Miracle-dz/UniFAR-FTUs huggingface dataset:
Solution NMR Structure and Histone Binding of the PHD Domain of Human MLL5

Mixed Lineage Leukemia 5 (MLL5) is a histone methyltransferase that plays a key role in hematopoiesis, spermatogenesis and cell cycle progression. In addition to its catalytic domain, MLL5 contains a PHD finger domain, a protein module that is often involved in binding to the N-terminus of histone H3. Here we report the NMR solution structure of the MLL5 PHD domain showing a variant of the canonical PHD fold that combines conserved H3 binding features from several classes of other PHD domains (including an aromatic cage) along with a novel C-terminal α-helix, not previously seen. We further demonstrate that the PHD domain binds with similar affinity to histone H3 tail peptides di- and tri-methylated at lysine 4 (H3K4me2 and H3K4me3), the former being the putative product of the MLL5 catalytic reaction. This work establishes the PHD domain of MLL5 as a bone fide ‘reader’ domain of H3K4 methyl marks suggesting that it may guide the spreading or further methylation of this site on chromatin.
Preclinical Pharmacological Evaluation of a Novel Multiple Kinase Inhibitor, ON123300, in Brain Tumor Models

ON123300 is a low molecular weight multikinase inhibitor identified through a series of screens that supported further analyses for brain tumor chemotherapy. Biochemical assays indicated that ON123300 was a strong inhibitor of Ark5 and CDK4, as well as growth factor receptor tyrosine kinases such as β-type platelet-derived growth factor receptor (PDGFRβ). ON123300 inhibited U87 glioma cell proliferation with an IC50 3.4 ± 0.1 μmol/L and reduced phosphorylation of Akt, yet it also unexpectedly induced Erk activation, both in a dose- and time-dependent manner that subsequently was attributed to relieving Akt-mediated C-Raf S259 inactivation and activating a p70S6K-initiated PI3K-negative feedback loop. Cotreatment with the EGFR inhibitor gefitinib produced synergistic cytotoxic effects. Pursuant to the in vitro studies, in vivo pharmacokinetic and pharmacodynamic studies of ON123300 were completed in mice bearing intracerebral U87 tumors following intravenous doses of 5 and 25 mg/kg alone, and also at the higher dose concurrently with gefitinib. ON123300 showed high brain and brain tumor accumulation based on brain partition coefficient values of at least 2.5. Consistent with the in vitro studies, single agent ON123300 caused a dose-dependent suppression of phosphorylation of Akt as well as activation of Erk in brain tumors, whereas addition of gefitinib to the ON123300 regimen significantly enhanced p-Akt inhibition and prevented Erk activation. In summary, ON123300 demonstrated favorable pharmacokinetic characteristics, and future development for brain tumor therapy would require use of combinations, such as gefitinib, that mitigate its Erk activation and enhance its activity. Mol Cancer Ther; 13(5); 1105–16. ©2014 AACR.
Towards a Reliable Distributed Web Service Execution Engine

This paper presents an approach for providing a reliable distributed Web service execution engine. Instead of using a Web service execution engine running on a single host to conduct the execution of a composite service, the responsibility of conducting the execution of the composite service has been delegated to the service providers that are chosen to provide the main functionalities of the tasks in the composite service. The operations of the tasks are represented as a set of XML-based notations. The notations are platform independent. Thus, they can be (a) retrieved by service providers based on different platforms, and, (b) interpreted and executed by the service providers. The approach also provides a mechanism for coping with possible failure in the system
Designing Behaviour in Bio-inspired Robots Using Associative Topologies of Spiking-Neural-Networks

This study explores the design and control of the behaviour of agents and robots using simple circuits of spiking neurons and Spike Timing Dependent Plasticity (STDP) as a mechanism of associative and unsupervised learning. Based on a "reward and punishment" classical conditioning, it is demonstrated that these robots learnt to identify and avoid obstacles as well as to identify and look for rewarding stimuli. Using the simulation and programming environment NetLogo, a software engine for the Integrate and Fire model was developed, which allowed us to monitor in discrete time steps the dynamics of each single neuron, synapse and spike in the proposed neural networks. These spiking neural networks (SNN) served as simple brains for the experimental robots. The Lego Mindstorms robot kit was used for the embodiment of the simulated agents. In this paper the topological building blocks are presented as well as the neural parameters required to reproduce the experiments. This paper summarizes the resulting behaviour as well as the observed dynamics of the neural circuits. The Internet-link to the NetLogo code is included in the annex.
Clinical Outcomes Associated with Depression, Anxiety and Social Support Among Cardiac Rehabilitation Attendees

Objective: To utilize existing medical record information in order to examine the relationship between depression, anxiety, levels of social support and clinical outcomes in cardiac rehabilitation attendees. Method: In a tertiary care centre 389 records for cardiac rehabilitation outpatients were analysed. Hospital Anxiety and Depression Scales scores collected at week 4 of their cardiac rehabilitation programme were linked with medical record information on demographic, lifestyle, medical and other coronary heart disease risk factors, as well as follow-up cardiovascular events and readmissions for an average of 2.6 years. Variables of interest were anxiety and depression scores and proxy measures of social support. Clinical outcome measures were number of hospital admissions, length of stay and mortality. Results: Multiple variable analysis revealed higher anxiety scores were associated with more hospital admissions and higher depression scores were associated with longer length of stay after controlling for other established prognostic risk factors. Depression, anxiety and social support were not associated with mortality, however there was a low mortality rate in the present study. Conclusion: A comprehensive summary of the characteristics of cardiac rehabilitation patients was gathered through the linkage and examination of existing clinical databases. The results of this study provide some support for a prognostic role of depressive and anxiety symptoms and highlight the need for screening for psychological distress and provision of appropriate interventions when indicated.
Screening of Feral and Wood Pigeons for Viruses Harbouring a Conserved Mobile Viral Element: Characterization of Novel Astroviruses and Picornaviruses

A highly conserved RNA-motif of yet unknown function, called stem-loop-2-like motif (s2m), has been identified in the 3′ end of the genomes of viruses belonging to different RNA virus families which infect a broad range of mammal and bird species, including Astroviridae, Picornaviridae, Coronaviridae and Caliciviridae. Since s2m is such an extremely conserved motif, it is an ideal target for screening for viruses harbouring it. In this study, we have detected and characterized novel viruses harbouring this motif in pigeons by using a s2m-specific amplification. 84% and 67% of the samples from feral pigeons and wood pigeons, respectively, were found to contain a virus harbouring s2m. Four novel viruses were identified and characterized. Two of the new viruses belong to the genus Avastrovirus in the Astroviridae family. We propose two novel species to be included in this genus, Feral pigeon astrovirus and Wood pigeon astrovirus. Two other novel viruses, Pigeon picornavirus A and Pigeon picornavirus B, belong to the Picornaviridae family, presumably to the genus Sapelovirus. Both of the novel picornaviruses harboured two adjacent s2m, called (s2m)2, suggesting a possible increased functional effect of s2m when present in two copies.
Protocol for Detection of Biofilms on Needleless Connectors Attached to Central Venous Catheters

ABSTRACT Central venous catheter needleless connectors (NCs) have been shown to develop microbial contamination. A protocol was developed for the collection, processing, and examination of NCs to detect and measure biofilms on these devices. Sixty-three percent of 24 NCs collected from a bone marrow transplant center contained biofilms comprised primarily of coagulase-negative staphylococci.
The Association between Invasive Group A Streptococcal Diseases and Viral Respiratory Tract Infections

Viral infections of the upper respiratory tract are associated with a variety of invasive diseases caused by Streptococcus pyogenes, the group A streptococcus, including pneumonia, necrotizing fasciitis, toxic shock syndrome, and bacteremia. While these polymicrobial infections, or superinfections, are complex, progress has been made in understanding the molecular basis of disease. Areas of investigation have included the characterization of virus-induced changes in innate immunity, differences in bacterial adherence and internalization following viral infection, and the efficacy of vaccines in mitigating the morbidity and mortality of superinfections. Here, we briefly summarize viral-S. pyogenes superinfections with an emphasis on those affiliated with influenza viruses.
The Torque Ripple Minimization Technique for a Low Cost Brushless DC Motor Drive

The torque produced in a brushless DC motor with trapezoidal back electromotive force (BEMF) is constant under ideal conditions. Some of these ripples result from the natural structure of the motor, while some are related to the motor design parameters. This paper introduces a torque ripple minimization technique for BLDC motor drive that is operated with a small DC link capacitor along with a fuzzy controller ,it uses a single switch control strategy, resembles buck converter during operation at any switching state.The model of the proposed drive is done Matlab/Simulink to verify the effectiveness of the proposed scheme.
Recombinant DNA production of spider silk proteins

Spider dragline silk is considered to be the toughest biopolymer on Earth due to an extraordinary combination of strength and elasticity. Moreover, silks are biocompatible and biodegradable protein‐based materials. Recent advances in genetic engineering make it possible to produce recombinant silks in heterologous hosts, opening up opportunities for large‐scale production of recombinant silks for various biomedical and material science applications. We review the current strategies to produce recombinant spider silks.
Metabolite Cross-Feeding Enhances Virulence in a Model Polymicrobial Infection

Microbes within polymicrobial infections often display synergistic interactions resulting in enhanced pathogenesis; however, the molecular mechanisms governing these interactions are not well understood. Development of model systems that allow detailed mechanistic studies of polymicrobial synergy is a critical step towards a comprehensive understanding of these infections in vivo. In this study, we used a model polymicrobial infection including the opportunistic pathogen Aggregatibacter actinomycetemcomitans and the commensal Streptococcus gordonii to examine the importance of metabolite cross-feeding for establishing co-culture infections. Our results reveal that co-culture with S. gordonii enhances the pathogenesis of A. actinomycetemcomitans in a murine abscess model of infection. Interestingly, the ability of A. actinomycetemcomitans to utilize L-lactate as an energy source is essential for these co-culture benefits. Surprisingly, inactivation of L-lactate catabolism had no impact on mono-culture growth in vitro and in vivo suggesting that A. actinomycetemcomitans L-lactate catabolism is only critical for establishing co-culture infections. These results demonstrate that metabolite cross-feeding is critical for A. actinomycetemcomitans to persist in a polymicrobial infection with S. gordonii supporting the idea that the metabolic properties of commensal bacteria alter the course of pathogenesis in polymicrobial communities.
A framework for identifying and analyzing non-functional requirements from text

Early identification of Non-Functional Requirements (NFRs) is important as this has direct bearing on the design and architecture of the system. NFRs form the basis for architects to create the technical architecture of the system which acts as the scaffolding in which the functionality of the same is delivered. Failure to identify and analyze NFRs early-on can result in unclassified, incomplete or conflicting NFRs, and this typically results in costly rework in later stages of the software development. In practice, this activity is primarily done manually. In this paper, we present a framework to automatically detect and classify non-functional requirements from textual natural language requirements. Our approach to identify NFRs is based on extracting multiple features by parsing the natural language requirement whereby the presence of a certain combination of and relationship among the features uniquely identifies the requirement as an NFR of a particular category. These features are specified as pattern based rules which can be specified in a human readable language through the use of a domain specific language that we have defined. This enables great ease and flexibility in creating and extending rules. Our approach has been implemented as a prototype tool and here we also present the results of applying our approach on a publicly available requirement corpus.
Array-Based Comparative Genomic Hybridization Identifies CDK4 and FOXM1 Alterations as Independent Predictors of Survival in Malignant Peripheral Nerve Sheath Tumor

Purpose: Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive sarcomas with variable patient survival and few known prognostically relevant genomic biomarkers. To identify survival-associated genomic biomarkers, we performed high-resolution array-based comparative genomic hybridization (aCGH) on a large set of MPNSTs. Experimental Design: Candidate gene alterations identified by aCGH in 38 MPNSTs were validated at the DNA, RNA, and protein levels on these same tumors and an independent set of 87 MPNST specimens. Results: aCGH revealed highly complex copy number alterations, including both previously reported and completely novel loci. Four regions of copy number gain were associated with poor patient survival. Candidate genes in these regions include SOX5 (12p12.1), NOL1 and MLF2 (12p13.31), FOXM1 and FKBP1 (12p13.33), and CDK4 and TSPAN31 (12q14.1). Alterations of these candidate genes and several others of interest (ERBB2, MYC and TP53) were confirmed by at least 1 complementary methodology, including DNA and mRNA quantitative real-time PCR, mRNA expression profiling, and tissue microarray-based fluorescence in situ hybridization and immunohistochemistry. Multivariate analysis showed that CDK4 gain/amplification and increased FOXM1 protein expression were the most significant independent predictors for poor survival in MPNST patients (P < 0.05). Conclusions: Our study provides new and independently confirmed candidate genes that could serve as genomic biomarkers for overall survival in MPNST patients. Clin Cancer Res; 17(7); 1924–34. ©2011 AACR.
Proteomic analysis of roots growth and metabolic changes under phosphorus deficit in maize (Zea mays L.) plants

Phosphorus (P) deficiency is a major limitation for plant growth and development. Plants can respond defensively to this stress, modifying their metabolic pathways and root morphology, and this involves changes in their gene expression. To better understand the low P adaptive mechanism of crops, we conducted the comparative proteome analysis for proteins isolated from maize roots treated with 1000 μM (control) or 5 μM KH2PO4 for 17 days. The results showed that approximately 20% of detected proteins on 2‐DE gels were increased or decreased by two‐fold or more under phosphate (Pi) stress. We identified 106 differentially expressed proteins by MALDI‐TOF MS. Analysis of these P starvation responsive proteins suggested that they were involved in phytohormone biosynthesis, carbon and energy metabolisms, protein synthesis and fate, signal transduction, cell cycle, cellular organization, defense, secondary metabolism, etc. It could be concluded that they may play important roles in sensing the change of external Pi concentration and regulating complex adaptation activities for Pi deprivation to facilitate P homeostasis. Simultaneously, as a basic platform, the results would also be useful for the further characterization of gene function in plant P nutrition.
Title: BALDEY: A database of auditory lexical decisions

In an auditory lexical decision experiment, 5,541 spoken content words and pseudo-words were presented to 20 native speakers of Dutch. The words vary in phonological makeup and in number of syllables and stress pattern, and are further representative of the native Dutch vocabulary in that most are morphologically complex, comprising two stems or one stem plus derivational and inflectional suffixes, with inflections representing both regular and irregular paradigms; the pseudo-words were matched in these respects to the real words. The BALDEY data file includes response times and accuracy rates, with for each item morphological information plus phonological and acoustic information derived from automatic phonemic segmentation of the stimuli. Two initial analyses illustrate how this data set can be used. First, we discuss several measures of the point at which a word has no further neighbors, and compare the degree to which each measure predicts our lexical decision response outcomes. Second, we investigate how well four different measures of frequency of occurrence (from written corpora, spoken corpora, subtitles and frequency ratings by 70 participants) predict the same outcomes. These analyses motivate general conclusions about the auditory lexical decision task. The (publicly available) BALDEY database lends itself to many further analyses.
A framework for realistic 3D tele-immersion

Meeting, socializing and conversing online with a group of people using teleconferencing systems is still quite different from the experience of meeting face to face. We are abruptly aware that we are online and that the people we are engaging with are not in close proximity. Analogous to how talking on the telephone does not replicate the experience of talking in person. Several causes for these differences have been identified and we propose inspiring and innovative solutions to these hurdles in attempt to provide a more realistic, believable and engaging online conversational experience. We present the distributed and scalable framework REVERIE that provides a balanced mix of these solutions. Applications build on top of the REVERIE framework will be able to provide interactive, immersive, photo-realistic experiences to a multitude of users that for them will feel much more similar to having face to face meetings than the experience offered by conventional teleconferencing systems.
Genetic and Genomic Tools for the Marine Annelid Platynereis dumerilii

The bristle worm Platynereis dumerilii displays many interesting biological characteristics. These include its reproductive timing, which is synchronized to the moon phase, its regenerative capacity that is hormonally controlled, and a slow rate of evolution, which permits analyses of ancestral genes and cell types. As a marine annelid, Platynereis is also representative of the marine ecosystem, as well as one of the three large animal subphyla, the Lophotrochozoa. Here, we provide an overview of the molecular resources, functional techniques, and behavioral assays that have recently been established for the bristle worm. This combination of tools now places Platynereis in an excellent position to advance research at the frontiers of neurobiology, chronobiology, evo-devo, and marine biology.
Role of Dopamine Receptors in the Nucleus Accumbens in the Rewarding Properties of Cocaine

Studies with intravenous self-administration strongly point to dopaminergic mechanisms in the reinforcing properties of psychomotor stimulants. Dopamine agonists function as positive reinforcers in the monkey1.2 and the rat,3 and lesion studies suggest that, a t least in part, the dopaminergic system in the nucleus accumbens plays a role as a neuroanatomical substrate for cocaine reinforcement in the rat.4. 5 Further, it is well known that low doses of both D1 and D2 dopaminergic antagonists will increase the response rates for intravenous injections of cocaine.69 This increase in selfadministration behavior is thought to be a compensatory mechanism for decreases in the magnitude of the reinforcer, similar to the rate increase observed when the dose of the self-administered stimulant is r e d ~ c e d . ~ The purpose of the following study was to explore the hypothesis that dopamine DI and/or Dz receptor subtypes in the nucleus accumbens are responsible for the rewarding properties of cocaine. Hence, the present study evaluated the effects of D1 and D2 dopamine receptor antagonists directly infused into the nucleus accumbens on cocaine self-administration behavior in the rat.
Real-time polygonal-light shading with linearly transformed cosines

In this paper, we show that applying a linear transformation---represented by a 3 x 3 matrix---to the direction vectors of a spherical distribution yields another spherical distribution, for which we derive a closed-form expression. With this idea, we can use any spherical distribution as a base shape to create a new family of spherical distributions with parametric roughness, elliptic anisotropy and skewness. If the original distribution has an analytic expression, normalization, integration over spherical polygons, and importance sampling, then these properties are inherited by the linearly transformed distributions. By choosing a clamped cosine for the original distribution we obtain a family of distributions, which we call Linearly Transformed Cosines (LTCs), that provide a good approximation to physically based BRDFs and that can be analytically integrated over arbitrary spherical polygons. We show how to use these properties in a realtime polygonal-light shading application. Our technique is robust, fast, accurate and simple to implement.
Multivariate Patterns in Object-Selective Cortex Dissociate Perceptual and Physical Shape Similarity

Prior research has identified the lateral occipital complex (LOC) as a critical cortical region for the representation of object shape in humans. However, little is known about the nature of the representations contained in the LOC and their relationship to the perceptual experience of shape. We used human functional MRI to measure the physical, behavioral, and neural similarity between pairs of novel shapes to ask whether the representations of shape contained in subregions of the LOC more closely reflect the physical stimuli themselves, or the perceptual experience of those stimuli. Perceptual similarity measures for each pair of shapes were obtained from a psychophysical same-different task; physical similarity measures were based on stimulus parameters; and neural similarity measures were obtained from multivoxel pattern analysis methods applied to anterior LOC (pFs) and posterior LOC (LO). We found that the pattern of pairwise shape similarities in LO most closely matched physical shape similarities, whereas shape similarities in pFs most closely matched perceptual shape similarities. Further, shape representations were similar across participants in LO but highly variable across participants in pFs. Together, these findings indicate that activation patterns in subregions of object-selective cortex encode objects according to a hierarchy, with stimulus-based representations in posterior regions and subjective and observer-specific representations in anterior regions.