Miracle-dz/UniFAR-FTUs huggingface dataset:
Angiotensin receptor blockers suppress antigen-specific T cell responses and ameliorate collagen-induced arthritis in mice.

OBJECTIVE The renin-angiotensin system plays an important role in the regulation of cardiovascular, renal, and endocrine functions. Recent studies have demonstrated that angiotensin II has proinflammatory effects that may contribute to the pathogenesis of immune-mediated diseases. We used the collagen-induced arthritis (CIA) model to investigate the influence of angiotensin II receptor blockers (ARBs) on antigen-specific immune responses and determine whether ARBs have preventive or therapeutic effects on the development of arthritis. METHODS We administered ARBs (olmesartan, candesartan, and telmisartan) to mice and evaluated antigen-specific T cell proliferation and cytokine production following immunization with ovalbumin (OVA) or type II collagen in Freund's complete adjuvant (CFA) or aluminum hydroxide (alum). Next, we induced CIA in DBA/1 mice and administered olmesartan. The severity and incidence of arthritis were scored according to clinical manifestations, and joint tissue sections were examined histopathologically. RESULTS ARBs severely suppressed lymphocyte proliferation and interferon-gamma production in mice immunized with OVA or type II collagen in CFA. Olmesartan also suppressed lymphocyte proliferation in mice immunized with ovalbumin in alum. In the CIA model, olmesartan reduced the mean arthritis score and the incidence of severe arthritis, even when it was administered only after disease onset. Histopathologic findings for joint destruction were improved in olmesartan-treated mice. CONCLUSION ARBs suppressed antigen-specific immune responses for Th1 and Th2 in vivo. Furthermore, olmesartan suppressed the development of severe arthritis and joint destruction in the CIA model. These findings suggest that ARBs may have therapeutic potential in rheumatoid arthritis.
Some effects of nicotine on cardiac automaticity, conduction, and inotropy.

The actions of nicotine upon the heart are numerous and varied, affecting rate,1contractile force,1-3and, in all likelihood, coronary flow.4It is generally considered that a large proportion of this alkaloid's cardiovascular affects are mediated via the autonomic nervous system1in accordance with nicotine's well-established1capacity to stimulate, then paralyze all autonomic ganglia. In the case of the heart, then, this drug initially produces cardiac slowing as a consequence of vagal stimulation. Subsequently, with paralysis of the vagal ganglia, there characteristically occurs an acceleration of heart rate, associated with release of cardiac stores of catecholamines. The characteristic enhancement of contractile force following nicotine administration has previously1been attributed to the above-described release of catecholamines. More recent studies3have demonstrated, however, that higher concentrations of the alkaloid produce a positive inotropic effect upon isolated cat papillary muscle and that the effect is unrelated
Stress resilience and physical fitness in adolescence and risk of coronary heart disease in middle age

Objective Psychosocial stress is a suggested risk for coronary heart disease (CHD). The relationship of stress resilience in adolescence with subsequent CHD risk is underinvestigated, so our objective was to assess this and investigate the possible mediating role of physical fitness. Methods In this register-based study, 237 980 men born between 1952 and 1956 were followed from 1987 to 2010 using information from Swedish registers. Stress resilience was measured at a compulsory military conscription examination using a semistructured interview with a psychologist. Some 10 581 diagnoses of CHD were identified. Cox regression estimated the association of stress resilience with CHD, with adjustment for established cardiovascular risk factors. Results Low-stress resilience was associated with increased CHD risk. The association remained after adjustment for physical fitness and other potential confounding and mediating factors, with adjusted HRs (and 95% CIs) of 1.17 (1.10 to 1.25), with some evidence of mediation by physical fitness. CHD incidence rates per 1000 person-years (and 95% CIs) for low-stress, medium-stress and high-stress resilience were 2.61 (2.52 to 2.70), 1.97 (1.92 to 2.03) and 1.59 (1.53 to 1.67) respectively. Higher physical fitness was inversely associated with CHD risk; however, this was attenuated by low-stress resilience, shown by interaction testing (p<0.001). Conclusions Low-stress resilience in adolescence was associated with increased risk of CHD in middle age and may diminish the benefit of physical fitness. This represents new evidence of the role of stress resilience in determining risk of CHD and its interrelationship with physical fitness.
Sex differences in the immune response to experimental stroke: Implications for translational research

Ischemic stroke is a leading cause of death and disability in the United States. It is known that males and females respond differently to stroke. Depending on age, the incidence, prevalence, mortality rate, and disability outcome of stroke differ between the sexes. Females generally have strokes at older ages than males and, therefore, have a worse stroke outcome. There are also major differences in how the sexes respond to stroke at the cellular level. Immune response is a critical factor in determining the progress of neurodegeneration after stroke and is fundamentally different for males and females. Additionally, females respond to stroke therapies differently from males, yet they are often left out of the basic research that is focused on developing those therapies. With a resounding failure to translate stroke therapies from the bench to the bedside, it is clearer than ever that inclusion of both sexes in stroke studies is essential for future clinical success. This Mini‐Review examines sex differences in the immune response to experimental stroke and its implications for therapy development. © 2016 Wiley Periodicals, Inc.
Herpes zoster and postherpetic neuralgia

Herpes zoster (HZ; shingles) results from reactivation of varicella–zoster virus that has been dormant in the spinal and cranial sensory ganglia following primary infection with varicella (chickenpox), usually during childhood. In developed countries more than 95% of the adult population are seropositive for varicella–zoster virus and are therefore at risk of developing HZ. Reactivation can occur at any age, but it is associated with an age-related decline in cell-mediated immunity and therefore occurs more frequently in older adults. Thus, HZ affects up to 25% of individuals during their lifetime, but approximately 50% of those aged 80 years or more. Whilst the disease is rarely life-threatening, it is associated with a number of acute symptoms such as a vesicular rash and pain. Longer-term complications include visual disturbances and postherpetic neuralgia (PHN), which is potentially the most troubling problem of all, and is associated with severe itching and allodynia. These can combine to negatively impact the day-to-day functioning and quality of life of the patient. Hospitalization associated with HZ and PHN is frequent in older individuals and a significant cost to healthcare providers. Current management of HZ with antiviral drugs and analgesics produces reasonable results in younger patients, in whom the disease is usually milder, and is effective against acute pain and skin rash. However, it is much less effective against PHN, which occurs more commonly and more severely in older patients. Once PHN has developed, current treatments offer only limited benefit and adverse effects are common. Management is challenging and often unsatisfactory (<50% of patients gain 50% relief of pain). With the older adult population steadily growing in size, the number of patients presenting with HZ is also likely to increase and this will place a greater burden on healthcare systems. Prevention strategies, such as vaccinating those at greatest risk, may offer the best option for the future.
Mycobacterium avium Infection and Modulation of Human Macrophage Gene Expression

Mycobacterium avium is a facultative intracellular pathogen cleared rapidly via intact host defense mechanisms. In the absence of adequate T cell function, as occurs in HIV-1-induced immunodeficiency, M. avium becomes an opportunistic infection with uncontrolled replication and reinfection of macrophage hosts. How M. avium infects, survives, and replicates in macrophages without signaling an effective microbicidal counterattack is unresolved. To address whether M. avium signals the expression of molecules, which influence mycobacterial survival or clearance, human monocyte-derived macrophage cultures were exposed to M. avium. Within minutes, M. avium, or its cell wall lipoarabinomannan, binds to the adherent macrophages and induces a spectrum of gene expression. In this innate response, the most abundant genes detected within 2 h by cDNA expression array involved proinflammatory chemokines, cytokines including TNF-α and IL-1, and adhesion molecules. Associated with this rapid initial up-regulation of recruitment and amplification molecules was enhanced expression of transcription factors and signaling molecules. By 24 h, this proinflammatory response subsided, and after 4 days, when some bacteria were being degraded, others escaped destruction to replicate within intracellular vacuoles. Under these conditions, inducible NO synthase was not up-regulated and increased transferrin receptors may facilitate iron-dependent mycobacterial growth. Sustained adhesion molecule and chemokine expression along with the formation of multinucleated giant cells appeared consistent with in vivo events. Thus, in the absence of T lymphocyte mediators, macrophages are insufficiently microbicidal and provide a nonhostile environment in which mycobacteria not only survive and replicate, but continue to promote recruitment of new macrophages to perpetuate the infection.
The Biomechanics of the Anterior Cruciate Ligament and Its Reconstruction

The anterior cruciate ligament (ACL) continues to be a major topic in orthopaedics and biomechanics. This is due to the high incidence of injury and its disabling consequences. That the disabling consequences have not yet been completely overcome guarantees continued interest. Injury to the ACL is associated with a range of problems, such as pain, instability, meniscal damage and osteoarthritis (Noyes et al., 1983; Segawa et al., 2001). This can be due to injury to other structures at the time of ACL injury, e.g. meniscus and articular cartilage, as well as developments secondary to the initial injury (Segawa et al., 2001). Although isolated injury to the ACL is considered uncommon, surgical transection of the ACL induces cartilage degeneration so reliably it is used to induce osteoarthritis in experimental animals (Desrochers et al., 2010). Simple repair is effective for some ligaments, but such repair of the ACL has had poor results, and the orthopaedic world currently awaits the development of a useful scaffold that can be placed between the torn ends of the ligament to promote effective healing (Murray, 2009). In the interim a popular choice of treatment with positive results is surgical reconstruction (replacement), using a graft fashioned typically from the patellar ligament or from hamstring tendons (Woo et al., 2002). But despite positive outcomes from ACL reconstruction problems still persist after ‘successful’ surgery, especially osteoarthritis (Oiestad et al., 2010). It is only possible to speculate that kinematic differences that remain after, or are caused by, surgical reconstruction lead to osteoarthritis (Scanlan et al., 2010), but post-surgical kinematic differences may lead to cartilage loading differences, which then predispose the knee to osteoarthritis (Andriacchi et al., 2004, 2006). These loading differences may lead to cartilage areas subsequently sustaining higher or lower loads or loads of a different nature (e.g. tension, compression) (Chaudhari et al., 2008). Development of a suitable ligament substitute is a straightforward matter: (1) determine the nature of the ligament, and (2) design a replacement that replicates this nature tolerably
Cell transplantation for myocardial injury: a preliminary comparative study.

BACKGROUND AIMS Cell transplantation may restore viable muscle after myocardial infarction. Because many studies have focused on one cell type, we compared the characteristics of skeletal myoblasts (SKM), bone marrow stromal/stem cells (BMSC) and smooth muscle cells (SMC) and their effects on cardiac function after myocardial injury. METHODS In vitro cell characteristics, including proliferation, hypoxic survival and vascular endothelial cell growth factor (VEGF) expression, of SKM, BMSC and SMC were compared. An in vivo left anterior descending artery ligation rat model was used, and cells were implanted into the infarct (n = 16 per cell type). Cell survival was determined by PKH26 staining and real-time polymerase chain reaction (PCR). Cardiac function, tissue VEGF and stem cell factor (SCF) expression and vasculogenesis were evaluated. RESULTS Although cell morphologies were distinct, in vitro proliferation was similar. In vitro studies showed that SKM had the highest hypoxic survival, whereas BMSC had the lowest hypoxic survival but the highest VEGF expression. After implantation, SKM showed the highest overall survival and in vivo SCF expression, and both SMC and SKM expressed the highest VEGF levels. Vasculogenesis was significantly (P < 0.001) improved after transplantation of each cell type. Overall, BMSC and SKM promoted the greatest improvement in cardiac function. CONCLUSIONS SKM, BMSC and SMC expressed VEGF and SCF and promoted vasculogenesis. Although BMSC showed the greatest regenerative potential relative to cell survival and growth factor expression, the greatest improvement in cardiac function was observed with BMSC and SKM.
Life and Words: Violence and the Descent into the Ordinary

Foreword 1. The Event and the Everyday 2. The Figure of the Abducted Woman: The Citizen as Sexed 3. Language and Body: Transactions in the Construction of Pain 4. The Act of Witnessing: Violence, Gender, and Subjectivity 5. Boundaries, Violence, and the Work of Time 6. Thinking of Time and Subjectivity 7. In the Region of Rumor 8. The Force of the Local 9. The Signature of the State: The Paradox of Illegibility 10. Three Portraits of Grief and Mourning 11. Revisiting Trauma, Testimony, and Political Community Notes Acknowledgments Index
A physiological criterion for setting thermal environmental limits for everyday work.

Three subjects walked continuously on a treadmill for periods of 1 hr or more at 180, 300, or 420 kcal/hr in a range of cool and hot climates from corrected effective temperature (CET) 10–32 C. At each rate of work rectal thermal equilibrium was practically independent of the influence of environment over a wide range of climates (“prescriptive” zone); the upper limit of the prescriptive zone appeared to be associated with the minimal bodily thermal gradient compatible with the transfer of adequate amounts of heat from the core to the periphery without placing the thermoregulatory system under disproportionately increased strain, in terms of circulatory response and elevated body core temperature; as such, this seems to be one possible criterion by which thermal environmental limits for everyday work may be assessed. The upper limits of prescriptive zones for work at an energy expenditure of 300 kcal/hr is CET 27.4 C and those for the lower and higher rates of work, respectively, were CET 30.2 C and 26.9 C. Submitted on June 15, 1962
The aerodynamics of Manduca sexta: digital particle image velocimetry analysis of the leading-edge vortex

SUMMARY Here we present the first digital particle image velocimetry (DPIV) analysis of the flow field around the wings of an insect (the tobacco hawkmoth Manduca sexta, tethered to a 6-component force-moment balance in a wind tunnel). A leading-edge vortex (LEV) is present above the wings towards the end of the downstroke, as the net upward force peaks. Our DPIV analyses and smoke visualisations match the results of previous flow visualisation experiments at midwing, and we extend the experiments to provide the first analysis of the flow field above the thorax. Detailed DPIV measurements show that towards the end of the downstroke, the LEV structure is consistent with that recently reported in free-flying butterflies and dragonflies: the LEV is continuous across the thorax and runs along each wing to the wingtip, where it inflects to form the wingtip trailing vortices. The LEV core is 2-3 mm in diameter (approximately 10% of local wing chord) both at the midwing position and over the centreline at 1.2 m s-1 and at 3.5 m s-1 flight speeds. At 1.2 m s-1 the measured LEV circulation is 0.012±0.001 m2 s-1 (mean ± s.d.) at the centreline and 0.011±0.001 m2 s-1 halfway along the wing. At 3.5 m s-1 LEV circulation is 0.011±0.001 m2 s-1 at the centreline and 0.020±0.004 m2 s-1 at midwing. The DPIV measurements suggest that if there is any spanwise flow in the LEV towards the end of the downstroke its velocity is less than 1 m s-1. Estimates of force production show that the LEV contributes significantly to supporting body weight during bouts of flight at both speeds (more than 10% of body weight at 1.2 m s-1 and 35-65% of body weight at 3.5 m s-1).
Teaching Economics at the University Level: Dynamics of Parameters and Implications

This paper investigates various changing aspects in the teaching of economics within the context of the dynamics of parameters. These include inter alia the role of effective communication, clarity of lecture notes, ability to focus on the centrality of theme, teaching and learning environment, and ability to illustrate with examples. It also notes the changing perception of indicators of good teaching over the two points in time in which data were collected. Two central ideas permeate the study. Firstly, the approach to teaching must be consistent with the needs and aspirations of the student population who collectively form a highly heterogeneous entity while at the same time displaying discernible stratification with distinctively identifiable group expectations and preferences. Herein lies the significance of a greater importance of contents rather than presentation per se. Secondly, it argues that teaching is much more than what can be realistically achieved during the classroom lectures. This paper underscores the critical importance of a teaching system research model embodying a holistic rather than a piecemeal approach to teaching and learning that is applicable to a range of circumstances with significant implications that extend far beyond the classroom.
Comparison of Lead Levels in Human Permanent Teeth from Strasbourg, Mexico City, and Rural Zones of Alsace

A comparative study of the mean lead concentrations in enamel and dentin of human premolars and permanent molars was conducted by means of a systematic sampling procedure with energy-dispersive x-ray fluorescence analysis. In a first series of analyses, no significant statistical differences in mean lead concentrations at various levels of enamel and dentin were noted between young patients of Strasbourg and those of small villages of Alsace, nor between elderly patients living in these two locations, despite the fact that motor traffic was significantly lower in the rural zones. However, in both locations, a significantly higher concentration of lead was observed in enamel and dentin in relation to age. In a second series of analyses, the mean lead concentrations of both dental hard tissues of premolars and permanent molars of young individuals from Strasbourg, rural Alsace, and Mexico City were compared. Significantly higher mean lead concentrations were found in enamel and dentin samples from Mexico City. This was most evident for inner coronal dentin (5.7 and 6.1 times greater than in teeth of Strasbourg and rural zones of Alsace, respectively) and for pulpal root dentin (6.9 and 8.9 times greater than in teeth of Strasbourg and rural zones of Alsace). It is proposed that the higher lead concentrations are related to the higher lead content of motor gasoline and to more intense traffic conditions. The dental hard tissues appear to be of value for the study of environmental lead pollution.
National identity, devolution and secession in Canada, Britain and Spain*

ABSTRACT. The aim of this article is twofold. First, it examines whether devolution fosters the rise of dual identities – regional and national. Second, it considers whether devolution encourages secession or, on the contrary, it stands as a successful strategy in accommodating intra-state national diversity. The article is divided into three parts. First it examines the changing attitudes towards Quebec's demands for recognition adopted by the Canadian government from the 1960s to the present. It starts by analysing the rise of Quebec nationalism in the 1960s and the efforts of the Canadian government to accommodate its demands within the federation. It then moves on to consider the radically new conception of Canadian unity and identity embraced by Prime Minister Pierre Elliott Trudeau and its immediate impact upon Quebec. The paper argues that Trudeau's ‘nation-building’ strategy represented a retreat from the pro-accommodation policies set in place to respond to the findings of the 1963 Royal Commission on Biculturalism & Bilingualism (known as the B&B Commission). Trudeau's definition of Canada as a bilingual and multicultural nation whose ten provinces should receive equal treatment alienated a significant number of Quebeckers. After Trudeau, various attempts were made to accommodate Quebec's demand to be recognised as a ‘distinct society’– Meech Lake Accord, Charlottetown Agreement. Their failure strengthened Quebec separatists, who obtained 49.4 per cent of the vote in the 1995 Referendum. Hence, initial attempts to accommodate Quebec in the 1960s were replaced by a recurrent confrontation between Canada's and Quebec's separate nation-building strategies. Second, the article explores whether devolution fosters the emergence of dual identities – regional and national – within a single nation-state. At this point, recent data on regional and national identity in Canada are presented and compared with data measuring similar variables in Spain and Britain. The three modern liberal democracies considered here include territorially circumscribed national minorities – nations without states (Guibernau 1999) – endowed with a strong sense of identity based upon the belief in a common ethnic origin and a sense of shared ethnohistory – Quebec, Catalonia, the Basque Country and Scotland. Third, the article examines whether devolution feeds separatism by assessing support levels for current devolution arrangements in Canada, Spain and Britain. The article concludes by examining the reasons which might contribute to replacing separatist demands with a desire for greater devolution.
Speech acts and unspeakable acts

L'auteur etudie la pornographie sous l'angle de la theorie de l'acte de parole. Deux denonciations feministes sont examinees : la pornographie subordonne les femmes et elle les reduit au silence. L'auteur demontre qu'en effet la pornographie est un acte illocutoire de subordination par sa force autoritaire (verdictif, exercitif) et que, en imposant la frustration perlocutoire, l'invalidite illocutoire, elle empeche les femmes d'acceder au statut de locuteur et de ce fait, de lutter par le recours a la parole.