A piecewise-linear reduced-order model of squeeze-film damping for deformable structures including large displacement effects

This paper presents a reduced-order model for the Reynolds equation for deformable structure and large displacements. It is based on the model established in [11] which is piece-wise linearized using two different methods. The advantages and drawbacks of each method are pointed out. The pull-in time of a microswitch is determined and compared to experimental and other simulation data.Comment: Submitted on behalf of EDA Publishing Association (http://irevues.inist.fr/handle/2042/16838

Identification of monogenic variants in more than ten per cent of children without type 1 diabetes-related autoantibodies at diagnosis in the Finnish Pediatric Diabetes Register

Peer reviewe

Structural and functional alterations in the brain gray matter among first-degree relatives of schizophrenia patients : A multimodal meta-analysis of fMRI and VBM studies

Objective: We conducted a multimodal coordinate-based meta-analysis (CBMA) to investigate structural and functional brain alterations in first-degree relatives of schizophrenia patients (FRs). Methods: We conducted a systematic literature search from electronic databases to find studies that examined differences between FRs and healthy controls using whole-brain functional magnetic resonance imaging (fMRI) or voxel-based morphometry (VBM). A CBMA of 30 fMRI (754 FRs; 959 controls) and 11 VBM (885 FRs; 775 controls) datasets were conducted using the anisotropic effect-size version of signed differential mapping. Further, we conducted separate meta-analyses about functional alterations in different cognitive tasks: social cognition, executive functioning, working memory, and inhibitory control. Results: FRs showed higher fMRI activation in the right frontal gyrus during cognitive tasks than healthy controls. In VBM studies, there were no differences in gray matter density between FRs and healthy controls. Furthermore, multi-modal meta-analysis obtained no differences between FRs and healthy controls. By utilizing the BrainMap database, we showed that the brain region which showed functional alterations in FRs (i) overlapped only slightly with the brain regions that were affected in the meta-analysis of schizophrenia patients and (ii) correlated positively with the brain regions that exhibited increased activity during cognitive tasks in healthy individuals. Conclusions: Based on this meta-analysis, FRs may exhibit only minor functional alterations in the brain during cognitive tasks, and the alterations are much more restricted and only slightly overlapping with the regions that are affected in schizophrenia patients. The familial risk did not relate to structural alterations in the gray matter. (C) 2019 Elsevier B.V. All rights reserved.Peer reviewe

Simulations of Aerodynamic Damping for MEMS Resonators

Aerodynamic damping for MEMS resonators is studied based on the numerical solution of Boltzmann-ESBGK equation. A compact model is then developed based on numerical simulations for a wide range of Knudsen numbers. The damping predictions are compared with both Reynold equation based models and several sets of experimental data. It has been found that the structural damping is dominant at low pressures (high Knudsen numbers). For cases with small length-to-width ratios and large vibration amplitudes, the threedimensionality effects must be taken into account. Finally, an uncertainty quantification approach based on the probability transformation method has been applied to assess the influence of pressure and geometric uncertainties. The output probability density functions (PDF) of the damping ratio has been studied for various input PDF of beam geometry and ambient pressure

Circulating beta cell-specific CD8(+) T cells restricted by high-risk HLA class I molecules show antigen experience in children with and at risk of type 1 diabetes

In type 1 diabetes (T1D), autoreactive cytotoxic CD8(+) T cells are implicated in the destruction of insulin-producing beta cells. The HLA-B*3906 and HLA-A*2402 class I genes confer increased risk and promote early disease onset, suggesting that CD8(+) T cells that recognize peptides presented by these class I molecules on pancreatic beta cells play a pivotal role in the autoimmune response. We examined the frequency and phenotype of circulating preproinsulin (PPI)-specific and insulin B (InsB)-specific CD8(+) T cells in HLA-B*3906(+) children newly diagnosed with T1D and in high-risk HLA-A*2402(+) children before the appearance of disease-specific autoantibodies and before diagnosis of T1D. Antigen-specific CD8(+) T cells were detected using human leucocyte antigen (HLA) class I tetramers and flow cytometry was used to assess memory status. In HLA-B*3906(+) children with T1D, we observed an increase in PPI5-12-specific transitional memory CD8(+) T cells compared to non-diabetic, age- and HLA-matched subjects. Furthermore, PPI5-12-specific CD8(+) T cells in HLA-B*3906(+) children with T1D showed a significantly more antigen-experienced phenotype compared to polyclonal CD8(+) T cells. In longitudinal samples from high-risk HLA-A*2402(+) children, the percentage of terminal effector cells within the InsB(15-24)-specific CD8(+) T cells was increased before diagnosis relative to samples taken before the appearance of autoantibodies. This is the first study, to our knowledge, to report HLA-B*3906-restricted autoreactive CD8(+) T cells in T1D. Collectively, our results provide evidence that beta cell-reactive CD8(+) T cells restricted by disease-associated HLA class I molecules display an antigen-experienced phenotype and acquire enhanced effector function during the period leading to clinical diagnosis, implicating these cells in driving disease.Peer reviewe

Enterovirus-associated changes in blood transcriptomic profiles of children with genetic susceptibility to type 1 diabetes

Aims/hypothesis Enterovirus infections have been associated with the development of type 1 diabetes in multiple studies, but little is known about enterovirus-induced responses in children at risk for developing type 1 diabetes. Our aim was to use genome-wide transcriptomics data to characterise enterovirus-associated changes in whole-blood samples from children with genetic susceptibility to type 1 diabetes. Methods Longitudinal whole-blood samples (356 samples in total) collected from 28 pairs of children at increased risk for developing type 1 diabetes were screened for the presence of enterovirus RNA. Seven of these samples were detected as enterovirus-positive, each of them collected from a different child, and transcriptomics data from these children were analysed to understand the individual-level responses associated with enterovirus infections. Transcript clusters with peaking or dropping expression at the time of enterovirus positivity were selected as the enterovirus-associated signals. Results Strong signs of activation of an interferon response were detected in four children at enterovirus positivity, while transcriptomic changes in the other three children indicated activation of adaptive immune responses. Additionally, a large proportion of the enterovirus-associated changes were specific to individuals. An enterovirus-induced signature was built using 339 genes peaking at enterovirus positivity in four of the children, and 77 of these genes were also upregulated in human peripheral blood mononuclear cells infected in vitro with different enteroviruses. These genes separated the four enterovirus-positive samples clearly from the remaining 352 blood samples analysed. Conclusions/interpretation We have, for the first time, identified enterovirus-associated transcriptomic profiles in whole-blood samples from children with genetic susceptibility to type 1 diabetes. Our results provide a starting point for understanding the individual responses to enterovirus infections in blood and their potential connection to the development of type 1 diabetes.Peer reviewe

Enterovirus-associated changes in blood transcriptomic profiles of children with genetic susceptibility to type 1 diabetes

Aims/hypothesis Enterovirus infections have been associated with the development of type 1 diabetes in multiple studies, but little is known about enterovirus-induced responses in children at risk for developing type 1 diabetes. Our aim was to use genome-wide transcriptomics data to characterise enterovirus-associated changes in whole-blood samples from children with genetic susceptibility to type 1 diabetes. Methods Longitudinal whole-blood samples (356 samples in total) collected from 28 pairs of children at increased risk for developing type 1 diabetes were screened for the presence of enterovirus RNA. Seven of these samples were detected as enterovirus-positive, each of them collected from a different child, and transcriptomics data from these children were analysed to understand the individual-level responses associated with enterovirus infections. Transcript clusters with peaking or dropping expression at the time of enterovirus positivity were selected as the enterovirus-associated signals. Results Strong signs of activation of an interferon response were detected in four children at enterovirus positivity, while transcriptomic changes in the other three children indicated activation of adaptive immune responses. Additionally, a large proportion of the enterovirus-associated changes were specific to individuals. An enterovirus-induced signature was built using 339 genes peaking at enterovirus positivity in four of the children, and 77 of these genes were also upregulated in human peripheral blood mononuclear cells infected in vitro with different enteroviruses. These genes separated the four enterovirus-positive samples clearly from the remaining 352 blood samples analysed. Conclusions/interpretation We have, for the first time, identified enterovirus-associated transcriptomic profiles in whole-blood samples from children with genetic susceptibility to type 1 diabetes. Our results provide a starting point for understanding the individual responses to enterovirus infections in blood and their potential connection to the development of type 1 diabetes.Peer reviewe

Prenatal exposure to maternal cigarette smoking and structural properties of the human corpus callosum

Alterations induced by prenatal exposure to nicotine have been observed in experimental (rodent) studies. While numerous developmental outcomes have been associated with prenatal exposure to maternal cigarette smoking (PEMCS) in humans, the possible relation with brain structure is less clear. Here we sought to elucidate the relation between PEMCS and structural properties of human corpus callosum in adolescence and early adulthood in a total of 1,747 youth. We deployed three community-based cohorts of 446 (age 25–27 years, 46% exposed), 934 (age 12–18 years, 47% exposed) and 367 individuals (age 18–21 years, 9% exposed). A mega-analysis revealed lower mean diffusivity in the callosal segments of exposed males. We speculate that prenatal exposure to maternal cigarette smoking disrupts the early programming of callosal structure and increases the relative portion of small-diameter fibres.</p

Neuropeptide precursor VGF is genetically associated with social anhedonia and underrepresented in the brain of major mental illness: its downregulation by DISC1

In a large Scottish pedigree, disruption of the gene coding for DISC1 clearly segregates with major depression, schizophrenia and related mental conditions. Thus, study of DISC1 may provide a clue to understand the biology of major mental illness. A neuropeptide precursor VGF has potent antidepressant effects and has been reportedly associated with bipolar disorder. Here we show that DISC1 knockdown leads to a reduction of VGF, in neurons. VGF is also downregulated in the cortices from sporadic cases with major mental disease. A positive correlation of VGF single-nucleotide polymorphisms (SNPs) with social anhedonia was also observed. We now propose that VGF participates in a common pathophysiology of major mental disease

A longitudinal plasma lipidomics dataset from children who developed islet autoimmunity and type 1 diabetes

Early prediction and prevention of type 1 diabetes (T1D) are currently unmet medical needs. Previous metabolomics studies suggest that children who develop T1D are characterised by a distinct metabolic profile already detectable during infancy, prior to the onset of islet autoimmunity. However, the specificity of persistent metabolic disturbances in relation T1D development has not yet been established. Here, we report a longitudinal plasma lipidomics dataset from (1) 40 children who progressed to T1D during follow-up, (2) 40 children who developed single islet autoantibody but did not develop T1D and (3) 40 matched controls (6 time points: 3, 6, 12, 18, 24 and 36 months of age). This dataset may help other researchers in studying age-dependent progression of islet autoimmunity and T1D as well as of the age-dependence of lipidomic profiles in general. Alternatively, this dataset could more broadly used for the development of methods for the analysis of longitudinal multivariate data