cssi/SciSciGPT-SciSciNet huggingface dataset:
Regulation of the CD8+ T cell responses against Plasmodium liver stages in mice.

Abstract CD8+ T cells induced by immunization with Plasmodium sporozoites play a major role in protective immunity against parasite infection, inhibiting the development of liver stages. The activation of these T cells is initiated just a few hours after exposure to parasites and progresses rapidly through a tightly regulated program. Effector functions in CD8+ T are detectable as early as 24 h after immunization and this event is followed 24–48 h later by an accelerated expansion of the CD8+ T cell numbers which reaches a peak 4–5 days after priming. Concomitantly with the development of anti-parasite activity, CD8+ T cells acquire a self-regulatory role limiting the magnitude of the CD8+ T cell response. Once activated, CD8+ T cells strongly inhibit the priming of additional naive CD8+ T cells by competing for antigen presenting cells. On days 6–8 after immunization, a sudden contraction of this T cell response occurs due to programmed cell death of 70-80% of the activated cells. After this contraction phase, 15–20 days after priming, activated cells establish memory populations. The development and maintenance of these memory populations strictly depends on the presence of CD4+ T cells and IL-4, and probably also IL-7, IL-15 and IL-2. These cytokines, some of which are produced by CD4+ T cells, provide signals to prevents apoptosis and also induce the differentiation of memory sub-populations, most of which acquire definitive phenotypes 20–30 days after immunization.
Advice on acquiring NSF funding in nanomechanics and surface engineering

Over the past three decades, new tools and techniques have been developed to image, synthesize, and manipulate nanoscale objects. Advanced materials synthesis and manufacturing techniques provide the technology not only to make nanoscale materials but to incorporate them into functional systems. Since the surface-to-volume ratio of a given object scales as the reciprocal of its size, surface and interfacial effects become dominant in these nanoscale systems. This paper will discuss U.S. National Science Foundation nanoscale funding initiatives that center on surface or interfacial effects.
The use of augmented-pressure colostography in imperforate anus.

Colostomy is recommended in most newborns with imperforate anus (IA), except those with low-type anorectal malformations (ARM). Accurate demonstration of the anatomy of any associated fistula between the rectum and the urogenital tract is essential for optimal surgical management. Augmented-pressure distal colostography is recommended to fulfill this requirement prior to definitive surgical repair of IA. We examined 12 cases of high or intermediate-type ARM using this technique, which clearly demonstrated the distal perineal anatomy. All were confirmed at posterior sagittal angorectoplasty.
Interaction of [3H]GBR 12935 and GBR 12909 with the dopamine uptake complex in nucleus accumbens

Although some behavioral effects of cocaine are hypothesized to be due to blockade of dopamine uptake in nucleus accumbens, it has been reported that in nucleus accumbens there are no specific cocaine binding sites and that cocaine is a weak inhibitor of dopamine uptake. [3H]GBR 12935 and an unlabelled analog, GBR 12909, are ligands that bind with great affinity and specificity to a site on dopamine uptake complex in striatum. We therefore investigated the interaction of these GBR compounds with the dopamine uptake complex in nucleus accumbens. We found specific high affinity [3H]GBR 12935 binding and a significant correlation between displacement of [3H]GBR 12935 binding by a series of compounds in striatum and nucleus accumbens. GBR 12909 inhibited dopamine uptake with equal potency in nucleus accumbens and striatum. Thus, there appear to be some aspects of the dopamine uptake complex in nucleus accumbens and striatum that are similar.
Site-specific Charge Interactions of α-Conotoxin MI with the Nicotinic Acetylcholine Receptor

Abstract We have tested the importance of charge interactions for α-conotoxin MI binding to the nicotinic acetylcholine receptor (AChR). Ionic residues on α-conotoxin MI were altered by site-directed mutagenesis or by chemical modification. In physiological buffer, removal of charges at the N terminus, His-5, and Lys-10 had small (2–4-fold) effects on binding affinity to the mouse muscle AChR and the Torpedo AChR. It was also demonstrated that conotoxin had no effect on the conformational equilibrium of either receptor, as assessed by the effects of the noncompetitive antagonist proadifen on conotoxin binding and, conversely, the effect of conotoxin on the affinity of phencyclidine, proadifen, and ethidium. Conotoxin displayed higher binding affinity in low ionic strength buffer; neutralization of Lys-10 and the N terminus by acetylation blocked this affinity shift at the αδ site but not at the αγ site. It is concluded that Ctx residues Lys-10 and the N terminal interact with oppositely charged receptor residues only at the αδ site, and the two sites have distinct arrangements of charged residues. Ethidium fluorescence experiments demonstrated that conotoxin is formally competitive with a small cholinergic ligand, tetramethylammonium. Thus, α-conotoxin MI appears to interact with the portion of the binding site responsible for stabilizing agonist cations but does not do so with a cationic residue and is, consequently, incapable of inducing a conformational change.
Dimethylether: A low velocity, low diffusion drift chamber gas☆

Abstract Excellent resolution (∼ 16 μm) has been obtained using dimethylether [(CH 3 ) 2 O] at 1 atm in a small drift chamber.
Aeroelastic design optimization for laminar and turbulent flows

Abstract The design of flexible structures undergoing aeroelastic deformations is a challenging task, in particular if the prediction of the fluid loads and the evaluation of the aerodynamic performance criteria require accounting for laminar and turbulent effects. This paper presents a general optimization methodology for fluid-structure interaction problems based on turbulent flow models. The structure is modeled via a geometrically nonlinear finite element method. The flow field is computed by solving a finite volume approximation of the Navier–Stokes equations on moving grids augmented by turbulence models. The global design sensitivity equations are presented and solution methods for computing the numerically consistent and approximated design sensitivities are introduced. The accuracy of the sensitivity analysis methods are studied by numerical examples for three-dimensional problems. The potential of the overall optimization methodology is illustrated by the shape and thickness optimization of a realistic wing. The numerical examples suggest that the derivatives of the turbulence variables can be neglected in the sensitivity analysis without noticeable errors. Comparing the optimization results for Euler and Navier–Stokes flow models shows the importance of accounting for viscous laminar and turbulent effects for fine-tuning the design and obtaining reliable optimization results.
Physical matching versus CD matching for CD SEM

CD-SEMs fleet matching is a widely discussed subject and various approaches and procedures to determine it were described in the literature. The different approaches for matching are all based on statistical treatment of regular CD measurements that are performed on dedicated test structures. The test structures are a limited finite set of features, thus the matching results should be treated as valid only for the specific defined set of test features. The credibility of the matching should be in question for different layers and specifically production layers. Since matching is crucial for reliable process monitoring by a fleet of CD-SEMs, the current matching approaches (such as TMU) must be extended so that the matching will be only tool dependent and reproducible on all layers regardless their specific material or topographic characteristics. In this work the term "Physical Matching" is introduced and a new matching procedure based on physical parameters is described. This approach extends the conventional matching methods to enable significant improvement of the matching between CD-SEM tools in production environment. To study and demonstrate the physical matching, we focus on the limited parameters set - the image brightness and Signal/Noise ratio(SNR). We test the sensitivity of CD measurements to changes in these parameters both on different test layers - Etch and Litho. We show that sensitivity of CD based measurements is low and reasonable change of the image brightness or SNR has small effect. The advantage of the physical matching approach for case study is demonstrated. The improved matching procedures are based on new targets that are used to measure the above image parameters directly. This way it is possible to characterize correctly the physical state of the measurement tool and guarantee the same image characteristics which in turn guarantee improved matching on all layers. In the framework of the proposed matching approach a proper determination of the minimal set of physical parameters that is needed to guarantee CD-SEM tools stability and matching should be included.
A Field-Tested Internal Tag for Crayfish (Decapoda, Astacidea)

[Nach einem kurzen Uberblick uber bei verschiedenen Tiergruppen bisher angewendete Markierungsmethoden wird eine neue Methode zur internen Kennzeichnung von Fluskrebsen beschrieben. Ein mit Farbcode versehener Nylonstab, der unter die Sternite der Pleons geschoben wird, ermoglicht Langzeitbeobachtung uber mehrere Hautungen hinweg, das Erkennen von Einzeltieren und die Identifizierung, ohne die markierten Tiere zu opfern. Versuche in der naturlichen Umwelt deuten darauf hin, das keine negativen Auswirkungen hinsichtlich Regeneration, Wachstum oder Lebensdauer der Fluskrebse auftreten. Der grundsatzliche Nachteil dieser Markierungsmethode liegt im Aufwand an Zeit, der fur Vorbereitung und Anbringung der Markierung erforderlich ist., Nach einem kurzen Uberblick uber bei verschiedenen Tiergruppen bisher angewendete Markierungsmethoden wird eine neue Methode zur internen Kennzeichnung von Fluskrebsen beschrieben. Ein mit Farbcode versehener Nylonstab, der unter die Sternite der Pleons geschoben wird, ermoglicht Langzeitbeobachtung uber mehrere Hautungen hinweg, das Erkennen von Einzeltieren und die Identifizierung, ohne die markierten Tiere zu opfern. Versuche in der naturlichen Umwelt deuten darauf hin, das keine negativen Auswirkungen hinsichtlich Regeneration, Wachstum oder Lebensdauer der Fluskrebse auftreten. Der grundsatzliche Nachteil dieser Markierungsmethode liegt im Aufwand an Zeit, der fur Vorbereitung und Anbringung der Markierung erforderlich ist.]
Comparison of slater and contracted gaussian basis sets in SCF and CI calculations on H2O

Abstract A series of SCF and CI calculations for the elctronic ground state of H 2 O have been carried out with two different 14-function basis sets; one a Clementi-type double zeta STO basis and the other a contracted GTO set. The results obtained with the two bases are compared and analyzed in terms of inner and outer shell correlation and of the contributions of different levels of excitation.
A fixed point theorem for plane separating continua

Abstract If an orientation preserving plane homeomorphism F has a fixed prime end associated with an invariant continuum Δ that separates the plane into exactly two domains, then F has a fixed point in Δ.
Oregon: Library automation developments

Several efforts cover the Oregon library automation landscape. They include Oregon Information Highway Project; Oregon Bibliographic Information System (ORBIS); Portland Area Library System (PORTALS); the Internet Connectivity Handbook; a statewide report on frame relay; and database licensing.
Student evaluation using lists of descriptive statements

The development of an evaluation system is discussed that uses a list of statements describing particular aspects of the student's work in a course. The instructor marks those statements which are applicable to the student's performance. The statement lists are read by an optical scanner and stored in a computer. When required, the computer produces a listing of the statements chosen. The system is intended to be more precise than letter grades, to be easier to handle (for both instructor and registrar) than evaluative paragraphs, and to guide the instructor in making an evaluation. The system has been implemented on an experimental basis for two years, and reactions have been obtained from students, faculty, and graduate and professional school admission officers.
Searching for cultural psyche in body type variance: American vs Japanese body type estimations

Purpose – The purpose of this study is to investigate cross‐cultural differences between American and Japanese college students' body type under/overestimation regarding their own bodies within the framework of self‐construal theory.Design/methodology/approach – Information from 137 American college students and 160 Japanese college students was collected in using a survey method. Their height, body weight, gender, and self‐estimated body types from three different options (underweight, normal weight, and overweight) was collected in order to assess the relationship between self‐estimated and real body types of these participants. The real body type based on one's body mass index and the self‐estimated body type were compared for each participant.Findings – Japanese students were found to be more in the underweight category and less in the overweight category than American students. It was also found that Japanese students, and female students in general, were more likely to overestimate their body types ...
Auditory Training for Children with Processing Disorders.

It is not surprisingly that most books and articles dealing with Central Auditory Processing (CAP) disorders place heavy emphasis on the diagnosis of the problem and its associated disabilities, with little mention of habilitation. In the natural course of events it is first necessary to know that a problem exists, what its impact may be, and how it can be identified before venturing to remediate it. To date, considerable research and clinical effort has been expended to better understand the problems and to identify the children who are impaired. A wide variety of procedures has also been used to measure CAP disabilites. It would follow that emphasis should now be directed toward what can be done to improve a child's ability to perform at school and home whne auditory difficulties are uncovered.
Radiosity based model for terrain effects on multi-angular views

The Multi-Angular Imaging Spectroradiometer (MISR) will image the Earth from 9 viewing angles and derive atmospheric parameters and surface reflectance. The authors investigate the effects of reflections within a rough terrain on reflectance retrievals with and without terrain correction. A simple wedge model is used to compute the surface radiosities as a function of solar illumination direction. For the 9 MISR view directions the authors compute the apparent reflectance and compare the results with a single scattering model. For a range of slopes and flat surface reflectances they compute how much the apparent reflectance changes. >
Roles of the Mammalian Cytosolic Cysteine Desulfurase, ISCS, and Scaffold Protein, ISCU, in Iron-Sulfur Cluster Assembly

Iron-sulfur clusters are prosthetic groups composed of sulfur and iron that are found in respiratory chain complexes and numerous enzymes. Iron-sulfur clusters are synthesized in a multistep process that utilizes cysteine desulfurases, scaffold proteins, chaperones, and iron donors. Assembly of iron-sulfur clusters occurs in the mitochondrial matrix of mammalian cells, but cytosolic isoforms of three major mammalian iron-sulfur cluster (ISC) assembly components have been found, raising the possibility that de novo iron-sulfur cluster biogenesis also occurs in cytosol. The human cysteine desulfurase, ISCS, has two isoforms, one of which targets to the mitochondria, whereas the other less abundant form is cytosolic and nuclear. The open-reading frame of cytosolic mammalian ISCS begins at the second AUG of the transcript and lacks mitochondrial targeting information. Yeast complementation experiments have suggested that the human cytosolic ISCS isoform (c-ISCS) cannot be functional. To evaluate function of c-ISCS, we overexpressed the human cytosolic ISCS in yeast Pichia pastoris and showed that the cytosolic form of ISCS is an active cysteine desulfurase that covalently binds 35S acquired from desulfuration of radiolabeled cysteine. Human cytosolic ISCS dimerized as efficiently as bacterial ISCS and formed a complex in vitro with overexpressed cytosolic human ISCU. When incubated with iron regulatory protein 1, cysteine, and iron, the cytosolic forms of ISCS and ISCU facilitated efficient formation of a [4Fe-4S] cluster on IRP1. Thus, the cytosolic form of ISCS is a functional cysteine desulfurase that can collaborate with cytosolic ISCU to promote de novo iron-sulfur cluster formation.
Inability of colchicine to inhibit newt epidermal cell migration or prevent concanavalin A-mediated inhibition of migration. Studies in vivo.

Abstract Adult newts injected with metaphase-accumulating doses of colchicine showed no inhibition of epidermal cell migration during wound closure, indicating that microtubules are unnecessary for locomotion of these epithelial cells. Neither could colchicine alter ConA-induced inhibition of migration, indicating further that there is no microtubule requirement for this phenomenon.
The Shifting Foundations of Political Communication: Responding to a Defense of the Media Effects Paradigm

Our earlier article (Bennett & Iyengar, 2008) argued that because news audiences are increasingly self-selected, communications scholars will be increasingly hard pressed to document media-induced persuasion effects. Holbert, Garrett, and Gleason’s critique does not address the fundamental problem of endogeneity, instead proposing attitude reinforcement as a substitute for persuasion. But the problem of endogeneity applies equally to reinforcement and attitude-change research. Our critics also argue that exposure to alternative news outlets and entertainment programming is exogenous and has the potential to shape political attitudes. We respond that the political content of these programs, while surely promoting other desirable political outcomes, is too sporadic to produce large-scale message effects of the sort described by the classic persuasion paradigm.
Investigating the potential of application-centric aggressive power management for HPC workloads

Energy efficiency of large-scale data centers is becoming a major concern not only for reasons of energy conservation, failures, and cost reduction, but also because such sys tems are soon reaching the limits of power available to them. Like High Performance Computing (HPC) systems, large-scale clu ster-based data centers can consume power in megawatts, and of all the power consumed by such a system, only a fraction is used for actual computations. In this paper, we study the potential of application-centric aggressive power management of data center's resources for HPC workloads. Specifically, we consider power management mechanisms and controls (currently or soon to be) available at different levels and for different subsystems, and leverage several innovative approaches that have been taken to tackle this problem in the last few years, can be effectively used in a application-aware manner for HPC workloads. To do this, we first profile sta ndard HPC benchmarks with respect to behaviors, resource usage and power impact on individual computing nodes. Based on a power and latency model and the workload profiles, we develop an algorithm that can improve energy efficiency with little or no performance loss. We then evaluate our proposed algorithm through simulations using empirical power characterization and quantification. Finally, we validate the simulation results with actual executions on real hardware. The obtained results show that by using application aware power management, we can re-du ce the average energy consumption without significant penalty in performance. This motivates us to investigate autonomic approaches for application-aware aggressive power management and cross layer and cross function predictive subsystem level power management for large-scale data centers.
Gentamicin is ototoxic to all hair cells in the fish lateral line system

Hair cells of the lateral line system in fish may differ in their susceptibility to damage by aminoglycoside antibiotics. Gentamicin has been reported to damage hair cells within canal neuromasts, but not those within superficial neuromasts. This finding, based on SEM imaging, indicates a distinction in the physiology of hair cells between the two classes of neuromast. Studies concerned with the individual roles of canal and superficial neuromasts in behavior have taken advantage of this effect in an attempt to selectively disable canal neuromasts without affecting superficial neuromast function. Here we present an experimental test of the hypothesis that canal neuromasts are more vulnerable to gentamicin than superficial neuromasts. We measured the effect of gentamicin exposure on hair cells using vital stains (DASPEI and FM1-43) in the neuromasts of Mexican blind cave fish (Astyanaxfasciatus) and zebrafish (Daniorerio). Contrary to the findings of prior studies that used SEM, gentamicin significantly reduced dye uptake by hair cells of both canal and superficial neuromasts in both species. Therefore, lateral line hair cells of both neuromast types are vulnerable to gentamicin ototoxicity. These findings argue for a re-evaluation of the results of studies that have used gentamicin to differentiate the roles of the two classes of neuromast in fish behavior.
GRIK1 Genotype moderates topiramate's effects on daily drinking level, expectations of alcohol's positive effects and desire to drink

We ([Kranzler et al., 2014][1]) reported that topiramate 200 mg/day reduced heavy drinking days and increased abstinent days in 138 heavy drinkers whose treatment goal was to reduce drinking to safe levels. In that 12-week, placebo-controlled study, we measured drinking using the Timeline Follow-back method at each treatment visit. In addition to the intent-to-treat effects of topiramate, we found that a single nucleotide polymorphism (rs2832407) in GRIK1 , encoding the GluK1 subunit of the kainate receptor, moderated the treatment effect in European Americans (EAs; n = 122). Topiramate reduced heavy drinking only in rs2832407*C allele homozygotes. Here, we augment those analyses by using patients’ daily reports obtained using interactive voice response technology; (a) to validate the interactive effects of GRIK1 and topiramate as predictors of drinking level; and, (b) to examine changes in expected positive effects of drinking (i.e. positive outcome expectancies) and desire to drink. We found that rs2832407*C allele homozygotes treated with topiramate drank less overall during treatment than those receiving placebo, validating our earlier findings for heavy drinking days ([Kranzler et al., 2014][1]). There was also a study day × medication group × genotype group interaction that predicted both positive alcohol expectancies and desire to drink, with rs2832407*C-allele homozygotes treated with topiramate showing the largest decreases in these outcomes during the study period. Changes in positive alcohol expectancies or desire to drink did not mediate the effects on drinking. These findings validate and extend our previous pharmacogenetic findings with topiramate. [1]: #ref-20
Water mobility in multicomponent model media as studied by 2H and 17O NMR.

Molecular mobility of water was studied in a microbiological media containing complex and heterogeneous mixtures of cellulose, l-sorbose, and orange serum broth (OSB) using 2H and 17O high-resolution NMR. All mixtures showed Lorentian 17O NMR spectra but complex 2H NMR line shapes. Sorbose, when solubilized, caused line-narrowing where as cellulose−OSB mixtures showed wide peaks with flat plateaus. Presence of liquid or solvent water had a profound effect on a marked increase in T2 relaxation time observed in sorbose-containing samples. 17O NMR data were not composition dependent, while 2H NMR data were highly sorbose dependent. Keywords: Water mobility; NMR; microbiological media
The effect of load cycling on nanoleakage of deproteinized resin/dentin interfaces as a function of time

Abstract Objectives To evaluate the effects of cyclic loading on nanoleakage as a function of time at resin–dentin interfaces with and without removal of collagen. Methods Bovine flat mid-coronal dentin received one of the following surface treatments: (1) acid-etch or (2) acid etched + 5% NaOCl for 2 m. The teeth were then bonded with Single Bond (3M ESPE), Scotchbond Multi-Purpose (3M ESPE), One-Step Plus (Bisco) or All-Bond 2 (Bisco) adhesive systems and restored with Z250 composite. Half of the bonded teeth were randomly assigned to receive 200,000 cycles of loading at 50 N. Teeth were sectioned into 1 mm × 1 mm thick slices and stored in distilled water for 24 h and 6 months. After water storage, beams were prepared for nanoleakage evaluation and observed under the SEM. Data were statistically analyzed using three-way ANOVA and Fisher's PLSD test (p Results Use of NaOCl did not affect nanoleakage at the interface of all adhesive systems (p > 0.05) when compared to their respective controls. After 6 months of immersion in water, except for One Step Plus, collagen-depleted groups and control groups presented similar leakage values. After cyclic loading, the deproteinized group revealed a higher degree of silver nitrate deposits when compared to the control group (p Significance The hybrid layer is important as a stress-absorbing layer and it may not represent the weak link for initiation of the nanoleakage phenomenon.
MAINTENANCE OF PARENTAL POPULATIONS BORDERING A BLUE MUSSEL HYBRID ZONE BY POST-SETTLEMENT SELECTION

A common question in studies of hybrid zones regards how nearby parental populations can remain distinct in the face of gene flow from the other species and hybrid populations. Environmentally dependent hybrid-zone models often invoke selection favouring each of the parental species in different habitats where immigrants will often fail to survive and reproduce. The present study tests whether a relatively pure population of Mytilus galloprovincialis, located on the edge of a hybrid zone with M. edulis, is being maintained by selection against hybrid immigrants. Comparisons of newly settled spat with members of the same cohort approximately 9 months later consistently show a reduction in M. edulis-specific alleles to levels observed in adult age classes at two diagnostic loci. These data provide evidence for selection against spat from the hybrid zone that settled at sites within the M. galloprovincialis population within the first year of life. The observed selection would result in removal of most M. edulis-specific alleles prior to reproduction and keep the M. galloprovincialis population distinct.
The 2005 Specification for Structural Steel Buildings: A Specification for the 21st Century

The American Institute of Steel Construction’s AISC most recent Specification for Structural Steel Buildings was introduced in 2005. This new standard replaces the two existing AISC Specifications: the 1989 Specification for Structural Steel BuildingsAllowable Stress Design, and Plastic Design, and the 1999 Load and Resistance Factor Design Specification for Structural Steel Buildings. A new “unified” format permits the use of either the allowable stress design ASD or load and resistance factor design LRFD methods. In addition to the usual historical commentary in the back of the specification, user notes will be interspersed throughout the text. The Specification is organized in a logical fashion with a roadmap at the front that leads to where specific provisions are located. The roadmap begins with the design basis for the entire document and then directs the user to analysis and stability provisions, member design including composite members , connection design, serviceability considerations, and ending with fabrication, erection, and quality control. Directions to special topics, such as evaluation and repair and fire design are also given.
Silencing calcineurin A subunit reduces SERCA2 expression in cardiac myocytes.

Resting intracellular Ca2+ can be raised, in neonatal rat cardiac myocytes, by exposure to very low concentration of thapsigargin (TG). Such a Ca2+ rise yields calcineurin (CN) activation demonstra...
Recessive MYH6 Mutations in Hypoplastic Left Heart With Reduced Ejection Fraction

Background— The molecular underpinnings of hypoplastic left heart are poorly understood. Staged surgical palliation has dramatically improved survival, yet eventual failure of the systemic right ventricle necessitates cardiac transplantation in a subset of patients. We sought to identify genetic determinants of hypoplastic left heart with latent right ventricular dysfunction in individuals with a Fontan circulation. Methods and Results— Evaluation of cardiac structure and function by echocardiography in patients with hypoplastic left heart and their first-degree relatives identified 5 individuals with right ventricular ejection fraction ≤40% after Fontan operation. Whole genome sequencing was performed on DNA from 21 family members, filtering for genetic variants with allele frequency <1% predicted to alter protein structure or expression. Secondary family-based filtering for de novo and recessive variants revealed rare inherited missense mutations on both paternal and maternal alleles of MYH6 , encoding myosin heavy chain 6, in 2 patients who developed right ventricular dysfunction 3 to 11 years postoperatively. Parents and siblings who were heterozygous carriers had normal echocardiograms. Protein modeling of the 4 highly conserved amino acid substitutions, residing in both head and tail domains, predicted perturbation of protein structure and function. Conclusions— In contrast to dominant MYH6 mutations with variable penetrance identified in other congenital heart defects and dilated cardiomyopathy, this study reveals compound heterozygosity for recessive MYH6 mutations in patients with hypoplastic left heart and reduced systemic right ventricular ejection fraction. These findings implicate a shared molecular basis for the developmental arrest and latent myopathy of left and right ventricles, respectively.
Interleukin 1‐β‐ and tumor necrosis factor‐α‐mediated regulation of ICAM‐1 gene expression in astrocytes requires protein kinase C activity

Several adhesion molecules including intercellular adhesion molecule-1 (ICAM-1) are expressed by astrocytes, the predominant glial cell of the central nervous system (CNS). Such molecules are important in the trafficking of leukocytes to sites of inflammation, and in lymphocyte activation. ICAM-1 is constitutively expressed by neonatal rat astrocytes, and expression is enhanced by the proinflammatory cytokines interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma), with IL-1 beta and TNF-alpha being the strongest inducers. In this study, we have examined the nature of the second messengers involved in ICAM-1 gene expression induced by the cytokines IL-1 beta and TNF-alpha. Our results indicate that stimuli related to protein kinase C (PKC) such as the phorbol ester phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187 increase ICAM-1 mRNA expression, whereas cyclic nucleotide analogs and PKA agonists have no effect. Pharmacologic inhibitors of PKC such as H7, H8, and calphostin C inhibit ICAM-1 gene expression inducible by IL-1 beta and TNF-alpha. Prolonged treatment of astrocytes with PMA results in a time-dependent downregulation of the PKC isoforms alpha, delta, and epsilon, and a concomitant diminution of ICAM-1 mRNA expression induced by IL-1 beta, TNF-alpha, and PMA itself at specific time points post-PMA treatment. These data, collectively, demonstrate a role for various PKC isoforms in IL-1 beta and TNF-alpha enhancement of ICAM-1 gene expression in rat astrocytes.
53BP1 is required for class switch recombination

53BP1 participates early in the DNA damage response and is involved in cell cycle checkpoint control. Moreover, the phenotype of mice and cells deficient in 53BP1 suggests a defect in DNA repair (Ward et al., 2003b). Therefore, we asked whether or not 53BP1 would be required for the efficient repair of DNA double strand breaks. Our data indicate that homologous recombination by gene conversion does not depend on 53BP1. Moreover, 53BP1-deficient mice support normal V(D)J recombination, indicating that 53BP1 is not required for “classic” nonhomologous end joining. However, class switch recombination is severely impaired in the absence of 53BP1, suggesting that 53BP1 facilitates DNA end joining in a way that is not required or redundant for the efficient closing of RAG-induced strand breaks. These findings are similar to those observed in mice or cells deficient in the tumor suppressors ATM and H2AX, further suggesting that the functions of ATM, H2AX, and 53BP1 are closely linked.
Response of AIDS-related plasmablastic lymphoma (PBL) to bortezomib

e19562 PBL are a group of highly aggressive neoplasms originally described in the oral cavity and jaws of HIV-infected patients. An AIDS-defining illness, PBL comprises 2.6% of AIDS-related lymphom...
COMPARISON OF SURFACE AND SUBSURFACE APPLICATION OF AN EXPERIMENTAL INSECTICIDE FOR THE CONTROL OF MOLE CRICKET NYMPHS IN TURF, 1998

COMPARISON OF SURFACE AND SUBSURFACE APPLICATION OF AN EXPERIMENTAL INSECTICIDE FOR THE CONTROL OF MOLE CRICKET NYMPHS IN TURF, 1998: A field efficacy trial was performed to evaluate rate and application placement of an experimental insecticide (CGA-293343) for the control of mole cricket nymphs. Plots 16 ft x 85 ft were established on a heavily infested bermudagrass driving range at Oyster Bay Golf Links near Sunset Beach in Brunswick Co., NC. Treatments were replicated four times and randomly assigned to the plots. The timing of application was targeted to coincide with peak hatch for the control of small nymphs. Two of the treatments (Dursban Pro 2E, subsurface appliedand surface-applied Merit 75 WP) were applied on 25 Jun. All subsurface treatments were applied using a tractor-drawn ToroR Subsurface Liquid Injector delivering a volume of 150 gpa of liquid insecticide mixture at 150 psi. All broadcast applications were applied using a John Deere Turf Gator-mounted research sprayer delivering 23 gpa. The fairway irrigation system was used to apply 0.25 inch of water to the entire test site immediately after application. All other treatments (CGA-293343 25WG) were applied on 28 Jun. Soapy water flush sampling of the test site indicated that the population was approximately 79% MC and 21% TMC. The first evaluation of the plots on 14 Jul involved flushing three separate one m2 previously damaged areas of each plot with soapy water and counting the number of nymphs that came to the surface. The average number of nymphs found in each plot is reported in the Table. Plots were evaluated for fresh damage on 21 Jul, and 5, 20 Aug using a 1 m2 grid. The grid, divided into nine subsections, was placed randomly in each plot and a damage rating (0-9) was given depending on the number of subsections in which fresh damage was observed (with 0 = no damage and 9 = severe damage). Ten damage ratings were taken in each plot on each sampling date. Actual damage means are presented in the Table. All data were transformed (check)X + 0.5 prior to ANOVA and Tukey's Studentized Range Test (HSD).
A MELUS Interview: Ishmael Reed

Recently, the International Writer's Workshop at The University of Iowa sponsored a program of events with the highly acclaimed poet and novelist Ishmael Reed. I was asked by The Iowa Journal of Literary Studies if I would arrange for an interview with Reed. However, by the time the editor had contacted me to do the interview, Reed's itinerary had already been planned. He was whisked from one engagement to the next meeting with student groups and organizations, being interviewed in a University radio interview, attending Workshop classes, a sponsored dinner, and student classes, meeting with Workshop faculty, presenting a public lecture, signing books at one of our local bookstores. Having persevered in my attempts to set up a meeting, I managed to take Reed back to our Cedar Rapids Airport, where I was able to conduct the interview.
Anion-Dependent Stimulation of CYP3A4 Monooxygenase

We co-crystallized human cytochrome P450 3A4 (CYP3A4) with progesterone (PRG) under two different conditions, but the resulting complexes contained only one PRG molecule bound to the previously identified peripheral site. A novel feature in one of our structures is a citrate ion, originating from the crystallization solution. The citrate-binding site is located in an area where the N-terminus splits from the protein core and, thus, is suitable for the interaction with the anionic phospholipids of the microsomal membrane. We investigated how citrate affects the function of a soluble CYP3A4 monooxygenase system consisting of equimolar amounts of CYP3A4 and cytochrome P450 reductase (CPR). Citrate was found to affect the properties of both redox partners and stimulated their catalytic activities in a concentration-dependent manner via a complex mechanism. CYP3A4-substrate binding, reduction of CPR with NADPH, and interflavin and interprotein electron transfer were identified as citrate-sensitive steps. Comparative analysis of various negatively charged organic compounds indicated that, in addition to alterations caused by changes in ionic strength, anions modulate the properties of CYP3A4 and CPR through specific anion-protein interactions. Our results help to better understand previous observations and provide new mechanistic insights into CYP3A4 function.
Influence of excessive dietary protein intake during late gestation on drylot beef cow performance and progeny growth, carcass characteristics, and plasma glucose and insulin concentrations

Spring-calving cows ( = 49) were used to investigate the effects of excessive prepartum dietary protein intake on late gestation cow performance as well as subsequent progeny growth, carcass characteristics, and plasma glucose and insulin concentrations. Treatments were formulated to be isocaloric and provide 100% (REQ) or 129% (HP) of CP requirement. Treatments were limit-fed 78 ± 12 d prepartum to calving. All cows were fed a common diet postpartum. Cow BW and BCS were recorded at initiation of treatments and within 48 h post-calving. Milk production was estimated via the weigh-suckle-weigh technique 69 ± 11 d postpartum. Calf BW was measured at birth and at weaning (121 ± 11 d of age). Progeny ( = 42) were weaned as a group and placed into a feedlot and fed a common finishing diet. Glucose and insulin concentrations were analyzed on a subset of progeny (12 per treatment) 90, 120, 150, 180, 210, and 240 min post-feeding, 2 d before slaughter (342 ± 11 d of age). Treatment had no effect ( ≥ 0.22) on cow BW, BCS, milk production, and subsequent reproduction or progeny preweaning growth. Progeny finishing growth and marbling scores were not affected ( ≥ 0.24) by treatment, yet 12th rib fat thickness ( < 0.01), KPH ( = 0.04), and YG ( = 0.01) were greater for progeny born to HP dams. Progeny born to HP dams had decreased ( ≤ 0.01) glucose and insulin concentrations, and insulin to glucose ratios, indicating greater insulin sensitivity. Although feeding cows 129% of CP requirement during late gestation did not affect cow performance or progeny preweaning or finishing period growth; carcass adiposity was increased by maternal treatment.
Role and mechanisms of regulation of the basolateral Kir4.1/Kir5.1K+ channels in the distal tubules

Epithelial K+ channels are essential for maintaining electrolyte and fluid homeostasis in the kidney. It is recognized that basolateral inward-rectifying K+ (Kir ) channels play an important role in the control of resting membrane potential and transepithelial voltage, thereby modulating water and electrolyte transport in the distal part of nephron and collecting duct. Monomeric Kir 4.1 (encoded by Kcnj10 gene) and heteromeric Kir 4.1/Kir 5.1 (Kir 4.1 together with Kir 5.1 (Kcnj16)) channels are abundantly expressed at the basolateral membranes of the distal convoluted tubule and the cortical collecting duct cells. Loss-of-function mutations in KCNJ10 cause EAST/SeSAME tubulopathy in humans associated with salt wasting, hypomagnesaemia, metabolic alkalosis and hypokalaemia. In contrast, mice lacking Kir 5.1 have severe renal phenotype that, apart from hypokalaemia, is the opposite of the phenotype seen in EAST/SeSAME syndrome. Experimental advances using genetic animal models provided critical insights into the physiological role of these channels in electrolyte homeostasis and the control of kidney function. Here, we discuss current knowledge about K+ channels at the basolateral membrane of the distal tubules with specific focus on the homomeric Kir 4.1 and heteromeric Kir 4.1/Kir 5.1 channels. Recently identified molecular mechanisms regulating expression and activity of these channels, such as cell acidification, dopamine, insulin and insulin-like growth factor-1, Src family protein tyrosine kinases, as well as the role of these channels in NCC-mediated transport in the distal convoluted tubules, are also described.
fMRI exploration of pedagogical benefits of repeated testing: when more is not always better

Introduction The testing effect refers to superior retention when study is followed by a test rather than followed by another study. Most research to date on why the testing effect occurs has been behavioral, but we employed neuroimaging methods in this study in order to shed light on the underlying processes. Methods Subjects were scanned while studying, restudying, and taking cued-recall tests of word pairs (with no feedback). We analyzed the BOLD responses by back sorting the encoding and test trials based on whether the subsequent test was correct or incorrect. We compared the subsequent memory patterns in initial study, restudy, and test trials. Results Overall, brain activity during test trials was a better predictor of later performance than brain activity during restudy trials. For test trials, we separately examined brain regions associated with the retrieval attempt process during successful retrieval and regions associated with the re-encoding process during retrieval in terms of prediction of subsequent memory. Regions associated with retrieval attempts were found to always predict subsequent memory success (the greater the activation, the more likely the correct recall); however, the regions associated with re-encoding would sometimes predict subsequent failure, specifically when subjects had correctly recalled the associated word several times already. Conclusions These results suggest that whether a testing effect advantage is observed depends on both on the retrieval process and the re-encoding process which follows that retrieval.
A counseling strategy was better than usual care for adopting and maintaining physical activity in type 2 diabetes.

Source Citation Di Loreto C, Fanelli C, Lucidi P, et al. Validation of a counseling strategy to promote the adoption and the maintenance of physical activity by type 2 diabetic subjects. Diabetes C...
Clofazimine biocrystal accumulation in macrophages upregulates interleukin 1 receptor antagonist production to induce a systemic anti-inflammatory state

Clofazimine (CFZ) is a poorly soluble antibiotic and anti-inflammatory drug indicated for the treatment of leprosy. In spite of its therapeutic value, CFZ therapy is accompanied by the formation of drug biocrystals that accumulate within resident tissue macrophages, without obvious toxicological manifestations. Therefore, to specifically elucidate the off-target consequences of drug bioaccumulation in macrophages, we compared the level of inflammasome activation in CFZ-accumulating organs (spleen, liver and lung) in mice after 2 and 8 weeks of CFZ treatment when the drug exists in soluble and insoluble (biocrystalline) forms, respectively. Surprisingly, the results showed a drastic reduction in caspase 1 and interleukin-1β (IL-1β) cleavage in the livers of mice treated with CFZ for 8 weeks (8-week-CFZ-treated mice) compared to 2-week-CFZ-treated and control mice, which was accompanied by a 3-fold increase in hepatic IL-1 receptor antagonist (IL-1RA) production and a 21-fold increase in serum IL-1RA levels. In the lung and spleen, IL-1β cleavage and tumor necrosis factor alpha expression were unaffected by soluble or biocrystal CFZ forms. Functionally, there was a drastic reduction of carrageenan- and lipopolysaccharide-induced inflammation in the footpads and lungs, respectively, of 8-week-CFZ-treated mice. This immunomodulatory activity of CFZ biocrystal accumulation was attributable to the upregulation of IL-1RA, since CFZ accumulation had minimal effect in IL-1RA knockout mice or 2-week-CFZ-treated mice. In conclusion, CFZ accumulation and biocrystal formation in resident tissue macrophages profoundly altered the host's immune system and prompted an IL-1RA-dependent, systemic anti-inflammatory response.
Gas-Hungry Sc Spirals

The various interactions between galaxies that have been the principal theme of this conference would be much too infrequent if they had to rely solely on the accidental passages of truly independent travelers in the vastness of space. Fortunately, we know now that there is a lot more to interacting galaxies than this charming old notion of “grand ships passing in the night”. Our ships seem to collide or suffer alarmingly close scrapes at their observed sizable rates mainly because they never quite managed to escape from each other amidst the great flying-apart known as the Hubble flow. Their own gravities and especially those from any associated dark matter seem to have been more than enough to overcome or “close” this flow in the vicinities referred to as pairs, groups or clusters — and in the likely graveyards that are elliptical in shape, slow in rotation, and de Vaucouleurs’ in profile. In short, it has been recognized more and more in recent years that our story of interacting galaxies must be primarily one of fallback, with greatly increased collision risks that would worry even Lloyd’s.
Expanding and tracking the capabilities of pesticide multiresidue methodology used in the Food and Drug Administration's pesticide monitoring programs.

Foods analyzed for pesticide residues in the monitoring programs of the U.S. Food and Drug Administration (FDA) are most often examined by using one or more of the multiresidue methods developed for this purpose over the years. Because no single method can be used for all potential residues, each commodity is examined by a method or methods which will identify and/or determine the chemicals most likely to have been used. FDA conducts research to develop new multiresidue methods, which are included in monitoring programs as needed to cover additional chemicals. FDA's multiresidue methods have undergone continuous study over a 20 year period to ascertain which compounds can and cannot be recovered by them. FDA continues to perform tests to discover a compound's analytical characteristics. Protocols have been published to direct the testing of additional compounds so that new information can be added to the existing compilations. Methods capable of determining residues of single pesticides are used to analyze selected commodities for residues of high priority that cannot be determined by existing multiresidue methods. Pestrak, a computerized listing of pesticide analytical information, has been developed by FDA to keep track of the capabilities of multiresidue methods and the coverage of residues by the single residue methods used in FDA monitoring.