Miracle-dz/UniFAR-FTUs huggingface dataset:
Purification, Characterization, and Immunogenicity of a Disulfide Cross-Linked Plasmodium vivax Vaccine Candidate Antigen, Merozoite Surface Protein 1, Expressed in Escherichia coli

ABSTRACT The Plasmodium vivax merozoite surface protein 1 (MSP-1) 42-kDa fragment (PvMSP-1 p42) is a promising vaccine candidate antigen against the blood stage of the malarial parasite. We have developed a process for the production of this vaccine target, keeping in mind its use in human volunteers. A novel strain, Origami(DE3), of Escherichia coli with mutations in the glutathione and thioredoxin reductase genes yielded 60% more soluble PvMSP-1 p42 than the conventional E. coliBL21(DE3) strain. Recombinant PvMSP-1 p42 was purified to ≥99% purity with a rapid two-step protocol designed for easy scaling up. The final product had a low endotoxin content and was stable in its lyophilized form. PvMSP-1 p42 was found to have the predicted primary and tertiary structures and consisted of a single conformer containing one free cysteine, as predicted. The product was recognized by conformational monoclonal antibodies against P. vivax MSP-1. Immunogenicity studies of PvMSP-1 p42 were carried out with two strains of mice and the adjuvants Montanide ISA51 and Montanide ISA720. Both formulations were found to induce high levels of immunoglobulin G1 (IgG1), IgG2b, and IgG2a antibodies along with low levels of IgG3. Lymphocytes from animals in all the PvMSP-1 p42-immunized groups showed proliferative responses upon stimulation with PvMSP-1 p42; the cytokines interleukin 2 (IL-2), gamma interferon, IL-4, and IL-10 were detected in the culture supernatants. These results indicate that PvMSP-1 p42 in combination with both of the adjuvants elicited cellular and humoral responses in mice.
Social functioning and facial expression recognition in children with neurofibromatosis type 1.

BACKGROUND This study examined social functioning and facial expression recognition (FER) in children with neurofibromatosis type 1 (NF1) compared to typically developing peers. Specifically, the current research aimed to identify hypothesised relationships between neurocognitive ability, FER and social functioning. METHOD Children, ages 8 to 16, with NF1 (n = 23) and typically developing peers (n = 23) were recruited during regularly scheduled clinic visits and through advertisements on an institutional clinical trials website, respectively. Participants completed a measure of FER, an abbreviated intelligence test and questionnaires regarding their quality of life and behavioural functioning. Parents were also asked to complete questionnaires regarding the social-emotional and cognitive functioning of their child. RESULTS As expected, there were significant differences between children with NF1 and typically developing peers across domains of social functioning and FER. Within the sample of children with NF1, there were no significant associations observed between cognitive measures, social functioning and facial recognition skills. CONCLUSION Children with NF1 exhibited high rates of social impairment and weak FER skills compared to controls. The absence of associations between FER with cognitive and social variables, however, suggests something unique about this skill in children with NF1. Theoretical comparisons are made to children with autism spectrum disorders, as this condition may serve as a potentially useful model in better understanding FER in children with NF1.
Inhibition of stress‐ or anxiogenic‐drug‐induced increases in dopamine release in the rat prefrontal cortex by long‐term treatment with antidepressant drugs

The effects of long‐term treatment with imipramine or mirtazapine, two antidepressant drugs with different mechanisms of action, on the response of cortical dopaminergic neurons to foot‐shock stress or to the anxiogenic drug FG7142 were evaluated in freely moving rats. As expected, foot shock induced a marked increase (+ 90%) in the extracellular concentration of dopamine in the prefrontal cortex of control rats. Chronic treatment with imipramine or mirtazapine inhibited or prevented, respectively, the effect of foot‐shock stress on cortical dopamine output. Whereas acute administration of the anxiogenic drug FG7142 induced a significant increase (+ 60%) in cortical dopamine output in control rats, chronic treatment with imipramine or mirtazapine completely inhibited this effect. In contrast, the administration of a single dose of either antidepressant 40 min before foot shock, had no effect on the response of the cortical dopaminergic innervation to stress. These results show that long‐term treatment with imipramine or mirtazapine inhibits the neurochemical changes elicited by stress or an anxiogenic drug with an efficacy similar to that of acute treatment with benzodiazepines. Given that episodes of anxiety or depression are often preceded by stressful events, modulation by antidepressants of the dopaminergic response to stress might be related to the anxiolytic and antidepressant effects of these drugs.
AmineDB: Large scale docking of amines with CYP2D6 and scoring for druglike properties—towards defining the scope of the chemical defense against foreign amines in humans

Organic amines are prevalent in nature and in drugs, especially the psychotherapeutic agents, and a major defense against potentially toxic amines is metabolism by CYP2D6. In order to understand better the constraints on the broad specificity of CYP2D6, 4207 amines were docked into the binding site of this enzyme. Docking poses were found predominantly with the positively charged amino groups closest to Asp301, with aromatic rings close to Phe120 and sometimes extending as far as Phe483. Organic amines that bind best to CYP2D6 tend to have larger molecular weights and logP values. Organic amines that score highly as being druglike, based on a Bayesian model constructed using a 5223-drug training set, are least likely to bind to CYP2D6. This correlation suggests that the set of known drugs, which have been largely designed or selected to avoid high affinity CYP binding, partially encodes the binding site preferences (or rather anti-preferences) of CYP2D6. Finally, in order to benchmark our docking and druglike scoring procedures, an analysis of psychotherapeutic agents is presented. All of these data, including the 4207 AM1-optimized ligand structures in proper ionization states, docking poses and scores, Druglike Scores and Lipinski properties, can be viewed from an online database, the AmineDB.
Lipoarabinomannan and lipid-free arabinomannan antigens of Mycobacterium paratuberculosis

Lipoarabinomannan (LAM) and lipid-free arabinomannan (AM) were prepared from Mycobacterium paratuberculosis. Purification of LAM was done by ultracentrifugation of the phenol-water-extracted crude polysaccharide, followed by affinity and anion exchange chromatography. AM was purified from the supernatant of the ultracentrifuged polysaccharide or from alkaline-extracted material by gel filtration and anion exchange chromatography. Chemical analysis revealed arabinose and mannose in LAM (1.4:1) and AM (3.5:1) and the presence of palmitic, stearic, and tuberculostearic acids for a total of 7.8% lipid in LAM. Traces of phosphorus were found in the AMs, particularly LAM (0.05%). Nuclear magnetic resonance confirmed the presence of alpha-arabinosyl residues and the acylated nature of LAM. LAM exhibited lipid-dependent aggregation, as indicated by a Triton-induced decrease in molecular weight. By using bovine sera, LAM was found to be active in the complement fixation test, whereas AM was inactive and inhibited this activity. Thus, the presence of AM in crude polysaccharide could explain the variable complement fixation results. Triton-dissociated LAM exhibited a precipitin (Cl) in common with that of AM, confirming shared determinants. LAM in its lipid-dependent aggregated form, however, exhibited a second precipitin (C2), which may be due to the disparity in antigen size or a novel epitope. The lipid content of LAM rendered it 100 times more effective for coating plates in the enzyme immunoassay than lipid-free AM.
Physiological properties of central amygdala neurons: species differences

The connections of limbic structures are remarkably constant across species. However, different species express fear in distinct ways. Because the central amygdaloid nucleus is considered an important mediator of fear responses, we compared the physiological properties of central amygdala neurons in guinea pigs, rats and cats using whole‐cell recordings in coronal slices in vitro. In guinea pigs, most central medial and lateral neurons displayed an outward rectification that delayed firing onset in response to depolarizing current pulses (hence the designation late‐firing neurons). Late‐firing neurons were also prevalent in the lateral sector of the cat central nucleus. In contrast, late‐firing neurons were rare in the rat central nucleus and the cat central medial nucleus. There, most neurons generated Ni2+‐sensitive low‐threshold bursts of Na+ spikes and/or displayed pronounced inward rectification in the hyperpolarizing direction. Species differences in passive properties were also observed, but they were mainly related to the relative prevalence of late‐firing cells. Indeed, late‐firing cells had a significantly lower input resistance and more negative membrane potential than other types of central neurons. Thus, there are marked species differences in the physiological properties of central neurons. Because the synaptic responsiveness of neurons is constrained by their physiological properties, our findings raise the possibility that the contrasting behavioural responsiveness observed across species is partly dependent on the species‐specific physiological properties of central neurons.
Validity of Dietary Assessment in Athletes: A Systematic Review

Dietary assessment methods that are recognized as appropriate for the general population are usually applied in a similar manner to athletes, despite the knowledge that sport-specific factors can complicate assessment and impact accuracy in unique ways. As dietary assessment methods are used extensively within the field of sports nutrition, there is concern the validity of methodologies have not undergone more rigorous evaluation in this unique population sub-group. The purpose of this systematic review was to compare two or more methods of dietary assessment, including dietary intake measured against biomarkers or reference measures of energy expenditure, in athletes. Six electronic databases were searched for English-language, full-text articles published from January 1980 until June 2016. The search strategy combined the following keywords: diet, nutrition assessment, athlete, and validity; where the following outcomes are reported but not limited to: energy intake, macro and/or micronutrient intake, food intake, nutritional adequacy, diet quality, or nutritional status. Meta-analysis was performed on studies with sufficient methodological similarity, with between-group standardized mean differences (or effect size) and 95% confidence intervals (CI) being calculated. Of the 1624 studies identified, 18 were eligible for inclusion. Studies comparing self-reported energy intake (EI) to energy expenditure assessed via doubly labelled water were grouped for comparison (n = 11) and demonstrated mean EI was under-estimated by 19% (−2793 ± 1134 kJ/day). Meta-analysis revealed a large pooled effect size of −1.006 (95% CI: −1.3 to −0.7; p < 0.001). The remaining studies (n = 7) compared a new dietary tool or instrument to a reference method(s) (e.g., food record, 24-h dietary recall, biomarker) as part of a validation study. This systematic review revealed there are limited robust studies evaluating dietary assessment methods in athletes. Existing literature demonstrates the substantial variability between methods, with under- and misreporting of intake being frequently observed. There is a clear need for careful validation of dietary assessment methods, including emerging technical innovations, among athlete populations.
Estimating investments in knowledge and planning activities for adaptation in developing countries: an empirical approach

ABSTRACT Costs of adaptation in the developing world have been mostly equated to those of climate proofing infrastructure under the assumption of unconstrained knowledge and planning capacities. To correct this, we introduce a cost-scaling methodology estimating sectoral investments to enhance the knowledge and planning capacities of countries based on an empirical collection of 385 climate-related projects. We estimate that circa 9.2 billion USD are required for financing knowledge and planning activities in developing countries in 2015. The agricultural and water sectors demand the higher investments – 3.8 and 3.5 billion USD, respectively. Average investments between 2015 and 2050 are projected at 7 billion USD per year – the largest fraction of which (4 billion) in Africa. Investments in this study were found to constitute approximately 40%, 20–60% and 5–15% of previous cost estimates to climate-proof infrastructure in the agricultural, water, and coastal sectors, respectively. The effort to finance the knowledge and planning capacities in developing countries is therefore not marginal relative to the costs of adapting infrastructure. The findings underline the potential of using empirical collections of climate-related projects for adaptation cost assessments as complementary to process and economic models.
Growth Patterns and Obesity Development in Overweight or Normal-Weight 13-Year-Old Adolescents: The STRIP Study

OBJECTIVE. Our goal was to study childhood growth patterns and development of overweight in children who were overweight or normal weight at 13 years of age. PARTICIPANTS AND METHODS. This study is part of a prospective atherosclerosis-prevention trial Special Turku Coronary Risk Factor Intervention Project for Children). At 7 months of age, 1062 children were randomly assigned to an intervention group (n = 540) receiving biannual fat-oriented dietary counseling or to a control group (n = 522). Height and weight of the children and their parents were monitored annually. Our study group comprised those children who participated in the 13-year study visit (n = 541). At 13 years of age, the child was classified as overweight (n = 84) if his or her BMI exceeded the international age- and gender-specific overweight criteria. RESULTS. In overweight girls, the annual weight gain increased from 2.8 kg during the third and fourth year of life to 7.5 kg during the 12th year of life, whereas the annual weight gain of the girls who were normal weight ranged from 2.1 to 4.8 kg during the same period. The annual weight gain was similar of overweight boys and in their normal-weight peers until the age of 5 years, but after that it increased from 3.5 to 7.9 kg in overweight and from 2.6 to 5.5 kg in normal-weight boys. The BMI of the girls and boys who were overweight at the age of 13 exceeded the international cutoff point for overweight from the age of 5 and 8 years onward, respectively. The mean BMIs of the mothers and fathers of the overweight children were higher than those of the parents of the normal-weight children. The STRIP intervention had no effect on the examined growth parameters or on parental BMI. CONCLUSIONS. The children who were overweight at 13 years of age gained more weight than their normal-weight peers by the age of 2 or 3 years onward. The girls became overweight by the age of 5 years, whereas the boys only after 8 years of age. Parental BMI and steep weight gain in early childhood indicate markedly increased risk for becoming overweight.
School-based management of chronic asthma among inner-city African-American schoolchildren in Dallas, Texas.

Asthma, a chronic disease of the respiratory tract, affects approximately five percent of the U.S. population, including almost five million children. Childhood asthma has been identified as the leading cause of school absences. This study was to examined efficacy of a school-based program to prevent exacerbation of asthma symptoms and manage asthma in school children using measured doses of an inhaled anti-inflammatory medication. The sample consisted of 22 African-American children in one inner-city elementary school in Dallas, Texas, ages 5-12 years with confirmed diagnoses of asthma. For three months, each child came to the school clinic two times per day for medication administration and measurement of respiratory peak flow rates. Data were collected for a number of variables including bronchodilator use, school absences, self-report of asthma symptoms, and number of visits to the physician. During the study, mean peak flow rates improved approximately 15%, and bronchodilator use decreased 66%. Improvement also was evident in several other areas.
Three-Year Immune Reconstitution in PI-Sparing and PI-Containing Antiretroviral Regimens in Advanced HIV-1 Disease

Background The long-term immunological benefit of protease inhibitor (PI)-sparing antiretroviral therapy (ART) using non-nucleoside reverse transcriptase inhibitors (NNRTIs) remains poorly investigated. Methods A total of 120 ART-naive, HIV-1-infected participants were included in the immunology substudy of INITIO, an international randomized trial comparing two NRTIs (didanosine + stavudine) combined with either: one NNRTI (efavirenz; EFV), one non-boosted PI (nelfinavir; NFV), or one NNRTI + one PI (EFV/NFV). CD4+ T-cell counts, HIV-1 plasma RNA load (VL), T-cell pheno-type, T-cell proliferation and IFN-γ production against opportunistic/recall and HIV-1 antigens/peptides were compared at baseline and at week (W) 96 and W156. Results Participants (37 EFV, 44 NFV, 39 EFV/NFV) had similar baseline VL; median CD4+ T-cell counts/mm3 were: 144 (64–303) EFV, 212 (42–313) NFV and 257 (86–331) EFV/NFV. At W156, the proportion of patients with VL ≤50 copies/ml was not different between the arms (P=0.3). From baseline to W156 there was a significant increase in CD4+ T-cell counts (P<0.001) and in naive CD4+ T cells (P<0.001), with no difference between arms and percentages of total and activated CD8+ T cells decreased significantly (P<0.001) in all arms. The decrease in activated memory CD4+T-cells was significantly greater in the EFV arm at W96 (P=0.03) and W156 (P=0.01), but did not persist after adjusting for baseline CD4+ T-cell counts. During follow-up, responses to opportunistic pathogens increased in all patients while specific T-cell responses to HIV-1-p24 and gp160 recombinant proteins or to Gag and Nef peptides were not restored. Conclusion Regimens using/sparing PIs provide similar levels of long-term immune reconstitution even in patients with low CD4+ T-cell counts.
Towards a formal link between inflation perceptions and inflation expectations in South Africa

This paper reports the finding of a survey of inflation perceptions and inflation expectations in South Africa undertaken in 2014. This survey posed questions on perceptions of past inflation (historic inflation) and expectations of future inflation to the same respondents and determined linkages between historic views and future expectations of each respondent. The analysis of the survey data shows that inflation expectations are anchored in inflation perceptions. This research aligns South Africa with other countries and jurisdictions where such surveys are undertaken. This paper shows conclusively, for the first time in South Africa, that there is a feed through from inflation perception to inflation expectations. Therefore, inflation perceptions play a crucial role in the formulation of inflation expectations in South Africa. These results suggest that policy makers are not just charged with containing inflation expectations, but they should also be aware that the confidence in official statistics, as well as the confidence in the SA Reserve Bank and government, impacts inflation perceptions which directly feed into inflation expectations. Keywords: Inflation perceptions; Inflation expectations; South Africa; Monetary policy
Cigar and pipe smoking, smokeless tobacco use and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND Cigarette smoking is the best-characterized risk factor for pancreatic cancer. However, data are limited for other tobacco smoking products and smokeless tobacco. MATERIALS AND METHODS We conducted a pooled analysis of cigar and pipe smoking and smokeless tobacco use and risk of pancreatic cancer using data from 11 case-control studies (6056 cases and 11,338 controls) within the International Pancreatic Cancer Case-Control Consortium (PanC4). Pooled odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated by unconditional multiple logistic regression models adjusted for study center and selected covariates. RESULTS Compared with never tobacco users, the OR for cigar-only smokers was 1.6 (95% CI: 1.2-2.3), i.e. comparable to that of cigarette-only smokers (OR 1.5; 95% CI 1.4-1.6). The OR was 1.1 (95% CI 0.69-1.6) for pipe-only smokers. There was some evidence of increasing risk with increasing amount of cigar smoked per day (OR 1.82 for ≥ 10 grams of tobacco), although not with duration. The OR for ever smokeless tobacco users as compared with never tobacco users was 0.98 (95% CI 0.75-1.3). CONCLUSION This collaborative analysis provides evidence that cigar smoking is associated with an excess risk of pancreatic cancer, while no significant association emerged for pipe smoking and smokeless tobacco use.
The Economic Value of Bitcoin: A Portfolio Analysis of Currencies, Gold, Oil and Stocks

We assess the out-of-sample performance of Bitcoin within portfolios of various asset classes and a well-diversified portfolio under four strategies and estimate the economic gains net of transaction costs. We find statistically significant diversification benefits from the inclusion of Bitcoin which are more pronounced for commodities. Most importantly, the decrease in the overall portfolio risk due to the low correlation of Bitcoin with other assets is not offset by its high volatility. However, the inclusion of Bitcoin pays off little if investors accommodate a battery of economic instruments. Considering non-bubble conditions that are not marked by explosive prices in cryptocurrencies, we document substantially diminished benefits.
Unexpected extensions of non-small-cell lung cancer diagnosed during surgery: revisiting exploratory thoracotomies and incomplete resections.

OBJECTIVES Only patients with a complete resection of non-small-cell lung cancer (NSCLC) may expect long-term survival. Despite the recent progress in imaging and induction therapy, a thoracotomy may remain exploratory or with incomplete resection (R2). Our purpose was to revisit these situations. METHODS A total of 5305 patients who underwent surgery for NSCLC between 1980 and 2009 were reviewed. We compared the epidemiology, pathology, causes and prognosis characteristics of exploratory thoracotomy (ET) and R2 resections. RESULTS ET and R2 resections were observed in 223 (4%) and 197 (4%) patients, respectively. The frequency of ET decreased with time, while the frequency of R2 resection remained almost stable. The indications for ET and R2 resections were not significantly different. In comparison with ET, R2 resections were characterized by a significantly higher frequency of induction therapy (22 vs 17%, P < 10(-3)), adenocarcinomas (49 vs 15%, P < 10(-6)), T1-T2 (53 vs 29%, P < 10(-6)) and N0-N1 extension (67 vs 42%, P = 10(-6)). R2 resections were also characterized by a higher rate of postoperative complications (19.1 vs 9.9%, P = 0.014), with no significant difference in postoperative mortality (6.9 vs 4.9%, P = non significant). R2 resections resulted in a higher 5-year survival compared with ET (11.1 vs 1.2%, P = 10(-3)). There was no long-term survivor after ET, except during the last decade. CONCLUSIONS ET and R2 remain unavoidable. In comparison with ET, R2 resection is associated with a higher rate of postoperative complications, but a higher long-term survival.