Miracle-dz/UniFAR-FTUs huggingface dataset:
TGF-Beta Auto-Induction and Connective Tissue Growth Factor Expression in Human Renal Tubule Epithelial Cells Requires N-Ras

Background/Aims: Transforming growth factor (TGF) β is strongly implicated in the progression of renal fibrosis. TGFβ1 is reported to cause epithelial-mesenchymal transition, inhibition of epithelial cell proliferation, increased apoptosis, auto-induction of TGFβ production and induction of secondary mediators of tissue fibrosis such as connective tissue growth factor (CTGF, CCN2). The aims of this study were to investigate the role of the Ras/MAP kinase pathway in TGFβ1 inhibition of proliferation, TGFβ auto-induction and TGFβ1-induced CTGF expression in HKC human renal tubule epithelial cells. Methods and Results: TGFβ1 (0–25 ng/ml) inhibited proliferation of HKC cells and at 25 ng/ml also induced apoptosis. After 5–10 min of incubation, TGFβ1 increased cellular levels of phospho-ERK1/2 and phospho-AKT with a bell-shaped dose-response curve with a maximally effective concentration of 2.5 ng/ml. TGFβ3 caused an increase in extracellular TGFβ1, which was significantly reduced in the presence of PD 98059. TGFβ1 increased cellular and secreted CTGF protein in HKC cells in a MEK-dependent manner. To identify the Ras isoform involved, specific antisense oligonucleotides targeted to Ha-Ras, Ki-Ras and N-Ras were employed. Only inhibition of N-Ras resulted in a significant reduction of auto-induced TGFβ1 secretion and TGFβ1-induced cellular and secreted CTGF. Conclusion: These results establish that the Ras/MAP kinase pathway, specifically through N-Ras, mediates TGFβ1 auto-induction and TGFβ1-induced CTGF expression in human renal tubule epithelial cells.
Contrasting Conditions in the U.K. Winter of 2015/16 as a Result of Remote Tropical Influences

Winter 2015/16 exhibited contrasting weather patterns in western Europe. Early winter saw a succession of high-impact storms, and December was the wettest calendar month recorded in the United Kingdom. February experienced a shift to relatively cooler conditions. Overall, the winter was well forecast by GloSea5, the Met Office’s seasonal prediction system, capturing the positive North Atlantic Oscillation (NAO) in early winter and the northwesterly pattern of flow in February. In this paper, we use a series of atmospheric relaxation experiments to investigate tropical drivers of these signals and the shift in pressure patterns over the course of the winter. While December’s positive NAO is highly consistent with the strong El Niño event in the tropical Pacific Ocean, this pattern is shown to be modified by wavelike activity from the tropical Atlantic Ocean. The result is a shift in the direction of the prevailing flow from westerly to southwesterly, helping to explain the unusually high U.K. precipitation. In February, the surface pressure pattern is characteristic of a strong (rather than a moderate) El Niño, driven by the eastward extension of the Walker circulation. The relaxation experiments indicate that both the Pacific and Atlantic basins play a role in explaining the phenomena of winter 2015/16. To correctly predict the extratropical response over northern Europe, an accurate representation of tropical forcings in both basins is required.
Characterization of an in vivo concentration-effect relationship for piperaquine in malaria chemoprevention

An in vivo concentration-effect relationship for the malaria drug piperaquine can be used for translational simulations of expected therapeutic outcomes in vulnerable populations. Guiding Malaria Chemoprevention Piperaquine (PQ) is a long-acting antimalarial drug used in combination with short-acting dihydroartemisinin (DHA) to treat and prevent malaria infections. PQ blood measurement and malaria infection data were collected after monthly or bimonthly standard 3-day treatment regimens of DHA-PQ. Bergstrand et al. then used these data to develop a mathematical model to characterize the relationship between PQ blood concentrations and the risk of acquiring a malaria infection. PQ concentrations of 6.7 and 20 ng/ml were found to reduce the risk of acquiring a malaria infection by 50 and 95%, respectively. The model was used to predict the expected outcome in vulnerable populations such as children and pregnant women living in malaria endemic areas. A randomized, placebo-controlled trial conducted on the northwest border of Thailand compared malaria chemoprevention with monthly or bimonthly standard 3-day treatment regimens of dihydroartemisinin-piperaquine. Healthy adult male subjects (N = 1000) were followed weekly during 9 months of treatment. Using nonlinear mixed-effects modeling, the concentration-effect relationship for the malaria-preventive effect of piperaquine was best characterized with a sigmoidal Emax relationship, where plasma concentrations of 6.7 ng/ml [relative standard error (RSE), 23%] and 20 ng/ml were found to reduce the hazard of acquiring a malaria infection by 50% [that is, median inhibitory concentration (IC50)] and 95% (IC95), respectively. Simulations of monthly dosing, based on the final model and published pharmacokinetic data, suggested that the incidence of malaria infections over 1 year could be reduced by 70% with a recently suggested dosing regimen compared to the current manufacturer’s recommendations for small children (8 to 12 kg). This model provides a rational framework for piperaquine dose optimization in different patient groups.
Present-day uplift of the western

Collisional mountain belts grow as a consequence of continental plate convergence and eventually disappear under the combined effects of gravitational collapse and erosion. Using a decade of GPS data, we show that the western Alps are currently characterized by zero horizontal velocity boundary conditions, offering the opportunity to investigate orogen evolution at the time of cessation of plate convergence. We find no significant horizontal motion within the belt, but GPS and levelling measurements independently show a regional pattern of uplift reaching ~2.5 mm/yr in the northwestern Alps. Unless a low viscosity crustal root under the northwestern Alps locally enhances the vertical response to surface unloading, the summed effects of isostatic responses to erosion and glaciation explain at most 60% of the observed uplift rates. Rock-uplift rates corrected from transient glacial isostatic adjustment contributions likely exceed erosion rates in the northwestern Alps. In the absence of active convergence, the observed surface uplift must result from deep-seated processes. The western Alps, the highest topography of Europe, formed during Oligocene-Miocene times, as a consequence of the convergence and indentation of the Adriatic microplate toward Europe 1 . As much as 280 km of shortening was accommodated by underthrusting of the European margin beneath the Adriatic microplate 1–3 . This process resulted in crustal thickening, nappe stacking, and exhumation of crystalline basement, contributing to the building of the present-day topography. During the last million year, the end of active subduction in the Apennines 4 led to a change of the regional plate-kinematics, with the progressive development of extension in the core of the Apennines and counter-clockwise rotation of the Adriatic micro-plate 5 . A decade of continuous GPS measurements show that, with respect to the Alpine foreland, the GPS sites in the western Po plain have an averaged residual motion of 0.1 mm/yr and provide an upper bound of 0.3 mm/yr (95% confidence level) for possible right-lateral strike slip motion across the western Alps (Supplementary Information). Similarly, south of the western Alps, sites in Corsica and Sardinia show less than 0.4 mm/yr of shortening with respect to the southern western Alps 6 . Therefore, the western Alps is presently a mountain range with virtually zero horizontal velocity boundary conditions, offering a unique opportunity to evaluate the contribution of processes unrelated to horizontal tectonics to the evolution of orogens. In addition to continuous GPS data, we use levelling data spanning a century in order to study the present-day vertical motion in the western Alps and its surroundings. We show in the Supplementary Information that both data sets have an average internal precision of 0.2 mm/yr and are mutually consistent at a level of 0.3 mm/yr over the studied area. GPS sites located west of the Alpine foreland all show zero vertical rates (± 0.2 mm/yr) and therefore define a stable reference frame that we use to express regional vertical rates.
Prediction with Limited Advice and Multiarmed Bandits with Paid Observations

We study two problems of online learning under restricted information access. In the first problem, prediction with limited advice, we consider a game of prediction with expert advice, where on each round of the game we query the advice of a subset of M out of N experts. We present an algorithm that achieves O(√N/M T ln N) regret on T rounds of this game. The second problem, the multiarmed bandit with paid observations, is a variant of the adversarial N-armed bandit game, where on round t of the game we can observe the reward of any number of arms, but each observation has a cost c. We present an algorithm that achieves O((cN lnN)1/3 T2/3 + √T lnN) regret on T rounds of this game in the worst case. Furthermore, we present a number of refinements that treat arm- and time-dependent observation costs and achieve lower regret under benign conditions. We present lower bounds that show that, apart from the logarithmic factors, the worst-case regret bounds cannot be improved.
Association of CFH, LOC387715, and HTRA1 polymorphisms with exudative age-related macular degeneration in a northern Chinese population

Purpose Variants in complement factor H (CFH), the hypothetical LOC387715, and the high-temperature requirement A-1 (HTRA1) genes have been reported to be associated with age-related macular degeneration (AMD). The purpose of this study was to investigate the association of reported common single-nucleotide polymorphisms (SNPs) in CFH, LOC387715, and HTRA1 with exudative AMD in a northern Chinese population. Methods A cohort of 121 unrelated patients with exudative AMD and 132 control subjects were enrolled in this study. Genomic DNA was extracted from blood leukocytes. Genotyping for SNPs rs1061170:T>C in CFH (Y402H), rs10490924:G>T in LOC387715 (A69S), and rs11200638:G>A in the promoter of HTRA1 was performed using a polymerase chain reaction (PCR) method followed by allele-specific restriction enzyme digestion and direct sequencing. Results The Y402H variant in CFH was not associated with exudative AMD in our study population. Frequencies of Y402H was 10.3% in AMD cases and 8.0% in controls (p=0.353). Significant associations were detected for exudative AMD with SNPs rs10490924:G>T in LOC387715 (A69S), and rs11200638:G>A in the promoter of HTRA1. The risk T-allele frequency of rs10490924 in LOC387715 was 64.9% in cases versus 43.2% in controls (p<0.001). The odds ratio for risk of AMD was 1.56 (95% CI; 0.80–3.03) for the GT genotype and 5.45 (95% CI; 2.59–11.49) for the TT genotype. The A allele frequency of rs11200638 in the HTRA1 promoter was 67.8% in cases versus 42.4% in controls (p<0.001). The odds ratio was 2.75 (95% CI; 1.34–5.64) for the GA genotype and 7.90 (95% CI; 3.61–17.26) for the AA genotype. An odds ratio of 7.94 (95% CI; 3.49–18.04) was obtained for carriers with both TT genotype in LOC387715 and AA genotype in the HTRA1 promoter. Conclusions Our data suggest that the LOC387715 and HTRA1 polymorphisms are associated with a higher risk of exudative AMD in northern Chinese. We found no association of CFH Y402H with exudative AMD. The low frequency of CFH Y402H variant was further confirmed in this study population.
Pre-diabetes in maternal nutrient reduced baboon offspring

34 Objective: Developmental programming of postnatal pancreatic β-cell and peripheral insulin 35 function by maternal nutrient reduction (MNR) has been extensively investigated in rodents and 36 sheep but no data exist from nonhuman primate offspring of MNR mothers. We hypothesized 37 that moderate levels of MNR would result in developmental programming of post-natal β-cell 38 function and peripheral insulin sensitivity that lead to emergence of a pre-diabetic state prior to 39 puberty. Research Design and Methods: Pre-pregnancy phenotype of 18 non-pregnant 40 baboons was matched. During pregnancy and lactation 12 mothers ate chow ad libitum 41 (controls) while six ate 70% of chow consumed by controls (weight adjusted MNR). Weaned 42 offspring ate normal chow. Results: At 3.5 + 0.18 years (mean ± SEM) in an IV glucose 43 tolerance test, conscious tethered MNR juvenile offspring (two females and four males) showed 44 increased fasting glucose (p < 0.04); fasting insulin (p < 0.04), and insulin area under curve 45 (AUC; p < 0.01) compared with controls (eight females and four males). Insulin AUC also 46 increased following an arginine challenge (p < 0.02). Baseline HOMA insulin β-cell sensitivity 47 were greater in MNR offspring than controls (p < 0.03). In a hyperinsulinemic, euglycemic clamp, 48 glucose disposal rate decreased 26% in MNR offspring. Changes observed were not sex 49 dependent. Conclusions: MNR in pregnancy and lactation programs offspring metabolic 50 responses, increasing insulin resistance and β-cell responsiveness, resulting in emergence of 51 an overall phenotype that would predispose to later life type-2 diabetes especially should other 52 dietary challenges such as a westernized diet be experienced. 53
Hybridizing novelty search for transfer learning

This study investigates the impact of genotypic and behavioral diversity maintenance methods on controller evolution in multi-robot (RoboCup keep-away soccer) tasks. The focus is to examine the impact of these methods on the transfer learning of behaviors, first evolved in a source task before being transferred for further evolution in different but related target tasks. The goal is to ascertain an appropriate controller design (NE: Neuro- Evolution) method for facilitating improved effectiveness given policy transfer between source and target tasks. Effectiveness is defined as the average task performance of transferred behaviors. The study comparatively tests and evaluates the efficacy of coupling policy transfer with several NE variants. Results indicate a hybrid of behavioral diversity maintenance and objective-based search yields significantly improved effectiveness for evolved behaviors across increasingly complex target tasks. Results also highlight the efficacy of coupling policy transfer with the hybrid of behavioral diversity maintenance and objective based search in order to address bootstrapping and deception problems endemic to complex tasks.
Rui-Jin Zhang’s Research on Sediment Transport

Professor, Dept. of Civil Engineering, Indian Institute of Technology Kharagpur, West Bengal 721302, India; Adjunct Professor, Physics and Applied Mathematics Unit, Indian Statistical Institute, Kolkata, West Bengal 700108, India; Distinguished Visiting Professor, Dept. of Hydraulic Engineering, State Key Laboratory of Hydro-Science and Engineering, Tsinghua Univ., Beijing 100084, China. Email: sdey@iitkgp.ac. in
Loss of Synchronized Retinal Phagocytosis and Age-related Blindness in Mice Lacking αvβ5 Integrin

Daily phagocytosis by the retinal pigment epithelium (RPE) of spent photoreceptor outer segment fragments is critical for vision. In the retina, early morning circadian photoreceptor rod shedding precedes synchronized uptake of shed photoreceptor particles by RPE cells. In vitro, RPE cells use the integrin receptor αvβ5 for particle binding. Here, we tested RPE phagocytosis and retinal function in β5 integrin–deficient mice, which specifically lack αvβ5 receptors. Retinal photoresponses severely declined with age in β5−/− mice, whose RPE accumulated autofluorescent storage bodies that are hallmarks of human retinal aging and disease. β5−/− RPE in culture failed to take up isolated photoreceptor particles. β5−/− RPE in vivo retained basal uptake levels but lacked the burst of phagocytic activity that followed circadian photoreceptor shedding in wild-type RPE. Rhythmic activation of focal adhesion and Mer tyrosine kinases that mediate wild-type retinal phagocytosis was also completely absent in β5−/− retina. These results demonstrate an essential role for αvβ5 integrin receptors and their downstream signaling pathways in synchronizing retinal phagocytosis. Furthermore, they identify the β5−/− integrin mouse strain as a new animal model of age-related retinal dysfunction.
HBase + + Extending HBase With Client-Centric Consistency Guarantees for Geo-Replication

Motivated by requirements of the growing social web applications, the necessity to store data across several data centres has become even more important in order to bring data as close to the users as possible. A plethora of non-relational databases raised in recent years in order to address this issue due to their ability to scale out. But in the presence of wide distances, to deliver high-availability and data consistency is not possible in the presence of partitions. Several works have have been developed that try to reach the panacea of consistency and availability, at times sacrificing consistency in other to provide a better service or sacrificing latency to provide strongly consistent data, without taking into account that not all data needs the same consistency and not all data needs to be readily available. To tackle this problem, we propose a consistency model that will reason about data through user defined divergence bounding values, causal relationships and transactional enforcement within the data centre, in order to provide urgency to data in a geo-replication scenario.
Cell Culture of Sporadic Hepatitis E Virus in China

ABSTRACT The isolation and identification of the 87A strain of epidemic hepatitis E virus (HEV) by means of cell culturing have been described previously. This paper reports the successful isolation of a sporadic HEV strain (G93-2) in human lung carcinoma cell (A549) cultures. The etiology, molecular and biological properties, and serological relationship of this new strain to other, epidemic HEV strains are described. The propagation of both sporadic and epidemic HEV strains in a cell culture system will facilitate vaccine research.
Word accent and emotion

In this paper, we address the question whether prosodically/linguistically prominent syllables carrying the word accent (stressed syllables) are better indicators for emotional marking than unstressed syllables. To this aim, we use a large spontaneous database with children interacting with Sony’s Aibo robot, annotated with word-based emotion labels, large acoustic-prosodic feature vectors, and support vector machines as classifiers. It turns out that, in most of the cases, stressed syllables are better emotion markers than unstressed syllables. Moreover, we discuss specific phenomena such as vocatives and other constellations, to be modelled in future studies. Index Terms: emotion, linguistics, paralinguistics, word accent, lexical stress, automatic classification
Limitations of GALDIT to map seawater intrusion vulnerability in a highly touristic coastal area

Coastal aquifers are susceptible to seawater intrusion, especially touristic areas where the overexploitation combined with the agricultural use of groundwater represent a severe issue for water management. GALDIT methodology was applied as a management tool to identify and prevent salinization of the aquifer. GALDIT methodology needs six input parameters: groundwater occurrence (G), aquifer hydraulic conductivity (A), groundwater head above sea level (L), distance from the shore (D), impact of the existing status of seawater intrusion (I), and thickness of the aquifer (T). Then a contour map is created using three degree of vulnerability: high, medium and low. The higher vulnerability zone ranges from 40 to 550 m towards the mainland with the rest of the aquifer characterized by medium vulnerability. The main problem affecting the selected field site is the large water requirement during the summer period due to the touristic activities, but the correct use of surplus water collected in the winter can overcome this problem. This study demonstrates that further investigation on groundwater hydrochemistry and on water demand trends from the different activities impacting the field site should be implemented, in order to guarantee environmental and touristic development sustainability.
Xylitol, Mutans Streptococci, and Dental Plaque

The authors declare no conflict of interest. The caries-controlling or preventing effect of xylitol is more than just excluding fermentable sugars from the diet. This review aims to discuss the specific effects of xylitol which could have contributed to the results of the caries trials. Xylitol promotes mineralization by increasing the flow of saliva, an effect it has in common with all sweeteners. What is unique for xylitol is that it is practically non-fermentable by oral bacteria. Xylitol is known to inhibit growth, metabolism, as well as polysaccharide production of mutans streptococci. During habitual xylitol consumption, the counts of mutans streptococci decrease and remain on a lower level as long as the consumption lasts. Habitual xylitol consumption also prevents mother-child transmission of mutans streptococci. In addition to growth inhibition, the reduction of insoluble extracellular polysaccharides is probably of importance for the xylitol-induced decrease in both counts and transmission of mutans streptococci.
Pac-man motility of kinetochores unleashed by laser microsurgery

Experiments reveal pac-man motility in kinetochores of X-Y chromosomes, even though their normal behavior is dominated by traction fiber mechanics. A laser microbeam is used to release kinetochores in anaphase from tension. There is a poleward motion of released kinetochores twice as fast as normal and faster than tubulin flux.
Analysis of 12 variants in the development of gastric and colorectal cancers

AIM To evaluate the relation between 12 polymorphisms and the development of gastric cancer (GC) and colorectal cancer (CRC). METHODS In this study, we included 125 individuals with GC diagnosis, 66 individuals with CRC diagnosis and 475 cancer-free individuals. All participants resided in the North region of Brazil and authorized the use of their samples. The 12 polymorphisms (in CASP8, CYP2E1, CYP19A1, IL1A, IL4, MDM2, NFKB1, PAR1, TP53, TYMS, UGT1A1 and XRCC1 genes) were genotyped in a single PCR for each individual, followed by fragment analysis. To avoid misinterpretation due to population substructure, we applied a previously developed set of 61 ancestry-informative markers that can also be genotyped by multiplex PCR. The statistical analyses were performed in Structure v.2. 3.4, R environment and SPSS v.20. RESULTS After statistical analyses with the control of confounding factors, such as genetic ancestry, three markers (rs79071878 in IL4, rs3730485 in MDM2 and rs28362491 in NFKB1) were positively associated with the development of GC. One of these markers (rs28362491) and the marker in the UGT1A1 gene (rs8175347) were positively associated with the development of CRC. Therefore, we investigated whether the joint presence of the deleterious alleles of each marker could affect the development of cancer and we obtained positive results in all analyses. Carriers of the combination of alleles RP1 + DEL (rs79071878 and rs28361491, respectively) are at 10-times greater risk of developing GC than carriers of other combinations. Similarly, carriers of the combination of DEL + RARE (rs283628 and rs8175347) are at about 12-times greater risk of developing CRC than carriers of other combinations. CONCLUSION These findings are important for the comprehension of gastric and CRC development, particularly in highly admixed populations, such as the Brazilian population.