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.
LINK
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.
DOCUMENT
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/
MULTIFILE
In this study we tested 39 Lactococcus lactis strains isolated from diverse habitats for their robustness under heat and oxidative stress, demonstrating high diversity in survival (up to 4 log units). Strains with an L. lactis subsp. lactis phenotype generally displayed more-robust phenotypes than strains with an L. lactis subsp. cremoris phenotype, whereas the habitat from which the strains had been isolated did not appear to influence stress survival. Comparison of the stress survival phenotypes with already available comparative genomic data sets revealed that the absence or presence of specific genes, including genes encoding a GntR family transcriptional regulator, a manganese ABC transporter permease, a cellobiose phosphotransferase system (PTS) component, the FtsY protein, and hypothetical proteins, was associated with heat or oxidative stress survival. Finally, 14 selected strains also displayed diversity in survival after spray drying, ranging from 20% survival for the most robust strains, which appears acceptable for industrial application, to 0.1% survival for the least-tolerant strains. The high and low levels of survival upon spray drying correlated clearly with the combined robustness under heat and oxidative stress. These results demonstrate the relevance of screening culture collections for robustness under heat and oxidative stress on top of the typical screening for acidifying and flavor-forming properties. © 2014, American Society for Microbiology.
DOCUMENT
Implementation of reliable methodologies allowing Reduction, Refinement, and Replacement (3Rs) of animal testing is a process that takes several decades and is still not complete. Reliable methods are essential for regulatory hazard assessment of chemicals where differences in test protocol can influence the test outcomes and thus affect the confidence in the predictive value of the organisms used as an alternative for mammals. Although test guidelines are common for mammalian studies, they are scarce for non-vertebrate organisms that would allow for the 3Rs of animal testing. Here, we present a set of 30 reporting criteria as the basis for such a guideline for Developmental and Reproductive Toxicology (DART) testing in the nematode Caenorhabditis elegans. Small organisms like C. elegans are upcoming in new approach methodologies for hazard assessment; thus, reliable and robust test protocols are urgently needed. A literature assessment of the fulfilment of the reporting criteria demonstrates that although studies describe methodological details, essential information such as compound purity and lot/batch number or type of container is often not reported. The formulated set of reporting criteria for C. elegans testing can be used by (i) researchers to describe essential experimental details (ii) data scientists that aggregate information to assess data quality and include data in aggregated databases (iii) regulators to assess study data for inclusion in regulatory hazard assessment of chemicals.
DOCUMENT
We summarize what we assess as the past year's most important findings within climate change research: limits to adaptation, vulnerability hotspots, new threats coming from the climate–health nexus, climate (im)mobility and security, sustainable practices for land use and finance, losses and damages, inclusive societal climate decisions and ways to overcome structural barriers to accelerate mitigation and limit global warming to below 2°C.
MULTIFILE
Objective: The majority of parents with a disabled child experience chronic sorrow, characterized by recurrent feelings of grief and loss related to their child’s disability. There is a significant lack of research on parents’ lived experiences of chronic sorrow, which limits our ability to understand parents’ needs and provide proper support. Design: Interpretative Phenomenological Analysis (IPA) was conducted based on in-depth interviews with six parents of severely disabled children. Results: In the literature on chronic sorrow, an important aspect has been consistently overlooked: the particular position of being a parent, experiencing an awareness of being ultimately responsible for their children. The analysis revealed how this awareness, experienced as a deeply felt ethical commitment, unconditional, largely in isolation, and without a limit in time, shaped the experience of chronic sorrow. Because of this awareness, the parents experienced themselves facing a Herculean task of navigating their intricate motions while struggling to maintain their ability to function. Conclusions: By revealing the importance of considering the unique parental position, the study enriches the concept of chronic sorrow, simultaneously offering insights into what it means to be a parent of a disabled child. These insights can improve care professionals’ responsiveness to parental needs.
DOCUMENT
In het winternummer van 2005, met het thema: Social Emergency and Crisis Intervention in Large European Cities, beschrijft Lia van Doorn de onderzoeksresultaten van een follow-up studie onder (voormalige) daklozen in Utrecht. Het betreft een kwalitatief onderzoek. In dit artikel worden drie fasen in het ontwikkelingsproces van de daklozen beschreven: Recente, langdurige en voormalige dakloosheid. De omstandigheden in deze fasen verschillen en daardoor ook de zorgbehoefte.
DOCUMENT
In this case study, we want to gain insights into how residents of three municipalities communicate about the new murder scenario of the cold case of Marianne Vaatstra and the possibility of a large-scale DNA familial searching. We investigate how stakeholders shape their arguments in conversation with each other and with the police. We investigate the repertoires that participants use to achieve certain effects in their interactions with others in three focus groups. The results show that the analyzed repertoires are strong normative orientated. We see two aspects emerge that affect the support for large-scale DNA familial searching. These are: 1. Cautious formulations: respondents showed restraint in making personal judgments and often formulated these on behalf of others. Participants would not fully express themselves, but adjusted to what seemed the socially desirable course. 2. Collective identity: respondents focused on the similarities between themselves and the needs, interests, and goals of other participants. Participants also tried in a discursive way to convince each other to participate in the large-scale familial searching. These two major discursive activities offered the communication discipline guidance for interventions into the subsequent communication strategy.
MULTIFILE
This year, OPTIMAX was warmly welcomed by University College Dublin. For the sixth time students and teachers from Europe, South Africa, South America and Canada have come together enthusiastically to do research in the Radiography domain. As in previous years, there were several research groups consisting of PhD-, MSc- and BSc students and tutors from the OPTIMAX partner Universities or on invitation by partner Universities. OPTIMAX 2018 was partly funded by the partner Universities and partly by the participants.
DOCUMENT
