cssi/SciSciGPT-SciSciNet huggingface dataset:
Structures of Pathogenic Fungal FKBP12s Reveal Possible Self-Catalysis Function

ABSTRACT Invasive fungal infections remain difficult to treat and require novel targeting strategies. The 12-kDa FK506-binding protein (FKBP12) is a ubiquitously expressed peptidyl-prolyl isomerase with considerable homology between fungal pathogens and is thus a prime candidate for future targeting efforts to generate a panfungal strategy. Despite decades of research on FKBPs, their substrates and mechanisms of action remain unclear. Here we describe structural, biochemical, and in vivo analyses of FKBP12s from the pathogenic fungi Candida albicans, Candida glabrata, and Aspergillus fumigatus. Strikingly, multiple apo A. fumigatus and C. albicans FKBP12 crystal structures revealed a symmetric, intermolecular interaction involving the deep insertion of an active-site loop proline into the active-site pocket of an adjacent subunit. Such interactions have not been observed in previous FKBP structures. This finding indicates the possibility that this is a self-substrate interaction unique to the A. fumigatus and C. albicans fungal proteins that contain this central proline. Structures obtained with the proline in the cis and trans states provide more data in support of self-catalysis. Moreover, cysteine cross-linking experiments captured the interacting dimer, supporting the idea that it forms in solution. Finally, genetic studies exploring the impact of mutations altering the central proline and an adjacent residue provide evidence that any dimeric state formed in vivo , where FKBP12 concentrations are low, is transient. Taken together, these findings suggest a unique mechanism of self-substrate regulation by fungal FKBP12s, lending further novel understanding of this protein for future drug-targeting efforts. IMPORTANCE FKBP12 is a cis-trans peptidyl-prolyl isomerase that plays key roles in cellular protein homeostasis. FKBP12s also bind the immunosuppressive drug FK506 to inhibit the phosphatase calcineurin (CaN). CaN is required for virulence of A. fumigatus, C. albicans, C. glabrata, and other deadly fungal pathogens, marking FKBP12 and CaN as potential broad-spectrum drug targets. Here we describe structures of fungal FKBP12s. Multiple apo A. fumigatus and C. albicans FKBP12 structures reveal the insertion of a proline, conspicuously conserved in these proteins, into the active sites of adjacent molecules. This suggests that these proteins might serve as their own substrates. Cysteine disulfide trapping experiments provide support for this self-interaction and hence possible intermolecular catalysis by these enzymes.
Early revascularization improved long-term survival after myocardial infarction with cardiogenic shock.

Source Citation Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization and long-term survival in cardiogenic shock complicating acute myocardial infarction. JAMA. 2006;295:2511-5. 16757723
Cross-Cultural Comparisons of Discounting Delayed and Probabilistic Rewards

In order to assess the cross-cultural generality of monetary decision-making processes, American, Chinese, and Japanese graduate students were studied on two tasks: In the delay discounting task, participants made choices between immediate and delayed hypothetical monetary rewards; in the probability discounting task, participants made choices between certain and probabilistic rewards. Some notable cross-cultural similarities were observed. Two-parameter hyperbola-like functions described both delay and probability discounting for all three groups. Moreover, for all three groups the rate at which delayed rewards were discounted was higher for the smaller amount whereas the rate at which probabilistic rewards were discounted was lower for the smaller amount. Some group differences were also observed. As measured by the area under the empirical discounting curve, the Americans and Chinese discounted delayed rewards more steeply than the Japanese. In addition, the Americans discounted probabilistic rewards the most, whereas the Chinese discounted probabilistic rewards the least. Despite these differences, the similarities in the form of the discounting functions and in the effects of amount suggest that there are fundamental commonalities among the three groups with respect to the processes underlying their evaluation of delayed and probabilistic rewards.
Self-sustainable OFDM transmissions with smooth energy delivery

Circuits and systems to simultaneously transmit energy and information using orthogonal frequency-division multiplexing (OFDM) that obtain receiver energy self-sufficiency have recently been proposed. To obtain smooth, rather than bursty energy delivery which may lead to energy outage, this paper develops a new architecture for self-sustainable OFDM that reduces the peak-to-average power ratio (PAPR) in the cyclic prefix through a novel frame-theoretic operation, similar to the erasure pattern selection technique. Numerical results demonstrate that this new approach outperforms prior self-sustainable OFDM techniques in terms of PAPR while maintaining nearly the same self-sustainability.
The Will to Consume: Schopenhauer and Consumer Society

Consumer society has negated Freud's thesis presented in Civilization and its Discontents. The hindrance of desire affirmation is no longer the foundation of discontent. The inverse is now true. A seemingly limitless number of desires have been manufactured and administered with a solitary route to their affirmation via consumption. Because of this, consumer society's members find themselves in a lifeworld of aimless striving, dissatisfaction, disappointment and boredom. I demonstrate that the attempt to flee the sufferings of estranged labour through consumption has pushed consumer society into a new web of suffering brought on by a continual development of manufactured desires, creating a minor yet perpetual pain that is best understood in the light of a sociologized and historicized Schopenhauerian philosophy.
Primary Central Nervous System Lymphoma (PCNSL) in Immunocompetent Patients: An Analysis of Prognostic Factors and Treatment Strategies

Abstract Abstract 4955 Background: The incidence of primary CNS lymphoma in immunocompetent patients is increasing for unknown reasons. Survival estimates from academic centers show an improvement in overall survival (OS) while community epidemiological data estimate minimal difference in OS in the last thirty years. Age greater than 60, poor performance status, elevated initial LDH, high CSF protein and involvement of deep regions of the brain have been associated with worse survival. Optimal dosing strategies and delivery of chemotherapy as well as the role of radiation therapy (RT) have yet to be clearly defined given the limitations of treatment related toxicity in patients achieving remissions. Purpose: To characterize the PCNSL patient population treated at a single institution by studying prognostic factors and assessing OS according to treatment strategies. Methods: 45 cases of confirmed CNS Lymphoma diagnosed at Rush University Medical Center between January 2000 and November 2010 were studied. Demographic, clinical and treatment data were collected and reviewed. Hospital records and the Social Security Death Index were used to determine death dates. Survival data were compared based on treatment groups. Results: 23 of the 45 cases met all inclusion criteria and had no evidence of previous systemic lymphoma or pre-morbid immunocompromised conditions (i.e. HIV). The age range at diagnosis was from 21 to 81 years old with a median age of 68. One patient had ocular involvement. Three patients had malignant cells in the CSF at diagnosis and 4 patients had multifocal tumors. Biopsies revealed one case of a cerebral T-cell lymphoma and 22 were diffuse large B-cell lymphoma (DLBCL). Elevated CSF protein above the mean (96.1 mg/dl) was associated with worse OS (p=0.02). Elevated LDH above the mean (227 U/L) was associated with worse OS (p= 0.039). Age, performance status and location of tumor within the brain (deep vs. superficial) did not correlate with survival patterns. Comparative survival analysis between treatment groups revealed no statistically significant difference (p=0.134). In addition to systemic chemotherapy, 15 patients received intrathecal chemotherapy Treatment Strategies Single-agent chemotherapy only Poly-chemotherapy only RT only Poly-chemotherapy +RT Single-agent chemotherapy +RT # patients 2 9 1 10 1 Conclusions: The description of PCNSL in immunocompetent patients outside of the clinical-trial setting is necessary to inform prospective trial designs. This study supports the use of LDH and CSF protein in determining prognosis and treatment strategy. This analysis of conventional treatment is ongoing. Collaboration on gathering descriptive data for PCNSL in immunocompetent patients should be pursued. Disclosures: Gregory: Genentech:.
A >2-MJ, 10 14 -W laser system for DT fusion—NIF: a note in celebration of the 75th birthday of Prof. Theodore Haensch

In 1970, Dr. Theodore Haensch joined A.L. Schawlow’s group in the physics department at Stanford, as a NATO postdoctoral researcher. Within a short time, he and his colleagues had invented a new, high-resolution, tunable laser system using expanded reflection gratings and an N2 laser for pumping the fluorescing dyes. This work resulted in a high-brightness, high-repetition-rate, narrow-band laser probe for conducting optical spectroscopy at extreme levels of precision. Dr. Haensch, and his many colleagues, particularly Prof. Arthur Schawlow and their students at Stanford, then proceeded to revolutionize optical spectroscopy and to train several generations of exceptional young scientists. At the same time, the Siegman, Harris, and Byer laboratories also at Stanford were making major contributions to the laser and quantum electronics fields. Several students from both groups joined the Livermore Laboratory. That early work, and that of others, encouraged teams at the Lawrence Livermore National Laboratory to design and build a series of increasing complicated, high-power multi-beam laser systems to investigate the potential of laser fusion. The National Ignition Facility, recently completed, is enabling investigations of matter at very high temperatures, T > 1 million K and densities 100-1000× normal. In addition, researchers are creating 1015 DT fusion neutrons per fusion experiment and generating new knowledge about unusual and important conditions of matter.
An empirical study of self-training and data balancing techniques for splice site prediction

Thanks to Next Generation Sequencing technologies, unlabelled data is now generated easily, while the annotation process remains expensive. Semi-supervised learning represents a cost-effective alternative to supervised learning, as it can improve supervised classifiers by making use of unlabelled data. However, semi-supervised learning has not been studied much for problems with highly skewed class distributions, which are prevalent in bioinformatics. To address this limitation, we carry out a study of a semi-supervised learning algorithm, specifically self-training based on Naive Bayes, with focus on data-level approaches for handling imbalanced class distributions. Our study is conducted on the problem of predicting splice sites and it is based on datasets for which the ratio of positive to negative examples is 1-to-99. Our results show that under certain conditions semi-supervised learning algorithms are a better choice than purely supervised classification algorithms.
Evaluating tradeoffs in granularity and overheads in supporting nonvolatile execution semantics

While pausing and resuming execution using nonvolatile storage has long been possible, nonvolatile processing as a fundamental paradigm has only recently been made practical by technology advances allowing on-chip nonvolatile memories. However, even with on-chip nonvolatile storage, the granularity of ensured forward progress that a nonvolatile processor offers can still vary widely from cycle-level guarantees to software-defined checkpoints spanning potentially significant quantities of execution. Choice of supported granularity influences not only the hardware overheads, but also the complexity of avoiding potential inconsistencies between architectural and microarchitectural state in realistic memory systems. In this paper, we examine the overheads, in terms of both complexity and efficiency, for non-volatile processor designs with different granularity of forward progress guarantees.
Toward a Droplet-Based Single-Cell Radiometric Assay

Radiotracers are widely used to track molecular processes, both in vitro and in vivo, with high sensitivity and specificity. However, most radionuclide detection methods have spatial resolution inadequate for single-cell analysis. A few existing methods can extract single-cell information from radioactive decays, but the stochastic nature of the process precludes high-throughput measurement (and sorting) of single cells. In this work, we introduce a new concept for translating radioactive decays occurring stochastically within radiolabeled single-cells into an integrated, long-lasting fluorescence signal. Single cells are encapsulated in radiofluorogenic droplets containing molecular probes sensitive to byproducts of ionizing radiation (primarily reactive oxygen species, or ROS). Different probes were examined in bulk solutions, and dihydrorhodamine 123 (DHRh 123) was selected as the lead candidate due to its sensitivity and reproducibility. Fluorescence intensity of DHRh 123 in bulk increased at a rate o...
The EVA Style Approach to Tactical Asset Allocation

We refine tactical asset allocation (TAA) by arguing that the equity style component of a TAA strategy should distinguish between—and rotate among—predefined value creators and value destroyers in the marketplace. We assess equity style in the context of an economic profit approach to securities analysis and active portfolio management. We illustrate TAA in the context of an economic value added style analysis, and we demonstrate both the macroeconomic aspects and cyclicality of economic profit and its equity rotational implications for TAA. We conclude with a look at some well-known value creators and value destroyers, as well as known market anomalies that can also drive an economic profit approach to TAA and active portfolio management.
Android Security via Static Program Analysis

Android is a popular platform designed for mobile devices. It consists of a customized Linux kernel, middleware, and a few core applications such as the Phone application. The middleware, commonly referred to as the Android framework, provides libraries and runtime services to applications. Applications in Android are written mainly in Java. Once compiled, Android transforms its applications into the Dalvik Executable (or DEX) format to minimize the memory footprint. Android uses a Java VM called Dalvik to execute DEX bytecode. Unlike other mobile OSes, Android has a unique permission mechanism. At development time, an application developer needs to explicitly request permissions by including them in an application configuration file. We refer to this configuration file simply as the manifest invthe remainder of the paper. At installation time, each uservneeds to review the permissions that the application requestsvand explicitly grant them.
Few-Node Transient Models

Try this experiment. Fill a ceramic mug with boiling water and immediately grab its side. Close your eyes and concentrate on what it feels like. You’ve just experienced the mug heating phase, the topic of this chapter. In order to observe the separate behavior of the coffee and the mug, the capacitance of the coffee and the mug must be treated separately, creating a 2-node model. The goal of this chapter is to develop a general scheme for doing so. The term “Few-Node Model” is loosely defined as one in which space is discretized into clearly identifiable regions that can be given clear names (as opposed to numbers). In the next chapter, called “multi-node,” space will be discretized into finer elements in a way that there is no clear sense of how many nodes there should be beforehand.
Health impacts of chemical irritants used for crowd control: a systematic review of the injuries and deaths caused by tear gas and pepper spray

Chemical irritants used in crowd control, such as tear gases and pepper sprays, are generally considered to be safe and to cause only transient pain and lacrimation. However, there are numerous reports that use and misuse of these chemicals may cause serious injuries. We aimed to review documented injuries from chemical irritants to better understand the morbidity and mortality associated with these weapons. We conducted a systematic review using PRISMA guidelines to identify injuries, permanent disabilities, and deaths from chemical irritants worldwide between January 1, 1990 and March 15, 2015. We reviewed injuries to different body systems, injury severity, and potential risk factors for injury severity. We also assessed region, context and quality of each included article. We identified 31 studies from 11 countries. These reported on 5131 people who suffered injuries, two of whom died and 58 of whom suffered permanent disabilities. Out of 9261 total injuries, 8.7% were severe and required professional medical management, while 17% were moderate and 74.3% were minor. Severe injuries occurred to all body systems, with the majority of injuries impacting the skin and eyes. Projectile munition trauma caused 231 projectile injuries, with 63 (27%) severe injuries, including major head injury and vision loss. Potentiating factors for more severe injury included environmental conditions, prolonged exposure time, and higher quantities of chemical agent in enclosed spaces. Although chemical weapons may have a limited role in crowd control, our findings demonstrate that they have significant potential for misuse, leading to unnecessary morbidity and mortality. A nuanced understanding of the health impacts of chemical weapons and mitigating factors is imperative to avoiding indiscriminate use of chemical weapons and associated health consequences.
Market orientation research: a qualitative synthesis and future research agenda

The prominence of market orientation as a core organizational concept, as well as recent discussions about its contributions and shortcomings, suggest that it is time to assess the large and expanding body of research surrounding the construct. Our research takes a systematic qualitative approach to assessing extant research on market orientation, identifying problems, patterns, and paradoxes in the literature. Specifically, we provide an integration of the burgeoning empirical research on market orientation, based on a thorough synthesis of articles published over more than 25 years of inquiry. Bringing together the different strands of inquiry that have guided knowledge accumulation on market orientation, we are able to identify major theoretical gaps and omissions in the literature. We also find that while market orientation research has made considerable strides over the years, much work still needs to be done as voids remain that need to be addressed in future investigations.
Inhibition of Mallard salt Gland Function by DDE and Organophosphates

The effects of selected environmental pollutants on avian salt gland function were studied in the mallard duck, Anas pZatyrhynchos. DDE and several organophosphates were found to have an inhibitory effect on the ability of these glands to concentrate and secrete salt from the body. DDE significantly reduced secretion rates from the salt glands. More severe effects were observed following exposure to organophosphate insecticides; reduction in gland size, reduced ability of the birds to secrete Na+ via the salt glands, and reductions in cholinesterase activities in the salt gland and hypothalamus all contributed to elevated mortality levels in treatment birds over controls.
Paravertebral block associated with decreased opioid use and less nausea and vomiting after reduction mammaplasty.

Abstract Background In light of data finding that postoperative pain, nausea, and vomiting worsen outcomes, a renewed emphasis has been placed on optimizing the perioperative period. Use of preoperative paravertebral block (PVB) has been shown to reduce opioid administration and postoperative nausea and vomiting (PONV) in many surgical populations, though its role in reduction mammaplasty remains undefined. Therefore, we seek to evaluate PVB as an adjunct to general anesthesia (GA) for reduction mammaplasty. Materials and methods We reviewed records for patients who underwent reduction mammaplasty at our institution from 2010 to 2015. Patients were categorized into two groups: GA alone and GA + PVB (GA with PVB adjunct). Demographic information, opioid administration, phase I/II pain scores, presence of PONV, and anesthesia time were analyzed. Analysis was performed using t -tests and Fisher's exact test, with P -values less than 0.05 statistically significant. Results We identified 264 patients meeting criteria: 209 (79%) received GA alone and 55 (21%) received GA + PVB. Intraoperative opioid administration were lower for GA + PVB patients (morphine equivalent of 44 mg versus 35 mg, P = 0.019), though there was no difference in postoperative opioid administration ( P = 0.915). Phase I and II pain scores were significantly lower for those receiving PVB (2.9 versus 3.9, P = 0.012, and 3.0 versus 4.2, P = 0.001, respectively). GA + PVB was associated with less PONV (14% versus 33%, P = 0.007) and longer anesthesia times (271 min versus 236 min; P = 0.001). Conclusions By improving pain control and reducing PONV, factors known to be associated with poor patient satisfaction and inferior outcomes, PVB is an attractive anesthetic adjunct in elective breast surgery.
Dermatitis (Contact, Seborrheic, Atopic)

Dermatitis is a nonspecific term encompassing a wide variety of skin conditions characterized by inflammation and erythema. Included in this group are contact dermatitis, seborrheic dermatitis, and atopic dermatitis.
Abstract TP348: Predicting 365 Day Outcomes for Spontaneous Intracerebral Hemorrhage And Intraventricular Hemorrhage Survivors With Poor Outcome on Day 30

Objective: Prediction of long-term functional outcome in spontaneous intracerebral and intraventricular hemorrhage (ICH/IVH) is typically based on a limited number of severity factors known on admi...
Chiral Specificity of Cholesterol Orientation Within Cholesterol Binding Sites in Inwardly Rectifying K+ Channels.

Cholesterol is an integral component of cellular membranes and has been shown to be an important functional regulator for many different ion channels, including inwardly rectifying potassium (Kir) channels. Consequently, understanding the molecular mechanisms underlying this regulation represents a critical field of study. Broadly speaking, cholesterol can mediate ion channel function either directly by binding to specific sites or indirectly by altering surrounding membrane properties. Owing to the similar effects of cholesterol and its chiral isomers (epicholesterol and ent-cholesterol) on membrane properties, comparative analysis of these sterols can be an effective tool for discriminating between these direct and indirect effects. Indeed, this strategy was used to demonstrate the direct effect of cholesterol on Kir channel function. However, while this approach can discriminate between direct and indirect effects, it does not account for the promiscuity of cholesterol binding sites, which can potentially accommodate cholesterol or its chiral isomers. In this chapter, we use docking analyses to explore the idea that the specificity of cholesterol’s effect on Kir channels is dependent on the specific orientation of cholesterol within its putative binding pocket which its chiral isomers cannot replicate, even when bound themselves.
Prediction of flow distribution of vertical upward co-current adiabatic annular flow in 8 × 8 rod bundle

Abstract Annular flow in rod bundle occurs frequently in boiling water reactor (BWR) under normal operation and in pressurized water reactor (PWR) under accident conditions. When annular flow occurs, rod film thickness is one of the most important parameters for safety concern. In order to calculate rod film thickness distribution inside rod bundle, both gas and liquid velocity distribution inside rod bundle is necessary. Also, flow distribution inside rod bundle is of importance for calculation of interfacial shear stress and other parameters in each sub-channel. However, entrained droplets in gas core can sharpen the gas velocity profile while existing rods can flatten the gas velocity profile, making it different from that of single phase flow. The liquid velocity distribution inside rod bundle is hard to obtain from experiment because of the complex structure of its geometry. Due to these reasons, this paper deducts gas and liquid velocity profiles from existing adiabatic rod film thickness data. Even the gas velocity profiles for different flow conditions are different, there exists a gas velocity profile that can be applied to all current flow conditions with minimum uncertainties. Based on that gas velocity profile, liquid velocity profile can be calculated. From these flow velocity profiles, film thickness on each rod and interfacial shear stress in each sub-channel can be calculated.
Improved quantitative contrast-enhanced ultrasound imaging of hepatocellular carcinoma response to transarterial chemoembolization

The purpose of this research project was to improve the quantification of microvascular networks depicted in contrast-enhanced ultrasound (CEUS) images of human hepatocellular carcinoma (HCC). Due to limited anatomical information in CEUS images, grayscale B-mode ultrasound (US) data is preferred when estimating tissue motion. Transformation functions derived from the B-mode data are one solution for registering a dynamic sequence of CEUS images. Microvessel density (MVD) can then be calculated from both the original and motion corrected CEUS images as the ratio of the number of contrast-enhanced image pixels with a value greater than zero to the number of pixels of the entire tumor space. Using US images of HCC before and after treatment with transarterial chemoembolization, results revealed that affine and non-rigid motion correction improves visualization and quantitative analysis of clinical data. Using the correlation coefficient (CC) between CEUS frames as metric of tissue motion, our motion correction strategy produced a 20% increase in the average CC from motion corrected frames compared to the data before correction (p $\lt$ 0.001). Furthermore, enhanced visualization of microvascular networks in the treated liver tumor space may improve determination of treatment efficacy and need for any repeat procedures.
Conclusion: Pragmatism and the Law in the Age of Neuroscience

This book has had a two-fold goal. One is to link a consideration of Oliver Wendell Holmes Jr. to the larger culture of pragmatism, inquiry, and the body politic. This has been the larger part of the book. The second is a consideration of neuroscience and the continuity of the law and science which Holmes represented.
Race, Response to Intervention, and Reading Research:

In this critique, race is centralized to draw attention to the role it plays in the complex evolution of response to intervention, past and present. I use a critical race theory analytical lens to ...
Carcinosarcoma of the endometrium.

Abstract 1. 1. A case of carcinosarcoma of the endometrium has been presented. 2. 2. The finding of rhabdomyoblasts is emphasized as important in establishing the diagnosis.
A mismatch between self-efficacy and performance: Undergraduate women in engineering tend to have lower self-efficacy despite earning higher grades than men

There is a significant underrepresentation of women in many Science, Technology, Engineering, and Mathematics (STEM) majors and careers. Prior research has shown that self-efficacy can be a critical factor in student learning, and that there is a tendency for women to have lower self-efficacy than men in STEM disciplines. This study investigates gender differences in the relationship between engineering students' self-efficacy and course grades in foundational courses. By focusing on engineering students, we examined these gender differences simultaneously in four STEM disciplines (mathematics, engineering, physics, and chemistry) among the same population. Using survey data collected longitudinally at three time points and course grade data from five cohorts of engineering students at a large US-based research university, effect sizes of gender differences are calculated using Cohen's d on two measures: responses to survey items on discipline-specific self-efficacy and course grades in all first-year foundational courses and second-year mathematics courses. In engineering, physics, and mathematics courses, we find sizeable discrepancies between self-efficacy and performance, with men appearing significantly more confident than women despite small or reverse direction differences in grades. In chemistry, women earn higher grades and have higher self-efficacy. The patterns are consistent across courses within each discipline. All self-efficacy gender differences close by the fourth year except physics self-efficacy. The disconnect between self-efficacy and course grades across subjects provides useful clues for targeted interventions to promote equitable learning environments. The most extreme disconnect occurs in physics and may help explain the severe underrepresentation of women in "physics-heavy" engineering disciplines, highlighting the importance of such interventions.
Multiplexed Cre-dependent selection yields systemic AAVs for targeting distinct brain cell types

Recombinant adeno-associated viruses (rAAVs) are efficient gene delivery vectors via intravenous delivery; however, natural serotypes display a finite set of tropisms. To expand their utility, we evolved AAV capsids to efficiently transduce specific cell types in adult mouse brains. Building upon our Cre-recombination-based AAV targeted evolution (CREATE) platform, we developed Multiplexed-CREATE (M-CREATE) to identify variants of interest in a given selection landscape through multiple positive and negative selection criteria. M-CREATE incorporates next-generation sequencing, synthetic library generation and a dedicated analysis pipeline. We have identified capsid variants that can transduce the central nervous system broadly, exhibit bias toward vascular cells and astrocytes, target neurons with greater specificity or cross the blood-brain barrier across diverse murine strains. Collectively, the M-CREATE methodology accelerates the discovery of capsids for use in neuroscience and gene-therapy applications.
The biology of human overfeeding: A systematic review

This systematic review has examined more than 300 original papers dealing with the biology of overfeeding. Studies have varied from 1 day to 6 months. Overfeeding produced weight gain in adolescents, adult men and women and in older men. In longer term studies, there was a clear and highly significant relationship between energy ingested and weight gain and fat storage with limited individual differences. There is some evidence for a contribution of a genetic component to this response variability. The response to overfeeding was affected by the baseline state of the groups being compared: those with insulin resistance versus insulin sensitivity; those prone to obesity versus those resistant to obesity; and those with metabolically abnormal obesity versus those with metabolically normal obesity. Dietary components, such as total fat, polyunsaturated fat and carbohydrate influenced the patterns of adipose tissue distribution as did the history of low or normal birth weight. Overfeeding affected the endocrine system with increased circulating concentrations of insulin and triiodothyronine frequently present. Growth hormone, in contrast, was rapidly suppressed. Changes in plasma lipids were influenced by diet, exercise and the magnitude of weight gain. Adipose tissue and skeletal muscle morphology and metabolism are substantially altered by chronic overfeeding.
The Role of Visioning in Supporting Equitable Spaces

Visioning connects images of what educational stakeholders aim to develop in their respective communities. For educators, visions help to conceptualize how to implement theories and beliefs about s...
Success Factors in Global Product Innovation: An Illustration from the Pharmaceutical Industry

Success in new product development is a critical management issue for many firms in high technology industries. No where is this statement more applicable than for firms in the pharmaceutical industry. This industry remains one of the most profitable among U.S. high technology industries. However, the decades of uninterrupted growth have been replaced by a period of dynamic change and instability brought about by spiralling health care expenditures, heightening generic competition, increasing R&D costs, and shortening patent lives.
A 150 MHz 0.6 /spl mu/m BiCMOS superscalar microprocessor

An implementation of the Pentium microprocessor architecture in 0.6 /spl mu/m BiCMOS technology is described. Power dissipation is reduced and performance is enhanced over the previous generation. Processor features, implementation technology, and circuit techniques are discussed. An internal clock rate of 150 MHz is achieved at 3.7 V and -55/spl deg/C. >
Social Darwinism and Race Consciousness In Japanese-American Relations

The relationship between Japan and the United States began at the same time as social Darwinism became an increasingly dominant paradigm in the social sciences, in the making of public policy, and in the public consciousness. This paradigm is better conceptualized as a corruption of imagination than as an "ideology." Further, this "corruption" has obscured the primary importance both of a zen Buddhist tradition to a proper understanding of Japanese culture, and of a classical philosophical tradition with roots in the works of Plato and Aristotle to a proper understanding of the West in Japan.
Inference of Ancestral Recombination Graphs through Topological Data Analysis

The recent explosion of genomic data has underscored the need for interpretable and comprehensive analyses that can capture complex phylogenetic relationships within and across species. Recombination, reassortment and horizontal gene transfer constitute examples of pervasive biological phenomena that cannot be captured by tree-like representations. Starting from hundreds of genomes, we are interested in the reconstruction of potential evolutionary histories leading to the observed data. Ancestral recombination graphs represent potential histories that explicitly accommodate recombination and mutation events across orthologous genomes. However, they are computationally costly to reconstruct, usually being infeasible for more than few tens of genomes. Recently, Topological Data Analysis (TDA) methods have been proposed as robust and scalable methods that can capture the genetic scale and frequency of recombination. We build upon previous TDA developments for detecting and quantifying recombination, and present a novel framework that can be applied to hundreds of genomes and can be interpreted in terms of minimal histories of mutation and recombination events, quantifying the scales and identifying the genomic locations of recombinations. We implement this framework in a software package, called TARGet, and apply it to several examples, including small migration between different populations, human recombination, and horizontal evolution in finches inhabiting the Galapagos Islands.
The Chrysanthemum versus the Sword in Suicide: Yasunari Kawabata and Yukio Mishima

: Within the last few years, two world-famous Japanese writers have committed suicide. Kawabata represents the chrysanthemum aspect of Japanese culture and resignation-despair. Mishima symbolizes the sword aspect and aggression. Kawabata described loneliness-helplessness and Mishima an ecstasy under the threat of imminent death. Their different childhood experiences produced an “orphan” complex in Kawabata and the problem of sexual identity with an inferiority complex in Mishima. The former sublimated his complex in literature, the latter overreacted to it. For both, an immediate cause of suicide was the conflict between their ideal and the postwar reality. For Mishima, there were also occasions that gave vital blows to his extremely narcissistic temperament.
Prognostics and Health Management of Electronics

In this paper, damage pre-cursors based residual life computation approach for various package elements to prognosticate electronic systems prior to appearance of any macro-indicators of damage has been presented. In order to implement the system-health monitoring system, precursor variables or leading indicators-of-failure have been identified for various package elements and failure mechanisms. Model-algorithms have been developed to correlate precursors with impending failure for computation of residual life. Package elements investigated include, first-level interconnects, dielectrics, chip interconnects, underfills and semiconductors. Examples of damage proxies include, phase growth rate of solder interconnects, intermetallics, normal stress at chip interface, and interfacial shear stress
‘Eat squid not fish’: poetics, aesthetics, and HIV/AIDS in Tanzania

This paper explores and compares musico-poetic perspectives on HIV/AIDS in Tanzania during the early stages of the epidemic (1990–1995). Popular song, poetry, and theatre constitute the raw data of an analysis that highlights epistemological misunderstandings and disjunctures between (1) biomedical discourses about the disease as forwarded by non-governmental organizations and public health officials, and (2) local discourses that ground the epidemic in intensely social concerns. This requires us to query the deployment of popular culture in activist agendas, the underlying assumptions about ‘popular culture’ held by culture brokers in these endeavours, and the role of aesthetics in assisting or arresting attempts to appropriate art forms for ideological purposes. This essay adds to the literature on cultural confrontations in AIDS interventions, and extends it by considering how aesthetic form can impose semantic limits.
Quo Vadis, Specificity?

Mutations in cancer cells can give rise to tumor-specific antigens, but abnormal processing of normal molecules in these cells can also elicit an immune response.
Investigation and Early Treatment of Acute Stroke

BACKGROUND: Stroke is defined by sudden loss of brain function due to interference to the blood supply of the brain or from compression of the brain related to intracerebral or subarachnoid hemorrhage. It is important to recognize that appropriate evaluation and management of patients with stroke can reduce the associated morbidity and risk of recurrence. METHODS: We review the guidelines for management of patients with ischemic stroke, intracerebral and subarachnoid hemorrhage provided by American Heart Association. We provide a concise account of the general principles of evaluation and management of patients who present with acute stroke. RESULTS: Since the availability of thrombolytic therapy, it is important to screen all patients with acute stroke for eligibility to receive intravenous (or intraarterial) thrombolysis. Familiarity to mandatory aspects about history, neuroimaging, and laboratory work-up is helpful in expedient decision-making. Appropriate diagnostic tests are important to detect an underlying predisposing condition that can result in recurrent ischemic events. Depending upon the predisposing condition long-term antiplatelet or antocoagulant therapy can reduce the risk of recurrence. CONCLUSION: Efforts directed towards appropriate evaluation and management of patients with acute stroke can reduce the associated morbidity and risk of recurrence.
A skew-symmetric form of the recursive Newton-Euler algorithm for the control of multibody systems

We derive a form of the recursive Newton-Euler algorithm that satisfies the skew-symmetry property M/spl dot/-2C=-(M/spl dot/-2C)/sup T/ required in a variety of nonlinear control laws occurring throughout the field of multibody dynamics. We show that the recently developed formulation of multibody dynamics based on Lie groups can be modified to accommodate the skew-symmetry requirement. Specifically, we demonstrate that explicit block-triangular factorizations of both M and C are embedded within the structure of the recursive algorithm. Furthermore, the factorization of the mass matrix M can be differentiated explicitly with respect to time. The resulting expressions for M, M/spl dot/, and C immediately lead to a proof based entirely on high-level matrix manipulations demonstrating the skew-symmetry of M/spl dot/-2C.
Properties and Food Uses of Duck Eggs

Abstract INTRODUCTION INDEPENDENT findings of two laboratories, Bose and Mahadevan (1956) and Rhodes and Feeney (1957), have demonstrated that duck eggs are much more resistant to deterioration than chicken eggs. In addition, some breeds of ducks, such as the Khaki Campbell, compare favorably with the chicken as to size and to rate of production of eggs. These facts have suggested the need for further comparisons of duck eggs and chicken eggs. Although ducks have been raised in the United States for many years and their eggs used to a certain degree for food, little technical information concerning their use as food appears to be available. Bose and Mahadevan (1956) stated that in India duck eggs could be substituted successfully for chicken eggs when they were hard boiled, fried, poached, or scrambled. Also the duck egg yolk was reported to be as satisfactory as the chicken egg yolk in cookery. However, the …
Between Apprehension and Support: Social Dialogue, Democracy, and Industrial Restructuring in Central and Eastern Europe

This article explores the attitudes of trade union organizations to restructuring and privatization of their enterprises to strategic foreign investors in Central and Eastern Europe's biggest steel producers: Poland, Czech Republic, Romania, and Slovakia. Contrary to advocates of insulating technocratic decision-makers from social partners, this article argues that higher quality of democracy and concomitant social dialogue carried out at the level of the sector with union organizations that are autonomous of the government in power (as was the case in the Czech Republic and Poland), are associated with greater restructuring and with support for privatization to strategic foreign investors. In these circumstances, the unions actually pressure reluctant governments to accelerate the privatization process. By contrast, politically motivated capture of individual enterprise-level unions and splitting them from sectoral-level organizations, as occurred in countries with lower quality of democracy (Romania and Slovakia), weakens the autonomous sectoral-level organizations, which are generally supportive of restructuring. Conversely, captured unions remain far more resistant to reform than their counterparts belonging to autonomous sectoral organizations. Thus, higher quality of democracy and concomitant vibrant social dialogue safeguard industrial restructuring.
The Relationship of Nocturnal Melatonin to Estradiol and Progesterone in Depressed and Healthy Pregnant Women

Abstract Purpose: To assess the relationship between nocturnal plasma melatonin and serum estradiol (E2) and progesterone (P4) levels in depressed pregnant women (DW) and matched healthy women (HW). Methods: We used analysis of variance (ANOVA) and linear regression analyses on data obtained from pregnant HW and DW. Results: Log E2 and log P4 were positively correlated with measures of melatonin quantity in HW (p<0.05) but not DW, controlling for age. Log E2 and log P4 were positively correlated with melatonin offset and duration in DW (p<0.01) but not HW. Conclusions: Pregnant DW may be less sensitive than HW to modulation of melatonin secretion by E2 and P4. That melatonin timing measures are more sensitive to E2 and P4 variation in DW may reflect a circadian system more attuned to the need for realignment in DW than in HW. These altered sensitivities to reproductive hormones may reflect a biologic vulnerability that predisposes some pregnant women to depression.
Hexamethylene diisocyanate (HDI) vapor reactivity with glutathione and subsequent transfer to human albumin.

Abstract Introduction Airway fluid glutathione (GSH) reactivity with inhaled vapors of diisocyanate, a common occupational allergen, is postulated to be a key step in exposure-induced asthma pathogenesis. Methods A mixed (vapor/liquid) phase exposure system was used to model the in vivo reactivity of inhaled HDI vapor with GSH in the airway fluid. HDI–GSH reaction products, and their capacity to transfer HDI to human albumin, were characterized through mass spectrometry and serologic assays, using HDI-specific polyclonal rabbit serum. Results HDI vapor exposure of 10 mM GSH solutions resulted in primarily S-linked, bis(GSH)–HDI reaction products. In contrast, lower GSH concentrations (100 μM) resulted in mainly mono(GSH)–HDI conjugates, with varying degrees of HDI hydrolysis, dimerization and/or intra-molecular cyclization, depending upon the presence/absence of H 2 PO 4 − /HPO 4 2− and Na + /Cl − ions. The ion composition and GSH concentration of the fluid phase, during HDI vapor exposure, strongly influenced the transfer of HDI from GSH to albumin, as did the pH and duration of the carbamoylating reaction. When carbamoylation was performed overnight at pH 7, 25 of albumin’s lysines were identified as potential sites of conjugation with partially hydrolyzed HDI. When carbamoylation was performed at pH 9, more rapid (within 3 h) and extensive modification was observed, including additional lysine sites, intra-molecular cross-linkage with HDI, and novel HDI–GSH conjugation. Conclusions The data define potential mechanisms by which the levels of GSH, H 2 PO 4 − /HPO 4 2− , and/or other ions (e.g. H + /OH − , Na + , Cl − ) affect the reactivity of HDI vapor with self-molecules in solution (e.g. airway fluid), and thus, might influence the clinical response to HDI respiratory tract exposure.
How to misidentify a type specimen

Type specimens are used to designate species. What is the nature of the relation between a type specimen and the species it designates? If species names are rigid designators, and type specimens ostensively define species, then that relation is, at the very least, a close one. Levine (Biol Philos 16(3):325–338, 2001) argues that the relationship of type specimen to a named species is one of necessity—and that this presents problems for the individuality thesis. Namely, it seems odd that a contingently selected specimen should belong to a species of necessity. In considering Levine’s argument, LaPorte (Biol Philos 18:583–588, 2003) suggests that recognizing the distinction between de re and de dicto necessity resolves Levine’s worries. I reconsider the motivating question: does a type specimen belong of necessity to the species that it designates? In light of taxonomic cases and practice the answer is clear: definitively not. This is particularly clear in the case of re-designation of types by taxonomic decree. I explain how this helps reveal how taxonomists prioritize competing (and sometimes conflicting) theoretical commitments, and offer a defense of the individuality thesis as applied to these particular cases. In short, I demonstrate how to misidentify a type specimen.