354 research outputs found
Picosecond strain dynamics in GeSbTe monitored by time-resolved x-ray diffraction
Coherent phonons (CP) generated by laser pulses on the femtosecond scale have
been proposed as a means to achieve ultrafast, non-thermal switching in
phase-change materials such as GeSbTe(GST). Here we use
ultrafast optical pump pulses to induce coherent acoustic phonons and
stroboscopically measure the corresponding lattice distortions in GST using 100
ps x-ray pulses from the ESRF storage ring. A linear-chain model provides a
good description of the observed changes in the diffraction signal, however,
the magnitudes of the measured shifts are too large to be explained by thermal
effects alone implying the presence of transient non-equilibrium electron
heating in addition to temperature driven expansion. The information on the
movement of atoms during the excitation process can lead to greater insight
into the possibilities of using CP-induced phase-transitions in GST.Comment: 7 pages, 4 figures, Phys. Rev. B, in pres
Scanning X-ray nanodiffraction: from the experimental approach towards spatially resolved scattering simulations
An enhancement on the method of X-ray diffraction simulations for applications using nanofocused hard X-ray beams is presented. We combine finite element method, kinematical scattering calculations, and a spot profile of the X-ray beam to simulate the diffraction of definite parts of semiconductor nanostructures. The spot profile could be acquired experimentally by X-ray ptychography. Simulation results are discussed and compared with corresponding X-ray nanodiffraction experiments on single SiGe dots and dot molecules
Significant impact of time-of-day variation on metformin pharmacokinetics
Aims/hypothesis The objective was to investigate if metformin pharmacokinetics is modulated by time-of-day in humans using
empirical and mechanistic pharmacokinetic modelling techniques on a large clinical dataset. This study also aimed to generate
and test hypotheses on the underlying mechanisms, including evidence for chronotype-dependent interindividual differences in
metformin plasma and efficacy-related tissue concentrations.
Methods A large clinical dataset consisting of individual metformin plasma and urine measurements was analysed using a newly
developed empirical pharmacokinetic model. Causes of daily variation of metformin pharmacokinetics and interindividual
variability were further investigated by a literature-informed mechanistic modelling analysis.
Results A significant effect of time-of-day on metformin pharmacokinetics was found. Daily rhythms of gastrointestinal, hepatic
and renal processes are described in the literature, possibly affecting drug pharmacokinetics. Observed metformin plasma levels
were best described by a combination of a rhythm in GFR, renal plasma flow (RPF) and organic cation transporter (OCT) 2
activity. Furthermore, the large interindividual differences in measured metformin concentrations were best explained by individual chronotypes affecting metformin clearance, with impact on plasma and tissue concentrations that may have implications
for metformin efficacy.
Conclusions/interpretation Metformin’s pharmacology significantly depends on time-of-day in humans, determined with the help of
empirical and mechanistic pharmacokinetic modelling, and rhythmic GFR, RPF and OCT2 were found to govern intraday variation.
Interindividual variation was found to be partly dependent on individual chronotype, suggesting diurnal preference as an interesting, but
so-far underappreciated, topic with regard to future personalised chronomodulated therapy in people with type 2 diabetes
Emergence of porcine epidemic diarrhea virus in southern Germany
Background
Over the last years, porcine epidemic diarrhea virus (PEDV) has caused devastating enteric diseases in the US and several countries in Asia, while outbreaks in Europe have only been reported sporadically since the 1980s. At present, only insufficient information is available on currently circulating PEDV strains in Europe and their impact on the European swine industry. In this case report, we present epidemic outbreaks of porcine epidemic diarrhea in three farms in South-Western Germany.
Case presentation
Epidemic outbreaks of diarrhea affecting pigs of all age groups were reported in three farms, one fattening farm and two piglet producing farms, in South-Western Germany between May and November 2014. In the fattening farm yellowish, watery diarrhea without evidence of mucus or blood was associated with a massive reduction of feed consumption. Severity of clinical signs and mortality in young suckling pigs varied significantly between the two affected sow farms. While mortality in suckling piglets reached almost 70 % in one sow herd, no increase in suckling piglet mortality was observed in the second sow farm. In all three cases, PEDV was confirmed in feces and small intestines by RT-qPCR. Phylogenetic analyses based on full-length PEDV genomes revealed high identity among strains from all three herds. Moreover, the German strains showed very high nucleotide identity (99.4 %) with a variant of PEDV (OH851) that was isolated in the United States in January 2014. This strain with insertions and deletions in the S-gene (so called INDEL strains) was reported to show lower virulence. Slightly lower identities were found with other strains from the US and Asia.
Conclusion
Phylogenetic information on the distribution of PEDV strains in Europe is severely lacking. In this case report we demonstrate that acute outbreaks of PEDV occurred in southern Germany in 2014. Current strains were clearly different from isolates found in the 1980s and were closely related to a PEDV variant found in the US in 2014. Moreover, the present case report indicates that variant strains of PEDV, containing insertions and deletions in the S gene, which were reported to be of lower virulence, might be able to cause high mortality in suckling piglets
Dose-Volume Histogram Parameters and Quality of Life in Patients with Prostate Cancer Treated with Surgery and High-Dose Volumetric-Intensity-Modulated Arc Therapy to the Prostate Bed.
INTRODUCTION
Prostate bed radiotherapy (RT) is a major affecter of patients' long-term quality of life (QoL). To ensure the best possible outcome of these patients, dose constraints are key for optimal RT planning and delivery. However, establishing refined dose constraints requires access to patient-level data. Therefore, we aimed to provide such data on the relationship between OAR and gastrointestinal (GI) as well as genitourinary (GU) QoL outcomes of a homogenous patient cohort who received dose-intensified post-operative RT to the prostate bed. Furthermore, we aimed to conduct an exploratory analysis of the resulting data.
METHODS
Patients who were treated with prostate bed RT between 2010 and 2020 were inquired about their QoL based on the Expanded Prostate Cancer Index Composite (EPIC). Those (n = 99) who received volumetric arc therapy (VMAT) of at least 70 Gy to the prostate bed were included. Dose-volume histogram (DVH) parameters were gathered and correlated with the EPIC scores.
RESULTS
The median age at the time of prostate bed RT was 68.9 years, and patients were inquired about their QoL in the median 2.3 years after RT. The median pre-RT prostate-specific antigen (PSA) serum level was 0.35 ng/mL. The median duration between surgery and RT was 1.5 years. The median prescribed dose to the prostate bed was 72 Gy. A total of 61.6% received prostate bed RT only. For the bladder, the highest level of statistical correlation (p < 0.01) was seen for V10-20Gy, Dmean and Dmedian with urinary QoL. For bladder wall, the highest level of statistically significant correlation (p < 0.01) was seen for V5-25Gy, Dmean and Dmedian with urinary QoL. Penile bulb V70Gy was statistically significantly correlated with sexual QoL (p < 0.05). A larger rectal volume was significantly correlated with improved bowel QoL (p < 0.05). Sigmoid and urethral DVH parameters as well as the surgical approach were not statistically significantly correlated with QoL.
CONCLUSION
Specific dose constraints for bladder volumes receiving low doses seem desirable for the further optimization of prostate bed RT. This may be particularly relevant in the context of the aspiration of establishing focal RT of prostate cancer and its local recurrences. Our comprehensive dataset may aid future researchers in achieving these goals
CcpA regulates arginine biosynthesis in Staphylococcus aureus through repression of proline catabolism.
Staphylococcus aureus is a leading cause of community-associated and nosocomial infections. Imperative to the success of S. aureus is the ability to adapt and utilize nutrients that are readily available. Genomic sequencing suggests that S. aureus has the genes required for synthesis of all twenty amino acids. However, in vitro experimentation demonstrates that staphylococci have multiple amino acid auxotrophies, including arginine. Although S. aureus possesses the highly conserved anabolic pathway that synthesizes arginine via glutamate, we demonstrate here that inactivation of ccpA facilitates the synthesis of arginine via the urea cycle utilizing proline as a substrate. Mutations within putA, rocD, arcB1, argG and argH abolished the ability of S. aureus JE2 ccpA::tetL to grow in the absence of arginine, whereas an interruption in argJBCF, arcB2, or proC had no effect. Furthermore, nuclear magnetic resonance demonstrated that JE2 ccpA::ermB produced (13)C(5) labeled arginine when grown with (13)C(5) proline. Taken together, these data support the conclusion that S. aureus synthesizes arginine from proline during growth on secondary carbon sources. Furthermore, although highly conserved in all sequenced S. aureus genomes, the arginine anabolic pathway (ArgJBCDFGH) is not functional under in vitro growth conditions. Finally, a mutation in argH attenuated virulence in a mouse kidney abscess model in comparison to wild type JE2 demonstrating the importance of arginine biosynthesis in vivo via the urea cycle. However, mutations in argB, argF, and putA did not attenuate virulence suggesting both the glutamate and proline pathways are active and they, or their pathway intermediates, can complement each other in vivo
Comparison of Monitoring Approaches for Selected Priority Pollutants in Surface Water - An Initiative in support to the Water Framework Directive Chemical Monitoring Activity
Laboratories from seven EU Member States under the coordination of the Joint Research Centre and in collaboration with the Provincia di Ferrara participated in a technical on-site project during which sampling and analytical methodologies for chemical monitoring according to proposed WFD provisions have been compared. Laboratories had been invited to take samples from a river according to their standard protocols and to analyse them for PAHs, PBDE and Nonyl-, Octylphenol. It was shown that it is possible to analyse contaminants at relevant levels. Results showed also that currently only experienced laboratories can achieve the required performance, indicating the need for improvement at European level.JRC.H.5-Rural, water and ecosystem resource
Bayesian reconstruction of the cosmological large-scale structure: methodology, inverse algorithms and numerical optimization
We address the inverse problem of cosmic large-scale structure reconstruction
from a Bayesian perspective. For a linear data model, a number of known and
novel reconstruction schemes, which differ in terms of the underlying signal
prior, data likelihood, and numerical inverse extra-regularization schemes are
derived and classified. The Bayesian methodology presented in this paper tries
to unify and extend the following methods: Wiener-filtering, Tikhonov
regularization, Ridge regression, Maximum Entropy, and inverse regularization
techniques. The inverse techniques considered here are the asymptotic
regularization, the Jacobi, Steepest Descent, Newton-Raphson,
Landweber-Fridman, and both linear and non-linear Krylov methods based on
Fletcher-Reeves, Polak-Ribiere, and Hestenes-Stiefel Conjugate Gradients. The
structures of the up-to-date highest-performing algorithms are presented, based
on an operator scheme, which permits one to exploit the power of fast Fourier
transforms. Using such an implementation of the generalized Wiener-filter in
the novel ARGO-software package, the different numerical schemes are
benchmarked with 1-, 2-, and 3-dimensional problems including structured white
and Poissonian noise, data windowing and blurring effects. A novel numerical
Krylov scheme is shown to be superior in terms of performance and fidelity.
These fast inverse methods ultimately will enable the application of sampling
techniques to explore complex joint posterior distributions. We outline how the
space of the dark-matter density field, the peculiar velocity field, and the
power spectrum can jointly be investigated by a Gibbs-sampling process. Such a
method can be applied for the redshift distortions correction of the observed
galaxies and for time-reversal reconstructions of the initial density field.Comment: 40 pages, 11 figure
Stripes in Doped Antiferromagnets: Single-Particle Spectral Weight
Recent photoemission (ARPES) experiments on cuprate superconductors provide
important guidelines for a theory of electronic excitations in the stripe
phase. Using a cluster perturbation theory, where short-distance effects are
accounted for by exact cluster diagonalization and long-distance effects by
perturbation (in the hopping), we calculate the single-particle Green's
function for a striped t-J model. The data obtained quantitatively reproduce
salient (ARPES-) features and may serve to rule out "bond-centered" in favor of
"site-centered" stripes.Comment: final version as appeared in PRL; (c) 2000 The American Physical
Society; 4 pages, 4 figure
Research and Education in Computational Science and Engineering
Over the past two decades the field of computational science and engineering
(CSE) has penetrated both basic and applied research in academia, industry, and
laboratories to advance discovery, optimize systems, support decision-makers,
and educate the scientific and engineering workforce. Informed by centuries of
theory and experiment, CSE performs computational experiments to answer
questions that neither theory nor experiment alone is equipped to answer. CSE
provides scientists and engineers of all persuasions with algorithmic
inventions and software systems that transcend disciplines and scales. Carried
on a wave of digital technology, CSE brings the power of parallelism to bear on
troves of data. Mathematics-based advanced computing has become a prevalent
means of discovery and innovation in essentially all areas of science,
engineering, technology, and society; and the CSE community is at the core of
this transformation. However, a combination of disruptive
developments---including the architectural complexity of extreme-scale
computing, the data revolution that engulfs the planet, and the specialization
required to follow the applications to new frontiers---is redefining the scope
and reach of the CSE endeavor. This report describes the rapid expansion of CSE
and the challenges to sustaining its bold advances. The report also presents
strategies and directions for CSE research and education for the next decade.Comment: Major revision, to appear in SIAM Revie
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