Miracle-dz/UniFAR-FTUs huggingface dataset:
ADAN: a database for prediction of protein-protein interaction of modular domains mediated by linear motifs

MOTIVATION Most of the structures and functions of proteome globular domains are yet unknown. We can use high-resolution structures from different modular domains in combination with automatic protein design algorithms to predict genome-wide potential interactions of a protein. ADAN database and related web tools are online resources for the predictive analysis of ligand-domain complexes. ADAN database is a collection of different modular protein domains (SH2, SH3, PDZ, WW, etc.). It contains 3505 entries with extensive structural and functional information available, manually integrated, curated and annotated with cross-references to other databases, biochemical and thermodynamical data, simplified coordinate files, sequence files and alignments. Prediadan, a subset of ADAN database, offers position-specific scoring matrices for protein-protein interactions, calculated by FoldX, and predictions of optimum ligands and putative binding partners. Users can also scan a query sequence against selected matrices, or improve a ligand-domain interaction. AVAILABILITY ADAN is accessible at http://adan-embl.ibmc. umh.es/ or http://adan.crg. es/.
A Phonological analysis of a deaf Parkinsonian signer

Abstract The study of deaf signers with distinct motor disorders can provide clues to the neural substrate underlying language as motor behaviour. Moreover, since the structure of intended limb movement targets can be so clearly specified in sign language, such studies provide as well an important new vehicle for illuminating the functional properties of the motor systems of the brain. This investigation brings to bear recent theoretical models of phonological representation of American Sign Language (ASL) on an analysis of the signing deficits of a deaf signer with Parkinson's disease. We provide a detailed analysis of this subject's particular profile of phonological and phonetic disturbances in ASL in order to (1) clarify the fine motor disruptions of the limbs during the production of sign language caused by Parkinson's disease, and (2) refine models of ASL phonology. The disturbances in the subject's signing can be characterised by reductions and timing disruptions that include distalisation of movem.
FGF19 promotes epithelial-mesenchymal transition in hepatocellular carcinoma cells by modulating the GSK3β/β- catenin signaling cascade via FGFR4 activation

Compelling evidence suggests that the epithelial-mesenchymal transition (EMT) correlates with aggressiveness of tumors and poor survival. FGF19 has been shown to be involved in EMT in cholangiocarcinoma and colorectal cancer, however, molecular mechanisms underlying FGF19-induced EMT process in hepatocellular carcinoma (HCC) remain largely unknown. Here, we show the expression of FGF19 is significantly elevated and negatively associated with the expression of E-cadherin in HCC tissues and cell lines. Ectopic FGF19 expression promotes EMT and invasion in epithelial-like HCC cells through repression of E-cadherin expression, whereas FGF19 knockdown enhances E-cadherin expression and hence diminishes EMT traits in mesenchymal-like HCC cells, suggesting FGF19 exerts its tumor progressing functions as an EMT inducer. Interestingly, depletion of FGF19 cannot abrogate EMT traits in the presence of GSK3β inhibitors. Furthermore, FGF19-induced EMT can be markedly attenuated when FGFR4 is knocked out. These observations clearly indicate that FGFR4/GSK3β/β-catenin axis may play a pivotal role in FGF19-induced EMT in HCC cells. As FGF19 and its specific receptor FGFR4 are frequently amplified in HCC cells, selective targeting this signaling node may lend insights into a potential effective therapeutic approach for blocking metastasis of HCC.
Regulation of Signaling Protein Function and Trafficking by the hsp90/hsp70-Based Chaperone Machinery 1

Nearly 100 proteins are known to be regulated by hsp90. Most of these substrates or “client proteins” are involved in signal transduction, and they are brought into complex with hsp90 by a multlprotein hsp90/hsp70-based chaperone machinery. In addition to binding substrate proteins at the chaperone site(s), hsp90 binds cofactors at other sites that are part of the heterocomplex assembly machinery as well as immunophllins that connect assembled substrate·hsp90 complexes to protein-trafficking systems. In the 5 years since we last reviewed this subject, much has been learned about hsp90 structure, nucleotide-binding, and cochaperone interactions; the most important concept is that ATP hydrolysis by an intrinsic ATPase activity results in a conformational change in hsp90 that is required to induce conformational change in a substrate protein. The conformational change induced in steroid receptors is an opening of the steroid-binding cleft so that it can be accessed by steroid. We have now developed a minimal system of five purified proteins—hsp90, hsp70, Hop, hsp40, and p23—that assembles stable receptor·hsp90 heterocomplexes. An hsp90·Hop·hsp70·hsp40 complex opens the cleft in an ATP-dependent process to produce a receptor·hsp90 heterocomplex with hsp90 in its ATP-bound conformation, and p23 then interacts with the hsp90 to stabilize the complex. Stepwise assembly experiments have shown that hsp70 and hsp40 first interact with the receptor in an ATP-dependent reaction to produce a receptor·hsp70·hsp40 complex that is “primed” to be activated to the steroid-binding state in a second ATP-dependent step with hsp90, Hop, and p23. Successful use of the five-protein system with other substrates Indicates that it can assemble signal protein-hsp90 heterocomplexes whether the substrate is a receptor, a protein kinase, or a transcription factor. This purified system should facilitate understanding of how eukaryotlc hsp70 and hsp90 work together as essential components of a process that alters the conformations of substrate proteins to states that respond in signal transduction.
Constructions and Grammatical Explanation: Comments on Goldberg

No one denies that the development of a biological organism is highly constrained by properties of the organism’s genetic endowment. This is obvious for gross physical properties such as number of limbs, but it holds also for cognitive properties, such as the capacity to perform dead reckoning calculations (see, e.g. Gallistel, 1999 on insect navigation), the capacity of a bird species to learn its own song, even when there are many other bird songs in the environment (Marler, 1991), or constraints on the capacity to cognitively represent space in rats (Cheng, 1986). Reading the literature in Construction Grammar (hence CxG), it appears that proponents of that approach are, in Quine’s phraseology, ‘knowingly and cheerfully up to [their] neck[s] in innate mechanisms of learning readiness’ (Quine, 1969). Indeed, going well beyond this, in her 2006 book, Adele Goldberg identifies many different nonlinguistic but innate cognitive constraints on both learning and representation, which are brought to bear in language learning, comprehension and production: abilities to make statistical generalisations, cognitively represented semantic structures and pragmatic strategies, general cognitive relations between form and meaning such as iconicity, and constraints on processing information and structure (Goldberg, 2006). To this we might add human-specific special social cognitive capacities (Tomasello, 2003) as well as more general capacities connected to memory and abstraction. The CxG hunch is that, although the human mind is teeming with innate cognitive capacities, none of these are specific to language: that is, every capacity that is used in acquiring language has a function elsewhere in human cognition. This proposal comes in a weak and a strong form. The strong form denies that human cognition is specialised for language: that is, there is no specific subset of particular capacities such that the human mind is configured to bring just these to bear when acquiring language. The strong form denies the existence of a faculty of language tout court. To clarify, imagine that the brain has a number of innate cognitive capacities used for various tasks (call these C, and assume nothing
Comment on Randall Collins/1. An Approach to Violence

How explain macro trends in violence, such as historical shifts in rates of crime, while using a micro-theory of situational interaction? Wieviorka argues that the world-wide rise in crime rates since the 1960s resulted from the combination of a macro cause—the breakdown of regulated and limited class conflict—plus a micro process of individual meaninglessnes, so that violence became the new means of constructing identities. Wieviowka’s theory clashes with evidence that on the micro level, humans are not proficient at violence. Violence is largely shaped by an emotional barrier of confrontational tension/fear [ct/f], so that most conflict goes no further than blustering gestures and words. Violence is messy, imprecise, and atrocious, because it happens only when local conditions allow pathways to circumvent ct/f. But how can this theory explain rising or falling macro-trends in violence? Interactional techniques are invented: such as football hooligans style of overwhelming police by maneuvering to assemble where they have huge local superiority of numbers; or another kind of technique, the clandestine approach to delivering a close attack by a suicide bomber. These techniques can be charted as they spread from one place to another. To complete the picture, authorities’ counter-techniques of violence control also evolve and spread; the balance between these two sides results in the historical macro-trends of violence.
Clinical pharmacology of oral all-trans retinoic acid in patients with acute promyelocytic leukemia.

All-trans retinoic acid (RA) induces leukemic cell differentiation and complete remission in a high proportion of patients with acute promyelocytic leukemia (APL). However, remissions induced by all-trans RA tend to be brief, and relapses are associated with resistance to further treatment in vivo, although the leukemic cells appear to retain sensitivity to the cytodifferentiating effects of all-trans RA in vitro. The clinical pharmacology of all-trans RA was examined in 13 patients with APL. The drug was administered at a constant dose of 45 mg/m2/day, given as a single dose on the first day of therapy and in two divided doses thereafter. Plasma and urinary concentrations of the parent drug and metabolites were quantitated by reverse-phase high-performance liquid chromatography and, where required, by a combination of normal-phase liquid chromatography/negative chemical ionization mass spectrometry. In patients with APL, basal levels of endogenous retinol and natural retinoids were within the normal range. Peak plasma levels of all-trans RA (347 +/- 266 ng/ml, mean +/- SD) were reached 1-2 h after drug ingestion and decayed in a monoexponential fashion with a half-life of 0.8 +/- 0.1 h. The only drug metabolite detected in plasma or urine was 4-oxo-all-trans RA (present in urine as the glucuronide conjugate). This metabolite accounted for less than 10% of the circulating drug in plasma, and its cumulative urinary excretion accounted for less than 1% of the administered dose. The drug was not found in cerebrospinal fluid. Continued oral administration of all-trans RA was associated with a significant decrease in both the plasma peak levels and the area under the concentration-time curve (P = 0.01 and 0.004, respectively) when measured after 2-6 weeks of treatment. We previously reported that a decrease in plasma area under the concentration-time curve was highly correlated with clinical relapse. Observations in a subset of patients in this study suggested that, in fact, the major decrease occurred early, within the first 7 days of treatment. These changes were associated with a 10-fold increase in urinary excretion of 4-oxo-all-trans RA glucuronide, suggesting that the accelerated clearance from plasma was associated with increased drug catabolism. The rapid disappearance may explain early relapse from remissions induced by all-trans RA; clinical "resistance" to all-trans RA may either wholly or in part result from an inability to sustain effective plasma concentrations of all-trans RA during continuous treatment. (ABSTRACT TRUNCATED AT 400 WORDS)
Qualités des dossiers universitaires : analyse d’un programme de formation en enseignement

Cette etude presente une lecture des dossiers academiques d’etudiants ayant complete une formation universitaire en education prescolaire et en enseignement primaire afin de verifier la validite et la fiabilite des evaluations realisees durant cette formation. L'importance de facteurs tels que la cote de rendement au college des etudiants, l'equivalence entre deux campus universitaires et les annees de diplomation, ainsi que l’equite entre le genre et l'âge des etudiants est egalement investiguee. La base de donnees se compose des dossiers academiques de 873 finissants du programme d'education prescolaire et d’enseignement primaire ayant gradue entre 2006 et 2012 dans l'un ou l'autre des deux campus de l'Universite du Quebec a Rimouski. Les resultats de l’analyse factorielle suggerent que les notes ne sont pas le produit d’un processus arbitraire et aleatoire. Ainsi, l’ensemble des notes aux cours du programme, telles qu’elles apparaissent dans le dossier academique des etudiants, se structure en facteurs qui permettent d’inferer, tel qu’attendu, la mesure de groupes de competences interreliees. L’ensemble possede une bonne fiabilite. Des regressions multiniveaux montrent que la cote de rendement au college est un bon predicteur de la moyenne cumulative et qu’il y a equivalence en fonction du campus d’etudes et de l’annee de diplomation. Cependant, il subsiste de legeres iniquites dans la moyenne cumulative en fonction de l’âge et du genre de l’etudiant, iniquites qui ne sont pas liees aux succes academiques anterieurs.
Practical implementation of adaptive friction compensation based on partially identified LuGre model

We present implementation of the proposed adaptive control algorithm working together with a partially identified LuGre friction model to improve performance of linear permanent magnet motor servo. Experimental verification of the system operation is described. We discuss in detail identification of the model parameters, we describe necessary tests and comment on the model accuracy. We give detailed information about control system parameter tuning and we discuss the effect of measurement errors and numerical limitations of a discrete controller on the system performance. We investigate effects of parameter variations on the obtained tracking accuracy for different desired position trajectories.
Vulnerability in high-functioning persons aged 65 to 70 years : the importance of the fear factor Aging Clinical and Experimental Research

Background and aims: Falls efficacy has been shown to predict functional decline, but whether it is independently associated with frailty is still unclear. This study investigated the cross-sectional association between falls efficacy and the frailty phenotype in high-functioning older persons. Methods: Subjects (n=861) were a sub-sample of community-dwelling persons aged 65 to 70 years enrolled in the “Lc65+” cohort, who had gait assessment. Data included demographics, functional, cognitive, affective and health status, as well as measures of physical performance. Falls efficacy was measured with the Falls Efficacy Scale-International (FES-I) and frailty with Fried’s criteria. Participants were categorized into robust (no frailty criterion) and vulnerable (1 or more criteria). Low falls efficacy was defined as a FES-I score in the lowest quartile. Results: Overall, 23.9% of participants were vulnerable. Compared with robust participants, they were more likely to report low falls efficacy (43.3% vs 19.1%, p<0.001) and had poorer health and functional and mental status. They had slower gait speed (1.07±0.18 vs 1.15±0.15 m/s, p<0.001) and increased gait speed variability (coefficient of variation 4.10±4.03 vs 3.33±1.45%, p<0.001), although only 6 participants (0.7%) fulfilled Fried’s slow walking criterion. In multivariate analysis, low falls efficacy remained associated with being vulnerable (adjusted OR 1.80, 95% CI 1.19-2.74, p=0.006), independent of comorbidity, functional status, falls history and gait performance. Conclusion: In high-functioning older persons, low falls efficacy was associated with vulnerability, even after controlling for gait performance and falls history. Whether low falls efficacy is a potential target on the pathway leading to frailty should be further examined prospectively. (Aging Clin Exp Res 2010; 22: 212-218) ©2010, Editrice Kurtis
Identifying the sources of unpredictability in COTS-based multicore systems

COTS-based multicores are now the preferred choice for hosting embedded applications owing to their immense computational capabilities, small form factor and low power consumption. Many of these embedded applications have real-time requirements and real-time system designers must be able assess them for their predictability and provide guarantees (at design time) that they deliver the correct functional behavior within predefined time bounds. However, the underlying architecture of commercially available multicores is extremely complex and non-amenable to straight-forward timing analysis. In this paper, we highlight the architectural features leading to temporal unpredictability, which mainly involve shared hardware resources, such as buses, caches, and memories. We explore some of the existing work in timing analysis with respect to these features, identify their limitations, and present some unaddressed issues that must be dealt with to ensure safe deployment of real-time systems.
Non-Euclidean Navigational Strategies of Women: Compensatory Response or Evolved Dimorphism?

The proposition underlying this study was that females' use of topographical, rather than Euclidean navigational strategies emanate from a separate evolved mechanism rather than a compensatory response due to lesser Euclidean abilities. In support of this contention, it was found that, in terms of ontogenetic development, females' advantages in object location memory emerged during the same age interval as their greater use of a landmark route learning strategy, while the male advantage in Euclidean abilities appeared during the same age interval as their greater use of an orientation route learning strategy.
Bradykinin does not mediate cutaneous active vasodilation during heat stress in humans.

To test the hypothesis that bradykinin effects cutaneous active vasodilation during hyperthermia, we examined whether the increase in skin blood flow (SkBF) during heat stress was affected by blockade of bradykinin B(2) receptors with the receptor antagonist HOE-140. Two adjacent sites on the forearm were instrumented with intradermal microdialysis probes for local delivery of drugs in eight healthy subjects. HOE-140 was dissolved in Ringer solution (40 microM) and perfused at one site, whereas the second site was perfused with Ringer alone. SkBF was monitored by laser-Doppler flowmetry (LDF) at both sites. Mean arterial pressure (MAP) was monitored from a finger, and cutaneous vascular conductance (CVC) was calculated (CVC = LDF/MAP). Water-perfused suits were used to control body temperature and evoke hyperthermia. After hyperthermia, both microdialysis sites were perfused with 28 mM nitroprusside to effect maximal vasodilation. During hyperthermia, CVC increased at HOE-140 (69 +/- 2% maximal CVC, P < 0.01) and untreated sites (65 +/- 2% maximal CVC, P < 0.01). These responses did not differ between sites (P > 0.05). Because the bradykinin B(2)-receptor antagonist HOE-140 did not alter SkBF responses to heat stress, we conclude that bradykinin does not mediate cutaneous active vasodilation.
Play or learning in Early Years curricula? And what about the cultures in which Early Years Education systems are embedded?

In Early Years Education there is a tension between the concepts of ‘play’ and ‘learning’, that is, for the most part, an artefact of the way Early Years discourse is embedded within the discourse of the wider community. Play is held to be essential both as a means of learning and as a route to healthy socio-emotional development, but it is not always reflected in practice and policy. In everyday discourse there is a clear distinction made between play on the one hand (trivial, optional, not assessable) and learning on the other (serious, compulsory, assessable) and the construction of these two as opposites can have a complicating effect on the way the early years curriculum is constructed and read. Subject learning is detailed and prescribed, with clear attainment levels for teachers to work to and assess by. Play activity is child-led rather than teacher-led, and early curricula that embed play activity emphasise very general outcomes, for the very reason that child-led activity is unpredictable. The first two papers in this issue address aspects of this conundrum and the next two demonstrate one way of progressing the debates around play and learning. Evanthia Synodi’s paper is a discussion of the way in which play is represented in the early years curricula of four countries. Her comparative analysis reveals that there is considerable variation between these countries in their implicit definitions of play, and in the way in which play is represented in their curriculum documents. Ken Blaiklock’s paper is set in the context of the New Zealand Te Whāriki curriulum. He discusses the division between the social pedagogic and primary curricular approach to Early Years Education, and raises the issue of whether subject content can sometimes get lost in a holistic curriculum. His paper illustrates the challenges that can arise from attempts to embed play activity in the early years curriculum, and the questions that he raises about the assessment of quality will undoubtedly provoke useful discussion. The debates around prescriptive and holistic curricula raise important issues about the education and training of the Early Years workforce, because a holistic curriculum relies on a knowledgeable workforce for its delivery. In order to work without prescriptive yardsticks, teachers and early years practitioners must know about all aspects of learning and be able to judge individual children’s needs against their own history of progression. There is something of a trade-off between the detail and prescription of a nation’s early years curriculum, on the one hand, and the knowledge of its early years workforce, on the other. While the previous two papers draw on debates in which play and learning are constructed as opposites, the next two papers show us one way out of the impasse created by such argument. If we observe children systematically, and describe their learning accurately, then it becomes possible to International Journal of Early Years Education Vol. 18, No. 3, September 2010, 183 184