695 research outputs found
Silicon-based photonic crystals fabricated using proton beam writing combined with electrochemical etching method
A method for fabrication of three-dimensional (3D) silicon nanostructures based on selective formation of porous silicon using ion beam irradiation of bulk p-type silicon followed by electrochemical etching is shown. It opens a route towards the fabrication of two-dimensional (2D) and 3D silicon-based photonic crystals with high flexibility and industrial compatibility. In this work, we present the fabrication of 2D photonic lattice and photonic slab structures and propose a process for the fabrication of 3D woodpile photonic crystals based on this approach. Simulated results of photonic band structures for the fabricated 2D photonic crystals show the presence of TE or TM gap in mid-infrared rang
Hemodynamic latency is associated with reduced intelligence across the lifespan: an fMRI DCM study of aging, cerebrovascular integrity, and cognitive ability
Changes in neurovascular coupling are associated with both Alzheimer’s disease and vascular dementia in later life, but this may be confounded by cerebrovascular risk. We hypothesized that hemodynamic latency would be associated with reduced cognitive functioning across the lifespan, holding constant demographic and cerebrovascular risk. In 387 adults aged 18–85 (mean = 48.82), dynamic causal modeling was used to estimate the hemodynamic response function in the left and right V1 and V3-ventral regions of the visual cortex in response to a simple checkerboard block design stimulus with minimal cognitive demands. The hemodynamic latency (transit time) in the visual cortex was used to predict general cognitive ability (Full-Scale IQ), controlling for demographic variables (age, race, education, socioeconomic status) and cerebrovascular risk factors (hypertension, alcohol use, smoking, high cholesterol, BMI, type 2 diabetes, cardiac disorders). Increased hemodynamic latency in the visual cortex predicted reduced cognitive function (p < 0.05), holding constant demographic and cerebrovascular risk. Increased alcohol use was associated with reduced overall cognitive function (Full Scale IQ 2.8 pts, p < 0.05), while cardiac disorders (Full Scale IQ 3.3 IQ pts; p < 0.05), high cholesterol (Full Scale IQ 3.9 pts; p < 0.05), and years of education (2 IQ pts/year; p < 0.001) were associated with higher general cognitive ability. Increased hemodynamic latency was associated with reduced executive functioning (p < 0.05) as well as reductions in verbal concept formation (p < 0.05) and the ability to synthesize and analyze abstract visual information (p < 0.01). Hemodynamic latency is associated with reduced cognitive ability across the lifespan, independently of other demographic and cerebrovascular risk factors. Vascular health may predict cognitive ability long before the onset of dementias
Population density, water supply, and the risk of dengue fever in Vietnam: cohort study and spatial analysis.
BACKGROUND: Aedes aegypti, the major vector of dengue viruses, often breeds in water storage containers used by households without tap water supply, and occurs in high numbers even in dense urban areas. We analysed the interaction between human population density and lack of tap water as a cause of dengue fever outbreaks with the aim of identifying geographic areas at highest risk. METHODS AND FINDINGS: We conducted an individual-level cohort study in a population of 75,000 geo-referenced households in Vietnam over the course of two epidemics, on the basis of dengue hospital admissions (n = 3,013). We applied space-time scan statistics and mathematical models to confirm the findings. We identified a surprisingly narrow range of critical human population densities between around 3,000 to 7,000 people/km² prone to dengue outbreaks. In the study area, this population density was typical of villages and some peri-urban areas. Scan statistics showed that areas with a high population density or adequate water supply did not experience severe outbreaks. The risk of dengue was higher in rural than in urban areas, largely explained by lack of piped water supply, and in human population densities more often falling within the critical range. Mathematical modeling suggests that simple assumptions regarding area-level vector/host ratios may explain the occurrence of outbreaks. CONCLUSIONS: Rural areas may contribute at least as much to the dissemination of dengue fever as cities. Improving water supply and vector control in areas with a human population density critical for dengue transmission could increase the efficiency of control efforts. Please see later in the article for the Editors' Summary
Community evolution in patent networks: technological change and network dynamics
When studying patent data as a way to understand innovation and technological change, the conventional indicators might fall short, and categorizing technologies based on the existing classification systems used by patent authorities could cause inaccuracy and misclassification, as shown in literature. Gao et al. (International Workshop on Complex Networks and their Applications, 2017) have established a method to analyze patent classes of similar technologies as network communities. In this paper, we adopt the stabilized Louvain method for network community detection to improve consistency and stability. Incorporating the overlapping community mapping algorithm, we also develop a new method to identify the central nodes based on the temporal evolution of the network structure and track the changes of communities over time. A case study of Germany’s patent data is used to demonstrate and verify the application of the method and the results. Compared to the non-network metrics and conventional network measures, we offer a heuristic approach with a dynamic view and more stable results
Community evolution in patent networks: technological change and network dynamics
When studying patent data as a way to understand innovation and technological change, the conventional indicators might fall short, and categorizing technologies based on the existing classification systems used by patent authorities could cause inaccuracy and misclassification, as shown in literature. Gao et al. (International Workshop on Complex Networks and their Applications, 2017) have established a method to analyze patent classes of similar technologies as network communities. In this paper, we adopt the stabilized Louvain method for network community detection to improve consistency and stability. Incorporating the overlapping community mapping algorithm, we also develop a new method to identify the central nodes based on the temporal evolution of the network structure and track the changes of communities over time. A case study of Germany’s patent data is used to demonstrate and verify the application of the method and the results. Compared to the non-network metrics and conventional network measures, we offer a heuristic approach with a dynamic view and more stable results
Long Time to Diagnosis of Medulloblastoma in Children Is Not Associated with Decreased Survival or with Worse Neurological Outcome
International audienceBACKGROUND: The long time to diagnosis of medulloblastoma, one of the most frequent brain tumors in children, is the source of painful remorse and sometimes lawsuits. We analyzed its consequences for tumor stage, survival, and sequelae. PATIENTS AND METHODS: This retrospective population-based cohort study included all cases of pediatric medulloblastoma from a region of France between 1990 and 2005. We collected the demographic, clinical, and tumor data and analyzed the relations between the interval from symptom onset until diagnosis, initial disease stage, survival, and neuropsychological and neurological outcome. RESULTS: The median interval from symptom onset until diagnosis for the 166 cases was 65 days (interquartile range 31-121, range 3-457). A long interval (defined as longer than the median) was associated with a lower frequency of metastasis in the univariate and multivariate analyses and with a larger tumor volume, desmoplastic histology, and longer survival in the univariate analysis, but not after adjustment for confounding factors. The time to diagnosis was significantly associated with IQ score among survivors. No significant relation was found between the time to diagnosis and neurological disability. In the 62 patients with metastases, a long prediagnosis interval was associated with a higher T stage, infiltration of the fourth ventricle floor, and incomplete surgical resection; it nonetheless did not influence survival significantly in this subgroup. CONCLUSIONS: We found complex and often inverse relations between time to diagnosis of medulloblastoma in children and initial severity factors, survival, and neuropsychological and neurological outcome. This interval appears due more to the nature of the tumor and its progression than to parental or medical factors. These conclusions should be taken into account in the information provided to parents and in expert assessments produced for malpractice claims
Geldanamycin Derivative Ameliorates High Fat Diet-Induced Renal Failure in Diabetes
Diabetic nephropathy is a serious complication of longstanding diabetes and its pathogenesis remains unclear. Oxidative stress may play a critical role in the pathogenesis and progression of diabetic nephropathy. Our previous studies have demonstrated that polyunsaturated fatty acids (PUFA) induce peroxynitrite generation in primary human kidney mesangial cells and heat shock protein 90β1 (hsp90β1) is indispensable for the PUFA action. Here we investigated the effects of high fat diet (HFD) on kidney function and structure of db/db mice, a widely used rodent model of type 2 diabetes. Our results indicated that HFD dramatically increased the 24 h-urine output and worsened albuminuria in db/db mice. Discontinuation of HFD reversed the exacerbated albuminuria but not the increased urine output. Prolonged HFD feeding resulted in early death of db/db mice, which was associated with oliguria and anuria. Treatment with the geldanamycin derivative, 17-(dimethylaminoehtylamino)-17-demethoxygeldanamycin (17-DMAG), an hsp90 inhibitor, preserved kidney function, and ameliorated glomerular and tubular damage by HFD. 17-DMAG also significantly extended survival of the animals and protected them from the high mortality associated with renal failure. The benefit effect of 17-DMAG on renal function and structure was associated with a decreased level of kidney nitrotyrosine and a diminished kidney mitochondrial Ca2+ efflux in HFD-fed db/db mice. These results suggest that hsp90β1 is a potential target for the treatment of nephropathy and renal failure in diabetes
Repeated cycles of Clostridium-directed enzyme prodrug therapy result in sustained antitumour effects in vivo
The unique properties of the tumour microenvironment can be exploited by using recombinant anaerobic clostridial spores as highly selective gene delivery vectors. Although several recombinant Clostridium species have been generated during the past decade, their efficacy has been limited. Our goal was to substantially improve the prospects of clostridia as a gene delivery vector. Therefore, we have assessed a series of nitroreductase (NTR) enzymes for their capacity to convert the innocuous CB1954 prodrug to its toxic derivative. Among the enzymes tested, one showed superior prodrug turnover characteristics. In addition, we established an efficient gene transfer procedure, based on conjugation, which allows for the first time genetic engineering of Clostridium strains with superior tumour colonisation properties with high success rates. This conjugation procedure was subsequently used to create a recombinant C. sporogenes overexpressing the isolated NTR enzyme. Finally, analogous to a clinical setting situation, we have tested the effect of multiple consecutive treatment cycles, with antibiotic bacterial clearance between cycles. Importantly, this regimen demonstrated that intravenously administered spores of NTR-recombinant C. sporogenes produced significant antitumour efficacy when combined with prodrug administration
Improvement of attention span and reaction time with hyperbaric oxygen treatment in patients with toxic injury due to mold exposure
It is, by now, well established that mold toxins (mycotoxins) can cause significant adverse health effects. In this study, 15 subjects who developed an attention deficit disorder (ADD) and slowing of reaction time at the time of exposure to mold toxins were identified. Deficits in attention span and reaction time were documented not only by taking a careful history, but also by performing a Test of Variables of Attention (TOVA). The TOVA test provides an objective measure of these two variables. It was found that mold-exposed subjects show statistically significant decreases in attention span and significant increases in reaction time to stimuli compared to controls. After ten sessions of hyperbaric oxygen treatment (HBOT), a statistically significant improvement was seen in both measures. This preliminary study suggests promising outcomes in treating mold-exposed patients with hyperbaric oxygen
Defining the Molecular Basis of Tumor Metabolism: a Continuing Challenge Since Warburg's Discovery
Cancer cells are the product of genetic disorders that alter crucial intracellular signaling pathways associated with the regulation of cell survival, proliferation, differentiation and death mechanisms. the role of oncogene activation and tumor suppressor inhibition in the onset of cancer is well established. Traditional antitumor therapies target specific molecules, the action/expression of which is altered in cancer cells. However, since the physiology of normal cells involves the same signaling pathways that are disturbed in cancer cells, targeted therapies have to deal with side effects and multidrug resistance, the main causes of therapy failure. Since the pioneering work of Otto Warburg, over 80 years ago, the subversion of normal metabolism displayed by cancer cells has been highlighted by many studies. Recently, the study of tumor metabolism has received much attention because metabolic transformation is a crucial cancer hallmark and a direct consequence of disturbances in the activities of oncogenes and tumor suppressors. in this review we discuss tumor metabolism from the molecular perspective of oncogenes, tumor suppressors and protein signaling pathways relevant to metabolic transformation and tumorigenesis. We also identify the principal unanswered questions surrounding this issue and the attempts to relate these to their potential for future cancer treatment. As will be made clear, tumor metabolism is still only partly understood and the metabolic aspects of transformation constitute a major challenge for science. Nevertheless, cancer metabolism can be exploited to devise novel avenues for the rational treatment of this disease. Copyright (C) 2011 S. Karger AG, BaselFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Fed ABC UFABC, CCNH, Santo Andre, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Ciencias Biol, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Bioquim, São Paulo, BrazilUniv Fed Sao Carlos UFSCar, DFQM, Sorocaba, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Ciencias Biol, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Bioquim, São Paulo, BrazilFAPESP: 10/16050-9FAPESP: 10/11475-1FAPESP: 08/51116-0Web of Scienc
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