330 research outputs found

    © Hindawi Publishing Corp. RELIABILITY OF COMMUNICATION NETWORKS WITH DELAY CONSTRAINTS: COMPUTATIONAL COMPLEXITY AND COMPLETE TOPOLOGIES

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    Let G = (V,E) be a graph with a distinguished set of terminal vertices K ⊆ V. We define the K-diameter of G as the maximum distance between any pair of vertices of K. If the edges fail randomly and independently with known probabilities (vertices are always operational), the diameter-constrained K-terminal reliability of G, RK(G,D), is defined as the probability that surviving edges span a subgraph whose K-diameter does not exceed D. In general, the computational complexity of evaluating RK(G,D) is NP-hard, as this measure subsumes the classical K-terminal reliability RK(G), known to belong to this complexity class. In this note, we show that even though for two terminal vertices s and t and D = 2, R{s,t}(G,D) can be determined in polynomial time, the problem of calculating R{s,t}(G,D) forfixedvaluesofD, D ≥ 3, is NP-hard. We also generalize this result for any fixed number of terminal vertices. Although it is very unlikely that general efficient algorithms exist, we present a recursive formulation for the calculation of R{s,t}(G,D) that yields a polynomial time evaluation algorithm in the case of complete topologies where the edge set can be partitioned into at most four equi-reliable classes. 2000 Mathematics Subject Classification: 05C99, 90B25

    International burden of cancer deaths and years of life lost from cancer attributable to four major risk factors: a population-based study in Brazil, Russia, India, China, South Africa, the United Kingdom, and United States

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    Background: We provide a comprehensive view of the impact of alcohol consumption, tobacco smoking, excess body weight, and human papillomavirus (HPV) infection on cancer mortality and years of life lost (YLLs) in Brazil, Russia, India, China, South Africa, the United Kingdom (UK), and United States (US). Methods: We collected population attributable fractions of the four risk factors from global population-based studies and applied these to estimates of cancer deaths in 2020 to obtain potentially preventable cancer deaths and their 95% confidence intervals (CIs). Using life tables, we calculated the number and age-standardised rates of YLLs (ASYR). Findings: In Brazil, Russia, India, China, South Africa, the UK, and the US in 2020, an estimated 5.9 million (3.3 million–8.6 million) YLLs from cancer were attributable to alcohol consumption, 20.8 million (17.0 million–24.6 million) YLLs to tobacco smoking, 3.1 million (2.4 million–3.8 million) YLLs to excess body weight, and 4.0 million (3.9 million–4.2 million) YLLs to HPV infection. The ASYR from cancer due to alcohol consumption was highest in China (351.4 YLLs per 100,000 population [95% CI 194.5–519.2]) and lowest in the US (113.5 [69.6–157.1]) and India (115.4 [49.7–172.7). For tobacco smoking, China (1159.9 [950.6–1361.8]) had the highest ASYR followed by Russia (996.8 [831.0–1154.5). For excess body weight, Russia and the US had the highest ASYRs (385.1 [280.6–481.2] and 369.4 [299.6–433.6], respectively). The highest ASYR due to HPV infection was in South Africa (457.1 [453.3–462.6]). ASYRs for alcohol consumption and tobacco smoking were higher among men than women, whereas women had higher ASYRs for excess body weight and HPV infection. Interpretation: Our findings demonstrate the importance of cancer control efforts to reduce the burden of cancer death and YLLs due to modifiable cancer risk factors and promote the use of YLLs to summarise disease burden. Funding: Cancer Research UK

    Development of an in vitro cell system from zebrafish suitable to study bone cell differentiation and extracellular matrix mineralization

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    Mechanisms of bone formation and skeletal development have been successfully investigated in zebrafish using a variety of in vivo approaches, but in vitro studies have been hindered due to a lack of homologous cell lines capable of producing an extracellular matrix (ECM) suitable for mineral deposition. Here we describe the development and characterization of a new cell line termed ZFB1, derived from zebrafish calcified tissues. ZFB1 cells have an epithelium-like phenotype, grow at 28 degrees C in a regular L-15 medium supplemented with 15% of fetal bovine serum, and are maintained and manipulated using standard methods (e.g., trypsinization, cryopreservation, and transfection). They can therefore be propagated and maintained easily in most cell culture facilities. ZFB1 cells show aneuploidy with 2n=78 chromosomes, indicative of cell transformation. Furthermore, because DNA can be efficiently delivered into their intracellular space by nucleofection, ZFB1 cells are suitable for gene targeting approaches and for assessing gene promoter activity. ZFB1 cells can also differentiate toward osteoblast or chondroblast lineages, as demonstrated by expression of osteoblast- and chondrocyte-specific markers, they exhibit an alkaline phosphatase activity, a marker of bone formation in vivo, and they can mineralize their ECM. Therefore, they represent a valuable zebrafish-derived in vitro system for investigating bone cell differentiation and extracellular matrix mineralization.FISHCELL project [PTDC/MAR/105313/2008]; Portuguese Science and Technology Foundation (FCT); European Regional Development Fund (ERDF) through the COMPETE Program; National Fund through FCT [PEst-C/MAR/LA0015/2011]; FCT [SFRH/BPD/39189/2007]; Association of European Marine Biological Laboratories through the ASSEMBLE project [FP7/227799]info:eu-repo/semantics/publishedVersio

    Adaptación del Brain Gym® al medio acuático: efectos en la función física y congnitiva de los adultos mayores

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    Diferentes investigaciones han propuesto que la práctica regular de la actividad física, especialmente el ejercicio aeróbico, se relaciona con beneficios cognitivos (Lautenschlager et al., 2008; Baker et al., 2010). Varios meta-análisis han informado que la actividad física se asocia con mejoras en la atención, velocidad de procesamiento, y la función ejecutiva en los adultos mayores con y sin discapacidades cognitivas (van Uffelen et al., 2008; Smith et al., 2010). Los movimientos empleados en Brain Gym® (BG) están diseñados para estimular la fluidez de comunicación entre las áreas intercerebrales. Este flujo de información debe liberarse debido a que, para realizar cualquier acción, el cerebro debe funcionar coordinado, integrado y relajado. El programa BG asocia estas dificultades con bloqueos en el flujo de comunicación entre las dimensiones del cerebro, debido a la falta de conexiones neuronales. Objetivo: Analizar el efecto que un programa de ejercicios de Brain Gym® adaptados al medio acuático provoca en la función cognitiva y en el nivel de forma física de las personas mayores de 60 años.Different researches has proposed that the regular practice of physical activity, especially aerobic exercise, is related to cognitive benefits (Lautenschlager et al., 2008; Baker et al., 2010). Several meta-analyzes have reported that physical activity is associated with improvements in the attention, processing speed and executive function in older adults with and without cognitive disabilities (van Uffelen et al., 2008; Smith et al., 2010). The movements used in Brain Gym® (BG) are designed to stimulate the flow of communication between the intercerebrales areas. This flow of information must be released because in order to perform any action, the brain must work coordinated, integrated and relaxed. The program BG associates these difficulties with blockages in the flow of communication between the dimensions of the brain, due to the lack of neural connections. Objective: To analyze the effect that a program of Brain Gym® exercises adapted to the aquatic environment causes on the cognitive function and on the physical fitness level of people over 60 years of age.peerReviewe

    Diário de uma expedição de Pirara ao Upper Corentyne, e dali a Demerara

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    Tradução de Journal of an Expedition from Pirara to the Upper Corentyne, and from thence to Demerara, de Robert H. Schomburgk

    Myelin-associated glycoprotein activation triggers glutamate uptake by oligodendrocytes in vitro and contributes to ameliorate glutamate-mediated toxicity in vivo

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    Background: Myelin-associated glycoprotein (MAG) is a key molecule involved in the nurturing effect of myelin on ensheathed axons. MAG also inhibits axon outgrowth after injury. In preclinical stroke models, administration of a function-blocking anti-MAG monoclonal antibody (mAb) aimed to improve axon regeneration demonstrated reduced lesion volumes and a rapid clinical improvement, suggesting a mechanism of immediate neuroprotection rather than enhanced axon regeneration. In addition, it has been reported that antibody-mediated crosslinking of MAG can protect oligodendrocytes (OLs) against glutamate (Glu) overload by unknown mechanisms. Purpose: To unravel the molecular mechanisms underlying the protective effect of anti-MAG therapy with a focus on neuroprotection against Glu toxicity. Results: MAG activation (via antibody crosslinking) triggered the clearance of extracellular Glu by its uptake into OLs via high affinity excitatory amino acid transporters. This resulted not only in protection of OLs but also nearby neurons. MAG activation led to a PKC-dependent activation of factor Nrf2 (nuclear-erythroid related factor-2) leading to antioxidant responses including increased mRNA expression of metabolic enzymes from the glutathione biosynthetic pathway and the regulatory chain of cystine/Glu antiporter system xc− increasing reduced glutathione (GSH), the main antioxidant in cells. The efficacy of early anti-MAG mAb administration was demonstrated in a preclinical model of excitotoxicity induced by intrastriatal Glu administration and extended to a model of Experimental Autoimmune Encephalitis showing axonal damage secondary to demyelination. Conclusions: MAG activation triggers Glu uptake into OLs under conditions of Glu overload and induces a robust protective antioxidant response.Fil: Vivinetto, Ana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Castañares, Clara Nicole. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Garcia Keller, Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Moyano, Ana Lis. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Investigacion Medica Mercedes y Martin Ferreyra. Grupo Vinculado Centro de Investigacion En Medicina Traslacional Severo R. Amuchastegui - Cimetsa | Universidad Nacional de Cordoba. Instituto de Investigacion Medica Mercedes y Martin Ferreyra. Grupo Vinculado Centro de Investigacion En Medicina Traslacional Severo R. Amuchastegui - Cimetsa | Instituto de Investigacion Medica Mercedes y Martin Ferreyra. Instituto de Investigacion Medica Mercedes y Martin Ferreyra. Grupo Vinculado Centro de Investigacion En Medicina Traslacional Severo R. Amuchastegui - Cimetsa.; ArgentinaFil: Falcón, Cristian Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Palandri, Anabela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Rozés Salvador, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Rojas, Juan Ignacio. Centro de Esclerosis Múltiple de Buenos Aires; Argentina. Hospital Italiano; ArgentinaFil: Patrucco, Liliana. Hospital Italiano; Argentina. Centro de Esclerosis Múltiple de Buenos Aires; ArgentinaFil: Monferran, Clara Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Cancela, Liliana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Cristiano, Edgardo. Centro de Esclerosis Múltiple de Buenos Aires; Argentina. Hospital Italiano; ArgentinaFil: Schnaar, Ronald L.. University Johns Hopkins; Estados UnidosFil: Lopez, Pablo H. H.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Psicología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentin

    Inter-annual variations of macrobenthic communities over three decades in a land-locked coastal lagoon (Santo André, SW Portugal)

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    Santo Andre is an enclosed brackish water coastal lagoon with temporary connections to the sea by a man-made channel. The exchange and mixture of saltwater and freshwater is irregular and the lagoon may show daily and seasonal fluctuations, but also long-term variation. Different benthic communities may be present along the annual cycle according to the magnitude of episodic freshwater and sea water inputs. In the last 30 years the communication with the sea has followed different regimes from year to year and, as a consequence, macrobenthic communities, assessed several times during the period before the opening to the sea, shifted from freshwater to marine affinities. Major differences were found between 1979 and 2010, with a preponderance of species with marine affinity, and the 1980s in which the organisms with freshwater affinity prevailed. Benthic communities are frequently used to assess aquatic environmental condition. Metrics used in the indices currently under discussion to assess ecological status of aquatic ecosystems within the scope of European Water Framework Directive were applied to Santo Andre data and the applicability of these metrics to assess quality in this coastal land-locked lagoon was discussed. (C) 2012 Elsevier Ltd. All rights reserved.National Institute of Scientific Research; ICNB (Nature, Conservation and Biodiversity Institute); EEC (European Economic Community); Cohesion Fund under Priority 111 of the Operational Programme for Territorial Development (POVT); FCT (Science and Technology Foundation) [PTDC/AAC-AMB/104639/2008, PEst-OE/MAR/UI0199/2011]; FCT [SFRH/BPD/29579/2006

    Phosphorus Is Associated with Coronary Artery Disease in Patients with Preserved Renal Function

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    High serum phosphorus levels have been associated with mortality and cardiovascular events in patients with chronic kidney disease and in the general population. In addition, high phosphorus levels have been shown to induce vascular calcification and endothelial dysfunction in vitro. The aim of this study was to evaluate the relation of phosphorus and coronary calcification and atherosclerosis in the setting of normal renal function. This was a cross-sectional study involving 290 patients with suspected coronary artery disease and undergoing elective coronary angiography, with a creatinine clearance >60 ml/min/1.73 m2. Coronary artery obstruction was assessed by the Friesinger score and coronary artery calcification by multislice computed tomography. Serum phosphorus was higher in patients with an Agatston score >10 than in those with an Agatston score ≤10 (3.63±0.55 versus 3.49±0.52 mg/dl; p = 0.02). In the patients with Friesinger scores >4, serum phosphorus was higher (3.6±0.5 versus 3.5±0.6 mg/dl, p = 0.04) and median intact fibroblast growth factor 23 was lower (40.3 pg/ml versus 45.7 pg/ml, p = 0.01). Each 0.1-mg/dl higher serum phosphate was associated with a 7.4% higher odds of having a Friesinger score >4 (p = 0.03) and a 6.1% greater risk of having an Agatston score >10 (p = 0.01). Fibroblast growth factor 23 was a negative predictor of Friesinger score (p = 0.002). In conclusion, phosphorus is positively associated with coronary artery calcification and obstruction in patients with suspected coronary artery disease and preserved renal function

    Polymorphisms in MGP gene and their association with lead toxicity

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    Matrix γ-carboxy glutamic acid protein (MGP) is a 10-kDa secreted protein containing five residues of the vitamin K-dependent calcium binding amino acid γ-carboxyglutamic acid (Gla). This study was carried out to examine the effects of MGP gene promoter polymorphism (T-138C) on blood lead levels (BLL) and hematological parameters in 113 battery manufacturing unit workers occupationally exposed to lead and 102 controls. Genotypes for the MGP T-138C polymorphism were determined by PCR and restriction fragment length digestion. BLL were determined by Anode Stripping Voltammetry using ESA Model 3010B Lead analyzer. Complete blood picture (CBP) was analyzed using ADVIA Cell counter for each sample. The frequencies of MGP–TT, CT and CC genotypes in our population were 38.6%, 44.3%, and 17.2%, respectively. The frequencies for T and C alleles were 0.612 and 0.386, respectively. Although BLL did not differ significantly among genotypes; they were higher in workers with TT/CT genotype compared to CC genotype subjects (76–88 μg/dL vs 22–45 μg/dL, p > 0.05). About 29.2% of volunteers (n = 33) from the occupationally exposed group had hemoglobin levels below 10.0 gms/dl. There was no significant difference in total white cell count and platelet count between occupational and non-exposed groups. The possible role of SNPs in the promoter region of MGP gene with relation to lead toxicity was investigated for the first time in the Indian population; although significance could not be achieved in this study, further assessments over a larger population size may help in better understanding of the consequences of lead exposure

    Development of Functional Genomic Tools in Trematodes: RNA Interference and Luciferase Reporter Gene Activity in Fasciola hepatica

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    The growing availability of sequence information from diverse parasites through genomic and transcriptomic projects offer new opportunities for the identification of key mediators in the parasite–host interaction. Functional genomics approaches and methods for the manipulation of genes are essential tools for deciphering the roles of genes and to identify new intervention targets in parasites. Exciting advances in functional genomics for parasitic helminths are starting to occur, with transgene expression and RNA interference (RNAi) reported in several species of nematodes, but the area is still in its infancy in flatworms, with reports in just three species. While advancing in model organisms, there is a need to rapidly extend these technologies to other parasites responsible for several chronic diseases of humans and cattle. In order to extend these approaches to less well studied parasitic worms, we developed a test method for the presence of a viable RNAi pathway by silencing the exogenous reporter gene, firefly luciferase (fLUC). We established the method in the human blood fluke Schistosoma mansoni and then confirmed its utility in the liver fluke Fasciola hepatica. We transformed newly excysted juveniles of F. hepatica by electroporation with mRNA of fLUC and three hours later were able to detect luciferase enzyme activity, concentrated mainly in the digestive ceca. Subsequently, we tested the presence of an active RNAi pathway in F. hepatica by knocking down the exogenous luciferase activity by introduction into the transformed parasites of double-stranded RNA (dsRNA) specific for fLUC. In addition, we tested the RNAi pathway targeting an endogenous F. hepatica gene encoding leucine aminopeptidase (FhLAP), and observed a significant reduction in specific mRNA levels. In summary, these studies demonstrated the utility of RNAi targeting reporter fLUC as a reporter gene assay to establish the presence of an intact RNAi pathway in helminth parasites. These could facilitate the study of gene function and the identification of relevant targets for intervention in organisms that are by other means intractable. More specifically, these results open new perspectives for functional genomics of F. hepatica, which hopefully can lead to the development of new interventions for fascioliasis
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