Periodic solution to a nonlinear oscillator arising in micro electro mechanical system

In this paper, a periodic solution of nonlinear oscillator arising in the micro-beam based microelectromechanical system (MEMS) has been analytically achieved. The Amplitude Frequency Formulation (AFF) and Max Min Approach (MMA) have been used. In the second method (which is called MMA), an approximate solution of the nonlinear equation can be easily deduced by finding Maximal and minimal solution thresholds of this nonlinear problem. What we understood is that both methods, works properly and scales down the deal of the work. Compare conclusions with the results from fourth order Runge-Kutta method and energy balance method (EBM) shows that obtained results are of high accuracy and convenient

UKP-SQuARE v3: A Platform for Multi-Agent QA Research

The continuous development of Question Answering (QA) datasets has drawn the research community's attention toward multi-domain models. A popular approach is to use multi-dataset models, which are models trained on multiple datasets to learn their regularities and prevent overfitting to a single dataset. However, with the proliferation of QA models in online repositories such as GitHub or Hugging Face, an alternative is becoming viable. Recent works have demonstrated that combining expert agents can yield large performance gains over multi-dataset models. To ease research in multi-agent models, we extend UKP-SQuARE, an online platform for QA research, to support three families of multi-agent systems: i) agent selection, ii) early-fusion of agents, and iii) late-fusion of agents. We conduct experiments to evaluate their inference speed and discuss the performance vs. speed trade-off compared to multi-dataset models. UKP-SQuARE is open-source and publicly available at http://square.ukp-lab.de

Molecular Alterations and Association with Clinical Parameters

Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR) genes, most frequently MLH1 and MSH2. Recently, MMR-deficient crypt foci (MMR- DCF) have been identified as a novel lesion which occurs at high frequency in the intestinal mucosa from Lynch syndrome mutation carriers, but very rarely progress to cancer. To shed light on molecular alterations and clinical associations of MMR-DCF, we systematically searched the intestinal mucosa from Lynch syndrome patients for MMR-DCF by immunohistochemistry. The identified lesions were characterised for alterations in microsatellite-bearing genes with proven or suspected role in malignant transformation. We demonstrate that the prevalence of MMR-DCF (mean 0.84 MMR-DCF per 1 cm2 mucosa in the colorectum of Lynch syndrome patients) was significantly associated with patients’ age, but not with patients’ gender. No MMR-DCF were detectable in the mucosa of patients with sporadic MSI-H colorectal cancer (n = 12). Microsatellite instability of at least one tested marker was detected in 89% of the MMR-DCF examined, indicating an immediate onset of microsatellite instability after MMR gene inactivation. Coding microsatellite mutations were most frequent in the genes HT001 (ASTE1) with 33%, followed by AIM2 (17%) and BAX (10%). Though MMR deficiency alone appears to be insufficient for malignant transformation, it leads to measurable microsatellite instability even in single MMR-deficient crypts. Our data indicate for the first time that the frequency of MMR-DCF increases with patients’ age. Similar patterns of coding microsatellite instability in MMR-DCF and MMR-deficient cancers suggest that certain combinations of coding microsatellite mutations, including mutations of the HT001, AIM2 and BAX gene, may contribute to the progression of MMR-deficient lesions into MMR-deficient cancers

High density of FOXP3-positive T cells infiltrating colorectal cancers with microsatellite instability

High-level microsatellite instability (MSI-H) in colorectal cancer accounts for about 12% of colorectal cancers and is typically associated with a dense infiltration with cytotoxic CD8-positive lymphocytes. The role of regulatory T cells that may interfere with the host's antitumoural immune response in MSI-H colorectal cancers has not been analysed yet. Using an antibody directed against the regulatory T-cell marker transcription factor forkhead box P3 (FOXP3), regulatory T cells were examined in 70 colorectal cancers with known MSI status (MSI-H, n=37; microsatellite stable, n=33). In MSI-H colorectal cancers, we found a significantly higher intraepithelial infiltration with FOXP3-positive cells (median: 8.5 cells per 0.25 mm2 vs 3.1 cells per 0.25 mm2 in microsatellite stable, P<0.001), and a significantly elevated ratio of intraepithelial to stromal infiltration (0.05 vs 0.01 in microsatellite stable, P<0.001). CD8-positive cell counts were related positively to the number of FOXP3-positive cells (Spearman's ρ=0.56 and 0.55, respectively). Our results show that the elevated number of CD8-positive lymphocytes found in MSI-H colorectal cancers is paralleled by an enhanced infiltration with CD8-negative FOXP3-positive cells. These data suggest that FOXP3-positive cells may play a role in the regulation of the immune response directed against MSI-H colorectal cancers at the primary tumour site

Neuroendocrine–immune disequilibrium and endometriosis: an interdisciplinary approach

Endometriosis, a chronic disease characterized by endometrial tissue located outside the uterine cavity, affects one fourth of young women and is associated with chronic pelvic pain and infertility. However, an in-depth understanding of the pathophysiology and effective treatment strategies of endometriosis is still largely elusive. Inadequate immune and neuroendocrine responses are significantly involved in the pathophysiology of endometriosis, and key findings are summarized in the present review. We discuss here the role of different immune mechanisms particularly adhesion molecules, protein–glycan interactions, and pro-angiogenic mediators in the development and progression of the disease. Finally, we introduce the concept of endometrial dissemination as result of a neuroendocrine-immune disequilibrium in response to high levels of perceived stress caused by cardinal clinical symptoms of endometriosis

Peripheral immune status, psychosocial stress and neuroendocrine-immune cross- talks in endometriosis

In der Entstehung von Endometriose gilt eine maßgebliche immunologische Komponente als gesichert. Symptome wie chronischer Schmerz und Infertilität gehen oft mit depressivem Verhalten und erhöhter Stresswahrnehmung einher, welche das Gleichgewicht des endokrinen und des Immunsystems stark beeinflussen kann. Ziel der Studie war es, die Wechselwirkung zwischen Psyche, Hormonen und Immunsystem bei infertilen Frauen mit Endometriose zu untersuchen. Bei 69 Teilnehmerinnen (38 mit, 31 ohne Endometriose) wurden psychosoziale Merkmale sowie Zytokine und Progesteron im Serum bestimmt. Weiterhin wurden peritoneale Leukozyten charakterisiert sowie deren Zytokinproduktion nach Stimulation mit einem Stresshormon (CRH) und/oder einem Progesteronderivat untersucht. Bei Patientinnen mit Endometriose fanden sich eine verminderte Lebensqualität, erhöhte Stresswahrnehmung und depressive Symptome. Im Serum zeigte sich hier ein pro-inflammatorisches Profil, in der Peritonealflüssigkeit eine Erhöhung von Neutrophilen, ein Abfall von CD25+ sowie CD4+CD25+CD103+ T-Zellen und ein Abfall von Monozyten, sowie von dendritischen Zellen und eine erhöhte Frequenz von PR+ Natürlichen Killerzellen (CD56+PR+) sowie CD8+PR+ T-Zellen. Die Spiegel von Progesteron im Serum waren erniedrigt und korrelierten bei fortgeschrittenem Krankheitsstadium invers mit Schmerzen. Die Produktion von TNF durch peritoneale Leukozyten in vitro war bei Patientinnen mit Endometriose erhöht, die TNF/IL-10 Ratio konnte durch CRH weiter erhöht werden. Die Zugabe des Progesteronderivates Dydrogesteron konnte die Inflammation aufheben. Psychosozialer Stress und erniedrigte Progesteronspiegel scheinen zur peritonealen Inflammation und Schmerzwahrnehmung bei Patientinnen mit Endometriose beizutragen. Die therapeutische Applikation von Progesteronderivaten, CRH-Blockern sowie verbessertes Stress-Coping könnten den Teufelskreis zwischen chronischer Entzündung und hohem psychologischen Stress durchbrechen.Published evidence has suggested a pivotal role of immune mechanisms in the pathogenesis of endometriosis. Symptoms like chronic pain and infertility are often accompanied by depression-like behaviour and an increased perception of psychological stress, which can highly influence the equilibrium between the endocrine and immune systems. The aim of this study was to investigate the potential cross-talks between psychological factors, hormones and the immune system in infertile women suffering from endometriosis. In 69 participants (38 with, 31 without endometriosis) psychosocial factors as well as cytokines and progesterone in serum were evaluated. Furthermore, peritoneal leukocytes were characterized and their cytokine production upon stimulation with a representative of stress hormones (CRH) and/or a progesterone derivative was investigated. In patients suffering from endometriosis a reduced quality of life, increased stress perception and depressive symptoms were found. In serum, a pro-inflammatory profile could be shown, moreover in peritoneal fluids an increase of neutrophiles, a reduction of CD25+ and CD4+CD25+CD103+ T cells and monocytes, dendritic cells and increased numbers of PR+ natural killer cells (CD56+PR+) and CD8+PR+ T cells. Progesterone in serum was decreased in endometriosis and inversely correlating with pain scores in advanced stages. The production of TNF by peritoneal leukocytes in vitro was increased in endometriosis, the TNF/IL-10 ratio could be further increased by CRH which could be dampended by dydrogesterone, a progesterone derivative. Psychosocial stress and low levels of progesterone are likely to contribute to the peritoneal inflammation and pain perception in endometriosis. The therapeutic application of progesterone derivatives, CRH blockers together with an improved stress coping could help to interrupt the vicious circle between chronic inflammation and high psychological stress

Monoallelic expression of human PEG1/MEST is paralleled by parent-specific methylation in fetuses

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