Rare-Event Sampling: Occupation-Based Performance Measures for Parallel Tempering and Infinite Swapping Monte Carlo Methods

In the present paper we identify a rigorous property of a number of tempering-based Monte Carlo sampling methods, including parallel tempering as well as partial and infinite swapping. Based on this property we develop a variety of performance measures for such rare-event sampling methods that are broadly applicable, informative, and straightforward to implement. We illustrate the use of these performance measures with a series of applications involving the equilibrium properties of simple Lennard-Jones clusters, applications for which the performance levels of partial and infinite swapping approaches are found to be higher than those of conventional parallel tempering.Comment: 18 figure

Mortality in Recreational Mountain-Biking in the Austrian Alps: A Retrospective Study over 16 Years.

Despite recreational mountain-biking's growing popularity worldwide, the literature on mortality in this leisure sporting activity is scarce. Therefore, the aim of the present study was to investigate the characteristics of fatal accidents as well as resulting dead victims during recreational mountain-biking in the Austrian Alps over the past 16 years. For this purpose, a retrospective study based on Austrian institutional documentation from 2006 to 2021 was conducted. In total, 97 fatalities (1 woman) with a mean age of 55.6 ± 13.9 years were recorded by the Austrian Alpine Police. Of those, 54.6% died due to a non-traumatic (mostly cardio-vascular) and 41.2% due to a traumatic event. Mountain-bikers fatally accidented for non-traumatic reasons frequently belonged to older age classes (p = 0.05) and mostly (73.6%) died during the ascent, whereas traumatic events mainly (70.0%) happened during the descent (p < 0.001). Throughout the examined period, the absolute number of fatalities slightly increased, whereas the mortality index (proportion of deaths/accidented victims) did not (mean value: 1.34 ± 0.56%). Factors such as male sex in general, above average age and uphill riding for non-traumatic accidents, as well as downhill riding for traumatic events, seem to be associated with fatalities during recreational mountain-biking in the Austrian Alps. These results should be considered for future preventive strategies in recreational mountain-biking

Abl Kinase Regulation by BRAF/ERK and Cooperation with Akt in Melanoma

The melanoma incidence continues to increase, and the disease remains incurable for many due to its metastatic nature and high rate of therapeutic resistance. In particular, melanomas harboring BRAFV600E and PTEN mutations often are resistant to current therapies, including BRAF inhibitors (BRAFi) and immune checkpoint inhibitors. Abl kinases (Abl/Arg) are activated in melanomas and drive progression; however, their mechanism of activation has not been established. Here we elucidate a novel link between BRAFV600E/ERK signaling and Abl kinases. We demonstrate that BRAFV600E/ERK play a critical role in binding, phosphorylating and regulating Abl localization and Abl/Arg activation by Src family kinases. Importantly, Abl/Arg activation downstream of BRAFV600E has functional and biological significance, driving proliferation, invasion, as well as switch in epithelial–mesenchymal–transition transcription factor expression, which is known to be critical for melanoma cells to shift between differentiated and invasive states. Finally, we describe findings of high translational significance by demonstrating that Abl/Arg cooperate with PI3K/Akt/PTEN, a parallel pathway that is associated with intrinsic resistance to BRAFi and immunotherapy, as Abl/Arg and Akt inhibitors cooperate to prevent viability, cell cycle progression and in vivo growth of melanomas harboring mutant BRAF/PTEN. Thus, these data not only provide mechanistic insight into Abl/Arg regulation during melanoma development, but also pave the way for the development of new strategies for treating patients with melanomas harboring mutant BRAF/PTEN, which often are refractory to current therapies

Changes in cortical beta activity related to a biceps brachii movement task while experiencing exercise induced muscle damage

AbstractExercise-induced-muscle-damage (EIMD) is a well-described phenomenon which leads to decreased force output and altered neuromuscular function. How these symptoms of EIMD affect brain function, in particular cortical activity has not been described. Therefore the aim of this study was to investigate the relationship between the symptoms of EIMD and cortical beta (β) activity during a submaximal biceps brachii movement. Half of the subjects participated in an EIMD protocol. Control and EIMD groups were monitored for 132h thereafter. Muscle pain scores in the EIMD group peaked after 36h with the lowest muscle torque reported at 12h. Beta-1 and -2 activity was increased in the frontal and parietal area in the experimental group at 12h. This suggests an impact of EIMD induced neuromuscular changes on the cortical proprioceptive and motor perceptive networks. Beta-2 activity decreased in the control group over time suggesting a loss in focused attention and greater familiarization with the protocol as the study progressed. These data suggest that a change in β-1 and -2 activity is associated with integrating movement perception and proprioception post-EIMD

Model sensitivity in the effect of Antarctic sea ice and stratification on atmospheric pCO2

Several recent papers have demonstrated a decrease in atmospheric pCO(2) resulting from barriers to communication between the deep sea and the atmosphere in the Southern Ocean. Stephens and Keeling [2000] decreased pCO(2) by increasing Antarctic sea ice in a seven-box model of the world ocean, and Toggweiler [1999] showed a similar response to Southern Ocean stratification. In box models the pCO(2) of the atmosphere is controlled by the region of the surface ocean that fills the deep sea [Archer et al., 2000a]. By severing the Southern Ocean link between the deep sea and the atmosphere, atmospheric pCO(2) in these models is controlled elsewhere and typically declines, although the models range widely in their responses. "Continuum models,'' such as three-dimensional (3-D) and 2-D general circulation models, control pCO(2) in a more distributed way and do not exhibit box model sensitivity to high-latitude sea ice or presumably stratification. There is still uncertainty about the high-latitude sensitivity of the real ocean. Until these model sensitivities can be resolved, glacial pCO(2) hypotheses and interpretations based on Southern Ocean barrier mechanisms (see above mentioned references plus Elderfield and Rickaby [2000], Francois et al. [1998], Gildor and Tziperman [2001], Sigman and Boyle [2000], and Watson et al. [2000]) are walking on thin ice

An Infinite Swapping Approach to the Rare-Event Sampling Problem

We describe a new approach to the rare-event Monte Carlo sampling problem. This technique utilizes a symmetrization strategy to create probability distributions that are more highly connected and thus more easily sampled than their original, potentially sparse counterparts. After discussing the formal outline of the approach and devising techniques for its practical implementation, we illustrate the utility of the technique with a series of numerical applications to Lennard-Jones clusters of varying complexity and rare-event character.Comment: 24 pages, 16 figure

Evaluation of a liquid chromatographic method for the determination of fumonisins in corn, poultry feed, and Fusarium culture material.

The performance of a liquid chromatographic method for determining fumonisins in corn, animal feeds, and culture material was evaluated. Efficiencies of extractions with the following solvent systems were determined: acetonitrile-water (50 + 50, v/v), methanol-water (75 + 25, v/v), and 100% water. The acetonitrile solvent gave both higher extraction efficiencies and faster extraction times than the other 2 solvents. Extraction was followed by C18 solid-phase extraction column cleanup. Fumonisin B1 (FB1), fumonisin B2 (FB2), and fumonisin B3 (FB3) were measured by precolumn derivatization with o-phthalaldehyde followed by isocratic separation on a C18 reversed-phase column with a mobile phase of 50 mM potassium dihydrogen phosphate (pH 3.3)-acetonitrile (60 + 40). Commercially prepared poultry feed, corn, and Fusarium spp. corn cultures were analyzed at the following levels: FB1, 1.5 to 15,000 micrograms/g; FB2, 0.5 to 4000 micrograms/g; FB3, and 0.17 to 1,500 micrograms/g. Recoveries were 91-94%, 90-100%, and 81-93% for FB1, FB2, and FB3, respectively. Precision (coefficient of variation) was determined with pooled field samples and ranged from 2% at 19 micrograms/g for FB1 to 9% at 0.17 microgram/g for FB3. Time and pH studies of the formation of the fluorescent derivative and its stability were conducted. Complete reaction occurred at pHs above 7.9, with optimal pH for chromatography between 8.0 and 8.5. No statistically significant response differences were detected for reaction times ranging from 4 to 40 min; however, the detector signal was significantly reduced when reaction times were shorter than 4 min. Chromatograms of samples were free of interferences for all feeds, corn, and culture material teste

Making SPIFFI SPIFFIER: Upgrade of the SPIFFI instrument for use in ERIS and performance analysis from re-commissioning

SPIFFI is an AO-fed integral field spectrograph operating as part of SINFONI on the VLT, which will be upgraded and reused as SPIFFIER in the new VLT instrument ERIS. In January 2016, we used new technology developments to perform an early upgrade to optical subsystems in the SPIFFI instrument so ongoing scientific programs can make use of enhanced performance before ERIS arrives in 2020. We report on the upgraded components and the performance of SPIFFI after the upgrade, including gains in throughput and spatial and spectral resolution. We show results from re-commissioning, highlighting the potential for scientific programs to use the capabilities of the upgraded SPIFFI. Finally, we discuss the additional upgrades for SPIFFIER which will be implemented before it is integrated into ERIS.Comment: 20 pages, 12 figures. Proceedings from SPIE Astronomical Telescopes and Instrumentation 201

Renal Volume Loss During Partial Nephrectomy Due to Resected Healthy Parenchyma: A Tool for Quick Estimation

Purpose: Our objective is to evaluate a technique for estimating the amount of healthy margin resected during partial nephrectomy (PN). Materials and Methods: The resected healthy margin volume was determined by planimetry (gold standard), which was performed in a prospective manner on 30 freshly resected renal masses by cross-sectional slicing every ∼5 mm. A single cross-sectional slice containing the largest tumor diameter (bivalved tumor) was chosen to build a model for estimating the amount of healthy kidney removed. This single-slice technique was then applied to a second series of patients (n = 39) status post PN. Three-dimensional models were created using pre- and postoperative CT scans to determine the overall volume loss following PN. Results: The median (range) for tumor diameter and tumor volume was 3.2 cm (1–6.1) and 10.7 cm3 (0.5–101.9), respectively, for the 30 PN specimens used to build the single-slice estimation equation. The median (range) healthy margin volume calculated by planimetry and single slice technique was 9.0 cm3 (1.0–22.1) and 7.8 cm3 (1.0–31.0), respectively (p = 0.37). The Pearson correlation was 0.84, and the median (range) percent difference between the planimetry and single slice techniques was −0.5% (−39% to 57%). For the 39 PN patients, the median (range) total renal volume loss, 25.8 cm3 (3–79), was significantly greater than the volume of healthy margin removed during resection, 5.7 cm3 (1–22), p < 0.001. Conclusions: The healthy margin resected during PN differs widely and can be estimated from a single cross-section. The healthy margin resected accounted for <50% of the total volume loss seen during PN