cssi/SciSciGPT-SciSciNet huggingface dataset:
Clarifying the neurobehavioral sequelae of moderate drinking lifestyles and acute alcohol effects with aging

Epidemiological estimates indicate not only an increase in the proportion of older adults, but also an increase in those who continue moderate alcohol consumption. Substantial literatures have attempted to characterize health benefits/risks of moderate drinking lifestyles. Not uncommonly, reports address outcomes in a single outcome, such as cardiovascular function or cognitive decline, rather than providing a broader overview of systems. In this narrative review, retaining focus on neurobiological considerations, we summarize key findings regarding moderate drinking and three health domains, cardiovascular health, Type 2 diabetes (T2D), and cognition. Interestingly, few investigators have studied bouts of low/moderate doses of alcohol consumption, a pattern consistent with moderate drinking lifestyles. Here, we address both moderate drinking as a lifestyle and as an acute event. Review of health-related correlates illustrates continuing inconsistencies. Although substantive reductions in risk for cardiovascular and T2D events are reported, robust conclusions remain elusive. Similarly, whereas moderate drinking is often associated with enhanced cognition and lower dementia risk, few benefits are noted in rates of decline or alterations in brain structure. The effect of sex/gender varies across health domains and by consumption levels. For example, women appear to differentially benefit from alcohol use in terms of T2D, but experience greater risk when considering aspects of cardiovascular function. Finally, we observe that socially relevant alcohol doses do not consistently impair performance in older adults. Rather, older drinkers demonstrate divergent, but not necessarily detrimental, patterns in neural activation and some behavioral measures relative to younger drinkers. Taken together, the epidemiological and laboratory studies reinforce the need for greater attention to key individual differences and for the conduct of systematic studies sensitive to age-related shifts in neurobiological systems.
Emerging Therapeutic Implications of STK11 Mutation: Case Series

STK11 was first recognized as a tumor suppressor gene in the late 1990s based on linkage analysis of patients with Peutz-Jeghers syndrome. STK11 encodes LKB1, an intracellular serine-threonine kinase involved in cellular metabolism, cell polarization, regulation of apoptosis, and DNA damage response. Recurrent somatic loss-of-function mutations occur in multiple cancer types, most notably in 13% of lung adenocarcinomas. Recent reports indicate that KRAS-mutant non-small cell lung cancers harboring co-mutations in STK11 do not respond to PD-1 axis inhibitors. We present three patients with STK11-mutated tumors and discuss the proposed mechanisms by which germline and somatic alterations in STK11 promote carcinogenesis, potential approaches for therapeutic targeting, and the new data on resistance to immune checkpoint inhibitors. KEY POINTS: STK11 is a tumor suppressor gene, and loss-of-function mutations are oncogenic, due at least in part to loss of AMPK regulation of mTOR and HIF-1-α. Clinical trials are under way, offering hope to patients whose STK11-mutated tumors are refractory and/or have progressed on chemotherapeutic regimens. Whether gastrointestinal cancers with STK11 loss of function will show the same outcome and potential refractoriness to immune therapy that were reported for lung cancer is unknown. However, physicians managing such patients should consider the experience in lung cancer, particularly outside the context of a clinical trial. In the CheckMate-057 trial lung tumors harboring co-mutations in KRAS and STK11 had an inferior response to PD-1 axis inhibitors. Coupled with the observation that STK11-mutated tumors were found to have a cold immune microenvironment regardless of KRAS status, the conclusion could extend to KRAS wild-type tumors with STK11 mutation. Current data suggest that the use of PD-1 axis inhibitors may be ill advised in the presence of STK11 mutation.
Crystal growth and scintillation properties of new ytterbium-activated scintillators Cs4CaI6:Yb and Cs4SrI6:Yb

Abstract Yb2+ was investigated as a potential alternative activator for Cs4SrI6 and Cs4CaI6 scintillators for the first time, as opposed to the previously studied Eu2+ activator. Single crystals with nominal Yb2+ concentrations of 0.5 mol%, 1 mol%, and 3 mol% were grown in O7 mm ampoules using the vertical Bridgman method. Luminescence and scintillation properties were evaluated as a function of Yb2+ concentration and host compound. The 5d → 4f electronic transition of Yb2+ was observed for both the Sr- and Ca-containing compositions. X-ray induced radioluminescence emission was centered between 449 nm and 463 nm depending on Yb2+ concentration and host compound. Both the spin-allowed and spin-forbidden transitions were observed in photoluminescence emission spectra and were centered at 446 nm and 476 nm, respectively, for both compounds. The best scintillation performance was achieved with Cs4CaI6:Yb 1 mol%, which had a 3.5% energy resolution at 662 keV and 43,000 ph/MeV light yield. To our knowledge this is the best energy resolution ever reported for a Yb2+-doped scintillator. Additional Cs4CaI6:Yb 1% crystals were grown in O12 mm ampoules to investigate the size dependence of scintillation properties, as well as crystal homogeneity.
Toxicant Effects on Mammalian Oocyte Mitochondria

Oocyte mitochondria are unique organelles that establish a founder population in primordial germ cells (PGCs). As the oocyte matures in the postnatal mammalian ovary during folliculogenesis it increases exponentially in volume, and the oocyte mitochondria population proliferates to about 100 000 mitochondria per healthy, mature murine oocyte. The health of the mature oocyte and subsequent embryo is highly dependent on the oocyte mitochondria. Mitochondria are especially sensitive to toxic insults, as they are a major source of reactive oxygen species (ROS), they contain their own DNA (mtDNA) that is unprotected by histone proteins, they contain the electron transport chain that uses electron donors, including oxygen, to generate ATP, and they are important sensors for overall cellular stress. Here we review the effects that toxic insults including chemotherapeutics, toxic metals, plasticizers, pesticides, polycyclic aromatic hydrocarbons (PAHs), and ionizing radiation can have on oocyte mitochondria. This is very clearly a burgeoning field, as our understanding of oocyte mitochondria and metabolism is still relatively new, and we contend much more research is needed to understand the detrimental impacts of exposure to toxicants on oocyte mitochondria. Developing this field further can benefit our understanding of assisted reproductive technologies and the developmental origins of health and disease (DOHaD).Summary sentence Oocyte mitochondria are unique organelles, which are sensitive targets to various toxicants.
THz Communications - a Boon and/or Bane for Security, Privacy, and National Security

The THz spectrum, ranging from 95 GHz to 10 THz, can enable multiple benefits and applications for wireless communications, passive, spectroscopy, and imaging system. Although there are multiple technical and economic challenges associated with THz deployment, the rarely discussed challenge of security and privacy-related risks needs attention from researchers, manufacturers, and even policymakers. THz spectrum could represent either a boon or a bane (or both) for security, privacy, and even national security. These include concerns over an array of increased risks, such as failure of devices, failure of the system, unauthorized or covert access, compromise of data, data integrity, impact on other services (apps), impact on critical infrastructure, securing dense deployment, and exposure of sensitive information. In this paper, we describe how the use of the THz spectrum could both introduce and negate security and privacy risks. We then present a set of technical and policy measures to mitigate such risks. We note that standards bodies and possibly government interventions will have a role in mitigating security, privacy and even national security risks.
ANÁLISE DA COMPOSIÇÃO QUÍMICA EM GRÃOS DE POPULAÇÕES LOCAIS DE MILHO UTILIZADOS NA MERENDA ESCOLAR

O objetivo do trabalho foi analisar a composicao quimica de graos de populacoeslocais de milho utilizados na alimentacao humana. Foram conduzidos quatro ensaiosem tres municipios de Santa Catarina. Foram avaliados 12 tratamentos emdelineamento de blocos casualizados, com tres repeticoes. Foram analisadas asvariaveis produtividade de carotenoides e os teores de carboidratos, lipideos eproteinas. Observou-se que ha variabilidade entre as populacoes analisadas emtodas as variaveis. Ha populacoes locais com constituintes quimicos emconcentracao tao elevada quanto as testemunhas. Algumas variedades locaispodem ser utilizadas na merenda escolar sem comprometer a qualidade nutricionaldos alimentos.
Use of contraception before and after a diabetes diagnosis: An observational matched cohort study.

Abstract Aims To determine how a diabetes diagnosis affects contraception use. Methods This retrospective cohort study used private insurance data from non-pregnant women aged 15–49 years, 2000−2014. We identified women with a new diabetes diagnosis and a control group without diabetes, matched on important potential confounders. We compared rates of prescription or procedural contraception use in the two groups before and after an index date (diabetes diagnosis and outpatient visit, respectively), yielding difference-in-differences estimates of the effect of a diabetes diagnosis on contraception use. Results We identified 75,355 women with a new diabetes diagnosis and 7.5 million women without a diabetes diagnosis. Overall rates of contraception use did not increase in the year after diagnosis (absolute difference-in-difference: 0.4% [99.9% CI, −2.1% to 2.9%]; p Conclusions Women with diabetes are less likely to use contraception after their diabetes diagnosis. Efforts are needed to ensure that women with diabetes receive the counseling and clinical services needed to carefully plan their pregnancies.
Effects of GO 4 IT . . . NOW! on Writing Skills of Students With Emotional and Behavioral Disorders

Students with emotional or behavioral disorders (EBD) perform academically below their peers. One area of particular challenge is written expression. Using a multiple-probe design across participants, this study evaluated the effects of GO 4 IT . . . NOW! strategy instruction on the writing skills of three students with EBD, ages 11–14. The researchers used GO 4 IT . . . NOW strategy instruction to teach students to write paragraphs in the context of their individualized education programs; in particular, students learned to write goals and objectives related to their self-identified academic and nonacademic needs. Researchers taught 19 GO 4 IT . . . NOW! lessons in a one-on-one format; lessons included explicit strategy instruction, feedback, self-evaluation, and practice with revising paragraphs. Results indicate a functional relation between GO 4 IT . . . NOW! strategy instruction and improved expository and IEP goal paragraphs. Students maintained gains into the following school year. Social validity, limitations, and future directions are discussed.
Survival of COVID-19 Patients With Respiratory Failure is Related to Temporal Changes in Gas Exchange and Mechanical Ventilation.

Background: Respiratory failure due to coronavirus disease of 2019 (COVID-19) often presents with worsening gas exchange over a period of days. Once patients require mechanical ventilation (MV), th...
Effect of Pulse Rise Time on OH Generation of a 10-NS Pulsed Helium Plasma Jet

Plasma-produced reactive oxygen species (ROS), such as hydroxyl radicals (OH), have a wide variety of applications, including sterilization of surfaces, food processing and even optimization of plasma ignition efficiency for combustion. Generation of these species is heavily dependent on the pulse parameters, including pulse width, pulse rise time and the energy per pulse. It has been reported that the majority of OH is generated during the rising and falling time of the pulse [1]. When using longer pulse durations (>200-ns), these events can be seen as separate OH generation events. But when a much shorter pulse duration is used (~ 10-ns), these events happen so close together that they overlap, affecting the plasma chemistry and energy deposition [2]. It is currently unknown if the pulse rise time has an effect on the production of OH at shorter pulse durations. Using a single needle electrode, a helium plasma jet was generated in air using a 10-ns pulse width and a rise time of either 3-ns or 9-ns. The spatially and temporally resolved OH production by 10-ns pulse helium plasma jets in ambient air were measured using laser induced fluorescence. The effect of the pulse rise time on OH production is discussed.
Database Management Model for SCADA Systems.

Water quality and hydrologic/hydraulic monitoring historically has been accomplished through manual techniques and recently with standalone computerized datalo…
UK doctors who go to Syria just want to alleviate suffering

As a doctor of Syrian descent, I am incensed by the inferences made in Gardham’s articles in The BMJ .1 2 Our colleagues in Syria are working in intolerable …
Divalent Ion Metabolism

The thrust of this review is directed to certain specific topics of divalent ion metabolism, rather than to providing a tedious, “index card” description of all topics related to divalent ion metabolism. Research and clinical studies in the field of altered vitamin D metabolism are appearing with great frequency with more investigators now involved. Thus, the focus of this review includes recent advances in the metabolism and actions of vitamin D, a discussion of clinical disorders that are believed to relate to altered vitamin D metabolism or action, the regulation of phosphate homeostasis, and a more recent update on the syndrome of phosphate depletion. Hyperparathyroidism and hypercalcemia are not included in this review; the reader may find such a review in Contemporary Endocrinology, Vol. 1 (Kleeman and Kleeman, 1979). Limiting the review to these few topics made possible a more cohesive text.
Actual and Perceived Strength Differences

(1981). Actual and Perceived Strength Differences. Journal of Physical Education and Recreation: Vol. 52, No. 5, pp. 20-64.
General MC: estimating boundary of positive class from small positive data

Single-class classification (SCC) seeks to distinguish one class of data from the universal set of multiple classes. We propose a SCC method called general MC that estimates an accurate classification boundary of positive class from small positive data using the distribution of unlabeled data. Our theoretical and empirical analyses show that, as long as the distribution of unlabeled data is not highly skewed in the feature space, general MC significantly outperforms other recent SCC methods when the positive data set is highly under-sampled.
Experiments with Merging Beams

Publisher Summary This chapter focuses on the merging beams (mb) technique that consists of two beams traveling in the same direction along a common axis. The technique can be used to investigate ion–neutral, ion–ion, neutral–neutral, and electron–ion reactions. It should be noted that the states of the mb reactants are unknown. If excited states did exist, cross sections for ground state reactants could be obtained, in principle, by applying corrections to the quoted values. The potential on the collision chamber permitted discrimination between ions created by charge transfer within the chamber and those created outside. It also accurately defined the length of the interaction region. The mutual neutralization experiments are fine examples of the use of merging beams for obtaining measurements that could not be made by other techniques. The merged beams then passed through an electric field between a set of condenser plates. Charged particles were eliminated by this field. After passage through a second collimating hole, the resultant neutral beams entered the interaction region.
A case-based data-driven prediction framework for machine fault prognostics

Fault prognosis is an important step to achieve condition-based maintenance for machinery systems. The existing fault prognostic methods can generally be categorized into three major classes: case-based, data-driven, and model-based methods. This paper proposes a novel case-based data-driven prognostic framework based on the adaptive neuro-fuzzy inference system (ANFIS) and big data concept. The framework contains two phases. One is an offline learning phase, in which big historical data are used to build an ANFIS model-case library. The other is the online prognostic phase, in which the fault prognosis of a new machinery system (i.e., a new case) is accomplished by using the proper ANFIS model(s) chosen from the model-case library. The proposed framework is tested by using the experimental data of bearing faults collected from a bearing test rig. Result shows that it has better fault prognostic accuracy than the traditional data-driven method.
What Copyright Teaches Patent Law About Fair Use: And Why Universities are Ignoring the Lesson

Copyright law has a clearly-established doctrine of "fair use." While its parameters and applications are frequently debated, the existence of the doctrine is statutory and undisputed. Patent and copyright law are closely related and they freely borrow from each other, yet this important area of copyright has not been "taught" to patent law. Instead, patentees and infringers alike are left with more draconian, typically all-or-nothing litigation options. A clear and comprehensive "fair use" doctrine would therefore be in the best interest of the patent community, technology users, and public policy. Yet there is resistance, due to the dilemma this article refers to as the "Paradox of the Patent Community" wherein the primary patent infringers are also primary patent owners. The "Paradox" results in a strong disincentive for technology users to fight for a clear doctrine of "fair use." Unfortunately, universities are major players in this scenario, arguing as much against "fair use" as for it. This article explores the rationale for a clear "fair use" doctrine in patent law; historical bases for applying one; analysis of the June, 2005 Supreme Court Integra decision; a discussion of how and why copyright's statutory "fair use" doctrine may be adapted to patent law; and scenarios where compulsory licensing should be considered. With this analysis, the article offers a logical scheme that would satisfy the intent of our Founding Fathers to "promote the Progress of Science and the useful Arts" by encouraging necessary and useful innovations at great benefit to society.
Factors Influencing Spatial Awareness and Orientation in Desktop Virtual Environments

This study investigated influences on human spatial orientation and representation resulting from manipulations in the geometric field of view (GFOV) of a perspective display. Also examined was the impact of incorporating symbolic virtual environment enhancements in the interface based on visual momentum (VM) techniques. Sixty participants, pretested for spatial ability, were required to navigate through a virtual office building while performing a variety of spatial orientation tasks. A 3 × 2 × 2 mixed-subjects design compared three levels of GFOV, two levels of VM, and two levels of Difficulty. The findings indicate that decreases in GFOV produce spatial orientation and representation errors, and as task difficulty increases, errors are more pronounced. Furthermore, VM was shown to alleviate errors in spatial orientation and representation, especially when task difficulty was increased. Design recommendations are discussed based on the implications of the results.
Comparison of magnitude estimation of loudness in children and adults

This study compared children (mean age 10.9 years) and college students on the magnitude estimation of loudness. Both the 20 children and the 20 adults were unpracticed observers. In one condition, the standard tone was assigned the number 10, and in the other condition, the number 20. Under both conditions the power function was found to fit the data of the children quite well, and to give approximately the same exponent. Of particular interest was the similarity between the data of the children and adults.
Analytical recovery of chromium from diet and faeces determined by colorimetry and atomic absorption spectrophotometry

The present study examined whether differences in mineral content of the diet or faecal samples contribute to variation in analytical recovery of marker chromium from these samples. Three corn/soya bean diets containing various levels of Ca, P and Mg, and the corresponding faeces of swine fed these diets were used. Diet and faecal samples were analysed by colorimetry and atomic absorption spectrophotometry with increments of Cr added to samples either preceding or following the acid digestion procedure. Results indicated significant differences (P <0·05) in analytical recovery of Cr between diets and corresponding faeces, between individual diets and faeces, and between methods of determination. The acid digestion step leads to the lower recovery of Cr (diets, P <0·05; faeces, P <0·01) whereas no significant differences were found in post-digestion procedure by either method of determination, indicating that marker-chromium loss due to the acid digestion procedure was not higher than the apparent loss due to the acid analytical method. Results suggest that the analytical recovery factors should be considered when estimating faecal recovery of marker chromium or digestibility of nutrients.
In Brief: Closed Tibial Shaft Fractures

Fractures of the tibial shaft are the most common long bone fractures, with an incidence greater than 75,000 per year in the US [14]; most of these fractures are found in young males (thought to be related to sports or motor vehicle accidents) with a second peak of incidence among elderly patients, whose injuries likely resulted from a simple fall [18]. Although intramedullary fixation has become the mainstay of treatment, many of these fractures are amenable to closed treatment.
Activation of Nuclear Factor‐κB in C6 Rat Glioma Cells After Transfection with Glia Maturation Factor

The 17-kDa endogenous brain protein glia maturation factor (GMF) was transfected into C6 rat glioma cells using a replication-defective human adenovirus vector. The cells overexpressed GMF but did not secrete the protein into the medium. Transfection with GMF led to the activation of the transcription factor nuclear factor-kappaB (NF-kappaB), as evidenced by electrophoretic mobility shift assay of the nuclear extract, using a double-stranded oligonucleotide probe containing the consensus binding sequence for NF-kappaB. The specificity of binding was demonstrated by competition with unlabeled probe and by the nonbinding of the mutant probe. Binding was detectable as early as 3 h after transfection, peaked at 6 and 12 h, and gradually declined thereafter. The observed NF-kappaB activation was reduced by cotransfection with catalase and by the presence of high concentrations of pyruvate in the medium, suggesting the involvement of H2O2. The p38 mitogen-activated protein kinase inhibitor SB-203580 also suppressed the GMF-activated NF-kappaB, suggesting the involvement of the p38 signal transduction cascade. On the other hand, the phorbol ester phorbol 12-myristate 13-acetate activated NF-kappaB whether or not GMF was overexpressed. Along with NF-kappaB activation was an enhanced expression of superoxide dismutase (SOD), which was suppressed if NF-kappaB nuclear translocation was blocked by its specific decoy DNA, implicating NF-kappaB as an upstream mediator of this antioxidant enzyme. The p38 inhibitor SB-203580 also blocked the GMF-activated SOD. As NF-kappaB and SOD are both pro-survival signals, the results suggest a cytoprotective role for endogenous GMF in glial cells.
Real-Time Reciprocal Space Mapping of Nano-Islands Induced by Quantum Confinement

The effects of quantum confinement have been observed pronouncedly in the island morphology of Pb thin films. The evolution of these nano-islands on Si (111)-(7 × 7) and sapphire (001) surfaces has been studied with a new X-ray diffraction method. A charge-coupled device (CCD) camera was used to collect two- and three-dimensional (2-D and 3-D, respectively) maps of the surface X-ray diffraction in real time. Large ranges of the reflectivity curves, with rocking curves at every point on the reflectivity curves, could be measured continuously in a relatively short amount of time. The abundance of information from 2-D k-space maps reveals clear changes in the growth modes of these thin Pb films. With the 3-D extension of this method, it was possible to observe the ordering of the islands. The islands maintain a nearly uniform interisland distance but lack any angular correlation. The interisland ordering is correlated well with the development of “magic” island heights caused by quantum confinement.
Monte Carlo Simulations of β-Hairpin Folding at Constant Temperature

Abstract Monte Carlo simulations were applied to β -hairpin folding of a valine-based peptide. Two valine residues in the middle of the peptide were substituted with glycine, to serve as turn residues. Unlike lattice model simulations, structure prediction methods, and unfolding simulations, our simulations used an atom-based model, constant temperature (274K), and non- β -hairpin initial conformations. Based on the concept of solvent reference, the effective energy function simplified the solvent calculation and overcame the multiple minima problem. Driven by the hydrophobic interaction, the peptide first folded into a compact U-shaped conformation with a central turn, in analogy to the initial collapse with simultaneous nucleation in protein folding. The peptide units in the U-shaped conformation then reoriented, gradually forming hydrogen bonds in the β -hairpin pattern from the β -turn to the ends of the strands. With the same energy function, an alanine-based peptide folded into helix-dominated structures. The basic structure types ( α -helix or β -hairpin) that formed during the simulations depended upon the amino acid sequence. Compared with helix, β -hairpin folding is driven mainly by the hydrophobic interaction. Hydrogen bonding is necessary to maintain the ordered secondary structure.
Dual-wavelength ratiometric fluorescence measurement of the membrane dipole potential

The electrostatic potentials associated with cell membranes include the transmembrane potential (delta psi), the surface potential (psi s), and the dipole potential (psi D). psi D, which originates from oriented dipoles at the surface of the membrane, rises steeply just within the membrane to approximately 300 mV. Here we show that the potential-sensitive fluorescent dye 1-(3-sulfonatopropyl)-4-[beta[2-(di-n-octylamino)-6- naphthyl]vinyl]pyridinium betaine (di-8-ANEPPS) can be used to measure changes in the intramembrane dipole potential. Increasing the content of cholesterol and 6-ketocholestanol (KC), which are known to increase psi D in the bilayer, results in an increase in the ratio, R, of the dye fluorescence excited at 440 nm to that excited at 530 nm in a lipid vesicle suspension; increasing the content of phloretin, which lowers psi D, decreases R. Control experiments show that the ratio is insensitive to changes in the membrane's microviscosity. The lack of an isosbestic point in the fluorescence excitation and emission spectra of the dye at various concentrations of KC and phloretin argues against 1:1 chemical complexation between the dye and KC or phloretin. The macromolecular nonionic surfactant Pluronic F127 catalyzes the insertion of KC and phloretin into lipid vesicle and cell membranes, permitting convenient and controlled modulation of dipole potential. The sensitivity of R to psi D is 10-fold larger than to delta psi, whereas it is insensitive to changes in psi S. This can be understood in terms of the location of the dye chromophore with respect to the electric field profile associated with each of these potentials.(ABSTRACT TRUNCATED AT 250 WORDS)
Extended resection for locally advanced colorectal carcinoma

Background: The purpose of this study was to determine the therapeutic benefit of multivisceral resection (MVR) in patients with locally advanced colorectal carcinomas.
Performance and Optimization of Induced Strain Actuated Structures Under External Loading

This paper addresses the actuator/substrate thickness ratio that maximizes the static/dynamic response of a beam for a variety of actuator-structure integration configurations, actuator activation levels, and inertia/external loading conditions. The three different actuator-structure integration configurations considered are actuators embedded inside the substrate, actuators bonded to the surface of the substrate, and actuators discretely attached and offset from the surface of the substrate. In the category of embedded actuators, a shallow embedment just beneath the surface usually maximizes the moment/induced curvature, but for stiffer actuators, a deeper embedment results in a greater induced curvature
Evaluation of ranirestat for the treatment of diabetic neuropathy

Introduction: Pharmacologic maintenance of normoglycemia in diabetes cannot prevent the eventual complications mainly due to protein glycation-induced cell death, dysregulated antioxidant defense and signal transduction in affected tissues. The rate-limiting enzyme of this process, aldose reductase, is therefore a pharmacologic target. To date, nine inhibitors of this enzyme have been developed. Ranirestat has completed two Phase III clinical trials. The objective of this evaluation is to summarize and provide expert opinion on the status of ranirestat with an emphasis on its pharmacokinetics in the context of its potential effects to prevent/treat diabetic complications.Areas covered: A qualitative systematic literature search of PubMed through November 2013 using MeSH terms – aldose reductase inhibitors, diabetic neuropathy, AS-3201, ranirestat, diabetic complications and pharmacokinetics/pharmacodynamics – identified relevant publications limited to human and rodent (mouse and rat) and English-language...
Peptoid mimics of agouti related protein.

Abstract The Agouti Related Protein (AGRP) is an endogenous antagonist of melanocortin-3 and -4 receptors, each of which plays a key role in body weight homeostasis. We designed a peptoid trimer based on AGRP 111–113 in which a single chiral atom is used to partially restrain the backbone structure. Peptoid 5 displaced both radiolabeled Nle4-α-MSH (IC50=3.1 μM) and AGRP (86–132) (IC50=1.9 μM) from the human melanocortin-4 receptor and functioned as an antagonist of α-MSH stimulated cAMP generation, thus providing an important lead in the development of AGRP mimetics.
A partial ordering that generates filtered Walsh series

The second author recently introduced modified Walsh–Dirichlet kernels which generated filtered Walsh–Fourier series. The purpose of this article is to show that those filtered Walsh series can be generated by a partial ordering on the natural numbers which may be of interest in its own right.
The protein-labeling reagent FLASH-EDT2 binds not only to CCXXCC motifs but also non-specifically to endogenous cysteine-rich proteins.

FLASH-EDT2 – 4′,5′-bis(1,3,2-dithioarsolan-2-yl)fluorescein-(1,2-ethanedithiol)2 – has been reported to fluoresce only after binding with high affinity to a specific tetracysteine motif (CCXXCC, "Cys4") and thus to provide a technique for labeling recombinant proteins in vivo (Griffin et al. Science 281:269–272). We have attempted to use FLASH-EDT2 as a site-specific label of the II-III loop of the dihydropyridine receptor (DHPR) in skeletal muscle. Upon expression in dysgenic myotubes (which lack endogenous α1S), an α1S mutated to contain CCRECC in the II-III loop was able to produce L-type calcium currents and to mediate skeletal-type excitation–contraction (EC) coupling, but FLASH-EDT2 labeling revealed no difference from non-transfected dysgenic myotubes. HeLa-S3 cells transfected with Cys4-containing calmodulin were significantly more fluorescent than non-transfected cells, whereas the difference between transfected and non-transfected cells was less apparent for CHO-K and HEK 293 cells. Because the fluorescence of non-transfected cells increased substantially after treatment with FLASH-EDT2, it suggested the possibility that FLASH binds to endogenous cysteine-containing proteins. This finding was confirmed in cuvette experiments in which FLASH-EDT2 fluorescence was observed after FLASH-EDT2 was added to protein homogenates from myotubes or cell lines. The enhanced fluorescence was abolished by pretreatment of cells or cell homogenates with coumarine maleimide (CPM), which modifies cysteine residues covalently. Thus, enhanced FLASH fluorescence appears to occur both after binding to an introduced Cys4 motif and to endogenous, cysteine-containing proteins. Therefore, FLASH-EDT2 may be useful only for labeling those recombinant proteins that express at a very high level.
Valence and dipole-bound anions of the most stable tautomers of guanine.

Anionic states of guanine, which is the only nucleic acid base of which the anions have not yet been studied in either photoelectron spectroscopic (PES) or Rydberg electron transfer (RET) experiments, have been characterized for the four most stable tautomers of neutral guanine using a broad spectrum of electronic structure methods from the density functional theory, with the B3LYP exchange−correlation functional, to the coupled-cluster method, with single, double, and perturbative triple excitations. Both valence and dipole-bound anionic states were addressed. We identified some of the difficulties facing future PES or RET experiments on the anion of guanine. Even if guanine is successfully transferred to the gas phase without thermal decomposition, it is critical to have the canonical amino−oxo (G) and both amino−hydroxy (GH and GHN7H) tautomers in the beam, not only the most stable, a noncanonical, amino−oxo tautomer (GN7H), as the latter does not support an adiabatically bound anionic state. We also s...
Computation of flows with shocks using the Spectral Difference method with artificial viscosity, I: Basic formulation and application

Abstract The present work combines the Spectral Difference method with an artificial viscosity based approach to enable high-order computation of compressible fluid flows with discontinuities. The study uses an artificial viscosity approach similar to the high-wavenumber biased artificial viscosity approach (Cook and Cabot, 2005, 2004; Kawai and Lele, 2008) [1–3], extended to an unstructured grid setup. The model employs a bulk viscosity for treating shocks, a shear viscosity for treating turbulence, and an artificial conductivity to handle contact discontinuities. The high-wavenumber biased viscosity is found to stabilize numerical calculations and reduce oscillations near discontinuities. Promising results are demonstrated for 1D and 2D test problems.
Mapping Curvilinear Structures with Local Anisotropy Kriging

Interpolating geo-data with curvilinear structures using geostatistics is often disappointing. Channels, for example, become disconnected sets of lakes when interpolated from point data. In order to improve the interpolation of geological structures (e.g., curvilinear structures), we present a new form of kriging, local anisotropy kriging (LAK). Local anisotropy kriging combines a gradient algorithm from image analysis with kriging in an iterative way. After an initial standard kriging interpolation, the gradient algorithm determines the local anisotropy for each cell in the grid using a search area around the cell. Subsequently, kriging is carried out with the spatially varying anisotropy. The anisotropy calculation and subsequent kriging steps will then succeed until the result is satisfactory in the way of reproducing the curvilinear structures. Depending on the size of the search area more or less detail in the geological structures can be reproduced with LAK. Using test examples we show that LAK interpolates data with curvilinear structures more realistically than standard kriging. In a real world case, using bathymetric data of the Oosterschelde estuary, LAK also proves to be quantitatively superior to standard kriging. Absolute interpolation errors are decreased by 23%. Local anisotropy kriging only uses information from point data, which makes the method very objective, it only presents “what the data can tell.”
Clogging of Fine Sediment within Gravel Substrates: Dimensional Analysis and Macroanalysis of Experiments in Hydraulic Flumes

AbstractAn understanding of the clogging of fine sediments within gravel substrates is advanced through use of dimensional analysis and macroanalysis of previously conducted clogging experiments in hydraulic flumes. Dimensional analysis via the Buckingham pi theorem is used to suggest that the dimensionless clogging depth can be potentially collapsed using the original and adjusted bed-to-grain ratios, i.e., ratio of substrate diameter to fine sediment diameter, substrate porosity, roughness Reynolds number, and Peclet number. Macroanalysis and statistical analysis is performed using 10 previously published studies that include a total of 146 different test conditions reporting noncohesive, fine sediment clogging, or deposition in porous gravel-beds with hydraulically rough turbulent open channel flow. Results suggest that the adjusted bed-to-grain ratio is a reliable predictor of the initiation of clogging with clogging occurring below 27 for the fine fluvial sediment clogging in a gravel bed substrate f...
Waveguide holography and its applications

Left to right channel differences of the transmission factors in a 3DTV system result in asymmetric multiplicative luminance deviations, which can impair picture quality and/or can reduce the visual comfort. Twenty non-expert observers assessed the impairment of overall as well as localized asymmetric deviations (as it may happen, e.g., with lenticular screen displays) in terms of the CCIR impairment scale. The luminance asymmetries were produced by processing the digitized stereo image pair of two natural scenes, according to a reduction of the transfer function of only one channel. Results show that (1) overall and localized luminance asymmetries are perceptible if the transmission factors differ by 3-6 dB, depending on the spatial extension and gradient of the deviation; and (2) if a pattern of a sharply localized luminance deviation is moving (as it may happen, e.g., when an observer moves his head in front of a lenticular screen display), it is perceptible if the transmission factor differs by only 0.2 dB.© (1991) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Reconsidering Bibliographic Instruction for Adult Reentry Students: Emphasizing the Practical

A survey conducted by the College Board and reported in the Chronicle of Higher Education revealed that six million adults study for college credit each year, and that 45 percent of all undergraduate and graduate students are over twenty‐five years of age. The survey also predicted the figure could rise to 50 percent by the year 2000. Recent adult education literature offers many papers advising colleges to gear up and embrace the reentry student. Academe's metamorphosis, demonstrated by independent degree programs, more weekend and evening classes, and other enticements, confirms this reorientation. A community adult education course entitled “Academia Revisited,” which is intended specifically as a preenrollment introduction for prospective reentrants, is a signal that colleges are actively courting the adult student. Increasing enrollments of adults attest a positive response to these changes.
Aerosol coating of silica fibers with nanoparticles

Ultrafine silica fibers were coated with nanosized particles by an aerosol process. The fibers were introduced in a diffusion flame reactor where silica particle formation took place by oxidation of SiCl4. Coagulation of particles with fibers resulted in fractal-like structures on the latter, enhancing the specific surface area of the product fibers. Ferrocene used as an additive at a mole fraction of 6.6 × 10−5 in the flame promoted the surface area enhancement. A sol-gel coating technique was also used to produce particle coated fibers.
Spark chamber with multi-track capability☆

Abstract A new type of optical spark chamber, capable of supporting many tracks, is described. The essential new feature is a thin conductive layer over a thin insulation layer which is attached to one of the plates of a conventional chamber. Theory of operation and experimental tests are described.
uPAR and cathepsin B knockdown inhibits radiation-induced PKC integrated integrin signaling to the cytoskeleton of glioma-initiating cells

Despite advances in radiotherapeutic and chemotherapeutic techniques and aggressive surgical resection, the prognosis of glioblastoma patients is dismal. Accumulation of evidence indicates that some cancer cells survive even the most aggressive treatments, and these surviving cells, which are resistant to therapy and are perhaps essential for the malignancy, may be cancer stem cells. The CD133 surface marker is commonly used to isolate these extremely resistant glioma-initiating cells (GICs). In the present study, GICs which tested positive for the CD133 marker (CD133+) were isolated from both the established U251 cell line and the 5310 xenograft glioma cell line to study the events related to the molecular pathogenesis of these cells. Simultaneous down-regulation of uPAR and cathepsin B by shRNA (pUC) treatment caused the disruption of radiation-induced complex formation of pPKC θ/δ, integrin β1 and PKC ζ, integrin β1 in glioma cells. Further, pUC treatment inhibited PKC/integrin signaling via FAK by causing disassociation of FAK and the cytoskeletal molecules vinculin and α-actinin. Also, we observed the inhibition of ERK phosphorylation. This inhibition was mediated by pUC and directed a negative feedback mechanism over the FAK signaling molecules, which led to an extensive reduction in the signal for cytoskeletal organization generating migratory arrest. Altogether, it can be hypothesized that knockdown of uPAR and cathepsin B using shRNA is an effective strategy for controlling highly invasive glioma cells and extremely resistant glioma-initiating cells.
Antimicrobial therapy for acute colonic diverticulitis.

Abstract Background: Although guidelines and reviews have systematically evaluated diagnosis and surgical management of acute diverticulitis, they have focused only minimally on antibiotic selection for the treatment of this disease. We undertook a review of the literature to assess more clearly the use of specific antimicrobial agents in the treatment of patients with acute diverticulitis of the colon. Methods: A MEDLINE search was conducted to identify original research, review papers, and guidelines on the use of antimicrobial agents for the treatment of acute diverticulitis. Results: The general recommendation to use antibiotics with activity against common gram-negative and anaerobic pathogens has remained consistent. A number of single agents and combination regimens provide such activity. However, there is little evidence on which to base selection of specific antimicrobial regimens, and no regimen has demonstrated superiority. In general, episodes of diverticulitis severe enough to warrant hospita...
Organ modeling in the quantitation of planar images for distribution studies.

Background. The advantage of whole-body imaging for distribution studies is that it accounts for all activities. The problem, however, is that the classic approach to determining distribution from planar images does not accommodate overlapping structures. That approach assumes implicitly that the sampling region is a prismoid whose cross-section, parallel to the detector plane, is defined by a region of interest and whose sides are orthogonal to the detector plane. Methods. In the proposed organ-model approach, the region of interest is assumed explicitly to be the projected shadow of an organ or structure, whose general shape is known from anatomic generality, and whose size or specific shape variation is defined by the shadow or region of interest
In-Hospital and Long-term Outcome After Reoperative Coronary Artery Bypass Graft Surgery

Background Increasingly over the past several years, patients have returned after coronary surgery for reoperative procedures, and the experience has become substantial. In this report, we describe immediate- and long-term outcomes after reoperative coronary artery bypass graft surgery. Methods and Results The source of data was the clinical database at Emory University. The surgical procedure and statistical methods were standard. Data were collected prospectively and entered into a computerized database. Follow-up was by letter, telephone, or hospital records documenting additional events resulting in readmission. In-hospital correlates of survival were determined by logistic regression, and long-term correlates were determined by Cox model analysis. There were 2030 patients with a mean age of 61 and a mean of 7.8±4.1 years since the first surgery. The mean ejection fraction was close to 50%, and the majority had three-vessel or left main disease. Urgent or emergency surgery was required in 16.6%. The internal mammary was used in 60.1%. Q-wave myocardial infarctions occurred in just over 5%. Neurological events increased from 1.2% at less than age 50 to 4.1% at more than age 70. The hospital mortality increased from 5.7% at less than age 50 to 10% at more than age 70, with an overall rate of 7.0%. Mortality was 5.7% for elective, 10.9% for urgent, and 16.4% for emergency cases. Angina was noted at follow-up in 41.3%. Urgent or emergency surgery, reduced ejection fraction, hypertension, older age, and female sex were univariate and multivariate correlates of in-hospital death. Diabetes was a univariate correlate only. Five- and 10-year survival rates were 76% and 55%, respectively. Five- and 10-year myocardial infarction–free survival rates were 63% and 40%, respectively. By 12 years, few patients were free of cardiac events. The univariate and multivariate correlates of long-term mortality were older age, reduced ejection fraction, hypertension, diseased vessels, presence of diabetes, congestive failure, and emergency surgery, with a strong trend for female sex. The use of the internal mammary artery was not a correlate for long-term mortality. Conclusions Patients undergoing reoperative procedures have higher mortality initially and at long term than patients undergoing a first procedure. Expected mortality based on covariates may help in the decision of whether to perform reoperative coronary artery bypass graft surgery.
Towards a model of student success in programming courses

Since the birth of computer science some 40 years ago, educators and researchers alike have struggled with improving student success, particularly in the introductory programming courses, which often have a very high failure rate. Although many researchers have studied how and why students succeed in programming courses, no research to date has analyzed multiple variables simultaneously to develop an integrated model of student success. Rather, the research has been fragmented and non-cumulative, with researchers studying hundreds of different variables, under different conditions, and reaching different conclusions. Educators are faced with the arduous task of developing interventions and pedagogical techniques based on a plethora of seemingly important variables. In this work, we begin to bring together previous research to develop a model of student success based on theoretical reasoning. The proposed model identifies variables in three categories: individual, organizational, and demographic.