluoride supplements. In all age groups considered, more than 90% of children and adolescents usually use fluoride toothpaste with the exception of 0.5- to 2-year-olds (63.4%). In 51.3% of the households of 0.5- to 5-year-olds, meals for the child were predominantly prepared with fluoridated salt, whereas this was the case in only 29.8% of the 6-17 year olds. Discussion: Compared to the KiGGS baseline study (2003-2006), the use of toothpaste with fluoride has increased; however, use among 0.5- to 2-year-olds is low, which can partly be explained by the recommendations at the time of data collection, but also by the fact that toothpaste was not (yet) used for some of these children. Fluoridated salt is still used too seldom for meal preparation, especially among children 6 years and older. This argues for improved communication of recommendations for caries prevention and promotion of a tooth-healthy diet
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 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 rad pitch arranged in eight -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 70:30 and
the RD51 scalable readout system. Four small GEM detectors with 2-D readout and
an average measured azimuthal resolution of 36 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 0.2 (stat)]\%. The azimuthal resolution is
found to be [123.5 1.6 (stat)] rad when operating in the center of
the efficiency plateau and using full pulse height information. The resolution
can be slightly improved by 10 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 2.5 stat] rad is measured, consistent
with the expected resolution of strip-pitch/ = 131.3 rad. Other
-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
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