Miracle-dz/UniFAR-FTUs huggingface dataset:
Inactivation of hnRNP K by Expanded Intronic AUUCU Repeat Induces Apoptosis Via Translocation of PKCδ to Mitochondria in Spinocerebellar Ataxia 10

We have identified a large expansion of an ATTCT repeat within intron 9 of ATXN10 on chromosome 22q13.31 as the genetic mutation of spinocerebellar ataxia type 10 (SCA10). Our subsequent studies indicated that neither a gain nor a loss of function of ataxin 10 is likely the major pathogenic mechanism of SCA10. Here, using SCA10 cells, and transfected cells and transgenic mouse brain expressing expanded intronic AUUCU repeats as disease models, we show evidence for a key pathogenic molecular mechanism of SCA10. First, we studied the fate of the mutant repeat RNA by in situ hybridization. A Cy3-(AGAAU)10 riboprobe detected expanded AUUCU repeats aggregated in foci in SCA10 cells. Pull-down and co-immunoprecipitation data suggested that expanded AUUCU repeats within the spliced intronic sequence strongly bind to hnRNP K. Co-localization of hnRNP K and the AUUCU repeat aggregates in the transgenic mouse brain and transfected cells confirmed this interaction. To examine the impact of this interaction on hnRNP K function, we performed RT–PCR analysis of a splicing-regulatory target of hnRNP K, and found diminished hnRNP K activity in SCA10 cells. Cells expressing expanded AUUCU repeats underwent apoptosis, which accompanied massive translocation of PKCδ to mitochondria and activation of caspase 3. Importantly, siRNA–mediated hnRNP K deficiency also caused the same apoptotic event in otherwise normal cells, and over-expression of hnRNP K rescued cells expressing expanded AUUCU repeats from apoptosis, suggesting that the loss of function of hnRNP K plays a key role in cell death of SCA10. These results suggest that the expanded AUUCU–repeat in the intronic RNA undergoes normal transcription and splicing, but causes apoptosis via an activation cascade involving a loss of hnRNP K activities, massive translocation of PKCδ to mitochondria, and caspase 3 activation.
Molecular and Cellular Pathobiology The SUMOE 3-ligase PIAS 1 Regulates the Tumor Suppressor PML and Its Oncogenic Counterpart PML-RARA

The ubiquitin-like SUMO proteins covalently modify protein substrates and regulate their functional properties. In a broad spectrum of cancers, the tumor suppressor PML undergoes ubiquitin-mediated degradation primed by CK2 phosphorylation. Here, we report that the SUMO E3-ligase inhibitor PIAS1 regulates oncogenic signaling through its ability to sumoylate PML and the PML-RARA oncoprotein of acute promyelocytic leukemia (APL). PIAS1-mediated SUMOylation of PML promoted CK2 interaction and ubiquitin/proteasomemediated degradation of PML, attenuating its tumor suppressor functions. In addition, PIAS1-mediated SUMOylation of PML-RARA was essential for induction of its degradation by arsenic trioxide, an effective APL treatment. Moreover, PIAS1 suppression abrogated the ability of arsenic trioxide to trigger apoptosis in APL cells. Lastly, PIAS1 was also essential for PML degradation in non–small cell lung carcinoma (NSCLC) cells, and PML and PIAS1 were inversely correlated in NSCLC cell lines and primary specimens. Together, our findings reveal novel roles for PIAS1 and the SUMOylation machinery in regulating oncogenic networks and the response to leukemia therapy. Cancer Res; 72(9); 2275–84. 2012 AACR.
Aspects of Total Variation Regularized L[sup 1] Function Approximation

The total variation--based image denoising model of Rudin, Osher, and Fatemi [Phys. D, 60, (1992), pp. 259--268] has been generalized and modified in many ways in the literature; one of these modifications is to use the L1 -norm as the fidelity term. We study the interesting consequences of this modification, especially from the point of view of geometric properties of its solutions. It turns out to have interesting new implications for data-driven scale selection and multiscale image decomposition.
Developing psychological capital in a student population

Psychological Capital (PsyCap) is a construct which comprises of four components Optimism, Self-Efficacy, Hope and Resilience. The state-like property of PsyCap suggests that it can be developed through a short training intervention. The aim of this study is to investigate if a Psychological Capital Intervention can enhance PsyCap in a student population. Using a convenience sample, data was collected from 24 students in Dublin Business School. An experimental, mixed within participant and between group design was applied. Participants were randomly assigned to complete either a treatment or control intervention. Levels of PsyCap were assessed pre and post each intervention. Data was analysed using a two-way mixed ANOVA. Results showed a significant increase in PsyCap from Time 1 to Time 2 for both interventions. PsyCap Intervention participants had greater PsyCap at Time 2 than participants in the control group. The results demonstrate the potential for PsyCap development in student populations.
Star Formation-Regulated Growth of Black Holes in Protogalactic Spheroids

The observed relation between central black hole mass and spheroid velocity dispersion is interpreted in terms of a self-regulation model that incorporates a viscous Keplerian accretion disk to feed the black hole, embedded in a massive, self-gravitating star-forming disk that eventually populates the spheroid. The model leads to a constant ratio between black hole mass and spheroid mass that is equal to the inverse of the critical Reynolds number for the onset of turbulence in the accretion disk surrounding the central black hole. Applying the fundamental plane correlation for spheroids, we find that the black hole mass has a power-law dependence on the spheroid velocity dispersion with a slope in the range of 4-5. We interpret the larger scatter in the Magorrian relation with respect to the black hole mass-spheroid velocity dispersion relationship as a result of secular evolution of the spheroid that primarily affects its luminosity and to a much lesser extent its velocity dispersion.
Minimally Invasive Surgery Combined with Regenerative Biomaterials in Treating Intra-Bony Defects: A Meta-Analysis

Background With the popularity of minimally invasive surgery (MIS) in periodontics, numerous publications have evaluated the benefits of MIS with or without various regenerative biomaterials in the treatment of periodontal intra-bony defects. However, it is unclear if it is necessary to use biomaterials in MIS. Thus, we conducted a meta-analysis of randomized clinical trials in patients with intra-bony defects to compare the clinical outcomes of MIS with regenerative biomaterials for MIS alone. Methods The authors retrieved English publications on relevant studies from Cochrane CENTRAL, PubMed, Medline, Embase, Clinical Evidence, and ClinicalTrails.gov (up to June 30, 2015). The main clinical outcomes were the reduction of probing pocket depths (PPDs), gain of clinical attachment level (CAL), recession of gingival margin (REC) and radiographic bone fill. Review Manager 5.2 (Cochrane Collaboration, Oxford, England) was used to calculate the heterogeneity and mean differences of the main clinical outcomes. Results In total, 464 studies in the literature were identified but only four were ultimately feasible. The results showed no significant difference regarding CAL gain (P = 0.32) and PPD reduction (P = 0.40) as well as REC increase (P = 0.81) and radiographic bone fill (P = 0.64) between the MIS plus biomaterials group and the MIS alone group. Conclusions The meta-analysis suggested no significant difference in treatment of intra-bony defects between the MIS plus biomaterials group and the MIS alone group, indicating that it is important to take costs and benefits into consideration when a decision is made about a therapeutic approach. There needs to be an in-depth exploration of the induction of intrinsic tissue healing of MIS without biomaterials to achieve optimal outcomes.
MENINGKATKAN KEMAMPUAN PENALARAN MATEMATIS MELALUI PEMBELAJARAN BERBASIS MASALAH

Kajian ini membahas hasil temuan kemampuan penalaran matematis siswa melalui pembelajaran berbasis masalah dengan desain Kuasi eksperimen Nonequivalent Control Group Design menggunakan teknik Purposive Sampling . Instrumen penelitian ini adalah tes kemampuan penalaran matematis dan lembar observasi yang dilakukan tiga sekolah menengah atas dengan kategori baik, cukup dan kurang di Kabupaten Bima. Analisis data dilakukan dengan menggunakan uji t , uji t' , uji U Mann-Whitney.Hasil penelitian menunjukkan bahwa ada peningkatan kemampuan penalaran matematis siswa melalui pendekatan pembelajaran berbasis masalah pada sekolah kategori baik, cukup dan kurang.
Lower Plasma Ghrelin Levels are Found in Women with Diabetes-Complicated Pregnancies

Objective: To evaluate the associations of glycemic control and gestational age with ghrelin and proinsulin levels in cord blood and mothers’ peripheral blood during pregnancy. Methods: This is a cross-sectional comparative study of twenty-four pregnant women with gestational diabetes (GD), 18 with type 2 diabetes mellitus (T2DM), and 36 without diabetes, as well as their neonates. Levels of proinsulin, ghrelin, and glycated hemoglobin A1c (HbA1c) were measured from maternal blood during the last week before caesarian delivery and in neonatal umbilical cord blood samples. Results: Mothers with GD and T2DM had significantly lower ghrelin levels compared to the healthy mothers (p<0.001). Maternal proinsulin was lower in women with GD than in women without diabetes (p<0.001). Proinsulin was significantly elevated in the neonates of women with GD and in women with HbA1c ≥6.5% (p<0.001). However, maternal ghrelin levels were higher (p=0.031) and neonate proinsulin levels lower in the pre-term offspring of mothers with GD (p=0.033). There was a negative correlation between HbA1c levels and birth weight (r=–0.407, p<0.001). Conclusion: Ghrelin levels were lower in pregnant women with diabetes, although pre-term birth appeared to reverse this trend in GD. Proinsulin levels were also low in pregnant women with diabetes and even lower in pre-term vs. at-term births. Both ghrelin and proinsulin levels were lower in pregnant women with diabetes and HbA1c of <6.5%. Thus, ghrelin participates in the adaptation to the caloric imbalance of diabetic pregnancy and may play a similar role in pregnancy-related complications, since high ghrelin concentrations may be necessary for normal fetal development.
‘Stumbling through’? Relationship-based social work practice in austere times

In recent times relationship-based practice has become a familiar term in social work practice and education. Despite its widespread adoption, how relationship-based practice is understood varies widely. Drawing on contemporary conceptualisations of the child and family and individuals as psychosocial subjects experiencing social suffering, this paper explores how current social work practice can be understood in the context of neoliberalism and austerity. Setting these ideas in an historical context helps to inform our understanding as to why social work seems to be the focus of sustained political discontent and scrutiny, making it difficult to retain a balanced relationship-based professional stance. Contemporary responses to the current challenges of everyday practice are outlined and the contribution of psychodynamic and systemic ideas to promoting relationship-based practice is explored. The paper concludes by considering how the concept of social systems as defences against anxiety can inform our understanding of the resistance amongst practitioners to relationship-based practice and emphasises the importance of reflective spaces and places for developing and maintaining integrated, mature relational approaches to practice which impact on practice at both the individual casework and social structural level.
Comprehending auditory speech: previous and potential contributions of functional MRI

ABSTRACT Functional neuroimaging revolutionised the study of human language in the late twentieth century, allowing researchers to investigate its underlying cognitive processes in the intact brain. Here, we review how functional MRI (fMRI) in particular has contributed to our understanding of speech comprehension, with a focus on studies of intelligibility. We highlight the use of carefully controlled acoustic stimuli to reveal the underlying hierarchical organisation of speech processing systems and cortical (a)symmetries, and discuss the contributions of novel design and analysis techniques to the contextualisation of perisylvian regions within wider speech processing networks. Within this, we outline the methodological challenges of fMRI as a technique for investigating speech and describe the innovations that have overcome or mitigated these difficulties. Focussing on multivariate approaches to fMRI, we highlight how these techniques have allowed both local neural representations and broader scale brain systems to be described.
Intervention Engagement Moderates the Dose–Response Relationships in a Dietary Intervention

Behavioral interventions could lead to changes in behavior through changes in a mediator. This dose–response relationship might only hold true for those participants who are actively engaged in interventions. This Internet study investigated the role of engagement in a planning intervention to promote fruit and vegetable consumption in addition to testing the intervention effect on planning and behavior. A sample of 701 adults (mean = 38.71 years, 81% women) were randomly assigned either to a planning intervention (experimental group) or to one of 2 control conditions (untreated waiting list control group or placebo active control group). Moderated mediation analyses were carried out. Significant changes over time and time × group effects revealed the effectiveness of the intervention. The effect of the intervention (time 1) on changes in behavior (time 3; 1 month after the personal deadline study participants set for themselves to start implementing their plans) was mediated by changes in planning (time 2; 1 week the personal deadline). Effects of planning on behavior were documented only at a moderate level of intervention engagement. This indicates an inverse U-shaped dose–response effect. Thus, examining participants’ intervention engagement allows for a more careful evaluation of why some interventions work and others do not.
Phase space transport in cuspy triaxial potentials: Can they be used to construct self-consistent equilibria?

This paper focuses on the statistical properties of chaotic orbit ensembles evolved in triaxial generalizations of the Dehnen potential which have been proposed recently to model realistic ellipticals that have a strong density cusp and manifest significant deviations from axisymmetry. Allowance is made for a possible supermassive black hole, as well as low-amplitude friction, noise, and periodic driving which can mimic irregularities associated with discreteness effects and/or an external environment. The chaos exhibited by these potentials is quantified by determining (1) how the relative number of chaotic orbits depends on the steepness of the cusp, as probed by γ, the power-law exponent with which density diverges, and MBH, the black hole mass, (2) how the size of the largest Lyapunov exponent varies with γ and MBH, and (3) the extent to which Arnold webs significantly impede phase-space transport, both with and without perturbations. The most important conclusions dynamically are (1) that, in the absence of irregularities, chaotic orbits tend to be extremely‘sticky’, so that different pieces of the same chaotic orbit can behave very differently for times ∼10000tD or more, but (2) that even very low-amplitude perturbations can prove efficient in erasing many – albeit not all – of these differences. The implications of these facts are discussed both for the structure and evolution of real galaxies and for the possibility of constructing approximate near-equilibrium models using Schwarzschild's method. For example, when trying to use Schwarzschild's method to construct model galaxies containing significant numbers of chaotic orbits, it seems advantageous to build libraries with chaotic orbits evolved in the presence of low-amplitude friction and noise, since such noisy orbits are more likely to represent reasonable approximations to time-independent building blocks. Much of the observed qualitative behaviour can be reproduced with a toy potential given as the sum of an anisotropic harmonic oscillator and a spherical Plummer potential, which suggests that the results may be generic.
Risk Averse Behavior in Asymmetric Matching Pennies Games

This paper studies several variants of 2 × 2 games with unique mixed strategy equilibria, which we call asymmetric matching pennies games. In experimental studies of behavior in these games, observed choice frequencies are typically much different from the mixed strategy Nash predictions. This paper reports experimental results for a variety of such games, and shows that a structural econometric model which incorporates risk aversion into a quantal response equilibrium explains the data very well. Moreover, risk aversion estimates are stable across the different games and are close to those obtained from laboratory and field auction data, as well as from individual lottery choice experiments. Our approach also provides a simple test of a model of inequality aversion. A nested model with risk aversion yields estimates of the inequality parameters that are insignificant.
Reconceptualizing foregrounding: Identifying response strategies to deviation in absorbing narratives

The experience of deviation is often referred to as foregrounding and contrasted with the experience of feeling absorbed in a narrative. However, instead of simply assuming that foregrounding and absorption are mutually exclusive, they should also be considered as co-occurring: being absorbed as a result of a deviating aspect of a story. In the present paper we examine the co-occurrence of responses by means of a data-driven qualitative approach. The analysis of interviews about absorbed experiences with written and cinematic fictional narratives focused on occurrences of and responses to perceived deviation. We identified seven strategies in response to deviation that may be described through three underlying dimensions: absorption, agency, and valence. Findings suggest that perceived deviation, rather than obstructing absorption, is associated with intense and meaningful engagement with narratives.
Collateral projections of neurons in laminae I, III, and IV of rat spinal cord to thalamus, periaqueductal gray matter, and lateral parabrachial area

Projection neurons in lamina I, together with those in laminae III–IV that express the neurokinin 1 receptor (NK1r), form a major route through which nociceptive information reaches the brain. Axons of these cells innervate various targets, including thalamus, periaqueductal gray matter (PAG), and lateral parabrachial area (LPb), and many cells project to more than one target. The aims of this study were to quantify projections from cervical enlargement to PAG and LPb, to determine the proportion of spinothalamic neurons at lumbar and cervical levels that were labelled from PAG and LPb, and to investigate morphological differences between projection populations. The C7 segment contained fewer lamina I spinoparabrachial cells than L4, but a similar number of spino‐PAG cells. Virtually all spinothalamic lamina I neurons at both levels were labelled from LPb and between one‐third and one‐half from PAG. This suggests that significant numbers project to all three targets. Spinothalamic lamina I neurons differed from those labelled only from LPb in that they were generally larger, were more often multipolar, and (in cervical enlargement) had stronger NK1r immunoreactivity. Most lamina III/IV NK1r cells at both levels projected to LPb, but few were labelled from PAG. The great majority of these cells in C7 and over one‐fourth of those in L4 were spinothalamic, and at each level some projected to both thalamus and LPb. These results confirm that neurons in these laminae have extensive collateral projections and suggest that different neuronal subpopulations in lamina I have characteristic patterns of supraspinal projection. J. Comp. Neurol. 515:629–646, 2009. © 2009 Wiley‐Liss, Inc.
Exploring the Performance of Service Innovation: Infrastructure Capability and Innovation Orientation Complementarity

This paper examines how firms bundle infrastructure capability and innovation orientation to enhance the service innovation with IT support (SIIT) and its impact on firm's performance outcomes of market performance and financial performance. The result of data gathered from 127 hotel service firms in Vietnam suggest that the impact of SIIT on firm outcomes begins with infrastructure capabilities and innovation orientation, and that the complementarity between these two factors appear to affect SIIT. In addition, market performance mediates the relationship between SIIT and financial performance.
Apical Sealing Ability of a Novel Material: Analysis by Fluid Filtration Technique.

AIM The aim of this study is to evaluate the sealing ability of Biodentine(TM), which is new calcium-silicate based dental cement and has endodontic indications similar to those of MTA. METHODS The study sample consists of 21extracted human mandibular anterior teeth. The teeth were submitted to root-end preparation and instrumented up to file #40 by step back technique and randomly divided into 3 study groups (n=7): White MTA Angelus(TM) (Angelus, Angelus Odontológica, Londrina, PR, Brazil), Biodentine(TM) (Septodont, SeptodontSpecialités, Saint-MaurdesFosses, France) and the controls. The length of dye penetration between the filling material and tooth structure was measured in millimetres, using a calibrated stereo microscope (Leica MZ75, Germany) at 20× magnification under the same conditions. One-way Analysis of Variance (ANOVA) was used to indicate differences between the experimental groups and the controls. In addition, Tukey Multiple Comparisons Test was used to indicate differences within each group. RESULTS The results showed that none of the groups were completely sealed. The mean and standard deviation for dye penetration in Biodentine(TM) group was 0.63±0.20 and in MTA Angelus(TM) group, it was 0.26±0.25. Regarding the comparisons between each group, significant differences were not observed (P=0.0193). The comparison between materials only found a significant difference only between MTA Angelus(TM) and Biodentine(TM) (P<0.05). CONCLUSIONS This study evaluated the possibility of Biodentine(TM)'s sealing ability and marginal adaptation, since no studies are available on Biodentine. However, further in vitro and in vivo investigations should be conducted to determine the suitability of Biodentine(TM) for clinical application.