Miracle-dz/UniFAR-FTUs huggingface dataset:
Modelling inequality in reported long term illness in the UK: combining individual and area characteristics.

STUDY OBJECTIVE: To assess the nature of the relation between health and social factors at both the aggregated scale of geographical areas and the individual scale. DESIGN AND SETTING: The individual data are derived from the sample of anonymised records (SAR) from the census of 1991 in Great Britain, and are combined with area data from this census. The ecological setting (context) was defined using multivariate methods to classify the 278 districts of residence identifiable in the SAR. The outcome health variable is the 1991 census long-term limiting illness question. Health variations were analysed by multilevel logistic regression to examine the compositional variation (at the level of the individual) and the contextual variation (variability operating at the level of districts) in reported illness. PARTICIPANTS: 10 per cent randomised subsample of the SAR who are aged 16+ and are resident in households. MAIN RESULTS: The multi-level modelling revealed that area factors have a significant association with individual health outcome but their effect is smaller than that of individual attributes. The results show evidence for both compositional and contextual effects in the pattern of variation in propensity to report illness. CONCLUSIONS: The results suggest generally higher levels of ill health for individuals who are older, not married, in a semi/unskilled manual social class, and socioeconomically deprived (as measured by a composite deprivation score). All individuals living in areas with high levels of illness (which tend to be more deprived areas) show greater morbidity, even after allowing for their individual characteristics. However, within affluent areas, where morbidity was generally lower, the health inequality (health gradient) between rich and poor individuals was particularly strong. We consider the implications of these findings for health and resource allocation policy.
In Vitro Evaluation of Hepatic Transporter-Mediated Clinical Drug-Drug Interactions: Hepatocyte Model Optimization and Retrospective Investigation

To assess the feasibility of using sandwich-cultured human hepatocytes (SCHHs) as a model to characterize transport kinetics for in vivo pharmacokinetic prediction, the expression of organic anion-transporting polypeptide (OATP) proteins in SCHHs, along with biliary efflux transporters, was confirmed quantitatively by liquid chromatography-tandem mass spectrometry. Rifamycin SV (Rif SV), which was shown to completely block the function of OATP transporters, was selected as an inhibitor to assess the initial rates of active uptake. The optimized SCHH model was applied in a retrospective investigation of compounds with known clinically significant OATP-mediated uptake and was applied further to explore drug-drug interactions (DDIs). Greater than 50% inhibition of active uptake by Rif SV was found to be associated with clinically significant OATP-mediated DDIs. We propose that the in vitro active uptake value therefore could serve as a cutoff for class 3 and 4 compounds of the Biopharmaceutics Drug Disposition Classification System, which could be integrated into the International Transporter Consortium decision tree recommendations to trigger clinical evaluations for potential DDI risks. Furthermore, the kinetics of in vitro hepatobiliary transport obtained from SCHHs, along with protein expression scaling factors, offer an opportunity to predict complex in vivo processes using mathematical models, such as physiologically based pharmacokinetics models.
Learning, forgetting, and retrieval of everyday material across the adult life span.

Levels and rates of acquisition and amounts of forgetting of name-face associations and grocery list items were assessed in a sample of 1,921 normal participants that was divided into five age groups (i.e., 17-39, 40-49, 50-59, 60-69, and 70+). Retrieval was assessed via the consistent long-term retrieval score (CLTR) from the Grocery List Selective Reminding Test (GLSRT). Substantial linear age-associated declines in level of acquisition were noted for both name-face associations and grocery list items. There was a significant age-related drop in rate of acquisition of name-face associations. Remarkably, very little forgetting occurred over a 40-min delay at any age on either measure. There was a significant linear age-related decline in retrieval efficiency for grocery list items, when variance due to both level of acquisition and retention was removed. The nature of age-associated memory decline and its possible neuroanatomic correlates is discussed.
AQP5 Is Expressed In Type-B Intercalated Cells in the Collecting Duct System of the Rat, Mouse and Human Kidney

We screened human kidney-derived multipotent CD133+/CD24+ ARPCs for the possible expression of all 13 aquaporin isoforms cloned in humans. Interestingly, we found that ARPCs expressed both AQP5 mRNA and mature protein. This novel finding prompted us to investigate the presence of AQP5 in situ in kidney. We report here the novel finding that AQP5 is expressed in human, rat and mouse kidney at the apical membrane of type-B intercalated cells. AQP5 is expressed in the renal cortex and completely absent from the medulla. Immunocytochemical analysis using segment- and cell type-specific markers unambiguously indicated that AQP5 is expressed throughout the collecting system at the apical membrane of type-B intercalated cells, where it co-localizes with pendrin. No basolateral AQPs were detected in type-B intercalated cells, suggesting that AQP5 is unlikely to be involved in the net trans-epithelial water reabsorption occurring in the distal tubule. An intriguing hypothesis is that AQP5 may serve an osmosensor for the composition of the fluid coming from the thick ascending limb. Future studies will unravel the physiological role of AQP5 in the kidney.
Caroli's Syndrome with Autosomal Recessive Polycystic Kidney Disease in a Two Month Old Infant

Caroli's syndrome is a rare congenital disorder that involves intrahepatic bile duct ectasia and congenital hepatic fibrosis, frequently seen with concomitant autosomal recessive polycystic kidney disease (ARPKD). Literature on infants with ARPKD is rare. Here, we present a case of a two month old boy who was diagnosed with Caroli's syndrome and ARPKD.
A Comprehensive Metabolic Profile of Cultured Astrocytes Using Isotopic Transient Metabolic Flux Analysis and 13C-Labeled Glucose

Metabolic models have been used to elucidate important aspects of brain metabolism in recent years. This work applies for the first time the concept of isotopic transient 13C metabolic flux analysis (MFA) to estimate intracellular fluxes in primary cultures of astrocytes. This methodology comprehensively explores the information provided by 13C labeling time-courses of intracellular metabolites after administration of a 13C-labeled substrate. Cells were incubated with medium containing [1-13C]glucose for 24 h and samples of cell supernatant and extracts collected at different time points were then analyzed by mass spectrometry and/or high performance liquid chromatography. Metabolic fluxes were estimated by fitting a carbon labeling network model to isotopomer profiles experimentally determined. Both the fast isotopic equilibrium of glycolytic metabolite pools and the slow labeling dynamics of TCA cycle intermediates are described well by the model. The large pools of glutamate and aspartate which are linked to the TCA cycle via reversible aminotransferase reactions are likely to be responsible for the observed delay in equilibration of TCA cycle intermediates. Furthermore, it was estimated that 11% of the glucose taken up by astrocytes was diverted to the pentose phosphate pathway. In addition, considerable fluxes through pyruvate carboxylase [PC; PC/pyruvate dehydrogenase (PDH) ratio = 0.5], malic enzyme (5% of the total pyruvate production), and catabolism of branched-chained amino acids (contributing with ∼40% to total acetyl-CoA produced) confirmed the significance of these pathways to astrocytic metabolism. Consistent with the need of maintaining cytosolic redox potential, the fluxes through the malate–aspartate shuttle and the PDH pathway were comparable. Finally, the estimated glutamate/α-ketoglutarate exchange rate (∼0.7 μmol mg prot−1 h−1) was similar to the TCA cycle flux. In conclusion, this work demonstrates the potential of isotopic transient MFA for a comprehensive analysis of energy metabolism.
A Peered Bulletin Board for Robust Use in Verifiable Voting Systems

The Secure Web Bulletin Board (WBB) is a key component of verifiable election systems. However, there is very little in the literature on their specification, design and implementation, and there are no formally analysed designs. The WBB is used in the context of election verification to publish evidence of voting and tallying that voters and officials can check, and where challenges can be launched in the event of malfeasance. In practice, the election authority has responsibility for implementing the web bulletin board correctly and reliably, and will wish to ensure that it behaves correctly even in the presence of failures and attacks. To ensure robustness, an implementation will typically use a number of peers to be able to provide a correct service even when some peers go down or behave dishonestly. In this paper we propose a new protocol to implement such a Web Bulletin Board, motivated by the needs of the vVote verifiable voting system. Using a distributed algorithm increases the complexity of the protocol and requires careful reasoning in order to establish correctness. Here we use the Event-B modelling and refinement approach to establish correctness of the peered design against an idealised specification of the bulletin board behaviour. In particular we have shown that for n peers, a threshold of t > 2n/3 peers behaving correctly is sufficient to ensure correct behaviour of the bulletin board distributed design. The algorithm also behaves correctly even if honest or dishonest peers temporarily drop out of the protocol and then return. The verification approach also establishes that the protocols used within the bulletin board do not interfere with each other. This is the first time a peered secure web bulletin board suite of protocols has been formally verified.
Proanthocyanidins Attenuation of Chronic Lead-Induced Liver Oxidative Damage in Kunming Mice via the Nrf2/ARE Pathway

Lead is harmful for human health and animals. Proanthocyanidins (PCs), a natural antioxidant, possess a broad spectrum of pharmacological and medicinal properties. However, its protective effects against lead-induced liver damage have not been clarified. This study was aimed to evaluate the protective effect of PCs on the hepatotoxicity of male Kunming mice induced by chronic lead exposure. A total of 70 healthy male Kunming mice were averagely divided into four groups: control group, i.e., the group exposed to lead, the group treated with PCs, and the group co-treated with lead and PCs. The mice exposed to lead were given water containing 0.2% lead acetate. Mice treated in the PCs and PCs lead co-treated groups were given PC (100 mg/kg) in 0.9% saline by oral gavage. Lead exposure caused a significant elevation in the liver function parameters, lead level, lipid peroxidation, and inhibition of antioxidant enzyme activities. The induction of oxidative stress and histological alterations in the liver were minimized by co-treatment with PCs. Meanwhile, the number of Transferase-Mediated Deoxyuridine Triphosphate-Biotin Nick End Labeling (TUNEL)-positive cells was significantly reduced in the PCs/lead co-treated group compared to the lead group. In addition, the lead group showed an increase in the expression level of Bax, while the expression of Bcl-2 was decreased. Furthermore, the lead group showed an increase in the expression level of endoplasmic reticulum (ER) stress-related genes and protein (GRP78 and CHOP). Co-treated with PCs significantly reversed these expressions in the liver. PCs were, therefore, demonstrated to have protective, antioxidant, and anti-ER stress and anti-apoptotic activities in liver damage caused by chronic lead exposure in the Kunming mouse. This may be due to the ability of PCs to enhance the ability of liver tissue to protect against oxidative stress via the Nrf2/ARE signaling pathway, resulting in decreasing ER stress and apoptosis of liver tissue.
Region-specific distribution of human immunodeficiency virus type 1 long terminal repeats containing specific configurations of CCAAT/enhancer-binding protein site II in brains derived from demented and nondemented patients

Previous studies have shown that two CCAAT/enhancer binding protein (C/EBP) binding sites (sites I and II) within the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) are critically important for efficient virus replication within cells of the monocyte lineage, a primary cell type infected by HIV-1. Sequence variation at C/EBP sites I and II has been shown to alter the affinity of C/EBP factors to these sites. Specifically, sequence variation within C/EBP binding site II has been shown to alter binding of purified C/EBP β protein and basal activity of the HIV-1 LTR. We have previously demonstrated that the C/EBP site II consensus cladeB (ConB) variant was highly conserved in brain- and peripheral blood-derived LTRs of individuals with advanced HIV-1 disease. Given these important observations, the regional distribution of LTRs containing the C/EBP site II ConB variant derived from brain tissues of patients with and without HIV-1-associated dementia (HIVD) was examined. A statistically significant difference was found in the distribution of LTRs containing the C/EBP site II ConB variant in brain regions derived from patients with and without HIVD. In addition, we have previously shown that LTRs containing C/EBP site II 4C and 6G variants (designated according to the position at which nucleotide change occurred relative to ConB, followed by the actual nucleotide found at the variant position) were only found in brain tissue of patients with HIVD. As an extension of these observations, the regional distribution of LTRs containing C/EBP site II 4C or 6G variants derived from the brains of patients with HIVD was examined and a statistically significant difference was observed. We have shown that LTRs containing a low-affinity C/EBP site II4C variant accumulated in the cerebellum. LTRs containing the 4C site variant in conjunction with the consensus cladeB (ConB) site I exhibited the lowest basal LTR activity of any of the LTRs examined. These results suggest that LTRs containing the C/EBP site II 4C configuration may promote the establishment of a latent provirus in the cerebellum, a region of the HIVD brain that exhibits little viral gene expression. Furthermore, LTRs containing a high affinity C/EBP site II 6G variant accumulated in the mid-frontal gyrus, a site of highly productive replication. In addition, LTRs containing the C/EBP site II 6G variant with the ConB at site I exhibited the highest basal LTR activity. In conclusion, distinct LTR populations with specific C/EBP site II configurations were found in different neuroanatomical regions of the brain, potentially due to differences in the molecular architecture of the LTR, viral entry pathways, and/or brain microenvironments.
ASPECTOS BIOLÓGICOS DE DUAS ESPÉCIES DE Astyanax (TELEOSTEI, CHARACIDAE) EM LAGOAS MARGINAIS DO ALTO RIO IGUAÇU, PARANÁ, BRASIL

Aspectos da biologia de duas especies endemicas de Astyanax da bacia do rio Iguacu sao descritos. Amostragens mensais em lagoas marginais do curso superior do rio Iguacu foram realizadas entre julho de 1995 e junho de 1996, dentro do Parque Municipal do Iguacu. Foram capturados 2.154 exemplares, sendo 46% pertencentes a Astyanax sp. B e 54% a Astyanax sp. C. Variacoes significativas nas medias de comprimento e peso totais foram observadas, com valores maiores durante verao/outono para Astyanax sp. B e inverno/primavera para Astyanax sp. C. O periodo reprodutivo das especies foi longo, com maior intensidade na primavera e verao, quando a proporcao sexual foi predominantemente 1:1. Variacoes dos aspectos biologicos estiveram relacionadas as alteracoes sazonais do ambiente.
Stabilization over frequency-selective channels subject to transmission delay and signal-to-noise ratio limitations

The stabilizability problem of an unstable non-minimum phase (NMP) plant, controlled over a signal-to-noise ratio (SNR) constrained channel with transmission delay, is investigated in this article. A dynamical output feedback controller is used to stabilize the single-input single-output plant where the control data are exchanged via an NMP bandwidth-limited communication medium. For the first time, a novel description of SNR is used to solve stabilizability problem when the NMP channel imposes a constant delay on transmitted data. It is demonstrated that the presence of time-delay in the channel model as well as its NMP zeros increases the value of SNR needed for stabilizability of the closed-loop system. The main results are illustrated and discussed through numerical examples. VC 2016 Wiley Periodicals, Inc. Complexity 000: 00–00, 2016
Targeted Disruption of Core 1 β1,3-galactosyltransferase (C1galt1) Induces Apical Endocytic Trafficking in Human Corneal Keratinocytes

Background Exposed mucosal surfaces limit constitutive endocytosis under physiological conditions to prevent uptake of macromolecules and pathogens and, therefore, cellular damage. It is now accepted that cell surface mucins, a group of high molecular weight glycoproteins on the epithelial glycocalyx, defined by their extensive O-glycosylation, play a major role in maintaining barrier function in these surfaces, but the precise mechanisms are unclear. Methodology/Principal Findings In this work, we utilized a stable tetracycline-inducible RNA interfering system targeting the core 1 ß1,3-galactosyltransferase (C1galt1 or T-synthase), a critical galactosyltransferase required for the synthesis of core 1 O-glycans, to explore the role of mucin-type carbohydrates in apical endocytic trafficking in human corneal keratinocytes. Using cell surface biotinylation and subcellular fractionation, we found increased accumulation of plasma membrane protein in endosomes after C1galt1 depletion. Confocal laser scanning microscopy and fluorometry revealed increased translocation of negatively charged fluorescent nanospheres after C1galt1 knockdown sustained by an active transport process and largely independent of apical intercellular junctions. Internalization of nanospheres could be blocked by dynasore, nocodazole, chlorpromazine, and hyperosmotic sucrose, suggesting a mechanism for clathrin-coated pit budding and vesicular trafficking. This possibility was supported by experiments showing nanosphere colocalization with clathrin heavy chain in the cytoplasm. Conclusions/Significance Together, the data suggest that core 1 O-glycans contribute to maintenance of apical barrier function on exposed mucosal surfaces by preventing clathrin-mediated endocytosis.
Cold Temperature Delays Wound Healing in Postharvest Sugarbeet Roots

Storage temperature affects the rate and extent of wound-healing in a number of root and tuber crops. The effect of storage temperature on wound-healing in sugarbeet (Beta vulgaris L.) roots, however, is largely unknown. Wound-healing of sugarbeet roots was investigated using surface-abraded roots stored at 6 and 12°C for 28 days. Surface abrasions are common injuries of stored roots, and the storage temperatures used are typical of freshly harvested or rapidly cooled roots. Transpiration rate from the wounded surface and root weight loss were used to quantify wound healing. At 12°C, transpiration rate from the wounded surface declined within 14 days and wounded roots lost weight at a rate similar to unwounded controls. At 6°C, transpiration rate from the wounded surface did not decline in the 28 days after injury, and wounded roots lost 44% more weight than controls after 28 days storage. Melanin formation, lignification, and suberization occurred more rapidly at 12°C than at 6°C, and a continuous layer of lignified and suberized cells developed at 12°C, but not at 6°C. Examination of enzyme activities involved in melanin, lignin, and suberin formation indicated that differences in melanin formation at 6 and 12°C were related to differences in polyphenol oxidase activity, although no relationships between suberin or lignin formation and phenylalanine ammonia lyase or peroxidase activity were evident. Wound-induced respiration was initially greater at 12°C than at 6°C. However, with continued storage, respiration rate of wounded roots declined more rapidly at 12°C, and over 28 days, the increase in respiration due to injury was 52% greater in roots stored at 6°C than in roots stored at 12°C. The data indicate that storage at 6°C severely slowed and impaired wound-healing of surface-abraded sugarbeet roots relative to roots stored at 12°C and suggest that postharvest losses may be accelerated if freshly harvested roots are cooled too quickly.
Gene-Sharing Networks Reveal Organizing Principles of Transcriptomes in Arabidopsis and Other Multicellular Organisms[W]

A novel computational pipeline was designed to study the distribution of gene expression levels across cell types, tissues, and organs in Arabidopsis, rice, human, and mouse. Thousands of cross-tissue gene-sharing events were identified and predicted gene functions were validated in Arabidopsis. Understanding tissue-related gene expression patterns can provide important insights into gene, tissue, and organ function. Transcriptome analyses often have focused on housekeeping or tissue-specific genes or on gene coexpression. However, by analyzing thousands of single-gene expression distributions in multiple tissues of Arabidopsis thaliana, rice (Oryza sativa), human (Homo sapiens), and mouse (Mus musculus), we found that these organisms primarily operate by gene sharing, a phenomenon where, in each organism, most genes exhibit a high expression level in a few key tissues. We designed an analytical pipeline to characterize this phenomenon and then derived Arabidopsis and human gene-sharing networks, in which tissues are connected solely based on the extent of shared preferentially expressed genes. The results show that tissues or cell types from the same organ system tend to group together to form network modules. Tissues that are in consecutive developmental stages or have common physiological functions are connected in these networks, revealing the importance of shared preferentially expressed genes in conferring specialized functions of each tissue type. The networks provide predictive power for each tissue type regarding gene functions of both known and heretofore unknown genes, as shown by the identification of four new genes with functions in guard cell and abscisic acid response. We provide a Web interface that enables, based on the extent of gene sharing, both prediction of tissue-related functions for any Arabidopsis gene of interest and predictions concerning the relatedness of tissues. Common gene-sharing patterns observed in the four model organisms suggest that gene sharing evolved as a fundamental organizing principle of gene expression in diverse multicellular eukaryotes.