cssi/SciSciGPT-SciSciNet huggingface dataset:
Determinants of Adoption of Cloud-based Accounting: A Paradigm Shift in Sri Lanka

Cloud-Based Accounting (CBA) transforms the accounting system into a sophisticated platform in a turbulent environment. Factors behind the adoption of the CBA are still scepticism. Therefore, the study mainly aims to examine perceived determinants of the adoption of Cloud-Based Accounting (CBA) in Sri Lanka. Human, technological, organisational, and environmental factors are used as independent variables for identifying the determinants of CBA. Data were collected from two hundred professional accountants by using a questionnaire. Descriptive statistics, correlation, and multiple regression were applied to analyse the collected data. The results show that the above four factors are at a high level, and they significantly and positively impact the adoption of CBA. The study provides insights into the policymakers to better understand and enable them to implement suitable strategies to minimise potential damaging factors and improve current trends in their development.
Family type and cognitive function in older Chinese Americans: acculturation as a moderator.

Acculturation to the mainstream culture and the settlement contexts could shape cognitive function of older immigrants. Guided by ecological theory, this study examines the interaction effect betwe...
Tierra de nadie, tierra de todos. Unidad y naturaleza en las figuras culturales de península Antártica y alrededores

This paper studies the history of the Antarctic territory disputed by Argentina, Chile, and the United Kingdom in the context of the processes that culminated in the recent “Edenic” resignification of the white continent: the attribution of positive cultural values to its condition of pristine space, the consequent withdrawal of commercial exploitation activities, the promotion of its preservation and the minimization of any impact. Being a “shared” place links its history to various processes of incorporation into collective imaginaries and national territories with different yearnings moving each country in the framework of actions, reactions, and territorial meanings this paper try to delve into. Regarding a morphological dimension, it is suggested that the wishes of each one was strengthened by integration projects, linked to international competition scenarios, and associated with notions of territorial unity, mostly catalysed by critical historic moments. Regarding its symbolic dimension, it is suggested that territorial cultural values depend on how Antarctic nature has been conceived in different visions of his future that were basically structured in two aspects. One of these is related to the understanding of its pristine status, perceived as a source of resources to extract or "Eden" to preserve. Another relates to those who should benefit from it, whether national, international, or global communities. These approaches allow delving into the different stages of the incorporation processes through architecture projects, infrastructure, geopolitical strategies, and cartographies or even novels and photographs. Trying to overcome the paradigm of a conceptual separation between transformations of the land and its representations, these are understood as “figures”, cultural manifestations and fragments of discourses underlying the incorporation dynamics: different kind of elements that can be transversally read through the notions of unity and meanings of nature they support.
Liability Attribution in the Context of AI Use

AI (artificial intelligence) systems represent a double-bladed sword. AI brings both benefits and harms to our society. When adverse consequences are produced by AI use in practice, responsibility ...
Effect of Varying Levels of Hempseed Meal Supplementation on Humoral and Cell-Mediated Immune Responses of Goats

The objective of this study was to evaluate the effect of varying levels of hempseed meal supplementation on antibody and cell-mediated immune responses, as well as the expression of some of the important immunoregulatory cytokines. Treatments consisted of hempseed meal supplementation at 0 (control), 10, 20, and 30% of the total diet. Goats were randomly assigned to one of the four treatments n = 10. Cell-mediated immune response was evaluated on day 59 of the feeding period by measuring skinfold thickness at 24 h following intradermal injection of phytohemagglutinin. A significant increase in skinfold thickness was observed with increasing levels of supplementation as compared to that of the control group. Serum antibody titers to chicken ovalbumin were not significantly different between treatment groups. Cytokine concentrations of IL-6 increased linearly with increasing level of supplementation (p < 0.05), contrarily to the linear decrease that was observed for TNF-α (p < 0.05). Although IL-2 tended to increase with the 10 and 30% levels of supplementation (p < 0.07), the result was not significant, and no significant differences were obtained with respect to IL-4 concentrations. Cytokine gene expression values measured by RT-PCR, however, demonstrated some significant differences. HSM supplementation had no significant effect on the expression of IL-2 or IL-6. However, significant differences were observed with the 30% supplementation for IL-4 and TNF-α as compared to that of the control group (p < 0.05). IL-4 was down regulated for the 10 and 20% treatment groups but was upregulated for the 30% treatment group. TNF-α was downregulated in the 10% but upregulated for the 20 and 30% treatment groups. No significant differences were observed for the serum cortisol concentration or white blood cell counts. These results suggested that hempseed meal supplementation may improve cell-mediated immune response while having no effect on antibody-mediated immune response. However, more research needs to be conducted to determine the most efficacious inclusion rate.
Chapter 3 Multiple pathways for signal transduction through the muscarinic cholinergic receptor

Publisher Summary This chapter describes the multiple pathways for signal transduction through the muscarinic cholinergic receptor (mAChR). There are three pharmacologically distinct mAChR subtypes, which appear to correspond to the receptors encoded by the M 1 , M 2 , and M 3 genes. The 1321N1 astrocytoma cell has muscarinic receptors that stimulate the cascade of responses typically associated with the actions of Ca 2+ -mobilizing hormones. The active isomer of InsP 3 is formed, Ca 2+ is released from intracellular stores, diacylglycerol is elevated, and protein base C is redistributed to the membrane. Two additional cellular responses are activated, apparently as a consequence of the activation of protein kinase C. First, mAChR stimulation increases the hydrolysis of phosphatidylcholine by a phospholipase D, resulting in the formation of choline and phosphatidic acid. The choline formed from phosphatidylcholine (PC) is important in ACh synthesis under certain conditions. The second consequence of protein kinase C (PKC) activation described in the chapter is an increase in c-fos mRNA. The possibility that the increase in c-fos serves as a “third messenger” for the induction of other gene products, particularly growth factors that may be secreted from astrocytes when they are stimulated, are examined.
Use of touch imprint cytology as a simple method to enrich tumor cells for molecular analysis.

BACKGROUND A relative excess of nonneoplastic cells in frozen carcinoma samples is often a cause of false-negative results in molecular assays. Given the greater cohesiveness of epithelial tumor cells compared with nonneoplastic epithelium and mesenchymal stroma, the authors hypothesized that tumor procurement by touch imprinting would provide a simple, cost-effective method of obtaining enriched neoplastic cells compared with frozen whole-tumor samples. METHODS Eleven adenocarcinomas with known KRAS gene mutations were tested. Two sets of 8 touch imprint (TP) slides and 1 frozen whole-tumor sample (FS), both with a corresponding hematoxylin and eosin-stained slide, were obtained from each tumor. DNA from unstained TP and FS samples was tested for KRAS exon 2 mutations by Sanger sequencing. The percentage of carcinoma cells was determined by light microscopy of hematoxylin and eosin-stained slides. The fold increase in the mutant-enriched DNA in TP versus FS samples was determined by calculating the height ratio between the mutant and wild-type peaks on the sequencing electropherogram. RESULTS Using light microscopy, TP demonstrated a 1.1-fold to 3.5-fold (mean, 1.8-fold) enrichment in neoplastic cells compared with the FS. The mutant–to–wild-type peak height ratio was 1.4-fold to 7.1-fold (mean, 3.1-fold) higher in TP compared with the corresponding FS samples. The average amount of extracted DNA ranged from 145 ng to 7.9 μg per TP slide. CONCLUSIONS The procurement of carcinoma samples by TP is rapid, simple, and inexpensive; consistently provides a tumor-enriched sample; is an excellent source of high-quality tumor DNA; and could compensate for the relatively low sensitivity of direct sequencing. Cancer (Cancer Cytopathol) 2013;121:354–360. © 2013 American Cancer Society.
Interactions between catecholamines and the amygdala in emotional memory: subclinical and clinical evidence.

Publisher Summary This chapter provides evidence to indicate that the amygdaloid complex (AC) has a particular role in brain memory mechanisms. It interacts with stress hormones released during and after emotional events to modulate memory for those events. The effect of endogenous stress hormones on memory follows a typical pattern. The chapter suggests that memory for emotionally arousing events requires activation of β-adrenergic receptors and the AC. The effect of β-adrenergic impairment has been examined on enhanced memory associated with emotional arousal in healthy humans. It has been found that the AC is involved in long-term, emotionally influenced, declarative memory in humans. The fact that both the β-adrenergic system and the AC are implicated in memory within a single experimental paradigm further argues for an interaction between the two in storing memory for emotional events. It has been also demonstrated that selective involvement of the amygdala in enhanced long-term, emotionally influenced, declarative memory in healthy humans using positron emission tomography (PET). These PET findings indicate that the amygdala is not required for declarative memory in all circumstances; rather, it is selectively important for the formation of enhanced memory normally associated with emotional arousal. Collectively, these experiments strongly support the view that memory for emotionally arousing events is modulated by endogenous, hormonally based systems.
3-D quantitative assessment of coronary luminal morphology using biplane digital angiography

A method of three-dimensional reconstruction and quantitative description of coronary luminal shape was developed using constrained binary reconstruction of serial vessel cross sections from biplane digital cineangiograms, followed by the application of a quantitative measure of luminal cross-sectional roundedness. Such roundedness is inversely related to luminal eccentricity and thus may provide prognostic information about the stability of coronary stenoses. Examples of validation, in plexiglass coronary phantoms, and clinical feasibility, during routine angioplasty, are discussed. The authors conclude that the reconstructions of an in vivo human coronary artery, pre- and post-angioplasty, demonstrate preliminary feasibility. However, further refinement, validation, and correction for a number of potential error sources are necessary before clinical utility can be realized. >
Threonine Deaminase from Salmonella typhimurium III. THE INTERMEDIATE SUBSTRUCTURE

Abstract Threonine deaminase (l-threonine hydrolyase deaminating, EC 4.2.1.16), molecular weight 194,000, was dissociated into stable intermediate substructures, molecular weight 94,000, by resolving the enzyme of its cofactor, pyridoxal 5'-monophosphate. The intermediate substructures were catalytically inactive and were found to be composed of two of the four identical polypeptide chains which constitute the native tetrameric enzyme. It was determined that the native enzyme contains two disulfide bonds and that these bonds are formed between the subunits of the apodimers. Addition of pyridoxal 5'-monophosphate to a mixture of the apodimers promotes a reassociation into a tetrameric form and a regain of enzymic activity. The reconstituted enzyme binds only 2 molecules of pyridoxal phosphate and its regulatory properties are the same as the native enzyme. The structure-function relationships with respect to the protomeric nature of this enzyme are discussed.
Enforcement of communal policies for P2P systems

We consider the question of how to establish and enforce communal policies for peer-to-peer (P2P) communities. Generally, members of each P2P community must conform to an application specific communal policy if the community is to operate smoothly and securely. An open question, however, is how can such communal policies be established reliably and in a scalable manner? While some communities can rely on voluntary compliance with their stated policies, voluntary compliance will not be sufficient for many future P2P applications. We illustrate the nature of policies that must be enforced to be reliable by means of an example of a community that operates like Gnutella, but which is established to exchange more sensitive and critical information than music files. Then, we propose to employ the intrinsically distributed control mechanism called Law-Governed Interaction (LGI) for the scalable enforcement of communal P2P policies. To demonstrate the efficacy of the proposed approach, we show how our example policy can be formulated and enforced under LGI. Finally, we modify an existing open-source Gnutella client to work with LGI and show that the use of LGI incurs little overhead.
Some experiments on the sinking characteristics of two freshwater diatoms

The sinking rates of living and heat-killed cells of Asterionella formosu and Tubelhia flocculosa and after treatment with CO other mechanisms of suspension seem likely for bluegreen algae (Fogg and Walsby 1971) and other nondiatomaceous taxa. Duthie (1965) has examined suspension in desmids. Freshwater diatom communities have a centric species component lower than that of marine communities; pennate species tend to predominate. Further, blue-green algae and chlorophyceans are more important and ubiquitous in limnetic environments. The capability of achieving suspension may be one factor underlying these floristic differences. Accordingly, I conducted some experiments with freshwater diatoms primarily to place into perspective the mechanisms of marine diatom suspen-
The ILC Beam Delivery System - Conceptual Design and RaD Plans

The Beam Delivery System of the ILC has many stringent and sometimes conflicting requirements. To produce luminosity, the beams must be focused to nanometer size. To provide acceptable detector backgrounds, particles far from the beam core must be collimated. Unique beam diagnostics and instrumentation are required to monitor parameters of the colliding beams such as the energy spectrum and polarization. The detector and beamline components must be protected against errant beams. After collision, the beams must also be transported to the beam dumps safely and with acceptable losses. An international team is actively working on the design of the ILC Beam Delivery System in close collaboration. Details of the design, recent progress and remaining challenges will be summarized in this paper.
“Hard probes” of strongly-interacting atomic gases

We investigate properties of an energetic atom propagating through strongly interacting atomic gases. The operator product expansion is used to systematically compute a quasiparticle energy and its scattering rate both in a spin-1/2 Fermi gas and in a spinless Bose gas. Reasonable agreement with recent quantum Monte Carlo simulations even at a relatively small momentum k/kF > 1.5 indicates that our large-momentum expansions are valid in a wide range of momentum. We also study a differential scattering rate when a probe atom is shot into atomic gases. Because the number density and current density of the target atomic gas contribute to the forward scattering only, its contact density (measure of short-range pair correlation) gives the leading contribution to the backward scattering. Therefore, such an experiment can be used to measure the contact density and thus provides a new local probe of strongly interacting atomic gases.
l-V-CS: an extended l-calculus for scheme

The l-v-CS-calculus is a conservative extension of the l-value-calculus for reasoning about programs in Scheme-like languages. The basis of the extended calculus is a symbolic rewriting semantics for imperative programs. We show with numerous examples how to state and prove equational properties of Scheme-programs in the calculus. The examples suggest that the algebraic manipulation of imperative-functional programs is as feasible and as fruitful as that of functional ones.
Advanced Nuclear Open Air-Brayton Cycles for Highly Efficient Power Conversion

Nuclear heated open air-Brayton cycles have been investigated both as topping cycles for combined cycle Brayton-Rankine cycles and as standalone recuperated Brayton cycles. The peak turbine inlet t...
High-resolution real-time 3D shape measurement on a portable device

Recent advances in technology have enabled the acquisition of high-resolution 3D models in real-time though the use of structured light scanning techniques. While these advances are impressive, they require large amounts of computing power, thus being limited to using large desktop computers with high end CPUs and sometimes GPUs. This is undesirable in making high-resolution real-time 3D scanners ubiquitous in our mobile lives. To address this issue, this work describes and demonstrates a real-time 3D scanning system that is realized on a mobile device, namely a laptop computer, which can achieve speeds of 20fps 3D at a resolution of 640x480 per frame. By utilizing a graphics processing unit (GPU) as a multipurpose parallel processor, along with a parallel phase shifting technique, we are able to realize the entire 3D processing pipeline in parallel. To mitigate high speed camera transfer problems, which typically require a dedicated frame grabber, we make use of USB 3.0 along with direct memory access (DMA) to transfer camera images to the GPU. To demonstrate the eectiveness of the technique, we experiment with the scanner on both static geometry of a statue and dynamic geometry of a deforming material sample in front of the system.
Rapid and simultaneous determination of hexapeptides (Ac-EEMQRR-amide and H2N-EEMQRR-amide) in anti-wrinkle cosmetics by hydrophilic interaction liquid chromatography-solid phase extraction preparation and hydrophilic interaction liquid chromatography with tandem mass spectrometry.

Abstract A rapid method for the simultaneous determination of Ac-EEMQRR-amide and H2N-EEMQRR-amide in cosmetic products was developed and evaluated. This analytical procedure involved extracting samples with 0.1:0.1:85:15 (v:v) trifluoroacetic acid (TFA):formic acid:acetonitrile (ACN):water and determination by hydrophilic interaction liquid chromatography with tandem mass spectrometry (HILIC–MS/MS). Samples showing serious ion suppression were further cleaned up using HILIC–SPE prior to HILIC–MS/MS analysis. Stable isotopically labeled peptides, corresponding to the above two peptides, were used as internal standards to correct for loss of recovery and matrix effects. Electrospray ionization (ESI) in the positive mode was used. The linear range was 2.0–1000 ng/mL for Ac-EEMQRR-amide and 25.0–2500 ng/mL for H2N-EEMQRR-amide. Thirteen commercial products were analyzed for the two peptides using this method. The amounts of Ac-EEMQRR-amide in the samples ranged from none detected to 42.3 μg/g. H2N-EEMQRR-amide was not detected in any of the samples. The recoveries for Ac-EEMQRR-amide and H2N-EEMQRR-amide ranged from 85% to 110% and 84% to 119%, respectively, at the spiking level of 30 μg/g.
Theory of transport in linear biological systems: I. Fundamental integral equation

The conditions under which the output,γ b (t), of a biological system is related to the input,γ a (t), by an integral equation of the typeγ b (t) = ∫ 0 t γ a (ω)w(t−ω)dω, where ω(t) is a transport functioncharacteristic of the system, are analyzed in detail. Methods of solving this type of integral equation are briefly discussed. The theory is then applied to problems in tracer kinetics in which input and output are sums of exponentials, and explicit formulae, which are applicable whether or not the pool is uniformly mixed, are derived for “turnover time” and “pool” size.
Visual Experience Modifies Distribution of Horizontally and Vertically Oriented Receptive Fields in Cats

Cats were raised from birth with one eye viewing horizontal lines and one eye viewing vertical lines. Elongated receptive fields of cells in the visual cortex were horizontally or vertically oriented—no oblique fields were found. Units with horizontal fields were activated only by the eye exposed to horizontal lines; units with vertical fields only by the eye exposed to vertical lines.
Beyond bodegas: affordable groceries through an innovative store format

Low‐income areas often face a “grocery gap” whereby residents lack accessible grocery stores and must spend disproportionate resources to shop outside their neighborhood or purchase food at less desirable stores. Traditional grocery stores will not locate in these neighborhoods for market‐based reasons. An alternative model appears feasible based on a literature review of current grocery industry practices and their theoretical application on a study neighborhood. The alternative store could be a satellite of a larger chain, stock a select product mix, and combine technology and customer service to provide groceries and community development. This model is promising: each part works profitably under market conditions, and planners are beginning to understand the need to work creatively with industry and communities to bring stores to underserved areas.
A comment on the effects of Cs on photon and secondary ion emission during sputtering

Abstract The effect of Cs on photon and negative ion emission is discussed for situations where the sputtered atom interacts either very weakly or very strongly with the target surface. The experimental data seem to favor the strong interaction case.
Cross-sensitization between caffeine- and L-dopa-induced behaviors in hemiparkinsonian mice.

Abstract Adenosine A 2A receptor (A 2A R) antagonists, including the non-specific adenosine antagonist caffeine, have been proposed as a novel, non-dopaminergic treatment strategy for Parkinson's disease (PD). However, the long-term interaction between caffeine and l -dopa treatment in PD models has not been characterized. We examined the interaction between caffeine and l -dopa following a repeated treatment paradigm in hemiparkinsonian mice. In contrast to the progressively sensitized rotational behavior induced by daily l -dopa (2.0 mg/kg) treatment, tolerance for the rotational response to daily caffeine (2.5 or 10 mg/kg) treatment tended to develop over several weeks. However, after a subsequent two-week washout, challenge with same drug demonstrated an extinction of the sensitized l -dopa-induced rotation, but a sensitization of the caffeine-induced rotation. In a cross-challenge paradigm, daily treatment of mice with l -dopa (compared to daily saline) produced a three-fold enhancement in the rotational response to a subsequent re-challenge with caffeine. Similarly, daily treatment of mice with caffeine produced a six-fold enhancement in the rotational response to a subsequent re-challenge with l -dopa. Furthermore, daily co-administration of caffeine plus l -dopa produced enhanced rotational behavior, compared to caffeine or l -dopa alone, indicating an additive or synergistic interaction between caffeine and l -dopa during repeated treatment. Cross-sensitization between caffeine and l -dopa following repeated treatment and their positive interaction during chronic co-adminstration in hemiparkinsonian mice suggest that repeated exposure to caffeine may alter l -dopa responses in PD.
Recent trends and developments in e-banking in an underdeveloped nation – an empirical study

This paper describes a case study about the major issues and challenges in the development of the electronic banking (e-banking) industry of a relatively underdeveloped nation. This research shows that even in many less developed nations, the application of e-banking can help their local banks reduce operating costs and provide a better and fast service to their customers. The research objectives are to investigate the current trends and developments in e-banking and provide managerial insights for the banking industry in those underdeveloped nations. The collected data are examined through statistical analysis tools. Managerial implications are discussed with suggestions for future research.
Intrinsic charm of light mesons and CP violation in heavy quark decay

We investigate the impact of the intrinsic heavy quark states on the predicted values of CP asymmetries in the decays of heavy mesons. It is shown that the intrinsic charm contribution, although dynamically suppressed in QCD, is favored by the weak interaction, and therefore it can significantly dilute the predicted values of CP-violating asymmetries. This introduces additional non-perturbative uncertainty into the estimate of direct CP violating effects.
A Reassessment of Fracture-Safe Operating Criteria for Reactor Vessel Steels Based on Charpy-V Performance

Abstract : Fracture-safe operating criteria for commerical nuclear pressure vessels based on Fracture Analysis Diagram procedures and Charpy-V energy trends are reappraised with respect to the effects of thick-section mechanical constraint and low Charpy-V shelf energies resulting from neutron irradiation. Comparisons of the Charpy-V test with the more definitive Dynamic Tear test procedures indicate the former to be an acceptable means of assessing the fracture toughness of A533-B steel. The mechanical constraint associated with 12-in. thicknesses of this steel suggests the addition of 70F (39C) to the existing criterion requiring vessel operation above NDT + 60F (33C). Ratio Analysis Diagram procedures are shown to be useful in interpreting Charpy-V shelf level data obtained from vessel surveillance programs in terms of critical toughness levels relating to brittle fracture. (Author)
A review and synthesis of recent research in intelligent computer-assisted instruction

Educational devices incorporating artificial intelligence (AI) would “understand” what , whom and how they were teaching and could therefore tailor content and method to the needs of an individual learner without being limited to a repertoire of prespecified responses (as are conventional computer assisted instruction systems). This article summarizes and synthesizes some of the most important research in the development of stand-alone intelligent computer-assisted instruction (ICAI) systems; a review of passive AI-based educational tools (e.g. microworlds, “idea processors”, empowering envionments) would require a separate discussion. ICAI tutors and coaches have four major components: a knowledge base, a student model, a pedagogical module and a user interface. Major current themes of research in the knowledge base include studies of expert cognition, the transfer of meaning, and the sequencing of content. Student-modelling issues focus on alternative ways to represent a pupiľs knowledge, errors and learning. Pedagogical strategies used by ICAI devices range over presenting increasingly complex concepts or problems, simulating phenomena, Socratic tutoring with correction of pupil misconceptions and modelling of expert problem solving via coaching; the central theme of research is finding overarching paradigms for explanation. Language comprehension and generation topics which have special relevence to intelligent tutors and coaches are also briefly reviewed. Overall, increasing availability, decreasing cost and growing commercial interest in AI-based educational devices are enhancing the development of ICAI systems. Limits on the sophistication of user interfaces, on the scope of subject domains and on current understanding of individual learning are all constraining the effectiveness of computer tutors and coaches. The explicitness required for constructing intelligent devices makes their evolution more difficult and time consuming, but enriches the theoretical perspective which emerges. In brief, the computational and economic enabling of ICAI is proceeding more rapidly than are its empirical and cognitive foundations, but significant overall progress is being made.
Performance of QO-STBC-OFDM in partial-band noise jamming

Quasi-orthogonal space-time block codes with orthogonal frequency division multiplexing (QO-STBC-OFDM) can exploit multipath diversity and achieve spectrally efficient communications. However, future wireless communication systems must be robust against both unintentional and intentional interference. As a result, there is a need for proper analytical tools to assess the performance of QO-STBC-OFDM in the presence of partial-band noise jamming. First, analytical expressions for the exact pairwise error probability (PEP) of the QO-STBC-OFDM system is derived using the moment generating function (MGF). Second, the PEP is calculated under various situations, and the closed-form expressions and union bound for the bit error probability (BEP) are derived. Finally, simulations are performed and compared with the theoretical results.
Analgesic effects of serotonergic, noradrenergic or dual reuptake inhibitors in the carrageenan test in rats: Evidence for synergism between serotonergic and noradrenergic reuptake inhibition

Abstract The efficacy of antidepressant drugs with serotonergic, noradrenergic, or dual reuptake inhibition was evaluated in reversing carrageenan-induced thermal hyperalgesia and mechanical allodynia in rats. Duloxetine (1–30 mg/kg, i.p.), a balanced serotonergic–noradrenergic reuptake inhibitor (SNRI), was equiefficacious and more potent than the SNRI venlafaxine (3–100 mg/kg, i.p.) in reversing both thermal hyperalgesia and mechanical allodynia induced by carrageenan. In addition, the selective noradrenergic reuptake inhibitors (NRIs) thionisoxetine (0.03–10 mg/kg, i.p.) and desipramine (1–30 mg/kg, i.p.) also produced complete reversals of carrageenan-induced thermal hyperalgesia. However, only thionisoxetine exhibited a greater than 80% reversal of the carrageenan-induced mechanical allodynia. In contrast, the selective serotonergic reuptake inhibitors (SSRIs) paroxetine, sertraline, and fluoxetine (0.3–10 mg/kg i.p.) had little or no effect in the carrageenan model. In order to understand whether the observed enhanced effectiveness of the dual SNRIs was due to a possible synergism between serotonergic and noradrenergic reuptake inhibition, the effects of the NRI thionisoxetine alone and in combination with an inactive dose of the SSRI fluoxetine were determined. In the presence of fluoxetine, the potency of thionisoxetine in reversing carrageenan-induced hyperalgesia and allodynia was significantly increased by approximately 100-fold and brain concentrations of thionisoxetine were increased by 1.1- to 5-fold. The present data indicate fluoxetine pharmacodynamically potentiated the analgesic effects of thionisoxetine over and above a metabolic interaction between these two drugs. The present findings thus indicate that, in the carrageenan model, dual serotonergic–noradrenergic reuptake inhibition by dual SNRIs, or SSRI–NRI combinations, produces synergistic analgesic efficacy.
Faites vos jeux anouveau: Still another look at sensation seeking and pathological gambling

Abstract This is a response to a critique of the role of sensation seeking in pathological gambling (PG) by Hammelstein (2004). In studies comparing pathological gamblers in treatment programs with controls most studies have shown no difference with control groups or even lower SSS scores in the pathological gamblers. However in most studies of gamblers in the community sensation seeking has been related to the characteristics of PG including high frequency of gambling, size of bets and expenditures on gambling, reported loss of control and the pattern of “chasing” (good money after bad). The failure to find differences using gamblers in programs may be due to the effect of the program on self-reported desire to take risks and need for excitement, or to a selective effect based on personality differences between those pathological gamblers who actually seek treatment compared to those who do not. These are like differences between two types of alcoholics and drug users. Furthermore sensation seeking is related to specific types of gambling activities and variety of activities. Hammelstein suggests that independent measures of impulsivity, novelty, and intensity seeking should be used but these can be measured with subscales of the standard SS measures.
A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. III. The neuroendocrine growth hormone axis during late prepuberty

Cross-sectional studies demonstrating that physiological GH secretion varies widely among normally and slowly growing children as well as adults have created uncertainty over the definition of normal GH secretion. Furthermore, recent data indicate that the pattern of GH released under identical physiological conditions may be unique for each individual, and suggest that normality may be an individually defined condition. To investigate and develop further this concept and to avoid the confounding effects of fluctuating gonadal steroid hormone levels, we chose as a model normally growing prepubertal boys and performed a longitudinal assessment of spontaneous GH release characteristics (36 24-h GH secretion studies in 9 boys over 9-19 months). Assessment of serum GH pulse characteristics was accomplished using the Cluster pulse detection algorithm. Characteristics of underlying pituitary GH secretory events were estimated by multiple parameter deconvolution analysis. Approximate entropy was used to quantify...
Diagnostic value and safety of endomyocardial biopsy in selected patients with heart failure

Abstract Background: The routine use of endomyocardial biopsy (EMB) as a diagnostic test in the evaluation of heart failure patients (HFP) is controversial and generally unadvisable because of low diagnostic yield and potential for significant procedural morbidity and mortality. Purpose: Therefore we reviewed our experience with EMB in a large and mostly referral HFP at our tertiary care center. Methods: We retrospectively reviewed 3419 EMB records from 3/1/97 to 2/28/02 and identified 78 (2.3%) HFP, who were screened and referred for EMB by the heart failure specialists. Pre-EMB clinical diagnosis included 55% dilated cardiomyopathy, 14% prior condition (amyloid, sarcoid, lupus), 7% probable myocarditis, 11% ischemia, 6% drug toxicity, 3% hypertrophic cardiomyopathy, 3% constrictive pericarditis, 1% restrictive cardiomyopathy. EMB samples were routinely submitted for light and electron microscopy, immunofluoresence, Congo red and iron staining. Results: There were 44 (56%) men and 34 (44%) women with mean age of 50.5±18.5 (13–81) years. EMB results were non-diagnostic in 57 (73.1%) and diagnostic in 21(26.9%). Diagnostic finding consisted of 8 (10.2%) amyloid, 5 (6.4%) drug toxicity, 4 (5.1%) myocarditis, 2 (2.6%) iron overload and 2 (2.6%) immunologic/lupus. In HFP undergoing EMB there were 2 (2.6%) of right ventricular perforations as the major procedural complication. In comparison in 3341 EMB performed routinely in heart transplant recipients there were 4 (0.12%) bleedings/hematoma, 3 (0.09%) life threatening arrhythmia, 3 (0.09%) carotid puncture and 1 (0.03%) right ventricular perforation. Conclusions: In HFP without established etiology for heart failure, EMB is of diagnostic value in 26.9% of cases. Contrary to prior concerns regarding the safety of the EMB in HFP this diagnostic test can be completed with low procedural morbidity and no mortality.
Design and Synthesis of 2-Amino-4-methylpyridine Analogues as Inhibitors for Inducible Nitric Oxide Synthase and in vivo Evaluation of [18F]6-(2-Fluoropropyl)-4-methyl-pyridin-2-amine as a Potential PET Tracer for Inducible Nitric Oxide Synthase

A series of position-6 substituted 2-amino-4-methylpyridine analogues was synthesized and compounds 9, 18, and 20 were identified as the inhibitors with the greatest potential to serve as PET tracers for imaging inducible nitric oxide synthase (iNOS). [(18)F]9 was synthesized and evaluated in a mouse model of lipopolysaccharide (LPS)-induced iNOS activation. In vivo biodistribution studies of [(18)F]9 indicate higher tracer uptake in the lungs of the LPS-treated mice when compared to control mice. Tracer uptake at 60 min postinjection was reduced in a blocking study using a known inhibitor of iNOS. The expression of iNOS was confirmed by Western blot analysis of lung samples from the LPS-treated mice. MicroPET studies also demonstrated accumulation of radiotracer in the lungs of the LPS-treated mice. Taken collectively, these data suggest that [(18)F]9 shows favorable properties as a PET tracer to image iNOS activation with PET.
Biophysical and structural studies of TCRs and ligands: implications for T cell signaling.

Abstract The availability of soluble αβ TCRs and the individual chains has now made it possible to carry out structural studies of these molecules and analyze their molecular interactions with peptide-MHC ligands. Recent X-ray crystallographic structures of TCR α and β chains have finally established their structural similarity with the Ig molecules. Kinetic measurements of the interaction between TCRs and their ligands have provided strong evidence in favour of an affinity/avidity model for T cell activation in the periphery as well as during development in the thymus.
Identification and Functional Analysis of Truncated Human Glutamic Acid Decarboxylase 65

Human brain glutamate decarboxylase 65 (hGAD65) was found to exist as full-length and truncated forms when the glutathione S-transferase-tagged hGAD65 fusion protein was subjected to factor Xa cleavage. The truncated form is produced by cleavage at arginine 69 based on N-terminal amino acid sequence analysis, and has a molecular weight of 58 kD. It is resistant to further factor Xa cleavage or mild trypsin treatment and is more active and more stable than the full-length form. Both the full-length and truncated forms of GAD are also observed in brain preparations in the presence of protease inhibitors. Furthermore, full-length GAD could be converted to the truncated form by endogenous proteases, suggesting that the conversion of full-length to truncated GAD mediated by endogenous protease may represent an important mechanism in the regulation of GABA biosynthesis in the brain.
Gene expression in slipped capital femoral epiphysis. Evaluation with laser capture microdissection and quantitative reverse transcription-polymerase chain reaction.

Background: Slipped capital femoral epiphysis is a poorly understood condition affecting adolescents. Prior studies have suggested that the etiology may be related to abnormal collagen in the growth plate cartilage, but we are not aware of any investigations analyzing collagen or other structural proteins on a molecular level in the affected tissue. This study was performed to evaluate expression of mRNA for key structural molecules in growth plate chondrocytes of patients with slipped capital femoral epiphysis. Methods: A core biopsy of the proximal femoral physis was performed in nine patients with slipped capital femoral epiphysis, and the specimens were compared with five specimens from the normal distal femoral and proximal tibial and fibular physes of age-matched patients treated surgically for a limb-length inequality. We utilized laser capture microdissection techniques followed by quantitative reverse transcription-polymerase chain reaction analysis to determine if a change or abnormality in type-II-collagen and/or aggrecan gene expression may be associated with slipped capital femoral epiphysis. With these techniques, we correlated chondrocyte spatial location and gene expression to provide greater insight into this pathological condition and a more complete understanding of growth plate biology in general. Results: Downregulation of both type-II collagen and aggrecan was found in the growth plates of the subjects with slipped capital femoral epiphysis when compared with the levels in the age-matched controls. In eight specimens from affected patients, the level of expression of type-II-collagen mRNA was, on the average (and standard error of the mean), 13.7% ± 0.2% of that in four control specimens and the aggrecan level averaged only 26% ± 0.2% of the control aggrecan level. Conclusions: The decreases that we identified in type-II-collagen and aggrecan expression would affect the quantity, distribution, and organization of both components in a growth plate, but these changes could be associated with either the cause or the result of a slipped capital femoral epiphysis. Clinical Relevance: With further study with use of laser capture microdissection and quantitative reverse transcription-polymerase chain reaction, as well as other molecular biological approaches, these observations may be found to lead to a more complete understanding, and be pertinent to the treatment and possible prevention, of this serious adolescent disorder.
Thermodynamics and Reduction Kinetics Properties of 2-Methyl-3-hydroxypyridine-5-carboxylic Acid Oxygenase†

The investigation by absorbance and fluorescence rapid reaction spectrophotometry of the binding of the substrate MHPC (2-methyl-3-hydroxypyridine-5-carboxylic acid) or the substrate analog 5HN (5-hydroxynicotinic acid) to the flavoprotein MHPCO (2-methyl-3-hydroxypyridine-5-carboxylic acid oxygenase) shows that the binding proceeds in two steps. An enzyme−substrate complex initially formed is followed by a ligand-induced isomerization. This binding process is required for efficient reduction of the enzyme-bound flavin, as evidenced by the fact that MHPCO−substrate complexes can be reduced by NADH much faster than the enzyme alone. Since redox potential values of MHPCO and MHPCO−substrate complexes are the same, steric factors, such as the relative orientation of MHPC to the enzyme-bound flavin, are important for efficient hydride transfer to occur.
Prenatal diagnosis for epidermolysis bullosa: a study of 144 consecutive pregnancies at risk.

Epidermolysis bullosa (EB) is a group of inherited disorders characterized by increased skin fragility, resulting in blisters and erosions after minor trauma. Mutations in 10 structural genes expressed in the cutaneous basement membrane zone have been reported. The DebRA Molecular Diagnostics Laboratory at Jefferson Medical College has performed 144 DNA-based prenatal diagnoses since 1993 in families at risk for recurrence of the most severe forms of EB, including the recessive dystrophic EB (RDEB), junctional EB (JEB), EB with pyloric atresia (EB-PA), and EB simplex (EBS). A mutation-detection strategy using either conformation-sensitive gel electrophoresis (CSGE) or denaturing high-performance liquid chromatography (dHPLC) scanning analysis, followed by nucleotide sequencing, was applied to most cases with DEB and to all JEB, EB-PA, and EBS families. For some RDEB families, linkage analysis was performed, either alone when the inheritance pattern was clear or in combination with one mutation. Among the 144 prenatal diagnoses, 63 were for RDEB, 69 for JEB, 6 for EB-PA, and 6 for EBS. Twenty-eight normal, 73 heterozygous carrier, and 28 affected RDEB, JEB, and EB-PA pregnancies were reported in these recessively inherited diseases. Two affected and four normal pregnancies were predicted in dominantly inherited EBS. Among the 144 pregnancies, 9 were terminated without confirmation, 13 cases were lost to follow-up, and 6 pregnancies are ongoing. There were 6 families with inconclusive results due either to recombination events between flanking markers, absence of informative markers for one allele, or lack of sample from the previously affected child. There were three discordant results, one that was explained by maternal contamination of the chorionic villus sample and two that were unresolved. Overall, the availability, relative ease, and over 98% success rate make molecular DNA-based prenatal diagnosis a viable option for EB families at risk. Copyright © 2003 John Wiley & Sons, Ltd.
Amygdala reactivity to negative stimuli is influenced by oral contraceptive use

The amygdala is a highly interconnected region of the brain that is critically important to emotional processing and affective networks. Previous studies have shown that the response of the amygdala to emotionally arousing stimuli can be modulated by sex hormones. Because oral contraceptive pills dramatically lower circulating sex hormone levels with potent analogs of those hormones, we performed a functional magnetic resonance imaging experiment to measure amygdala reactivity in response to emotional stimuli in women using oral contraceptives, and compared their amygdala reactivity with that of naturally cycling women. Here, we show that women who use oral contraceptive pills have significantly decreased bilateral amygdala reactivity in response to negatively valenced, emotionally arousing stimuli compared with naturally cycling women. We suggest that by modulating
SCHOLARSHIP ABOVE THE VEIL

W. E. B. Du Bois is a figure of legendary stature, with accomplishments that run from the purely academic to the profoundly political. In the Du Bois Review: Social Science Research on Race, we at once memorialize and aim to continuously re-energize one core strand of the great man's life work: namely, Du Bois's legacy as a producer and catalyst for critical scholarship on the global problem of race. As had no other social scientist of his generation when he began, nor any other over his long life course, Du Bois gazed with the most penetrating intensity into what may figuratively be called “the soul” of the problem of race and he saw just how central a role race would play in the future of human affairs far into an unwritten future.
Robustness analysis of descriptor systems with parameter uncertainties

This paper investigates the problem of robustness analysis for descriptor systems with parameter uncertainties in both the derivative and state matrices. Using a parameter dependent Lyapunov function, we derive a linear matrix inequality (LMI) based sufficient condition for the admissibility of the system. Unlike the existing results, our criterion has no restriction on the rank of the derivative matrix. Further, we use the obtained method to study interval descriptor systems and multi-parameter singular perturbed systems. The proposed approaches overcome some drawbacks of the existing results. Finally, we present two numerical examples to show the effectiveness of the main results.
Microscopic glass-transition in Ni-based metallic glass-forming melts

Quasielastic neutron scattering (QENS) has been used to investigate microscopic dynamics in the glass-forming Ni80P20, Pd40Ni40P20 and Pd43Ni10Cu27P20 melts. These melts are characterized by a high-packing fraction that is similar at their liquidus temperatures. Increasing the number of components in these melts increases the viscosity at their liquidus temperature. However, the fragility of these melts did not show a composition dependence. Atomic dynamics in these liquids agree well with mode-coupling theory (MCT) predictions. From the MCT analysis of the QENS data the critical packing fractions for the microscopic glass-transition (c) were obtained. The values obtained for c are well within the MCT theoretical predictions for hard-sphere liquids.