2,763 research outputs found

    Sex distribution of offspring-parents obesity: Angel's hypothesis revisited

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    This study, which is based on two cross sectional surveys' data, aims to establish any effect of parental obesity sex distribution of offspring and to replicate the results that led to the hypothesis that obesity may be associated with sex-linked recessive lethal gene. A representative sample of 4,064 couples living in Renfrew/Paisley, Scotland was surveyed 1972-1976. A total of 2,338 offspring from 1,477 of the couples screened in 1972-1976, living in Paisley, were surveyed in 1996. In this study, males represented 47.7% among the total offspring of the couples screened in 1972-1976. In the first survey there was a higher male proportion of offspring (53%, p < 0.05) from parents who were both obese, yet this was not significant after adjustment for age of parents. Also, there were no other significant differences in sex distribution of offspring according to body mass index, age, or social class of parents. The conditions of the original 1949 study of Angel (1949) (which proposed a sex-linked lethal recessive gene) were simulated by selecting couples with at least one obese daughter. In this subset, (n = 409), obesity in fathers and mothers was associated with 26% of offspring being male compared with 19% of offspring from a non-obese father and obese mother. Finally we conclude that families with an obese father have a higher proportion of male offspring. These results do not support the long-established hypotheses of a sex-linked recessive lethal gene in the etiology of obesity

    Systematic analysis of off-target effects in an RNAi screen reveals microRNAs affecting sensitivity to TRAIL-induced apoptosis.

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    BACKGROUND: RNA inhibition by siRNAs is a frequently used approach to identify genes required for specific biological processes. However RNAi screening using siRNAs is hampered by non-specific or off target effects of the siRNAs, making it difficult to separate genuine hits from false positives. It is thought that many of the off-target effects seen in RNAi experiments are due to siRNAs acting as microRNAs (miRNAs), causing a reduction in gene expression of unintended targets via matches to the 6 or 7 nt 'seed' sequence. We have conducted a careful examination of off-target effects during an siRNA screen for novel regulators of the TRAIL apoptosis induction pathway(s). RESULTS: We identified 3 hexamers and 3 heptamer seed sequences that appeared multiple times in the top twenty siRNAs in the TRAIL apoptosis screen. Using a novel statistical enrichment approach, we systematically identified a further 17 hexamer and 13 heptamer seed sequences enriched in high scoring siRNAs. The presence of one of these seeds sequences (which could explain 6 of 8 confirmed off-target effects) is sufficient to elicit a phenotype. Three of these seed sequences appear in the human miRNAs miR-26a, miR-145 and miR-384. Transfection of mimics of these miRNAs protects several cell types from TRAIL-induced cell death. CONCLUSIONS: We have demonstrated a role for miR-26a, miR-145 and miR-26a in TRAIL-induced apoptosis. Further these results show that RNAi screening enriches for siRNAs with relevant off-target effects. Some of these effects can be identified by the over-representation of certain seed sequences in high-scoring siRNAs and we demonstrate the usefulness of such systematic analysis of enriched seed sequences

    Autonomous Light Management in Flexible Photoelectrochromic Films Integrating High Performance Silicon Solar Microcells

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    Commercial smart window technologies for dynamic light and heat management in building and automotive environments traditionally rely on electrochromic (EC) materials powered by an external source. This design complicates building-scale installation requirements and substantially increases costs for applications in retrofit construction. Self-powered photoelectrochromic (PEC) windows are an intuitive alternative wherein a photovoltaic (PV) material is used to power the electrochromic device, which modulates the transmission of the incident solar flux. The PV component in this application must be sufficiently transparent and produce enough power to efficiently modulate the EC device transmission. Here, we propose Si solar microcells (ÎŒ-cells) that are i) small enough to be visually transparent to the eye, and ii) thin enough to enable flexible PEC devices. Visual transparency is achieved when Si ÎŒ-cells are arranged in high pitch (i.e. low-integration density) form factors while maintaining the advantages of a single-crystalline PV material (i.e., long lifetime and high performance). Additionally, the thin dimensions of these Si ÎŒ-cells enable fabrication on flexible substrates to realize these flexible PEC devices. The current work demonstrates this concept using WO₃ as the EC material and V₂O₅ as the ion storage layer, where each component is fabricated via sol-gel methods that afford improved prospects for scalability and tunability in comparison to thermal evaporation methods. The EC devices display fast switching times, as low as 8 seconds, with a modulation in transmission as high as 33%. Integration with two Si ÎŒ-cells in series (affording a 1.12 V output) demonstrates an integrated PEC module design with switching times of less than 3 minutes, and a modulation in transmission of 32% with an unprecedented EC:PV areal ratio

    The Impact of Presentence Investigations on Plea Bargained Dispositions in Kings County Supreme Court

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    This study examines the presentence function of probation from an historical and empirical perspective which argues that the purported diminution of the role of the presentence report (PSR) in the sentencing process–as a result of sentence bargaining–is more reflective of a prevailing disenchantment with the rehabilitative ideal than any thoroughly considered, reliable validation of the PSR\u27s dispensibility. It is demonstrated, through a review of the literature, that poorly conceived, polemically biased empirical research has helped to perpetuate the notion that these reports have little value. A survey of studies and inquiries conducted in New York over the past twenty years highlights this argument. PSRs, formerly considered an enlightened fulcrum for the ameliorating correctional and sentencing reforms of the Progressive era, eventually were linked to the potential and/or actual abuses of indeterminate sentencing schemes by civil libertarians (concerned with sentencing disparity) and anti-positivist criminologists (critical of rehabilitation-directed correctional theory and practice). Such arguments, absent any sustained or substantive rebuttal from the probation community, bolstered executive branch efforts to scapegoat the judiciary and gain more control over an instrument potentially regulative of jail/prison intake during an era of chronic overcrowding and attendant federal court intervention. The author\u27s own study of a random sample of PSRs from Kings County Supreme Court in New York City finds considerable evidence for the proposition that PSRs account for a significant proportion of the observed variance between sentence promised and sentence imposed. Path analysis finds that the custodial status has the most effect on the plea bargain and the recommendation of the probation officer, but the latter is the single most important predictor of the eventual disposition. Further analysis suggests that PSRs containing the most relevant information are more likely to result in amendments of the sentence bargain, while perfunctory reports are most likely merely to endorse the sentence already promised. An examination of reaction to a recent attempt to eviscerate the PSR\u27s content in New York lends further support to this study\u27s hypothesis that presentence reports have much more utility in the criminal justice system than the revisionist literature suggests

    Denominator identities for finite-dimensional Lie superalgebras and Howe duality for compact dual pairs

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    We provide formulas for the denominator and superdenominator of a basic classical type Lie superalgebra for any set of positive roots. We establish a connection between certain sets of positive roots and the theory of reductive dual pairs of real Lie groups. As an application of our formulas, we recover the Theta correspondence for compact dual pairs. Along the way we give an explicit description of the real forms of basic classical type Lie superalgebras.Comment: Latex, 75 pages. Minor corrections. Final version, to appear in the Japanese Journal of Mathematic

    Defining forgiveness: Christian clergy and general population perspectives.

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    The lack of any consensual definition of forgiveness is a serious weakness in the research literature (McCullough, Pargament &amp; Thoresen, 2000). As forgiveness is at the core of Christianity, this study returns to the Christian source of the concept to explore the meaning of forgiveness for practicing Christian clergy. Comparisons are made with a general population sample and social science definitions of forgiveness to ensure that a shared meaning of forgiveness is articulated. Anglican and Roman Catholic clergy (N = 209) and a general population sample (N = 159) completed a postal questionnaire about forgiveness. There is agreement on the existence of individual differences in forgiveness. Clergy and the general population perceive reconciliation as necessary for forgiveness while there is no consensus within psychology. The clergy suggests that forgiveness is limitless and that repentance is unnecessary while the general population suggests that there are limits and that repentance is necessary. Psychological definitions do not conceptualize repentance as necessary for forgiveness and the question of limits has not been addressed although within therapy the implicit assumption is that forgiveness is limitless.</p

    The impact of the gut microbiota on drug metabolism and clinical outcome

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    The significance of the gut microbiota as a determinant of drug pharmacokinetics and accordingly therapeutic response is of increasing importance with the advent of modern medicines characterised by low solubility and/or permeability, or modified-release. These physicochemical properties and release kinetics prolong drug residence times within the gastrointestinal tract, wherein biotransformation by commensal microbes can occur. As the evidence base in support of this supplementary metabolic “organ” expands, novel opportunities to engineer the microbiota for clinical benefit have emerged. This review provides an overview of microbe-mediated alteration of drug pharmacokinetics, with particular emphasis on studies demonstrating proof of concept in vivo. Additionally, recent advances in modulating the microbiota to improve clinical response to therapeutics are explored

    The Morphological Effects of Two Antimicrobial Peptides, Hecate-1 and Melittin, on Escherichia Coli

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    The effects of the 26 amino acid, cationic, amphipathic, antibacterial peptide melittin and hecate-1, a 23 amino acid analog of it, on the gram negative bacterium Escherichia coli were investigated using scanning electron microscopy (SEM), transmission electron micros-copy (TEM), and freeze-fracture. Both peptides killed virtually all bacteria at the peptide concentration and cell density used. TEM and SEM revealed aggregates of bacteria entangled with material extruded from the bacterial surfaces. SEM revealed irregular bacterial surfaces with bleb-like projections. TEM and freeze-fracture indicate that the bacterial inner and outer membranes, as well as the peptidoglycan layer between, were extensively damaged. The cytoplasmic contents of the cells, however, did not appear radically disturbed, providing little evidence for osmotically induced cytolysis
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