434 research outputs found
Black hole collisions from Brill-Lindquist initial data: predictions of perturbation theory
The Misner initial value solution for two momentarily stationary black holes
has been the focus of much numerical study. We report here analytic results for
an astrophysically similar initial solution, that of Brill and Lindquist (BL).
Results are given from perturbation theory for initially close holes and are
compared with available numerical results. A comparison is made of the
radiation generated from the BL and the Misner initial values, and the physical
meaning is discussed.Comment: 11 pages, revtex3.0, 5 figure
The future of human nature: a symposium on the promises and challenges of the revolutions in genomics and computer science, April 10, 11, and 12, 2003
This repository item contains a single issue of the Pardee Conference Series, a publication series that began publishing in 2006 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future. This was the Center's Symposium on the Promises and Challenges of the Revolutions in Genomics and Computer Science took place during April 10, 11, and 12, 2003. Co-organized by Charles DeLisi and Kenneth Lewes; sponsored by Boston University, the Frederick S. Pardee Center for the Study of the Longer-Range Future.This conference focused on scientific and technological advances in genetics, computer science, and their convergence during the next 35 to 250 years. In particular, it focused on directed evolution, the futures it allows, the shape of society in those futures, and the robustness of human nature against technological change at the level of individuals, groups, and societies. It is taken as a premise that biotechnology and computer science will mature and will reinforce one another. During the period of interest, human cloning, germ-line genetic engineering, and an array of reproductive technologies will become feasible and safe. Early in this period, we can reasonably expect the processing power of a laptop computer to exceed the collective processing power of every human brain on the planet; later in the period human/machine interfaces will begin to emerge. Whether such technologies will take hold is not known. But if they do, human evolution is likely to proceed at a greatly accelerated rate; human nature as we know it may change markedly, if it does not disappear altogether, and new intelligent species may well be created
The future of human nature: a symposium on the promises and challenges of the revolutions in genomics and computer science, April 10, 11, and 12, 2003
This repository item contains a single issue of the Pardee Conference Series, a publication series that began publishing in 2006 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future. This was the Center's Symposium on the Promises and Challenges of the Revolutions in Genomics and Computer Science took place during April 10, 11, and 12, 2003. Co-organized by Charles DeLisi and Kenneth Lewes; sponsored by Boston University, the Frederick S. Pardee Center for the Study of the Longer-Range Future.This conference focused on scientific and technological advances in genetics, computer science, and their convergence during the next 35 to 250 years. In particular, it focused on directed evolution, the futures it allows, the shape of society in those futures, and the robustness of human nature against technological change at the level of individuals, groups, and societies. It is taken as a premise that biotechnology and computer science will mature and will reinforce one another. During the period of interest, human cloning, germ-line genetic engineering, and an array of reproductive technologies will become feasible and safe. Early in this period, we can reasonably expect the processing power of a laptop computer to exceed the collective processing power of every human brain on the planet; later in the period human/machine interfaces will begin to emerge. Whether such technologies will take hold is not known. But if they do, human evolution is likely to proceed at a greatly accelerated rate; human nature as we know it may change markedly, if it does not disappear altogether, and new intelligent species may well be created
The Role of Industry, Geography and Firm Heterogeneity in Credit Risk Diversification
In theory the potential for credit risk diversification for banks could be substantial. Portfolio diversification is driven broadly by two characteristics: the degree to which systematic risk factors are correlated with each other and the degree of dependence individual firms have to the different types of risk factors. We propose a model for exploring these dimensions of credit risk diversification: across industry sectors and across different countries or regions. We find that full firm-level parameter heterogeneity matters a great deal for capturing differences in simulated credit loss distributions. Imposing homogeneity results in overly skewed and fat-tailed loss distributions. These differences become more pronounced in the presence of systematic risk factor shocks: increased parameter heterogeneity greatly reduces shock sensitivity. Allowing for regional parameter heterogeneity seems to better approximate the loss distributions generated by the fully heterogeneous model than allowing just for industry heterogeneity. The regional model also exhibits less shock sensitivity
Lipids modulate the conformational dynamics of a secondary multidrug transporter
Direct interactions with lipids have emerged as key determinants of the folding, structure and function of membrane proteins, but an understanding of how lipids modulate protein dynamics is still lacking. Here, we systematically explored the effects of lipids on the conformational dynamics of the proton-powered multidrug transporter LmrP from Lactococcus lactis, using the pattern of distances between spin-label pairs previously shown to report on alternating access of the protein. We uncovered, at the molecular level, how the lipid headgroups shape the conformational-energy landscape of the transporter. The model emerging from our data suggests a direct interaction between lipid headgroups and a conserved motif of charged residues that control the conformational equilibrium through an interplay of electrostatic interactions within the protein. Together, our data lay the foundation for a comprehensive model of secondary multidrug transport in lipid bilayers
Human Pancreatic Acinar Cells Do Not Respond to Cholecystokinin
Pancreatic secretion can be influenced by cholecystokinin (CCK) either directly via actions on acinar cells or indirectly via actions on nerves. The presence and functional roles of CCK receptors on human pancreatic acinar cells remains unclear. In the current study human pancreatic acini were isolated and then treated with CCK-8, gastrin and/or carbachol. Functional parameters were measured including intracellular [Ca2+] and amylase secretion. It was observed that human acini did not respond to CCK agonists but did respond to carbachol with robust increases in functional parameters. Adenoviral-mediated gene transfer of CCK1 or CCK2 receptors to the human cells resulted in cell responses to CCK agonists. In order to determine the reason for the lack of responsiveness of the human acini, expression of receptor mRNAs was determined using quantitative RT-PCR and localized by in situ hybridization. mRNA levels for CCK1 receptors were ∼30 times lower than those of CCK2 receptors, which were ∼10 times lower than those of m3 Ach receptors as measured by quantitative PCR. Neither CCK1 nor CCK2 receptors were localized in adult human pancreas by i n situ hybridization. These results indicate that human pancreatic acinar cells do not respond directly to CCK receptor activation and this is likely due to an insufficient level of receptor expression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73903/1/j.1600-0773.2002.910610.x.pd
The creatine kinase pathway is a metabolic vulnerability in EVI1-positive acute myeloid leukemia
Expression of the MECOM (also known as EVI1) proto-oncogene is deregulated by chromosomal translocations in some cases of acute myeloid leukemia (AML) and is associated with poor clinical outcome. Here, through transcriptomic and metabolomic profiling of hematopoietic cells, we reveal that EVI1 overexpression alters cellular metabolism. A screen using pooled short hairpin RNAs (shRNAs) identified the ATP-buffering, mitochondrial creatine kinase CKMT1 as necessary for survival of EVI1-expressing cells in subjects with EVI1-positive AML. EVI1 promotes CKMT1 expression by repressing the myeloid differentiation regulator RUNX1. Suppression of arginine-creatine metabolism by CKMT1-directed shRNAs or by the small molecule cyclocreatine selectively decreased the viability, promoted the cell cycle arrest and apoptosis of human EVI1-positive cell lines, and prolonged survival in both orthotopic xenograft models and mouse models of primary AML. CKMT1 inhibition altered mitochondrial respiration and ATP production, an effect that was abrogated by phosphocreatine-mediated reactivation of the arginine-creatine pathway. Targeting CKMT1 is thus a promising therapeutic strategy for this EVI1-driven AML subtype that is highly resistant to current treatment regimens. Keywords: AML; RUNX1; CKMT1; cyclocreatine; arginine metabolismNational Cancer Institute (U.S.) (NIH 1R35 CA210030-01)Stand Up To CancerBridge ProjectNational Cancer Institute (U.S.) (David H. Koch Institute for Integrative Cancer Research at MIT. Grant P30-CA14051
School Effects on the Wellbeing of Children and Adolescents
Well-being is a multidimensional construct, with psychological, physical and social components. As theoretical basis to help understand this concept and how it relates to school, we propose the Self-Determination Theory, which contends that self-determined motivation and personality integration, growth and well-being are dependent on a healthy balance of three innate psychological needs of autonomy, relatedness and competence. Thus, current indicators involve school effects on children’s well-being, in many diverse modalities which have been explored. Some are described in this chapter, mainly: the importance of peer relationships; the benefits of friendship; the effects of schools in conjunction with some forms of family influence; the school climate in terms of safety and physical ecology; the relevance of the teacher input; the school goal structure and the implementation of cooperative learning. All these parameters have an influence in promoting optimal functioning among children and increasing their well-being by meeting the above mentioned needs. The empirical support for the importance of schools indicates significant small effects, which often translate into important real-life effects as it is admitted at present. The conclusion is that schools do make a difference in children’s peer relationships and well-being
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