94 research outputs found
QUANTITATIVE NON-DESTRUCTIVE NEUTRON ACTIVATION ANALYSIS OF SILVER IN COINS
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65909/1/j.1475-4754.1967.tb00617.x.pd
IDENTIFICATION OF THE GEOLOGIC ORIGINS OF ARCHAEOLOGICAL ARTIFACTS: AN AUTOMATED METHOD OF Na and Mn NEUTRON ACTIVATION ANALYSIS
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66345/1/j.1475-4754.1967.tb00618.x.pd
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Flourishing workplaces: a multisensory approach to design and POE
How can we design workplaces which occupants thrive in, which are functional but are also expressive? Drawing on research about the senses and office related studies this paper demonstrates how buildings can be designed to allow for positive multi-sensory experiences. In order to design a creative and productive workplace, it is essential to consider how the environment is making us feel, behave and act within it. As the workplace continues to evolve, the case is made for a sensory palette framework to drive a systems approach to building environmental design enabling the integration of the multi-modal sensory relationship of people’s reactions within various environmental settings. Technological advances, in the form of wearables that monitor our physiological and stress responses offer the opportunity to capture empirical data, further enabling the investigation to see how a diverse range of environmental settings affect our physical, mental and social wellbeing. The paper goes on to develop the established conceptual theories of ‘Flourish’ proposing a move beyond comfort when designing the interiors and the mechanics of facility controls towards a sensory impacts framework that considers a whole life costing approach using the Flourish Model sets the basis for a design and post-occupancy evaluation toolkit
Ser80Ile mutation and a concurrent Pro25Leu variant of the VHL gene in an extended Hungarian von Hippel-Lindau family
Von Hippel-Lindau disease (VHL) is a rare autosomal dominant disease characterized by development of cystic and tumorous lesions at multiple sites, including the brain, spinal cord, kidneys, adrenals, pancreas, epididymis and eyes. The clinical phenotype results from molecular abnormalities of the VHL tumor suppressor gene, mapped to human chromosome 3p25-26. The VHL gene encodes two functionally active VHL proteins due to the presence of two translational initiation sites separated by 53 codons. The majority of disease-causing mutations have been detected downstream of the second translational initiation site, but there are conflicting data as to whether few mutations located in the first 53 codons, such as the Pro25Leu could have a pathogenic role. In this paper we report a large Hungarian VHL type 2 family consisting of 32 members in whom a disease-causing AGT80AAT (Ser80Ile) c.239G>A, p.Ser80Ile mutation, but not the concurrent CCT25CTT (Pro25Leu) c.74C>T, p.Pro25Leu variant co-segregated with the disease. To our knowledge, the Ser80Ile mutation has not been previously described in VHL type 2 patients with high risk of pheochromocytoma and renal cell cancer. Therefore, this finding represents a novel genotype-phenotype association and VHL kindreds with Ser80Ile mutation will require careful surveillance for pheochromocytoma. We concluded that the Pro25Leu variant is a rare, neutral variant, but the presence such a rare gene variant may make genetic counseling difficult
Enhanced modulation bandwidth of GaAlAs double heterostructure lasers in high magnetic fields: Dynamic response with quantum wire effects
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Creative and productive workplaces: a review
The built environment affects our well-being and this in turn influences our effectiveness in the workplace. Poor environments contribute to absenteeism and to people not working as well as they might. This is an enormous cost to the nation. High-quality environmental design is an investment, as occupants are healthier, staff-retention rates are higher, productivity is higher and sustainability ideals are more likely to be met. Workplaces reflect the culture of companies and are places that are not just functional and convenient but give the occupant a wholesome experience in terms of body and spirit
Knock Down of Heat Shock Protein 27 (HspB1) Induces Degradation of Several Putative Client Proteins
Hsp27 belongs to the heat shock protein family and displays chaperone properties in stress conditions by holding unfolded polypeptides, hence avoiding their inclination to aggregate. Hsp27 is often referenced as an anti-cancer therapeutic target, but apart from its well-described ability to interfere with different stresses and apoptotic processes, its role in non-stressed conditions is still not well defined. In the present study we report that three polypeptides (histone deacetylase HDAC6, transcription factor STAT2 and procaspase-3) were degraded in human cancerous cells displaying genetically decreased levels of Hsp27. In addition, these proteins interacted with Hsp27 complexes of different native size. Altogether, these findings suggest that HDAC6, STAT2 and procaspase-3 are client proteins of Hsp27. Hence, in non stressed cancerous cells, the structural organization of Hsp27 appears to be a key parameter in the regulation by this chaperone of the level of specific polypeptides through client-chaperone type of interactions
Differences in regulation of tight junctions and cell morphology between VHL mutations from disease subtypes
Human cytomegalovirus immediate-early 1 protein rewires upstream STAT3 to downstream STAT1 signaling switching an IL6-type to an IFNγ-like response
MN and CP were supported by the Wellcome Trust (www.wellcome.ac.uk) Institutional Strategic Support Fund and CP was supported by the Deutsche Forschungsgemeinschaft (PA 815/2-1; www.dfg.de).The human cytomegalovirus (hCMV) major immediate-early 1 protein (IE1) is best known for activating transcription to facilitate viral replication. Here we present transcriptome data indicating that IE1 is as significant a repressor as it is an activator of host gene expression. Human cells induced to express IE1 exhibit global repression of IL6- and oncostatin M-responsive STAT3 target genes. This repression is followed by STAT1 phosphorylation and activation of STAT1 target genes normally induced by IFNγ. The observed repression and subsequent activation are both mediated through the same region (amino acids 410 to 445) in the C-terminal domain of IE1, and this region serves as a binding site for STAT3. Depletion of STAT3 phenocopies the STAT1-dependent IFNγ-like response to IE1. In contrast, depletion of the IL6 receptor (IL6ST) or the STAT kinase JAK1 prevents this response. Accordingly, treatment with IL6 leads to prolonged STAT1 instead of STAT3 activation in wild-type IE1 expressing cells, but not in cells expressing a mutant protein (IE1dl410-420) deficient for STAT3 binding. A very similar STAT1-directed response to IL6 is also present in cells infected with a wild-type or revertant hCMV, but not an IE1dl410-420 mutant virus, and this response results in restricted viral replication. We conclude that IE1 is sufficient and necessary to rewire upstream IL6-type to downstream IFNγ-like signaling, two pathways linked to opposing actions, resulting in repressed STAT3- and activated STAT1-responsive genes. These findings relate transcriptional repressor and activator functions of IE1 and suggest unexpected outcomes relevant to viral pathogenesis in response to cytokines or growth factors that signal through the IL6ST-JAK1-STAT3 axis in hCMV-infected cells. Our results also reveal that IE1, a protein considered to be a key activator of the hCMV productive cycle, has an unanticipated role in tempering viral replication.Publisher PDFPeer reviewe
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