Miracle-dz/UniFAR-FTUs huggingface dataset:
Monitoring dynamic alterations in calcium homeostasis by T 1‐weighted and T 1‐mapping cardiac manganese‐enhanced MRI in a murine myocardial infarction model

Manganese has been used as a T1‐weighted MRI contrast agent in a variety of applications. Because manganese ions (Mn2+) enter viable myocardial cells via voltage‐gated Ca2+ channels, manganese‐enhanced MRI is sensitive to the viability and inotropic state of the heart. In spite of the established importance of Ca2+ regulation in the heart both before and after myocardial injury, monitoring strategies to assess Ca2+ homeostasis in affected cardiac tissues are limited. This study implements a T1‐mapping method to obtain quantitative information both dynamically and over a range of MnCl2 infusion doses. To optimize the current Mn2+ infusion protocols, we performed both dose‐dependent and temporal washout studies. A non‐linear relationship between infused MnCl2 solution dose and increase in left ventricular wall relaxation rate (ΔR1) was observed. Control mice also exhibited significant Mn2+ clearance over time, with a decrease in ΔR1 of ∼50% occurring in just 2.5 h. The complicated efflux time dependence possibly suggests multiple efflux mechanisms. With the use of the measured relationship between infused Mn2+ dose, ΔR1, and inductively coupled plasma mass spectrometry data analysis provided a means of estimating the absolute heart Mn concentration in vivo. We show that this technique has the sensitivity to observe or monitor potential alterations in Ca2+ handling in vivo because of the physiological remodeling after myocardial infarction. Left ventricular free wall ΔR1 values were significantly lower (P = 0.005) in the adjacent zone, surrounding the injured myocardial tissue, than in healthy tissue. This inferred reduction in Mn concentration can be used to estimate potentially salvageable myocardium in vivo for future treatment or evaluation of disease progression. Copyright © 2008 John Wiley & Sons, Ltd.
Lymphoma risk in livestock farmers: Results of the Epilymph study

We explored the risk of lymphoma and its most prevalent subtypes associated with occupational contact with livestock, and whether risk was modified by age at first contact, in 2,348 incident lymphoma cases and 2,462 controls who participated in the EPILYMPH case–control study. A detailed occupational history was collected in cases and controls, including working in a livestock farm, species of livestock, its approximate number and circumstances of contact. For each disease outcome, and each type of livestock, odds ratios (OR) and their 95% confidence intervals (95% CI) were calculated using unconditional logistic regression, adjusting for age, gender, education and center. Lymphoma risk (all subtypes combined) was not increased amongst those exposed to contact with any livestock (OR = 1.0, 95% CI 0.8–1.2). Overall, we did not observe an association between occupational contact with livestock and risk of lymphoma (all types) and B‐cell lymphoma. The risk of diffuse large B cell lyphoma (DLBCL) was significantly lower amongst subjects who started occupational contact with any species of livestock before or at age 12 (OR = 0.5, 95% CI 0.2–0.9), but not at older ages. A significant heterogeneity in risk of B cell lymphoma by age at first contact was detected for contact with cattle, poultry and swine. Early occupational contact with livestock might be associated with a decrease in risk of B cell lymphoma.
Equilibrium Exchange Rate in the Czech Republic: How Good is the Czech Beer?

This paper investigates the equilibrium exchange rate of the Czech koruna using the reduced form equation of the stock-ow approach advocated, for instance, by Faruqee (1995) and Alberola and others (1999). We investigate whether or not the observed real exchange rate of the Czech koruna is close to its equilibrium value over the period from 1993 to 2004. Our empirical approach is tantamount to the Behavioural Equilibrium Exchange Rate (BEER) popularised by MacDonald (1997) and Clark and MacDonald (1998) in that the Czech real exchange rate vis-? -vis the euro is regressed on the dual productivity differential and the net foreign assets position, based on which actual and total misalignment gures are derived in a time series context. In other words, we check the quality of the Czech BEER. We also study the impact of a possible initial undervaluation on the estimated equilibrium exchange rate. Employing monthly time series from 1993:M1 to 2004:M9 and applying several alternative cointegration techniques, we identify a period of an overvaluation in 1997 and in 1999, an increasing overvaluation till 2002, an undervaluation in 2003 and a correction towards equilibrium in the second half of 2004
Co-evolution in tourism: the case of Albergo Diffuso

An important aspect of competitiveness between destinations concerns the way in which historical and cultural heritage is used. Thus, the relationship between territories and firms grows stronger, shifting the focus on the innovation processes within and across destinations. To increase our understanding of how these processes take place in a tourism destination, more theoretical and empirical research is required. This paper aims to respond to this call by examining the central role played by the Italian phenomenon of Albergo Diffuso (AD) through a co-evolutionary approach, fertilized by the evolutionary economic geography literature. The study focuses on the dynamics of the relationship between this new hospitality model, territories and tourists, by analysing 14 case studies of ADs rooted in historical villages. Findings show that AD can be considered as a new sustainability-oriented hospitality model which, by creating synergies with its territory, positively affects the competitiveness of the destinations where ADs are located. The theoretical implications suggest that the creation and development of these innovative firms are the result of effective multi-level co-evolutionary adaptations, adding new elements to the existing literature on innovation in tourism. Moreover, implications for both entrepreneurs and policy-makers emerge, together with suggestions for future research.
Expression Patterns and Post-translational Modifications Associated with Mammalian Histone H3 Variants*

Covalent histone modifications and the incorporation of histone variants bring about changes in chromatin structure that in turn alter gene expression. Interest in non-allelic histone variants has been renewed, in part because of recent work on H3 (and other) histone variants. However, only in mammals do three non-centromeric H3 variants (H3.1, H3.2, and H3.3) exist. Here, we show that mammalian cell lines can be separated into two different groups based on their expression of H3.1, H3.2, and H3.3 at both mRNA and protein levels. Additionally, the ratio of these variants changes slightly during neuronal differentiation of murine ES cells. This difference in H3 variant expression between cell lines could not be explained by changes in growth rate, cell cycle stages, or chromosomal ploidy, but rather suggests other possibilities, such as changes in H3 variant incorporation during differentiation and tissue- or species-specific H3 variant expression. Moreover, quantitative mass spectrometry analysis of human H3.1, H3.2, and H3.3 showed modification differences between these three H3 variants, suggesting that they may have different biological functions. Specifically, H3.3 contains marks associated with transcriptionally active chromatin, whereas H3.2, in contrast, contains mostly silencing modifications that have been associated with facultative heterochromatin. Interestingly, H3.1 is enriched in both active and repressive marks, although the latter marks are different from those observed in H3.2. Although the biological significance as to why mammalian cells differentially employ three highly similar H3 variants remains unclear, our results underscore potential functional differences between them and reinforce the general view that H3.1 and H3.2 in mammalian cells should not be treated as equivalent proteins.
Volatility Forecasts Using Nonlinear Leverage Effects

The leverage effect-- the correlation between an asset's return and its volatility-- has played a key role in forecasting and understanding volatility and risk. While it is a long standing consensus that leverage effects exist and improve forecasts, empirical evidence paradoxically do not show that most individual stocks exhibit this phenomena, mischaracterizing risk and therefore leading to poor predictive performance. We examine this paradox, with the goal to improve density forecasts, by relaxing the assumption of linearity in the leverage effect. Nonlinear generalizations of the leverage effect are proposed within the Bayesian stochastic volatility framework in order to capture flexible leverage structures, where small fluctuations in prices have a different effect from large shocks. Efficient Bayesian sequential computation is developed and implemented to estimate this effect in a practical, on-line manner. Examining 615 stocks that comprise the S\&P500 and Nikkei 225, we find that relaxing the linear assumption to our proposed nonlinear leverage effect function improves predictive performances for 89\% of all stocks compared to the conventional model assumption.
Acceptance, Cognitions, and Resourcefulness in Women with Diabetes

The coexistence of diabetes and depression occurs frequently among young and middle-age women. Unless one is resourceful, simultaneous management of the symptoms of both conditions is especially challenging. Skills constituting resourcefulness are learned throughout life and are important for the optimal performance of daily activities. Little is known about specific factors that influence resourcefulness. In this study, contextual factors (diabetic and depressive symptoms) and cognitive factors (positive cognitions and acceptance of diabetes) were examined as antecedents of learned resourcefulness in 82 women with type 2 diabetes. Regression analyses showed that depressive symptoms and positive cognitions were significant antecedents of learned resourcefulness: Positive cognitions mediated the effects of depressive symptoms on learned resourcefulness. The findings suggest the need for interventions that focus on development of positive cognitions to better promote resourcefulness in women with type 2 diabetes who are at risk for depression.
The birth, life, and death of policy instruments: 35 years of EU gender equality policy programmes

Abstract Policy instruments research is an essential part of studying European Union governance. A growing interest in processes of (de-)legalisation and patterns of instrument choice requires a more process- and context-oriented analysis of the EU’s instrument selection. Using a political sociology approach, the article analyses patterns of instrument choice in soft law policy programmes, by examining the life cycle of EU gender equality policy programmes from 1982 to the present day. Gender equality policy programmes offer an in-depth understanding of how the Commission upgrades and downgrades policy instruments. The analysis indicates that patterns of policy instrument choice are not necessarily inflexible once a policy instrument is selected. Instead, patterns vary while the instrument is (de-)legalised. Investigating gender equality policy programmes provides explanations for the shifts in the use of legislative instruments and their limitations.
Portrait of a successful small-town water service provider in Nepal's changing landscape

This study was made in Nepal9s Tarai plains, where rapid population growth over the past decade has transformed a large number of rural bazaars and roadside hubs into vibrant small towns. This study draws a portrait of a distinctly successful small-town water supply scheme and its service provider, the Murgia Water Users and Sanitation Association. Exploring this particular case with regards to social, technological, financial and organisational systems, and by comparing the performance of this case against 63 other water service providers in Nepal, the study asks: how could there be more of this type of successful water service provider? This scheme was constructed during the bilateral Rural Water Supply and Sanitation Support Programme Phase III, Nepal-Finland cooperation (1999–2005), using the typical rural approach, namely community management, with strong capacity building. Since then the service modality in this study case has evolved towards a professional community-managed service delivery. The success is rooted in good water governance principles: participation, responsiveness, financial transparency, accountability and overall strong commitment and vision, as well as strong technical assistance. They have resulted in re-investment in both the capital maintenance expenditure and into new infrastructure, even into an entirely new water supply scheme.
Cost–distance ratio in change: transmission rates of commercial correspondence in the North and Baltic Sea region, 1732–1808

ABSTRACT Postage accounts kept by merchants active in North and Baltic Sea trade are used to track the development of transmitting costs of remote information. As a long-run aggregated trend in terms of the real price, the postage stayed approximately at the same level until 1770s and decreased substantially thereafter. War factor proved to have had a variable influence. Increased demand on information exchange, driven by booming trade in this period, arguably promoted lower-cost transmission. The present paper also reveals that, over time, international postage was increasingly a function of geographical distance and, due to the changes in means of transmission and also due to the specific tariff policy of national Posts, there was significant cost–space convergence regarding domestic transmission while the same trend was much less dominant at an international level.
A helix-breaking mutation in TRPML3 leads to constitutive activity underlying deafness in the varitint-waddler mouse

Homozygote varitint-waddler (Va) mice, expressing a mutant isoform (A419P) of TRPML3 (mucolipin 3), are profoundly deaf and display vestibular and pigmentation deficiencies, sterility, and perinatal lethality. Here we show that the varitint-waddler isoform of TRPML3 carrying an A419P mutation represents a constitutively active cation channel that can also be identified in native varitint-waddler hair cells as a distinct inwardly rectifying current. We hypothesize that the constitutive activation of TRPML3 occurs as a result of a helix-breaking proline substitution in transmembrane-spanning domain 5 (TM5). A proline substitution scan demonstrated that the inner third of TRPML3's TM5 is highly susceptible to proline-based kinks. Proline substitutions in TM5 of other TRP channels revealed that TRPML1, TRPML2, TRPV5, and TRPV6 display a similar susceptibility at comparable positions, whereas other TRP channels were not affected. We conclude that the molecular basis for deafness in the varitint-waddler mouse is the result of hair cell death caused by constitutive TRPML3 activity. To our knowledge, our study provides the first direct mechanistic link of a mutation in a TRP ion channel with mammalian hearing loss.
Access to medicines: relations with the institutionalization of pharmaceutical services

ABSTRACT OBJETIVE To analyze the relationship between access to medicines by the population and the institutionalization of pharmaceutical services in Brazilian primary health care. METHODS This study is part of the Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos – Serviços 2015 (PNAUM – National Survey on Access, Use and Promotion of Rational Use of Medicines – Services 2015), a cross-sectional, exploratory, and evaluative study composed of an information survey in a representative sample of cities, stratified by Brazilian regions. Access was defined based on the acquisition of medicines reported by the patient, ranging between: total, partial, or null. The institutionalization of pharmaceutical services was analyzed based on information provided by pharmaceutical services providers and by those responsible for medicines delivery. Chi-square test and multinomial logistic regression were used in the statistical analysis. RESULTS Full access to medicines was greater when professionals affirmed there were the following aspects of the dimensions: “management tools,” “participation and social control,” “financing,” and “personnel structure,” with significant associations in the bivariate analysis. The “pharmaceutical care” dimension did not achieve such an association. After multinomial logistic regression, full access was more prevalent when those in charge of pharmaceutical services stated that: they always or repeatedly attend meetings of the Municipal Health Council, OR = 3.3 (95%CI 1.5-7.3); there are protocols for medicines delivery, OR = 2.7 (95%CI 1.2-6.1); there is computerized system for managing pharmaceutical services, OR = 3.9 (95%CI 1.9-8.0); those responsible for medicines delivery reported having participated in a course or training for professionals in the past two years, OR = 2.0 (95%CI 1.1-3.5); there is computerized system for pharmaceutical services management, OR = 4.3 (95%CI 2.4-7.5). CONCLUSIONS Aspects related to the institutionalization of pharmaceutical services have been strongly related to access to medicines. Our results indicate the need to prioritize its implementation, contributing to its consolidation in Brazil and to the effectiveness of health services regarding the purposes of pharmaceutical services policies.
Effect of milk-borne epidermal growth factor on the hepatic microcirculation and Kupffer cell function in suckling rats.

Epidermal growth factor (EGF) is contained in breast milk, is transported intact across the gastrointestinal mucosa during the suckling period, retains its biological activity, and affects hepatic growth. Whether or not EGF also influences postnatal hepatic development by affecting nonparenchymal cells or by modifying intrahepatic blood is not clear. As a result, the effect of EGF on the hepatic microvasculature was studied in suckling rats fed rat milk substitute (RMS) with and without EGF (100 ng/ml, i.e. twice the normal intake in breast milk) between days 11 and 14 and compared to pups breast-fed for 14 days. The livers of anesthetized pups were examined by in vivo microscopy to determine the numbers of sinusoids with flow (SCF) in each of 10 microscopic fields and the numbers of phagocytic Kupffer cells (KC) in the same fields following an intraportal injection of fluorescent 1-micron latex particles. Phagocytic activity was expressed as the ratio KC/SCF. In pups fed RMS without EGF, SCF and KC/SCF was 75 and 45%, respectively, of that in breast-fed animals. The addition of EGF to the RMS restored SCF and KC/SCF nearly to the levels measured in breast-fed pups. Thus, the results suggest that milk-borne EGF plays a role in the development of KC phagocytic function and affects the amount of blood that perfuses the sinusoidal bed in the suckling.
Conscious and anaesthetised Göttingen mini-pigs as an in-vivo model for buccal absorption – pH-dependent absorption of metoprolol from bioadhesive tablets

Abstract The potential of buccal mucosa as a site for systemic absorption has attracted increased attention in recent years creating a need for new predictive in-vivo models. The aim of this study was to evaluate anaesthetised and conscious Göttingen mini-pigs as a model for buccal drug absorption by testing pH-dependent absorption of metoprolol from a solid dosage form. Buccal tablets buffered to pH 6.2 and pH 8.9, oral liquid and intravenous injection were tested in four conscious and anaesthetised Göttingen mini-pigs in a non-randomised cross-over study. Blood samples were collected and processed before analysis by ultra-performance liquid chromatography with tandem mass spectrometry detection. An ex-vivo flow retention model was applied to study release and retention of the bioadhesive buccal tablets. The Tmax obtained from the two buccal conscious groups (55 ± 5 and 35 ± 5 min) were significantly different to the buccal anaesthetised groups (120 ± 0 and 165 ± 15 min) for buccal tablet pH 6.2 and pH 8.9, respectively. Also, the absolute bioavailability from the anaesthetised buccal tablet pH 8.9 (20.7 ± 4.0%) had a significant increase compared to all other buccal tablet groups. In conclusion, this study showed a pH-dependent absolute bioavailability of metoprolol when administrated as bioadhesive buccal tablets to anaesthetised mini-pigs. The anaesthesia was found to delay the time to reach maximal plasma concentration of metoprolol as compared to the conscious pig model when administrated as buccal tablets.
ISOLATED CENTRAL NERVOUS SYSTEM INVOLVEMENT BY LYMPHOMATOID GRANULOMATOSIS IN AN ADOLESCENT: A Case Report and Review of Literature

Lymphomatoid granulomatosis is an Epstein-Barr virus–associated multisystem disease that combines granulomatous inflammatory process with lymphoproliferative potential. It predominantly affects lungs, skin, and brain and is characterized by multifocal, transmural, angiocentric, and angiodestructive pleomorhic lymphoid infiltrate in a perivascular distribution. Lymphomatoid granulomatosis is generally considered to be a neoplastic B-cell proliferation that has traditionally been associated with poor prognosis, evolving as a progressive multisystem disease transforming into B-cell lymphoma, with a median survival of 14 to 16 months only. Its lymphomatous nature explains prompt response to steroids and systemic chemotherapy, although appropriate optimal management still remains to be defined. The authors report on a young boy who presented with features of raised intracranial tension and sudden onset seizures. Neuroimaging showed 2 space-occupying lesions, larger in the left frontoparietal region with heterogeneous enhancement, moderate perifocal edema, compression, and mass effect. He underwent surgical decompression of the dominant lesion with prompt relief of symptoms. The diagnosis of lymphomatoid granulomatosis was confirmed on light microscopy and immunohistochemistry. An extensive systemic work-up ruled out other site(s) of involvement. He was successfully treated with aggressive systemic chemotherapy and moderate dose of whole-brain radiotherapy. Awareness of disease spectrum in the central nervous system may permit early diagnosis and thus allow institution of timely appropriate therapy.
Multi-Agent Systems with Dynamical Topologies: Consensus and Applications

It is well known that a multi-agent system (MAS) is a specific system consisting of multiple interacting autonomous agents. Consensus or synchronization, as one of the typical collective behaviors, is ubiquitous in nature. Over the last decades, consensus has been widely investigated in various disciplines, including mathematics, physics, biology, engineering, and social sciences. In particular, consensus of MAS with dynamical topology is an emerging new topic motivated by many real-world applications, such as wireless communication and sensor networks. However, the collective behavior of MAS with dynamical topology is very complex and cannot be easily analyzed by the traditional approaches. To resolve the issue of dynamical topology, various techniques and methods have been developed in the last decade. This paper aims to review the main advances in the consensus of MAS with dynamical topology, including several fundamental models and the corresponding methods. The main purpose is to promote this emerging topic on multi-agent systems, with emphasis on the interdisciplinary interest from the circuits and systems engineering communities.