cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 7: Targeted Mutagenesis of Antithrombin III in Zebrafish Results in Disseminated Intravascular Coagulation and Thrombosis

Pathologic blood clotting (thrombosis) is a leading cause of morbidity and mortality in the developed world, underlying deep vein thrombosis, myocardial infarction, and stroke. Identification of small molecule modifiers using an in vivo thrombosis would facilitate novel and improved therapeutics for patients. The zebrafish is a powerful genetic model in which the hemostatic system is nearly entirely conserved with mammals and its ability to generate thousands of offspring at low cost makes it a powerful tool to screen chemical modifiers of coagulation disorders. We have generated a zebrafish model of complete antithrombin III (at3) deficiency by targeted mutagenesis using zinc finger nucleases. at3 heterozygotes with 22 and 90 base pair deletions (at3[[Unable to Display Character: ∆]]22 and at3[[Unable to Display Character: ∆]]90) were intercrossed, and no homozygotes have survived beyond 7 months of age. Offspring were genotyped at various time points revealing a significant reduction of expected homozygotes compared to the expected Mendelian frequency as early as 1-2 months post fertilization. This lethality was rescued by an at3 cDNA transgene, enabling survival to at least 15 months of age. Analysis of adult homozygous mutants revealed evidence of large intravascular thrombi and externally visible secondary hemorrhage. We induced thrombosis at 3-4 days post fertilization in at3[[Unable to Display Character: ∆]]90 mutant larvae by laser injury and injection of bovine thrombin. Contrary to our expectations, we observed diminished rates of cardinal vein occlusion in homozygous mutants, and this could be rescued by an at3 cDNA transgene. We hypothesized that this was due to disseminated intravascular coagulation (DIC), and observed reduced fibrinogen levels in at3 homozygous mutant plasma. Furthermore, injection of mutant larvae with human fibrinogen prior to laser injury rescued the mutant phenotype. In conclusion, loss of At3 protein results in subclinical DIC in zebrafish larvae secondary to unopposed thrombin activity, but they survive and succumb to lethal thrombosis in adults. Future studies will adapt this model for high throughput screening for genetic and chemical modifiers of DIC and thrombosis. Genes and small molecules identified will be potential novel diagnostic and therapeutic modalities for patients with these disorders.
Health and Psychiatric Issues in Children of Rural Methamphetamine Abusers and Manufacturers

Many abusers of methamphetamine in rural areas manufacture the drug for their personal use. These "mom-and-pop cooks" produce methamphetamine in and around homes where children are also living. This article provides an overview of the mental health of children whose parents abuse methamphetamine.
Reducing the thermal conductivity of chemically ordered binary alloys below the alloy limit via the alteration of phonon dispersion relations

We investigate the effect of crystalline configuration on the thermal conductivity of binary Lennard-Jones based solid solutions via classical molecular dynamics simulations and harmonic lattice dynamics calculations. We show that the pronounced effect of Umklapp scattering causes the cross-plane thermal conductivity of the chemically ordered alloy (1 × 1 monolayer period superlattice) to approach the thermal conductivity of the disordered counterpart (alloy limit) at elevated temperatures. However, we find that for superlattices with thicker periods and larger acoustic mismatch between the layers, the thermal conductivity can approach a minimum that is well below the alloy limit and can even approach the theoretical minimum limit of the corresponding amorphous phase. Our simulations over a wide range of mass ratios between the species suggest two contrasting effects of increasing mass ratio: (i) flattening of modes that leads to lower group velocities and lower overall thermal conductivity and (ii) reduc...
Bezlotoxumab: anti-toxin B monoclonal antibody to prevent recurrence of Clostridium difficile infection.

ABSTRACTIntroduction: Clostridium difficile infection (CDI) is the most common nosocomial infection in the U.S. 25% of CDI patients go on to develop recurrent CDI (rCDI) following current standard of care (SOC) therapy, leading to morbidity, mortality and economic loss. The first passive immunotherapy drug targeting C.difficile toxin B (bezlotoxumab) has been approved recently by the FDA and EMA for prevention of rCDI.Areas covered: A body of key studies was selected and reviewed by the authors. The unmet needs in CDI care were ascertained with emphasis in rCDI, including the epidemiology, pathophysiology and current management. The current knowledge about the immune response to C. difficile toxins and how this knowledge led to the development and the clinical use of bezlotoxumab is described. Current and potential future competitors to the drug were examined.Expert commentary: A single 10 mg/kg intravenous infusion of bezlotoxumab has been shown to decrease rCDI by ~40% (absolute reduction ~10%) in patie...
Characterization of Undercoordinated Zr Defect Sites in UiO-66 with Vibrational Spectroscopy of Adsorbed CO

The highly studied metal–organic framework (MOF), UiO-66, has been touted for its high surface area, stability, and tunability of structural defects for particular applications in catalysis and gas storage. However, atomic-level characterization and quantification of defects remain challenging for traditional methods. Motivated by this knowledge gap, coordinatively unsaturated zirconium (Zrcus) defect sites within UiO-66 have been determined through infrared spectroscopic studies of the highly sensitive probe molecule, carbon monoxide. A characteristic blue shift of the vibrational frequency for CO adsorbed at nodes within the MOF was used to identify the presence of Zrcus defects. The identification of these coordinatively unsaturated metal sites was further corroborated via exposure of the MOF to the Lewis base, D2O, which was shown to block CO binding to the Lewis acidic Zrcus sites. The infrared spectroscopic signature for CO binding at the Zrcus sites was further employed to track the emergence of mi...
Accumulation and Storage of Phosphate and Minerals

Developing seeds store reserve levels of phosphorus and minerals, mobilization of which during germination provides the mineral nutrition essential for optimal early seedling growth. This process also functions as a component of the inorganic P and mineral homeostasis mechanisms necessary for nominal cellular function. The storage and resup-ply of phosphorus centers around the synthesis and breakdown of phytic acid (myo-inositol 1,2,3,4,5,6-hexakisphosphate). Phytic acid is often deposited as a mixed, ‘phytin’ salt, primarily of potassium and magnesium. Thus phytin deposition and re-mobilization also represents an important component of mineral cation storage. Exceptions to this may include iron and calcium storage and homeostasis, for which non-phytin mechanisms may play major roles. There has been recent progress in the molecular biology of several components of phosphorus and mineral storage pathways. These include studies of myo-inositol synthesis, some aspects of myo-inositol phosphate metabolism, protein body transport functions, and calcium and iron storage proteins. Recent genetic studies bring into question the paradigm that phytic acid synthesis is essential to phosphorus storage or inorganic P homeostasis. Much additional progress is required, particularly concerning the synthetic pathway to phytic acid, before a thorough or truly detailed understanding of the molecular biology of P and mineral storage processes is obtained.
Ancillary Statistics, Pivotal Quantities and Confidence Statements

The most commonly used expression in Statistics is information; yet, we have no agreement on the definition or usage of this concept. However, in the particular situation where the problem is to predict a future value of a random variable X with a known probability distribution p(.), we all seem to agree that the information on the yet unobserved future value of X may be characterized by the function p(.) itself. And if we have another variable Y such that the conditional distribution p(. |Y) of X, given Y, is also known then, having observed Y, we can claim that the information on X has shifted from p(.) to p(. | Y). [To avoid a multiplicity of notations, we do not distinguish between a random variable X, an observed value of X and a typical point in the sample space of X.] If p(.|Y)is the same for all values of Y, then X is stochastically independent of Y. In this case Y is said to have no information on X. And we know how to prove then that X has no information on Y.
Ancillary studies in pleural, pericardial, and peritoneal effusion cytology

Pleural, pericardial, and peritoneal effusion specimens present diagnostic challenges and clinical opportunities for cytology. For the patient, these specimens may be the first diagnosis of malignancy or the first sign of disease recurrence. This review aims to provide useful approaches with which to resolve key difficulties in cytologic diagnosis through the use of ancillary studies, focusing on immunohistochemistry. These approaches are suggested in concert with clinical, radiographic, and morphologic findings. The differentiation of reactive mesothelial cells from malignant mesothelioma and adenocarcinoma is a recurring theme, and Wilms tumor 1 (WT1)/AE1/AE3, claudin 4, and BRCA1-associated protein 1 (BAP1) immunostains are useful new tools in the armamentarium. A targeted workup is suggested for patients with no known primary site or with multiple prior malignancies. Molecular and other biomarker testing can be performed on even modestly cellular fluid specimens and may allow patients to benefit from targeted therapy without the need for additional tissue biopsies. Cancer Cytopathol 2018;000:000-000. © 2018 American Cancer Society.
Who are the Self-Employed in Bankruptcy?

Because of the relatively high numbers of self-employed in bankruptcy in previous cohorts, the 2007 cohort of the Consumer Bankruptcy Project (CBP) collected extensive data from debtors who identified as self-employed. The self-employed in U.S. bankruptcy court remain present in relatively high numbers. Contrary to government statistics that would suggest business filers are, at most 2-3% of all bankruptcy filings and these new data again confirm that as many as one in seven bankruptcy filers report self-employment at the time of bankruptcy. This paper is the first in a series of papers from the CBP on the self-employed in bankruptcy and reports on the demographics. The data show that the self-employed in bankruptcy do not differ from their nonbankrupt counterparts on age, gender, or marital status. African Americans, however, are disproportionately represented among the self-employed in bankruptcy. These findings have implications both for our construction of the concept of entrepreneurship and for what type of legal or nonlegal institutions would best ease the burden of financial distress among the self-employed.
Electric grid reliability research

Energy informatics (EI) is the area of research that addresses the application of technology to resolve complex problems in the energy domain. Goebel et al. (BISE 6:25–31, 2014) provided an EI research framework to encompass all aspects of EI research. Due to rapid EI improvements, many current research areas have not been incorporated into this framework. Specifically, this research posits that grid reliability is an underrepresented research area and should be incorporated into the framework. The rapidly changing nature of energy generation, and new developments in the electric-power network, are driving the need for grid reliability research. The goal of this paper is to extend the EI research framework offered by the Goebel et al. through a systematic review of current literature. This literature review includes current publications (2015–2017) in power utility and technical reference libraries together with the earlier foundational EI papers. The systematic literature review is based on a broad automated search of appropriate digital sources (IEEE Xplore and the Web of Science) using relevant search terms. The paper also details the components of grid reliability research as well as their accompanying use cases. The expanded EI research framework presented in this literature review should help researchers identify areas for future research endeavors. In the extended EI research framework, service reliability is now included as a third research component adding to the existing energy efficiency and renewable-energy supply components.
Adjusting finite sample bias in traffic safety modeling

Poisson and negative binomial regression models are fundamental statistical analysis tools for traffic safety evaluation. The regression parameter estimation could suffer from the finite sample bias when event frequency is low, which is commonly observed in safety research as crashes are rare events. In this study, we apply a bias-correction procedure to the parameter estimation of Poisson and NB regression models. We provide a general bias-correction formulation and illustrate the finite sample bias through a special scenario with a single binary explanatory variable. Several factors affecting the magnitude of bias are identified, including the number of crashes and the balance of the crash counts within strata of a categorical explanatory variable. Simulations are conducted to examine the properties of the bias-corrected coefficient estimators. The results show that the bias-corrected estimators generally provide less bias and smaller variance. The effect is especially pronounced when the crash count in one stratum is between 5 and 50. We apply the proposed method to a case study of infrastructure safety evaluation. Three scenarios were evaluated, all crashes collected in three years, and two hypothetical situations, where crash information was collected for "half-year" and "quarter-year" periods. The case-study results confirm that the magnitude of bias correction is larger for smaller crash counts. This paper demonstrates the finite sample bias associated with the small number of crashes and suggests bias adjustment can provide more accurate estimation when evaluating the impacts of crash risk factors.
The Impact of Sociosexualization and Sexual Identity Development on the Sexual Well-Being of Youth Formerly in the Foster Care System.

Abstract Purpose Youth in the child welfare system experience disproportionate rates of negative sexual health outcomes as well as increased engagement in risky sexual behaviors. This study explored the impact of sociosexualization and sexual identity development on the sexual well-being of youth formerly in the foster care system. Methods Two hundred and nineteen youth formerly in the foster care system completed an Internet-based survey, including measures of the level of sexuality-related topics discussion, relationship quality with the individual with whom the topics were discussed, adverse childhood experiences, severity of sexual abuse history, sexual identity development, and sexual well-being. Hierarchical regressions examined the impact of youths' sociosexualization experiences and four domains of sexual identity development on their sexual well-being. Results Sexual Identity Commitment was the strongest positive predictor of youths' sexual well-being (β = .428) followed by Sexual Identity Synthesis/Integration (β = .350) and Sexual Identity Exploration (β = .169). Sexual Orientation Identity Uncertainty negatively impacted sexual well-being (β = −.235), as did adverse childhood experiences (β range = −.150 to −.178) and sexual abuse severity (β range = −.208 to −.322). Sexuality-related discussions with foster parents negatively impacted youths' sexual well-being, whereas discussions with peers were a positive predictor. Conclusion Enhancing youths' sexual identity development and reducing the impact of traumatic experience are critical to improving sexual well-being. The influence of sexuality-related discussions on sexual well-being requires further analysis as impacts varied widely. Public policies should provide guidance to professionals on what services should be provided to enhance youths' sexual development.
Integrating evolutionarily novel horns within the deeply conserved insect head

How novel traits integrate within ancient trait complexes without compromising ancestral functions is a foundational challenge in evo-devo. The insect head represents an ancient body region patterned by a deeply conserved developmental genetic network, yet at the same time constitutes a hot spot for morphological innovation. However, the mechanisms that facilitate the repeated emergence, integration, and diversification of morphological novelties within this body region are virtually unknown. Using horned Onthophagus beetles, we investigated the mechanisms that instruct the development of the dorsal adult head and the formation and integration of head horns, one of the most elaborate classes of secondary sexual weapons in the animal kingdom. Using region-specific RNAseq and gene knockdowns, we (i) show that the head is compartmentalized along multiple axes, (ii) identify striking parallels between morphological and transcriptional complexity across regions, yet (iii) fail to identify a horn-forming gene module. Instead, (iv) our results support that sex-biased regulation of a shared transcriptional repertoire underpins the formation of horned and hornless heads. Furthermore, (v) we show that embryonic head patterning genes frequently maintain expression within the dorsal head well into late post-embryonic development, thereby possibly facilitating the repurposing of such genes within novel developmental contexts. Lastly, (vi) we identify novel functions for several genes including three embryonic head patterning genes in the integration of both posterior and anterior head horns. Our results illuminate how the adult insect head is patterned and suggest mechanisms capable of integrating novel traits within ancient trait complexes in a sex- and species-specific manner. More generally, our work underscores how significant morphological innovation in developmental evolution need not require the recruitment of new genes, pathways, or gene networks but instead may be scaffolded by pre-existing developmental machinery.
Suicide and Suicidal Behavior

From 1950 to 1982, the death rate from suicide among youth (15 to 24 years old) increased dramatically. The costs associated with suicide are considerable and include direct medical costs for treatment prior to death, medicolegal costs for autopsies, police investigations, and treatment for physical and mental health problems in family survivors. It has been estimated that each youth suicide equals $432,000 of lost economic productivity and 53 years of human life (Weinstein & Saturno, 1989). Despite these statistics and general public alarm, the resources that are available for prevention of suicidal behavior in the United States are scant compared to what is available for the prevention of other injuries such as motor vehicle crashes (Diekstra, 1993).
Clinically identifiable autoreactivity is common in severe SARS-CoV-2 Infection

Abstract Severe SARS-CoV-2 infection is linked to the presence of autoantibodies against multiple targets, including phospholipids and type-I interferons. We recently identified activation of an autoimmune-prone B cell response pathway as correlate of severe COVID-19, raising the possibility of de novo autoreactive antibody production during the antiviral response. Here, we identify autoreactive antibodies as a common feature of severe COVID-19, identifying biomarkers of tolerance breaks that may indicate subsets of patients that may particularly benefit from immunomodulation.
Examining the Virtual Diffusion of Educational Resources across Teachers’ Social Networks over Time:

ContextIndividuals’ curation within social media provides a window into their sensemaking and conceptions of what is worth knowing. Within education, a majority of teachers use social media for pro...
Genetics of the fuzzless ovule phenotype of Gossypium arboreum accession PI 615733 (cv. Zi-Hua Guang Zi)

Abstract Lint and fuzz are the two types of fiber that develop on cotton seeds. Lint is an economically important fiber used in the textile industry. Fuzz fibers remain attached to seeds, and reducing the amount of fuzz could improve ginning efficiency. The Gossypium arboreum accession PI 615733 from the United States Department of Agriculture cotton germplasm collection showed the fuzzless trait, where no fuzz fibers were observed on seeds. Accession PI 615733 was crossed with the fuzzy seeded G. arboreum accession PI 529729 to develop an F2 population. Seeds from F1 plants showed no fuzz fiber. For the F2 population of 409 plants, 239 plants were classified as fuzzless and 170 were classified as fuzzy. These data support a two-gene model with incomplete dominance. A greater understanding of the genetic mechanisms controlling fiber development on cotton seeds could contribute to breeding efforts to improve lint fiber yields and quality.
Vocal Fold Paralysis and Dysphagia

Dysphagia secondary to unilateral vocal fold paralysis (UVFP) is the result of glottic incompetence, reduced supraglottic sensation, and impaired function of the upper esophageal sphincter (UES). UVFP resultant dysphagia is of the utmost importance for those patients who have undergone thoracic and mediastinal surgeries. Management options for UVFP associated dysphagia are aimed at improving glottic closure including injection laryngoplasty and type I thyroplasty. This article presents a state-of-the-art overview of pathophysiology, presentation, and treatment of dysphagia in vocal fold paralysis. Patients with UVFP report significantly increased dysphagia symptom scores and demonstrate pharyngeal muscle weakness. The risk of dysphagia in UVFP is increased by the inability of the bolus to develop adequate speed or consistency and compromised UES opening. Injection laryngoplasty within 4.5 days of onset of UVFP is associated with decreased incidence of aspiration pneumonia and shortened length of stay. Cough strength increases after injection laryngoplasty in those patients with UVFP. Patients with UVFP are more likely to develop aspiration pneumonia. Patient outcomes are best with early intervention restoring glottic competence.
Trajectories of pain during pregnancy predict symptoms of postpartum depression

Introduction Postpartum depression imparts a significant and long-lasting burden on maternal and child health. Successful prevention or early detection of postpartum depression will rely on the identification of early risk factors. Pain during pregnancy (before childbirth) is a key potential predictor of postpartum depression risk. However, longitudinal studies characterizing pregnancy pain, its normal trajectory over time, and its prospective relations with symptoms of postpartum depression are lacking. Methods We used data from a longitudinal study of maternal emotion that included assessments of pain and depressive symptoms at 3 time points-during the second and third trimester of pregnancy and at 4 months postpartum. Structural equation modelling was used to estimate longitudinal patterns of change in maternal pain over time. Latent growth curve parameters were tested as predictors of symptoms of postpartum depression. Results Ninety-three healthy pregnant women enrolled in this study. Although the sample comprised women with relatively low-risk pregnancies, more than 90% of participants experienced pregnancy pain. Greater linear increases and less negative quadratic change in maternal pain over time were associated with greater levels of postpartum depression, even when controlling for prenatal depressive symptoms. Interpreting both parameters together, pain that increased in late pregnancy, when normative patterns had either levelled off or begun to decline, was associated with greater levels of postpartum depression. Conclusion A developmental trajectory of pain experience that did not subside after childbirth was associated with greater postpartum depressive symptoms, suggesting that atypical trajectories of pain may be a risk factor for postpartum depression.
Risk and Valuation of Collateralized Debt Obligations

In this discussion of risk analysis and market valuation of collateralized debt obligations, we illustrate the effects of correlation and prioritization on valuation and discuss the "diversity score" (a measure of the risk of the CDO collateral pool that has been used for CDO risk analysis by rating agencies) in a simple jump diffusion setting for correlated default intensities.
A Robotic Approach towards Quantifying Epipelagic Bound Plastic Using Deep Visual Models.

The quantification of positively buoyant marine plastic debris is critical to understanding how plastic litter accumulates across the world's oceans and is also crucial to identifying hotspots for targeted cleanup efforts. Currently, the most common method to quantify marine plastic is using manta trawls for manual sampling. However, this method is cost-intensive and requires human labor. This study removes the need for manual sampling by using an autonomous method using neural networks and computer vision models, which trained on images captured from various layers of the ocean column to perform real-time plastic quantification. The best performing model has a Mean Average Precision of 85% and an F1-Score of 0.89 while maintaining near real-time processing speeds ~2 ms/img.
Studies on the mechanism of fatty acid synthesis. 13. The role of beta-hydroxy acids in the synthesis of palmitate and cis vaccenate by the Escherichia coli enzyme system.

Abstract The fatty acid-synthesizing system of Escherichia coli was fractionated by chromatography on diethylaminoethyl cellulose into three different enzyme fractions: Eii, Eiii, and Eiv. Incubation of Fraction Eii with acetyl coenzyme A, malonyl coenzyme A, reduced triphosphopyridine nucleotide, and acyl carrier protein (ACP) yielded β-hydroxydecanoyl-ACP, β-hydroxylauryl-ACP, and β-hydroxymyristyl-ACP in variable amounts depending on the Eii preparations. Addition of Fraction Eiii to reaction mixtures of Fraction Eii yielded mainly palmitic acid, whereas the addition of Fraction Eiv to the same Eii reaction mixture yielded mainly cis-vaccenic acid. Therefore, Fractions Eiii and Eiv must have directed the synthesis of saturated and unsaturated fatty acids from β-hydroxydecanoyl-ACP, respectively. Isolated β-hydroxyacyl-ACPs could be converted to their saturated homologues by incubation with Fraction Eiii and TPNH or could be elongated to palmitic acid by incubation with Fraction Eiii, TPNH, malonyl-CoA, and Fraction Eii. Incubation of Fraction Eiii or its subfractions with β-hydroxydecanoyl-CoA yielded the 2-decenoyl derivative. Incubation of Fraction Eiv or its subfractions with β-hydroxydecanoyl-CoA yielded a mixture of cis-3-decenoyl and trans-2-decenoyl derivatives. The relationship between the two dehydrases and the various products formed are discussed as well as their role in the synthesis of saturated and unsaturated fatty acids.
The well-tempered vessel.

Although gene therapy studies of angiogenesis have focused on the ability of endothelial cells to form new structures, it has recently become clear that the subsequent stages of remodeling are crucial to attaining stable and functional vessels. A precise balance of cell types and molecules is required for normal vessel maturation and must be considered in the design of therapeutic angiogenic strategies.
Occupational choices of working children in Bangladesh

The article looks into the determinants of occupational choices of working children in Bangladesh. Using data from 6668 Bangladeshi working children aged 5 through 14, the article estimates several binary and multinomial logit regressions, separately for boys and girls. The article confirms that most children work in the informal sector where formal sector’s jurisdiction and regulations are absent. Specifically, the article finds that children are least likely to work in the service occupation and are more likely to work in the textile sector. The findings highlight the diversity in the occupational distribution of child workers by gender and show how their individual and family characteristics influence occupational choices. The service sector, which comprises of mostly maids, is a hidden sector. This sector makes children vulnerable to abuse. Thus, it is suggested that policy makers need to come up with effective legislations that would protect the children who work in the ‘hidden informal’ sector.
Chapter 32 To Market, To Market – 2006

Publisher Summary This chapter describes 27 new molecular entities (NMEs) for therapeutic use, including five first-in-class drugs which were manufactured in the year 2007. The new anticancer drugs of the year included eight NMEs and the vaccine for cervical cancer that are Merck's Gardasil®, Sutent® (sunitinib), Sprycel™ (dasatinib), Zolinza™ (vorinostat), Dacogen™ (decitabine), DacogenTM (decitabine), Panitumumab (Vectibix™), and nimotuzumab (Biomab EGFR). In the area of endocrine and metabolic diseases, two landmark products were introduced for the treatment of diabetes Exubera® and Januvia™ (sitagliptin). Also entering the diabetes market were two new combination drugs: Avandaryl™ and Duetact™. A high profile entry into the metabolic disease market last year was Acomplias (rimonabant), a first-in-class oral drug for obesity. For the treatment of Pompe's disease Myozyme® (alglucosidase alfa) was launched. Elaprase™ (idursulfase) was introduced for the treatment of mucopolysaccharidosis II, also known as Hunter's syndrome. In the cardiovascular sector, two new oral drugs were introduced for treating chronic stable angina (CSA): Procorolan™ (ivabradine) and Ranexa™ (ranolazine). In addition to the new angina therapies, the cardiovascular area also saw the launch of Thelin® (sitaxsentan) for the treatment of pulmonary arterial hypertension. The CNS area was represented by the entry of two new drugs: Neupro® (rotigotine) for the treatment of Parkinson's disease and Chantix™. Three new urologic drugs were introduced Vaprisols (conivaptan), Physuline (mozavaptan), and Urief (silodosin). The field of gastrointestinal drugs saw the entry of AmitizaTM (lubiprostone). The rheumatoid arthritis (RA) market and the ophthalmic market each had a new biological agent added to the portfolio last year with the launch of Orencia® (abatacept) and Lucentis™ (ranibizumab). Two new diagnostic agents were also introduced last year: Vasovist™ and and Sonazoids (perflubutane).
Pension funds in Central Europe and Russia : their prospects and potential role in corporate governance

The severe financial pressures on the social pension systems of transitional countries in Central Europe and Russia could be alleviated by downsizing and restructuring the public pillar of the system and by creating private pension funds. Private pension funds could help modernize capital markets and also help improve corporate governance. Social pension systems in most countries in Eastern Europe and the former Soviet Union face severe financial pressure. Aging populations are increasing that pressure, which stems mainly from design flaws and incompatible incentives in the systems. Vittas and Michelitsch describe the features of the pension systems that have led to the current dire predicament: A big discrepancy between system and demographic dependency ratios, unsustainable targeted replacement rates, the high contribution rates needed, growing evasion, and growing deficits. Radical basic reform is inevitable, they say, but may not be politically feasible or even advisable in the short run. After reviewing experience in other countries, they conclude that restructuring and downsizing the social pension system will leave adequate but affordable (thus sustainable) benefits and will allow for the creation and growth of private pension funds. The shortcomings of company-based defined benefit plans (limited portability, restricted vesting, inadequate funding) suggest that transitional economies should opt in the longer run for nonemployer, defined contribution plans based on individual capitalization accounts with full immediate vesting, full portability, and full funding. To cope with the need for a targeted replacement rate, such schemes could operate with variable contribution rates, reset each year in accord with the salary growth of each worker, the cumulative investment return on his/her account, and the targeted pension benefit. Once private pension funds are established, long-term financial resources should accumulate rapidly. They can then play a major role in modernizing securities markets, stimulating innovation, fostering better accounting and auditing standards, and promoting more disclosure of information. They could also greatly help improve corporate governance and the monitoring of corporate performance. Their voice in corporate affairs could be exercised more effectively through collective bodies. They could thus help create more robust structures of corporate governance, lower monitoring costs, and avoid the problems caused by free riding. This paper is a product of the Financial Sector Development Department. It is a slightly revised version of a paper presented at the Conference on Corporate Governance in Central Europe and Russia, December 15­16, 1994, organized by the World Bank and the Central European University Privatization Project.
Locus of Control Among Black and White Women with Breast Cancer: A Preliminary Study

Abstract Although black women are less likely to be diagnosed with breast cancer than are white women, they are more likely to be adversely affected. However, little attention has been paid to how these women cope with the disease or whether black and white women differ in their beliefs regarding control of breast cancer. Using a comparative design, this study analyzed the differences in health locus of control between black and white women with breast cancer. The findings suggest that the health locus of control among women in both groups tends to be external. They attributed control of their breast cancer to their physicians, to other people, and to chance to a greater extent than to their own control. The findings point to the importance of assessing women with breast cancer for feelings of powerlessness and providing interventions that help them gain a sense of control regarding treatment decisions and prognosis.
A stable and accurate projection method on a locally refined staggered mesh

In this paper, a robust projection method on a locally refined mesh is proposed for two- and three-dimensional viscous incompressible flows. The proposed method is robust not only when the interface between two meshes is located in a smooth flow region but also when the interface is located in a flow region with large gradients and/or strong unsteadiness. In numerical simulations, a locally refined mesh saves many grid points in regions of relatively small gradients compared with a uniform mesh. For efficiency and ease of implementation, we consider a two-level blocked structure, for which both of the coarse and fine meshes are uniform Cartesian ones individually. Unfortunately, the introduction of the two-level blocked mesh results in an important but difficult issue: coupling of the coarse and fine meshes. In this paper, by properly addressing the issue of the coupling, we propose a stable and accurate projection method on a locally refined staggered mesh for both two- and three-dimensional viscous incompressible flows. The proposed projection method is based on two principles: the linear interpolation technique and the consistent discretization of both sides of the pressure Poisson equation. The proposed algorithm is straightforward owing to the linear interpolation technique, is stable and accurate, is easy to extend from two- to three-dimensional flows, and is valid even when flows with large gradients cross the interface between the two meshes. The resulting pressure Poisson equation is non-symmetric on a locally refined mesh. The numerical results for a series of exact solutions for 2D and 3D viscous incompressible flows verify the stability and accuracy of the proposed projection method. The method is also applied to some challenging problems, including turbulent flows around particles, flows induced by impulsively started/stopped particles, and flows induced by particles near solid walls, to test the stability and accuracy. Copyright © 2010 John Wiley & Sons, Ltd.
Insights into the mechanism and catalysis of the native chemical ligation reaction.

Native chemical ligation of unprotected peptide segments involves reaction between a peptide-α-thioester and a cysteine-peptide, to yield a product with a native amide bond at the ligation site. Peptide-α-thioalkyl esters are commonly used because of their ease of preparation. These thioalkyl esters are rather unreactive so the ligation reaction is catalyzed by in situ transthioesterification with thiol additives. The most common thiol catalysts used to date have been either a mixture of thiophenol/benzyl mercaptan, or the alkanethiol MESNA. Despite the use of these thiol catalysts, ligation reactions typically take 24−48 h. To gain insight into the mechanism of native chemical ligaton and in order to find a better catalyst, we investigated the use of a number of thiol compounds. Substituted thiophenols with pKa > 6 were found to best combine the ability to exchange rapidly and completely with thioalkyl esters, and to then act as effective leaving groups in reaction of the peptide-thioester with the thiol...
Are women carrying "basketballs" really having boys? Testing pregnancy folklore.

Background: Antenatal ascertainment of fetal sex is a common feature of modern pregnancies. Women who opt not to learn fetal sex typically employ a variety of methods to forecast it. This study investigated the validity of prevalent folklore used to identify fetal sex before birth. Method: One hundred four pregnant women, who did not know the sex of the fetus, were administered a questionnaire to explore their perceptions of fetal sex and the basis for these predictions.Results: Fetal sex was not systematically related to the shape of the woman's abdomen, prevalence of morning sickness, or compari- sons with previous pregnancies. However, women who had more than twelve years of education correctly predicted fetal sex greater than chance (71% correct), in contrast to less educated women (43% correct). Contrary to expectations, women whose forecasts were based on psychological criteria (i.e., dreams or feelings) were more likely to be correct than those employing prevalent folklore criteria (i.e., the way a woman was carrying the pregnancy). Conclusions: In general, women were not good predictors of fetal sex. The mechanisms that promote maternal accuracy in predicting fetal sex for highly educated women are unknown. It is reasonable to expect that maternal perceptions of fetal sex contribute to the process of fetal attachment. (BIRTH 26:3 September 1999)
Hematology in developing guinea pigs—I. normal maturation

Abstract 1. 1. Newborn to 24 week old male guinea pigs were studied at 22°C and an ambient Po2 of 133 torr. The following hematological variables were measured once on each animal: hematocrit, [Hb], RBC indices, WBC differentials, and the molar ratio of 2,3-diphosphoglycerate (2,3-DPG) tq [Hb]. 2. 2. [Hb] declined from 15.8 g/100ml at birth (BW = 90 g) to 12.6 g/100 ml when BW = 252 g, and then increased linearly with increasing BW. Red cell indices were nearly constant at all BWs: MCV = 81.7 μm3; MCH = 25.1 pg; and MCHC = 30.7%. In newborn guinea pigs, lymphocytes comprised the majority (73%) of WBC's, but this percentage fell to 55% in mature animals. The ratio of [2,3-DPG]/[Hb] rose from 1.40 M/M following birth to 1.95 M/M (BW = 154 g) and then declined to 0.92 M/M in mature animals. 3. 3. The relative maturity of the hematological profile in newborn guinea pigs contrasts with those in the laboratory mouse and laboratory rat.
On the significance of dimensionless failure criteria

This technical note briefly discusses Mohr-type failure criteria, a condition for the existence of a Mohr-envelope, and dimensionless forms that are guaranteed to fit rock strength test data regardless of scale. A peculiarity of Bieniawski and Hock-Brown criteria is also noted that suggests an additional restriction on functions used to fit laboratory strength data.
A linear backward Euler scheme for a class of degenerate advection–diffusion equations: A mathematical analysis of the convergence in L∞(0, T0;L2(Ω)) and in L2(0, T0;H1(Ω))

This paper concerns itself with establishing convergence estimates for a linearized scheme for solving numerically the saturation equation. In a previous paper, error estimates were obtained for the same scheme in L2(0, T0;L2(Ω)). In this work, we establish error estimates for the linear scheme in L∞(0, T0;L2(Ω)) and in L2(0, T0;H1(Ω)) (in the discrete norms). Under certain realistic conditions, we show that, if the regularization parameter β and the spatial discretization parameter h are carefully chosen in terms of the time-stepping parameter Δt, the convergence, in these spaces, is at least of order O((Δt)α) for some determined α > 0, function of a parameter μ > 0 defined in the problem. Examples of possible choices of β and h in terms of Δt are given.
Geographical Proximity to Parent Firms and the Knowledge Impact of New Ventures

Research examining new ventures founded by individuals leaving their prior employers (parent firms) highlights the importance of parent knowledge inherited by these ventures though their founders. However, this research has not examined whether ventures continue to draw on valuable parent firm knowledge after founding. We examine how a venture’s geographical proximity to its parent firms allows it continued access to parent firm knowledge and argue that this access significantly influences the impact of the knowledge the venture creates. However, we predict that proximity matters less when the venture has established more direct, substitutive mechanisms for transferring knowledge from its parents through technological overlap, scientist migration, and its own recombinative capability. Controlling for endogenous effects, we test our predictions on a sample of 242 biotechnology ventures founded during the period 1990–2000 and tracked till 2009. We discuss contributions of this study to research on entrepren...
Excess histone levels mediate cytotoxicity via multiple mechanisms

The accumulation of excess histone proteins in cells has deleterious consequences such as genomic instability in the form of excessive chromosome loss, enhanced sensitivity to DNA damaging agents and cytotoxicity. Hence, the synthesis of histone proteins is tightly regulated at multiple steps and transcriptional as well as posttranscriptional regulation of histone proteins is well established. Additionally, we have recently demonstrated that histone protein levels are regulated posttranslationally by the DNA damage checkpoint kinase Rad53 and ubiquitin-proteasome dependent proteolysis in the budding yeast. However, the underlying mechanism/s via which excess histones exert their deleterious effects in vivo are not clear. Here we have investigated the mechanistic basis for the deleterious effects of excess histones in budding yeast. We find that the presence of excess histones saturates certain histone modifying enzymes, potentially interfering with their activities. Additionally, excess histones appear to bind non-specifically to DNA as well as RNA, which can adversely affect their metabolism. Microarray analysis revealed that upon overexpression of histone gene pairs, about 240 genes were either up or downregulated by 2-fold or more. Overall, we present evidence that excess histones are likely to mediate their cytotoxic effects via multiple mechanisms that are primarily dependent on inappropriate electrostatic interactions between the positively charged histones and diverse negatively charged molecules in the cell. Our findings help explain the basis for the existence of multiple distinct mechanisms that contribute to the tight control of histone protein levels in cells and highlight their importance in maintaining genomic stability and cell viability.
On the Formation of Jupiter

Arguments are presented to show that Jupiter could not have been formed as a star of mass 0.001M⊙ and that the observed excess energy is not due to gravitational contraction from an extended, gaseous state.
Vascular Compression of the Eighth Cranial Nerve as a Cause of Vertigo

Some patients have vertigo that is more or less constant, associated with varying degrees of nausea, and only relieved by bedrest. This disorder, named disabling positional vertigo (DPV), was found to be caused by a blood vessel or vessels compressing the eighth cranial nerve in its intracranial portion, and it can be relieved by microvascular decompression (MVD) of the nerve. Important in the differential diagnosis of DPV are a detailed history, the results of audiometry (10 to 15 dB interaural threshold difference or a small mid-frequency notch), acoustic middle ear reflex response testing (may be abnormal), and recordings of brainstem auditory evoked potentials (BAEP). BAEP in such cases show increased conduction time in the auditory nerve and/or prolonged latency of wave V recorded from the contralateral ear, possibly the result of brainstem compression. Abnormalities on vestibular testing often do not reflect the severity of the illness. Forty-one patients who underwent MVD to treat DPV in one year at the author's institution have been followed for 4.5 to 5.5 years. By self-evaluation, 20 had excellent and 10 good results of the operation. The success of this procedure is even higher today, since it was found that very small blood vessels, including veins, can cause DPV; thus all vessels touching the nerve are now managed. Complications of MVD are rare. The most frequent, hearing loss, occurred in only one patient in this series.
Lipid lowering effects of statins and fibrates in the management of HIV dyslipidemias associated with antiretroviral therapy in HIV clinical practice.

Abstract Objectives. Dyslipidemia associated with antiretroviral therapy is a common clinical problem among HIV-infected patients. Considering that the challenge of adherence to drugs (both antiretroviral and lipid lowering) may be substantial in routine HIV care, our objective was to evaluate the lipid-lowering effects of statins and fibrates in the management of HIV dyslipidemias in clinical practice setting. Methods. Retrospective review of 103 ethnically diverse dyslipidemic HIV patients on antiretroviral therapy treated with lipid-lowering drugs (using National Cholesterol Education and Prevention II [NCEP II] guidelines) who were followed for a median of 70 weeks. Results. An overall mean reduction of 16% in total cholesterol, 20% non-HDL cholesterol, and 18% in triglycerides was noted. There were no significant changes in HDL levels. On evaluation of the different drug classes, the mean (median) change in total cholesterol, were −9 (−7)% with fibrates, −11 (−14)% with statins and −23 (−22)% for dual therapy with fibrates and statins. The triglycerides decreased by −11 (−40)% in those treated with fibrates; −1 (−21)% in those with statins alone, and −32 (−42)% in those with dual therapy. Overall less than a fifth of patients reached the defined NCEP target goal reduction. On logistic regression analysis, only stopping protease inhibitors/ritonavir was independently associated with significant cholesterol reduction (OR: 10.14; 95% CI: 2.1–48.9; p Conclusion. In a primary care setting, the use of statins and/or fibrates may add to the complexity of HIV care, with only modest lipid lowering effects.