Miracle-dz/UniFAR-FTUs huggingface dataset:
A Mouse Model of the Human Fragile X Syndrome I304N Mutation

The mental retardation, autistic features, and behavioral abnormalities characteristic of the Fragile X mental retardation syndrome result from the loss of function of the RNA–binding protein FMRP. The disease is usually caused by a triplet repeat expansion in the 5′UTR of the FMR1 gene. This leads to loss of function through transcriptional gene silencing, pointing to a key function for FMRP, but precluding genetic identification of critical activities within the protein. Moreover, antisense transcripts (FMR4, ASFMR1) in the same locus have been reported to be silenced by the repeat expansion. Missense mutations offer one means of confirming a central role for FMRP in the disease, but to date, only a single such patient has been described. This patient harbors an isoleucine to asparagine mutation (I304N) in the second FMRP KH-type RNA–binding domain, however, this single case report was complicated because the patient harbored a superimposed familial liver disease. To address these issues, we have generated a new Fragile X Syndrome mouse model in which the endogenous Fmr1 gene harbors the I304N mutation. These mice phenocopy the symptoms of Fragile X Syndrome in the existing Fmr1–null mouse, as assessed by testicular size, behavioral phenotyping, and electrophysiological assays of synaptic plasticity. I304N FMRP retains some functions, but has specifically lost RNA binding and polyribosome association; moreover, levels of the mutant protein are markedly reduced in the brain specifically at a time when synapses are forming postnatally. These data suggest that loss of FMRP function, particularly in KH2-mediated RNA binding and in synaptic plasticity, play critical roles in pathogenesis of the Fragile X Syndrome and establish a new model for studying the disorder.
The European Union polity: a union of regulative, normative and cognitive pillars

This article regards the EU as a social construction which can be understood as an institutional field characterized by three pillars. The three pillars are not the usual ones associated with the constitutional framework: the community pillar, the common foreign and security policy, and justice and home affairs. The pillars in question are the regulative, normative and cognitive structures that together characterize an institution. The objective of this article is to analyse the three pillars and their interaction. This approach enables us to identify the logic of different processes at work in the Union and the existence of different foundations of legitimacy.
Competing Risk of Death When Comparing Tibial Implant Types in Total Knee Arthroplasty.

BACKGROUND In the presence of a competing risk of death, the Kaplan-Meier method is known to overestimate the probability of implant failure. To our knowledge, the magnitude of the competing risk of death in survivorship analyses in total knee arthroplasty has not been studied. The purpose of this study was to determine the extent of the competing risk of death in different age groups during a long-term follow-up of patients who had undergone primary total knee arthroplasty. METHODS The study population comprised 22,864 primary total knee arthroplasties at a large medical center in the United States. We compared the overall revision outcomes estimated using the Kaplan-Meier method and the cumulative incidence function over a mean follow-up of 7.8 years (range, 0.1 to 26.3 years). RESULTS The risk of death exceeded the risk of revision by a factor of 4 at twelve years following the surgical procedure. The Kaplan-Meier method overestimated the risk of revision by 3% at five years, 14% at ten years, 32% at fifteen years, and 57% at twenty years. At ten years after the surgical procedure, the risk of death exceeded the risk of revision by a factor of 15 in the all-polyethylene group and by a factor of 3.5 in the metal modular group. The Kaplan-Meier method overestimated the ten-year risk of revision by 18% in the all-polyethylene group and by 11% in the metal modular group. After accounting for the higher competing risk of death in the all-polyethylene group, the cumulative incidence of revision in the metal modular group was about 2.5 to three times higher than that in the all-polyethylene group at ten years. CONCLUSIONS Although the Kaplan-Meier and cumulative incidence methods yielded different implant survival estimates beyond ten years (Kaplan-Meier overestimates implant failure), the size of the bias was small at earlier time points. The extent of overestimation depends on the duration of follow-up and the magnitude of the competing risk of death. CLINICAL RELEVANCE This study examines the clinical relevance of the competing risk of death in total knee arthroplasty.
Beyond format-specificity: Is analogue magnitude really the core abstract feature of the cultural number representation?

The issue of abstractness raises two distinct questions. First, is there a format-independent magnitude representation? Second, does analogue magnitude really play a crucial role in the development of human mathematics? We suggest that neither developmental nor cultural studies support this notion. The field needs to redefine the properties of the core number representation as used in human arithmetic.
Erythrocytes inhibit ligament fibroblast proliferation in a collagen scaffold

In this work, we hypothesized that the concentration of erythrocytes in a provisional scaffold would have a significant effect on three of the major biological processes occurring in early wound healing. ACL fibroblast proliferation, collagen production, and scaffold contraction were measured in collagen gels containing fibroblasts and erythrocytes in subphysiologic (1 × 108 erythrocytes/ml), physiologic (1 × 109 erythrocytes/ml), and supraphysiologic (1 × 1010 erythrocytes/ml) concentrations. Fibroblast‐seeded gels containing only platelet‐poor plasma were used as a control group. All gels were cultured for 1, 14, and 21 days. DNA, ELISA for procollagen and scaffold size measurements were used to quantify the three above parameters of wound healing. Samples with concentrations of erythryocytes lower than that in whole blood stimulated greater fibroblast proliferation and scaffold contraction than those with erythrocyte concentrations similar to that in whole blood (p < 0.027; p < 0.03). Increasing the erythrocyte concentration over that in the whole blood stimulated fibroblast collagen production (p < 0.009) and limited scaffold contraction (p < 0.031). Further work examining the role of the erythrocyte in the early provisional scaffold is warranted. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1361–1366, 2011
New Properties of Complex Noncentral Quadratic Forms and Bounds on MIMO Mutual Information

This paper presents new statistical properties of complex noncentral matrix-variate quadratic forms. In contrast to previous results, the expressions do not involve infinite sums over partitions, or matrix-variate polynomials, and are easily and efficiently computable. These properties are used to derive new upper and lower bounds on the ergodic mutual information of double-sided correlated Rician MIMO channels with arbitrary-rank channel mean matrices. The bounds are shown to be tighter than previous reported bounds in the literature
Reappraisal of Research on Executive Function Training in Children with Learning Disabilities

This review inspects the empirical literature on training in executive functions for children with learning disabilities (LD). Despite average to above average levels of intelligence, adequate sensory or body health, ample schooling opportunities such children show poor academic performance and run a great risk for deficits in executive functions. Executive functions refer to the cognitive processes and behavioural competencies that enable people to engage in goal directed or problem-solving behaviours. It includes goal setting, identifying a problem, developing a plan, ability to execute the plan, show the required flexibility, attention and memory systems to guide, evaluate and/or self-monitor oneself till the end of an effective problem solving activity. Computerized and non-computerized training programmes are now being floated as beneficial in enhancing executive functions of such children. Such programs incorporate simple strategies for amelioration of attention and working memory. While this review seeks to piece together the available research on the chosen topic; in doing so, it also attempts to lay a base and explore the possibility of expatiating future studies relevant to developing training programmes in executive functions for the benefit of children with LD in our country.
Corporate Social Responsibility and Business Performance: The Role of Mexican SMEs

The new millennium brings a new uncertain environment in business, besides a strong pressure in companies to improve and establish new company strategies that allow, not only to increase its market participation and to obtain a major level of company performance, but to survive in a market every time more globalized and competitive. Therefore, in the current literature various researchers and academics consider Corporate Social Responsibility (CSR) as one of the current company strategies, overall for Small and Medium Enterprises (SMEs) that adopt this type of activities, to obtain greater performance. Therefore, the central objective of this empirical study is to analyse and discus the existing relationship between CSR and business performance, using for that a sample of 397 SMEs. The results obtained shown the existence of a positive and significant relationship between CSR and business performance.
Phonological and linguistic–cognitive precursors of reading abilities

This paper reports a longitudinal study of the oral and written language development of a randomly selected sample of 74 children who were followed from age 4 to 9 years. The focus of this report is the oral language precursors of reading difficulties. The relative contribution of semantic/syntactic and phonological precursors was assessed. Regression analyses indicated that phonological awareness at age 6 was the strongest predictor of reading abilities, though syntax and semantics also had an impact. The results are related to ‘the phonological deficit hypothesis’ of dyslexia and also to the problems involved in prediction of the outcome for individual children. © 1997 John Wiley & Sons, Ltd.
Effective Hamiltonian for the superconducting Cu oxides.

Although assuming that doping creates holes primarily on oxygen sites, we derive explicitly a single-band effective Hamiltonian for the high-${T}_{c}$ Cu-oxide superconductors. Cu-O hybridization strongly binds a hole on each square of O atoms to the central ${\mathrm{Cu}}^{2+}$ ion to form a local singlet. This moves through the lattice in a similar way as a hole in the single-band effective Hamiltonian of the strongly interacting Hubbard model.
Prevention of MRSA pneumonia by oral vancomycin decontamination: a randomised trial

This study was undertaken to assess whether oropharyngeal vancomycin may control oropharyngeal carriage and lower airway infection due to methicillin‐resistant Staphylococcus aureus (MRSA) acquired in the intensive care unit (ICU). Secondary endpoints were the emergence of vancomycin-resistant enterococci, vancomycin-intermediate S. aureus and vancomycin consumption. A total of 84 patients, admitted to a medical/surgical ICU and mechanically ventilated for >72 h, were randomly assigned to control (n=42) or test (n=42) group. Both groups received the protocol of selective decontamination of the digestive tract, including polymyxin E, tobramycin and amphotericin B. Patients in the test group received 0.5 g of a 4% vancomycin gel at 6‐h intervals in the oropharynx. Lower airway infections due to MRSA acquired on the ICU were reduced in the test group, as was oropharyngeal carriage. Neither vancomycin-resistant enterococci nor vancomycin-intermediate S. aureus were isolated from either surveillance or diagnostic samples during the study period. The vancomycin costs were lower in the test group. This study demonstrates that oropharyngeal vancomycin, which controls intensive care unit‐acquired lower airway infections and secondary carriage due to methicillin-resistant Staphylococcus aureus, is cost-effective and safe in terms of vancomycin-resistant enterococci and vancomycin-intermediate Staphylococcus aureus.
Masculinity Femininity, Personality and Sexual Attitudes.

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Overloaded By the News: Effects of News Exposure and Enjoyment on Reporting Information Overload

Recent increases in the amount of news and information available in society have prompted claims that citizens are becoming psychologically “overloaded. ” To investigate the validity of these claims, a secondary data analysis on the 2008 Pew Biennial Media Consumption Survey is performed. Results show increased news exposure is indeed positively associated with feeling overloaded. Conversely, news enjoyment is negatively associated with overload. There is also a moderating effect of news enjoyment, such that high news enjoyment reduces overload effects of high news exposure. These results imply that while news exposure may have various beneficial outcomes, such as increased political knowledge, it simultaneously relates to greater psychological discomfort. Motivated news processors, however, appear to be better insulated from this discomfort. Implications for news exposure and democratic citizenship are discussed.
A discrete mechanics approach to dislocation dynamics in BCC crystals

A discrete mechanics approach to modeling the dynamics of dislocations in BCC single crystals is presented. Ideas are borrowed from discrete differential calculus and algebraic topology and suitably adapted to crystal lattices. In particular, the extension of a crystal lattice to a CW complex allows for convenient manipulation of forms and fields defined over the crystal. Dislocations are treated within the theory as energy-minimizing structures that lead to locally lattice-invariant but globally incompatible eigendeformations. The discrete nature of the theory eliminates the need for regularization of the core singularity and inherently allows for dislocation reactions and complicated topological transitions. The quantization of slip to integer multiples of the Burgers’ vector leads to a large integer optimization problem. A novel approach to solving this NP-hard problem based on considerations of metastability is proposed. A numerical example that applies the method to study the emanation of dislocation loops from a point source of dilatation in a large BCC crystal is presented. The structure and energetics of BCC screw dislocation cores, as obtained via the present formulation, are also considered and shown to be in good agreement with available atomistic studies. The method thus provides a realistic avenue for mesoscale simulations of dislocation based crystal plasticity with fully atomistic resolution. r 2006 Elsevier Ltd. All rights reserved.
Enhanced radiosensitization of enzalutamide via schedule dependent administration to androgen‐sensitive prostate cancer cells

Prostate cancer (PCa) is a progressive disease and the most diagnosed cancer in men. The current standard of care for high‐risk localized PCa is a combination of androgen deprivation therapy (ADT) and radiation (XRT). The majority of these patients however become resistant due to incomplete responses to ADT as a result of selective cells maintaining androgen receptor (AR) activity. Improvement can be made if increasing radiosensitivity is realized. Therefore, the aim of this study is to investigate the efficacy of the next‐generation PCa drug Enzalutamide (ENZA), as a radiosensitizer in XRT therapy.
Neurophysiological Correlates of Auditory and Language Development: A Mismatch Negativity Study

During child development, physiological changes occur in the auditory cortex, which are reflected by differences in the electrophysiological signals. This study aimed to examine the age-related changes of the Mismatch Negativity component (MMN) in response to speech and non-speech stimuli in a cross-sectional design. Results revealed distinct patterns of activation according to stimulus type and age. Age-related differences for tone discrimination occurred earlier in children's development than did the discriminative process for speech sounds. Therefore, networks involved in speech processing are still immature in late childhood and may be more vulnerable to physiological changes.
When context hinders! Learn–test compatibility in face recognition

Some theories of holistic face processing propose that parts in faces (eyes, nose, mouth, etc.) are not explicitly represented. So far, the empirical evidence has shown that whole-to-part superiority is found when wholes are learned. We substantiated this using photographic faces. More importantly, we investigated whether learning parts also reveals holistic effects. This has not been attempted before. Four experiments showed that after learning facial parts, recognition of these parts was disrupted when the part was shown in the full face. This distraction effect was strongest when perceivers were not directed to focus on a particular facial feature. Thus, it is very difficult to ignore irrelevant parts in faces. In fact, this might be the essence of holistic face processing.
Decline in bone marrow proliferative capacity as a function of age.

Bone marrow from old (greater than 2 yr of age) and young (8-10 wk of age) male C3H/HeJ mice was grown in long-term bone marrow cultures and assayed for weekly hematopoietic stem cell (CFUs) production and interval self-renewal capacity (R5). Greater numbers of CFUs were noted in old marrow as compared to young marrow cultures over the first 4 wk duration, but subsequently, greater numbers of CFUs were seen weekly in the young marrow cultures. Over 1 3 wk in culture, the total CFUs determination was greater in young marrow cultures. Similarly. self-renewal capacity (R1) was greater in old as compared to young marrow-adherent CFUs over the first 4-5 wk. but subsequently, young marrow CFUs had a greater self-renewal. In an attempt to separately study stroma from hematopoietic cells. old and young hematoN ORMAL MAMMALIAN diploid cells appear to have limited proliferative capacity in vitro. Hayflick and Moorehead, in studies with human embryonic lung fibroblasts, found that only a limited number of population doublings were obtained before the culture failed. This limitation appears to be related to the in vivo age of the fibroblasts; the older the donor fibroblast, the fewer subcultivations obtained. ”2 In vivo there are data suggesting that the proliferative capacity of the hematopoietic stem cell is limited.35 Marrow appears capableof undergoing only a limited number of serial transfers regardless of the number of cells initially transferred or the amount of time between transfers. Increasing the time between transfers allows recovery of the hematopoietic system initially, but after 4-5 transfers, donor marrow cannot be found in the recipient, and survival of irradiated recipients is due to surviving recipient cells rather than to trans
Collective Pairwise Classification for Multi-Way Analysis of Disease and Drug Data

Interactions between drugs, drug targets or diseases can be predicted on the basis of molecular, clinical and genomic features by, for example, exploiting similarity of disease pathways, chemical structures, activities across cell lines or clinical manifestations of diseases. A successful way to better understand complex interactions in biomedical systems is to employ collective relational learning approaches that can jointly model diverse relationships present in multiplex data. We propose a novel collective pairwise classification approach for multi-way data analysis. Our model leverages the superiority of latent factor models and classifies relationships in a large relational data domain using a pairwise ranking loss. In contrast to current approaches, our method estimates probabilities, such that probabilities for existing relationships are higher than for assumed-to-be-negative relationships. Although our method bears correspondence with the maximization of non-differentiable area under the ROC curve, we were able to design a learning algorithm that scales well on multi-relational data encoding interactions between thousands of entities.We use the new method to infer relationships from multiplex drug data and to predict connections between clinical manifestations of diseases and their underlying molecular signatures. Our method achieves promising predictive performance when compared to state-of-the-art alternative approaches and can make "category-jumping" predictions about diseases from genomic and clinical data generated far outside the molecular context.
P. gingivalis in Periodontal Disease and Atherosclerosis – Scenes of Action for Antimicrobial Peptides and Complement

According to the NHS, it is estimated that over 50% of the adult population are, to some extent, affected by gum disease and approximately 15% of UK population have been diagnosed with severe periodontitis. Periodontitis, a chronic polymicrobial disease of the gums, causes inflammation in its milder form, whereas in its severe form affects the surrounding tissues and can result in tooth loss. During periodontitis, plaque accumulates and sits between the junctional epithelium and the tooth itself, resulting in inflammation and the formation of a periodontal pocket. An interface is formed directly between the subgingival bacteria and the junctional epithelial cells. Bacterial pathogens commonly associated with periodontal disease are, among others, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola, together known as the “red complex. ” This review will mostly concentrate on the role of P. gingivalis, a Gram-negative anaerobic bacterium and one of the major and most studied contributors of this disease. Because periodontal disease is associated with the development of atherosclerosis, it is important to understand the local immune response to P. gingivalis. Innate immune players, in particular, complement and antimicrobial peptides and their effects with regard to P. gingivalis during periodontitis and in the development of atherosclerosis will be presented.