cssi/SciSciGPT-SciSciNet huggingface dataset:
MicroRNA-627 mediates the epigenetic mechanisms of vitamin D to suppress proliferation of human colorectal cancer cells and growth of xenograft tumors in mice

Background & Aims Vitamin D protects against colorectal cancer through unclear mechanisms. We investigated the effects of calcitriol (1α,25-dihydroxyvitamin D 3 ; the active form of vitamin D) on levels of different microRNAs (miRNAs) in colorectal cancer cells from humans and xenograft tumors in mice. Methods Expression of miRNAs in colorectal cancer cell lines was examined using the Ambion mirVana miRNA Bioarray. The effects of calcitriol on expression of miR-627 and cell proliferation were determined by real-time polymerase chain reaction and WST-1 assay, respectively; growth of colorectal xenograft tumors was examined in nude mice. Real-time polymerase chain reaction was used to analyze levels of miR-627 in human colon adenocarcinoma samples and nontumor colon mucosa tissues (controls). Results In HT-29 cells, miR-627 was the only miRNA significantly up-regulated by calcitriol. Jumonji domain containing 1A ( JMJD1A ), which encodes a histone demethylase, was found to be a target of miR-627. By down-regulating JMJD1A, miR-627 increased methylation of histone H3K9 and suppressed expression of proliferative factors, such as growth and differentiation factor 15. Calcitriol induced expression of miR-627, which down-regulated JMJD1A and suppressed growth of xenograft tumors from HCT-116 cells in nude mice. Overexpression of miR-627 prevented proliferation of colorectal cancer cell lines in culture and growth of xenograft tumors in mice. Conversely, blocking the activity of miR-627 inhibited the tumor suppressive effects of calcitriol in cultured colorectal cancer cells and in mice. Levels of miR-627 were decreased in human colon adenocarcinoma samples compared with controls. Conclusions miR-627 mediates tumor-suppressive epigenetic activities of vitamin D on colorectal cancer cells and xenograft tumors in mice. The messenger RNA that encodes the histone demethylase JMJD1A is a direct target of miR-627. Reagents designed to target JMJD1A or its messenger RNA, or increase the function of miR-627, might have the same antitumor activities of vitamin D without the hypercalcemic side effects.
Quantifying Diurnal Cloud Radiative Effects by Cloud Type in the Tropical Western Pacific

AbstractCloud radiative effects are examined using long-term datasets collected at the U.S. Department of Energy’s three Atmospheric Radiation Measurement Program Climate Research Facilities in the tropical western Pacific Ocean. The surface radiation budget, cloud populations, and cloud radiative effects are quantified by partitioning the data by cloud type, time of day, and large-scale modes of variability such as El Nino–Southern Oscillation (ENSO) phase and wet/dry seasons at Darwin, Australia. The novel aspect of this analysis is the breakdown of aggregate cloud radiative effects by cloud type across the diurnal cycle. The Nauru Island (Republic of Nauru) cloud populations and subsequently the surface radiation budget are strongly impacted by ENSO variability, whereas the cloud populations over Manus Island (Papua New Guinea) shift only slightly in response to changes in ENSO phase. The Darwin site exhibits large seasonal monsoon-related variations. When present, deeper convective clouds have a stron...
Bottleneck generalized assignment problems

Abstract We discuss bottleneck (or minimax) versions of the generalized assignment problem. The basic problem involves the assignment of a number of jobs to a number of agents such that each job is performed by a unique agent, and capacity limitations on the agents are not exceeded. Two versions of the bottleneck generalized assignment problem (BGAP) are defined. The first of these is called the Task BGAP and has as its objective the minimization of the maximum of the costs of the assignments that are made. The second version is referred to as the Agent BGAP and has as its objective the minimization of the maximum of the total costs assigned to each agent. Both problems are formulated, and applications are discussed. Procedures for solving the Task BGAP are presented, and one of the procedures is illustrated in an example.
Adaptive evolution of degrees and kinds of neoplastic transformation in cell culture.

Abstract Human cancers undergo protracted complex development from benign to malignant states, as most thoroughly documented in the mole-to-melanoma sequence. The early stages of the sequence tend to redifferentiate into normal tissues; the later stages progress to ever increasing multiplication and malignancy. When placed under the growth constraint of either crowding or low serum concentrations, the NIH 3T3 line of mouse cells readily undergoes transformation, expressed in the development of foci of cells that continue to multiply at confluence when the rest of the population has stopped. If the nontransformed cells are maintained for 3 months by frequent low-density passages in high concentrations of calf serum, they gradually lose the capacity to undergo transformation when the constraints are applied. The same conditions of passage have been used to reverse the transformation, both processes resembling in principle the reversal of the early stages of the mole-to-melanoma sequence. When the frequent low-density passages are made in high concentrations of fetal bovine serum, which supports a slightly lower growth rate than an equal concentration of calf serum, the degree of transformation is gradually increased, so that the foci become more numerous, broader, and thicker, reaching a maximum in successive assays at about 3 months of passaging. A diversity of focal morphologies is sporadically generated in the calf serum passage by exposing the cells to various concentrations of calf serum for 14 days of growth and confluency before assaying them. The dependence of the number, density, and morphology of foci on the environment in which the cells had been grown before assay reinforces the evidence that the transformation is an epigenetic process. The fact that these effects develop in culture gradually over an extended period of time suggests parallels to the characteristically long-term early regression and later progression, as well as the diversity of the mole-to-melanoma sequence, and may also be representative of other cancers.
Branding Behavior: The Strategy behind the TruthSM Campaign:

The American Legacy Foundation's truthSM campaign uses a branding strategy to change adolescent and young adults' attitudes and behavior and to encourage them to adopt a nonsmoking lifestyle. This strategy and its execution represent an evolution from previous antismoking social marketing efforts. It offers lessons not only for future antismoking campaigns, but also for social marketing aimed at preventing or controlling many other youth risk behaviors. The persuasive mechanisms by which truth's branding strategy works need to be understood within the context of existing social psychological theories of attitude and belief formation, as well as behavior change.Brand equity is a central measure of the truth campaign's strategy. We describe a new brand equity scale based on previous work in advertising research and present data from a campaign tracking survey. We conclude that the campaign has high brand equity among its target audience, 12- to 17-year-olds, and has changed important attitudes and beliefs r...
Polymer nanostructure development of fluorinated and aliphatic monoacrylates in smectic liquid crystals via photopolymerization

To develop viable polymer stabilized liquid crystal systems, it is crucial to understand the factors that affect polymer nanostructure evolution. This work examines the influence of the photopolymerization of aliphatic and fluorinated monoacrylate monomer within a room temperature smectic liquid crystal (LC). Additionally, the effect of LC order on polymerization kinetics, monomer and polymer organization, and the effect of the polymer on LC properties have been examined. Through this work, insight has been gained regarding the impact that the introduction of a fluorinated monoacrylate monomer has on polymerization kinetics, LC organization, and monomer/polymer segregation and organization within a polymer/LC system. Fluorinated moieties lower the surface energy of the monomer to enhance segregation between the smectic layers of the LC as compared with an analogous aliphatic monomer. Additionally, the enhanced segregation significantly increases the polymerization rate in the smectic phase and drives the ...
Probes for Narcotic Receptor Mediated Phenomena

The synthesis of a series of epoxy 5-phenylmorphans is being explored in order to determine the conformational requirements of the phenolic ring in a phenylmorphan molecule that may be needed both for binding to a specific opioid receptor and for exhibiting opioid agonist or antagonist activity. Of the twelve possible ortho- and para-bridged isomers (a–f) (Fig. 1), we now report the synthesis of the para-d isomer, rac-(3R,6aS,11aR)-2-methyl-1,3,4,5,6,11a-hexahydro-2H-3,6a-methanobenzofuro[2,3-c]azocin-8-ol (3). Compound 3 was synthesized via construction of the 5-phenylazabicyclo[3.3.1]non-3-ene skeleton (Scheme 1) and subsequent closure of the epoxy bridge (Scheme 2). As determined by an X-ray diffraction study, the epoxy bridge, restricting the phenyl-ring rotation, fixed the dihedral angle between the least-squares planes through the phenyl ring and atoms N(2), C(3), C(11a), and C(6a) of the piperidine ring (Fig. 2) at 43.0°, and the torsion angle C(12)C(6a)C(6b)C(10a) at −95.0°.
The Evolution of the Biosphere: Towards a new Mythology

Abstract Any changing system both develops and evolves (individuates). The evolution of the biosphere must therefore be taken in context of the development of the earth, which appears to have followed typical developmental rules of dissipative structures. Two different perspectives are possible on dissipative structures—the classical externalist perspective, which views open systems as becoming progressively negentropic, and the newer, internalist perspective, which views them from within as becoming increasingly disorderly. A history of the universe can be traced, alternately stressing the one and the other perspective, which can form the basic structure of a modern, science‐based creation myth.
An Analysis of Tenure and House Structure Type by Household Composition

This study examined the relation of household composition and characteristics with each of two variables, tenure status and structural type of residence. Past research related to tenure status has considered household composition and characteristics in a limited manner, and very little empirical work has addressed the relations of those variables with house structure type. The three structure types assessed were manufactured housing, multifamily site-built homes, and single-family site-built homes. The authors extended past research by considering more complicated household compositions and also identified the importance of knowing more complete information about all the residents of a home to understand both tenure and house structure type. Family composition and the presence of extended family members, an unmarried partner, and other unrelated individuals all explained di ferences in tenure and house structure type. The findings suggest the significance of family and household characteristics when understanding variations in tenure and house structure type.
Optical properties of silicon related insulators

We report a study of the optical properties of silicon related insulators. Essentially, the following materials have been considered in this study; noncrystalline Si3N4, SiO2, SiO, and crystalline SiO2. Utilizing the available data of the refractive index and the extinction coefficient in the literature, the related optical properties such as (i) the real (e1) and imaginary (e2) parts of the complex‐dielectric constant, (ii) absorption coefficient (α), and (iii) electronic polarizability (αe) are calculated. The optical gaps EG of these materials have been estimated employing the Tauc rule and the Cody alternative. Extrapolation of the band‐structural and spectroscopic models of Penn [Phys. Rev. 128, 2093 (1962)] and Wemple and Didomenico [Phys. Rev. B 3, 1338 (1971)] are then made to evaluate some band‐structural parameters of these materials. Interpretations of the energy corresponding to the peak in e2 are then sought in terms of the Penn gap Ep. Whenever relevant, comparisons and correlations of the o...
Electrochemical impedance spectroscopy response of water uptake in organic coatings by finite element methods

Abstract The corrosion of metals is a long standing topic of research which is of immense economic importance. One of the principal means of preventing surface corrosion of metals is thin polymer coatings, i.e. paint. These coatings often fail because of the passage of water or other active ionic species into and through the polymer coating. Since both the capacitance and the resistance of a polymer coating change as it absorbs water, electrochemical impedance spectroscopy (EIS) gives a general idea of how much water a polymer has been absorbed. Theories, such as the Brasher–Kingsbury approximation, are effective medium theories based on the assumption that the absorbed water is randomly distributed in spherical inclusions. The water in a coating may be distributed as spherical inclusions, as discrete channels, or as some combination that transports water from the coating surface until the water reaches the metal substrate and corrosion can begin. The resistance and the capacitance of a coating depend on both the amount of water (volume fraction) and the shape of the water inclusions. EIS gives only a general idea of how much water has been absorbed by a coating but does not provide the distribution or shape of the water inclusions. EIS circuit response is often modeled with the equivalent circuit elements describing the material properties for water inclusions that are implicitly assumed to be randomly distributed spherical inclusions. Numerical calculations using the finite element analysis (FEA) are reported here to solve Maxwell's equations for various shapes and sizes of water inclusions within the polymer. Calculations here have been based on the electrical properties of a polyvinyl fluoride film, as an exemplar, with water inclusions of different shapes and concentrations (water volume fraction). The Brasher–Kingsbury approximation gives the correct outcome only for a random distribution of spherical inclusions, as expected. Other shapes and distributions can vary from the Brasher–Kingsbury prediction of water volume fraction by more than 50% of the actual gravimetric water volume fraction. Results are presented here for spherical and cylindrical randomly distributed water inclusions. Understanding the sensitivity to different distributions and numbers of inclusions is an objective planned for future research.
The genetics of cell death: approaches, insights and opportunities in Drosophila

Cell death is ubiquitous in metazoans and involves the action of an evolutionarily conserved process known as programmed cell death or apoptosis. In Drosophila melanogaster, it is now uniquely possible to screen for genes that determine the fate — life or death — of any cell or population of cells during development and in the adult. This review describes these genetic approaches and the key insights into cell-death mechanisms that have been obtained, as well as the outstanding questions that these techniques can help to answer.
Effect of Pressure on the Dielectric Constant of Vitreous Silica

SINCE there are, to our knowledge, no reported observations of the effect of pressure on the dielectric constant of any solid, the data that we have obtained on this effect in vitreous silica may be of some interest, even though the precision of our results is low, and vitreous silica is far from being a typical solid.
A geographical analysis of the Atalanti alluvial plain and coastline as the location of a potential tourist site, Bronze through Early Iron Age Mitrou, East-Central Greece

Abstract Tourism accounts for 15% of Greece’s gross domestic product. In the wake of a struggling economy many of Greece’s coastal villages have turned to tourism to supplement local economies. Preliminary analysis of structural and cultural materials recovered from an excavation on Mitrou, a small islet near the coastal village Tragana located 140 km north of Athens has established the site’s contribution to a fuller understanding of settlement practices in Central Greece from the end of the Bronze Age through the Early Iron Age. The site’s historic importance combined with its scenic coastal setting has considerable potential to be developed into an important tourist site. The physical geography of the region is the product of the complex interaction of coastal, alluvial, fluvial, and seismic processes. This investigation integrates the archaeological material with a geographical analysis employing a variety of geographical techniques (soil and sediment analysis, past climatic data, environmental surveys, and geospatial modeling) to reconstruct the geomorphological history of the site and to evaluate the area as a potential tourist site.
Polarization multiplexed (D)QPSK InP receiver photonic integrated circuits

In this paper we review recent developments in the area of receiver photonic integrated circuits for the implementation of polarization multiplexed (differentially coded), quadrature phase shift keying (DQPSK) transmission formats.
Topography of the simian rotavirus nonstructural glycoprotein (NS28) in the endoplasmic reticulum membrane.

Abstract The simian rotavirus SA11 genome segment 10 codes for a nonstructural glycoprotein, NS28, that has been hyphthesized to be involved in budding of viral particles into the endoplasmic reticulum (ER) membrane. Previous studies had suggested that NS28 is an integral membrane protein of the ER, possibly a transmembrane protein. We have examined the topography of NS28 inserted in microsomal membranes following cell-free translation of genome segment 10 transcripts. These transcripts were obtained either by hybrid selection of mRNA synthesized by the endogenous viral RNA polymerase or by in vitro transcription of genome segment 10 cDNA using SP6 polymerase. Full-length and truncated gene 10 transcripts were translated in a cell-free system supplemented with dog pancreatic microsomes. The existence of a cytoplasmic domain of the translation product was demonstrated by protease protection experiments. An 18,000 (18K) mol wt glycosylated polypeptide was protected from digestion with proteinase K and trypsin, whereas chymotrypsin digestion yielded a 23K mol wt glycosylated polypeptide. Correlation of these biochemical data with the known sequence of NS28 that a 10K mol wt hydrophilic, carboxy-terminal fragment (from amino acid number 86 to amino acid number 175) of this glycoprotein is exposed on the cytoplasmic side of the ER membrane. A model of how NS28 folds in the ER membrane is proposed.
Continuing implications of the early evidence against the drive-reduction hypothesis of the behavioral effects of drugs.

Abstract Rationale. Early psychopharmacologists often explained the behavioral effects of drugs as due to changes in the hypothetical construct of motivation, implying that drug effects would depend on the inherent properties of the reinforcer that maintains responding. The work of Dews, Morse, and Kelleher offered an alternative explanation that the scheduling of reinforcers, and the patterns and rates of responding maintained, were more important determinants of drug effects. Objective. The present paper reviews the literature on the influence on drug effects of the type of reinforcer that maintains responding. Methods. Studies that examined the effects of drugs on behaviors maintained by different reinforcers were compared with studies that examined behaviors maintained by the same reinforcer under various conditions. Results. Over a wide range of conditions, the effects of drugs depend more on the schedule-controlled patterns and rates of responding than on the particular reinforcer. However, there are some conditions under which the reinforcer that maintains behavior can also determine drug effects. The broad implications of these findings in selected areas of psychopharmacology are discussed. Conclusions. Under some conditions drug effects are ostensibly consistent with explanations in terms of traditional hypothetical constructs, though under a wide range of other conditions they are not. A more general understanding of the behavioral effects of drugs comes from directing the emphasis of research away from hypothetical constructs and towards the empirically defined determinants of the behavioral effects of drugs.
On the mechanical behaviour of fibre-reinforced crystalline materials

Abstract A theoretical analysis of the mechanical behaviour of fibre-reinforced crystalline materials is presented in terms of the elastic and plastic properties of the components. Certain room temperature mechanical behaviour of fibre-reinforced composites is predicted using an ‘inclusion’ concept and from geometric, clastic, statistical distribution and plastic strength considerations. Certain elevated temperature mechanical behaviour of fibre-reinforced composites is predicted using a universal viscoelastic concept.
Antenna reception of nonisotropic stochastic fields

Abstract The response of an antenna with specified bandwidth characteristics to a complex, partially polarized, random process of arbitrary bandwidth is treated from the combined viewpoint of the theory of statistical communications, antenna theory, and the theory of optics. A stochastic spectral representation that accounts for the spatial variations of a random wave process is developed and used to determine the open circuit voltage excited in an antenna via the interaction of the incident process with the frequency varying far field pattern of the antenna. A general formula is derived for the autocorrelation function at the terminals of a receiving antenna in terms of the coherency matrix of the incident process and the antenna height function. This formulation applies for incoherent stochastic processes. The available power at the terminals of the antenna is related to this autocorrelation function.
Subfair “Red-and-Black” in the presence of inflation

The gambling problem of “Red-and-Black” casinos in the presence of inflation is introduced. The optimality of the bold strategy is shown when the lottery is subfair or fair. The non-optimality of the bold strategy is also shown when the lottery is superfair.
The 85-kD Cytosolic Phospholipase A2 Knockout Mouse A New Tool for Physiology and Cell Biology

Phospholipases are enzymes that hydrolyze phospholipids ([Figure 1][1]). These enzymes may be placed into two broad classes: ( 1 ) acyl hydrolases (phospholipase A1 [PLA1], which hydrolyzes the lipid at the sn-1 -acyl ester bond; phospholipase A2 [PLA2], which acts at the sn-2 position; and
Cyanobiphenyl‐substituted polymethylsiloxane encapsulated particles for packed capillary column supercritical fluid chromatography

Nine isomeric cyanobiphenyl-substituted (25%) polymethylsiloxane (CBP) stationary phases were coated and immobilized by free-radical crosslinking on silica packing materials for use in supercritical fluid chromatography (SFC). The selectivities of these packing materials to benzene derivatives, polycyclic aromatic hydrocarbons (PAHs), and double bonds in fatty acid methylesters (FAMEs) were determined. Among the nine isomeric CBP-coated packing materials, the o, p-CBP phase was found to be the most selective to both double bonds and aromatic isomers under SFC conditions. The durability of the packing materials was evaluated by measuring the changes in selectivity with SFC use. The loss in selectivity was less than 0.20% after being continuously washed by supercritical carbon dioxide at 100°C and 300 atm for more than 100 h.
SULFHYDRYL GROUPS AND THE INTERACTION BETWEEN THE HEMES IN HEMOGLOBIN

1. Dialysis of a hemoglobin solution against slightly alkaline buffer (pH 8.68) causes a decrease in heme-heme interaction. The value of n in Hill's equation drops from 2.9 to 2.0, while the oxygen affinity increases slightly. Addition of glutathione largely reverses the effects of dialysis ( n rises from 2.0 to 2.5 to 2.6). 2. Addition of the sulfhydryl reagent, p -chloromercuribenzoate (1.8 x 10–3 M), results in a large though not complete blocking of heme-heme interaction. The value of n drops from 2.9 to 1.4. This effect is largely reversed with glutathione ( n rises to 2.6).
Electronic Submission Process

The National Institutes of Health (NIH) has been in the process of replacing the paper grant application submission process with an electronic submission process since the year 2005, and, as of January, 2009, has completed a substantial portion of that transition. The shift to electronic submission is part of a larger process known as Electronic Research Administration (eRA) at NIH. eRA provides information technology solutions and support for the full life cycle of grants administration functions for the NIH, Operating Divisions of the Department of Health and Human Services (DHHS), and other federal agencies. This chapter provides a guide to the key steps of the electronic submission process.
Equivalent Moving Dipole Localization of Cardiac Ectopic Activity in a Swine Model During Pacing

Localization of the initial site of cardiac ectopic activity has direct clinical benefits for treating focal cardiac arrhythmias. The aim of the present study is to experimentally evaluate the performance of the equivalent moving dipole technique on noninvasively localizing the origin of the cardiac ectopic activity from the recorded body surface potential mapping (BSPM) data in a well-controlled experimental setting. The cardiac ectopic activities were induced in four well-controlled intact pigs by either single-site pacing or dual-site pacing within the ventricles. In each pacing study, the initiation sites of cardiac ectopic activity were localized by estimating the locations of a single moving dipole (SMD) or two moving dipoles (TMDs) from the measured BSPM data and compared with the precise pacing sites (PSs). For the single-site pacing, the averaged SMD localization error was 18.6 ± 3.8 mm over 16 sites, while the averaged distance between the TMD locations and the two corresponding PSs was slightly larger (24.9 ± 6.2 mm over five pairs of sites), both occurring at the onset of the QRS complex (10-25 ms following the pacing spike). The obtained SMD trajectories originated near the stimulus site and then traversed across the heart during the ventricular depolarization. The present experimental results show that the initial location of the moving dipole can provide the approximate site of origin of a cardiac ectopic activity in vivo, and that the migration of the dipole can portray the passage of an ectopic beat across the heart.
The Spread of Statistical Significance Testing in Psychology The Case of the Journal of Applied Psychology, 1917-1994

Because the widespread use of statistical significance testing has deleterious consequences for the development of a cumulative knowledge base, the American Psychological Association's Board of Scientific Affairs is in the process of appointing a Task Force whose charge includes the possibility of phasing out such testing in textbooks and journal articles. Just how popular is significance testing in psychology? This issue is examined in the present historical study, which uses data from randomly selected issues of the Journal of Applied Psychology for the period 1917-94. Results indicate that the practice of significance testing, at one time of restricted usage, has expanded to the point that it is virtually synonymous with empirical analysis. The data also lend support to Gigerenzer and Murray's (1987) allegation that an inference revolution occurred in psychology during the period 1940-55. Unfortunately, it is concluded that the ubiquity of significance testing constitutes a classic example of the overa...
Mechanisms of Activation of Slo2.1 Channels by Intracellular Na

The open probability of Slo2 K+ channels is low under physiological conditions, but is increased dramatically by elevation of [Na+]i. Mutation of the Asp in the Na+ coordination motif (DXRXXH) of Kir3 or Slo2.2 channels was previously reported to greatly reduce channel sensitivity to [Na+]i. The intracellular C-terminus of Slo2.1 subunits contains five potential Na+ binding motifs. The Asp residue in each of these five sequences was mutated to Arg. Surprisingly, unlike Slo2.2, Slo2.1 channel currents showed little or no activity with high [Na+]i (100 or 300 mM) in excised inside-out macro-patches from Xenopus oocytes or HEK cells. Addition of PIP2, Ca2+, cAMP, NAD+, GTP and ATP to the high Na+ solution also failed to activate Slo2.1. The presence of functional Slo2.1 channels in the patch was confirmed by activation with niflumic acid (NFA). To circumvent this problem, activation of channels by elevated [NaCl]i was studied using whole cell currents. Channels containing a single Asp to Arg mutation were expressed in Xenopus oocytes and currents were recorded by using two-microelectrode voltage clamp. [NaCl]i was elevated by using microelectrodes filled with 2M NaCl. All mutant channels other than D757R responded to intracellular NaCl loading similar to WT channels. D757R channels were activated by 1 mM NFA, confirming their functional expression. Similar results were obtained for whole cell currents recorded in HEK cells expressing WT or D757R Slo2.1 channels. With 70 mM NaCl in the pipette solution, WT Slo2.1 current increased 30-fold, whereas D757R currents were not activated. Both WT and D757R channel currents were increased >150-fold by 0.5-1 mM NFA. Together these findings indicate that a crucial soluble cofactor required for activation of channels is lost upon patch excision and that Asp757 is the primary determinant of Na+ activation of Slo2.1.
Perceptions of the Extent of Problem Gambling Within New Casino Communities

Several recent studies using objective measures have found that the rate of pathological gambling in the U.S. is less than 5%. To determine the general population's perception of the prevalence of pathological gambling, a survey was conducted in seven communities where casinos have recently opened. Of the 1631 respondents who provided an estimate, the mean response was that 16% of the community residents were problem gamblers, more than three times the rate found by studies using specific diagnostic criteria. A regression equation found several demographic and attitudinal items are associated with higher prevalence estimates. In addition, the data support a “close to home” hypothesis that respondents who have relatives who have experienced problems with gambling will tend to perceive higher rates of problem gambling in the community.
JAK2 inhibition prevents innate immune responses and rescues animals from sepsis

Sepsis, a leading cause of death in hospitalized patients, is characterized by lethal systemic inflammatory responses. JAK2 is an essential tyrosine kinase modulating immune responses. However, the implications of JAK2 in infectious disorders remain undetermined. Here, we report that JAK2 inhibitors rescue animals from polymicrobial sepsis in a clinically relevant time frame. JAK2 inhibition with AG490 prevents NF-κB activation, modulates macrophage activation, and restrains the production of inflammatory cytokines. The inhibition of JAK2 blunted TNF production in both macrophages and splenocytes in a concentration-dependent manner. JAK2 inhibition specifically prevents LPS-induced STAT3 tyrosine phosphorylation without affecting serine phosphorylation in macrophages. JAK2 inhibitor prevents the activation of the canonical p65RelA/p50NF-κB1 pathway but not the other NF-κB proteins. In vivo, JAK2 inhibition restrains serum TNF levels by modulating TNF production in the lung and the spleen and protects mice from lethal endotoxemia in a concentration-dependent manner. AG490 also inhibits extracellular release of HMGB1 from macrophages and prevents an increase in serum HMGB1 levels during sepsis. JAK2 inhibition started at 24 h after the onset of sepsis rescued the mice from polymicrobial sepsis. Our study is the first experimental evidence that JAK2 inhibitors may provide a pharmacological advantage for the treatment of sepsis in a clinically relevant time frame.
Ralstonia solanacearum Needs Motility for Invasive Virulence on Tomato

Ralstonia solanacearum, a widely distributed and economically important plant pathogen, invades the roots of diverse plant hosts from the soil and aggressively colonizes the xylem vessels, causing a lethal wilting known as bacterial wilt disease. By examining bacteria from the xylem vessels of infected plants, we found that R. solanacearum is essentially nonmotile in planta, although it can be highly motile in culture. To determine the role of pathogen motility in this disease, we cloned, characterized, and mutated two genes in the R. solanacearum flagellar biosynthetic pathway. The genes for flagellin, the subunit of the flagellar filament (fliC), and for the flagellar motor switch protein (fliM) were isolated based on their resemblance to these proteins in other bacteria. As is typical for flagellins, the predicted FliC protein had well-conserved N- and C-terminal regions, separated by a divergent central domain. The predicted R. solanacearum FliM closely resembled motor switch proteins from other proteobacteria. Chromosomal mutants lacking fliC or fliM were created by replacing the genes with marked interrupted constructs. Since fliM is embedded in the fliLMNOPQR operon, the aphA cassette was used to make a nonpolar fliM mutation. Both mutants were completely nonmotile on soft agar plates, in minimal broth, and in tomato plants. The fliC mutant lacked flagella altogether; moreover, sheared-cell protein preparations from the fliC mutant lacked a 30-kDa band corresponding to flagellin. The fliM mutant was usually aflagellate, but about 10% of cells had abnormal truncated flagella. In a biologically representative soil-soak inoculation virulence assay, both nonmotile mutants were significantly reduced in the ability to cause disease on tomato plants. However, the fliC mutant had wild-type virulence when it was inoculated directly onto cut tomato petioles, an inoculation method that did not require bacteria to enter the intact host from the soil. These results suggest that swimming motility makes its most important contribution to bacterial wilt virulence in the early stages of host plant invasion and colonization.
Object recognition using multi-layer Hopfield neural network

An object recognition approach based on concurrent coarse-and-fine matching using a multi-layer Hopfield neural network is presented. The proposed network consists of several cascaded single layer Hopfield networks, each encoding object features at a distinct resolution, with bidirectional interconnections linking adjacent layers. The interconnection weights between nodes associating adjacent layers are structured to favor node pairs for which model translation and rotation, when viewed at the two corresponding resolutions, are consistent. This inter-layer feedback feature of the algorithm reinforces the usual intra-layer matching process in conventional single layer Hopfield nets in order to compute the model-object match which is most consistent across several resolution levels. The performance of the algorithm is demonstrated in cases of images containing single and multiple occluded objects. These results are compared with recognition results obtained using a single layer Hopfield network. >
Sensitivity study of rock-physics parameters for modeling time-lapse seismic response of Norne field

ABSTRACTTime-lapse seismic modeling is an important step in joint inversion of time-lapse seismic and production data of a field. Rock-physics analysis is the basis for modeling the time-lapse seismic data. However, joint inversion of both types of data for estimation of reservoir parameters is highly nonlinear and complex with uncertainties at each step of the process. So it is essential, before proceeding with large-scale history matching, to investigate sensitive rock-physics parameters in modeling the time-lapse seismic response of a field. We used the data set of the Norne field to investigate sensitive parameters in time-lapse seismic modeling. We first investigated sensitive parameters in the Gassmann’s equation. The investigated parameters include mineral properties, water salinity, pore pressure, and gas-oil ratio. Next, we investigated parameter sensitivity for time-lapse seismic modeling of the Norne field. The investigated rock-physics parameters are clay content, cement fraction, average numb...
Biosensor for Direct Determination of Fenitrothion and EPN Using Recombinant Pseudomonas putida JS444 with Surface Expressed Organophosphorus Hydrolase. 1. Modified Clark Oxygen Electrode

A whole cell-based amperometric biosensor for highly selective, sensitive, rapid, and cost-effective determination of the organophosphate pesticides fenitrothion and ethyl p-nitrophenol thiobenzenephosphonate (EPN) is discussed. The biosensor comprised genetically engineered p-nitrophenol (PNP)-degrading bacteria Pseudomonas putida JS444 anchoring and displaying organophosphorous hydrolase (OPH) on its cell surface as biological sensing element and carbon paste electrode as the amperometric transducer. Surface-expressed OPH catalyzed the hydrolysis of organophosphorous pesticides such as fenitrothion and EPN to release PNP and 3-methyl-4-nitrophenol, respectively, which were subsequently degraded by the enzymatic machinery of P. putida JS444 through electrochemically active intermediates to the TCA cycle. The electrooxidization current of the intermediates was measured and correlated to the concentration of organophosphates. Operating at optimum conditions, 0.086 mg dry wt of cell operating at 600 mV of applied potential (vs Ag/AgCl reference) in 50 mM citratephosphate buffer, pH 7.5, with 50 μM CoCl2 at room temperature, the biosensor measured as low as 1.4 ppb of fenitrothion and 1.6 ppb of EPN. There was no interference from phenolic compounds, carbamate pesticides, triazine herbicides, or organophosphate pesticides without nitrophenyl substituent. The service life of the biosensor and the applicability to lake water were also demonstrated.
Twinsburg, Ohio; Twinsburg Research Institute; Twin study summaries; The outside world.

Recent plans to establish a Twinsburg Research Institute in Twinsburg, Ohio, home of the annual Twins Days Festival, are reviewed. Included among the topics under discussion were the development of an Ohio and/or national United States twin registry and the appropriate location for such a facility. Next, recent findings on chromosomal anomalies and other adverse consequences of artificial reproduction are summarized - some results are surprising and unexplained. This information is followed by further examination of epigenetic twin studies, supplementing a review in a previous issue. The last section of this article presents insightful material about twin leaders, scholars, athletes, designers and parents.
Relative efficiency of the sequential probability ratio test in signal detection

The relative efficiency of a sequential hypothesis test compared to a fixed sample size test is defined as the ratio of the expected sample size of the sequential test to the sample size of the fixed sample size test with the same size and power. Asymptotic behavior of the relative efficiency is studied for the detection of a constant signal in additive noise. With some regularity conditions imposed on the noise density, the asymptotic relative efficiency of the sequential probability ratio test with respect to the corresponding fixed sample size likelihood ratio test is a function of the size and the power. As the size a approaches zero and the power approaches unity, this asymptotic relative efficiency has a limiting value depending on the functional relationship of a and 1 - \beta as they approach zero. Comparison of the power functions is also studied.
THE FIRST MODERN REALIST: FELIX GILBERT'S MACHIAVELLI AND THE REALIST TRADITION IN INTERNATIONAL THOUGHT*

In the disciplines of political science and international relations, Machiavelli is unanimously considered to be “the first modern realist.” This essay argues that the idea of a realist tradition going from the Renaissance to postwar realism founders when one considers the disrepute of Machiavelli among early international relations theorists. It suggests that the transformation of Machiavelli into a realist thinker took place subsequently, when new historical scholarship, informed by strategic and political considerations related to the transformation of the US into a global power, generated a new picture of the Renaissance. Focusing on the work of Felix Gilbert, and in particular his Machiavelli and Guicciardini, the essay shows how this new interpretation of Machiavelli was shaped by the crisis of the 1930s, the emergence of security studies, and the philanthropic sponsorship of international relations theory.
Logic controller design for multivariable systems

The essential features of the proposed class of logic controllers are: (i) an overlapping polar partition of the m-dimensional output space into m+1 regions with a common vertex at the origin, (ii) an efficient parameterization of these regions, and (iii) the systematic construction of the output space to guarantee stability and performance of a nonlinear system when sufficient information on plant dynamics exists to enable design.
Characterization of a Goα Mutant That Binds Xanthine Nucleotides

Several GTP binding proteins, including EF-Tu, Ypt1, rab-5, and FtsY, and adenylosuccinate synthetase have been reported to bind xanthine nucleotides when the conserved aspartate residue in the NKXD motif was changed to asparagine. However, the corresponding single Goα mutant protein (D273N) did not bind either xanthine nucleotides or guanine nucleotides. Interestingly, the introduction of a second mutation to generate the Goα subunit D273N/Q205L switched nucleotide binding specificity to xanthine nucleotide. The double mutant protein GoαD273N/Q205L (GoαX) bound xanthine triphosphate, but not guanine triphosphate. Recombinant GoαX (GoαD273N/Q205L) formed heterotrimers with βγ complexes only in the presence of xanthine diphosphate (XDP), and the binding to βγ was inhibited by xanthine triphosphate (XTP). Furthermore, as a result of binding to XTP, the GoαX protein underwent a conformational change similar to that of the activated wild-type Goα. In transfected COS-7 cells, we demonstrate that the interaction between GoαX and βγ occurred only when cell membranes were permeabilized to allow the uptake of xanthine diphosphate. This is the first example of a switch in nucleotide binding specificity from guanine to xanthine nucleotides in a heterotrimeric G protein α subunit.
Tiered Models of Integrated Academic and Behavioral Support: Effect of Implementation Level on Academic Outcomes

This exploratory study examined (a) Integrated Systems Model (ISM) implementation levels, and (b) the effect of implementation of the academic and behavioral components of ISM on student academic outcomes. Participants included 2,660 students attending six suburban elementary schools. Hierarchical linear regression was conducted using a control block of three school demographic variables (initial student oral reading fluency from one year prior, percentage of economically disadvantaged students, and percentage of non-minority students), and a block of three implementation variables (academic, behavioral, and overall implementation of ISM). A mean of 55% overall implementation was found, with higher implementation of the behavioral than the academic components of ISM. Three significant regression models were found, and a positive effect of academic implementation emerged. Limitations and implications are discussed.
Design and operation of a small unmanned aerial vehicle with multiple tentacles

In this paper the author presents preliminary and developmental stages of a multi-tentacle MAV (micro air vehicle) platform and its first flight, to be used for various possible operations. The platform consists of a quadcopter base and three of 4 DOF (degrees of freedom) small finger-sized tentacles attached. Unlike mobile manipulating research, which focuses more on the stability and control of manipulators and floating platform, the multiple tentacle system presented in this paper introduces a new design and uncultivated aspects of operational applications of small-scaled aerial robots. The most meaningful implication of the mobile manipulating system in general and multiple tentacle aerial vehicles in this paper is its extended locomotion. Unlike the flying-only vehicles that currently exist and the current trends of unmanned aerial vehicles for achieving only aerial missions while navigation, tentacles enable vehicles to interact with the environment. Some of the mechanisms include object pickup/release, landing on irregular surfaces, perching, and even additional propulsion force for taking off. These concepts are easily observed by almost all types of animals including humans.
Microfabricated Devices for Studying the Metabolism and Cytotoxicity of Drug Candidates

During drug development, large libraries of new chemical entities (NCEs) are generated and undergo in vitro screens of metabolism and cytotoxicity. These screens are heavily relied upon to select lead compounds with the highest chance of success in pre-clinical studies and clinical trials, but suffer from limited in vivo predictive power despite using human liver-derived components. There is a need for new assays that utilize smaller reagent volumes to reduce the cost of these high-throughput screens; better mimic the liver environment; and ultimately account for toxicities in other major organ systems. Microfabricated devices, in their current state, integrate multiple reaction steps in a single device, decreasing the cost of a single metabolism or cytotoxicity screen by lowering the reagent consumption and increasing throughput. The incorporation of three-dimensional co-cultures in these devices promise increased accuracy of in vitro screens, because cellular phenotype and response of hepatocytes in these cultures are more representative of the liver. In this review, we focus on microfabricated devices developed over the past decade and highlight technologies that we believe have the potential of reaching shorter- and longer-term goals of reducing the cost of bringing new drugs to market and revolutionizing the discovery stage of the drug development pipeline.
The Pericardial Sinus, a Neurohemal Organ in Cyclorrhaphan Flies

An ultrastructural study of the heart of the stable fly, Stomoxys calcitrans (Meola and Cook, 1986) revealed that the pericardial sinus (PS) associated with this heart is a neurohemal site for the release of products of the segmental nerves. This neurohemal area extends from the metathoracic apodeme to that of the 5th abdominal segment and is bounded dorsally by the heart (Ht) and ventrally by the pericardial septum (dorsal diaphram) (Figs. 1, 2). A study was initiated to determine whether this neurohemal area was present in other cyclorrhaphans. Eight species consisting of four families were prepared for ultrastructural analysis. In addition to S. calcitrans, four other species of muscids were studied: Haematobia irritans, Musca domestica, Glossina morsitans and Orthellia caesarion. Other families included Sarcophagidae (Ravinia derelicta), Calliphoridae (Lucilia cuprina), and Drosophilidae (Drosophila melanogaster).