cssi/SciSciGPT-SciSciNet huggingface dataset:
The propensity of psychological strategies used by collegiate soccer players at risk for anxiety and depression

Psychological strategies (PS) developed for performance enhancement are common in therapeutic approaches for mitigating mental health risks; however, associations between common PS used by collegia...
Predicting localized affinity of RNA binding proteins to transcripts with convolutional neural networks

RNA binding proteins (RBPs) are important regulators of transcriptional and post-transcriptional processes. Computational prediction of localized RBP binding affinity with transcripts is important for interpretation of genetic variation, especially variants outside of protein coding region. Here we describe POLARIS (Prediction Of Localized Affinity for RBPs In Sequence), a new deep-learning method for achieving fast, site-specific binding affinity predictions of RNA-binding proteins (RBPs) to the transcribed genome. POLARIS has two modules: 1. a convolutional neural network (CNN) to predict overall RBP binding within a region based on transcript sequence content and expression level; 2. a Gradient-weighted Class Activation Mapping (GradCAM) implementation for efficient signal backpropagation to individual sequence positions. We trained the model using enhanced crosslinking and immunoprecipitation (eCLIP) data from ENCODE. POLARIS has good performance with a median AUC ~ 0.96 for 160 RBPs across three different cell lines, substantially higher than selected popular published methods trained and tested on the same data sets. When tested on data from a different cell line with the same RBPs, the overall performance is maintained, supporting the ability of cell-type specific affinity prediction. Finally, the GradCAM module allows the model to identify the informative sites in a region that drive prediction. The localized prediction facilitates interpretation of the results and provides basis for inference of functional impact of noncoding variants.
Chromatin perturbations during the DNA damage response in higher eukaryotes

The DNA damage response is a widely used term that encompasses all signaling initiated at DNA lesions and damaged replication forks as it extends to orchestrate DNA repair, cell cycle checkpoints, cell death and senescence. ATM, an apical DNA damage signaling kinase, is virtually instantaneously activated following the introduction of DNA double-strand breaks (DSBs). The MRE11-RAD50-NBS1 (MRN) complex, which has a catalytic role in DNA repair, and the KAT5 (Tip60) acetyltransferase are required for maximal ATM kinase activation in cells exposed to low doses of ionizing radiation. The sensing of DNA lesions occurs within a highly complex and heterogeneous chromatin environment. Chromatin decondensation and histone eviction at DSBs may be permissive for KAT5 binding to H3K9me3 and H3K36me3, ATM kinase acetylation and activation. Furthermore, chromatin perturbation may be a prerequisite for most DNA repair. Nucleosome disassembly during DNA repair was first reported in the 1970s by Smerdon and colleagues when nucleosome rearrangement was noted during the process of nucleotide excision repair of UV-induced DNA damage in human cells. Recently, the multi-functional protein nucleolin was identified as the relevant histone chaperone required for partial nucleosome disruption at DBSs, the recruitment of repair enzymes and for DNA repair. Notably, ATM kinase is activated by chromatin perturbations induced by a variety of treatments that do not directly cause DSBs, including treatment with histone deacetylase inhibitors. Central to the mechanisms that activate ATR, the second apical DNA damage signaling kinase, outside of a stalled and collapsed replication fork in S-phase, is chromatin decondensation and histone eviction associated with DNA end resection at DSBs. Thus, a stress that is common to both ATM and ATR kinase activation is chromatin perturbations, and we argue that chromatin perturbations are both sufficient and required for induction of the DNA damage response.
An Examination of Past and Current Influences of Rurality on Lesbians' Overweight/Obesity Risks.

Abstract Purpose: The purpose of our study was to separately examine past (i.e., rural or non-rural background) and present (i.e., current rural or urban location) influences of rurality on the weight status and diet/exercise behaviors of lesbians. Methods: A total of 895 lesbians participated in the online study. Participants were surveyed regarding their rurality status, weight/height, and diet/exercise patterns. A 2×2 (location×background) ANCOVA was conducted to explore influences of rurality on body mass index (BMI), while controlling for age, race, and education. Chi-square analyses were used to examine the relationship between dimensions of rurality and diet/exercise behaviors. Results: There was a significant main effect of current location on BMI. No significant interaction between location and background on BMI was found nor was there a significant main effect of background. Lesbians currently living in rural areas were on average obese (M=30.61), with significantly higher BMIs than urban-residi...
Response selection in the human anterior cingulate cortex

The anterior cingulate cortex (ACC) has been proposed as part of the brain's attentional control network, but the exact nature of its involvement in cognitive and motor operations is under debate. Assessing effects of human ACC damage directly addresses the problem of ACC function. We report that executive control processes of a patient with a focal right hemisphere anterior cingulate lesion were not compromised. However, her performance level depended on the response modality used. Under the same task requirements, she was impaired when giving manual responses, but not vocal responses. Thus, we provide neuropsychological evidence for functional specialization within the human ACC.
Role of Partner Homology in DNA Recombination COMPLEMENTARY BASE PAIRING ORIENTS THE 5′-HYDROXYL FOR STRAND JOINING DURING Flp SITE-SPECIFIC RECOMBINATION (*)

Abstract Absolute homology between partner substrates within the strand exchange region is an essential requirement for recombination mediated by the yeast site-specific recombinase Flp. Using combinations of specially designed half- and full-site Flp substrates, we demonstrate that the strand joining step of recombination is exquisitely sensitive to spacer homology. At each exchange point, 2-3 spacer nucleotides adjacent to the nick within the cleaved strand of one substrate must base pair with the corresponding segment of the un-nicked strand from the second substrate for efficient strand joining in the recombinant mode. In accordance with the “cis-activation/trans-nucleophilic attack” model for each of the two transesterification steps of Flp recombination (strand cleavage and strand joining), we propose that the limited strand pairing orients the DNA-nucleophile (5′-hydroxyl) for attack on its target diester (3′-phosphotyrosyl-Flp). During one round of recombination, 4-6 terminal base pairs of the spacer (2-3 base pairs at each spacer end) must unpair, following strand cleavage, within a DNA substrate and pair with the partner substrate prior to strand union. In this model, the extent of branch migration of the covalently closed Holliday intermediate is limited to the central core of the spacer. The templated positioning of reactive nucleic acid groups (which is central to the model) may be utilized by other recombination systems and by RNA splicing reactions.
Dengue virus type 2: replication and tropisms in orally infected Aedes aegypti mosquitoes

Background To be transmitted by its mosquito vector, dengue virus (DENV) must infect midgut epithelial cells, replicate and disseminate into the hemocoel, and finally infect the salivary glands, which is essential for transmission. The extrinsic incubation period (EIP) is very relevant epidemiologically and is the time required from the ingestion of virus until it can be transmitted to the next vertebrate host. The EIP is conditioned by the kinetics and tropisms of virus replication in its vector. Here we document the virogenesis of DENV-2 in newly-colonized Aedes aegypti mosquitoes from Chetumal, Mexico in order to understand better the effect of vector-virus interactions on dengue transmission.
Differences Between Traditional and Distance Education Academic Performances: A Meta-Analytic Approach

This meta-analysis research estimated and compared the differences between the academic performance of students enrolled in distance education courses relative to those enrolled in traditional settings, as demonstrated by their final course grades/ scores within the 1990-2002 period. Eighty-six experimental and quasi-experimental studies met the established inclusion criteria for the meta-analysis (including data from over 15,000 participating students), and provided effect sizes, clearly demonstrating that: (1) in two thirds of the cases, students taking courses by distance education outperformed their student counterparts enrolled in traditionally instructed courses; (2) the overall effect size d+ was calculated as 0.37 standard deviation units (0.33
Concurrent Mentor: A Visualization System for Distributed Programming Education.

The study of distributed systems is increasingly fundamental to a Computer Science curriculum. Yet, the design of applications to run over distributed systems is complex and mastery of fundamental concepts is challenging for students. In order to assist in distributed systems instruction, we have developed ConcurrentMentor, a visualization system for distributed programming. This system reveals the behavior of a distributed program and its underlying communication protocols while the program executes. Input to the visualization system is generated by an accompanying communication library that closely follows abstractions of communication found in distributed systems literature. No program instrumenta-
In vivo and in vitro footprinting of a light-regulated promoter in the cyanobacterium Fremyella diplosiphon.

Certain filamentous cyanobacteria, such as Fremyella diplosiphon, modulate the components of their light-harvesting complexes, the phycobilisomes, and undergo complex morphological changes in response to the wavelength of incident light, or light quality. The operon encoding the subunits of phycoerythrin, cpeBA, is transcriptionally activated in green light and is expressed at very low levels in red light. To begin elucidating the signal transduction pathway between the detection of specific light wavelengths and changes in gene expression, we have used in vivo footprinting to show that a protein is bound to the region upstream of the cpeBA transcription start site in both red and green light: two guanosine residues at -55 and -65 bp are protected from dimethyl sulfate modification in vivo. Using DNA mobility shift gel electrophoresis, we have shown that partially purified extracts of F. diplosiphon from both red and green light contain DNA-binding activity specific for the cpeBA promoter region. Using in vitro footprinting with dimethyl sulfate and DNase I, we have defined a binding site for this putative transcription factor, designated PepB (phycoerythrin promoter-binding protein), that extends from -67 to -45 bp on the upper strand and from -62 to -45 bp on the bottom strand, relative to the transcription start site. The binding site includes two hexameric direct repeats separated by 4 bp, TTGTTAN4TTGTTA. We conclude from these results that PepB is bound to the region upstream of the cpeBA promoter in F. diplosiphon in both red and green light. Therefore, additional factors or protein modifications must be required to allow light-regulated transcription of this operon. Images
PAC Quasi-automatizability of Resolution over Restricted Distributions

We consider principled alternatives to unsupervised learning in data mining by situating the learning task in the context of the subsequent analysis task. Specifically, we consider a query-answering (hypothesis-testing) task: In the combined task, we decide whether an input query formula is satisfied over a background distribution by using input examples directly, rather than invoking a two-stage process in which (i) rules over the distribution are learned by an unsupervised learning algorithm and (ii) a reasoning algorithm decides whether or not the query formula follows from the learned rules. In a previous work (2013), we observed that the learning task could satisfy numerous desirable criteria in this combined context -- effectively matching what could be achieved by agnostic learning of CNFs from partial information -- that are not known to be achievable directly. In this work, we show that likewise, there are reasoning tasks that are achievable in such a combined context that are not known to be achievable directly (and indeed, have been seriously conjectured to be impossible, cf. (Alekhnovich and Razborov, 2008)). Namely, we test for a resolution proof of the query formula of a given size in quasipolynomial time (that is, "quasi-automatizing" resolution). The learning setting we consider is a partial-information, restricted-distribution setting that generalizes learning parities over the uniform distribution from partial information, another task that is known not to be achievable directly in various models (cf. (Ben-David and Dichterman, 1998) and (Michael, 2010)).
Effect of Framing of Reentry Program on Perceptions of Ex-Offenders

We examine the effect of the framing of reentry programs on participantsâ€™ perceptions of ex-offenders. Across four studies, participants expressed more favorable attitudes toward an ex-offender who completed a global citizen reentry program than an ex-offender who did not complete a reentry program. The results show that ex-offenders who complete a global citizen reentry program (vs. no program) are viewed as more likeable and similar to oneself, which then predicts reduced prejudice and greater endorsement to hire the ex-offender. The results are discussed in relation to the crossed categorization model of prejudice reduction.
L.O. limited frequency stability for passive atomic frequency standards using "square wave" frequency modulation

Atomic frequency standards using square-wave frequency modulation effectively interrogate the atomic line by switching back and forth between two frequencies with equal atomic absorption values. For a symmetric absorption line, the slope of the responses will also be equal. In the quasi-static limit this would seem to be an ideal interrogation process-the sign reversal of frequency slope can be removed by detection electronics to give an essentially unvarying and constant sensitivity to L.O. frequency variations. Such an interrogation would seem to eliminate L.O. aliasing and so relieve stringent requirements on local oscillator phase noise. However, sign changes in the interrogation and detection processes mean that the sensitivity is actually zero at some point in the cycle. We derive consequences of this fact for white phase and flicker phase noise models by an explicitly time-dependent analysis in terms of the sensitivity function g(t). We find that an optimal strategy exists for white phase L.O. noise for which g(t) takes the form of a sequence of parabolic arches, and which gives a small (/spl times/96//spl pi//sup 4/) improvement over simple sine-wave demodulation. We also find limiting forms that could in principle eliminate L.O, aliasing for flicker-phase noise. However, in practice the improvement shows only a logarithmic dependence on available response time and bandwidth.
Injury to Penetrating Blood Vessels in Cerebral Contusion

Traumatic brain injury (TBI), a devastating cause of death and disability [1, 2], commonly includes injury to the cerebral blood vessels [3]. Contusion has been called the hallmark of head injury [4], and includes damage to both blood vessels and surrounding parenchyma in the cortex. Vessels within the subarachnoid space, those penetrating the cortex, and capillaries within the cortical capillary plexus are all subject to injury and dysfunction. Contusion is primarily caused by traumatic interactions between the inner skull and brain surfaces, particularly in the inferior frontal and temporal lobe regions. However, little is known about the associated mechanisms of vessel damage. Definition of these mechanisms, and their thresholds, will inform prevention efforts. Improved understanding of the nature of vessel loading and injury may also lead to improved treatment.Copyright © 2012 by ASME
Thermodynamic calculation of the Mg-Mn-Zn and Mg-Mn-Ce systems and re-optimization of their constitutive binaries

The Mg–Mn-Ce and Mg–Mn–Zn ternary systems are modeled using the CALPHAD approach. Each constituent binary is critically reviewed in light of available experimental information. Consequently, binaries are re-optimized or directly adopted from the literature. All the binary liquids in the present optimization are modeled by the modified quasi-chemical model (MQM) while the random mixing model is used to describe the terminal solid solutions. The sub-lattice model is applied to the compounds with well-defined solubility range in contrast to the stoichiometric phases which are described as line compounds. Binaries are then extrapolated to form the ternaries without adding any ternary parameters. Very little experimental data is available on these two systems. Nonetheless, the present optimization reproduces most of experimental findings on these binaries as well as ternary systems with reasonable accuracy. Incorporation of future experimental data, as and when available, will refine the present optimization.
Plasma diagnostic requirements for Tokamak Fusion Core Experiment and International Tokamak Reactor (abstract)

The preconceptual design phase of the Tokamak Fusion Core Experiment (TFCX) and Phase IIA of the International Tokamak Reactor (INTOR) workshop have included reassessment of the plasma diagnostic requirements for the large rf heated, neutron‐generating plasmas in these devices. The three principal components of the work have been (i) to reassess the present level of diagnostic capability, (ii) to identify the diagnostics required for measurement before and during the burn phases of the two devices and (iii) to define a program of research and development activities of new or upgraded diagnostics. Both devices are expected to start operation in the early 1990’s; it is, therefore, necessary to set up development programs on U.S. tokamaks to evaluate fusion product measurements, and to establish capability of reliable, radiation‐hardened instruments. The adequacy of the operational information available with very limited access through the shielding and structure of the tokamaks also must be determined. This...
A calcium-binding protein in bile and gallstones.

Calcium salts are often present in the center of all types of gallstones. Matrix proteins are known to be essential for biomineralization and may therefore also be important in the formation and growth of gallstones. Other researchers have described an anionic peptide fraction of a biliary lipoprotein complex in bile and a low—molecular weight acidic glycoprotein present in gallstones. Our goal was to determine whether such a protein was present in bile and whether this protein has any calcium-binding properties. We identified a pigment-associated, highly acidic protein that precipitates from bile on addition of CaCl2 0.5 mol/L. In addition, the protein is selectively concentrated in cholesterol and pigment stones. We have, therefore, confirmed the findings of these other researchers, and we have extended the study of this protein's interactions with calcium. Sodium dodecylsulfate—polyacrylamide gel electrophoresis demonstrates a single band (molecular weight ≤ 14 kD) that reacts positively with cationic stains. The protein was shown to inhibit the precipitation of CaCO3 from a supersaturated solution. The capacity to bind calcium was further confirmed by autoradiography with 45Ca++ and by a membrane adsorption—binding assay. Calcium-induced aggregation was demonstrated by equilibrium dialysis and by quasielastic light scattering studies. Protein measured by Lowry's assay method and amino acid analysis constitutes only 2% to 4% of the harvested material. We speculate that a substantial lipid component may also be present. The presence of this material in bile, its ability to bind pigment and calcium, its presumed lipid content, its self-aggregation in the presence of calcium and its selective incorporation into gallstones suggest that it may play a functional role in the pathogenesis of gallstones.
Numerical Modeling of Electrothermal Effects in Silicon Nanowires

Asymmetric melting was observed in electrically pulsed n-type (phosphorus) nanocrystalline silicon (nc-Si) wires fabricated lithographically. Scanning electron microscope (SEM) images taken from the pulsed wires showed that melting initiates from the ground terminal end of the wires instead of the center as initially expected. Asymmetry in the temperature profile is caused by heat exchanged between charge carriers and phonons when an electrical current is passed along a temperature gradient. This effect is known as Thomson effect, a thermoelectric heat transfer mechanism. One dimensional (1D) time dependent heat diffusion equation including Thomson heat term was solved to model the temperature profile on our structures. The modeling results show that Thomson effect introduces significant shifts in the temperature distribution. The effect of Thomson heat is modeled for various electrical pulse conditions and wires dimensions. Our results indicate that Thomson effect is significant in small scale electronic devices operating under high current densities.
Effect of patent ductus arteriosus on doppler-derived right ventricular systolic time intervals

Right ventricular systolic time intervals (RVSTI) and noninvasive Dopplerderived pulmonary blood flow were measured before and after surgical ductus ligation in 18 otherwise healthy infants and children who were older than 3 months of age. Right ventricular preejection period (PEP) and the ratio of preejection period and right ventricular ejection time (PEP/REVET), both corrected or uncorrected for heart rate, decreased significantly following surgery (PEP 71±14 vs. 50±13,p<0.001 and PEP/RVET 0.29±0.06 vs. 0.21±0.05,p<0.001). The volume of pulmonary blood flow correlated with PEP/RVET (r=0.48,p=0.003). The magnitude of the change in pulmonary blood flow correlated with the change in PEP/RVET (r÷0.56,p=0.016). The velocity of circumferential fiber shortening (VCFc) increased after surgery, but not significantly. We speculate that patent ductus arteriosus has a similar effect on right ventricular performance when other congenital heart defects are present.
Effects of cation field strength on the structure of aluminoborosilicate glasses: High-resolution 11B, 27Al and 23Na MAS NMR

Among the most important adjustable compositional variables in controlling glass and glass-melt properties are the relative proportions of network modifiers with varying cation field strength (ratio of charge to radius). Here we determine the details of structural changes caused by variations in the ratio CaO/Na2O in two series of aluminoborosilicate glasses with different contents of boron oxide. Using high-resolution, high field 11B and 27Al MAS NMR, we report precise values of contents of three- and four-coordinated boron (N4) and of four- and five-coordinated aluminum ([5]Al), and calculate fractions of non-bridging oxygens (NBOs). Increasing CaO/Na2O dramatically lowers N4 and increases NBO and [5]Al, but effects are non-linear with composition. Boron content affects these trends because of energetic constraints of mixing of various network cations. 23Na spectra reveal slight but systematic increases in the mean Na–O distance with increasing CaO/Na2O, suggesting that in Ca-rich glasses, Na+ has a higher ratio of bridging to non-bridging oxygens in its coordination shell. All of these changes can be understood by the tendency of higher field strength modifier cations to promote the concentration of negative charges on non-bridging oxygens in their local coordination environment, systematically converting four- to three-coordinated boron.
The question of alleys, revisited

In 1919, American planner Karl B. Lohmann pondered ‘the question of alleys’ within a published review of town-planning principles for contemporary master-planned communities. In the early 20th century the back-alley was not necessarily ubiquitous in urban and suburban America, but it was commonplace; Frank Lloyd Wright, among others, had decreed residential back-alleys to be wasteful, unsightly anachronisms (Wright, 1916). Lohmann considered both the aesthetic pathologies of back-alleys and their added cost, while acknowledging their valuable ‘backstage’ utility; he concluded that back-alleys were still appropriate for commercial development, but were perhaps no longer necessary components of modern residential neighborhoods (Lohmann, 1919). Back-alleys were almost unknown in post-Second World War American suburbs, until advocates of the recent planning trend known as ‘new urbanism’ began an attempt to rehabilitate the back-alley as a streetscape-enhancing strategy, particularly for residential blocks. The new urbanist critical position is selective – reaffirming the argument for utility, without due consideration for the problematic side of the issue that was so much in evidence in planning discussions of the earlier era. In neither era, however, have the arguments for or against back-alleys in residential environments concerned much beyond utility, cost, and aesthetics; almost completely overlooked is the residential back-alley's value or potential as a unique cultural landscape and as a vital, block-scale neighborhood social realm.
Hard X-Ray Spectral Evolution and Production of Solar Energetic Particle Events during the January 2005 X-Class Flares

High-resolution hard X-ray observations provided by the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) are used to study the spectral evolution of ~50-200 keV nonthermal electron bremsstrahlung emissions of five X-class flares observed during the January 2005 solar storm events. Four of these flares show progressive spectral hardening during at least some hard X-ray peaks, while only one event shows the otherwise more commonly observed soft-hard-soft behavior. Imaging observations reveal that ~50-100 keV nonthermal electron bremsstrahlung emissions originate from footpoints of flare loops at all times, including during times of progressive spectral hardening, indicating that the spectral hardening component is produced by precipitating electrons, and not by electrons trapped in the corona. The four flares with progressive spectral hardening are all related to solar energetic particle (SEP) events, while the only X-class flare with soft-hard-soft behavior is not. This finding is consistent with earlier studies, suggesting that electron acceleration and transport in flares is somehow linked to the production of SEPs escaping into interplanetary space.
Improved Estimators for Ratios of Variance Components

Abstract The problem of estimating a ratio of variance components in the balanced one-way random effects model is considered. It is shown that in terms of mean squared error, the ML, REML (or truncated ANOVA), and Bayes modal estimators (using the noninformative prior) are inadmissible. An estimator that dominates all three is derived. Two other estimators that are adaptive in nature are also introduced. The new estimators are shown to possess much-improved mean squared error properties. The results easily extend to balanced higher-way random or mixed effects models.
Polymer‐supported salen complexes for heterogeneous asymmetric synthesis: Stability and selectivity

This paper details the enantioselective performance of styrene/divinylbenzene-supported Mn- and Cr-based salen complexes for the epoxidation of olefins and the ring-opening of epoxides to azido-silyl ethers. The Mn catalyst produced the epoxides of 1,2-dihydronaphthalene, styrene, and cis-β-methylstyrene with enantiomeric excesses (ee's) of 46, 9, and 79%, respectively. For the Cr catalyst, the enantioselective ring-opening of epoxyhexane, propylene oxide, and cyclohexene oxide with trimethylsilyl azide proceeded with ee's of 34, 36, and 6%, respectively. Upon recycle of these heterogeneous catalysts, a degradation process was noted for the Mn-catalyst under the conditions for epoxidation that resulted in oxidation and decomposition of the ligand. This process also affects the homogeneous catalyst, thereby limiting the recyclability of both the homogeneous Mn catalyst and its heterogenized version for this reaction. The Cr-catalyzed reaction to ring-open epoxides employs milder conditions and allowed reuse of the heterogeneous catalyst without loss of activity or enantioselectivity through three runs with epoxyhexane. During reaction, the leaching of Cr from the heterogeneous catalyst is less than 0.1%, suggesting possible reuse of the catalyst over hundreds of cycles before reloading the polymer-supported salen ligand with metal would be necessary. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 3888–3898, 1999
Ergodic and statistical properties of piecewise linear hyperbolic automorphisms of the 2-torus

We study generic piecewise linear hyperbolic automorphisms of the 2-torus. We explain why the resulting dynamical system is ergodic and mixing and prove the exponential decay of correlations.
c-Met gene amplification is associated with advanced stage colorectal cancer and liver metastases ☆

The c-Met proto-oncogene encodes a receptor tyrosine kinase (TK) that promotes tumor invasive growth and metastasis. Recent studied shown that presence of c-Met gene amplification is predictive for selective c-Met TK inhibitors in gastric cancer and lung cancer. In this study, we utilized a highly quantitative PCR/ligase detection reaction technique to quantify c-Met gene copy number in primary colorectal cancer (CRC) (N=247), liver metastases (N=147) and paired normal tissues. There were no differences in c-Met gene copy number between normal colonic mucosa and liver tissue. Mean c-Met gene copy number was significantly elevated in CRC compared to normal mucosa (P<0.001) and in liver metastases compared to normal liver (P<0.001) respectively. Furthermore, a significant increase c-Met was seen in liver metastases compared to primary CRC (P<0.0001). c-Met gene amplification was observed in 2% (3/177) of localized cancers, 9% (6/70) of cancers with distant metastases (P<0.02) and in 18% (25/147) of liver metastases (P<0.01). Among patients treated by liver resection, there was a trend toward worse 3-year survival associated with c-Met gene amplification (P=0.07). Slight increases in c-Met copy number can be detected in localized CRCs, but gene amplification is largely restricted to Stage IV primary cancers and liver metastases. c-Met gene amplification is linked to metastatic progression and is a viable target for a significant subset of advanced CRC.
Modeling the Relaxation of DNA Supercoils

Essential cellular processes such as replication and transcription induce torsional stresses in DNA which lead to an accumulation of supercoils. Excessive, as well as insufficient, levels of supercoiling can impede the progress of these processes. Therefore, topoisomerases are necessary to maintain an optimal degree of DNA supercoiling. Recent experiments have considered the relaxation dynamics of DNA supercoils by both Topo1B and nicking endonucleases. In these experiments, nicking endonucleases or topoisomerases act on individual torsionally constrained DNA molecules which are held at constant tension. Unfortunately, supercoil relaxation dynamics occur faster than can be measured by observing merely the end-to-end extension of the DNA, as in magnetic or optical trap assays. Our objective is to simulate the relaxation of DNA supercoils to better understand the dynamics and quantify the relaxation timescales. We represent DNA with a coarse-grained Brownian dynamics model which accounts for DNA bending, torsion, electrostatics, and hydrodynamics. Our simulations are designed to parallel experiments and permit direct comparisons to the experiments.
The acoustical cues to sound location in the guinea pig (Cavia porcellus).

There are three main acoustical cues to sound location, each attributable to space- and frequency-dependent filtering of the propagating sound waves by the outer ears, head, and torso: Interaural differences in time (ITD) and level (ILD) as well as monaural spectral shape cues. While the guinea pig has been a common model for studying the anatomy, physiology, and behavior of binaural and spatial hearing, extensive measurements of their available acoustical cues are lacking. Here, these cues were determined from directional transfer functions (DTFs), the directional components of the head-related transfer functions, for 11 adult guinea pigs. In the frontal hemisphere, monaural spectral notches were present for frequencies from ∼10 to 20 kHz; in general, the notch frequency increased with increasing sound source elevation and in azimuth toward the contralateral ear. The maximum ITDs calculated from low-pass filtered (2 kHz cutoff frequency) DTFs were ∼250 μs, whereas the maximum ITD measured with low-frequency tone pips was over 320 μs. A spherical head model underestimates ITD magnitude under normal conditions, but closely approximates values when the pinnae were removed. Interaural level differences (ILDs) strongly depended on location and frequency; maximum ILDs were 10 kHz. Removal of the pinna reduced the depth and sharpness of spectral notches, altered the acoustical axis, and reduced the acoustical gain, ITDs, and ILDs; however, spectral shape features and acoustical gain were not completely eliminated, suggesting a substantial contribution of the head and torso in altering the sounds present at the tympanic membrane.
First-Principles Characterization of Potassium Intercalation in Hexagonal 2H-MoS2

Periodic density functional theory calculations were performed to study the structural and electronic properties of potassium intercalated into hexagonal MoS2 (2H-MoS2). Metallic potassium (K) atoms are incrementally loaded in the hexagonal sites of the interstitial spaces between MoS2 layers of the 2H-MoS2 bulk structure generating KxMoS2 (0.125 ≤ x ≤ 1.0) structures. To accommodate the potassium atoms, the interstitial spacing c parameter in the 2H-MoS2 bulk expands to 15.871 A in K0.125MoS2. The second lowest potassium loading concentration (K0.25MoS2) results in the largest interstitial spacing expansion (to c = 16.617 A). Our calculations show that there is a small gradual contraction of the interstitial spacing as the potassium loading increases with c = 14.785 A for KMoS2. This interstitial contraction is correlated with an in-plane expansion of the MoS2 layers, which is in good agreement with experimental X-ray diffraction (XRD) measurements. The electronic analysis shows that potassium readily do...
Proteasome inhibition augments new protein accumulation early in long-term synaptic plasticity and rescues adverse Aβ effects on protein synthesis.

Protein degradation plays a critical role in synaptic plasticity, but the molecular mechanisms are not well understood. Previously we showed that proteasome inhibition enhances the early induction part of long-term synaptic plasticity for which protein synthesis is essential. In this study, we tested the effect of proteasome inhibition on protein synthesis using a chemically induced long-lasting synaptic plasticity (cLTP) in the murine hippocampus as a model system. Our metabolic labeling experiments showed that cLTP induction increases protein synthesis and proteasome inhibition enhances the amount of newly synthesized proteins. We then found that amyloid beta (Aβ), a peptide contributing to Alzheimer’s pathology and impairment of synaptic plasticity, blocks protein synthesis increased by cLTP. This blockade can be reversed by prior proteasome inhibition. Thus, our work reveals interactions between protein synthesis and protein degradation and suggests a possible way to exploit protein degradation to res...
Precise determination of aluminum by instrumental neutron activation

Abstract Because of the short half life of Al-28, the determination of aluminum by neutron activation is subject to many inaccuracies: variation of irradiation conditions between sample and standard, uncertainties in timing, and the effects of high and varying count rate, in addition to other sources of error that must be controlled even in work with long-lived nuclides. These errors can all be made smaller than the fundamental limit set by counting statistics, even when that limit is below 0.5 percent. The transfer function from the observed number of net counts to the counting rate at the end of irradiation is modeled as a product of three processes: radioactive decay and extending and nonextending dead time.The procedure has been applied to the analysis of NBS SRM 1633a Fly Ash. The mean concentration measured was 14.085% Al, with a standard deviation of the mean 0.023% Al for four determinations. The final results showed no significant imprecision beyond counting statistics. The accuracy of the metho...
Transmission in a 1D split-ring resonator metamaterial containing a nonlinear barrier: soliton modes

The transmission properties of electromagnetic waves in a 1d split ring resonator meta-material containing a nonlinear barrier are studied theoretically. Within the barrier the split ring resonator gaps contain a Kerr nonlinear dielectric media and outside the barrier the split ring resonator gaps contain a linear dielectric media. The focus of the study is on the transmission maxima (resonant transmissions) through the barrier determined as a function of the parameters characterizing the barrier dielectric media. The resonant transmissions are associated with the excitation of resonant modes in the barrier, and these resonantly excited barrier modes can in many instances be associated with various bright, dark, and grey solitons. The excitation of the modes is studied as a function of the dielectric media of the barrier and the dispersion of the wave incident on the barrier. Soliton modes are found to appear in the system at a lower critical value of the Kerr nonlinearity of the barrier media. In other cases, solitons arise through the breakup of modes evolving from the modes of the linear media barrier limit as nonlinearity is applied and allowed to increase.
Cyclosporine and psoriasis: 2008 National Psoriasis Foundation Consensus Conference.

Background Cyclosporine is a valuable option for the treatment of psoriasis. This report summarizes studies regarding the use of cyclosporine since the last guidelines were published in 1998. Objective A task force of the National Psoriasis Foundation Medical Board was convened to evaluate treatment options. Our aim was to achieve a consensus on new updated guidelines for the use of cyclosporine in the treatment of psoriasis. Methods Reports in the literature were reviewed regarding cyclosporine therapy. Limitations There are few evidence-based studies on the treatment of psoriasis with cyclosporine. Results A consensus was achieved on the use of cyclosporine in psoriasis including specific recommendations on dosing, monitoring, and use of cyclosporine in special situations. The consensus received approval from members of the National Psoriasis Foundation Medical Board. Conclusions Cyclosporine is a safe and effective drug for the treatment of psoriasis. It has a particularly useful role in managing psoriatic crises, treating psoriasis unresponsive to other modalities, bridging to other therapies, and treating psoriasis within a rotational scheme of other medications. Appropriate patient selection and monitoring will significantly decrease the risks of side effects.
C fibre innervation of a mechanoreceptor.

Pacinische Korperchen besitzen eine doppelte Innervation. Ausser der bekannten markhaltigen mechanorezeptorischen Faser (A-Faser, Ubertragungsgeschwindigieit 35 m/sec) tritt noch eine feine marklose Faser (C-Faser) in das Korperchen ein. Die C-Faser lasst sich mit elektrophysiologischen und histologischen Methoden in den mesenteralen Nerven, im Stiel des Pacinischen Korperchens sowie in seinem Innern (Proximalsegment) nachweisen.
All y’all need to know ‘bout retroelements in cancer

Genetic instability is one of the principal hallmarks and causative factors in cancer. Human transposable elements (TE) have been reported to cause human diseases, including several types of cancer through insertional mutagenesis of genes critical for preventing or driving malignant transformation. In addition to retrotransposition-associated mutagenesis, TEs have been found to contribute even more genomic rearrangements through non-allelic homologous recombination. TEs also have the potential to generate a wide range of mutations derivation of which is difficult to directly trace to mobile elements, including double strand breaks that may trigger mutagenic genomic rearrangements. Genome-wide hypomethylation of TE promoters and significantly elevated TE expression in almost all human cancers often accompanied by the loss of critical DNA sensing and repair pathways suggests that the negative impact of mobile elements on genome stability should increase as human tumors evolve. The biological consequences of elevated retroelement expression, such as the rate of their amplification, in human cancers remain obscure, particularly, how this increase translates into disease-relevant mutations. This review is focused on the cellular mechanisms that control human TE-associated mutagenesis in cancer and summarizes the current understanding of TE contribution to genetic instability in human malignancies.
Effects of extended sidestream smoke exposure on components of the C-fiber axon reflex

Abstract We have previously shown that young guinea pigs repeatedly exposed to sidestream cigarette smoke (SS) develop decreased airway reactivity of the C-fiber system without changing reactivity to one of its neurotransmitters, substance P (SP). This study was designed to determine whether the decreased reactivity was due to decreased responsiveness to another neurotransmitter, neurokinin A (NKA), decreased lung SP content, decreased affinity or number of NK 1 receptors, and/or decreased number of C-fibers. Duncan Hartley guinea pigs were exposed to filtered air (FA) or to SS for 6 h/day, 5 days/week for 5 weeks starting at 1 week of age. SS exposure did not change, (1) airway reactivity to NKA injected into the pulmonary artery of their isolated perfused lungs ( n = 6–7 each group), (2) lung SP content as measured by enzyme immunoassay ( n = 12 each group), (3) NK, receptor number or affinity as measured by radioligand binding ( n = 7 each group), or (4) SP-immunoreactive nerve profiles of the terminal bronchioles or small airways ( n = 6 each group). Thus, SS exposure does not decrease C-fiber system by reducing NKA responsiveness, decreasing SP content, changing NK 1 receptors, or decreasing the number of C-fibers.
Examining the disorder–crime connection in Philadelphia parks

Recent research on urban parks and crime in Philadelphia has shown that some parks have higher crime densities than other places within the city. Why that relationship exists is an open question. Here, field survey data collected through primary observation, along with official Philadelphia crime data from 2008 to 2009, is used to evaluate one possible explanation: the relationship between assessed physical disorder and crime. Regression models are used to examine both the influence of crime on incivilities and the inverse relationship, over an approximate 1-year time period. Findings show that contrary to what theories of incivilities would suggest, assessed physical disorder in parks in 1 year has no significant connection to crime in the next. However, both disorder and violent crime counts are significantly related to subsequent levels of observed incivilities. Results suggest that increasing the police presence in urban parks may serve to reduce both future criminal activity and physical disorder. The findings have implications for residents, park managers and police.
Five-alpha-reductase expression in benign and malignant urothelium: correlation with disease characteristics and outcome.

Objectives To evaluate 5-alpha-reductase (5αR) expression in benign and malignant urothelium and to assess the relationship between 5αR expression and tumor stage, tumor grade, and clinical outcome in patients with urothelial carcinoma/transitional cell carcinoma. Methods We performed immunohistochemistry for 5αR on 53 urothelial specimens from 36 patients with transitional cell carcinoma treated at our institution between June 2002 and July 2003. For each tumor and the adjacent nontumor urothelium, a semiquantitative staining score was calculated. We used t tests and analysis of variance to compare the staining score across groups. Kaplan-Meier and logistic regression analyses were performed to assess the relationship between 5αR expression and clinical outcome. Results 5αR was expressed throughout the non-neoplastic urothelium. Nontumor urothelium had greater mean staining scores than did tumor specimens (160.1 versus 105.5, P <0.01). Low staining scores were associated with high grade (P <0.05), Stage pT3, pT4, and pTis (P <0.05), and disease progression (P <0.05). A staining score less than the median was a risk factor for progression (odds ratio 6.2, P <0.01) on univariate regression analysis. Patients with a staining score less than the median had a greater likelihood of disease progression (log-rank P <0.05) and cause-specific mortality (log-rank P <0.05). Conclusions We demonstrated 5αR expression in human urothelium and found that expression is decreased in transitional cell carcinoma in relation to tumor grade and stage. Decreased 5αR expression was associated with disease progression and cause-specific mortality.
Human T lymphocytes specific for the immunodominant 83-99 epitope of myelin basic protein: recognition of golli MBP HOG 7.

Myelin basic protein (MBP) is a candidate auto-antigen in the disease multiple sclerosis. Although MBP was thought to be sequestered behind the blood-brain barrier, isoforms of MBPs have recently been demonstrated in lymphoid tissues. These isoforms, termed golli MBPs, contain sequences that are shared with “classic” MBP within the CNS. In the present study, we have determined that epitopes within golli MBP isoforms may be recognized by human T lymphocyte clones specific for classic MBP. Ten of 12 T-cell clones recognized golli MBP. Although 11 clones were specific for the immunodominant 83–99 sequence, the clones differed with respect to human leukocyte antigen (HLA) restriction, T-helper phenotype, cytolytic activity, and T-cell receptor usage. Greater responses to classic MBP than to golli MBP suggested a difference in the ability of the two proteins to be processed and to present epitopes therein. These data advance the hypothesis that golli MBP sequences expressed within lymphoid tissues may be recognized by classic MBP-specific T lymphocytes during central or peripheral tolerance. © 1996 Wiley-Liss, Inc.