Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamic regimes and correlated structural dynamics in native and denatured alpha-lactalbumin.

Understanding the mechanisms of protein folding requires knowledge of both the energy landscape and the structural dynamics of a protein. We report a neutron-scattering study of the nanosecond and picosecond dynamics of native and the denatured alpha-lactalbumin. The quasielastic scattering intensity shows that there are alpha-helical structure and tertiary-like side-chain interactions fluctuating on sub-nanosecond time-scales under extremely denaturing conditions and even in the absence of disulfide bonds. Based on the length-scale dependence of the decay rate of the measured correlation functions, the nanosecond dynamics of the native and the variously denatured proteins have three dynamic regimes. When 0.05<Q<0.5 A(-1) (where the scattering vector, Q, is inversely proportional to the length-scale), the decay rate, Gamma, shows a power law relationship, Gamma proportional to Q(2.42+/-0.08), that is analogous to the dynamic behavior of a random coil. However, when 0.5<Q<1.0 A(-1), the decay rate exhibits a Gamma proportional to Q(1.0+/-0.2) relationship. The effective diffusion constant of the protein decreases with increasing Q, a striking dynamic behavior that is not found in any chain-like macromolecule. We suggest that this unusual dynamics is due to the presence of a strongly attractive force and collective conformational fluctuations in both the native and the denatured states of the protein. Above Q>1.0 A(-1) is a regime that displays the local dynamic behavior of individual residues, Gamma proportional to Q(1.8+/-0.3). The picosecond time-scale dynamics shows that the potential barrier to side-chain proton jump motion is reduced in the molten globule and in the denatured proteins when compared to that of the native protein. Our results provide a dynamic view of the native-like topology established in the early stages of protein folding.
Reflective Ethical Decision: A Model for Ethics in Accounting Education

This conceptual paper describes a Reflective Ethical Decision Model (REDM), which uses the underpinnings of philosophical humanism in collaboration with self-directed learning to help students determine and design their own personal model construct of ethical values. This model analyzes the necessary ingredients for applying ethics in accounting and business education and offers a hands-on pedagogical approach to the ethics curriculum. It is an illustration that students can use to reflect on personal orientations to ethical behavior and lifelong values. The rationale for proffering such an approach is the notion that the “operational orientations” that guide human behavior are not fully developed until early adulthood. This concept is also applicable in professional training and development as a move towards improving ethical decision-making constructs in organizations. The idea is to evoke the personal ethics each of us has, not to promote more avenues to extend the fallacy surrounding “business ethics. ” The designer and author hopes this model concept will encourage future research about ethical decision-making as a result of any critique that may arise from this endeavor. Key words: Ethics, philosophy, self-directed learning, reflective decision model
What works centre for local economic growth

I wrote yesterday about the problem with Portas Pilots, arguing that the way the scheme was implemented will make it almost impossible to figure out whether the projects actually have an impact. This is just one example of a more general failure - government is often very bad at generating convincing evaluation evidence and (arguably) even worse at using that evidence to inform policy making. Could a NICE for social policy help fix this? It appears that we may be about to find out as the government has announced the establishment of four 'What Works centres' covering the areas of crime, ageing, early intervention and local economic growth.
A Soluble Carotenoid Protein Involved in Phycobilisome-Related Energy Dissipation in Cyanobacteria

Photosynthetic organisms have developed multiple protective mechanisms to survive under high-light conditions. In plants, one of these mechanisms is the thermal dissipation of excitation energy in the membrane-bound chlorophyll antenna of photosystem II. The question of whether or not cyanobacteria, the progenitor of the chloroplast, have an equivalent photoprotective mechanism has long been unanswered. Recently, however, evidence was presented for the possible existence of a mechanism dissipating excess absorbed energy in the phycobilisome, the extramembrane antenna of cyanobacteria. Here, we demonstrate that this photoprotective mechanism, characterized by blue light–induced fluorescence quenching, is indeed phycobilisome-related and that a soluble carotenoid binding protein, ORANGE CAROTENOID PROTEIN (OCP), encoded by the slr1963 gene in Synechocystis PCC 6803, plays an essential role in this process. Blue light is unable to quench fluorescence in the absence of phycobilisomes or OCP. The fluorescence quenching is not ΔpH-dependent, and it can be induced in the absence of the reaction center II or the chlorophyll antenna, CP43 and CP47. Our data suggest that OCP, which strongly interacts with the thylakoids, acts as both the photoreceptor and the mediator of the reduction of the amount of energy transferred from the phycobilisomes to the photosystems. These are novel roles for a soluble carotenoid protein.
NPHS1 gene mutations confirm congenital nephrotic syndrome in four Brazilian cases: A novel mutation is described

Autosomal recessive mutations in NPHS1 gene are a common cause of congenital nephrotic syndrome (CNS). The disorder is characterized by massive proteinuria that manifests in utero or in the neonatal period during the first 3 months of life. NPHS1 encodes nephrin, a member of the immunoglobulin family of cell adhesion molecules and the main protein expressed at the renal slit diaphragm. Currently, there are approximately 250 mutations described in the NPHS1 gene distributed among all nephrin domains. The main objective of this study was to perform the analysis of the NPHS1 gene in patients with congenital nephrotic syndrome in order to determine the molecular cause of the disease.
Turbulent Bubbly Flow in a Vertical Pipe Computed By an Eddy-Resolving Reynolds Stress Model

Abstract : Turbulent incompressible bubbly flow in a vertical pipe in a Reynolds number range is studied computationally by using second-moment closure models. A corresponding instability sensitive eddy-resolving Reynolds stress model is applied in addition to the conventional Reynolds averaged Navier-Stokes approach. The two-phase flow computations are performedby utilizing an Eulerian two-fluid model. The numerical results are compared with available experimental data and data from Direct Numerical Simulation. The implementations of the described models and the computations are done in the numerical code OpenFOAM(registered trademark) .
Lotteries, loopholes and luck: Misdiagnosis in the vegetative state patient

Many factors contribute to the alarmingly high rates of misdiagnosis in the Vegetative State (VS) patient 1. These include the differential diagnosis and definitions, inconsistencies in the assessors’ knowledge, expertise and their approaches to the assessment of awareness. Variability in the patient's medical and physical management adds to this confusion, leading to the potential to misdiagnose an aware patient in Minimally Conscious State (MCS) as being in VS. Subsequently, this range of variables leads to inconsistencies in the assessment, clinical diagnosis and management of this patient group. This concept is clearly of great importance in terms of the patient's future management and life or death decisions when considering withdrawal of nutrition and hydration. Further exploration of the frequency and causes of misdiagnosis and a review of current guidelines will illustrate the potential loopholes in diagnosis and reveal possible solutions to this modern-day dilemma.
Effects of disruption of xylanase-encoding genes on the xylanolytic system of Streptomyces lividans

Wild-type Streptomyces lividans produced the three xylanases (XlnA, XlnB, and XlnC) when xylan, xylan hydrolysates obtained by the action of XlnA, XlnB, and XlnC, or purified small xylo-oligosaccharides (xylobiose [X2], xylotriose [X3], xylotetraose [X4], and xylopentaose [X5]) were used as the carbon source. The three xylanase genes of S. lividans (xlnA, xlnB, and xlnC) were disrupted by using vectors that integrate into the respective genes. Disruption of one or more of the xln genes resulted in reduced growth rates and reduced total xylanase activities when the strain was grown in xylan. The greatest effect was observed when xlnA was disrupted. In medium containing xylan, disruption of xlnA did not affect expression of xlnB and xlnC; disruption of xlnB did not affect expression of xlnA but affected expression of xlnC; and disruption of xlnC did not affect expression of xlnA but affected expression of xlnB. A fraction of XlnB or XlnC hydrolytic products (those with a degree of polymerization greater than 11 [X11]) was found to stimulate expression of xlnB and xlnC in strains disrupted in xlnC and xlnB, respectively, whereas lower-molecular-weight fractions as well as purified small xylo-oligosaccharides did not. The stimulating molecule(s) lost its effect when it was hydrolyzed further by XlnA. A mechanism of transglycosylation reactions by the S. lividans xylanases is postulated to be involved in the regulation of xln genes.
Numerical Implementation of Low Field Resistance Drift for Phase Change Memory Simulations

Phase change memories (PCM) are strongly believed to be an important technology for the memory application field, aiming to be at leading edge beyond 32 nm. Among the basic physical mechanisms related to the PCM device operation, low field resistance drift is actually one of the most interesting features of chalcogenides affecting the electrical behavior of the amorphous phase and thus having important implications in the PCM multilevel memory design. In this paper we present a drift model based on the electrically active defect formation theory. The model has been integrated in a physically-based numerical solver and a quantitative agreement with the electrical data is shown. An explanation of the experimentally observed dependence of the drift coefficient on the resistance values is finally provided.
Confidence Intervals and Survival Estimates: A Systematic Review of 3 Oncology Journals

Purpose:Kaplan-Meier methods generate an estimate of survival when follow-up is less than complete. Confidence intervals (CI) provide a range of values that is likely to contain the true result. We hypothesized that reporting of CI around survival estimates is not uniform. Methods:We searched all articles in randomly selected issues of Journal of Clinical Oncology (JCO), Cancer, and International Journal of Radiation Oncology Biology, and Physics (IJROBP) years 1999, 2001, and 2004. Articles reporting overall or median survival were reviewed to determine if CI were reported in text or graphical form. Data regarding disease site, intervention, study size, and type of study were collected. Results:A total of 313 articles reported overall or median survival from 35 issues of the 3 journals (IJROBP 115, JCO 132, Cancer 66). CI were reported in 97/313 (31.0%) articles reviewed. CI reporting was more common in prospective clinical trials (38%) than retrospective reviews (25%), P = 0.018. If patients were treated with chemotherapy the article was more likely to report CI (no chemo 20% versus chemo 40%; P = 0.001). CI reporting varied with journal (IJROBP 20%, Cancer 29%, JCO 42%, P = 0.001). CI reporting increased according to year of publication (25% in 1999, 27% in 2001, and 41% in 2004, P = 0.03). Conclusion:A majority of studies in major oncology journals do not report CI with survival estimates. The likelihood of reporting CI is associated with study type (prospective versus retrospective), use of chemotherapy, journal, and year of publication.
Social movements and political outcomes: why both ends fail to meet

The relationships between social movement challenges and political outcomes remain strongly underresearched in the field of social movements. Here, we use the labels “social” and “political” in a broad sense to comprise many types of challenges and many types of outcomes, such as economic and social outcomes for specific movements as well as general policy outcomes. Four theories are crucial for understanding successful mobilization of social movements: relative deprivation, resource mobilization, framing , and the theoretical figure of the opening political opportunity structure . Political outcomes, at least in democratic political systems, are usually the result of a parallelogram of different claims and means of influencing outcomes, in short, of compromises. Here, we list various forms of outcomes, from successful acceptance of movement demands to part-time successes or entire failures, and also the various strategies incumbents have in dealing with social movement challenges. Researchers usually have focused on the individual and structural conditions of the emergence of social movements but less so on the conditions of processing social movement demands and the outcomes for movements themselves, for the electorate and for policy changes. Consequently, there is little research available that would meet the requirements of an adequate research design in view of the numerous factors spelled out here as a theoretical control list. The idea of a response hierarchy of incumbents is suggested as a sort of a dispositional concept for further, more consolidated, research in this area. Also the notion of cycles of various sorts has to be kept in mind in order to avoid misjudging of both, the persistence of social movements over time, and their eventual successes and failures.
Widening 6-DOF haptic devices workspace with an additional degree of freedom

The aim of haptic interfaces is to enhance the user's immersion in a virtual environment through the stimulation of the haptic sense. In the context of scale one applications in immersive environments, the haptic interface must provide a very large workspace without degrading transparency. To reach this goal, we investigated the addition of a 7th axis with larger range to a 6-DOF haptic device. This way, the workspace is increased while with a proper control scheme the dynamic properties of the initial device are saved. To ensure good control on this redundant system we use the notion of generalised dynamically consistent inverse of the Jacobian within a position-position control approach
The modified Medical Research Council dyspnoea scale is a good indicator of health-related quality of life in patients with chronic obstructive pulmonary disease.

INTRODUCTION Health-related quality of life (HRQoL) is an important patient-centred outcome in chronic obstructive pulmonary disease (COPD). The aim of the current study is to compare the discriminative capacity of the modified Medical Research Council (mMRC) dyspnoea scale and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric classification of COPD on HRQoL, as well as determine other factors that are simple and determinative of HRQoL. METHODS In this cross-sectional observational study, a total of 328 patients with COPD were enrolled from the pulmonology outpatient clinic. HRQoL was measured using the St George's Respiratory Questionnaire (SGRQ) and the World Health Organization Quality of Life-BREF (WHOQOL-BREF). HRQoL scores were compared between the four GOLD stages and the five grades of the mMRC scale. Significant differences were determined using analysis of variance with Scheffe post-hoc test. Multiple linear regression was applied to explore the major determinants of HRQoL and exclude confounding factors. RESULTS Signiﬁcant differences were found in many more domains of the two questionnaires between mMRC grades than between GOLD stages. In the multiple linear regression model, the mMRC scale was the only factor that remained determinative of all the domains of SGRQ and WHOQOL-BREF. Patients with chronic productive cough, sleep disorders and frequent exacerbations had poorer HRQoL, as reflected by higher scores in SGRQ or lower scores in WHOQOL-BREF. CONCLUSION The mMRC dyspnoea scale is a concise and practical tool to assess the HRQoL of patients with COPD in daily clinical practice.
Best Practices for Compact Modeling in Verilog-A

Verilog-A is the de facto standard language that the semiconductor industry uses to define compact models. Unfortunately, it is easy to write models poorly in Verilog-A, and this can lead to unphysical model behavior, poor convergence, and difficulty in understanding and maintaining model codes. This paper details best practices for writing compact models in Verilog-A, to try to help raise the quality of compact modeling throughout the industry.
“It's easy to throw rocks at a corporation”: wind energy development and distributive justice in Canada

ABSTRACT In places like Canada, fast-paced wind turbine development combined with policy that limits local decision-making power has resulted in strong opposition to specific projects. Some studies suggest that anti-wind sentiment is tied to inadequate financial benefits – especially sharing at the local level. Thus, ideas of distributive economic justice have received traction, particularly in the form of praise for community-based development models. This paper reports on the findings from a mixed-methods study concerning preferred distributive justice elements in rural communities in Ontario (technocratic-based model) and Nova Scotia (community-based model) living with turbines. Residents’ perceptions of economic benefits are nuanced, but unlike other studies, this empirical work shows that both the fair distribution and the amount of local benefits are important predictors of project support. Yet, concerns around the fair distribution of benefits dominate in a regression on the adequacy of those benefits. A variety of interview and survey findings further point to the strength of traditional, profit-sharing community-based models for distributing benefits, but also more novel ideas including lowered electricity bills and tax rebates in areas home to turbines.
The Cathepsin B Inhibitor, z-FA-FMK, Inhibits Human T Cell Proliferation In Vitro and Modulates Host Response to Pneumococcal Infection In Vivo1

The cathepsin B inhibitor, benzyloxycarbonyl-phenyl-alanyl-fluoromethylketone (z-FA-FMK) at nontoxic doses was found to be immunosuppressive and repressed human T cell proliferation induced by mitogens and IL-2 in vitro. We showed that z-FA-FMK suppresses the secretion of IL-2 and IFN-γ as well as the expression of IL-2R α-chain (CD25) in activated T cells, whereas the expression of the early activated T cell marker, CD69, was unaffected. Furthermore, z-FA-FMK blocks NF-κB activation, inhibits T cell blast formation, and prevents cells from entering and leaving the cell cycle. z-FA-FMK inhibits the processing of caspase-8 and caspase-3 to their respective subunits in resting T cells stimulated through the Ag receptor, but has no effect on the activation of these caspases during Fas-induced apoptosis in proliferating T cells. When administered in vivo, z-FA-FMK significantly increased pneumococcal growth in both lungs and blood, compared with controls, in a mouse model of intranasal pneumococcal infection. Because host response to bronchopneumonia in mice is T cell dependent, our collective results demonstrated that z-FA-FMK is immunosuppressive in vitro and in vivo.
HA1-2-fljB Vaccine Induces Immune Responses against Pandemic Swine-Origin H1N1 Influenza Virus in Mice

In 2009, a novel pandemic swine-origin influenza A (H1N1) virus caused a public emergency of international concern. Vaccination is the primary strategy for the control of influenza epidemics. However, the poor immunopotency of many vaccine antigens is a major barrier to the development of effective vaccines against influenza. Flagellin, a Toll-like receptor 5 (TLR5) ligand, has been used as an adjuvant to enhance the immunopotency of vaccines in preclinical studies. Here, we developed a recombinant candidate vaccine, HA1-2-fljB, in which the globular head of the hemagglutinin (HA) antigen (residues 62-284) from H1N1 virus was fused genetically to the N-terminus of Salmonella typhimurium ﬂjB. The recombinant HA1-2-fljB protein was expressed efficiently in Escherichia coli, and the immunogenicity and protective efficacy of recombinant HA1-2-fljB were evaluated in a mouse model. Immunization with HA1-2-fljB elicited robust IgG antibodies and neutralizing antibodies and completely protected the mice against infection by swine-origin influenza A/swine/Jangsu/38/2010 (H1N1). These results suggest that HA antigen placed at the N-terminus of flagellin is also an excellent starting point for creating a fusion HA1-2-fljB protein as a candidate vaccine, and the recombinant HA1-2-fljB protein will contribute to the development of a more effective vaccine against swine-origin influenza virus infection.
Singlet Oxygen Luminescence Dosimetry (SOLD) for Photodynamic Therapy: Current Status, Challenges and Future Prospects

Abstract As photodynamic therapy (PDT) continues to develop and find new clinical indications, robust individualized dosimetry is warranted to achieve effective treatments. We posit that the most direct PDT dosimetry is achieved by monitoring singlet oxygen (1O2), the major cytotoxic species generated photochemically during PDT. Its detection and quantification during PDT have been long-term goals for PDT dosimetry and the development of techniques for this, based on detection of its near-infrared luminescence emission (1270 nm), is at a noteworthy stage of development. We begin by discussing the theory behind singlet-oxygen luminescence dosimetry (SOLD) and the seminal contributions that have brought SOLD to its current status. Subsequently, technology developments that could potentially improve SOLD are discussed, together with future areas of research, as well as the potential limitations of this method. We conclude by examining the major thrusts for future SOLD applications: as a tool for quantitative photobiological studies, a point of reference to evaluate other PDT dosimetry techniques, the optimal means to evaluate new photosensitizers and delivery methods and, potentially, a direct and robust clinical dosimetry system.
Method for improving container ship's squat prediction using optical fiber technology

In the recent years much research effort has been devoted to practical navigation problems in getting larger ships safely, especially liner mega size container ships, into existing harbours. The important point of any navigational analysis lies in the accurate determination of the ship's hull additional sinkage and possible trim changes (squat) generated by hydrodynamic forces when the ship is sailing in restricted waters. This paper aims at presenting the possibility of using optical fiber technology for precise static draft reading which will be used as a datum for further proceedings to determine current draft as one of the important elements on calculating ship's squat in a seaway, and their possible application in pilotage services. The loaded ships passage plan on pilot portable computer can be upgraded by the data of under keel clearance and ship's squat using appropriate software for predicting dangerous situation of grounding at seaway. The main goal is to point out that pilot on board ship can determine the ship's hull squat of the ship underway, and predict imminent danger of grounding due to reduce under keel clearance.