cssi/SciSciGPT-SciSciNet huggingface dataset:
Active-site mutants of the VanC2 d-alanyl-d-serine ligase, characteristic of one vancomycin-resistant bacterial phenotype, revert towards wild-type d-alanyl-d-alanine ligases

Abstract Background : The rising number of vancomycin-resistant enterococci (VREs) is a major concern to modern medicine because vancomycin is currently the ‘last resort' drug for life-threatening infections. The d-alanyl-d-X ligases (where X is an hydroxy or amino acid) of bacteria catalyze a critical step in bacterial cell-wall peptidoglycan assembly. In bacteria that produce glycopeptide antibiotics and in opportunistic pathogens, including VREs, d, d-ligases serve as switches that confer antibiotic resistance on the bacteria themselves. Peptidoglycans in vancomycin-sensitive bacteria end in d-alanyl-d-alanine, whereas in vancomycin-resistant bacteria they end in d-alanyl-d-lactate or d-alanyl-d-serine. Results : We demonstrate that the selective utilization of D-serine by the Enterococcus casseliflavus VanC2 ligase can be altered by mutagenesis of one of two residues identified by homology to the X-ray structure of the Escherichia coli d-alanyl-d-alanine ligase (DdIB). The Arg322→Met (R322M) and Phe250→Tyr (F250Y) ligase mutants show a 36–44-fold decrease in the use of d-serine, as well as broadened specificity for utilization of other D-amino acids in place of D-serine. The F250Y R322M double mutant is effectively disabled ass a d-alanyl-d-serine ligase and retains 10% of the catalytic activity of wild-type d-alanyl-d-alanine ligases, reflecting a 6,000-fold switch to the d-alanyl-d-alanine peptide. Correspondingly, the Leu282→Arg mutant of the wild-type E. coli DdIB produced a 560-fold switch towards d-alanyl-d-serine formation. Conclusions : Single-residue changes in the active-site regions of d, d-ligases can cause substantial changes in recognition and activation of hydroxy or amino acids that have consequences for glycopeptide antibiotic efficacy. The observations reported here should provide an approach for combatting antibiotic-resistant bacteria.
Myristoylation-dependent and Electrostatic Interactions Exert Independent Effects on the Membrane Association of the Myristoylated Alanine-rich Protein Kinase C Substrate Protein in Intact Cells

The myristoylated alanine-rich protein kinase C substrate (MARCKS) is a widely expressed, prominent substrate for protein kinase C. MARCKS is largely associated with membranes in cells, and hydrophobic interactions involving the amino-terminal myristoyl moiety are thought to play a role in anchoring MARCKS to cellular membranes. In addition, experiments in cell-free systems have suggested that electrostatic interactions between the positively charged phosphorylation site/calmodulin binding domain (PSD) of MARCKS and negatively charged membrane lipids are also involved in this association. Although it has been inferred from phosphorylation experiments, the electrostatic nature of the interaction between the PSD and membranes has not been demonstrated directly in intact cells. We expressed human MARCKS mutated in the myristoylation site and the PSD in REF52 cells; the cells were then fractionated by ultracentrifugation. Both nonmyristoylatable MARCKS and MARCKS in which the four serines in the PSD were mutated to aspartic acids, mimicking phosphorylation, exhibited decreased membrane affinity when compared to the fully myristoylated, wild-type, tetra-Ser protein or a myristoylated, tetra-Asn mutant. A double mutant, nonmyristoylatable protein in which the four serines in the PSD were mutated to aspartic acids exhibited negligible membrane association. Similar results were obtained in 293 cells that stably expressed chicken MARCKS mutated in the same domains. The double mutant, nonmyristoylatable tetra-Asp chicken protein exhibited little membrane association as determined by both subcellular fractionation and immunoelectron microscopy. These results indicate that myristoylation and electrostatic interactions involving the PSD exert independent, essentially additive effects on the membrane association of MARCKS in intact cells.
Hemispheric asymmetry in the matching of melodies to rhythm sequences tapped in the right and left palms.

Abstract Two experiments were conducted to investigate the ability of the cerebral hemispheres to match rhythm sequences tapped in the palms of the hands to tape-recorded melodies. Reaction time (RT) for same/different judgments and accuracy of responses served as the dependent measures. In Experiment 1, for the RT data, a left palm/right hemisphere (LP/RH) advantage was found in the ability to match tapped rhythms to tape-recorded melodies, but only on Different trials. On Same trials (which were found to be somewhat easier), both hemispheres were equally efficient at making such comparisons. In Experiment 2, there was no reliable difference between the LP/RH and the RP/LH in the ability to match tapped rhythms to tape-recorded rhythm sequences which were devoid of melodic intonation (i.e., the sound of two blocks of wood struck together in a specified rhythm). The results of these experiments taken in composite lend support to the contention that the right hemisphere advantage typically reported for the processing of musical stimuli is primarily related to pitch and/or intonation rather than rhythm.
Gene therapy in transplantation: pathological consequences of unavoidable plasmid contamination with lipopolysaccharide.

Abstract Experimental studies evaluated the responses of murine cardiac graft recipients to high and low levels of lipopolysaccharide (LPS) contaminating plasmid DNA preparations. Immediately prior to transplantation, graft recipients were transfected by injecting the quadriceps muscles with plasmids that encoded the murine interleukin (IL)-4 gene and β-galactosidase (β-gal) gene. Graft recipients transfected with plasmids encoding only the β-gal gene served as negative plasmid controls. Three groups of mice were transfected with plasmids containing high levels of contaminating LPS: (a) nontransplanted C57Bl/6 mice, (b) C57Bl/6 cardiac isograft recipients, (c) DBA/2 (H-2d) → C57BL/6 (H-2b) cardiac allograft recipients. Unexpectedly, graft failure within 24 h was observed in IL-4 transfected isograft and allograft recipients, but not in mice transfected with the β-gal gene alone. However, histopathological findings, for example, vascular cell adhesion molecule-1 (VCAM-1) expression in cardiac grafts and mononuclear lung infiltration, were remarkably similar for both treatment groups and consistent with LPS-induced pathology. LPS assays were used to evaluate four different methods of plasmid purification for degree of LPS contamination. A successful strategy for reducing levels of LPS contamination was identified and transfection experiments repeated in cardiac allograft recipients receiving LPS inoculum that were minimized and standardized (6.4 EU/mouse) for all treatment groups. Despite receiving substantially lower levels of LPS, in all treatment groups there was persistent cardiac graft endothelial cell activation manifested by VCAM-1 expression and persistent, albeit less severe, lung pathology. We found that plasmid contamination with LPS was unavoidable and that even very low levels can alter immune responses in transplant recipients confounding data interpretation. Thus, it is imperative to account for LPS contamination in experiments utilizing plasmid DNA for gene transfer, especially in experimental models of immunity and inflammation.
Differential effects of stress on release of thyroid-stimulating hormone in young and old male rats.

SummaryIn response to the stress of serial bleeding, ether exposure, or physical restraint, serum TSH was depressed more quickly and to a greater extent in young than in old male rats. These results suggest that the hypothalamo-hypophy-seal mechanisms which mediate inhibition of TSH release are less sensitive in old than in young male rats.
Venlafaxine-Associated Interstitial Pneumonitis

A 55-year-old woman was hospitalized with a 7-month history of progressive dyspnea on exertion and hypoxia despite a normal echocardiogram. The onset of her symptoms correlated with a dosage increase of venlafaxine. A multichannel computed tomography scan showed ground-glass opacities, and an open lung biopsy revealed interstitial pneumonitis consistent with extrinsic allergic alveolitis. Venlafaxine was discontinued, and corticosteroid therapy was started; the patient's hypoxia improved and the infiltrates evident on chest radiographs were reduced. The patient continued to improve after discontinuing venlafaxine, and other potential etiologies for interstitial pneumonitis were excluded. Thus, venlafaxine may have triggered extrinsic allergic alveolitis in this patient.
Luminescence of spark-processed materials

Abstract High-frequency spark discharges were applied to the following semiconducting and semi-metallic materials: Sb, Bi, Sn, As, Ge, GaAs, Si, Te and Se. The spark-processed (sp) samples were characterized by photoluminescence (PL) measurements using an excitation wavelength of 325 nm. With the exception of Se, PL signals in the visible region were obtained for all of the above-specified materials. The strongest and most stable PL was found in sp-Si and sp-Ge layers with peak wavelengths centred at 525 and 416 nm, respectively. The estimated increase of the bandgap energy due to the formation of nanocrystals was calculated using the effective mass approximation. The results are in accordance with the PL data. The particle sizes are expected to range from 3 to 8 nm. The findings support the quantum confinement model.
Dental education in the prevention and treatment of substance use disorders

(2002). Dental education in the prevention and treatment of substance use disorders. Substance Abuse: Vol. 23, No. sup1, pp. 185-206.
The 2013 eruption of Pavlof Volcano, Alaska: a spatter eruption at an ice- and snow-clad volcano

The 2013 eruption of Pavlof Volcano, Alaska began on 13 May and ended 49 days later on 1 July. The eruption was characterized by persistent lava fountaining from a vent just north of the summit, intermittent strombolian explosions, and ash, gas, and aerosol plumes that reached as high as 8 km above sea level and on several occasions extended as much as 500 km downwind of the volcano. During the first several days of the eruption, accumulations of spatter near the vent periodically collapsed to form small pyroclastic avalanches that eroded and melted snow and ice to form lahars on the lower north flank of the volcano. Continued lava fountaining led to the production of clastogenic lava flows that extended to the base of the volcano, about 3–4 km beyond the vent. The generation of fountain-fed lava flows was a dominant process during the 2013 eruption; however, episodic collapse of spatter accumulations and formation of hot spatter-rich granular avalanches was a more efficient process for melting snow and ice and initiating lahars. The lahars and ash plumes generated during the eruption did not pose any serious hazards for the area. However, numerous local airline flights were cancelled or rerouted, and trace amounts of ash fall occurred at all of the local communities surrounding the volcano, including Cold Bay, Nelson Lagoon, Sand Point, and King Cove.
Assay of prolyl hydroxylase in cultured fibroblast monolayers.

Abstract Prolyl hydroxylase may be assayed in cultured cell monolayers after a cold acetone treatment or air-drying. Enzyme activity of dried cells is stable when cell monolayers are stored frozen and desiccated, thus permitting simultaneous assay of cells harvested at different times, e.g., on different days of a culture cycle. Uniformity of cell monolayers permits use of separate dishes for assay of protein or DNA to determine specific enzyme activity. This procedure greatly facilitates harvesting and assay of cells for a variety of biochemical measurements.
Statistical energy analysis by finite elements for middle frequency vibration

Statistical energy analysis (SEA) is commonly used in industry to predict high-frequency vibrational response of structures. Since only local modes are used in SEA, only high-frequency responses can be predicted. This study extends SEA to the middle-frequency region by additionally using global modes. Methods using impedance matrices that can be found by NASTRAN are developed. Then the results are post processed to determine coupling loss factors.
Actin monomer binding proteins

Small actin monomer binding proteins are essential components of the actin polymerization machinery. Originally thought of as passive buffers that prevent polymerization of actin monomers, recent discoveries elucidate how some actin monomer binding proteins can promote as well as inhibit polymerization, and how they cooperate to regulate actin assembly.
Collection-level analysis tools for books online

Efforts to develop ebook-based functionality have focused thusfar on the individual artifact--the hardware and software reader--and on promoting user engagement with the page by supporting annotation, clipping, and navigation. In this position paper, I will discuss collection-level analytic functionality that will take advantage of the characteristics of online bodies of literature. This functionality includes (1) wisdom-of-crowds tools; (2) analytic tools for gathering; and (3) form- and function-based discovery tools.
Increase in manganese superoxide dismutase activity in the mouse heart after X-irradiation☆

Local X-irradiation of mouse heart caused a large increase in manganese superoxide dismutase activity (MnSOD) in this organ but not in copper and zinc containing superoxide dismutase (Cu-Zn SOD) activity. MnSOD induction was both dose and time dependent. Another mitochondrial enzyme, citrate synthase, was not induced by X-irradiation. The amount of immunoreactive MnSOD also increased after X-irradiation, showing that the amount of MnSOD protein increased after X-irradiation. The response to X-irradiation was found to be biphasic--with one large peak and one smaller peak of manganese superoxide dismutase activity. The effect of various inhibitors of cellular activities on these two peaks of MnSOD activity was examined. Cycloheximide, a cytosolic protein synthesis inhibitor, abolished both peaks of MnSOD activity, while chloramphenicol, a mitochondrial protein synthesis inhibitor, has no effect on either peak. Actinomycin D, a RNA-synthesis inhibitor, lowered both peaks, but had more of an effect on the second peak than on the first. In vivo protein synthesis studies using [3H]arginine showed that an increase in new protein synthesis occurred during the time period of the second peak, but did not occur during the first peak. These results are consistent with the hypothesis that MnSOD induction occurs in two peaks with the first peak due to a preformed MnSOD protein or mRNA for MnSOD and the second peak due to an increase in new protein synthesis.
Heritable and life-style determinants of bone mineral density

Familial resemblance in bone mineral density at five skeletal sites was measured among 160 adult members of 40 families. Each family included a postmenopausal mother, one premenopausal daughter, one son, and the children's father. Similarities in selected life-style factors thought to influence bone density, such as physical activity, smoking, alcohol use, and diet, were also evaluated. Bone density was measured by dual-energy (total body, femoral neck, and lumbar spine) or single-photon (radius and os calcis) absorptiometry. Correlation coefficients between the midparent Z score and offspring Z scores of bone mineral density ranged from 0.22 to 0.52 among daughters and from 0.27 to 0.58 among sons. Adjustment of bone density for age, height, weight, and significant life-style or environmental factors yielded heritability estimates for the five skeletal sites between 0.46 and 0.62. That is, 46-62% of variance in bone density was attributable to heredity. Most estimates derived from the group of daughters were similar to those from the sons. These observations provide support for a significant contribution of heredity to bone density. However, an individual's life-style may account for a potentially large proportion of the nonheritable variance in bone density.
Trainer Style and Patterns of Group Development

Developmental trends in two lo-man training groups were studied by checklist and rating scale techniques throughout a four-day laboratory. In one group, the trainers were inactive and nondirective ...
Field Estimation of Demographic Parameters: Influence of Sigmodon hispidus Population Structure

A method of removal trapping was initiated to test the hypothesis that different portions of a population of Sigmodon hispidus responded differently to live-trap sampling. Four plots of 3.7 hectares were live-trapped in 7 two-night trapping periods during one year. Animals captured the first night were temporarily removed until after the second night captures were recorded. Mean body weights and numbers were treated separately for males and females. During certain parts of the year, there were significant differences in body weight and distribution of size class between first and second night samples, but no significant differences in sex ratio. Such differences, unless accounted for by modification of sampling methods, violate assumptions of density estimators and hence markedly influence calculations of demographic parameters.
The effect of evaluative dispositions and amount and credibility of information on forming impressions of personality

An experiment is reported in which Ss varying in evaluative dispositions, or initial impressions existing prior to presentation of stimulus traits, rated sets of traits of varying size. High or low credibility was ascribed to traits via instructions. Positive dispositions were associated with greater positivity of ratings. This disposition effect was more pronounced under low credibility instructions. Both findings were in agreement with previous findings and with a weighted average model of information and disposition integration. Contrary to predictions, an increase in the number of like-valued traits did not reduce the disposition effect. Several alternatives were advanced to account for the latter unexpected finding.
Generation of Controllable Nano-Gaps on Single Wall Carbon Nanotube

We demonstrated the application of the atomic force microscope (AFM) in generation of controllable nano-gaps on single wall carbon nano-tubes (SWCNTs). Tapping mode AFM combined with interleave mode was used to image and manipulate the CNTs. By precise control of the loading force and the scan rate, we were able to generate desired gaps on CNT nanowires ranging from 10.6 nm to 58.8 nm. The gap size dependence on loading force and scan rate was discussed. Such a structure can be applied in fabrication of capacitancebased nano-device toward sensor applications.Copyright © 2006 by ASME
The influence of cell shape on the induction of functional differentiation in mouse mammary cells in vitro.

To define more clearly the in vitro conditions permissive for hormonal induction of functional differentiation, we cultured dissociated normal mammary cells from prelactating mice in or on a variety of substrates. Cultivation of an enriched epithelial cell population in association with living adult mammary stroma in the presence of lactogenic hormones resulted in both morphological and biochemical differentiation. This differentiation, however, was not enhanced over that seen when the cells were associated with killed stroma, provided that the killed stroma had a flexibility similar to that of the living stroma. Cells cultured in inflexible killed stroma usually did not differentiate. Cells cultured within the flexible environment of a collagen gel, but removed from the gas-medium interface, differentiated in a manner similar to those cultured in flexible stroma. Cells cultured on the surface of an attached collagen gel were squamous, and their basolateral surfaces were sequestered from the medium; they did not differentiate. Cells cultured on floating collagen gels were cuboidal-columnar, with basolateral surfaces exposed to the medium, and showed good functional differentiation. Cells cultured on inflexible floating collagen gels were extremely flattened and had exposed basolateral surfaces, and showed no evidence of functional differentiation. We infer that assumption of cuboidal to columnar shapes similar to those of mammary cells in vivo may be important to the induction of functional differentiation in vitro. The additional requirement of basolateral cell surface exposure also is important.
Standing between intransient history and transient memories: The statue of MacArthur in South Korea

Since its inception in 1957, the statue of General Douglas MacArthur at Incheon City in South Korea has been a robust signifier of the American rescuing mission during the Korean War that originally was meant to evoke gratitude among the South Koreans. Yet, South Korean activists in 2005 took iconoclastic actions against the statue, calling the public’s critical attention to both MacArthur’s actions and to the role of the United States during the Korean War. This case study of MacArthur’s statue reveals two processes at work: first, how a statue, in a time of transition, transforms itself from a mere signifier of intransigent history into a reflexive medium of transient memories of a past event and second, how a statue, in its surrounding space, can embrace the conflicting gestures that audiences from two different generational and ideological positions simultaneously perform. I conclude that a statue, reconfigured in time and space, has a strong potential to become a dissenting medium that effectively re...
Pattern and Regulation of Acetyl-CoA Carboxylase Gene Expression

Acetyl-CoA carboxylase is the rate-limiting enzyme in the biogenesis of long chain fatty acids. There is a single copy of the gene for acetyl-CoA carboxylase per haploid chromosome set. The gene contains two promoters whose primary transcripts are differentially spliced resulting in multiple forms of acetyl-CoA carboxylase mRNA. These mRNA species are different in the 5'-untranslated region, but contain the same coding region. Generation of different forms of the mRNA is tissue specific and controlled by physiological conditions. Two promoters contain an extensive array of cis-elements that perceive changes in the cellular environment signalling repression and induction of long chain fatty acid synthesis. The ability of the gene to respond to various lipogenic signals and the presence of the same coding sequence in all acetyl-CoA carboxylase mRNA species suggest that the biosynthesis of fatty acids required for multiple functions in the cells is primarily regulated at the gene level.
Ultradian Photosynchronization in Tetrahymena Pyriformis Glc is Related to Modal Cell Generation Time: Further Evidence for a Common Timer Model

This study contains the first report of the photosynchronization of Tetrahymena in the ultradian mode of cell division. Ultradian mode cultures of T. pyriformis GLC were grown at low cell titers in a nephelostat under five different ultradian photocycles and also under constant conditions of illumination. Entrainment was achieved only when the period of the synchronizer did not exceed the nearest modal generation time observed in free-running single cells. Thus, the discrete ranges for photentrainment of ultradian rhythms in Tetrahymena were restricted to modal windows for the generation times in free-run. Cell division was found to be a function of the phase of the ultradian zeitgeber cycle. The cells did not behave as if they had been forced into synchrony by physiological shock; the synchronous populations obtained by this technique behaved like the populations commonly used in circadian studies which had been phased by a cyclic variation within the tolerance range of the organism.
Streptomyces scopuliridis sp. nov., a bacteriocin-producing soil streptomycete.

Actinomycete strain RB72T was isolated from woodland bluff soil in northern Alabama, USA, and shown to produce a broad spectrum bacteriocin. Based on morphological and chemotaxonomic characteristics, the strain was determined to belong to the genus Streptomyces. Phylogenetic analysis of the near-complete 16S rRNA gene sequence indicated that it differed from those of the described streptomycetes available in public databases. The distinctive white aerial hyphae and lack of sporulation suggest a deficiency in the whi pathway of the organism. A combination of substrate utilization patterns, morphological and chemotaxonomic characteristics and DNA–DNA hybridization results supported the affiliation of strain RB72T to the genus Streptomyces and enabled the genotypic and phenotypic differentiation of strain RB72T from closely related reference strains. Strain RB72T therefore represents a novel species of the genus Streptomyces, for which the name Streptomyces scopuliridis sp. nov. is proposed. The type strain is RB72T ( = DSM 41917T = NRRL B-24574T).
Emotion Deficits in Schizophrenia: Timing Matters

The past two decades of research on emotional response in schizophrenia has demonstrated that people with schizophrenia do not have a marked deficit in reported emotional experience in the presence of emotionally evocative stimuli. However, the extent to which people with schizophrenia maintain their emotional state to guide future behavior remains a largely unexplored area of investigation. In the present study, we tested hypotheses about whether people with schizophrenia maintained their emotional state in the absence of emotionally evocative stimuli. In addition to reported emotional experience, we measured startle response magnitude both during the viewing and after the offset of emotional pictures to assess whether people with schizophrenia (n = 31) and without schizophrenia (n = 28) differ in their patterns of immediate response to emotional pictures and in their patterns of maintenance of these responses. Our findings indicated that people with and without schizophrenia did not differ in their self-report or startle response magnitude during presentation of emotional pictures. However, healthy controls maintained these responses after the stimuli were removed from view, but people with schizophrenia did not.
Intracellular Localization of the Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein: Absence of Nucleolar Accumulation during Infection and after Expression as a Recombinant Protein in Vero Cells

The nucleocapsid (N) protein of several members within the order Nidovirales localizes to the nucleolus during infection and after transfection of cells with N genes. However, confocal microscopy of N protein localization in Vero cells infected with the severe acute respiratory syndrome coronavirus (SARS-CoV) or transfected with the SARS-CoV N gene failed to show the presence of N in the nucleoplasm or nucleolus. Amino acids 369 to 389, which contain putative nuclear localization signal (NLS) and nucleolar localization signal motifs, failed to restore nuclear localization to an NLS-minus mutant Rev protein. These data indicate that nuclear localization is not a conserved property among all nidoviruses.
Embedded Multi-Processor System-on-chip (MPSoC) design considering process variations

As technology scales, the delay uncertainty caused by process variations has become increasingly pronounced in deep sub-micron designs. As a result, a paradigm shift from deterministic to statistical design methodology at all levels of the design hierarchy is inevitable (Borkar, 2005). As part of two NSF projects (NSF CNS CAREER 0643902 and NSF CNS 0720659), a variation-aware task allocation and scheduling method for multiprocessor system-on-chip (MPSoC) architectures is proposed, to mitigate the impact of parameter variations. A new design metric, called performance yield and defined as the probability of the assigned schedule meeting the predefined performance constraints, is used to guide the task allocation and scheduling procedure. An efficient yield computation method for task scheduling complements and significantly improves the effectiveness of the proposed variation-aware scheduling algorithm. Experimental results show that our variation-aware scheduler achieves significant yield improvements.
Physician Emigration from Sub-Saharan Africa to the United States: Analysis of the 2011 AMA Physician Masterfile

Background The large-scale emigration of physicians from sub-Saharan Africa (SSA) to high-income nations is a serious development concern. Our objective was to determine current emigration trends of SSA physicians found in the physician workforce of the United States. Methods and Findings We analyzed physician data from the World Health Organization (WHO) Global Health Workforce Statistics along with graduation and residency data from the 2011 American Medical Association Physician Masterfile (AMA-PM) on physicians trained or born in SSA countries who currently practice in the US. We estimated emigration proportions, year of US entry, years of practice before emigration, and length of time in the US. According to the 2011 AMA-PM, 10,819 physicians were born or trained in 28 SSA countries. Sixty-eight percent (n = 7,370) were SSA-trained, 20% (n = 2,126) were US-trained, and 12% (n = 1,323) were trained outside both SSA and the US. We estimated active physicians (age ≤70 years) to represent 96% (n = 10,377) of the total. Migration trends among SSA-trained physicians increased from 2002 to 2011 for all but one principal source country; the exception was South Africa whose physician migration to the US decreased by 8% (−156). The increase in last-decade migration was >50% in Nigeria (+1,113) and Ghana (+243), >100% in Ethiopia (+274), and >200% (+244) in Sudan. Liberia was the most affected by migration to the US with 77% (n = 175) of its estimated physicians in the 2011 AMA-PM. On average, SSA-trained physicians have been in the US for 18 years. They practiced for 6.5 years before US entry, and nearly half emigrated during the implementation years (1984–1999) of the structural adjustment programs. Conclusion Physician emigration from SSA to the US is increasing for most SSA source countries. Unless far-reaching policies are implemented by the US and SSA countries, the current emigration trends will persist, and the US will remain a leading destination for SSA physicians emigrating from the continent of greatest need. Please see later in the article for the Editors' Summary
The Cost-effectiveness of Community Services in a Frail Elderly Population

We use an integrated model incorporating simple principles of decision analysis and marginal cost analysis to discuss cost-effectiveness of community long-term care services as a substitute for nursing home care. By taking individuals as the unit of analysis and analyzing different types of community services separately, the model defines the targeting issue precisely and permits key policy parameters to be estimated empirically. When applied to data from the National Long Term Care Channeling Demonstration, 41% of those screened into the control group were found to have some potential for net long-term care cost reduction through program services.
Architectural implications and process development of 3-D VLSI Z-axis interconnects using through silicon vias

A through-silicon via (TSV) process provides a means of implementing complex, multichip systems entirely in silicon, with a physical packing density many times greater than today's advanced multichip modules. This technology overcomes the resistance-capacitance (RC) delays associated with long, in-plane interconnects by bringing out-of-plane logic blocks much closer electrically, and provides a connection density that makes using those blocks for random logic possible by even small system partitions. TSVs and three dimensional (3-D) stacking technology have the potential to reduce significantly the average wire length of block-to-block interconnects by stacking logic blocks vertically instead of spreading them out horizontally. Although TSVs have great potential, there are many fabrication obstacles that must be overcome. This paper discusses the architectural possibilities enabled by TSVs, and the necessary TSV dimensions for dense Z-axis interconnect among logic blocks. It then describes the TSV requirements for the Defense Advanced Research Projects Agency (DARPA)-funded Vertically Integrated Sensor Arrays (VISA) program, and how those requirements differ from a more general purpose TSV technology. Finally, the TSV fabrication process being implemented at the University of Arkansas (UA) is described in detail. Though this process is being developed for the VISA program, it embodies many of the characteristics of a widely applicable TSV technology.
Potential new uses of non–vitamin K antagonist oral anticoagulants to treat and prevent stroke

Background: Non–vitamin K antagonist oral anticoagulant (NOAC) drugs are at least equivalent to warfarin for ischemic stroke prevention in patients with atrial fibrillation and have a lower risk of intracranial hemorrhage. The role of these agents in the prevention and treatment of other types of cerebrovascular disease remains unclear. Methods: We reviewed the literature (randomized trials, exploratory comparative studies, and case series) on the use of NOACs in patients with atrial fibrillation, venous thromboembolism, and cerebrovascular disease independent of atrial fibrillation. Results: The literature on the use of NOACs for treatment and prevention of cerebrovascular disease in patients without atrial fibrillation is sparse. The potential benefit of vitamin K antagonists over antiplatelet agents for primary and secondary prevention in certain subsets of patients with cerebrovascular disease is offset by the increased risk of major and intracranial hemorrhage. Given that NOACs are equivalent to vitamin K antagonists in preventing ischemic stroke and systemic embolism in patients with atrial fibrillation with less bleeding risk, clinical trials are needed to investigate the short- and long-term use of NOACs in populations of patients with other forms of cerebrovascular disease, including those with cryptogenic stroke with or without evidence of patent foramen ovale and low ejection fraction, cervical artery dissection, large artery atherosclerosis, venous thrombosis, and stuttering lacunar stroke. Conclusion: There may be a role for NOACs in stroke prevention and treatment beyond atrial fibrillation. Randomized controlled trials are needed to compare NOACs to current stroke prevention and treatment strategies in certain subgroups of patients with cerebrovascular disease.
A morphologic analysis of sessile serrated polyps observed during routine colonoscopy (with video)

Background Proximal colorectal cancer may arise from sessile serrated polyps (SSPs), which are often inconspicuous during colonoscopy. The gross morphologic characteristics of SSPs have not been systematically described, and this omission may contribute to colonoscopists overlooking them. Objectives To analyze the gross morphologic characteristics of SSPs detected during routine colonoscopy. Design Retrospective analysis of high-resolution endoscopic video clips depicting SSPs in situ. Setting Outpatient gastroenterology practice. Patients A total of 124 subjects undergoing surveillance or screening colonoscopy after split-dose bowel preparation. Interventions Analysis of 158 SSPs performed by using validated descriptors. Main Outcome Measurements The prevalence of morphologic characteristics related to polyp shape, color, and texture. Results A total of 158 SSPs were studied. For 7 visual descriptors, a κ coefficient of ≥0.7 was achieved, indicating good to excellent intraobserver agreement. The most prevalent visual descriptors were the presence of a mucous cap (63.9%), rim of debris or bubbles (51.9%), alteration of the contour of a fold (37.3%), and interruption of the underlying mucosal vascular pattern (32.3%). The most common "sentinel signs" were the presence of a mucous cap and alteration of the contour of a mucosal fold (each 24.6%), rim of debris or bubbles (21.7%), and a dome-shaped protuberance (20.3%). When comparing SSPs with adenomatous polyps, the frequencies of 5 of 7 morphologic characteristics and the distribution of sentinel signs differed ( P Limitations Single-site, retrospective analysis. Conclusions SSPs exhibit distinct, variable morphologic characteristics. Many do not display classic features such as a mucous cap. Enhanced appreciation of these morphologic characteristics may improve SSP detection and thereby colorectal cancer prevention.
Viability of a Drug-Resistant Human Immunodeficiency Virus Type 1 Protease Variant: Structural Insights for Better Antiviral Therapy

Under the selective pressure of protease inhibitor therapy, patients infected with human immunodeficiency virus (HIV) often develop drug-resistant HIV strains. One of the first drug-resistant mutations to arise in the protease, particularly in patients receiving indinavir or ritonavir treatment, is V82A, which compromises the binding of these and other inhibitors but allows the virus to remain viable. To probe this drug resistance, we solved the crystal structures of three natural substrates and two commercial drugs in complex with an inactive drug-resistant mutant (D25N/V82A) HIV-1 protease. Through structural analysis and comparison of the protein-ligand interactions, we found that Val82 interacts more closely with the drugs than with the natural substrate peptides. The V82A mutation compromises these interactions with the drugs while not greatly affecting the substrate interactions, which is consistent with previously published kinetic data. Coupled with our earlier observations, these findings suggest that future inhibitor design may reduce the probability of the appearance of drug-resistant mutations by targeting residues that are essential for substrate recognition.
V(D)J Recombinase-Mediated TCR β Locus Gene Usage and Coding Joint Processing in Peripheral T Cells during Perinatal and Pediatric Development

The generation of TCR proteins is the result of V(D)J recombinase-mediated genomic rearrangements at recombination signal sequences (RSS) in human lymphocytes. V(D)J recombinase can also mediate rearrangements at nonimmune or "cryptic" RSS in normal and leukemic human peripheral T cells. We previously demonstrated age- and gender-specific developmental differences in V(D)J coding joint processing at cryptic RSS within the HPRT locus in peripheral T cells from healthy children (Murray et al. 2006. J. Immunol. 177: 5393-5404). In this study, we investigated developmentally specific V(D)J recombinase TCRβ immune gene rearrangements and coding joint processing at RSS in peripheral T cells in the same pediatric population. This approach provided a unique opportunity to investigate site-specific V(D)J recombinase rearrangements and coding joint processing at immune and nonimmune genes from the same individual T cell population. We determined the genomic sequence of 244 TCRβ coding junctions from 112 (63 male, 49 female) subjects from the late stages of fetal development through 9 y of age. We observed both age- and gender-specific V(D)J recombinase-mediated TCRβ gene usage and coding joint processing at immune RSS. To the best of our knowledge, these data represent the first description of age- and gender-specific developmental differences in TCR gene usage and coding joint processing that could directly influence TCR diversity and immune specificity. It will be important for future studies to ascertain the mechanistic etiology of these developmental and gender differences in TCR diversity and specificity, as well as their importance with respect to the age and gender risks for infectious and autoimmune diseases in humans.
Liquid transport properties of porcine tracheal epithelium.

Because of its possible importance to the etiology of cystic fibrosis lung disease, the ion and water transport properties of tracheal epithelium were studied. Net liquid flux (J V) across porcine ...
Patogenicidad y susceptibilidad a Phoma exigua Desm. de tres portainjertos y dos variedades de limonero (Citrus lemon L.)

En la localidad de La Serena, IV Region del pais, se detectaron plantas de limonero de dos anos de edad con sintomas de atizonamiento a nivel de brotes y presencia de cancros en el tronco con abundante exudacion de goma, produciendo en algunos casos la muerte de las plantas. A partir de la zona de avance de estas lesiones se aislo en forma consistente micelio correspondiente a Phoma exigua Desm. A partir de aislamientos puros de este hongo se inocularon frutos y plantas de limonero, obteniendose en estas ultimas los mismos sintomas antes descritos. De este inodo se demostro la patogenicidad de la cepa obtenida, la que fue recuperada a partir de las lesiones, manteniendose la mismas caracteristicas del cultivo. Se realizaron ademas pruebas de susceptibilidad de dos variedades de limon crecidas sobre tres portainjertos y la de estos por separado. Los resultados demostraron que todas las combinaciones fueron afectadas, existiendo diferencias en susceptibilidad, siendo la variedad Genov a mas susceptible que la variedad Eureka. Se concluye que esta sintomatologia, seria una nueva enfermedad que afecta al cultivo del limon, la que denominamos. "Cancrosis y atizonamiento del limonero ", causada por Phoma exigua Desm.
Sustainment of Commercial Aircraft Gas Turbine Engines: An Organizational and Cognitive Engineering Approach

In this paper, we present a novel cognitive engineering approach to creating a framework that more fully captures the decision support needs of commercial aircraft gas turbine engine maintenance, repair and overhaul (MRO) organizations. Current MRO decision support tools focus largely on engine condition monitoring and fault diagnostic systems, and most of the existing literature has focused on developing algorithms for these systems. Few researchers have suggested how to design a broader set of computer-based decision support tools to meet various other decision support needs of the engine MRO community such as fault prognostics, maintenance planning, workscope generation and configuration management. Using field studies of various airlines, engine MRO providers and engine manufacturers across North America, Asia-Pacific and Europe, the analyses presented in this paper offer a thorough understanding of the cognitive needs and the decision-making process in engine MRO organizations. We present preliminary recommendations for a design framework for new decision support tools for engine sustainment and how such tools can be implemented in future engine MRO operations. Suggestions are also provided for future tools that are currently lacking, of which some are greatly needed by the industry and should be developed and implemented first. We also discuss some of the challenges that may impede the development and implementation of future decision support tools in the engine MRO industry.
Active and Passive Flow Control over the Flight Deck of Small Naval Vessels

Helicopter operations in the vicinity of small naval surface vessels require excessive pilot workload. Because of the unsteady flow field and large mean velocity gradients, the envelope for flight operations is limited. This experimental investigation uses a 1:144 scale model of the U.S. Navy destroyer DDG-81 to explore the problem. Both active and passive flow control techniques were used to improve the flow field in the helicopter's final decent onto the flight deck. Data were collected at a set of grid points using a single component hotwire. Results show that the use of porous surfaces decreases the unsteadiness of the flow field. Further improvements are found by injecting air through these porous surfaces, causing a reduction in unsteadiness in the landing region of 6.6% at 0 degrees wind-over- deck (WOD) and 8.3% at 20 degrees WOD. Other passive configurations tested include fences placed around the hangar deck edges which move the unsteady shear layer away from the flight deck. Although these devices cause an increase in unsteadiness downstream of the edge of the fence when compared to the baseline, the reticulated foam fence caused an overall decrease in unsteadiness in the landing region of 12.1% at 20 degrees WOD.
Numerical Prediction of Pitch Damping Derivatives for a Finned Projectile at Angles of Attack

This study extends the time-accurate forced-oscillation planar pitching ReynoldsAveraged method to predict the pitch damping dynamic stability derivative at non-zero angles of attack for projectile munitions. The simulations were performed for two configurations of the Army-Navy Finner Missile at Mach 1.96, for two Reynolds number test conditions, and for angles of attack ranging from 0–85°. Comparisons with archival wind tunnel data indicated good to excellent numerical prediction for the pitch damping moment. For the static aerodynamic coefficients, the method predicts the pitching moment with excellent accuracy, and the pitching moment slope with fair accuracy.
Coping with Laboratory Workforce Shortages

Thank you for the Forum article by Kaplan and Burgess in February Microbe discussing alarming workforce shortages in the diagnostic laboratories of the United States (Microbe, February 2011, p. 52). The writers are correct—it is critical to improve the visibility of clinical lab careers among teachers, youngsters, and the general public. However, it is disturbing that, were there to be a big influx of potential students, we could not handle them. The laboratory community needs to address the diminished capacity and vibrancy of educational programs, many of which were closed in recent decades.
Assessment of Range Caterpillar (Lepidoptera: Saturniidae) Effects with a Grassland Simulation Model

An empirical consumption submodel for range caterpillar, Hemileuca oliviae Cockerell, which integrated consumption and mortality, was developed. This submodel was used in conjunction with a process-oriented producer submodel and abiotic submodel to assess the effects of various range caterpillar population densities, and heterogeneous environmental conditions, on above-ground and below-ground productivity of blue grama rangeland. Economic injury levels were calculated based on current caterpillar population suppression costs and forage values, and on variable caterpillar population densities and environmental conditions.
Health Insurance Market Risk Assessment: Covariate Shift and k-Anonymity.

Health insurance companies prefer to enter new markets in which individuals likely to enroll in their plans have a low annual cost. When deciding which new markets to enter, health cost data for the new markets is unavailable to them, but health cost data for their own enrolled members is available. To address the problem of assessing risk in new markets, i.e., estimating the cost of likely enrollees, we pose a regression problem with demographic data as predictors combined with a novel three-population covariate shift. Since this application deals with health data that is protected by privacy laws, we cannot use the raw data of the insurance company’s members directly for training the regression and covariate shift. Therefore, to construct a full solution, we also develop a novel method to achieve k-anonymity with the workload-driven quality of data distribution preservation achieved through dithered quantization and Rosenblatt’s transformation. We illustrate the efficacy of the solution using real-world, publicly available data.
Quantifying drivers of population dynamics for a migratory bird throughout the annual cycle

Worldwide, migratory species are undergoing rapid declines but understanding the factors driving these declines is hindered by missing information about migratory connectivity and the lack of data ...