cssi/SciSciGPT-SciSciNet huggingface dataset:
Arsenate reductase II. Purine nucleoside phosphorylase in the presence of dihydrolipoic acid is a route for reduction of arsenate to arsenite in mammalian systems.

An arsenate reductase has been partially purified from human liver using ion exchange, molecular exclusion, hydroxyapatite chromatography, preparative isoelectric focusing, and electrophoresis. When SDS−β-mercaptoethanol−PAGE was performed on the most purified fraction, two bands were obtained. One of these bands was a 34 kDa protein. Each band was excised from the gel and sequenced by LC-MS/MS, and sequest analyses were performed against the OWL database SWISS−PROT with PIR. Mass spectra analysis matched the 34 kDa protein of interest with human purine nucleoside phosphorylase (PNP). The peptide fragments equal to 40.1% of the total protein were 100% identical to the corresponding regions of the human purine nucleoside phosphorylase. Reduction of arsenate in the purine nucleoside arsenolysis reaction required both PNP and dihydrolipoic acid (DHLP). The PNP rate of reduction of arsenate with the reducing agents GSH or ascorbic acid was negligible compared to that with the naturally occurring dithiol DHLP ...
Poster: Non-invasive Human Activity Monitoring using a Low-cost Doppler Sensor and an RF Link

This paper presents a non-invasive human activity monitoring system with a low-cost Doppler sensor and a pair of radio frequency (RF) sensors. This radio-based system combines the strengths of two sensing modalities: fine granularity from a Doppler sensor and large sensing coverage from an RF link. The system is capable of detecting subtle human motion such as breathing, as well as walking in a large area. We deploy the system and perform experiments in a 5.5 m by 7.5 m room to classify four activities. Experimental results show that the average classification rate is 90%, 31% more accurate than a single Doppler system.
Self-aligned resist patterning by backside flood exposure in photomask

As a minimum pattern size on photomask decreases, a patterning accuracy is very important. Especially pattern repair needs the perfect positioning accuracy. But the positioning accuracy of equipment stage has its limit and therefore cannot meet a required accuracy. We can form the resist patterns with no positioning error on Cr or MoSiN patterns of photomask. We named this process 'the self-aligned resist patterning' and investigated the various patterning performance. In this process, a photoresist is coated on Cr/MoSiN pattern side and the photomask is exposed to KrF light on a backside and is developed. The principle of this self-aligned resist patterning is the difference between the transmittances of Cr and quartz. This self-aligned resist patterning can form the resist patterns on sub-patterns of Cr or MoSiN which had been formed on photomask. First of all, the alignment accuracy of this process is perfect and the alignment error is zero.
Electric field dependence of charge carrier generation in alkane solutions of N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD)

Abstract Studies of the electric field dependence or photocurrents from solutions of TMPD in non-polar solvents are interpreted using Onsager's theory of geminate charge recombination. For all solvents and photon energies, a simple exponential form of the radial distribution function for geminate pairs accounts for the observed field dependence.
Pyrazolylthiazole as ΔF508-Cystic Fibrosis Transmembrane Conductance Regulator Correctors with Improved Hydrophilicity Compared to Bithiazoles

Deletion of phenylalanine residue 508 (ΔF508) in the cystic fibrosis (CF) transmembrane conductance regulator protein (CFTR) is a major cause of CF. Small molecule ‘correctors’ of defective ΔF508-CFTR cellular processing hold promise for CF therapy. We previously identified and characterized bithiazole CF corrector 1 and s-cis-locked bithiazole 2. Herein, we report the regiodivergent synthesis of Nγ and Nβ isomers of thiazole-tethered pyrazoles with improved hydrophilicity compared to bithiazoles. We synthesized a focused library of fifty-four pyrazolylthiazoles 3, which included examples of both regioisomers 4 and 5. The thiazole-tethered pyrazoles allowed incorporation of property-modulating functionality on the pyrazole ring – ester, acid, and amide – while retaining ΔF508-CFTR corrector activity (EC50) of under 1 μM. The most active pyrazolylthiazole (14h) has an experimentally determined logP of 4.1, which is 1.2 log units lower than bithiazole CF corrector 1.
Safety, feasibility, and efficacy of a resistance training program in preadolescent obese children.

ABSTRACT Background: Safe and effective exercise programs are needed to prevent and treat chronic diseases in childhood. In particular, preadolescent obese children should participate in activities that are specific to their special needs. Resistance or strength training has been prescribed for adult obese persons. Research is limited concerning the use of resistance training in programs that treat obese preadolescents. Methods: Nineteen treatment subjects (7-12 years of age) were enrolled in a 1 O-week weight management program which included diet, behavior modification, and aerobic and flexibi lity exercises. Forty-eight control subjects (7-12 years of age) participated in the diet, behavior modification program, and a thrice-a-week walking program. The efficacy of the overall weight management program was examined by anthropometry at 10 weeks and 1 year. Results: Fifteen treatment subjects completed the 10-week program (retention rate, 78.9%). Thereafter compliance decreased by approximately 33% for the long-term study. Seventeen control subjects completed the program (retention rate, 35%). Weight, percent of ideal body weight, and body mass index were reduced significantly at 10 weeks (P and did not increase significantly at 1-year follow-up in both treatment and control groups. Height increased significantly at 1 year in both treatment and control subjects. In the treatment subjects, percent fat decreased significantly (p P > 0.05). Conclusions: A resistance-training program may be included safely in a multidisciplinary weight management program for obese preadolescent male and female children. The addition of specific exercise regimes such as resistance training may improve program retention especially in severely obese youth.
Active Sound Attenuation in Finite-Length Ducts Using Close-Form Transfer Function Models

In this paper, the problem of active sound cancellation in finite-length ducts is investigated. The closed-form solution of a one-dimensional wave equation is obtained as the plant model. The controllability, observability, and transmission zeros are discussed based on the transfer function model. For ducts with totally reflective boundaries, stabilization can be achieved by using a speaker (actuator) and a microphone (sensor). Cases of collocated and noncollocated sensors and actuators are presented. A repetitive control algorithm was developed to drive the actuator so that harmonic noises in a duct are attenuated. For a duct with partially reflective boundaries, the application of repetitive control prevents sound from leaking out of the duct at a chosen end. A simulation study demonstrating the effects of this feedback control scheme is also presented.
Aspects of the hydrodynamic loading on towed arrays and flexible risers

Abstract The hydrodynamic loads on towed arrays and flexible risers can be divided into ‘inertial’ loads, due the basic need for the water to move aside as the array or riser passes, and ‘drag’ loads reflecting the size of the wake left behind. The latter must inevitably be calculated empirically from experimental data, because of the great inherent complexity of the turbulent processes in wakes. The former, however, can be calculated analytically, and this has been done for many years on towed arrays, although not on flexible risers. It is first shown under which circumstances the analytical formula used on towed arrays gives a worthwhile improvement over the Morison-type semi-empirical inertial forces used in the analysis of flexible risers. The improvements occur when the array or riser is tightly curved, which is of course a practically important situation, because it can lead to mechanical damage. It is next shown, however, that in this tightly-curved case the analytical formula itself breaks down, because an assumption used in its derivation is violated. The question is therefore posed of how the analytical formula might be generalized, and a number of alternative approaches to that problem are considered.
The developing bronchial arteries in a fetus of the twelfth week.

In the human fetus bronchial arteries appear, as such, between the ninth and twelfth week as highly variable arteriolar outgrowths from the aorta itself or from proximal portions of right (or left) posterior intercostal rami of the aorta. Thus, they constitute a secondary system implanted relatively late upon the peripheral coats of the bronchial tree and large pulmonary vessels. The process is thought to be an inductive one depending partly upon the approximation of parts during the descent of heart and lungs into the thorax and partly upon the advancing degree of maturity of the bronchial tree. In the fetus of the twelfth week, to be described below, there are three bronchial arteries to the left lung and at least one to the right. The lowest of these (the left aorticobronchial artery) can be traced along the superficial coasts of the left lower lobe bronchus to the level just preceding that in which cartilages are differentiating: for example, to the third of what will comprise, eventually, some 25 generations of branches of the posterior basal segmental bronchus. Beyond this shifting level of differentiation the segmental pulmonary arteries constitute the sole arterial supply to the bronchi and parenchyma of the lung. It is assumed from recent reports in the literature that the bronchial arterioles will have established continuity with pulmonary arteries and with the pulmouary parenchyma not later than the twenty-sixth week of gestation.
T-cell lineage fate: Instructed by receptor signals?

Mechanisms of lineage choice represent a challenging problem in developmental biology. Recent studies have shown that different T-cell receptor signals can affect CD4 or CD8 lineage choice. Thus, all the ingredients for instructive mechanisms of lineage fate are in place but other mechanisms cannot be completely ruled out.
Reversible cell cycle entry in adult kidney podocytes through regulated control of telomerase and Wnt signaling

Mechanisms of epithelial cell renewal remain poorly understood in the mammalian kidney, particularly in the glomerulus, a site of cellular damage in chronic kidney disease. Within the glomerulus, podocytes--differentiated epithelial cells crucial for filtration--are thought to lack substantial capacity for regeneration. Here we show that podocytes rapidly lose differentiation markers and enter the cell cycle in adult mice in which the telomerase protein component TERT is conditionally expressed. Transgenic TERT expression in mice induces marked upregulation of Wnt signaling and disrupts glomerular structure, resulting in a collapsing glomerulopathy resembling those in human disease, including HIV-associated nephropathy (HIVAN). Human and mouse HIVAN kidneys show increased expression of TERT and activation of Wnt signaling, indicating that these are general features of collapsing glomerulopathies. Silencing transgenic TERT expression or inhibiting Wnt signaling through systemic expression of the Wnt inhibitor Dkk1 in either TERT transgenic mice or in a mouse model of HIVAN results in marked normalization of podocytes, including rapid cell-cycle exit, re-expression of differentiation markers and improved filtration barrier function. These data reveal an unexpected capacity of podocytes to reversibly enter the cell cycle, suggest that podocyte renewal may contribute to glomerular homeostasis and implicate the telomerase and Wnt-β-catenin pathways in podocyte proliferation and disease.
Critical surface pairs and triplets

In this paper, we study situations where a perspective image motion field can have multiple interpretations. We show that the ambiguity in interpretation of the three-dimensional instantaneous motion of curved surfaces is at most three-fold, and can occur only in the case of certain hyperboloids of one sheet, saddle surfaces, and hyperbolic paraboloids. We also present analytical expressions for the relationship among multiple interpretations.
Differential SERM activation of the estrogen receptors (ERα and ERβ) at AP-1 sites

Abstract Background: The selective estrogen receptor modulators (SERMs) raloxifene and tamoxifen are triphenylethylene derivatives that affect transcriptional regulation by the estrogen receptors (ERα and ERβ) but show different effects in different tissues. A third triphenylethylene derivative, GW-5638, displays tissue selectivity in rats identical to that of raloxifene, suggesting that GW-5638 and raloxifene share a mechanism of action that is different from that of tamoxifen. Results: Both GW-5638 and its hydroxylated analog GW-7604 were tested for their ability to bind to ERα and ERβ and their ability to affect transcription of ERα and ERβ at a consensus estrogen response element and an ER/AP-1 response element. The drugs were found to have the same affinity for ERα and ERβ, although they were also found to activate transcription from an AP-1 promoter element more potently with ERβ than with ERα. Derivatives of GW-5638 with alterations at the carboxylic acid still showed increased ERβ potency compared to ERα, but the magnitude of the activation with ERα was much higher than with ERβ. Conclusions: Despite similar binding affinities to isolated ERα and ERβ, GW-5638 and GW-7604 show markedly lower EC 50 values with ERβ at an AP-1-driven promoter as compared to ERα. This suggests that the two compounds produce a more active ER/AP-1 conformation of the ER/AP-1 transcription factor complex when bound to ERβ than when bound to ERα.
The oral microbiome and the immunobiology of periodontal disease and caries

The composition of the oral microbiome differs from one intraoral site to another, reflecting in part the host response and immune capacity at each site. By focusing on two major oral infections, periodontal disease and caries, new principles of disease emerge. Periodontal disease affects the soft tissues and bone that support the teeth. Caries is a unique infection of the dental hard tissues. The initiation of both diseases is marked by an increase in the complexity of the microbiome. In periodontitis, pathobionts and keystone pathogens such as Porphyromonas gingivalis appear in greater proportion than in health. As a keystone pathogen, P. gingivalis impairs host immune responses and appears necessary but not sufficient to cause periodontitis. Historically, dental caries had been causally linked to Streptococcus mutans. Contemporary microbiome studies now indicate that singular pathogens are not obvious in either caries or periodontitis. Both diseases appear to result from a perturbation among relatively minor constituents in local microbial communities resulting in dysbiosis. Emergent consortia of the minor members of the respective microbiomes act synergistically to stress the ability of the host to respond and protect. In periodontal disease, host protection first occurs at the level of innate gingival epithelial immunity. Secretory IgA antibody and other salivary antimicrobial systems also act against periodontopathic and cariogenic consortia. When the gingival immune response is impaired, periodontal tissue pathology results when matrix metalloproteinases are released from neutrophils and T cells mediate alveolar bone loss. In caries, several species are acidogenic and aciduric and appear to work synergistically to promote demineralization of the enamel and dentin. Whereas technically possible, particularly for caries, vaccines are unlikely to be commercialized in the near future because of the low morbidity of caries and periodontitis.
Feedback and regularity in the lexicon

Phonologies are characterised by regularity, from the stereotyped phonetic characteristics of allophones to the contextually conditioned alternations between them. Most models of grammar account for regularity by hypothesising that there is only a limited set of symbols for expressing underlying forms, and that an independent grammar algorithm transforms symbol sequences into an output representation. However, this explanation for regularity is called into question by research which suggests that the mental lexicon records rich phonetic detail that directly informs production. Given evidence for biases favouring previously experienced forms at many levels of production and perception, I argue that positive feedback within a richly detailed lexicon can produce regularity over many cycles of production and perception. Using simulation as a tool, I show that under the influence of positive feedback, gradient biases in usage can convert an initially gradient and variable distribution of lexical behaviours into a more categorical and simpler pattern.
Asystoles during infancy recorded by home memory monitors: Benign events?

Objectives: To assess the frequency and clinical significance of asystole (sinus arrest ≥2.0 seconds) and the incidence of bradycardia in infants prescribed home cardiorespiratory monitors and to test the hypothesis that asystoles are more likely to occur in preterm infants. Design: Prospective, consecutive sample of monitor printouts. Methods: All 291 printouts from the memory monitors of 161 patients received during a 2-month period were analyzed. Setting: University hospital providing primary and referral care. Main Outcome Measures: Asystoles and bradycardias; clinical course of patients with asystoles. Results: Eight patients (5.0%) had 32 episodes of asystole lasting 2.0 to 4.3 seconds (group 1). Fifty-three patients (32.9%) had true bradycardia alarms but no asystoles (group 2). One hundred patients (62.1%) had neither asystoles nor bradycardias (group 3). Preterm infants constituted 88% of group 1 and 81% of group 2 but only 58% of group 3. Infants were more likely to be full-term in group 3 than in the other 2 groups (χ2, P=.02). Birth weights were lower in group 1 than in group 3 (P Conclusions: Asystoles occur more commonly in preterm infants; those pauses in the 2.0- to 4.0-second range seem to be benign. Studies of long-term recordings are needed to redefine asystole in both normal preterm and full-term infants. These data would help further refine current guidelines for pacemaker implantation during infancy. Arch Pediatr Adolesc Med. 1996;150:901-905
Human Rights Education and Student Self-Conception in the Dominican Republic.

In 2001, a 3-month course in human rights based on critical inquiry was offered to 8th graders in a slum area of Santo Domingo. The students' attitudes, behaviors and knowledge of human rights principles were measured before and after the course. The curriculum focused on international principles and entrenched local problems such as discrimination against Haitian migrants, police brutality, violence against women and exploitation of child labor in free trade zones. This paper will discuss the field of human rights education, the study's findings about the nature of student response to the course and its impact on student identity, solidarity with victims of human rights abuses and self-confidence as a result of human rights education.
Analysis of potential expression of highly related members of the ribosomal protein L32 gene family

The processed gene L32', a member of the mouse gene family for ribosomal protein L32, could encode a 135 amino acid protein nearly identical to L32. The 5'-flanking region of the gene contains CAAT and TATA sites at positions commonly found in expressed genes. The L32' gene lies within highly methylated, DNase I-insensitive chromatin of mouse L1210 cells. Although S1 nuclease digestion studies suggested that an L32' transcript might be produced, an oligonucleotide probe specific for L32' mRNA, and RNase digestion of a cRNA probe to L32', indicated fewer than 0.1 L32' transcripts/cell. These results demonstrate that extreme caution is required when measuring transcription from related genes.
Stage-based mortality of grassland grasshoppers (Acrididae) from wandering spider (Lycosidae) predation

Abstract Mortality rates in insects, including grasshoppers (Acrididae), are often stage- or size-specific. We estimated stage-specific mortality rates for three common grasshopper species from a Nebraska (USA) sandhills grassland ( Ageneotettix deorum, Melanoplus sanguinipes and Phoetaliotes nebrascensis ), and partitioned the impact due to wandering spider predation from remaining sources. Survivorship was estimated for multiple developmental stages (3rd instar through adult) under experimental conditions that either prevented or permitted predation from free-living, wandering spiders (primarily Schizocosa species). Total stage-specific mortality, including spider predation, examined over the period of single stages was greatest for the youngest stages (91% for 3rd instar, 73% for 4th instar, 63.5% for 5th instar and 30.4% for adults). For the developmental stages considered and averaged for all species, the contribution to total mortality from spider predation over the 10-d period (approximately the length of a developmental stage) ranged from 17% for 3rd instar nymphs to 23% for 4th and 5th instars, and an undetectable level for adults. While spiders may depress grasshopper numbers, contributions from spider predation to grasshopper population dynamics are uncertain.
Island roots, global reach: A case study in internationalizing Kapi'olani Community College

This chapter offers a case study of Kapi'olani Community College, an institution that initiated its Asia-Pacific emphasis in 1988, strengthened the emphasis throughout the 1990s, and expanded it to an integrated international emphasis in 2007.
Effect of surfactant type on the stability of oil-in-water emulsions to dispersed phase crystallization

Abstract Confectionery coating fat (CCF ) emulsions (40 wt.%) were prepared by mixing liquid fat with solutions (1–4 wt.%) of selected polymeric and small molecule surfactants, and homogenizing to a mean particle diameter of 0.71±0.05 μm. Aliquots of the emulsions were temperature cycled (40 to −10 to 40 °C at 1.5 °C min−1) four times in a differential scanning calorimeter. The stable emulsion droplets crystallized at 0–6 °C (depending on the type of emulsifier) while the non-emulsified fat crystallized at ∼15 °C. The ratio of the enthalpies at these temperatures was used to calculate the proportion of the emulsion that had destabilized after each thermal cycle. All of the small molecule-stabilized emulsions largely destabilized after one cycle. The caseinate-stabilized emulsions were relatively resistant to several thermal cycles unless ethanol (30 wt.%) was added or the pH lowered to 5, in both cases they destabilized during the first cycle. When a small molecule surfactant was added to displace the caseinate from the interface, there was a sharp reduction in stability at the surfactant to protein molar ratio R>25. Whey protein-stabilized emulsions were partly unstable to freeze–thaw even following a thermal pretreatment to denature the proteins. Cryo-SEM confirmed the destabilization of the emulsions was due to partial coalescence.
Hypothalamic-pituitary vasculature: evidence for retrograde blood flow in the pituitary stalk.

Retrograde transport of pituitary hormones in the pituitary stalk vasculature was investigated in anesthetized male rats in which the pituitary gland was intact and in animals in which the anterior pituitary, posterior pituitary, or entire pituitary gland had been removed 30 to 60 min before use. Blood was collected for 1.5 to 2 h by free flow from a single long portal vessel through a microcannula, the tip of which was pointed toward the hypothalamus. An arterial blood sample was obtained at the end of each collection of portal blood. The concentrations (ng\ml) of LH, TSH, prolactin, ACTH, α-MSH, and vasopressin, determined by radioimmunoassay, in portal plasma from rats with intact pituitary glands were as follows: LH, 2,320 ± 874 (mean and SE); TSH, 10,180 ± 1,471; prolactin, 4,858 ± 884; ACTH, 82 ± 17.0; a-MSH, 103 ± 17.8; vasopressin, 2.4 ± 1.0. The concentrations of these hormones in arterial plasma of these rats were as follows: LH, <20; TSH, 149 ± 22; prolactin, 25 ± 5.0; ACTH, 0.36 ± 0.05; α-MSH,...
Prospective blinded trial of the colonoscopic miss-rate of large colorectal polyps

We prospectively studied the colonoscopic miss-rate of large colorectal polyps in a blinded trial featuring tandem colonoscopy. Sixty-three lesions ≥1cm in size were discovered and none were missed. Confidence intervals of 95% are a miss-rate of 0 to 4.6%. We conclude that
Toll-like receptor 4 functions intracellularly in human coronary artery endothelial cells: roles of LBP and sCD14 in mediating LPS responses

Endothelial cells are activated by microbial agonists through Toll-like receptors (TLRs) to express inflammatory mediators; this is of significance in acute as well as chronic inflammatory states such as septic shock and atherosclerosis, respectively. We investigated mechanisms of lipopolysaccharide (LPS)-induced cell activation in human coronary artery endothelial cells (HCAEC) using a combination of FACS, confocal microscopy, RT-PCR, and functional assays. We found that TLR4, in contrast to TLR2, is not only located intracellularly but also functions intracellularly. That being the case, internalization of LPS is required for activation. We further characterized the HCAEC LPS uptake system and found that HCAEC exhibit an effective LPS uptake only in the presence of LPS binding protein (LBP). In addition to its function as a catalyst for LPS-CD14 complex formation, LBP enables HCAEC activation at low LPS concentrations by facilitating the uptake, and therefore delivery, of LPS-CD14 complexes to intracellular TLR4-MD-2. LBP-dependent uptake involves a scavenger receptor pathway. Our findings may be of pathophysiological relevance in the initial response of the organism to infection. Results further suggest that LBP levels, which vary as LBP is an acute phase reactant, could be relevant to initiating inflammatory responses in the vasculature in response to chronic or recurring low LPS.
Plasma free amino acids in hibernation and arousal

Abstract 1. 1. Compared to hibernating or normothermic ground squirrels, immediate arousal from hibernation is associated with markedly elevated levels of plasma free amino acids. 2. 2. The data indicate an increase in protein catabolism during the initial stages of arousal from hibernation.
Methods and challenges in timing chromosomal abnormalities within cancer samples

Motivation: Tumors acquire many chromosomal amplifications, and those acquired early in the lifespan of the tumor may be not only important for tumor growth but also can be used for diagnostic purposes. Many methods infer the order of the accumulation of abnormalities based on their occurrence in a large cohort of patients. Recently, Durinck et al. (2011) and Greenman et al. (2012) developed methods to order a single tumor’s chromosomal amplifications based on the patterns of mutations accumulated within those regions. This method offers an unprecedented opportunity to assess the etiology of a single tumor sample, but has not been widely evaluated. Results: We show that the model for timing chromosomal amplifications is limited in scope, particularly for regions with high levels of amplification. We also show that the estimation of the order of events can be sensitive for events that occur early in the progression of the tumor and that the partial maximum likelihood method of Greenman et al. (2012) can give biased estimates, particularly for moderate read coverage or normal contamination. We propose a maximum-likelihood estimation procedure that fully accounts for sequencing variability and show that it outperforms the partial maximum-likelihood estimation method. We also propose a Bayesian estimation procedure that stabilizes the estimates in certain settings. We implement these methods on a small number of ovarian tumors, and the results suggest possible differences in how the tumors acquired amplifications. Availability and implementation: We provide implementation of these methods in an R package cancerTiming, which is available from the Comprehensive R Archive Network (CRAN) at http://CRAN.R
A 12-bit successive-approximation-type ADC with digital error correction

A correction algorithm has been implemented that gives an almost twofold improvement in conversion speed without loss of accuracy or changes to the analog circuitry of a slower design. The design of a smart successive-approximation register chip, which has been fabricated in a double poly CMOS process and takes up 18 mil/SUP 2/ in die area, is described. The area is 13% larger than that of an A/D converter utilizing the same analog chip but a conventional digital chip without error correction. A speed improvement from 12 to 7 /spl mu/s was obtained with digital error correction.
Multiple-infection and recombination in HIV-1 within a longitudinal cohort of women

Background: Recombination between strains of HIV-1 only occurs in individuals with multiple infections, and the incidence of recombinant forms implies that multiple infection is common. Most direct studies indicate that multiple infection is rare. We determined the rate of multiple infection in a longitudinal study of 58 HIV-1 positive participants from The Women's Interagency HIV Study with a richer sampling design than previous direct studies, and we investigated the role of recombination and sampling design on estimating the multiple infection rate. Results: 40% of our sample had multiple HIV-1 infections. This rate of multiple infection is statistically consistent with previous studies once differences in sampling design are taken into account. Injection drug use significantly increased the incidence of multiple infections. In general there was rapid elimination of secondary strains to undetectable levels, but in 3 cases a superinfecting strain displaced the initial infecting strain and in two cases the strains coexisted throughout the study. All but one secondary strain was detected as an inter- and/or intra-genic recombinant. Injection drug use significantly increased the rate of observed recombinants. Conclusion: Our multiple infection rate is consistent with rates estimated from the frequency of recombinant forms of HIV-1. The fact that our results are also consistent with previous direct studies that had reported a much lower rate illustrates the critical role of sampling design in estimating this rate. Multiple infection and recombination significantly add to the genetic diversity of HIV-1 and its evolutionary potential, and injection drug use significantly increases both.
Trends in processing and manufacturing that will affect implementation of the Chemical Weapons Convention

Several new developments in synthesis science and manufacturing technology may affect the task of implementing the Chemical Weapons Convention (CWC) constraints on the production of toxic agents for military or terrorist purposes. The combination of auto- mated synthesis methods and high-throughput screening protocols could potentially yield new toxic agents not specifically proscribed by the CWC, but such approaches are unlikely to seriously impact the work of the Organisation for the Prohibition of Chemical Weapons (OPCW) in the near future. On the other hand, new developments in manufacturing may have a serious impact on the work of the OPCW inspectors. The wide use of versatile, multipur- pose production facilities in making fine chemicals complicates the task of discerning whether a particular facility is used only for nonprohibited purposes under the CWC. New catalytic processes and automated process control permit production of toxic chemicals with fewer emissions that contaminate the environment and might provide clues to the nature of the processes being conducted. Tiny microreactors operated continuously under computer control can produce significant quantities of toxic chemicals (including CWC-scheduled compounds) with a very small "footprint" within a larger production facility. These techni- cal developments together with the dispersal of chemical production facilities and skills may seriously complicate the tasks of the OPCW inspectors.
Psychophysical evaluation of in-situ ultrasound visualization

We present a novel psychophysical method for evaluating ultrasonography based on real-time tomographic reflection (RTTR), in comparison to conventional ultrasound (CUS). The method measures the user's perception of the location of an ultrasound-imaged target independently from assessing the action employed to reach it. Three experiments were conducted with the sonic flashlight (SF), an RTTR device, and CUS. The first two experiments determined subjects' perception of target location with a triangulation-by-pointing task. Depth perception with the SF was comparable to direct vision, while CUS caused considerable underestimation of target depth. Binocular depth information in the SF was shown to significantly contribute to its superiority. The third experiment tested subjects in an ultrasound-guided needle insertion task. Because the SF provides visualization of the target at its actual location, subjects performed insertions faster and more accurately by using the SF rather than CUS. Furthermore, the trajectory analysis showed that insertions with the SF generally went directly to the target along the desired path, while CUS often led to a large deviation from the correct path consistent with the observed underestimation of target depth. These findings lend great promise to the use of RTTR-based imaging in clinical practice and provide precise means of assessing efficacy.
Descriptive and injunctive norms in college drinking: a meta-analytic integration.

Objective: Many college students overestimate both the drinking behaviors (descriptive norms) and the approval of drinking (injunctive norms) of their peers. As a result, consistent self-other discrepancies (SODs) have been observed, in which self-perceptions of drinking behaviors and approval of drinking usually are lower than comparable judgments of others. These SODs form the foundation of the currently popular "social norms approach" to alcohol abuse prevention, which conveys to students the actual campus norms regarding drinking behaviors and approval of alcohol use. However, little attention has been paid to the factors that can influence the magnitude of SODs. This research was conducted to address these issues. Method: This meta-analytic integration of 23 studies evaluated the influence of five predictors of SODs: norm type (injunctive or descriptive), gender, reference group, question specificity and campus size. These studies rendered 102 separate tests of SODs in descriptive and injunctive form...
Structure of fosfomycin resistance protein FosA from transposon Tn2921

The crystal structure of fosfomycin resistance protein FosA from transposon Tn2921 has been established at a resolution of 2.5 A. The protein crystallized without bound Mn(II) and K+, ions crucial for efficient catalysis, providing a structure of the apo enzyme. The protein maintains the three-dimensional domain-swapped arrangement of the paired βαβββ-motifs observed in the genomically encoded homologous enzyme from Pseudomonas aeruginosa (PA1129). The basic architecture of the active site is also maintained, despite the absence of the catalytically essential Mn(II). However, the absence of K+, which has been shown to enhance enzymatic activity, appears to contribute to conformational heterogeneity in the K+-binding loops.
Nocturnin suppresses igf1 expression in bone by targeting the 3' untranslated region of igf1 mRNA.

IGF-I is an anabolic factor that mediates GH and PTH actions in bone. Expression of skeletal Igf1 differs for inbred strains of mice, and Igf expression levels correlate directly with bone mass. Previously we reported that peroxisome proliferator-activated receptor-γ2 activation in bone marrow suppressed Igf1 expression and that peroxisome proliferator-activated receptor-γ2 activation-induced Nocturnin (Noc) expression, a circadian gene with peak expression at light offset, which functions as a deadenylase. In 24-h studies we found that Igf1 mRNA exhibited a circadian rhythm in femur with the lowest Igf1 transcript levels at night when Noc transcripts were highest. Immunoprecipitation/RT-PCR analysis revealed a physical interaction between Noc protein and Igf1 transcripts. To clarify which portions of the Igf1 3′ untranslated region (UTR) were necessary for regulation by Noc, we generated luciferase constructs containing various lengths of the Igf1 3′UTR. Noc did not affect the 170-bp short-form 3′UTR, bu...
Rationalizing 5000-Fold Differences in Receptor-Binding Rate Constants of Four Cytokines

The four cytokines erythropoietin (EPO), interleukin-4 (IL4), human growth hormone (hGH), and prolactin (PRL) all form four-helix bundles and bind to type I cytokine receptors. However, their receptor-binding rate constants span a 5000-fold range. Here, we quantitatively rationalize these vast differences in rate constants by our transient-complex theory for protein-protein association. In the transient complex, the two proteins have near-native separation and relative orientation, but have yet to form the short-range specific interactions of the native complex. The theory predicts the association rate constant as ka=ka0exp(−ΔGel∗/kBT) where ka0 is the basal rate constant for reaching the transient complex by random diffusion, and the Boltzmann factor captures the rate enhancement due to electrostatic attraction. We found that the vast differences in receptor-binding rate constants of the four cytokines arise mostly from the differences in charge complementarity among the four cytokine-receptor complexes. The basal rate constants (ka0) of EPO, IL4, hGH, and PRL were similar (5.2 × 105 M−1s−1, 2.4 × 105 M−1s−1, 1.7 × 105 M−1s−1, and 1.7 × 105 M−1s−1, respectively). However, the average electrostatic free energies (ΔGe1∗) were very different (−4.2 kcal/mol, −2.4 kcal/mol, −0.1 kcal/mol, and −0.5 kcal/mol, respectively, at ionic strength = 160 mM). The receptor-binding rate constants predicted without adjusting any parameters, 6.2 × 108 M−1s−1, 1.3 × 107 M−1s−1, 2.0 × 105 M−1s−1, and 7.6 × 104 M−1s−1, respectively, for EPO, IL4, hGH, and PRL agree well with experimental results. We uncover that these diverse rate constants are anticorrelated with the circulation concentrations of the cytokines, with the resulting cytokine-receptor binding rates very close to the limits set by the half-lives of the receptors, suggesting that these binding rates are functionally relevant and perhaps evolutionarily tuned. Our calculations also reproduced well-observed effects of mutations and ionic strength on the rate constants and produced a set of mutations on the complex of hGH with its receptor that putatively enhances the rate constant by nearly 100-fold through increasing charge complementarity. To quantify charge complementarity, we propose a simple index based on the charge distribution within the binding interface, which shows good correlation with ΔGe1∗. Together these results suggest that protein charges can be manipulated to tune ka and control biological function.
Synthesis and evaluation of arylaminoethyl amides as noncovalent inhibitors of cathepsin S. Part 3: heterocyclic P3.

Abstract A series of N α -2-benzoxazolyl-α-amino acid-(arylaminoethyl)amides were identified as potent, selective, and noncovalent inhibitors of cathepsin S. Structure–activity relationships including strategies for modulating the selectivities among cathepsins S, K, and L, and in vivo pharmacokinetics are discussed. A X-ray structure of compound 3 bound to the active site of cathepsin S is also reported.
The Association Between State Laws Regulating Handgun Ownership and Statewide Suicide Rates

Objectives. We examined the impact of 3 state laws (permit to purchase a handgun, registration of handguns, license to own a handgun) on suicide rates.Methods. We used 2010 data from publicly available databases and state legislatures to assess the relationships between our predictors and outcomes.Results. Results largely indicated that states with any of these laws in place exhibited lower overall suicide rates and suicide by firearms rates and that a smaller proportion of suicides in such states resulted from firearms. Furthermore, results indicated that laws requiring registration and license had significant indirect effects through the proportion of suicides resulting from firearms. The latter results imply that such laws are associated with fewer suicide attempts overall, a tendency for those who attempt to use less-lethal means, or both. Exploratory longitudinal analyses indicated a decrease in overall suicide rates immediately following implementation of laws requiring a license to own a handgun.Co...
Geospatial intelligence workforce

A report on the future U.S. workforce for geospatial intelligence, requested by the U.S. National Geospatial-Intelligence Agency (NGA), found that the agency—which hires about 300 scientists and analysts annually—is probably finding sufficient experts to fill the needs in all of its core areas, with the possible exception of geographic information systems (GIS) and remote sensing. The report by the U.S. National Research Council, released on 25 January, noted that competition for GIS applications analysts is strong. While there appear to be enough cartographers, photogrammetrists, and geodesists to meet NGA's current needs in those core areas, the report cautioned that future shortages in these areas seem likely because of a relatively small number of graduates.
On-orbit performance of HST Wide Field Camera 3

The Wide Field Camera 3 (WFC3) was installed into the Hubble Space Telescope during Servicing Mission 4 in May 2009. This panchromatic camera considerably improves the ultraviolet, visible, and infrared imaging capabilities of HST. Commissioned over the summer of 2009, WFC3 is now fully functional and responsible for approximately half of the Cycle 17 HST Science Program. This paper will review the scientific performance of WFC3 including its sensitivity in absolute terms and relative to other HST instruments. The paper will also discuss the calibration programs for WFC3 and the achieved photometric and astrometric calibration accuracies. Lessons learned from the ground calibration and in-flight commissioning will also be considered.
Effects of a traditionally-dosed creatine supplementation protocol and resistance training on the skeletal muscle uptake and whole-body metabolism and retention of creatine in males

Background A typical oral creatine supplementation regimen involving a 5-7 day “loading phase” of 20-25 grams/day followed by a “maintenance phase” of 5-7 grams/day is typically considered as necessary to adequately saturate skeletal muscle as a lesser dose of creatine is insufficient in doing so. This rationale also assumes that the majority, if not all, of the creatine ingested at this dosage is fully utilized by skeletal muscle as a phosphate reservoir in which to re-synthesize ATP during high-intensity, short-term exercise. The purpose of this study was simply to determine the effects of this “typical” creatine dosing strategy previously mentioned on skeletal muscle creatine uptake as well as the whole-body metabolism and retention of creatine in males while engaged in resistance training.
AGENCY AND MORAL RELATIONSHIP IN DEMENTIA

: This essay examines the goals of care and the exercise of guardianship authority in the long-term care of persons with Alzheimer's disease and other forms of chronic, progressive dementia. It counters philosophical views that deny both agency and personhood to individuals with Alzheimer's on definitional or analytic conceptual grounds. It develops a specific conception of the quality of life and offers a critique of hedonic conceptions of quality of life and models of guardianship that are based on a hedonic legal standard of “best interests.” As an alternative, it proposes a conception of quality of life based on the notions of “semantic agency” and “memorial personhood.”
The Toyota Way in Services: The Case of Lean Product Development

Executive Overview Toyota's Production System (TPS) is based on “lean” principles including a focus on the customer, continual improvement and quality through waste reduction, and tightly integrated upstream and downstream processes as part of a lean value chain. Most manufacturing companies have adopted some type of “lean initiative,” and the lean movement recently has gone beyond the shop floor to white-collar offices and is even spreading to service industries. Unfortunately, most of these efforts represent limited, piecemeal approaches—quick fixes to reduce lead time and costs and to increase quality—that almost never create a true learning culture. We outline and illustrate the management principles of TPS that can be applied beyond manufacturing to any technical or service process. It is a true systems approach that effectively integrates people, processes, and technology—one that must be adopted as a continual, comprehensive, and coordinated effort for change and learning across the organization.
Rise kinetics of light‐induced modulation of absorption for a CdS crystal

An experimental study has been made of the rise kinetics for changes in optical absorption in a single crystal of CdS which was bulk excited by pulsed laser light. The experimental data were compared to calculations from a simple model involving a bimolecular process. Experimental and calculated values agreed to within the experimental error and confirmed that light‐induced modulation of absorption is a bimolecular process.
Accurate representation of time-varying signals using mixed transforms with applications to speech

Basis functions from two transforms, the discrete Fourier transform (DFT) and the Walsh-Hadamard transform are used. An iterative algorithm to implement the mixed representation is developed. A finite number of DFT components, either fixed or variable, is used to represent the selective (narrowband) dominant spectrum of the signal on a frame-by-frame basis. The whitened (broadband) residual signal is represented using a small number of Walsh components. The mixed partial sets are applied to speech representation. Preliminary results and informal listening using this model produced good quality speech. >
Peace and War in the Qur'an and Juridical Literature: A Comparative Perspective

The Qur'anic period of Islamic history took place in a social context of significant diversity. A number of important verses in the Qur'an reflect this diversity and encourage Islamic believers to seek peaceful coexistence with those of other faiths, especially those designated as "people of the Book," specifically Christians, Jews and Sabeans. In the later classical period of Islamic history, the exegesis of Islamic jurists markedly de-emphasized peaceful coexistence in favor of interpretations encouraging conquest and religious uniformity. Although the classical jurists have exercised enormous interpretive authority in subsequent Islamic history, their authority was never understood to be absolute or equal to the authority of the Qur'an itself. It is the challenge for Muslims in contemporary times to recover the authority of Qur'anic verses encouraging peaceful coexistence and respect for human diversity, not merely as a social strategy, but as an integral devotional aspect of better understanding the God who transcends all human understanding.