cssi/SciSciGPT-SciSciNet huggingface dataset:
Surface Heating Effect on Local Heat Transfer in a Rotating Two-Pass Square Channel With 60 deg Angled Rib Turbulators

The influence of uneven wall temperature on the local heat transfer coefficient in a rotating, two-pass, square channel with 60 deg ribs on the leading and trailing walls was investigated for Reynolds numbers from 2500 to 25,000 and rotation numbers from 0 to 0.352. Each pass, composed of six isolated copper sections, had a length-to-hydraulic diameter ratio of 12. The mean rotating radius-to-hydraulic diameter ratio was 30. Three thermal boundary condition cases were studied: (A) all four walls at the same temperature, (B) all four walls at the same heat flux, and (C) trailing wall hotter than leading with side walls unheated and insulated. Results indicate that rotating ribbed wall heat transfer coefficients increase by a factor of 2 to 3 over the rotating smooth wall data and at reduced coefficient variation from inlet to exit. As rotation number (or buoyancy parameter) increases, the first pass (outflow) trailing heat transfer coefficients increase and the first pas leading heat transfer coefficients decrease, whereas the reverse is true for the second pass (inflow). The direction of the Coriolis force reverses from the outflow trailing wall to the inflow leading wall. Differences between the first pass leading and trailing heat transfer coefficients increase with ratotation number. A similar behavior is seen for the second pass leading and trailing heat transfer coefficients, but the differences are reduced due to buoyancy changing from aiding to opposing the inertia force. The results suggest that uneven wall temperature has a significant impact on the local heat transfer coefficients.
Metal artifact reduction in x-ray computed tomography (CT) by constrained optimization

Purpose: The streak artifacts caused by metal implants have long been recognized as a problem that limits various applications of CTimaging. In this work, the authors propose an iterative metal artifact reduction algorithm based on constrained optimization. Methods: After the shape and location of metal objects in the image domain is determined automatically by the binary metal identification algorithm and the segmentation of “metal shadows” in projection domain is done, constrained optimization is used for image reconstruction. It minimizes a predefined function that reflectsa priori knowledge of the image, subject to the constraint that the estimated projection data are within a specified tolerance of the available metal-shadow-excluded projection data, with image non-negativity enforced. The minimization problem is solved through the alternation of projection-onto-convex-sets and the steepest gradient descent of the objective function. The constrained optimization algorithm is evaluated with a penalized smoothness objective. Results: The study shows that the proposed method is capable of significantly reducing metal artifacts, suppressing noise, and improving soft-tissue visibility. It outperforms the FBP-type methods and ART and EM methods and yields artifacts-free images. Conclusions: Constrained optimization is an effective way to deal with CTreconstruction with embedded metal objects. Although the method is presented in the context of metal artifacts, it is applicable to general “missing data” image reconstruction problems.
Apical vesicles and microtubules in rhizoids of Blastocladiella emersonii: effects of actinomycin D and cycloheximide on development during germination.

The ultrastructure of untreated germinating cells ofBlastocladiella emersonii was compared with that of cells inhibited by Actinomycin D and cycloheximide. The rhizoids and germ tubes of the fungus contained longitudinally oriented microtubules and apical clusters of cytoplasmic vesicles. The vesicles, apparently derived from Golgi apparatus equivalents also described in this paper, were involved in the tip growth of the germ tubes and rhizoids. Zoospores germinated in Actinomycin D encysted and developed short germ tubes containing microtubules and apical vesicles before further development was arrested. Zoospores treated with cycloheximide encysted but did not develop germ tubes.
Colonization and slavery in central America

(1994). Colonization and slavery in central America. Slavery & Abolition: Vol. 15, Unfree labour in the development of the Atlantic world, pp. 11-25.
Comparison of 3190 Alcohol-Dependent Individuals With and Without Suicide Attempts

INTRODUCTION: Suicidal behaviors are often seen in alcohol-dependent individuals. The aim of this study is to identify and confirm risk factors for suicide attempts in a large, family-based sample of alcoholics. METHODS: Semistructured, detailed interviews were administered to 3190 alcohol-dependent individuals as part of the Collaborative Study on the Genetics of Alcoholism (COGA). Information about suicidal behavior, socioeconomic characteristics, psychiatric comorbidity, substance use disorders, and characteristics of alcohol dependence were obtained from alcohol-dependent probands, controls, and their relatives. RESULTS: As determined by both univariate comparison and multivariate logistic regression analysis, alcohol-dependent individuals with a history of suicide attempts were found to have a significantly more severe course of alcohol dependence and a higher prevalence of both independent and substance-induced psychiatric disorders and other substance dependence. First-degree relatives of subjects with suicide attempts showed a significantly higher rate of suicide attempts, even after controlling for additional relevant diagnoses. CONCLUSION: These results support the hypothesis that alcohol-dependent individuals with a history of suicide attempts are more severely impaired. Screening and subsequent treatment of alcohol use disorder, psychiatric comorbidity, and substance use disorders among alcoholics may be crucial in preventing suicide attempts and completions. Language: en
F116, D3 and G101: Temperate bacteriophages of Pseudomonas aeruginosa

Abstract The temperate P. aeruginosa phages F116, D3, and G101 have been characterized with respect to particle structure and the properties of their DNAs. The three phages are of similar size, but they differ from one another in morphology. The DNA of all three phages is packaged within the head as linear structures with molecular weights varying from 38 × 10 6 for F116 and G101, to 44 × 10 6 for D3. The densities of F116 DNA (ϱ = 1.720 g/cc) and G101 DNA (ϱ = 1.722 g/cc) are close to the density of the host DNA (ϱ = 1.726 g/cc), while D3 DNA has a density of 1.710 g/cc.
111-In-capromab pendetide imaging using hybrid-γ camera-computer tomography technology is not reliable in detecting seminal vesicle invasion in patients with prostate cancer.

Abstract Objectives In this study, we evaluate the diagnostic utility of a hybrid γ-camera-computer tomography (SPECT-CT) indium-111 (111-In)-capromab pendetide scan in detecting seminal vesicle invasion (SVI) in select patients evaluated for primary surgical treatment of prostate cancer (CaP). Methods and materials We retrospectively analyzed a prospective database of patients who underwent preoperative SPECT-CT imaging with 111-In-capromab-pendetide as part of a staging evaluation who were subsequently treated with radical surgery in our center. Only patients with clinically localized disease were included. We calculated diagnostic properties of the hybrid scan in detecting SVI compared with final pathology. Regression analyses were performed, including scan and preoperative variables to predict SVI. Results We retrieved 50 medical records matching our criteria. Median patient age was 61 years (range 45–74). Most patients had a clinical T1c CaP and biopsy Gleason score of 7 or higher. On final pathology, SVI was found in 12 (24%) specimens and radiotracer signal in the seminal vesicle region was reported in 15 (30%) imaging studies. Hybrid SPECT-CT imaging had a sensitivity of 25%, specificity of 61.9%, positive and negative predictive values of 20% and 74.3%, respectively, for detecting SVI. SPECT-CT results did not contribute significantly to SVI prediction on univariate (P = 0.627) or multivariate (P = 0.754) analyses. Conclusions SPECT-CT imaging with 111-In-capromab-pendetide is not reliable in detecting or excluding SVI in this select cohort. High rates of positive radiotracer signals from healthy seminal vesicles raise concerns regarding pharmacologic properties of this radiotracer molecule.
Radiographic evidence for a digestive cellulase in the sea hare,Aplysia vaccaria (Gastropoda: Opisthobranchia)

Abstract Labeled glucose is demonstrated as a product when labeled cellulose is incubated with crop fluid from Aplysia .
Estimating the transition probabilities from censored Markov renewal processes

Abstract The problem of estimating the transition probabilities for the Markov chain associated to a Markov renewal process is considered. The estimators are to be based on censored observations of the Markov renewal process. For a class of Markov renewal processes whose transition distributions factor, nonparametric estimators are defined. They are shown to be consistent and to converge weakly go Gaussian random variables. The result builds upon those in Gill (1980) for nonparametric estimation in this setting.
A Breastfeeding Teaching Tool Using a Sandwich Analogy for Latch-On

Effective latch-on is central to comfortable, efficient breastfeeding. Since breastfeeding involves taking a large mouthful of an even larger object, a latch-on teaching model based on bottle-feeding or on suction alone may be inappropriate. A model based on the way in which an adult approaches a large sandwich, using a water balloon to demonstrate, can help a mother and baby achieve an effective latch-on for breastfeeding.
Modeling biological systems by means of flowgraphs

This brief article is intended to expose the biologi cal modeler to a powerful technique for writing models and for the notation, dimensional analysis, simulation, and solution of biological models. The technique is based on the well-known engineering tecnhique of flowgraph analysis and uses flowgraph notation.
Optimal motion and communication for persistent information collection using a mobile robot

In this paper, we study the problem of persistent information collection using a mobile robot. We consider the scenario where information bits are generated with certain rates at a given set of points of interest (POIs) in a workspace. A mobile robot is then tasked with moving along a periodic trajectory, collecting the information bits from the POIs, and transmitting them to a fixed remote station over realistic fading communication channels. The goal is to minimize the total energy (the summation of motion and communication energies) consumed in one period, while guarantying the following: 1) the number of generated information bits at each POI remains bounded at all the times, 2) the collected information bits in one period are transmitted to the remote station, in the same period, with an acceptable reception quality, and 3) the number of collected information bits in one period is less than the memory size of the robot at all the times. Assuming that the trajectory of the robot defines a Hamiltonian cycle on the POIs, we propose a novel mixed-integer linear program (MILP) to design the optimal trajectory of the robot as well as its motion (velocity profile) and communication (transmission power and rate profiles) along its trajectory. The solution of the MILP is analyzed through several simulations. Our results show the effectiveness of the proposed MILP approach for persistent information collection in fading communication environments.
Crustal contamination in the petrogenesis of a calc-alkalic rock series: Josephine Mountain intrusion, California

The Josephine Mountain intrusion is a Cretaceous calc-alkalictonalite-granite pluton emplaced at 22 km depth in a continental margin arc. Variable uplift of adjacent terranes in southern California since mid-Cretaceous time allows us to reconstruct the local crustal column and evaluate its role as a contaminant of mantle-derived arc magmas in this region. The parental magma of the intrusion was high-alumina basalt whose isotopic signature ( 87 Sr/ 86 Sr = 0.7087; δ 18 O = 7.5; ϵ Nd = −10) cannot have been generated by intracrustal assimilation of known or inferred rock types in the middle or lower crust. Such a signature could have resulted from high-pressure fractionation of primary low-alumina basalt coupled with assimilation of felsic/pelitic lower crust, partial melting of enriched subcontinental mantle followed by high-pressure fractionation, or a combination of these processes. Tonalite of the intrusion was formed by fractionation of the parent magma coupled with assimilation of local felsic wall rocks or by crustal melts similar to slightly younger granite. Assessment of the magnitude of crustal contamination is hampered by uncertainty regarding the existence and role of partial melting of previously enriched subcontinental mantle in generating the parental basaltic magma, leading to concomitant uncertainty in the fraction of new continental crust created by such arc plutonism.
Accurate characterization of high-speed photodetectors

We designed a simple heterodyne system for frequency domain photodetector characterization which is intended to avoid many of the disadvantages of earlier characterization systems and to minimize errors due to intensity fluctuation, frequency calibration, and source impedance mismatch without using vector network analysis. A detailed uncertainty analysis for the system indicates 95% confidence intervals between +/- 0.25 and +/- 0.6 dB at 25 GHz, depending on the photodetector output impedance.
Laminar Flow Forced Convection Heat Transfer Behavior of Phase Change Material Fluid in Microchannels With Staggered Pins

Microchannels have been extensively studied for electronic cooling applications ever since they were found to be effective in removing high heat flux from small areas. Many configurations of microchannels have been studied and compared for their effectiveness in heat removal. However, there is little data available in the literature on the use of pins in microchannels. Staggered pins in microchannels have higher heat removal characteristics because of the continuous breaking and formation of the boundary layer, but they also exhibit higher pressure drop because pins act as flow obstructions. This paper presents numerical results of two characteristic staggered pins (square and circular) in microchannels. The heat transfer performance of a single phase fluid in microchannels with staggered pins, and the corresponding pressure drop characteristics are also presented. An effective specific heat capacity model was used to account for the phase change process of PCM fluid. Comparison of heat transfer characteristics of single phase fluid and PCM fluid are made for two pins geometries for three different Reynolds numbers. Circular pins were found to be more effective in terms of heat transfer by exhibiting higher Nusselt number. Circular pin microchannels were also found to have lower pressure drop compared to the square pin microchannels.Copyright © 2010 by ASME
Cloning and characterization of a member of the rat multidrug resistance (mdr) gene family.

Abstract The rat mdr gene family [genes encoding P-glycoprotein (Pgp)] was characterized and the complete sequence of a rat mdr cDNA was determined based on seven independent cDNA clones that correspond to the same gene. The longest of these clones contains a 4.3-kb insert which represents a full-length rat mdr cDNA. The longest open reading frame of this sequence is 3933 bp; the first ATG is at 103 bp, making the deduced protein 1277 amino acids long (141 kDa). This correlates well with previously identified Pgp. The sequence of this gene has a very high, > 90%, degree of identity to the mouse mdr1b gene (also known as the mdr1 gene) therefore, we designate it the rat mdr1b gene. Transcription of this gene begins at a single start point 151 nucleotides upstream from the start codon. We show here that the rat gene family is comprised of three members, which is consistent with previous data on other rodent species.
Experimenting with database segmentation size vs time performance for mpiBLAST on an IBM HS21 blade cluster

Background Large-scale genomic projects such as the Epichloe festucae Genome Project require regular use of bioinformatic tools. When using BLAST in conjunction with larger databases, processing complex sequences often uses substantial computation time. Parallelization is considered a standard method of curbing extensive computing requirements and parallel implementations of BLAST, such as mpiBLAST, are freely available.
Feto-maternal production and transfer of cortisol in the rhesus (Macaca mulatta).

Abstract Four pregnant rhesus monkeys cnd their fetuses. were infused constantly with 14 C-cortisol and 3 H-cortisol. Steady state plasma specific activities for 14 C and 3 H-cortisol were obtained after 80 to 90 minutes in both mother and fetus. These data and the rates of infusion of radioactivity were used to calculate the following parameters for both mother and fetus: 1) metabolic clearance rates, 2) production rates, 3) mean adrenal secretory rates, 4) transfer rates from mother to fetus and fetus to mother cnd, 5) the fraction of cortisol in each vascular compartment derived from the maternal and fetal edrenals. Plasma cortisone concentrations, as well as the fraction of cortisone derived from fetal and maternal cortisol were determined. Tetrahydrocortisol and tetrahydrocortisone concentrations were calculated. Mean cortisol secretory rates for the maternal and fetal adrenals were 60.0±11.8 and 1.82±0.42 mg/day. Fifty-eight % of the cortisol in the fetal compartment was of maternal origin. During transfer across the placenta to the fetus, cortisol was largely converted to cortisone. In fetal plasma 76% of the cortisone was of maternal origin. Cortisone concentrations in fetal plasma were higher than those of cortisol.
Influence of behavior modification on overactive bladder

Behavioral interventions have been used for decades to treat urge incontinence and other symptoms of overactive bladder. Perhaps the earliest form of treatment was the bladder drill, an intensive intervention designed to increase the interval between voids to establish a normal frequency of urination and normalization of bladder function. Bladder training is a modification of bladder drill that is conducted more gradually on an outpatient basis and has resulted in significant reduction of incontinence in older, community-dwelling women. Multicomponent behavioral training is another form of behavioral treatment that includes pelvic floor muscle training and exercise. This intervention focuses less on voiding habits and more on altering the physiologic responses of the bladder and pelvic floor muscles. Using biofeedback or other teaching methods, patients learn strategies to inhibit bladder contraction using pelvic floor muscle contraction and other urge suppression strategies. Although behavioral and drug therapies are known to be highly effective for reducing urge incontinence, few patients are cured with either treatment alone. Thus, future research should explore ways to enhance the effectiveness of these conservative therapies. Although the mechanisms by which behavioral treatments work have not been established, there is some evidence that behavioral and drug interventions may operate by different mechanisms, suggesting that they may have additive effects and that combining them may result in better outcomes. Future research needs to examine the mechanisms by which these therapies reduce incontinence and whether combining behavioral and drug treatment will result in better outcomes than either therapy alone.
A mutually inclined interpenetrated cobalt benzenetricarboxylate/organodiimine layered coordination polymer containing “infinite” water chains and its irreversible crystal-to-crystal structural transformation upon dehydration

Abstract The novel coordination polymer {[Co(Hbtc)(4-bpmp)(H2O)] · 3H2O} (1, btc = 1,3,5-benzenetricarboxylate, 4-bpmp = N,N′-bis(4-pyridylmethyl)piperazine) has been prepared by hydrothermal synthesis and characterized by single crystal X-ray diffraction, IR and thermogravimetric analysis. Individual [Co(Hbtc)(4-bpmp)(H2O)]n layers mutually interpenetrate in a 2d + 2d → 3D inclined fashion to produce channels coursing down the c crystal direction, occupied by “infinite” 1D water molecule chains. Dehydration of 1 results in structural reorganization to a monoclinic phase, which is converted to an amorphous phase upon rehydration.
Post-glacial relaxation of a viscously stratified compressible mantle

The postglacial relaxation phenomenon of a viscously compressible nonself-gravitating spherical-shell model is investigated. Analytical solutions to an exponentially depth-dependent viscosity are developed with various types of compressible density models such as those with an exponential dependence of the radius and an algebraic-root dependence of the radius. The solutions of a viscously compressible multilayered model with constant thermodynamic properties and viscosity are developed by the propagator matrix method. The results show that inferences of deep mantle viscosity from postglacial rebound would be hampered by mantle compressibility for long-wavelength harmonics because of the smaller excitation of compressible eigenfunctions in the lower mantle. The relaxation times and velocity fields are more sensitive to higher viscosity contrast for the exponentially varying viscosity than for models with discrete jumps in the viscosity structure.
Post-treatment surveillance of patients with lymphoma treated with curative intent

Abstract Hodgkin’s lymphoma and aggressive non-Hodgkin’s lymphoma (NHL) are common, potentially curable cancers. Despite modern therapy, many patients will relapse. A number of relapsing patients may be cured with subsequent treatment, including high-dose chemotherapy. Risk of relapse after potentially curative therapy is greatest in the first 2 years, and post-treatment surveillance should be concentrated during this time. Most patients will present with symptoms or physical findings at relapse. Physicians and patients should be aware of common symptoms associated with relapse, and laboratory and radiological testing should be used to assess such concerns.
DEVIATIONS FROM STOICHIOMETRY AND LATTICE DEFECTS IN IV-VI COMPOUNDS AND THEIR ALLOYS. GENERAL FEATURES AND EXPERIMENTAL METHODS

Considerably more information concerning deviations from stoichiometry is available for the IV-VI compounds than for any other group of semiconducting compounds. This paper first describes the unusual combination of properties exhibited by the IV-VI compounds which makes them especially suitable materials for experimental studies of stoichiometric deviations. The results of these studies are most conveniently presented in the form of temperature-composition, pressure-composition, and pressure-temperature projections of the three-dimensional phase diagram. The general features of these projections for the IV-VI compounds are described, together with the principal experimental methods which have been employed to determine them. The paper concludes by summarizing the types of data which have been reported for the individual compounds.
A new methodology for building energy performance benchmarking: An approach based on intelligent clustering algorithm

Abstract Though many building energy benchmarking programs have been developed during the past decades, they hold certain limitations. The major concern is that they may cause misleading benchmarking due to not fully considering the impacts of the multiple features of buildings on energy performance. The existing methods classify buildings according to only one of many features of buildings—the use type, which may result in a comparison between two buildings that are tremendously different in other features and not properly comparable as a result. This paper aims to tackle this challenge by proposing a new methodology based on the clustering concept. The clustering concept, which reflects on machine learning algorithms, classifies buildings based on a multi-dimensional domain of building features, rather than the single dimension of use type. Buildings with the greatest similarity of features that influence energy performance are classified into the same cluster, and benchmarked according to the centroid reference of the cluster. The proposed methodology contains four steps: feature selection, clustering algorithm adaptation, results validation, and interpretation. The experimentation was carried out with a comparison between the proposed methodology and the Energy Star approach. It was shown that the proposed methodology could account for the total building energy performance and was able to provide a more comprehensive approach to benchmarking. In addition, the multi-dimensional clustering concept enables energy benchmarking among different types of buildings, and inspires a new perspective to investigate building performance typology.
Stackelberg rent-seeking

In this paper I present a formal analysis of rent-seeking games in which the players do not move simultaneously. I consider rent-seeking situations where the players are risk neutral and may value the prize differently. The subgame perfect equilibrium outcome in this Stackelberg game provides several surprising and interesting results. I extend the problem to deal with cases of in- complete information concerning the value a player has for the politically contestable rent.
Biopolis: Village on a Hill

Since the opening of Biopolis in 2003, Singapore's 18 acre science complex on a hill has attracted the rest of the world's curiosity.
Formation and consumption of SiO in powder synthesis flames

Profiles of SiO mole fraction have been obtained in low pressure premixed hydrogen/oxygen/hexamethyldisilazane (HMDS) flames by laser-induced fluorescence and emission spectroscopy. SiO is observed to form early in the flame at temperatures near 1100 K. The flame equivalence ratio has only a small effect on the SiO mole fraction, but the precursor concentration has a marked effect on both the peak mole fraction and shape of the profile. The SiO observed in the flame appears to be from two sources: SiO produced directly from precursor pyrolysis, and SiO that is generated as the partial pressure from the solid SiO in the flame. A comparison of ground state and excited state profiles indicates that the emission from SiO is chemiluminescence rather than thermal emission. A computational flow model incorporating current Si/H/O chemical mechanisms is able to qualitatively reproduce some aspects of the observed profiles, but significant discrepancies remain. The profiles presented in this study can serve as a test against which future chemical and process models may be validated.
The electrocardiogram in ventricular aneurysm

Abstract 1. 1. The case histories and findings of eight patients with proved cardiac aneurysms are described. 2. 2. Q waves and the persistent elevation of the RS-T segments in the precordial leads were the essential electrocardiographic findings in all eight patients. It is also true that of seven patients with necropsy findings of ventricular aneurysm, three did not shown the persistent RS-T elevation in the precordial leads. 3. 3. Present concepts of electrophysiology do not explain the persistence of elevated RS-T segments in cases of cardiac aneurysm.
Cuba, Castro and Anti-Semitism

The Soviets provided Cuba with the model of attacking human rights activities and organizations as a necessary extension of the Jewish Zionist conspiracy. The identification of Castro with forces dedicated to the destruction of Israel was made plain in proclamation and practice. The Cuban position is that the war on terrorism is actually an example of “Liberation Imperialism.” Cubans make no reference to the repeated assaults on Israel, or the actual causes of the Middle East conflict—the denial of the right of Israel to exist as a Nation-State in that region. Anti-Semitism is so powerfully rooted as a cultural element in authoritarian cultures that even when, as in the case of Cuban communism, it entails the tortured twisting of doctrinal elements within Marxism–Leninism, such as doctrinal claims about the “materialist foundations of society,” its leaders will sacrifice the ideology to the reality. Part of the Castro attachment to communism is an overall contempt for the Jewish mini-Diaspora within the larger flight of Cubans to the United States and other places where the practice of free speech remain unimpeded. The regime of Fidel Castro has changed little in the past 49 years, compared to the rest of the world.
Micro-organisms adapted to High Temperatures

Blue-green algae can grow in hot springs at temperatures of 50°–75° C. In algae taken from hot springs in the Yellowstone National Park, photosynthesis has now been shown to be most efficient at the temperature of the environment.
Electron Speckle and Higher-Order Correlation Functions from Amorphous Thin Films

We obtain valuable information about medium-range order in amorphous semiconductors from variable coherence microscopy, a new quantitative approach to TEM. The technique reveals three-body and higher-order atomic correlation functions, which are sensitive to medium-range order. Preliminary experimental evidence for structural changes on annealing has been found for amorphous semiconductor films, with pronounced medium-range order seen only in unannealed films.
The Calcimimetic R-467 Potentiates Insulin Secretion in Pancreatic β Cells by Activation of a Nonspecific Cation Channel

The extracellular, G protein-linked Ca(2+)-sensing receptor (CaSR), first identified in the parathyroid gland, is expressed in several tissues and cells and can be activated by Ca(2+) and some other inorganic cations and organic polycations. Calcimimetics such as NPS (R)-N-(3-phenylpropyl)-alpha-methyl-3-methoxybenzylamine hydrochloride (R-467), a phenylalkylamine, are thought to activate CaSR by allosterically increasing the affinity of the receptor for Ca(2+). When tested for its effect on insulin release in C57BL/6 mice, R-467 had no effect under basal conditions but enhanced both phases of glucose-stimulated release. The betaHC9 cell also responded to R-467 and to the enantiomer S-467 with a stimulation of insulin release. In subsequent studies with the betaHC9 cell, it was found that the stimulatory effect was due to activation of a nonspecific cation channel, depolarization of the beta-cell, and increased Ca(2+) entry. No other stimulatory mechanism was uncovered. The depolarization of the cell induced by the calcimimetic could be due to a direct action on the channel or via the CaSR. However, it appeared not to be mediated by G(i), G(o), G(q/11), or G(s). The novel mode of action of the calcimimetic, combined with the glucose-dependence of the stimulation on islets, raises the possibility of a totally new class of drugs that will stimulate insulin secretion during hyperglycemia but which will not cause hypoglycemia.
Analysis of small amines in pharmaceuticals by capillary ion electrophoresis with conductivity detection

Capillary ion electrophoresis (CIE) with direct conductivity detection is a simple, fast, and versatile method for analysis of ions. In this study CIE with conductivity detection was used to analyze for hydroxylamine which is often used in the synthesis of pharmaceutical intermediates and drug substances. The conductivity response of hydroxylamine was investigated by using different buffer types and buffer concentrations. Other small amines were also studied with this method and were correlated with the molecular weight of the amines. The response of hydroxylamine increased significantly with MES glycylglycine buffer as compared to MES-histidine buffer (LOD from 10 to 1 ppm). The detection of trace level of hydroxylamine in a drug substance proved to be possible with this method. The developed method was also tested for the linearity range, reproducibility, and selectivity with several small amines. The method developed in this study was demonstrated as a sensitive and reliable method for detection and quantification of small amines in pharmaceutical substances.
Building a biomedical cyberinfrastructure for collaborative research.

Abstract For the potential power of genome-wide association studies (GWAS) and translational medicine to be realized, the biomedical research community must adopt standard measures, vocabularies, and systems to establish an extensible biomedical cyberinfrastructure. Incorporating standard measures will greatly facilitate combining and comparing studies via meta-analysis. Incorporating consensus-based and well-established measures into various studies should reduce the variability across studies due to attributes of measurement, making findings across studies more comparable. This article describes two well-established consensus-based approaches to identifying standard measures and systems: PhenX (consensus measures for phenotypes and eXposures), and the Open Geospatial Consortium (OGC). NIH support for these efforts has produced the PhenX Toolkit, an assembled catalog of standard measures for use in GWAS and other large-scale genomic research efforts, and the RTI Spatial Impact Factor Database (SIFD), a comprehensive repository of geo-referenced variables and extensive meta-data that conforms to OGC standards. The need for coordinated development of cyberinfrastructure to support measures and systems that enhance collaboration and data interoperability is clear; this paper includes a discussion of standard protocols for ensuring data compatibility and interoperability. Adopting a cyberinfrastructure that includes standard measures and vocabularies, and open-source systems architecture, such as the two well-established systems discussed here, will enhance the potential of future biomedical and translational research. Establishing and maintaining the cyberinfrastructure will require a fundamental change in the way researchers think about study design, collaboration, and data storage and analysis.
Synthesis and photo-conversion of androsta- and pregna-5,7-dienes to vitamin D3-like derivatives.

Calcitriol (3β,5Z,7E)-9,10-secocholesta-5,7,10(19)-trien-1α,3β,25-triol) is a powerful oncostatic form of vitamin D3 that is of limited clinical utility due to hypercalcemic (toxic) effects. Since the removal of the side chain reduces or eliminates the calcemic activity of vitamin D3, secosteroidal compounds lacking or with a shortened side chain are good candidates for anti-cancer drugs. In addition, 5,7-steroidal dienes without a side chain can be generated in vivo under pathological conditions. A series of androsta- and pregna-5,7-dienes was efficiently synthesized from their respective 3-acetylated 5-en precursors by bromination-dehydrobromination and deacetylation reactions. Ultraviolet B (UVB) irradiation was used to generate corresponding 9,10-secosteroids with vitamin D-like structures. Additional products with tachysterol-like (T-like) structures or 5,7-dienes with inverted configuration at C-9 and C-10 (lumisterol, L-like) were also detected. Different doses of UVB resulted in formation of various products. At low doses, previtamin D-, T- or L-like compounds were formed as the main products, while higher doses induced further isomerization, with formation of potentially oxidized derivatives. In summary, we describe dynamic UVB induced conversion of androsta- and pregna-5,7-dienes into vitamin D-like compounds and their rearranged analogues; additionally novel T-like and L-like structures were also produced and characterized. Further biological evaluation of newly synthesized compounds should help to select the best candidate(s) for potential treatment of hyperproliferative diseases including cancer.
Synthesis and in vitro cytotoxic activity of N-, F-, and S-ether derivatives of podophyllotoxin fatty acid adducts

This paper represents the first synthesis, spectroscopic characterization, and antitumor evaluation of F-, N-, and S-containing C4α-FA derivatives of podophyllotoxin. In a synthetic strategy, a FA unit of 4-O-podophyllotoxinyl 12-hydroxyoctadec-Z-9-enoate 2, a derivative of podophyllotoxin, was functionalized at the C−12 position by incorporating the F atom and N-containing moieties. The FA olefin (Z, C−9/C−10) of 2 was hydrogenated to produce a derivative possessing a hydroxy function (C−12) on a saturated C18 FA chain. In another synthetic strategy, two S-ethers of podophyllotoxin (C4α) were synthesized from a terminal unsaturated FA analog, 4-O-podophyllotoxinyl undec-10-enoate. Syntheses were achieved through effective synthetic procedures; 1H NMR, 13C NMR, IR, and high-resolution mass data proved excellent tools to characterize these derivatives. In vitro antitumor activity was investigated against a panel of five human neoplastic cell lines, SK-MEL (malignant, melanoma), KB (epidermal carcinoma, oral), BT-549 (ductal carcinoma, breast), SK-OV-3 (ovary carcinoma), and HL-60 (human leukemia). Keeping in view the severe lack of tumor selectivity of podophyllotoxin over normal cells, we assayed new analogs against noncancerous mammalian VERO (African green monkey kidney fibroblast) cell lines to gauge their extent of toxicity. Several of these compounds showed excellent moderation of antitumor activity. In general, we found excellent growth inhibition against the human leukemia cell line (HL-60), particularly for the analogs containing S-ethers and carbamates. None of the compounds were toxic to normal cell lines.
We‐Language and Sustained Reductions in Drinking in Couple‐Based Treatment for Alcohol Use Disorders

Couple-based treatments for alcohol use disorders (AUDs) produce higher rates of abstinence than individual-based treatments and posit that active involvement of both identified patients (IPs) and significant others (SOs) is partly responsible for these improvements. Separate research on couples' communication has suggested that pronoun usage can indicate a communal approach to coping with health-related problems. The present study tested whether communal coping, indicated by use of more first-person plural pronouns ("we" language), fewer second-person pronouns ("you" language), and fewer first-person singular pronouns ("I" language), predicted improvements in abstinence in couple-based AUD treatment. Pronoun use was measured in first- and mid-treatment sessions for 188 heterosexual couples in four clinical trials of alcohol behavioral couple therapy (ABCT). Percentages of days abstinent were assessed during treatment and over a 6-month follow-up period. Greater IP and SO "we" language during both sessions was correlated with greater improvement in abstinent days during treatment. Greater SO "we" language during first- and mid-treatment sessions was correlated with greater improvement in abstinence at follow-up. Greater use of IP and SO "you" and "I" language had mixed correlations with abstinence, typically being unrelated to or predicting less improvement in abstinence. When all pronoun variables were entered into regression models, only greater IP "we" langue and lower IP "you" language predicted improvements in abstinence during treatment, and only SO "we" language predicted improvements during follow-up. Most pronoun categories had little or no association with baseline relationship distress. Results suggest that communal coping predicts better abstinence outcomes in couple-based AUD treatment.
On stock trading using a PI controller in an idealized market: The robust positive expectation property

In a number of recent papers, a new line of research has been unfolding which is aimed at using classical linear feedback control in a model-free stock trading context. The salient feature of this approach is that no model for stock price dynamics is used to determine the dollar amount invested I(t). Instead, the investment level is performance driven and generated in a model-free manner via an adaptive feedback on the cumulative gains and losses g(t). One of the main results obtained to date is paraphrased as follows: Under idealized market conditions with stock prices governed by a non-trivial Geometric Brownian Motion (GBM), a combination of two static linear feedbacks, one long and one short, leads to a positive expected value for the trading gain g(t) for all t > 0. Since this holds independently of the parameters underlying the GBM process, it is called the “robust positive expectation” property. Working in this same GBM setting, the main objective in this paper is to generalize this result from static to dynamic feedback. To this end, we consider a Proportional-Integral (PI) controller for the investment function I(t). Subsequently, we reduce the stochastic trading equations for the expectation of g(t) to a classical second order system and use the closed- form solution to prove that the robust positive expectation property still holds. We also consider a number of other issues such as the analysis of the variance of g(t) and the monotonic dependence of g(t) on the feedback gains. Finally, we provide simulations showing how the PI controller performs in a real market with prices obtained from historical data.
JAK3 Maps to Human Chromosome 19p12 within a Cluster of Proto-oncogenes and Transcription Factors

The gene for the most recently discoverd member of a family of cytoplasmic tyrosine kinases, JAK3, was mapped to human chromosome 19p12 using polymerase chain reaction. JAK3 plays a role in the interleukin (IL)-2 signaling pathway that regulates T and B lymphocyte development and proliferation. 20 refs., 1 fig.
Reversible abnormalities in postheparin lipolytic activity during the late phase of release in diabetes mellitus (postheparin lipolytic activity in diabetes).

To test whether abnormalities in multiphasic release of lipoprotein lipase are associated with hypertriglyceridemia in diabetes mellitus, postheparin lipolytic activity (PHLA) was measured during a high-dose, constant heparin infusion in 20 diabetic subjects with hypertriglyceridemia, 25 nondiabetic hypertriglyceridemic subjects and 7 normal subjects. The standard low heparin dose PHLA and the PHLA during the early phase of the heparin infusion were the same in all groups. In contrast, the PHLA during the late phase of the heparin infusion was lower in the 12 untreated diabetic subjects than in the 25 nondiabetic hypertriglyceridemic and the 7 normal subjects (p < 0.001). An abnormality in late phase PHLA in the untreated diabetic subjects was more apparent when it was compared to the level of PHLA attained during the early phase of the heparin infusion (Equilibrium PHLA60 min PHLA). The relative PHLA in the late phase of the infusion was lower in the untreated diabetic subjects (0.671 ± 0.147) than in the nondiabetic hypertriglyceridemic subjects (0.847 ± 0.019, p < 0.001), or in the chronically treated diabetic subjects (0.823 ± 0.108, p < 0.05). Among the untreated diabetic subjects, increasing fasting glucose levels were associated with both decreasing absolute PHLA levels at the late phase of the infusion (r = −0.61, p < 0.02) and greater decreases in relative PHLA during the infusion (r = −0.80, p < 0.001). Treatment of the diabetes with long-term oral sulfonylurea or insulin therapy corrected the abnormality in the late phase PHLA with an associated decrease in plasma triglyceride levels (p < 0.001). In five subjects with a deficient PHLA response to a standard, low dose of heparin, the PHLA response was low throughout the heparin infusion. With treatment, the PHLA response to the low heparin dose corrected rapidly toward normal in those two diabetic subjects with PHLA deficiency, and the early PHLA response during the heparin infusion increased. However, the late phase abnormality in all untreated diabetic subjects did not correct to normal until after several months of antihyper-glycemic therapy. In the untreated diabetic subjects the degree of elevation of the plasma triglyceride level appeared to result from the interaction of the abnormality in PHLA with the presence or absence of an inherited familial lipid disorder.
Surface structure sensitivity of alloy catalysis: catalytic conversion of n-hexane over Au-Pt(111) and Au-Pt(100) alloy crystal surfaces

Alloys have become important catalysts for many chemical processes due to their superior properties over single component catalysts. These include increased reaction selectivity and greater resistance to deactivation. The reasons for their superior performance are not well understood, however. Catalytic studies, using single component metal single crystal catalysts, coupled with the use of surface science techniques, have proven useful in understanding the nature of the working catalyst. Extension of these investigations to alloy single crystal at high pressures should be useful for elucidating the role of alloying in altering catalytic behavior. In this note the authors report the surface structure sensitivity of the catalytic properties of platinum-gold alloys in the conversion reaction of n-hexane and present evidence for a mixed Au-Pt site on the (111) surface for the isomerization reaction. Experiments were carried out in an ultrahigh vacuum system equipped with Auger electron spectroscopy (AES), low energy electron diffraction (LEED) optics, a quadrupole mass spectrometer, and a sample isolation cell which was connected to the reactor loop and gas chromatograph equipped with a flame ionization detector. 11 references.
Glial uptake of excitatory amino acids influences neuronal survival in cultures of mouse hippocampus.

Abstract Several reports have described apparently normal survival and development of hippocampal and spinal cord culture preparations grown in Ham's F-12 medium, which contains 100 μM each of l -glutamate and l -aspartate. As at this concentration these amino acids are neurotoxic, some adaptive mechanism must occur to allow neuronal survival. We have investigated the mechanism underlying such adaptation. Dissociated cultures of mouse hippocampal neurons were grown in either Eagle's minimum essential medium or Ham's F-12 medium, supplemented with 5% horse serum. Analysis of neuronal density in cultures stained for neuron-specific enolase showed that although large numbers of neurons were present in mature cultures grown in either medium, neuronal survival in cultures grown continuously in F-12 was reduced to 41%, compared to controls grown in Eagle's minimum essential medium. Physiological studies showed that those neurons which survived in F-12 did not lose their sensitivity to excitatory amino acids. In addition, the acute application of fresh, serum-free F-12 to 10–14-day-old cultures grown in either minimum essential medium or F-12 was highly neurotoxic. Three lines of evidence suggest that glial uptake of amino acids, and reduction of the extracellular concentration of glutamate and aspartate below neurotoxic levels, rather than receptor desensitization underlies the adaptive mechanism allowing neuronal survival. First, application of fresh F-12 produced large depolarizations, and profound neuronal swelling in cultures grown in F-12; however, after several hours swelling reversed suggesting a slow onset of the adaptive process. Second, pressure application of conditioned F-12 obtained from sister cultures also elicited depolarizations in neurons grown in F-12, but the amplitude of the underlying inward current was only 25–30% of that produced by fresh F-12, suggesting a loss of potency of F-12 exposed to prolonged contact with hippocampal cultures. Third, measurement by high performance liquid chromatography showed reduction of aspartate concentrations to around 10% of those present in fresh F-12, within 24h after exposing glial cell cultures to fresh F-12. It is concluded that cellular uptake mechanisms for amino acids have a strong impact on excitotoxicityin vitro, and most likely play an important role in protecting neurons from the potentially damaging action of high concentrations of excitatory transmittersin vivo. In addition our experiments help to explain the mechanisms permitting neuronal survival in cultures grown in Ham's F-12 medium, which when applied acutely to mature cultures is strikingly neurotoxic.