cssi/SciSciGPT-SciSciNet huggingface dataset:
Stock Options and Incentives: Employee-Level Evidence from Google

We examine whether stock option and restricted stock grants motivate higher performance using employee-level data from Google. Employees who received more equity grants than peers hired at the same time and job grade perform slightly better in the future across a variety of measures. To attempt to determine the direction of causality in this relationship, we exploit the fact that employees' option strike prices, and thus their exposure to Google stock, depend on Google's stock price the week they start work. Employees who start work when the stock price is lower than surrounding weeks, and who thus receive more equity exposure from their options, do not perform significantly better than their peers. Even if the correlation between equity grants and performance is interpreted causally, the incentive effects of stock options are still small relative to those from being eligible for promotion. On the other hand, we do find evidence that unvested equity encourages retention and that employees may jointly make retention and performance decisions.
Physiological linkage among successful high-status women in international teams

In contemporary society, decisions are often made by teams whose members represent different nationalities and genders. In the current work, participants from 55 countries formed groups of 3 to 4 people to select one of the 5 firms in a mock firm search. In all groups, one woman was randomly assigned to have higher status than her groupmates; she was also surreptitiously instructed to persuade her group to select one (randomly assigned) firm. We measured cardiac interbeat intervals for participants throughout the decision-making process to assess physiological linkage-the degree to which a 'sender's' physiological response predicts a 'receiver's' physiological response at a subsequent time interval. On average, high-status women were successful at persuasion. The physiological responses of successful high-status women were also predicted by the responses of their female groupmates: stronger linkage to female group members during the task was associated with success at persuading the group. Successful high-status women were also perceived as more persuasive than others in the group. This work shows that the link between status and successful persuasion generalizes to women among heterogeneous international teams. It also suggests that attention to others-often associated with physiological linkage-may be useful in persuading others during decision-making.
Abstract 3807: Exposure to environmental chemicals leads to extensive branching and expression of cancer-promoting proteins in human mammary gland organoids

Bisphenol A (BPA) is a chemical compound used as a plasticizer in a variety of plastic goods. Environmental chemicals like BPA haven been detected in the blood of women and girls. Yet, they are thought to interact with the endocrine system, thereby having carcinogenic effects on the tissue. While BPA is removed from many commercial products because of its potential carcinogenic effect, surprisingly little is known about its replacement chemicals, such as bisphenol S (BPS) and bisphenol F (BPF). In this study, we aim to link the exposure to those environmental chemicals to changes in human mammary gland morphology and to the underlying alterations at the protein level. We established organoid cultures from non-malignant primary human mammary gland tissue as advanced disease model. Human breast organoids were treated with physiological levels of various environmental chemicals, includingBPA, BPF, BPS, 17-β-estradiol (E2), or DMSO as vehicle control. Effects on organoid morphology were studied using brightfield and confocal microscopy. We analyzed relative protein abundances by quantitative mass spectrometry to define proteome changes between the different treatments. The exposure to the environmental chemicals as well as E2 resulted in altered branching morphology while organoid size was not affected. It is already known that BPA has oncogenic potential. Surprisingly, in our study, BPA has the least severe effects when compared to the other bisphenols. BSF or BPS treatment lead to more extensive branching and changed morphology.On protein level, each environmental chemical resulted in distinct protein profiles which show proteins alterations independent of endocrine signaling. Moreover, the exposure to the different bisphenols resulted in the upregulation of proteins which are involved in carcinogenesis, tumor progression and metastasis in various cancer types including breast cancer and thus may support tumor development. In this study, we identified BPS and BPF as potential carcinogens. Not only BPA, but also BPF and in particular BPS alter branching morphology of mammary organoids and influence various biological processes that are distinct from endocrine signaling. Our study highlights the desperate need of a thorough characterization of environmental chemicals to prevent the development of breast cancer caused by the exposure to potential harmful and carcinogenic substances. Citation Format: Johanna H. Hinrichs, Juliane Winkler, Pengyuan Liu, Nassim Ataii, Susan Fisher, Zena Werb. Exposure to environmental chemicals leads to extensive branching and expression of cancer-promoting proteins in human mammary gland organoids [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3807.
Assessing the pipeline: Perceived barriers to applying to dental school among pipeline program alumni.

Purpose/objectives The aim of this study was to increase the understanding of perceived barriers to applying to dental school experienced by underrepresented minority (URM), pipeline program alumni. Methods A qualitative study of alumni of New York University College of Dentistry pipeline programs, aimed at increasing the number of URM and low-income students in the dental profession, was conducted in 2020. Focus groups were convened to examine perceived barriers to applying to dental school and identified through a combination inductive and deductive thematic analysis. Results Twenty-three pipeline program alumni, ranging in age from 18 to 30 years old, participated in focus groups held between January and April 2020. All students identified as underrepresented minorities and 78% were first generation college students. Fifteen (65%) of the participants had not yet applied to dental school. Eight participants (35%) had applied to dental school, 3 (13%) were currently enrolled in dental school, and 5 (22%) were matriculating into dental school in Fall 2020. The following themes emerged as the most prominent challenges to applying to dental school: pre-health advisors (e.g., lack of knowledge about the pre-dental process and discouragement), and the cost of the application process (e.g., application fees, DAT and DAT preparation course costs, and interview costs). Conclusion Through pre-dental pipeline programs, participants have access to informational resources and mentorship; however, despite participation in these programs, perceived barriers are still prevalent. Identification of the alumni's perceived barriers offer targeted areas where increased intervention may be helpful to reduce challenges and strengthen the pipeline.
Collagen expression of intra acinar pulmonary arteries and right ventricle and intervention of Radix Astragali in rats with hypoxic pulmonary hypertension

Objective To investigate the collagen expression effect of intra acinar pulmonary arteries and the right ventricle and to observe the intervention effect of Radix Astragali in rats with hypoxic pulmonary hypertension Methods Wistar male rats were divided into three groups: hypoxia group, which was fed in hypoxic environment (oxygen concentration was 9%～12%) under normal atmospheric pressure for three weeks (12 hours every day); intervention group, which was abdomenly injected with Radix Astragali and fed in the same environment as hypoxia group; and control group, which was fed in normal environment Pulmonary artery pressure and cardiac output of the right ventricle were measured with catheterization and Fick's method Protein expression of collagen in intra acinar pulmonary arteries was assessed with histopathologic method mRNA expressions of collagen in the right ventricle, and endothelin 1 and nitric oxide synthase in lung tissue were evaluated by RT PCR technique Results Compared with those in control group, pulmonary artery pressure and protein expression of collagen in intra acinar pulmonary arteries and mRNA expression of typeⅠcollagen in the right ventricle and endothelin 1 in lung tissue were obviously increased in hypoxia group (mean pulmonary artery pressure: (24 8±3 6) mm Hg vs (18 8±1 7) mm Hg, P 0 01; protein expression of collagen: (20 4±4 5) AU vs (3 4±1 1) AU ( P 0 01), but mRNA expression of nitric oxide synthase in lung tissue was declined Compared with the data obtained in hypoxia group, cardiac output and mRNA expression of nitric oxide synthase in lung tissue were raised in intervention group (cardiac output: [(141±20) ml/min vs (118±40) ml/min, P 0 01], but protein expression of collagen in intra acinar pulmonary arteries and mRNA expression of typeⅠcollagen in the right ventricle and endothelin 1 in lung tissue were markedly decreased (protein expression of collagen: [(5 6±1 2) AU vs (20 4±4 5) AU, P 0 001] Conclusion Changes of collagen expression in intra acinar pulmonary arteries and right ventricle are one of the most important features in remodeling of pulmonary arteries and right ventricle in hypoxic pulmonary hypertension Radix Astragali can partly inhibit the remodeling of pulmonary arteries and right ventricle, and regulate mRNA expression of endothelin 1, nitric oxide synthase, and collagen, thus contributing to the treatment of hypoxic pulmonary hypertension
Alpha, beta, and gamma crystallins in the ocular lens of rabbits: preparation and partial characterization.

Alpha, beta, and gamma crystallins from rabbit eye lens have been prepared by continuousflow paper electrophoresis and gel filtration. These methods yielded well-defined fractions in a highly reproducible manner with essentially quantitative recovery of material. The behavior of each of the crystallins in diethylaminoethyl cellulose has been examined. Sulfhydryl contents of 2.9, 6.1, and 26.0 moles per 10 5 Gm. of protein were found for alpha, beta, and gamma crystallin, respectively. These values were altered to 5.9 and 8.5 for alpha and beta crystallin in 8 M urea, but that for gamma crystallin tvas unchanged. Extinction coefficients, E^so, of 8.3, 21.5, and 17.6 were found for alpha, beta, and gamma crystallin, respectively. Sedimentation constants of 18.9 S and 2.5 S toere calculated for alpha and gamma crystalline, respectively. Glycine tvas found to be the N-terminal amino acid of gamma crystallin. The presence of free N-terminal amino acids for alpha and beta crystallins could not be demonstrated. For these parameters, the characteristics of the rabbit lens crystallins are similar to those of bovine origin.
Foucault’s Untimely Struggle

In his series of essays on Kant written during the 1980s, Michel Foucault attempted to discern the difference today made with respect to yesterday. As his essays as well as his lectures (especially at the College de France and Berkeley) during the early 1980s demonstrate, he was drawn — and devoted the bulk of his scholarly efforts to a renewed form of genealogical work on themes, venues, practices and modes of governing the subject and others — to experiments in new forms of friendship, sociability and transformations of the self and others that he saw taking shape, or imagined were taking shape around him. This work, which has come to be known unfortunately as the ‘late Foucault’, arose out of deep dissatisfaction with his own life conditions, the broader political climate of the time, and a profound and unexpected rethinking not only of the specific projects he had intended to carry out but of what it meant to think. This article explores some of the elements at play during these deeply (re)formative s...
Alterations in binding characteristics of peripheral benzodiazepine receptors in testes by vitamin A deficiency in guinea pigs.

The correlation of vitamin A with the binding characteristics of peripheral benzodiazepine receptors (PBRs) in testes have been implicated on the basis of findings of involvement of vitamin A in testicular physiology and the abundance of PBRs in testicular tissue. Both vitamin A and PBRs are involved in the control of cell proliferation and differentiation but no data exists regarding the relationship between them. In the present study, we have examined the effects of vitamin A deficiency on the affinity and density of PBRs in testes of guinea pigs. Weanling guinea pigs were divided into three groups: control, pair-fed control and vitamin A deficient. They were fed a complete semipurified diet. The vitamin A deficient diet was similar to the control diet except vitamin A palmitate was omitted. Vitamin A deficiency status was achieved after 90 days of feeding. Binding of [3H]Ro 5-4864, a specific ligand for peripheral benzodiazepine receptors was determined in whole homogenate of testicular tissue. There was a 77% decrease in the receptor density (Bmax) in vitamin A deficient group compared to control. The Bmaxvalues for control, pair-fed control and vitamin A deficient groups were: 12.4 ± 0.4, 8.8 ± 0.2 and 3.0 ± 0.6 pmol/g, respectively. The equilibrium dissociation constant (KD) values were also 86% decreased in the vitamin A deficient group compared to the other groups. The KD values for control, pair-fed control and vitamin A deficient groups were: 3.4 ± 0.7, 2.8 ± 0.5 and 0.5 ± 0.01, respectively. The decrease in the binding characteristics of PBRs in testes due to vitamin A deficiency was accompanied with a corresponding decrease in the levels of testosterone in plasma. These results suggest a close functional relationship of vitamin A with PBRs in testes.
Design goals and system description of the flight support system/servicing aid tool

The flight support system/servicing aid tool (FSS/SAT) consists of two systems: the FSS, a cradle used with the Shuttle to berth, position, and power satellites, and the SAT, a telerobot to be attached to the FSS. The author identifies the design goals of the FSS/SAT and discusses the major features of the SAT. Particular attention is given to the main components of the protoflight system, a motorized Mini-Master, integrated into the Shuttle's aft flight deck, and an electric slave, integrated into the FSS and installed in the Shuttle's cargo bay. >
Modulation of Sp1 Phosphorylation by Human Immunodeficiency Virus Type 1 Tat

We previously reported (K. T. Jeang, R. Chun, N. H. Lin, A. Gatignol, C. G. Glabe, and H. Fan, J. Virol. 67:6224–6233, 1993) that human immunodeficiency virus type 1 (HIV-1) Tat and Sp1 form a protein-protein complex. Here, we have characterized the physical interaction and a functional consequence of Tat-Sp1 contact. Using in vitro protein chromatography, we mapped the region in Tat that contacts Sp1 to amino acids 30 to 55. We found that in cell-free reactions, Tat augmented double-stranded DNA-dependent protein kinase (DNA-PK)-mediated Sp1 phosphorylation in a contact-dependent manner. Tat mutants that do not bind Sp1 failed to influence phosphorylation of the latter. In complementary experiments, we also found that Tat forms protein-protein contacts with DNA-PK. We confirmed that in HeLa and Jurkat cells, Tat expression indeed increased the intracellular amount of phosphorylated Sp1 in a manner consistent with the results of cell-free assays. Furthermore, using two phosphatase inhibitors and a kinase inhibitor, we demonstrated a modulation of reporter gene expression as a consequence of changes in Sp1 phosphorylation. Taken together, these findings suggest that activity at the HIV-1 promoter is influenced by phosphorylation of Sp1 which is affected by Tat and DNA-PK.
Longitudinal correlates of aggressive behavior in help-seeking U.S. veterans with PTSD

The current study examined the longitudinal effects of clinical and treatment utilization factors on aggressive behavior among 376 help-seeking U.S. veterans recently diagnosed with posttraumatic stress disorder (PTSD) who were followed for 5-12 months. Participants were sampled from 4 strata: male Iraq/Afghanistan veterans, female Iraq/Afghanistan veterans, male prior-era veterans, and female prior-era veterans. Hierarchical regression analyses indicated that changes in PTSD severity were significantly associated with changes in aggressive behavior among veterans who reported any aggression at baseline (β = .15). Changes in days of alcohol intoxication also were positively associated with changes in aggressive behavior (β = .16). Participants with both a benzodiazepine prescription and any baseline aggression were significantly more likely to increase in aggressive behavior over time (β = .14). Contrary to our hypotheses, reductions in aggressive behavior were not related to the number of outpatient mental health visits or to first-line recommended psychotropic medications. Results inform assessment and clinical research on changes in aggressive behavior among veterans with PTSD.
Decreases in Evoked Overflow of Dopamine in Rat Striatum after Neurotoxic Doses of Methamphetamine

The repeated administration of methamphetamine (METH) can result in long-lasting decreases in dopamine (DA) levels, tyrosine hydroxylase activity and DA uptake sites in the striatum. However, whether these changes lead to functional alterations in the dynamics of DA release and uptake has not been extensively examined. The present study used in vivo electrochemistry and microdialysis to examine potassium- and amphetamine-evoked release of DA in the striatum and nucleus accumbens (NAc) of METH-treated rats. Male Fischer-344 rats were administered METH (5 mg/kg s.c.) or saline four times in 1 day, at 2-hr intervals. One week later the animals were anesthetized with urethane and prepared for in vivo electrochemical recordings. The METH treatment resulted in dramatic decreases in potassium-evoked release of DA and in the rate of DA clearance in the striatum, whereas the NAc was not significantly affected. In vivo microdialysis studies demonstrated significant decreases in basal DA levels and in potassium- and amphetamine-evoked overflow of DA in the striatum of METH-treated animals. Basal and evoked DA levels in the NAc were not altered. Post-mortem levels of tissue DA were decreased by 41 to 67% in the striatum and 25 to 31% in the NAc. These results indicate that the striatum is more sensitive than the NAc to the neurotoxic effects of METH, both in measures of functional dynamics of DA signaling and in tissue levels of DA. It remains to be determined whether these functional changes in DA release and uptake are permanent or tend to recover over time.
Predicting visual acuity from the structure of visual cortex

Three decades ago, Rockel et al. proposed that neuronal surface densities (number of neurons under a square millimeter of surface) of primary visual cortices (V1s) in primates is 2.5 times higher than the neuronal density of V1s in nonprimates or many other cortical regions in primates and nonprimates. This claim has remained controversial and much debated. We replicated the study of Rockel et al. with attention to modern stereological precepts and show that indeed primate V1 is 2.5 times denser (number of neurons per square millimeter) than many other cortical regions and nonprimate V1s; we also show that V2 is 1.7 times as dense. As primate V1s are denser, they have more neurons and thus more pinwheels than similar-sized nonprimate V1s, which explains why primates have better visual acuity.
Antennas for distributed nanosatellite networks

Distributed nanosatellite networks have the advantage of being reconfigurable, redundant, and readily deployable. Two types of antennas designed for this application are presented: a flexible UHF antenna for Earth-to-satellite communications, and an X-band retrodirective array for secure satellite-to-satellite crosslink communications.
Meson-nucleon coupling constants in a quark model

An effective vector exchange in a quark model, previously used for nucleon-antinucleon annihilation and meson decays, is applied to nucleon-meson and decuplet baryon-meson couplings. A reasonable fit to experimental data is obtained.
Getting to the “graphics” in a graphics exercise

An "algorithms" course in Computer Graphics relies heavily upon programming exercises to teach students the intricacies of graphics techniques. Such exercises should be substantial enough to avoid "trivializing" the problem and, at the same time, be interesting to the student. Unfortunately, substantial exercises also introduce a lot of overhead not directly related to the central graphics concepts being demonstrated. Overhead such as complex data structure definition and manipulation, external file input and output, low-level user interfaces, and graphics device drivers add a significant programming burden to the student. This overhead also detracts from the desired learning experience of the exercise. Various alternatives for solving this problem while maintaining the complexity of the exercise include: 1) designing the exercise to allow previous solution reusability, 2) providing a conceptual solution, 3) supplying actual code, both "white box" and "black box", and 4) making development tools and aids available, This paper will describe these different approaches, examine their advantages and disadvantages, and summarize our experience in the graphics course at the Air Force Academy.
Effects of forest road amelioration techniques on soil bulk density, surface runoff, sediment transport, soil moisture and seedling growth

Abstract Although numerous methods have been used to retire roads, new technologies have evolved that can potentially ameliorate soil damage, lessen the generation of nonpoint source pollution and increase tree productivity on forest roads. In this study we investigated the effects of three forest road amelioration techniques, subsoiling, recontouring and traditional retirement (control treatment), on soil bulk density, surface runoff, sediment production, soil moisture and seedling growth. As a point of comparison, surface runoff, sediment production and soil moisture was also measured on relatively undisturbed forested reference sites. The recontoured treatment had significantly lower bulk densities, surface runoff and sediment production than either the subsoiled or control treatments. The relatively undisturbed reference sites had very little runoff and hence, very low sediment production. Reference sites also had generally lower soil moisture at 0–15 and 15–25 cm than above, within and below the treatment road sections. Among treatments, few differences were found in soil moisture among treatment:landscape position combinations. Recontoured and subsoiled treatments had significantly greater white pine diameter growth than control plots. Yellow-poplar diameter and height growth was greatest for recontoured plots followed by the subsoiled plots and the control plots. The combination of data indicates that the use of recontouring techniques on forest roads generally leads to lower bulk densities, less surface runoff and sediment production and greater seedling growth than both traditional and subsoiling road retirement methods, however, the cost of recontouring is greater than subsoiling or traditional retirement and the preliminary analysis indicates that subsoiling may represent the most economically viable retirement method.
A new mouse lymphoid alloantigen (Lgp100) recognized by a monoclonal rat antibody

A new genetically polymorphic cell surface antigen recognized by a monoclonal rat anti-mouse antibody is expressed on mouse lymphoid cells. Fluorescence analysis on the fluorescence-activated cell sorter (FACS) locates the antigen on thymocytes, lymph node cells, and both T and B cells in the spleen. It also appears on approximately 40% of cells in the bone marrow. Immune precipitations from surface iodinated spleen cells followed by 2-D gel electrophoresis demonstrate that the antigen is a glycoprotein of approximately 100,000 daltons. Since it is expressed in all lymphoid tissues and on both T and B cells, we designate it lymphoid glycoprotein 100 (Lgp100). Strains with Lgp100 include A/J, AKR/J, AKR/Cu, BALB/c, 129/J, CBA/N, C3H/HeJ, CBA/2J, and SJL/J. Strains with no detectable antigen include C57BL/6J, C57BL/10J, C57BR/cdJ, C57L/J, and C58/J. Intercrosses and backcrosses establish a pair of alleles, a positive and a negative one, at a single locus. Heterozygotes display about 50% as much antigen as homozygotes by quantitative membrane immunofluorescence on the FACS. Tests for Lgp100 in 35 recombinant inbred strains from three crosses (CXB, BXB, and BXH) locate this locus on chromosome 1, closely linked to theMls locus.
Protective value of TIPS against the development of hydrothorax/ascites and upper gastrointestinal bleeding after balloon-occluded retrograde transvenous obliteration (BRTO)

Protective Value of TIPS Against the Development of Hydrothorax/Ascites and Upper Gastrointestinal Bleeding after Balloon-Occluded Retrograde Transvenous Obliteration (BRTO)
A finite element method for the solution of a potential theory integral equation

A finite element approximation for an integral equation of the second kind deduced from a potential theory boundary-value problem in two variables is discussed. The equation is shown to admit a unique solution, to be variational and coercive in the Hilbert space of functions sigma an element of H/sup 1/2/(GAMMA), integral/sub GAMMA/sigma d..gamma.. = 0. The Galerkin method with finite elements as trial functions is shown to lead to an optimal rate of convergence.
Career Preparedness Survey Outcomes of Food Science Graduates—A Follow-Up Assessment

Abstract: Fifty-eight recent graduates (1998–2008) from the joint Washington State University (WSU) and University of Idaho (UI) BiState School of Food Science program and 27 of their employers participated in a survey assessing learning outcomes based on the 2001 Institute of Food Technologists (IFT) core competencies for undergraduate food science programs. Parallel web-based survey instruments for the graduates and employers using the WSU Skylight Matrix Survey System© were employed to assess the attitudes of the respondents to the frequency of usage of IFT defined skills and the adequacy of the graduates’ preparation from the program. Graduates responded that they were generally satisfied with their education; however, they reported lower rates of adequate or better preparation in Success Skill involving group dynamics, processing and engineering skills, and government regulations. Most of these skills were also the least frequently used by graduates in their careers. Success Skills were the most frequently performed competencies, while food microbiology and safety, and some engineering and processing skills were used less frequently by graduates of the Food Science program. Greater than 80% of the employers reported that the graduates’ performance was adequate or better in all skill areas. The assessment suggested program improvement since a similar survey in 2004, but also illuminated areas for improvement in teaching and learning, particularly in light of the revised IFT 2011 Guidelines. Specifically, graduates and employers emphasized the need for more course work that weaves critical thinking skills, group dynamics, and government regulations into the classroom. Graduates also highlighted the importance of internships and extracurricular activities for career preparation.
Resource competition induces heterogeneity and can increase cohort survivorship: selection-event duration matters

Determining when resource competition increases survivorship can reveal processes underlying population dynamics and reinforce the importance of heterogeneity among individuals in conservation. We ran an experiment mimicking the effects of competition in a growing season on survivorship during a selection event (e.g., overwinter starvation, drought). Using a model fish species (Poecilia reticulata), we studied how food availability and competition affect mass in a treatment stage, and subsequently survivorship in a challenge stage of increased temperature and starvation. The post-treatment mean mass was strongly related to the mean time to mortality and mass at mortality at all levels of competition. However, competition increased variance in mass and extended the right tail of the survivorship curve, resulting in a greater number of individuals alive beyond a critical temporal threshold ([Formula: see text]) than without competition. To realize the benefits from previously experienced competition, the duration of the challenge ([Formula: see text]) following the competition must exceed the critical threshold [Formula: see text] (i.e., competition increases survivorship when [Formula: see text]). Furthermore, this benefit was equivalent to increasing food availability by 20 % in a group without competition in our experiment. The relationship of [Formula: see text] to treatment and challenge conditions was modeled by characterizing mortality through mass loss in terms of the stochastic rate of loss of vitality (individual's survival capacity). In essence, when the duration of a selection event exceeds [Formula: see text], competition-induced heterogeneity buffers against mortality through overcompensation processes among individuals of a cohort. Overall, our study demonstrates an approach to quantify how early life stage heterogeneity affects survivorship.
Understanding the Molecular Mechanism of Synergistic Inhibition in the Hepatitis C Virus (HCV) Polymerase Using Molecular Dynamics Simulations and Free Energy Calculations

The Hepatitis C Virus (HCV) affects close to 200 million globally. A major challenge in treating this infection is the emergence of resistance to current treatment regimens. An approach to reducing the rate of drug resistance is to increase the inhibitory effects of allosteric inhibitors by using them in combination to target the HCV polymerase (NS5B). Although recent biochemical studies show the use of multiple allosteric inhibitors has a synergistic inhibitory effect on NS5B, the molecular mechanisms by which this synergistic inhibition occurs still have not been clearly elucidated. To garner insight into the mechanism of synergistic inhibition of NS5B, we employ conventional and temperature accelerated molecular dynamics simulations of the enzyme simultaneously bound to two allosteric ligands. In concert with covariance and principal component analyses, data from the simulations allow us to compare specific structural and dynamic properties of the free and ligand-bound protein. Results thus far suggest that different allosteric ligands induce distinct protein conformations. Furthermore, when two ligands are present we observe that one inhibitor has a dominant impact in determining protein conformation. We have also carried out free energy calculations to understand differences in binding free energy that arise when one or both inhibitors are bound to NS5B. Understanding the molecular mechanism that mediate synergistic inhibition in NS5B may allow us to optimize the inhibitory activity of these compounds against the enzyme. In addition, these studies can provide fundamental insights into how ligand binding regulates protein function. Such information has direct applications in the areas of drug discovery, regulation of metabolic pathways and other signal transduction processes.
Induction and prevention of carcinogenesis in rat skin exposed to space radiation

Quantitative cancer incidence data exist for various laboratory animal models, but little of this information is usable for estimating human risks, primarily because of uncertainties about possible mechanistic differences among species. Acceptance and utilization of animal data for human risk assessment will require a much better understanding of the comparative underlying mechanisms than now exists. A dual-lesion, radiation-track model in rat skin has proven to be consistent with tumor induction data with respect to acute radiation doses ranging from 0.5 up to 10 Gy and higher, and average LETs ranging from 0.34 to 150 keV microm(-1) according to the form neoplastic risk (D,L) = CLD + BD2. A recent result with the 56Fe ion beam showed dose-response consistency for malignant (carcinomas) and benign (fibromas) tumor induction with earlier results utilizing argon and neon ion beams. A discrepancy between the model and experiment was found indicating that proportionality of cancer yield with LET did not occur at 150 versus 125 keV microm(-1), i.e. tumor yield did not increase in spite of a 20% increase of LET, which suggests that a LET response maximum exists at or within this dose range. Concordance between the model and tumor induction data in rat skin implies that potential intervening complexities of carcinogenic progression fail to obscure the basic radiobiological assumptions underpinning the model. Gene expression microarray analysis shows that vitamin A inhibits the expression of about 80% of the inflammation-related genes induced by the radiation and prevents about 46% of the neoplasms associated with 56Fe ion radiation without appearing to interfere with the underlying dose and LET response patterns. Further validation is needed, but the model has the potential to provide quantitative estimates of cancer risk as a function of dose and LET for almost any type of radiation exposure and even for combinations of different radiations provided only three empirical parameters can be established for each type of radiation and organ system.
Bracken and Locust Ecdysones: Their Effects on Molting in the Desert Locust

Bracken contains ecdysone derivatives that are active when injected into locusts. However, when fed to the desert locust as its sole or chief diet, it does not affect molting, growth, or development. There is evidence that, in locusts, the active ecdysones are dehydroxylated to α -ecdysone and passed out through the gut in the feces. There is no evidence for any uptake of ecdysones from the gut.
Phase behavior of the monoerucin/water system.

Abstract Monoerucin is a monoacylglycerol incorporating a cis monounsaturated fatty acid, 22 carbon atoms long, with the double bond at carbon number 13. The original temperature-composition phase diagram for the monoerucin/water system, constructed on the basis of ‘consistency’ and light microscopy, includes unexpectedly only the lamellar and fluid isotropic phases [Lutton, E.S., 1965. J. Am. Oil Chem. Soc. 42:1068–1070]. In separate studies using X-ray diffraction, the cubic phase [Larsson et al., 1978. J. Sci. Food Agric. 29:909–914] and the inverted hexagonal (HII) phase [Caffrey, M., 1989. Biophys. J. 95:11–21] were shown to be the dominant phases. We have resorted to the traditional isoplethal diffraction method for constructing the equilibrium phase diagram of monoerucin in water with a view to resolving the controversy regarding the thermotropic and lyotropic properties of the system. The study confirms the presence of the pure HII phase that extends from ca. 10 to 22% (w/w) water and from ca. 35 to 125°C, and its coexistence with excess water above ca. 24%(w/w) water in the same temperature range. The low temperature region of the diagram is dominated by the lamellar crystal (Lc) phase, with the existence of the lamellar liquid crystal (Lα) and cubic-Ia3d phases at intermediate temperatures and hydration levels. Differential scanning calorimetry and polarizing light microscopy were used to confirm the reported equilibrium phase behavior. Full structure characterization of the system and how phase microstructure depends on sample hydration and temperature are reported.
Fluorescent labeling of peptides on solid phase

N α-Fmoc-Ne-[(7-methoxycoumarin-4-yl)acetyl]-L-lysine (Nα-Fmoc-L-Lys(Mca)-OH) 3 is conveniently prepared by benzotriazole methodology (52% over two steps). N-Acylbenzotriazoles Mca-Bt 2, Nα-Fmoc-L-Lys(Mca)-Bt 4, coumarin-3-ylcarbonyl (Cc)-Bt 5, Nα-Fmoc-L-Lys(Cc)-Bt 7 and Nα-(Cc)-L-Lys(Fmoc)-Bt 9 enable the efficient microwave enhanced solid-phase fluorescent labeling of peptides.
Molecular approaches to the diagnosis of male infertility

The introduction of the polymerase chain reaction (PCR) as a technique to selectively amplify and identify specific DNA and RNA sequences has revolutionized the field of molecular medicine. Application of these newly developed molecular techniques to the field of male infertility has made the delineation of subtle causes of infertility-an inapparent genital tract infection, immune system activation within the genital tract, mutations in sperm mitochondrial or chromosomal DNA, alterations in sperm components involved in receptor-ligand interactions, and production of sperm autoantibodies-all increasingly amenable to clinical analysis. Continued investigations at the molecular level of the causes of male infertility will also lead to novel treatment regimens as well as development of new methods of fertility regulation.
Role of Angiotensin‐Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Aldosterone Antagonists in the Prevention of Atrial and Ventricular Arrhythmias

Atrial arrhythmias, ventricular arrhythmias, and sudden cardiac death (SCD) are significant health problems and an economic burden to society. The renin-angiotensin-aldosterone system (RAAS) may play a key role in the occurrence of structural and electrical remodeling, potentially explaining the development of atrial and ventricular arrhythmias. Angiotensin II has been shown to regulate cardiac cell proliferation and to modulate cardiac myocyte ion channels. Results of post hoc analyses from prospective clinical trials appear to show that angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are most effective in the prevention of new-onset atrial fibrillation in patients with heart failure. It is difficult to determine if these agents are useful in the prevention of new-onset atrial fibrillation after myocardial infarction, and available evidence suggests that the benefit of ACE inhibitors and ARBs for prevention of new-onset atrial fibrillation in patients with hypertension appears limited to those with left ventricular hypertrophy. Patients with structural changes in cardiac muscle, such as those with heart failure and left ventricular hypertrophy, appear to benefit the most from RAAS blockade, possibly due to the theory of reversal of cardiac remodeling. There is no evidence, to our knowledge, that either ACE inhibitors or ARBs facilitate direct electrical current cardioversion in patients with atrial fibrillation; however, it appears that RAAS blockade may be useful in the prevention of recurrent atrial fibrillation after direct electrical current cardioversion. Whether ACE inhibitors may prevent life-threatening ventricular arrhythmias or SCD is unclear. Aldosterone antagonists appear to be useful for the prevention of SCD in patients with left ventricular systolic dysfunction. Results from ongoing clinical trials are anticipated to provide further insight on the potential roles of RAAS inhibitors for the prevention of cardiac arrhythmias.
Programming cellular function

The process of cellular engineering is rapidly accelerating owing to advances in technologies to manipulate DNA and other biomolecules, giving rise to the field of synthetic biology. A meeting was held in August 2005 to present progress in the field and to discuss topics in ethics, safety and security.
Group Structural Realism

We present a precise form of structural realism, called group structural realism, which identifies 'structure' in quantum theory with symmetry groups. However, working out the details of this view actually illuminates a major problem for structural realism; namely, a structure can itself have structure. This article argues that, once a precise characterization of structure is given, the 'metaphysical hierarchy' on which group structural realism rests is overly extravagant and ultimately unmotivated.
Free energy model for piezoceramic materials

This paper addresses the development of a free energy model for quantifying the hysteresis and constitutive nonlinearities inherent to piezoceramic materials. In the first step of the development, free energy relations for a single crystal with uniform lattice are considered and used to construct evolution equations which quantify the polarization as a function of the applied field. The effects of nonuniform lattice structures, nonhomogeneous effective fields and polycrystalline materials are then incorporated through the use of appropriate distributions in the free energy formulation. The resulting model, which is an extension of the Muller-Achenbach-Seelecke theory for shape memory alloys, is low-order and hence highly efficient to implement. Attributes of the model are illustrated through comparison with experimental data.
Primary realignment of posterior urethral ruptures in children.

Summary— Primary realignment was used in the treatment of 12 children with complete rupture of the posterior urethra; 10 developed strictures but 7 of these responded to dilatation. Problems of continence were encountered only in patients who developed strictures. Since primary realignment results in dilatable strictures in most patients, it is suggested that this should be the treatment of choice in children.
Robust Control of Uncertain Systems with Time-Varying Uncertainty: A Computer-Aided Setup with Illustrations

The problem of stabilising a class of linear uncertain systems by using linear state feedback is addressed. The system possesses uncertainty which is time-varying, unknown, but lies within a prescribed set (hence bounded). No statistical information of the uncertainty is imposed. Nor any match condition is required. Necessary and sufficient conditions for quadratic stabilisability are formulated. The controller synthesis and stability analysis are investigated by a two level optimisation process. The result is believed to be practical (in the sense that it can be implemented for non-trivial physical systems) and non-conservative.
The use of adjunctive drugs to alter uptake of 99mTc-Sn-pyrophosphate by myocardial lesions and bone

Abstract A single intravenous injection of 1.25 mgm of vitamin D3 (50,000 U.S.P. units) in rats caused a significant decrease in the uptake of 99mTc-Sn-Pyrophosphate by bone when the radioactive compound was given 16 or 22 hours after vitamin D3 and the rats were sacrificed 2 hours thereafter for determination of uptake. In rats with myocardial infarcts, produced by cautery under anesthesia, vitamin D3 did not cause a significant decrease in uptake by infarct and in some instances even appeared to increase the latter uptake. Vitamin D3 thus caused a significant increase in the ratio, uptake by infarct/uptake by bone. A single oral dose of 1.25 mgm of dihydrotachysterol had a similar effect, increasing the ratio, uptake by infarct/uptake by bone. In the large single dose used here, vitamin D3 caused the expected increase in the concentrations of calcium and phosphorus in the serum. The effect on uptakes shown here is an example of the ability of a stable drug to influence significantly the distribution of a radioactive diagnostic drug. As bone is the chief non-target tissue degrading the quality of the image when 99mTc-Sn-pyrophosphate is used clinically as a scintigraphic agent for the visualization of myocardial infarcts, an increase in the ratio, uptake by infarct/uptake by bone, is of interest.
Record for measuring interocclusal distance in fixed implant prosthodontics.

VOLUME 86 NUMBER 6 In implant prosthodontics, knowledge of the interocclusal distance is critical for planning treatment1 and ordering prosthetic components such as abutments, analogs, and protective caps. The best technique for measuring the interocclusal distance makes use of mounted diagnostic casts.1 However, occasionally it may be necessary to have a quicker yet reliable method for measuring this distance. This article describes an easy, inexpensive method for measuring the interocclusal distance to aid in proper selection of implant prosthetic components.
Specific high affinity binding sites for somatostatin-28 on pancreatic beta-cells: differences with brain somatostatin receptors.

Saturable and high affinity binding sites have been obtained for an iodinated somatostatin-28 (SS-28) analog, [Leu8,D-Trp22125I-pyr25] SS-28, in a membrane preparation from hamster insulinoma, mainly composed of pancreatic β-cells. Specific binding is maximal after 1 hour incubation at 22 C and represents 65% of the total binding. KD for [Leu8,D-Trp22,Tyr25] SS-28 is 0.25 nM with the number of sites corresponding to 68 fmol/mg protein. The KD for SS-28 (lnM) is more than 5 times lower than that for SS-14. SS-28 analogs, such as [D-Trp22] SS-28 and analogs which selectively inhibit insulin releass in vivo (Des-Asn5[D-Trp8,D-Ser13] SS-14 and Des-Asn 19[D-Trp22D-ser27] SS-28), are the most potent compounds in this assay. C-terminal replacement of Lcysteine by D-cysteine reduces the apparent affinity of SS analogs. Unrelated peptides and the inactive analog Des-Trp8-SS-14 have no affinity for insulinoma binding sites. There are differences between the insulinoma SS binding sites and those monitored under simi...
Emission mössbauer spectroscopy for biologically important molecules. vitamin B12, its analogs, and cobalt phthalocyanine

Abstract It has been shown that complex molecules with conjugated ring systems, such as vitamin B12. its analogs, and cobalt phthalocyanine, escape fragmentation during the Auger event following electron-capture decay of cobalt-57. Consequently, Mossbauer spectra are characteristic of the entire molecues. This opens up very interesting possibilities for the use of emission Mossbauer spectroscopy for biologically important molecues.
CAVITY QUANTUM ELECTRODYNAMICS AT OPTICAL FREQUENCIES

Quantum electrodynamics (QED) tells us that the electromagnetic field is, on a mode-by-mode basis, quantized according to the harmonic oscillator model. Each mode is ascribed a lowest energy (or dark) state possessing one half quanta of non-removable energy plus an infinite ladder of equally spaced excited states accessed through the addition or removal of energy quanta from the mode. In the optical regime and under normal thermal conditions, electromagnetic field modes are typically in their dark state. Nevertheless, a residual dark-state atom-field coupling remains, and it is this coupling that mediates shifts and spontaneous radiative decay of atomic states. The experimental reality of dark-state atom-field coupling is frequently interpreted as proof of the quantum description of light.
Effects of stress and ACTH on plasma corticosterone levels in the caiman Caiman crocodilus.

Abstract Corticosterone levels in blood plasma of the caiman were measured in response to the collection of blood and to the administration of mammalian ACTH. Blood collection resulted in an increase in plasma corticosterone levels; the highest levels of corticosterone were observed 2 hr after the initial sample, and corticosterone levels declined thereafter despite continued blood collection. Prior treatment of caimans with dexamethasone abolished the response to blood collection. Administration of mammalian ACTH to dexamethasone-treated caimans resulted in elevated corticosterone levels. The levels of corticosterone measured in plasma did not vary with the amount of ACTH administered, but the duration of the steroidogenic response was dose-dependent.
Noise-induced hearing loss: an occupational medicine perspective.

Purpose of reviewUp to 30 million workers in the United States are exposed to potentially detrimental levels of noise. Although reliable medications for minimizing or reversing noise-induced hearing loss (NIHL) are not currently available, NIHL is entirely preventable. The purpose of this article is