950 resultados para Calculus of variations
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The distribution of Lutzomyia longipalpis is heterogeneous with a pattern of high abundance areas (HAAs) embedded in a matrix of low abundance areas (LAAs). The objective of this study was to describe the variability in the abundance of Lu. longipalpis at two different spatial levels and to analyse the relationship between the abundance and multiple environmental variables. Of the environmental variables analysed in each household, the condition that best explained the differences in vector abundance between HAA-LAA was the variable "land_grass", with greater average values in the peridomestic environments within the LAA, and the variables "#sp tree", "#pots" and "dist_water" that were higher in the HAA. Of the environmental variables analysed in the patches, the variable "unpaved_streets" was higher in the LAAs and the variable "prop_inf_dogs" was higher in the HAAs. An understanding of the main environmental variables that influence the vector distribution could contribute to the development of strategies for the prevention and control of visceral leishmaniasis (VL). This is the first work in which environmental variables are analysed at the micro-scale in urban areas at the southern edge of the current range of Lu. longipalpis. Our results represent a significant contribution to the understanding of the abundance of the vector in the peridomestic habitats of the region.
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Pitch is a fundamental musical factor; however, findings about its contribution to the elicitation of emotions are contradictory. The purpose of this work was to assess the effect of systematic pitch variations on self-reports of felt valence and arousal. In a within-subject design, 49 subjects listened to four 1-minute classical piano excerpts, each presented at three different pitch levels (one octave lower than the original version, the original version and one octave higher than the original version). Compared to excerpts both without octave modification and in the +1 octave variant, pleasantness of excerpts in the -1 octave variant was significantly lower. This main effect was stronger for women than men and, importantly, was modulated by the specific characteristics of the stimuli. There was also a significant, yet smaller, negative relationship between pitch level and arousal, moderated by gender: Compared to higher pitch, lower pitch was associated with higher arousal in men only. Regarding the complex outcomes of this study, future studies should investigate to which extent our findings can be generalized to other musical works. The ultimate goal might be to demonstrate how pitch level interacts with other musical features and listeners' characteristics in eliciting diverse affective experiences.
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INTRODUCTION: Symptomatic foraminal stenosis has been observed in patients with degenerative disc disease, scoliosis, asymmetrical disc degeneration and spondylolisthesis. Nevertheless not all patients with the above pathologies will develop symptomatic foraminal stenosis. We hypothesised that symptomatic patients have anatomical predisposition to foraminal stenosis, namely a larger pedicle height (PH) to vertebral body height (VH) ratio, leaving less room below the pedicle for the exiting nerve root compared to asymptomatic patients. PATIENT SAMPLE: 66 Patients were divided in two groups. The surgical group consisted of 37 patients (average age of 61 years) who presented with severe radicular symptoms resisting to conservative measures and requiring decompression and transforaminal lumbar interbody fusion (TLIF). The control group consisted of 29 patients (average age of 51 years) presenting with low back pain (LBP) but with no radicular symptoms and who were treated conservatively. METHODS: We measured VH at the level of the posterior wall as well as PH on parasagittal images (CT or MRI) on all lumbar levels (L1 to L5). Statistical analysis was performed using Student's t test. RESULTS: No difference in PH was found between the two groups for L1 to L4 levels. By contrast, there was a highly statistically significant difference in VH between the two groups from L1 to L4 level. In the surgical group, the VH was smaller (p < 0.001). CONCLUSIONS: Symptomatic patients with foraminal stenosis have smaller VH leading to lesser space beneath the pedicle and putting the exiting nerve root at risk in cases of spondylolisthesis or disc degeneration.
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In Switzerland like in most developed countries, the number of births is strongly related to the hour of the day and the day of the week: this pattern is very probably related to the current practice in obstetrics. Less expected is the fact that the perinatal mortality shows a striking circadian rhythm according to the hour of birth. The paper presents this pattern and comments some related issues.
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Background: Single nucleotide polymorphisms (SNPs) are the most frequent type of sequence variation between individuals, and represent a promising tool for finding genetic determinants of complex diseases and understanding the differences in drug response. In this regard, it is of particular interest to study the effect of non-synonymous SNPs in the context of biological networks such as cell signalling pathways. UniProt provides curated information about the functional and phenotypic effects of sequence variation, including SNPs, as well as on mutations of protein sequences. However, no strategy has been developed to integrate this information with biological networks, with the ultimate goal of studying the impact of the functional effect of SNPs in the structure and dynamics of biological networks. Results: First, we identified the different challenges posed by the integration of the phenotypic effect of sequence variants and mutations with biological networks. Second, we developed a strategy for the combination of data extracted from public resources, such as UniProt, NCBI dbSNP, Reactome and BioModels. We generated attribute files containing phenotypic and genotypic annotations to the nodes of biological networks, which can be imported into network visualization tools such as Cytoscape. These resources allow the mapping and visualization of mutations and natural variations of human proteins and their phenotypic effect on biological networks (e.g. signalling pathways, protein-protein interaction networks, dynamic models). Finally, an example on the use of the sequence variation data in the dynamics of a network model is presented. Conclusion: In this paper we present a general strategy for the integration of pathway and sequence variation data for visualization, analysis and modelling purposes, including the study of the functional impact of protein sequence variations on the dynamics of signalling pathways. This is of particular interest when the SNP or mutation is known to be associated to disease. We expect that this approach will help in the study of the functional impact of disease-associated SNPs on the behaviour of cell signalling pathways, which ultimately will lead to a better understanding of the mechanisms underlying complex diseases.
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During their development, immature CD4+ CD8+ thymocytes become committed to either the CD4 or CD8 lineage. Subsequent complete maturation of CD4+ and CD8+ cells requires a molecular match of the expressed coreceptor and the MHC specificity of the TCR. The final size of the mature CD4+ and CD8+ thymic compartments is therefore determined by a combination of lineage commitment and TCR-mediated selection. In humans and mice, the relative size of CD4+ and CD8+ peripheral T cell compartments shows marked genetic variability. We show here that genetic variations in thymic lineage commitment, rather than TCR-mediated selection processes, are responsible for the distinct CD4/CD8 ratios observed in common inbred mouse strains. Genetic variations in the regulation of lineage commitment open new ways to analyze this process and to identify the molecules involved.
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BACKGROUND: Sodium wasting during the night has been postulated as a potential pathophysiological mechanism in patients suffering from orthostatic hypotension due to severe autonomic deficiency. METHODS: In this study, the diurnal variations in creatinine clearance, sodium excretion and segmental renal tubular handling of sodium were evaluated in 18 healthy subjects and 20 young patients with orthostatic hypotension (OH). In addition, 24-hour ambulatory blood pressure and the neuro-hormonal response to changes in posture were determined. The patients and their controls were studied on a free sodium intake. In a second protocol, 10 controls and 10 patients were similarly investigated after one week of a high salt diet (regular diet + 6 g NaCl/day). RESULTS: Our results demonstrate that, in contrast to normal subjects in whom no significant changes in glomerular filtration, sodium excretion and segmental sodium reabsorption were observed throughout the day, patients with OH were characterized by a significant increase in glomerular filtration rate during the nighttime (P = 0.03) and significant increases in urinary lithium excretion (P < 0.05) and lithium clearance (P = 0.05) during the night, suggesting a decreased proximal reabsorption of sodium. On a high sodium diet, the symptoms of orthostatic hypotension and the circadian variations in sodium reabsorption were significantly blunted. CONCLUSIONS: These results suggest that, while the patient is in a supine position the effective blood volume of those with OH becomes excessive due to the increased venous return. Hence, the kidney responds with an increase in glomerular filtration and a relative escape of sodium from the proximal tubular segments. These circadian variations in renal sodium handling may contribute to the maintenance of the orthostatic syndrome.
Genetic Variations and Diseases in UniProtKB/Swiss-Prot: The Ins and Outs of Expert Manual Curation.
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During the last few years, next-generation sequencing (NGS) technologies have accelerated the detection of genetic variants resulting in the rapid discovery of new disease-associated genes. However, the wealth of variation data made available by NGS alone is not sufficient to understand the mechanisms underlying disease pathogenesis and manifestation. Multidisciplinary approaches combining sequence and clinical data with prior biological knowledge are needed to unravel the role of genetic variants in human health and disease. In this context, it is crucial that these data are linked, organized, and made readily available through reliable online resources. The Swiss-Prot section of the Universal Protein Knowledgebase (UniProtKB/Swiss-Prot) provides the scientific community with a collection of information on protein functions, interactions, biological pathways, as well as human genetic diseases and variants, all manually reviewed by experts. In this article, we present an overview of the information content of UniProtKB/Swiss-Prot to show how this knowledgebase can support researchers in the elucidation of the mechanisms leading from a molecular defect to a disease phenotype.
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We previously reported that interleukin-1beta (IL-1beta) alone does not cause apoptosis of beta-cells, whereas when combined with gamma-interferon (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), it exerts a distinct apoptotic effect. Studies in beta-cell lines indicated that IL-1beta reduced expression of islet brain (IB)-1/JNK interacting protein (JIP)-1, a JNK scaffold protein with antiapoptotic action. We examined whether variations in IB1/JIP-1 expression in purified primary beta-cells affect their susceptibility to cytokine-induced apoptosis. Exposure to IL-1beta for 24 h decreased cellular IB1/JIP-1 content by 66 +/- 17%; this IL-1beta effect was maintained in the presence of TNF-alpha + IFN-gamma, which did not influence IB1/JIP-1 levels by themselves. Addition of IL-1beta to TNF-alpha + IFN-gamma increased apoptosis from 20 +/- 2% to 59 +/- 5%. A similar increase in TNF-alpha + IFN-gamma-induced apoptosis was produced by adenoviral expression of antisense IB1/JIP-1 and was not further enhanced by addition of IL-1beta, indicating that IL-1beta-mediated suppression of IB1/JIP-1 in beta-cells increases their susceptibility to cytokine-induced apoptosis. However, adenovirally mediated overexpression of IB1/JIP-1 also potentiated TNF-alpha + IFN-gamma-induced apoptosis, suggesting that the antiapoptotic effect of IB1/JIP-1 depends on well-defined cellular levels. We conclude that the IB1/JIP-1 level in beta-cells can control their susceptibility to apoptosis independent of JNK signaling.
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In short space of time increase in temperature and rainfall can affect vector populations and, consequently, the diseases for them transmitted. The present study analyzed the effect of small temperature and humidity variations on the fecundity, fertility and survival of Aedes aegypti. These parameters were analyzed using individual females at temperatures ranging from 23 to 27 °C (mean 25 °C); 28 to 32 °C (mean 30 °C) and 33 to 37 °C (mean 35 ºC) associated to 60±8% and 80±6% relative humidity. Females responded to an increase in temperature by reducing egg production, oviposition time and changing oviposition patterns. At 25 ºC and 80% relative humidity, females survived two-fold more and produced 40% more eggs when compared to those kept at 35 ºC and 80% relative humidity. However, in 45% of females kept at 35 ºC and 60% relative humidity oviposition was inhibited and only 15% females laid more than 100 eggs, suggesting that the intensity of the temperature effect was influenced by humidity. Gradual reductions in egg fertility at 60% relative humidity were observed with the increase in temperature, although such effect was not found in the 80% relative humidity at 25 º C and 30 º C. These results suggest that the reduction in population densities recorded in tropical areas during seasons when temperatures reach over 35 ºC is likely to be strongly influenced by temperature and humidity, with a negative effect on several aspects of mosquito biology.
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OBJECTIVE: To measure the in vivo variations of CYP3A activity induced by anti-HIV drugs in human immunodeficiency virus (HIV)1-positive patients. METHODS: A low oral dose of midazolam (MID) (0.075 mg) was given to the patients and the 30-min total 1-OH midazolam (1-OHMID)/MID ratio was determined. Patients were phenotyped either before the introduction of antiretroviral treatments (control group, 90 patients) or after a variable period of antiretroviral treatment (56 patients). Twenty-one subjects underwent multiple phenotyping tests (before and during the course of the treatment). RESULTS: The median MID ratio was 3.51 in the control group (range 0.20-14.6). It was 5-fold higher in the group with efavirenz (28 patients; median, range: 16.0, 3.81-367; P < 0.0001), 13-fold lower with nelfinavir (18 patients; 0.27, 0.06-36.3; P < 0.0001), 17-fold lower with efavirenz + ritonavir (three patients; 0.21, 0.05-0.47; P = 0.006), 50-fold lower with ritonavir (four patients; 0.07, 0.06-0.17; P = 0.0007), and 7-fold lower with nevirapine + (ritonavir or nelfinavir or grapefruit juice) (three patients; 0.48, 0.03-1.83; P = 0.03). CYP3A activity was lower in the efavirenz + ritonavir group (P = 0.01) and in the ritonavir group (P = 0.04) than in the nelfinavir group, although already strongly inhibited in the latter. CONCLUSION: The low-dose MID phenotyping test was successfully used to measure the in vivo variations of CYP3A activity induced by antiretroviral drugs. Efavirenz strongly induces CYP3A activity, while ritonavir almost completely inhibits it. Nelfinavir strongly decreases CYP3A activity, but to a lesser extent than ritonavir. The inhibition of CYP3A by ritonavir or nelfinavir offsets the inductive effects of efavirenz or nevirapine administered concomitantly. Finally, no induction of CYP3A activity was noticeable after long-term administration of ritonavir at low dosages (200 mg/day b.i.d.) or of nelfinavir at standard dosages (2,500 mg/day b.i.d.).
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The geochemical compositions of biogenic carbonates are increasingly used for palaeoenvironmental reconstructions. The skeletal delta O-18 temperature relationship is dependent on water salinity, so many recent studies have focused on the Mg/Ca and Sr/Ca ratios because those ratios in water do not change significantly on short time scales. Thus, those elemental ratios are considered to be good palaeotemperature proxies in many biominerals, although their use remains ambiguous in bivalve shells. Here, we present the high-resolution Mg/Ca ratios of two modern species of juvenile and adult oyster shells, Crassostrea gigas and Ostrea edulis. These specimens were grown in controlled conditions for over one year in two different locations. In situ monthly Mn-marking of the shells has been used for day calibration. The daily Mg/Ca.ratios in the shell have been measured with an electron microprobe. The high frequency Mg/Ca variation of all specimens displays good synchronism with lunar cycles, suggesting that tides strongly influence the incorporation of Mg/Ca into the shells. Highly significant correlation coefficients (0.70<R<0.83, p<0.0001) between the Mg/Ca ratios and the seawater temperature are obtained only for juvenile C. gigas samples, while metabolic control of Mg/Ca incorporation and lower shell growth rates preclude the use of the Mg/Ca ratio in adult shells as a palaeothermometer. Data from three juvenile C. gigas shells from the two study sites are selected to establish a relationship: T = 3.77Mg/Ca + 1.88, where T is in degrees C and Mg/Ca in mmol/mol. (c) 2012 Elsevier B.V. All rights reserved.
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study of channel catfish in the Mississippi River to determine differences in year class abundance and causative factors
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BACKGROUND: Previous published studies have shown significant variations in colonoscopy performance, even when medical factors are taken into account. This study aimed to examine the role of nonmedical factors (ie, embodied in health care system design) as possible contributors to variations in colonoscopy performance. METHODS: Patient data from a multicenter observational study conducted between 2000 and 2002 in 21 centers in 11 western countries were used. Variability was captured through 2 performance outcomes (diagnostic yield and colonoscopy withdrawal time), jointly studied as dependent variables, using a multilevel 2-equation system. RESULTS: Results showed that open-access systems and high-volume colonoscopy centers were independently associated with a higher likelihood of detecting significant lesions and longer withdrawal durations. Fee for service (FFS) payment was associated with shorter withdrawal durations, and so had an indirect negative impact on the diagnostic yield. Teaching centers exhibited lower detection rates and longer withdrawal times. CONCLUSIONS: Our results suggest that gatekeeping colonoscopy is likely to miss patients with significant lesions and that developing specialized colonoscopy units is important to improve performance. Results also suggest that FFS may result in a lower quality of care in colonoscopy practice and highlight the fact that longer withdrawal times do not necessarily indicate higher quality in teaching centers.