bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychiatry trainees’ views and educational needs regarding the care of patients with a life-limiting illness
Authors: Forster Benjamin C. , Proskurin Helen , Kelly Brian , Lovell Melanie R. , Ilchef Ralf , Clayton Josephine M. 
Published: June 2016

AbstractObjective:People with a life-limiting physical illness experience high rates of significant psychological and psychiatric morbidity. Nevertheless, psychiatrists often report feeling ill-equipped to respond to the psychiatric needs of this population. Our aim was to explore psychiatry trainees’ views and educational needs regarding the care of patients with a life-limiting physical illness.Method:Using semistructured interviews, participants’ opinions were sought on the role of psychiatrists in the care of patients with a life-limiting illness and their caregivers, the challenges faced within the role, and the educational needs involved in providing care for these patients. Interviews were audiotaped, fully transcribed, and then subjected to thematic analysis.Results:A total of 17 psychiatry trainees were recruited through two large psychiatry training networks in New South Wales, Australia. There were contrasting views on the role of psychiatry in life-limiting illness. Some reported that a humanistic, supportive approach including elements of psychotherapy was helpful, even in the absence of a recognizable mental disorder. Those who reported a more biological and clinical stance (with a reliance on pharmacotherapy) tended to have a nihilistic view of psychiatric intervention in this setting. Trainees generally felt ill-prepared to talk to dying patients and felt there was an educational “famine” in this area of psychiatry. They expressed a desire for more training and thought that increased mentorship and case-based learning, including input from palliative care clinicians, would be most helpful.Significance of Results:Participants generally feel unprepared to care for patients with a life-limiting physical illness and have contrasting views on the role of psychiatry in this setting. Targeted education is required for psychiatry trainees in order to equip them to care for these patients.
CHARACTER AND OBJECT
Authors: AVIGAD JEREMY , MORRIS REBECCA 
Published: June 2016

AbstractIn 1837, Dirichlet proved that there are infinitely many primes in any arithmetic progression in which the terms do not all share a common factor. Modern presentations of the proof are explicitly of higher-order, in that they involve quantifying over and summing overDirichlet characters, which are certain types of functions. The notion of a character is only implicit in Dirichlet’s original proof, and the subsequent history shows a very gradual transition to the modern mode of presentation.In this essay, we study the history of Dirichlet’s theorem with an eye towards understanding the methodological pressures that influenced some of the ontological shifts that occurred in nineteenth century mathematics. In particular, we use the history to understand some of the reasons that functions are treated as ordinary objects in contemporary mathematics, as well as some of the reasons one might want to resist such treatment.
Arithmetical Difficulties and Low Arithmetic Achievement: Analysis of the Underlying Cognitive Functioning
Authors: Iglesias-Sarmiento Valentín , Deaño Manuel 
Published: June 2016

AbstractThis study analyzed the cognitive functioning underlying arithmetical difficulties and explored the predictors of arithmetic achievement in the last three grades of Spanish Primary Education. For this purpose, a group of 165 students was selected and divided into three groups of arithmetic competence: Mathematical Learning Disability group (MLD,n =27), Low Achieving group (LA,n =39), and Typical Achieving group (TA,n =99). Students were assessed in domain-general abilities (working memory and PASS cognitive processes), and numerical competence (counting and number processing) during the last two months of the academic year. Performance of children from the MLD group was significantly poorer than that of the LA group in writing dictated Arabic numbers (d= –0.88), reading written verbal numbers (d= –0.84), transcoding written verbal numbers to Arabic numbers (–0.75) and comprehension of place value (d= –0.69), as well as in simultaneous (d= –0.62) and successive (d= –0.59) coding. In addition, a specific developmental sequence was observed in both groups, the implications of which are discussed. Hierarchical regression analysis revealed simultaneous coding (β = .47,t(155) = 6.18,p< .001) and number processing (β = .23,t(155) = 3.07,p< .01) as specific predictors of arithmetical performance.
Are Entrepreneurial Intentions Self-Regulated? Self-Consciousness, Core Self-Evaluations and Entrepreneurial Intentions of Higher Education Students
Authors: Auzoult Laurent , Lheureux Florent , Abdellaoui Sid 
Published: June 2016

AbstractThe main aim of this study is to demonstrate that private self-consciousness (SC) and core self-evaluations (CSEs) influence their formation, via the perceived feasibility and desirability of entrepreneurship or in interaction with it. Two hundred and sixteen students, from a university, an engineering college and a management school, participated in a survey questionnaire which measured these variables as well as controlled factors (e.g. entrepreneurship education, presence of entrepreneurs in their close social network). The results confirm that CSEs have a positive effect on feasibility and desirability (p < .001) which mediate their effect on intention (p < .007). They also show that private SC has a positive direct effect on intention (p < .001). Additionally, the positive interaction effects of desirability and feasibility and public SC and feasibility on intention are highlighted (p < .05). Unexpectedly, none of the hypothesized moderation effects of private SC were corroborated. The convergence of these results with prior research, the limitations of the study and practical implications are discussed.
Translation control during prolonged mTORC1 inhibition mediated by 4E-BP3
Authors: Tsukumo Yoshinori , Alain Tommy , Fonseca Bruno D. , Nadon Robert , Sonenberg Nahum 
Published: June 2016

AbstractTargeting mTORC1 is a highly promising strategy in cancer therapy. Suppression of mTORC1 activity leads to rapid dephosphorylation of eIF4E-binding proteins (4E-BP1–3) and subsequent inhibition of mRNA translation. However, how the different 4E-BPs affect translation during prolonged use of mTOR inhibitors is not known. Here we show that the expression of 4E-BP3, but not that of 4E-BP1 or 4E-BP2, is transcriptionally induced during prolonged mTORC1 inhibition in vitro and in vivo. Mechanistically, our data reveal that 4E-BP3 expression is controlled by the transcription factor TFE3 through a cis-regulatory element in the EIF4EBP3 gene promoter. CRISPR/Cas9-mediated EIF4EBP3 gene disruption in human cancer cells mitigated the inhibition of translation and proliferation caused by prolonged treatment with mTOR inhibitors. Our findings show that 4E-BP3 is an important effector of mTORC1 and a robust predictive biomarker of therapeutic response to prolonged treatment with mTOR-targeting drugs in cancer.
Loss of the RNA-binding protein TACO1 causes late-onset mitochondrial dysfunction in mice
Authors: Richman Tara R. , Spåhr Henrik , Ermer Judith A. , Davies Stefan M. K. , Viola Helena M. , Bates Kristyn A. , Papadimitriou John , Hool Livia C. , Rodger Jennifer , Larsson Nils-Göran , Rackham Oliver , Filipovska Aleksandra 
Published: June 2016

AbstractThe recognition and translation of mammalian mitochondrial mRNAs are poorly understood. To gain further insights into these processes in vivo, we characterized mice with a missense mutation that causes loss of the translational activator of cytochrome oxidase subunit I (TACO1). We report that TACO1 is not required for embryonic survival, although the mutant mice have substantially reduced COXI protein, causing an isolated complex IV deficiency. We show that TACO1 specifically binds the mt-Co1 mRNA and is required for translation of COXI through its association with the mitochondrial ribosome. We determined the atomic structure of TACO1, revealing three domains in the shape of a hook with a tunnel between domains 1 and 3. Mutations in the positively charged domain 1 reduce RNA binding by TACO1. The Taco1 mutant mice develop a late-onset visual impairment, motor dysfunction and cardiac hypertrophy and thus provide a useful model for future treatment trials for mitochondrial disease.
The power of a critical heat engine
Authors: Campisi Michele , Fazio Rosario 
Published: June 2016

AbstractSince its inception about two centuries ago thermodynamics has sparkled continuous interest and fundamental questions. According to the second law no heat engine can have an efficiency larger than Carnot’s efficiency. The latter can be achieved by the Carnot engine, which however ideally operates in infinite time, hence delivers null power. A currently open question is whether the Carnot efficiency can be achieved at finite power. Most of the previous works addressed this question within the Onsager matrix formalism of linear response theory. Here we pursue a different route based on finite-size-scaling theory. We focus on quantum Otto engines and show that when the working substance is at the verge of a second order phase transition diverging energy fluctuations can enable approaching the Carnot point without sacrificing power. The rate of such approach is dictated by the critical indices, thus showing the universal character of our analysis.
Oncogenic PIK3CA mutations reprogram glutamine metabolism in colorectal cancer
Authors: Hao Yujun , Samuels Yardena , Li Qingling , Krokowski Dawid , Guan Bo-Jhih , Wang Chao , Jin Zhicheng , Dong Bohan , Cao Bo , Feng Xiujing , Xiang Min , Xu Claire , Fink Stephen , Meropol Neal J. , Xu Yan , Conlon Ronald A. , Markowitz Sanford , Kinzler Kenneth W. , Velculescu Victor E. , Brunengraber Henri , Willis Joseph E. , LaFramboise Thomas , Hatzoglou Maria , Zhang Guo-Fang , Vogelstein Bert , Wang Zhenghe 
Published: June 2016

AbstractCancer cells often require glutamine for growth, thereby distinguishing them from most normal cells. Here we show that PIK3CA mutations reprogram glutamine metabolism by upregulating glutamate pyruvate transaminase 2 (GPT2) in colorectal cancer (CRC) cells, making them more dependent on glutamine. Compared with isogenic wild-type (WT) cells, PIK3CA mutant CRCs convert substantially more glutamine to α-ketoglutarate to replenish the tricarboxylic acid cycle and generate ATP. Mutant p110α upregulates GPT2 gene expression through an AKT-independent, PDK1–RSK2–ATF4 signalling axis. Moreover, aminooxyacetate, which inhibits the enzymatic activity of aminotransferases including GPT2, suppresses xenograft tumour growth of CRCs with PIK3CA mutations, but not with WT PIK3CA. Together, these data establish oncogenic PIK3CA mutations as a cause of glutamine dependency in CRCs and suggest that targeting glutamine metabolism may be an effective approach to treat CRC patients harbouring PIK3CA mutations.
Structural insights of ZIP4 extracellular domain critical for optimal zinc transport
Authors: Zhang Tuo , Sui Dexin , Hu Jian 
Published: June 2016

AbstractThe ZIP zinc transporter family is responsible for zinc uptake from the extracellular milieu or intracellular vesicles. The LIV-1 subfamily, containing nine out of the 14 human ZIP proteins, is featured with a large extracellular domain (ECD). The critical role of the ECD is manifested by disease-causing mutations on ZIP4, a representative LIV-1 protein. Here we report the first crystal structure of a mammalian ZIP4-ECD, which reveals two structurally independent subdomains and an unprecedented dimer centred at the signature PAL motif. Structure-guided mutagenesis, cell-based zinc uptake assays and mapping of the disease-causing mutations indicate that the two subdomains play pivotal but distinct roles and that the bridging region connecting them is particularly important for ZIP4 function. These findings lead to working hypotheses on how ZIP4-ECD exerts critical functions in zinc transport. The conserved dimeric architecture in ZIP4-ECD is also demonstrated to be a common structural feature among the LIV-1 proteins.
Specific frontal neural dynamics contribute to decisions to check
Authors: Stoll Frederic M. , Fontanier Vincent , Procyk Emmanuel 
Published: June 2016

AbstractCuriosity and information seeking potently shapes our behaviour and are thought to rely on the frontal cortex. Yet, the frontal regions and neural dynamics that control the drive to check for information remain unknown. Here we trained monkeys in a task where they had the opportunity to gain information about the potential delivery of a large bonus reward or continue with a default instructed decision task. Single-unit recordings in behaving monkeys reveal that decisions to check for additional information first engage midcingulate cortex and then lateral prefrontal cortex. The opposite is true for instructed decisions. Importantly, deciding to check engages neurons also involved in performance monitoring. Further, specific midcingulate activity could be discerned several trials before the monkeys actually choose to check the environment. Our data show that deciding to seek information on the current state of the environment is characterized by specific dynamics of neural activity within the prefrontal cortex.
Role of dimensionality in complex networks
Authors: Brito Samuraí , da Silva L. R. , Tsallis Constantino 
Published: June 2016

AbstractDeep connections are known to exist between scale-free networks and non-Gibbsian statistics. For example, typical degree distributions at the thermodynamical limit are of the form "Equation missing", where the q-exponential form "Equation missing" optimizes the nonadditive entropy Sq (which, for q → 1, recovers the Boltzmann-Gibbs entropy). We introduce and study here d-dimensional geographically-located networks which grow with preferential attachment involving Euclidean distances through "Equation missing". Revealing the connection with q-statistics, we numerically verify (for d = 1, 2, 3 and 4) that the q-exponential degree distributions exhibit, for both q and k, universal dependences on the ratio αA/d. Moreover, the q = 1 limit is rapidly achieved by increasing αA/d to infinity.
The histone deacetylase inhibiting drug Entinostat induces lipid accumulation in differentiated HepaRG cells
Authors: Nunn Abigail D. G. , Scopigno Tullio , Pediconi Natalia , Levrero Massimo , Hagman Henning , Kiskis Juris , Enejder Annika 
Published: June 2016

AbstractDietary overload of toxic, free metabolic intermediates leads to disrupted insulin signalling and fatty liver disease. However, it was recently reported that this pathway might not be universal: depletion of histone deacetylase (HDAC) enhances insulin sensitivity alongside hepatic lipid accumulation in mice, but the mechanistic role of microscopic lipid structure in this effect remains unclear. Here we study the effect of Entinostat, a synthetic HDAC inhibitor undergoing clinical trials, on hepatic lipid metabolism in the paradigmatic HepaRG liver cell line. Specifically, we statistically quantify lipid droplet morphology at single cell level utilizing label-free microscopy, coherent anti-Stokes Raman scattering, supported by gene expression. We observe Entinostat efficiently rerouting carbohydrates and free-fatty acids into lipid droplets, upregulating lipid coat protein gene Plin4, and relocating droplets nearer to the nucleus. Our results demonstrate the power of Entinostat to promote lipid synthesis and storage, allowing reduced systemic sugar levels and sequestration of toxic metabolites within protected protein-coated droplets, suggesting a potential therapeutic strategy for diseases such as diabetes and metabolic syndrome.
Nucleus downscaling in mouse embryos is regulated by cooperative developmental and geometric programs
Authors: Tsichlaki Elina , FitzHarris Greg 
Published: June 2016

AbstractMaintaining appropriate nucleus size is important for cell health, but the mechanisms by which this is achieved are poorly understood. Controlling nucleus size is a particular challenge in early development, where the nucleus must downscale in size with progressive reductive cell divisions. Here we use live and fixed imaging, micromanipulation approaches and small molecule analyses during preimplantation mouse development to probe the mechanisms by which nucleus size is determined. We find a close correlation between cell and nuclear size at any given developmental stage and show that experimental cytoplasmic reduction can alter nuclear size, together indicating that cell size helps dictate nuclear proportions. Additionally, however, by creating embryos with over-sized blastomeres we present evidence of a developmental program that drives nuclear downscaling independently of cell size. We show that this developmental program does not correspond with nuclear import rates, but provide evidence that PKC activity may contribute to this mechanism. We propose a model in which nuclear size regulation during early development is a multi-mode process wherein nucleus size is set by cytoplasmic factors and fine-tuned on a cell-by-cell basis according to cell size.
Phosphodiesterase 3B (PDE3B) regulates NLRP3 inflammasome in adipose tissue
Authors: Ahmad Faiyaz , Chung Youn Wook , Tang Yan , Hockman Steven C. , Liu Shiwei , Khan Yusuf , Huo Kevin , Billings Eric , Amar Marcelo J. , Remaley Alan T. , Manganiello Vincent C. 
Published: June 2016

AbstractActivation of inflammation in white adipose tissue (WAT), includes infiltration/expansion of WAT macrophages, contributes pathogenesis of obesity, insulin resistance and metabolic syndrome. The inflammasome comprises an intracellular sensor (NLR), caspase-1 and the adaptor ASC. Inflammasome activation leads to maturation of caspase-1 and processing of IL1β, contributing to many metabolic disorders and directing adipocytes to a more insulin-resistant phenotype. Ablation of PDE3B in WAT prevents inflammasome activation by reducing expression of NLRP3, caspase-1, ASC, AIM2, TNFα, IL1β and proinflammatory genes. Following IP injection of lipopolysaccharide (LPS), serum levels of IL1β and TNFα were reduced in PDE3B−/−mice compared to WT. Activation of signaling cascades, which mediate inflammasome responses, were modulated in PDE3B−/−mice WAT, including smad, NFAT, NFkB and MAP kinases. Moreover, expression of chemokine CCL2, MCP-1 and its receptor CCR2, which play an important role in macrophage chemotaxis, were reduced in WAT of PDE3B−/−mice. In addition, atherosclerotic plaque formation was significantly reduced in the aorta of apoE−/−/PDE3B−/−and LDL-R−/−/PDE3B−/−mice compared to apoE−/−and LDL-R−/−mice, respectively. Obesity-induced changes in serum-cholesterol were blocked in PDE3B−/−mice. Collectively, these data establish a role for PDE3B in modulating inflammatory response, which may contribute to a reduced inflammatory state in adipose tissue.
Newly-formed emotional memories guide selective attention processes: Evidence from event-related potentials
Authors: Schupp Harald T. , Kirmse Ursula , Schmälzle Ralf , Flaisch Tobias , Renner Britta 
Published: June 2016

AbstractEmotional cues can guide selective attention processes. However, emotional stimuli can both activate long-term memory representations reflecting general world knowledge and engage newly formed memory representations representing specific knowledge from the immediate past. Here, the self-completion feature of associative memory was utilized to assess the regulation of attention processes by newly-formed emotional memory. First, new memory representations were formed by presenting pictures depicting a person either in an erotic pose or as a portrait. Afterwards, to activate newly-built memory traces, edited pictures were presented showing only the head region of the person. ERP recordings revealed the emotional regulation of attention by newly-formed memories. Specifically, edited pictures from the erotic compared to the portrait category elicited an early posterior negativity and late positive potential, similar to the findings observed for the original pictures. A control condition showed that the effect was dependent on newly-formed memory traces. Given the large number of new memories formed each day, they presumably make an important contribution to the regulation of attention in everyday life.
Dynamic Behavior of Engineered Lattice Materials
Authors: Hawreliak J. A. , Lind J. , Maddox B. , Barham M. , Messner M. , Barton N. , Jensen B. J. , Kumar M. 
Published: June 2016

AbstractAdditive manufacturing (AM) is enabling the fabrication of materials with engineered lattice structures at the micron scale. These mesoscopic structures fall between the length scale associated with the organization of atoms and the scale at which macroscopic structures are constructed. Dynamic compression experiments were performed to study the emergence of behavior owing to the lattice periodicity in AM materials on length scales that approach a single unit cell. For the lattice structures, both bend and stretch dominated, elastic deflection of the structure was observed ahead of the compaction of the lattice, while no elastic deformation was observed to precede the compaction in a stochastic, random structure. The material showed lattice characteristics in the elastic response of the material, while the compaction was consistent with a model for compression of porous media. The experimental observations made on arrays of 4 × 4 × 6 lattice unit cells show excellent agreement with elastic wave velocity calculations for an infinite periodic lattice, as determined by Bloch wave analysis and finite element simulations.
OncoScape: Exploring the cancer aberration landscape by genomic data fusion
Authors: Schlicker Andreas , Michaut Magali , Rahman Rubayte , Wessels Lodewyk F. A. 
Published: June 2016

AbstractAlthough large-scale efforts for molecular profiling of cancer samples provide multiple data types for many samples, most approaches for finding candidate cancer genes rely on somatic mutations and DNA copy number only. We present a new method, OncoScape, which exploits five complementary data types across 11 cancer types to identify new candidate cancer genes. We find many rarely mutated genes that are strongly affected by other aberrations. We retrieve the majority of known cancer genes but also new candidates such as STK31 and MSRA with very high confidence. Several genes show a dual oncogene- and tumor suppressor-like behavior depending on the tumor type. Most notably, the well-known tumor suppressor RB1 shows strong oncogene-like signal in colon cancer. We applied OncoScape to cell lines representing ten cancer types, providing the most comprehensive comparison of aberrations in cell lines and tumor samples to date. This revealed that glioblastoma, breast and colon cancer show strong similarity between cell lines and tumors, while head and neck squamous cell carcinoma and bladder cancer, exhibit very little similarity between cell lines and tumors. To facilitate exploration of the cancer aberration landscape, we created a web portal enabling interactive analysis of OncoScape results (http://ccb.nki.nl/software/oncoscape).