cssi/SciSciGPT-SciSciNet huggingface dataset:
The formation and development of individual and ethnic identity: insights from psychiatry and psychoanalytic theory.

This paper describes the concept of identity formation, examining the historical development of identity, particularly ethnic identity. The author distinguishes the normative developmental achievement of self and group identity with pathological identity diffusion due to an earlier attachment disorder. The clinical case of a young male’s experience of his Persian family’s immigration to a new host country details the challenges encountered in ethnic identity formation and its interference in consolidating this ongoing process. The complicated task of self identity formation during this phase of development in the face of parental unresolved and ambivalent attitudes toward their own sense of threatened self and group identity diffusion is discussed. Parental intrapsychic conflict combined with environmental conflict such as racism, prejudice, and more recent paranoia toward Middle Eastern immigrant families interferes further with the normal identity formation process. The paper elaborates the compromised bicultural identity of a youngster who struggles through his developmental life phases.
Experience with Euthanasia Is Associated with Fearlessness about Death in Veterinary Students.

Veterinarians have an increased risk for suicide compared with the general population, yet there is little consensus regarding why this might be. We hypothesized that veterinarians become relatively fearless about death due to their repeated exposure to euthanasia. Accordingly, we predicted that there would be a positive relationship between experience with euthanasia and fearlessness about death, due to emotional habituation to the process of euthanasia. In a sample of 130 veterinary students, results conformed to expectation and indicated that the relationship with fearlessness about death was specific to euthanasia and did not generalize to experience with surgery or necropsy.
Epigenetic gene regulation in the adult mammalian brain: multiple roles in memory formation.

Brain-derived neurotrophic factor (bdnf) is one of numerous gene products necessary for long-term memory formation and dysregulation of bdnf has been implicated in the pathogenesis of cognitive and mental disorders. Recent work indicates that epigenetic-regulatory mechanisms including the markings of histone proteins and associated DNA remain labile throughout the life-span and represent an attractive molecular process contributing to gene regulation in the brain. In this review, important information will be discussed on epigenetics as a set of newly identified dynamic transcriptional mechanisms serving to regulate gene expression changes in the adult brain with particular emphasis on bdnf transcriptional readout in learning and memory formation. This review will also highlight evidence for the role of epigenetics in aberrant bdnf gene regulation in the pathogenesis of cognitive dysfunction associated with seizure disorders, Rett syndrome, Schizophrenia, and Alzheimer’s disease. Such research offers novel concepts for understanding epigenetic transcriptional mechanisms subserving adult cognition and mental health, and furthermore promises novel avenues for therapeutic approach in the clinic.
HERCULES: A Pattern Driven Code Transformation System

New parallel computers are emerging, but developing efficient scientific code for them remains difficult. A scientist must manage not only the science-domain complexity but also the performance-optimization complexity. HERCULES is a code transformation system designed to help the scientist to separate the two concerns, which improves code maintenance, and facilitates performance optimization. The system combines three technologies, code patterns, transformation scripts and compiler plugins, to provide the scientist with an environment to quickly implement code transformations that suit his needs. Unlike existing code optimization tools, HERCULES is unique in its focus on user-level accessibility. In this paper we discuss the design, implementation and an initial evaluation of HERCULES.
GnRH Increases c-Fos Half-Life Contributing to Higher FSHβ Induction

GnRH is a potent hypothalamic regulator of gonadotropin hormones, LH and FSH, which are both expressed within the pituitary gonadotrope and are necessary for the stimulation of gametogenesis and steroidogenesis in the gonads. Differential regulation of LH and FSH, which is essential for reproductive fitness, is achieved, in part, through the varying of GnRH pulse frequency. However, the mechanism controlling the increase in FSH during the periods of low GnRH has not been elucidated. Here, we uncover another level of regulation by GnRH that contributes to differential expression of the gonadotropins and may play an important role for the generation of the secondary rise of FSH that stimulates folliculogenesis. GnRH stimulates LHβ and FSHβ subunit transcription via induction of the immediate early genes, Egr1 and c-Fos, respectively. Here, we determined that GnRH induces rapidly both Egr1 and c-Fos, but specifically decreases the rate of c-Fos degradation. In particular, GnRH modulates the rate of c-Fos protein turnover by inducing c-Fos phosphorylation through the ERK1/2 pathway. This extends the half-life of c-Fos, which is normally rapidly degraded. Confirming the role of phosphorylation in promoting increased protein activity, we show that a c-Fos mutant that cannot be phosphorylated by GnRH induces lower expression of the FHSβ promoter than wild-type c-Fos. Our studies expand upon the role of GnRH in the regulation of gonadotropin gene expression by highlighting the role of c-Fos posttranslational modification that may cause higher levels of FSH during the time of low GnRH pulse frequency to stimulate follicular growth.
Effect of orphanin FQ/nociceptin (OFQ/N) and isoflurane on the prolactin secretory response in OFQ/N knockout mice

The prolactin secretory response to subcutaneous injection of orphanin FQ/nociceptin (OFQ/N) was measured in wild-type and OFQ/N knockout mice. These injections were given with and without isoflurane anesthesia, to determine if isoflurane would affect the prolactin secretory response. OFQ/N injection significantly increased prolactin levels in males and females, regardless of genotype, with a more robust response in females. Isoflurane pretreatment did not affect prolactin levels in controls or in animals injected with OFQ/N. This is the first report that exogenously administered OFQ/N stimulates prolactin secretion in mice and that brief isoflurane exposure does not significantly affect this response.
Enhanced ductility in an aluminum-4 Pct magnesium alloy at elevated temperature

A considerable enhancement of the tensile ductility in a commercial Al-4 pct Mg alloy is observed during deformation at elevated temperatures (up to 250°C) and slow strain rates. Total elongations of ∼175 pct at 250°C were obtained compared to 27 pct at ambient temperature. Much of this ductility was a result of large increases with temperature in the post uniform or diffuse necking strain. Measurements of strain rate sensitivity,m, as a function of strain, strain rate, and temperature showed thatm near fracture was linearly related to total elongation. The mechanisms controllingm in this Al-4 pct Mg alloy were dynamic strain aging at the lower temperature range and dynamic recovery at the higher temperatures.m was found to be a function of strain only when the relative fraction of dynamic recovery was greater than ∼35 pct. A comparison ofm as measured in pure aluminum and in the commercial Al-4 pct Mg alloy suggests that Mg additions can significantly increasem during dynamic recovery.
Drive Voltage Reduction of a GaAs Quantum Well Electroabsorption Waveguide Modulator Obtained with a Displaced p-n Junction

Quantum well lasers and modulators are key components of optoelectronic integrated circuits, and the ability to use a laser heterostructure as a modulator simplifies the fabrication process. 1. Since the laser requires only low positive bias voltages which draw appreciable current, designing a modulator to operate with only low negative bias voltages can simplifj. the system design.
Specific fears as predictors of generalized anxiety

Three hundred thirty-seven female undergraduates completed the Trait Form of the State-Trait Anxiety Inventory (STAI) and the Fear Survey Schedule-II (FSS) to determine if any specific fear factor was significantly related to STAI score. All fear factor scores and the total FSS-II score were significantly correlated with the STAI score and with each other. A stepwise regression procedure indicated that Factor 1, Fear of Social Interaction, accounted for 25.2% of the variance in STAI scores (p <.001), while Factor 4, of Negative Social Evaluation, accounted for an additional 1.8% of the variance (p <.01). The implications for theory, assessment, and intervention are discussed.
Antropologia no campo da saúde global

Neste artigo, eu exploro os limites de abordagens baseadas em balas magicas para os problemas de saude global e mostro como as iniciativas centradas nas pessoas desafiam as ortodoxias economicas e dos direitos humanos e ampliam nossa percepcao daquilo que e socialmente possivel e desejavel. Utilizo o meu estudo etnografico de longo prazo sobre a resposta terapeutica brasileira ao HIV/AIDS e suas repercussoes nos âmbitos de governo, mercados, sistemas de saude e vida pessoal. Faco tambem o relato de um novo projeto comparativo sobre as consequencias de grandes intervencoes farmaceuticas em contextos com recursos limitados. Considerando tanto os processos mais amplos quanto as singularidades humanas, o artigo abre uma janela critica para os valores e os resultados de intervencoes farmaceuticas e humanitarias contemporâneas na vida real. Ao criticar as praticas institucionais de producao de evidencia, tambem reconsidero as nocoes de responsabilidade e cuidado dentro da antropologia e da medicina.
Clearing a Frequency Subband for Enhanced Aeronautical Communications

The Federal Aviation Administration (FAA) is exploring the feasibility of clearing part of the 117.975-137 MHz air/ground (A/G) radio band for use by a VHF digital aeronautical data communications network beginning in the 2010-2015 time frame. The cleared subband would be taken from the 13.4 MHz of spectrum currently allocated to air traffic services (ATS) that use the present-day analog A/G voice radio system. The growing spectral congestion in the band makes it a challenge to clear any part of it for the future aeronautical data network without adversely affecting the existing A/G voice system. In this paper we analyze key issues that would arise when clearing a subband in conjunction with a transition to a new A/G voice system architecture, in which many users would operate in 8.33-kHz channels rather than the 25-kHz channels used today. Our analysis examines the tradeoffs among the amount of spectrum cleared, the effort involved in clearing it, and the impact on the remaining capacity of the A/G voice ATS system. We establish bounds on the amounts of ATS spectrum likely to be clearable in a wide variety of scenarios, and recommend measures for approaching those bounds while controlling implementation complexity and preserving enough voice spectrum to accommodate anticipated future growth of ATS demand.
Generalizing Fisher's "reproductive value": "Incipient" and "penultimate" reproductive-value functions when environment limits growth; linear approximants for nonlinear Mendelian mating models.

Abstract In the usual Darwinian case in which struggle for existence leads to density limitations on the environment's carrying capacity, R. A. Fisher's reproductive-value concept reduces to zero for every initial age group. To salvage some meaning for Fisher's notion, two variant reproductive-value concepts are defined here: an “incipient reproductive-value function,” applicable to a system's early dilute stage when density effects are still ignorable; and a “second-order penultimate reproductive-value function,” linking to a system's initial conditions near equilibrium its much later small deviations from carrying-capacity equilibrium. Also, slowly changing age-structured mortality and fertility parameters of Lotka and Mendelian mating systems are shown to suggest linear reproductive-value surrogates that provide approximations for truly nonlinear diploid and haploid models.
Mass spectrometric differentiation of linear peptides composed of L-amino acids from isomers containing one D-amino acid residue.

MS/MS of electrosprayed ions is shown to have the capacity to discriminate between peptides that differ by configuration about their α-carbons. It is not necessary for the peptides to possess tertiary structures that are affected by stereochemistry, since five epimers of the pentapeptide, H2N-Gly-Leu-Ser-Phe-Ala-OH (GLSFA) all display different collisionally activated dissociation (CAD) patterns of their protonated parent ions. The figure of merit, r, is a ratio of ratios of fragment ion abundances between stereoisomers, where r = 1 corresponds to no stereochemical effect. Values of r as high as 3.8 are seen for diastereomer pairs. Stereochemical effects are also seen for the diprotonated dodecapeptide H2N-Leu-Val-Phe-Phe-Ala-Glu-Asp-Val-Gly-Ser-Asn-Lys-OH (LVFFAEDVGSNK), a tryptic fragment from the amyloid β-protein. Triply charged complexes of the protonated dodecapeptide with cobalt(II) ions undergo CAD at lower collision energies than do doubly protonated LVFFAEDVGSNK ions. Statistically significant (...
Generating pictorial storylines via minimum-weight connected dominating set approximation in multi-view graphs

This paper introduces a novel framework for generating pictorial storylines for given topics from text and image data on the Internet. Unlike traditional text summarization and timeline generation systems, the proposed framework combines text and image analysis and delivers a storyline containing textual, pictorial, and structural information to provide a sketch of the topic evolution. A key idea in the framework is the use of an approximate solution for the dominating set problem. Given a collection of topic-related objects consisting of images and their text descriptions, a weighted multi-view graph is first constructed to capture the contextual and temporal relationships among these objects. Then the objects are selected by solving the minimum-weighted connected dominating set problem defined on this graph. Comprehensive experiments on real-world data sets demonstrate the effectiveness of the proposed framework.
Indirect rotator graph networks

The indirect rotator graph networks are proposed. The proposed networks are the indirect networks obtained by unfolding the rotator graphs, which are the indirect rotator graph network (IRGN) and the enhanced indirect rotator graph network (EIRGN). The authors show that the indirect network based on the rotator graph performs better than the indirect network based on the star graph in terms of having a reduced number of a switch stages. After proposing the IRGNs, the authors introduce the fault tolerant indirect rotator graph network (FT-IRGN) for use in large scale parallel and distributed systems constructed from the IRGN by adding extra stages, the indirect rotator graph network with (2/spl times/2) switches called the IRGN-2/spl times/2 that is modular and is constructed from (2/spl times/2) crossbar switches, and the ATM switch fabrics based on the IRGN with the various forms.
Is Runx a linchpin for developmental signaling in metazoans

The Runt domain (Runx) is a 128 amino acid sequence motif that defines a metazoan family of sequence-specific DNA binding proteins, which appears to have originated in concert with the intercellular signaling systems that coordinate multicellular development in animals. In the model organisms where they have been studied (fruit fly, mouse, sea urchin, and nematode) Runx genes are essential for normal development, and in humans they are causally associated with a variety of cancers, manifesting both oncogenic and tumor suppressive attributes. During development Runx proteins support both cell proliferation and differentiation, and function in both transcriptional activation and repression. Runx function is thus context-dependent, with the context provided genetically by cis-regulatory sequence architecture and epigenetically by development. This context dependency makes it difficult to formulate reductionistic generalizations concerning Runx function in normal and carcinogenic development. However, a growing body of literature links Runx function to each of the major intercellular signaling systems in animals, suggesting that the general function of Runx transcription factors may be to potentiate and govern genomic responsiveness to developmental signaling.
Board certification in internal medicine and cardiology: Historical success and future challenges

Board certification is at a critical juncture. As physicians face increased regulation and pressures from both inside and outside the profession, board certification and Maintenance of Certification (MOC) are coming under increased scrutiny from the public and the medical community. At this challenging time, it is important to remind ourselves what board certification is (and what it is not) and revisit the origins of this tangible expression of professional self-regulation, even as we contemplate how it needs to improve. Board certification has evolved over time and must continue to evolve; it is our collective responsibility as physicians that peer-developed standards meet the needs of both the profession and the public. In this article, we will reflect on the history of the American Board of Internal Medicine (ABIM), especially which related to Cardiology, and describe some of ABIM׳s challenges and new directions.
On Crossing Numbers of Complete Tripartite and Balanced Complete Multipartite Graphs

The crossing number cr(G) of a graph G is the minimum number of crossings in a nondegenerate planar drawing of G. The rectilinear crossing number cr(G) of G is the minimum number of crossings in a rectilinear nondegenerate planar drawing (with edges as straight line segments) of G. Zarankiewicz proved in 1952 that cr(Kn1;n2 ) Z(n1;n2) := n1 2 n1 1 2 n2 2 n2 1 2 . We dene an analogous bound for the complete tripartite graph Kn1;n2;n3 ,
Hierarchical description of deformation in block copolymer TPEs

We report on the deformation behavior of commercially relevant lamellar and cylindrical tri-block copolymers poly (styrene-b-ethylene-co-butylene-b-styrene) (SEBS) with two different compositions. The structural changes that occur at various length scales have been studied using a simultaneous small- and wide-angle X-ray scattering (SAXS/WAXS) during uni-axial tensile deformation of the polygrain samples. SAXS provides information about changes that occur upon deforming the glassy cylindrical or lamellar PS domains. WAXS, on the other hand, is sensitive to the crystallographic structure of the rubbery mid-block. Deformation calorimetry has been used to determine the energetics involved. The combined results from the various techniques indicate that the deformation takes place in three stages. First, at small strains, dilation occurs in the rubbery phase. At intermediate strains, the hard lamellar or cylindrical domains undergo micro-buckling, which is associated with a downturn in the stress–strain curve. Finally, we interpret that at higher strains, the bent lamellar/cylindrical domains rotate in the stretching direction resulting in a significant shear on the rubbery mid-block. This in turn leads to strain-induced crystallization in these materials. Although we could not prove it by WAXS, deformation calorimetry (which is more sensitive than the WAXS) was utilized to show its presence.
Voltage flicker mitigation using PWM-based distribution STATCOM

Voltage flicker, a phenomenon of annoying fight intensity fluctuation, caused by large rapid industrial load changes, has been a major concern for both power companies and customers in the area of power quality. The fast response of the distribution static compensator (DSTATCOM) makes it the efficient solution for improving power quality in distribution systems. In this paper, a voltage flicker phenomena in a 69/13.8 kV distribution system Is modeled and simulated using MATLAB/Simulink Power System Blockset (PSB). Voltage flicker mitigation studies with a current controlled PWM-based DSTATCOM are also performed and discussed.
A U.S.-China Grand Bargain? The Hard Choice between Military Competition and Accommodation

Despite the intense focus on China's rise, the United States has yet to confront the most challenging question posed by this power shift: Should it pursue a strategy of limited geopolitical accommo...
Color night vision: fusion of intensified visible and thermal IR imagery

We introduce an apparatus and methodology to support realtime color imaging for night operations. Registered imagery obtained in the visible through near IR band is combined with thermal IR imagery using principles of biological color vision. The visible imagery is obtained using a Gen III image intensifier tube optically coupled to a conventional CCD, while the thermal IR imagery is obtained using an uncooled thermal imaging array, the two fields of view being matched and imaged through a dichroic beam splitter. Remarkably realistic color renderings of night scenes are obtained, and examples are given in the paper. We also describe a compact integrated version of our system in the form of a color night vision device, in which the intensifier tube is replaced by a high resolution low-light sensitive CCD. Example CCD imagery obtained under starlight conditions is also shown. The system described here has the potential to support safe and efficient night flight, ground, sea and search & rescue operations, as well as night surveillance.
Prebiotic Chemistry and the Origin of the RNA World

The demonstration that ribosomal peptide synthesis is a ribozyme-catalyzed reaction makes it almost certain that there was once an RNA World. The central problem for origin-of-life studies, therefore, is to understand how a protein-free RNA World became established on the primitive Earth. We first review the literature on the prebiotic synthesis of the nucleotides, the nonenzymatic synthesis and copying of polynucleotides, and the selection of ribozyme catalysts of a kind that might have facilitated polynucleotide replication. This leads to a brief outline of the Molecular Biologists' Dream, an optimistic scenario for the origin of the RNA World. In the second part of the review we point out the many unresolved problems presented by the Molecular Biologists' Dream. This in turn leads to a discussion of genetic systems simpler than RNA that might have “invented” RNA. Finally, we review studies of prebiotic membrane formation.
An efficient synthetic route to stable bis(carbene)borylenes [(L1)(L2)BH]

Two-electron reduction of bis(carbene) boronium salts allows for the preparation of unsymmetrically substituted nucleophilic boron derivatives of type (L1)(L2)BH, which are characterized by X-ray crystallography. A single electron reduction of the same starting materials leads to the corresponding boron-centered radical cations (L1)(L2)BH˙+, X−.
Absorber intercooling in co2 absorption by piperazine-promoted potassium carbonate

Intercooling was evaluated as a process option in CO2 absorption by piperazine (PZ) promoted potassium carbonate. The system performance with 4.5 m K+/4.5 m PZ was simulated by a model in Aspen Plus® RateSep™. The absorber was evaluated for use with a double matrix stripper by optimizing the position of the semilean feed and intercooling stages to maximize CO2 removal. Additionally, a simple absorber system was modeled to observe the effect of intercooling on systems with variable CO2 lean loading. Intercooling increases CO2 removal by as much as 10% with the double matrix configuration. With a simple absorber, the effectiveness of intercooling depends on solvent rate. Near a critical liquid/gas ratio (L/G) there is a large improvement with intercooling. This is related to the position of the temperature bulge. An approximation is proposed to estimate the critical L/G where intercooling may maximize removal. © 2009 American Institute of Chemical Engineers AIChE J, 2010
B#: a battery emulator and power profiling instrument

This paper describes B# (B-sharp), a programmable power supply that emulates the behavior of a battery. It measures the current load, calls a battery simulation program to compute the voltage in real time, and controls a linear regulator to mimic the voltage output of a battery. This instrument enables validation of battery-aware power-optimization techniques with accurate, controllable, reproducible results. This instrument also supports training mode with actual batteries, and it can even be used for recording and playback of a solar power source. This design has been prototyped and tested on hand-held devices with high accuracy and fast response time.
Epitope Escape Mutation and Decay of Human Immunodeficiency Virus Type 1-Specific CTL Responses

To investigate possible mechanisms behind HIV-1 escape from CTL, we performed detailed longitudinal analysis of Gag (SLYNTVATL)- and RT (ILKEPVHGV)-specific CTL responses and plasma epitope sequences in five individuals. Among those with CTL against consensus epitope sequences, epitope mutations developed over several years, invariably followed by decay of the CTL targeting the consensus epitopes. The maturation state of the CTL varied among individuals and appeared to affect the rate of epitope mutation and CTL decay, despite similar IFN-gamma production. Escape mutations were oligoclonal, suggesting fitness constraints. The timing of escape indicated that the net selective advantage of escape mutants was slight, further underscoring the importance of understanding factors determining selective pressure and viral fitness in vivo. Our data show surprisingly consistent decay of CTL responses after epitope escape mutation and provide insight into potential mechanisms for both immune failure and shifting CTL specificities.
Absolute Oscillator Strengths for the Iron Group : a Correction to the data of Warner for the Second Spectra and a Comment on Some of the Semiempirical Results of Kurucz and Peytremann

It has already been shown that the Fe II absolute oscillator strengths (f-values) measured by Warner (1967) contain a systematic error, the magnitude of which depends on the energy of the transition's upper level. The present paper demonstrates that this error affects all of Warner's oscillator strengths for the second spectra of the iron group and develops a correction formula for Warner's results. A comparison of the corrected f-values with other measured f-values for Ti II, V II, and Fe II indicates that the correction improves the usefulness of Warner's data and that the corrected f-values have no large systematic dependence on wavelength, level energy, or line strength. Solar abundances for iron-group elements computed using the original and corrected f-values are compared with recently suggested abundances, and it is found that the corrected f-values yield more consistent results. Semiempirical oscillator strengths calculated by Kurucz and Peytremann (1975) for Fe I, Ti II, and V II are also compared with measured data to evaluate the accuracy of the calculations. It is found that the absolute scales of these results are roughly correct, but some of them are subject to very large errors.
Comstock, Originalism and the Necessary and proper Clause

Constitutional law is plagued by meaning conflict at both the doctrinal and the theoretical levels. This article takes up two loci of such conflict and contest of constitutional meaning - the Necessary and Proper Clause (recently visited by the Supreme Court in the Comstock case) and the reasonable person device in the New Originalism - so that insight might be gained from the mutual comparison and illumination of their problems. In this process, dialogue replaces just “looking for one’s friends” in constitutional argument as various voices are considered and not silenced so that a favored one may be privileged. The result of this reciprocal examination is a paired argument for a fiduciary, agency law model of the Necessary and Proper Clause and also for a Dialogic Originalism as a replacement for the currently fashionable reasonable person New Originalism.
Does Founder Exit Impact Venture Performance in New Ventures

The role of founder exit in shaping organizational outcomes is an interesting phenomenon that has attracted research interest in recent years. In the present study, we advance and test theory on the impact of founder exits from new venture teams on firm performance. While exits ease coordination problems in founding teams of new ventures, they also deprive the venture of critical resources needed for a venture's growth. We hypothesize and find that founder exits have an inverted-U shaped relationship with venture performance. The relationship between exits and performance varies by context and is attenuated when ownership is consolidated and accented when the venture pursues valuable opportunities and owners are actively engaged in management of the firm.
Militant Islam: A Sociology of Characteristics, Causes, and Consequences by Stephen Vertigans

Ultimately, Militant Islam: A Sociology of Characteristics, Causes, and Consequences identifies and underscores how far two areas of academic inquiry still remain from one another and the pressing need for their synthesis: our ability to understand the making of geopolitically-informed (and not just Western) discourses of political violence, change, and resistance, on the one hand, and the actual, often local sociological processes, structures, and contexts that help explain extremist organizations and the nature of their responses, on the other. Insofar as Militant Islam attempts to bring these research areas together, it has set the research agenda in this area for academics into the current decade – one that will, at its best, help us to understand new formations of political resistance showcased in the ‘Arab Spring’ and emerging paradigms for political stability.
Neutrophil oscillations: temporal and spatiotemporal aspects of cell behavior.

Neutrophil activation is an essential event in inflammatory responses. How cells coordinate, integrate, manage, and distribute information on physiologically-relevant timescales are not well understood. Although neutrophil oscillators have been known for many years, their biological roles have not been identified. We suggest that intracellular oscillators (such as NAD(P)H, pH, calcium, and so on) account for functional oscillations (e.g., superoxide and NO production, cytolytic marker release, pericellular proteolysis, and actin assembly). In addition to these well-known temporal oscillations, we have recently discovered self-organized traveling chemical waves in neutrophils; these waves respond to extracellular signals and have distinct origins that coincide with a cell's uropod, lamellipodium, or adherence site. The fundamental physico-chemical features of cell chemistry will have an increasing role in our understanding of leukocyte function.
TNF-α increases transcription of Gαi-2 in human airway smooth muscle cells

Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that has an important role in the regulation of airway smooth muscle tone and reactivity. We have shown previously that TNF-alpha upregulates the expression of Galpha(i-2) protein without significantly increasing G(s)alpha protein and enhances adenylyl cyclase inhibition by carbachol in cultured human airway smooth muscle cells (Hotta K, Emala CW, and Hirshman CA. Am J Physiol Lung Cell Mol Physiol 276: L405-L411, 1999). The present study was designed to investigate the molecular mechanisms by which TNF-alpha upregulates Galpha(i-2) protein in these cells. TNF-alpha pretreatment for 48 h increased the expression of Galpha(i-2) protein without significantly altering the Galpha(i-2) protein half-life (41.0 +/- 8.2 h for control and 46.8 +/- 5.2 h for TNF-alpha-treated cells). Inhibition of new protein synthesis by cycloheximide blocked the increase in Galpha(i-2) protein induced by TNF-alpha. Furthermore, TNF-alpha treatment for 12-24 h increased the steady-state level of Galpha(i-2) mRNA without significantly altering Galpha(i-2) mRNA half-life (9.0 +/- 0.75 h for control and 8.9 +/- 1.1 h for TNF-alpha-treated cells). The transcription inhibitor actinomycin D blocked the increase in Galpha(i-2) mRNA induced by TNF-alpha. These observations indicate that the increase in Galpha(i-2) protein induced by TNF-alpha is due to an increased rate of Galpha(i-2) protein synthesis, most likely as a consequence of the transcriptional increase in the steady-state levels of its mRNA.
Management of Atrial Fibrillation in Hypertrophic Cardiomyopathy

Case Presentation: A 38-year-old man with hypertrophic cardiomyopathy (HCM) was referred for management of intermittent palpitations and exertional dyspnea with routine activities despite escalated β-blocker therapy. His initial examination was notable for a regular pulse at 72 bpm and harsh systolic murmur that increased with the Valsalva maneuver. A 12-lead electrocardiography revealed sinus rhythm with increased QRS voltage, repolarization abnormalities, and a QTc of 430 milliseconds. Echocardiography was notable for severe asymmetrical hypertrophy (septal thickness, 22 mm), normal systolic function, severe outflow tract obstruction (70 mm Hg), and left atrial (LA) enlargement. A 24-hour Holter monitor detected 6 minutes of rapid atrial fibrillation (AF) that coincided with his palpitations. Therapy was recommended with warfarin to prevent stroke and with disopyramide to minimize outflow tract obstruction and frequency of AF. HCM, which affects 0.2% of the population, is an important cause of heart failure and is the leading cause of nonviolent sudden death in the young. Traditionally defined as left ventricular hypertrophy that develops in the absence of abnormal hemodynamics, it is caused by dominant mutations in sarcomere genes.1 Prevention of sudden death and management of left ventricular outflow tract obstruction (LVOTO) have been the primary focus of HCM clinical research and management since its original descriptions. However, AF is more prevalent than either sudden death or medically refractory obstruction and is the most common sustained arrhythmia in HCM.2 The combination of HCM and AF is associated with a markedly increased risk of stroke, overall mortality, and heart failure. This Clinician Update focuses on the epidemiology, pathophysiology, and clinical management of AF in patients with HCM. AF represents the most common sustained arrhythmia in both the general and HCM populations. In the general population, AF prevalence increases progressively with age and occurs predominantly in patients >60 years of age.3 …
MRI of Fetal Spine and Extremities

The primary imaging modality for routine examination of the fetal nervous system, including the spine and the fetal extremities, is ultrasonography (US). Magnetic resonance (MR) imaging with its multi-plantar imaging capability and high inherent signal to noise ratio is highly accurate in demonstrating the morphological changes of the developing fetal spine and extremities. Fetal MRI is a valuable adjunct to US and has the advantage of better depiction of associated CNS and non-CNS anomalies. Fetal MRI can provide information which can better assess postnatal outcome, especially neurological function, and quality of life and thus help the maternal-fetal medicine specialist and the parents to determine choices for management.
A Cautionary Tale About a Bridesmaid’s DRESS

A previously healthy 18-year-old girl with no significant medical history presented to her pediatrician in the summer with a sore throat and fatigue. Results of a rapid Streptococcus (strep) screening test and a mononucleosis spot test were both negative, and she was prescribed a 10-day course of amoxicillin for the pharyngitis. One week later, the patient returned with a diffuse rash consisting of small red macules and papules on her trunk, arms, and face, consistent with amoxicillin use in the setting of infectious mononucleosis (IM). Laboratory tests for Epstein-Barr virus (EBV) immunoglobulin G and immunoglobulin M returned positive, the amoxicillin was discontinued, and a 6-day course of prednisone was prescribed in an effort to help manage her symptoms. Ten days later, after completing the course of steroids, the patient visited a dermatologist for painful pustules that had developed on her legs and buttocks. Concerned about infection with methicillin-resistant Staphylococcus aureus (MRSA), her dermatologist cultured the pustules and prescribed topical mupirocin 2% cream and 100 mg twice daily of minocycline for the folliculitis while awaiting culture results (which later returned as methicillin-sensitive S aureus ). One week after the patient started the minocycline, she noticed a pruritic rash on her legs that spread to her trunk, arms, and face over the next few days. She subsequently developed a fever of 104°F with chills and fatigue; she visited the emergency department, where she was prescribed triamcinolone cream, hydroxyzine, and cetirizine and was discharged. The rash continued to worsen, and the patient developed swelling of her face, lips, neck, hands, and feet. …
Addressing Suicide Risk in Emergency Department Patients

In their Viewpoint, Dr Olfson and colleagues1 called for “enhanced training of emergency physicians in the management of suicidal patients and patients with deliberate self-harm” due to the “shortages of mental health specialists in emergency medical settings.” Studies show that 1 in 5 emergency department patients may be depressed, yet the diagnosis is often missed for a variety of reasons including that patients do not complain of depression but of somatic depression symptoms.2 Similarly, overt suicidal behavior accounts for 0.6% of emergency department visits but the incidental suicidal ideation that is found in 3% to 11.6% of visits is often missed.3 There are 130 million patient visits to emergency departments each year, so there is much room for improvement.4
IR testing of microwave circulator bonds

The results of an effort to determine if IR imaging methods can be used to assess adhesive bond quality in a microwave circulator are reported. The circulator to be tested was of a somewhat standard three-port design, consisting of an aluminum housing that sandwiched two triangular ferrite slabs separated by a dielectric between potted magnets. The adhesive bondlines of interest were those between the ferrite and the aluminum housing. A testing scheme was developed whereby the aluminum housing was heated in a controlled fashion while an IR camera was used to monitor the thermal response of both ferrite triangles. As expected, it was found that if both ferrite triangles were properly bonded, a similar thermal response was observed. However, if one of the triangles had a partial or cracked adhesive bond, it resulted in a measurable thermal response difference.
POSTER: KXRay: Introspecting the Kernel for Rootkit Timing Footprints

Kernel rootkits often hide associated malicious processes by altering reported task struct information to upper layers and applications such as ps and top. Virtualized settings offer a unique opportunity to mitigate this behavior using dynamic virtual machine introspection (VMI). For known kernels, VMI can be deployed to search for kernel objects and identify them by using unique data structure "signatures". In existing work, VMI-detected data structure signatures are based on values and structural features which must be (often exactly) present in memory snapshots taken, for accurate detection. This features a certain brittleness and rootkits can escape detection by simply temporarily "un-tangling" the corresponding structures when not running. Here we introduce a new paradigm, that defeats such behavior by training for and observing signatures of timing access patterns to any and all kernel-mapped data regions, including objects that are not directly linked in the "official" list of tasks. The use of timing information in training detection signatures renders the defenses resistant to attacks that try to evade detection by removing their corresponding malicious processes before scans. KXRay successfully detected processes hidden by four traditional rootkits.
Mmu-Mir-181a Regulates Terminal Erythroid Nuclear Maturation By Regulating Levels of Xpo7

Abstract Mammalian terminal erythroid differentiation involves cell cycle arrest, termination of transcription, and finally progressive chromatin condensation culminating in enucleation. The mechanisms underlying these final events are not completely understood. We have previously published that an erythroid-specific variant of the protein Exportin 7 (Xpo7) plays an important role in terminal erythroid nuclear maturation. Xpo7 is highly induced and highly abundant in late erythroblasts. Xpo7 knockdown in mouse erythroblasts inhibits the final stages of normal erythroid development such as chromatin condensation and enucleation without affecting such important processes as cell surface Ter119 acquisition or hemoglobin accumulation. Migration of nuclear proteins such as core histones into the cytoplasm during normal erythropoiesis is also inhibited by Xpo7 knockdown (1). In order to interrogate the function of Xpo7 in erythropoiesis, we next investigated Xpo7’s genomic structure and how it is regulated during mouse red blood cell development. Xpo7 exerts its effect on the erythroid nucleus after erythroblasts have left the cell cycle and transcription has ended so the timing of its induction must be tightly regulated. We have previously published that Xpo7 has an erythroid–specific start site and first exon (1). Using 5’ RACE, we determined that the erythroid variant of Xpo7 has a different 5’ UTR than the non-erythroid transcript. In contrast, the 3’ UTR is identical in both erythroid and non-erythroid transcripts, and contains a miR-181a binding site. MiR-181a has been previously shown to be abundant in hematopoietic stem cells and to regulate normal B-cell (2) and megakaryocyte development (3). However, in erythropoiesis, miR-181a decreases in expression just as Xpo7 increases, with lowest levels of miR-181a when Xpo7 is most abundant and presumably exerting its effect on erythroid nuclear maturation. Through luciferase reporter assay experiments, we have found that miR-181a directly binds the 3-UTR binding site of Xpo7. Moreover, miR-181a overexpression results in decreased Xpo7 transcript levels via qPCR and decreased enucleation via flow cytometry. Based on these results, we conclude that miR-181a regulates enucleation by repressing Xpo7 expression while the nucleus is active during terminal erythroid development. Our next step is to examine how miR-181a itself is downregulated during erythroid development, such as perhaps through the expression of a complementary long-noncoding RNA. 1. Hattangadi, SM, et. al. Histones to the cytosol: Exportin 7 plays an important role in terminal erythroid nuclear maturation. Blood 2014, in press. 2. Chen,CZ; Li, L; Lodish, HF; Bartel,DP. MicroRNAs modulate hematopoietic lineage differentiation. Science 2004; 303: 83–86 3. Li, X; Zhang J; Gao, L; McClellan, S; Finan, MA; Butler TW; Owen, BL; Piazza, GA; Xi, Y. MiR-181 mediates cell differentiation by interrupting the Lin28 and let-7 feedback circuit. Cell Death and Differentiation (2012) 19, 378–386. Disclosures No relevant conflicts of interest to declare.
Predictors of Liver Fibrosis in HCV+ Hemophilic Men.

Abstract Hepatitis C is a major cause of chronic liver disease in hemophilia. Liver biopsy is typically not performed in this population because of potential bleeding risk, and, thus, the proportion with liver fibrosis is not known. A number of laboratory tests, including AST, ALT, ALT/AST ratio, PT, platelet count and AST/platelet ratio (APRI) have been evaluated as surrogate tests for liver fibrosis in other HCV risk groups, but not in individuals with hemophilia. If laboratory tests could be validated as surrogate markers of fibrosis in the hemophilic population, it might be possible to predict the extent of their HCV liver disease. We, therefore, evaluated the above laboratory tests as potential surrogate markers of fibrosis in HCV (+) hemophilic men undergoing liver biopsy and enrolled in an ongoing prospective, cross-sectional multi-center NHLBI-funded study of hepatitis C in hemophilia (HHH Study). Liver biopsies were evaluated by independent, central review for fibrosis using the Ishak, Metavir, and Knodell classification systems. Statistical analyses were performed by Spearman rank correlation, logistic regression, and area under receiver operating characteristic curves (AUROC). Only significant predictors in univariate models were used in the final multivariate model. Of 301 enrolled subjects, 75 (24.9%) had undergone liver biopsy, of whom 53 (17.6%) with slides/blocks/tissue available for pathologic review, were analyzed. Of the 53, 24 (45.3%) had biopsy evidence of fibrosis by Ishak score ≥ 3 (F3–F6). Those with fibrosis (F3–F6) did not differ in proportion HIV (+) or in proportion treated with interferon/ribavirin, from those without fibrosis (F0–F2). As compared with the HIV(–) group (n= 26), the HIV(+) group (n=27) was older, 40 vs. 33 yr, and had higher AST, 64 vs. 40 IU/ml, higher APRI scores, 0.48 vs. 0.21, and lower platelet counts, 180,000/μl vs. 235,000/μl, all p 0.1. Although all three fibrosis scoring systems, Ishak, Metavir, Knodell showed good correlation with all lab markers studied, the Ishak system showed the best correlation. In the logistic regression model, the best predictor of Ishak fibrosis (F3–F6), was the AST/platelet ratio (APRI), p = 0.008. The APRI score was a better predictor of fibrosis (F3 –F6) in HIV (−) than among HIV (+) men, area under the receiver operating characteristics curve (AUROC), 88.9% vs. 66.1%, respectively. In the HIV (+) group, only the Knodell system showed good correlation with lab markers. In conclusion, APRI score is a potentially useful surrogate marker for fibrosis on liver biopsy in HIV (−) hemophilic men with hepatitis C, but less so in HIV (+) hemophilic men with hepatitis C. The reason for differences in the APRI score as a predictor of fibrosis between HIV(−) and HIV(+) is not known, but may suggest that AST and/or platelet count may be affected by HIV infection, rendering these parameters less specific and/or predictive for HCV liver fibrosis. It will be important to test this hypothesis in a large number of patients.
Fixing the Prevention Gap Using Imaging-Guided Risk Estimates.

For nearly 2 decades, coronary artery calcium (CAC) has been considered a vital component of screening programs, with abundant prognostic evidence supporting its utility for an accurate long-term prediction of all-cause mortality, stroke, coronary artery disease, and many other clinical outcomes [(1
Test Philosophies for the New Millennium

Current research at the Jet Propulsion Laboratory (JPL) is directed toward the optimization of future spacecraft testing. Force-limited vibration studies, conducted during several recent space vehicle programs, have been extremely successful in improving the quality and realism of hardware trials. Single versus triaxial vibration research is also in progress, with a similar objective of test realism enhancement. In addition, use of the Environmental Test Effectiveness Assessment (ETEA) process has helped to identify those tests which most effectively isolate hardware defects. In an effort to streamline the development of requirements, JPL has recently begun to establish a "2-sigma" generic environmental envelope. In the future, such an envelope could allow "off-the-shelf" hardware to be flown on a number of standard launch vehicles. In a related study, the Accurate, Cost Effective Qualification (ACEQ) program has been developed to correlate system requirements with failure modes, and then assess the effec...