Miracle-dz/UniFAR-FTUs huggingface dataset:
Business Return in New Orleans: Decision Making Amid Post-Katrina Uncertainty

Background Empirical observations on how businesses respond after a major catastrophe are rare, especially for a catastrophe as great as Hurricane Katrina, which hit New Orleans, Louisiana on August 29, 2005. We analyzed repeated telephone surveys of New Orleans businesses conducted in December 2005, June 2006, and October 2007 to understand factors that influenced decisions to re-open amid post-disaster uncertainty. Methodology/Principal Findings Businesses in the group of professional, scientific, and technical services reopened the fastest in the near term, but differences in the rate of reopening for businesses stratified by type became indistinguishable in the longer term (around two years later). A reopening rate of 65% was found for all businesses by October 2007. Discriminant analysis showed significant differences in responses reflecting their attitudes about important factors between businesses that reopened and those that did not. Businesses that remained closed at the time of our third survey (two years after Katrina) ranked levee protection as the top concern immediately after Katrina, but damage to their premises and financing became major concerns in subsequent months reflected in the later surveys. For businesses that had opened (at the time of our third survey), infrastructure protection including levee, utility, and communications were the main concerns mentioned in surveys up to the third survey, when the issue of crime became their top concern. Conclusions/Significance These findings underscore the need to have public policy and emergency plans in place prior to the actual disaster, such as infrastructure protection, so that the policy can be applied in a timely manner before business decisions to return or close are made. Our survey results, which include responses from both open and closed businesses, overcome the “survivorship bias” problem and provide empirical observations that should be useful to improve micro-level spatial economic modeling of factors that influence business return decisions.
A robust optimization approach to backup network design with random failures

This paper presents a scheme in which a dedicated backup network is designed to provide protection from random link failures. Upon a link failure in the primary network, traffic is rerouted through a preplanned path in the backup network. We introduce a novel approach for dealing with random link failures, in which probabilistic survivability guarantees are provided to limit capacity over-provisioning.We show that the optimal backup routing strategy in this respect depends on the reliability of the primary network. Specifically, as primary links become less likely to fail, the optimal backup networks employ more resource sharing amongst backup paths. We apply results from the field of robust optimization to formulate an ILP for the design and capacity provisioning of these backup networks. We then propose a simulated annealing heuristic to solve this problem for largescale networks, and present simulation results that verify our analysis and approach.
Combination of vildagliptin and rosiglitazone ameliorates nonalcoholic fatty liver disease in C57BL/6 mice

Objectives: To evaluate the effect of vildagliptin alone and in combination with metformin or rosiglitazone on murine hepatic steatosis in diet-induced nonalcoholic fatty liver disease (NAFLD). Materials and Methods: Male C57BL/6 mice were fed with high fat diet (60 Kcal %) and fructose (40%) in drinking water for 60 days to induce NAFLD. After the induction period, animals were divided into different groups and treated with vildagliptin (10 mg/kg), metformin (350 mg/kg), rosiglitazone (10 mg/kg), vildagliptin (10 mg/kg) + metformin (350 mg/kg), or vildagliptin (10 mg/kg) + rosiglitazone (10 mg/kg) orally for 28 days. Following parameters were measured: body weight, food intake, plasma glucose, triglyceride (TG), total cholesterol, liver function tests, and liver TG. Liver histopathology was also examined. Results: Oral administration of vildagliptin and rosiglitazone in combination showed a significant reduction in fasting plasma glucose, hepatic steatosis, and liver TGs. While other treatments showed less or no improvement in the measured parameters. Conclusions: These preliminary results demonstrate that administration of vildagliptin in combination with rosiglitazone could be a promising therapeutic strategy for the treatment of NAFLD.
The Impact of Realistic Age Structure in Simple Models of Tuberculosis Transmission

Background Mathematical models of tuberculosis (TB) transmission have been used to characterize disease dynamics, investigate the potential effects of public health interventions, and prioritize control measures. While previous work has addressed the mathematical description of TB natural history, the impact of demography on the behaviour of TB models has not been assessed. Methods A simple model of TB transmission, with alternative assumptions about survivorship, is used to explore the effect of age structure on the prevalence of infection, disease, basic reproductive ratio and the projected impact of control interventions. We focus our analytic arguments on the differences between constant and exponentially distributed lifespans and use an individual-based model to investigate the range of behaviour arising from realistic distributions of survivorship. Results The choice of age structure and natural (non-disease related) mortality strongly affects steady-state dynamics, parameter estimation and predictions about the effectiveness of control interventions. Since most individuals infected with TB develop an asymptomatic latent infection and never progress to active disease, we find that assuming a constant mortality rate results in a larger reproductive ratio and an overestimation of the effort required for disease control in comparison to using more realistic age-specific mortality rates. Conclusions Demographic modelling assumptions should be considered in the interpretation of models of chronic infectious diseases such as TB. For simple models, we find that assuming constant lifetimes, rather than exponential lifetimes, produces dynamics more representative of models with realistic age structure.
Comparative Genomics Identifies a Potential Marker of Human-Virulent Anaplasma phagocytophilum

We have previously described a comparative genome analysis of nine strains of Anaplasma phagocytophilum that showed similarity between strains infecting humans and U.S. dogs and a more distant relationship with horse and ruminant strains. This suggested that it may be possible to distinguish human-infective strains using simple DNA sequence-based diagnostic tests. This would be of epidemiologic significance in identifying and tracking the presence of virulent strains in tick vector populations. Further analysis identified a gene that was present in several strains, including U.S. Ap-variant 1 (ruminant), MRK (horse), and European sheep, but was deleted in strains infecting U.S. humans and dogs, suggesting that it could be a useful marker of human virulence. A simple PCR test was developed to identify the presence/absence of this gene. The PCR test discriminated A. phagocytophilum strains from clinically affected humans and U.S. dogs from the strains more distantly related in genome sequence. This warrants further testing of globally diverse A. phagocytophilum strains to examine world-wide conservation of this gene.
Human Immunodeficiency Virus Type 1 (HIV-1) Tat Induces Nitric-oxide Synthase in Human Astroglia*

Human immunodeficiency virus type 1 (HIV-1) infection is known to cause neuronal injury and dementia in a significant proportion of patients. However, the mechanism by which HIV-1 mediates its deleterious effects in the brain is poorly defined. The present study was undertaken to investigate the effect of the HIV-1tat gene on the expression of inducible nitric-oxide synthase (iNOS) in human U373MG astroglial cells and primary astroglia. Expression of the tat gene as RSV-tat but not that of the CAT gene as RSV-CAT in U373MG astroglial cells led to the induction of NO production and the expression of iNOS protein and mRNA. Induction of NO production by recombinant HIV-1 Tat protein and inhibition of RSV-tat-induced NO production by anti-Tat antibodies suggest that RSV-tat-induced production of NO is dependent on Tat and that Tat is secreted from RSV-tat-transfected astroglia. Similar to U373MG astroglial cells, RSV-tat also induced the production of NO in human primary astroglia. The induction of human iNOS promoter-derived luciferase activity by the expression of RSV-tat suggests that RSV-tat induces the transcription of iNOS. To understand the mechanism of induction of iNOS, we investigated the role of NF-κB and C/EBPβ, transcription factors responsible for the induction of iNOS. Activation of NF-κB as well as C/EBPβ by RSV-tat, stimulation of RSV-tat-induced production of NO by the wild type of p65 and C/EBPβ, and inhibition of RSV-tat-induced production of NO by Δp65, a dominant-negative mutant of p65, and ΔC/EBPβ, a dominant-negative mutant of C/EBPβ, suggest that RSV-tat induces iNOS through the activation of NF-κB and C/EBPβ. In addition, we show that extracellular signal-regulated kinase (ERK) but not that p38 mitogen-activated protein kinase (MAPK) is involved in RSV-tat induced production of NO. Interestingly, PD98059, an inhibitor of the ERK pathway, and ΔERK2, a dominant-negative mutant of ERK2, inhibited RSV-tat-induced production of NO through the inhibition of C/EBPβ but not that of NF-κB. This study illustrates a novel role for HIV-1 tat in inducing the expression of iNOS in human astrocytes that may participate in the pathogenesis of HIV-associated dementia.
Simvastatin Inhibits Staphylococcus aureus Host Cell Invasion through Modulation of Isoprenoid Intermediates

Patients on a statin regimen have a decreased risk of death due to bacterial sepsis. We have found that protection by simvastatin includes the inhibition of host cell invasion by Staphylococcus aureus, the most common etiologic agent of sepsis. Inhibition was due in part to depletion of isoprenoid intermediates within the cholesterol biosynthesis pathway and led to the cytosolic accumulation of the small GTPases CDC42, Rac, and RhoB. Actin stress fiber disassembly required for host invasion was attenuated by simvastatin and by the inhibition of phosphoinositide 3-kinase (PI3K) activity. PI3K relies on coupling to prenylated proteins, such as this subset of small GTPases, for access to membrane-bound phosphoinositide to mediate stress fiber disassembly. Therefore, we examined whether simvastatin restricts PI3K cellular localization. In response to simvastatin, the PI3K isoform p85, coupled to these small-GTPases, was sequestered within the cytosol. From these findings, we propose a mechanism whereby simvastatin restricts p85 localization, inhibiting the actin dynamics required for bacterial endocytosis. This approach may provide the basis for protection at the level of the host in invasive infections by S. aureus.
Acquisition by processing: A modular perspective on language development

The paper offers a model of language development, first and second, within a processing perspective. We first sketch a modular view of language, in which competence is embodied in the processing mechanisms. We then propose a novel approach to language acquisition (Acquisition by Processing Theory, or APT), in which development of the module occurs as a natural product of processing activity, without any acquisition mechanisms as such. The approach is illustrated and explicated through examples of the development of content words, derivational morphology, the functional category I with its variable features, and Case and thematic roles, as well as apparent cross-linguistic variation in processing strategies and the status of bootstrapping in the model. We then examine some possible applications to issues in second language acquisition – noticing the gap, the initial state, transfer, and the apparent limits of SLA – and finally offer a broader perspective on the model: its scope, its relations to other approaches, and its possible limits.
Spatio-Temporal Dynamics of Blood coagulation and Pattern Formation: a Theoretical Approach

We constructed a mathematical model of clotting, which is based on a current view of the molecular pathways of blood coagulation. Several hypothetical reactions are introduced to allow accurate description of the spatio-temporal dynamics of blood clotting. The resulting model describes well all spatio-temporal aspects of clotting, as well as data obtained in the homogeneous systems.
Pleomorphic Characteristics of a Germ-Line KIT Mutation in a Large Kindred with Gastrointestinal Stromal Tumors, Hyperpigmentation, and Dysphagia

Purpose: Somatic mutations that result in the activation of the growth factor receptor KIT are commonly found in gastrointestinal stromal tumors (GISTs). Six families have been reported in which a germ-line mutation in KIT is associated with an autosomal dominant predisposition to the development of GISTs. Hyperpigmentation, urticaria pigmentosa, and dysphagia have been described in some, but not all, families. Preliminary correlations between the site of mutation and the clinical phenotype have been proposed, but the strength of these associations is not defined. Design: A large kindred with multiple GISTs, hyperpigmentation, and dysphagia was identified after the index case presented with multiple GISTs. A germ-line mutation in KIT (W557R) was identified in an affected cousin, after which a large family meeting was held and testing offered. Clinical data were obtained by interview and, whenever possible, medical record documentation. Results: To date, 19 individuals have been tested, and the mutation has been shown to cosegregate with the syndrome. The phenotypic expression, however, is variable. GISTs, often presenting as upper gastrointestinal bleeding, and hyperpigmentation are common, but not diagnosed in all documented or obligate carriers. Dysphagia is a less prevalent complaint. The diagnosis of GISTs appears to be made at a younger age in more recent generations. Metastatic disease is uncommon. Conclusions: A germ-line mutation in KIT resulting in an amino acid substitution in the juxtamembrane region is associated with a syndrome of GIST, hyperpigmentation, and dysphagia, although the prominence of each component varies.
Polymer-Induced Swelling of Solid-Supported Lipid Membranes

In this paper, we study the interaction of charged polymers with solid-supported 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) membranes by in-situ neutron reflectivity. We observe an enormous swelling of the oligolamellar lipid bilayer stacks after incubation in solutions of poly(allylamine hydrochloride) (PAH) in D2O. The positively charged polyelectrolyte molecules interact with the lipid bilayers and induce a drastic increase in their d-spacing by a factor of ~4. Temperature, time, and pH influence the swollen interfacial lipid linings. From our study, we conclude that electrostatic interactions introduced by the adsorbed PAH are the main cause for the drastic swelling of the lipid coatings. The DMPC membrane stacks do not detach from their solid support at T > Tm. Steric interactions, also introduced by the PAH molecules, are held responsible for the stabilizing effect. We believe that this novel system offers great potential for fundamental studies of biomembrane properties, keeping the membrane’s natural fluidity and freedom, decoupled from a solid support at physiological conditions.
Correlation of polymerase replication fidelity with genetic evolution of influenza A/Fujian/411/02(H3N2) viruses

Influenza virus evolves continuously through mutations presumed to result from evolutionary pressure driving viral replication. This study examined the relationship between the genetic evolution and replication fidelity of influenza viruses. Analysis of influenza sequences from National Centre for Biotechnology Information (NCBI) database revealed a gradual decrease in the rate of genetic evolution of A/Fujian/411/02(H3N2)‐like variants after the emergence and predominance of the A/H3N2 Fujian strain in 2002. This decrease may be related to an increase in replication fidelity, which was investigated by assessing mutation frequencies of reassortant viruses carrying the PB1 segment of Fujian variants isolated between 2003 and 2005 in a sequencing‐based plaque assay. The data revealed a threefold decrease in substitution per site of the reassortant viruses carrying the Fujian PB1 segments isolated in 2004–2005 compared with those circulating in 2003. The decrease in mutation frequency paralleled a decrease in genetic evolution of the Fujian variants from the NCBI database. This correlation implicates changes in the polymerase replication fidelity as contributing to altered genetic evolution of influenza viruses. J. Med. Virol. 83:510–516, 2011. © 2011 Wiley‐Liss, Inc.
Energetic Contribution of Residues in the Runx1 Runt Domain to DNA Binding*

Core-binding factors (CBFs) are a small family of heterodimeric transcription factors that play critical roles in hematopoiesis and in the development of bone, stomach epithelium, and proprioceptive neurons. Mutations in CBF genes are found in leukemias, bone disorders, and gastric cancer. CBFs consist of a DNA-binding CBFα subunit and a non-DNA-binding CBFβ subunit. DNA binding and heterodimerization with CBFβ are mediated by the Runt domain in CBFα. Here we report an alanine-scanning mutagenesis study of the Runt domain that targeted amino acids identified by structural studies to reside at the DNA or CBFβ interface, as well as amino acids mutated in human disease. We determined the energy contributed by each of the DNA-contacting residues in the Runt domain to DNA binding both in the absence and presence of CBFβ. We propose mechanisms by which mutations in the Runt domain found in hematopoietic and bone disorders affect its affinity for DNA.
The Progression and Impact of Vascular Calcification in Peritoneal Dialysis Patients

Background Progression of coronary artery calcification (CAC) has been described in hemodialysis patients, and severe CAC has been associated with the occurrence of cardiovascular events in this population. Little information is available regarding peritoneal patients. Aim To prospectively evaluate peritoneal dialysis patients in order to identify the variables associated with the rate of CAC progression, as well as to determine the impact that baseline CAC has on clinical outcomes over a 1-year follow-up period. Methods Using multislice coronary tomography, calcium scores were estimated at baseline and after 12 months in 49 peritoneal dialysis patients. Patients with and without CAC progression were compared with respect to clinical characteristics and biochemical variables, including lipid profile, parameters of mineral metabolism, and markers of inflammation. Cardiovascular events, hospitalizations, and all-cause mortality were recorded. Results At baseline, 29 patients (59%) presented CAC and a median calcium score of 234.7 (range 10.3 – 2351) Agatston units. Progression of CAC was observed in 13 patients (43%) who, in comparison with those presenting no CAC progression, were older, presented higher baseline calcium scores, and had higher mean glucose levels, lower mean high density lipoprotein cholesterol levels, and more months using low calcium peritoneal solution. We also observed a trend toward more often presenting with a history of hypertension, exhibiting more hyperphosphatemic and hyperglycemic events, and having lower albumin levels. In multiple logistic regression, only baseline calcium score was independently associated with progression of CAC. A shorter cardiovascular event-free time and a trend toward lower survival rates were observed in the group with CAC. Hospitalization event-free time did not differ between the groups. Conclusion Determining CAC provides important prognostic data in peritoneal dialysis patients. Baseline calcium score and disturbances in glucose, mineral, and lipid metabolism were indicative of higher risk of CAC progression in this population.
Towards detecting BGP route hijacking using the RPKI

Prefix hijacking has always been a big concern in the Internet. Some events made it into the international world-news, but most of them remain unreported or even unnoticed. The scale of the problem can only be estimated. The Resource Publication Infrastructure (RPKI) is an effort by the IETF to secure the inter-domain routing system. It includes a formally verifiable way of identifying who owns legitimately which portion of the IP address space. The RPKI has been standardized and prototype implementations are tested by Internet Service Providers (ISPs). Currently the system holds already about 2% of the Internet routing table. Therefore, in theory, it should be easy to detect hijacking of prefixes within that address space. We take an early look at BGP update data and check those updates against the RPKI---in the same way a router would do, once the system goes operational. We find many interesting dynamics, not all can be easily explained as hijacking, but a significant number are likely operational testing or misconfigurations.
Efficacy and safety of oral SK3530 for the treatment of erectile dysfunction in Korean men: a multicenter, randomized, double-blind, placebo-controlled, fixed dose, parallel group clinical trial.

AIM To evaluate the efficacy and safety of SK3530, a newly developed type 5 phosphodiesterase inhibitor (PDE5I), in Korean men with erectile dysfunction (ED). METHODS A total of 119 patients were randomized at 10 centers in Korea to receive either SK3530 (50, 100, or 150 mg; n = 89) or placebo (n = 30) taken l h before anticipated sexual activity for an 8-week period. The patients were evaluated at baseline and 4 and 8 weeks after beginning therapy. Efficacy was assessed using the International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP), and the Global Assessment Question (GAQ). Safety was analyzed by adverse events, laboratory values and vital signs. RESULTS At the end of the study, all the primary and secondary efficacy end-points were statistically significantly improved by SK3530 compared with placebo (P<0.05). Of the 89 patients in the treatment arm, 36 (42.3%) achieved normal erectile function after treatment, including six patients with severe ED. Treatment-related adverse events occurred in 32 patients. The most common adverse events were flushing, headache, dizziness and eye redness (10.9%, 7.6%, 2.5% and 2.5%, respectively), and most were mild. Only two patients discontinued treatment during the study period because of adverse events. CONCLUSION The results of our phase II study have confirmed the efficacy and safety of SK3530 in a broad population of men with ED of various etiologies and severity. The optimal doses in terms of efficacy and safety were determined to be 50 mg and 100 mg, respectively.