cssi/SciSciGPT-SciSciNet huggingface dataset:
Medical Therapy: The Future

Recent studies have demonstrated that early disease control with mucosal healing in patients with Crohn’s disease is associated with improved long-term outcomes, furthering the need to identify new effective treatment options. Increased understanding of mechanisms of disease activity in IBD through preclinical and genetic association studies has led to the development of numerous novel therapeutic agents in Crohn’s disease. This includes biological therapies in development which target tumor necrosis factor α, lymphocyte adhesion as well as Il-12/23, JAK/STAT, and IL-6 signaling pathways. In addition to these targeted therapies, clinical trials are currently examining the effectiveness of mesenchymal stem cell treatment and therapies aimed at targeting the gut microbiome, including antibiotics and fecal microbiota transplantation. With a larger number of therapeutic options in Crohn’s disease, there will be an increased focus on optimizing therapy and development of tools to predict a response to treatment. The combination of increased therapeutic possibilities and a personalized approach to treatment is likely to improve overall response rates to medical therapy in patients with Crohn’s disease.
Structure-Based Design of Head-Only Fusion Glycoprotein Immunogens for Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) is a significant cause of severe respiratory illness worldwide, particularly in infants, young children, and the elderly. Although no licensed vaccine is currently available, an engineered version of the metastable RSV fusion (F) surface glycoprotein-stabilized in the pre-fusion (pre-F) conformation by "DS-Cav1" mutations-elicits high titer RSV-neutralizing responses. Moreover, pre-F-specific antibodies, often against the neutralization-sensitive antigenic site O in the membrane-distal head region of trimeric F glycoprotein, comprise a substantial portion of the human response to natural RSV infection. To focus the vaccine-elicited response to antigenic site O, we designed a series of RSV F immunogens that comprised the membrane-distal head of the F glycoprotein in its pre-F conformation. These "head-only" immunogens formed monomers, dimers, and trimers. Antigenic analysis revealed that a majority of the 70 engineered head-only immunogens displayed reactivity to site O-targeting antibodies, which was similar to that of the parent RSV F DS-Cav1 trimers, often with increased thermostability. We evaluated four of these head-only immunogens in detail, probing their recognition by antibodies, their physical stability, structure, and immunogenicity. When tested in naive mice, a head-only trimer, half the size of the parent RSV F trimer, induced RSV titers, which were statistically comparable to those induced by DS-Cav1. When used to boost DS-Cav1-primed mice, two head-only RSV F immunogens, a dimer and a trimer, boosted RSV-neutralizing titers to levels that were comparable to those boosted by DS-Cav1, although with higher site O-directed responses. Our results provide proof-of-concept for the ability of the smaller head-only RSV F immunogens to focus the vaccine-elicited response to antigenic site O. Decent primary immunogenicity, enhanced physical stability, potential ease of manufacture, and potent immunogenicity upon boosting suggest these head-only RSV F immunogens, engineered to retain the pre-fusion conformation, may have advantages as candidate RSV vaccines.
Synthesis and Reactivity of Neutral Palladium(II) Alkyl Complexes that Contain Phosphinimine-Arenesulfonate Ligands

The synthesis and characterization of ortho-phosphiniminium-arenesulfonate zwitterions 1a–1d, the corresponding sodium salts 3a–3d, methyl(pyridine)palladium(II) complex 4a, and methyl(4-tert-butylpyridine)palladium(II) 5a–5d complexes are reported. Complex 4a suffers from limited solubility in aromatic hydrocarbons, while 5a–5d are soluble in benzene and toluene. Complex 5a forms a tridentate orthopalladated species 6a upon heating to 80 °C in toluene. Introduction of alkyl substituents on the phosphinimine phosphorus atom retards orthopalladation, and the (nBu)3P functionalized complex 5d does not undergo orthopalladation after heating at 80 °C for 24 h. The Pd–C bond in the orthopalladated complex 6a is inert toward ethylene insertion. Complexes 5a–5d do not react with ethylene at 80 °C and decompose to Pd0 and zwitterions 1a–1d.
What Is the Best Approach to a Pediatric Patient with an Unexplained Intraoperative Cardiac Arrest

Still bleary-eyed from a long night on call doing a liver transplant, you stumble into the local coffee shop looking for a jolt of caffeine before the drive home. One of your new colleagues, fresh out of fellowship, bounces in the front door.
Controlled Molecular Release Using Nanoporous Alumina Capsules

The use of mechanically robust nanoporous alumina capsules, with highly uniform pores of 25 nm to 55 nm, for controled drug delivery is demonstrated. The nanoporous alumina capsules were fabricated by anodization of an aluminum tube, resulting in a highly uniform, large surface area, relatively inexpensive device suitable for biofiltration applications. Characterization of diffusion from the nanoporous capsules using fluorescein isothiocyanate and dextran conjugates of varying molecular weight, showed that molecular transport could be readily controlled by selection of capsule pore size. A branched membrane structure, with a stepwise change in pore size from large to small, is used to provide small pore-sized membranes with sufficient mechanical strength for handling.
PERENCANAAN STRATEGIS SISTEM DAN TEKNOLOGI INFORMASI DALAM MENUNJANG PELAYANAN RUMAH SAKIT (STUDI KASUS RUMAH SAKIT DAAN MOGOT TANGERANG)

Abstract— Strategic plan IS/IT is an identification process portofolio application IS bases on computer that will support organization in execution of business plan and implement its business target. In course of strategic plan IS/IT with object of Daan Mogot Hospital Tangerang research this, Writer uses framework according to Jhon Ward and Peppard. Concept of idea from strategic plan IS/IT from Jhon Ward left from existence of invesment condition IS and TI in the past that less can give benefit for target of organization business, catch business opportunity, and existence of phenomenon growing of competitive excellence organization because can exploit potency IS and IT. Situation is referred can happen because strategic plan IS and TI that out of focus at business, conducted by part that less understand business opportunity, and make only strategy because technology need. The result of research this is the have the shape of proposal of strategy planning framework Information system/Information Technology that can be used at Daan Mogot Hospital Tangerang I ntisari — Perencanaan strategik SI/TI merupakan suatu proses identifikasi portofolio aplikasi SI berbasis komputer yang akan mendukung organisasi dalam pelaksanaan rencana bisnis dan merealisasikan tujuan bisnisnya. Dalam proses perencanaan strategik SI/TI dengan obyek riset Rumah sakit Daan Mogot Tangerang. Penulis menggunakan framework menurut Jhon Ward dan Peppard. Konsep pemikiran dari perencanaan strategik SI/TI dari Jhon Ward berangkat dari adanya kondisi investasi SI dan TI di masa lalu yang kurang dapat memberikan manfaat bagi tujuan bisnis organisasi, menangkap peluang bisnis, dan adanya fenomena semakin meningkatnya keunggulan kompetitif organisasi karena mampu memanfaatkan potensi SI dan TI. Keadaan tersebut dapat terjadi karena rencana strategik SI dan TI yang kurang fokus pada bisnis, dilakukan oleh bagian yang kurang mengerti peluang bisnis, dan hanya membuat strategi karena kebutuhan teknologi semata. Hasil dari penelitian ini adalah berupa usulan kerangka kerja perencanaan strategi Sistem Informasi/Teknologi Informasi yang dapat digunakan pada Rumah sakit Daan Mogot Tangerang. Kata kunci: Perencanaan Strategik Sistem Informasi/Teknologi Informasi, Metodologi SI/TI
Small non-coding RNA expression in developing mouse nephron progenitor cells

MicroRNAs (miRNAs) are small non-coding RNAs that are essential for the regulation of gene expression and play critical roles in human health and disease. Here we present comprehensive miRNA profiling data for mouse nephron progenitors, which give rise to most of the cell-types of the nephron, the functional units of the kidney. We describe a miRNA expression profile for nephron progenitors, with 162 miRNAs differentially expressed in nephron progenitors when compared to whole kidney. We also annotated 52, and experimentally validated 4 novel miRNAs, which are expressed in developing kidney. Our data is available as a public resource, so that it can be integrated into future studies and analyzed in the context of other functional and epigenomic data in kidney development. Specifically, it will be useful in the effort to shed light on molecular mechanisms underlying processes essential for normal kidney development, such as nephron progenitor specification, self-renewal and differentiation.
An introduction to nonparametric regression in demographic research.

"My intent in this...paper is to alert demographers to the existence of useful new methods, known collectively as nonparametric (NP) regressions, that have been made possible by reductions in computing costs over the last several decades. NP regressions use brute force computing power to free researchers from the need to make strong a priori assumptions about functional forms, thus allowing greater flexibility and accuracy in modelling relationships than in standard parametric approaches. Increased flexibility and computing power do not eliminate the central role of theory in guiding social science research, but they free empirical analysis from the requirement that relationships between variables must have mathematically convenient shapes....I begin this paper with a discussion of bias-variance tradeoffs in regression models, followed by a discussion of localized regression. Subsequent sections discuss specific NP techniques for bivariate and multivariate regressions, with examples. Throughout this paper I will illustrate with data from 17,851 mothers aged 15-45 who were interviewed in the 1988 U.S. National Maternal and Infant Health Survey." (SUMMARY IN FRE)
Origin of Sex for Error Repair: III. Selfish Sex☆

According to the repair hypothesis, sex originated as a cooperative interaction-the benefit being damage repair. As with all cooperative strategies, cooperative sex may be vulnerable to selfish mutants. The purpose of the present paper is to understand what implications such selfish mutants may have both for the origin of sex, especially in competition with asexual diploidy, and for the elaboration of the sexual cycle, especially in facultatively sexual organisms. Asexual diploids are assumed to effectively and instantaneously repair all damages without expression of deleterious recessive mutations. Costs to asexual diploidy are considered in terms of its birth rate and mortality rate. The main results of the present paper are as follows. (i) Asexual diploidy wins when the costs of diploidy are small, mortality rates low, and damage rates high. (ii) Beginning with an ancestral state in which cells are asexual haploids, the sexual life cycle would emerge before asexual diploidy as a response to increasing DNA damage. (iii) Selfish sex is a far more robust repair strategy than cooperative sex, especially in competition with asexual diploidy. (iv) Although cooperative sex is more adaptive in extreme environments characterized by high damage and high mortality, selfish sex can still invade in these regions and take the entire system to extinction. (v) Once it is present, selfish sex is stable to asexual diploidy over a wide range of parameter values and can persist in regions of parameter space forbidded to the asexual diploid. These results help to address a concern of the gene repair theory of sex, which is that efficient repair in an asexual diploid is a better strategy than sex. Data from microbes bearing on the results are discussed as is the relationship between facultative sex in multicellular organisms and selfish sex in microbes.
The Ethics of Care as a Universal Framework for Global Journalism

The search for universal ethics among journalists has yet to receive general acceptance because previous attempts have sought a code of ethics to which all journalists around the globe could agree....
Ousting South Africa: Olympic clashes of 1968

South Africa modified its sport policy, though not its national policy of apartheid, prior to the 1968 Mexico City Olympic Games. Black and white South African athletes would compete as one team at the Olympics for the first time. This reversal of its previous all- white policy persuaded the majority of IOC members to accept South Africa’s participation at the 1968 Olympics. African nations were the first to withdraw in protest. Taking this stand, despite South Africa’s concessions, they sought nothing less than the end of apartheid itself. Recognising that a detailed historical interrogation can shed light on the struggles, politics, limitations, and achievements of social justice in and through sport, this article demonstrates when and how these different visions of social justice emerged, gained traction, and were resisted when it came to apartheid South Africa.
The politics of attack. Communiqués and insurrectionary violence

If today we live in a new Gilded Age of billionaires, weak labor organizations, and a widening gap between the rich and the rest, then the reemergence of anarchist (and anarchoid) violence after de...
“Mussel Watch”—Measurements of Chemical Pollutants in Bivalves as One Indicator of Coastal Environmental Quality

The utility of the bivalve sentinel organism approach to monitoring for some chemicals of environmental concern in coastal and estuarine areas has been evaluated by regional and national programs and by smaller-scale research efforts during the past 15 years. The extent and severity of coastal contamination by chemicals such as polychlorinated biphenyls, chlorinated pesticides, trace metals, and plutonium was assessed in several bivalve sentinel organism programs. Advantages and limitations of this approach are presented and discussed briefly within the context of both national and international efforts.
Embodied Design Improvisation: A Method to Make Tacit Design Knowledge Explicit and Usable

We present a design generative and evaluative technique that we call embodied design improvisation, which incorporates aspects of storyboarding, Wizard of Oz prototyping, domain expert improvisation, video prototyping and crowdsourced experimentation to elicit tacit knowledge about embodied experience. We have been developing this technique over the last year for our research on physical interaction design, where practitioners often rely on subtle, shared cues that are difficult to codify, and are therefore often left underexplored. Our current technique provides an approach to understanding how everyday objects can transition into mobile, actuated, robotic devices, and prescribing how they should behave while interacting with humans. By codifying and providing an example of this technique, we hope to encourage its adoption in other design domains.
Should CT replace IVUS for evaluation of CAD in large-scale clinical trials: Effects of medical therapy on atherosclerotic plaque

Clinical trials assessing the effect of medical therapies on atherosclerotic plaques have hitherto employed invasive imaging techniques such as intravascular ultrasound (IVUS). This has limited the study population to high-risk patients in whom invasive coronary angiography is indicated; moreover, IVUS typically is performed utilizing a target lesion-based analysis. Recently, comprehensive quantitative analysis of all atherosclerotic plaques in the complete coronary artery network has become possible through the use of coronary computed tomography angiography (CCTA). Excellent inter-observer and inter-scan reproducibility of CCTA has been reported. Several studies have already tested the applicability of CCTA-measured plaque volume changes as an imaging surrogate endpoint in clinical trials and have found positive results. Further, substantial evidence supports the use of CCTA as a novel imaging surrogate that can accurately assess the changes in plaque characteristics according to medical treatment. In this review, we summarize current evidences that support the use of CCTA as a novel imaging surrogate that can replace IVUS in evaluating the results of treatment. We also attempt to determine whether the technological advances in CCTA will extend its application beyond use as a diagnostic method in clinical practice to use in large-scale clinical trials.
Confronting Wartime Sexual Violence: Public Support for Survivors in Bosnia

Existing research on conflict-related sexual violence focuses on the motivations of perpetrators and effects on survivors. What remains less clear is how postconflict societies respond to the hards...
Separation of Bioactive Small Molecules, Peptide from Natural Products and Proteins from Pathogenic Microbe by Rotofor-based Preparative Isoelectric Focusing (IEF) Method

The primary purpose of purifying the bioactive small molecules is obtaining enough amount of specific molecules for their downstream applications. There are various methods available for serving this purpose. However, not all can afford for cost-effective purification methods, especially for complex biological samples. Here we demonstrate, the Rotofor based preparative IEF separation which shows the high possibility of separating and enriching desired molecules, including small molecules and peptides from the complex plant extract. This method is well-suited for use at any stage of a purification scheme and has been used for complex biological samples quantification and characterization. As a proof of concept, we fractionated Gymnema sylvestre plant extract and isolated a family of terpenoid saponin molecules at the acidic end and small peptide molecule near the basic end. To our knowledge, this is a first report that Rotofor can be used to fractionate bioactive small molecules from natural product sources. We also showed effective microbial protein separation using Candida albicans fungus as a model system. The Rotofor based IEF has appealing features such as low cost, simplicity, high application potential and can be performed in any laboratory with the instrument setup.
Who’s modeling STEM for kids? A character analysis of children’s STEM-focused television in the U.S.

Character portrayals are important to consider when investigating the effects of educational television on young viewers. When it comes to academic interests and career aspirations, children take c...
A molecular dynamics study of the binding effectiveness between undoped conjugated polymer binders and tetra-sulfides in lithium–sulfur batteries

Abstract Full atomistic molecular dynamics simulations are performed on tetra-sulfides and undoped conjugated polymers pernigraniline base polyaniline (PNB), leucoemeraldine base polyaniline (LEB), poly (3,4-ethylenedioxythiophene) (PEDOT) and polypyrrole (PPY) to investigate the binding effectiveness between polysulfides and polymer binders. The weight ratio between sulfur and binder in lithium–sulfur cells is considered in 1:1 v/v mixture of dioxolane/dimethoxyethane. The simulations reveal that the end group 2 of PNB can effectively bind a lithium tetra-sulfide (i.e. Li2S4) cluster or 2 out of 43 Li2S4 molecules with the effect of solvent. However, repeat units of PNB, LEB, PEDOT and PPY seem ineffective in binding solvated Li2S4 through non-bonded interaction, especially when the concentration of tetra-sulfide/binder in a local domain of the cathode is low. Therefore, polymers with this specific functional group (i.e. the end group 2 of PNB) are suggested to be further studied as potential effective binders to inhibit the shuttle effect of solvated lithium polysulfides. Also, since the solvent has considerable impact on the binding effectiveness between tetra-sulfides and binder, it is suggested to take advantage of the explicit solvation models, such as those built in this work, to predict how other influencing factors affect binding between polysulfides and polymers.
I Need Help! Physical Educators Transition to Distance Learning During COVID-19

During the spring of 2020, school districts across the United States were required to shift to distance learning modalities due to the COVID-19 pandemic The pandemic forced schools to close their doors to face-to-face instruction and quickly shift to an online format While online education is prevalent in the United States, it only serves about 2% to 4% of the total K-12 population Literature related to K-12 online physical education is sparse and there are concerns regarding accountability This study used a grounded theory approach and collected data through open-ended questions as part of an online survey Data clearly indicate that physical educators need assistance in the transition to distance learning, especially in developing plans for teaching motor skills and online pedagogies Many of the teachers in this study expressed frustration with how their school leadership handled the shift to distance learning, partially due to the marginalization of the subject matter Physical educators need the tools to expand their pedagogical technological knowledge as well as resources to advocate for themselves and their subject during adverse situations in schools The shift to distance learning has the potential to have positive outcomes, as teachers were forced out of their comfort zones to learn new technology skills that may translate to enhanced learning in the face-to-face environment Future studies should focus on development of distance learning pedagogies and seek to understand how to support teachers during crisis learning situations
Endovascular repair of aortic perforation and type B aortic dissection after axillary intra-aortic balloon pump insertion.

Abstract We present the successful endovascular repair of an iatrogenic aortic dissection in a 57-year-old woman with decompensated heart failure. An intra-aortic balloon pump was inserted in the patient via a percutaneous axillary approach for circulatory support. Six days later, she developed symptoms of abdominal pain and lower extremity malperfusion. Computed tomography angiography demonstrated a type B aortic dissection with associated retroperitoneal hematoma secondary to aortic perforation. The patient underwent emergent endovascular aortic repair and intra-aortic balloon pump removal with return of lower extremity perfusion. She recovered well and underwent heart and kidney transplant less than 2 months postoperatively.
Tectonic influence on Cenozoic mammal richness and sedimentation history of the Basin and Range, western North America

Tectonic activity can drive speciation and sedimentation, potentially causing the fossil and rock records to share common patterns through time. The Basin and Range of western North America arose t...
Html 4.0 User's Resource

From the Publisher: Get a head start on the programming pack and supercharge your Web pages with HTML 4.0. Get up to speed quickly with HTML and learn the new features that HTML 4.0 provides. Pappas and Murray take you step-by-step through the creation of simple but complete HTML code as each new topic is introduced. Early chapters start with topics and examples revolving around traditional HTML tags such as , , , , , , , , and more. In addition to a discussion on various tags and containers you'll learn how to format text and include graphics, links, tables, forms, animation, and more in your projects. More advanced topics include frames, scripting, cascading style sheets, layers, and Dynamic HTML. You'll also be introduced to CGI, JavaScript, and VBScript programming concepts.
Reimbursement in Teleneurology

Reimbursement for telemedicine services is a complex, dynamic, and continuously evolving issue. Despite advances and expansion in Medicare reimbursement for telemedicine, the provision of these services is still limited by compliance requirements. Additionally, the inherent variability of reimbursement policy and legislation from state to state for Medicaid and private payers further complicates the issue. This chapter discusses the current requirements for telemedicine reimbursement, with a focus on Medicare, which remains the de facto standard for many state Medicaid and private insurance programs.
Policy Science as Metaphysical Madness

In the past dozen years or so, policy-oriented social science research and analysis has become a growth industry in the United States. This has occurred in response to demand created by the spate of social welfare programs initiated by the Great Society and, for the most part, continued and expanded by the later administrations. Whereas in 1965 federal agencies spent about $235 million on applied social science research, in 1975 they spent almost $1 billion. Of the approximately $7.4 billion spent in these eleven years about two-thirds was under contract.1 This brought into being several large independent research bodies, some quasi-public and others private, and it greatly increased the amount of university-based policy-oriented social research and the supply of social scientists. According to the 1970 census, the number of social scientists increased by 163 percent in the 1960s, an increase larger than that of any other major occupational group nearlythree times that of professional and technical workers as a whole.
5HT7 Receptor Induced Phrenic Motor Facilitation Requires EPAC and mTORC1, But Not PKA Activity

Serotonin type-7 (5HT7) receptors in the cervical spinal cord elicit complex effects on respiratory motor activity. For example, intermittent 5HT7 receptor activation gives rise to long-lasting phr...
Relative importance of dispersion and rate-limited mass transfer in highly heterogeneous porous media: Analysis of a new tracer test at the Macrodispersion Experiment (MADE) site

[1] A single-well injection-withdrawal (SWIW) bromide tracer test was conducted to further investigate transport processes at the Macrodispersion Experiment (MADE) site on Columbus Air Force Base in Mississippi. The bromide breakthrough curve is highly asymmetric and exhibits an early time high-concentration peak followed by an extended period of low-concentration tailing. Comparisons of results simulated by advection-dispersion (AD) and dual-domain mass transfer (DDMT) models with the field data show that the DDMT model more accurately represents the magnitudes of both the early high-concentration peak and the later low-concentration tail. For both the AD and DDMT models, the match with field data is enhanced by incorporating hydraulic conductivity information from new direct-push profiling methods. The Akaike information criterion for the DDMT models is much smaller than that for the AD models in both the homogeneous and heterogeneous cases investigated in this work. The improved match of the DDMT model with the SWIW test data supports the hypothesis of mass transfer processes occurring at this highly heterogeneous site.
Catecholamines in the periphery. Overview.

Publisher Summary Recent research related to catecholamines in the periphery has dealt with assessment of peripheral catecholaminergic function, catecholamines and stress, catecholamines and pain, catecholamines and neuroimmunology, adrenomedullary secretion and cosecretion, neurocardiology, catecholamines and metabolism, and roles of catecholamines in the brain in regulation of the cardiovascular system. All of these are discussed in this chapter. Peripheral catecholaminergic systems probably play a role in many neurocardiologic disorders, either secondarily as homeostatic effectors or primarily as etiologic factors. The hemodynamic hallmark of neurocardiogenic syncope is systemic vasodilation, with or without bradycardia. The vasodilation results from sudden, marked decreases in sympathoneural outflows. In contrast, plasma epinephrine (Epi) levels generally increase in this setting. Studies show a close association between lymphocyte concentrations of catecholamines and of cyclic adenosine monophosphate (cAMP). The usefulness of lymphocyte norepinephrine (NE) concentrations in evaluating sympathoneural function remains unknown. Studies using microdialysis, specific activity of [ 3 H]normetanephrine, and NE concentrations in lymph is likely to enable estimates of NE concentrations in interstitial fluid and, thereby, estimates of release of NE from sympathetic nerves. More convincing, consistent evidence is required to understand the role of catecholaminergic systems in components of immune responses. Increased use of microdialysis in adipose tissue and skeletal muscle is likely to enhance understanding of catecholaminergic systems in patients with a variety of metabolic disorders, including insulin-dependent diabetes mellitus (IDDM) and obesity.
Mass spectrum of the two dimensional λφ4−1/4φ2−μφ quantum field model

It is shown thatr-particle irreducible kernels in the two-dimensional λφ4−1/4φ2−μφ quantum field theory have (r+1)-particle decay for |μ|≦λ2≪1. As a consequence there is an upper mass gap and, in the subspace of two-particle states, a bound state. The proof extends Spencer's expansion [20] to handle fluctuations between the two wells of the classical potential. A new method for resumming the low temperature cluster expansion is introduced.
Metabolomics in Systems Toxicology: Towards Personalized Medicine

Metabolomics along with systems biology technologies such as transcriptomics and proteomics has the capability of providing translational diagnostic, prognostic and mechanistic biomarkers of drug-induced injury. Metabolomics has several advantages over the other omics platforms, such as ease of sample preparation, data acquisition and use of biofluids collected through minimally invasive procedures in pre-clinical and clinical studies. The role of metabolomics in systems toxicology is reviewed and examples of metabolomics in pre-clinical and clinical studies are provided. The role of metabolomics in personalized medicine is provided with special sections focusing on drug–drug and drug–nutrient interactions, metabolic fluxes and challenge tests. Keywords: metabolomics; metabonomics; metabolic fluxes; biomarkers; personalized medicine; systems biology
Multidimensional analysis of fission gas transport following fuel element failure in sodium fast reactor

Abstract Significant progress in several areas will have to be made to achieve the required technological and safety standards for future Gen. IV reactors, including both novel experimental methods (starting with separate-effect, then followed by integral experiments) and high performance computational models characterized by the necessary level of modeling detail and high accuracy of predictions. Furthermore, it is important that the experimental and theoretical/computational research complement each other, so that the results of measurements could be directly used for model validation purposes, whereas the results of simulations should provide input to identify modeling uncertainties and provide guidelines for prioritizing future experiments. The purpose of this paper is to present the modeling concept for mechanistic computer simulations of the injection of a jet of gaseous fission products into a partially blocked SFR coolant channel following localized cladding overheat and breach. A three-dimensional model of gas/liquid-sodium interaction has been developed based on a multifield modeling framework implemented in the NPHASE-CMFD code. The boundary conditions used as input to NPHASE-CMFD have been obtained by averaging the results of direct numerical simulations (DNS) performed using the PHASTA code. The novel aspects of the results discussed in the paper include the demonstration of advantages of using a multiscale approach to model local phenomena governing gas/liquid-sodium two-phase flow inside reactor coolant channels following cladding breach, as well as the observations about areas where future experiments are needed to improve the predictive capabilities of two-phase flow models.
Vertical distribution and temporal variation of marine planktonic archaea in the Gerlache Strait, Antarctica, during early spring

A station located in the Gerlache Strait (Antarctic Peninsula) was sampled during early spring to determine the vertical distribution of marine planktonic archaea and to further describe the dynamic environment where they live. Chlorophyll concentration indicated that sampling occurred during the early stages of austral spring algal development. As expected, prokaryote abundance was higher at surface than at depth, and prokaryotic activity estimated by leucine incorporation was low at the surface and extremely low at 500 m. The relative abundance of planktonic archaeal, eucaryal, and bacterial ribosomal RNA was determined by quantitative rRNA hybridization, and the performance of two different universal probes used to normalize group-specific probe hybridization response was compared. Archaeal rRNA was detected in all samples analyzed, and was more abundant at depth (up to 25% of total rRNA) than at the surface. In both years, the archaeal signal decreased during the sampling period, particularly at surface. Most of the archaeal signal was attributable to group I archaea, affiliated with the kingdom Crenarchaeota. Planktonic euryarchaeotes (group II archaea) showed a larger contribution to the archaeal assemblage in surface waters than at depth. In total, our results verify that planktonic archaea are dynamic and abundant components in marine picoplankton assemblages of the Antarctic Peninsula.
Impacts of Climate Change on Regional Hydrological Regimes in the Spokane River Watershed

This study develops and implements a methodology to estimate the impacts of global climate change on regional hydrological regimes using ArcGIS Geostatistical Analyst. The model is easily used and can be expanded to different watersheds. The ArcGIS Geostatistical Analyst interface provides a comprehensive set of tools for creating surfaces from measured sample points compared with the previous method of using adjustable tension continuous curvature surface gridding. As a result, users can rapidly compare different interpolation techniques in order to obtain the best solution. Model results can subsequently be used in GIS models for visualization and analyses. The methodology was applied to the Spokane River Watershed. Results indicate that a 30% precipitation increase causes a 50% increase of streamflow when the temperature is normal compared to only a 20–30% increase in streamflow if the average annual air temperature is 1.5°C higher than normal. Conversely, a 20% precipitation decrease results in approx...
Accumulation of the polychlorinated biphenyl aroclor 1242 from contaminated detritus and water by the saltmarsh detritivore, Uca pugnax.

The uptake of Aroclor 1242 from ingested detritus and in contaminated water is compared in the fiddler crab. Analysis was by gas chromatography. Results show that uptake from water was about one-half that of the uptake from PCB-laden (85 ng/g dry wt) detritus after 34 days. Respiration and egestion rates may not be the only factors controlling accumulation and concentration. The concentration of PCBs in detritus may have a major effect. (JMT)
Attenuated cardiovascular hypertrophy and oxidant generation in response to angiotensin II infusion in glutaredoxin-1 knockout mice

Glutaredoxin-1 (Glrx) is a thioltransferase that regulates protein S-glutathiolation. To elucidate the role of endogenous Glrx in cardiovascular disease, Glrx knockout (KO) mice were infused with angiotensin II (Ang II) for 6 days. After Ang II infusion, body weight and blood pressure were similar between WT and Glrx KO mice. However, compared to WT mice, Glrx KO mice demonstrated (1) less cardiac and aortic medial hypertrophy, (2) less oxidant generation in aorta as assessed by dihydroethidium staining and nitrotyrosine, (3) decreased phosphorylation of Akt in the heart, and (4) less expression of inducible NOS in aorta and heart. In cultured embryonic fibroblasts from Glrx KO mice, S-glutathiolation of actin was enhanced and actin depolymerization was impaired after hydrogen peroxide stimulation compared with WT cells. Furthermore, oxidant generation in phorbol ester-stimulated fibroblasts and RAW 264.7 macrophage-like cells was lower with Glrx siRNA knockdown. These data indicate that Ang II-induced oxidant production and hypertrophic responses were attenuated in Glrx KO mice, which may result from impaired NADPH oxidase activation.
Interconnection of Distributed Generators to Distribution Networks

Screening methodology for evaluation of interconnection of distributed generation (DG) to distribution feeder is presented. Applicable regulatory documents are used as guidelines for the approach. DG applications are screened into three categories: those that should be approved without further actions; those which are not acceptable under any circumstances; and those which require further study. Detailed interconnection studies are proposed for further investigation of the proposed interconnection. Additional considerations for siting and capacity allocation of DG are discussed. Application of a screening tool to a realistic feeder model is demonstrated.
Mitochondrial dysfunction induced by a post-translationally modified amyloid linked to a familial mutation in an alternative model of neurodegeneration

Familial British dementia (FBD) is an early-onset non-amyloid-β (Aβ) cerebral amyloidosis that presents with severe cognitive decline and strikingly similar neuropathological features to those present in Alzheimer's disease (AD). FBD is associated with a T to A single nucleotide transition in the stop codon of a gene encoding BRI2, leading to the production of an elongated precursor protein. Furin-like proteolytic processing at its C-terminus releases a longer-than-normal 34 amino acid peptide, ABri, exhibiting amyloidogenic properties not seen in its 23 amino acid physiologic counterpart Bri1-23. Deposited ABri exhibits abundant post-translational pyroglutamate (pE) formation at the N-terminus, a feature seen in truncated forms of Aβ found in AD deposits, and co-exists with neurofibrillary tangles almost identical to those found in AD. We tested the impact of the FBD mutation alone and in conjunction with the pE post-translational modification on the structural properties and associated neurotoxicity of the ABri peptide. The presence of pE conferred to the ABri molecule enhanced hydrophobicity and accelerated aggregation/fibrillization properties. ABri pE was capable of triggering oxidative stress, loss of mitochondrial membrane potential and activation of caspase-mediated apoptotic mechanisms in neuronal cells, whereas homologous peptides lacking the elongated C-terminus and/or the N-terminal pE were unable to induce similar detrimental cellular pathways. The data indicate that the presence of N-terminal pE is not in itself sufficient to induce pathogenic changes in the physiologic Bri1-23 peptides but that its combination with the ABri mutation is critical for the molecular pathogenesis of FBD.
The effect of glycine in the production of toxic volatile aldehydes from heated corn oil

The fatty aldehydes generated from heated corn oil and from several corn oil/glycine mixtures were collected by a dynamic headspace sampling method and subsequently reacted with cysteamine to yield corresponding thiazolidines. Derivatized aldehydes were analyzed by a capillary gas chromatograph with flame photometric detector. Six fatty aldehydes, including formaldehyde and acetaldehyde, decreased in concentration in relation to increasing amounts of glycine in the oil.
Whole-cell recordings from visualized C1 adrenergic bulbospinal neurons: ionic mechanisms underlying vasomotor tone

The membrane properties of visually identified, DiI retrogradely labeled bulbospinal neurons of the C1 adrenergic cell group were studied by whole-cell recordings in brainstem slices from 7- to 10-day-old rats. A post-hoc histochemical analysis allowed us to evaluate the electrophysiological properties of the C1 adrenergic neurons, a group of cells known to project to the sympathetic preganglionic neurons. Two types of cells were labeled: pacemaker and non-pacemaker neurons. In voltage-clamp mode, C1 pacemaker neurons exhibited a TTX-sensitive, persistent inward current that was activated between -55 and -50 mV and reached a peak between -40 and -30 mV. This current was significantly larger in the pacemaker neurons as compared to the non-pacemaker neurons and appeared to be a principal conductance driving the C1 pacemaker activity. Two other conductances modulated the frequency of pacemaker discharge: (1) an anomalous rectifier accelerated pacemaker frequency by three synergistic actions: (a) depolarizing it at rest, (b) increasing the slope of the pacemaker potentials, and (c) limiting hyperpolarizing membrane excursions; and (2) an A-type current which had two opposing actions: (a) slowing it by decreasing the slope of the pacemaker potential, and (b) accelerating it by repolarizing the fast action potential. Persistent sodium current functions as the driver potential responsible for the tonic firing pattern of the C1 bulbospinal neurons providing a cellular mechanism responsible for the descending excitatory drive imposed onto sympathetic preganglionic neurons. Thus, it may explain how C1 neurons may function to maintain vasomotor tone or modulate other autonomic functions. This study is the first attempt to analyze voltage-activated membrane conductances of RVLM neurons of known phenotype and axonal connections.
The effect of changes in arterial CO2 tension on plasma lidocaine concentration.

The authors studied the effect of changes in arterial carbon dioxide tension on plasma tidocaine concentrations during a constant lidocaine infusion in eight healthy volunteers. With a PaCO2 of 41.4 ±. 0.9mmHg (mean ± SE), total plasma lidocaine concentrations were 3.97 ± 0.20 μg·ml-1. There was no significant change associated with hypercarbia (PaCO2 = 55.7 ± 1.5mmHg, lidocaine = 3.93 ± 0.18 μg±ml-1)or hypocarbia (PaCO2 = 19.5 ± 1.4mmHg, lidocaine = 4.29 ± 0.25 μg·ml-1), despite the known effects of changes in CO2 tension on hepatic blood flow and lidocaine protein binding. During hypercarbia, plasma lidocaine binding decreases while total plasma lidocaine remains essentially constant; therefore, increased CO2 tensions could cause toxicity if total lidocaine concentrations were in the high therapeutic range (5 μg·ml-1). Four subjects experienced transient symptoms of mild lidocaine toxicity during acute increases in carbon dioxide tension.
Mutations in the N-terminal region of RecA that disrupt the stability of free protein oligomers but not RecA-DNA complexes

We have introduced targeted mutations in two areas that make up part of the RecA subunit interface. In the RecA crystal structure, cross-subunit interactions are observed between the Lys6 and Asp139 side-chains, and between the Arg28 and Asn113 side-chains. Unexpectedly, we find that mutations at Lys6 and Arg28 impose severe defects on the oligomeric stability of free RecA protein, whereas mutations at Asn113 or Asp139 do not. However, Lys6 and Arg28 mutant proteins showed an apparent normal formation of RecA-DNA complexes. These results suggest that cross-subunit contacts in this region of the protein are different for free RecA protein filaments versus RecA-DNA nucleoprotein filaments. Mutant proteins with substitutions at either Lys6 or Arg28 show partial inhibition of DNA strand exchange activity, yet the mechanistic reasons for this inhibition appear to be distinct. Although Lys6 and Arg28 appear to be more important to the stability of free RecA protein, as opposed to the stability of the catalytically active nucleoprotein filament, our results support the idea that the cross-subunit interactions made by each residue play an important role in optimizing the catalytic organization of the active RecA oligomer.
Comparison of Risk of Conductive Hearing Loss Among Three Ethnic Groups of Arctic Audiology Patients

The purpose of the study was to investigate the relative contributions of age, gender, ethnic background, and a history of middle ear disease on the amount of conductive hearing impairment among native and non-native audiology patients in the Canadian North. A second goal of the study was to determine risk factors for conductive hearing loss in the patients studied. Three ethnic groups were represented among the 3,094 patients: Inuit, American Indian, and non-native. Loglinear and logit statistical models were applied, and these data were best explained by a 3-way interaction of history of middle ear disease, ethnic group, and hearing loss, and the 2-way interaction of age and hearing loss. The Inuit appear to be at higher risk for conductive hearing impairment than the other ethnic groups. Conductive hearing loss also appears to increase as age increases through the teenage years for all the patients regardless of ethnic group membership. Preschoolers were at the lowest risk for conductive hearing loss. ...
Miniature detector measures deep space radiation

[1] The 1972 journey of Apollo 17 marked not only the last time a human walked on the Moon but also the most recent manned venture beyond the outer reaches of the Earth's atmosphere. With preparations being made for humans to once again explore deep space, important steps are under way to quantify the hazards of leaving low-Earth orbit. One significant risk for long-distance missions is the increased exposure to ionizing radiation—energetic particles that can strip electrons off of otherwise neutral materials, affecting human health and the functioning of spacecraft equipment. The deep space probes that are being sent to measure the risks from ionizing radiation and other hazards can be costly, so maximizing the scientific value of each launch is important. With this goal in mind, Mazur et al. designed and developed a miniature dosimeter that was sent into lunar orbit aboard NASA's Lunar Reconnaissance Orbiter (LRO) in 2009. Weighing only 20 grams, the detector is able to measure fluctuations in ionizing radiation as low as 1 microrad (equivalent to 1.0 × 10-8 joules of energy deposited into 1 kilogram) while requiring minimal power and computer processing. The postage stamp—sized detector tracked radiation dosages for the first year of LRO's mission, with the results being confirmed by other onboard and near-Earth detectors. (Space Weather, doi:10.1029/2010SW000641, 2011)
Theoretical predictor for candidate structure assignment from IMS data of biomolecule-related conformational space.

The ability to correlate experimental ion mobility data with candidate structures from theoretical modeling provides a powerful analytical and structural tool for the characterization of biomolecules. In the present paper, a theoretical workflow is described to generate and assign candidate structures for experimental trapped ion mobility and H/D exchange (HDX-TIMS-MS) data following molecular dynamics simulations and statistical filtering. The applicability of the theoretical predictor is illustrated for a peptide and protein example with multiple conformations and kinetic intermediates. The described methodology yields a low computational cost and a simple workflow by incorporating statistical filtering and molecular dynamics simulations. The workflow can be adapted to different IMS scenarios and CCS calculators for a more accurate description of the IMS experimental conditions. For the case of the HDX-TIMS-MS experiments, molecular dynamics in the “TIMS box” accounts for a better sampling of the molecular intermediates and local energy minima.