According to the "membrane sensor" hypothesis, the membrane's physical properties and microdomain organization play an initiating role in the heat shock response. Clinical conditions such as cancer, diabetes and neurodegenerative diseases are all coupled with specific changes in the physical state and lipid composition of cellular membranes and characterized by altered heat shock protein levels in cells suggesting that these "membrane defects" can cause suboptimal hsp-gene expression. Such observations provide a new rationale for the introduction of novel, heat shock protein modulating drug candidates. Intercalating compounds can be used to alter membrane properties and by doing so normalize dysregulated expression of heat shock proteins, resulting in a beneficial therapeutic effect for reversing the pathological impact of disease. The membrane (and lipid) interacting hydroximic acid (HA) derivatives discussed in this review physiologically restore the heat shock protein stress response, creating a new class of "membrane-lipid therapy" pharmaceuticals. The diseases that HA derivatives potentially target are diverse and include, among others, insulin resistance and diabetes, neuropathy, atrial fibrillation, and amyotrophic lateral sclerosis. At a molecular level HA derivatives are broad spectrum, multi-target compounds as they fluidize yet stabilize membranes and remodel their lipid rafts while otherwise acting as PARP inhibitors. The HA derivatives have the potential to ameliorate disparate conditions, whether of acute or chronic nature. Many of these diseases presently are either untreatable or inadequately treated with currently available pharmaceuticals. Ultimately, the HA derivatives promise to play a major role in future pharmacotherapy.
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This paper describes the results of a second year Expo project team of Fontys Engineering, department Mechanical Engineering. During this research the design of a configurable damped spring design has been investigated. A calculation tool has been defined and validated using a Nylon 3D printed spring prototype. Also a theoretical design of a stainless steel spring has been made including stress calculations. Finally characterization tests on damping properties have been performed.
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Global society is confronted with various challenges: climate change should be mitigated, and society should adapt to the impacts of climate change, resources will become scarcer and hence resources should be used more efficiently and recovered after use, the growing world population and its growing wealth create unprecedented emissions of pollutants, threatening public health, wildlife and biodiversity. This paper provides an overview of the challenges and risks for sewage systems, next to some opportunities and chances that these developments pose. Some of the challenges are emerging from climate change and resource scarcity, others come from the challenges emerging from stricter regulation of emissions. It also presents risks and threats from within the system, next to external influences which may affect the surroundings of the sewage systems. It finally reflects on barriers to respond to these challenges. http://dx.doi.org/10.13044/j.sdewes.d6.0231 LinkedIn: https://www.linkedin.com/in/sabineeijlander/ https://www.linkedin.com/in/karel-mulder-163aa96/
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