cssi/SciSciGPT-SciSciNet huggingface dataset:
Improving the informativeness of Mendelian disease-derived pathogenicity scores for common disease

Despite considerable progress on pathogenicity scores prioritizing variants for Mendelian disease, little is known about the utility of these scores for common disease. Here, we assess the informativeness of Mendelian disease-derived pathogenicity scores for common disease and improve upon existing scores. We first apply stratified linkage disequilibrium (LD) score regression to evaluate published pathogenicity scores across 41 common diseases and complex traits (average N = 320K). Several of the resulting annotations are informative for common disease, even after conditioning on a broad set of functional annotations. We then improve upon published pathogenicity scores by developing AnnotBoost, a machine learning framework to impute and denoise pathogenicity scores using a broad set of functional annotations. AnnotBoost substantially increases the informativeness for common disease of both previously uninformative and previously informative pathogenicity scores, implying that Mendelian and common disease variants share similar properties. The boosted scores also produce improvements in heritability model fit and in classifying disease-associated, fine-mapped SNPs. Our boosted scores may improve fine-mapping and candidate gene discovery for common disease.
Intra-pore tortuosity and diverging-converging pore geometry controls on flow enhancement due to liquid boundary slip

Abstract The liquid boundary slip, in contrast to the conventional no-slip boundary condition, exists due to a less wetting or the non-wetting nature of sediment grains, which can significantly control fluid hydraulics of porous media, specifically which consists of smaller pore-throats, e.g., siltstones and mudstones. Most studies to date presume a no-slip boundary condition and a few who have investigated the aspects of slip-boundary presume a simplified straight tube or a non-tortuous pore shape. Therefore, how the degree of tortuosity and pore-geometry control flow enhancement in porous media remains underexplored. In this computational study, we design a set of diverging-converging staggered tortuous (DCST) pores, which account for a variable amount of intra-pore tortuosity. To compare, a set of capillary pores are designed that can account for tortuosity by taking the form of sinusoidal and helical shapes. Our results quantify how the diverging-converging nature of pore geometry and its intra-pore tortuosity alone have a significant impact on modifying the microscopic flow behavior -accounting of which is a key in upscaling these effects to a macroscopic continuum or the Darcy-scale. We find, DCST pores contribute to an asymptotic flow enhancement behavior in response to boundary slip. In comparison, capillary pores lead to a linearly ‘unlimited’ flow enhancement. This unlimited nature of flow enhancement can lead to differences over several orders in magnitude. We test theoretical models to predict flow enhancement from all pores. We determine constitutive relations that can predict flow enhancement as a function of intra-pore tortuosity and hydraulic shape factor. We examine the physical mechanisms of energy dissipation and find that the microscopic fluid-structure interactions can contribute to significant variation in how intra-pore geometry and boundary slip manifest as the flow enhancement factor relevant to the continuum-scale. We find that the ‘asymptote’ in the flow enhancement factor of DCST pores manifests as a result of an equilibrium between energy dissipation and enhancing flow due to boundary slip, at least in the laminar flow regime.
Bootstrapping Large Sense Tagged Corpora

The performance of Word Sense Disambiguation systems largely depends on the availability of sense tagged corpora. Since the semantic annotations are usually done by humans, the size of such corpora is limited to a handful of tagged texts. This paper proposes a generation algorithm that may be used to automatically create large sense tagged corpora. The approach is evaluated through comparative sense disambiguation experiments performed on data provided during the SENSEVAL-2 English all words and English lexical sample tasks.
Returns Policies for a Pessimistic Retailer

Manufacturer buy-back policies are studied in the context of asymmetric demand information. A manufacturer offers a new product for sale to a retailer who makes a single stocking decision prior to the sales period. The two parties formulate different demand forecasts, either because they cannot share all relevent information or because the shared information lacks suffcient credibility. The manufacturer's pro t is, therefore, limited by the retailer's forecast which is relatively pessimistic. Offering to buy-back unsold items can induce the retailer to order more while supporting higher wholesale prices. It can also signal credibility for the manufacturer's optimistic forecast. Yet, the actual effect of buy-back depends on how the retailer regards the manufacturer's information. This paper characterizes two extremes: the retailer either deems the manufacturer to be better informed or less informed about demand. Buy-back serves as a signaling mechanism on the one hand and as an inducement on the other.
Lectures on Counterexamples in Several Complex Variables

Some notations and definitions Holomorphic functions Holomorphic convexity and domains of holomorphy Stein manifolds Subharmonic/Plurisubharmonic functions Pseudoconvex domains Invariant metrics Biholomorphic maps Counterexamples to smoothing of plurisubharmonic functions Complex Monge Ampere equation $H^\infty$-convexity CR-manifolds Pseudoconvex domains without pseudoconvex exhaustion Stein neighborhood basis Riemann domains over $\mathbb{C}^n$ The Kohn-Nirenberg example Peak points Bloom's example D'Angelo's example Integral manifolds Peak sets for A(D) Peak sets. Steps 1-4 Sup-norm estimates for the $\bar{\partial}$-equation Sibony's $\bar{\partial}$-example Hypoellipticity for $\bar{\partial}$ Inner functions Large maximum modulus sets Zero sets Nontangential boundary limits of functions in $H^\infty(\mathbb{B}^n$ Wermer's example The union problem Riemann domains Runge exhaustion Peak sets in weakly pseudoconvex boundaries The Kobayashi metric Bibliography.
A Syntactic Bias in Scope Ambiguity Resolution in the Processing of English-French Cardinality Interrogatives: Evidence for Informational Encapsulation.

This article presents a reading-time study of scope resolution in the interpretation of ambiguous cardinality interrogatives in English-French and in English and French native sentence processing. Participants were presented with a context, a self-paced segment-by-segment presentation of a cardinality interrogative, and a numerical answer that respondents either accepted or rejected. Very narrowly distributed and interpretation-dependent reading-time asymmetries arose in English-French processing and in French and English native processing. A syntactic account of scope resolution characterizes the reading-time asymmetries produced by English-French learners and differences between French and English native respondents. In contrast, a context-driven theory of scope resolution encounters many severe problems that render its plausibility exceedingly remote.
A Lockean Theory of Intellectual Property

What follows is a brief introduction to the domain or subject matter of intellectual property, an examination of the most widely supported rule-utilitarian argument, a defense of a new Lockean model, and suggested revisions in Anglo- American intellectual property law based on the Lockean model. I will argue that incentives based rule-utilitarian arguments fail to justify anything remotely close to modern Anglo-American copyright, patent, and trade secret institutions. Moreover, rule-utilitarian moral theory is beset with a number of problems that undermine its initial plausibility. If I am correct, and rule-utilitarian models of intellectual property fail, justification for intellectual property rights must be found elsewhere.In the most general terms, my hope is to change public policy and the way judges and lawyers think about protect- ing the creative efforts of authors and inventors. Rights to control intellectual works are not ultimately based solely on grounds of social utility. This is clear in the most trivial of case; independent of social utility, individuals have the right to control the contents of their minds. I will argue that we must recast institutions of intellectual property in a Lockean light, thereby providing a firmer foundation for rights and a closer fit with other rights found within the Anglo- American tradition.
Polymerizable amphiphiles, 2. Micellization of 1‐O‐3‐(4‐vinylphenyl)propyl‐β‐D‐glucopyranose

1-O-3-(4-Vinylphenyl)propyl-β-D-glucopyranose (1) undergoes in water a closed association under formation of N-mers. The unimer/N-mer association is directly visible in the Schlieren pattern of ultracentrifugal synthetic boundary experiments. Association numbers and mass-concentration-based equilibrium constants of association were calculated from the variation of N-mer concentrations with unimer concentrations and from the concentration dependence of inverse apparent average molar masses as measured by both vapor phase osmometry and sedimentation equilibrium. Association numbers were also calculated from the combination of sedimentation coefficients with diffusion coefficients, sedimentation coefficients with intrinsic viscosities, and diffusion coefficients with interinsic viscosities as well as from the dependence of apparent mass-average molar masses on inverse apparent number-average molar masses. All methods gave in general different association numbers and equilibrium constants. The effect, which was not found for other non-ionic amphiphiles, is probably due to the existence of consecutive equilibria between the unimer and a low molar mass P-mer which associates to a higher molar mass R-mer. Viscosity data are in agreement with the picture of a spherical micelle for the dominant P-mers with about 10 water molecules per glucose residue. The micellization of 1 is both enthalpy- and entropy-driven, in contrast to the micellization of 1-O-octyl-β-D-glucopyranose which is a strictly entropy-driven process.
Para-bromophenacyl bromide inhibits endothelium-dependent arterial relaxation and cyclic GMP accumulation by effects produced exclusively in the smooth muscle

The alkylating agent para-bromophenacyl bromide (PBPB) has been reported to block endothelium-dependent relaxation of arteries, presumably by inhibiting phospholipase in the endothelium. We have investigated the site of action of PBPB-induced inhibition of melittin (MEL)- and bradykinin (BK)-stimulated endothelium-dependent relaxation and vascular smooth muscle (VSM) cyclic GMP (cGMP) accumulation. Studies were performed using short-term co-cultures of bovine pulmonary artery endothelial cells (EC) grown on microcarrier beads and rat aortic VSM. The culture system allowed separate pretreatment of ECs and VSM cells with PBPB (3 X 10(-5) M) before placement of the two cell types in co-culture. Because PBPB is an alkylating agent, it was felt that any blockade would endure after washout. Intracellular (VSM) concentrations of cGMP rose in response to MEL or BK stimulation only when EC were present, and were not decreased when only the EC had been pretreated with PBPB. cGMP accumulation induced by MEL or BK was significantly (P less than .01) inhibited in co-cultures where either the VSM alone or VSM and EC combined were pretreated with PBPB. The PBPB pretreatment adequately blocked EC phospholipase activity as measured by attenuation of the release of [3H]arachidonate from prelabeled EC by MEL. In parallel studies, when endothelium-derived relaxing factor was transferred by superfusion of EC to denuded rabbit aortic rings contracted with phenylephrine and pretreated with PBPB, the relaxation response induced by MEL or BK was inhibited. Similarly, when endothelium-derived relaxing factor was transferred to wells of cultured VSM pretreated with PBPB, cGMP accumulation was inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)
Carbon-13 magnetic resonance shifts in triscyclopentadienyl uranium(IV) chloride

Abstract Carbon-13 NMR shift of (C 5 H 5 ) 3 UCl in THF for 160 ⩽ 320 K consists of a Curie-Weiss part with a Weiss temperature of 140 ± 10 K and a temperature-independent part of +59 ppm with respect to TMS. The contact shift is −309 ± 120 ppm at 290 K and is larger than the pseudocontact shift by about a factor of two.
Ground arthropod community structure in a heterogeneous urban environment

Despite being conspicuous and influential features of the biosphere, urban ecosystems have been neglected in ecological research. Arthropods are abundant in urban settings, but little is known about how these animals respond to urbanization. We systematically monitored the structure of ground arthropod communities for 12 months at 16 sites representing the four most abundant forms of urban land use (residential, industrial, agricultural, and desert remnant) in a rapidly growing metropolitan area (Phoenix, AZ). Although taxonomic richness was comparable among land-use types, community composition differed, with certain taxa being uniquely associated with each form of land use. Three taxa (springtails, ants, and mites) were extremely widespread and abundant, accounting for over 92% of captures; when these three taxa were excluded from analysis, however, differences were revealed in arthropod community composition with urban land use. Trophic dynamics also varied with land use: predators, herbivores, and detritivores were most abundant in agricultural sites, while omnivores were equally abundant in all forms of land use. These community-level differences resulted from taxon-specific responses to habitat structure, which varied with land use. Because arthropod community structure is affected by habitat structure and land use, and because arthropods play key roles in nutrient cycling, organic matter decomposition, pollination, and soil aeration, the spatial heterogeneity of urban ecosystems therefore may affect ecosystem functioning.
Population structure and gene flow in a heavily disturbed habitat: implications for the management of the imperilled Red Hills salamander (Phaeognathus hubrichti)

Estimating levels of gene flow and assessing levels of population connectivity are of critical importance to the field of conservation genetics, especially for imperiled species. Many factors can influence dispersal and therefore gene-flow patterns across a natural landscape. These patterns can be substantially altered by the impacts of habitat modification by humans or natural phenomena. Landscape-genetic studies that address both historical and contemporary influences on gene flow can be critical to demonstrating whether isolated populations with low levels of genetic variation are typical of the species or a result of strong negative effects of such modification. We used 10 microsatellite markers to investigate the spatial genetic patterns of the Red Hills salamander (Phaeognathus hubrichti), a federally listed species. Bayesian clustering revealed five well-supported demes within the range of P. hubrichti. Gene-flow analysis suggested that overall migration levels for P. hubrichti are low, but coalescent methods indicate that migration levels were significantly higher before habitat modification by humans. By accounting for history and species characteristics, our results suggest that loss and fragmentation of habitat have strongly negatively affected P. hubrichti by reducing migration, increasing bottlenecks, and promoting high levels of inbreeding.
IMAGING OF SALIVARY GLAND PATHOLOGY

Calcifications in the salivary glands may occur in calculi, chronic infection or inflammation, phleboliths, lymph nodes, chronic hematoma, amyloidosis, and tumors including pleomorphic adenomas, schwannomas, and mucoepidermoid cancers. This article discusses the different types of salivary gland conditions and the best methods of imaging for diagnosis.
Public Health Spending and Population Health: A Systematic Review

Context This systematic review synthesizes what is known about the relationship between public health spending and population health outcomes, as well as the pathways that may explain how outcomes vary with spending. It also discusses the limitations of the existing literature and identifies areas in need of future research. Evidence acquisition Studies included in this review were retrieved through an iterative process, primarily through key word searches in two literature databases (PubMed and JSTOR) conducted in 2013. All retrieved studies underwent initial and secondary screening. Articles were included if they (1) examined the link between spending and outcomes or (2) explored pathways that mediate the relationship between spending and outcomes. Evidence synthesis Seventeen empirical studies and five literature reviews published between 1985 and 2012 were included in this review. Existing evidence suggests that increases in public health spending are associated with improved population health, at least for some outcomes. However, there is little evidence to suggest that increased spending contributes to meaningful reductions in health disparities. Moreover, the pathways through which greater spending translates into better outcomes are not well understood. Conclusions Although the complexity of the public health delivery system makes it difficult to demonstrate definitive associations between spending and outcomes, financial investments in public health have the potential to improve community health. Additional research is needed to explore the pathways that mediate this relationship. This research would benefit public health practitioners who need evidence on how to best spend financial resources to achieve better health outcomes.
Thermal Conductivity Reduction of SiGe Nanocomposites

High figure of merit has been reported in superlattice structures in recent years mainly due to a large reduction in thermal conductivity, while maintaining or even enhancing the power factor. These findings suggest the possibility of using nanocomposites to reduce a material's thermal conductivity and thereby increasing the thermoelectric figure of merit. The current work reports on the thermal conductivity of various Si-Ge nanocomposites synthesized in a simple and straightforward process that allows one to exploit nanoscale physics while rapidly producing macroscale devices. Composite synthesis consisted of combining Si nanoparticles approximately 70 nm in diameter with micron-sized Ge particles in various atomic ratios via hotpressing to form macroscale samples. Room-temperature thermal conductivity was measured for each of the nanocomposite samples and compared with the values of SiGe bulk alloys. In this preliminary work, we observed a significant reduction in bulk thermal conductivity in such materials.
Techniques for outcomes research in chronic sinusitis

Accurate assessment of patient outcome after sinus surgery requires the collection of valid and reliable data. Symptom-based surveys were administered in a prospective manner to 104 patients with chronic sinusitis. Test-retest reliability for the Chronic Sinusitis Survey based on duration of symptoms (0.86, P<.0001) was superior to that for a similar survey based on severity of symptoms (0.57, P<.0001). Results of the Chronic Sinusitis Survey also correlated significantly with subscales of a general health assessment in the extent to which chronic sinusitis limits physical activity (0.40, P<.01), interferes with work or other activities (0.36, P<.01), and affects patient perception of bodily pain (0.46, P<.001). The Chronic Sinusitis Survey is an efficient and reliable method to follow health status and health-related quality of life outcomes in patients with chronic sinusitis
Effects of chronic cocaine administration on dopamine transporter mRNA and protein in the rat.

Male Sprague-Dawley rats were administered cocaine (10, 15 or 25 mg/kg) or vehicle, i.p., once daily for 8 consecutive days and killed 1 h after the last injection. Acute cocaine administration produced dose-dependent increases in spontaneous locomotor activity. These levels of activity were further enhanced by 8 days of chronic treatment, indicating the emergence of behavioral sensitization. Chronic cocaine administration resulted in dose-dependent decreases in the density of dopamine transporter (DAT) mRNA in both the substantia nigra pars compacta and ventral tegmental area as shown by in situ hybridization histochemistry. Changes in DAT binding sites were assessed using [3H]mazindol quantitative autoradiography. In contrast to the levels of mRNA, there were few changes in the number of [3H]mazindol binding sites. Although the density of binding sites was unaltered in most regions, [3H]mazindol binding was increased in the anterior nucleus accumbens. This study extends previous findings by demonstrating the dose-dependent nature of the changes in DAT mRNA that accompanies chronic cocaine administration. The levels of DAT binding sites within the dorsal and ventral striatum, however, were largely unchanged. This mismatch suggests that cocaine may differentially influence the gene expression of DAT in the ventral midbrain as compared to the density of DAT binding sites in the basal forebrain.
Elementary and Secondary School Counselors' Perceptions of Graduate Preparation Programs: A National Study.

In a national survey, members from the American School Counselor Association were asked to rate the importance of graduate-level training for 24 course content areas. Analysis indicated that there were similarities and significant differences between elementary school counselors and secondary school counselors on their perception of the importance of various course content areas. Implications for school counselor education were discussed.
Activity-dependent change in morphology of the glial tubular lattice of the crayfish medial giant nerve fiber.

An evaluation of electron micrographs of stimulated nerve fibers used to investigate the effect of action potential generation on the structure–function relationship between axons and its associated glial cells revealed that what was at first thought to be stimulation-induced damage to the glia was, in fact, limited to volume expansion and disaggregation of the glial tubular lattice. All other structures appeared well preserved and otherwise normal. Using a 4-point subjective scale for evaluation by two investigators, 50-Hz stimulation for 2 min was observed to cause a volume expansion and disaggregation of the tubular lattice. Quantitatively, the internal diameter of the stimulated tubular lattice increased 65% above the unstimulated control (50.96 ± 2.09 nm and 30.81 ± 0.87 nm, respectively, P ≤ 0.001). Stimulation had its greatest effect on tubular lattice volume and organization in the adaxonal glial layer and a decreasing effect as distance from the giant axon increased. These effects are reversible since the tubular lattice diameter and degree of disaggregation preserved 10 min after the cessation of stimulation were not found to be different from their unstimulated paired controls. Axons injected with TEA, a voltage-gated potassium channel blocker, prevented stimulation-induced volume expansion and disaggregation of tubular lattice structure. These results are consistent with an active uptake of K+ with obligated water or, alternatively, hyperosmotic K+ uptake and a fixation-induced increase in water permeation. Either mechanism of K+ uptake would result in tubular lattice volume expansion and disaggregation and suggests that the tubular lattice serves a larger role than a simple trans-glial diffusion pathway. © 2005 Wiley-Liss, Inc.
Over-the-counter access changing WHO guidelines and contraindicated oral contraceptive use in Mexico.

This study examines the prevalence of contraindications to the use of oral contraceptives in Mexico by sociodemographic characteristics and by whether this family planning method was obtained with or without a doctor's prescription. Using data on smoking behavior and blood-pressure measurements from the 2000 Mexican National Health Survey, the authors found that, under the 1996 World Health Organization (WHO) medical eligibility guidelines, the prevalence of contraindications is low and that no significant differences in contraindications exist at any level between those who obtain oral contraceptives at clinics and those who obtain them at pharmacies. In 2000, however, WHO substantially revised its criteria regarding the level of hypertension that would constitute a contraindication for oral contraceptive use. Applying the new guidelines, the authors found that 10 percent of pill users younger than 35 and 33 percent aged 35 and older have health conditions that are either relative or absolute (Category 3 or 4) contraindications. The relevance of these findings to the larger debate concerning screening and over-the-counter access to oral contraceptives is discussed.
Antidepressants in panic disorder and agoraphobia.

Abstract A survey of the literature on the use of antidepressants for treating patients with panic disorder and agoraphobia with panic attacks suggests that both tricyclic antidepressants and monoamine oxidase inhibitors have efficacy in blocking panic attacks. While we have witnessed dramatic progress in the pharmacological treatment of panic-related disorders over the past 20 years, many unresolved questions remain. Further understanding of dose—response relationships, optimal duration of treatment and predictors of relapse are needed to optimize pharmacological treatment of panic-related disorders. Studies comparing the relative efficacy and side effects spectrum of various effective medications are needed. It is not presently possible to specify which patients will require medication or behavioral treatment alone, and studies to date have incompletely examined this murky issue. Further prospective studies directly comparing the pharmacological and behavioral treatments will help further elucidate the relative contribution of each treatment and possibly clarify which patients require both treatments. Controlled studies in the future which standardize dosage and duration of treatment and use comparable, objective outcome variables promise to provide important theoretical and clinical information regarding the pharmacological treatment of panic-related disorders.
Dynamic metabolic flux analysis of plant cell wall synthesis.

The regulation of plant cell wall synthesis pathways remains poorly understood. This has become a bottleneck in designing bioenergy crops. The goal of this study was to analyze the regulation of plant cell wall precursor metabolism using metabolic flux analysis based on dynamic labeling experiments. Arabidopsis T87 cells were cultured heterotrophically with 13C labeled sucrose. The time course of 13C labeling patterns in cell wall precursors and related sugar phosphates was monitored using liquid chromatography tandem mass spectrometry until steady state labeling was reached. A kinetic model based on mass action reaction mechanisms was developed to simulate the carbon flow in the cell wall synthesis network. The kinetic parameters of the model were determined by fitting the model to the labeling time course data, cell wall composition, and synthesis rates. A metabolic control analysis was performed to predict metabolic regulations that may improve plant biomass composition for biofuel production. Our results describe the routes and rates of carbon flow from sucrose to cell wall precursors. We found that sucrose invertase is responsible for the entry of sucrose into metabolism and UDP-glucose-4-epimerase plays a dominant role in UDP-Gal synthesis in heterotrophic Aradidopsis cells under aerobic conditions. We also predicted reactions that exert strong regulatory influence over carbon flow to cell wall synthesis and its composition.
Reconstruction of chaotic orbits under finite resolution

Abstract In this paper, it is shown how information about an orbit of a chaotic dynamical system can be recovered given only measurements with “large” error. Assuming that the imprecision of measurements manifests itself as a finite partition of the phase space, general, necessary, and sufficient conditions under which it is possible to reconstruct orbits are presented. Two reconstructing methods and their pseudocodes are presented and analyzed. The applicability of those methods is tested using a series of computer experiments for various one-dimensional mappings on the unit interval. Potential applications are also discussed.
Radiosynthesis of N-(4-chloro-3-[11C]methoxyphenyl)-2-picolinamide ([11C]ML128) as a PET radiotracer for metabotropic glutamate receptor subtype 4 (mGlu4)

N-(Chloro-3-methoxyphenyl)-2-picolinamide (3, ML128, VU0361737) is an mGlu4 positive allosteric modulator (PAM), which is potent and centrally penetrating. 3 is also the first mGlu4 PAM to show efficacy in a preclinical Parkinson disease model upon systemic dosing. As a noninvasive medical imaging technique and a powerful tool in neurological research, positron emission tomography (PET) offers a possibility to investigate mGlu4 expression in vivo under physiologic and pathological conditions. We synthesized a carbon-11 labeled ML128 ([(11)C]3) as a PET radiotracer for mGlu4, and characterized its biological properties in Sprague Dawley rats. [(11)C]3 was synthesized from N-(4-chloro-3-hydroxyphenyl)-2-picolinamide (2) using [(11)C]CH3I. Total synthesis time was 38±2.2min (n=7) from the end of bombardment to the formulation. The radioligand [(11)C]3 was obtained in 27.7±5.3% (n=5) decay corrected radiochemical yield based on the radioactivity of [(11)C]CO2. The radiochemical purity of [(11)C]3 was >99%. Specific activity was 188.7±88.8GBq/mol (n=4) at the end of synthesis (EOS). PET images were conducted in 20 normal male Sprague Dawley rats including 11 control studies, 6 studies blocking with an mGlu4 modulator (4) to investigate specificity and 3 studies blocking with an mGlu5 modulator (MTEP) to investigate selectivity. These studies showed fast accumulation of [(11)C]3 (peak activity between 1-3min) in several brain areas including striatum, thalamus, hippocampus, cerebellum, and olfactory bulb following with fast washout. Blocking studies with the mGlu4 modulator 4 showed 22-28% decrease of [(11)C]3 accumulation while studies of selectivity showed only minor decrease supporting good selectivity over mGlu5. Biodistribution studies and blood analyses support fast metabolism. Altogether this is the first PET imaging ligand for mGlu4, in which the labeled ML128 was used for imaging its in vivo distribution and pharmacokinetics in brain.
A numerical study of field-aided diffusion

Abstract A numerical method for determining the effect of the internal electric field on the diffusion of impurity ions in semiconductors is described. The model of the diffusion process is defined by the flux equations, the continuity equations and Gauss' law. Due to the complexity of this model, there is no known analytical solution. However, the system of nonlinear equations is solved numerically using an iteration technique. Diffusion profiles are presented for boron diffusing in silicon at 1100°C for various values of surface concentration C 0 . These profiles are compared to the complementary error function which is the correct solution neglecting the internal electric field. The impurity profiles are also compared to those obtained by solving an approximate diffusion equation derived by using the concept of a concentration dependent “effective” diffusion coefficient. It is shown that the influence of the electric field on the motion of the impurities is a strong function of the surface concentration. For high values of C 0 , the impurity profile becomes exponential. The accuracy of the solutions obtained by solving the approximate diffusion equation depends on both the value of C 0 and the diffusion time.
Effects of naloxone on ethanol induced alterations of locomotor activity in C57BL/6 mice.

Abstract Ethanol (2 g or 3 g/kg) or water vehicle was injected intraperitoneally into C57BL/6 mice 15 min after injections of naloxone, a narcotic analgesic antagonist, or its saline vehicle. Locomotor activity was monitored for 60 min beginning 30 min (Experiment 1) or immediately (Experiment 2) following the ethanol injection. In both experiments, animals injected with the lower dose of ethanol were more active than controls during the second half of the activity test. Animals injected with the high dose of ethanol were less active than controls during the first half of the activity test but returned to control levels or above during the second half of the test. Naloxone at the doses used injected 45 min prior to the activity test (Experiment 1) did not alter locomotor activity and did not influence ethanol induced activity changes. When injected 15 min prior to testing (Experiment 2), however, naloxone alone produced a transient reduction in activity observed only during the first half of testing. During the second half of testing all animals injected with naloxone had activity levels similar to controls and lower than those of animals injected with ethanol in the absence of naloxone. Hence, it appears that naloxone at a dose and time period which does not alter the locomotor activity of mice is capable of blocking ethanol induced excitatory effects.
Modeling the transport of passive tracers in sea ice

[1] A model for the vertical transport of passive tracers in sea ice is presented. Two Reynolds flux closure approximations are proposed for the tracer velocity dispersion term in the new ice tracer model (IceT). The schemes, “enhanced molecular diffusion” (EMD) and “mixing length diffusion” (MLD), are suggested parameterizations of gravity drainage, the dominant mechanism of desalination in growing sea ice. The performance of IceT using each parameterization is tested against two experimental studies: simulations I compare profiles of brine salinity with passive tracer concentrations during sea ice growth and melt, and simulations II compare bottom boundary salt and brine volume fluxes with passive tracer fluxes and bottom diffusivities. IceT behavior is evaluated under three salinity forcing prescriptions. Both schemes successfully reproduce expected tracer concentrations in simulations I when the salinity forcing evolves logarithmically. However in simulations II, the MLD scheme outperforms EMD in two significant ways: 1) growth rate trends in the MLD diffusivity parallel measurements of brine volume flux, while EMD bottom diffusivities remain almost constant; and 2) MLD bottom tracer concentrations decrease with ice growth rate similar to excluded brine salinity, while EMD trends are contrary. Hence, enhanced molecular diffusion is highly questionable for implementation in models of reactive passive tracers. The IceT mixing length diffusivity is a viable choice in sea ice biogeochemical modeling. It remains a challenge to assess whether MLD can provide quantitative estimates of desalination at each time step for use in forcing IceT or for implementation in a model of sea ice salinity.
Fabrication of the 6.5-m primary mirror for the Multiple Mirror Telescope Conversion

The Steward Observatory Mirror Lab is in the process of fabricating the 6.5 m mirror for the conversion of the multiple mirror telescope (MMT) to a single primary mirror. For this purpose the lab has developed a versatile polishing system built around the stressed lap polishing tool. The system must produce an f/1.25 parabolic surface with an accuracy corresponding to 0.09 arcsecond FWHM seeing and 1.5% scattering loss at 500 nm wavelength.© (1997) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Influence of stem geometry on mechanics of cemented femoral hip components with a proximal bond.

Nonlinear, three-dimensional, finite element models of cemented femoral hip components with a proximal stem-Cement bond were developed with use of a Charnley stem geometry and a modified Charnley stem geometry that had a cylindrical cross section over the distal two-thirds of the stem (Distal-Round). Peak tensile stresses in the proximal cement mantle increased 63 and 74% for the Charnley and Distal-Round stems, respectively, when the proximal stem-cement interface was debonded, The shear stresses over the stem-cement interface with a proximal bond were 29%. larger for the Distal-Round stem than for the Charnley stem. After the proximal stem-cement interface was debonded. the peak tensile stresses in the cement mantle were 15% larger for the Distal-Round stem than for the Charnley stem. The results illustrate that stresses within the proximal cement mantle could be substantially reduced for both Charnley and Distal-Round stems through use of a proximal stem-cement bond. However, the risk of debonding may be higher for the Distal-Round stem because of increased shear stresses, and once debonded the risk of further loosening due to failure of the cement mantle would also be higher for the Distal-Round stem.
Inhibition of heme crystal growth by antimalarials and other compounds: implications for drug discovery

Abstract During intraerythrocytic infection, Plasmodium falciparum parasites crystallize toxic heme released during hemoglobin catabolism. The proposed mechanism of quinoline inhibition of crystal growth is either by a surface binding or a substrate sequestration mechanism. The kinetics of heme crystal growth was examined in this work using a new high-throughput crystal growth determination assay based on the differential solubility of free vs. crystalline FP in basic solutions. Chloroquine ( ic 50 =4.3 μM) and quinidine ( ic 50 =1.5 μM) showed a previously not recognized reversible inhibition of FP crystal growth. This inhibition decreased by increasing amounts of heme crystal seed, but not by greater amounts of FP substrate. Crystal growth decreases as pH rises from 4.0 to 6.0, except for a partial local maxima reversal from pH 5.0 to 5.5 that coincides with increased FP solubility. The new crystal growth determination assay enabled a partial screen of existing clinical drugs. Nitrogen heterocycle cytochrome P450 inhibitors also reversibly blocked FP crystal growth, including the azole antifungal drugs clotrimazole ( ic 50 =12.9 μM), econazole ( ic 50 =19.7 μM), ketoconazole ( ic 50 =6.5 μM), and miconazole ( ic 50 =21.4 μM). Fluconazole did not inhibit. Both subcellular fractionation of parasites treated with subinhibitory concentrations of ketoconazole and in vitro hemozoin growth assays demonstrated copurification of hemozoin and ketoconazole. The chemical diversity of existing CYP inhibitor libraries that bind FP presents new opportunities for the discovery of antimalarial drugs that block FP crystal growth by a surface binding mechanism and possibly interfere with other FP-sensitive Plasmodium pathways.
Controlling the Polymorph of LnIII(NO3)3-x(OH)x[15-MCCuII(N)S-pheHA-5] Complexes through Solvent Type and LnIII Ion Choice

Two general polymorphs of LnIII(NO3)3-x(OH)x[15-MCCuII(N)S-pheHA-5] (where LnIII = LaIII, SmIII, GdIII, TbIII, DyIII, HoIII, ErIII, LuIII, or YIII and x = 0, 0.5, or 1) have been previously reported; however, no general hypothesis had been proposed for a method to control the resulting polymorph. We now demonstrate that both solvent and LnIII ion choice play a pivotal role in the resulting three-dimensional structure. By using only water as the solvent, a dimer structure can be achieved; however, if a 5:1 methanol/water solvent is used, a helical chain is produced. Of interest, even in the 5:1 methanol/water solvent, LaIII 15-MC-5 complexes will only produce dimer structures in the solid state, and the helical chain has never been produced. We suggest that this restriction is due to the difference in size and preferred coordination number for LaIII, which does not allow for the proper positioning of nitrate anions to form the helical structure.
Methodological issues in the recruitment of ethnic minority subjects to research via the Internet: a discussion paper

In this paper, issues in Internet recruitment of ethnic minorities in the US are explored through an analysis of an Internet survey study. The issues include those related to: (a) the difficulties in ensuring authenticity; (b) a lack of cooperation by gate keepers; (c) the flexibility required in the recruitment process; (d) a very low response rate; and (e) selected groups of ethnic minorities. Based on the discussions on the issues, we propose regular updates of knowledge and skills related to Internet interactions and technologies, usage of multiple recruitment sources, pluralistic recruitment approaches, and a quota sampling method.
A High-Power and Scalable 2-D Phased Array for Terahertz CMOS Integrated Systems

This work introduces a 2-D phased array architecture that is suitable for high power radiation at mm-Wave and Terahertz frequencies. We address the challenge of signal generation above the cut-off frequency of transistors by presenting a radiation method based on the collective performance of a large number of synchronized sources. As theory shows, both frequency locking/tuning and beam steering can be independently achieved by manipulating the local coupling between the nearest neighbors. This control method results in a dynamical network that is insensitive to array dimensions and is scalable to the point that can achieve a level of output power and spectral purity beyond the reach of conventional sources. To demonstrate the concept, we implement a 4 $\times$ 4 version of this phased array at 340 GHz using a 65 nm bulk CMOS process. The paper presents the design and implementation of the oscillators, couplings and the integrated antennas. The measured results at 338 GHz reveal a peak equivalent isotropically radiated power (EIRP) of +17.1 dBm and a phase noise of -93 dBc/Hz at the 1 MHz offset frequency. This chip presents the first fully integrated terahertz phased array on silicon. Furthermore, the output power is higher than any lens-less silicon-based source above 200 GHz and the phase noise is lower than all silicon radiating sources above 100 GHz.
Perceived racism and suicide ideation: mediating role of depression but moderating role of religiosity among African American adults.

Suicide is a public health problem for African Americans who are young and of working age. The purpose of this study was to examine mediated and moderated effects of perceived racism on suicide ideation in a community sample of 236 African American men and women. Measures of suicide ideation, depression symptoms, intrinsic/extrinsic religiosity, and perceived racism were administered. Perceived racial discrimination was directly and indirectly associated with suicide ideation. For participants who reported low levels of extrinsic religiosity, the mediated effect of perceived racism (via depression symptoms) was significant. These findings provide some insight into suicide vulnerability for specific subgroups of African Americans.
Nucleon spin-polarisabilities from polarisation observables in low-energy deuteron Compton scattering

We investigate the dependence of polarisation observables in elastic deuteron Compton scattering below the pion production threshold on the spin-independent and spin-dependent iso-scalar dipole polarisabilities of the nucleon. The calculation uses Chiral Effective Field Theory (\( \chi\) EFT) with dynamical \( \Delta\)(1232) degrees of freedom in the Small Scale Expansion (SSE) at next-to-leading order. Resummation of the NN intermediate rescattering states and including the \( \Delta\) induces sizeable effects. The analysis considers cross-sections and the analysing power of linearly polarised photons on an unpolarised target, and cross-section differences and asymmetries of linearly and circularly polarised beams on a vector-polarised deuteron. An intuitive argument helps one to identify kinematics in which one or several polarisabilities do not contribute. Some double-polarised observables are only sensitive to linear combinations of two of the spin-polarisabilities, simplifying a multipole analysis of the data. Spin-polarisabilities can be extracted at photon energies ≳ 100 MeV, after measurements at lower energies of \( \lesssim\) 70 MeV provide high-accuracy determinations of the spin-independent ones. An interactive Mathematica 7.0 notebook of our findings is available from hgrie@gwu.edu.
Investigations of image contrast space defined by variations on histogram equalization

Abstract This paper describes how a family of images of varying levels of contrast can be efficiently calculated and displayed. We show that a contrast space defined in terms of histogram equalization can be specified in terms of two parameters: region size and histogram blurring level. Based on these observations, we describe one exact algorithm and two efficient algorithms for computing sequences of images within this contrast space. These precomputed images can be displayed and interactively explored to examine image features of interest. By working with a family of contrast enhanced images the difficult task of selecting the single level of contrast enhancement appropriate for a particular image is avoided, increasing the usefulness of low contrast images.
Earth resources instrumentation for the Space Station Polar Platform

The spacecraft and payloads of the Space Station Polar Platform program are described in a brief overview. Present plans call for one platform in a descending morning-equator-crossing orbit at 824 km and two or three platforms in ascending afternoon-crossing orbits at 542-824 km. The components of the NASA Earth Observing System (EOS) and NOAA payloads are listed in tables and briefly characterized, and data-distribution requirements and the mission development schedule are discussed. A drawing of the platform, a graph showing the spectral coverage of the EOS instruments, and a glossary of acronyms are provided.
Mutations That Decrease DNA Binding of the Processivity Factor of the Herpes Simplex Virus DNA Polymerase Reduce Viral Yield, Alter the Kinetics of Viral DNA Replication, and Decrease the Fidelity of DNA Replication

The processivity subunit of the herpes simplex virus DNA polymerase, UL42, is essential for viral replication and possesses both Pol- and DNA-binding activities. Previous studies demonstrated that the substitution of alanine for each of four arginine residues, which reside on the positively charged surface of UL42, resulted in decreased DNA binding affinity and a decreased ability to synthesize long-chain DNA by the polymerase. In this study, the effects of each substitution on the production of viral progeny, viral DNA replication, and DNA replication fidelity were examined. Each substitution mutant was able to complement the replication of a UL42 null mutant in transient complementation assays and to support the replication of plasmid DNA containing herpes simplex virus type 1 (HSV-1) origin sequences in transient DNA replication assays. Mutant viruses containing each substitution and a lacZ insertion in a nonessential region of the genome were constructed and characterized. In single-cycle growth assays, the mutants produced significantly less progeny virus than the control virus containing wild-type UL42. Real-time PCR assays revealed that these UL42 mutants synthesized less viral DNA during the early phase of infection. Interestingly, during the late phase of infection, the mutant viruses synthesized larger amounts of viral DNA than the control virus. The frequencies of mutations of the virus-borne lacZ gene increased significantly in the substitution mutants compared to those observed for the control virus. These results demonstrate that the reduced DNA binding of UL42 is associated with significant effects on virus yields, viral DNA replication, and replication fidelity. Thus, a processivity factor can influence replication fidelity in mammalian cells.