cssi/SciSciGPT-SciSciNet huggingface dataset:
Cobalamin-dependent and cobalamin-independent methionine synthases in Escherichia coli: two solutions to the same chemical problem.

Two genes encoding proteins with methionine synthase activity are found in Escherichia coli. Both enzymes use methyltetrahydrofolate as a methyl donor to catalyze the conversion of homocysteine to methionine, as shown below: $$ C{H_3} -{H_4}PteGl{u_n} + Homocysteine(RHS) -------->{H_4}PteGl{u_n} + Methionine(RSC{H_3}) $$ The metH gene encodes a cobalamin-dependent methionine synthase (MetH). This protein is monomelic, with a deduced molecular weight of 136,055.1 It can use CH3-H4PteGlu1 as a substrate, and requires a reducing system and AdoMet for activation.2,3 The metE gene encodes a cobalamin-independent methionine synthase that requires methyltetrahydrofolate substrates with at least two glutamyl residues and is completely inactive with CH3-H4PteGlu1.4 This enzyme shows no requirement for reductive activation, but does require phosphate ion and magnesium for optimal rates of catalysis.5 It has a deduced molecular weight of 84,654,6 in good agreement with the value of 84,000 obtained by ultracentrifugation of the native enzyme.5 Both the metH 1,7,8 and metE 6,9genes have been sequenced, and their coding sequences show no detectable homologies. Thus these two proteins appear to have evolved independently to perform highly similar methyl transfers from N5 of methyltetrahydrofolate to the sulfur of homocysteine.
Film as a Tool for Philosophical Investigation

The previous chapter summarizes existentialist positions from a purely philosophical approach. While existentialism is most commonly thought of as a philosophical enterprise, there are certainly other means of conveying existentialist insights. For example, philosophers like Sartre, Camus, and Marcel wrote plays and novels with existentialist themes. Non-philosophers have also written works of fiction that have been described as existentialist; Dostoevsky, Hesse, Kafka, and Beckett are obvious examples. And films provide another medium where one can find existentialist content, as this book will extensively demonstrate. But literature, film, and other artistic media are not the same as philosophy, and there is considerable debate on how these artistic activities can impact the practice of philosophy. I contend that film indeed can be used as a tool in developing our philosophical positions, because it has a unique potential to describe the essential elements of the human condition. But what exactly does this mean? Can film do philosophy in some way? Or does it simply show us certain things about ourselves that philosophers can reflect on? To what extent can it contribute novel insights that are not easily attainable in the context of a philosophical essay? In this chapter and the next, I will confront the debate on these theoretical issues, identifying and resolving any difficulties that might arise from the use of film as a tool for philosophical investigation.
Physician participation in executions

Chemical dependence in the form of addiction is a chronic relapsing disease characterized by the overwhelming compulsion to use drugs in spite of adverse consequences. The practice of anesthesiology provides the setting for a susceptible host by offering an environment in which powerfully addictive drugs are immediately available for abuse. Addictive disease in the form of chemical dependency is present in all classes, cultures, and professions including healthcare professionals. A major occupational hazard of anesthesiologists is the development of addictive disease, which, in the light of the specialty's powerful drugs, often involves a rapidly progressive, life- and career-threatening pattern of behavior. Anesthesiologists have an ethical responsibility to be knowledgeable about addiction, to detect it in its earliest stages, and to support the treatment, rehabilitation, and eventually, if appropriate, reentry into the workplace of a recovering colleague.
An Experimental Approach to Social Support Communications: Interactive Coping in Close Relationships

This review covers four major topics. First, the authors discuss previous studies on social support that document the content of supportive communications. Next, the discussion turns to the development and validation of the Interactive Coping Behavior Coding System and its converse, the Support Activation Behavior Coding System. A third focus is research stemming from sensitive interaction systems theory, which makes predictions, based on numerous variables, concerning whether an interaction will be ameliorative or harmful. The final section presents findings on the effects of interactive coping variables on relationship maintenance.
Complications of Arthroscopic Surgery

The technique of arthroscopic shoulder surgery requires extreme caution, because complications have often been reported. Serious sequelae may occur in hypoxic encephalopathy, and pulmonary embolism caused by upper limb deep vein thrombosis may result in mortality. This chapter briefly describes rare complications as well as frequent complications that have been reported to date. Also, we describe our experience with complications of arthroscopic shoulder surgery, such as deviation of the anchor, breakage of surgical instruments, burns from heated irrigation fluid from a radiofrequency device, bone absorption in areas surrounding the absorbable anchor, osteolysis of the undersurface of the acromion from knot impingement, postoperative infection and pneumothorax, and subcutaneous emphysema after arthroscopic rotator cuff repair. Especially, we had 15 patients of pneumothorax or subcutaneous emphysema after arthroscopic rotator cuff repair. The incidence of pneumothorax or subcutaneous emphysema after arthroscopic rotator cuff repair was 2.3 %. Possible causes of pneumothorax and subcutaneous emphysema include the following: (1) positive pressure on the lung from the respirator under endotracheal intubation; (2) extensive infiltration of irrigation fluid into subcutaneous tissue in the thoracic wall, thereby diminishing movement of the thorax, resulting in insufficient extension of the thorax; (3) load imposition on the thoracic region from water pressure of the perfusion pump; and (4) low-temperature burn in the thoracic region by heated irrigation fluid from using a radiofrequency device.
In Vivo Biomechanics: Laxity Versus Dynamic Stability

Musahl et al. described laxity as the passive response of a joint to an externally applied force or torque in biomechanical terms [60]. Thus, laxity tests for evaluating knee injury assess the passive limits of motion in a particular direction or plane. Through comprehensive laxity testing, it is possible to describe the range of a passive envelope of motion that the joint can achieve within the limits of the low forces typically employed for such testing.
Torque density comparison of axial and radial Halbach couplings

This digests presents the closed form 3-D analytical equations for an axial and radial Halbach rotor magnetic coupling. The closed form equations give insight into the upper torque density limits of NdFeB based magnetic devices. The performance of the axial and radial coupling is compared.
Sexual selection constrains the body mass of male but not female mice

Sexual size dimorphism results when female and male body size is influenced differently by natural and sexual selection. Typically, in polygynous species larger male body size is thought to be favored in competition for mates and constraints on maximal body size are due to countervailing natural selection on either sex; however, it has been postulated that sexual selection itself may result in stabilizing selection at an optimal mass. Here we test this hypothesis by retrospectively assessing the influence of body mass, one metric of body size, on the fitness of 113 wild-derived house mice (Mus musculus) residing within ten replicate semi-natural enclosures from previous studies conducted by our laboratory. Enclosures possess similar levels of sexual selection, but relaxed natural selection, relative to natural systems. Heavier females produced more offspring, while males of intermediate mass had the highest fitness. Female results suggest that some aspect of natural selection, absent from enclosures, acts to decrease their body mass, while the upper and lower boundaries of male mass are constrained by sexual selection.
EarSketch, a Web-application to Teach Computer Science through Music (Abstract Only)

Participants of the session will discover EarSketch (https://earsketch.gatech.edu), a free, web-based learning environment that teaches introductory computer science through music. It aligns with Computer Science Principles and has been used in a variety of other educational contexts as well, ranging from late elementary through College. EarSketch provides an in-depth introduction to computer science and programming through composing, producing, and remixing music with Python and JavaScript code. No previous knowledge or experience in music, Python, or JavaScript is required to begin learning or teaching with EarSketch. Results from pilot studies show that EarSketch facilitates student learning about computation and improves student engagement in computing through parameters such as self-confidence, motivation, or intent to persist. This trend is particularly true for female and minority students, who are underrepresented today in US computer science classrooms. EarSketch comprises a curriculum, teacher materials, a coding environment, a DAW (Digital Audio Workstation), a sound database, and sharing tools. Fundamental computing concepts are introduced through curricular modules that teach how to place sounds, create rhythms, and manipulate effects, with a focus on popular genres such as hip hop and dubstep. The platform has over 77,000 users in computer science classrooms across the US and internationally. EarSketch receives funding from the National Science Foundation, the Scott Hudgens Family Foundation, the Arthur M. Blank Family Foundation, and the Google Inc. Fund of Tides Foundation.
The cost-effectiveness of three interventions for providing preventive services to low-income children.

Objective We evaluated the impact of loan repayment programmes, revising Medicaid fee-for-service rates, and changing dental hygienist supervision requirements on access to preventive dental care for children in Georgia. Methods We estimated cost savings from the three interventions of preventive care for young children after netting out the intervention cost. We used a regression model to evaluate the impact of changing the Medicaid reimbursement rates. The impact of supervision was evaluated by comparing general and direct supervision in school-based dental sealant programmes. Results Federal loan repayments to dentists and school-based sealant programmes (SBSPs) had lower intervention costs (with higher potential cost savings) than raising the Medicaid reimbursement rate. General supervision had costs 56% lower than direct supervision of dental hygienists for implementing a SBSP. Raising the Medicaid reimbursement rate by 10 percentage points would improve utilization by <1% and cost over $38 million. Given one parameter set, SBSPs could serve over 27 000 children with an intervention cost between $500 000 and $1.3 million with a potential cost saving of $1.1 million. Loan repayment could serve almost 13 000 children for a cost of $400 000 and a potential cost saving of $176 000. Conclusions The three interventions all improved met need for preventive dental care. Raising the reimbursement rate alone would marginally affect utilization of Medicaid services but would not substantially increase acceptance of Medicaid by providers. Both loan repayment programmes and amending supervision requirements are potentially cost-saving interventions. Loan repayment programmes provide complete care to targeted areas, while amending supervision requirements of dental hygienists could provide preventive care across the state.
The association between myopia and various subtypes of lens opacity: SEE (Salisbury Eye Evaluation) project.

Purpose To establish the relationship between myopia and lens opacity. Design Population-based cross-sectional study. Participants Two thousand five hundred twenty participants from the Salisbury Eye Evaluation aged 65 to 84 years. Methods Participants filled out questionnaires regarding medical history, social habits, and a detailed history of distance spectacle wear. They underwent a full ocular examination. Lens photographs were taken for assessment of lens opacity using the Wilmer grading system. Multivariate logistic regression models using generalized estimating equations were used to analyze the relationship between lens opacity type and degree of myopia, while accounting for potential confounders. Main Outcome Measures Presence of posterior subcapsular opacity, cortical opacity, or nuclear opacity. Results Significant associations were found between myopia and both nuclear and posterior subcapsular opacities. For nuclear opacity, the odds ratios (ORs) were 2.25 for myopia between −0.50 diopters (D) and −1.99 D ( P P P P = 0.002). For posterior subcapsular cataracts, ORs were 1.59 for myopia between −0.50 D and −1.99 D ( P = 0.11), 3.22 for myopia between −2.00 D and −3.99 D ( P = 0.002), 5.36 for myopia between −4.00 D and −5.99 D ( P P Conclusions These results confirm the previously reported association between myopia, posterior subcapsular opacity, and nuclear opacity. Furthermore, the strong association between early spectacle wear and posterior subcapsular opacity among myopes, absent for nuclear opacity, suggests that myopia may precede opacity in the case of posterior subcapsular opacity, but not nuclear opacity. Measures of association between posterior subcapsular opacity and myopia were stronger in the current study than have previously been found. Longitudinal studies to confirm the association are warranted.
Abstract 18552: Ulk1-Dependent Mitochondrial Autophagy Protects the Heart Against Pressure Overload-Induced Heart Failure

Mitochondrial autophagy (MA) degrades damaged mitochondria during heart failure. MA is activated after transverse aortic constriction (TAC) with a time course distinct from general autophagy, suggesting that MA is activated by a mechanism distinct from conventional autophagy. In order to elucidate the mechanism of MA during pressure overload (PO), loss-of-function mouse models of autophagy, including beclin1 systemic heterozygous knockout (KO) ( beclin1 -hetKO), atg7 cardiac-specific KO ( atg7 -CKO), and ulk1 cardiac-specific KO ( ulk1 -CKO) mice, and respective control mice were subjected to TAC for 7-28 days. In electron microscopic analyses, MA was observed in control and atg7 -CKO mice (0.32±0.04%, 0.93±0.57%; MA number/mitochondria number) but rarely in beclin 1 -hetKO (0.02±0.02%) and ulk1 -CKO mice (0.01±0.02%) at 7 days of TAC. Cox I/GAPDH and mitochondrial DNA content, indexes of mitochondrial content, were significantly decreased in control and atg7 -CKO but were increased in beclin 1 -hetKO mice and ulk1 -CKO mouse hearts at 7 days of TAC. These results suggest that both Beclin1 and Ulk1 mediate MA in response to PO. As expected, LC3-II, an index of conventional autophagy, was significantly decreased and more p62 was accumulated in control, atg7 -CKO, and beclin 1 -hetKO mice but not in ulk1 -CKO mice at 14 days of TAC, suggesting that PO-induced activation of conventional autophagy is Beclin 1- and Atg7-dependent. Left ventricular ejection fraction (EF) was decreased at 7 days (60.4±3.5, 75.6±1.7, p beclin 1 -hetKO compared to control mice. In atg7 -CKO mice, although EF was decreased at 7 days (54.0±2.3%, p ulk1 -CKO mice. In summary, both Beclin1 and Atg7 mediate conventional autophagy, whereas Beclin1 and Ulk1 mediate MA in response to PO. Beclin1/Atg7-dependent general autophagy protects the heart during the acute phase, whereas Beclin1/Ulk1-mediated MA protects the heart during the later phase of PO-induced cardiac hypertrophy.
True Detective (2014), Looking (2014), and the Televisual Long Take

This chapter juxtaposes two recent experiments in the televisual long take, both featured in eight-episode HBO seasons from 2014: the crime drama True Detective and the serio-comic Looking. True Detective foregrounded a “declarative” long take halfway through its first season, an elaborate Steadicam immersion that quickly became one of the most celebrated shots in American television. By contrast with that one-off tour de force, Looking made “stealth” long takes part of its vocabulary from the beginning, including a shot from the eighth episode describing an awkward post-break-up San Francisco street scene. These two very different articulations of the shot as extended time mapped out divergent trajectories for the language of “cinema” in the territory of television: the auteurist announcement of mastery and the observational expression of uncertainty.
Directly patching high-level exchange-correlation potential based on fully determined optimized effective potentials.

The key element in Kohn-Sham (KS) density functional theory is the exchange-correlation (XC) potential. We recently proposed the exchange-correlation potential patching (XCPP) method with the aim of directly constructing high-level XC potential in a large system by patching the locally computed, high-level XC potentials throughout the system. In this work, we investigate the patching of the exact exchange (EXX) and the random phase approximation (RPA) correlation potentials. A major challenge of XCPP is that a cluster’s XC potential, obtained by solving the optimized effective potential equation, is only determined up to an unknown constant. Without fully determining the clusters’ XC potentials, the patched system’s XC potential is “uneven” in the real space and may cause non-physical results. Here, we developed a simple method to determine this unknown constant. The performance of XCPP-RPA is investigated on three one-dimensional systems: H20, H10Li8, and the stretching of the H19–H bond. We investigated...
Optimizing Diagnosis of Urothelial Bladder Cancer with Blue Light Cystoscopy via Recognition of False-Positive Lesions.

Abstract Introduction: Blue light cystoscopy (BLC) using hexaminolevulinate (Cysview®) improves the detection of nonmuscle invasive bladder cancer (NMIBC).1–3 BLC results in lower recurrence rate a...
Physics-driven deep training of dictionary-based algorithms for MR image reconstruction

Techniques involving learned dictionaries can outperform conventional approaches involving (nontrained) analytical sparsifying models for MR image reconstruction. Inspired by iterative dictionary learning-based reconstruction methods, we propose a novel efficient image reconstruction framework involving multiple iterations (or layers). Each layer involves applying a transformation to image patches, thresholding, and then reconstructing the patches in a dictionary, followed by an update of the image using observed k-space measurements. We train the transforms, thresholds, and dictionaries within the multi-layer algorithm to minimize reconstruction errors. Our experiments demonstrate that for highly undersampled k-space data, such trained reconstruction algorithms provide high quality results.
Acute alcohol prevents the refeeding-induced decrease in autophagy but does not alter the increased protein synthetic response in heart.

Abstract Ethanol produces a state of anabolic resistance in skeletal muscle; however, whether the heart displays a similar defect is unknown. Hence, the purpose of this study was to determine the impact of acute ethanol administration on the major signal transduction pathways in the heart that are responsible for regulating the protein synthetic and degradative response to refeeding. Adult male C57Bl/6 mice were fasted for 12 h. Mice were then either refed normal rodent chow for 30 min or a separate group of mice remained food deprived prior to administration of 3-g/kg ethanol. Cardiac tissue and blood were collected 1 h thereafter and analyzed. Acute ethanol prevented the nutrient-induced stimulation of S6K1 phosphorylation in heart, but did not alter the phosphorylation of S6, eIF4B, and eEF2, known downstream substrates for this kinase. The refeeding-induced redistribution of eIF4E into the active eIF4F complex was also not changed by acute ethanol. Consistent with the above-mentioned changes in signaling proteins, ethanol did not impair the refeeding-induced increase in cardiac protein synthesis. Proteasome activity was not altered by alcohol and/or refeeding. In contrast, ethanol antagonized the refeeding-induced increase in ULK1 phosphorylation and p62 as well as the reduction in LC3B-II and Atg5/12 complex proteins. These data indicate that acute ethanol prevents the normally observed inhibition of autophagy seen after refeeding, while the mTOR-dependent increase in protein synthesis remains largely unaltered by alcohol.
Effects of source and level of dietary energy supplementation on in vitro digestibility and methane production from tall fescue-based diets

Abstract There is a lack of information about the effect of different sources, levels, and the mixtures of energy supplements commonly fed to cattle grazing tall fescue. Therefore, the objective of this study was to evaluate different common energy sources for beef cattle grazing tall fescue using an in vitro fermentation system. Four ruminally cannulated Holstein steers (571 ± 16.1 kg BW) were fed tall fescue hay once daily and served as donors of rumen contents for an in vitro fermentation experiment. Treatments were tall fescue hay (CON), soybean hulls (SBH), corn gluten feed (CGF), corn (CORN), or combinations (SBH + CGF, SBH + CORN, CGF + CORN, SBH + CGF + CORN) of these. Flasks were incubated for 48 h and then assessed for digestion by measuring true DM digestibility, VFA and ammonia concentrations, and total gas and methane production. Supplemental energy sources did not affect total VFA concentration, ammonia concentration, valerate proportion, isobutyrate proportion, isovalerate proportion, or acetate:propionate ratio. True digestibility and digestible energy were generally greater than CON (Table 3; P
Intermediate asymptotics for Richards' equation in a finite layer

Perturbation methods are applied to study an initial-boundary-value problem for Richards' equation, describing vertical infiltration of water into a finite layer of soil. This problem for the degenerate diffusion equation with convection and Dirichlet/Robin boundary conditions exhibits several different regimes of behavior. Boundary-layer analysis and short-time asymptotics are used to describe the structure of similarity solutions, traveling waves, and other solution states and the transitions connecting these different intermediate asymptotic regimes.
The Deterministic Prediction Of Damage

In this paper, the deterministic prediction of damage, via damage function analysis (DFA), which provides a robust technology for estimating the damage function at future times, is described. General analytical expressions for calculating the damage functions that can be used with arbitrary dependencies of pit nucleation rate, pit growth law and repassivation rate on the system parameters have been obtained. The application of DFA to the prediction of pitting damage is illustrated by reference to pitting corrosion of iron in neutral solutions.
Genetic variability in Russian wildrye (Psathyrostachys juncea) assessed by RAPD

To assess the genetic variation within and among accessions of Russian wildrye (Psathyrostachys juncea), 88 individuals of 11 accessions originated from geographically diverse locations were analyzed using randomly amplified polymorphic DNA (RAPD). Under the optimized condition, 56% of the 200 tested primers produced polymorphic RAPDs among accessions. High level RAPD marker variations existed both within and among accessions. About 56% and 44% of the amplified fragments were polymorphic within and among accessions, respectively. Accessions from neighboring geographical regions are more similar than those from distant regions. These results are comparable with those obtained from studies on chromosome C-banding and isozyme electrophoresis.
Therapeutic Strategies to Block the Hypoxic Response.

Patients with the low levels of O2 (hypoxia) in their primary tumors have a higher risk for metastasis and death, indicating a need to therapeutically inhibit the effectors of hypoxia. Many strategies have been developed and investigated to block the hypoxic response. For example, inhibitors of HIF-1 and HIF-2 function by altering the transcription, translation, dimerization, nuclear translocation, DNA-binding, or ubiquitination of the HIF proteins. Hypoxia-activated prodrugs inhibit the hypoxic response through hypoxia-mediated reduction of an inactive, or minimally active, chemical to a cytotoxic agent. Most hypoxia-activated prodrugs function by inducing DNA damage, but others with more novel functions, including prodrugs that release EGFR/HER2 inhibitors also exist. Despite the existence of many therapeutics to combat the hypoxic response, there has been very little success in late phase clinical trials, potentially due to a lack of biomarkers that can be used to stratify patients who would benefit from a hypoxia-targeted therapy.
Estimating Dynamic Functional Brain Connectivity With a Sparse Hidden Markov Model

Estimating dynamic functional network connectivity (dFNC) of the brain from functional magnetic resonance imaging (fMRI) data can reveal both spatial and temporal organization and can be applied to track the developmental trajectory of brain maturity as well as to study mental illness. Resting state fMRI (rs-fMRI) is regarded as a promising task since it reflects the spontaneous brain activity without an external stimulus. The sliding window method has been successfully used to extract dFNC but typically assumes a fixed window size. The hidden Markov model (HMM) based method is an alternative approach for estimating time-varying connectivity. In this paper, we propose a sparse HMM based on Gaussian HMM and Gaussian graphical model (GGM). In this model, the time-varying neural processes are represented as discrete brain states which are described with functional connectivity networks. By enforcing the sparsity on the precision matrix, we can get interpretable connectivity between different functional regions. The optimization of our model can be realized with the expectation maximization (EM) and graphical least absolute shrinkage and selection operator (glasso) algorithms. The proposed model is validated on both simulated blood oxygenation-level dependent (BOLD) time series and rs-fMRI data. Results indicate that the proposed model can capture both stationary and abrupt brain activity fluctuations. We also compare dFNC patterns between children and young adults from the Philadelphia Neurodevelopmental Cohort (PNC) study. Both spatial and temporal behavior of the dFNC are analyzed and compared. The results provide insight into the developmental trajectory across childhood and motivate further research on brain connectivity.
Making a Case for MLNs for Data-Driven Analysis: Modeling, Efficiency, and Versatility.

Datasets of real-world applications are characterized by entities of different types, which are defined by multiple features and connected via varied types of relationships. A critical challenge for these datasets is developing models and computations to support flexible analysis, i.e., the ability to compute varied types of analysis objectives in an efficient manner. To address this problem, in this paper, we make a case for modeling such complex data sets as multilayer networks (or MLNs), and argue that MLNs provide a more informative model than the currently popular simple and attribute graphs. Through analyzing communities and hubs on homogeneous and heterogeneous MLNs, we demonstrate the flexibility of the chosen model. We also show that compared to current analysis approaches, a network decoupling-based analysis of MLNs is more efficient and also preserves the structure and result semantics. We use three diverse data sets to showcase the effectiveness of modeling them as MLNs and analyzing them using the decoupling-based approach. We use both homogeneous and heterogeneous MLNs for modeling and community and hub computations for analysis. The data sets are from US commercial airlines and IMDb, a large international movie data set. Our experimental analysis validate modeling, efficiency of computation, and versatility of the approach. Correctness of results are verified using independently available ground truth. For the data sets used, efficiency improvement is in the range of 64% to 98%.
Spillover effects of job skills training on substance misuse among low-income youths with employment barriers: a longitudinal cohort study

Objectives. To examine spillover effects of job skills training (vs basic services only [e.g., adult basic education, job readiness training]) on substance misuse among low-income youths with emplo...
Predicting Generalization in Deep Learning via Local Measures of Distortion.

We study generalization in deep learning by appealing to complexity measures originally developed in approximation and information theory. While these concepts are challenged by the high-dimensional and data-defined nature of deep learning, we show that simple vector quantization approaches such as PCA, GMMs, and SVMs capture their spirit when applied layer-wise to deep extracted features giving rise to relatively inexpensive complexity measures that correlate well with generalization performance. We discuss our results in 2020 NeurIPS PGDL challenge.
Selective Inhibition of PDE4B Reduces Binge Drinking in Two C57BL/6 Substrains.

Cyclic AMP (cAMP)-dependent signaling is highly implicated in the pathophysiology of alcohol use disorder (AUD), with evidence supporting the efficacy of inhibiting the cAMP hydrolyzing enzyme phosphodiesterase 4 (PDE4) as a therapeutic strategy for drinking reduction. Off-target emetic effects associated with non-selective PDE4 inhibitors has prompted the development of selective PDE4 isozyme inhibitors for treating neuropsychiatric conditions. Herein, we examined the effect of a selective PDE4B inhibitor A33 (0-1.0 mg/kg) on alcohol drinking in both female and male mice from two genetically distinct C57BL/6 substrains. Under two different binge-drinking procedures, A33 pretreatment reduced alcohol intake in male and female mice of both substrains. In both drinking studies, there was no evidence for carry-over effects the next day; however, we did observe some sign of tolerance to A33's effect on alcohol intake upon repeated, intermittent, treatment (5 injections of 1.0 mg/kg, every other day). Pretreatment with 1.0 mg/kg of A33 augmented sucrose intake by C57BL/6NJ, but not C57BL/6J, mice. In mice with a prior history of A33 pretreatment during alcohol-drinking, A33 (1.0 mg/kg) did not alter spontaneous locomotor activity or basal motor coordination, nor did it alter alcohol's effects on motor activity, coordination or sedation. In a distinct cohort of alcohol-naive mice, acute pretreatment with 1.0 mg/kg of A33 did not alter motor performance on a rotarod and reduced sensitivity to the acute intoxicating effects of alcohol. These data provide the first evidence that selective PDE4B inhibition is an effective strategy for reducing excessive alcohol intake in murine models of binge drinking, with minimal off-target effects. Despite reducing sensitivity to acute alcohol intoxication, PDE4B inhibition reduces binge alcohol drinking, without influencing behavioral sensitivity to alcohol in alcohol-experienced mice. Furthermore, A33 is equally effective in males and females and exerts a quantitatively similar reduction in alcohol intake in mice with a genetic predisposition for high versus moderate alcohol preference. Such findings further support the safety and potential clinical utility of targeting PDE4 for treating AUD.
On the Optimal Control of Propagation Fronts

We consider a controlled reaction-diffusion equation, motivated by a pest eradication problem. Our goal is to derive a simpler model, describing the controlled evolution of a contaminated set. In this direction, the first part of the paper studies the optimal control of 1-dimensional traveling wave profiles. Using Stokes' formula, explicit solutions are obtained, which in some cases require measure-valued optimal controls. In the last section we introduce a family of optimization problems for a moving set. We show how these can be derived from the original parabolic problems, by taking a sharp interface limit.
STYLISTIC ANALYSIS OF TE DEUM LAUDAMUS

The aim of this essay is to do a stylistic analysis on Te Deum Laudamus. Stylistic techniques and methods are employed for this task under the aspects of syntactic semantic, phonological and graphological patterns. Effects of linguistic foregrounding are also highlighted in the paper. The analysis revealed that the poet made use of stylistic and linguistic tools not only to deepen his message but also to make it effective and aesthetic. Article visualizations:
From iron to bacterial electroconductive filaments: Exploring cytochrome diversity using Geobacter bacteria

Abstract Iron is the most versatile of all biochemically active metals, with variability encompassing its electronic configuration, number of unpaired electrons, type of ligands and iron-complexes stability. The versatility of iron properties is transposed to the proteins it can be associated to, especially relevant in the case of heme proteins. In this Review, the structural and functional properties of heme proteins are revisited, with particular focus on c-type cytochromes. The genome of Geobacter bacteria encodes for an unusually high number of assorted c-type cytochromes and, for this reason, they are used in this Review as a showcase of the cytochrome diversity. In the last decades, a vast portfolio of cytochromes has been revealed in these bacteria, with most of them defining new classes, ranging from monoheme to the recently identified polymeric assembly of multiheme cytochromes that forms micrometer-long electrically conductive filaments. These discoveries were on pace with the development of modern NMR equipment and advances in protein isotopic labeling methods, which are also revisited in this Review. Finally, following the description of the current state of the art of Geobacter cytochromes, examples on how the available structural and functional information was explored to structurally map protein–protein and protein–ligand interacting regions in redox complexes, and hence elucidate Geobacter’s respiratory pathways, are presented.
Do the Eyes Have It? Apraxia and Oculomotor Control in Autism (IN4-2.005)

OBJECTIVE: The current study had two hypotheses: that the saccade parameters of the autism group (ASD) would differ from a typically developing control group (TD); and that poorer saccadic control would be associated with more severe apraxia. BACKGROUND: Autism research has demonstrated deficits in gait, balance, motor planning and motor coordination, but little research has investigated oculomotor function. Available data is inconsistent, however several studies suggest that children with ASD struggle with oculomotor control. Many children with ASD also struggle performing learned, skilled movements (i.e. apraxia). Studies have shown an association between basic motor function and apraxia, but the relationship between oculomotor function and apraxia is unknown. DESIGN/METHODS: 40 adolescents age 8-15 (20 ASD and 20 TD) were administered a battery of standardized tests including the Beery VMI and supplemental tests of Visual Perception and Motor Coordination. IQ and social development was also tested. Saccade parameters were examined with a simple, single target paradigm and measured with the Eyelink 1000 remote eye-tracking system. Apraxia was assessed with a 30-item test designed to evaluate three subtypes of apraxia and basic motor function. RESULTS: ASD children displayed deficits in VMI, motor coordination, fine motor and gross motor skills compared to TD children. Ideational and buccofacial apraxia were greater in ASD. ASD children made more saccades, and their saccades showed increased latency and decreased accuracy. Ideational apraxia was negatively correlated with saccadic control as well as measures of social skill. CONCLUSIONS: The increased variability of timing and decreased accuracy of eye movements in ASD, suggests poorer oculomotor control. These deficits are associated with apraxia suggesting that a generalized praxis defect contributes to oculomotor control deficits. Similarly, the association of apraxia with tests of social skills suggests that praxis deficits may contribute to the development of social deficits. Supported by: NIH 2 T35 HL 7491-31 (MM), NINDS R21-NS070296 (JT) and NINDS P50-NS22343 (DT). Disclosure: Dr. Miller has nothing to disclose. Dr. Chukoskie has nothing to disclose. Dr. Townsend has nothing to disclose. Dr. Trauner has nothing to disclose.
A ρ-recognition site on phage λ cro-gene mRNA

The synthesis of RNA catalysed by RNA polymerase from Escherichia coli is terminated at specific sites on DNA templates through the action of a multimeric basic protein known as ρ (refs 1, 2). Three lines of evidence suggest that an interactions of ρ with the nascent RNA is important for this termination. First, ρ binds strongly to RNA3; second, ρ expresses an RNA–dependent ATPase activity which is essential for termination4,5; third, RNA polymerase does not terminate RNA synthesis at ρ-dependent sites when the nascent RNA is digested by ribonuclease during transcription2,6. From the fact that certain RNAs, particularly single-stranded, pyrimidine-rich polymers containing at least 10% cytidylate residues, are more effective than other RNAs at promoting ρ-ATPase, it has been proposed7 that ρ recognises specific sites on a nascent RNA for its action. We present evidence here that ρ does bind at a specific region on a mRNA transcribed from bacteriophage λ DNA.
Optimal Put Exercise: An Empirical Examination of Conditions for Mortgage Foreclosure

Implicit in option-pricing models of mortgage valuation are threshold levels of put-option value that must be crossed to induce borrower default. There has been little research into what these threshold values are that come out of pricing models or how they compare to exercised option values seen in empirical data. This study decomposes boundary conditions for optimal default exercise to look at the economic dynamics that should lead to optimal default timing. Empirical data on FHA insured mortgage foreclosures is then examined to discern the predictive influence of optimal-option-valuation-and-exercise variables on observed default timing and values. Interesting results include a new understanding of how to measure and use property equity variables during economic downturns, house-price index ranges over which default is exercised for various classes of borrowers, and implied differences in appreciation rates between market-price indices and foreclosed properties.
Historias sin fin: Negritud, creolización y narración en el Caribe

La historia es un concepto polemico en el Caribe. En este contexto, se escriben relatos que sirven o bien para reforzar la idea del pasado como algo completo y definitivo, como punto de arranque para el presente y el futuro, o bien como una carga de la que hay que liberarse. O, como se aprecia desde Joseph Zobel y Edouard Glissant, escritores martiniquenos, la historia se puede ver como un relato sin final simple. Estas tres visiones condensadas como eurogenesis, afrogenesis y bricolaje cultural se estudian aqui a partir de varios prominentes escritores.
Ammonia emission inventory for the state of Wyoming

AMMONIA EMISSION INVENTORY FOR THE STATE OF WYOMING Prepared for Susan Caplan Bureau of Land Management Department of Interior by Thomas W. Kirchstetter TWKirchstetter@lbl.gov Colette R. Maser CRMaser@lbl.gov Nancy J. Brown, Principal Investigator NJBrown@lbl.gov Atmospheric Sciences Department Lawrence Berkeley National Laboratory Berkeley, California 94720
Estabrook-Wahlquist Prolongations and Infinite-Dimensional Algebras

Detailed mappings between zero-curvture equations for prolongation structures of nonlinear pde's and Estabrook-Wahlquist algorithms for same are given. The differences are exemplified by studies of the sine-Gordon equation. An example where the prolongation structure must be infinite-dimensional is given by the Robinson-Trautman equation, where the minimal algebra is $K_2$. In general these algorithms require integration of vector-field valued pde's; solutions of simultaneous flow equations are given. Applications to coupled systems of flow equations are given, where the result describes Lie algebras of vector fields vertical over fibers of pseudopotentials over a jet bundle appropriate for a given system of pde's; algebras invariant under sl(2,C) are of special interest.
Tumor necrosis factor induces skeletal muscle protein breakdown in rats

The metabolic response to infection includes loss of lean tissue and increased nitrogen excretion. The loss of muscle tissue during infection results in large part from accelerated skeletal muscle protein breakdown. Recent studies suggest that macrophage-derived products secreted during infection may signal increased muscle proteolysis. To test this, in the present report the ability of interleukin (IL-1) and tumor necrosis factor (TNF) to enhance muscle proteolysis was examined. Young rats were injected intravenously with either recombinant human IL-1 or TNF. For comparison some rats were injected with bacterial endotoxin. Eight hours after each treatment, the extensor digitorum longus muscles were isolated and incubated in vitro to assess muscle proteolysis by measuring tyrosine and 3-methyl-L-histidine release by the incubated muscles. Treatment of rats with either IL-1, TNF, or endotoxin all induced fever, increased serum lactate, and reduced serum zinc levels. Despite similar metabolic changes, muscle proteolysis responded differently. As expected, endotoxin treatment enhanced muscle protein breakdown, whereas IL-1 treatment was without effect. On the other hand, TNF was effective in accelerating muscle protein breakdown. TNF addition in vitro failed to enhance muscle proteolysis by incubated muscles, suggesting that its effects may be mediated in an indirect manner; however, a direct mode of action cannot yet be ruled out. Overall, the data indicate that the acute administration of TNF can signal increased muscle proteolysis similar to that observed during infection.
Membrane Expansion Increases Endocytosis Rate during Mitosis

Mitosis in mammalian cells is accompanied by a dramatic inhibition of endocytosis. We have found that the addition of amphyphilic compounds to metaphase cells increases the endocytosis rate even to interphase levels. Detergents and solvents all increased endocytosis rate, and the extent of increase was in direct proportion to the concentration added. Although the compounds could produce a variety of different effects, we have found a strong correlation with a physical alteration in the membrane tension as measured by the laser tweezers. Plasma membrane tethers formed by latex beads pull back on the beads with a force that was related to the in-plane bilayer tension and membrane– cytoskeletal adhesion. We found that as cells enter mitosis, the membrane tension rises as the endocytosis rate decreases; and as cells exited mitosis, the endocytosis rate increased as the membrane tension decreased. The addition of amphyphilic compounds decreased membrane tension and increased the endocytosis rate. With the detergent, deoxycholate, the endocytosis rate was restored to interphase levels when the membrane tension was restored to interphase levels. Although biochemical factors are clearly involved in the alterations in mitosis, we suggest that endocytosis is blocked primarily by the increase in apparent plasma membrane tension. Higher tensions inhibit both the binding of the endocytic complex to the membrane and mechanical deformation of the membrane during invagination. We suggest that membrane tension is an important regulator of the endocytosis rate and alteration of tension is sufficient to modify endocytosis rates during mitosis. Further, we postulate that the rise in membrane tension causes cell rounding and the inhibition of motility, characteristic of mitosis.
The epidemiology of problem drinking in gay men and lesbians: A critical review

Abstract This review examines research on the prevalence of problem drinking among gays and lesbians, and discusses various theories as to the etiology of drinking problems in this population. Early reports on alcohol problems in this population suggested that gay men and lesbians were at alarmingly high risk for alcohol problems; however, methodological flaws call these results into question. More recent research suggests that gay men are not at significantly higher risk for drinking heavily or for developing drinking problems than heterosexual men. Problem drinking may exist at somewhat higher rates among lesbians than among heterosexual women, although not at the high rates reported in early studies. Both gay men and lesbians appear to be less likely to abstain from alcohol than their heterosexual counterparts. Numerous theories have been proposed to explain the etiology of problem drinking in this population, including subcultural phenomena, self-medication hypotheses, and social and cultural pressures. However, none of these theories has more than minimal empirical support. Clinical implications and recommendations for further research are discussed.
Characterization of dopaminergic influence on striatal-nigral neurotensin systems.

Dopamine depletion by treatment withα-methyl-p-tyrosine had no effect on methamphetamine-mediated increases in striatal neurotensin (NT) concentrations but significantly attenuated nigral increases; the attenuation in the nigral response was reversed byl-DOPA. Blockade of D2-receptors, with sulpiride, by itself increased striatal NT levels, while having no effect on the nigral NT system or its response to methamphetamine. In contrast, D1 blockade with SCH 23390 had no effect of its own on NT levels but significantly blocked the methamphetamine-induced actions in both the striatal and nigral NT systems.
Behavioural determinants of distribution and survival in early stages of walleye pollock, Theragra chalcogrammai a synthesis of experimental studies

This review summarizes results of an extensive series of laboratory studies on the behavioural responses of early life stages of walleye pollock, Theragra chakogramma to key environmental factors including light, temperature, gravity, turbulence, food availability and predator presence. Experiments focused on vertical distribution of egg through 0-age stages, and social interactions of age-0 juveniles. Key factors were modified either singly or in concert to determine their direct and indirect influence on fish behaviour. The observed results suggest that the behaviour of individual fish depends on the integration of a continually changing hierarchy of both intrinsic and extrinsic factors, with the relative importance of a specific factor varying with ontogeny and over time and space. The broad range of responses displayed by early life stages suggests that behaviour plays an important role in determining the consequences of environmental variability on walleye pollock populations. In general, results from our laboratory experiments are consistent with patterns observed in field studies, supporting the efficacy of using experimental behavioural research to define some of the underlying mechanisms controlling distribution and survival in the field, and eventual recruitment to adult populations.