Miracle-dz/UniFAR-FTUs huggingface dataset:
A Role for the Saccharomyces cerevisiae ATX1 Gene in Copper Trafficking and Iron Transport*

The ATX1 gene of Saccharomyces cerevisiae was originally identified as a multi-copy suppressor of oxidative damage in yeast lacking superoxide dismutase. We now provide evidence that Atx1p helps deliver copper to the copper requiring oxidase Fet3p involved in iron uptake. atx1Δ null mutants are iron-deficient and are defective in the high affinity uptake of iron. These defects due to ATX1 inactivation are rescued by copper treatment, and the same has been reported for strains lacking either the cell surface copper transporter, Ctr1p, or the putative copper transporter in the secretory pathway, Ccc2p. Atx1p localizes to the cytosol, and our studies indicate that it functions as a carrier for copper that delivers the metal from the cell surface Ctr1p to Ccc2p and then to Fet3p within the secretory pathway. The iron deficiency of atx1 mutants is augmented by mutations in END3 blocking endocytosis, suggesting that a parallel pathway for intracellular copper trafficking is mediated by endocytosis. As additional evidence for the role of Atx1p in iron metabolism, we find that the gene is induced by the same iron-sensing trans-activator, Aft1p, that regulates CCC2 and FET3
Availability and Acceptability of Canadian Home and Community-Based Services: Perspectives of Family Caregivers of Persons with Dementia

ABSTRACT Thirty-five percent of Canadians over the age of 85 have dementia, and up to 90% of their home care is provided by family and friends. The purpose of this study was to explore the use and satisfaction with home and community-based services for persons with dementia from the perspectives of family caregivers. The study was conducted using an interpretive, descriptive, qualitative approach. Six focus groups (N = 36) and three personal interviews were conducted with rural and urban caregivers in Ontario, Manitoba, and Saskatchewan, Canada. Using Lubrosky's (1994) thematic analysis, the overarching themes identified were availability and acceptability of services. The findings suggest a need for an integrated continuing care model that includes the person living with dementia and their family caregivers as partners in care, addresses all of the determinants of health, and embraces sensitivity, diversity, flexibility, and supportive services to enhance the availability and acceptability of Canadian home and community-based services.
Family Structure and Severe Food Insecurity in Maputo and Matola, Mozambique

The rapid growth of Maputo and Matola (neighbouring cities in Mozambique) has dramatically shifted the vulnerability profiles of these cities. Poor neighbourhoods across these two cities may now face the prospect of becoming food deserts. Scholars have defined African urban food deserts by the co-occurrence of poverty and food insecurity. This study aims to assess the assumed relationship between resource poverty and food insecurity in the African urban food desert concept and to assess the contribution of household demographics to this relationship. Using household survey data collected in 2014 across Maputo and Matola, this investigation demonstrated that inconsistent access to water, electricity, medical care, cooking fuel, and cash was associated with increased odds of severe household food insecurity across both cities. In addition, a nuclear household family structure was associated with reduced odds of severe food insecurity in both cities (even when taking limited resource access into account). These findings suggest that the severe food insecurity vulnerabilities associated with African urban food deserts may differ according to the family structure of households in Maputo and Matola.
Pelvic-floor therapy in girls with recurrent urinary tract infections and dysfunctional voiding.

OBJECTIVE To analyse the treatment of girls with recurrent urinary tract infections (UTIs, at least two periods confirmed) and urodynamically confirmed dysfunctional voiding with pelvic-floor therapy. PATIENTS AND METHODS Forty-two girls with recurrent UTIs were treated prospectively during a study period of 18 months. Training consisted of an individually adapted voiding and drinking schedule, pelvic-floor relaxation biofeedback, instructions on toilet behaviour and biofeedback uroflowmetry; residual urine was estimated by ultrasonography. All the girls received prophylactic antibiotics during treatment and those girls with urodynamically proven detrusor instability (33) received anticholinergics. Therapy was considered successful when the girls remained free of infection with no further prophylactic antibiotics for at least 6 months. RESULTS Four girls younger than 6 years all suffered nocturnal and diurnal incontinence and two had reflux. Treatment was effective for recurrent UTI in all and the reflux resolved in two. All four girls became dry during the day and one became dry at night. In the 38 girls older than 6 years, the treatment was successful for recurrent UTI in 24 from the out-patient and in all three from the clinical programme. Reflux, which was seen in six of these girls, resolved in five; one girl underwent bilateral reimplantation. Incontinence was treated in all 23 girls with incontinence problems before treatment (four of whom were initially dry). Twelve girls needed a wetting alarm to become dry during the night. In four girls the treatment was effective for recurrent UTI but the incontinence persisted; in seven the treatment was considered unsuccessful as they all had UTIs after treatment; all remained incontinent. Reflux persisted in all four girls in this group who had reflux before treatment. CONCLUSION The training programme was effective in treating recurrent UTI in 35 of 42 girls (83%). The persistence of incontinence problems is a bad prognostic factor for the recurrence of UTI after the training programme. Pelvic-floor therapy seems a reasonable and meaningful component in the treatment of recurrent UTIs in which detrusor-sphincter dyssynergia plays a role.
Acute Community-Acquired Sinusitis

Acute sinusitis can be classified into categories on the basis of several characteristics, including the immune status of the patient; infectious or noninfectious nature; occurrence in the community or hospital setting; and viral, bacterial, or fungal etiology (table 1). These categories are of both theoretical and practical importance for understanding the pathogenesis and clinical expression of the infection and for optimizing approaches to diagnosis and treatment. This review is confined to sinus infections of viral and bacterial etiology acquired in the community.
A Phase I Study of Nonmyeloablative Chemotherapy and Adoptive Transfer of Autologous Tumor Antigen-Specific T Lymphocytes in Patients With Metastatic Melanoma

This report describes a phase I clinical trial using nonmyeloablative, lympho-depleting chemotherapy in combination with adoptive immunotherapy in patients with metastatic melanoma. The chemotherapy-conditioning schedule that induced transient lymphopenia consisted of cyclophosphamide (30 or 60 mg/kg per day for 2 days) followed by fludarabine (25 mg/m2 per day for 5 days). Immunotherapy for all patients consisted of in vitro expanded, tumor-reactive, autologous T-cell clones selected for high avidity recognition of melanoma antigens. Cohorts of three to six patients each received either no interleukin (IL)-2, low-dose IL-2 (72,000 IU/kg intravenously three times a day to a maximum of 15 doses), or high-dose IL-2 (720,000 IU/kg intravenously three times a day for a maximum of 12 doses). The toxicities associated with this treatment were transient and included neutropenia and thrombocytopenia that resolved in all patients. High dose intravenous IL-2 was better tolerated by patients after chemotherapy than during previous immunotherapy cycles without chemotherapy. No patient exhibited an objective clinical response to treatment, although five patients demonstrated mixed responses or transient shrinkage of metastatic deposits. This study established a nonmyeloablative-conditioning regimen that could be safely administered in conjunction with adoptive T-cell transfer and IL-2 in patients with metastatic melanoma.
Circulating endothelial cells in renal disease: markers and mediators of vascular damage.

During the last decade, circulating endothelial cells (CECs) have been used as a surrogate marker of endothelial damage in a variety of vascular disorders. The severely damaged phenotype of CECs in vasculitis led to the hypothesis that such circulating apoptotic and/or necrotic debris may itself be a mediator of disease. Very recently, first evidence has emerged to support this assumption [1]. The aim of this editorial comment is to provide a brief review of CECs, describe clinical applications with an emphasis on renal disease, and put the new pathogenetic findings into perspective. We also suggest further avenues of research.
Analysis of insulation coordination for dual motion mechanism gas circuit breaker

In this paper, we propose the technology to analyze the insulation coordination for dual motion mechanism (DMM) gas circuit breaker (GCB). To estimate the insulation level of SF6 gas in GCB, we calculate the permitted electric field strength in accordance with the SF6 gas pressure. Through an electric field simulation along the dual motion travel, we estimate the insulation performance of GCB. We control the delay time of the second moving part travel for insulation coordination. As a case study, we analyze the electric field simulation along the dual motion travel about three kinds of delay times for the second moving part of 420kV GCB model.
Effect of dietary protein quality on energy metabolism in growing chickens

A slaughter experiment was carried out to study the effect of dietary protein quality on maintenance energy requirements and energy costs for protein accretion and fat deposition in fast-growing broiler-type male chickens. Three isonitrogenous (200 g crude protein/kg DM) and isoenergetic (14 kJ metabolizable energy (ME)/g DM) semipurified diets based on soyabean meal unsupplemented (diet S) or supplemented with 20 g L-lysine/kg (diet SL) or 2 g DL-methionine/kg (diet SM), in order to promote a decrease or an increase in growth rate respectively, were selected and given at four feeding levels (ad lib. or restricted to 40, 28 and 18 g DM/d, on average) to 10-d-old fast-growing male broiler-type chicks for 2 weeks. Both the efficiency with which ME was used to support growth (kg) and the maintenance requirements (MEm) significantly decreased inversely to the biological value of the dietary protein (kg = 0·660, 0·600 and 0·572; MEm = 597, 522 and 464 k.J/kg W0·75 per d, for diets SI, S and SM respectively). The partial efficiencies of use of ME for protein accretion (kp) or fat deposition (kf) were also inversely related, the former increasing with the quality of the protein offered. An alternative procedure was used to try to overcome the statistical problems inherent in the partition of ME between fat and protein.
The Dawn Phenomenon Is Related To Overnight Growth Hormone Release In Adolescent Diabetics

We have investigated the relation between nocturnal insulin requirements and nocturnal growth hormone (GH) release in 26 diabetic adolescents at various puberty stages and have examined the effect of nocturnal GH suppression on pre‐breakfast insulin requirement. In all the studies, euglycaemia was maintained overnight using a computer‐calculated variable‐rate insulin infusion, and 15‐min blood samples were collected for GH assay. During initial clamp studies, insulin infusion rates were greater from 0500–0800 h (15.22 ± 0.95 mU/kg/h, mean ± SEM) than from 0100–0400 h (12.42 ± 0.84 mU/kg/h, P < 0.001). The increase in insulin infusion rate correlated with mean overnight GH concentration (r = 0.68, P < 0.001), and was maximal at puberty stage 3 in both sexes. In seven of the subjects, a second identical clamp was performed following administration of 100 mg oral pirenzepine. During these studies, mean overnight GH levels were reduced by 11–85%, from 17.6 ± 1.6 to 7.5 ± 2.2 mU/l; P < 0.01. Insulin requirements were not significantly different between the periods 0100–0400 and 0500–0800 h during these studies, and the reduction in pre‐breakfast (0500–0800 h) insulin requirement when compared with the baseline studies correlated with the fall in GH secretion (r, = 0.82, P < 0.01). The dawn increase in insulin requirement in adolescents with IDDM is related to the overnight GH secretion during puberty, and pre‐breakfast insulin requirement can be reduced by suppressing nocturnal GH release.
Beta-catenin signaling induces CYP1A1 expression by disrupting adherens junctions in Caco-2 human colon carcinoma cells.

BACKGROUND The aryl hydrocarbon (Ah) receptor is one of the best known ligand-activated transcription factors. The present study has focused on the wound-healing process on Ah receptor function. METHODS Depletion of calcium from culture medium of Caco-2 human colon carcinoma cells by transfer to Minimal Essential Medium (Spinner Modification; S-MEM) destroyed adherens junctions and the cells were used as the model of wound-healing process. RESULTS Calcium depletion induced both nuclear translocation of the Ah receptor, and increased expression of CYP1A1 and Slug mRNAs in Caco-2 cells. However, expression of Slug mRNA was not significantly induced by treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Knockdown of the Ah receptor and treatment with Ah receptor antagonists decreased level of CYP1A1 mRNA. The fragment of E-cadherin released by gamma-secretase was not involved in induction of CYP1A1 mRNA following S-MEM treatment. Knockdown of beta-catenin increased levels of Ah receptor mRNA, which may be attributable to direct or indirect involvement of beta-catenin in suppression of the Ah receptor gene. CONCLUSIONS Our results suggest that mRNA induction of some genes by destruction of adherens junctions depends on the Ah receptor. beta-Catenin, one of the components of the adherens junction, was released from the E-cadherin complex, which resulted in its increased interaction with the Ah receptor, and was translocated into the nucleus, and consequently the target genes would be transcribed. GENERAL SIGNIFICANCE Our observations suggest that some aspects of the molecular mechanism of wound healing involve the Ah receptor.
Severe Financial Crises and Fundamental Reforms: The Benefits of Risk-Sharing

Over the last decade, we have established a number of ideas about Islamic finance. Most importantly, the core of Islamic finance; the concept of sharing of risk and the prohibition of such debt contracts that include the payment of interest has attracted a lot of attention. ( ) Risk-sharing serves one of the most important objectives of Islam: the unity of humanity. Humanity faces a multitude of risks from shocks, over which individuals and families have little or no control, but which significantly affect their livelihood and wellbeing. Risk-sharing has many benefits.These include among others: reducing human angst, increasing human interactions, enhancing trust (an important factor in economic growth), increasing social capital (another impetus to growth), promoting social cohesion, linking the real and financial sectors of the economic system, and ameliorating financial conditions to potentially preclude financial crises. --
The dynamic core microbiome: structure, stability and resistance

The long-term stability of microbiomes is crucial as the persistent occurrence of beneficial microbes and their associated functions ensure host health. Microbiomes are highly diverse and dynamic, but are they complex to the point of being impossible to understand? We present an approach that while embracing this complexity it allows to identifying meaningful patterns: the dynamic core microbiome. We study the structure, dynamics and stability of microbiomes belonging to six marine sponges sampled monthly over three years. We show that microbiome temporal stability is not determined by the diversity of their microbial assemblages, but by the abundance density of those microbes that conform their core microbiome. High-density cores confer hosts resistance against the establishment of occasional taxa to which sponges are constantly exposed through their filter-feeding activities. The core microbial interaction network consisted of complementary members interacting weakly with a dominance of commensal and amensal interactions that have likely coevolved to maintain host functionality and fitness.
The Cobas Amplicor MTB Test for Detection of Mycobacterium tuberculosis Complex from Respiratory and Non-respiratory Clinical Specimens

The Cobas Amplicor MTB test is a polymerase chain reaction (PCR) technique commonly used for direct detection of Mycobacterium tuberculosis in clinical samples. This assay is only validated for respiratory specimens, but many physicians also request PCR analyses for non-respiratory ones. 877 respiratory and 564 non-respiratory specimens were analysed by this test. Using culture results as standard, the sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the PCR were, respectively, 97.9%, 100%, 100% and 94.4% for smear-positive respiratory specimens, 68.8%, 99.2%, 87.5% and 97.5% for smear-negative respiratory samples, 57.8%, 98.6%, 78.8% and 96.4% for all non-respiratory specimens, and 42.4%, 98.6%, 66.7% and 96.4% for smear-negative non-respiratory specimens. 154 cerebrospinal fluid samples were analysed and the sensitivity, specificity, PPV and NPV were 55.6%, 97.2%, 55.6% and 97.2%, respectively. These results indicate that the Cobas Amplicor MTB test enables detection of tuberculosis in respiratory specimens, but does not perform well enough in non-respiratory specimens. The method fails particularly in cases where a reliable and rapid test is urgently needed, e.g. in tuberculous meningitis.
Adherence to national guidelines for drug treatment of suspected acute myocardial infarction: evidence for undertreatment in women and the elderly.

BACKGROUND Evidence-based guidelines for the treatment of patients with acute myocardial infarction (AMI) have been published and disseminated by the American College of Cardiology and the American Heart Association. Few studies have examined the rates of adherence to these guidelines in eligible populations and the influence of age and gender on highly effective AMI treatments in community hospital settings. METHODS Medical records of 2409 individuals admitted to 37 Minnesota hospitals between October 1992 and July 1993 for AMI, suspected AMI, or rule-out AMI, and meeting electrocardiographic, laboratory, and clinical criteria suggestive of AMI were reviewed to determine the proportion of eligible patients who received thrombolytic, beta-blocker, aspirin, and lidocaine hydrochloride therapy. The effects of patient age, gender, and hospital teaching status on the use of these treatments were estimated using logistic regression models. RESULTS Eligibility for treatment ranged from 68% (n=1627) for aspirin therapy, 38% (n=906) for lidocaine therapy, and 30% (n=734) for thrombolytic therapy to 19% (n=447) for beta-blocker therapy. Seventy-two percent of patients eligible to receive a thrombolytic agent received this therapy; 53% received beta-blockers; 81% received aspirin; and 88% received lidocaine. Among patients ineligible for lidocaine therapy (n=1503), 20% received this agent. Use of study drugs was lower among eligible elderly patients, especially those older than 74 years (thrombolytic agent: odds ratio, 0.2; 95% confidence interval, 0.1 to 0.4; aspirin: odds ratio, 0.4, 95% confidence interval, 0.3 to 0.6; beta-blocker: odds ratio, 0.4; 95% confidence interval, 0.2 to 0.8). Female gender was associated with lower levels of aspirin use among eligible patients (odds ratio, 0.7; 95% confidence interval, 0.6 to 0.9); and there was a trend toward lower levels of beta-blocker and thrombolytic use among eligible women. CONCLUSIONS Use of lifesaving therapies for eligible patients with AMI is higher than previously reported, particularly for aspirin and thrombolytic use in nonelderly patients. Lidocaine is still used inappropriately in a substantial proportion of patients with AMI. Increased adherence to AMI treatment guidelines is required for elderly patients and women.
The politics and economics of regulatory impact assessment

This Handbook of Regulatory Impact Assessment provides a balanced account of what it is to design, make and implement regulatory impact assessment (RIA) across a range of major policy sectors, countries and regions. Our account is theoretically informed and empirically rich. The notion of RIA comes from the North American experience where regulators have to carry out an economic analysis of regulatory proposals, send it to oversight regulatory units in the Executive and publish it for notice and comment. In the United States of America (USA) and Canada, for example, RIA applies to draft regulations generated by agencies with delegated regulatory power. It does not cover primary legislation, only secondary legislation, that is, the regulations of agencies like the Environmental Protection Agency in the USA or Health Canada and it is confined to regulatory policies, not taxation and public expenditure. When other countries adopted RIA, it was often extended to different types of policies. Today in most countries (but, for example, not in the USA), impact assessment is an instrument to design primary legislation. Since across countries, government departments and agencies draw on impact assessment to develop both regulatory and nonregulatory policies, in this volume we will use the abbreviation IA instead of RIA. Another qualification is that we deal with instruments for the appraisal of public policies, thus we do not look at impact assessment as business tool and elsewhere in the public sector. In short, we are inside the broader field of government, governance and comparative public policy, and consider both regulations issued by agencies and draft legislation originating in central government departments. In this volume, international academic and practitioner experts guide us through the state of the art of IA in five parts: (1) the analytical approaches that underpin IA; (2) the preeminent tools, actors and dimensions; (3) major policy sectors where IA is featured; (4) the regional diffusion of IA; and (5) its implementation analytically, pedagogically and in the field. This introduction fulfils the function of a scenesetting chapter.