Subunit interactions influence the biochemical and biological properties of Hsp104

Point mutations in either of the two nucleotide-binding domains (NBD) of Hsp104 (NBD1 and NBD2) eliminate its thermotolerance function in vivo. In vitro, NBD1 mutations virtually eliminate ATP hydrolysis with little effect on hexamerization; analogous NBD2 mutations reduce ATPase activity and severely impair hexamerization. We report that high protein concentrations overcome the assembly defects of NBD2 mutants and increase ATP hydrolysis severalfold, changing V(max) with little effect on K(m). In a complementary fashion, the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate inhibits hexamerization of wild-type (WT) Hsp104, lowering V(max) with little effect on K(m). ATP hydrolysis exhibits a Hill coefficient between 1.5 and 2, indicating that it is influenced by cooperative subunit interactions. To further analyze the effects of subunit interactions on Hsp104, we assessed the effects of mutant Hsp104 proteins on WT Hsp104 activities. An NBD1 mutant that hexamerizes but does not hydrolyze ATP reduces the ATPase activity of WT Hsp104 in vitro. In vivo, this mutant is not toxic but specifically inhibits the thermotolerance function of WT Hsp104. Thus, interactions between subunits influence the ATPase activity of Hsp104, play a vital role in its biological functions, and provide a mechanism for conditionally inactivating Hsp104 function in vivo

A Model for Managing Civil Construction Company Systems

At the beginning of the 20th century, organizations in a globalized and highly competitive environment face two options—either they stagnate by keeping their traditional old fashioned procedures, or they make the decision to look forward and change their current procedure, as they attempt to survive competition and become new competitive organizations that can play a more active role in the future market. Organizational changes are naturally linked to risks, and risks mean opportunities, as well as losses. However, as companies try to modify their procedures and adapt their staff and routine to some novelty, they have a good chance to change risks into opportunities. For most companies, adaptation means the use of modern quality management techniques, such as QCC (Quality Control Circle) or other similar techniques and procedures aimed at improvements such as developing their functions, doing their job, and acting as an organization. Actually, civil engineering companies operating in Brazil have had their success closely related to the way they understand, face, and conduct their adaptation. Although such procedures are useful for a traditional organization to change into a modern one with a competitive edge, there is a previous step that should not be overlooked when considering civil construction companies renewal. This paper presents a management systems model for civil engineering companies that desire to renew and improve their performance. It combines appropriate tools according to their proper uses and creates several subsystems: a functional scope subsystem, a management subsystem, an operational subsystem, an information management subsystem, and an organizational behavior subsystem. The use of this model will provide engineers and managers with efficient and efficacious techniques and procedures for civil construction companies to survive in today’s global, competitive world market

Field hospitals to face COVID-19: Requirements and lessons learned in the design and construction of the Lagoa Barra Hospital - Brazil

The construction of field hospitals has been a strategy adopted worldwide to face the consequences of the pandemic impacts caused by COVID-19 on healthcare systems. Specific characteristics of this pandemic, such as different ways and speeds of the disease transmission, and the implications at the population health and the productive system, has made the project, management, and construction of field hospitals for the patients with COVID-19 present specific features. In this work, for each phase of the FHLB  implantation, we present the main concepts, premises, restrictions, and challenges, focusing mainly on the needs programs of the project that guided the configuration of the environments, the definition of the circulation flows,  the typology of the beds, the main management tools used during the project's planning and control process, and in the lessons learned

Sustainability Indicators to Assess Infrastructure Projects: Sector Disclosure to Interlock with the Global Reporting Initiative

Infrastructure projects have great potential to impact the sustainability of cities due to typically being large-sized projects and having a high level of intervention. Thus, evaluating the sustainability of these projects through sustainability reports is highly relevant, mainly regarding their impacts on the environment, public health, and the local economy. The Global Reporting Initiative (GRI) is the most widespread and internationally accepted Sustainability report tool. However, the GRI does not have an infrastructure sector disclosure. This research addresses this gap by providing a sustainability assessment instrument for infrastructure projects that interlocks with the Global Reporting Initiative (GRI). An extensive and detailed literature review was conducted, identifying 97 potential indicators to measure the sustainability of infrastructure projects. These indicators were evaluated following a top-down approach, conducting a survey of professionals experienced in the relevant field using Lawshe's content validity ratio. The results showed that 42 indicators were validated as essential, with 21 of them, not specifically related to infrastructure projects, already covered by the standard disclosure of the GRI. This assessment enabled the proposal of a sector disclosure formed by 21 new indicators related to the environmental, economic, and social dimensions. This study closes a gap in the evaluation of the sustainability of infrastructure projects and contributes to the discussion about sustainability indicators in infrastructure projects

Hazardous Drinking Prevalence and Correlates in Older New Zealanders: A Comparison of the AUDIT-C and the CARET

Objectives: The study compared the proportion of older adults identified as drinking hazardously based on the Alcohol Use Disorders Identification Test–Consumption (AUDIT-C) with the older adult-specific Comorbidity Alcohol Risk Evaluation Tool (CARET) and investigated whether sociodemographics, comorbidities, health, medication use, and alcohol-related risk behaviors explained discrepancies between the screens in classification of hazardousness. Method: The AUDIT-C and the CARET were administered to 3,673 adults aged 55 to 89 years. Classification agreement between the screens was evaluated using Cohen’s kappa. Hazardous drinking groups were compared using logistic regression. Results: Analysis indicated moderate agreement between the screens. Drinkers classified as “hazardous on the CARET only” consumed less alcohol, but were more likely to drink-drive. Introducing a drink-driving criterion into the calculation of hazardousness on the AUDIT-C substantially decreased the classification discrepancy between the measures. Discussion: Standard screening can be improved by investigating comorbidities, medication use, and alcohol-related risk behaviors in those initially identified as nonhazardous drinkers

Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS).

OBJECTIVES: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. METHODS: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. RESULTS: Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. CONCLUSIONS: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed. TRIAL REGISTRATION NUMBER: NCT02339441

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

Christine Kowal: stories about the adoption experience in Australia

This story is part of the History of Adoption, a four year national research project funded by the Australian Research Council, 2009-2012

Christine Kowal: stories about the adoption experience in Australia

This story is part of the History of Adoption, a four year national research project funded by the Australian Research Council, 2009-2012. <div><br></div><div>Contributors: Monash University. Faculty of Arts. School of Philosophical, Historical and International Studies ; History of Adoption Project ; Quartly, Marian ;</div><div><br></div><div>Coverage: Metropolitan Australia, VIC 1950s </div><div><br></div><div>Rights: Copyright 2010. Monash University. Faculty of Arts. History of Adoption Project</div