Miracle-dz/UniFAR-FTUs huggingface dataset:
Mathematical Modeling of Subgenomic Hepatitis C Virus Replication in Huh-7 Cells

ABSTRACT Cell-based hepatitis C virus (HCV) replicon systems have provided a means for understanding HCV replication mechanisms and for testing new antiviral agents. We describe here a mathematical model of HCV replication that assumes that the translation of the HCV polyprotein occurs in the cytoplasm, that HCV RNA synthesis occurs in vesicular-membrane structures, and that the strategy of replication involves a double-stranded RNA intermediate. Our results shed light on the intracellular dynamics of subgenomic HCV RNA replication from transfection to steady state within Huh-7 cells. We predict the following: (i) about 6 × 103 ribosomes are involved in generating millions of HCV NS5B-polymerase molecules in a Huh-7 cell, (ii) the observed 10:1 asymmetry of plus- to minus-strand RNA levels can be explained by a higher-affinity (200-fold) interaction of HCV NS5B polymerase-containing replication complexes with HCV minus-strand RNA over HCV plus-strand RNA in order to initiate synthesis, (iii) the latter higher affinity can also account for the observed ∼6:1 plus-strand/minus-strand ratio in vesicular-membrane structures, and (iv) the introduction of higher numbers of HCV plus-strand RNA by transfection leads to faster attainment of steady-state but does not change the steady-state HCV RNA level. Fully permissive HCV replication systems have been developed, and the model presented here is a first step toward building a comprehensive model for complete HCV replication. Moreover, the model can serve as an important tool in understanding HCV replication mechanisms and should prove useful in designing and evaluating new antivirals against HCV.
Response of bovine endothelial cells to FGF‐2 and VEGF is dependent on their site of origin: Relevance to the regulation of angiogenesis

Angiogenesis, the formation of new capillary blood vessels, occurs almost exclusively in the microcirculation. This process is controlled by the interaction between factors with positive and negative regulatory activity. In this study, we have compared the effect of two well described positive regulators, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF‐2) on bovine adrenal cortex‐derived microvascular endothelial (BME) and bovine aortic endothelial (BAE) cells. The parameters we assessed included (a) cellular reorganization and lumen formation following exposure of the apical cell surface to a three‐dimensional collagen gel; (b) organization of the actin cytoskeleton; (c) expression of thrombospondin‐1 (TSP‐1), an endogenous negative regulator of angiogenesis; and (d) extracellular proteolytic activity mediated by the plasminogen activator (PA)/plasmin system. We found that (a) collagen gel overlay induces rapid reorganization and lumen formation in BME but not BAE cells; (b) FGF‐2 but not VEGF induced dramatic reorganization of actin microfilaments in BME cells, with neither cytokine affecting BAE cells; (c) FGF‐2 decreased TSP‐1 protein and mRNA expression in BME cells, an effect which was specific for FGF‐2 and BME cells, since TSP‐1 protein levels were unaffected by VEGF in BME cells, or by FGF‐2 or VEGF in BAE cells; (d) FGF‐2 induced urokinase‐type PA (uPA) in BME and BAE cells, while VEGF induced uPA and tissue‐type PA in BME cells with no effect on BAE cells. Taken together, these findings reveal endothelial cell‐type specific responses to FGF‐2 and VEGF, and point to the greater specificity of these cytokines for endothelial cells of the microvasculature than for large vessel (aortic) endothelial cells. Furthermore, when viewed in the context of our previous observation on the synergistic interaction between VEGF and FGF‐2, our present findings provide evidence for complementary mechanisms which, when acting in concert, might account for the synergistic effect. J. Cell. Biochem. 82: 619–633, 2001. © 2001 Wiley‐Liss, Inc.
Expression of Rice Chitinase Gene in Genetically Engineered Tomato Confers Enhanced Resistance to Fusarium Wilt and Early Blight

This is the first study reporting the evaluation of transgenic lines of tomato harboring rice chitinase (RCG3) gene for resistance to two important fungal pathogens Fusarium oxysporum f. sp. lycopersici (Fol) causing fusarium wilt and Alternaria solani causing early blight (EB). In this study, three transgenic lines TL1, TL2 and TL3 of tomato Solanum lycopersicum Mill. cv. Riogrande genetically engineered with rice chitinase (RCG 3) gene and their R1 progeny was tested for resistance to Fol by root dip method and A. solani by detached leaf assay. All the R0 transgenic lines were highly resistant to these fungal pathogens compared to non-transgenic control plants. The pattern of segregation of three independent transformant for Fol and A. solani was also studied. Mendelian segregation was observed in transgenic lines 2 and 3 while it was not observed in transgenic line 1. It was concluded that introduction of chitinase gene in susceptible cultivar of tomato not only enhanced the resistance but was stably inherited in transgenic lines 2 and 3.
Evaluation of a three-dimensional chemical transport model (PMCAMx) in the European domain during the EUCAARI May 2008 campaign

PMCAMx-2008, a detailed three dimensional chemical transport model (CTM), was applied to Europe to simulate the mass concentration and chemical composition of particulate matter (PM) during May 2008. The model includes a state-of-the-art organic aerosol module which is based on the volatility basis set framework treating both primary and secondary organic components to be semivolatile and photochemically reactive. The model performance is evaluated against high time resolution aerosol mass spectrometer (AMS) ground and airborne measurements. Overall, organic aerosol is predicted to account for 32% of total PM1 at ground level during May 2008, followed by sulfate (30%), crustal material and sea-salt (14%), ammonium (13%), nitrate (7%), and elemental carbon (4%). The model predicts that fresh primary OA (POA) is a small contributor to organic PM concentrations in Europe during late spring, and that oxygenated species (oxidized primary and biogenic secondary) dominate the ambient OA. The Mediterranean region is the only area in Europe where sulfate concentrations are predicted to be much higher than the OA, while organic matter is predicted to be the dominant PM1 species in Central and Northern Europe. The comparison of the model predictions with the ground measurements in four measurement stations is encouraging. The model reproduces more than 94% of the daily averaged data and more than 87% of the hourly data within a factor of 2 for PM1 OA. The model tends to predict relatively flat diurnal profiles for PM1 OA in many areas, both rural and urban, in agreement with the available measurements. The model performance against the high time resolution airborne measurements at multiple altitudes and locations is as good as its performance against the ground level hourly measurements. There is no evidence of missing sources of OA aloft over Europe during this period. © Author(s) 2011.
A Large Non-immunized Human Fab Fragment Phage Library That Permits Rapid Isolation and Kinetic Analysis of High Affinity Antibodies*

We report the design, construction, and use of the first very large non-immunized phage antibody library in Fab format, which allows the rapid isolation and affinity analysis of antigen-specific human antibody fragments. Individually cloned heavy and light chain variable region libraries were combined in an efficient two-step cloning procedure, permitting the cloning of a total of 3.7 × 1010 independent Fab clones. The performance of the library was determined by the successful selection of on average 14 different Fabs against 6 antigens tested. These include tetanus toxoid, the hapten phenyl-oxazolone, the breast cancer-associated MUC1 antigen, and three highly related glycoprotein hormones: human chorionic gonadotropin, human luteinizing hormone, and human follicle-stimulating hormone. In the latter category, a panel of either homone-specific or cross-reactive antibodies were identified. The design of the library permits the monitoring of selections with polyclonal phage preparations and to carry out large scale screening of antibody off-rates with unpurified Fab fragments on BIAcore. Antibodies with off-rates in the order of 10−2 to 10−4s−1 and affinities up to 2.7 nm were recovered. The kinetics of these phage antibodies are of the same order of magnitude as antibodies associated with a secondary immune response. This new phage antibody library is set to become a valuable source of antibodies to many different targets, and to play a vital role in target discovery and validation in the area of functional genomics.
Air Pollution and Incidence of Hypertension and Diabetes Mellitus in Black Women Living in Los Angeles

Background— Evidence suggests that longer-term exposure to air pollutants over years confers higher risks of cardiovascular morbidity and mortality than shorter-term exposure. One explanation is that the cumulative adverse effects that develop over longer durations lead to the genesis of chronic disease. Preliminary epidemiological and clinical evidence suggests that air pollution may contribute to the development of hypertension and type 2 diabetes mellitus. Methods and Results— We used Cox proportional hazards models to assess incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for incident hypertension and diabetes mellitus associated with exposure to fine particulate matter (PM2.5) and nitrogen oxides in a cohort of black women living in Los Angeles. Pollutant levels were estimated at participants' residential addresses with land use regression models (nitrogen oxides) and interpolation from monitoring station measurements (PM2.5). Over follow-up from 1995 to 2005, 531 incident cases of hypertension and 183 incident cases of diabetes mellitus occurred. When pollutants were analyzed separately, the IRR for hypertension for a 10-&mgr;g/m3 increase in PM2.5 was 1.48 (95% CI, 0.95–2.31), and the IRR for the interquartile range (12.4 parts per billion) of nitrogen oxides was 1.14 (95% CI, 1.03–1.25). The corresponding IRRs for diabetes mellitus were 1.63 (95% CI, 0.78–3.44) and 1.25 (95% CI, 1.07–1.46). When both pollutants were included in the same model, the IRRs for PM2.5 were attenuated and the IRRs for nitrogen oxides were essentially unchanged for both outcomes. Conclusion— Our results suggest that exposure to air pollutants, especially traffic-related pollutants, may increase the risk of type 2 diabetes mellitus and possibly of hypertension.
Disease Load at Conception Predicts Survival in Later Epidemics in a Historical French-Canadian Cohort, Suggesting Functional Trans-Generational Effects in Humans

Objective Functional trans-generational and parental effects are potentially important determinants of health in several mammals. For humans, the existing evidence is weak. We investigate whether disease exposure triggers functional trans-generational response effects among humans by analyzing siblings who were conceived under different disease loads, and comparing their mortality in later epidemics. Under functional trans-generational response mechanisms, we expect that those who were conceived under high pathogenic stress load will have relatively low mortality during a later epidemic. Methods We use data from the Registre de la Population du Québec Ancien, which covers the historical population living in St. Lawrence Valley, Québec, Canada. Children born in 1705–1724 were grouped according to their exposure during conception to the measles 1714–15 epidemic. The 1714–15 epidemic was followed by two mortality crises in 1729–1734. The cause of the first crises in 1729 is not exactly known. The second crisis in 1732 was caused by a smallpox epidemic. Using proportional hazard Cox regression models with multivariate adjustment and with fixed-effects approach that compare siblings, we analyze whether mortality in 1729–1734 is affected by exposure to the 1714–15 epidemic. Results Children who were conceived during the peak of the measles epidemic of 1714–15 exhibited significantly lower mortality during the 1729–1734 crisis than those who were born before the 1714–15 epidemic (mortality hazard ratio 0.106, p<.05 in multivariate adjusted models; 0.142 p<.1 in sibling comparison models). Conclusions The results are consistent with a trans-generational mechanism that functionally responds to pathogen stress and suggest that early disease exposure may be protective later in life. Alternative explanations for the mortality patterns are discussed and shown to be problematic.
Determining Cystic Fibrosis-Affected Lung Microbiology: Comparison of Spontaneous and Serially Induced Sputum Samples by Use of Terminal Restriction Fragment Length Polymorphism Profiling

ABSTRACT Sampling of the lower airways of the adult cystic fibrosis (CF) lung has received insufficient detailed consideration, with the importance of sampling strategies for bacteriological outcome not known. Although spontaneously expectorated sputum (SES) samples are often used for diagnostic bacteriological analysis, induced sputum (IS) methods have advantages. This study examined whether significant differences in bacterial content were detected when using a culture-independent, molecular profiling technique to analyze SES or IS samples. Moreover, this work examined what trends relating to bacterial species distributions and reproducibility were found in sequentially induced sputum samples and what implications this has for pathogen detection. Terminal restriction fragment length polymorphism (T-RFLP) analysis was performed on a SES sample and 4 subsequent IS samples taken at 5-min intervals from 10 clinically stable, adult CF patients. This was repeated over 3 sampling days, with variability between samples, induction periods, and sampling days determined. A diverse range of bacterial species, including potentially novel pathogens, was found. No significant difference in bacterial content was observed for either SES or serial IS samples. On average, the analysis of a single sample from any time point resolved ∼58% of total bacterial diversity achieved by analysis of an SES sample and 4 subsequent IS samples. The reliance on analysis of a single respiratory sample was not sufficient for the detection of recognized CF pathogens in all instances. Close correlation between T-RFLP and microbiological data in the detection of key species indicates the importance of these findings in routine diagnostics for the detection of recognized and novel CF pathogens.
Congenital heart disease and rheumatic heart disease in Africa: recent advances and current priorities

Africa has one of the highest prevalence of heart diseases in children and young adults, including congenital heart disease (CHD) and rheumatic heart disease (RHD). We present here an extensive review of recent data from the African continent highlighting key studies and information regarding progress in CHD and RHD since 2005. Main findings include evidence that the CHD burden is underestimated mainly due to the poor outcome of African children with CHD. The interest in primary prevention for RHD has been recently re-emphasised, and new data are available regarding echocardiographic screening for subclinical RHD and initiation of secondary prevention. There is an urgent need for comprehensive service frameworks to improve access and level of care and services for patients, educational programmes to reinforce the importance of prevention and early diagnosis and a relevant research agenda focusing on the African context.
GIS-BASED MULTICRITERIA LAND SUITABILITY EVALUATION USING ORDERED WEIGHT AVERAGING WITH FUZZY QUANTIFIER : A CASE STUDY IN SHAVUR PLAIN , IRAN

Cell-based Multicriteria Evaluation (MCE) methods are used to analyse the land suitability evaluation. Land evaluation is carried out to estimate the suitability of land for a specific use such as arable farming or irrigated agriculture. land suitability evaluation is a prerequisite for land-use planning and development (Sys 1985; Van Ranst and others 1996). It provides information on the constraints and opportunities for the use of the land and therefore guides decisions on optimal utilization of land resources (FAO1983). The aim in integrating Multicriteria Decision Analysis (MCDA) with Geographical Information Systems (GIS) is to provide more flexible and more accurate decisions to the decision makers in order to evaluate the effective factors. Furthermore, By changing the parameters in this type of method, a wide range of decision strategies or scenarios can be generated in some procedures. The goal of this research is to take the advantage of incorporation of fuzzy (linguistic) quantifiers into GIS-based land suitability analysis by ordered weighted averaging (OWA). OWA is a multicriteria evaluation procedure (or combination operator). The nature of the OWA procedure depends on some parameters, which can be specified by means of fuzzy (linguistic) quantifiers. The quantifier-guided OWA procedure is illustrated using land-use suitability analysis in Shavur plain,Iran.
Tornado: maximizing locality and concurrency in a shared memory multiprocessor operating system

We describe the design and implementation of Tornado, a new operating system designed from the ground up specifically for today's shared memory multiprocessors. The need for improved locality in the operating system is growing as multiprocessor hardware evolves, increasing the costs for cache misses and sharing, and adding complications due to NUMAness. Tornado is optimized so that locality and independence in application requests for operating system services-whetherfrom multiple sequential applications or a single parallel application-are mapped onto locality and independence in the servicing of these requests in the kernel and system servers. By contrast, previous shared memory multiprocessor operating systems all evolved from designs constructed at a time when sharing costs were low, memory latency was low and uniform, and caches were small; for these systems, concurrency was the main performance concern and locality was not an important issue. Tornado achieves this locality by starting with an object-oriented structure, where every virtual and physical resource is represented by an independent object. Locality, as well as concurrency, is further enhanced with the introduction of three key innovations: (i) clustered objects that support the partitioning of contended objects across processors, (ii) a protected procedure call facility that preserves the locality and concurrency of IPC's, and (iii) a new locking strategy that allows all locking to be encapsulated within the objects being protected and greatly simplifies the overall locking protocols. As a result of these techniques, Tornado has far better performance characteristics, particularly for multithreaded applications, than existing commercial operating systems. Tornado has been fully implemented and runs both on Toronto's NUMAchine hardware and on the SimOS simulator.
Clinicopathological characteristics and outcome of patients with small cell neuroendocrine carcinoma of the uterine cervix: case series and literature review.

OBJECTIVE To analyze the clinicopathological data of 13 cases of small cell neuroendocrine carcinoma (SCNEC) of the uterine cervix who received treatment at this medical institutions over the past five years with patient survival as the primary endpoint. MATERIALS AND METHODS The clinicopathologic data of 13 cases were reviewed. Immunohistochemistry was performed using antibodies against synaptophysin and chromogranin A and Ki-67. Survival was analyzed using the Kaplan-Meier method and log-rank tests. RESULTS The median age of these patients was 37 years (range 21-62). Immunohistochemistry showed that the positive rate of synaptophysin and chromogranin A was 100% (13/13) and 69.23% (9/13), respectively. The median survival of patients with early-Stage I-II SCNEC of the uterine cervix (17.5 months) was significantly higher than that of patients with advanced stage SCNEC of the uterine cervix (four months) (p < 0.05). There was no local recurrence in all 13 patients. Five patients died of distant metastasis in less than six months. CONCLUSION SCNEC of the uterine cervix is a highly-malignant disease and early-stage patients showed significantly longer survival compared to late-stage patients. Early diagnosis and prompt combination treatment may improve the outcome of patients with SCNEC of the uterine cervix.
Power output regularization in the active reproduction of sound fields in rooms

In this paper we address the problem of using a multi‐channel active control system in order to reproduce a harmonic sound field in a large part of the volume of a reverberant room. The problems associated with the calculation of the inverse system matrix are confronted by introducing a term that is proportional to the sound power‐output of the system in the cost function that is obtained by the multiple point method. Simulation results show that this technique results to a better conditioning of the system matrix at low frequencies, comparing to other traditional regularization techniques. Moreover, it is shown that this method can be employed to increase the spatial robustness of the control sensor array inside the listening room.
Synaptic defects in spinal muscular atrophy animal models

Proximal spinal muscular atrophy, the most frequent genetic cause of childhood lethality, is caused by homozygous loss or mutation of the SMN1 gene on human chromosome 5, which codes for the survival motor neuron (SMN) protein. SMN plays a role in the assembly of small nuclear ribonucleoproteins and, additionally, in synaptic function. SMN deficiency produces defects in motor neuron β‐actin mRNA axonal transport, neurofilament dynamics, neurotransmitter release, and synapse maturation. The underlying molecular mechanisms and, in particular, the role of the cytoskeleton on the pathogenesis of this disease are starting to be revealed. © 2011 Wiley Periodicals, Inc. Develop Neurobiol 72: 126–133, 2012
A hybrid ant algorithm for scheduling independent jobs in heterogeneous computing environments

The efficient scheduling of independent computational jobs in a heterogeneous computing (HC) environment is an important problem in domains such as grid computing. Finding optimal schedules for such an environment is (in general) an NP-hard problem, and so heuristic approaches must be used. In this paper we describe an ant colony optimisation (ACO) algorithm that, when combined with local and tabu search, can find shorter schedules on benchmark problems than other techniques found in the literature.