1,186 research outputs found

    Pore fluid constraints on deep ocean temperature and salinity during the Last Glacial Maximum

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    Pore water records of δ^(18)O and [Cl] from ODP Site 1063A on the Bermuda Rise constrain the change in seawater δ^(18)O and salinity from the Last Glacial Maximum (LGM) to the Holocene to be 0.75±0.05‰ and 2.5±0.1% respectively. Coupled with a measured benthic foraminiferal δ^(18)O change, this result means that bottom waters were 4.6±0.8°C cooler than the Holocene at the LGM and therefore at or near the seawater freezing point. Coupled δ^(18)O and chlorinity results give an extrapolated mean ocean LGM to Holocene change in δ^(18)O of 0.95±0.09‰. These data also constrain the past southern source deep‐water salinity to be 35.76±0.04 psu, which is within error of the mean deep ocean value for this time

    Insights into interfacial activation from an open structure of Candida rugosa lipase.

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    The structure of the Candida rugosa lipase determined at 2.06-A resolution reveals a conformation with a solvent-accessible active site. Comparison with the crystal structure of the homologous lipase from Geotrichum candidum, in which the active site is covered by surface loops and is inaccessible from the solvent, shows that the largest structural differences occur in the vicinity of the active site. Three loops in this region differ significantly in conformation, and the interfacial activation of these lipases is likely to be associated with conformational rearrangements of these loops. The "open" structure provides a new image of the substrate binding region and active site access, which is different from that inferred from the structure of the "closed" form of the G. candidum lipase

    Repositioning the Catalytic Triad Aspartic Acid of Haloalkane Dehalogenase: Effects on Stability, Kinetics, and Structure

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    Haloalkane dehalogenase (DhlA) catalyzes the hydrolysis of haloalkanes via an alkyl-enzyme intermediate. The covalent intermediate, which is formed by nucleophilic substitution with Asp124, is hydrolyzed by a water molecule that is activated by His289. The role of Asp260, which is the third member of the catalytic triad, was studied by site-directed mutagenesis. Mutation of Asp260 to asparagine resulted in a catalytically inactive D260N mutant, which demonstrates that the triad acid Asp260 is essential for dehalogenase activity. Furthermore, Asp260 has an important structural role, since the D260N enzyme accumulated mainly in inclusion bodies during expression, and neither substrate nor product could bind in the active-site cavity. Activity for brominated substrates was restored to D260N by replacing Asn148 with an aspartic or glutamic acid. Both double mutants D260N+N148D and D260N+N148E had a 10-fold reduced kcat and 40-fold higher Km values for 1,2-dibromoethane compared to the wild-type enzyme. Pre-steady-state kinetic analysis of the D260N+N148E double mutant showed that the decrease in kcat was mainly caused by a 220-fold reduction of the rate of carbon-bromine bond cleavage and a 10-fold decrease in the rate of hydrolysis of the alkyl-enzyme intermediate. On the other hand, bromide was released 12-fold faster and via a different pathway than in the wild-type enzyme. Molecular modeling of the mutant showed that Glu148 indeed could take over the interaction with His289 and that there was a change in charge distribution in the tunnel region that connects the active site with the solvent. On the basis of primary structure similarity between DhlA and other ι/β-hydrolase fold dehalogenases, we propose that a conserved acidic residue at the equivalent position of Asn148 in DhlA is the third catalytic triad residue in the latter enzymes.

    Transient, unsettling and creative space: Experiences of liminality through the accounts of Chinese students on a UK-based MBA

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    This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ The Author(s) 2009.This article explores the experiences of liminality through the accounts of Chinese students on a UK-based MBA programme. The transient nature of the MBA experience, as well as the international status of the Chinese student, is resonant with conceptualizations of liminality as ‘in between’ space. Based on semi-structured interviews with 20 MBA graduates who had subsequently returned to China with their qualification, we explored their perceptions of outcomes from the course and their experiences as international students on a programme imbued with western norms and values. Results support the unsettling yet creative implications of liminality, as well as the fragmented insecure nature of identities, as individuals pass through the MBA ‘rite of passage’ in terms of ‘becoming’ a manager and entering a new phase of career. Accounts suggest the creation of hierarchical structures within liminal space whereby Chinese students, through their positioning at the margin, have uncomfortable yet illuminating encounters with alterity. At the same time, they experience levels of ambiguity and uncertainty in the post-liminal phase of China-located employments, as new western-based managerial identities collide with dominant discourses of Chinese organization

    Climate Engineering Responses to Climate Emergencies

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    Despite efforts to stabilize CO_2 concentrations, it is possible that the climate system could respond abruptly with catastrophic consequences. Intentional intervention in the climate system to avoid or ameliorate such consequences has been proposed as one possible response, should such a scenario arise. In a one-week study, the authors of this report conducted a technical review and evaluation of proposed climate engineering concepts that might serve as a rapid palliative response to such climate emergency scenarios. Because of their potential to induce a prompt (less than one year) global cooling, this study concentrated on Shortwave Climate Engineering (SWCE) methods for moderately reducing the amount of shortwave solar radiation reaching the Earth. The study's main objective was to outline a decade-long agenda of technical research that would maximally reduce the uncertainty surrounding the benefits and risks associated with SWCE. For rigor of technical analysis, the study focused the research agenda on one particular SWCE concept--stratospheric aerosol injection--and in doing so developed several conceptual frameworks and methods valuable for assessing any SWCE proposal.Comment: 66 pp., 5 figs., published by Novim, Santa Barbara, Cal., revised referenc

    The Non-Motor Symptoms Scale in Parkinson's disease: validation and use

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    The Non‐Motor Symptoms Scale (NMSS) was developed and validated in 2007 as the first instrument for the comprehensive assessment of a range of non‐motor symptoms in Parkinson's disease (PD). Thirteen years have elapsed since its introduction and extensive international validation with good psychometric attributes has been carried out. Here, we review the validation data of the NMSS and its cross‐validity with other scales, and describe the key evidence derived from use of the NMSS in clinical studies. To date, over 100 clinical studies and trials have made use of it as an outcome measure, showing consistent and strong correlations between NMSS burden and health‐related quality of life measures. Moreover, the scale has shown to be capable of detecting longitudinal changes in non‐motor symptoms, where studies have shown differential changes over time of several of the NMSS domains. The scale has become a key outcome in several randomized clinical trials. Highlighting the prevalence and importance of non‐motor symptoms to quality of life in patients with PD, the development of NMSS has also been useful in signposting clinical and biomarker based research addressing non‐motor symptoms in PD

    ‘Like the stranger at a funeral who cries more than the bereaved’: ethical dilemmas in ethnographic research with children

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    This article contributes to debates on the practicality and utility of prior ethical review in ethnography and qualitative research using an ethnography of children’s involvement in artisanal gold mining work in Ghana as a case study. Reflecting on dilemmas and obstacles encountered in attempts to employ prescribed institutional ethical guidance modelled for childhood research in the UK during the fieldwork, the discussion brings to attention some of the problems that can arise when ethical guidance is not anchored in the lived realities or value systems of the setting in which fieldwork is conducted. The article seeks to rejuvenate calls for more flexible and socio-culturally responsive ethical review and practice as an alternative to the prescriptive ethical regimes

    Symptoms and quality of life in late stage Parkinson syndromes: a longitudinal community study of predictive factors

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    BACKGROUND Palliative care is increasingly offered earlier in the cancer trajectory but rarely in Idiopathic Parkinson's Disease(IPD), Progressive Supranuclear Palsy(PSP) or Multiple System Atrophy(MSA). There is little longitudinal data of people with late stage disease to understand levels of need. We aimed to determine how symptoms and quality of life of these patients change over time; and what demographic and clinical factors predicted changes. METHODS We recruited 82 patients into a longitudinal study, consenting patients with a diagnosis of IPD, MSA or PSP, stages 3-5 Hoehn and Yahr(H&Y). At baseline and then on up to 3 occasions over one year, we collected self-reported demographic, clinical, symptom, palliative and quality of life data, using Parkinson's specific and generic validated scales, including the Palliative care Outcome Scale (POS). We tested for predictors using multivariable analysis, adjusting for confounders. FINDINGS Over two thirds of patients had severe disability, over one third being wheelchair-bound/bedridden. Symptoms were highly prevalent in all conditions - mean (SD) of 10.6(4.0) symptoms. More than 50% of the MSA and PSP patients died over the year. Over the year, half of the patients showed either an upward (worsening, 24/60) or fluctuant (8/60) trajectory for POS and symptoms. The strongest predictors of higher levels of symptoms at the end of follow-up were initial scores on POS (AOR 1.30; 95%CI:1.05-1.60) and being male (AOR 5.18; 95% CI 1.17 to 22.92), both were more predictive than initial H&Y scores. INTERPRETATION The findings point to profound and complex mix of non-motor and motor symptoms in patients with late stage IPD, MSA and PSP. Symptoms are not resolved and half of the patients deteriorate. Palliative problems are predictive of future symptoms, suggesting that an early palliative assessment might help screen for those in need of earlier intervention
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