Miracle-dz/UniFAR-FTUs huggingface dataset:
Chimeric antibodies to proteinase 3 of IgG1 and IgG3 subclasses induce different magnitudes of functional responses in neutrophils

Background: Antineutrophil cytoplasmic antibodies (ANCA) are associated with small-vessel vasculitis and have been implicated in its pathogenesis. The subclass distribution of ANCA IgG deviates from normal patterns, and it has been suggested that the IgG3 subclass may have pathogenic potential over the IgG1 subclass and may be more likely to be associated with active disease and renal involvement. Objective: To deal with potential pathogenicity, chimeric antibodies were constructed of IgG1 and three subclasses with human IgG1 or three constant regions and a murine-derived variable region that binds an epitope within the ANCA antigen proteinase 3 (PR3) that is recognised by human autoantibodies. Methods: The antibodies were characterised for binding to PR3, including affinity and avidity, before being used as tools to explore their ability to activate human neutrophils for superoxide release, cytokine release, degranulation and ability to induce neutrophil adhesion under flow. Results: Both subclass antibodies elicited similar neutrophil responses for superoxide release, degranulation and interleukin (IL) 8 production, although quantitative responses showed that the IgG1 subclass favoured degranulation and the IgG3 subclass favoured IL8 production. Both antibodies were able to convert neutrophils from selectin-dependent rolling adhesion to integrin-dependent stationary adhesion in a flow assay. Conclusions: These findings indicate that humanised antibodies directed against a single epitope of PR3 can recapitulate the effects of polyclonal human ANCA, which recognises multiple PR3 epitopes. Further, PR3-ANCA of both IgG1 and IgG3 subclasses can activate neutrophils, although the more potent IL8 response by IgG3 PR3-ANCA may encourage further neutrophil recruitment and amplify injury.
Some Considerations in Evaluating Spoken Word Recognition by Normal‐Hearing, Noise‐Masked Normal‐Hearing, and Cochlear Implant Listeners. I: The Effects of Response Format

Objective: The purpose of the present studies was to assess the validity of using closed‐set response formats to measure two cognitive processes essential for recognizing spoken words‐perceptual normalization (the ability to accommodate acoustic‐phonetic variability) and lexical discrimination (the ability to isolate words in the mental lexicon). In addition, the experiments were designed to examine the effects of response format on evaluation of these two abilities in normal‐hearing (NH), noise‐masked normal‐hearing (NMNH), and cochlear implant (CI) subject populations. Design: The speech recognition performance of NH, NMNH, and CI listeners was measured using both open‐ and closed‐set response formats under a number of experimental conditions. To assess talker normalization abilities, identification scores for words produced by a single talker were compared with recognition performance for items produced by multiple talkers. To examine lexical discrimination, performance for words that are phonetically similar to many other words (hard words) was compared with scores for items with few phonetically similar competitors (easy words). Results: Open‐set word identification for all subjects was significantly poorer when stimuli were produced in lists with multiple talkers compared with conditions in which all of the words were spoken by a single talker. Open‐set word recognition also was better for lexically easy compared with lexically hard words. Closed‐set tests, in contrast, failed to reveal the effects of either talker variability or lexical difficulty even when the response alternatives provided were systematically selected to maximize confusability with target items. Conclusions: These findings suggest that, although closed‐set tests may provide important information for clinical assessment of speech perception, they may not adequately evaluate a number of cognitive processes that are necessary for recognizing spoken words. The parallel results obtained across all subject groups indicate that NH, NMNH, and CI listeners engage similar perceptual operations to identify spoken words. Implications of these findings for the design of new test batteries that can provide comprehensive evaluations of the individual capacities needed for processing spoken language are discussed.
The developmental and physiological basis of body size evolution in an insect

The evolution of body size is a dominant feature of animal evolution. However, little is known about how the underlying developmental mechanisms that determine size change as body size evolves. Here we report on a case of body size evolution in the tobacco hornworm Manduca sexta that occurred over a period of nearly 30 years. We take advantage of an extensive series of physiological studies performed in the early 1970s that established the parameters that regulate body size in this species and compare their values with those of modern individuals that are descendants of the same colony. We show that three of the five processes that determine adult body size changed during this period, while two remained constant. Changes in these three developmental processes completely account for the observed evolutionary change in body size.
Methadone dosage and retention of patients maintenance treatment

Retention of patients in methadone treatment was studied in a cohort of 238 heroin addicts who entered maintenance programmes between February 1986 and August 1987. All subjects had been assessed at a centralised unit and referred to one of two other units for maintenance. Of the ten client characteristics that we analysed, three ‐ a history of imprisonment, a history of dependence on barbiturates or benzodiazepines and employment status at entry ‐ were included with “clinic” and maximum dose of methadone in the Cox regression models. Allowing for the other four variables, the maximum daily dose of methadone dispensed during the study period was a highly significant predictor of retention (P < 0.00001). With maximum dose stratified into three levels < 60 mg, 60‐79 mg, 80 + mg ‐ and with the lowest stratum used as the baseline, the relative risk (RR)of leaving treatment was halved (RR 0.47, 95% confidence interval [C1] 0.33‐0.67) for subjects receiving 60‐79 mg, and halved again (RR0.21,95% Cl 0.12‐0.38) for those who received 80 + mg. Clinic dosage policies contribute significantly to retention in methadone maintenance treatment. Clinics need to develop dosage policies in negotiation with individual patients.
Comparative Study on Semantic Search Engines

Current World Wide Web also recognized as Web 2.0 is an immense library of interlinked documents that are transferred by computers and presented to people. Search engine is considered the most important tool to discover any information from WWW. Inspite of having lots of development and novel research in current search engines techniques, they are still syntactic in nature and display search results on the basis of keyword matching without understanding the meaning of query, resulting in the production of list of WebPages containing a large number of irrelevant documents as an output. Semantic Web (Web 3.0), the next version of World Wide Web is being developed with the aim to reduce the problem faced in Web 2.0 by representing data in structured form and to discover such data from Semantic Web, Semantic Search Engines (SSE) are being developed in many domains. This paper provides a survey on some of the prevalent SSEs focusing on their architecture; and presents a comparative study on the basis of technique they follow for crawling, reasoning, indexing, ranking etc.
Graphical Models for Planning and Imitation in Uncertain Environments

We show that the problems of planning, policy learning, and goal-based imitation can be addressed within a unified framework based on probabilistic inference in graphical models. Planning is viewed as probabilistic inference of an action sequence in a Dynamic Bayesian Network (DBN), given an initial state and a desired goal state. We describe how planning can be used to bootstrap the learning of goal-dependent policies by utilizing feedback from the environment and a learned environment model. We demonstrate several different strategies for plan execution and policy learning in the context of the standard navigation problem for a stochastic maze environment. In contrast to conventional planning and policy learning methods, our approach does not require a reward or utility function, although constraints such as shortest path to goal can be incorporated within the graphical model. Our results demonstrate that the approach can be used to handle the challenging case of partially observable states (e.g., POMDPs). To illustrate the versatility of the approach, we show that the same graphical model that was used for planning and policy learning can also be used for inferring the goals of an observed teacher, for executing actions under uncertain goals, and for imitating the teacher even when the demonstration by the teacher was incomplete.
Treatment of melanoma cells with the synthetic retinoid CD437 induces apoptosis via activation of AP-1 in vitro, and causes growth inhibition in xenografts in vivo

Human malignant melanoma is notoriously resistant to pharmacological modulation. We describe here for the first time that the synthetic retinoid CD437 has a strong dose-dependent antiproliferative effect on human melanoma cells (IC50: 5 x 10(-6) M) via the induction of programmed cell death, as judged by analysis of cell morphology, electron microscopical features, and DNA fragmentation. Programmed cell death was preceded by a strong activation of the AP-1 complex in CD437- treated cells as demonstrated by gel retardation and chloramphenicol transferase (CAT) assays. Northern blot analysis showed a time- dependent increase in the expression of c-fos and c-jun encoding components of AP-1, whereas bcl-2 and p53 mRNA levels remained constant. CD437 also exhibited a strong growth inhibitory effect on MeWo melanoma cells in a xenograft model. In tissue sections of CD437- treated MeWo tumors from these animals, apoptotic melanoma cells and c- fos overexpressing cells were colocalized by TdT-mediated deoxyuridine triphosphate-digoxigenin nick end labeling (TUNEL) staining and in situ hybridization. Taken together, this report identifies CD437 as a retinoid that activates and upregulates the transcription factor AP-1, leading eventually to programmed cell death of exposed human melanoma cells in vitro and in vivo. Further studies are needed to evaluate whether synthetic retinoids such as CD437 represent a new class of retinoids, which may open up new ways to a more effective therapy of malignant melanoma.
Effect of technological parameters and wood properties on cutting power in plane milling of juvenile poplar wood

This paper presents the results of experimental measurements aimed at observing the effect of technological parameters (cutting speed vc and feed speed vf ), type of wood (juvenile wood and mature wood) and wood species (aspen Populus tremula, L. and hybrid poplar Populus Euramericana „Serotina“) on cutting power during plane milling of poplar wood. The results showed the reduction of cutting power with the decrease of cutting speed and feed speed. Lower cutting power was also measured in milling hybrid poplar than in milling aspen. The test also confirmed the effect of different anatomical and chemical structure of juvenile wood in relation to mature wood on different physical and mechanical properties of such wood and hence also on the cutting power in processing juvenile wood.
Cepstral compensation by polynomial approximation for environment-independent speech recognition

Speech recognition systems perform poorly on speech degraded by even simple effects such as linear filtering and additive noise. One possible solution to this problem is to modify the probability density function (PDF) of clean speech to account for the effects of the degradation. However, even for the case of linear filtering and additive noise, it is extremely difficult to do this analytically. Previously attempted analytical solutions to the problem of noisy speech recognition have either used an overly simplified mathematical description of the effects of noise on the statistics of speech, or they have relied on the availability of large environment specific adaptation sets. Some of the previous methods required the use of adaptation data that consists of simultaneously recorded or "stereo" recordings of clean and degraded speech. We introduce an approximation based method to compute the effects of the environment on the parameters of the PDF of clean speech. We perform compensation by vector polynomial approximations (VPS) for the effects of linear filtering and additive noise on the clean speech. We also estimate the parameters of the environment, namely the noise and the channel, by using piecewise linear approximations of these effects. We evaluate the performance of this method (VPS) using the CMU SPHINX-II system and the 100 word alphanumeric CENSUS database. Performance is evaluated at several SNRs, with artificial white Gaussian noise added to the database. VPS provides improvements of up to 15 percent in relative recognition accuracy.
Molecular Control of Smooth Muscle Cell Differentiation Marker Genes by Serum Response Factor and Its Interacting Proteins

Vascular smooth muscle cells (SMCs) exhibit a wide range of different phenotypes at different stages of development (Owens, 1995; Owens et al., 2004; Yoshida & Owens, 2005). Even in mature animals, SMCs retain the capability to change their phenotype in response to multiple local environmental cues. The plasticity of SMCs enables them to play a critical role in physiological processes in the vasculature, as well as the pathogenesis of numerous vascular diseases including atherosclerosis, re-stenosis after percutaneous coronary intervention, aortic aneurysm, and hypertension. Thus, it is important to understand the precise mechanisms whereby SMCs exhibit different phenotypes under distinct conditions. Because one of the most remarkable differences among SMC subtypes is the difference in expression levels of SMC-specific/-selective genes, elucidation of the molecular mechanisms controlling SMC differentiation marker gene expression may shed light on this issue.
FUNCTIONAL INDUCTION AND DE-INDUCTION OF P-GLYCOPROTEIN BY ST. JOHN'S WORT AND ITS INGREDIENTS IN A HUMAN COLON ADENOCARCINOMA CELL LINE

Continuous use of St. John's wort decreases the bioavailabilities of a variety of drugs. This interaction is attributed to the induction of cytochrome P450 3A4 and/or P-glycoprotein. In this study, we aimed to examine the chronic effects of St. John's wort and its constituents, hyperforin and hypericin, on the expression and function of P-glycoprotein in an intestinal cell line, LS 180. We also examined the acute inhibitory effect of St. John's wort on P-glycoprotein by using LLC-GA5-COL150 cells, which overexpress P-glycoprotein. St. John's wort and hyperforin but not hypericin increased the expression of P-glycoprotein in LS 180 cells. Removal of St. John's wort resulted in a restoration of P-glycoprotein level within 48 h. The content of hyperforin in St. John's wort extract was high enough to induce P-glycoprotein, suggesting that the induction of P-glycoprotein by St. John's wort can be almost attributable to hyperforin. The LS 180 cells chronically exposed to St. John's wort or hyperforin exhibited the increase in the function of P-glycoprotein assessed by the efflux of digoxin, and the activities correlated well with P-glycoprotein level. On the other hand, St. John's wort and its two constituents did not show any acute effect on P-glycoprotein-mediated transport of digoxin. St. John's wort induced P-glycoprotein in vitro that functions as a drug efflux pump. Hyperforin is considered to be a primary cause of the inductive effect of St. John's wort. Long-term administration of St. John's wort may cause clinically significant decrease in the plasma concentrations of P-glycoprotein substrates.
Outdoor air pollution as a possible modifiable risk factor to reduce mortality in post-stroke population

Outdoor air pollution is a known risk factor for mortality and morbidity. The type of air pollutant most reliably associated with disease is particulate matter (PM), especially finer particulate matter that can reach deeper into the lungs like PM2.5 (particulate matter diameter < 2.5 μm). Some subpopulations may be particularly vulnerable to PM pollution. This review focuses on one subgroup, long-term stroke survivors, and the emerging evidence suggesting that survivors of a stroke may be at a higher risk from the deleterious effects of PM pollution. While the mechanisms for mortality are still under debate, long-term stroke survivors may be vulnerable to similar mechanisms that underlie the well-established association between PM pollution and cardiovascular disease. The fact that long-term stroke survivors of ischemic, but not hemorrhagic, strokes appear to be more vulnerable to the risk of death from higher PM pollution may also bolster the connection to ischemic heart disease. Survivors of an ischemic stroke may be more vulnerable to dying from higher concentrations of PM pollution than the general population. The clinical implications of this association suggest that reduced exposure to PM pollution may result in fewer deaths amongst stroke survivors.
Brownian motion of inert tracer macromolecules in polymerized and spontaneously bundled mixtures of actin and filamin

By use of light microscopy and fluorescence photobleaching recovery, we have studied (a) structures that form in a system composed of copolymerized rabbit muscle actin and chicken gizzard filamin and (b) the Brownian motion of inert tracer macromolecules in this matrix. We have used as tracers size-fractionated fluorescein-labeled ficoll and submicron polystyrene latex particles. In F-actin solutions, the relative diffusion coefficient of the tracer was a decreasing function of both tracer size and actin concentration. Also, a percolation transition for latex particle mobility was found to follow a form suggested by Ogston (Ogston, A. G. 1958. Trans. Faraday Soc. 54:1754- 1757) for random filament matrices. The inclusion of filamin before polymerization resulted in increased tracer mobility. Below a filamin dimer-to-actin monomer ratio of 1:140, no structural features were observed in the light microscope. At or above this ratio for all actin concentrations tested, a three-dimensional network of filament bundles was clearly discriminated. Latex particles were always excluded from the bundles. By use of a dialysis optical cell in which polymerization could be initiated with very little hydrodynamic stress, we found that filamin can spontaneously bundle F-actin. A simple physical picture explains how dynamics can affect the structural result of coassembly and provides a further hypothesis on the balance between random filament cross-linking and large-scale bundling. Control of this balance may be important in cytoplasmic motile events.
Anosognosia for Motor Impairment Following Left Brain Damage

Anosognosia for motor impairment has been linked to lesions of the right hemisphere. However, left hemisphere damaged patients have often been excluded from investigation because of their associated language deficits. In this study we assessed anosognosia for motor disorders in a group of left hemisphere damaged patients using 2 tools that assess the presence of unawareness—a structured interview that is a common method of assessment of anosognosia in clinical settings, and a new tool, the Visual-Analogue Test for Anosognosia for Motor Impairment (VATAm; Della Sala, Cocchini, Beschin, & Cameron, in press). The structured interview relies heavily on language and enquires about general motor ability whereas the VATAm is less dependent on language abilities and enquires about specific motor tasks. Results suggest that the frequency of anosognosia in left brain damaged patients may have been underestimated due to methodological reasons, and that anosognosia for motor impairment can also be associated with lesions of the left hemisphere.
Value-Based Observation with Robot Teams ( VBORT ) Using Probabilistic Techniques

We present a behavior-based approach for directing the movements of robot teams engaged in mapping target objects in their environment. The resulting paths of the robots optimize the vantage points for all the robots on the team, maximizing information gain. At each step, each robot selects a movement to maximize the utility (in this case, reduction in uncertainty) of its next observation. Trajectories are not guaranteed to be optimal, but team behavior serves to maximize the team's knowledge since each robot considers the observational contributions of teammates. The VBORT approach is evaluated in simulation by measuring the resulting uncertainty about target locations compared to that obtained by robots acting without regard to teammate locations and to that of global optimization over all robots for each single step. The qualitative behavior of the team is sensible and close to the single-step optimal set of trajectories.
Southampton

Adult health In 2012, 25.1% of adults are classified as obese. The rate of alcohol related harm hospital stays was 726*, worse than the average for England. This represents 1,528 stays per year. The rate of self-harm hospital stays was 348.7*, worse than the average for England. This represents 899 stays per year. The rate of smoking related deaths was 325*, worse than the average for England. This represents 331 deaths per year. Estimated levels of adult smoking are worse than the England average. Rates of sexually transmitted infections and people killed and seriously injured on roads are worse than average.
Tools for Observational Gait Analysis in Patients With Stroke: A Systematic Review

Background Stroke severely affects walking ability, and assessment of gait kinematics is important in defining diagnosis, planning treatment, and evaluating interventions in stroke rehabilitation. Although observational gait analysis is the most common approach to evaluate gait kinematics, tools useful for this purpose have received little attention in the scientific literature and have not been thoroughly reviewed. Objectives The aims of this systematic review were to identify tools proposed to conduct observational gait analysis in adults with a stroke, to summarize evidence concerning their quality, and to assess their implementation in rehabilitation research and clinical practice. Methods An extensive search was performed of original articles reporting on visual/observational tools developed to investigate gait kinematics in adults with a stroke. Two reviewers independently selected studies, extracted data, assessed quality of the included studies, and scored the metric properties and clinical utility of each tool. Rigor in reporting metric properties and dissemination of the tools also was evaluated. Results Five tools were identified, not all of which had been tested adequately for their metric properties. Evaluation of content validity was partially satisfactory. Reliability was poorly investigated in all but one tool. Concurrent validity and sensitivity to change were shown for 3 and 2 tools, respectively. Overall, adequate levels of quality were rarely reached. The dissemination of the tools was poor. Conclusions Based on critical appraisal, the Gait Assessment and Intervention Tool shows a good level of quality, and its use in stroke rehabilitation is recommended. Rigorous studies are needed for the other tools in order to establish their usefulness.