Miracle-dz/UniFAR-FTUs huggingface dataset:
Transactivation of the EGR1 Gene Contributes to Mutant p53 Gain of Function

Tumor-associated mutants of the p53 tumor suppressor protein exert biological activities compatible with an oncogenic gain of function. To explore the underlying molecular mechanism, we performed microarray analysis, comparing p53-null cells to mutant p53-expressing cells. One of the genes up-regulated in the presence of mutant p53 was EGR1, a transcription factor implicated in growth control, apoptosis, and cancer. EGR1 induction by various types of stress is markedly augmented in cells expressing mutant p53. Moreover, chromatin immunoprecipitation analysis indicates that mutant p53 is physically associated with the EGR1 promoter. Functional assays indicate that induction of EGR1 by mutant p53 contributes to enhanced transformed properties and resistance to apoptosis. We propose that EGR1 is a significant contributor to mutant p53 gain of function.
Structural Features Determining Differential Receptor Regulation of Neuronal Ca Channels

Dihydropyridine-insensitive Ca channels are subject to direct receptor G-protein-mediated inhibition to differing extents. α1B channels are much more strongly modulated than α1E channels. To understand the structural basis for this difference, we have constructed and expressed various α1Band α1E chimeric Ca channels and examined their regulation by κ-opioid receptors. Replacement of the first membrane-spanning domain of α1E with the corresponding region of α1B resulted in a chimeric Ca channel that was modulated by κ-opioid receptors to a significantly greater extent than α1E. Transfer of the N terminus and I/II loop from α1B in addition to domain I resulted in a chimeric channel that was modulated to the same extent as α1B. Other regions of the molecule do not appear to contribute significantly to the degree of inhibition obtained, although the C terminus may contribute to facilitation.
Alterations of Intrinsic Brain Connectivity Patterns in Depression and Bipolar Disorders: A Critical Assessment of Magnetoencephalography-Based Evidence

Despite being the object of a thriving field of clinical research, the investigation of intrinsic brain network alterations in psychiatric illnesses is still in its early days. Because the pathological alterations are predominantly probed using functional magnetic resonance imaging (fMRI), many questions about the electrophysiological bases of resting-state alterations in psychiatric disorders, particularly among mood disorder patients, remain unanswered. Alongside important research using electroencephalography (EEG), the specific recent contributions and future promise of magnetoencephalography (MEG) in this field are not fully recognized and valued. Here, we provide a critical review of recent findings from MEG resting-state connectivity within major depressive disorder (MDD) and bipolar disorder (BD). The clinical MEG resting-state results are compared with those previously reported with fMRI and EEG. Taken together, MEG appears to be a promising but still critically underexploited technique to unravel the neurophysiological mechanisms that mediate abnormal (both hyper- and hypo-) connectivity patterns involved in MDD and BD. In particular, a major strength of MEG is its ability to provide source-space estimations of neuromagnetic long-range rhythmic synchronization at various frequencies (i.e., oscillatory coupling). The reviewed literature highlights the relevance of probing local and interregional rhythmic synchronization to explore the pathophysiological underpinnings of each disorder. However, before we can fully take advantage of MEG connectivity analyses in psychiatry, several limitations inherent to MEG connectivity analyses need to be understood and taken into account. Thus, we also discuss current methodological challenges and outline paths for future research. MEG resting-state studies provide an important window onto perturbed spontaneous oscillatory brain networks and hence supply an important complement to fMRI-based resting-state measurements in psychiatric populations.
What constitutes effective support in obtaining and maintaining employment for individuals with intellectual disability? A scoping review

ABSTRACT Background: Employment rates for Australians with an intellectual disability remain low. Effective evidence-based strategies are required to guide future interventions, to enable people with intellectual disability achieve better employment outcomes. Methods: A literature search of peer-reviewed articles published between 2001 and 2015 was conducted using four electronic databases. Articles were reviewed and sorted according to employment setting and type of support provided. Results: Twenty-two studies were identified. Four studies of open employment examined workplace level strategies and 17 investigated individual level strategies. A single study of supported employment examined individual level change. Results suggested potential strategies that can be utilised to support people with intellectual disability obtain and maintain employment. Conclusions: Existing evidence regarding open employment for people with intellectual disabilities could be enhanced through the conduct of rigorous outcomes-focused studies that attend to specific strategies at both individual and organisation levels.
Symptom severity is more closely associated with social functioning status in inpatients with schizophrenia than cognitive deficits

Background Prior research has determined that impairment in neurocognition and psychiatric symptoms contribute to reduced occupational and social functioning in schizophrenia. Objective Evaluate the relationships of neurocognition, psychiatric symptoms, and psychosocial functioning in male inpatients with schizophrenia in China. Methods Fifty-one male patients currently hospitalised at the Shanghai Mental Health Center with a diagnosis of schizophrenia were recruited and 40 of them were included in the final analysis. Participants were assessed with Chinese versions of the Personal and Social Performance Scale (PSP), Clinical Global Impression-Severity (CGI-S) scale, Positive and Negative Symptom Scale (PANSS), Letter-Number Sequencing Task, and Hong Kong List Learning Test. Results Robust negative correlations were found between three clinical subscale scores derived from the PANSS and the global measures of social function (the total PSP score and the CGI-S score). Performance on the neurocognitive tasks was not associated with either symptoms or social functioning status. Conclusions Among inpatients in the acute phase of schizophrenia, the severity of the clinical symptoms—not the degree of the neurocognitive impairment—is closely associated with the level of social functioning.
Maximum likelihood estimation of Gaussian graphical models : Numerical implementation and topology selection

We describe algorithms for maximum likelihood estimation of Gaussian graphical models with conditional independence constraints. It is well-known that this problem can be formulated as an unconstrained convex optimization problem, and that it has a closed-form solution if the underlying graph is chordal. The focus of this paper is on numerical algorithms for large problems with non-chordal graphs. We compare different gradient-based methods (coordinate descent, conjugate gradient, and limited-memory BFGS) and show how problem structure can be exploited in each of them. A key element contributing to the efficiency of the algorithms is the use of chordal embeddings for the fast computation of gradients of the log-likelihood function. We also present a dual method suited for graphs that are nearly chordal. In this method, results from matrix completion theory are applied to reduce the number of optimization variables to the number of edges added in the chordal embedding. The paper also makes several connections between sparse matrix algorithms and the theory of normal graphical models with chordal graphs. As an extension we discuss numerical methods for topology selection in Gaussian graphical models.
A study of the guidance counselling needs of adults with dyslexia within the Irish adult educational guidance service

A Study of the Guidance Counselling Needs of Adults with Dyslexia within the Irish Adult Educational Guidance Service, by Petra Elftorp Guidance counselling is identified in policy discourse as an important supporting structure for adults who experience social injustice and barriers in their education and career progression (OECD 2004; SOLAS 2014). To date, social justice debates in the guidance counselling field have primarily focused on gender, socioeconomic class and ethnicity (Reid 2016). However, this current study broadens this discourse to include disabilities such as dyslexia, as adults with dyslexia often face disproportionate barriers and inequalities in relation to their personal/social, educational and career development (Mooney and O’Rourke 2017). Therefore, this study addresses an identified knowledge gap which relates to the contextualised experiences of adults with dyslexia within the Further Education and Training (FET) sector in Ireland. The aim of this study is to investigate the guidance counselling needs of adults with dyslexia within the Irish Adult Educational Guidance Service (AEGS) in order to inform future policy and practice. Critical pragmatism underpins this study, where the focus is on practical problems and human experience, and it has the advantages of allowing for a flexible and reflexive methodology (Dewey 1973; Morgan 2014). This qualitatively-led sequential mixed methods study was conducted in two phases. First, the perceptions and experiences of AEGS guidance counsellors were gathered through an online questionnaire and analysed using descriptive statistics. In Phase 2, semi-structured face-to-face interviews were conducted with 14 dyslexic adults about their experiences, which was subject to thematic analysis. The findings were then synthesised and a number of core issues emerged which relate to identity and recognition, barriers and facilitating factors to the educational and career development of adults with dyslexia and guidance counselling provision to this cohort. Based on these empirical findings, an Irish framework for practice is presented. This framework draws on the World Health Organisation (WHO) (2011) model of disabilities where barriers and enablers to personal/social, educational and career progression are identified on three interlinked levels: biological, psychological and social. Additionally, identified guidance counselling needs and appropriate interventions for clients with dyslexia are outlined. The findings have implications for policy, practice and research, specifically in relation to the need to address the identified variations of knowledge about dyslexia, experiences of misrecognition, and the limited access to assessment services, support and reasonable accommodations. Finally, a number of recommendations for policy, practice and research conclude this thesis.
Reducing the Symptomatology of Panic Disorder: The Effects of a Yoga Program Alone and in Combination with Cognitive-Behavioral Therapy

Introduction: Yoga is a holistic system of different mind–body practices that can be used to improve mental and physical health. It has been shown to reduce perceived stress and anxiety as well as improve mood and quality of life. Research documenting the therapeutic benefits of yoga has grown progressively for the past decades and now includes controlled trials on a variety of mental health conditions such as depression, anxiety, and panic disorder. Objectives: The primary goal of this study was to investigate the effects of yoga in patients suffering from panic disorder. We aimed at observing the efficacy of yoga techniques on reducing the symptomatology of panic disorder (anxiety and agoraphobia), compared to a combined intervention of yoga and psychotherapy. Method: Twenty subjects previously diagnosed with panic disorder were selected. Subjects were randomly assigned to both experimental groups: Group 1 (G1-Yoga: 10 subjects) attended yoga classes and Group 2 (G2-CBT + Yoga: 10 subjects) participated in a combined intervention of yoga practice followed by a cognitive-behavioral therapy (CBT) session. Both interventions occurred weekly for 100 min and lasted 2 months. Subjects were evaluated two times during the study: pre-test and post-test. Psychometric tools included the Beck Anxiety Inventory (BAI), Hamilton Anxiety Rating Scale (HAM-A), The Panic Beliefs Inventory (PBI), and Body Sensations Questionnaire (BSQ). Results: Statistical analysis showed significant reductions in anxiety levels associated with panic disorder (G1: BAI – p = 0.035, HAM-A – p = 0.000; G2: BAI – p = 0.002, HAM-A – p = 0.000), panic-related beliefs (G1: PBI – p = 0.000; G2: PBI – p = 0.000) and panic-related body sensations (G1: BSQ – p = 0.000; G2: BSQ – p = 0.000) both in G1 and G2. However, the combination of yoga and CBT (G2) showed even further reductions in all observed parameters (mean values). Conclusion: This study observed significant improvement in panic symptomatology following both the practice of yoga and the combination of yoga and psychotherapy. While contemplative techniques such as yoga promote a general change in dealing with private events, CBT teaches how to modify irrational beliefs and specific cognitive distortions. The results observed in G2 might indicate that the techniques complemented each other, increasing the intervention efficacy. These findings are in agreement with many investigations found in the literature which observed improvements in different mental health parameters after the practice of contemplative techniques alone or combined to psychotherapy. Future research joining psychological and physiological variables could help better elucidate the mechanisms through which mind-body practices work to improve mental health.
The science of interruption

There has been a steady growth of research into interruption spanning two decades. The first observations indicating that interruptions appeared to be commonplace in busy clinical settings like the emergency department1–5 were soon followed by a potential link between interruptions and clinical error.6 We now know that the act of interruption is pervasive,7–9 perhaps universal, in clinical practice (and indeed most of life). Even apparently quiet and controlled spaces like the operating theatre are home to frequent interruption.10 11 There are now also robust studies demonstrating the sometimes negative impact of interruption on clinical work,12 and in the genesis of error.13–15 Interruption science is thus important in its own right. As importantly, it also provides us with a model for how we can approach the broader study of socio-technical systems in patient safety. The realisations that clinical work is complex, and that safety is an emergent property of local context, are all mirrored in the study of interruption. There is thus much to be learnt from the specific analysis of interruptions for the broader study of clinical work and patient safety. Studying interruptions is, however, challenging.16 17 It is still hard to predict the impact of interventions designed to minimise the effects of interruptions, or even to understand when such interventions are needed. Untangling this nuanced story could take a while, were it not for the work of researchers from other disciplines. Psychology, in particular, has a large corpus of research, often from controlled laboratory studies, that tease apart the mechanics of how interruption disrupts cognition.18 19 The field of human computer interaction (HCI) explores how interruption disrupts the way we interact with technology, how technology design can be interruptive (think pager or mobile phone) and, crucially, how technology can be designed …
The Influence of Zinc Oxide Eugenol (ZOE) and Glass Ionomer (GI) Base Materials on the Microhardness of Various Composite and GI Restorative Materials

Objective: Re-examining the well accepted concept that Zinc-Oxide-Eugenol bases (ZOE) have a negative effect on composite restoration materials microhardness, in light of the advancement in composite materials and newer publications. Methods: Five modern composite restoration materials were used, including hybrid (Xtra-fill and Z250), micro-fill hybrid (G-aenial and Gradia-direct) and methacrylate-free restorative material (Silorane- oxirane). Two base materials were used IRM (ZOE-base) and Fuji-IX (GI-base). Samples were made using a designed mold, in which composite discs were cured on top and in close relation to base materials. Micro-hardness testing was performed using a DMH-2 microhardness tester utilizing the Knoop method. Results: Statistic analysis demonstrated significantly better microhardness of three composite materials when IRM was used as base in comparison to control (G-aenial, Gradia direct and Filtek silorane), and no differences in two materials (Filtek universal Z250 and Voco Xtra-fil). Fuji-IX bases showed a significant positive effect on the microhardness of four composite materials, and a negative effect on one material (Voco Xtra-fill). In comparison with other tested restoration materials, both Voco Xtra-fill and Fuji-IX showed higher microhardness results (P<0.05). Significance: Related to microhardness, both ZOE and GI bases can be used safely as bases under composite restorations. The results of this study together with the results published recently showed that the concept of not using ZOE or GI bases under composite must be reconsidered. Fuji IX showed microhardness results similar to the best composite material and therefore it can be used as a restorative material.
The predictors of foreign-accentedness in the home language of Polish–English bilingual children

We investigated the speech patterns and accentedness of Polish–English bilingual children raised in Great Britain to verify whether their L1 Polish would be perceived as different from that of monolinguals matched for age and socioeconomic status. To this end, Polish-language speech samples of 32 bilinguals and 10 monolinguals (a 3:1 ratio, MAge = 5.79) were phonetically analysed by trained phoneticians and rated by 55 Polish raters, who assessed the degree of native accent, intelligibility, acceptability and perceived age. The results show significant differences in the phonetic performance of bilingual and monolingual children – both in terms of atypical speech patterns uncovered in the phonetic analysis and in terms of the holistic accentedness ratings. We also explored the socio-linguistic predictors of accent ratings in bilingual speech and found that the amount of L1 Polish input was the main predictor of accentedness in children's L1 Polish speech, while L2 English input was marginally significant. (149)
Climatology of Sign Reversals of the Meridional Potential Vorticity Gradient over Africa and Australia

Abstract A 10-yr climatology (1986–95) was performed using ECMWF gridded analyses on isentropic surfaces to identify regions where the lower-tropospheric meridional potential vorticity (PV) gradient changes sign across Africa and Australia during their respective summer seasons. While an African sign reversal has been documented, no similar study has been performed for the Australian region, which also has desert on the poleward side of open ocean. In each hemisphere, a northward decrease of PV is sufficient to produce a sign reversal. It was found that PV decreases northward in the lower troposphere across northern Australia, with the maximum reversal on the 315-K surface. It had comparable magnitude but smaller zonal extent (∼3000 km) than that on the 320-K surface in Africa (∼5000 km). In each region the sign reversal was associated with cyclonic PV anomalies on the equatorward side and anticyclonic anomalies on the poleward side. OLR was used as a proxy for deep convective heating in order to evaluate.
A reappraisal of the allochthonous nature of the Rosenberg slice and Stanbridge Group of southern Quebec and northwestern Vermont

The Ordovician Stanbridge Group of Quebec has long been considered an allochthonous nappe. It is an in- ternally coherent unit that consists of lower slaty limestone overlain by slate, which is correlated with the Highgate and Morses Line formations, respectively, in Vermont. In Quebec, the basal limestones have been inferred to be thrust over Cambrian dolomites (Gorge Formation in Vermont) of the Rosenberg slice, part of the parauthochthonous shelf, although this contact is not exposed there. In the Missisquoi River gorge of Vermont, a conformable sequence of upper Gorge- Highgate-Morses Line formations is exposed. The map distribution of rock units indicates that this conformable relation - ship probably extends up to at least the middle unit of the Stanbridge Group. Therefore, the relationships in Vermont re - quire that the Stanbridge Group must be part of the parauthochthonous Taconic foreland rather than a far-traveled nappe. The Rosenberg slice in Quebec forms a large anticline (Highgate anticline) whose western limb is truncated by the Rosenberg thrust. In Vermont, the anticline is internally cut by the Highgate Falls Thrust, which is an out-of- sequence thrust that decreases in displacement northwards to the International Border. Resume : Le Groupe de Stanbridge au Quebec (Ordovicien) a longtemps ete considere comme une nappe allochtone. Il s'agit d'une unite interne coherente qui comprend un calcaire schisteux inferieur recouvert par de l'ardoise. Ces roches sont correlees respectivement au Vermont avec les formations de Highgate et de Morses Line. Au Quebec, les calcaires de base auraient ete chevauches par-dessus les dolomies cambriennes (la Formation de Gorge au Vermont) du copeau tectonique de Rosenberg, lequel fait partie de la plate-forme parautochtone, bien que ce contact n'affleure pas a cet endroit. Une sequence conforme des formations Gorge-Highgate-Morses Line affleure dans la gorge de la riviere Missis- quoi au Vermont. Sur les cartes, l'etendue des unites rocheuses indique que cette relation concordante s'etend probable- ment au moins jusqu'a l'unite centrale du Groupe de Stanbridge. Les relations au Vermont exigent donc que le Groupe de Stanbridge fasse partie de l'avant-pays parautochtone taconique plutot que d'une nappe provenant de loin. Le copeau tectonique de Rosenberg forme un grand anticlinal au Quebec (anticlinal de Highgate) dont le membre ouest est tron- que par le chevauchement de Rosenberg. Au Vermont, le chevauchement de Highgate Falls recoupe l'interieur de l'anticlinal; ce chevauchement est irregulier et presente un deplacement qui decroit en direction nord vers la frontiere internationale. (Traduit par la Redaction) Schoonmaker and Kidd 169
Distinct Visual Pathways Mediate Drosophila Larval Light Avoidance and Circadian Clock Entrainment

Visual organs perceive environmental stimuli required for rapid initiation of behaviors and can also entrain the circadian clock. The larval eye of Drosophila is capable of both functions. Each eye contains only 12 photoreceptors (PRs), which can be subdivided into two subtypes. Four PRs express blue-sensitive rhodopsin5 (rh5) and eight express green-sensitive rhodopsin6 (rh6). We found that either PR-subtype is sufficient to entrain the molecular clock by light, while only the Rh5-PR subtype is essential for light avoidance. Acetylcholine released from PRs confers both functions. Both subtypes of larval PRs innervate the main circadian pacemaker neurons of the larva, the neuropeptide PDF (pigment-dispersing factor)-expressing lateral neurons (LNs), providing sensory input to control circadian rhythms. However, we show that PDF-expressing LNs are dispensable for light avoidance, and a distinct set of three clock neurons is required. Thus we have identified distinct sensory and central circuitry regulating light avoidance behavior and clock entrainment. Our findings provide insights into the coding of sensory information for distinct behavioral functions and the underlying molecular and neuronal circuitry.