cssi/SciSciGPT-SciSciNet huggingface dataset:
Extemporaneous preparation strategy for early phase clinical studies.

Abstract Extemporaneous preparations (EPs) of investigational drugs, which are compounded at the clinical study site by a pharmacist, are being increasingly used in early phase clinical studies to accelerate the development of new medicines. The successful application of EP strategies in clinical studies requires ‘fit-for-purpose’ formulation design and preparation processes, as well as administration procedures that are safe, flexible, cost-effective, and simple to adapt by a compounding pharmacist at the clinical site. DNS-7801 is a weakly basic investigational compound that exhibits a higher aqueous solubility at lower pH with its solubility dropping off precipitously with increase in pH. This phenomenon is known to result in potential risk of variable and decreased exposure in vivo. Combination of citrate buffer at pH 3.0 and hydroxypropylbetadex enabled formulation of DNS-7801 solutions that were stable as formulated and up on manipulation for oral administration. The solutions were compatible with apple juice, used to mask (blind) the potential taste differences between the placebo and DNS-7801 solutions when dosing study subjects. The oral administration of the solutions resulted in dose proportional Cmax, AUC0-24, and AUC0–∞ of DNS-7801 in non-elderly and elderly subjects. A key advantage of the use of an EP approach with DNS-7801 was the flexibility in dose selection that this approach offered because DNS-7801 concentration in the preparation and/or volume could be readily adjusted based on real-time cohort data.
Classic papers in natural resource economics revisited

This book is an excellent compendium of classic papers in the field of natural resource economics, spanning the period 1930 to 2015, along with original papers by scholars in the field commenting o...
Cytomegalovirus Colitis in Primary Hypogammaglobulinemia With Normal CD4+ T Cells: Deficiency of CMV-Specific CD8+ T Cells.

CMV colitis has been reported in immunocompromized patients with severe deficiency of CD4+ T cells and T cell functions. In this study we present an extensive immunological analysis in a patient with primary hypogammaglobulinemia and CMV colitis who had normal numbers of CD3+T, CD4+T and CD8+T cells, and normal T cell proliferative responses to mitogens and recall antigens. Naive (TN), central (TCM), and effector (TEM) memory subsets of CD4+ and CD8+ T cells, Granzyme+ and Perforin+ CD8+ T cells, PD-1+ T cells, CD4 Treg, CD8 Treg, and CMV tetramer specific CD8+ T cells were analyzed with specific antibodies and isotype controls using multicolor flow cytometry. CD8 TEM, Granzyme+ and Perforin+, and PD-1 CD8+T cells were increased, whereas CD8 TN and CD8 TCM cells were decreased in the patient as compared to controls. CMV tetramer+ CD8+ T cells were decreased in the patient. These data demonstrate that a deficiency of CMV-specific CD8+ T cells even in the presence of normal CD4+ T cell numbers and normal T cell functions may predispose patients with primary hypogammaglobulinemia to CMV colitis.
Biclonal splenic marginal zone lymphoma with T cell-rich background and aggressive transformation to large cell lymphoma

Marginal zone B cell lymphomas (MZL) are biologically heterogeneous, rarely demonstrating biclonality, complex cytogenetic abnormalities, or T cell predominance. We report a case of biclonal splenic MZL, T cell-rich variant with an abnormal karyotype that progressed to large B cell lymphoma. A 74-year-old female presented with pancytopenia, weight loss, fever, and splenomegaly. Microscopically, the spleen revealed an extensive, vaguely nodular lymphoid proliferation, composed of small lymphocytes, majority of which were reactive T cells. B cells were mostly small and < 5% of total lymphocytes. Focal follicular dendritic cell networks were present, but germinal centers were absent. Flow cytometric analysis revealed two distinct CD5 and CD10 negative B cell clones, one kappa positive and one lambda positive. Conventional cytogenetic analysis revealed the following abnormal karyotype: 47,XX,add(7)(q36),del(7)(q22),add(21)(p11.2),+mar[10]/46,XX[10]. Immunoglobulin heavy chain gene rearrangement showed two monoclonal peaks of different magnitude, consistent with biclonality. Overall, these features favored a low-grade splenic MZL. The staging bone marrow biopsy was normocellular with few interstitial lymphoid aggregates, composed of small lymphocytes, consistent with minimal involvement by low-grade B cell lymphoma. The patient improved without adjuvant chemotherapy; however, 12 months later, she developed anemia and lymphocytosis. Subsequent bone marrow biopsy showed extensive involvement by a large B cell lymphoma and complex karyotype with the previously identified abnormalities, as well as additional numerical and structural aberrations, consistent with cytogenetic evolution and biclonal gene rearrangement. These findings were consistent with transformation. This case demonstrates a unique pathological presentation of splenic MZL with disease progression, highlighting the importance of an integrated approach for lymphoma classification and the difficulties in diagnosing such cases.
Gender Moderates Chronic Nicotine Cigarette Effects on Verbal Memory in Young Adults

Background: Rates of nicotine use remain a prominent public health concern, especially among young adults. Previous findings have demonstrated that chronic exposure to nicotine during adolescence may be linked to various neurocognitive deficits. Nicotine differentially affects the brain by gender. Objectives: The present study investigated the effects of gender and chronic nicotine use on cognition in the developing brain. Methods: From 2008 to 2011, 57 young adult (ages 18-25) participants were recruited as part of a larger cross-sectional neuroimaging study and divided into 21 nicotine users (12 female) and 36 non-using controls (17 female). Participants completed various questionnaires, drug use interview, neuropsychological battery, and MRI scan in a university setting. A series of multiple regressions was conducted with nicotine group and gender*nicotine group interaction as predictors. Results: After controlling for gender, nicotine group status alone was not associated with neuropsychological performance. A gender x nicotine interaction was significantly associated with performance on trial 1, short delay free recall, and long delay free recall of the CVLT-II. Female smokers demonstrated better performance on trial 1 and short and long delay free recall than female controls. Male smokers performed more poorly than male controls on short and long delay free recall. Conclusions: These preliminary findings suggest that cognitive effects of chronic nicotine use are moderated by gender. Further research is needed to determine causality, and identify underlying brain structures and function that may be responsible for differences in verbal memory.
Steady-State Activation and Modulation of the Concatemeric α1β2γ2L GABAA Receptor.

The two-state coagonist model has been successfully used to analyze and predict peak current responses of the γ-aminobutyric acid type A (GABAA) receptor. The goal of the present study was to provide a model-based description of GABAA receptor activity under steady-state conditions after desensitization has occurred. We describe the derivation and properties of the cyclic three-state resting-active-desensitized (RAD) model. The relationship of the model to receptor behavior was tested using concatemeric α1β2γ2 GABAA receptors expressed in Xenopus oocytes. The receptors were activated by the orthosteric agonists GABA or β-alanine, the allosteric agonist propofol, or combinations of GABA, propofol, pentobarbital, and the steroid allopregnanolone, and the observed steady-state responses were compared with those predicted by the model. A modified RAD model was employed to analyze and describe the actions on steady-state current of the inhibitory steroid pregnenolone sulfate. The findings indicate that the steady-state activity in the presence of multiple active agents that interact with distinct binding sites follows standard energetic additivity. The derived equations enable prediction of peak and steady-state activity in the presence of orthosteric and allosteric agonists, and the inhibitory steroid pregnenolone sulfate. SIGNIFICANCE STATEMENT The study describes derivation and properties of a three-state resting-active-desensitized model. The model and associated equations can be used to analyze and predict peak and steady-state activity in the presence of one or more active agents.
Differential Expression of a Classic Cadherin Directs Tissue-Level Contractile Asymmetry during Neural Tube Closure.

Summary Embryos control force generation at tissue boundaries, but how they do so remains poorly understood. Here we show how tissue-specific expression of the type II cadherin, Cadherin2, patterns actomyosin contractility along tissue boundaries to control zippering and neural tube closure in the basal chordate, Ciona robusta. Cadherin2 is differentially expressed and homotypically enriched in neural cells along the neural/epidermal (Ne/Epi) boundary, where RhoA and myosin are activated during zipper progression. Homotypically enriched Cadherin2 sequesters the Rho GTPase-activating protein, Gap21/23, to homotypic junctions. Gap21/23 in turn redirects RhoA/myosin activity to heterotypic Ne/Epi junctions. By activating myosin II along Ne/Epi junctions ahead of the zipper and inhibiting myosin II along newly formed Ne/Ne junctions behind the zipper, Cadherin2 promotes tissue-level contractile asymmetry to drive zipper progression. We propose that dynamic coupling of junction exchange to local changes in contractility may control fusion and separation of epithelia in many other contexts.
Why the WTO Adjudicatory Crisis Will Not Be Easily Solved: Defining and Responding to “Judicial Activism”

The World Trade Organization (WTO) adjudicatory crisis, namely, the specific blockage over the approval of candidates to fill vacancies on the Appellate Body, and general impasse over changes to the Agreement on Rules and Procedures Governing the Settlement of Disputes (DSU), will not be resolved easily or quickly. There is a mismatch between the (1) proposals to reform Appellate Body and DSU reform proposals, and (2) central criticisms the United States raises. America arguments are about the right way to interpret disputed texts in a trade treaty, and about the right weight to give prior decisional rulings. None of the reform proposals raised by the European Union (EU) or Canada, squarely address America’s arguments. The Euro-Canadian suggestions are about procedures, whereas America challenges foundations of multilateral trade adjudication.
H+-ATPase-mediated cytoplasmic pH-responses associated with elevation of cytoplasmic calcium in cultured rabbit nonpigmented ciliary epithelium.

Studies were conducted to test whether an increase of cytoplasmic calcium concentration influences H+-ATPase activity in cultured rabbit nonpigmented ciliary epithelium (NPE). Cytoplasmic calcium concentration or cytoplasmic pH was measured by a fluorescence ratio technique in cells loaded with either Fura-2 or BCECF. Cytoplasmic calcium was increased in three ways; by exposure to BAY K 8644 (1 μm), by exposure to a mixture of epinephrine (1 μm) + acetylcholine (10 μm) or by depolarization with potassium-rich solution. In each case cytoplasmic pH increased significantly. In all three cases 100 nm bafilomycin A1, a specific H+-ATPase inhibitor, significantly inhibited the pH increase. These results suggest an increase of cytoplasmic calcium might initiate events that lead to activation of proton export from the cytoplasm by a mechanism involving H+-ATPase. This notion is supported by the observation that the pH increase was suppressed when either verapamil or nifedipine was used to prevent the cytoplasmic calcium increase in cells exposed to potassium-rich solution. Protein kinase C activation might also be involved in the mechanism of H+-ATPase stimulation since staurosporine suppressed the pH response to potassium-rich solution. A transient rise of cytoplasmic calcium concentration was observed when cytoplasmic acidification was induced by exposure to high pCO2. This suggests a rise of cytoplasmic calcium might represent part of a physiological mechanism to stimulate H+-ATPase-mediated protein export under acid conditions.
Mate Choice: Should I Mate or Should I Go?

Summary A mature virgin female fruit fly will initially resist copulation, while she assesses the desirability of her suitor. A new study identifies a neural circuit that controls rejection and shows how it changes from rejection to acceptance and copulation.
Transitioning from global to local computational strategies during brain-machine interface learning

When learning to use a brain-machine interface (BMI), the brain modulates neuronal activity patterns, exploring and exploiting the state space defined by their neural manifold. Neurons directly involved in BMI control can display marked changes in their firing patterns during BMI learning. However, whether these changes extend to neurons not directly involved in BMI control remains unclear. To clarify this issue, we studied BMI learning in animals that were required to control the position of a platform with their neural signals. Animals that learned to control the platform and improved their performance in the task shifted from a global strategy, where both direct and indirect neurons modified their firing patterns, to a local strategy, where only direct neurons modified their firing rate, as animals became expert in the task. These results provide important insights into what differentiates successful and unsuccessful BMI learning and the computational mechanisms adopted by the neurons.
Transtornos de ansiedade em mulheres: gênero influencia o tratamento?

Mulheres apresentam um risco significativamente maior comparado com o dos homens para o desenvolvimento de transtornos de ansiedade ao longo da vida. Alem disso, diversos estudos sugerem maior gravidade de sintomas, maior cronicidade e maior prejuizo funcional dos transtornos de ansiedade entre as mulheres. Apesar disso, os motivos que levam a este aumento de risco no sexo feminino sao ainda desconhecidos e precisam ser adequadamente investigados. Varios estudos apresentam evidencias de que, entre as provaveis causas dessa diferenca entre os sexos, estao os fatores geneticos e a influencia exercida pelos hormonios sexuais femininos. As diferencas de genero encontradas nos transtornos de ansiedade em relacao ao inicio e a evolucao da doenca indicam que e necessario investigar a necessidade de tratamentos diferenciados para homens e mulheres. Entretanto, as evidencias de que as diferencas de genero modifiquem a resposta ao tratamento dos transtornos ansiosos ainda sao inconsistentes e amplamente inconclusivas. Este artigo procura rever a literatura existente a respeito da prevalencia, epidemiologia e fenomenologia dos transtornos ansiosos entre as mulheres e as implicacoes destas peculiaridades para a melhor eficacia no seu tratamento.
An updated review of the epidemiological factors associated with recurrent respiratory papillomatosis.

Objectives To identify studies evaluating the epidemiology of recurrent respiratory papillomatosis (RRP), including patient demographics, human papillomavirus (HPV) immunology, clinical course, surgical and medical treatments, and psychosocial factors. Methods A systematic literature search through PubMed was performed to identify studies evaluating the epidemiological factors associated with RRP. All studies were screened through a priori selection criteria using the titles and abstracts. Results A total of 208 studies were identified, of which 54 met eligibility criteria and were included in the review. Conclusions RRP is a rare disease most commonly caused by HPV 6 and 11. It is characterized by recurring benign papillomatous lesions in the respiratory tract, particularly the larynx. Existing evidence about disease risk factors is limited but includes both maternal HPV infection and patient smoking and sexual behaviors. Disease management involves a combination of routine surgical and medical treatment. Surgical techniques include CO2-laser, sharp dissection, coblation, microdebridement, and photoangiolytic laser. Medical treatments which have been found to facilitate disease control off-label include interferon-alpha (IFN-α), indole-3-carbinol, acyclovir, bevacizumab, retinoids, and the Gardasil and mumps vaccines. Many patients suffer from additional psychosocial challenges related to their diagnosis. Current disease knowledge remains limited, and more robust controlled trials about risk factors, medical therapies, and surgical options are needed. Level of evidence 5.
Criminal Choice in Sentencing

Courts have long relied on the experience and expertise of judges to craft criminal sentences. Unfortunately, judge-based sentencing is systematically inefficient for two reasons. First, despite the key roles played by an individual’s preferences, capabilities, and future expectations in the calculation of an efficient sentence, offenders cannot credibly convey encouraging information to judges. Offenders of all stripes have overwhelming incentives to mimic the “best” offenders, those most likely to receive the least severe sentences, and they can generally do so at low cost. Second, even if offenders are sometimes able to credibly convey promising future prospects, judges have limited time, energy, and resources to evaluate this information and are subject to cognitive and behavioral biases. As a result, judges know far too little to fashion sentences that will efficiently minimize social harm. Fortunately, and remarkably, sentencing efficiency can be enhanced under some circumstances by removing judges from the process altogether. Rather than attempt to improve the quantity and quality of a judge’s information stock, the offender would simply choose his sentence from a carefully limited set of options, taking into account his preferences, capabilities, and future expectations. A choice-based regime works by requiring that criminals select from a “menu” of sentencing options structured by the government to “screen” for nonverifiable data essential to constructing their optimal sentences. A well-designed set of options can result in sentences that are closer to what society would prefer.
The HOLC Maps: How Race and Poverty Influenced Real Estate Professionals’ Evaluation of Lending Risk in the 1930s

During the late 1930s, the Home Owners’ Loan Corporation (HOLC) developed a series of area descriptions with color-coded maps of cities that summarized mortgage lending risk. We provide evidence that these maps were not the primary source used by the FHA to create their “redlining” maps for insuring mortgages. Instead, the HOLC maps provide a unique snapshot of how real estate professionals perceived lending risk in the 1930s. These perceptions were shaped by a wide range of factors including race, income, and housing quality. We use the maps to explore the mechanisms behind the prevalence of black residents in the lowest-rated neighborhoods. Our results suggest that racial bias in the construction of the HOLC maps can explain at most 4 to 20 percent of the observed concentration of black households in the lowest-rated zones. Instead, our results suggest that the majority of black households were located in such zones because decades of disadvantage and discrimination had already pushed them into the core of economically distressed neighborhoods prior to the federal government’s involvement in mortgage markets. Institutional subscribers to the NBER working paper series, and residents of developing countries may download this paper without additional charge at www.nber.org.
Culture and Style in Extended Discourse

This paper will propose a method for analyzing extended discourse, with sample analyses from Hidatsa, a Siouan language spoken in North Dakota. There are several lines of investigation which might lead one to analyze extended discourse. One such line of investigation is a direct continuation of descriptive linguistics: Descriptive linguistics yields statements about the occurrence of morphemes, words, and the like within a sentence. That is to say, it states how the occurrence of one class of morphemes (or words) is restricted in terms of the occurrence of some other class of morphemes (or words) within the same sentence. Having obtained this result, one might readily ask how the occurrence of one sentence is restricted in terms of the occurrence of other sentences within the larger discourse. It is clear that there is some restriction of this kind; for if we stop short in the course of any text, for example at the end of the present sentence in this paper, the pro-bability that certain particular English sentences will occur next is greater than the probability that certain others will occur. (It is more probable that the next sentence here would contain certain linguistic terms, or English learned words, or that it should have assertion-intonation and be of con-siderable length, than that it should contain names of automobiles, or specifically colloquial words, or that it should have exclamation-intonation and be short. This has indeed just been the case.) Nevertheless, it has not in general been possible to state how the occurrence of one sentence is re-stricted in terms of the occurrence of another within the larger discourse. Attempts to find regular sequences of particular sentence types within a text have generally been unsuccessful.
Security infrastructure for commercial and military ports

Battelle has been developing robust detection and scanning technologies that integrate with existing and future port security systems as part of overall integrated security networks that can be tailored to meet individual requirements for commercial ports or Navy facilities. Major challenges include the water side issues such as geography, bathymetry, channel dimensions, changing bottom topology, environmental conditions, operation under all conditions and sea states suitable for vessel and small craft operation, harbor arrangement, and port-specific unique threats. However, many port security systems develop and implement new sensor technologies rather than assess the overall security need—that is, they follow a technology push rather than a market pull approach. While stated security approaches may integrate sensor data, stored data, intelligence databases, and human observations in various forms and formats, they generally do not provide the port-specific vulnerability and threat information required to alert security personnel with an integrated, composite threat analysis. Most approaches depend upon real-time person-in-the-loop detection strategies that can falter when faced with real world constraints: limited personnel resources, human fatigue and error, distractions, and misinterpretation of anomalies. Statistical and probabilistic analyses for anomaly identification are necessary to provide viable potential threat solution sets.
Improving traffic estimation and prediction through dynamic traffic assignment development

The FHWA R&D initiated a dynamic traffic assignment (DTA) research project in 1994 to meet these data needs and to address complex traffic control and management issues in the information-based, dynamic ITS environment. Under this project, Oak Ridge National Laboratory (ORNL) was designated as the manager for the development of a deployable, real-time traffic estimation and prediction system (TrEPS) as well as an offline, planning version (TrEPS-P). In October 1995, two contracts were awarded to teams from the University of Texas at Austin (UTX) and the Massachusetts Institute of Technology (MIT) to develop these systems for use in ITS environments. To date, four sets of products have been developed, laboratory experiment completed, and the systems are being deployed.
Optimal investment and consumption models with non-linear stock dynamics

We study a generalization of the Merton's original problem of optimal consumption and portfolio choice for a single investor in an intertemporal economy. The agent trades between a bond and a stock account and he may consume out of his bond holdings. The price of the bond is deterministic as opposed to the stock price which is modelled as a diffusion process. The main assumption is that the coefficients of the stock price diffusion are arbitrary nonlinear functions of the underlying process. The investor's goal is to maximize his expected utility from terminal wealth and/or his expected utility of intermediate consumption. The individual preferences are of Constant Relative Risk Aversion (CRRA) type for both the consumption stream and the terminal wealth. Employing a novel transformation, we are able to produce closed form solutions for the value function and the optimal policies. In the absence of intermediate consumption, the value function can be expressed in terms of a power of the solution of a homogeneous linear parabolic equation. When intermediate consumption is allowed, the value function is expressed via the solution of a non-homogeneous linear parabolic equation.
Differences in perceptions of parental and personal characteristics between generalized and nongeneralized social phobics

Abstract Perceptions of generalized social phobics, nongeneralized social phobics, and nondisordered controls regarding their parents' childrearing attitudes and their own adolescent experience were compared. Generalized social phobics perceived one or both parents as having isolated them from others and having promoted less socialization of the family with others compared to other subjects. In contrast to controls, generalized and nongeneralized social phobics perceived their parents as placing undue importance of the opinions of others and as using shame as a means of discipline. Generalized, compared to nongeneralized, social phobics evidenced more pervasive symptoms of shyness (e.g., reported that they were more labeled as shy by others, dated less frequently, etc.) during adolescent years, although the patient groups did not differ in the age of onset of feelings of shyness. Both patient groups were high in public self-consciousness in contrast to controls, who achieved scores comparable to norm groups. Subtype differences remained after controlling for initial level of clinical impairment.
Critical Metals Handbook (Gus Gunn, ed.)

Critical Metals Handbook. Gus Gunn, Editor. 2014. John Wiley and Sons, Ltd., West Sussex, United Kingdom. 439 Pp. ISBN 978-0-470-67171-9 (hardcover). Price $149.95. (Also available as e-book for $119.99). The growing global economy, with developments of new technologies and national defense systems, has placed an increased importance on the so-named critical metals. There is a lack of general consensus on specifically what group of elements comprise those best defined as “critical” and are thus at greatest risk due to volatility in the global supply chain. The new volume, Critical Metals Handbook , published mainly under the direction of the British Geological Survey and edited by Gus Gunn, uses the criticality index of the 2010 European Commission to select the metals described in this book. The volume is divided into three introductory chapters and then 13 chapters that focus on a variety of critical metals, which are authored by an excellent collection of experts on the various metals. The chapters on the metals include material on their physical and chemical properties, mineralogy, geology and, most particularly, their economic issues. The initial chapter of the volume by Graedel et al. introduces the key concepts of mineral resources and criticality to what will likely be a broad readership. It points out problems and issues inherent to resource estimates and reserve calculations, particularly for the less well known deposit types and mineral commodities. As the critical metals are mainly by-products from the mining of major metals, the economics of their recovery is complex and their degree of criticality is shown to reflect fluctuations in supply and demand. Among those critical metals or “coupled” metals (i.e., the rare earth elements [REE] and the platinum group metals) selected for study in this volume are the 12 metals with a calculated supply risk >1.0; these metals include Be, Co, Ga, Ge, In, Mg, Nb, platinum group metals [PGM], REE, Sb, Ta, and W. In addition, there are chapters focused on Li and Re. Other critical commodities …
Endogenous feline (RD-114) and baboon type C viruses have related specific RNA-binding proteins and genome binding sites.

Abstract The major structural phosphoproteins (p16) purified from the endogenous cat type C virus (RD-114) and from independent isolates of endogenous baboon type C viruses bind to viral RNAs purified from these viruses but not from other groups of mammalian or avian type C viruses. The specific RNA-binding function of the viral phosphoproteins as well as their binding sites on the viral RNA genomes appear to have been evolutionarily conserved even though the baboon and cat type C viruses have been genetically transmitted in two different mammalian orders.
Accuracy of Self-reported Weight Among Bariatric Surgery Candidates: The Influence of Race and Weight Cycling

Objective: Research on the accuracy of self-reported weight has indicated that the degree of misreporting (underestimating) weight is associated with increasing weight but is variable across patient groups. We examined the degree of discrepancy between actual and self-reported BMI in severely obese bariatric surgery candidates, and whether the degree of accuracy varied by race and by eating-related and psychological factors. Research Methods and Procedures: Participants were 179 obese female gastric bypass surgery candidates (31 black, 22 Hispanic, 126 white) who were asked to self-report height and weight as part of a larger assessment battery. Actual height and weight were then measured and a discrepancy score was generated (actual BMI − reported BMI). Results: In this group of severely obese patients, degree of misreporting was unrelated to BMI. The race groups did not differ in actual or self-reported BMI but differed significantly in the degree of misestimation between self-reported and actual BMI. Post hoc tests indicated that black women underestimated their BMI significantly more than white women; Hispanic women did not differ from the other race groups. No eating-related or psychological variables assessed predicted percentage discrepancy; however, the accuracy in self-reported weight was related to history of weight cycling. Discussion: Overall, obese bariatric surgery candidates were accurate in self-report of weight, although the degree of accuracy differed by race and weight cycling history.
Framatome operating transients monitoring system used for equipment mechanical surveillance

Abstract Detailed understanding of the evolution of equipment ageing is a key factor in plant life assessment. The aim of the system described in the present paper is real time assessment of the structural damage in power plant main components. The Framatome Operating Transients Monitoring System (OTMS) comprises a computer which accesses existing plant instrumentation to provide data logging; OTMS software is designed to record actual operating conditions and perform structural analysis. The structural analysis consists first of real time stress calculation. From the stress history, the OTMS can derive a fatigue usage factor and a transient logging based on a fatigue damage equivalence concept. It can compute crack propagation and assess crack stability. Results from this analysis and their interpretations are very advantageous for making decisions concerning plant operation, inspection, maintenance, repair and replacement of equipment.
CHARACTERIZATION OF THE MOLECULAR BASIS FOR PMN DYSFUNCTION & RECURRENT INFECTION IN THE GP-138 DEFICIENCY SYNDROME

CHARACTERIZATION OF THE MOLECULAR BASIS FOR PMN DYSFUNCTION & RECURRENT INFECTION IN THE GP-138 DEFICIENCY SYNDROME
DNA polymerase from maize seedlings.

Abstract 1. A protein fraction which promotes the incorporation of deoxyribonucleotides into acid-insoluble product has been extracted and partially purified from young maize seedlings ( Zea mays L.). The characteristics of this enzyme are analogous to those of DNA polymerases (deoxyribonucleosidetriphosphate: DNA deoxyribonucleotidyltransferase, EC 2.7.7.7) isolated from other organisms. The bulk of the activity was recovered in the supernatant fraction of a seedling homogenate after centrifugation at 105 000 × g and was precipitated from (NH 4 ) 2 SO 4 solution between 40 and 50% saturation. Chromatography of the solubilized precipitate on DEAE-cellulose resulted in a preparation which incorporated 100 pmoles dAMP/min per mg of protein into acid-insoluble product. 2. DNA polymerase activity depended upon the simultaneous presence of dATP, dCTP, dGTP, dTTP, DNA and Mg 2+ . The rate of formation of the acid-insoluble product was 2–4-fold greater with heat-denatured DNA than native DNA. All species of DNA tested effectively promoted product formation. Incorporation of deoxyribonucleotides was linear with time for at least 1 h of incubation at 30° and was first order with respect to enzyme concentration. The optimal pH was 8.4 in Tris-HCl and 8.8 in glycine-NaOH. 3. The product of the reaction was insoluble in acid, ethanol and ether. It was hydrolyzed by pancreatic deoxyribonuclease and was resistant to the action of pancreatic ribonuclease. The incorporation of each of the four deoxyribonucleotides into the product was a function of the base composition of native DNA. With heat-denatured DNA, the incorporation of dAMP was increased relative to the other deoxyribonucleotides.
Mode of action of acyclovir triphosphate on herpesviral and cellular DNA polymerases

The effect of 5'-triphosphate of acyclovir (ACV) on DNA polymerases of two human herpes-viruses, herpes simplex virus type-1 (HSV-1) and Epstein-Barr virus (EBV) as well as human cellular DNA polymerases alpha and beta has been examined. Of the enzymes tested, HSV-1 DNA polymerase was the most sensitive to inhibition by acyclovir triphosphate (ACVTP). The EBV DNA polymerase and DNA polymerase beta were less sensitive. ACVTP inhibition was competitive with dGTP with Ki values of 0.03, 0.15, 9.8 and 11.9 microM for HSV-1 DNA polymerase, DNA polymerase alpha, EBV DNA polymerase and DNA polymerase beta, respectively. Substituting a synthetic primer template (dG) approximately 15 x (dC)n for activated DNA template did not alter the pattern of inhibition. In a time course experiment, addition of ACVTP instead of dGTP did not increase DNA synthesis and it appeared to act as a chain terminator in DNA replication catalyzed by either HSV-1 DNA polymerase or DNA polymerase alpha. Although EBV DNA polymerase was less sensitive to ACVTP inhibition, the nucleoside analog itself was inhibitory to EB virus production by P3HR1 cell line as determined by a reduction in the percentage of cells expressing virus capsid antigen (VCA). On day 4, ACV at 10 and 25 micrograms/ml reduced the cell growth by 10% and 32%, respectively, while it reduced the VCA-positive cells by 80% and 84%, respectively. These results indicate that inhibition of EBV DNA polymerase activity by ACVTP may not be the primary mechanism responsible for ACV inhibition of EBV replication.
The etched multiple vertical junction silicon photovoltaic cell

Abstract In this paper a silicon concentrator cell with a novel design which greatly reduces internal series resistance losses, permitting operation to 1000 suns or more, is described. In this etched multiple vertical junction (EMVJ) design, diffusions and metallizations are both embedded in deeply etched grooves, normal to the cell surface, formed by anisotropic etching in Si〈110〉. As a result, there is no current flow within the junction planes and the surface area available for metallization is large compared with the obscured surface area. Unlike horizontal junction concentrator cells, the efficiency of the EMVJ cell continues to increase with increasing intensity, to incident intensities of 500–1000 suns. At the present time, cells with only an SiO 2 antireflection coating yield an efficiency of 18.5% at 500 suns. With an improved antireflection coating and other optimizations, efficiencies of well over 20% can be realized.
Strain improvement by metabolic engineering: lysine production as a case study for systems biology

A central goal of systems biology is the elucidation of cell function and physiology through the integrated use of broad based genomic and physiological data. Such systemic approaches have been employed extensively in the past, as they are a central element of metabolic flux analysis, the distribution of kinetic control in pathways, and the key differentiating characteristic of metabolic engineering. In one case study, these tools have been applied to the improvement of lysine-producing strains of Corynebacterium glutamicum. The systematic study of the physiology of this organism allowed the identification of specific metabolic targets and subsequently led to significant improvements in product yield and productivity. This case study can serve as a guide for the development of systems biology tools for the utilization of large volumes of cell- and genome-wide transcriptional and physiological data.
Balloon angioplasty with stent implantation in experimental coarctation of the aorta.

BACKGROUNDBalloon angioplasty of coarctation of the aorta is an effective method of treatment but is complicated by tearing of the aortic intima, formation of aneurysms, and restenosis. Stent placement at the time of balloon dilation could prevent restenosis and could also prevent progression of intimal tears to aneurysms. The purpose of this study was to evaluate the feasibility of balloon dilation and implantation of balloon-expandable stents in an experimental model of coarctation and to examine the effect of stent placement at the site of surgically created stenosis.METHODS AND RESULTSCoarctation of the aorta was surgically produced in 11 juvenile swine. Simultaneous coarctation angioplasty and stent implantation was performed in 10 animals 34 +/- 7.8 days after surgery. Repeat catheterization was performed 59 +/- 6 days after stent implantation. Five animals underwent reexpansion of stents with subsequent follow-up catheterization. Aortic specimens were examined by light microscopy and scanning elect...
Validation of Cognitive Sensitivity for Item Response Curves

This study sought a scientific way to examine whether item response curves are influenced systematically by the cognitive processes underlying solution of the items in a procedural domain (addition of fractions). Starting from an expert teacher's logical task analysis and prediction of various erroneous rules and sources of misconceptions, an error diagnostic program was developed. This program was used to carry out an error analysis of test performance by three samples of students. After the cognitive structure of the subtasks was validated by a majority of the students, the items were characterized by their underlying subtask patterns. It was found that item response curves for items in the same categories were significantly more homogeneous than those in different categories. In other words, underlying cognitive subtasks appeared to systematically influence the slopes and difficulties of item response curves.
African Swine Fever Virus Multigene Family 360 and 530 Genes Affect Host Interferon Response

African swine fever virus (ASFV) multigene family 360 and 530 (MGF360/530) genes affect viral growth in macrophage cell cultures and virulence in pigs (L. Zsak, Z. Lu, T. G. Burrage, J. G. Neilan, G. F. Kutish, D. M. Moore, and D. L. Rock, J. Virol. 75:3066-3076, 2001). The mechanism by which these novel genes affect virus-host interactions is unknown. To define MGF360/530 gene function, we compared macrophage transcriptional responses following infection with parental ASFV (Pr4) and an MGF360/530 deletion mutant (Pr4Δ35). A swine cDNA microarray containing 7,712 macrophage cDNA clones was used to compare the transcriptional profiles of swine macrophages infected with Pr4 and Pr4Δ35 at 3 and 6 h postinfection (hpi). While at 3 hpi most (7,564) of the genes had similar expression levels in cells infected with either virus, 38 genes had significantly increased (>2.0-fold, P < 0.05) mRNA levels in Pr4Δ35-infected macrophages. Similar up-regulation of these genes was observed at 6 hpi. Viral infection was required for this induced transcriptional response. Most Pr4Δ35 up-regulated genes were part of a type I interferon (IFN) response or were genes that are normally induced by double-stranded RNA and/or viral infection. These included monocyte chemoattractant protein, transmembrane protein 3, tetratricopeptide repeat protein 1, a ubiquitin-like 17-kDa protein, ubiquitin-specific protease ISG43, an RNA helicase DEAD box protein, GTP-binding MX protein, the cytokine IP-10, and the PKR activator PACT. Differential expression of IFN early-response genes in Pr4Δ35 relative to Pr4 was confirmed by Northern blot analysis and real-time PCR. Analysis of IFN-α mRNA and secreted IFN-α levels at 3, 8, and 24 hpi revealed undetectable IFN-α in mock- and Pr4-infected macrophages but significant IFN-α levels at 24 hpi in Pr4Δ35-infected macrophages. The absence of IFN-α in Pr4-infected macrophages suggests that MGF360/530 genes either directly or indirectly suppress a type I IFN response. An inability to suppress host type I IFN responses may account for the growth defect of Pr4Δ35 in macrophages and its attenuation in swine.
Patient delay and receipt of thrombolytic therapy among patients with acute myocardial infarction from a community-wide perspective

The duration of patient delay from the time of onset of symptoms of acute myocardial infarction (AMI) to hospital presentation, and the relation of delay time and various patient characteristics to receipt of thrombolytic therapy were examined as part of a community-based study of patients hospitalized with AMI in the Worcester, Massachusetts, metropolitan area. In all, 800 patients with validated AMI hospitalized at 16 hospitals in the Worcester metropolitan area in 1986 and 1988 constituted the study sample. Patients delayed on average 4 hours between noting symptoms suggestive of AMI and presenting to area-wide emergency departments with no significant change observed between 1986 and 1988. The shorter the time interval of delay, the greater the likelihood of receiving thrombolytic therapy; patients arriving at the emergency department within 1 hour of the onset of acute symptoms were approximately 2.5 and 6.5 times more likely to receive thrombolytic agents than were those presenting to the hospital between 4 and 6, and greater than 6 hours, respectively, after the onset of symptoms. Results of a multivariate analysis showed increasing length of delay, older age, history of hypertension or AMI and non-Q-wave AMI to be significantly associated with failure to receive thrombolytic therapy.
Z/sub 1//sup 3/ dependence of the energy loss of an ion passing through an electron gas

The theory of the energy loss of an ion with charge Z/sub 1/e passing through an electron gas is considered. The term proportional to Z/sub 1//sup 3/ in the expression for the stopping power of the medium is derived by taking a second functional derivative of the induced charge in the medium and is expressed as a product of three Green's functions. The actual evaluation is effected by separately treating the momentum transfer to distant and close collisions. Also, it is assumed that the Fermi energy E/sub F/ is less than h..omega../sub p/, the plasmon energy of the medium. The contribution to the Z/sub 1//sup 3/ term from distant collisions is similar to that obtained by others using an atomic model for the stopping medium if one replaces the atomic binding energy by h..omega../sub p/. The contribution from the region of close collisions is shown to be unimportant compared to that from distant collisions because screening of close collisions is expected to be negligible in the electron gas. This work will discuss related work by Lindhard and Esbensen, and by Arista, who arrive at different conclusions with respect to this impact-parameter dependence.
A phase II trial of high-dose hydroxyurea administered parenterally in patients with epithelial ovarian carcinoma refractory to platinum

Verschraegen CF, Kudelka AP, Loyer E, Edwards CL, Freedman RS, Kavanagh JJ. A phase II trial of high-dose hydroxyurea administered parenterally in patients with epithelial ovarian carcinoma refractory to platinum. Int J Gynecol Cancer 1998; 8: 494–498. This phase II study was designed to analyze the efficacy and toxicity of an intravenous infusion of hydroxyurea in patients with ovarian cancer in which previous chemotherapy with platinum failed. Another phase II study of paclitaxel was run in the same patient population. Twenty-six patients with measurable ovarian cancer were entered in the hydroxyurea phase II study at The University of Texas M. D. Anderson Cancer Center. Treatment consisted of a loading dose of 2,100 mg/m2 of hydroxyurea followed by a continuous intravenous infusion of 16,800 mg/m2 over 24 h repeated every 3 weeks. Patients with disease unresponsive to hydroxyurea could then be crossed over to paclitaxel. Disease in one patient responded, but the patient refused further treatment with hydroxyurea. Disease in 3 was stable. The median survival time was 8.8 months. The main toxic effect was neutropenia, with 31% of patients experiencing grade 3 or 4 neutropenia. No episodes of neutropenic fever were observed. Twenty seven percent of patients presented with anemia and thrombocytopenia. Other side effects were all lower than grade 2 and included gastrointestinal dysfunction (35% of patients), alopecia (12%), dermatitis (12%), headache (8%), and stomatitis (4%). We conclude that high-dose hydroxyurea administered parenterally as a single agent over 24 h is not active in patients with platinum-refractory ovarian cancer but is subjectively well tolerated.
Malaria-Infected Mice Live Until at Least Day 30 after a New Artemisinin-Derived Thioacetal Thiocarbonate Combined with Mefloquine Are Administered Together in a Single, Low, Oral Dose

In only three steps and in 21–67% overall yields from the natural trioxane artemisinin, a series of 21 new trioxane C-10 thioacetals was prepared. Upon receiving a single oral dose of only 6 mg/kg of the monomeric trioxane 12c combined with 18 mg/kg of mefloquine hydrochloride, Plasmodium berghei-infected mice survived on average 29.8 days after infection. Two of the four mice in this group had no parasites detectable in their blood on day 30 after infection, and they behaved normally and appeared healthy. One of the mice had 11% blood parasitemia on day 30, and one mouse in this group died on day 29. Of high medicinal importance, the efficacy of this ACT chemotherapy is much better than (almost double) the efficacy under the same conditions using as a positive control the popular trioxane drug artemether plus mefloquine hydrochloride (average survival time of only 16.5 days).
Length reduction of multi-walled carbon nanotubes via high energy ultrasonication and its effect on their dispersibility

Length dependent dispersibility of carboxylated multiwalled carbon nanotubes is presented using a novel approach that ensures the same diameter and the degree of functionalization. The longer multiwalled nanotubes were reduced in length by ultrasonication and then their dispersibility was studied in comparison to the original tubes. Colloidal studies showed dependence on the length where the shorter tubes showed higher aggregation in terms of larger particle size, zeta potential and lower critical coagulation concentrations in the presence of electrolytes. It is hypothesized that the longer tubes entangled more leading to a more complex electrostatic double layer that increased their stability.