cssi/SciSciGPT-SciSciNet huggingface dataset:
Association of novel polymorphisms with the expression of SPARC in normal fibroblasts and with susceptibility to scleroderma

Objective Fibroblasts from patients with systemic sclerosis (SSc) have an activated phenotype characterized by increased synthesis of extracellular matrix (ECM) components. SPARC (secreted protein, acidic and rich in cysteine) regulates the deposition or assembly of ECM components. The aim of this study was to investigate the role of SPARC in SSc susceptibility by functional and genetic association studies. Methods Complementary DNA (cDNA) microarrays were used to obtain gene expression data on cultured dermal fibroblasts from SSc patients. SPARC protein levels were assessed by Western blotting. Five polymorphic microsatellite markers within 5 cM of the SPARC gene (chromosome 5q31-32) were genotyped in Choctaw Indians, a population previously shown to have a high prevalence of SSc. Discovery of single-nucleotide polymorphisms (SNPs) was accomplished by sequencing the SPARC cDNA. These SNPs were then genotyped in a multi-ethnic cohort of SSc patients to determine potential associations with disease susceptibility in a broader population of SSc patients, as well as with various clinical and immunologic features of SSc. The functional relevance of these SNPs with regard to transcript stability of SPARC was also assessed. Results Microarrays demonstrated increased expression of SPARC, along with other ECM genes, in SSc patients compared with normal controls. SSc fibroblasts also had increased SPARC protein levels. Three of 5 microsatellite markers near SPARC showed significant associations with SSc in the Choctaw SSc patients. Sequencing of SPARC cDNA revealed 3 novel SNPs in the 3′-untranslated region at +998 (CG), +1551 (CG), and +1922 (TG). Homozygosity for the C allele at SNP +998 was significantly increased in SSc patients across ethnic lines. SPARC SNPs +1551 and +1922 demonstrated correlations with Raynaud's phenomenon and pulmonary fibrosis, respectively. Functional studies of SPARC SNP +998 in normal fibroblast cultures suggested a correlation between the SNP +998 C allele polymorphism and an increased messenger RNA half-life. Conclusion This study is the first to show that polymorphisms of the SPARC gene are associated with susceptibility to, and clinical manifestations of, SSc and that they may also be functionally important in influencing SPARC expression in skin fibroblasts.
Revisionism Triumphant: Hanoi's Diplomatic Strategy in the Nixon Era

After the Tet Offensive of early 1968, Hanoi agreed to hold talks with U.S. representatives in Paris. The North Vietnamese, however, used the resulting talks with the Johnson administration not to negotiate in any traditional sense but to probe the intentions of Washington and to manipulate domestic and world opinion. Hanoi continued this charade for approximately a year, until domestic and international circumstances forced a meaningful reassessment of its position on a negotiated settlement of the war with the United States. This article explores that reassessment, as well as the evolution of North Vietnam's diplomatic strategy thereafter. Specifically, it considers the factors that conditioned the thinking and policies of Vietnamese Communist leaders, including the balance of forces below the seventeenth parallel and the behavior of close allies in Beijing and Moscow vis-a-vis the United States. The article proposes that military and economic setbacks in the South and in the North combined with recogni...
Technical news feature

Soybeans from different maturation stages were tested for their chemical composition and storage stability. Maturation was arrested at specified times by spraying paraquat on the plant. The same level of trypsin inhibitor activity was found regardless of maturation. However, the lipoxygenase activity and phytate content were significantly lower in immature beans. Crude oil and protein contents were similar, regardless of maturation. The crude oils from immature samples were greener in color and higher in free fatty acid content than those from mature ones. Both yield of isolated soy protein and ratio of 7S to 11S protein in immature soybeans were lower than that from mature soybeans. During storage, lipoxygenase activity decreased independently of maturation but free fatty acid content in the crude oil increased at a faster rate in immature beans than that from mature ones.
Maximal species richness in Conus: diversity, diet and habitat on reefs of northeast Papua New Guinea

The gastropod genus Conus is shown to be among many marine taxa that attain maximal known diversity along the northeast coast of Papua New Guinea. Thirty-six species co-occurred on the reef platform fringing Laing Island in Hansa Bay, 33% more than previously documented on any single reef. Near Madang, 32 species occurred on four small reefs. Maximal density at both sites was 3/m2, with overall density 0.1–0.2/m2. Species richness, diversity, and general patterns of microhabitat use were similar at both, but composition differed markedly. Only 23 species were found at both sites, and proportional similarity was 44%. The most common species at each site were uncommon at the other. The diets of 34 species were determined; 26, including the most abundant, preyed exclusively on polychaetes. As on other Indo-Pacific reefs, species partitioned prey types more finely than substrate types. Among vermivores, a different polychaete dominated the diet of each predator. Other species specialized on an enteropneust, other gastropods, and fishes. Most prey were herbivores or deposit feeders, indicating that the major trophic role of Conus species in the reef community is as primary carnivores. The results suggest that species are not more specialized than where fewer congeners co-occur, but rather overlap somewhat more in resource use.
Research in nonverbal communication

(1971). Research in nonverbal communication. Theory Into Practice: Vol. 10, The Challenge of Nonverbal Awareness, pp. 250-258.
Fragmentation study of simvastatin and lovastatin using electrospray ionization tandem mass spectrometry

The fragmentation mechanism of simvastatin and lovastatin was investigated using both triple quadrupole and ion trap mass spectrometers. The elimination of the ester side-chain followed by dehydration and dissociation of the lactone moiety were observed as the main fragmentation pathways for both compounds. Another major fragmentation process was a CC double-bond facilitated rearrangement. Our tandem mass spectrometric (MS/MS) data suggested that the β-hydroxy group was involved in the fragmentation by interacting with the carboxyl group generated from the ring opening of the lactone. As a result, a facile neutral loss of 60 Da (CH3COOH or a combination of CH2CO and H2O) was detected. MS/MS studies of the structural analogs also provided evidence that the dehydration of the β-hydroxy lactone generated preferentially the β,γ-unsaturated lactones. Copyright © 2001 John Wiley & Sons, Ltd.
The manipulation of immunity. Conference on from allergy to cancer: new perspectives for therapeutic vaccination.

The 89th Boehringer Ingelheim Fonds International Titisee Conference—‘From Allergy to Cancer: New Perspectives for Therapeutic Vaccination’—took place between 17 and 21 March 2004 and was organized by R. Valenta and T. Brocker. The meeting brought together a diverse spectrum of scientists concerned with understanding the function of individual immune system components and exploiting this basic knowledge to manipulate the immune response. ![][1] The immune system has been evolutionarily selected such that it can execute wanted immune reactions and prevent unwanted immunity. There has been steady progress in understanding the essential role of the various mechanisms that result in immunity—or the lack thereof—and this knowledge is beginning to bear fruit as shown by the successful manipulation of immunity when natural processes fail. One key component of the immune system are the lymphocytes, each of which is equipped with a unique antigen‐binding receptor that is carefully selected in order to match the needs of the individual organism. Developing T lymphocytes are screened for the specificity of their randomly generated receptors through processes termed positive and negative selection in the thymus (hence the name T lymphocytes; von Boehmer et al , 2003). This not only eliminates (by inducing apoptotic cell death) cells with receptors that are specific for self‐antigens, but also positively selects (by avoiding premature death) cells that are able to detect pieces of foreign proteins when presented by the individual's own major histocompatibility (MHC)‐encoded molecules. Class II MHC proteins present peptides from proteins that are endocytosed (such as bacterial proteins), whereas class I MHC molecules present peptides from proteins that are made inside the cell (such as viral proteins). There is also a process named cross‐presentation through which proteins from a variety of different cells can be taken up and presented by class II or class I MHC molecules of antigen presenting cells … [1]: /embed/graphic-1.gif
Effects of rock climbing on cliff plant communities at Joshua Tree National Park, California

We compared the plant communities on cliffs used for rock climbing with cliffs not used for climbing. Eighteen cliffs in Joshua Tree National Park, California (six each with no climbing, moderate climbing, and intensive climbing) were sampled for plant diversity and community structure. Plants were sampled on cliff faces and at the base of cliffs. The dominant taxa were Quercus cornelius-mulleri, Ericameria cuneata var. cuneata, and Bromus madritensis ssp. rubens. Plant species richness on cliff faces and at the base of cliffs was greater for cliffs with no evidence of climbing and lowest for cliffs with intensive use. Numbers of individual plants decreased with increased climbing use. Trees, shrubs, forbs, and cacti had greater relative abundances on cliffs without climbing than on cliffs with climbing. Plant cover on cliff faces decreased with increased climbing use. Adaptive management will be necessary to minimize the deleterious effects of rock climbing on plant communities associated with cliffs. Efectos de Alpinismo sobre las Comunidades de Plantas en Acantilados en el Parque Nacional Joshua Tree, California Comparamos las comunidades de plantas en acantilados usados para alpinismo contra acantilados no usados para esta actividad. Dieciocho acantilados del Parque Nacional Joshua Tree, California (seis con alpinismo, seis con alpinismo moderado y seis sin alpinismo) fueron muestreados para determinar la diversidad de plantas y la estructura de la comunidad. Las plantas fueron muestreadas en las caras y bases de los acantilados. Los taxones dominantes fueron Quercus cornelius-mulleri, Ericameria cuneata var. cuneata y Bromus madritensis ssp. rubens. La riqueza de especies en las caras y bases de los acantilados fue mayor en aquellos sin evidencia de alpinismo y menor para aquellos acantilados con uso intensivo. Los numeros individuales de plantas disminuyeron con un incremento en el uso para alpinismo. Arboles, arbustos, pastos y cactus tuvieron una abundancia relativa mayor en acantilados sin alpinismo que en aquellos con alpinismo. La cobertura de las plantas en las caras de los acantilados disminuyo con un incremento en el alpinismo. Sera necesario emplear un manejo adaptable para minimizar los efectos daninos del alpinismo en roca sobre comunidades de plantas asociadas con acantilados.
Open label study of long-term effectiveness of cisapride in patients with idiopathic gastroparesis

Cisapride induces acetylcholine release in cells of the myenteric plexus, thus promoting gastrointestinal motility. We studied the effects of cisapride on 11 patients with idiopathic gastroparesis. All had negative gastrointestinal endoscopy, normal glucose, and took no drugs capable of influencing motility. Most (9/11) were prior metoclopramide treatment failures. Patients' symptoms were scored (0-60) for pain, satiety, bloating, nausea, vomiting, and heartburn. All underwent a solid gastric emptying study using a Technetium-99-labeled egg meal and received placebo prior to cisapride. There were 10 females and one male with a mean (+/- SE) age of 37.8 +/- 2.6 years. Disease duration was 7.9 +/- 2.8 years. The dose of cisapride was 30-60 mg/day and the duration of therapy was 12.6 +/- 2.6 months (range 2.5-25 months). The symptom score improved on cisapride from 30.9 +/- 3.6 to 14.4 +/- 2.7 (P < 0.002 signed rank test). Emptying half-time improved from 113 +/- 4 min to 94 +/- 6 min, and 46.9 +/- 2.4% food remaining at 120 min decreased to 35.5 +/- 3.6% (both P < 0.05). Emptying half-time in normals was 68 +/- 5 min with 16.9 +/- 2.9% remaining at 120 min. Nine of 11 patients gained weight, with a mean increase of 6.7 +/- 1.6 lb (range 2-12 lb). We conclude that cisapride significantly reduces gastrointestinal symptoms and promotes weight gain in patients with idiopathic gastroparesis and is associated with improvement in solid gastric emptying. The drug is useful in patients who previously failed metoclopramide.
Optimized content caching and request capture in CNF networks

In order to meet the overwhelming demands of content retrieval for mobile end users, a novel architecture for the next-generation Internet called Cache-and-Forward (CNF) has been proposed to transport content as large packages in a hop by hop manner towards the destination, instead of transporting a stream of small packets along an established TCP/IP connection. In this paper, we investigate how CNF network architecture can be designed for efficient content retrieval for wireless mobile nodes. In particular, we look at Integrated Caching in which we assume each CNF router on the future Internet can cache contents that pass by and reply to content requests with its local copy. We name this content delivery method Cachingn-Capture(CC). We develop a mathematical model for CC to optimize the average content retrieval latency with limited storage on each CNF router. We propose Sequential Reassignment(SR) algorithm to solve the optimization problem. We compare the performance of the derived optimal solutions against our integrated caching and routing heuristics. The results show the Sequential Reassignment algorithm significantly reduces the average content retrieval latency by as high as 70%.
Rural development: A minor problem in the Netherlands?

In the Netherlands there are no large areas with typical rural charactersitics. Existing differences in culture and economic performance between more and less urbanized regions have gradually been reduced by economic development that was stimulated by regional policy. The main problem now is how the non-urban areas can fulfill the growing needs of urban residents and others concerning outdoor recreation, nature conservation, and landscape. The development of policies and instruments of physical planning and rural reconstruction in recent years is closely linked with the above problems. Copyright 1986 by Oxford University Press.
Properties of Starch Films and their Improvement

The tensile strengths and elongations of starch films prepared from various unmodified and modified starches were measured. These properties were improved by addition of urea and polyvinyl alcohol to the starch paste. The results obtained were as follows. 1 The heating temperature greatly affected the tensile strength and elongation of various unmodified starches. Potato starch gave the best film. 2 Introduction of hydroxyethyl groups into corn starch had unexpectedly little affect on the properties of the films. 3 A combination of hydroxyethylation and acid-modification slightly improved the properties of the films. 4 No film could be obtained after combinations of hydroxyethylation and hypochlorite-oxidation, pyrodextrinization or α-amylase-dextrinization. However, addition of urea to these modified starches resulted in good films. 5 On addition of urea the elongation of starch films increased and the pastes adhered uniformly to water repellent surfaces. 6 A film with the best properties was prepared from a mixture of 67% acid-modified hydroxyethyl starch, 13% urea and 20% polyvinyl alcohol.
Complex by Design: Investigating Pathways into Teaching in New York City Schools.

New York City represents a microcosm of the changes that are shaking the very foundations of teacher education in this country. In their efforts to find teachers for hard-to-staff schools by creating multiple pathways into teaching, districts from New York City to Los Angeles are in the midst of what amounts to a national experiment in how best to recruit, prepare, and retain teachers. This article provides an overview of a research project that examines features of these different pathways into teaching in New York City schools and the impact of these features on where teachers teach, how long they remain in the classroom, and student achievement in reading and math as measured by value-added analyses. The article provides both a conceptual framework for the study and a discussion of some of the methodological challenges involved in such research, including problems of selection bias, difficulties in documenting programmatic features, and challenges of estimating teacher effects on student achievement.
Quantum Molecular Dynamics Simulations of Low-Temperature High Energy Density Matter: Solid p-H2/Li and p-H2/B

The metastability of atomic impurities, Li and B, trapped in solid parahydrogen is studied by employing path integral molecular dynamics (PIMD) and centroid molecular dynamics (CMD) simulations at 4 K and zero external pressure. Starting from pure solid hydrogen consisting of 1440 particles, doped systems are prepared by substituting impurity atoms for hydrogen molecules at substitutional defect sites. For various concentrations, thermodynamic quantities are then calculated and the stability of the systems is monitored. For the case of lithium, systems containing 2.5 mol % dopants remain metastable with convergent thermodynamic quantities, but systems with 3.3 mol % or more dopants become unstable. For the case of boron, systems containing as high as 15 mol % dopants remain metastable on the time scale of the simulation, while systems with 25 mol % dopants do not. These results provide evidence of the transition from metastability to global instability and a rough estimate of the maximum doping density of...
Arthropod management in vineyards: pests, approaches and future directions

This book, covering insect and mite management in vineyards worldwide, fills a significant void in the literature on this subject. Grape entomologists from North America, Europe, South Africa, the ...
Hydroxyurea dermopathy: A unique lichenoid eruption complicating long-term therapy with hydroxyurea

Abstract Background: Hydroxyurea is usually a well tolerated antitumor agent. Objective: Our purpose was to describe a distinct clinical and histologic eruption in patients receiving long-term hydroxyurea therapy. Methods: The clinical, histologic, and immunopathologic features of six patients with hydroxyurea dermopathy are described. Results: Three women and three men were identified. The average age was 61 years. Hydroxyurea had been used for an average of 5 years. Lichenoid papules, telangiectasia, and poikilodermatous lesions on the dorsal hands and digits were the most common findings. Interface dermatitis, focal lichenoid reaction with epidermal atrophy, and Civatte bodies were the most common histologic findings. Endothelial swelling also was noted. Cytoid staining with multiple conjugates was the most common immunopathologic finding. Four patients showed significant improvement after discontinuation of hydroxyurea. Conclusion: A distinct cutaneous reaction to long-term administration of hydroxyurea has been characterized. Cessation of treatment is necessary for healing or improvement. We have designated this eruption hydroxyurea dermopathy. (J Am Acad Dermatol 1997;36:178-82.)
Crystal Structure of Human Plasma Platelet-activating Factor Acetylhydrolase STRUCTURAL IMPLICATION TO LIPOPROTEIN BINDING AND CATALYSIS

Human plasma platelet-activating factor (PAF) acetylhydrolase functions by reducing PAF levels as a general anti-inflammatory scavenger and is linked to anaphylactic shock, asthma, and allergic reactions. The enzyme has also been implicated in hydrolytic activities of other pro-inflammatory agents, such as sn-2 oxidatively fragmented phospholipids. This plasma enzyme is tightly bound to low and high density lipoprotein particles and is also referred to as lipoprotein-associated phospholipase A2. The crystal structure of this enzyme has been solved from x-ray diffraction data collected to a resolution of 1.5A. It has a classic lipase α/β-hydrolase fold, and it contains a catalytic triad of Ser273, His351, and Asp296. Two clusters of hydrophobic residues define the probable interface-binding region, and a prediction is given of how the enzyme is bound to lipoproteins. Additionally, an acidic patch of 10 carboxylate residues and a neighboring basic patch of three residues are suggested to play a role in high density lipoprotein/low density lipoprotein partitioning. A crystal structure is also presented of PAF acetylhydrolase reacted with the organophosphate compound paraoxon via its active site Ser273. The resulting diethyl phosphoryl complex was used to model the tetrahedral intermediate of the substrate PAF to the active site. The model of interface binding begins to explain the known specificity of lipoprotein-bound substrates and how the active site can be both close to the hydrophobic-hydrophilic interface and at the same time be accessible to the aqueous phase.
Perspective on the Psychology of Self

The present perspective on the psychology of self developed out of a search for an adequate conception of the person to round out an incompleteness in a model of friendship. After a review of five major points of disagreement among self theorists, a perspective is presented which distinguishes between the self as an identifiable entity and the specific attributes the individual regards as characteristic of that entity. Processes are proposed by which the person comes to develop a conception of himself as an identifiable entity, and the way in which his self-attributions, i.e., conceptions of what that entity is like, develop and change. A key motivational variable is the individual's concern with the well-being and worth of the entity identified as self. This key variable not only has important implications for the internal organization of self-attributes but also is manifest in four behavioral tendencies that provide a motivational link between the self and dyadic and person-group relations.
Effects of Polycyclic Aromatic Hydrocarbons in Northern Bobwhite Quail (Colinus virginianus)

Polycyclic aromatic hydrocarbons (PAH) are ubiquitous contaminants of aquatic and terrestrial ecosystems, and are known to induce biochemical alterations in exposed organisms. Aside from a variety of adverse physiological effects associated with exposure to petroleum products, oils, and oil sludges, little is known about the effects of individual PAH on birds. Acute toxicity of naphthalene, pyrene, and benz[a]anthracene (BAA) was examined in adult northern bobwhite quail (Colinus virginianus). Additionally, subacute (8 d) and subchronic (60 d) studies were conducted to assess alterations in metabolic enzyme activity. Neither naphthalene, nor pyrene, nor BAA exposure via oral gavage produced acute toxicity up to the limit dose of 2 g/kg body weight. In the subacute study, quail provided feed containing the highest concentration of BAA for 5 d had significantly increased renal ethoxyresorufin O‐deeththylase (EROD) activity compared to controls. Following a 3-d recovery period, significant increases between ...
Inverse relationship between GLUT-4 phosphorylation and its intrinsic activity

Abstract In this study, we examined the effect of phosphorylation on GLUT-4 function in isolated rat adipocytes. Adipocytes labeled with 32P for 2 h were incubated with parathyroid hormone (PTH) (20 ng/ml) for 60 min and then exposed to insulin (25 ng/ml) for an additional 30 min. 32P-GLUT-4 was immunoprecipitated from the plasma membrane and low density microsomal fractions, and its degree of phosphorylation was determined by autoradiography and densitometry. Results were expressed as 32P-GLUT-4 specific activity (phosphorylation/unit of protein). GLUT-4 intrinsic activity was measured using [14C]2-deoxyglucose uptake in plasma membrane vesicles. PTH significantly increased GLUT-4 phosphorylation and eliminated the insulin-stimulated dephosphorylation of GLUT-4. Western blotting revealed normal distribution of GLUT-4 before and after insulin stimulation in control and PTH-treated cells, suggesting that phosphorylation of GLUT-4 does not interfere with its recruitment to the plasma membrane. In contrast, intrinsic activity of phosphorylated GLUT-4 was significantly reduced (p < 0.01). Preincubation of adipocytes with calcium channel blocker (nitrendipine) and cyclic AMP antagonist (RpcAMP) restored GLUT-4 intrinsic activity in the PTH-treated cells. In several experiments, GLUT-4 was phosphorylated in vitro in plasma membrane vesicles isolated from normal adipocytes exposed to insulin. This in vitro phosphorylation reduced GLUT-4 intrinsic activity by approximately 35% (p < 0.01). We conclude that phosphorylation of GLUT-4 significantly impairs the ability of insulin to stimulate its intrinsic activity.
A Comparison of Pay-As-Bid and Market-Clearing Price Bidding Processes in Electric Utility Auctions

As the electric utility industry moves to Regional Transmission Organizations, there are more opportunities for merchant plants in selling wholesale energy to electric utilities. Two alternative bidding regimes are considered: (i) pay-as-bid and (ii) pay with market-clearing bid. With stochastic price-sensitive demand, we show that pay-as-bid has greater average price, but lower price variance than does market-clearing price. Copyright © 2013 John Wiley & Sons, Ltd.
Small-world characteristics of the Internet and multicast scaling

Recent work has shown that the physical connectivity of the Internet exhibits small-world behavior. Characterizing such behavior is important not only for generating realistic Internet topologies, but also for the proper evaluation of network algorithms and protocols. Along this line, this paper tries to answer how small-world behavior arises in the Internet topologies and how it impacts the performance of multicast techniques. First, we attribute small-world behavior to two possible causes: the variability of vertex degree and the preference of vertices to have local connections. We found that both factors contribute with different relative degrees to the small-world behavior of the AS-level and router-level Internet topologies. For the AS-level topology, we have observed that extremely high variability of vertex degree is sufficient to cause small-world behavior, but for the router-level topology, preference for local connectivity plays a more important role. Second, we propose simple models to generate more realistic small-world Internet topologies. Our models consider both causes of small-world behavior. Third, we demonstrate the significance of our work by studying the scaling behavior of IP multicast tree size. We show that if topology generators capture only the variability of vertex degree, they are likely to underestimate the efficacy of multicast techniques.
Forest sector carbon management, measurement and verification, and discussion of policy related to climate change

The objective of this review is to give ecologists, land managers and policy makers a better understanding of important issues related to forest sector carbon management, measurement and verification, as well as policy related to mitigation and the adaptation of forests to climate change. The focus is on carbon sequestration processes; appropriate measurements for international, regional and local scale assessment of net ecosystem carbon balance; and life cycle analysis, with special attention given to the concept of substitution of fossil fuels with bioenergy from forests. Given the slow dynamic of forest carbon, life cycle analysis needs to account for pre-existing forest conditions, since carbon neutrality (i.e., net ecosystem carbon balance of forests is zero) can take at least a century to achieve in many cases. The substitution of wood for more energy-intensive materials has probably been overestimated compared with cases in which additionality, permanence and saturation of wood building stores are ...
A Market Theory of Religion

Il est devenu frequent, en sociologie de la religion, de recourir a la notion de marche. Toutefois, et malgre les nombreuses recherches empiriques portant sur l'appartenance a une Eglise qui ont tente de verifier la carte des concepts lies a l'idee de marche religieux, peu de chercheurs ont entrepris de developper une theorie en mesure d'en definir le fonctionnement. On note, par consequent, dans la litterature sociologique, un manque d'analyses capables d'etablir s'il existe une reelle correspondance entre les phenomenes et s'il en existe d'analogues dans le domaine religieux. L'etude de ces phenomenes economiques devrait se fixer comme objectif de comprendre quelles en sont les implications pour la religion plutot que de discuter, meme de maniere critique, de ce qu'a apporte la recherche en sociologie de la religion a l'idee de marche.
Smoke-free parks and beaches: an interrupted time-series study of behavioural impact in New York City

Background In 2011, New York City (NYC) parks and beaches became smoke-free. There is currently little research evaluating the impact of such laws on smoking behaviour at the population level. Methods We used an interrupted time-series study design to analyse data from the New York State Adult Tobacco Survey to assess the law9s impact using the rest of New York State as a comparison. Trends in how frequently respondents noticed people smoking in parks and beaches were analysed between the third quarter of 2009 and the fourth quarter of 2012, comparing NYC to the rest of the state. Results The trend in the frequency of NYC residents noticing people smoking in local parks and beaches decreased significantly over the six quarters after the law took effect. There was no comparable decline among residents in the rest of the state. An increase in the number of respondents who never noticed people smoking in NYC contributed to this decline. Conclusions These results are consistent with previous studies and provide population-level evidence that suggest the law has reduced smoking in parks and on beaches.
Foreign Language Teacher Development: MLJ Perspectives—1916–1999

The preparation of U.S. foreign language (FL) teachers has been a frequently discussed topic during the past century. As the oldest, continuously published American journal devoted to FL learning and teaching, the MLJ provides an overview of the many issues pertinent to FL teacher education that the profession has grappled with. This historical review traces discussions and developments in teacher preparation and certification since the MLJ 's inception in 1916. In three sections, each covering a quarter century of the Journal 's publications, the article describes the most relevant discussions and events that have helped shape FL teacher education in the United States. Although many efforts —and doubtlessly many advances —have been made to assure a supply of qualified FL teachers for the nation 's schools, many of the problems discussed more than 80 years ago still remain unsolved. The author hopes that a critical look at the past will help the profession to focus on those proposals that are finding emerging consensus and to prioritize those needs and activities that help effect meaningful change in improving the qualifications of FL teachers.
A fully replication-competent adenovirus vector with enhanced oncolytic properties

We have studied the oncolytic efficacy of two adenovirus vectors named KD3 and INGN 007, which differ from each other only in that whereas KD3 has two small deletions in its e1a gene that restrict its replication to rapidly cycling cells, INGN 007 has wild-type e1a gene. Both vectors overexpress the adenovirus death protein (ADP). Both KD3 and INGN 007 effectively suppressed the growth of subcutaneous human A549 and Hep3B tumors in nude mice upon intratumoral injection, and contained the growth of subcutaneous LNCaP tumors after intravenous injection, making some tumors shrink or disappear. However, in a more demanding model, intravenous injections of neither KD3 nor wild-type Ad5 were effective against subcutaneous A549 tumors, whereas INGN 007 increased the mean survival time by 35%. INGN 007 was also effective in suppressing tumor growth in a challenging A549 orthotopic lung cancer model. INGN 007 was superior to dl1520 (ONYX-015) in repressing subcutaneous A549 tumors. Our results suggest that vectors such as INGN 007 might provide better antitumor efficacy in the clinic as well.
Wisdom before knowledge--appraisal of the scientific evidence used to develop guidelines for the diagnosis of arrhythmogenic right ventricular dysplasia

Background Guidelines are an important vehicle in the era of evidence-based medicine and diagnosis. They represent a culmination of expert opinions and the best available evidence. There can be a tendency for practitioners to view and apply guidelines as the absolute truth. However, it is important to remember that guidelines are only as robust as the strength of the studies that are used in their development. Arrhythmogenic right ventricular dysplasia (ARVD) is a relatively rare disease that primarily affects the right ventricle and can be potentially fatal if left untreated. Cardiac MRI (CMR) plays a supportive role in the diagnosis. A task force was established in 1994 and another convened in 2009, in order to develop guidelines for the diagnosis of ARVD. The aim of this exhibit is to critically appraise the studies that were used to classify the findings on CMR into major and minor criteria for the diagnosis of ARVD. The studies will be critiqued particularly for statistical biases and the potential for overdiagnosis.
Critical path analysis of concurrent Ada programs using colored Petri nets: rewrite rules

The authors use a colored Petri net model of a substantial subset of Ada to do critical path analysis. They are primarily interested in determining the circumstances under which a concurrent program will take the most time. This is done by finding the critical path. The authors associate with each transition a cost representing the time necessary to execute the corresponding instruction. They define the critical path as a generalization of the usual PERT notion. The critical path in a colored Petri net takes into account the special semantics of firing only enabled transitions. The authors do not modify the semantics to take into account time as in various models of Petri nets with time. They do critical path analysis by transforming the net to an equivalent net whose critical path takes the same amount of time. The Petri net is rewritten over and over again until the net is reduced to a single transition. >
Synthetic lethality: a framework for the development of wiser cancer therapeutics

The challenge in medical oncology has always been to identify compounds that will kill, or at least tame, cancer cells while leaving normal cells unscathed. Most chemotherapeutic agents in use today were selected primarily for their ability to kill rapidly dividing cancer cells grown in cell culture and in mice, with their selectivity determined empirically during subsequent animal and human testing. Unfortunately, most of the drugs developed in this way have relatively low therapeutic indices (low toxic dose relative to the therapeutic dose). Recent advances in genomics are leading to a more complete picture of the range of mutations, both driver and passenger, present in human cancers. Synthetic lethality provides a conceptual framework for using this information to arrive at drugs that will preferentially kill cancer cells relative to normal cells. It also provides a possible way to tackle 'undruggable' targets. Two genes are synthetically lethal if mutation of either gene alone is compatible with viability but simultaneous mutation of both genes leads to death. If one is a cancer-relevant gene, the task is to discover its synthetic lethal interactors, because targeting these would theoretically kill cancer cells mutant in the cancer-relevant gene while sparing cells with a normal copy of that gene. All cancer drugs in use today, including conventional cytotoxic agents and newer 'targeted' agents, target molecules that are present in both normal cells and cancer cells. Their therapeutic indices almost certainly relate to synthetic lethal interactions, even if those interactions are often poorly understood. Recent technical advances enable unbiased screens for synthetic lethal interactors to be undertaken in human cancer cells. These approaches will hopefully facilitate the discovery of safer, more efficacious anticancer drugs that exploit vulnerabilities that are unique to cancer cells by virtue of the mutations they have accrued during tumor progression.
Improvement of tuberous sclerosis complex (TSC) skin tumors during long-term treatment with oral sirolimus.

Background Oral mechanistic target of rapamycin inhibitors have been shown to reduce visceral tumor volume in patients with tuberous sclerosis complex (TSC). Objective We sought to evaluate the cutaneous response to oral sirolimus in patients with TSC and an indication for systemic treatment, including long-term effects. Methods A retrospective analysis of 14 adult patients with TSC prescribed sirolimus to treat lymphangioleiomyomatosis was performed. Serial photographs of angiofibromas, shagreen patches, and ungual fibromas taken before, during, and after the treatment period were blinded, then assessed using the Physician Global Assessment of Clinical Condition (PGA). Microscopic and molecular studies were performed on skin tumors harvested before and during treatment. Results Sirolimus significantly improved angiofibromas (median treatment duration 12 months; median PGA score 4.5 [range 1.5-5]; Wilcoxon signed rank test, P = .018) and shagreen patches (median treatment duration 10 months; median PGA score 4.5 [range 3.5-5]; Wilcoxon signed rank test, P = .039), whereas ungual fibromas improved in some patients (median treatment duration 6.5 months; median PGA score 4.66 [range 2.75-5]; Wilcoxon signed rank test, P = .109). Clinical, immunohistochemical, or molecular evidence of resistance was not observed (range 5-64 months of treatment). Limitations This was a retrospective analysis limited to adult women with lymphangioleiomyomatosis. Conclusion Oral sirolimus is an effective long-term therapy for TSC skin tumors, particularly angiofibromas, in patients for whom systemic treatment is indicated.
The Dynamics of Crowdfunding: Determinants of Success and Failure

Crowdfunding allows founders of for-profit, artistic, and cultural ventures to fund their efforts by drawing on relatively small contributions from a relatively large number of individuals using the internet, without standard financial intermediaries. Drawing on a dataset of over 48,500 projects with combined funding over $237M, this paper offers a description of the underlying dynamics of success and failure among crowdfunded ventures. It suggests that personal networks and underlying project quality are associated with the success of crowdfunding efforts, and that geography is related to both the type of projects proposed and successful fundraising. Finally, I find that the vast majority of founders seem to fulfill their obligations to funders, but that over 75% deliver products later than expected, with the degree of delay predicted by the level and amount of funding a project receives. These results offer insight into the emerging phenomenon of crowdfunding, and also shed light more generally on the ways that the actions of founders may affect their ability to receive entrepreneurial financing.
Simultaneous Repair of Bilateral Renal Artery Aneurysms: A Case Report

Abstract Renal artery aneurysms are rare and most are clinically silent until discovery. Indications for repair include aneurysm growth and difficult to control hypertension. This case report highlights a rare occurrence of bilateral renal artery aneurysms requiring surgical intervention. In order to avoid a reoperative laparotomy, we undertook a simultaneous repair of the aneurysms.
Identification of serum markers of glioblastoma multiforme patients using image-guided genomic and proteomic analysis

20008 Background: Biomarkers in serum has been demonstrated to play a critical role in caner diagnostics. Glioblastoma multiforme (GBM) is a primary brain tumor with poor prognosis and low survival...
"Keeping up the Good Fight": The Said and Unsaid in "Flores v. Arizona".

The authors' purpose in this article is to interrogate the mediated and political discourses that emerged alongside the Flores v. Arizona case. The authors endeavor to offer another voice, framewor...
Early body mass index and other anthropometric relationships between parents and children.

OBJECTIVE: To assess longitudinally the relationship between measures of adiposity in children over the first 8 y of life with that of their parents and to explore the role of parental adiposity in the development of childhood adiposity. DESIGN: Longitudinal study of measures of adiposity in children. SUBJECTS: A community sample from three health service systems including 114 children followed annually from infancy to age 8 and their 228 biological parents. METHODS: Measurements were assessed at baseline for parents (6 months post-partum for mothers) and at regular intervals for children beginning at age 2 months. Measurements included weight, height, triceps skinfold, subscapular skinfold, midarm circumference, waist and hip. RESULTS: The major findings were: (1) significant correlations between parental body mass index (BMI), both maternal and paternal, and their biological offspring first emerged at age 7; (2) children with two overweight parents had consistently elevated BMI compared to children with either no overweight parents or one overweight parent. These differences became significant beginning at age 7. CONCLUSIONS: This study supports the hypothesis that familial factors (biological and/or environmental) affecting the development of adiposity emerge at specific ages and are related to the adiposity of both parents.
Lignin peroxidase compound. III: formation, inactivation, and conversion to the native enzyme

Abstract At pH 3.0 in the absence of a reducing substrate and the presence of only 20 equivalents of H2O2, lignin peroxidase (LiP) is readily converted to LiP compound III (LiPIII) (Fe(III)O−2 - complex). LiPIII which is produced via the reaction of LiP compound II (LiPII) with H2O2 is not part of the peroxidase catalytic cycle, and is readily and irreversibly inactivated. Veratryl alcohol (VA), a Phanerochaete chrysosporium secondary metabolite, protects the enzyme from inactivation via two mechanisms. Acting as a substrate, VA reduces LiPII to regenerate the native enzyme. Secondly, the binding of VA to LiPIII rapidly displaces O.−2/HO.−2, thereby converting LiPIII directly to the native enzyme. VA is not consumed during this displacement reaction. These results help to explain the role of VA in stabilizing the enzyme in the presence of excess H2O2.
Unlocking the Black Box: A Multilevel Analysis of Preadolescent Children’s Coping

This random assignment experimental study examined the intersection of children's coping and physiologic stress reactivity and recovery patterns in a sample of preadolescent boys and girls. A sample of 82 fourth-grade and fifth-grade (Mage = 10.59 years old) child-parent dyads participated in the present study. Children participated in the Trier Social Stress Test and were randomly assigned to one of two post-Trier Social Stress Test experimental coping conditions-behavioral distraction or cognitive avoidance. Children's characteristic ways of coping were examined as moderators of the effect of experimental coping condition on cortisol reactivity and recovery patterns. Multilevel modeling analyses indicated that children's characteristic coping and experimental coping condition interacted to predict differential cortisol recovery patterns. Children who characteristically engaged in primary control engagement coping strategies were able to more quickly down-regulate salivary cortisol when primed to distract themselves than when primed to avoid, and vice versa. The opposite pattern was true for characteristic disengagement coping in the context of coping condition, suggesting that regulatory fit between children's characteristic ways of coping and cues from their coping environment may lead to more and less adaptive physiologic recovery profiles. This study provides some of the first evidence that coping "gets under the skin" and that children's characteristic ways of coping may constrain or enhance a child's ability to make use of environmental coping resources.
Theoretical Investigation of the Primary Event in Proteorhodopsin Activation

Retinal proteins are α-helical transmembrane proteins that have the potential for applications such as memory storage (bacteriorhodopsin) and optogenetics (channelrhodopsin). Proteorhodopsin (PR) is a recently discovered microbial retinal protein which acts as a proton pump, similar to bacteriorhodopsin. Initial activation of PR occurs when the covalently bound chromophore, retinal, absorbs a photon and undergoes an all-trans → 13-cis isomerization. Despite several similarities between bacteriorhodopsin and PR, the details of the activation process remain unclear. We investigated the photoisomerization of retinal in PR using a hybrid quantum mechanical (QM) and molecular mechanics (MM) approach. Two photoexcited states were identified. Both retinal structures have a 13-cis, 15-anti conformation. However, one does not involve a hydrogen bond between the Schiff base and a water molecule, while the other structure does, dependent on the rotational direction of the isomerization. The former is more stable than the latter by about 0.9 eV and the former also has a lower energy barrier of the photoisomerization by about 0.2 eV than the latter. Upon photoisomerization, PR reaches the former excited state, subsequently proceeding through a slow rearrangement to form the hydrogen bond between the Schiff base and water and generate the latter excited state. We believe the former structure to be indicative of the K state, with the latter structure more characteristic of an L-like state. This L-like state is spectroscopically silent and most likely extremely transient, due to the low energy barrier (0.1 eV) of the proton transfer from the Schiff base to the proton acceptor, D97. A detailed understanding of the initial events in the activation process is essential to utilizing PR as a light-driven component in potential technological applications.