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Autism spectrum disorder (ASD) is a heterogeneous, behaviorally defined, neurodevelopmental disorder that has been modeled as a brain-based disease. The behavioral and cognitive features of ASD are associated with pervasive atypicalities in the central nervous system (CNS). To date, the exact mechanisms underlying the pathophysiology of ASD still remain unknown and there is currently no cure or effective treatment for this disorder. Many publications implicated the association of ASD with inflammation, immune dysregulation, neurotransmission dysfunction, mitochondrial impairment and cell signaling dysregulation. This review attempts to highlight evidence of the major pathophysiology of ASD including abnormalities in the brain structure and function, neuroglial activation and neuroinflammation, glutamatergic neurotransmission, mitochondrial dysfunction and mechanistic target of rapamycin (mTOR) signaling pathway dysregulation. Molecular and cellular factors that contributed to the pathogenesis of ASD and how they may affect the development and function of CNS are compiled in this review. However, findings of published studies have been complicated by the fact that autism is a very heterogeneous disorder; hence, we addressed the limitations that led to discrepancies in the reported findings. This review emphasizes the need for future studies to control study variables such as sample size, gender, age range and intelligence quotient (IQ), all of which that could affect the study measurements. Neuroinflammation or immune dysregulation, microglial activation, genetically linked neurotransmission, mitochondrial dysfunctions and mTOR signaling pathway could be the primary targets for treating and preventing ASD. Further research is required to better understand the molecular causes and how they may contribute to the pathophysiology of ASD.The COVID-19 global pandemic is caused by SARS-CoV-2, and represents an urgent medical and social issue. Unfortunately, there is still not a single proven effective drug available, and therefore, current therapeutic guidelines recommend supportive care including oxygen administration and treatment with antibiotics. Recently, patients have been also treated with off-label therapies which comprise antiretrovirals, anti-inflammatory compounds, antiparasitic agents and plasma from convalescent patients, all with controversial results. The ubiquitin-proteasome system (UPS) is important for the maintenance of cellular homeostasis, and plays a pivotal role in viral replication processes. In this review, we discuss several aspects of the UPS and the effects of its inhibition with particular regard to the life cycle of the coronaviruses (CoVs). In fact, proteasome inhibition by various chemical compounds, such as MG132, epoxomycin and bortezomib, may reduce the virus entry into the eucariotic cell, the synthesis of RNA, and the subsequent protein expression necessary for CoVs. Importantly, since UPS inhibitors reduce the cytokine storm associated with various inflammatory conditions, it is reasonable to assume that they might be repurposed for SARS-CoV-2, thus providing an additional tool to counteract both virus replication as well as its most deleterious consequences triggered by abnormal immunological response.A concise synthesis of (16S,20S)-3β-hydroxy-5α-pregnane-20,16-carbolactam from tigogenin via the corresponding lactone is described. The most efficient synthetic route consisted of the lactone ring-opening with aminoalane reagent followed by PDC or Dess-Martin oxidation. The oxo-amide obtained was subjected to cyclization with Et3SiH/TFA or Et3SiH/Bi(TfO)3. Alternately, the lactone was converted first to the oxo-acid, which was then subjected to the microwave-assisted reductive amination. N-Alkyl derivatives were also obtained in a similar way.The pursuit of polymer parts produced through foam injection moulding (FIM) that have a comparable surface roughness to conventionally processed components are of major relevance to expand the application of FIM. Within this study, 22% talc-filled copolymer polypropylene (PP) parts were produced through FIM using both a physical and chemical blowing agent. A design of experiments (DoE) was performed whereby the processing parameters of mould temperatures, injection speeds, back-pressure, melt temperature and holding time were varied to determine their effect on surface roughness, Young's modulus and tensile strength. The results showed that mechanical performance can be improved when processing with higher mould temperatures and longer holding times. Also, it was observed that when utilising chemical foaming agents (CBA) at low-pressure, surface roughness comparable to that obtained from conventionally processed components can be achieved. This research demonstrates the potential of FIM to expand to applications whereby weight saving can be achieved without introducing surface defects, which has previously been witnessed within FIM.The current needs in terms of ballistic protection for armed forces require an almost constant improvement in performance to face the constantly evolving threats and scenarios. Ballistic tests are conventionally carried out in order to assess and validate the levels of protection. The challenge is to be able to set up a digital protocol and only carry out final validation tests. Indeed, the advantage of digital simulation lies in the possibility of being able to evaluate a wide variety of configurations. In order to obtain reliable results, it is necessary to use sufficiently precise material behavior models to transcribe the phenomena observed during the impact. Our study focuses on the behavior of a small caliber ammunition with a ductile core impacting personal protection. More particularly on the mechanical behavior of the lead alloy core. Thus, compression tests have been carried out on a wide range of deformation rates, from quasi-static behavior to dynamic regime, at different temperatures. The study in dynamic conditions was carried out using split Hopkinson pressure bars. Lapatinib nmr Due to the material properties, the experimental device had to be adapted in order to optimize the propagation of the waves allowing to measure signals (elastic waves). These tests demonstrate the dependency of the stress with strain rate and temperature. Dynamic restoration and recrystallization phenomena, characteristic of a material deformed in its hot working area, have also been identified. The associated oscillations due to Pochhammer-Chree effect, observable on the stress-strain curves, constitute the major problem for the implementation of behavioral models. Finally, a constitutive model sensitive to strain rate and temperature is investigated for ballistic purposes.
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