cssi/SciSciGPT-SciSciNet huggingface dataset:
Tackling HIV through robust diagnostics in the developing world: current status and future opportunities

Over the last thirty years, the world has seen HIV circulate the globe, affecting 33 million people to date and killing 2 million people a year. The disease has affected developed and developing countries alike, and in the U.S., remains one of the top ten leading causes of death. Many regions of the world are highly impacted by this disease, including sub-Saharan Africa, South and South-East Asia, and Eastern Europe. Fortunately, multilateral, global efforts, along with successful developments in diagnostic tools and anti-retroviral drugs (ARVs) have successfully curbed the spread of HIV over the last ten years. In spite of this fact, access to HIV treatment and preventive healthcare is varying and limited in developing countries. A lack of healthcare infrastructure, financial support, and healthcare workers are some logistical factors that are responsible. HIV stigmatization, discrimination, and inadequate education pose additional social challenges that are hindering countries from advancing in HIV prevention. This review focuses on current technological tools that are used for HIV diagnosis and ongoing research that is aimed at addressing the conditions in low-resource settings. Recent developments in microfluidic applications and mobile health technologies are promising approaches to building a compact, portable, and robust device that can provide information-rich, real-time diagnoses. We also discuss the role that governments, healthcare workers, and even researchers can play in order to increase the acceptance of newly introduced devices and treatments in rural communities.
Enhancing Departments and Graduate Education in Geography: A Disciplinary Project in Professional Development

This paper describes the development, implementation, and preliminary outcomes of Enhancing Departments and Graduate Education (EDGE) in Geography, a multiyear project begun in 2005 to study the process of professional development in graduate geography in the U.S and sponsored by the National Science Foundation. As a research and action project responding to the needs of graduate geography programs, EDGE seeks to provide academic geographers with an empirical perspective of disciplinary as well as interdisciplinary and generic skills that M.A./M.S. and Ph.D. students develop as a result of graduate education. Related objectives are to understand how disciplinary skills are applied by geography graduates once they enter the professional workforce in both academic and nonacademic professional settings, and to gauge the extent graduate programs are sufficiently preparing geography graduates for those careers. We begin by summarizing the research goals and design of EDGE, highlighting the roles and contributions of geographers and educational researchers, and noting the interplay and synergy between disciplinary and interdisciplinary methodologies and practices. To date, research has focused on: (1) assessing contemporary workforce competencies in professional geography and (2) examining the role of department climate and culture on student experience and faculty development within masters and doctoral programs. Although the EDGE research efforts are still underway, we present some preliminary research findings and discuss the implications of those outcomes for professional development in geography and related social and environmental sciences. Also discussed is the complementary nature of disciplinebased and interdisciplinary professional development efforts.
The case for accretion of the tectosphere by buoyant subduction

This paper tests three hypotheses for the origin of the tectosphere. Continental collision cannot explain the low metamorphic grade of crust that predates the tectosphere. Halfspace cooling and buoyant underlating can both fit the diamond age data, although underplating by buoyant subduction is the favored model. Thermal models provide a further test. If half space cooling formed the tectosphere, diamonds from 150km depth will be at least 200 m.y. younger than diamonds from 190km. If buoyant subduction formed the tectosphere, diamonds from 150km depth will be the same age or older than diamonds from 190km.
Statistical Challenges in Sequence-Based Association Studies with Population- and Family-Based Designs

Over the past few years, association analysis has become the primary tool for finding genes that underlie complex traits. Both population-based and family-based designs are commonly used designs in genetic association studies. Recent technological advances in exome and whole genome sequencing afford the next generation of sequence-based association studies. We review here recent developments in statistical methodology and remaining challenges related to sequence-based association studies with both population-based and family-based designs.
The association between county political inclination and obesity: Results from the 2012 presidential election in the United States.

Abstract Objective We examined whether stable, county-level, voter preferences were significantly associated with county-level obesity prevalence using data from the 2012 US Presidential election. County voting preference for the 2012 Republican Party presidential candidate was used as a proxy for voter endorsement of personal responsibility approaches to reducing population obesity risk versus approaches featuring government-sponsored, multi-sectoral efforts like those recommended by the Centers for Disease Control Centers for Disease Control (CDC, 2009). Method Cartographic visualization and spatial analysis were used to evaluate the geographic clustering of obesity prevalence rates by county, and county-level support for the Republican Party candidate in the 2012 U.S. presidential election. The spatial analysis informed the spatial econometric approach employed to model the relationship between political preferences and other covariates with obesity prevalence. Results After controlling for poverty rate, percent African American and Latino populations, educational attainment, and spatial autocorrelation in the error term, we found that higher county-level obesity prevalence rates were associated with higher levels of support for the 2012 Republican Party presidential candidate. Conclusion Future public health efforts to understand and reduce obesity risk may benefit from increased surveillance of this and similar linkages between political preferences and health risks.
Intraductal Papilloma of the Male Breast: An Ultrastructural and Immunohistochemical Study

A case of intraductal papilloma of the male breast was studied by electron microscopy and immunohistochemistry. The major components of this lesion were the epithelial and myoepithelial cells. Intermediate cells showing ultrastructural features of both cell types were also observed. Squamous metaplasia was noted in many areas. Numerous intranuclear helioid inclusions were seen in the tumor cells. The features of this lesion are similar to those of papillomas of the female breast.
Directional Viscous Multigrid Using Adaptive Prismatic Meshes

The paper describes the development and application of a new multigrid method using adaptive-prismatic grids for viscous flow computations. The three-dimensional Navier-Stokes equations are solved on the prismatic grids that are adaptively refined locally. The multigrid method is employed to propagate the fine grid corrections more rapidly by redistributin g the changes in time of the solution from the fine grid to the coarser grids to accelerate convergence. The present approach uses the parent cells of the fine grid cells in an adapted mesh to generate successively coarser levels of multigrid. Furthermore, the prismatic grid is semi-unstruct ured and is constituted by layers of cells that are constructed from the triangulation on the surface of the body in a direction normal to the surface. This inherent structure of the prismatic grid is used in generating further coarser multigrid levels by deleting every other layer of cells. The solver is an explicit, vertex-based, finite volume scheme. Spatial discretization is of central-differencing type and temporal discretization is of Lax-Wendroff type. Application cases include adaptive solutions obtained with multigrid acceleration for flows with both shear layers and shock waves present. Convergence acceleration obtained by employing various levels of multigrid is investigated.
UNCERTAINTIES OF ASPHALT LAYER THICKNESS DETERMINATION IN FLEXIBLE PAVEMENTS-INFLUENCE DIAGRAM APPROACH

Abstract The thickness of pavement layers is an important parameter used in Pavement Management Systems (PMS). Thickness data are used for pavement condition assessment, performance predictions, selection of maintenance strategies and rehabilitation treatments, basic quality assessment, and as input to overlay thickness design. Pavement thickness is usually determined from direct testing such core samples, nondestructive testing such as radar, or historical records such as pavements network database. This paper proposes the use of Bayesian Influence Diagrams as a tool in providing a probabilistic model for thickness determination procedure in flexible pavements. The Bayesian Influence Diagram Model is presented as a framework for addressing uncertainties involved in capturing quantitative and qualitative information in the asphalt layer thickness determination procedures. The model is also used to perform value of information analysis in the determination of pavement layer thickness. The Influence Diagram...
Social anxiety and socially prescribed perfectionism: Unique and interactive relationships with maladaptive appraisal of interpersonal situations

Abstract Although investigators have suggested that maladaptive appraisal of interpersonal situations may be related to perfectionist characteristics of socially anxious persons, little research has addressed this notion. In this study, the joint role of social anxiety and socially prescribed perfectionism (SPP; Hewitt & Flett, 1991a) was assessed relative to participants’ appraisal of an interpersonal situation. Results showed that social anxiety and SPP were related with the discrepancy between participants’ ratings of others’ performance standards for them and ratings of their own self-efficacy for an upcoming conversation, and that SPP moderated the relationship between social anxiety and the discrepancy. Second, only social anxiety was related with the frequency of negative self-statements; however, SPP moderated the relationship between social anxiety and participants’ negative self-statements relative to the conversation. For both interactions, the greater an anxious person’s SPP, the greater their degree of maladaptive appraisal. Results are discussed relative to theoretical and clinical implications of the findings.
New genome size estimates of 134 species of arthropods

Insect genome size diversity remains poorly sampled, with sparse and sporadic sampling of a few select orders and with many orders unrepresented or underrepresented in the genome size database. Here, we present 134 genome size estimates for 18 orders, including the first ever genome size estimates for eight orders, 38 families, 102 genera, and 131 species. Also reported here are three insect species genome size estimates that are corrections for unpublished genome size values that made it into the literature, including the smallest arthropod genome of the two spot spider mite (1C = 91 Mb). These estimates range from 91 to 7,752 Mb and provide a broader picture of genome size variation within Insecta and among all Arthropods. Proposed developmental constraints for holometabolous insect genome sizes are supported, with the majority of the species examined falling well under the hypothesized 1,978 Mb (2 pg) limit. The only exceptions occur in the highly diverse beetles (Coleoptera) (154 < 1C < 2,578) and the Mecoptera (1,890 < 1C < 2,134). Hemimetabolous orders include species with larger genomes. Of these, the Orthopteran genomes remain the largest (675 < 1C < 7,752). Hemipteran genomes are smaller (407 < 1C < 1,230), but with a very notable exception, the Cicadidae family, with bloated genomes (5,238 < 1C < 7,000 Mb) of a size previously known to exist only within Orthoptera. The genome sizes in all other Hemimetabolous orders (521 Mb < 1C < 3,860 Mb) fall within the range exhibited by the Hemiptera. New preparations and procedures for insect genome estimates with frozen material are described and discussed. To further improve and extend the number and quality of arthropod genome size estimates, a new flow cytometry insect standard, Blattaria: Periplaneta americana♂ (1C = 3,338 Mb) is established for genome size determination of insect genomes in excess of 2,000 Mb.
Tumor Cell Killing Enabled by Listeriolysin O-liposome-mediated Delivery of the Protein Toxin Gelonin

Gelonin is a type I plant toxin that has potential as an effective anti-tumor agent by virtue of its enzymatic capacity to inactivate ribosomes and arrest protein synthesis, thereby effectively limiting the growth of cancer cells. Being a hydrophilic macromolecule, however, gelonin has limited access to its target subcellular compartment, the cytosol; it is effectively plasma membrane-impermeant and subject to rapid degradation within endosomes and lysosomes upon cellular uptake as it lacks the membrane-translocating capability that is typically provided by a disulfide-linked B polypeptide found in the type II toxins (e.g. ricin). These inherent characteristics generate the need for the development of a specialized cytosolic delivery strategy for gelonin as an effective anti-tumor therapeutic agent. Here we describe an efficient means of delivering gelonin to the cytosol of B16 melanoma cells. Gelonin was co-encapsulated inside pH-sensitive liposomes with listeriolysin O, the pore-forming protein that mediates escape of the intracellular pathogen Listeria monocytogenes from the endosome into the cytosol. In in vitro experiments, co-encapsulated listeriolysin O enabled liposomal gelonin-mediated B16 cell killing with a gelonin IC50 of approximately 0.1 nM with an extreme efficiency requiring an incubation time of only 1 h. By contrast, cells treated with equivalent concentrations of unencapsulated gelonin or gelonin encapsulated alone in pH-sensitive liposomes exhibited no detectable cytotoxicity. Moreover, treatment by direct intratumor injection into subcutaneous solid tumors of B16 melanoma in a mouse model showed that pH-sensitive liposomes containing both listeriolysin O and gelonin were more effective than control formulations in curtailing tumor growth rates.
"almost touching": parent-child remote communication using the sharetable system

We deployed the ShareTable - a system that provides easy-to-initiate videochat and a shared tabletop task space - in four divorced households. Throughout the month of its use, the families employed the ShareTable to participate in shared activities, share emotional moments, and communicate closeness through metaphorical touch. The ShareTable provided a number of advantages over the phone and was easier to use than standard videoconferencing. However, it did also introduce concerns over privacy and new sources of conflict about appropriate calling practices. We relate our findings to the larger research landscape and present implications for future work.
Identification of glutathione S-transferase isozymes and γ-glutamylcysteine synthetase as negative acute-phase proteins in rat liver

Because acute infection and inflammation affect drug metabolism and drug-metabolizing enzymes, the effect of the acute-phase response on the expression of glutathione S-transferase (GST) isoenzymes, glutathione synthesis, and several antioxidant enzymes was investigated. Hepatic expression of GST isozymes, positive and negative acute-phase reactants, and antioxidant enzymes were determined by Northern blotting and hybridization with gene-specific oligonucleotide probes after lipopolysaccharide treatment of rats. Lipopolysaccharide caused the expected acute-phase response as judged by the increased expression of positive and decreased expression of negative acute-phase proteins. The messenger RNA (mRNA) expression of the major hepatic rat GST isozymes A1, A2, A3, M1, and M2 was decreased 50% to 90%. Total hepatic GST activity toward 1-chloro-2,4-dinitrobenzene was also significantly decreased. mRNA expression of gamma-glutamylcysteine synthetase (GCS) large subunit and catalase was reduced by approximately 60%. GCS enzyme activity was also decreased, resulting in a 35% decrease in the hepatic content of reduced glutathione 4 days after lipopolysaccharide challenge. Mn-Superoxide dismutase expression was increased 13-fold, and thioredoxin level was elevated 3-fold after lipopolysaccharide challenge. The expression of all parameters determined returned to near control levels 7 days after treatment. Together, these data show that GSTs and GCS are negative acute-phase proteins and that decreased GCS activity results in a decrease in hepatic glutathione content. Thus, in addition to the phase I drug-metabolizing enzymes known to be decreased during the acute-phase response, some phase II enzymes involved in the elimination of xenobiotics and carcinogens are also decreased.
Alteration of Human and Bovine Prolactins by a Chloramine T Radioiodination: Comparison with Lactoperoxidase-Iodinated Prolactins

ABSTRACT Iodination of human and bovine prolactins by a chloramine T (CT) method (mol ratio CT/PRL = 1500–4000, 60 sec incubation) yielded iodoprolactins slightly more excluded from Sephadex G-100 than lactoperoxidase-iodinated prolactins, which coeluted with unlabeled pituitary prolactin. This minor alteration in physicochemical properties of the CT-iodoprolactins was associated with profound loss of desirable immunochemical properties for radioimmunoassay.
A new species of Stenopus from Australia, with a redescription of Stenopus cyanoscelis (Crustacea: Decapoda: Stenopodidea)

A new species of shrimp in the genus Stenopus collected from off Queensland, Australia, is described and figured. Specimens have been collected from two widely separated locations on the Great Barrier Reef, at Heron Island to the south and Wheeler Reef northeast of Townsville. A preliminary diagnosis and colour plate of another Stenopus from Australia, S. cyanoscelis, was presented by Goy (1984). Recent collections of additional specimens of S. cyanoscelis from Indonesia and Kenya allow a detailed redescription of the holotype and morphological variation within the species. Both the new species, Stenopus chrysexanthus and S. cyanoscelis, are closely related to two Atlantic species, S. spinosus and S. scutellatus. However, both species are easily distinguished by differences in morphology and colour pattern. A key to the eight described Indo-West Pacific species of Stenopus is presented.
Evolutionary developmental linguistics: Naturalization of the faculty of language

Abstract Since language is a biological trait, it is necessary to investigate its evolution, development, and functions, along with the mechanisms that have been set aside, and are now recruited, for its acquisition and use. It is argued here that progress toward each of these goals can be facilitated by new programs of research, carried out within a new theoretical framework—one that could be called “evolutionary developmental linguistics” (EDL)—respecting current developments in biology, anthropology, psychology, and cognitive neuroscience. EDL is concerned with the evolution of developmental properties, processes, and stages (evo → devo) that independently, or in concert with other environmental changes, facilitated the emergence of language in the species (devo → evo). I describe recent work carried out within this framework, and suggest future lines of research. The faculty of language stands to benefit from a synthesis of evolution and development, as does the field of linguistics.
An accuracy assessment of the refinement of partial metal disorder in solid solutions of Al(acac)3 and Cr(acac)3

A series of solid solutions have been prepared by co-crystallization of Al(acac)3 and Cr(acac)3 and studied by X-ray diffraction. The end members and seven isotopic members of the series Al1 − xCrx(acac)3, with x varying from 0.02 to 0.91, crystallize in the monoclinic space group P21/c with Z = 4. The unit cell parameters vary slightly with composition, and fall into the following ranges: a, 13.987–14.009; b, 7.534–7.553; c, 16.308–16.348 A; β, 98.78–98.99°. The cell axes do not vary in a linear manner with the mole% Cr. The Al ∶ Cr molar ratio in each crystal studied by X-ray diffraction was determined by wavelength dispersive spectroscopy (WDS) and compared with the refinement of the Al ∶ Cr site occupancy, which was attempted by the following methods: (1) refinement based upon bulk sample analysis, (2) refinement of occupancy with common displacement parameters, (3) refinement of occupancy and displacement parameters, and (4) construction of a mixed atom type based on the results of all three methods. Results from methods 2 and 3 were found to agree with WDS data within experimental error for all crystals studied. Method 1 was the least successful, the refinement often being significantly problematic. A discussion of suitable methods for refinement of partial site occupancy in solid solutions for isomorphous structures is presented. The variance of crystal lattice parameters and the M–O and O–M–O structural parameters with Al ∶ Cr ratio is investigated.
Rapid Eye Movement Sleep in Relation to Overweight in Children and Adolescents

Context Short sleep duration is associated with obesity, but few studies have examined the relationship between obesity and specific physiological stages of sleep.
Kinetics of Alkaline Hydrolysis of a Polyimide Surface

The alkaline hydrolysis of a polyimide (PMDA-ODA) surface was studied as a function of time, temperature and hydroxide ion concentration. Quantification of the number of carboxylic acid groups formed on the modified polyimide surface was accomplished by analysis of data from contact angle titration experiments. Using a large excess of base, pseudo-first-order kinetics were found, yielding kobs ≈ 0.1−0.9 min-1 for conversion of polyimide to poly(amic acid) depending on [OH-]. From the dependence of kobs on [OH-], a rate equation is proposed. Conversion of the polyimide surface to one of poly(amic acid) was found to reach a limiting value with a formation constant, K, in the range 2−10 L·mol-1.
Management of 1- to 2-cm Carcinoid Tumors of the Appendix: Using the National Cancer Data Base to Address Controversies in General Surgery

Background The management of 1- to 2-cm appendiceal carcinoid tumors remains controversial. Here we use the National Cancer Data Base (NCDB) to compare long-term outcomes for patients treated via resection of the primary tumor alone vs right hemicolectomy (RHC). Study Design The 1998 to 2011 NCDB User File was queried to identify patients with 1- to 2-cm appendiceal carcinoids. Patients were stratified by surgical technique: resection of the primary tumor alone vs RHC with regional lymphadenectomy. Multivariable logistic regression was used to compare short-term outcomes. Survival was estimated using the Kaplan-Meier method with comparisons based on the log-rank test. Results A total of 916 patients were identified, including 42% managed with primary resection and 58% with RHC. Patients who underwent RHC had slightly larger tumors and higher-stage tumors; otherwise, there were no baseline differences between groups. The rates of positive margins were similar (5.5% vs 4.5%; p = 0.60). Among all patients, 1- and 5-year survival were 98.1% and 88.7% vs 96.7% and 87.4% (p = 0.52) for those managed via primary resection vs RHC, respectively. Among patients with moderate/high-grade/anaplastic carcinoids, 1- and 5-year survival were 93.3% and 72.0% vs 92.3% and 71.9%, respectively (p = 0.78). After adjustment with Cox proportional hazards modeling, we confirmed that there was no survival benefit for patients undergoing RHC (hazard ratio = 1.14; p = 0.72). Conclusions For 1- to 2-cm appendiceal carcinoids, formal resection of the right colon does not appear to improve survival, even for higher-grade tumors. Our findings suggest that resection of the primary tumor alone is adequate for all carcinoids
Role of Staphylococcus aureus protein A in adherence to silastic catheters.

Background Communities of bacteria, termed biofilms, frequently develop on central venous catheters, and bacterial contamination of central venous catheters is the most common cause of nosocomial bloodstream infections. Little is known about the initial events in bacterial adherence to the catheter surface, and experiments were designed to clarify the role of staphylococcal protein A, serum, and immunoglobulin in adherence of Staphylococcus aureus to silastic catheters. We hypothesized that S. aureus protein A in the presence of serum and immunoglobulin would alter S. aureus adherence to silastic catheters. Materials and Methods Three strains of S. aureus with varying expression of staphylococcal protein A were incubated 15 min at room temperature with silastic catheters, and bacterial adherence to the catheter surface was quantified. In addition, the effects of serum, albumin, and purified IgG on bacterial adherence were assessed. Results Both serum and albumin had an inhibitory effect on S. aureus adherence to the catheter surface, and protein A expression did not appreciably modulate these effects. Purified serum IgG also inhibited S. aureus adherence, with IgG having a greater inhibitory effect on the adherence of an S. aureus strain deficient in protein A compared with an S. aureus strain expressing high levels of protein A. Conclusion S. aureus adherence to silastic catheters was inhibited by whole serum, albumin, and purified IgG. Expression of staphylococcal protein A interfered with IgG mediated inhibition of bacterial binding to the catheter surface. Protein A altered S. aureus adherence to silastic catheters in the presence of immunoglobulin, but not in the presence of serum or albumin.
Weak ferroelectricity in antiferroelectric lead zirconate.

Sawyer-Tower polarization (P-E) measurements have revealed dielectric hysteresis loops in antiferroelectric lead zirconate (PZ), suggestive of weak ferroelectric tendencies. Both polarization saturation and reemergence were observed which were on the order of 0.1 and 0.05 \ensuremath{\mu}C/${\mathrm{cm}}^{2}$, respectively. Laser interferometry investigations, then, revealed a strain of approximately 2\ifmmode\times\else\texttimes\fi{}${10}^{\mathrm{\ensuremath{-}}7}$ under a field strength of 15 kV/cm. The strain curve has a butterfly shape indicating a contribution from the piezoelectric effect. These results suggest that antiferroelectric PZ may possess a small reversible spontaneous polarization along the c direction, which is consistent with previous structural studies. The weak ferroelectricity is found to disappear in lanthanum-modified lead zirconate, excluding the possibility of defect-induced ferroelectricity in PZ. A competition between zone center (which leads to ferroelectricity) and zone boundary (which leads to antiferroelectricity) transverse phonon modes is discussed with respect to the observed weak ferroelectricity.
Preliminary toxicity profile of arotinoids SMR-2 and SMR-6 in male B6D2F1 mice.

Abstract Arotinoids, which are analogs of retinoic acid (RA) and retinol (RO) with the carbon skeleton in a rigid conformation, have more favorable therapeutic indices relative to all-trans-RA and all-trans-RO. The purpose of this investigation was to obtain preliminary in vivo toxicity data on SMR-2 (analog of RO) and SMR-6 (analog of RA), arotinoids with promising activity (ED50's of 20 × 10−11 and 5 × 10−11 m , respectively; ED50 of RA = 1 × 10−11 m ) for reversal of keratinization in tracheal organ culture. A preliminary toxicity study was conducted in male B6D2F1 mice with gavage of retinoids in corn oil (0.01, 0.05, and 0.1 mg/kg/day of SMR-2 or SMR-6; 1, 5, and 10 mg/kg/day of RA as reference control). Due to lack of toxicity, each dose level for SMR-2 and SMR-6 was increased by 4-fold on Day 29 of dosing. The study was terminated on Day 57. Hypervitaminosis A (weight loss, alopecia, skin scaling, and bone thinning) was induced in the mid- and high-dose SMR groups; weight-gain depression was predominant in the high-dose RA group. The SMR compounds were approximately 100-fold more toxic, based on weight loss, than RA. In the SMR dose groups with hypervitaminosis A, white blood cell counts were elevated 2- to 4-fold; and there were microscopic lesions in skin, testes, epididymis, bone, thymus, bone marrow, peripheral lymph nodes, spleen, stomach, adrenal, and pituitary. The leukocytosis was attributed to leukopoiesis in spleen and bone marrow, which may be due to either a direct effect and/or a secondary response to a subacute inflammatory reaction in skin. Only peripheral lymph node hyperplasia was observed in SMR-2 and RA low-dose groups. Enlarged thymus, lymph node hyperplasia, leukopoiesis in spleen and bone marrow, elevated alkaline phosphatase with bone hypertrophy, and testicular degeneration were observed in the mid-dose RA group. The results indicate that immune stimulation may be a primary early response to retinoids and that skin, leukopoietic tissues, reproductive organs, stomach, and bone are primary targets for retinoid toxicity.
Depletion and replacement of protein metal ligands

Recently, site-directed mutagenesis has been applied to protein-derived metal ligands in a way that permits the replacement in trans of protein ligands. The chemical diversity of ligands available using this method far exceeds that attainable using standard mutagenesis. Non-conservative ligand replacement can yield novel metalloproteins with altered ligand-binding, enzymatic activities, and spectroscopic properties. Conservative ligand substitution, or 'ligand detachment', allows the structural and functional effects of the covalent linkage between the ligand and the protein to be evaluated; this linkage is often proposed to play a critical role in modulating the structure and reactivity of the metal center. Furthermore, this method can be exploited to study the details of molecular recognition at the structural, thermodynamic, and dynamic levels.
Metabolic balance studies in primary renal tubular acidosis: Effects of acidosis on external calcium and phosphorus balances

The relationship between acidosis and calcium metabolism was investigated in a 4-year-old child with primary renal tubular acidosis uncomplicated by either skeletal changes or renal insufficiency. The results of metabolic balance studies obtained from an initial period of complete correction of the acidosis through the development of acidosis by cessation of alkali therapy and during the subsequent correction of the acidosis indicate that metabolic acidosis is associated with a negative calcium balance. An altered intestinal transport of calcium was found to be the major factor responsible for the negative calcium balance. Complete correction of the acidosis resulted in restoration of a positive calcium balance.
Pathogenesis of Cervical Discovertebral Destruction in Rheumatoid Arthritis

A review of 20 cases of rheumatoid arthritis strongly supported the concept that the cervico-disco-vertebral destruction seen radiologically is a consequence of cervical instability caused by apophyseal arthritis and ligamentous laxity. It is postulated that such instability results in chronic trauma to the discovertebral joints leading to destruction of the disc cartilage and vertebral endplates. "Rheumatoid inflammation" of the disc has previously been described, but it is uncertain that such inflammation in the disc is the primary cause of these destructive lesions.
Web, education, and computational physics; good, bad, and ugly

A critical overview of the use of the World Wide Web for education in general and computational physics education in particular is given. Some strengths and weaknesses in teaching physics on the Web are indicated, with samples taken from the author's research group. The Web is shown to be a natural for CP education. It is argued that the Web is useful elsewhere when the focus is kept on pedagogy and usability before technology, and when there is some way of imposing structural coherence, such as provided by a printed text or a course. It is concluded that the best use of the Web is probably when it provides elements that would be difficult or impossible to obtain otherwise, and when it is intermixed with a human element.
The interaction of the vitamin D receptor with nuclear receptor corepressors and coactivators

The vitamin D receptor (VDR), thyroid hormone receptor (TR), and retinoic acid receptor (RAR) are ligand-dependent transcription factors that function via the formation of heterodimeric complexes with retinoid X receptor (RXR). Although TR and RAR are known to act as transcriptional repressors in the absence of cognate ligands, it is not clear whether VDR exhibits this property. Recently, transcriptional repression (basal silencing) by TR and RAR was shown to be mediated by nuclear receptor corepressors (CoRs), such as NCoR and SMRT. In this report, we examined the silencing ability of VDR and its interaction with NCoR and SMRT using mammalian two-hybrid assays. The Gal4-VDR fusion protein silenced the basal expression of a reporter that contains Gal4 binding sites, but the degree of silencing activity was weaker than that of Gal4-TR. In mammalian two-hybrid assays, the interaction of VP16-SMRT or VP16-NCoR was also stronger with Gal4-TR than with Gal4-VDR. Similar results were obtained when the assay was performed using the opposite configuration. Gal4-SMRT or Gal4-NCoR interacted better with VP16-TR than with VP16-VDR. These interactions were disrupted by the addition of cognate ligands. In contrast, VP16-VDR interacted better than VP16-TR when studied with a coactivator, Gal4-SRC1, or with the heterodimeric partner, Gal4-RXR. Consistent with these findings, relatively weak transcriptional silencing by the native VDR was observed using the osteopontin VDRE. Thus, in comparison to TR, VDR exhibits relatively weak ligand-independent transcriptional silencing, but it possesses strong dimerization with RXR and ligand-induced binding to transcriptional coactivators.
Photon pair production with soft gluon resummation in hadronic interactions

The production rate and kinematic distributions of isolated photon pairs produced in hadron interactions are studied. The effects of the initial-state multiple soft-gluon emission to the scattering subprocesses $q\overline{q},qg,$ and $g\stackrel{\ensuremath{\rightarrow}}{g}\ensuremath{\gamma}\ensuremath{\gamma}X$ are resummed with the Collins-Soper-Sterman soft gluon resummation formalism. The effects of fragmentation photons from $q\stackrel{\ensuremath{\rightarrow}}{g}\ensuremath{\gamma}q,$ followed by $\stackrel{\ensuremath{\rightarrow}}{q}\ensuremath{\gamma}X,$ are also studied. The results are compared with data from the Fermilab Tevatron collider. A prediction of the production rate and kinematic distributions of the diphoton pair in proton-nucleon reactions is also presented.
Stellar encounters as the origin of distant Solar System objects in highly eccentric orbits

The Kuiper belt1 extends from the orbit of Neptune at 30 au to an abrupt outer edge about 50 au from the Sun2. Beyond the edge is a sparse population of objects with large orbital eccentricities3,4. Neptune shapes the dynamics of most Kuiper belt objects, but the recently discovered planet 2003 VB12 (Sedna5) has an eccentric orbit with a perihelion distance of 70 au, far beyond Neptune's gravitational influence6,7,8. Although influences from passing stars could have created the Kuiper belt's outer edge and could have scattered objects into large, eccentric orbits9,10, no model currently explains the properties of Sedna. Here we show that a passing star probably scattered Sedna from the Kuiper belt into its observed orbit. The likelihood that a planet at 60–80 au can be scattered into Sedna's orbit is about 50 per cent; this estimate depends critically on the geometry of the fly-by. Even more interesting is the ∼10 per cent chance that Sedna was captured from the outer disk of the passing star. Most captures have very high inclination orbits; detection of such objects would confirm the presence of extrasolar planets in our own Solar System.
Parietal and Septal Atrioplasty for Total Correction of Anomalous Pulmonary Venous Connection with Superior Vena Cava

Abstract An operative procedure is described for correction of anomalous drainage of the right pulmonary veins into the superior vena cava. The procedure is technically simple and has the advantage of providing ample drainage of the pulmonary veins and superior vena cava without resorting to the use of prosthetic materials. Four case reports are presented.
Tebufenozide disrupts ovarian development and function in silkmoths

Abstract Adult development and production of up to 400 eggs within the pupal case of female silkmoths are both dependent on 20-hydroxyecdysone (20E), the steroid hormone of insects. When adult development was initiated with tebufenozide, the non-steroidal ecdysteroid agonist, instead of 20E, full development of all epidermal tissues like the wing was witnessed, but ovarian growth and egg formation was minimal. Administration of tebufenozide to female pharate adults caused disruption of the follicular epithelium, produced nurse cell damage, and inhibited oogenesis. Reduced ability to synthesize RNA and protein accompanied these tebufenozide induced morphological disturbances of the follicles. In vivo accumulation of vitellogenin (Vg) from the hemolymph was reduced in tebufenozide treated female ovaries as well as their ability to accumulate Vg in vitro. Determination of protein staining intensity and antibody reactivity of Vg pointed out that hemolymph Vg level remained fairly constant all through adult development whether induced by 20E or tebufenozide. Measurement of hemolymph volumes and hemolymph Vg levels of control and experimental animals allowed us to conclude that egg development involves the uptake of all the hemolymph proteins and not Vg alone. The loss of hemolymph that accompanies egg maturation was considerably reduced in tebufenozide initiated female pharate adults. 20E could not overcome ovarian growth inhibitory effects of tebufenozide. Dual mechanisms, one involving ecdysteroid antagonist action at the beginning of development, and the other unrelated to that function during heightened egg formation, are needed explain the biphasic inhibitory actions of tebufenozide on silkmoth ovaries.
The effect of previous exposure to amphetamine on drug-induced locomotion and self-administration of a low dose of the drug.

Rationale and objectives: In order to assess directly the relationship between locomotor activity and drug self-administration, the present experiment simultaneously measured these two behaviors in rats with different histories of pre-exposure to amphetamine either following or in the absence of priming injections of the drug. Methods: Different groups of rats were exposed to ten daily injections of either saline (1.0 ml/kg, i.p.) or amphetamine (1.5 mg/kg, i.p.) and, in each of 13 daily sessions starting 10 days later, were given the opportunity to lever press for a low dose of amphetamine (10 µg/kg per i.v. infusion) in a two-lever (active versus inactive) continuous reinforcement task. Animals were administered a priming injection of amphetamine (1.0 mg/kg, i.p.) immediately before testing on the first 8 days, a saline injection (1.0 ml/kg, i.p.) on the next 3 days and amphetamine on the final 2 days of testing. Results: Consistent with previous reports, prior exposure to amphetamine led to an enhanced locomotor response to the priming injection of amphetamine on the first day of testing. Little pressing for drug was observed on this day. Following priming injections on the subsequent test days, evidence for enhanced locomotion by amphetamine-pre-exposed rats diminished and both groups showed comparable and progressive increases in active versus inactive lever pressing. When priming injections were not made, however, only animals previously exposed to amphetamine maintained lever pressing for the drug. Under these conditions, these animals emitted more active lever presses and time-out responses and exhibited higher levels of locomotor activation in proximity to the active drug administering lever than did saline-pre-exposed rats. Conclusions: These results are consistent with the view that previous exposure to amphetamine produces a long-lasting enhancement in the behavioral activation animals will direct toward stimuli associated with the drug. This enhancement was displayed initially as a sensitized locomotor response to amphetamine on the first day of testing and was subsequently observed on those test days when no priming injections were given when animals continued to self-administer a low dose of amphetamine under a simple schedule of reinforcement. The implications of these findings for our understanding of the excessive expression of drug-directed behaviors are discussed.
CLINICAL AND HEMATOLOGICAL PHENOTYPE IN 9 FAMILIES WITH THE RARE β-GENE C>G MUTATION AT nt POSITION 6 3′ TO THE TERMINATION CODON. 119

CLINICAL AND HEMATOLOGICAL PHENOTYPE IN 9 FAMILIES WITH THE RARE β-GENE C>G MUTATION AT nt POSITION 6 3′ TO THE TERMINATION CODON. 119
Relationship between coping and depression in heart transplant candidates and their spouses.

Context—Survival rates for heart transplantation are encouraging, but the pretransplant period can be extremely stressful for patients and their spouses. Although a relationship between patients' depression levels and the coping strategies employed by their spouses has been demonstrated, this association has not been examined in heart transplant candidates and their spouses. Depression in this group of patients is important because heart transplant patients with preoperative depression have been found to have a higher mortality rate after transplantation.Objective—To determine if a relationship exists between spousal coping strategies and heart transplant candidates' depression.Methods—A descriptive, exploratory pilot study.Participants—Twenty-two individuals with end-stage heart disease who were undergoing an inpatient evaluation for heart transplantation, plus their spouses.Design—Heart transplant candidates were assessed via the Structured Interview Guide for the Hamilton Depression Scale. Spouses comp...
In suspected PE with Wells score > 4 or positive D-dimer, multiorgan ultrasonography had 90% sensitivity for PE

Source Citation Nazerian P, Vanni S, Volpicelli G, et al. Accuracy of point-of-care multiorgan ultrasonography for the diagnosis of pulmonary embolism. Chest. 2014;145:950-7. 24092475
Biochemical paths in humans and cells: Frontiers of AMS bioanalysis

Abstract The publication rate of 3 H and 14 C use in biomedical research decreased by a factor of three since 1990 when the first applications of AMS in biomedicine were published. Against this decrease, the high sensitivity of AMS for these isotopes in small isolated samples has made significant contributions. New smaller spectrometers and increased commercial availability of AMS have solved some of the issues surrounding availability and cost, but improved quantitation in non-isotopic methods now compete with some early uses of AMS. We review the strength of AMS for quantifying rare biochemical events and chemical passages through individual people or cells and consider these as the frontiers of quantitation leading to profitable science unavailable to other techniques.
Alliance Institutionalization and Alliance Performance

Military alliances are formed with varying degrees of institutionalization. While some alliances involve little initial investment or joint planning, others involve significant peacetime costs in establishing formal structures and engaging in military coordination. Several scholars have addressed the reasons states are willing to pay these governance costs in establishing cooperation—through controlling the risks of opportunism and coordinating policy more extensively, state leaders may be able to achieve higher benefits from cooperation. What has received less systematic empirical attention, however, is the comparative performance of highly institutionalized alliances. Are alliances that represent “deeper” cooperation more reliable than their less institutionalized counterparts? The newly expanded Alliance Treaty Obligations and Provisions (ATOP) dataset includes detailed information about the institutionalization of alliances formed between 1815 and 1989. Using these data, we evaluate the effects of ins...
Understanding fragile X syndrome

Abstract Fragile X syndrome (FXS), the most common form of inherited mental retardation, results from a mutation that silences transcription of the F ragile X Mental R etardation gene ( FMRI ), and translation of the FMRI protein ( FMRP ). Individuals with FXS have a highly variable level of cognitive disability, typical physical features such as large ears and a long face and behavioural dysfunction including hyperactivity, anxiety, perseveration, tactile defensiveness and autistic-like behaviour. Common medical problems include gastro-oesophageal reflux, otitis media and sinusitis, orthopaedic problems, hypotonia, mitral valve prolapse, seizures and sleep disorders. Diagnosis of FXS by DNA analysis is important to provide targeted treatment for the patient and appropriate genetic counselling for the family. Supportive strategies to maximize functioning include aggressive management of medical problems, educational programming tailored specifically for the FXS profile and medications targeting problematic behaviours. Insights into the functions of FMRP may lead to new therapies to improve cognitive functioning.
Multifactor dimensionality reduction-phenomics: a novel method to capture genetic heterogeneity with use of phenotypic variables.

Complex human diseases do not have a clear inheritance pattern, and it is expected that risk involves multiple genes with modest effects acting independently or interacting. Major challenges for the identification of genetic effects are genetic heterogeneity and difficulty in analyzing high-order interactions. To address these challenges, we present MDR-Phenomics, a novel approach based on the multifactor dimensionality reduction (MDR) method, to detect genetic effects in pedigree data by integration of phenotypic covariates (PCs) that may reflect genetic heterogeneity. The P value of the test is calculated using a permutation test adjusted for multiple tests. To validate MDR-Phenomics, we compared it with two MDR-based methods: (1) traditional MDR pedigree disequilibrium test (PDT) without consideration of PCs (MDR-PDT) and (2) stratified phenotype (SP) analysis based on PCs, with use of MDR-PDT with a Bonferroni adjustment (SP-MDR). Using computer simulations, we examined the statistical power and type I error of the different approaches under several genetic models and sampling scenarios. We conclude that MDR-Phenomics is more powerful than MDR-PDT and SP-MDR when there is genetic heterogeneity, and the statistical power is affected by sample size and the number of PC levels. We further compared MDR-Phenomics with conditional logistic regression (CLR) for testing interactions across single or multiple loci with consideration of PC. The results show that CLR with PC has only slightly smaller power than does MDR-Phenomics for single-locus analysis but has considerably smaller power for multiple loci. Finally, by applying MDR-Phenomics to autism, a complex disease in which multiple genes are believed to confer risk, we attempted to identify multiple gene effects in two candidate genes of interest—the serotonin transporter gene (SLC6A4) and the integrin beta 3 gene (ITGB3) on chromosome 17. Analyzing four markers in SLC6A4 and four markers in ITGB3 in 117 white family triads with autism and using sex of the proband as a PC, we found significant interaction between two markers—rs1042173 in SLC6A4 and rs3809865 in ITGB3.