cssi/SciSciGPT-SciSciNet huggingface dataset:
Transcription of RORγt in developing Th17 cells is regulated by E-proteins

In the present study we investigated the molecular mechanisms regulating the expression of RAR-related orphan receptor gamma t (RORγt), the central factor controlling interleukin (IL)-17 transcription and Th17 differentiation. In key studies, we found that cells from mice with major deletions of E-protein transcription factors, E2A and HEB, display greatly reduced RORγt/IL-17 expression and that E-protein-deficient mice exhibit greatly diminished IL-17-dependent inflammation in experimental allergic encephalitis models. In additional studies, we unexpectedly found that cells from mice with deletion of Id3, a protein that inhibits E-protein binding to DNA, display diminished RORγt/IL-17 expression and mice deficient in this protein exhibit decreased Th17-mediated inflammation in a cell-transfer colitis model. The explanation of these initially paradoxical findings came from studies showing that Id3 deficiency leads to increased IL-4-induced GATA-3 expression, the latter a negative regulator of RORγt transcription; thus, increased Id3 expression likely has a net positive effect on RORγt expression via its inhibition of IL-4 production. Finally, we found that both E-proteins and Id3 are upregulated in tandem by the cytokines that induce Th17 differentiation, transforming growth factor-β, and IL-6, implying that these transcription factors are critical regulators of Th17 induction.
AN EXPOSITION OF THE CONCEPT OF LIFELONG SELF‐EDUCATION

Education has been conceived as a continuing lifelong activity that is important for increasing the quality of life. The changing population structure of the world will present us with a variety of social and economic problems, including the design of educational or learning systems throughout adult development and aging. This paper discusses the concept of self‐education as it applies to the utility of continuing educational opportunities in age‐graded societies.
Blood levels of S-100 calcium-binding protein B, high-sensitivity C-reactive protein, and interleukin-6 for changes in depressive symptom severity after coronary artery bypass grafting: prospective cohort nested within a randomized, controlled trial.

Background: Cross-sectional and retrospective studies have associated major depressive disorder with glial activation and injury as well as blood–brain barrier disruption, but these associations have not been assessed prospectively. Here, we aimed to determine the relationship between changes in depressive symptom severity and in blood levels of S-100 calciumbinding protein B (S-100B), high-sensitivity C-reactive protein, and interleukin-6 following an inflammatory challenge. Methods: Fifty unselected participants were recruited from a randomized, controlled trial comparing coronary artery bypass grafting procedures performed with versus without cardiopulmonary bypass for the risk of neurocognitive decline. Depressive symptom severity was measured at baseline, discharge, and six-month follow-up using the Beck Depression Inventory II (BDI-II). The primary outcome of the present biomarker study was acute change in depressive symptom severity, defined as the intra-subject difference between baseline and discharge BDI-II scores. Blood biomarker levels were determined at baseline and 2 days postoperative. Results: Changes in S-100B levels correlated positively with acute changes in depressive symptom severity (Spearman r, 0.62; P=0.0004) and accounted for about one-fourth of their observed variance (R 2 , 0.23; P=0.0105). This association remained statistically significant after adjusting for baseline S-100B levels, age, weight, body-mass index, or b-blocker use, but not baseline BDI-II scores (P=0.064). There was no statistically significant association between the primary outcome and baseline S-100B levels, baseline high-sensitivity C-reactive protein or interleukin-6 levels, or changes in high-sensitivity Creactive protein or interleukin-6 levels. Among most participants, levels of all three biomarkers were normal at baseline and markedly elevated at 2 days postoperative. Conclusions: Acute changes in depressive symptom severity were specifically associated with incremental changes in S100B blood levels, largely independent of covariates associated with either. These findings support the hypothesis that glial activation and injury and blood–brain barrier disruption can be mechanistically linked to acute exacerbation of depressive symptoms in some individuals.
Dietary and dental adaptations in the Pitheciinae.

Since Mivart (1865), Cacajao, Chiropotes, and Pithecia have been grouped into a single taxon, which he called the subfamily Pitheciinae but which I, following Rosenberger (this issue), refer to as the living members of the tribe Pitheciini. While few today doubt the association of these three living genera, not all would place them together with Aotus and Callicebus in the subfamily Pitheciinae. This is an attempt to sort out the behavioral and morphological features of feeding and dental morphology in these taxa. Extant members of the tribe Pitheciini are adapted for sclerocarpic foraging, morphological evidence for which is found in the fossils of Soriacebus and Cebupithecia. Sclerocarpic foraging in living pitheciins is a two-stage process of seed predation involving 1) specialized features of the anterior dentition that allow removal of a hard pericarp that protects a seed or seeds, followed by 2) mastication by the posterior dentition having low cusp relief to triturate nutritious seeds of a relatively soft and uniformly pliable consistency. The dentitons of fossil pitheciins, Soriacebus and Cebupithecia, demonstrate that the hypertrophy of lower incisors plus the robustness and flaring of the canine precede development of low cusp relief on molars and premolars in the evolution of morphological features associated with sclerocarpic foraging. Features of sclerocarpic foraging are found less uniformly in the other two pitheciines, Callicebus and Aotus. © 1992 Wiley-Less, Inc.
9.1.2 An Ontology for Unmanned and Autonomous Systems of Systems Test and Evaluation

With the advent of unmanned systems and the movement toward greater complexity, the test and evaluation community faces new challenges. This paper presents an ontology for the unmanned and autonomous systems of systems test and evaluation (UASoS T&E) domain that is intended to help support addressing these challenges in T&E. The development of a UASoS T&E ontology provides a means for those interested in the field of UASoS T&E to understand the entities, relationships, and terminology within the domain. The ontology provides a common language and basis of understanding for UASoS T&E that can be leveraged as a foundation for other efforts.
Universal Lessons from Unique Events: Perspectives from Columbia and Katrina

he United States has recently witnessed two tragic, dramatic, and very different large-scale disasters. On February 1, 2003, the space shuttle Columbia broke up over the western United States, destroying the shuttle, killing its crew, and jeopardizing the space program. In August 2005, Hurricane Katrina slammed into the Gulf Coast, devastating more than 90,000 square miles from Florida to Texas. Each of these events affected thousands of people. In addition to the estimated 1,800 people who lost their lives as a result of the hurricane, some 2 million people were displaced when their homes and livelihoods were ravaged (Hsu 2006). The breakup of Columbia strewed hazardous debris more than 2,000 square miles of populated east Texas and Louisiana. The direct property loss and other costs associated with each of these events was substantial. Katrina caused more than $100 billion in damage. The nation lost its first space-rated orbiter, one of only four remaining after the loss of Challenger, when Columbia was destroyed. And each of these events triggered a massive response. The response to the Columbia crash involved 25,000 people from 450 organizations working for 100 days to recover the shuttle crew and debris.
Chlorpromazine-ultraviolet interaction on mouse ear

Abstract Two methods of assessing hyperpigmentation and phototoxic liability in mice were studied with chlorpromazine (CPZ) and ultraviolet (UV) light used as the test stimuli. Photoresistance and water content of the ear were found to be increased in both albino and C57B1 mice receiving both CPZ and UV. Label incorporation from 3,4-dihydroxyphenylalanine-2-14C into the ear was increased in the C57B1 mice, but not in the albino mice. It is suggested that measurement of photoresistance would be useful in assessing phototoxic and/or inflammatory liability while label incorporation would be useful in assessing hyperpigmentation liability.
Selected bibliography on information theory applications to information science and related subject areas

Importante bibliographie commentee de 440 references, en langue anglaise, parues ces quinze dernieres annees, dans la presse specialisee et consacree essentiellement aux methodes mathematiques appliquees a la science de l'information. Un classement alphabetique par nom d'auteur ordonne ces references
Triton WR‐1339, A Lysosomotropic Compound, Is Excreted into Bile and Alters the Biliary Excretion of Lysosomal Enzymes and Lipids

In these experiments, we tested two hypothesis: first, that Triton WR-1339, a nonionic detergent which is sequestered in hepatocyte lysosomes, undergoes biliary excretion; and second, that Triton WR-1339, which also alters serum lipid levels and modifies hepatic catabolism of lipoproteins, affects the biliary output of proteins and lipids. When 3H-Triton WR-1339 was administered to rats, biochemical and morphologic studies showed that hepatocyte lysosomes sequestered Triton WR-1339: (i) the subcellular distribution of 3H was identical to that of lysosomal enzymes after liver fractionation by differential or isopycnic centrifugation, and (ii) lysosomes appeared engorged with Triton WR-1339 on electron microscopy. 3H was also excreted into bile in parallel to three lysosomal enzymes. Triton WR-1339 administration caused a coordinate increase in the biliary excretion of three lysosomal enzymes and also increased the biliary output of total protein, bile acids, and phospholipid. Triton WR-1339 administration did not affect bile flow or the biliary outputs of cholesterol, plasma membrane, and cytosolic enzymes, but did decrease biliary cholesterol saturation by 50%. These results demonstrate that an exogenous compound which is sequestered in hepatocyte lysosomes may be excreted directly into bile in parallel with endogenous lysosomal constituents. The data also show that such a lysosomotropic agent may also selectively modify the biliary excretion of proteins and lipids. The findings are consistent with the existence of a lysosome-to-bile hepatic excretory pathway and suggest that hepatocyte lysosomes may be important in modulating biliary protein and lipid secretion.
Work and personality : Use of the NEO-PI-R in industrial/organisational psychology

L'inventaire NEO Revise de la Personnalite (NEO-PI-R) est une mesure actuelle de 30 traits qui renvoient aux cinq facteurs de base de la personnalite normale. II a fourni des preuves de sa fidelite et de sa validite aussi bien dans des recherches theoriques qu'appliquees et plusieurs etudes montrent qu'il contribue a predire la performance professionnelle. Le domaine et les facettes du NEO-PI-R sont analyses avec quelques resultats issus de son application en psychologie des organisations. The Revised NEO Personality Inventory (NEO-PI-R) is a contemporary measure of 30 traits that define the five basic factors of normal personality. In both research and applied samples it has shown evidence of reliability and validity, and several studies suggest that it has utility in the prediction of job performance. The domain and facet features of the NEO-PI-R are discussed along with some issues in its use in industrial/organisational psychology.
Interpretation Coherent Anti-Stokes Raman Spectroscopy (CARS) Spectral Profiles

CARS spectral profiles are functionally described by the variation of the square of the total third-order, nonlinear susceptibility with the anti-Stokes frequency shift. This inherent, squared susceptibility signal dependence, when weighted by an experiment dependent convolution, produces a CARS spectral profile which is a problem specific to the experiment design.
A Price-driven Mechanism to Arrest Voltage Deviations in Stressed Electric Power Networks

Voltage security of modern power system remains an important aspect of sustaining our economies and high standards of living. The operation of such systems requires adhering to regulations to ensure that the system voltages throughout the network are kept within safe, contractual limits. Several researchers have investigated ways to determine voltage security that is affected by heavy loading conditions, switching of large loads, line switching, and/or unpredictable use of power from customers. These may result in local voltage swings, affecting the control systems. In this paper, we implement a control option, namely distributed generation (DG), with the added value of improving voltage deviation and the resulting energy transactions for the system operator. The implementation approach features the use of a value-based index that incorporates the use of locational marginal prices and the price differential at each node, with or without DG. The scheme was tested on a small-scale 30-bus benchmarked system.
Characterization and Solubilization of Vasoactive Intestinal Peptide Receptors from Rat Lung Membranes

Receptors for vasoactive intestinal peptide (VIP) were characterized in rat lung membranes by binding and covalent cross-linking of [125I] VIP using ethylene glycolbis-(succinimidylsuccinate). Binding studies indicated the presence of two classes of binding sites for VIP in rat lung membranes: 0.28 ± 0.11 pmol/mg protein high affinity receptors (Kd = 79.2 ± 26.4 pM) and 3.3 ± 0.9 pmol/mg protein lower affinity receptors (Kd = 4.8 ± 2.1 nM). Furthermore, binding of [125I]VIP to rat lung receptors was inhibited by micromolar concentrations of GTP analogs, guanosine-5′-O-(3-thiotriphosphate) (GTPγS), and guanylylimidodiphosphate, suggesting that VIP receptors in rat lung membranes were tightly coupled to the guanine nucleotide regulatory protein (N8). Scatchard analysis of VIP binding in the presence of GTPγS revealed selective inhibition of binding to high affinity sites. A 58K band was specifically labeled when membranes covalently labeled with [125I]VIP were analyzed by sodium dodecyl sulfate-polyacrylami...
Mode coupling in optical waveguide horns

Mode coupling in optical waveguide horns is described in detail. Analytic approximations for the coupling constant and phase difference are derived. For a parabolic-shaped horn an expression for the power transferred out of the lowest order mode is obtained, which demonstrates that long structures will be needed to maintain adiabatic operation.
Policy languages for digital identity management in federation systems

The goal of service provider federations is to support a controlled method by which distributed organizations can provide services to qualified individuals and manage their identity attributes at an inter-organizational level. In order to make access control decisions the history of activities should be accounted for, therefore it is necessary to record information on interactions among the federation entities. To achieve these goals we propose a comprehensive assertion language able to support description of static and dynamic properties of the federation system. The assertions are a powerful means to describe the behavior of the entities interacting in the federation, and to define policies controlling access to services and privacy policies. We also propose a log-based approach for capturing the history of activities within the federation implemented as a set of tables stored at databases at the various organizations in the federation. We illustrate how, by using different types of queries on such tables, security properties of the federation can be verified.
Vibration Testing and Finite Element Analysis of an Inflatable Structure

Vibration testing and e nite element analysis of an ine ated thin-e lm torus are presented. Ine atable structures show signie cant promises for future space applications. However, their extremely lightweight, e exible, and high damping properties pose dife cult problems in vibration testing and analysis. Smart materials are used as sensors andactuatorsforperformingvibrationtestsofanine atedtorus.Inaddition,apredictivemodelhasbeendeveloped, which can be compared with experimental results. A commercial e nite element package, ANSYS, is used to model a prestressed ine atable structure. Both experimental and e nite element results are in reasonable agreement with each other. The predictive model can be used for analyzing the dynamics of ine ated structures and for designing control systems to attenuate vibration in an ine ated torus.
Fabrication Facilities and Operational Model at MIT's Microsystems Technology Labs

The mission of the Microsystems Technology Laboratories (MTL) is to provide facilities for education and research in micro and nano technology and innovative devices. This paper describes details of its operation, including cost structure, fab management and billing software, interactions with industry, government labs and other universities will be described.
Development and validation of a clinical prediction score (the SCOPE score) to predict sedation outcomes in patients undergoing endoscopic procedures.

Summary Background Use of anaesthesia services during endoscopy has increased, increasing cost of endoscopy. Aim To identify risk factors for and develop a clinical prediction score to predict difficult conscious sedation. Methods We performed a retrospective cross-sectional study of all patients who underwent oesophagogastroduodenoscopy (OGD) and colonoscopy with endoscopist-administered conscious sedation. The endpoint of difficult sedation was a composite of receipt of high doses (top quintile) of benzodiazepines and opioids, or the documentation of agitation or discomfort. Univariate and multivariate analyses were performed to measure association of the outcome with: age, sex, body mass index (BMI), procedure indication, tobacco use, self-reported psychiatric history, chronic use of benzodiazepines, opioids or other psychoactive medications, admission status and participation of a trainee. A clinical prediction score was constructed using statistically significant variables. Results We identified 13 711 OGDs and 21 763 colonoscopies, 1704 (12.4%) and 2299 (10.6%) of which met the primary endpoint, respectively. On multivariate analysis, factors associated with difficulty during OGD were younger age, procedure indication, male sex, presence of a trainee, psychiatric history and benzodiazepine and opioid use. Factors associated with difficulty during colonoscopy were younger age, female sex, BMI <25, procedure indication, tobacco, benzodiazepine, opioid and other psychoactive medication use. A clinical prediction score was developed and validated that may be used to risk-stratify patients undergoing OGD and colonoscopy across five risk classes. Conclusions Using the Stratifying Clinical Outcomes Prior to Endoscopy (SCOPE) score, patients may be risk stratified for difficult sedation/high sedation requirement during OGD and colonoscopy.
Diagnosis of Alzheimer's disease with [18F]PET in mild and asymptomatic stages

With longer life expectancy, dementia based on the age-related Alzheimers' disease (AD) has turned into one of the most prevalent disorders of older age, representing a serious medical and socio-economic issue. There has been growing interest in early diagnosis of this disease, particularly regarding the initiation of new treatment strategies ahead of the onset of irreversible neuronal damage. It is accepted that the pathologic changes underlying AD appear in the brain years to decades before the symptomatic stages. Consequently, clinical measures of cognitive impairment, as used for definition of dementia, will not allow early diagnosis of AD-pathology in the mild or asymptomatic stages. Thus, a need for complementary sensitive biomarkers is apparent. Brain imaging markers are among the most promising candidates for this diagnostic challenge. Particularly, (18F)FDG PET as a marker of regional neuronal function has been demonstrated to represent a most sensitive and specific method for early identification of AD-pathology and thus for prediction of dementia of the Alzheimer type (DAT), even in the mild and asymptomatic stages. Currently, systematic data of comparable quality are hardly available for any other imaging procedure. The purpose of this article is to describe the typical findings of (18F)FDG PET in different stages of AD and to demonstrate its value for early and reliable diagnosis of Alzheimer's disease, particularly ahead of the stage of dementia of the Alzheimer's type.
Early Management of Stroke Patients in the Emergency Department

Stroke continues to be one of the leading causes of death and adult disability. Increasing public awareness of stroke has led to a rise in the number of patients presenting to emergency departments (EDs) who qualify for emergent and time-sensitive treatments such as t-PA, clot extraction, and surgery. Timely treatment and supportive care of the stroke patient in the ED is crucial for patient outcomes. Emergency medicine (EM) pharmacists are the medication experts and can have a significant impact on the care of a stroke patient. Thus, it is essential for EM pharmacists to have a solid knowledge of the current guidelines and evidence-based literature or lack there of. In this article, we describe the epidemiology of stroke, review the classifications of stroke, and discuss the present treatment strategies for emergent and supportive care.
Terminal-to-Terminal Hybrid Full-Wave Simulation of Low-Profile, Electrically-Small, Near-Ground Antennas

An investigation into the simulation and performance of low-profile, electrically-small antennas for unattended ground sensor (UGS) networks is featured in this study. Because UGS transceivers are intended for operation near the ground, ground proximity effects become extremely important for considerations related to antenna efficiency, input matching, radiation pattern, and the overall path loss between the transmitter and receiver nodes. While vertical wire antennas are shown to be less susceptible to path loss, a low-profile alternative is desired for UGS applications and is often required in the fabrication of low-cost, monolithic on-chip, miniaturized systems. In this work, the performances of different transceiver systems utilizing different types of near-ground antenna structures including the dipole, loop, ordinary circular slot, and cavity-backed circular slot are analyzed using a full-wave hybrid approach consisting of the moment method in conjunction with a near-ground asymptotic field propagation model. The figure of merit for comparison among the various configurations is identified as the efficiency factor calculated from the ratio of the input power at the transmitting antenna terminal to the received power at the receiving antenna terminal. The unique features of ground proximity effects as pertaining to near-ground operation are discussed and an optimal radiator is identified from the set of structures analyzed.
Accelerated Chip-Level Thermal Analysis Using Multilayer Green's Function

Continual scaling of transistors and interconnects has exacerbated the power and thermal management problems in the design of ultralarge-scale integrated (ULSI) circuits. This paper presents an efficient thermal-analysis method of O(NlgN) complexity, where N is the number of blocks that discretize the heat-source or temperature-observation regions. The method is named LOTAGre and formulated using the Green's function for heat conduction through multiple-layer materials, which account for the structure of ULSI chips and the accompanying heat sinks and mounting accessories. In addition to analyzing the thermal effects of the distributive heat sources, LOTAGre also considers the ambient temperature effects that are generally excluded in conventional Green's function-based thermal-analysis tools in order to avoid the concomitant analytical complexity. By employing the well-known eigen-expansion technique and classical transmission-line theory, fully analytical and explicit formulas are derived in this paper for the multilayer Green's function with the inclusion of the s-domain version, the homogeneous and inhomogeneous solutions to the heat-conduction equation. Then, the discrete cosine transform and its inversion are employed to accelerate the numerical computation of the homogeneous and inhomogeneous solutions. This paper includes extensive experimental results to demonstrate that LOTAGre can be as accurate as FLUENT, a sophisticated computational fluid dynamics tool, while speeding up the simulation run time by two to three orders of magnitude in comparison to FLUENT as well as conventional Green's function-based thermal-analysis methods. This paper also discusses the limitations of using the traditional single-layer thermal model in thermal analysis for approximating a multilayer chip structure
Update on the management of ulcerative colitis: treatment and maintenance approaches focused on MMX ® mesalamine

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon that typically manifests as diarrhea, abdominal pain, and bloody stool. Complications, such as colorectal cancer and extraintestinal manifestations, may also develop. The goals of management are to induce and maintain clinical remission and to screen for complications of this disease. Mesalamine is a 5-aminosalicylic acid compound that is the first-line therapy to induce and maintain clinical remission in patients with mild-to-moderate UC. For patients who are refractory to mesalamine or have more severe disease, steroids, azathioprine/mercaptopurine, cyclosporine, or infliximab may be used, induce and/or maintain remission. The various formulations of mesalamine avail- able are primarily differentiated by the methods of delivery of the active compound of the drug to the colon. Mesalamine with Multi-Matrix System ® (MMX) technology (Cosmo SpA, Milan, Italy) is an oral (1.2 g), once-daily tablet formulation of mesalamine used for the treatment of UC (Lialda ®
Evaluating hypermedia: a methodology and case study

Multimedia applications, particularly educational applications, represent one of the fastest growing markets. Hypermedia represents one major segment in this market. Though the advances in multimedia technology have enabled us to create dazzling displays of hypermedia instructional material, its instructional efficacy is somewhat unclear. In part this is due to the often simplistic cause and effect models used to evaluate hypermedia applications. Such simplistic models tend to obscure outcomes. Moreover, they ignore the theories that would explain when and how hypermedia instruction might be efficacious. To this effect, the authors offer a research methodology which incorporates an evaluation model. The model, heavily based in hypermedia learning theories, is used to examine the efficacy of a hypermedia system called KARTT, the Knowledge Acquisition Research Training and Teaching Tool.
Do high concentrations of microcystin prevent Daphnia control of phytoplankton

Toxin-producing cyanobacteria have frequently been hypothesized to limit the ability of herbivorous zooplankton (such as Daphnia) to control phytoplankton biomass by inhibiting feeding, and in extreme cases, causing zooplankton mortality. Using limnocorral experiments in hyper-eutrophic ponds located in Alabama and Michigan (U.S.A.), we tested the hypothesis that high levels of cyanobacteria and microcystin, a class of hepatotoxins produced by several cyanobacterial genera, prevent Daphnia from strongly reducing phytoplankton abundance. At the start of the first experiment (Michigan), phytoplankton communities were dominated by toxic Microcystis and Anabaena (∼96% of total phytoplankton biomass), and concentrations of microcystin were ∼3 μg L⁻¹. Two weeks after adding Daphnia pulicaria from a nearby eutrophic lake, microcystin levels increased to ∼6.5 μg L⁻¹, yet Daphnia populations increased exponentially (r = 0.24 day⁻¹). By the third week, Daphnia had suppressed phytoplankton biomass by ∼74% relative to the no Daphnia controls and maintained reduced phytoplankton biomass until the conclusion of the five-week experiment. In the second experiment (Alabama), microcystin concentrations were greater than 100 μg L⁻¹, yet a mixture of three D. pulicaria clones from eutrophic lakes in southern MI increased and again reduced phytoplankton biomass, in this case by over 80%. The ability of Daphnia to increase in abundance and suppress phytoplankton biomass, despite high initial levels of cyanobacteria and microcystin, indicates that the latter does not prevent strong control of phytoplankton biomass by Daphnia genotypes that are adapted to environments with abundant cyanobacteria and associated cyanotoxins.
Self-Discipline Outdoes IQ in Predicting Academic Performance of Adolescents

In a longitudinal study of 140 eighth-grade students, self-discipline measured by self-report, parent report, teacher report, and monetary choice questionnaires in the fall predicted final grades, school attendance, standardized achievement-test scores, and selection into a competitive high school program the following spring. In a replication with 164 eighth graders, a behavioral delay-of-gratification task, a questionnaire on study habits, and a group-administered IQ test were added. Self-discipline measured in the fall accounted for more than twice as much variance as IQ in final grades, high school selection, school attendance, hours spent doing homework, hours spent watching television (inversely), and the time of day students began their homework. The effect of self-discipline on final grades held even when controlling for first-marking-period grades, achievement-test scores, and measured IQ. These findings suggest a major reason for students falling short of their intellectual potential: their failure to exercise self-discipline.
The universal YrdC/Sua5 family is required for the formation of threonylcarbamoyladenosine in tRNA

Threonylcarbamoyladenosine (t6A) is a universal modification found at position 37 of ANN decoding tRNAs, which imparts a unique structure to the anticodon loop enhancing its binding to ribosomes in vitro. Using a combination of bioinformatic, genetic, structural and biochemical approaches, the universal protein family YrdC/Sua5 (COG0009) was shown to be involved in the biosynthesis of this hypermodified base. Contradictory reports on the essentiality of both the yrdC wild-type gene of Escherichia coli and the SUA5 wild-type gene of Saccharomyces cerevisiae led us to reconstruct null alleles for both genes and prove that yrdC is essential in E. coli, whereas SUA5 is dispensable in yeast but results in severe growth phenotypes. Structural and biochemical analyses revealed that the E. coli YrdC protein binds ATP and preferentially binds RNAThr lacking only the t6A modification. This work lays the foundation for elucidating the function of a protein family found in every sequenced genome to date and understanding the role of t6A in vivo.
Differential Regulation of the Cell-Surface Targeting and Function of β- and α1-Adrenergic Receptors by Rab1 GTPase in Cardiac Myocytes

The molecular mechanism underlying the export from the endoplasmic reticulum (ER) to the cell surface and its role in the regulation of signaling of adrenergic receptors (ARs) remain largely unknown. In this report, we determined the role of Rab1, a Ras-like GTPase that coordinates protein transport specifically from the ER to the Golgi, in the cell surface targeting and function of endogenous beta- and alpha1-ARs in neonatal rat ventricular myocytes. Adenovirus-driven expression of Rab1 into myocytes selectively increased the cell-surface number of alpha1-AR, but not beta-AR, whereas the dominant-negative mutant Rab1N124I significantly reduced the cell-surface expression of beta-AR and alpha1-AR. Brefeldin A inhibited beta-AR and alpha1-AR export and antagonized the Rab1 effect on alpha1-AR expression. Manipulation of Rab1 function similarly influenced the transport of alpha1A- and alpha1B-ARs as well as beta1- and beta2-ARs. Fluorescent microscopy analysis demonstrated that expression of Rab1N124I and Rab1 small interfering RNA induced a marked accumulation of GFP-tagged beta2-AR and alpha1B-AR in the ER. Consistent with the effects on receptor cell-surface targeting, Rab1 selectively enhanced ERK1/2 activation and hypertrophic growth in response to the alpha1-AR agonist phenylephrine but not to the beta-AR agonist isoproterenol. Rab1N124I inhibited both agonist-mediated ERK1/2 activation and hypertrophic growth in neonatal myocytes. These results demonstrate that the cell-surface targeting and signaling of beta- and alpha1-ARs require Rab1 and are differentially modulated by augmentation of Rab1 function. Our data provide strong evidence implicating the ER-to-Golgi traffic as a site for selective manipulation of distinct AR function in cardiac myocytes.
A direct radioimmunoassay for estriol-16α-glucosiduronate: Its use in the determination of plasma and urine levels and renal clearance of this conjugate in pregnancy

A direct radioimmunoassay which does not require hydrolysis or chromatography has been developed for estriol-16alpha-glucosiduronate in pregnancy plasma and urine. The antigen used in the development of this antiserum was prepared by joining the carboxylic acid group of estriol-16alpha-glucosiduronate covalently to the epsilon-amino group of the lysine residues in bovine serum albumin. Results indicate that the direct radioimmunoassay yields levels of estriol-16alpha-glucosiduronate in late pregnancy urine that are comparable to those obtained by mroe elaborate procedures involving chromatographic separation of the estriol conjugates, followed by enzymic hydrolysis and measurement of the freed estriol. In addition, good correlation was found between the total estrogen values in urine obtained by currently used chemical procedures and urinary levels of estriol-16alpha-glucosiduronate. The renal clearance of estriol-16alpha-glucosiduronate was determined in eight normal women during the third trimester, and the mean value +/- S.D. was 404 +/- 81 ml. per minute (range, 248 to 494). This method is suitable for the evaluation of variations in the plasma and urine levels of estriol-16alpha-glucosiduronate in pregnancy and offers significant advantages over the presently used chemical methods for monitoring fetal well-being.
Congenital Laryngomalacia: Disease Spectrum and Management

Laryngomalacia is the most common laryngeal anomaly, affecting 45–75 % of infants with congenital stridor. Laryngomalacia is due to the dynamic prolapse of supraglottic tissues into the airway during inspiration. Prolapse of supraglottic tissues produces a variable amount of airway obstruction and inspiratory stridor. A majority of infants have mild disease and are managed expectantly. Those with moderate and severe disease are managed with gastroesophageal reflux therapy, feeding modifications, and surgical intervention. Surgical intervention is required in 20 % of infants. Supraglottoplasty is the mainstay of surgical treatment; tracheostomy is rarely needed.
Enhancer-binding activity of the tal-1 oncoprotein in association with the E47/E12 helix-loop-helix proteins.

Almost 30% of patients with T-cell acute lymphoblastic leukemia (T-ALL) bear structural alterations of tal-1, a presumptive proto-oncogene that encodes sequences homologous to the helix-loop-helix (HLH) DNA-binding and dimerization domain. Analysis of the tal-1 gene product reveals that its HLH domain mediates protein-protein interactions with either of the ubiquitously expressed HLH proteins E47 and E12. The resultant tal-1/E47 and tal-1/E12 heterodimers specifically recognize the E-box DNA sequence motif found in eucaryotic transcriptional enhancers. Hence, the tal-1 protein shares biochemical properties with other tissue-specific HLH proteins that control cell type determination during myogenesis (e.g., MyoD1) and neurogenesis (e.g., achaete-scute). The data suggest that HLH heterodimers involving tal-1 may function in vivo as transcriptional regulatory factors that influence cell type determination during hematopoietic development.
Federal Regulation of Family Settlements

Can the Congress of the United States levy a tax of that character? The proposition that it cannot rests upon the assumption that, since the transmission of property by death is exclusively subject to the regulating authority of the several states, therefore the levy by Congress of a tax on inheritances or legacies, in any form, is beyond the power of Congress, and is an interference by the national government with a matter which falls alone within the reach of State legislation.3
Microsensor and transcriptomic signatures of oxygen depletion in biofilms associated with chronic wounds

Biofilms have been implicated in delayed wound healing, although the mechanisms by which biofilms impair wound healing are poorly understood. Many species of bacteria produce exotoxins and exoenzymes that may inhibit healing. In addition, oxygen consumption by biofilms and by the responding leukocytes, may impede wound healing by depleting the oxygen that is required for healing. In this study, oxygen microsensors to measure oxygen transects through in vitro cultured biofilms, biofilms formed in vivo within scabs from a diabetic (db/db) mouse wound model, and ex vivo human chronic wound specimens was used. The results showed that oxygen levels within mouse scabs had steep gradients that reached minima ranging from 17 to 72 mmHg on live mice and from 6.4 to 1.1 mmHg on euthanized mice. The oxygen gradients in the mouse scabs were similar to those observed for clinical isolates cultured in vitro and for human ex vivo specimens. To characterize the metabolic activities of the bacteria in the mouse scabs, transcriptomics analyses of Pseudomonas aeruginosa biofilms associated with the db/db mice wounds was performed. The results demonstrated that the bacteria expressed genes for metabolic activities associated with cell growth. Interestingly, the transcriptome results also indicated that the bacteria within the wounds experienced oxygen-limitation stress. Among the bacterial genes that were expressed in vivo were genes associated with the Anr-mediated hypoxia-stress response. Other bacterial stress response genes highly expressed in vivo were genes associated with stationary-phase growth, osmotic stress, and RpoH-mediated heat shock stress. Overall, the results supported the hypothesis that bacterial biofilms in chronic wounds promote chronicity by contributing to the maintenance of localized low oxygen tensions, through their metabolic activities and through their recruitment of cells that consume oxygen for host defensive processes.
Stockholder-Bondholder Conflict: Application of Binomial Option Pricing Methodology

This paper discusses how the stockholder-bondholder conflict can be analyzed using the binomial option pricing model. Although the potential conflicts between stockholders and bondholders are recognized and discussed in most intermediate corporate finance textbooks, these textbooks, generally do not illustrate the valuation of the relevant options involved in those situations; this article fills that void. Further, it takes explicit account of financial distress of the firm - which is usually the cause of the conflict - in analyzing the underinvestment and asset substitution problems.
Templating Highly Crystalline Organic Semiconductors Using Atomic Membranes of Graphene at the Anode/Organic Interface

Charge and energy transport in organic semiconductors is highly anisotropic and dependent on crystalline ordering. Here, we demonstrate a novel approach for ordering crystalline organic semiconductors, with orientations optimized for optoelectronics applications, by using a single monolayer of graphene as a molecular template. We show, in particular, that large-area graphene can be integrated on metals and oxides to modify their surface energies and used to template copper phthalocyanine (CuPc), a prototypical organic semiconductor. On unmodified substrates, thermally evaporated films of CuPc are small-grained, and the molecules are in the "standing-up" (100) orientation. On graphene modified substrates, CuPc is templated in favorable "lying-down" (112) and (012) orientations with drastically larger crystal sizes. This results in an 86% increase in the absorption coefficient at 700 nm and should furthermore result in enhanced energy and charge transport. The use of highly conductive and transparent (>95%) graphene membranes as templates is expected to be a foundation for developing future planar and nanostructured organic light-emitting diodes and organic photovoltaics with improved performance.
Clinical factors associated with the development of Crohn's disease in inflammatory bowel disease-unclassified patients undergoing ileal pouch-anal anastomosis

BACKGROUND Patients with inflammatory bowel disease-unclassified (IBDU) undergoing ileal pouch-anal anastomosis (IPAA) are at the risk of developing Crohn's disease (CD) after surgical procedure. In these patients, a clinically centered set of preoperative risk factors has not been prospectively defined. We report a single-center analysis of clinical factors associated with the development of CD after IPAA. METHODS Consecutive IBDU patients undergoing IPAA were identified. The diagnosis of IBDU was based on the presence of atypical disease distribution, presence of granulomas on endoscopic biopsy, and/or perianal disease. The diagnosis of CD after IPAA included the presence of afferent limb inflammation on pouchoscopy in the absence of nonsteroidal anti-inflammatory drug use and/or the development of pouch fistulizing disease more than 3 months after ileostomy closure. RESULTS Of the 149 study patients, 33 (22%) were diagnosed with CD after IPAA at a median of 37 months (interquartile range, 11-83 mo) after ileostomy closure. CD was diagnosed by mucosal inflammation above the pouch (n = 23; 70%), pouch fistulizing disease (n = 4; 12%), anorectal septic complications (n = 2; 6%), or the presence of ≥2 of the above complications (n = 4; 12%). The sole clinical predictor for the development of CD after IPAA was younger age at disease onset even after controlling for relevant clinical factors in a multivariate analysis. The odds of developing CD increased by 4% for each year that IBDU was diagnosed at a younger age. CONCLUSIONS Younger age at disease onset is the only clinical factor associated with the development of CD after IPAA for IBDU. Patients with IBDU undergoing IPAA with young age at disease onset should be counseled about the potentially higher risk of developing CD.
Investigation Of YBa2Cu3O7-δ Films Grown on Vicinally-Polished MgOSubstrates

X-ray diffraction and transmission electron microscopy have been used to study the morphology and defect structure of YBa2Cu3O7-δ films on [001] MgO substrates polished away from the [001] crystallographic axis towards either [010] or [110] by angles ranging from 1° to 20°. On the [010] off-axis substrates it was found that growth of the YBCO film was highly influenced by the surface normal of the substrate with only very weak alignment to the substrate [001] direction. All [010]-angled samples maintained Tc's of 86K. Angles of 1°, 2.5°, and 5° toward [010] produced films with large mosaic spread parallel to the direction of the angle, as high as 4° FWHM for the 5° sample. Critical current densities of these films remained as high as those of films grown on on-axis substrates, e.g. 4.4×107 A/cm2 at 4.2 K and zero applied field. Larger off-axis angles led to samples with reduced mosaic spread but still alignment to the surface normal, and reduced Jc's of 2×107 A/cm2 and 1×l05 A/cm2 for 10° and 20° angles, respectively. TEM investigation and in-plane x-ray examination of the 5°, 10°, and 20° samples show good in-plane texture except for the 20° sample, and increased granularity with angle. Films on substrates polished off-axis towards [110] have degraded Tc's and Jc's for all angles.
Mikulicz syndrome associated with a malignant large cell gastric lymphoma: a case report and review of the literature.

There is much confusion in the literature regarding the differences between Mikulicz disease and Mikulicz syndrome. This may be because there seems to be a connection between the disease and disease processes associated with the syndrome. This article provides historical data discussing the emergence of Mikulicz disease, confusions regarding its definition, and finally offers an explanation to the interrelationships of these two entities. This case report hypothesizes that the non-Hodgkin’s lymphoma (NHL), which in association with Sjogren’s syndrome and Mikulicz disease in this patient comprised the Mikulicz syndrome, may have transformed into his malignant large-cell gastric lymphoma. It supports conclusions in the literature that Mikulicz disease, benign lymphoepithelial lesion, and Sjogren’s syndrome may all be a part of the same disease process as graduated variants of one another, with malignant lymphoma being a recognized complication of these entities.
Group Design: Bereavement Group for Widows

The death of a mate has been described as one of the number one stressors in our society today. This article proposes a group design for bereaved widows for the purpose of support and preventive an...
N-Terminal Peptide Detection with Optimized Peptide-Spectrum Matching and Streamlined Sequence Libraries

We identified tryptic peptides in yeast cell lysates that map to translation initiation sites downstream of the annotated start sites using the peptide-spectrum matching algorithms OMSSA and Mascot. To increase the accuracy of peptide-spectrum matching, both algorithms were run using several standardized parameter sets, and Mascot was run utilizing a, b, and y ions from collision-induced dissociation. A large fraction (22%) of the detected N-terminal peptides mapped to translation initiation downstream of the annotated initiation sites. Expression of several truncated proteins from downstream initiation in the same reading frame as the full-length protein (frame 1) was verified by western analysis. To facilitate analysis of the larger proteome of Drosophila, we created a streamlined sequence library from which all duplicated trypsin fragments had been removed. OMSSA assessment using this “stripped” library revealed 171 peptides that map to downstream translation initiation sites, 76% of which are in the s...
“To think, to decide, and to act”: Radical Fictions of Transgression and Vindication

Like Mary Wollstonecraft’s The Wrongs of Woman, Mary Hays’s The Victim of Prejudice (1799) and Amelia Opie’s Father and Daughter (1801) are experimental fictions that require the reader’s identification with a sexualized heroine marked as transgressive and persecuted by society. Indeed, as I suggest in the first chapter, Wollstonecraft’s Wrongs of Woman models the rebellious and outspoken Romantic heroine I am delineating. In many ways, Maria Venables represents an extreme of the type; she leaves her husband, takes a lover, and presents her case for divorce to a court of law. Her suit fails, but it is a noble failure. Furthermore, as Tilottama Rajan has taught us to recognize, Wollstonecraft’s unfinished narrative invites its readers to “complete the text by unfolding a truth it does not yet contain” (“Wollstonecraft and Godwin” 223). As I note in the Coda to Chapter 1, The Wrongs of Woman was published with six different endings, all drawn from the author’s working notes, most of which end with the heroine’s death but one of which ends with her and Jemima co-mothering Maria’s long lost daughter. Rajan argues for the potent political power of the unfinished text; it invites its readers to move beyond the page and enact its revolutionary potential in the “real” world outside of the book.