Miracle-dz/UniFAR-FTUs huggingface dataset:
The effects in vivo and in vitro of oxidative damage to purified alpha1-antitrypsin and to the enzyme-inhibiting activity of plasma.

The association of pulmonary emphysema with low blood concentrations of α1-antitrypsin is well known. Recently, other investigations have shown that oxidizing agents can block the elastase-inhibitory activity of human α1-antitrypsin and that methionyl residues may play an important part in the mechanism of action of α1-antitrypsin. We examined the kinetics of the interaction of purified chloramine T-treated α1-antitrypsin with porcine pancreatic elastase and trypsin. Oxidized α1-antitrypsin did not inactivate elastase. However, the oxidized inhibitor could still slowly inactivate trypsin. Oxidation as carried out in these studies converted methionyl residues in α1-antitrypsin to methionyl sulfoxide. The data indicate that the oxidized methionyl residue was more critical to elastase inhibition than to trypsin inhibition and add further weight to the hypothesis that trypsin and elastase bind to 2 different sites. We also examined the elastase-inhibiting activities of rabbit, dog, and monkey plasma for susce.
Cortical mechanisms underlying low-level motion processing in the visual system of human and non-human primates

RJE Bours, RJA van Wezel and MJM Lankheet. Step size tuning in macaque area MT. 619.8. Washington, DC: Society for Neuroscience, 2005 RJE Bours, S Stuur and MJM Lankheet. Tuning for temporal interval in human apparent motion detection. Perception, 34 ECVP Abstract Supple- ment 2005 RJE Bours, M Kroes, MJM Lankheet. Spatiotemporal properties of apparent- motion detection. Perception, 35 ECVP Abstract Supplement 2006
Simian virus 40 host range/helper function mutations cause multiple defects in viral late gene expression

Simian virus 40 (SV40) deletion mutants dlA2459 and dlA2475 express T antigens that lack the normal carboxy terminus. These mutants are called host range/helper function (hr/hf) mutants because they form plaques at 37 degrees C on BSC-1 and Vero monkey kidney cell lines but not on CV-1p monkey kidney cells. Wild-type SV40 can provide a helper function to permit growth of human adenoviruses in monkey kidney cells; the hr/hf mutants cannot. Progeny yields of hr/hf mutants are also cold sensitive in all cell lines tested. Patterns of viral macromolecular synthesis in three cell lines (Vero, BSC-1, and CV-1) at three temperatures (40, 37, and 32 degrees C) were examined to determine the nature of the growth defect of hr/hf mutants. Mutant viral DNA replication was similar to that of the wild type in all three cell lines, indicating that the mutations affect late events in the viral lytic cycle. In mutant-infected Vero cells, in which viral yields were highest, late mRNA levels were similar to those observed during wild-type infection. Levels of viral late mRNA from mutant-infected CV-1 and BSC-1 cells at 32 and 37 degrees C were reduced relative to those of wild-type-infected cells. The steady-state level of the major viral capsid protein, VP1, in mutant-infected CV-1 cells was reduced to the same extent as was late mRNA. The synthesis of agnoprotein could not be detected in mutant-infected CV-1 cells but was readily detected in CV-1 cells infected by wild-type SV40. Primer extension analyses indicated that most late mRNAs from mutant-infected CV-1 cells utilize start sites downstream from the major wild-type cap site (nucleotide 325) and the agnoprotein initiation codon (nucleotide 335). These results indicate that deletion of the carboxyl-terminal domain of T antigen affects viral late mRNA production, both quantitatively and qualitatively. The agnoprotein is detected late in the wild-type SV40 lytic cycle and is thought to play a role in the assembly or maturation of virions. Reduced hr/hf progeny yields could result from decreased capsid protein synthesis and, in the absence of detectable levels of agnoprotein, from inefficient use of available capsid proteins.
Targets for botulinum toxin in the lower urinary tract

Botulinum toxin type A (BoNT/A), one of the seven subtypes of Botulinum toxin, is commercially available naked or complexed to other proteins. Onabotulinum toxin type A is the most extensively studied BoNT/A brand. Dose equivalence studies between the different brands have never been carried out. BoNT/A is internalized by nerve fibers after binding synaptic vesicle proteins, and the final target of action is synaptosome‐associated protein 25 kDa (SNAP‐25), a membrane protein essential for synaptic vesicle fusion with the neuronal membrane.
Feasibility and tolerability of whole‐body, low‐intensity vibration and its effects on muscle function and bone in patients with dystrophinopathies: a pilot study

Dystrophinopathies are X‐linked muscle degenerative disorders that result in progressive muscle weakness complicated by bone loss. This study's goal was to evaluate feasibility and tolerability of whole‐body, low‐intensity vibration (WBLIV) and its potential effects on muscle and bone in patients with Duchenne or Becker muscular dystrophy.
Gestural Manifestation of Knowledge in Conceptual Frames

Frames are cognitive structures of knowledge grounded in people's social interaction in recurrent sociocultural activities or individual incidences. Discussion concerning the knowledge in frames largely focuses on its linguistic manifestation with regard to roles and role relations in scenes. Little attention has been paid to the scriptal knowledge in conceptual frames. The present study provides empirical evidence that frame knowledge is also readily manifested in gesture in daily conversation. Gesture not only reveals roles and role relations in a scene as distinct from those in speech, but it also collaborates with speech to jointly manifest part of a script of the frame. In addition, in line with the view of prominence, the part of frame knowledge being selected for manifestation in gesture is the speaker's focus of attention on a certain aspect of the scene during speaking. Finally, the temporal patterning of gesture and speech further bears out growth point theory, in that the planning of an utterance involves the interplay of imagery thinking and linguistic thinking.
Determinantes de la actividad física en México

14.00 Segun la Organizacion para la Cooperacion y el Desarrollo Economico (2010), Mexico ocupa el primer lugar mundial en sobrepeso y el segundo en obesidad. El Programa Nacional de Cultura Fisica y Deporte (2008) busca elevar a treinta y cinco millones el numero de habitantes fisicamente activos en el pais para 2012. El objetivo del presente estudio es la deteccion y dimensionamiento de los factores que inciden en la realizacion de actividad fisica (AF) entre los residentes de Mexico. Utilizando datos de la Encuesta Nacional Sobre Uso del Tiempo (2009), se estimaron dos modelos econometricos. Normal 0 21 false false false ES-MX X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tabla normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:. 0001pt; line-height:150%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Arial Narrow","sans-serif"; mso-fareast-language:EN-US;}
Micro vs macro electrode DBS stimulation: A dosimetric study

Deep Brain Stimulation (DBS) is a clinically suitable technique for the treatment of the Parkinson's disease. Recently, also other neurological disorders such as Tourette syndrome, obsessive-compulsive disorder, epilepsy are being to be treated with DBS. However, the debate on its therapeutic mechanisms of action is still open. In order to a better understanding of such mechanisms, in this work the attention is focused on the DBS micro-stimulation. Indeed, a micro electrodes registration and stimulation is a fundamental step, during the surgical phase, to optimize the technique in terms of DBS lead positioning and DBS signal parameters. In this paper a dosimetric analysis with micro electrodes has been carried out, showing a more focused distribution of the electrical potential induced in the neuroanatomical tissues and changes of the excited/inhibited regions, respect to a macro electrodes stimulation.
Global modernity: Levels of analysis and conceptual strategies

This article tackles some methodological issues in sociological theory, in particular as a way to resume the discussion of modernity with a systematic intent. Descriptions and descriptive concepts are distinguished from middle-range analytical categories, which are distinguished from general analytical categories. History and evolution are also included methodologically in the analysis. Trend-concepts, which imply the development of some features of modernity in the long run, have not been adequately dealt with by sociology recently, so their status therefore remains undefined. It is these that offer the focus of this article. This is discussed initially in general terms, and the theme is then deepened through an analysis of secularization processes, drawing on the concept of collective subjectivity in order to take the discussion beyond individual action and structural-functional features. Analytical concepts receive pride of place in the methodological strategies suggested in the article.
Who will look after England’s rural disadvantaged now?

For more than 100 years, non-landed and non-Establishment interests in rural England were represented by a succession of three quasi-independent government bodies (quangos). These were the Development/Rural Development Commissions, the Countryside Agency, and the Commission for Rural Communities (CRC). Their roles embraced, to varying degrees, policy, practice, and advocacy. In 2013 the British government closed the CRC and absorbed aspects of its responsibilities into the civil service. The implications of this decision for the disadvantaged people and places of rural England are explored. The potential for land-related interest groups and traditional elites to increase their influence as a consequence, is considered. First, by way of context, the histories of the three quangos and the main interest groups are described. The views of the latter – and others with related interests - were sought (unsuccessfully), together with the opinions of people involved in one or more of the quangos, and, or, the civil service successor unit. These are presented and discussed. Conclusions relating to consequential ‘gaps’ in independent policy and research are drawn. The aim is to stimulate discussion about the implications for rural England of closing the CRC, for it is possible that the loss of this small organization may have unexpected long-term consequences. The eventual significance of this decision has yet to be determined.
Persistence and Effectiveness of Pyrethroids in Plastic Strips Against Varroa jacobsoni (Acari: Varroidae) and Mite Resistance in a Mediterranean Area

Abstract An apiary trial was conducted in 1997 in Sardinia, Italy, to verify the effectiveness of fluvalinate in polyvinyl chloride strips and flumethrin in polyethylene strips against Varroa jacobsoni Oudemans. Two indices to evaluate the efficacy of the treatments were adopted: percentage change in mite infestation of worker-sealed brood cells considering only treated hives and percentage change in mite mortality, and the natural variation in mite populations recorded in control hives during the trial. All acaricide treatments reduced the level of mite infestation of both sealed brood and adult bees. However, their effectiveness was slightly reduced in comparison to previous studies because of mite resistance phenomena. Portions of polyethylene strips of flumethrin from treated hives were sampled weekly to determine acaricide persistence using gas chromatography. After 4 wk, a slight reduction (≈9%) of the active ingredient content was observed. A laboratory bioassay also was performed to establish the resistance of adult female mites to fluvalinate. Mites were sampled from the experimental apiary and from various Sardinian apiaries which had primarily been subjected to fluvalinate applications in plastic strips or wood inserts for years. Mite resistance varied from 0 to 96%, depending on the acaricide management adopted. The lowest resistance level occurred in an apiary where pyrethroids had never been used, whereas the highest level occurred in an apiary with intensive use of fluvalinate in wood inserts.
Pilot study of a primary care internet-based depression prevention intervention for late adolescents.

INTRODUCTION There is currently no depression prevention intervention available to adolescents in primary care. METHOD Fourteen late adolescents evaluated the acceptability (performance and ratings), potential adverse effects (negative emotions), and benefits (pre/post measures of three risk factors for depression) of a combined primary care Internet-based depression prevention intervention. Nearly all participants engaged the website (13/14) and 8/14 completed the entire intervention. RESULTS Completers reported high levels of readability and ease of understanding and low levels of negative emotions. Completers showed favorable trends for the targeted risk factors: depressive symptoms, dysfunctional thinking, and low social support. CONCLUSION A primary care/prevention intervention may be acceptable and favorably impact risk factors for depression.
Infant Mortality and the Health of Survivors: Britain, 1910-50

The first half of the twentieth century saw rapid improvements in the health and height of British children. Average height and health can be related to infant mortality through a positive selection effect and a negative scarring effect. Examining town-level panel data on the heights of school children, no evidence is found for the selection effect, but there is some support for the scarring effect. The results suggest that the improvement in the disease environment, as reflected by the decline in infant mortality, increased average height by about half a centimetre per decade in the first half of the twentieth century.
Calcitriol ameliorates renal damage in a pre-established proteinuria model

Proteinuria is critical in the tubulointerstitial changes that ultimately lead to renal insufficiency. Increased protein filtration has direct toxic effects on tubular epithelial cells, leading to epithelial mesenchymal transition (EMT) to a myofibroblast phenotype. Angiotensin II and transforming growth factor (TGF)-β1 are the main mediators of EMT. Calcitriol may exert a potential renoprotective effect by reducing the activity of the renin angiotensin system by suppressing renin gene expression and also by inhibiting the proinflammatory nuclear factor-κB pathway. The present study investigated the benefits of calcitriol treatment in a puromycin-induced protein-uric nephropathy model. Uninephrectomized adult male Wistar rats received intraperitoneal administration of a single dose of puromycin (100 mg/kg) or vehicle. After eight weeks, the animals were divided into two groups and received vehicle or calcitriol (0.5 μg/kg) for four weeks. The vehicle-treated, proteinuric rats developed progressive proteinuria and tubulointerstitial fibrosis after 12 weeks. Increased collagen deposition and fibrosis were significantly ameliorated by calcitriol treatment. Calcitriol was effective in preventing an increase in the EMT markers, α-smooth muscle actin and fibroblast-specific protein 1, reducing macrophage infiltration as evidenced by levels of ED-1. In addition, calcitriol increased the anti-inflammatory cytokine interleukin-10 and reduced the pro-oxidant p47 phox enzyme. These effects were paralleled by a reduction in TGF-β/Smad3 expression. Calcitriol may have therapeutic potential in the proteinuric nephropathy model used in the present study by inhibiting the TGF-β1 axis.
SPREAD OF TUBERCULOSIS VIA RECIRCULATED AIR IN A NAVAL VESSEL: THE BYRD STUDY

The Greek physician Hippocrates was the first to offer a clear description of tuberculosis, and in the fifth century B.c., Isocrates suggested that tuberculosis was transmitted from person to person. However, there was no tangible evidence of a means of transmission, and so interest in this theory declined. Then, in 1882, Robert Koch’s discovery of the tubercle bacillus reawakened speculation about the communicability of tuberculosis. The mechanism of infection with Mycobocterium tuberculosis became a subject of serious and, at times, intensive investigation. By 1966, these investigations had led to the generally held theory that tuberculosis infection was acquired from the inhalation of the tubercle bacillus in a droplet-nucleus form. It was at this time that we were suddenly presented with an excellent opportunity to test this theory and shed more light on the epidemiology of tuberculosis infection.
Splines in Statistics

Abstract This is a survey article that attempts to synthesize a broad variety of work on splines in statistics. Splines are presented as a nonparametric function estimating technique. After a general introduction to the theory of interpolating and smoothing splines, splines are treated in the nonparametric regression setting. The method of cross-validation for choosing the smoothing parameter is discussed and the general multivariate regression/surface estimation problem is addressed. An extensive discussion of splines as nonparametric density estimators is followed by a discussion of their role in time series analysis. A comparison of the spline and isotonic regression methodologies leads to a formulation of a hybrid estimator. The closing section provides a brief overall summary and formulates a number of open/unsolved problems relating to splines in statistics.
CD8+ T Cells Induce Fatal Brainstem Pathology during Cerebral Malaria via Luminal Antigen-Specific Engagement of Brain Vasculature

Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection that results in thousands of deaths each year, mostly in African children. The in vivo mechanisms underlying this fatal condition are not entirely understood. Using the animal model of experimental cerebral malaria (ECM), we sought mechanistic insights into the pathogenesis of CM. Fatal disease was associated with alterations in tight junction proteins, vascular breakdown in the meninges / parenchyma, edema, and ultimately neuronal cell death in the brainstem, which is consistent with cerebral herniation as a cause of death. At the peak of ECM, we revealed using intravital two-photon microscopy that myelomonocytic cells and parasite-specific CD8+ T cells associated primarily with the luminal surface of CNS blood vessels. Myelomonocytic cells participated in the removal of parasitized red blood cells (pRBCs) from cerebral blood vessels, but were not required for the disease. Interestingly, the majority of disease-inducing parasite-specific CD8+ T cells interacted with the lumen of brain vascular endothelial cells (ECs), where they were observed surveying, dividing, and arresting in a cognate peptide-MHC I dependent manner. These activities were critically dependent on IFN-γ, which was responsible for activating cerebrovascular ECs to upregulate adhesion and antigen-presenting molecules. Importantly, parasite-specific CD8+ T cell interactions with cerebral vessels were impaired in chimeric mice rendered unable to present EC antigens on MHC I, and these mice were in turn resistant to fatal brainstem pathology. Moreover, anti-adhesion molecule (LFA-1 / VLA-4) therapy prevented fatal disease by rapidly displacing luminal CD8+ T cells from cerebrovascular ECs without affecting extravascular T cells. These in vivo data demonstrate that parasite-specific CD8+ T cell-induced fatal vascular breakdown and subsequent neuronal death during ECM is associated with luminal, antigen-dependent interactions with cerebrovasculature.
Substitutions of Thr30 provide mechanistic insight into tryptophan-mediated activation of TRAP binding to RNA

TRAP is an 11 subunit RNA binding protein that regulates expression of genes involved in tryptophan biosynthesis and transport in Bacillus subtilis. TRAP is activated to bind RNA by binding up to 11 molecules of l-tryptophan in pockets formed by adjacent subunits. The precise mechanism by which tryptophan binding activates TRAP is not known. Thr30 is in the tryptophan binding pocket. A TRAP mutant in which Thr30 is substituted with Val (T30V) does not bind tryptophan but binds RNA constitutively, suggesting that Thr30 plays a key role in the activation mechanism. We have examined the effects of other substitutions of Thr30. TRAP proteins with small β-branched aliphatic side chains at residue 30 bind RNA constitutively, whereas those with a small polar side chain show tryptophan-dependent RNA binding. Several mutant proteins exhibited constitutive RNA binding that was enhanced by tryptophan. Although the tryptophan and RNA binding sites on TRAP are distinct and are separated by ∼7.5 Å, several substitutions of residues that interact with the bound RNA restored tryptophan binding to T30V TRAP. These observations support the hypothesis that conformational changes in TRAP relay information between the tryptophan and RNA binding sites of the protein.
Contextual Dynamics in Foreign Language Learning Motivation

Learning context has increasingly been postulated to exert an influence on the dynamics of individual differences in language learning. In a longitudinal design that tested the proficiency gains of 1,682 learners over a 2-year foreign language program, a multilevel modeling approach was deployed in this study to account for variation in second language (L2) growth over time. Different aspects of learner career and social aspiration were postulated as individual difference factors in addition to the more conventional constructs of extrinsic and intrinsic L2 learning motivation. Perceived attitudinal norms operating within 72 streamed classes were posited as contextual factors. Results of multilevel analyses indicate that the mediating effects of class context on the relation between the L2 proficiency growth and individual difference factors exert both positive and negative influences, suggesting malleability of individual differences factors.
New Technologies, Ancient Archetypes: The Boston Globe's Discursive Construction of Internet Connectivity in Africa

This article analyzed the Boston Globe's discursive construction of Internet connectivity in Africa in its series entitled “The Wiring of a Continent: Africa Goes Online. ” The study was carried out within the theoretical framework of journalism as mythic narrative. It was found that the Boston Globe constructed the reality of the Internet in Africa within the framework of the primeval Western archetype of Africa as the “Dark Continent. ” This archetype was expressed through 4 myths: “Duality,” the “Last Frontier,” “New Beginnings,” and the “Frontier Hero. ” These myths reified Africa as the foil of the Western world, explained the digital divide, and naturalized a deterministic ideology of information technology. The story that was not told in this series is that the African fiber optic system was the single most significant African-funded telecommunications accomplishment in the history of the continent because it effectively reversed many of the colonial communication barriers between and within many African countries.