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Selected AbstractsInformation security: Designing a stochastic-network for throughput and reliability,,NAVAL RESEARCH LOGISTICS: AN INTERNATIONAL JOURNAL, Issue 7 2009Jeffrey Schavland Abstract Todas information and communication network requires a design that is secure to tampering. Traditional performance measures of reliability and throughput must be supplemented with measures of security. Recognition of an adversary who can inflict damage leads toward a game-theoretic model. Through such a formulation, guidelines for network designs and improvements are derived. We opt for a design that is most robust to withstand both natural degradation and adversarial attacks. Extensive computational experience with such a model suggests that a Nash-equilibrium design exists that can withstand the worst possible damage. Most important, the equilibrium is value-free in that it is stable irrespective of the unit costs associated with reliability vs. capacity improvement and how one wishes to trade between throughput and reliability. This finding helps to pinpoint the most critical components in network design. From a policy standpoint, the model also allows the monetary value of information-security to be imputed. © 2009 Wiley Periodicals, Inc. Naval Research Logistics, 2009 [source] Covalent Linkage Mediates Communication between ACP and TE Domains in Modular Polyketide SynthasesCHEMBIOCHEM, Issue 6 2008Lucky Tran Abstract Polyketide natural products such as erythromycin A and epothilone are assembled on multienzyme polyketide synthases (PKSs), which consist of modular sets of protein domains. Within these type I systems, the fidelity of biosynthesis depends on the programmed interaction among the multiple domains within each module, centered around the acyl carrier protein (ACP). A detailed understanding of interdomain communication will therefore be vital for attempts to reprogram these pathways by genetic engineering. We report here that the interaction between a representative ACP domain and its downstream thioesterase (TE) is mediated largely by covalent tethering through a short "linker" region, with only a minor energetic contribution from protein,protein molecular recognition. This finding helps explain in part the empirical observation that TE domains can function out of their normal context in engineered assembly lines, and supports the view that overall PKS architecture may dictate at least a subset of interdomain interactions. [source] Differential sensitivity of medium- and large-sized striatal neurons to NMDA but not kainate receptor activation in the ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2001Carlos Cepeda Abstract Infrared videomicroscopy and differential interference contrast optics were used to identify medium- and large-sized neurons in striatal slices from young rats. Whole-cell patch-clamp recordings were obtained to compare membrane currents evoked by application of N -methyl- d -aspartate (NMDA) and kainate. Inward currents and current densities induced by NMDA were significantly smaller in large- than in medium-sized striatal neurons. The negative slope conductance for NMDA currents was greater in medium- than in large-sized neurons and more depolarization was required to remove the Mg2+ blockade. In contrast, currents induced by kainate were significantly greater in large-sized neurons whilst current densities were approximately equal in both cell types. Spontaneous excitatory postsynaptic currents occurred frequently in medium-sized neurons but were relatively infrequent in large-sized neurons. Excitatory postsynaptic currents evoked by electrical stimulation were smaller in large- than in medium-sized neurons. A final set of experiments assessed a functional consequence of the differential sensitivity of medium- and large-sized neurons to NMDA. Cell swelling was used to examine changes in somatic area in both neuronal types after prolonged application of NMDA or kainate. NMDA produced a time-dependent increase in somatic area in medium-sized neurons whilst it produced only minimal changes in large interneurons. In contrast, application of kainate produced significant swelling in both medium- and large-sized cells. We hypothesize that reduced sensitivity to NMDA may be due to variations in receptor subunit composition and/or the relative density of receptors in the two cell types. These findings help define the conditions that put neurons at risk for excitotoxic damage in neurological disorders. [source] Genotype,phenotype correlation in skin fragility-ectodermal dysplasia syndrome resulting from mutations in plakophilin 1EXPERIMENTAL DERMATOLOGY, Issue 2 2002T. Hamada Abstract: We report a 42-year-old Japanese man with an unusual autosomal recessive genodermatosis. The clinical features comprised normal skin at birth, loss of scalp hair at 3-months of age after a febrile illness, progressive nail dystrophy during infancy, palmoplantar keratoderma starting around the age of 18 years and trauma-induced skin fragility and blisters noted from the age of 20 years. Skin biopsy of rubbed non-lesional skin revealed widening of spaces between adjacent keratinocytes from the suprabasal layer upwards. Electron microscopy demonstrated a reduced number of hypoplastic desmosomes. Immunohistochemical labeling showed a reduction in intercellular staining for the desmosome component plakophilin 1. Mutation analysis revealed a homozygous intron 11 donor splice site mutation in the plakophilin 1 gene, 2021+1 G>A (GenBank no. Z34974). RT-PCR, using RNA extracted from the skin biopsy, provided evidence for residual low levels of the full-length wild-type transcript (,8%) as well as multiple other near full-length transcripts, one of which was in frame leading to deletion of 17 amino acids from the 9th arm-repeat unit of the plakophilin 1 tail domain. Thus, the molecular findings help explain the clinical features in the patient, who has a similar but milder phenotype to previously reported patients with skin fragility-ectodermal dysplasia syndrome associated with complete ablation of plakophilin 1 (OMIM 604536). This new ,mitis' phenotype provides further clinicopathological evidence for the role of plakophilin 1 in keratinocyte cell,cell adhesion and ectodermal development. [source] Examining the statistical properties of fine-scale mapping in large-scale association studiesGENETIC EPIDEMIOLOGY, Issue 3 2008Steven Wiltshire Abstract Interpretation of dense single nucleotide polymorphism (SNP) follow-up of genome-wide association or linkage scan signals can be facilitated by establishing expectation for the behaviour of primary mapping signals upon fine-mapping, under both null and alternative hypotheses. We examined the inferences that can be made regarding the posterior probability of a real genetic effect and considered different disease-mapping strategies and prior probabilities of association. We investigated the impact of the extent of linkage disequilibrium between the disease SNP and the primary analysis signal and the extent to which the disease gene can be physically localised under these scenarios. We found that large increases in significance (>2 orders of magnitude) appear in the exclusive domain of genuine genetic effects, especially in the follow-up of genome-wide association scans or consensus regions from multiple linkage scans. Fine-mapping significant association signals that reside directly under linkage peaks yield little improvement in an already high posterior probability of a real effect. Following fine-mapping, those signals that increase in significance also demonstrate improved localisation. We found local linkage disequiliptium patterns around the primary analysis signal(s) and tagging efficacy of typed markers to play an important role in determining a suitable interval for fine-mapping. Our findings help inform the interpretation and design of dense SNP-mapping follow-up studies, thus facilitating discrimination between a genuine genetic effect and chance fluctuation (false positive). Genet. Epidemiol. 2007. © 2007 Wiley-Liss, Inc. [source] Ethics of studies involving human volunteers I. Historical backgroundINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 6 2007P. A. Carson The evaluation of personal products using panels of human volunteers is crucial to the continued development of the industry. Nowadays, however, it is increasingly important to ensure that such studies are both safe for the participants and are ethical. As a means of defining general rules for judging and justifying the ethics of human testing, historical milestones in the development of human experimentation are given. While most experience originates from biomedical research, findings help establish standards of ethical review of non-therapeutic human testing used in the cosmetics industry. [source] Transcriptional activation of human mu-opioid receptor gene by insulin-like growth factor-I in neuronal cells is modulated by the transcription factor RESTJOURNAL OF NEUROCHEMISTRY, Issue 6 2008Andrea Bedini Abstract The human mu-opioid receptor gene (OPRM1) promoter contains a DNA sequence binding the repressor element 1 silencing transcription factor (REST) that is implicated in transcriptional repression. We investigated whether insulin-like growth factor I (IGF-I), which affects various aspects of neuronal induction and maturation, regulates OPRM1 transcription in neuronal cells in the context of the potential influence of REST. A series of OPRM1-luciferase promoter/reporter constructs were transfected into two neuronal cell models, neuroblastoma-derived SH-SY5Y cells and PC12 cells. In the former, endogenous levels of human mu-opioid receptor (hMOPr) mRNA were evaluated by real-time PCR. IGF-I up-regulated OPRM1 transcription in: PC12 cells lacking REST, in SH-SY5Y cells transfected with constructs deficient in the REST DNA binding element, or when REST was down-regulated in retinoic acid-differentiated cells. IGF-I activates the signal transducer and activator of transcription-3 signaling pathway and this transcription factor, binding to the signal transducer and activator of transcription-1/3 DNA element located in the promoter, increases OPRM1 transcription. We propose that a reduction in REST is a critical switch enabling IGF-I to up-regulate hMOPr. These findings help clarify how hMOPr expression is regulated in neuronal cells. [source] Illiquidity and Pricing Biases in the Real Estate MarketREAL ESTATE ECONOMICS, Issue 3 2007Zhenguo Lin This article addresses the micro-analytic foundations of illiquidity and price dynamics in the real estate market by integrating modern portfolio theory with models describing the real estate transaction process. Based on the notion that real estate is a heterogeneous good that is traded in decentralized markets and that transactions in these markets are often characterized by costly searches, we argue that the most important aspects defining real estate illiquidity in both residential and commercial markets are the time required for sale and the uncertainty of the marketing period. These aspects provide two sources of bias in the commonly adopted methods of real estate valuation, which are based solely on the prices of sold properties and implicitly assume immediate execution. We demonstrate that estimated returns must be biased upward and risks downward. These biases can be significant, especially when the marketing period is highly uncertain relative to the holding period. We also find that real estate risk is closely related to investors' time horizons, specifically that real estate risk decreases when the holding period increases. These results are consistent with the conventional wisdom that real estate is more favorable to long-term investors than to short-term investors. They also provide a theoretical foundation for the recent econometric literature, which finds evidence of smoothing of real estate returns. Our findings help explain the apparent risk-premium puzzle in real estate,that is, that ex post returns appear too high, given their apparent low volatility,and can lead to the formal derivation of adjustments that can define real estate's proper role in the mixed-asset portfolio. [source] In vitro stage-specific chondrogenesis of mesenchymal stem cells committed to chondrocytesARTHRITIS & RHEUMATISM, Issue 2 2009Wei-Hong Chen Objective Osteoarthritis is characterized by an imbalance in cartilage homeostasis, which could potentially be corrected by mesenchymal stem cell (MSC),based therapies. However, in vivo implantation of undifferentiated MSCs has led to unexpected results. This study was undertaken to establish a model for preconditioning of MSCs toward chondrogenesis as a more effective clinical tool for cartilage regeneration. Methods A coculture preconditioning system was used to improve the chondrogenic potential of human MSCs and to study the detailed stages of chondrogenesis of MSCs, using a human MSC line, Kp-hMSC, in commitment cocultures with a human chondrocyte line, hPi (labeled with green fluorescent protein [GFP]). In addition, committed MSCs were seeded into a collagen scaffold and analyzed for their neocartilage-forming ability. Results Coculture of hPi-GFP chondrocytes with Kp-hMSCs induced chondrogenesis, as indicated by the increased expression of chondrogenic genes and accumulation of chondrogenic matrix, but with no effect on osteogenic markers. The chondrogenic process of committed MSCs was initiated with highly activated chondrogenic adhesion molecules and stimulated cartilage developmental growth factors, including members of the transforming growth factor , superfamily and their downstream regulators, the Smads, as well as endothelial growth factor, fibroblast growth factor, insulin-like growth factor, and vascular endothelial growth factor. Furthermore, committed Kp-hMSCs acquired neocartilage-forming potential within the collagen scaffold. Conclusion These findings help define the molecular markers of chondrogenesis and more accurately delineate the stages of chondrogenesis during chondrocytic differentiation of human MSCs. The results indicate that human MSCs committed to the chondroprogenitor stage of chondrocytic differentiation undergo detailed chondrogenic changes. This model of in vitro chondrogenesis of human MSCs represents an advance in cell-based transplantation for future clinical use. [source] | |||||||||||||