cssi/SciSciGPT-SciSciNet huggingface dataset:
Bringing dynamic languages to .NET with the DLR

From the beginning, Microsoft's .NET framework was designed to support a broad range of different programming languages on a Common Language Runtime (CLR). The CLR provides shared services to these languages ranging from a world-class GC and JIT to a sandboxed security model to tools integration for debugging and profiling. Sharing these features has two huge benefits for languages on the CLR. First, it's easier to implement a language because lots of difficult engineering work is already done for you. Second, and more importantly, these languages can seamlessly work together and share libraries and frameworks so that each language can build on the work of the others. The CLR has good support for dynamic languages today. IronPython-1.0 demonstrates this. The new Dynamic Language Runtime (DLR) adds a small set of key features to the CLR to make it dramatically better. It adds to the platform a set of services designed explicitly for the needs of dynamic languages. These include a shared dynamic type system, standard hosting model and support to make it easy to generate fast dynamic code. With these additional features it becomes dramatically easier to build high-quality dynamic language implementations on .NET. More importantly, these features enable all of the dynamic languages which use the DLR to freely share code with other dynamic languages as well as with the existing powerful static languages on the platform such as VB.NET and C#.
Relationship between the Reciprocity Theorems of Onsager and of Callen-Greene

Onsager's reciprocity theorem is extended to linear non-Markoffian processes; the recipricity relation due to Callen-Green is also extended to include the imaginary (as well as the real) part of the admittance matrix. In terms of these extensions, the two theorems are shown to be completely equivalent.
Intertrial interval shift and avoidance behavior in fish

The possibility that length of intertriai interval serves a reinforcement function was investigated by shifting ITI for two groups of fish, while holding ITI constant for their controls. ITI shift resulted in performance changes which could not be accounted for by either a reinforcement or a distribution of practice hypothesis. The possibility that a generalization decrement led to the changes was suggested.
Behavioral assessments of auditory sensitivity in transgenic mice.

This report summarizes positive reinforcement conditioning procedures for assessing sensory function in transgenic mice. To illustrate these behavioral methods auditory sensitivity was measured in mice lacking ! 9 acetylcholine receptor subunits (! 9 knock-out mice). These receptors are known to play an important role in the efferent pathways that modify cochlear responses to sound stimuli. The strategies of parameter manipulation that led these subjects through their preliminary training stages to stable threshold performances are described in detail. Techniques for estimating and interpreting sensory thresholds are discussed from the perspective of signal detection analyses. This study found no significant differences between ! 9 knock-out mice and control subjects when hearing thresholds were measured under quiet conditions, as predicted by previous behavioral and electrophysiological evidence. © 2000 Elsevier Science B.V. All rights reserved.
A Unified Beta Pricing Theory

Abstract This paper derives Ross's mutual fund separation theory and a new, equilibrium version of Ross's arbitrage pricing theory as special cases of a general theory. The paper also reveals that the two theories are identical in their predictions of asset prices and portfolio returns. The capital asset pricing model (a restricted case of the mutual fund separation theory) receives special treatment.
AVERAGING ESTIMATORS FOR REGRESSIONS WITH A POSSIBLE STRUCTURAL BREAK

This paper investigates selection and averaging of linear regressions with a possible structural break. Our main contribution is the construction of a Mallows criterion for the structural break model. We show that the correct penalty term is nonstandard and depends on unknown parameters, but it can be approximated by an average of limiting cases to yield a feasible penalty with good performance. Following Hansen (2007, Econometrica 75, 1175–1189) we recommend averaging the structural break estimates with the no-break estimates where the weight is selected to minimize the Mallows criterion. This estimator is simple to compute, as the weights are a simple function of the ratio of the penalty to the Andrews SupF test statistic. To assess performance we focus on asymptotic mean-squared error (AMSE) in a local asymptotic framework. We show that the AMSE of the estimators depends exclusively on the parameter variation function. Numerical comparisons show that the unrestricted least-squares and pretest estimators have very large AMSE for certain regions of the parameter space, whereas our averaging estimator has AMSE close to the infeasible optimum.
Managerial Style and Firm Value

This study analyzes the effect of managerial style on firm value by partitioning general and administrative (G&A) expenses in the real estate investment trust industry into a nondiscretionary “structural” component associated with the costs of asset and liability management and a discretionary or “style” component. The discretionary component is significantly related to at least one measure of style—specifically, the portfolio focus/diversification of the firm. Gross (project-level) cash flows are invariant to the nondiscretionary or structural component of G&A but are positively related to the style component of G&A. The structural component has a negative impact on share price while the style component has a neutral impact. Therefore, for this industry, creating larger, less-levered firms would result in enhanced value.
Defining nucleic acid-binding properties of avian retrovirus integrase by deletion analysis.

Abstract Integration of retroviral DNA into the host genome requires the activity of retrovirus-encoded integration protein IN. We expressed Rous sarcoma virus (RSV) IN, 286 amino acid residues in length, by using in vitro transcription, followed by in vitro translation in rabbit reticulocyte lysate. The nucleic acid-binding activity of in vitro-translated IN was assessed by using DNA-cellulose affinity chromatography and poly(U)-Sepharose affinity chromatography and by sedimentation analysis in the presence or absence of DNA. In vitro-translated RSV IN exhibited nucleic acid-binding activity similar to that of IN purified from avian myeloblastosis virus. To identify regions of IN which bind to nucleic acids, several deletions of RSV IN were generated. The NH2-terminal 26 amino acids, including the two His residues of a His-Cys box, were not necessary for IN nucleic acid binding with any of the substrates tested. The substrates included native calf thymus DNA, poly(U), and a double-stranded linear DNA molecule with RSV long terminal repeat sequences at its termini. The COOH-terminal region (residues 178 to 286) of IN bound quantitatively (greater than 90%) to poly(U) and to single-stranded circular phi X174 DNA but did not exhibit the double-stranded linear DNA-binding ability of the entire IN molecule.
Lack of difference in the rates of hypopigmentation with 90-microsecond pulsed and longer dwell time carbon-dioxide laser resurfacing.

Abstract Background Hypopigmentation is an adverse outcome associated with carbon-dioxide (CO 2 ) laser resurfacing. A 90-microsecond pulse produces a more favorable postoperative course of healing, erythema, and pain compared with a 900-microsecond dwell time. The rate of hypopigmentation after 90-microsecond pulsed CO 2 resurfacing may also be reduced. To date, there have been no comprehensive reports on the effect of varying pulse duration on the occurrence of hypopigmentation. Objective We sought to investigate the relationship between pulse duration and the occurrence of hypopigmentation after CO 2 laser resurfacing. Methods We conducted a retrospective review of 447 consecutive patients who were treated with a 90-microsecond pulsed CO 2 laser (n = 229) or a continuous wave CO 2 laser with a modifiable dwell time (100-950 microseconds, n=218). Follow-up ranged from 8 to 61 months (median: 27). Results A series of 4 threshold dwell times (range: 90-950 microseconds) were used to divide patients into 2 treatment groups (above and below) at each threshold. The rates of hypopigmentation between groups were similar (range: 6.37%-9.09%) and serial chi-square testing revealed no statistical differences between groups for each dwell time tested ( P Conclusion No significant relationship between pulse duration and the occurrence of hypopigmentation was observed.
Preservice Teacher Preparation for Inclusion An Exploration of Higher Education Teacher-Training Institutions

Performance mandates of the No Child Left Behind Act of 2001 and the Individuals with Disabilities Improvement Act of 2004 have demanded ever-greater access to the general curriculum for all students, including those with disabilities. Inclusive classrooms and the elevated expectations for all students have a profound impact on preservice teacher preparation. This study obtained information about preservice teacher preparation for inclusive classrooms from a national sample of faculty members in special education, elementary and secondary education, and curriculum and instruction at teacher-education institutions. Faculty perceptions of training efforts used to prepare preservice teachers for inclusion were assessed through electronic survey methods. The survey instrument used a 5-point, Likert-type scale and open-ended questions focused on program elements and perceived effectiveness of inclusion and collaboration. Results indicated a high level of agreement among respondents regarding training efforts a...
A two-parameter Margules method for modelling the thermodynamic mixing properties of albite-water melts

A two-parameter Margules method has been developed for modelling the thermodynamic mixing properties and hypersolidus phase relations of albite-water (ab-w) melts. The method is based largely on phase-equilibrium and calorimetric data that are either currently available or readily obtainable; P-V-T data are not required. The new modelling method has been applied to calculate: (1) thermodynamic mixing properties for ab-w melts at 2.5 kbar, 815°C; and (2) hypersolidus phase relations for the ab-w system at 2.5 kbar
Comparison of species and trait-based approaches for describing sagebrush steppe response to range management

Question: Is valuable information lost when plant trait group composition is used, rather than species composition, to describe plant community response to range management? Location: Elkhead Watershed, Colorado, US. Methods: Current model-building efforts use species composition to define changes in ecosystem state, but plant traits may offer a faster and more broadly applicable alternative. We (1) compare states defined by species composition to those defined by trait-based groups of differing complexity and (2) determine how management and environmental site characteristics relate to species- and trait group-defined states. We sampled 72 plots with different grazing and chemical shrub treatment histories on two soil types. We measured plant species composition in each plot and categorized species into trait groups using three classification schemes, which represented increasing numbers of traits and levels of classification complexity. The classifications employed easily measured traits that affect plant response to range management: life form, life history, resprouting ability, height, vegetative reproduction and N-fixation. Using hierarchical cluster analysis, we identified states with similar species or trait group composition. We explored relationships between each set of potential states and management history and environmental factors using logistic regression. Results: Trait-based group composition and species composition identified many of the same potential states and responses to grazing and chemical shrub treatment. Relationships between species and trait group composition and management and environmental characteristics differed on the two soil types. Species composition was sensitive to more different management practices, on average, than trait group composition. Trait group composition revealed some relationships to management and environmental drivers that were not detected using species composition.
Malignant Histiocytosis of Bernese Mountain Dogs

A second histiocytic proliferative disorder, which resembled malignant histiocytosis of man, was identified in 13 Bernese mountain dogs. Malignant histiocytosis was clearly distinct from systemic histiocytosis, which was reported earlier in this breed. Eleven cases involved male dogs. Ten dogs occurred in the same family line as the dogs afflicted with systemic histiocytosis. Clinical or radiological evidence of pulmonary involvement was present in nine dogs. Neurological disturbances were present in five dogs. Anemia was observed in five dogs and was associated with prominent erythrophagocytosis in two instances. The clinical course was rapidly progressive. Necropsy examinations revealed that infiltrates were especially frequent in the lungs and hilar lymph nodes. Other lymph nodes, liver, spleen, and central nervous system were also frequently involved. Evidence for primary pulmonary involvement was present in seven dogs. The original diagnosis in seven cases was large cell anaplastic carcinoma of the lung by light microscopy only. The infiltrates were composed of large, pleomorphic, phagocytic mononuclear cells and multinucleated giant cells which also manifested marked cytological atypia and numerous, frequently bizarre, mitotic figures. Ultrastructural studies and the immunohistochemical demonstration of lysozyme and alpha 1-antitrypsin in the tumor cells in the majority of cases were consistent with a macrophage origin.
CEBS object model for systems biology data, SysBio-OM

Motivation: To promote a systems biology approach to understanding the biological effects of environmental stressors, the Chemical Effects in Biological Systems (CEBS) knowledge base is being developed to house data from multiple complex data streams in a systems friendly manner that will accommodate extensive querying from users. Unified data representation via a single object model will greatly aid in integrating data storage and management, and facilitate reuse of software to analyze and display data resulting from diverse differential expression or differential profile technologies. Data streams include, but are not limited to, gene expression analysis (transcriptomics), protein expression and protein--protein interaction analysis (proteomics) and changes in low molecular weight metabolite levels (metabolomics). Results: To enable the integration of microarray gene expression, proteomics and metabolomics data in the CEBS system, we designed an object model, Systems Biology Object Model (SysBio-OM). The model is comprehensive and leverages other open source efforts, namely the MicroArray Gene Expression Object Model (MAGE-OM) and the Proteomics Experiment Data Repository (PEDRo) object model. SysBio-OM is designed by extending MAGE-OM to represent protein expression data elements (including those from PEDRo), protein--protein interaction and metabolomics data. SysBio-OM promotes the standardization of data representation and data quality by facilitating the capture of the minimum annotation required for an experiment. Such standardization refines the accuracy of data mining and interpretation. The open source SysBio-OM model, which can be implemented on varied computing platforms is presented here. Availability: A universal modeling language depiction of the entire SysBio-OM is available at http://cebs.niehs.nih.gov/SysBioOM/. The Rational Rose object model package is distributed under an open source license that permits unrestricted academic and commercial use and is available at http://cebs.niehs.nih.gov/cebsdownloads. The database and interface are being built to implement the model and will be available for public use at http://cebs.niehs.nih.gov.
Computational cognitive linguistics

The talk will describe an ongoing project (modestly named the Neural Theory of Language) that is attempting to model language behavior in a way that is both neurally plausible and computationally practical. The cornerstone of the effort is a formalism called Embodied Construction Grammar (ECG). I will describe the formalism, a robust semantic parser based on it, and a variety of applications of moderate scale. These include a system for understanding the (probabilistic and metaphorical) implications of news stories, and the first cognitively plausible model of how children learn grammar.
A tribute, not a memorial: understanding ambiguous loss

In this paper, I discuss ambiguous loss, why it is so traumatizing, what to do to lower the distress when someone disappears without a trace, and why a tribute is more appropriate than a memorial. The paper is dedicated to the family, friends, and colleagues of Jim Gray.
Sourcing carbonate pointed stones from the barrier beach of Mantoloking, New Jersey, USA

Over 500 previously unidentified, symmetric pointed stones of similar size, shape, color, and texture have been found on the barrier beach of Mantoloking, New Jersey, since 1940. Petrographic, stereo, and scanning electron microscopy analysis reveals that the stones are made of either a biomicritic packstone composed of 50% siliceous microfossil remains ( including sponge spicules and radiolaria) embedded in a micrite matrix or a limestone with abundant angular quartz grains (50–150 μm wide) surrounded by a calcite matrix. The distinctive shape of the Mantoloking stones is most similar to whetstones used for sharpening scythes. We conducted a worldwide search and discovered one producer of carbonate whetstones: a company in the town of Pradalunga in Northern Italy. Microscope analysis reveals that the Pradalunga source rocks are exact matches for the spicule-rich limestone and angular quartz-rich limestone found in the Mantoloking collection. The whetstones are most likely lost cargo from a wreck offshore of Mantoloking, but the exact source may never be known. © 2006 Wiley Periodicals, Inc.
Moral decision-making by analogy: generalizations versus exemplars

Moral reasoning is important to model accurately as AI systems become ever more integrated into our lives. Moral reasoning is rapid and unconscious; analogical reasoning, which can be unconscious, is a promising approach to model moral reasoning. This paper explores the use of analogical generalizations to improve moral reasoning. Analogical reasoning has already been used successfully to model moral reasoning in the MoralDM model, but it exhaustively matches across all known cases, which is computationally intractable and cognitively implausible for human-scale knowledge bases. We investigate the performance of an extension of MoralDM to use the MAC/FAC model of analogical retrieval over three conditions, across a set of highly confusable moral scenarios.
Radiation and radon gas

The element uranium is widely distributed within the crust and oceans of the earth. It has been estimated that crustal rocks contain an average of some 4 g of uranium per tonne. The structure of the uranium atom is unstable; emission of subatomic particles from the nucleus causes uranium to change or decay into a new element, thorium. The process of radioactive decay continues down through a series of elements until it reaches a stable form of lead. This process has existed on earth from before the crust was formed. All forms of life on earth have evolved and exist within a constant bombardment of natural radiation including that from the uranium series of elements.
Induced alterations in the biologic activity of estrogen

Phenobarbital reduces the biologic effectiveness of endogenous and exogenous estrogen in sexually mature virgin mice. This function of phenobarbital is documented by failure in maintenance of uterine weight and nitrogen content. Phenobarbital significantly increased liver weights and total nitrogen content. The ability of phenobarbital to act as an enzyme-inducing agent is curtailed in animals after ovariectomy.
MYC as a Multifaceted Regulator of Pluripotency and Reprogramming

Pluripotent stem cells have the ability to generate cellular descendants of the three primary germ layers. For this reason, they are a viable resource in the generation of specialized cells for tissue regeneration and drug development. In the embryo and in vitro culture, pluripotent cells express specific factors that maintain the pluripotent state. Such factors promote the expression of other pluripotency genes to maintain self-renewal and impede differentiation. The proto-oncogene Myc is a central regulator that holds multiple roles in the control of pluripotency. Key functions include maintenance of the pluripotent cell cycle, metabolic regulation and suppression of differentiation pathways. Myc target genes number in the thousands, so it is likely that novel aspects of Myc function in pluripotent stem cell biology remain to be fully elucidated. This chapter deals with our current understanding of Myc’s contribution to pluripotency, its involvement in reprogramming and its contribution to cancer stem cell biology.
Use of Transalveolar Sutures in Conjunction With Grafting to Preserve Vestibular Depth and Augment Gingival Thickness Around Mandibular Implants

Preservation or reconstruction of the soft tissues around dental implants is an essential component of implant dentistry. Increased width and thickness of the keratinized tissue surrounding dental implants has been recognized as an important factor associated with long-term implant success. When extractions and ridge reduction are performed concurrently with implant placement, maintaining vestibular depth also is of utmost importance. A previous report described a technique for applying bone-anchoring sutures to preserve keratinized tissue and vestibular depth around implants. The present report describes a variation of the procedure for the simultaneous correction of situations in which the existing keratinized tissue is thin and narrow and preserving and apically positioning it might not provide an appropriate gingival cuff.
Spatial and Temporal Variability of Live Loads

A probabilistic model of sustained live occupancy loads on buildings is presented, compared with data, and analyzed to produce equivalent uniformly distributed loads (EUDLs) for structural load effects corresponding to a specified probability of being exceeded. The model of load intensity is a linear form including building, floor, and local spatial variation. The latter term is assumed to have exponentially decaying spatial correlation. Temporal variation is assumed to occur at random times associated with changes of one or more independent occupants. Influence surfaces permit translation to structural load effects. The model is compared and fitted to data from the English Building Research Station office loads survey. Results for sustained and maximum lifetime sustained load effects are shown. Figures compare 99% EUDLs for column axial forces and beam moments versus model U. S. and Canadian building codes.
The EST Model for Predicting Progressive Damage and Failure of Open Hole Bending Specimens

Progressive damage and failure in open hole composite laminate coupons subjected to flexural loading is modeled using Enhanced Schapery Theory (EST). Previous studies have demonstrated that EST can accurately predict the strength of open hole coupons under remote tensile and compressive loading states. This homogenized modeling approach uses single composite shell elements to represent the entire laminate in the thickness direction and significantly reduces computational cost. Therefore, when delaminations are not of concern or are active in the post-peak regime, the version of EST presented here is a good engineering tool for predicting deformation response. Standard coupon level tests provides all the input data needed for the model and they are interpreted in conjunction with finite element (FE) based simulations. Open hole bending test results of three different IM7/8552 carbon fiber composite layups agree well with EST predictions. The model is able to accurately capture the curvature change and deformation localization in the specimen at and during the post catastrophic load drop event.
Effects of insulin on muscle tissue

The anabolic nature of insulin on muscle protein has been recognized since the initial clinical use of insulin therapy in type 1 diabetes about sixty years ago, but the exact mechanism whereby insulin effects muscle protein metabolism in human subjects remains unclear. In particular, the effect of insulin on muscle protein synthesis has been debated. In vitro studies document a stimulatory effect of insulin on muscle protein synthesis, but in vivo results are conflicting. Everything from decreased muscle protein synthesis to increased muscle protein synthesis in response to insulin has been reported. A recent publication suggests that the response of muscle protein synthesis to insulin is dose dependent, and that only supraphysiological dose of insulin stimulate muscle protein synthesis. On the other hand, some studies show a stimulatory effect of insulin in low doses. It is possible to form a more coherent picture of the effect of insulin if the results from various experiments are expressed in the context of the availability of amino acids. In general, insulin stimulated muscle protein synthesis in studies in which intramuscular amino acid availability was maintained or increased regardless of the dose of insulin. In contrast, insulin was ineffective in stimulating muscle protein synthesis when amino acid availability was allowed to drop, irrespective of the dose of insulin. Thus, whereas insulin has a potential stimulatory effect on human muscle protein synthesis, an adequate availability of amino acids is required for that potential to be expressed in an actual increase in the synthetic rate.
A mixed quantum-classical molecular dynamics study of anti-tetrol and syn-tetrol dissolved in liquid chloroform II: infrared emission spectra, vibrational excited-state lifetimes, and nonequilibrium hydrogen-bond dynamics.

The effect of vibrational excitation and relaxation of the hydroxyl stretch on the hydrogen-bond structure and dynamics of stereoselectively synthesized syn-tetrol and anti-tetrol dissolved in deuterated chloroform are investigated via a mixed quantum-classical molecular dynamics simulation. Emphasis is placed on the changes in hydrogen-bond structure upon photoexcitation and the nonequilibrium hydrogen-bond dynamics that follows the subsequent relaxation from the excited to the ground vibrational state. The propensity to form hydrogen bonds is shown to increase upon photoexcitation of the hydroxyl stretch, thereby leading to a sizable red-shift of the infrared emission spectra relative to the corresponding absorption spectra. The vibrational excited state lifetimes are calculated within the framework of Fermi’s golden rule and the harmonic-Schofield quantum correction factor, and found to be sensitive reporters of the underlying hydrogen-bond structure. The energy released during the relaxation from the ...
Glycan specificity of neuraminidases determined in microarray format

Neuraminidases hydrolytically remove sialic acids from glycoconjugates. Neuraminidases are produced by both humans and their pathogens, and function in normal physiology and in pathological events. Identification of neuraminidase substrates is needed to reveal their mechanism of action, but high-throughput methods to determine glycan specificity of neuraminidases are limited. Here we use two glycan labeling reactions to monitor neuraminidase activity toward glycan substrates. While both periodate oxidation and aniline-catalyzed oxime ligation (PAL) and galactose oxidase and aniline-catalyzed oxime ligation (GAL) can be used to monitor neuraminidase activity toward glycans in microtiter plates, only GAL accurately measured neuraminidase activity toward glycans displayed on a commercial glass slide microarray. Using GAL, we confirm known linkage specificities of three pneumococcal neuraminidases and obtain new information about underlying glycan specificity.
Global displacements : the making of uneven development in the Caribbean

Series Editors Preface vi List of Abbreviations vii List of Figures and Tables ix Acknowledgements x 1 Introduction: Power and Difference in Global Production 1 2 Two Stories of Caribbean Development: Garments -as -Globalization and Garments -as-Regional Entrepreneurialism 28 3 From Manufactura to Mentefactura? Gender and Industrial Restructuring in the Dominican Republic 54 4 Embodied Negotiations: Geographies of Work after Trade Zones 85 5 Reworking Coloniality through the Haitian Dominican Border 113 6 Haiti, the Global Factory and the Politics of Reconstruction 141 7 Unsettling Dominant Crisis Narratives of the Caribbean 163 8 Conclusion 181 Bibliography 187 Index 206
Robot Hand-Eye Calibration Using Unscented Kalman Filtering

An online robot hand-eye calibration method using unscented Kalman filtering(UKF) is presented to solve the homogeneous transformation equations of the form AX=XB.The hidden Markov model(HMM) of the hand-eye calibration is constructed,based on which UKF is performed to estimate calibration parameters recursively according to the Bayesian theory,and the evolution of calibration parameters can be visualized in real time.Monte Carlo simulation shows that the proposed algorithm possesses better accuracy than the traditional least squares(LS) based method under low isotropic,high isotropic and anisotropic Gaussian noises.Real robot hand-eye calibration experiment is also performed and the result shows stable convergence of the proposed algorithm with better accuracy comparing with the LS based method.
Epidemiological investigation on 3 cases of serogroup A epidemic cerebrospinal meningitis

Objective To analyze epidemic characters and causes of an outbreak of serogroup A epidemic cerebrospinal meningitis in Puan County of Guizhou Province for providing experience for future prevention and control of epidemic cerebrospinal meningitis.Methods Epidemiological investigation in the affected area and retrospective analysis on epidemic situation of epidemic cerebrospinal meningitis in the southwest of Guizhou Province in recent years were carried out. Results 3 cases were reported as meningitis which included 1 laboratory and 2 clinical diagnosis cases. The attack rate was 5.70‰. The serogroup A neisseria meningitides was identified in laboratory. Conclusion The major cause of the breakout is that the vaccination rate of meningitis is too low, resulting in that the children of any age cannot be protected by vaccination. Floating and left-behind children should be paid more attention in vaccine plan and service to increase the inoculation rate. Surveillance, report and diagnosis of meningitis should be focused in professional training to improve the meningitis control and prevention in the future.
Military Graduate Medical Education Research: Challenges and Opportunities

INTRODUCTION Over the past 150 years, military medical research has made significant contributions to American health care. In the past decade alone, military medicine has achieved significant advances in combat casualty care by demonstrating the value of tourniquets, damage control resuscitation and surgery, new infection management guidelines, transcontinental critical care transport, advanced prosthetics, and new techniques in rehabilitation. This pioneering research cannot occur in a vacuum. As in civilian settings, medical research must be nested in an academic architecture. In the Military Health System (MHS) the foundation for cuttingedge research is built at the Uniformed Services University of the Health Sciences and through military Graduate Medical Education (GME).
Prediction of rates of thromboembolic and major bleeding outcomes with dabigatran or warfarin among patients with atrial fibrillation: new initiator cohort study

Objectives To compare stratified event rates from randomized controlled trials with predicted event rates from models developed in observational data, and assess their ability to accurately capture observed rates of thromboembolism and major bleeding for patients treated with dabigatran or warfarin as part of routine care. Design New initiator cohort study. Setting Data from United Health (October 2009 to June 2013), a commercial healthcare claims database in the United States. Participants 21 934 adults with atrial fibrillation initiating dabigatran (150 mg dose only) or warfarin treatment as part of routine care. Main outcome measures Predicted annual rates of thromboembolism or major bleeding, based on estimates from randomized controlled trials, models developed in routine care patients, and baseline risk scores (CHADS 2 , CHA 2 DS 2 -VASc, and HAS-BLED). Thromboembolism was a composite outcome, including primary inpatient diagnosis codes for ischemic or ill defined stroke, transient ischemic attack, pulmonary embolism, deep vein thrombosis, and systemic embolism. Major bleeding was a composite outcome including codes occurring in an inpatient setting for hemorrhagic stroke; major upper, lower, or unspecified gastrointestinal bleed; and major urogenital or other bleed. Results 6516 (30%) and 15 418 (70%) of patients initiated dabigatran and warfarin, respectively. Annual event rates per 100 patients were 1.7 for thromboembolism and 4.6 for major bleeding. For thromboembolism, calibration of estimates from randomized controlled trials was similar to calibration for model based predictions; however, trial estimates for major bleeding consistently underestimated the rate of bleeding among patients in routine care. Underestimation of bleeding rates was particularly pronounced in warfarin initiators with high HAS-BLED scores, where event rates were underestimated by up to 4.0 per 100 patient years. Harrell’s c indices for discrimination for thromboembolism or major bleeding in dabigatran and warfarin initiators ranged between 0.59 and 0.66 for randomized controlled trial predictions, and between 0.52 and 0.70 for cross validated model based predictions. Conclusion Estimated rates of thromboembolism under dabigatran or warfarin treatment in randomized controlled trials were close to observed rates in routine care patients. However, rates of major bleeding were underestimated. Models developed in routine care patients can provide accurate, tailored estimates of risk and benefit under alternative treatment to enhance patient centered care.
Hyperspectral Measurements Allow Separation of FRET Signals from Non-Uniform Background Fluorescence

In recent years Forster resonance energy transfer (FRET) has become a standard imaging approach to gain insight into localized biochemical processes within cells. These processes include changes in protein colocalization, second messenger concentration, and activation of effector proteins such as protein kinase A (PKA). However, there are several limitations in FRET measurements that are not often considered. In recent years our group has used hyperspectral imaging approaches to address a subset of these limitations, including the inherently low signal-to-noise ratio of standard two and three filter set FRET measurements. Here we present data demonstrating that hyperspectral imaging approaches can be used to correct for non-uniform background fluorescence in low intensity FRET measurements. We utilized the FRET-based cAMP probe H188. The H188 probe contains a cAMP binding domain between donor (Turquoise) and acceptor (Venus) fluorescent proteins. The probe was transfected into pulmonary microvascular endothelial cells plated on glass coverslips. Hyperspectral image stacks were acquired using a Nikon A1R inverted confocal microscope. Changes in cAMP were triggered by addition of 0.1 µM isoproterenol (a beta adrenergic receptor agonist) 0.1 µM PGE1 (a prostanoid receptor agonist) or 50 µM forskolin (an adenylyl cyclase activator). Data were analyzed using Nikon Elements software and custom MATLAB scripts. Results demonstrate that non-uniform background fluorescence associated with glass coverslips can contaminate FRET measurements from weak fluorescence signals. Linear unmixing approaches were able to separate the abundances of background, donor and acceptor fluorescence signals. Thus, results from this study demonstrate that hyperspectral unmixing approaches can readily separate non-uniform background fluorescence from other fluorescence signatures, allowing for more accurate quantification of FRET efficiency. This work was supported by NIH P01HL066299, NIH S10RR027535, NIH T32HL076125, AHA 16PRE27130004, USA SURF Program, and the Abraham Mitchell Cancer Research Fund.
Meeting Its Mission: Does Psychosomatics Align With the Mission of Its Parent Organization, the Academy of Psychosomatic Medicine?

Background The vision and mission statements of the Academy of Psychosomatic Medicine (APM) indicate that the APM should promote excellence in clinical care for patients with comorbid psychiatric and general medical conditions by seeking to influence research, public policy, and interdisciplinary education. Objective As the APM owns the journal, Psychosomatics , we sought to assess whether the APM's journal was fulfilling the vision and mission of its parent organization by reviewing the content of articles published in the journal to determine whether it sufficiently addresses the various clinical care knowledge areas it seeks to influence. Methods We categorized content in all review articles, case reports, and original research articles published in Psychosomatics in 2015 and 2016. Each article was assigned to as many categories that it covered. Results In the 163 articles reviewed, the most frequently covered fund of knowledge area was psychiatric morbidity in medical populations (44.2%); among psychiatric disorders, mood disorders (22.1%), psychiatric disorders due to a general medical condition or toxic substance (21.5%), anxiety disorders (14.7%), and delirium (13.5) were the most frequently covered. Of the medical and surgical topics, neurology (19.6%), coping with chronic illness/psychological response to illness (17.8%), toxicology (11.7%), outpatient medicine (10.4%), and cardiology (9.8%) appeared most often. Conclusions Psychosomatics appears to be successfully providing content relevant to the APM's vision and mission statements and to practitioners of psychosomatic medicine.
Psychodynamic Intervention in Crisis

This paper presents a framework for brief, intensive psychotherapeutic intervention for acute distress, manifested by feelings of depression, anxiety or anger, isolation and loneliness, that arise when crises provoke unconscious conflict. This therapy uses a technique to develop a "benevolent transference" for symptom relief and as a groundwork for gaining insight. Interventions to facilitate this process will be illustrated with case illustrations.
Common source inductance introduced self-turn-on in MOSFET turn-off transient

While fast switching brings many benefits, it also presents unwanted ringing during switching transient. In this paper, an increasing magnitude ringing phenomenon is observed during the MOSFET turn-off transient. The unusual phenomenon is replicated in simulation and it is found the MOSFET channel is turned on again after it is turned off. The major cause to this unexpected turn on is found to be common source inductance and a moderate 3 nH one in simulation replicates the severe self-turn-on ringing observed in experiment. This paper reveals the detrimental effect of common source inductance in fast switching. Therefore, Kelvin source connection in circuit and package design is strongly recommended.
Abstract TP79: Patient Refusal and Informed Consent-related Delays for Stroke Thrombolysis in Chicago

Objective: To describe consent-related failures in patients eligible for tissue plasminogen activator (tPA) and to assess if race-ethnic disparities exist in the informed consent process for intrav...
Sortase ligation enables homogeneous GPCR phosphorylation to reveal diversity in β-arrestin coupling.

The ability of G protein-coupled receptors (GPCRs) to initiate complex cascades of cellular signaling is governed by the sequential coupling of three main transducer proteins, G protein, GPCR kinase (GRK), and β-arrestin. Mounting evidence indicates these transducers all have distinct conformational preferences and binding modes. However, interrogating each transducer’s mechanism of interaction with GPCRs has been complicated by the interplay of transducer-mediated signaling events. For example, GRK-mediated receptor phosphorylation recruits and induces conformational changes in β-arrestin, which facilitates coupling to the GPCR transmembrane core. Here we compare the allosteric interactions of G proteins and β-arrestins with GPCRs’ transmembrane cores by using the enzyme sortase to ligate a synthetic phosphorylated peptide onto the carboxyl terminus of three different receptors. Phosphopeptide ligation onto the β 2 -adrenergic receptor (β 2 AR) allows stabilization of a high-affinity receptor active state by β-arrestin1, permitting us to define elements in the β 2 AR and β-arrestin1 that contribute to the receptor transmembrane core interaction. Interestingly, ligation of the identical phosphopeptide onto the β 2 AR, the muscarinic acetylcholine receptor 2 and the μ-opioid receptor reveals that the ability of β-arrestin1 to enhance agonist binding relative to G protein differs substantially among receptors. Furthermore, strong allosteric coupling of β-arrestin1 correlates with its ability to attenuate, or “desensitize,” G protein activation in vitro. Sortase ligation thus provides a versatile method to introduce complex, defined phosphorylation patterns into GPCRs, and analogous strategies could be applied to other classes of posttranslationally modified proteins. These homogeneously phosphorylated GPCRs provide an innovative means to systematically study receptor–transducer interactions.
ABP 980: promising trastuzumab biosimilar for HER2-positive breast cancer.

ABSTRACTIntroduction: Approval of the HER2-targeted antibody trastuzumab dramatically improved outcomes for patients with HER2-positive breast cancer. Multiple trastuzumab biosimilars, including ABP 980, are in clinical development. Biosimilars are not identical to the reference biologic, but exhibit equivalence and safety in analytical and clinical studies.Areas covered: A brief introduction to trastuzumab, overview of trastuzumab biosimilars, and detailed review of ABP 980 preclinical and clinical studies are included. We searched PubMed and 2016–2017 ASCO and ESMO conference proceedings for ‘ABP 980’ or ‘trastuzumab biosimilar’. ‘ABP 980 and breast cancer’ or ‘trastuzumab biosimilar and breast cancer’ were used to search clinicaltrials.gov for phase III trials. Analytical studies of ABP 980 pharmacokinetics (PK) or pharmacodynamics (PD), phase I studies of ABP 980 safety and PK/PD, and phase III studies of clinical efficacy vs trastuzumab are included.Expert opinion: Questions remain regarding long-ter...
Tardive dyskinesia: placing vesicular monoamine transporter type 2 (VMAT2) inhibitors into clinical perspective.

Introduction: Tardive dyskinesia (TD) is an iatrogenic movement disorder caused by exposure to dopamine receptor blocking agents. Two vesicular monoamine transporter type 2 (VMAT2) inhibitors for t...
An Automation Scheme for Emergency Operation of a Multi-Microgrid Industrial Park

Many modern industrial plants are equipped with local generation and are designed to operate as a microgrid. Under normal conditions, the plant is connected to and often mainly supplied by the utility's network. However, during a disturbance on the utility side, it may island from the grid and continue supplying its load using available on-site generation. When this generation is not sufficient to supply the entire load (which is often the case), some of the noncritical loads must be shed so as to ensure that the remaining loads receive the required quality of service. The decision to island and the amount of load to be curtailed are determined based on the values of the frequency/voltage. In this paper, we first propose a hybrid undervoltage/under frequency islanding scheme for an industrial park consisting of multiple substations (microgrids) each supplying one or more industrial plants. It is assumed that once the park is islanded from the grid, the substations are instantly formed into multiple islands where all noncritical loads are automatically disconnected. This is done to ensure that individual islands are not affected by potential instability of their neighboring networks. However, once the individual islands are stabilized, it is possible to share their available generation capacities to maximize the total load served. This would mean connecting one or more islands together to form bigger ones. We formulate this as a network reconfiguration problem that tries to maximize the amount of load served by reconfiguring the network topology and using backup energy resources. The problem is solved and analyzed for a simplified version of an industrial park, both at steady state and during transients.
Structural Determinants of Functional Brain Dynamics

Neural connections of the mammalian cerebral cortex exhibit specific patterns ranging in scale from interconnections linking whole brain regions to intra-areal patterns of connections between cell populations or individual cortical neurons (Cajal, 1909; Brodmann, 1909; Zeki, 1993; Salin and Bullier, 1995; Swanson, 2003). Detailed anatomical and physiological studies have revealed many of the basic components and interconnections of cortical microcircuitry (Douglas and Martin, 1991), and of their arrangement into columns and minicolumns (Mountcastle, 1978; 1997). Columns and other localized populations of neurons maintain connections within and between brain regions, constituting large-scale patterns of anatomical connectivity. While the large-scale networks of human cortex remain largely unmapped (Sporns et al., 2005), comprehensive descriptions of anatomical patterns of cortical connectivity have been collated for several other mammalian species (e.g. Felleman and Van Essen, 1991; Scannell et al., 1999). Closer analysis has revealed that these patterns are neither completely regular nor completely random, but combine structural aspects of both of these extremes (reviewed in Sporns et al., 2004). This basic insight has sparked significant interest in characterizing the structure of brain networks, using methods that are also applied in parallel efforts to map and describe other biological networks, e.g. those of cellular metabolism, gene regulation, or ecology. This chapter is intended as an overview of recent quantitative approaches to brain networks (see also Sporns, 2005), with an emphasis on theoretical and computational studies that inform us about the structural features that determine functional brain dynamics.
CHIP-TO-MODULE INTERCONNECTIONS

The architectural construction of an electronic system from individual integrated circuits (ICs) and other components is dependent upon effective interconnection substrates and means of connecting to them (chip-to-module connections). Traditionally, general packaging, assembly, and chip-to-module connections were available and applied to devices. A close interaction between IC design and substrate technology was not required. Early ICs used transistor-transistor logic which had long internal delays (e.g. 15 ns) making the interconnect and module delays irrelevant. The number of input and output (I/O) connections was small, the DC power was minimal, and packaging density of silicon on boards was sparse. This made cost, reliability, and yield the focus of the chip-to-module connection technology.