Low-interference sensing electronics for high-resolution error-correcting biomechanical ground reaction sensor cluster

Journal ArticleAbstract- This paper presents a low-interference and low -power sensing electronics design for a high-resolution errorcorrecting biomechanical ground reaction sensor cluster (GRSC) developed for improving inertial measurement unit (IMU) positioning resolution and accuracy. The GRSC is composed of 13 x 13 sensing nodes, which can measure dynamic ground forces, shear strains, and sole deformation associated with a ground locomotion gait. The integrated sensing electronics consist of a front-end multiplexer that can sequentially connect individual sensing nodes in a GRSC to a capacitance-to-voltage converter followed by an ADC, digital control unit, and driving circuitry to interrogate the GRSC. The sensing electronics are designed in a 0.15 μm CMOS process and occupy an area of approximately 3 mm2 with an expected resolution of 10-bits and 14-bits for the z-axis pressure sensing and the x and y-axes shear strain sensing, respectively, while dissipating a DC power less than 2 mW from a 3V supply

Detailed immunohistochemical characterization of temporal and spatial progression of Alzheimer's disease-related pathologies in male triple-transgenic mice

<p>Abstract</p> <p>Background</p> <p>Several transgenic animal models genetically predisposed to develop Alzheimer's disease (AD)-like pathology have been engineered to facilitate the study of disease pathophysiology and the vetting of potential disease-modifying therapeutics. The triple transgenic mouse model of AD (3xTg-AD) harbors three AD-related genetic loci: human PS1^M146V, human APP^swe, and human tau^P301L. These mice develop both amyloid plaques and neurofibrillary tangle-like pathology in a progressive and age-dependent manner, while these pathological hallmarks are predominantly restricted to the hippocampus, amygdala, and the cerebral cortex the main foci of AD neuropathology in humans. This model represents, at present, one of the most advanced preclinical tools available and is being employed ever increasingly in the study of mechanisms underlying AD, yet a detailed regional and temporal assessment of the subtleties of disease-related pathologies has not been reported.</p> <p>Methods and results</p> <p>In this study, we immunohistochemically documented the evolution of AD-related transgene expression, amyloid deposition, tau phosphorylation, astrogliosis, and microglial activation throughout the hippocampus, entorhinal cortex, primary motor cortex, and amygdala over a 26-month period in male 3xTg-AD mice. Intracellular amyloid-beta accumulation is detectable the earliest of AD-related pathologies, followed temporally by phospho-tau, extracellular amyloid-beta, and finally paired helical filament pathology. Pathology appears to be most severe in medial and caudal hippocampus. While astrocytic staining remains relatively constant at all ages and regions assessed, microglial activation appears to progressively increase temporally, especially within the hippocampal formation.</p> <p>Conclusion</p> <p>These data fulfill an unmet need in the ever-widening community of investigators studying 3xTg-AD mice and provide a foundation upon which to design future experiments that seek to examine stage-specific disease mechanisms and/or novel therapeutic interventions for AD.</p

A combined genome-wide approach identifies a new potential candidate marker associated with the coat color sidedness in cattle

Coat color is one of the most important phenotypic features in livestock breeds. Cinisara is a local cattle breed generally of uniform black color which occasionally presents a particular phenotype, with animals typically display a white band along their spine, from the head to the tail, and on the ventral line (color sidedness). Therefore, this breed provides an ideal model to study the genetic components underlying phenotypic variation in coat color. A total of 63 animals, ten with sidedness phenotype and 53 with uniform black color were genotyped with Illumina Bovine 50 K. The comparison among genome-wide association study and FST analysis revealed a single nucleotide polymorphism (SNP), ARS-BFGL-NGS-55928, significantly associated with the trait. Only one gene (PLK2)was annotated near the associated SNP in a window of ±200 kb. The protein encoded by this gene is a member of the polo-like kinases, the same family of several known coat-color candidate genes. Based on the reported results, we draw the possible conclusion that the identified marker is potentially associated with the coat color sidedness in Cinisara. The local breeds with their genetic variability represent an important resource and model to study the genetic basis affecting peculiar traits. Future studies would be particularly relevant to refine these results and to better understand the genetic basis for this phenotype

Clinical and Pathophysiological Insights Into Immunological Mediated Glomerular Diseases in Childhood

The kidney is often the target of immune system dysregulation in the context of primary or systemic disease. In particular, the glomerulus represents the anatomical entity most frequently involved, generally as the expression of inflammatory cell invasion or circulant or in situ immune-complex deposition. Glomerulonephritis is the most common clinical and pathological manifestation of this involvement. There are no universally accepted classifications for glomerulonephritis. However, recent advances in our understanding of the pathophysiological mechanisms suggest the assessment of immunological features, biomarkers, and genetic analysis. At the same time, more accurate and targeted therapies have been developed. Data on pediatric glomerulonephritis are scarce and often derived from adult studies. In this review, we update the current understanding of the etiologic events and genetic factors involved in the pathogenesis of pediatric immunologically mediated primitive forms of glomerulonephritis, together with the clinical spectrum and prognosis. Possible new therapeutic targets are also briefly discussed

Micromixing and microchannel design: Vortex shape and entropy

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.In very recent years microdevices, due to their potency in replacing large-scale conventional laboratory instrumentation, are becoming a fast and low cost technology for the treatment of several chemical and biological processes. In particular microfluidics has been massively investigated, aiming at improving the performance of chemical reactors. This is because of the fact that reaction is often an interface phenomenon where the greater the surface to volume ratio, the higher the reaction speed, and microscale mixing increases the interfacial area (in terms of mixing-induced-by-vortices generation). However, microfluidic systems suffer from the limitation that they are characterized mostly by very low Reynolds numbers, with the consequence that (i) they cannot take advantage from the turbulence mixing support, and (ii) viscosity hampers proper vortex detection. Therefore, the proper design of micro-channels (MCs) becomes essential. In this framework, several geometries have been proposed to induce mixing vortices in MCs. However a quantitative comparison between proposed geometries in terms of their passive mixing potency can be done only after proper definition of vortex formation (topology, size) and mixing performance. The objective of this study is to test the ability of different fluid dynamic metrics in vortex detection and mixing effectiveness in micromixers. This is done numerically solving different conditions for the flow in a classic passive mixer, a ring shaped MC. We speculate that MCs design could take advantage from fluidic metrics able to rank properly flow related mixing

Structural bases of the altered catalytic properties of a pathogenic variant of apoptosis inducing factor

The apoptosis-inducing factor (AIF) is a FAD-containing protein playing critical roles in caspase-independent apoptosis and mitochondrial respiratory chain biogenesis and maintenance. While its lethal role is well known, the details of its mitochondrial function remain elusive. So far, nineteen allelic variants of AIF have been associated to human diseases, mainly affecting the nervous system. A strict correlation is emerging between the degree of impairment of its ability to stabilize the charge-transfer (CT) complex between FAD and NAD+ and the severity of the resulting pathology. Recently, we demonstrated that the G307E replacement in murine AIF (equivalent to the pathogenic G308E in the human protein) dramatically decreases the rate of CT complex formation through the destabilization of the flavoprotein interaction with NAD(H). To provide further insights into the structural bases of its altered functional properties, here we report the first crystal structure of an AIF pathogenic mutant variant in complex with NAD+ (murine AIF-G307ECT) in comparison with its oxidized form. With respect to wild type AIF, the mutation leads to an altered positioning of NAD+ adenylate moiety, which slows down CT complex formation. Moreover, the altered balance between the binding of the adenine/nicotinamide portions of the coenzyme determines a large drop in AIF-G307E ability to discriminate between NADH and NADPH

New Implant Design with Midcrestal and Apical Wing Thread for Increased Implant Stability in Single Postextraction Maxillary Implant

Background. The immediate placement of a dental implant could represent an option treatment for the rehabilitation of a postextractive missing tooth socket to replace compromised or untreatable teeth, with the advantage of single-session surgery. In this way, the anatomy of the alveolar bone defect, the preservation of the buccal cortical bone, and the primary stability of the fixture represent the critical factors that consent a precise implant placement. Objective. This case report describes a novel fixture design for postextractive alveolar socket immediate implant. Methods. Two patients (25 and 31 years old) were treated for postextractive dental implant placement to replace both central upper incisor teeth with four implants. The residual bone implant gap was not filled with graft or bone substitute. The restoration was provided following a standard loading protocol by a cement-sealed prosthetic abutment. Results. Clinically, all implants positioned showed an excellent insertion torque. No postoperative complications were reported. At 6 months of healing, the buccal cortical bone and the implant stability were present and well maintained. Conclusion. The evidence of this study allows us to underline the possible advantages of this new fixture design for postextractive implant technique

Genomic diversity and population structure analysis reveal few genetic differences among Ethiopian indigenous sheep populations

African sheep, like other domestic sheep, are domesticated from the Asiatic mouflon (Ovis orientalis). They entered the continent through the North and the Horn of Africa regions following maritime and terrestrial trading routes. Ethiopia is one of the main entry points of various plant and animal domesticates into Africa. It is characterised by diverse agro-ecologies, ancient human ethnic diversity and the presence of indigenous sheep breeds/populations of unprecedented morphological diversity (e.g. tail types). Here, we investigate the genome diversity and population structure of 146 unrelated animals from 11 Ethiopian indigenous sheep populations. DNA was extracted from ear tissue punches and genotyped with the Illumina Ovine 50K SNP BeadChip assay. Sheep populations from The Caribbean, Europe, Middle East and China as well as from western, northern and southern Africa were included to clarify the genetic history of origin, introduction and dispersal of the species into Ethiopia. Principal component analysis (PCA), clearly separated all Ethiopian sheep from the other populations. Population structure and phylogenetic (neighbour-joining tree) analysis subdivided the Ethiopian indigenous sheep into three genetic clusters corresponding to their tail morphology (rump fat-tailed, short fat-tailed and long fat/thin-tailed population). It supports a common genetic ancestry for populations of each tail type in the country. Genetic distances among the Ethiopian populations were positively correlated with geographic distances (Mantel test, P < 0.001, r = 0.465) and the highest genetic diversity was recorded in the fat-tailed (short, rump and/or long fat-tailed) close to the Bab-el-Mandeb strait. However, despite their distinct morphology and separate geographic distribution, little genetic differentiation between Ethiopian populations are observed. This is most likely a consequence of their ancient and modern intermixing following their introduction into the country

Genome-wide scan for Runs of Homozygosity in Valle del Belice sheep

The current availability of very large numbers of single nucleotide polymorphisms (SNPs) throughout the genome makes these markers particularly suitable for the detection of genomic regions where a reduction in heterozygosity occurred and offers new opportunities to improve the accuracy of inbreeding (F) estimates. Runs of homozygosity (ROH) are contiguous lengths of homozygous segments of the genome where the two haplotypes inherited from the parents are identical. Here, we investigated the occurrence and the distribution of ROH in medium-density SNP genotypes (~ 50 000) in order to characterize autozygosity in 512 individuals of Valle del Belice sheep and identify the regions of the genome with high ROH frequencies. A total of 11 629 ROH were identified. All individuals displayed at least one ROH &gt; 1 Mb. The mean value of FROH&gt;1Mb was 0.084\ub10.061. ROH that were shorter than 10 Mb predominated. The highest coverage of chromosome (OAR) by ROH was observed on OAR24, whereas the lowest one was observed on OAR1. A typical pattern was observed for the number of ROH per OAR with higher values in the first three chromosomes. There was a considerable difference among animals for the number of ROH segments and the length of the genome covered by ROH. The genomic regions most commonly associated with ROH were identified by selecting the top 1% of the SNPs most commonly observed in ROH within breed. A total of 239 SNPs were considered as candidate SNPs and we identified 107 potential candidate genes that may be under directional selection. Six genomic regions located on six chromosomes (OAR2, OAR3, OAR4, OAR10, OAR11 and OAR23), corresponding to ROH island, presented hotspot of autozygosity. According to KEGG database, a majority of the genes were involved in multiple signaling and signal transduction pathways in a wide variety of cellular and biochemical processes. The ROH islands spanned several candidate genes which influence traits that are associated with adaptability and with the regulation of immune responses (NPAS2, PDCL3, SERPINF1 and SERPINF2) and we did not identified candidate genes with important influence on milk production traits in sheep. The Valle del Belice breed is subjected to limited breeding selection programs for milk production traits, but shows excellent adaptability to the local environments. Therefore, these results suggest at least a partial role of natural selection in shaping the genome of Valle del Belice sheep breed

Birth control knowledge among freshmen of four Italian universities

Since sexual health education (SHE) is not mandatory in Italian schools, we conducted a survey on freshmen of four Italian university campuses in 2012 to investigate the respective level of sexual health knowledge (SHK) in relation to birth control, with the aim to inform public health policy makers. A convenience strategy was employed to sample 4,552 freshmen registered with various undergraduate courses at four Italian universities: Padua university (Veneto Region); university of Milan (Lombardy Region); university of Bergamo (Lombardy Region); university of Palermo (Sicily Region). We investigated the level of SHK on birth control using 6 proxy indicators: (1) the average length of a woman\u2019s period [outcome with 3 levels: wrong (base) vs. acceptable vs. correct]; (2) the most fertile interval within a woman\u2019s period (binary outcome: correct vs. wrong answer); (3) the event between the end of a period and the beginning of the next cycle (binary outcome: correct vs. wrong answer); (4) the average survival of spermatozoa in the womb (binary outcome: correct vs. wrong answer); (5) the concept of contraception (binary outcome: correct vs. wrong answer); (6) the efcacy of various contraceptives to prevent unintended pregnancies (linear score: 0\u201317). We ftted 6 separate models of multiple regression: multinomial for outcome 1; logistic for outcomes 2, 3, 4, 6; linear for outcome 6. Statistical estimates were adjusted for a number of socio-demographic factors. Results were expressed as odds ratios (OR) for the 4 multiple logistic regression models, linear coefcients (RC) for the linear regression model and relative risk ratio (RRR) for the multinomial logistic regression model. The level of signifcance of each risk estimate was set at 0.05. The level of SHK of freshmen sampled was rather low, as 60% interviewees did not know the average length of a woman\u2019s period, the average survival of spermatozoa in the womb and the concept of contraception, whilst the most fertile interval within a woman\u2019s period was known only to 55% of interviewees. The mean score of SHK on the efcacy of various contraceptive methods was only 5 (scale 0\u201317). Some categories of students were consistently and signifcantly less knowledgeable on birth control at multivariable analysis: males; students from the university of Palermo; those with vocational secondary school education and those not in a romantic relationship at the time the survey was conducted. The results of this survey clearly call for the introduction of SHE programs in Italian schools, as already done in several European countries. School SHE should start as early as possible, ideally even before secondary school. SHE should be holistic and delivered with a multiple agency coordinated approach involving the Ministry of Health, the Ministry of Education, University and Scientifc Research (MIUR), families, schools, public health departments, primary health care providers, pharmacists, media, other