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Penance is often said to be a part of the process of making amends for wrongdoing. Here I clarify the nature of penance as a remedial action, highlighting the differences between it and more familiar corrective actions such as reparation and apology, and I offer an account of how penance contributes to the expiation of wrongdoing. In doing so, I reject a popular view according to which one does penance primarily by either punishing oneself or voluntarily submitting to punishment at the hands of others. I contend that non‐punitive actions such gifts or acts of service are typically more conducive to achieving the reparative aims of penance. [ABSTRACT FROM AUTHOR]

It's often assumed, especially in discussions of free will and moral responsibility, that unavoidable actions are possible. In recent years, however, several philosophers have questioned that assumption. Their views are considered here, and the possibility of unavoidable actions is defended and then applied to issues in action theory and in the literature on moral responsibility. [ABSTRACT FROM AUTHOR]

Libertarianism about free will conjoins the thesis that free will requires indeterminism with the thesis that we have free will. Here the claim that we have experiential evidence for the libertarian position is assessed. It is argued that, on a straightforward reading, the claim is false, for our experiences as agents don't support the claim that free will requires indeterminism. However, our experiences as agents may still have a role to play in an overall case for libertarianism, insofar as they give us some (defeasible) reason to think that we have free will. This latter claim is defended against a pair of objections that have been leveled against it. [ABSTRACT FROM AUTHOR]

I defend the principle of alternative possibilities (PAP) against what are sometimes known as buffer cases, which are supposed by some to be counterexamples to the principle. I develop an existing problem with the claim that standard buffer cases are counterexamples to PAP, before responding to a recent attempt by Michael McKenna (2018) to modify the cases in a way that circumvents this problem. While McKenna's strategy does avoid the problem, I argue that it faces a different difficulty. I conclude that (modified) buffer cases pose no threat to PAP. [ABSTRACT FROM AUTHOR]

Introduction: Central diabetes insipidus is a heterogeneous condition characterized by decreased release of antidiuretic hormone by the neurohypophysis resulting in a urine concentration deficit with variable degrees of polyuria. The most common causes include idiopathic diabetes insipidus, tumors or infiltrative diseases, neurosurgery and trauma. Temozolomide is an oral DNA-alkylating agent capable of crossing the blood-brain barrier and used as chemotherapy primarily to treat glioblastoma and other brain cancers. Cases: Two men (aged 38 and 54 years) suddenly developed polyuria and polydispsia approximately four weeks after the initiation of temozolomide for a glioblastoma. Plasma and urine parameters demonstrated the presence of a urinary concentration defect. Management: The clinical and laboratory abnormalities completely resolved with intranasal desmopressin therapy, allowing the continuation of temozolomide. The disorder did not relapse after cessation of temozolomide and desmopressin and relapsed in one patient after rechallenge with temozolomide. Discussion: Our report highlights the importance of a quick recognition of this exceptional complication, in order to initiate promptly treatment with desmopressin and to maintain therapy with temozolomide. [ABSTRACT FROM AUTHOR]

Human cell lines (CLs) are key assets for biomedicine but lack ancestral diversity. Here, we explore why genetic diversity among cell-based models is essential for making preclinical research more equitable and widely translatable. We lay out practical actions that can be taken to improve inclusivity in study design. [ABSTRACT FROM AUTHOR]

Mining occurs in highly variable, spatially dynamic environments. Existing methods of planning and operations management are insufficient to adequately account for variability. Managing variability within the value chain aims to maximise business value. This paper presents a methodology for managing variability. This includes: assessing the impact of variability on a deterministic mine schedule; applying guiding principles based on Theory of Constraints to stabilise and exploit the value chain; developing a risk approach to minimise costs of plan delivery; and establishing tools for critical path planning, reconciling performance against plan and establishing corrective actions to deliver plan outcomes. A case study is presented from the Olympic Dam mine. Conclusions include: operations contain significant variability that if not managed will fail to deliver the mine plan; the proposed methodology can be applied to reduce variability and robustly deliver the best-value mine plan; and this methodology has broad application across the mining industry. [ABSTRACT FROM AUTHOR]

The use of misidentified and contaminated cell lines continues to be a problem in biomedical research. Research Resource Identifiers (RRIDs) should reduce the prevalence of misidentified and contaminated cell lines in the literature by alerting researchers to cell lines that are on the list of problematic cell lines, which is maintained by the International Cell Line Authentication Committee (ICLAC) and the Cellosaurus database. To test this assertion, we text-mined the methods sections of about two million papers in PubMed Central, identifying 305,161 unique cell-line names in 150,459 articles. We estimate that 8.6% of these cell lines were on the list of problematic cell lines, whereas only 3.3% of the cell lines in the 634 papers that included RRIDs were on the problematic list. This suggests that the use of RRIDs is associated with a lower reported use of problematic cell lines. [ABSTRACT FROM AUTHOR]

Rule A: if it's metaphysically necessary that p, we may validly infer that no one is even partly morally responsible for the fact that p. Our principal aim in this article is to highlight the importance of this rule and to respond to two recent challenges to it. We argue that rule A is more important to contemporary theories of moral responsibility than has previously been recognized. We then consider two recent challenges to the rule and argue that neither challenge successfully undermines the rule's initial appeal. [ABSTRACT FROM AUTHOR]

Highlights • Comparison of ambient groundwater temperature profiles in sealed bedrock boreholes. • Thermal deviation logs were more consistent during intra-seasonal periods. • Free-convection enabled detection of deeper active flow zones. • Angled boreholes enhanced detection of vertical hydraulic pathways. • Deviation logs improved conceptualization of active groundwater flow. Abstract This study evaluates the utility of ambient temperature profiles collected in sealed bedrock boreholes to assess variability in groundwater flow in discretely fractured shallow bedrock environments. A conceptual model for groundwater flow and groundwater-surface water temperature conditions and their interaction in a temperate climate is developed through a statistical interpretation of time-lapse thermal deviation logs. Temperature profiles were collected in three angled and three vertical boreholes drilled to 24–32 mbgs (meters below ground surface) and temporarily sealed with an impermeable fabric liner in a fractured dolostone bedrock aquifer adjacent to and extending beneath a bedrock river to monitor seasonal hydrodynamics. Ambient borehole temperature profiles collected every 1–8 weeks over a 12 month period identified zones of hydraulic activity during periods of intra-seasonal stability without the interference of open borehole cross-connection. Signal cross-correlation and Fourier spectra analysis of thermal deviation logs provided a novel way to observe the shallow bedrock flow system's temperature evolution due to advection along discrete fractures in response to seasonal transience, and to identify and isolate noise caused by free-convection cells within the sealed borehole. This approach represents a diagnostic tool that improves confidence in identifying depth discrete, hydraulically active fracture zones from thermal deviation data sets in a shallow, fractured sedimentary bedrock environment. Variably scaled free-convection cells were observed within the borehole water columns during the colder winter periods. Although these periods were accompanied by higher signal noise near the river/atmospheric interface, these cells led to a temporary thermal disequilibrium between the borehole water column and formation water deeper in the bedrock. These conditions increased the maximum depth of thermal detections associated with discrete groundwater flow features from 14 mbgs in the summer to 26 mbgs in the winter, thereby enhancing the understanding of shallow groundwater flow systems under the direct influence of surface water. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the impact of a lay health worker support role in the inpatient setting. Background: Healthcare systems are facing critical nursing and nurse assistant staffing shortages. These disciplines can be challenging to recruit and retain, leading healthcare leaders to identify innovative staffing models. Whereas lay health workers have been used in the community and low-income setting, there is scant evidence of their use in the inpatient setting. We implemented a lay health worker role, called Patient Attendant Service Aides (PASAs), on two medical/surgical units at a community hospital. Methods: A pre/post-implementation design was used for this study. An online survey was provided to nurses, nursing assistants, and PASAs on the two medical/surgical units to assess their satisfaction and perceptions of the role. Nursing quality metrics, patient satisfaction, and nursing and nursing assistant turnover were evaluated before and after implementing the role. Results: The online survey showed that nurses and nursing assistants felt that PASAs helped offload their workload, allowing them to focus on nursing-related tasks. PASAs felt supported by the team and believed they were making a meaningful contribution to the unit. There were slight improvements in patient satisfaction, although not significant. There was a significant improvement in nursing turnover on Unit A, from 71.1% to 21.6% (p = 0.009). Conclusions: This is one of the first studies to evaluate the use of lay health workers in the inpatient setting; we found this role to be a feasible way to offload tasks from clinical staff. This role may serve as a pathway for workforce development, as several PASAs are now enrolled in nursing assistant training. Nurse managers may consider using lay health workers in the inpatient setting as they face severe clinical staff shortages. [ABSTRACT FROM AUTHOR]

The use of the allometric model $$y = \beta x ^{\alpha }$$ to describe the relative growth of morphological traits of trees is a source of contention in ecology. This is particularly so in a specific form, the West, Brown and Enquist model, which predicts values of $$\alpha $$ that are multiples of 1/4 for various allometric relationships-the quarter-power scaling law. We use statistical techniques to test the appropriateness of the quarter-power scaling allometric model in a number of different relative growth relationships of trees. Two separate datasets are used, one of repeated measures of Abies grandis (Grand fir) trees, another of independent measures of Eucalyptus trees. Nonlinear mixed-effects modelling is used to fit allometric models to the datasets. Generalised additive models, equivalence testing and traditional significance testing are used to assess the adequacy of the allometric models fitted and the values of the estimated exponents relative to those predicted by the WBE model. In only one of the five models fitted was there empirical evidence for the WBE-predicted quarter-power exponent. However, the adequacy of the allometric models was generally supported, though a need for further analysis over a larger range of tree ages/sizes is indicated. Supplementary materials accompanying this paper appear online. [ABSTRACT FROM AUTHOR]

The article focuses on public perceptions about the poor prospects of looked-after children or disrupted children. It refers to a sense of the inevitability of the future fate of look-after children to provide better care. It highlights attitudes towards looked-after children as they move into adulthood. It also explains disrupted parenting that has been a feature of the lives of the heroes of comic book fictions.

Urban geological hazards involving ground instability can be costly, dangerous, and affect many people, yet there is little information about the extent or distribution of geohazards within Europe’s urban areas. A reason for this is the impracticality of measuring ground instability associated with the many geohazard processes that are often hidden beneath buildings and are imperceptible to conventional geological survey detection techniques. Satellite radar interferometry, or InSAR, offers a remote sensing technique to map mm-scale ground deformation over wide areas given an archive of suitable multi-temporal data. The EC FP7 Space project named PanGeo (2011–2014), used InSAR to map areas of unstable ground in 52 of Europe’s cities, representing ∼15% of the EU population. In partnership with Europe’s national geological surveys, the PanGeo project developed a standardised geohazard-mapping methodology and recorded 1286 instances of 19 types of geohazard covering 18,000 km 2 . Presented here is an analysis of the results of the PanGeo -project output data, which provides insights into the distribution of European urban geohazards, their frequency and probability of occurrence. Merging PanGeo data with Eurostat’s GeoStat data provides a systematic estimate of population exposures. Satellite radar interferometry is shown to be as a valuable tool for the systematic detection and mapping of urban geohazard phenomena. [ABSTRACT FROM AUTHOR]

Cell lines are used in life science research worldwide as biological surrogates. All cell lines are subject to major limitations when used as research tools, including (i) cross-contamination with other cells cultured in the same laboratory environment and (ii) evolution in vitro that renders a given cell line inappropriate as a surrogate for a specific biological hypothesis. There is ample evidence that cross-contamination or phenotypic drift of cells in culture can generate irreproducible or misleading data. A small number of scientific journalsÐthe International Journal of Cancer being at the forefrontÐand funding agencies have recently moved forward to ask for obligatory cell line authentication data. The history of implementing such rules by the International Journal of Cancer exemplifies the difficulties encountered when installing mandatory quality measures in life sciences. [ABSTRACT FROM AUTHOR]

Frankfurt cases are supposed to provide us with counterexamples to the principle of alternative possibilities. Among the most well known responses to these cases is what John Fischer has dubbed the flicker of freedom strategy. Here we revisit a version of this strategy, which we refer to as the fine-grained response. Although a number of philosophers, including some who are otherwise unsympathetic to Frankfurt's argument, have dismissed the fine grained response, we believe there is a good deal to be said on its behalf. We argue, in particular, that reflection on certain cases involving omissions undermines the main objections to the response and also provides the groundwork for an argument in support of it. [ABSTRACT FROM AUTHOR]

Frankfurt cases are designed to be counterexamples to the principle of alternative possibilities (PAP), a version of which states that an agent is blameworthy for what she did only if there was an alternative course of action available to her at the time, the availability of which is relevant per se to an explanation of why the agent is blameworthy for her action. In this article, I argue that the buffer cases, which are among the most promising and influential Frankfurt cases produced in recent years, are not counterexamples to PAP. While the agent in these examples may be blameworthy for what she did, I contend that there was an alternative course of action available to her at the time, the availability of which is relevant per se to an explanation of why the agent is blameworthy for her action. I then compare my objection to the buffer cases with a similar, though importantly different objection to them. Whatever merits this other objection may have, I contend that the one on offer here has important advantages over it. [ABSTRACT FROM AUTHOR]

Reproducibility and transparency in biomedical sciences have been called into question, and scientists have been found wanting as a result. Putting aside deliberate fraud, there is evidence that a major contributor to lack of reproducibility is insufficient quality assurance of reagents used in preclinical research. Cell lines are widely used in biomedical research to understand fundamental biological processes and disease states, yet most researchers do not perform a simple, affordable test to authenticate these key resources. Here, we provide a synopsis of the problems we face and how standards can contribute to an achievable solution. [ABSTRACT FROM AUTHOR]

Arguments for the incompatibility of determinism and moral responsibility sometimes make use of various transfer of non-responsibility principles. These principles purport to specify conditions in which lack of moral responsibility is transmitted to the consequences of things for which people are not morally responsible. In this paper, after developing what I take to be the most serious objections to extant principles of this sort, I identify and defend a new transfer of non-responsibility principle that is immune to these and other objections. This new principle says, roughly, that if you are not morally responsible for any of the circumstances that led to a particular outcome, and if you are not morally responsible for those circumstances leading to that outcome, then you are not morally responsible for the outcome either. After defending this principle against a number of objections, I use it to argue for the conclusion that no one is even partly morally responsible for anything, if determinism is true. [ABSTRACT FROM AUTHOR]

Background: High blood glucose concentration may increase risk of death and poor outcome after acute myocardial infarction. We did a systematic review and meta-analysis to assess the risk of in-hospital mortality or congestive heart failure after myocardial infarction in patients with and without diabetes who had stress hyperglycaemia on admission.Methods: We did two searches of MEDLINE for English-language articles published from 1966 to October, 1998, a computerised search of Science Citation Index from 1980 to September, 1998, and manual searches of bibliographies. Two searchers identified all cohort studies or clinical trials reporting in-hospital mortality or rates of congestive heart failure after myocardial infarction in relation to glucose concentration on admission. We compared the relative risks of in-hospital mortality and congestive heart failure in hyperglycaemic and normoglycaemic patients with and without diabetes.Findings: 14 articles describing 15 studies were identified. Patients without diabetes who had glucose concentrations more than or equal to range 6.1-8.0 mmol/L had a 3.9-fold (95% CI 2.9-5.4) higher risk of death than patients without diabetes who had lower glucose concentrations. Glucose concentrations higher than values in the range of 8.0-10.0 mmol/L on admission were associated with increased risk of congestive heart failure or cardiogenic shock in patients without diabetes. In patients with diabetes who had glucose concentrations more than or equal to range 10.0-11.0 mmol/L the risk of death was moderately increased (relative risk 1.7 [1.2-2.4]).Interpretation: Stress hyperglycaemia with myocardial infarction is associated with an increased risk of in-hospital mortality in patients with and without diabetes; the risk of congestive heart failure or cardiogenic shock is also increased in patients without diabetes. [ABSTRACT FROM AUTHOR]

Objective: Clinical proteinuria is a risk factor for both end-stage renal disease and cardiovascular disease. The prevalence of clinical proteinuria, its correlates and predictive value, and the effect of ACE inhibitors in preventing clinical proteinuria in diabetic and nondiabetic patients with left ventricular (LV) dysfunction are unknown.Research Design and Methods: The Studies of Left Ventricular Dysfunction (SOLVD) trials were analyzed to determine the baseline distribution of clinical proteinuria and related cardiovascular risk factors, the effect of baseline proteinuria on the risk of hospitalization for congestive heart failure (CHF) and mortality, and the effect of enalapril in preventing new clinical proteinuria.Results: A total of 5,487 out of 6,797 SOLVD participants (81%) were assessed for proteinuria at baseline. A total of 177 patients (3.2%) had baseline proteinuria. These patients had significantly higher systolic (137 vs. 125 mmHg, P < or = 0.001) and diastolic (83 vs. 77 mmHg, P < or = 0.001) blood pressure levels, a higher prevalence of diabetes (41 vs. 18%, P < or = 0.001), a lower ejection fraction (26.2 vs. 27.3%, P < or = 0.05), and greater degree of CHF (New York Heart Association [NYHA] class III/IV in 22 vs. 10%, P < or = 0.001) than patients without baseline proteinuria. Patients with baseline proteinuria also had higher rates of hospitalization for CHF (relative risk 1.81 [95% CI 1.37-2.41], P = 0.0001) and mortality (1.73 [1.34-2.24], P = 0.0001). Enalapril prevented clinical proteinuria in diabetic patients (0.38 [0.17-0.81], P = 0.0123) but not in nondiabetic patients (1.43 [0.77-2.63], P = 0.2622) without baseline proteinuria.Conclusions: Clinical proteinuria is an independent predictor of hospitalization for CHF and mortality in diabetic and nondiabetic patients with LV dysfunction. Enalapril significantly reduces the risk of clinical proteinuria in diabetic patients with LV dysfunction. [ABSTRACT FROM AUTHOR]

In a fascinating article in The Journal of Ethics, Eleonore Stump contends that while the flicker of freedom defense is the best available strategy for defending the principle of alternative possibilities against the threat posed to that principle by the Frankfurt cases, the defense is ultimately unsuccessful. In this article I identify a number of difficulties with Stump's criticism of the flicker strategy. Along the way, I also clarify various nuances of the strategy that often get overlooked, and I highlight the advantages of one version of it in particular. [ABSTRACT FROM AUTHOR]

Cell-line misidentification and contamination with microorganisms, such as mycoplasma, together with instability, both genetic and phenotypic, are among the problems that continue to affect cell culture. Many of these problems are avoidable with the necessary foresight, and these Guidelines have been prepared to provide those new to the field and others engaged in teaching and instruction with the information necessary to increase their awareness of the problems and to enable them to deal with them effectively. The Guidelines cover areas such as development, acquisition, authentication, cryopreservation, transfer of cell lines between laboratories, microbial contamination, characterisation, instability and misidentification. Advice is also given on complying with current legal and ethical requirements when deriving cell lines from human and animal tissues, the selection and maintenance of equipment and how to deal with problems that may arise. [ABSTRACT FROM AUTHOR]

Stochastic processes may be used as an efficient model for the line shapes affected by Stark effect in edge plasma conditions. We check the accuracy of this approach on the Lyman γ line of hydrogen perturbed by ions only. We also use a stochastic process to investigate the effect of plasma oscillations on a line shape. Our model assumes that Langmuir waves are a sequence of oscillating electric fields changing their amplitude and phase according to an exponential waiting time distribution. The possible effects of Langmuir waves on the Lyman α Stark profile are discussed in edge plasma conditions. (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Highlights: [•] First non-substrate analogue inhibitor of the trypanosome GPI pathway. [•] Active against recombinant enzyme and cell-free system. [•] Low molecular weight and good ligand efficiency. [ABSTRACT FROM AUTHOR]

Background: Although still experimental, natural orifice translumenal endoscopic surgery (NOTES) aims to use the natural orifices for intraabdominal surgery. Pure transvaginal umbilical hernia repair has been reported. However, mesh protection devices were used to minimize mesh contamination during mesh insertion. The authors believe that before widespread implementation of this technique, more foundational research is indicated to establish the sterility of hernia mesh insertion through this route. This prospective study aimed to compare transvaginal ventral hernia mesh insertion sterility with laparoscopic trocar-site insertion sterility to establish baseline data to help promote the safety of NOTES tranvaginal hernia repair. Methods: This was a prospective descriptive study (Canadian Task Force classification 2A). With institutional review board approval, 10 patients undergoing laparoscopic surgery for benign gynecologic disease were enrolled in the study. Atrium Prolite mesh (polypropylene monofilament) was inserted into the vagina before and after standard surgical preparation with 10 % povidone-iodine. As a control, mesh also was inserted through a prepped laparoscopic port site. The mesh was cultured for bacterial, fungal, and viral contamination. All patients received standard infection prophylaxis that included preoperative intravenous cefazolin and metronidazole. Results: The unprepped vaginal canal was cultured and demonstrated normal multiorganism vaginal flora in all 10 cases. Of the 10 skin incision mesh samples, 3 (30 %) grew bacteria, including Staphylococcus lugdunensis, a potentially pathogenic organism. In contrast, none of the prepped vaginal mesh specimens yielded any growth of microorganisms or potential pathogens. Conclusions: This study showed that a surgically prepped vaginal canal can be a sterile conduit for insertion of polypropylene mesh for transvaginal ventral hernia repair without the use of additional mesh protection. Surprisingly, the prepped vaginal conduit in our patients was more sterile than a prepped skin incision. [ABSTRACT FROM AUTHOR]

The article focuses on the concept of compatibilism and determinism which is compatible to free action and moral responsibility. It mentions that compatibilism feature thought-experiments including a deity, devil or sophisticated behavioral engineer. It states that determinism is incompatible with various kinds of morally relevant control.

Voltage-gated sodium channels are critical for the generation and propagation of electrical signals in most excitable cells. Activation of Na+ channels initiates an action potential, and fast inactivation facilitates repolarization of the membrane by the outward K+ current. Fast inactivation is also the main determinant of the refractory period between successive electrical impulses. Although the voltage sensor of domain IV (DIV) has been implicated in fast inactivation, it remains unclear whether the activation of DIV alone is sufficient for fast inactivation to occur. Here, we functionally neutralize each specific voltage sensor by mutating several critical arginines in the S4 segment to glutamines. We assess the individual role of each voltage-sensing domain in the voltage dependence and kinetics of fast inactivation upon its specific inhibition. We show that movement of the DIV voltage sensor is the rate-limiting step for both development and recovery from fast inactivation. Our data suggest that activation of the DIV voltage sensor alone is sufficient for fast inactivation to occur, and that activation of DIV before channel opening is the molecular mechanism for closed-state inactivation. We propose a kinetic model of sodium channel gating that can account for our major findings over a wide voltage range by postulating that DIV movement is both necessary and sufficient for fast inactivation. [ABSTRACT FROM AUTHOR]

Autoimmune hemolytic anemia (with warm or cold antibodies) was recently described in 7 patients with Covid-19 disease [[1]]. In our case, PCR testing was negative on the sputum, and there was no significant increase in IgG antibody titer over time. [Extracted from the article]

The halophilic Archaeon Halorubrum lacusprofundi, isolated from the perennially cold and hypersaline Deep Lake in Antarctica, was recently sequenced and compared to 12 Haloarchaea from temperate climates by comparative genomics. Amino acid substitutions for 604 H. lacusprofundi proteins belonging to conserved haloarchaeal orthologous groups (cHOGs) were determined and found to occur at 7.85% of positions invariant in proteins from mesophilic Haloarchaea. The following substitutions were observed most frequently: (a) glutamic acid with aspartic acid or alanine; (b) small polar residues with other small polar or non-polar amino acids; (c) small non-polar residues with other small non-polar residues; (d) aromatic residues, especially tryptophan, with other aromatic residues; and (e) some larger polar residues with other similar residues. Amino acid substitutions for a cold-active H. lacusprofundi β-galactosidase were then examined in the context of a homology modeled structure at residues invariant in homologous enzymes from mesophilic Haloarchaea. Similar substitutions were observed as in the genome-wide approach, with the surface accessible regions of β-galactosidase displaying reduced acidity and increased hydrophobicity, and internal regions displaying mainly subtle changes among smaller non-polar and polar residues. These findings are consistent with H. lacusprofundi proteins displaying amino acid substitutions that increase structural flexibility and protein function at low temperature. We discuss the likely mechanisms of protein adaptation to a cold, hypersaline environment on Earth, with possible relevance to life elsewhere. [ABSTRACT FROM AUTHOR]

Background: Halorubrum lacusprofundi is a cold-adapted halophilic archaeon isolated from Deep Lake, a perennially cold and hypersaline lake in Antarctica. Its genome sequencing project was recently completed, providing access to many genes predicted to encode polyextremophilic enzymes active in both extremely high salinity and cold temperatures. Results: Analysis of the genome sequence of H. lacusprofundi showed a gene cluster for carbohydrate utilization containing a glycoside hydrolase family 42 β-galactosidase gene, named bga. In order to study the biochemical properties of the β-galactosidase enzyme, the bga gene was PCR amplified, cloned, and expressed in the genetically tractable haloarchaeon Halobacterium sp. NRC-1 under the control of a cold shock protein (cspD2) gene promoter. The recombinant β-galactosidase protein was produced at 20-fold higher levels compared to H. lacusprofundi, purified using gel filtration and hydrophobic interaction chromatography, and identified by SDSPAGE, LC-MS/MS, and ONPG hydrolysis activity. The purified enzyme was found to be active over a wide temperature range (--5 to 60°C) with an optimum of 50°C, and 10% of its maximum activity at 4°C. The enzyme also exhibited extremely halophilic character, with maximal activity in either 4 M NaCl or KCl. The polyextremophilic β-galactosidase was also stable and active in 10-20% alcohol-aqueous solutions, containing methanol, ethanol, nbutanol, or isoamyl alcohol. Conclusion: The H. lacusprofundi β-galactosidase is a polyextremophilic enzyme active in high salt concentrations and low and high temperature. The enzyme is also active in aqueous-organic mixed solvents, with potential applications in synthetic chemistry. H. lacuprofundi proteins represent a significant biotechnology resource and for developing insights into enzyme catalysis under water limiting conditions. This study provides a system for better understanding how H. lacusprofundi is successful in a perennially cold, hypersaline environment, with relevance to astrobiology. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: This study aims to compare the prognostic value of two obstetric fistula classification systems. Methods: Prospective analysis of 202 patients evaluated for obstetric fistula (OF) at the General Referral Hospital of Panzi, Bukavu, DRC, from April through December 2009. Fistula classification using both Goh's and Waaldijk's systems, as well as preoperative, surgical, and follow-up assessment were included. Receiver operating characteristics (ROC) curves were used to compare the accuracy of the two systems to discriminate successful closure from persistent fistula. Results: Two hundred two women underwent fistula repair. Ten were lost to follow-up. At longest follow-up, 181 patients (88.3%) had successful fistula closure. On multivariate analysis, the independent variables of multiparity and a primary or secondary repair were more likely to have a successful closure. In Waaldijk's system, no single component was more predictive of successful closure than another. In Goh's system, type 4 fistulae were more likely to have failed closure compared to those with type 1 or 2 ( p = 0.0144). When comparing ROC curves, Goh's system had significantly better ability to predict successful closure than the Waaldijk's system, p = 0.0421. Conclusions: Waaldijk and Goh are the two most commonly used obstetric fistula classification systems. In this series of OF patients at Panzi Hospital in the Democratic Republic of Congo, Goh's classification system demonstrated a significantly better prediction of OF closure than the Waaldijk's system. [ABSTRACT FROM AUTHOR]

An investigation of spectral line broadening in plasmas is carried out within a kinetic-theory approach, based on the Bogoliubov-Born-Green-Kirkwood-Yvon (BBGKY) hierarchy. The model employs a resummation procedure to account for correlated emitter-perturber collisions. Applications to hydrogen lines indicate that such collisions strongly affect the width and the shape in the core region. This argument is supported by comparisons to numerical simulations. It is also shown that the usual collision operator models, based on a binary description of emitter-perturber collisions, can be extremely inaccurate. The present model, in a better agreement with numerical simulations, is suggested as an extension suitable for the design of fast and accurate numerical routines for plasma diagnostics. [ABSTRACT FROM AUTHOR]

The Bogoliubov-Born-Green-Kirkwood-Yvon (BBGKY) formalism is revisited in the framework of plasma spectroscopy. We address the issue of Stark line shape modeling by using kinetic transport equations. In the most simplified treatment of these equations, triple correlations between an emitter and the perturbing charged particles are neglected and a collisional description of Stark effect is obtained. Here we relax this assumption and retain triple correlations using a generalization of the Kirkwood truncature hypothesis to quantum operator. An application to hydrogen lines is done in the context of plasma diagnostic. It is shown that the neglect of triple correlations can lead to a significant overestimate of the line width. [ABSTRACT FROM PUBLISHER]

In this article I argue that it is possible to be blameworthy for doing something that was not objectively morally wrong. If I am right, this would have implications for several debates at the intersection of metaphysics and moral philosophy. I also float a view about which actions can serve as legitimate bases for blame that allows for the possibility of blameworthiness without objective wrongdoing and also suggests an explanation for the appeal of the commonly held view that blameworthiness requires objective wrongdoing. [ABSTRACT FROM AUTHOR]

The impact approximation used in the modelling of Stark profiles is examined when a magnetic field is present. Motivated by tokamak plasma spectroscopy, we calculate line shapes and S-matrix elements for the first Lyman lines of hydrogen with two models proposed for retaining simultaneously Stark and Zeeman effects in the impact limit. An evaluation of the accuracy of the two approaches is made with the help of a numerical simulation. [ABSTRACT FROM AUTHOR]

Here it is argued that in order for something someone 'does' to count as a genuine action, the person needn't have been able to refrain from doing it. If this is right, then two recent defenses of the principle of alternative possibilities, a version of which says that a person is morally responsible for what he has done only if he could have refrained from doing it, are unsuccessful. [ABSTRACT FROM AUTHOR]

Abstract: Quinols have been developed as a class of potential anti-cancer compounds. They are thought to act as double Michael acceptors, forming two covalent bonds to their target protein(s). Quinols have also been shown to have activity against the parasite Trypanosoma brucei, the causative organism of human African trypanosomiasis, but they demonstrated little selectivity over mammalian MRC5 cells in a counter-screen. In this paper, we report screening of further examples of quinols against T. brucei. We were able to derive an SAR, but the compounds demonstrated little selectivity over MRC5 cells. In an approach to increase selectivity, we attached melamine and benzamidine motifs to the quinols, because these moieties are known to be selectively concentrated in the parasite by transporter proteins. In general these transporter motif-containing analogues showed increased selectivity; however they also showed reduced levels of potency against T. brucei. [Copyright &y& Elsevier]

Voltage-dependent ion channels are crucial for generation and propagation of electrical activity in biological systems. The primary mechanism for voltage transduction in these proteins involves the movement of a voltage-sensing domain (D), which opens a gate located on the cytoplasmic side. A distinct conformational change in the selectivity filter near the extracellular side has been implicated in slow inactivation gating, which is important for spike frequency adaptation in neural circuits. However, it remains an open question whether gating transitions in the selectivity filter region are also actuated by voltage sensors. Here, we examine conformational coupling between each of the four voltage sensors and the outer pore of a eukaryotic voltage-dependent sodium channel. The voltage sensors of these sodium channels are not structurally symmetric and exhibit functional specialization. To track the conformational rearrangements of individual voltage-sensing domains, we recorded domain-specific gating pore currents. Our data show that, of the four voltage sensors, only the domain IV voltage sensor is coupled to the conformation of the selectivity filter region of the sodium channel. Trapping the outer pore in a particular conformation with a high-affinity toxin or disulphide crossbridge impedes the return of this voltage sensor to its resting conformation. Our findings directly establish that, in addition to the canonical electromechanical coupling between voltage sensor and inner pore gates of a sodium channel, gating transitions in the selectivity filter region are also coupled to the movement of a voltage sensor. Furthermore, our results also imply that the voltage sensor of domain IV is unique in this linkage and in the ability to initiate slow inactivation in sodium channels. [ABSTRACT FROM AUTHOR]

Abstract: We report the extension of the copper(II) tetrafluoroborate catalysed opening of epoxides with alcohols to include a wider variety of alcohols, a range of solvents and a method to purify the products from the reaction. [Copyright &y& Elsevier]