Miracle-dz/UniFAR-FTUs huggingface dataset:
Experimental Contribution to a Theory of Thinking.

FOR this thesis a long series of experiments was carried out. Several htilr(e(d voiturns of common occurrence were printed in big type on cards and were shown to the observing subject one at a time by means of an automatic cacre-chea ger (Dr Ach's). A metal plate, which covered the card, sprang up, when a string was pulled, and by so doing closed an electric current, which flowed through a Hipp chronaoscope and a speakag twelv (Cattell's). Tile chronoscope therefore marked the time which passed from the appearance of the printed word until the first vibrations from the subject's voice broke the current in the speaking tube. This constituted the measure of the duration of the reaction and formed, with a full account of all the reproducible experiences of the observing subject, which were at once written down ill full, and any other remarks he had to make, the experimental data of the thesis. In contrast to previous experiments, on association definite tasks (A ttitjben) were given, which the subject had to accomplish ill the reaction. These referred to what the printed word on the card signified, and were as follows: to classify it, to name an example of it, to name a whole to which it belonged, to name a part, to name another of the same class or another part of the same whole. Each subject performed
Analysis of a Bacillus subtilis Proteinase Mutant

A Bacillus subtilis mutant having a phenotype manifesting reduced extracellular proteolytic activity was investigated. An extracellular protein was isolated and shown by fingerprint analysis to be a fragment of the wild-type enzyme. By using previously established molecular weights for the wild-type enzyme (2.9 × 104) and the two polypeptide chains derived from it (1.4 × 104 each), with the amino acid analysis and fingerprints of both wild-type and mutant proteins, a molecular weight of 1.57 × 104 was assigned to the mutant protein. 32P-diisopropylphosphate labeling of the mutant protein showed only 1 in 53 molecules to be functional. Thin-layer chromatography on Sephadex G-75 demonstrated that the active molecules were separable from the bulk of the isolated protein and had the same mobility as the wild-type enzyme. Fingerprints of tryptic digests of 32P-diisopropylphosphate-labeled wild-type and mutant proteins showed that the labeled peptides had identical characteristics.
Indoor particles affect vascular function in the aged: an air filtration-based intervention study.

RATIONALE Exposure to particulate matter is associated with risk of cardiovascular events, possibly through endothelial dysfunction, and indoor air may be most important. OBJECTIVES We investigated effects of controlled exposure to indoor air particles on microvascular function (MVF) as the primary endpoint and biomarkers of inflammation and oxidative stress as secondary endpoints in a healthy elderly population. METHODS A total of 21 nonsmoking couples participated in a randomized, double-blind, crossover study with two consecutive 48-hour exposures to either particle-filtered or nonfiltered air (2,533-4,058 and 7,718-12,988 particles/cm(3), respectively) in their homes. MEASUREMENTS AND MAIN RESULTS MVF was assessed noninvasively by measuring digital peripheral artery tone after arm ischemia. Secondary endpoints included hemoglobin, red blood cells, platelet count, coagulation factors, P-selectin, plasma amyloid A, C-reactive protein, fibrinogen, IL-6, tumor necrosis factor-alpha, protein oxidation measured as 2-aminoadipic semialdehyde in plasma, urinary 8-iso-prostaglandin F(2alpha), and blood pressure. Indoor air filtration significantly improved MVF by 8.1% (95% confidence interval, 0.4-16.3%), and the particulate matter (diameter < 2.5 mum) mass of the indoor particles was more important than the total number concentration (10-700 nm) for these effects. MVF was significantly associated with personal exposure to iron, potassium, copper, zinc, arsenic, and lead in the fine fraction. After Bonferroni correction, none of the secondary biomarkers changed significantly. CONCLUSIONS Reduction of particle exposure by filtration of recirculated indoor air for only 48 hours improved MVF in healthy elderly citizens, suggesting that this may be a feasible way of reducing the risk of cardiovascular disease.
The History and Pharmacology of Dopamine Agonists

ABSTRACT The recognition of the dopaminergic properties of some ergot derivatives has initiated new therapeutical approaches in endocrinology as well as in neurology. The pharmacological characterization of the different ergot derivatives during the last decade has largely improved our understanding of central dopaminergic systems. Their development has yielded valuable information on the pharmacology of dopamine receptors involved in the regulatory mechanisms of prolactin secretion and in striatal functions. The clinical application of such new neurobiological concepts has underlined the therapeutical interest of such compounds either in the control of prolactin-dependent endocrine disorders or in the treatment of parkinsonism. Owing to their pharmacological profiles, dopaminergic agonists represent a valuable clinical option especially in the management of Parkinson’s disease in view of the problems arising from chronic L-Dopa treatment.
Mechanisms of mitochondrial diseases

Abstract Mitochondria are essential organelles with multiple functions, the most well known being the production of adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). The mitochondrial diseases are defined by impairment of OXPHOS. They are a diverse group of diseases that can present in virtually any tissue in either adults or children. Here we review the main molecular mechanisms of mitochondrial diseases, as presently known. A number of disease-causing genetic defects, either in the nuclear genome or in the mitochondria's own genome, mitochondrial DNA (mtDNA), have been identified. The most classical genetic defect causing mitochondrial disease is a mutation in a gene encoding a structural OXPHOS subunit. However, mitochondrial diseases can also arise through impaired mtDNA maintenance, defects in mitochondrial translation factors, and various more indirect mechanisms. The putative consequences of mitochondrial dysfunction on a cellular level are discussed.
Lower Aorto-Iliac Bifurcation Position and Incident Cardiovascular Disease: A Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract Background: With increasing age, a downward shift of the aorto-iliac bifurcation relative to the lumbar spine occurs. A lower bifurcation position is an independent marker for adverse vascular aging and is associated with increased burden of cardiovascular disease (CVD) risk factors; however, the associations between lower bifurcation position and CVD events remain unknown. Methods: Abdominal computed tomography scans were used to measure the aorto-iliac bifurcation distance (AIBD, distance from the aorto-iliac bifurcation to the L5/S1 disc space). Cox proportional hazard analysis was used to determine the independent hazard of a lower bifurcation position (smaller AIBD) for incident coronary heart disease (CHD, defined as myocardial infarction, resuscitated cardiac arrest, or sudden cardiac death), CVD (CHD plus stroke or stroke death), and all-cause mortality (ACM). Results: In the 1,711 study participants (51% male), the mean AIBD was 26 ± 15 mm. After a median follow-up of 10 years, 63 (3.7%) developed CHD, 100 (5.8%) developed CVD, and 129 (7.5%) were deceased. Compared to the 4th quartile of AIBD (highest bifurcation position), participants in the 1st quartile (lowest bifurcation position) had increased risk for CHD (hazard ratio (HR) = 1.5, 95% confidence interval (CI): 0.8-3.0, P = 0.2), CVD (HR = 1.8, 95% CI: 0.9-2.7, P = 0.1), and ACM (HR = 2.2, 95% CI: 1.3-3.6, P = 0.01). After adjustments for CVD risk factors, the HR for ACM was no longer significant. Conclusion: Despite being an independent marker for adverse vascular changes in the aorta, a lower aorto-iliac bifurcation position was not independently associated with future CVD events. The opposing effects of atherosclerosis and stiffness in the aorta may, in part, explain our null findings.
Evolution of Human Immunodeficiency Virus Type 1 Cytotoxic T-Lymphocyte Epitopes: Fitness-Balanced Escape

ABSTRACT CD8+ cytotoxic T lymphocytes (CTL) are strong mediators of human immunodeficiency virus type 1 (HIV-1) control, yet HIV-1 frequently mutates to escape CTL recognition. In an analysis of sequences in the Los Alamos HIV-1 database, we show that emerging CTL escape mutations were more often present at lower frequencies than the amino acid(s) that they replaced. Furthermore, epitopes that underwent escape contained amino acid sites of high variability, whereas epitopes persisting at high frequencies lacked highly variable sites. We therefore infer that escape mutations are likely to be associated with weak functional constraints on the viral protein. This was supported by an extensive analysis of one subject for whom all escape mutations within defined CTL epitopes were studied and by an analysis of all reported escape mutations of defined CTL epitopes in the HIV Immunology Database. In one of these defined epitopes, escape mutations involving the substitution of amino acids with lower database frequencies occurred, and the epitope soon reverted back to the sensitive form. We further show that this escape mutation substantially diminished viral fitness in in vitro competition assays. Coincident with the reversion in vivo, we observed the fixation of a mutation 3 amino acids C terminal to the epitope, coincident with the ablation of the corresponding CTL response. The C-terminal mutation did not restore replication fitness reduced by the escape mutation in the epitope and by itself had little effect on replication fitness. Therefore, this C-terminal mutation presumably impaired the processing and presentation of the epitope. Finally, for one persistent epitope, CTL cross-reactivity to a mutant form may have suppressed the mutant to undetected levels, whereas for two other persistent epitopes, each of two mutants showed poor cross-reactivity and appeared in the subject at later time points. Thus, a viral dynamic exists between the advantage of immune escape, peptide cross-reactivity, and the disadvantage of lost replication fitness, with the balance playing an important role in determining whether a CTL epitope will persist or decline during infection.
The Size of the Synaptic Cleft and Distinct Distributions of Filamentous Actin, Ezrin, CD43, and CD45 at Activating and Inhibitory Human NK Cell Immune Synapses 12

In this study, we report the organization of cytoskeletal and large transmembrane proteins at the inhibitory and activating NK cell immunological or immune synapse (IS). Filamentous actin accumulates at the activating, but not the inhibitory, NK cell IS. However, surprisingly, ezrin and the associated protein CD43 are excluded from the inhibitory, but not the activating, NK cell IS. This distribution of ezrin and CD43 at the inhibitory NK cell IS is similar to that previously seen at the activating T cell IS. CD45 is also excluded from the inhibitory, but not activating, NK cell IS. In addition, electron microscopy reveals wide and narrow domains across the synaptic cleft. Target cell HLA-C, located by immunogold labeling, clusters where the synaptic cleft spans the size of HLA-C bound to the inhibitory killer Ig-like receptor. These data are consistent with assembly of the NK cell IS involving a combination of cytoskeletal-driven mechanisms and thermodynamics favoring the organization of receptor/ligand pairs according to the size of their extracellular domains.
Perceived security determinants in e-commerce among Turkish university students

Perceived security is defined as the level of security that users feel while they are shopping on e-commerce sites. The aims of this study were to determine items that positively influence this feeling of security by users during shopping, and to develop guidelines for perceived security in e-commerce. An experiment allowed users with different security assurances to shop on simulated e-commerce sites. The participants were divided into three groups, shopping for cheap, mid-range, and expensive products, respectively. Following the shopping environment, the virtual shopping security questionnaire (VSSQ), consisting of fourteen perceived security items, was presented to the users. The VSSQ was presented to the participants to validate these perceived security items. The VSSQ had a Cronbach's alpha internal reliability value of 0.70. With the exception of two items, there were no significant differences in item ratings between the groups of different shopping item values. A factor analysis procedure determined two main factors concerning perceived security in e-commerce. The perceived operational factor includes: the site's blocking of unauthorized access; emphasis on login name and password authentication; funding and budget spent on security; monitoring of user compliance with security procedures; integration of state-of-the-art systems; distribution of security items within the site; website's encryption strategy; and consolidation with network security vendors. The perceived policy-related factor includes: the website's emphasis on network security; top management commitment; effort to make users aware of security procedures; the website's keeping up-to-date with product standards; the website's emphasis on security in file transfers; and issues concerning the web browser.
Mucosal Th17 Cell Function Is Altered during HIV Infection and Is an Independent Predictor of Systemic Immune Activation

Mucosal Th17 cells maintain the gut epithelial barrier and prevent invasion by luminal bacteria through a delicate balance of immunosuppressive and proinflammatory functions. HIV infection is characterized by mucosal Th17 depletion, microbial translocation, and immune activation. Therefore, we assessed the function of blood and sigmoid Th17 cells during both early and chronic HIV infection, as well as the impact of short- and long-term antiretroviral therapy. Th17 cells were defined as IL-17a+ CD4 T cells, and their functional capacity was assessed by the coproduction of the inflammatory cytokines IL-22, TNF-α, and IFN-γ, as well as the immunoregulatory cytokine IL-10. Gut Th17 cells had a much greater capacity to produce proinflammatory cytokines than did those from the blood, but this capacity was dramatically reduced from the earliest stages of HIV infection. Immunoregulatory skewing of mucosal Th17 cell function, characterized by an increased IL-10/TNF-α ratio, was uniquely seen during early HIV infection and was independently associated with reduced systemic immune activation. Antiretroviral therapy rapidly restored mucosal Th17 cell numbers; however, normalization of mucosal Th17 function, microbial translocation, and mucosal/systemic immune activation was much delayed. These findings emphasize that strategies to preserve or to more rapidly restore mucosal Th17 function may have important therapeutic benefit.
Mini-dose intrathecal morphine for post-cesarean section analgesia.

Dose-response relationship of mini-dose intrathecal morphine (0.025-0.125 mg) for analgesia after Cesarean section was studied. Sixty-three patients were randomly divided into six groups by the following intrathecal morphine injection: group 1 (0 mg), group 2 (0.025 mg), group 3 (0.05 mg), group 4 (0.075 mg), group 5 (0.1 mg), and group 6 (0.125 mg). The selected dose of morphine mixed with 2 ml 0.5% hyperbaric bupivacaine (10 mg) was administered intrathecally to induce spinal anesthesia. The mean analgesia duration in each group was 3.6 +/- 2.0, 10.6 +/- 7.1, 17.3 +/- 13.8, 25.6 +/- 7.5, 33.9 +/- 10.1, and 39.5 +/- 11.9 h respectively (mean +/- SD). In morphine groups, duration of analgesia was significantly longer (p less than 0.05) than control group (0 mg), and the first 24 h pain scores were also lower (p less than 0.01). Furthermore, a significant linear dose-response relationship between analgesic duration and the dose of intrathecal morphine was revealed (y = 3.28 + 295.5x, r2 = 0.64, p less than 0.05). Among morphine groups, analgesic quality was significantly better in patients in groups 4-6 than those in group 2 and 3 (p less than 0.05), so as in the proportion of effective analgesia in the first 24 h (p less than 0.01). Neonatal condition was not adversely affected by such mini-dose of intrathecal morphine. The most common maternal adverse effect observed was pruritus, and its incidence was significantly greater in groups 3-6 than in the control group (p less than 0.05). However, no significant difference was observed among all morphine groups. (ABSTRACT TRUNCATED AT 250 WORDS)
Changes in intracellular and cell surface localization of Le(x) epitope during germ cell differentiation in fetal mice.

Changes in the intracellular and cell surface localization of Lewis x (Le(x)) determinants in germ cells during fetal development in mice were examined by light and electron microscopy. Light microscopically, in undifferentiated gonads on day 12 post coitum (p.c.), the anti-Le(x) monoclonal antibody (MAb) was specifically bound to the plasma membranes and to the cytoplasmic granule-like structures of germ cells. In the testes on day 13 p.c. , most of the germ cells were enclosed within the testicular cords and showed an MAb-positive reaction which was restricted mainly to the cytoplasmic granule-like structures. The reaction on the plasma membranes almost disappeared. On the other hand, the ectopic germ cells still showed a positive reaction on their plasma membranes. In the ovaries on day 13 p.c. , the germ cells also exhibited positive reactions both on the plasma membranes and on the granule-like structures. Immunoelectron microscopic observations agreed well with these light microscopic observations in such a way that both the plasma membranes and the "small dense bodies" (SDB) were positive in undifferentiated gonads on day 12 p.c. In the germ cells organized into the testicular cords, the reaction to anti-Le(x) MAb became restricted to the SDB. These results may indicate that such intracellular changes in Le(x) determinants during germ cell differentiation are associated with the enclosure of germ cells within the testicular cords.
Clonotypic analysis of T cell reconstitution after haematopoietic stem cell transplantation (HSCT) in patients with severe combined immunodeficiency

Haematopoietic stem cell transplantation (HSCT) is performed for treatment of a broad spectrum of illnesses. Reconstitution of an intact immune system is crucial after transplantation to avoid infectious complications, and above all, the establishment of T cell receptor (TCR) diversity is the most important goal in the procedure. Until recently, little has been known of the mechanism of T cell reconstitution in the very early period after HSCT. In this study, we analysed TCR repertoires sequentially in four patients with severe combined immunodeficiency (SCID) before and after HSCT. In all patients, the TCR repertoires were extremely abnormal before HSCT, whereas after transplantation there was progressive improvement in TCR diversity, based on analysis of the TCR Vβ repertoire and CDR3 size distributions. Somewhat unexpectedly, there was a significant but transient expansion of TCR diversity 1 month after transplantation in all cases. Clonotypic analysis of TCRs performed in one case showed that many T cell clones shared identical CDR3 sequences at 1 month and that the shared fraction decreased progressively. These results indicate that early expansion of TCR diversity may reflect transient expansion of pre‐existing mature T cells from the donor blood, independent of de novo T cell maturation through the thymus.
Association of HER-2/neu overexpression with the number of involved axillary lymph nodes in hormone receptor positive breast cancer patients.

AIM To evaluate the prognostic significance of HER-2/neu overexpression in hormone receptor and axillary lymph node positive breast cancer patients treated in a single institution. METHODS Paraffin-embedded primary breast cancers from 40 patients with invasive ductal carcinoma were studied immunohistochemically. HER-2/neu staining was classified as negative (0, 1+), weak/moderate positive (2+), or moderate/strong positive (3+) and was assessed for effectiveness as a predictor of outcome in univariate and Cox model multivariate analyses. RESULTS 20% of patients were positive for HER-2/neu. Significant associations were observed between HER-2/neu and increasing number of involved nodes (p = 0.014), p53 positivity (p = 0.039), the presence of vascular invasion (p = 0.029) and metastases (p = 0.01). Multivariate analysis demonstrated that HER-2/neu overexpression (p = 0.016) and age (p = 0.005) were independent predictors for disease-free survival (DFS) where the number of involved nodes (p = 0.032) was shown to be independent predictor for overall survival. In the HER-2/neu positively stained tumors, significant number of patients developed distant metastases than the patients with HER-2/neu negatively stained tumors (87.5% vs 34.4%, p = 0.01). CONCLUSION For node positive patients, HER-2/neu overexpression was a significant predictor of DFS.
Interlaboratory Optimization and Evaluation of a Serological Assay for Diagnosis of Human Baylisascariasis

ABSTRACT A Western blot assay using a recombinant protein, recombinant Baylisascaris procyonis RAG1 protein (rBpRAG1), was developed for the diagnosis of human baylisascariasis concurrently by the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and the National Reference Centre for Parasitology (NRCP) in Montreal, Canada. Assay performance was assessed by testing 275 specimens at the CDC and 405 specimens at the NRCP. Twenty specimens from 16 cases of baylisascariasis were evaluated. Eighteen were positive, with the assay correctly identifying 14 of 16 patients. The rBpRAG1 Western blot assay showed no cross-reactivity with Toxocara-positive serum and had an overall sensitivity of 88% and a specificity of 98%.
Bullying, abuse and family conflict as risk factors for chronic pain among Dutch adolescents

Psychosocial stress seems to serve as an important risk factor for the occurrence of pain. The present study aims to examine if early adversities, e.g. bullying, abuse and family conflict are risk factors for chronic pain in adolescents. The secondary aim of the present study was to describe the pain characteristics of chronic pain in adolescents in a community sample of Dutch adolescents.