Mathematical model and experimental characterization of vertically stacked capacitive tactile sensors

Capacitive sensors are widely used in robotics for their compactness, high resolution, high sensitivity, and large dynamic range. In this article, we present a design solution for the manufacturing of capacitive tactile sensors with enhanced dynamic range and sensitivity. Herein, we adopted the approach of exploiting the vertical direction of the sensors by creating stacks of capacitors. The validation of the proposed model is conducted by means of finite element simulations and the effectiveness of stacked capacitors in suboptimal configurations has been experimentally tested by using inkjet printing and spin coating-based fabrication techniques. Results show that these sensors exhibit an enhanced dynamic range and sensitivity with respect to common single capacitors, for a given sensors area budget. Sensitivity increases of 235% passing from one-stack to two-stack capacitors (from 5.75 to 19.3 fF/kPa) and a growth of 23% from two-stack to three-stack capacitors (from 19.3 to 23.7 fF/kPa). These results suggest that the proposed methodology could be adopted for designing tactile sensors with higher spatial resolution and higher transduction sensitivity and dynamic range, in the perspective of an integration over large areas

Imatinib-mesylate for all patients with hypereosinophilic syndrome?

Some recent papers have focused on the activity of imatinib-mesylate, a selective inhibitor of tyrosine kinase, in idiopathic hypereosinophilic syndrome (HES) [1], [2], [3] and [4]. In this setting, a possible therapeutic target was identified by Cools et al. [2], who described the fusion tyrosine-kinase gene FIP1L1/PDGFRA as the result of an interstitial deletion within chromosome 4 in nine out of sixteen (56%) patients affected by HES. Of interest, although in this study the response to imatinib was strictly correlated with the presence of FIP1L1/PDGFRA rearrangement (all patients with such a molecular lesion treated with imatinib responded), only five out of nine responding patients evidenced the abnormal transcript [2]. Among the possible alternative mechanisms for the activation of the PDGFRA tyrosine-kinase domain, these authors suggested there may be a different fusion gene

Evaluation of the effectiveness of three therapeutic protocols used in the treatment of visceral canine leishmaniosis

Leishmaniasis is a tropical and subtropical disease caused by an intracellular protozoan transmitted by a bite from a vector, mainly from the genera Phlebotomus and Lutzomyia, and affects humans and other mammals, especially dogs. The main objective in controlling canine visceral leishmaniasis is to reduce the number of human cases by reducing its prevalence in dogs. In Brazil, glucantime antimoniate and Amphotericin B, utilized for treating the disease in humans, are prohibited so that only miltefosine, which is not employed for treatment of humans, is permitted for use in dogs. This work aimed to evaluate the efficacy of three different therapeutic protocols employed in the treatment of dogs naturally infected with visceral leishmaniasis. Fifty-six (56) dogs, of both sexes, were treated and evaluated utilizing three treatment protocols. The following protocols were utilized: association of several drugs; miltefosine associated with allopurinol; and immunotherapy with anti- Leishmania vaccine associated with Allopurinol. Immunotherapy was the most efficient protocol, followed by an association of drugs and miltefosine. The use of these protocols diminishes the constant relapses of the disease. Associations of therapeutic protocols produced clinical improvement of patients even with presentation of subsequent negative serology. However, the study did not include aspects related to hemoparasitoses, thus a further study is required

An apparatus for in-situ direct shear tests on snow

The article presents a prototype of a new device for measuring the shear strength of snow specimens in situ. The resistance to sliding of a snow slab on a mountain slope is a key parameter in snow mechanics. The proposed apparatus acts as a sampler, to obtain a nearly undisturbed specimen, and as a shear box, similar to those used in the laboratory, with complete control of the test procedure. The main components of the device are a pneumatic system, for the application of normal and shear forces to the specimen, a real-time controller for commanding and recording of the data, and a computer. The apparatus can be carried to the place of the experiments and operated by a team of two researchers. Calibration and preliminary tests are also described in the article

Inheritance of DNA Transferred from American Trypanosomes to Human Hosts

Interspecies DNA transfer is a major biological process leading to the accumulation of mutations inherited by sexual reproduction among eukaryotes. Lateral DNA transfer events and their inheritance has been challenging to document. In this study we modified a thermal asymmetric interlaced PCR by using additional targeted primers, along with Southern blots, fluorescence techniques, and bioinformatics, to identify lateral DNA transfer events from parasite to host. Instances of naturally occurring human infections by Trypanosoma cruzi are documented, where mitochondrial minicircles integrated mainly into retrotransposable LINE-1 of various chromosomes. The founders of five families show minicircle integrations that were transferred vertically to their progeny. Microhomology end-joining of 6 to 22 AC-rich nucleotide repeats in the minicircles and host DNA mediates foreign DNA integration. Heterogeneous minicircle sequences were distributed randomly among families, with diversity increasing due to subsequent rearrangement of inserted fragments. Mosaic recombination and hitchhiking on retrotransposition events to different loci were more prevalent in germ line as compared to somatic cells. Potential new genes, pseudogenes, and knockouts were identified. A pathway of minicircle integration and maintenance in the host genome is suggested. Thus, infection by T. cruzi has the unexpected consequence of increasing human genetic diversity, and Chagas disease may be a fortuitous share of negative selection. This demonstration of contemporary transfer of eukaryotic DNA to the human genome and its subsequent inheritance by descendants introduces a significant change in the scientific concept of evolutionary biology and medicine

Epigenetic alterations in hippocampus of SAMP8 senescent mice and modulation by voluntary physical exercise

The senescence-accelerated SAMP8 mouse model displays features of cognitive decline and Alzheimer's disease. With the purpose of identifying potential epigenetic markers involved in aging and neurodegeneration, here we analyzed the expression of 84 mature miRNAs, the expression of histone-acetylation regulatory genes and the global histone acetylation in the hippocampus of 8-month-old SAMP8 mice, using SAMR1 mice as control. We also examined the modulation of these parameters by 8 weeks of voluntary exercise. Twenty-one miRNAs were differentially expressed between sedentary SAMP8 and SAMR1 mice and seven miRNAs were responsive to exercise in both strains. SAMP8 mice showed alterations in genes involved in protein acetylation homeostasis such as Sirt1 and Hdac6 and modulation of Hdac3 and Hdac5 gene exprssion by exercise. Global histone H3 acetylation levels were reduced in SAMP8 compared with SAMR1 mice and reached control levels in response to exercise. In sum, data presented here provide new candidate epigenetic markers for aging and neurodegeneration and suggest that exercise training may prevent or delay some epigenetic alterations associated with accelerated aging

Epigenetic alterations in hippocampus of SAMP8 senescent mice and modulation by voluntary physical exercise

The senescence-accelerated SAMP8 mouse model displays features of cognitive decline and Alzheimer's disease. With the purpose of identifying potential epigenetic markers involved in aging and neurodegeneration, here we analyzed the expression of 84 mature miRNAs, the expression of histone-acetylation regulatory genes and the global histone acetylation in the hippocampus of 8-month-old SAMP8 mice, using SAMR1 mice as control. We also examined the modulation of these parameters by 8 weeks of voluntary exercise. Twenty-one miRNAs were differentially expressed between sedentary SAMP8 and SAMR1 mice and seven miRNAs were responsive to exercise in both strains. SAMP8 mice showed alterations in genes involved in protein acetylation homeostasis such as Sirt1 and Hdac6 and modulation of Hdac3 and Hdac5 gene expression by exercise. Global histone H3 acetylation levels were reduced in SAMP8 compared with SAMR1 mice and reached control levels in response to exercise. In sum, data presented here provide new candidate epigenetic markers for aging and neurodegeneration and suggest that exercise training may prevent or delay some epigenetic alterations associated with accelerated aging

Long-term exercise modulates hippocampal gene expression in sencescent females mice

Altres ajuts: FI-DGR 2011 de la Generalitat de CatalunyaThe senescence-accelerated SAMP8 mouse is considered a useful non-transgenic model for studying aspects of progressive cognitive decline and Alzheimer's disease (AD). Using SAMR1 mice as controls, here we explored the effects of 6 months of voluntary wheel running in 10-month-old female SAMP8 mice. Exercise in SAMP8 mice improved phenotypic features associated with premature aging (i.e., skin color and body tremor) and enhanced vascularization and BDNF gene expression in the hippocampus compared with controls. With the aim of identifying genes involved in brain aging responsive to long-term exercise, we performed whole genome microarray studies in hippocampus from sedentary SAMP8 (P8sed), SAMR1 (R1sed), and exercised SAMP8 (P8run) mice. The genes differentially expressed in P8sed versus R1sed were considered as putative aging markers (i) and those differentially expressed in P8run versus P8sed were considered as genes modulated by exercise (ii). Genes differentially expressed in both comparisons (i and ii) were considered as putative aging genes responsive to physical exercise. We identified 34 genes which met both criteria. Gene ontology analysis revealed that they are mainly involved in functions related to extracellular matrix maintenance. Selected genes were validated by real-time quantitative PCR assays, i.e., collagen type 1 alpha 1 (col1a1), collagen type 1 alpha 2 (col1a2), fibromodulin (fmod), prostaglandin D(2) synthase (ptgds), and aldehyde dehydrogenase (Aldh1a2). As a whole, our study suggests that exercise training during adulthood may prevent or delay gene expression alterations and processes associated with hippocampal aging in at-risk subjects

Somatic genome editing with CRISPR/Cas9 generates and corrects a metabolic disease

Germline manipulation using CRISPR/Cas9 genome editing has dramatically accelerated the generation of new mouse models. Nonetheless, many metabolic disease models still depend upon laborious germline targeting, and are further complicated by the need to avoid developmental phenotypes. We sought to address these experimental limitations by generating somatic mutations in the adult liver using CRISPR/Cas9, as a new strategy to model metabolic disorders. As proof-of-principle, we targeted the low-density lipoprotein receptor (Ldlr), which when deleted, leads to severe hypercholesterolemia and atherosclerosis. Here we show that hepatic disruption of Ldlr with AAV-CRISPR results in severe hypercholesterolemia and atherosclerosis. We further demonstrate that co-disruption of Apob, whose germline loss is embryonically lethal, completely prevented disease through compensatory inhibition of hepatic LDL production. This new concept of metabolic disease modeling by somatic genome editing could be applied to many other systemic as well as liver-restricted disorders which are difficult to study by germline manipulation