IN-VITRO RECONSTITUTION OF SULFITE REDUCTASE FROM PSEUDOMONAS AERUGINOSA

Recent work has established a link between a ferredoxin:NAD(P)H oxidoreductase (FprA) and sulfite assimilation in members of the genus Pseudomonas.  This suggested that FprA is a component of a novel sulfite reductase enzyme.  That hypothesis is consistent with the fact that only one component of the well-characterized E. coli a8?4 sulfite reductase has been identified in Pseudomonas genomes; i.e the ? siroheme subunit CysI is present but not the a flavoprotein subunit CysJ.  This led to the hypothesis that FprA is a component of a novel sulfite reductase enzyme.  Our aim is to test that hypothesis by in-vitro reconstitution using the purified proteins CysI and FprA.  We have successfully overexpressed and purified FprA from Pseudomonas aeruginosa.  The strategy for production of purified CysI has been complicated by the requirement for concomitant expression of CysG (siroheme synthase).  We are also investigating the possibility that a downstream, overlapping reading frame (PA1837) may also be necessary for functional CysI production

How can transport provision and associated built environment infrastructure be enhanced and developed to support the mobility needs of individuals as they age?

First paragraph: Mobility touches every aspect of most of our lives. Restrictions on our mobility are perceived as a loss of freedom, and we seek wherever possible to regain that mobility, or replace it with other forms of mobility. While we immediately think of physical mobility, virtual mobility is increasingly becoming another world that we inhabit and move around in. Older people, however, are the most likely to experience mobility deprivation. The need to be mobile and to travel is related to psychological well-being in older age, and a reduction in mobility can lead to an increase in isolation, loneliness and depression and overall a poorer quality of life. Mobility is important to older people. There are also benefits to society as a whole in increasing travel for older people, including the economic benefits of older people spending more in shops, of them looking after grandchildren, undertaking voluntary work, and carrying out other caring responsibilities. In order to develop a framework of the mobility of people as they age, we formulated a set of guiding principles that underpin this Evidence Review. These principles are drawn from current thinking in applied gerontology in the many differing fields that cover mobility issues and represent a shift from individual discipline-based silo thinking to person-centred thinking that attempts to cross traditional disciplinary boundaries

Variability in water column respiration in Salish Sea waters and implications for coastal and ocean acidification

Water column respiration is a key driver of carbon cycling, ocean acidification, and oxygen dynamics in marine ecosystems. However, empirical estimates of the range and variability of respiration and its relative contribution to ocean acidification are seldom measured. In 2014, we began measuring respiration rates at multiple sites in the central Salish Sea (San Juan Islands, Bellingham Bay) and then initiated routine monitoring of water column respiration at multiple sites in Padilla Bay National Estuarine Research Reserve (NERR). Measurements in Padilla Bay were integrated into the well-established NERR System Wide Monitoring Program (SWMP). Our investigation revealed that 1) rates of respiration vary seasonally and appear to be associated with changes in organic matter supply and, to a lesser extent, temperature, and 2) incoming deeper waters of marine origin are characterized by relatively low rates of respiration (i.e. ~5ugO2/L/h). To further explore underlying mechanisms, we conducted a series of manipulative experiments to investigate the direct effect of increasing ocean temperature and organic matter supply on rates of respiration. These experiments revealed that respiration can more than triple in response to increases in organic carbon supply and that this response may be influenced by seasonal changes in the export of organic matter and detritus from the extensive eelgrass meadows of Padilla Bay. Our field sampling and manipulative experiments have produced empirical estimates of respiration that can be included in models and projections of water quality and ocean acidification for the Puget Sound, and provide insight into the response of inland marine waters of the Pacific Northwest to a warmer, more acidified ocean

Towards Understanding Sycophancy in Language Models

Human feedback is commonly utilized to finetune AI assistants. But human feedback may also encourage model responses that match user beliefs over truthful ones, a behaviour known as sycophancy. We investigate the prevalence of sycophancy in models whose finetuning procedure made use of human feedback, and the potential role of human preference judgments in such behavior. We first demonstrate that five state-of-the-art AI assistants consistently exhibit sycophancy across four varied free-form text-generation tasks. To understand if human preferences drive this broadly observed behavior, we analyze existing human preference data. We find that when a response matches a user's views, it is more likely to be preferred. Moreover, both humans and preference models (PMs) prefer convincingly-written sycophantic responses over correct ones a non-negligible fraction of the time. Optimizing model outputs against PMs also sometimes sacrifices truthfulness in favor of sycophancy. Overall, our results indicate that sycophancy is a general behavior of state-of-the-art AI assistants, likely driven in part by human preference judgments favoring sycophantic responses.Comment: 32 pages, 20 figure

Glutamine supplementation and renal health

Gemstone Team JuicedTeam Juiced designed a multi-faceted research project surrounding the potential risk of college students using protein supplements developing kidney disease. Survey research showed that participants taking protein supplements were ingesting double the recommended allowance based on literature values for average American dietary protein intake. Participants predisposed to kidney disease were no less likely to take protein supplements. Kidney cell modeling showed the molecular response to glutamine, an important protein building block. A significant increase in the gene expression of low-density lipoprotein receptor and two sclerotic markers was found in response to glutamine exposure. Gene expression was time- and dose-dependent. Enzymatic degradation and high performance liquid chromatography showed that three popular protein supplements contained more glutamine than stated by the manufacturers

Specific versus General Principles for Constitutional AI

Human feedback can prevent overtly harmful utterances in conversational models, but may not automatically mitigate subtle problematic behaviors such as a stated desire for self-preservation or power. Constitutional AI offers an alternative, replacing human feedback with feedback from AI models conditioned only on a list of written principles. We find this approach effectively prevents the expression of such behaviors. The success of simple principles motivates us to ask: can models learn general ethical behaviors from only a single written principle? To test this, we run experiments using a principle roughly stated as "do what's best for humanity". We find that the largest dialogue models can generalize from this short constitution, resulting in harmless assistants with no stated interest in specific motivations like power. A general principle may thus partially avoid the need for a long list of constitutions targeting potentially harmful behaviors. However, more detailed constitutions still improve fine-grained control over specific types of harms. This suggests both general and specific principles have value for steering AI safely

High self-efficacy: a vital element in teaching

Thesis (M.A., Education (Curriculum and Instruction))--California State University, Sacramento, 2009Past research has shown that teachers who feel that they are effective display characteristics that indeed make them more effective (Bandura, 1996). Researchers have\ud also studiedfactors that determine what activities increase self-efficacy and what decrease it. The purpose of this study is to investigate teacher self-efficacy in regards to teaching beginning reading to English Language Learners as well as English only students and to examine factors that may have influenced teachers examine self-efficacy. The data gatheredfrom the study revealed that the most prominentfactors influencing teacher self-efficacy to teach beginning reading are field experience involving mentor teachers and on-going staff development training throughout the career of the teacher. It was also concluded that teachers' are more efficacious when teaching English only students beginning reading as opposed to English Language Learners regardless of the\ud factors influencing their self-efficacy.Education (Curriculum and Instruction

Risk of COVID-19 after natural infection or vaccinationResearch in context

Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health