An innovative design of actuation mechanism for active seat suspension of an off-road vehicle

In recent years human-machine interaction attracts scientific community attention because of human quality and health issues. Driver seat should be designed so that it would ensure occupational health as well as increase work efficiency. The aim of this research is to maintain seat height at constant level with regard to chassis excitation at different levels of frequency and amplitude by means of new design of pneumatic actuation circuit. Sinusoidal function was used for base vibration since almost all of excitation functions can be derived from it. System response shows in low frequency/high amplitude and high frequency/low amplitude chassis vibration, transmissibility decreased about 60% and 40% compared to solid suspension respectivel

The importance of small non-coding RNAs in human reproduction: A review article

Background: MicroRNAs (miRNA) play a key role in the regulation of gene expression through the translational suppression and control of post-transcriptional modifications. Aim: Previous studies demonstrated that miRNAs conduct the pathways involved in human reproduction including maintenance of primordial germ cells (PGCs), spermatogenesis, oocyte maturation, folliculogenesis and corpus luteum function. The association of miRNA expression with infertility, polycystic ovary syndrome (PCOS), premature ovarian failure (POF), and repeated implantation failure (RIF) was previously revealed. Furthermore, there are evidences of the importance of miRNAs in embryonic development and implantation. Piwi-interacting RNAs (piRNAs) and miRNAs play an important role in the post-transcriptional regulatory processes of germ cells. Indeed, the investigation of small RNAs including miRNAs and piRNAs increase our understanding of the mechanisms involved in fertility. In this review, the current knowledge of microRNAs in embryogenesis and fertility is discussed. Conclusion: Further research is necessary to provide new insights into the application of small RNAs in the diagnosis and therapeutic approaches to infertility

The Politics of Institutional Reform and Post-Conflict Violence in Nepal

How does the reform of state institutions shape prospects for peace after war? Existing research on the institutional causes of peace focuses on how institutional designs, as the outcomes of reform processes, reduce post-conflict violence and promote peace. The literature does not, however, adequately address how the politics that characterise reform processes affect the legitimacy of institutions and whether or not violent protest against these institutions ultimately takes place. This focus risks omitting key explanations of how institutional reforms contribute to peace and the mechanisms by which this occurs. By examining the case of Nepal, where clashes between protesters and security forces killed almost 60 people between August 2015 and January 2016, this study shows that emotional rhetoric, elite control of decision-making, backtracking on previous commitments, the acceleration of reform processes, and the embedding of single reforms in a 'concert' of reforms that, as a whole, sparks fears of discrimination are all factors that can lead to post-conflict violence

Timescapes of Himalayan hydropower: promises, project life cycles, and precarities

In this paper, we review the existing social science scholarship focused on hydropower development in the Himalayan region, using an interpretive lens attuned to issues of time and temporality. While the spatial politics of Himalayan hydropower are well examined in the literature, an explicit examination of temporal politics is lacking. In this paper, we present a conceptual framework organized around the heuristic of timescapes, highlighting temporal themes implicit in the existing literature. In three sections, we explore the temporal politics of anticipation that shape hydropower dreams, the intersecting temporalities and rhythms that modulate the life cycles of hydropower projects, and the ways that geological and hydrological time affect both hydropower development and broader Himalayan futures. Along the way, we pose a series of questions useful for framing future research given the significant climatic, geophysical, and sociopolitical changes underway in the Himalayan bioregion, calling for greater analytical attention to time, temporality, and temporal ethics in future studies of hydropower in the Himalayas and beyond.Austin Lord, Georgina Drew, Mabel Denzin Gerga

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Determining Protease Substrate Selectivity and Inhibition by Label-Free Supramolecular Tandem Enzyme Assays

An analytical method has been developed for the continuous monitoring of protease activity on unlabeled peptides in real time by fluorescence spectroscopy. The assay is enabled by a reporter pair comprising the macrocycle cucurbit[7]uril (CB7) and the fluorescent dye acridine orange (AO). CB7 functions by selectively recognizing N-terminal phenylalanine residues as they are produced during the enzymatic cleavage of enkephalin-type peptides by the metalloendopeptidase thermolysin. The substrate peptides (e.g., Thr-Gly-Ala-Phe-Met-NH2) bind to CB7 with moderately high affinity (K ≈ 104 M–1), while their cleavage products (e.g., Phe-Met-NH2) bind very tightly (K \u3e 106 M–1). AO signals the reaction upon its selective displacement from the macrocycle by the high affinity product of proteolysis. The resulting supramolecular tandem enzyme assay effectively measures the kinetics of thermolysin, including the accurate determination of sequence specificity (Ser and Gly instead of Ala), stereospecificity (d-Ala instead of l-Ala), endo- versus exopeptidase activity (indicated by differences in absolute fluorescence response), and sensitivity to terminal charges (−CONH2 vs −COOH). The capability of the tandem assay to measure protease inhibition constants was demonstrated on phosphoramidon as a known inhibitor to afford an inhibition constant of (17.8 ± 0.4) nM. This robust and label-free approach to the study of protease activity and inhibition should be transferable to other endo- and exopeptidases that afford products with N-terminal aromatic amino acids