6,232 research outputs found
U.S. and U.K. Interest Rates 1890 - 1934: New Evidence on Structural Breaks
This paper presents econometric evidence on whether the founding of the Federal Reserve in 1914 caused a structural change from level-stationarity to difference-stationarity in U.S. and U.K. short-term nominal interest rates. We develop new econometric tests that allow for parameter transitions to test for a break of this kind and undertake a grid search analysis of dates and speeds for the change. We find that U.S. nominal interest rates most likely evolved rapidly to difference-stationarity in June 1917. For the U.K. we fail to reject the null that U.K. interest rate series follow a difference stationary process over the entire period 1890-1934. Our analysis differs from previous research on this topic in that we take care to explore statistical uncertainty around parameter estimates, and incorporate higher order dynamics into our econometric analysis.
New approaches for estimating risk from exposure to diethylstilbestrol.
A subgroup from a National Institute of Environmental Health Sciences, workshop concerned with characterizing the effects of endocrine disruptors on human health at environmental exposure levels considered the question, If diethylstilbestrol (DES) were introduced into the market for human use today and likely to result in low-dose exposure of the human fetus, what would be required to assess risk? On the basis of an analysis of the quality of data on human DES exposure, the critical times and doses for inducing genital tract malformations and cancer must be determined. This would be facilitated through analysis of the ontogeny of estrogen receptor expression in the developing human genital tract. Models of low-dose estrogenic effects will have to be developed for human and rodent genital tract development. Mouse models offer many advantages over other potential animal models because of the wealth of the earlier literature, the availability of sensitive end points, the availability of mutant lines, and the possibility of generating genetically engineered model systems. Through multidisciplinary approaches, it should be possible to elucidate the cellular and molecular mechanisms of endocrine disruption elicited by estrogens during development and facilitate an assessment of risk to humans
Gene identification for the cblD defect of vitamin B12 metabolism
Background Vitamin B12 (cobalamin) is an essential cofactor in several metabolic pathways. Intracellular conversion of cobalamin to its two coenzymes, adenosylcobalamin in mitochondria and methylcobalamin in the cytoplasm, is necessary for the homeostasis of methylmalonic acid and homocysteine. Nine defects of intracellular cobalamin metabolism have been defined by means of somatic complementation analysis. One of these defects, the cblD defect, can cause isolated methylmalonic aciduria, isolated homocystinuria, or both. Affected persons present with multisystem clinical abnormalities, including developmental, hematologic, neurologic, and metabolic findings. The gene responsible for the cblD defect has not been identified.
Methods We studied seven patients with the cblD defect, and skin fibroblasts from each were investigated in cell culture. Microcell-mediated chromosome transfer and refined genetic mapping were used to localize the responsible gene. This gene was transfected into cblD fibroblasts to test for the rescue of adenosylcobalamin and methylcobalamin synthesis.
Results The cblD gene was localized to human chromosome 2q23.2, and a candidate gene, designated MMADHC (methylmalonic aciduria, cblD type, and homocystinuria), was identified in this region. Transfection of wild-type MMADHC rescued the cellular phenotype, and the functional importance of mutant alleles was shown by means of transfection with mutant constructs. The predicted MMADHC protein has sequence homology with a bacterial ATP-binding cassette transporter and contains a putative cobalamin binding motif and a putative mitochondrial targeting sequence.
Conclusions Mutations in a gene we designated MMADHC are responsible for the cblD defect in vitamin B12 metabolism. Various mutations are associated with each of the three biochemical phenotypes of the disorder
Examining Student Identification With The Alumni Organization At A 4-Year Commuter Campus
Past research has identified several institutional and individual antecedents that lead to greater intent to support an organization. This paper takes an organizational identification approach in developing an Alumni Relationship Model (ARM) that can be used by universities to generate greater support for their Alumni services activities. This paper shows that by going beyond traditional organizational identification models and by introducing new variables, it is possible to broaden and enrich both practice and theory of organizational identification within a university setting
Adolescents' experiences of street harassment: creating a typology and assessing the emotional impact
Purpose: Research examining young people's experiences of harassment has tended to focus on the school and digital environment. Despite street harassment being identified as a common experience for adult women, very few studies have explored adolescents' experiences of street harassment.
Methodology: A person centred analytical approach, based on experienced reporting, was used to create a typology of street harassment. Reports of street harassment were received from 118 (68 female, 43 male, 7 no gender reported) 11- to 15-year-olds over a 6 to 8 week period.
Findings: Cluster analysis revealed four distinct groups: "predominately verbal", "non-verbal/non-direct", "other incident", and "all forms". Young women and those in the "all forms" group reported experiencing greater negative emotions following the episode of street harassment. Young men were equally as likely as young women to report experiencing street harassment.
Value: The findings uniquely highlight that adolescents experience distinct types of street harassment and some of which are associated with negative emotions
A GABAergic projection from the centromedial nuclei of the amygdala to ventromedial prefrontal cortex modulates reward behavior
The neural circuitry underlying mammalian reward behaviors involves several distinct nuclei throughout the brain. It is widely accepted that the midbrain dopamine (DA) neurons are critical for the reward-related behaviors. Recent studies have shown that the centromedial nucleus of the amygdala (CeMA) has a distinct role in regulating reward-related behaviors. However, the CeMA and ventromedial PFC (vmPFC) interaction in reward regulation remains poorly understood. Here, we identify and dissect a GABAergic projection that originates in the CeMA and terminates in the vmPFC (VGat-Cre(CeMA-vmPFC)) using viral-vector-mediated, cell-type-specific optogenetic techniques in mice. Pathway-specific optogenetic activation of the VGat-Cre(CeMA-vmPFC) circuit in awake, behaving animals produced a positive, reward-like phenotype in real-time place preference and increased locomotor activity in open-field testing. In sucrose operant conditioning, the photoactivation of these terminals increased nose-poking effort with no effect on licking behavior and robustly facilitated the extinction of operant behavior. However, photoactivation of these terminals did not induce self-stimulation in the absence of an external reward. The results described here suggest that the VGat-Cre(CeMA-vmPFC) projection acts to modulate existing reward-related behaviors. SIGNIFICANCE STATEMENT Many studies have shown that the interactions between the centromedial nucleus of the amygdala (CeMA) and ventromedial PFC (vmPFC) have critical roles for emotional regulation. However, most studies have associated this circuit with fear and anxiety behaviors and emphasized top-down processing from vmPFC to CeMA. Here, we provide new evidence for bottom-up CeMA to vmPFC influence on reward-related behaviors. Although previous work implicated the CeMA in incentive salience, our results isolate the investigation to a specific CeMA GABAergic projection to the vmPFC. This long-range GABAergic interaction between amygdala and frontal cortex adds a new dimension to the complex regulation of reward-related behaviors
Cell transformation assays for prediction of carcinogenic potential: State of the science and future research needs
Copyright @ 2011 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits
unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Cell transformation assays (CTAs) have long been proposed as in vitro methods for the identification of potential chemical carcinogens. Despite showing good correlation with rodent bioassay data, concerns over the subjective nature of using morphological criteria for identifying transformed cells and a lack of understanding of the mechanistic basis of the assays has limited their acceptance for regulatory purposes. However, recent drivers to find alternative carcinogenicity assessment methodologies, such as the Seventh Amendment to the EU Cosmetics Directive, have fuelled renewed interest in CTAs. Research is currently ongoing to improve the objectivity of the assays, reveal the underlying molecular changes leading to transformation and explore the use of novel cell types. The UK NC3Rs held an international workshop in November 2010 to review the current state of the art in this field and provide directions for future research. This paper outlines the key points highlighted at this meeting
HAL/S-360 compiler system specification
A three phase language compiler is described which produces IBM 360/370 compatible object modules and a set of simulation tables to aid in run time verification. A link edit step augments the standard OS linkage editor. A comprehensive run time system and library provide the HAL/S operating environment, error handling, a pseudo real time executive, and an extensive set of mathematical, conversion, I/O, and diagnostic routines. The specifications of the information flow and content for this system are also considered
In Vivo Effects of Bisphenol A in Laboratory Rodent Studies
Concern is mounting regarding the human health and environmental effects of bisphenol A (BPA), a high-production-volume chemical used in synthesis of plastics. We have reviewed the growing literature on effects of low doses of BPA, below 50 mg/kg/day, in laboratory exposures with mammalian model organisms. Many, but not all, effects of BPA are similar to effects seen in response to the model estrogens diethylstilbestrol and ethinylestradiol. For most effects, the potency of BPA is approximately 10 to 1,000-fold less than that of diethylstilbestrol or ethinylestradiol. Based on our review of the literature, a consensus was reached regarding our level of confidence that particular outcomes occur in response to low-dose BPA exposure. We are confident that adult exposure to BPA affects the male reproductive tract, and that long-lasting, organizational effects in response to developmental exposure to BPA occur in the brain, the male reproductive system, and metabolic processes. We consider it likely, but requiring further confirmation, that adult exposure to BPA affects the brain, the female reproductive system, and the immune system, and that developmental effects occur in the female reproductive system
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