1,674 research outputs found

    Walking Quadrupedal Platform

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    The goal of this project was to continue developing a functioning quadrupedal platform for the WPI robotics department. The quadruped is a forty-pound robot with four independently moving legs built by a previous MQP. This project consists of testing and implementing motion control systems. The primary goal of the project was to ensure that the robot quadrupedal chassis built by a previous MQP could move stably and intelligently so that it can be useful for future projects. Three main motion gaits were studied, a crawl gait, a walking gait, and a turning gait. The project implemented stable motion for the three gaits mentioned. In addition, the team also made significant system design improvements in the structure, electrical circuit, and code

    AL Amyloidosis for Cardiologists: Awareness, Diagnosis, and Future Prospects: JACC: CardioOncology State-of-the-Art Review

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    Amyloid light chain (AL) amyloidosis is a rare, debilitating, often fatal disease. Symptoms of cardiomyopathy are common presenting features, and patients often are referred to cardiologists. Cardiac amyloid infiltration is the leading predictor of death. However, the variable presentation and perceived rarity of the disease frequently lead to delay in suspecting amyloidosis as a cause of heart failure, leading to misdiagnoses and a marked delay in diagnosis, with devastating consequences for the patient. A median time from symptom onset to correct diagnosis of about 2 years is often too long when median survival from diagnosis for patients with AL amyloidosis and cardiomyopathy is 4 months to 2 years. The authors highlight the challenges to diagnosis, identify gaps in the current knowledge, and summarize novel treatments on the horizon to raise awareness about the critical need for early recognition of symptoms and diagnosis of AL amyloidosis aimed at accelerating treatment and improving outcomes for patients

    The World Will Never be the Same: The Russia-Ukraine Conflict as a Trigger Point for Deglobalisation

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    This paper makes the case for why we believe that the Russia-Ukraine crisis signals the end of a global era defined by globalisation. Even though Russia’s economy is only a fraction of the US, EU or China, its role in the world is much more relevant and the events in Ukraine are triggering a cascade of effects that will redefine the political, social and economic thinking and interactions among nations long into the future. With the Russian invasion of Ukraine, the “peace dividend” of recent decades is gone as military budgets are increasing significantly around the world. Energy and raw material dependency on other countries is considered a strategic weakness. The war has disrupted global supply chains and nations are now shunning the exposure to other countries, especially ones that do not share similar values. The macroeconomic environment has changed as growth prospects are depressed and inflation is on the rise. The world is moving to a period of reorganisation and instability

    Претензионная работа по топливу для предприятий энергетики

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    Background and aims: CREB (cAMP response element binding protein) transcription factors are key regulators of homeostatic functions in the liver, and CRE binding is increased in hepatic inflammation. During chronic hepatitis B virus (HBV) infection, mutations or deletions in the pre-S region are frequently observed. These mutations can affect the pre-S2/S promoter controlling HBV envelope protein expression (hepatitis B surface antigen (HBsAg)) and have been associated with worsened clinical outcome. We aimed to test if CREB activation impacts on HBsAg expression. Methods: The effect of the CREB inducer protein kinase A (PKA) was tested by coexpression with HBV wild-type vector in vitro. Luciferase reporter gene constructs were cloned to identify novel regulatory regions for the HBV pre-S2/S promoter. Electrophoretic mobility shift assay (EMSA) gelshift and supershift experiments were conducted to confirm DNA transcription factor binding. Results: Coexpression of HBV and PKA resulted in HBV-S mRNA induction and enhanced small envelope protein expression. We identified a CREB binding motif in the transcribed part of the pre-S2 region, contributing to basal S promoter activity via binding of activating transcription factor 2 (ATF2). A second CREB motif closely linked to the S-ATG showed a similar binding pattern involving ATF2 and CREB1, without appearing essential for basal promoter activity. Moreover, a sequence in the pre-S2 region is responsible for further transcriptional induction via CREB activators such as PKA and forskolin. EMSA experiments indicate that CREB1 and ATF4 are involved in complex formation conferring PKA dependent promoter activation. Conclusions: Our data suggest a novel mechanism by which HBV may utilise CREB/PKA signal transduction pathways of hepatocytes to enhance its HBsAg expression during homeostasis and hepatic inflammation

    An antibody that prevents serpin polymerisation acts by inducing a novel allosteric behavior

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    Serpins are important regulators of proteolytic pathways with an antiprotease activity that involves a conformational transition from a metastable to a hyperstable state. Certain mutations permit the transition to occur in the absence of a protease; when associated with an intermolecular interaction, this yields linear polymers of hyperstable serpin molecules, which accumulate at the site of synthesis. This is the basis of many pathologies termed the serpinopathies. We have previously identified a monoclonal antibody (mAb4B12) that, in single-chain form, blocks α1-Antitrypsin (α1-AT) polymerisation in cells. Here, we describe the structural basis for this activity. The mAb4B12 epitope was found to encompass residues Glu32, Glu39 and His43 on helix A and Leu306 on helix I. This is not a region typically associated with the serpin mechanism of conformational change, and correspondingly the epitope was present in all tested structural forms of the protein. Antibody binding rendered β-sheet A - on the opposite face of the molecule - more liable to adopt an 'open' state, mediated by changes distal to the breach region and proximal to helix F. The allosteric propagation of induced changes through the molecule was evidenced by an increased rate of peptide incorporation and destabilisation of a preformed serpin-enzyme complex following mAb4B12 binding. These data suggest that prematurely shifting the β-sheet A equilibrium towards the 'open' state out of sequence with other changes suppresses polymer formation. This work identifies a region potentially exploitable for a rational design of ligands that is able to dynamically influence α1-AT polymerisation

    White-light OLEDs using liquid crystal polymer networks

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    We have mixed nematic light-emitting liquid crystals and incorporated them as insoluble cross-linked polymer networks in a liquid crystal white-light organic light-emitting diode (LC-WOLED). The light emission is not voltage-dependent and polarized white light emission is also demonstrated. This wet-chemistry approach to WOLEDs is compatible with patterning by photolithography as well as by inkjet printing at room temperature on plastic substrates by roll-to-roll manufacturing

    Reversible and Irreversible Interactions of Poly(3-hexylthiophene) with Oxygen Studied by Spin-Sensitive Methods

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    Understanding of degradation mechanisms in polymer:fullerene bulk-heterojunctions on the microscopic level aimed at improving their intrinsic stability is crucial for the breakthrough of organic photovoltaics. These materials are vulnerable to exposure to light and/or oxygen, hence they involve electronic excitations. To unambiguously probe the excited states of various multiplicities and their reactions with oxygen, we applied combined magneto-optical methods based on multifrequency (9 and 275 GHz) electron paramagnetic resonance (EPR), photoluminescence (PL), and PL-detected magnetic resonance (PLDMR) to the conjugated polymer poly(3-hexylthiophene) (P3HT) and polymer:fullerene bulk heterojunctions (P3HT:PCBM; PCBM = [6,6]-phenyl-C61-butyric acid methyl ester). We identified two distinct photochemical reaction routes, one being fully reversible and related to the formation of polymer:oxygen charge transfer complexes, the other one, irreversible, being related to the formation of singlet oxygen under participation of bound triplet excitons on the polymer chain. With respect to the blends, we discuss the protective effect of the methanofullerenes on the conjugated polymer bypassing the triplet exciton generation
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