Miracle-dz/UniFAR-FTUs huggingface dataset:
No exclusions - developing an autism diagnostic service for adults irrespective of intellectual ability

Purpose – Autism is a spectrum condition, yet many autism services limit access based on IQ score. The Department of Health 2009 enabled enthusiastic clinicians in Leeds with a strong interest in autism to apply for funding to develop an all IQ adult autism diagnostic service and here we present the experience. The paper aims to discuss this issue. Design/methodology/approach – The process of establishing and then expanding the service is described. Details of the diagnostic pathway and tools used are provided. Findings – The number of referrals was higher than expected – a baseline of 20 per year rose to 150 per year as soon as the service opened. Other unexpected findings include relatively low diagnosis rates (32 per cent), high rates of past trauma and patient dissatisfaction when a diagnosis of autism is not given. Originality/value – To date, the service has assessed 517 patients, and plans are underway to collaborate with the local adult ADHD team to form a unified adult neurodevelopmental disorder.
Identification of STAT1 and STAT3 Specific Inhibitors Using Comparative Virtual Screening and Docking Validation

Signal transducers and activators of transcription (STATs) facilitate action of cytokines, growth factors and pathogens. STAT activation is mediated by a highly conserved SH2 domain, which interacts with phosphotyrosine motifs for specific STAT-receptor contacts and STAT dimerization. The active dimers induce gene transcription in the nucleus by binding to a specific DNA-response element in the promoter of target genes. Abnormal activation of STAT signaling pathways is implicated in many human diseases, like cancer, inflammation and auto-immunity. Searches for STAT-targeting compounds, exploring the phosphotyrosine (pTyr)-SH2 interaction site, yielded many small molecules for STAT3 but sparsely for other STATs. However, many of these inhibitors seem not STAT3-specific, thereby questioning the present modeling and selection strategies of SH2 domain-based STAT inhibitors. We generated new 3D structure models for all human (h)STATs and developed a comparative in silico docking strategy to obtain further insight into STAT-SH2 cross-binding specificity of a selection of previously identified STAT3 inhibitors. Indeed, by primarily targeting the highly conserved pTyr-SH2 binding pocket the majority of these compounds exhibited similar binding affinity and tendency scores for all STATs. By comparative screening of a natural product library we provided initial proof for the possibility to identify STAT1 as well as STAT3-specific inhibitors, introducing the ‘STAT-comparative binding affinity value’ and ‘ligand binding pose variation’ as selection criteria. In silico screening of a multi-million clean leads (CL) compound library for binding of all STATs, likewise identified potential specific inhibitors for STAT1 and STAT3 after docking validation. Based on comparative virtual screening and docking validation, we developed a novel STAT inhibitor screening tool that allows identification of specific STAT1 and STAT3 inhibitory compounds. This could increase our understanding of the functional role of these STATs in different diseases and benefit the clinical need for more drugable STAT inhibitors with high specificity, potency and excellent bioavailability.
PD-1 Antibody-induced Guillain-Barré Syndrome in a Patient with Metastatic Melanoma.

Guillain-Barré syndrome (GBS) presents as acute inflammatory demyelinating polyneuropathy, which leads to rapid-onset muscle weakness classically caused by immune-mediated damage to the peripheral nervous system. We report here a case of GBS occurring during treatment with nivolumab. Nivolumab is a fully human IgG4 programmed death 1 (PD-1) immune-checkpointinhibitor antibody that selectively blocks the interaction of the PD-1 receptor with its 2 known programmed death ligands, PD-L1 and PD-L2. Nivolumab can thereby restore anticancer immune responses by abrogating PD-1 pathway-mediated T-cell inhibition (1). In addition, we discuss possible underlying disease mechanisms and treatment options.
The power of cartoons: Depicting the political images of Mahinda Rajapakse and Sarath Fonseka as presidential candidates

As a visual medium of mass communication, cartoons appeal to the young and the old, professionals and laymen. Using the semiotic analysis of Manifest and Latent meanings in editorial cartoons supported by Medhurst and DeZousa’s (1981) Taxonomy, the researcher scrutinised 168 editorial cartoons for a total of 33 days from widely read dailies in Sinhalese, Tamil and English before the recent Sri Lankan presidential elections. One key point among the findings is that to decode some of the editorial cartoons that appeared during this period one needs to be familiar with the literary or cultural sources to which they refer. Examples cited in this paper shows that editorial cartoons in election times can provide a cathartic outlet for all voters.
Phosphatidylinositol 3-Monophosphate Is Involved in Toxoplasma Apicoplast Biogenesis

Apicomplexan parasites cause devastating diseases including malaria and toxoplasmosis. They harbour a plastid-like, non-photosynthetic organelle of algal origin, the apicoplast, which fulfils critical functions for parasite survival. Because of its essential and original metabolic pathways, the apicoplast has become a target for the development of new anti-apicomplexan drugs. Here we show that the lipid phosphatidylinositol 3-monophosphate (PI3P) is involved in apicoplast biogenesis in Toxoplasma gondii. In yeast and mammalian cells, PI3P is concentrated on early endosomes and regulates trafficking of endosomal compartments. Imaging of PI3P in T. gondii showed that the lipid was associated with the apicoplast and apicoplast protein-shuttling vesicles. Interference with regular PI3P function by over-expression of a PI3P specific binding module in the parasite led to the accumulation of vesicles containing apicoplast peripheral membrane proteins around the apicoplast and, ultimately, to the loss of the organelle. Accordingly, inhibition of the PI3P-synthesising kinase interfered with apicoplast biogenesis. These findings point to an unexpected implication for this ubiquitous lipid and open new perspectives on how nuclear encoded proteins traffic to the apicoplast. This study also highlights the possibility of developing specific pharmacological inhibitors of the parasite PI3-kinase as novel anti-apicomplexan drugs.
The reliability-validity studies for the Student-Teacher Relationship Scale (STRS)

The purpose of this study is to conduct reliability-validity studies of the Student-Teacher Relationship Scale (STRS). The study is a survey for scale's adaptation to measures language equivalence, reliability and validity of the STRS in Turkish. The original scale was developed by Pianta to measure a teacher’s perception of his or her relationship with a particular student. The STRS is the only self-report measure that assesses a teachers’ perception of his or her relationship with a particular student, from preschool to Grade 3. The STRS measures student-teacher relationship patterns in terms of conflict, closeness, and dependency, as well as the overall quality of the relationship. The 28-item scale is a 5-point likert-type measuring instrument. The Turkish version of the scale was applied to the teachers of 280 preschool children and primary school students and the validity and reliability of the scale were tested. The STRS was translated into Turkish by five experts who were competent in both languages, English and Turkish. Translations made by the experts were compared and some changes were made in terms of cultural meaning and linguistic rules. Another expert who was competent in Turkish and English languages translated the scale back to English. The original and the Turkish translation of the scale were compared by the researchers and the final form of the Turkish version was completed. Statistics of internal consistency coefficients (Cronbach Alpha), factor analysis, and test re-test reliability were calculated for validity and reliability of the STRS as whole scale and its subscales. © 2014European Journal of Research on Education by IASSR.
Optimizing a global alignment of protein interaction networks

Motivation: The global alignment of protein interaction networks is a widely studied problem. It is an important first step in understanding the relationship between the proteins in different species and identifying functional orthologs. Furthermore, it can provide useful insights into the species’ evolution. Results: We propose a novel algorithm, PISwap, for optimizing global pairwise alignments of protein interaction networks, based on a local optimization heuristic that has previously demonstrated its effectiveness for a variety of other intractable problems. PISwap can begin with different types of network alignment approaches and then iteratively adjust the initial alignments by incorporating network topology information, trading it off for sequence information. In practice, our algorithm efficiently refines other well-studied alignment techniques with almost no additional time cost. We also show the robustness of the algorithm to noise in protein interaction data. In addition, the flexible nature of this algorithm makes it suitable for different applications of network alignment. This algorithm can yield interesting insights into the evolutionary dynamics of related species. Availability: Our software is freely available for non-commercial purposes from our Web site, http://piswap.csail.mit.edu/. Contact: bab@csail.mit.edu or csliao@ie.nthu. edu.tw Supplementary information: Supplementary data are available at Bioinformatics online.
The effects of the SLCO2B1 c.1457C>T polymorphism and apple juice on the pharmacokinetics of fexofenadine and midazolam in humans

Objective The objective was to determine the effects of the SLCO2B1 c.1457C>T polymorphism and apple juice on the pharmacokinetics of fexofenadine and midazolam in humans. Methods Individuals were divided based on the genotype of SLCO2B1 c.1457C>T (n=14, c.[1457C]+c.[=] 5, c.[1457C]+c.[1457C>T] 5, and c.[1457C>T]+c.[1457C>T] 4). The oral pharmacokinetics of 60 mg fexofenadine and 5 mg midazolam were assessed with water or apple juice (1200 ml/day) in a randomized crossover study. OATP2B1-mediated uptake of fexofenadine and midazolam was evaluated with Xenopus laevis oocyte gene-expression system. Results When fexofenadine was administered with water, subjects with c. [1457C>T] allele showed a significant decrease in fexofenadine in the area under the plasma concentration–time curve (AUC) compared with c. [1457C]+c[=] subjects (1110±347 vs. 1762±542 ng·h/ml, P<0.05). When administered with apple juice, a significant decrease in the fexofenadine AUC was observed compared with water (1342±519 vs. 284±79.2 ng·h/ml, P<0.05). The apple juice induced decrease in fexofenadine AUC was significantly lower in subjects carrying the c. [1457C>T] allele. Neither the genotype nor the apple juice showed significant effects on the pharmacokinetics of midazolam except for a marginally significant decrease in Cmax after administration with apple juice. The uptake of fexofenadine by OATP2B1 cRNA-injected oocytes was significantly higher than that by water-injected oocytes. Apple juice, but not midazolam, significantly decreased the uptake of fexofenadine by OATP2B1 cRNA-injected oocytes. Conclusion The results suggest that fexofenadine is a substrate of OATP2B1, and the transport function of OATP2B1 is subject to the genotype of SLCO2B1 c.1457C>T and apple juice. It is likely that apple juice has little effect on CYP3A.
Deep Deconvolutional Networks for Scene Parsing

Scene parsing is an important and challenging prob- lem in computer vision. It requires labeling each pixel in an image with the category it belongs to. Tradition- ally, it has been approached with hand-engineered features from color information in images. Recently convolutional neural networks (CNNs), which automatically learn hierar- chies of features, have achieved record performance on the task. These approaches typically include a post-processing technique, such as superpixels, to produce the final label- ing. In this paper, we propose a novel network architecture that combines deep deconvolutional neural networks with CNNs. Our experiments show that deconvolutional neu- ral networks are capable of learning higher order image structure beyond edge primitives in comparison to CNNs. The new network architecture is employed for multi-patch training, introduced as part of this work. Multi-patch train- ing makes it possible to effectively learn spatial priors from scenes. The proposed approach yields state-of-the-art per- formance on four scene parsing datasets, namely Stanford Background, SIFT Flow, CamVid, and KITTI. In addition, our system has the added advantage of having a training system that can be completely automated end-to-end with- out requiring any post-processing.
A fixed-point decoding approach for statistical machine translation on mobile terminals

The demand for statistical machine translation on mobile terminals is increasing rapidly, but translation speed is restricted by the embedded processors without a floating-point unit. This paper proposes an approach to convert floating-point numbers into fixed-point numbers for SMT decoding on mobile terminals in order to reduce the impact of the processors without a floating-point unit on translation speed. The experiments based on PC and mobile terminal show that this approach ensures the quality of translation and the speed of fixed-point arithmetic operations is 135.6% faster than that of floating-point arithmetic operations. Therefore, this approach can efficiently improve translation speed of SMT systems on mobile terminals with weak ability in floating-point arithmetic operations.
Excess mortality associated with diuretic therapy in diabetes mellitus.

OBJECTIVE To determine whether the high mortality among diabetic patients receiving treatment for hypertension can be explained by associated risk factors or must be attributed to a deleterious effect of antihypertensive treatment. DESIGN Cohort analytic study with a median follow-up of 4.5 years. SETTING Outpatients with diabetes and severe retinopathy who were enrolled in a multicenter, randomized clinical trial of laser treatment to prevent blindness had ophthalmologic examinations every 4 months and annual medical examinations that included measurement of blood pressure and recording of anti-hypertensive treatment. Only 5.5% of the patients were unavailable for follow-up. When a patient died, the circumstances surrounding the death were reviewed and classified by a mortality review committee. PARTICIPANTS --There were 759 participants in the study; they were white, were aged 35 to 69 years, and had normal serum creatinine levels at the baseline examination. MEASUREMENTS AND MAIN RESULTS --Patients were classified into five groups according to information recorded at the baseline and first annual follow-up examinations: normotensive (diastolic blood pressure less than 90 mm Hg), untreated hypertensive, hypertensive treated by diuretics alone, hypertensive treated by other agents alone, and hypertensive treated by both agents. Cardiovascular mortality was higher in patients treated for hypertension than in patients with untreated hypertension. The excess was primarily found in patients treated with diuretics alone, although that group had the lowest blood pressure with treatment. After adjusting for differences in risk factors, cardiovascular mortality was 3.8 times higher in patients treated with diuretics alone than in patients with untreated hypertension (P less than .001). CONCLUSIONS --In individuals with diabetes, intervention with diuretics to reduce hypertension is associated with excess mortality. Until there is a clinical trial showing a beneficial effect of diuretic treatment in diabetic patients, there is urgent need to reconsider its continued usage in this population.
Co-Evolution of Content Spread and Popularity in Mobile Opportunistic Networks

We consider a setting in which a single item of content is disseminated in a population of mobile nodes by opportunistic copying when pairs of nodes come in radio contact. The nodes in the population may either be interested in receiving the content (referred to as destinations) or not yet interested in receiving the content (referred to as relays). We consider a model for the evolution of popularity, the process by which relays get converted into destinations. A key contribution of our work is to model and study the joint evolution of content popularity and its spread in the population. Copying the content to relay nodes is beneficial since they can help spread the content to destinations, and could themselves be converted into destinations. We derive a fluid limit for the joint evolution model and obtain optimal policies for copying to relay nodes in order to deliver content to a desired fraction of destinations, while limiting the fraction of relay nodes that get the content but never turn into destinations. We prove that a time-threshold policy is optimal for controlling the copying to relays, i.e., there is an optimal time-threshold up to which all opportunities for copying to relays are exploited, and after which relays are not copied to. We then utilize simulations and numerical evaluations to provide insights into the effects of various system parameters on the optimally controlled co-evolution model.
Parameter estimation with missing input/output data

The problem of recursive parameter estimation with missing input/output data is studied in this paper. A fictitious measurement noise model is presented for missing data, and a noise-robust minimum component analysis based algorithm is developed to recursively estimate parameters from the new ‘noisy’ input/output data. Convergence properties of the proposed algorithm are analyzed. The simulation results verify the effectiveness of the proposed algorithm.
Designing pedagogical interventions to support student use of learning analytics

This article addresses a relatively unexplored area in the emerging field of learning analytics, the design of learning analytics interventions. A learning analytics intervention is defined as the surrounding frame of activity through which analytic tools, data, and reports are taken up and used. It is a soft technology that involves the orchestration of the human process of engaging with the analytics as part of the larger teaching and learning activity. This paper first makes the case for the overall importance of intervention design, situating it within the larger landscape of the learning analytics field, and then considers the specific issues of intervention design for student use of learning analytics. Four principles of pedagogical learning analytics intervention design that can be used by teachers and course developers to support the productive use of learning analytics by students are introduced: Integration, Agency, Reference Frame and Dialogue. In addition three core processes in which to engage students are described: Grounding, Goal-Setting and Reflection. These principles and processes are united in a preliminary model of pedagogical learning analytics intervention design for students, presented as a starting point for further inquiry.
The amino acid composition of the organic matrix and the neutral-soluble and acid-soluble components of embryonic bovine enamel.

The proteins of developing dental enamel matrix, although among the least studied of all the extracellular proteins, have nevertheless been found to possess certain unique and interesting properties. The amino acid composition has been characterized by the highest content of proline thus far reported for any protein (approx. 200-250 residues/1000 amino acid residues), a relatively large number of glutamic acid and histidine residues, and the presence of hydroxyproline and hydroxylysine (Eastoe, 1960, 1963; Glimcher, Mechanic, Bonar & Daniel, 1961 a; Piez, 1961). Except for collagen and polyproline, the configurations proposed for fibrous proteins cannot accommodate such large amounts of proline (Lindley, 1955; Szent-Gyorgyi & Cohen, 1957; Glimcher et al. 1961 a). By constructing models a possible configuration was found which permitted as many as 250 residues of proline/1000 amino acid residues to be randomly incorporated into the polypeptide chains (Glimcher et al. 1961 a). The structure proposed was composed of anti-parallel pleated sheets with a 1800 bend of the polypeptide chains for each proline residue and was similar to the cross: configuration suggested by Astbury, Beighton & Parker (1959). Cross-. X-ray-diffraction patterns have been obtained from histologically identified embryonic bovine enamel matrix that had the characteristic amino acid composition (Glimcher, Bonar & Daniel, 1961 b). Further characterization of the proteins has been hampered by the extremely limited amount oftissue available and the relative insolubility of the proteins (Eastoe, 1963). In the present study, most of the proteins of the decalcified organic matrix of developing bovine tooth enamel were found to be soluble in cold neutral buffer solution of low ionic strength, and the residue remaining after exhaustive neutral-buffer extraction dissolved in mild acid. The amino acid composition of these fractions was investigated.
A review of imaging methods for measuring drug release at nanometre scale: a case for drug delivery systems

Introduction: Current drug delivery research is focused on improving the efficacy of drug delivery systems, with emphasis on precise targeting, accurate dose delivery, strategies for overcoming the tissue barrier and monitoring the effects of drugs on their targets. To realize these goals, it is essential to determine the spatio-temporal bio-distribution of particles in the whole animal. Enabling such a measurement at the nanometer scale helps in the design of efficient systems. Areas covered: This article discusses the need for molecular imaging in drug delivery development and also reviews promising imaging methods. Moreover, the physics behind each method is explained and evaluated to derive advantages and limitations. The review enables the readers to select, use and modify the existing methods to implement imaging protocols for studying drug release from particular drug delivery. Expert opinion: Currently, the difference in pharmacodynamics obtained via various imaging modalities cannot be verified and hinders clinical use. To establish imaging as a scientific tool, its translation into clinical use is vital. Presently, there is no single imaging method suitable for drug-release studies. However, hybrid imaging has the potential to provide the desired imaging system.
Responses of glutathione‐related antioxidant defense system in serum of Nile tilapia (Oreochromis niloticus) exposed to sublethal concentration of methomyl and recovery pattern

Tilapia were exposed to sublethal concentrations of 0, 0.2, 2, 20, or 200 μg/L for 30 days, and then transferred to methomyl‐free water for 18 days. GST, GPx, GR, GSH, and GSSG in tilapia serum were examined at 0, 6, 12, 18, 24, and 30 days after methomyl exposure and at 18 days after transferring to methomyl‐free water. There were no significant changes in antioxidants activities and contents in serum of tilapia exposed to 0.2 μg/L. Significant increases in GST, GR, GPx, and GSSG accompanied by a decrease in GSH were observed following methomyl exposure to 2, 20, or 200 μg/L, suggesting the presence of oxidative stress. Thus, it would appear the 0.2 μg/L methomyl might be considered the no observed adverse effect level. Recovery data showed that the effects produced by lower concentration of 20 μg/L were reversible but not at the higher 200 μg/L concentration. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 483–489, 2015.