cssi/SciSciGPT-SciSciNet huggingface dataset:
Pilot study of the antiplatelet effect of increased clopidogrel maintenance dosing and its relationship to CYP2C19 genotype in patients with high on-treatment reactivity

Objectives The objective of this study was to evaluate the antiplatelet effect of clopidogrel 150 mg/day in patients with high on-treatment reactivity (OTR) and to further assess this effect according to CYP2C19 genotype. Background High OTR is associated with ischemic events in clopidogrel-treated patients after percutaneous coronary intervention. Alternative dosing regimens might enhance platelet inhibition. Methods Patients with high OTR receiving a standard clopidogrel regimen were identified with the VerifyNow P2Y12 assay and administered clopidogrel 150 mg daily for 7 days, after which OTR was reassessed. Comprehensive CYP2C19 genotyping was performed with the BeadXpress platform (Illumina, San Diego, California) for the *2, *3, *4, *5, *6, *7, *8, and *17 variants. Results A total of 41 subjects were enrolled, 20 of whom were carriers of a CYP2C19 loss-of-function (LoF) allele. High-dose clopidogrel significantly reduced OTR from 285 ± 47 P2Y12 reaction units (PRU) to 220 ± 91 PRU (p Conclusions In patients with high OTR, clopidogrel 150 mg/day results in a significant reduction in platelet reactivity. Carriage of an LoF CYP2C19 polymorphism does not seem to have a major influence on dose effect. The observed lack of effect in patients with 2 copies of a CYP2C19 LoF allele must be confirmed by larger studies.
Relationship between life expectancy, endogenous antioxidants and products of oxygen free radical reactions in the housefly, Musca domestica.

Abstract The general objective of this study was to identify biochemical correlates of life expectancy in the adult male housefly. All houseflies lose flying ability prior to death, whereby, in an aging population, shorter-lived flies can be identified as flightless ‘crawlers’ from their longer-lived cohorts, the ‘fliers’; the average lifespan of crawlers is about one-third shorter than the fliers. Neither crawlers nor fliers exhibited any physical damage to their chemoreceptive tarsi, thereby ruling out starvation as a probable cause of death. Levels of antioxidant defenses (superoxide dismutase, catalase and glutathione) and products of oxygen free radical reactions (inorganic peroxides and thiobarbituric acid [TBA]-reactants) were compared between crawlers and fliers. The fliers showed higher superoxide dismutase and catalase activities and glutathione concentration than crawlers, whereas, the amount of inorganic peroxides (H 2 O 2 ) and TBA-reactants was higher in the crawlers than in fliers. Results of this study demonstrate, for the first time, that longer life expectancy of organisms belonging to the same cohort group is associated with relatively higher levels of antioxidants and lower concentrations of products of oxygen free radical reactions.
Host factor for coliphage Q beta RNA replication: presence in procaryotes and association with the 30S ribosomal subunit in Escherichia coli.

The Host Factor required for in vitro coliphage Qβ RNA replication, a heat-stable RNA binding protein present in uninfectedEscherichia coli, has been detected by both immunological and functional tests inAcinetobacter calcoaceticus, Klebsiella pneumoniae, Pseudomonas aeruginosa andPseudomonas putida. It was not detectable by these criteria inBacillus stearothermophilus, Bacillus subtilis, Caulobacter crescentus, Micrococcus lysodeikticus, Rhodopseudomonas capsulata orSaccharomyces cerevisiae. InEscherichia coli the Host Factor protein has been shown to be associated with ribosomes. It is demostrated here that this association is specific for the 30S ribosomal subunit.
Increased Pre- and Early-Adolescent Stress in Youth with a Family History of Substance Use Disorder and Early Substance Use Initiation

Individuals with a family history of substance use disorders (Family History Positive) are more likely to have early-onset substance use (i.e., prior to age 15), which may contribute to their higher rates of substance use disorders. One factor that may differentiate Family History Positive youth who engage in early-onset substance use from other Family History Positive youth is exposure to stressors. The aim of this study was to quantify how exposure to stressors from age 11–15 varies as a function of family history of substance use disorders and early-onset substance use. Self-reported stressors were prospectively compared in a sample of predominately (78.9 %) Hispanic youth that included 68 Family History Positive youth (50 % female) who initiated substance use by age 15 and demographically matched non-users with (n = 136; 52.9 % female) and without (n = 75; 54.7 % female) family histories of substance use disorders. Stressors were assessed at 6-month intervals for up to 4 years. Both the severity of stressors and the degree to which stressors were caused by an individual’s own behavior were evaluated. All three groups differed from one another in overall exposure to stressors and rates of increase in stressors over time, with Family History Positive youth who engaged in early-onset substance use reporting the greatest exposure to stressors. Group differences were more pronounced for stressors caused by the participants’ behavior. Family History Positive users had higher cumulative severity of stressors of this type, both overall and across time. These results indicate greater exposure to stressors among Family History Positive youth with early-onset substance use, and suggest that higher rates of behavior-dependent stressors may be particularly related to early-onset use.
Prognosis of medulloblastoma in infants.

The prognosis of medulloblastoma in children less than 3 years old is usually considered to be rather poor. However, recent experiences with this type of tumour seem to indicate that survival in this specific subgroup of patients can be longer than expected. Nineteen infants with posterior fossa tumours treated by the authors in the period 1983–1994, all of them with symptoms presenting during the 1st year of life and all operated on before the end of the 2nd year of life, have been retrospectively analysed. Total tumour removal was achieved in 14 cases, subtotal in 1 and partial in 3. One subject underwent only a biopsy of the tumour. In 14 patients a CSF shunt was inserted. Chemotherapy was administered to 18 out of the 19 patients in the series. At the time of the study, 11 children had died (57.9%) and 8 were alive (42.1%; mean survival 86.5 months). One patient died of complications secondary to the surgical treatment. Three patients died because of local recurrence of the tumour after apparent total excision, death supervening 5, 12 and 18 months after the surgical treatment. A further 2 patients in whom total tumour removal had been performed died 3 and 17 months after surgery of local recurrence of the disease associated with regional metastases. Progression of the residual tumour, accompanied by metastatic dissemination in 3 cases, accounted for death in the other 5 patients who did not survive. Brain stem infiltration appeared to be the most significant adverse prognostic factor. All 8 long-term survivors had their tumour totally excised. Five of them underwent radiotherapy when at least 2 years old. On the basis of the results, the authors conclude that the current prognosis of infants with medulloblastoma is not necessarily any worse than that of older children with the same disease and that chemotherapy can be particularly useful in this subgroup of patients, as shown by 3 long-term survivals obtained in children treated with this type of therapy only.
Potassic and sodic metasomatism in the Southern Province of the Canadian Shield: Evidence from the Paleoproterozoic Serpent Formation, Huronian Supergroup, Canada

Abstract Major element geochemistry, petrographic observations, and microprobe analyses of the Paleoproterozoic Serpent Formation, Huronian Supergroup, Canada, suggest that these strata experienced both potassium and sodium metasomatism. Major element data, plotted in Al2O3CaO∗ + Na2OK2O compositional space, form an array nearly identical to data from sub-Huronian paleosols reported elsewhere, suggesting that Serpent fluvial systems captured materials from entire weathering profiles. Potassium metasomatism was concentrated in shales, and represents the illitization of kaolinite, which is a residual product of plagioclase weathering. Sodium metasomatism principally affected silt- and sand-sized particles. Microprobe analyses of plagioclase grains indicate that they are nearly pure albite (>Ab96). Corresponding whole-rock major element data plot in bulk albite space on an (Al2O3K2O)CaO∗Na2O ternary diagram, whereas basement rocks plot in bulk andesine and oligoclase space. End member compositions and the absence of luminescence when bombarded with an electron beam indicate that the albites are of secondary origin. Extremely pure albite cements (>Ab99) commonly fringe detrital grains. There has been little replacement of detrital K-feldspars, despite the complete albitization of plagioclase grains. The timing of metasomatism, at least the last stage, is constrained to the period between ∼ 1700 and 1750 Ma (based on geochronologic data reported elsewhere), when the Southern Province of the Canadian Shield experienced considerable felsic plutonism, possibly related to arc collision. This plutonism may have resulted in the heating of deep basinal brines. Stresses associated with orogenic build-up, or gravity driven groundwater circulation working in concert with the plutonism, expelled these brines through the Serpent Formation (and the entire Huronian Supergroup), thoroughly metasomatizing the region. Such processes associated with collisional tectonics are akin to the development of Mississippi Valley-type PbZn mineralization in the mid-continent of the United States.
The association of female circumcision with HIV status and sexual behavior in Mali: a multilevel analysis.

OBJECTIVE: In the regions of Africa where female circumcision (FC) is practiced it is often regarded as a protective against HIV infection because it is believed to help women resist "illicit" sexual acts. This study examines the association between FC HIV status and sexual risk behavior in Mali while taking into account multilevel factors. The following hypothesis was tested: FC is associated with HIV-positive status but not with decreased sexual behavior. DESIGN: The sample consists of 13015 Malian women of reproductive age (15-49 years old). The sample is a nationally representative survey of randomly selected respondents using a stratified multistage sampling strategy. Measures included biospecimens for HIV antibody testing and survey results reporting on number of partners sexual debut premarital sex and sociodemographics. METHODS: Multilevel modeling was used to assess the significance of difference in HIV status and sexual behavior with FC. Multilevel modeling was also used to adjust for age education ethnicity wealth religion region household and community membership. Multiple imputation with 10 imputations corrected for 10% missing data. RESULTS: Participants with FC were at 2.100 (P < 0.001; 95% confidence interval: 1.844 to 2.389) higher odds of being HIV positive. Women with FC did not significantly differ from women without FC in number of sexual partners (P = 0.634) age of sexual debut (P = 0.888) or odds of having premarital sex (P = 0.575). CONCLUSIONS: FC is associated with HIV-positive status but not with a decrease in sexual risk behavior. These findings have important implication for FC and HIV prevention.
Why Crashaw was not Catholic: The Passion and Popular Protestant Devotion

AbstractFor centuries, the poetry of Richard Crashaw has been marginalized as fundamentally alien to the mainstream of English devotional literature. In this prevailing view, Crashaw's poetry is sensuous rather than intellectual, affective rather than spiritual, and Roman Catholic rather than natively English and Protestant. This essay challenges this view, and argues that Crashaw's poetry (written while he was a conforming Protestant) is immersed in a mainstream English crucifixion piety derived from the writings of St. Bernard of Clairvaux, a devotional tradition that was immensely popular among Protestant readers and writers throughout the sixteenth and seventeenth centuries. Ultimately, when we examine Crashaw's poetry within the contexts of Bernardine Passion piety and the print histories of Bernardine devotional texts, Crashaw becomes a central figure in mainstream English religious writing of his time, as native to the period's devotional traditions as Donne or Herbert. (J. R. T.)
Tertiary Motifs Revealed in Analyses of Higher-Order RNA Junctions

RNA junctions are secondary-structure elements formed when three or more helices come together. They are present in diverse RNA molecules with various fundamental functions in the cell. To better understand the intricate architecture of three-dimensional (3D) RNAs, we analyze currently solved 3D RNA junctions in terms of base-pair interactions and 3D configurations. First, we study base-pair interaction diagrams for solved RNA junctions with 5 to 10 helices and discuss common features. Second, we compare these higher-order junctions to those containing 3 or 4 helices and identify global motif patterns such as coaxial stacking and parallel and perpendicular helical configurations. These analyses show that higher-order junctions organize their helical components in parallel and helical configurations similar to lower-order junctions. Their sub-junctions also resemble local helical configurations found in three- and four-way junctions and are stabilized by similar long-range interaction preferences such as A-minor interactions. Furthermore, loop regions within junctions are high in adenine but low in cytosine, and in agreement with previous studies, we suggest that coaxial stacking between helices likely forms when the common single-stranded loop is small in size; however, other factors such as stacking interactions involving noncanonical base pairs and proteins can greatly determine or disrupt coaxial stacking. Finally, we introduce the ribo-base interactions: when combined with the along-groove packing motif, these ribo-base interactions form novel motifs involved in perpendicular helix-helix interactions. Overall, these analyses suggest recurrent tertiary motifs that stabilize junction architecture, pack helices, and help form helical configurations that occur as sub-elements of larger junction networks. The frequent occurrence of similar helical motifs suggest nature's finite and perhaps limited repertoire of RNA helical conformation preferences. More generally, studies of RNA junctions and tertiary building blocks can ultimately help in the difficult task of RNA 3D structure prediction.
Photoaffinity labelling of a thromboxane A2/prostaglandin H2 antagonist binding site in human platelets.

Abstract The diazonium salt of 9,11-dimethylmethano-11,12-methano-16-(4-aminophenoxy)13,14-dihydro-13-aza-15αβ-ω-tetranor TXA 2 (PTA-POA) was synthesized and used as a photoaffinity ligand for the putative human platelet TXA 2 PGH 2 receptor. Incubation of human platelet membranes with the diazonium salt of PTA-POA followed by photolysis at 290 nm(hν) resulted in a 40% decrease in the specific binding of [ 125 I]PTA-OH as measured in the radioligand binding assay. Co-incubation with a TXA 2 PGH 2 agonist followed by photolysis resulted in no decrease in specific binding. Incubation of the diazonium salt of PTA-POA with solubilized platelet membranes without photolysis followed by Scatchard analysis resulted in no change in the K d for [ 125 I]PTA-OH (38 nM) and the preparation which was incubated with the diazonium salt (42 nM). However, the B max for [ 125 I]PTA-OH binding was reduced from 2.4 pmole/mg protein for control to 1.4 pmole/mg protein. These studies show that the diazonium salt of PTA-POA may be a useful photoaffinity ligand for human platelet TXA 2 PGH 2 receptors.
The Omega Limit Sets of Ray-Contractive Operators

Abstract In this paper, we study the omega limit sets of a ray-contractive map T without the compactness assumption on the orbits. If there exists a compact subset Ω of K (the interior of a closed convex cone K ) such that T (Ω) = Ω and T ( K − {0}) ⊂ K , then we are able to prove that ω( x ) either consists of a single point or forms a cycle 2 periodic orbit for any x ∈ K − Ω.
Inorganic N analysis of soil extracts by automated and distillation procedures

Abstract A comparison was made of automated procedures and steam distillation for analysis of NH4 + and NO3 ‐ in KCl extracts of soils. Automated analysis of NH4 + utilized the phenate‐hypochlorite reaction. Nitrate was analyzed by E. coli reduction of NO3 ‐ to NO2‐which was then determined colorimetrically by reaction with sulfanilamide and napthylethylenediamine diHCl. Soil extracts were made with 1 M and 2 M KCl. Extracting with 1 M KCl was as effective as 2 M KCl. Extracts in 1 M KCl did not interfere with E. coli reduction of NO3‐, but 2 M KCl did. The automated procedures when compared to distillation gave similar if not better precision and reduced variation particularly at low N concentrations. The automated procedure tended to give higher values at higher NO3‐concentrations. Reduced time required for the analyses provided an additional advantage for the automated procedures.
Optical Correlation Analysis of Two-Phase Micrographs

The application of coherent optical techniques to the study of correlations in the detailed structure of electron (or light) micrographs was considered for the case when the structure appears to be random. A statistical autocorrelation analysis was made for a random array of transparent disks on an opaque background, relating the radii of the central and first autocorrelation maxima to the radius and mean separation, respectively, of the disks. Experimental determinations of the two-dimensional autocorrelation function were made both for arrays of disks and ellipses. In each case, the shape of the central maximum was similar to the shape of the objects (when all had the same shape and orientation). In addition, the shape of the first autocorrelation maximum was dependent only upon the distribution of centroids of the objects in the array and exhibited the proper asymmetry when the mean separation of centroids differed for the two dimensions. In this latter case, a rectangular first autocorrelation maximum was observed, implying separability of the two-dimensional autocorrelation function and providing a technique for direct quantitative determinations of the mean separations.
Studies of the Decomposition Rates of Tree Litter

In 1953 Daubenmire published the results of some analyses of freshly fallen tree litter for nitrogen, phosphorus, potassium, and calcium. The samples were collected from different habitat types in eastern Washington and northern Idaho with the purpose of finding possible correlations between the pattern of natural vegetation and chemical composition of foliage. Composition proved more a character of the species, however, than of the environment. Portions of the same litter collections have been used to study rates of biological decomposition at different temperature levels, with certain organic constituents determined before microbial action. METHODS One collection representing each of 13 species was used in the present study, and where possible those collections were selected which had a medial composition with respect to N, P, K, and Ca, according to the earlier analyses. The needles of the coniferous species were collected from trees of reproductive age by shaking the branches vigorously in the fall, allowing the dead needles to fall on a cloth spread beneath the tree. All material other than discolored leaves, such as bark, lichens, and insects, was removed. Leaves of Betula and Populus were collected by picking them up from the ground on days when they were being shed. All material was air-dried and stored in paper bags at room temperature. Petioles of the angiosperm leaves were included. Needles and leaves were broken by hand so that no
Citrus limonin glucoside supplementation decreased biomarkers of liver disease and inflammation in overweight human adults

Mixtures of limonoid glucosides demonstrated health benefits in human and animal studies; however, the specific metabolic effects of purified citrus limonin glucoside (LG) in humans are unknown. We determined effects of LG on circulating biomarkers of chronic inflammatory diseases such as nonalcoholic fatty liver disease (NAFLD), diabetes, CVD, and cancer in a cross-over, placebo controlled, double-blind study in overweight/obese individuals. LG had no specific adverse effects. It did not alter circulating concentrations of blood lipids, lipoproteins or their particle sizes, glucose, insulin, hematological parameters, and markers of inflammation except MMP-9 and TNF-α which were decreased by 38.7% and 10.7%, respectively. LG significantly decreased concentrations of liver proteins: gamma-glutamyl transferase (33.8%), alanine aminotransferase (13.1%), alkaline phosphatase (10.1%), and complement C3 (6.4%). Since liver enzymes are elevated in metabolic syndrome, NAFLD, diabetes, CVD, and chronic kidney disease and liver cancer, LG may be useful in the prevention and/or treatment of those diseases.
Does trastuzumab increase the risk of isolated central nervous system metastases in patients with breast cancer

Does trastuzumab increase the risk of isolated central nervous system metastases in patients with breast cancer?
Borings and etchings in the Upper Bathonian-Lower Callovian oolite of the Paris Basin (France)

The oolite of the "Dalle Nacree" Formation in the Paris Basin is made of marine calcareous ooids with, from base to top, radial (and therefore likely to have been calcite), concentric and micritic fabrics, each corresponding to a discrete stratigraphic unit. Several hardgrounds and oolitic pebble-cobble layers in the succession are encrusted and bored. Three main types of boring have been identified ranging in sizes from some tens of µm (sponge borings) to centimeters (bivalve borings), with an intermediate category (worm borings). Some worm borings have rough walls, where early marine fibrous cement is less corroded than the cortices of cemented ooids. The key to understanding this differential dissolution could be related to organic matter, present within the ooid cortices but lacking in the fibrous cement. Polychaete worms that use chemical means (enzymes or acids) to bore are probably responsible for these peculiar borings. A secondary conclusion is that partly or fully leached ooid cortices do not necessarily indicate an original aragonitic mineralogy of the dissolved parts.
Cellular Function of RhoGDI-α Mediates the Cycling of Rac1 and the Regulation of Pancreatic Beta Cell Death

Mycophenolic acid (MPA) is an immunosuppressive agent that is widely used in clinical therapy, including pancreas and islet transplantation. Previously, we showed that MPA induces significant apoptosis of insulin-secreting cells by downregulating RhoGDI-α and increasing JNK expression. In this study, we investigated Rac1 directly associated with RhoGDI-α during MPA-induced apoptosis in INS-1E cells (an insulin-secreting cell line). Cells were treated with MPA for 24 and 36 hours. Immunoprecipitation was used to examine physical interactions between RhoGDI-α and Rac1. Activation and immunoprecipitation assays showed expressions of Rac1 and RhoGDI-α to be directly correlated. Rac1 binding to RhoGDI-α decreased after MPA treatment, and Rac1 was induced and subsequently activated by MPA. We concluded that this novel RhoGDI-α/Rac1/JNK pathway induced apoptosis of transplanted islet cells after MPA treatment.
What Price Pain Relief

Chronic pain affects more than 50 million Americans and results in more than 25 million physician visits a year for lower back pain alone.1 The burden is particularly great in the elderly, in whom associated cardiovascular disease is the leading cause of death. Nonselective, nonaspirin, nonsteroidal antiinflammatory agents (NSAIDs) are effective analgesic, antiinflammatory, and antipyretic agents, but associated gastrointestinal toxicity led to the development and widespread use of selective cyclooxygenase (COX)-2 inhibitors. Originally introduced for use in chronic conditions such as osteoarthritis, they are today used to mitigate acute pain in numerous conditions. Their benefit was presumed to be from their selective inhibition of COX 2, which along with COX-1 is responsible for the conversion of arachidonic acid to prostaglandin H2. Adverse events associated with NSAIDs were attributed to their inhibition of COX 1, which downstream would normally result in the production of prostaglandins responsible for maintenance of gastrointestinal integrity.2 More recent investigations, however, have identified that both COX-1 and COX-2 are involved in vascular hemostasis, and selective COX-2 inhibitors can have net prothrombotic effects. COX-2 inhibitors lower levels of prostacyclin, a platelet inhibitor and vasodilator, whereas uninhibited COX-1 action results in continued thromboxane A2 production, which promotes platelet aggregation.3 There is mounting evidence that nonselective NSAIDs, previously thought to be neutral or beneficial for risk of cardiovascular disease, may also confer harm because of each agent’s relative COX-1/COX-2 prothrombotic effects and potential to reduce glomerular filtration, exacerbate congestive heart failure, and raise blood pressure.4 Article p 2906 In this issue of Circulation , Gislason and colleagues5 report on the risk of death and reinfarction associated with the use of both nonselective, nonaspirin NSAIDs and selective COX-2 inhibitors in post–myocardial infarction (MI) patients in Denmark. The advanced database system in Denmark is …
Research is needed to determine optimal screening methods to lessen the burden of type 2 diabetes in youth.

This editorial discusses screening methods to lessen the burden of type 2 diabetes in young people.
Ethical issues in empirical studies of software engineering

The popularity of empirical methods in software engineering research is on the rise. Surveys, experiments, metrics, case studies, and field studies are examples of empirical methods used to investigate both software engineering processes and products. The increased application of empirical methods has also brought about an increase in discussions about adapting these methods to the peculiarities of software engineering. In contrast, the ethical issues raised by empirical methods have received little, if any, attention in the software engineering literature. This article is intended to introduce the ethical issues raised by empirical research to the software engineering research community and to stimulate discussion of how best to deal with these ethical issues. Through a review of the ethical codes of several fields that commonly employ humans and artifacts as research subjects, we have identified major ethical issues relevant to empirical studies of software engineering. These issues are illustrated with real empirical studies of software engineering.
Snapin Recruits Dynein to BDNF-TrkB Signaling Endosomes for Retrograde Axonal Transport and Is Essential for Dendrite Growth of Cortical Neurons

Neurotrophin signaling is crucial for neuron growth. While the "signaling endosomes" hypothesis is one of the accepted models, the molecular machinery that drives retrograde axonal transport of TrkB signaling endosomes is largely unknown. In particular, mechanisms recruiting dynein to TrkB signaling endosomes have not been elucidated. Here, using snapin deficient mice and gene rescue experiments combined with compartmentalized cultures of live cortical neurons, we reveal that Snapin, as a dynein adaptor, mediates retrograde axonal transport of TrkB signaling endosomes. Such a role is essential for dendritic growth of cortical neurons. Deleting snapin or disrupting Snapin-dynein interaction abolishes TrkB retrograde transport, impairs BDNF-induced retrograde signaling from axonal terminals to the nucleus, and decreases dendritic growth. Such defects were rescued by reintroducing the snapin gene. Our study indicates that Snapin-dynein coupling is one of the primary mechanisms driving BDNF-TrkB retrograde transport, thus providing mechanistic insights into the regulation of neuronal growth and survival.
Optimal Source Codes for Geometrically Distributed Integer Alphabets

An approach is shown for using the Huffman algorithm indirectly to prove the optimality of a code for an infinite alphabet if an estimate concerning the nature of the code can be made. Attention is given to nonnegative integers with a geometric probability assignment. The particular distribution considered arises in run-length coding and in encoding protocol information in data networks. Questions of redundancy of the optimal code are also investigated.
Television's function as a “third parent” for black and white teen‐agers

One of the most interesting lines of rsearch to be found in the pages of the Journal in recent years is that which concerns racial and social class differences in television program choices by young children. Both authors were doctoral candidates in the Department of Communication of Michigan State University when this study was conducted, but now are assistant professors in the School of Journalism at the University of Georgia (Surlin), and the Department of Communications Arts and Sciences of Queens College (Dominick).
Effects of metformin on weight loss: potential mechanisms.

Purpose of reviewDespite the known glucose-lowering effects of metformin, more recent clinical interest lies in its potential as a weight loss drug. Herein, we discuss the potential mechanisms by which metformin decreases appetite and opposes unfavorable fat storage in peripheral tissues.Recent find
Controlling the Wrinkling of the Bilayer Thin Films Electrothermally

Wrinkling of thin sheets under strain is a universal phenomenon. The amplitude and period of the wrinkles formed in a thin sheet clamped at both ends are dependent on its strain and material parameters. In our study, wrinkling is observed in microscale for double clamped thin films (L>W>>t) consisting of 200nm deposited low stress silicon nitride bridges fabricated by bulk micromachining. A bilayer system is formed with 30nm aluminum evaporated on to these bridges. At room temperature the bridges are essentially flat. When an electrical current passes through the aluminum layer electrothermal, heating results in thermal expansion that wrinkles the bilayer. In addition we investigated various dimensions of the bridges and their correlation to the amplitude and the number of wrinkles. The observations are compared to existing wrinkling theory.
The Kline of Sarapis

Among the Graeco-Oriental cults that shared the loyalties of the Mediterranean peoples during the first four centuries of our era, the religion of Sarapis occupied a commanding position. Throughout his career Sarapis was a worker of miracles, but no miracle of his doing ever equalled in historical significance the political thaumaturgy by which he was brought to life. A composite figure created in the last years of the fourth century B.C. by the first Ptolemy, for the purpose of binding together the divergent ethnic elements of Egypt, he was the Greek Pluto imposed on Apis, the Egyptian bull-god of Memphis, who became at death another Osiris, and specifically Osiris-Apis. The identification was of the usual syncretistic type, since Pluto and Osiris were both gods of the dead. As a newcomer Sarapis underwent a long probation at the side of Osiris and Isis, and although with characteristic inconsequence Sarapis never wholly supplanted Osiris, by the second century A.D. he had become, together with Isis, the most beloved figure of the native pantheon, while outside Egypt he was receiving the reverent attention of Greeks of the rank of Plutarch and Aristides. In great measure, the prestige of his magnificent temple at Alexandria and the unceasing flow of propaganda literature account for his eminence at this time. His greatest glory, however, was still to come. In the fourth century, when the approaching victory of the Christian cult threatened all pagan beliefs with extermination, Sarapis took on the role of a universal solar deity.
The Effects of Presenting Imprecise Probabilities in Intelligence Forecasts

How to assess and present analytic uncertainty to policymakers has emerged as an important topic in risk and policy analysis. Due to the complexity and deep uncertainty present in many forecasting domains, these reports are often fraught with analytic uncertainty. In three studies, we explore the effect of presenting probability assessments and analytic uncertainty through probability ranges. Participants were presented with mock intelligence forecasts that include narrative evidence as well as numerical probability assessments. Participants were sensitive to the ambiguity communicated through the confidence range. The narrative appeared to have a smaller effect on judgments when accompanied by a probability range as opposed to a point assessment. In one study, participants also thought that the probability range was more useful for decision making at a higher probability whereas the point estimate was more useful at a lower probability. When evaluating a forecast in hindsight, decisionmakers tended to report lower levels of blame and higher levels of source credibility for forecasts that reported ranges as compared to point assessments. These findings suggest that decisionmakers are not necessarily "ambiguity averse" in the forecasting context. Presenting ranges of probability may have distinct advantages as a way to communicate probability and analytic confidence to decisionmakers.
The effect of prisonization on female criminality

Prisonization theory asserts that inmates who internalize the attitudes and behaviors of a criminal lifestyle are most likely to continue their criminal careers and thus less likely to desist from crime. Unfortunately, virtually all prior studies of prisonization have used male samples and ignored female inmates. Using official data from 174 female inmates in Arizona, the current study examined predictors of 10 forms of institutional misconduct. Net the effects of demographic, social history, criminal career, and other risk factors, women who had served prior prison terms were significantly likely to commit all forms of misconduct. The effect of prior prison experience was separate from other measures of criminal career/criminal propensity, which suggests that recurrently going to prison exerts a unique and powerful effect on inmate behavior. Implications for prisonization research are provided.
Electron microscopy of semithick sections: Advantages for biomedical research

Many transmission electron microscopes are available which can be used to examine biological material in 0.25–0.50-μm-thick sections. When compared to the traditional thin section, these “semithick” sections possess a number of inherent advantages: They can be screened for content with the phase contrast light microscope, they facilitate many types of studies requiring an analysis of serial sections, and they are frequently the optimum thickness for stereomicroscopy. Structures such as microtubule-associated components, as well as structural relationships between cellular constituents, may also be clearly visible in semithick sections which are not visible, or go unnoticed, in thin sections. Together these advantages enable an investigator to obtain a more complete three-dimensional picture of a cell or cell component in a significantly (i.e., up to 90%) shorter period of time than would be required if thin sections were used. Semithick sections may, therefore, make a study feasible which is not approachable, or which is approachable only with great difficulty, by conventional thin sectioning techniques.
Fun in teaching counting using the powerball lottery

One of the many challenges in teaching a required course in discrete mathematical structures to students in computing-related curricula is undoubtedly the teaching of counting techniques and their applications. Traditionally, a technique-driven approach is often adopted in which basic counting principles are introduced one at a time and then unrelated examples are used to illustrate the application of each counting principle. Unfortunately, students often mistake each cleverly constructed solution as a "trick" and fail to understand the underlying counting principle involved under different conditions. In this paper, we propose a problem-driven approach using the powerball lottery and its variations. By examining how numbers can be selected, fundamental counting principles such as the sum and product rules, permutations and combinations, the pigeonhole principle, and other counting principles can easily be introduced and explored. Using this approach, we are able to motivate our students to study and enjoy doing counting.
Chapter 5 Calcium homeostasis and learning deficits in aging

Publisher Summary This chapter describes the intriguing roles of calcium homeostasis in learning and memory and how alterations in calcium handling in neurons may lead to deficits in learning and memory during aging. Normal brain aging is associated with physiological alterations in Ca 2+ homeostasis and deficits in learning and memory. The chapter reviews the aging-related changes in Ca 2+ homeostasis and Ca 2+ -mediated signaling cascades in hippocampal pyramidal neurons. Two hippocampus-dependent learning tasks, trace eyeblink conditioning and Morris water maze training, that are useful to examine learning and aging-related learning deficits are also discussed. The hippocampus, a structure critical for proper learning and memory functions, is frequently implicated in aging-related learning deficits. Consistent with the “Ca 2+ hypothesis of aging,” there are many reports of aging-related changes in Ca 2+ signaling cascades in hippocampal pyramidal neurons, including enhancement in the Ca 2+ -dependent afterhyperpolarization (AHP) caused by an enhanced sIAHP. The changes in protein kinase C gamma (PKCγ) in the context of aging and learning are outlined in the chapter. It is suggested that calcium dependent after hyper-polarizations are altered in a manner that reduces potentiation of synapses in neuronal circuits involved in learning and memory.
Women's choices under the law: marriage, divorce, and illicit sex in the Qing and the Republic.

This chapter examines separately Qing and Republican Chinese law's constructions of women's will, and uses each to illuminate the other. Qing law's construction, though differing greatly from the Guomindang's Republican law that modelled itself after the 1900 German Civil Code, nevertheless did not view women simply as passive entities devoid of will and choice, but rather as beings who chose between "consenting to" and resisting abusive treatment what this article terms "passive agency". It also examines actual legal practice on the basis of 193 (what are termed by archivists) "marriage-related" (or "marriage and illicit sex") cases collected by the author. The chapter considers just how the law worked in practice. Court actions often deviated from codified intent, especially under the transplanted laws of the Republic. On balance, Qing law actually afforded women who were in weak positions more protection than Guomindang law. Keywords: Guomindang Law; legal practice; Qing law; Republican Chinese law
Stenting of superior mesenteric and celiac arteries

A 72-year-old woman with a complex medical history, which included abdominal pain in both lower quadrants for many years, presented to the emergency room with increased complaint of abdominal pain. She was evaluated for this complaint and a 30-pound weight loss. She had been seen the previous day for evaluation in the department of vascular surgery. A duplex ultrasound was performed, which demonstrated high-grade stenosis in the superior mesenteric artery (SMA) and celiac artery. An angiogram was scheduled to evaluate with possible intervention. That evening her abdominal pain increased, and she was instructed to go to the emergency room for evaluation. Because her lactate levels had increased to 2.6 mmol/L and she demonstrated the progressive symptoms of postprandial abdominal pain, it was decided to urgently perform a mesenteric angiogram. Arterial access was obtained in an antegrade manner through a left brachial approach by using micropuncture techniques. A 0.035-inch floppy glide wire was advanced from the brachial into the axillary and subclavian arteries and then to the descending thoracic aorta, and the sheath was up-sized to 6 French. A pigtail catheter was placed over the wire; the wire was removed, and an aortogram was performed. This demonstrated severe three-vessel mesenteric occlusive disease (Fig 1). Lateral aortograms and selective views of the SMA were performed. This demonstrated a lesion in the SMA, which was treated with balloon angioplasty and stented with a 6 24 Genesis Stent (Cordis, Johnson & Johnson Company, Warren, NJ). There was a residual lesion that was dilated with a 7 2 Opta-Pro balloon (Cordis, Johnson & Johnson Company). Next, selective views of the celiac artery were performed. This demonstrated a lesion that was treated with balloon angioplasty and stented with a 7 14 Genesis stent (Cordis, Johnson & Johnson Company). An 8 20 Opta-Pro balloon (Cordis, Johnson & Johnson Company) was used to post-dilate the residual lesion. Post-angiograms were taken of the aorta, demonstrating brisk flow through both vessels (Fig 2). The
Bigrams and the richness of the stimulus.

Recent challenges to Chomsky’s poverty of the stimulus thesis for language acquisition suggest that children’s primary data may carry “indirect evidence” about linguistic constructions despite containing no instances of them. Indirect evidence is claimed to suffice for grammar acquisition, without need for innate knowledge. This article reports experiments based on those of Reali and Christiansen (2005), who demonstrated that a simple bigram language model can induce the correct form of auxiliary inversion in certain complex questions. This article investigates the nature of the indirect evidence that supports this learning, and assesses how reliably it is available. Results confirm the original finding for one specific sentence type but show that the model’s success is highly circumscribed. It performs poorly on inversion in related constructions in English and Dutch. Because other, more powerful statistical models have so far been shown to succeed only on the same limited subset of cases as the bigram model, it remains to be seen whether stimulus richness can be substantiated more generally.
Another Way That Passive Funds Help CreateAsset Allocation Alpha

This is a brief introduction to our special section on Asset Allocation Alpha. TOPICS:Style investing, portfolio construction, exchange-traded funds and applications
A Revised Concept of the Consumer's Co-operative:

The usually accepted concept of consumer co-operators as penny-pinching, radically-minded citizens is challenged by the author.The concept is developed that the modern, urban co-operative movement ...
4D Seismic Repeatability: Lessons From Hoover-Madison-Marshall

A time-lapse (4D) seismic repeatability analysis of HooverMadison-Marshall QC seismic volumes associated with major steps in both fast track and co-processing flows has allowed for quantitative documentation of seismic repeatability. NRMS calculations show the significant impact that trace selection, match filters, migration, and cross-equalization can make on improving seismic repeatability. Maps of dNRMS show the importance of residual velocity adjustment after migration to allow for small spatial wavelengths in the velocity model. In addition, fast track results show the importance of mitigating intra-survey amplitude anomalies and properly matching undershoot data to prime data, to avoid degradation of the 4D signal.
The Bacteriology of Normal Skin; A New Quantitative Test Applied to a Study ofthe Bacterial Flora and the Disinfectant Action of Mechanical Cleansing

Classically, the bacteriology of normal skin has been investigated along three main lines?quantitative studies, qualitative studies, and skin disinfection. A huge amount of work has been done in this field. The reports in the aggregate fill a large place in medical literature. Yet present day knowledge of the subject remains fragmentary and uncertain. There has been, for example, no exact knowledge or unanimity of opinion regarding the size of the bacterial flora of skin. Certain investigators, such as Wigura1 and Hohein,2 were able to collect enormous numbers of germs from skin?even from unexposed skin of cleanly persons. Tinker and Sutton,3 on the contrary, found that "the superficial and deeper layers of the skin of protected areas in cleanly individuals are frequently [25^0 of those tested] free from bacteria." Meleney4 probably expresses the view of many when he says: 'The body surface is covered with countless pathogenic and nonpathogenic organisms, which penetrate for a variable distance into the cracks and crevices of the skin, and into the openings of the hair follicles and sweat glands." Qualitative studies have been made, for the most part, by bacteriologists of an earlier generation. Maggiora,5 Preindlsberger,6 and others, isolated and identified scores of different sorts of bacteria from normal skin. Welch7 found the predominant organism to be a staphylococcus of low pathogenicity, which he termed Staphylococcus epidermis albus. Welch8 wrote an excellent summary of these qualitative studies, appending a bibliography. Many questions have been left unanswered, however. Where are skin-bacteria located? How are they attached to the skin? What proportion of them is pathogenic? Are pathogenic organisms more readily removed or killed than nonpathogenic?
Optimization of return electrodes in neurostimulating arrays

Objective. High resolution visual prostheses require dense stimulating arrays with localized inputs of individual electrodes. We study the electric field produced by multielectrode arrays in electrolyte to determine an optimal configuration of return electrodes and activation sequence. Approach. To determine the boundary conditions for computation of the electric field in electrolyte, we assessed current dynamics using an equivalent circuit of a multielectrode array with interleaved return electrodes. The electric field modeled with two different boundary conditions derived from the equivalent circuit was then compared to measurements of electric potential in electrolyte. To assess the effect of return electrode configuration on retinal stimulation, we transformed the computed electric fields into retinal response using a model of neural network-mediated stimulation. Main results. Electric currents at the capacitive electrode-electrolyte interface redistribute over time, so that boundary conditions transition from equipotential surfaces at the beginning of the pulse to uniform current density in steady state. Experimental measurements confirmed that, in steady state, the boundary condition corresponds to a uniform current density on electrode surfaces. Arrays with local return electrodes exhibit improved field confinement and can elicit stronger network-mediated retinal response compared to those with a common remote return. Connecting local return electrodes enhances the field penetration depth and allows reducing the return electrode area. Sequential activation of the pixels in large monopolar arrays reduces electrical cross-talk and improves the contrast in pattern stimulation. Significance. Accurate modeling of multielectrode arrays helps optimize the electrode configuration to maximize the spatial resolution, contrast and dynamic range of retinal prostheses.