Miracle-dz/UniFAR-FTUs huggingface dataset:
Structure of the Brd4 ET domain bound to a C-terminal motif from γ-retroviral integrases reveals a conserved mechanism of interaction

Significance Bromodomain and extraterminal domain (BET) proteins recruit a variety of cellular factors to epigenetic marks on chromatin to modulate essential cellular processes, including DNA repair and transcription. To facilitate their recruitment to chromosomal DNA made accessible by epigenetically modified chromatin dynamics, conserved sequences in γ-retroviral integrases bind to the highly conserved extraterminal (ET) domains of BET proteins. The solution structure of the complex between the Brd4 ET domain and a conserved sequence from murine leukemia virus integrase reveals the basis for γ-retroviral integration pattern, with implications for retrovirus-based gene therapy. Moreover, the studies suggest how BET proteins might interact with cognate binding partners involved in a diverse array of cellular phenomena including transcriptional activation, cancer, viral latency, and viral integration. The bromodomain and extraterminal domain (BET) protein family are promising therapeutic targets for a range of diseases linked to transcriptional activation, cancer, viral latency, and viral integration. Tandem bromodomains selectively tether BET proteins to chromatin by engaging cognate acetylated histone marks, and the extraterminal (ET) domain is the focal point for recruiting a range of cellular and viral proteins. BET proteins guide γ-retroviral integration to transcription start sites and enhancers through bimodal interaction with chromatin and the γ-retroviral integrase (IN). We report the NMR-derived solution structure of the Brd4 ET domain bound to a conserved peptide sequence from the C terminus of murine leukemia virus (MLV) IN. The complex reveals a protein–protein interaction governed by the binding-coupled folding of disordered regions in both interacting partners to form a well-structured intermolecular three-stranded β sheet. In addition, we show that a peptide comprising the ET binding motif (EBM) of MLV IN can disrupt the cognate interaction of Brd4 with NSD3, and that substitutions of Brd4 ET residues essential for binding MLV IN also impair interaction of Brd4 with a number of cellular partners involved in transcriptional regulation and chromatin remodeling. This suggests that γ-retroviruses have evolved the EBM to mimic a cognate interaction motif to achieve effective integration in host chromatin. Collectively, our findings identify key structural features of the ET domain of Brd4 that allow for interactions with both cellular and viral proteins.
New Existence Proofs for 2-Nets

We describe a new technique for proving the existence of small 2-nets for hypergraphs satisfying certain simple conditions. The technique is particularly useful for proving o( 1 2 log 1 2 ) upper bounds which is not possible using the standard VC dimension theory. We apply the technique to several geometric hypergraphs and obtain simple proofs for the existence of O( 1 2 ) size 2-nets for them. This includes the geometric hypergraph in which the vertex set is a set of points in the plane and the hyperedges are defined by a set of pseudo-disks. This result was not known previously. We also get a very short proof for the existence of O( 1 2 ) size 2-nets for halfspaces in R .
Impact of Salient Vocal Qualities on Causal Attribution for a Speaker ' s Behavior

Considerable research has demonstrated an illusory causation effect in which visually salient people are perceived as more causal of events in a social interaction than their nonsalient counterparts. The present studies extended this work to the realm of auditory salience. Two determinants of auditory salience were manipulated—the intensity of a speaker's voice and the sex of a speaker's voice. As predicted, subjects attended more to a 75-dB (A) than to a 70-dB voice on a binaural listening test, and subjects attributed more causality to an actor in a two-person conversation when his voice was 75 dB in intensity than when it was 70 dB. Contrary to expectation, subjects did not attend more to the voice whose sex matched their own on the binaural listening test. Rather, all subjects listened more to the actor with the male voice. Consistent with this tendency for the male voice to be more salient, subjects attributed more causality to an actor when the voice was-male than when it had been electronically converted to a female voice of the same intensity and intonation. Vocal salience also influenced subjects' impressions of the actors, but it had no impact on recall of the actors' verbalizations. Theoretical and practical implications of these findings are discussed.
COMPREHENSION OF DEFINITE AND INDEFINITE ARTICLES IN CHILDREN WITH SLI

INTRODUCTION Recent research on the language of children of SLI shows a marked delay in their acquisition of grammatical morphemes, especially those associated with the verbal system (e.g., Rice and Oetting, 1993; Rice, Wexler and Cleaver, 1996). In English, the nominal system is morphologically poorer than the verbal system, which may account for the discrepancy observed in the two systems of children with SLI. Researchers of SLI in other languages have found that there are deficits in the nominal system as well, for example children with SLI learning German show difficulty using gender agreement and case marking on articles and nouns (e.g., Clahsen, 1989). English articles are not inflected, but children with SLI often omit articles in their spontaneous language productions (Leonard, 1995).
Extinction of Behavior in Infant Rats: Development of Functional Coupling Between Septal, Hippocampal, and Ventral Tegmental Regions

Learning of a behavior at a particular age during the postnatal period presumably occurs when the functional brain circuit mediating the behavior matures. The inability to express a learned behavior, such as inhibition, may be accounted for by the functional dissociation of brain regions comprising the circuit. In this study we tested this hypothesis by measuring brain metabolic activity, as revealed by fluorodeoxyglucose (FDG) autoradiography, during behavioral extinction in 12- and 17-d-old rat pups. Subjects were first trained on a straight alley runway task known as patterned single alternation (PSA), wherein reward and nonreward trials alternate successively. They were then injected with FDG and given 50 trials of continuous nonreward (i.e., extinction). Pups at postnatal day 12 (P12) demonstrated significantly slower extinction rates compared to their P17 counterparts, despite the fact that both reliably demonstrated the PSA effect, i.e., both age groups distinguished between reward and nonreward trials during acquisition. Covariance analysis revealed that the dentate gyrus, hippocampal fields CA1–3, subiculum, and lateral septal area were significantly correlated in P17 but not P12 pups. Significant correlations were also found between the lateral septal area, ventral tegmental area, and the medial septal nucleus in P17 pups. Similar correlative patterns were not found in P12 and P17 handled control animals. Taken together, these results suggest that septal, hippocampal, and mesencephalic regions may be functionally dissociated at P12, and the subsequent maturation of functional connectivity between these regions allows for the more rapid expression of behavioral inhibition during extinction at P17.
Correlation between Semaphorin3A-Induced Facilitation of Axonal Transport and Local Activation of a Translation Initiation Factor Eukaryotic Translation Initiation Factor 4E

An impressive body of evidence has been accumulated indicating that local protein synthesis is implicated in navigation of neurite extension induced by guidance cues, such as semaphorin3A (Sema3A). We found previously that a Src type tyrosine kinase Fyn and cyclin-dependent kinase 5 (Cdk5) mediate Sema3A-signaling. We also showed that Sema3A elicits axonal transport through neuropilin-1, a receptor for Sema3A, located at the growth cones. Here, we investigate the relationship between Sema3A-induced local signaling, protein synthesis, and axonal transport. Lavendustin A, a tyrosine kinase inhibitor, and olomoucine, a cyclin-dependent kinase inhibitor, suppressed Sema3A-induced facilitation of anterograde and retrograde axonal transport in dorsal root ganglion (DRG) neuron with and without the cell body. Sema3A-induced facilitation of axonal transport was attenuated in DRG neurons of fyn- (fyn-/-) and a Cdk5 activator, p35 (p35-/-)-deficient mice when compared with those of wild-type or heterozygous mice. Inhibition of protein synthesis suppressed Sema3A-induced facilitation of axonal transport in the DRG neuron with and without the cell body. Sema3A enhanced the level of immunoreactivity of phosphorylated eukaryotic translation initiation factor 4E (eIF-4E) within 5 min in growth cones in a time course similar to that of the facilitated axonal transport. This enhanced signal for phospho-eIF4E was blocked by lavendustin A or olomoucine and was not detected in the fyn-/- and p35-/- neurons. These results provide evidence for a mutual regulatory mechanism between local protein synthesis and axonal transport.
Impact of an educational programme in Portuguese people with diabetes

This study, conducted in the north of Portugal, is the result of a group of nurses’ intent to develop a closer and meaningful person-centered care for patients with diabetes, empowering them with skills to better manage their therapeutic regimen. Through a participatory action research process, the group of nurses involved in this study, reflected on the current healthcare enabling them an in-depth analysis of the best scientific evidence, aiming to design context tailored solutions, which would contribute to patients’ empowerment. Through a longitudinal study developed over several stages, the nurses outlined the educational programme Living in harmony with diabetes, which was applied to 85 patients with diabetes mellitus type 2. The programme had a positive impact on the psychosocial variables, in self-care behaviour and in the metabolic control, helping patients to better cope with their disease and have greater control over their health condition. Throughout the process of participatory action research, the nurses were able to increase their self-efficacy and empowerment on person-centered care implementation.
Towards a Theory of Cultural Influence on the Development of Accounting Systems Internationally

Research has shown that accounting follows different patterns in different parts of the world. There have been claims that national systems are determined by environmental factors. In this context, cultural factors have not been fully considered. This paper proposes four hypotheses on the relationship between identified cultural characteristics and the development of accounting systems, the regulation of the accounting profession and attitudes towards financial management and disclosure. The hypotheses are not operationalized, and empirical tests have not been carried out. They are proposed here as a first step in the development of a theory of cultural influence on the development of accounting systems.
TOPOLOGY OPTIMIZATION METHOD APPLIED TO OBTAIN IMAGES FROM ELECTRICAL IMPEDANCE TOMOGRAPHY TECHNIQUE

The Electrical Impedance Tomography (EIT) is a recent monitoring technique of biological tissues that allows us to obtain images of a transversal plane in any section of human body. The images are generated from voltage values measured around the plane section of human body. These voltages are obtained by applying an alternated sequence of low amplitude electrical currents in according to an excitation pattern (adjacent or diametral). The EIT deals with inverse problem solution. The main objective of the current work is to study the application of Topology Optimization Method (TOM) to obtain images of body section by using EIT. The problem of applying TOM to obtain images consists in finding a conductivity distribution in the body section domain that minimizes the difference between electric potential measured on electrodes and electric potential calculated by using a computational model. TOM allows us to include several constraints, which reduces the solution space expected in tomography examination. The solution of the topology optimization problem is obtained by combining Finite Element Method (FEM) and Sequential Linear Programming (SLP). To illustrate the implementation of the method, image reconstruction results obtained by using voltage numerical data of well-know domains are shown.
Heuristics and biases – Insights from developmental studies.

Pierre Barrouillet & Caroline Gauffroy Introduction: From Piaget to Dual-Process Theories: The Complexities of Thinking and Reasoning Development. PART 1: Thinking and Reasoning: Beyond Piaget's Conceptions. David Moshman Epistemic Cognition and Development. Julie E. Meehan & Ruth M.J. Byrne The Development of the Rational Imagination: How Children Create Counterfactual Alternatives to Reality. Usha Goswami The Development of Reasoning by Analogy. Henry Markovits The Development of Abstract Conditional Reasoning. PART 2: Dual-Processes Approaches. Pierre Barrouillet & Caroline Gauffroy Dual Processes and Mental Models in the Development of Conditional Reasoning. Kinga Morsanyi & Simon J. Handley Heuristics and Biases - Insights from Developmental Studies. Paul Klackzynski Culture and Developments in Heuristics and Biases from Preschool through Adolescence: Challenges and Implications for Social development. Valerie F. Reyna Intuition, Reasoning and Development: A Fuzzy-Trace Theory. Carlos F. Gomes & Charles J. Brainerd Dual Processes in the Development of Reasoning: The Memory Side of the Theory.
HIGH ANGULAR RESOLUTION INTEGRAL-FIELD SPECTROSCOPY OF THE GALAXY'S NUCLEAR CLUSTER: A MISSING STELLAR CUSP?

We report on the structure of the nuclear star cluster in the innermost 0.16 pc of the Galaxy as measured by the number density profile of late-type giants. Using laser guide star adaptive optics in conjunction with the integral field spectrograph, OSIRIS, at the Keck II telescope, we are able to differentiate between the older, late-type (∼ 1 Gyr) stars, which are presumed to be dynamically relaxed, and the unrelaxed young (∼ 6 Myr) population. This distinction is crucial for testing models of stellar cusp formation in the vicinity of a black hole, as the models assume that the cusp stars are in dynamical equilibrium in the black hole potential. In the survey region, we classified 60 stars as early-type (22 newly identified) and 74 stars as late-type (61 newly identified). We find that contamination from young stars is significant, with more than twice as many young stars as old stars in our sensitivity range (K′ < 15.5) within the central arcsecond. Based on the late-type stars alone, the surface stellar number density profile, Σ(R) ∝ R−Γ, is flat, with Γ = −0.27 ± 0.19. Monte Carlo simulations of the possible de-projected volume density profile, n(r) ∝r−γ, show that γ is less than 1.0 at the 99.7% confidence level. These results are consistent with the nuclear star cluster having no cusp, with a core profile that is significantly flatter than that predicted by most cusp formation theories, and even allows for the presence of a central hole in the stellar distribution. Of the possible dynamical interactions that can lead to the depletion of the red giants observable in this survey—stellar collisions, mass segregation from stellar remnants, or a recent merger event—mass segregation is the only one that can be ruled out as the dominant depletion mechanism. The lack of a stellar cusp around a supermassive black hole would have important implications for black hole growth models and inferences on the presence of a black hole based upon stellar distributions.
Limited performance of DNA barcoding in a diverse community of tropical butterflies

DNA ‘barcoding’ relies on a short fragment of mitochondrial DNA to infer identification of specimens. The method depends on genetic diversity being markedly lower within than between species. Closely related species are most likely to share genetic variation in communities where speciation rates are rapid and effective population sizes are large, such that coalescence times are long. We assessed the applicability of DNA barcoding (here the 5′ half of the cytochrome c oxidase I) to a diverse community of butterflies from the upper Amazon, using a group with a well-established morphological taxonomy to serve as a reference. Only 77% of species could be accurately identified using the barcode data, a figure that dropped to 68% in species represented in the analyses by more than one geographical race and at least one congener. The use of additional mitochondrial sequence data hardly improved species identification, while a fragment of a nuclear gene resolved issues in some of the problematic species. We acknowledge the utility of barcodes when morphological characters are ambiguous or unknown, but we also recommend the addition of nuclear sequence data, and caution that species-level identification rates might be lower in the most diverse habitats of our planet.
Stereological Analysis of the Brain in Methamphetamine Abusers Compared to the Controls

Background: Methamphetamine (MA) is an addictive and stimulant drug that its abuse causes psychological and cognitive symptoms. MA abuse can cause structural changes in the brain. Objectives: The current study aimed to evaluate stereological changes of the brains of MA abusers, compared to the controls. Patients and Methods: The current case-control study was conducted on magnetic resonance (MR) images from MA abusers and healthy controls (n = 10 in each group), in Zahedan, Iran. The convenience sampling method was employed to select the subjects. MR images of the brains of the 2 groups in frontal, coronal, and sagittal axes with 4-mm slide thickness and 0.5-mm intervals were acquired. Parameters including total volume (V) and volume density (Vv) of different parts of the brain were estimated based on the Cavalieri point counting stereological method. To analyze the data, descriptive statistics and the Mann-Whitney U-test were applied. The significance level was considered P < 0.05. Results: The results showed that the volume of the cerebellum, the volume and volume density of the ventricles, and gray matter volume and volume density, and the basal ganglia volume density in MA group was significantly smaller than those of the controls (P < 0.05). But, white matter volume and volume density in the MA abusers were significantly larger than those of the healthy subjects (P < 0.05). In addition, there were no significant differences between the total brain, the hippocampus, and the basal ganglia volumes between the 2 groups. Conclusions: According to the results of the current study, MA abuse can cause structural changes in the brain components. MR imaging by the stereological methods can be employed as a technique to determine the level of such damages in substance abusers.
Selected CSF biomarkers indicate no evidence of early neuroinflammation in Huntington disease

Objective: To investigate CSF biomarkers of neuroinflammation and neurodegeneration in Huntington disease (HD) gene-expansion carriers compared to controls and to investigate these biomarkers in association with clinical HD rating scales and disease burden score. Methods: We collected CSF from 32 premanifest and 48 manifest HD gene-expansion carriers and 24 gene-expansion negative at-risk controls. We examined biomarkers of neuroinflammation (matrix metalloproteinase 9, C-X-C motif chemokine 13, terminal complement complex, chitinase-3-like-protein 1 [CHI3L1], and osteopontin [OPN]) and neurodegeneration (microtubule-associated protein tau, neurofilament light polypeptide [NFL], and myelin basic protein [MBP]). The study was approved by the Ethics Committee of the Capital Region of Denmark (H2-2011-085) and written informed consent was obtained from each participant before enrollment. Results: NFL was the only biomarker that increased in premanifest stages and no evidence of early involvement of neuroinflammation in HD was found. However, we found that the biomarkers for neurodegeneration, MBP and tau, increased during the disease course in manifest HD gene-expansion carriers and were associated with an increase of the neuroinflammation biomarkers CHI3L1 and OPN. Tau was also increased in all gene-expansion carriers with psychiatric symptoms compared to gene-expansion carriers without psychiatric symptoms. Conclusions: Neuroinflammation, which seems not to be an early event in our cohort, may be secondary to neurodegeneration in late HD. NFL is a possible disease burden correlate in HD, reflecting neuronal loss even before motor symptom onset, and may be useful as a dynamic biomarker in intervention studies.
Improving Throughput for Small Disk Requests with Proximal I/O

This paper introduces proximal I/O, a new technique for improving random disk I/O performance in file systems. The key enabling technology for proximal I/O is the ability of disk drives to retire multiple I/Os, spread across dozens of tracks, in a single revolution. Compared to traditional update-in-place or write-anywhere file systems, this technique can provide a nearly seven-fold improvement in random I/O performance while maintaining (near) sequential on-disk layout. This paper quantifies proximal I/O performance and proposes a simple data layout engine that uses a flash memory-based write cache to aggregate random updates until they have sufficient density to exploit proximal I/O. The results show that with cache of just 1% of the overall disk-based storage capacity, it is possible to service 5.3 user I/O requests per revolution for random updates workload. On an aged file system, the layout can sustain serial read bandwidth within 3% of the best case. Despite using flash memory, the overall system cost is just one third of that of a system with the requisite number of spindles to achieve the equivalent number of random I/O operations.
NF1 gene loss of heterozygosity and expression analysis in sporadic colon cancer

Background and aim: Colon cancer tumorigenesis is a multistep process of mutation accumulation in a number of oncogenes and tumour suppressor genes. NF1 gene protein, neurofibromin, acts as a tumour suppressor by turning the active form of Ras into an inactive form. This molecular switch has an important role in the control of the cell cycle and differentiation, and changes in Ras activity are present in many different cancers. This is the first study to investigate the role of NF1 in sporadic colon cancer. Methods: We investigated loss of heterozygosity (LOH) at the NF1 locus. Real time reverse transcription-polymerase chain reaction was used to determine NF1 mRNA expression in tumours and corresponding normal tissue. Expression of neurofibromin was analysed by immunohistochemistry. Relative ratio of NF1 mRNA type I and II isoform expression was also examined. Results: LOH of the NF1 gene was detected in 20.7% of heterozygous samples. NF1 mRNA expression was significantly increased in tumour tissue compared with corresponding normal tissue (p = 0.04291). There was a statistically significant increase in NF1 type I isoform expression (p = 0.0005) in tumour tissue compared with corresponding normal colon tissue. NF1 isoform type II was predominantly expressed in normal tissue while the NF1 isoform type I prevailed in tumour samples. The transition from dominant expression of isoform type II in normal mucous tissue 15 cm away from the tumour to dominant expression of isoform type I in tumour tissue itself was detected. Total neurofibromin expression increased as tumours were more advanced but expression of wild-type neurofibromin remained the same. Conclusions: Our findings suggest that the NF1 gene may play a role in the development and progression of colon cancer and the NF1 gene may be a potential tumour marker and a new potential target for colon cancer therapy.