Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of myosin VI reduces secretion and the size of the Golgi in fibroblasts from Snell's waltzer mice

Golgi morphology and function are dependent on an intact microtubule and actin cytoskeleton. Myosin VI, an unusual actin‐based motor protein moving towards the minus ends of actin filaments, has been localized to the Golgi complex at the light and electron microscopic level. Myosin VI is present in purified Golgi membranes as a peripheral membrane protein, targeted by its globular tail domain. To investigate the function of myosin VI at the Golgi complex, immortal fibroblastic cell lines of Snell's waltzer mice lacking myosin VI were established. In these cell lines, where myosin VI is absent, the Golgi complex is reduced in size by ∼40% compared with wild‐type cells. Furthermore, protein secretion of a reporter protein from Snell's waltzer cells is also reduced by 40% compared with wild‐type cells. Rescue experiments showed that fully functional myosin VI was able to restore Golgi complex morphology and protein secretion in Snell's waltzer cells to the same level as that observed in wild‐type cells.
Submitted to the Annals of Applied Probability CONTINUOUS-TIME MEAN – VARIANCE EFFICIENCY : THE 80 % RULE By

This paper studies a continuous-time market where an agent, having specified an investment horizon and a targeted terminal mean return, seeks to minimize the variance of the return. The optimal portfolio of such a problem is called mean–variance efficient à la Markowitz. It is shown that, when the market coefficients are deterministic functions of time, a mean–variance efficient portfolio realizes the (discounted) targeted return on or before the terminal date with a probability greater than 0.8072. This number is universal irrespective of the market parameters, the targeted return, and the length of the investment horizon.
Occurrence of aminoglycoside-modifying enzymes among isolates of Escherichia coli exhibiting high levels of aminoglycoside resistance isolated from Korean cattle farms

This study investigated 247 Escherichia coli isolates collected from four cattle farms to characterize aminoglycoside-modifying enzyme (AME) genes, their plasmid replicons and transferability. Out of 247 isolates a high number of isolates (total 202; 81.78%) were found to be resistant to various antibiotics by disc diffusion. Of the 247 strains, 139 (56.3%) were resistant to streptomycin, and other antibiotic resistances followed as tetracycline (12.15%), ampicillin (7%), chloramphenicol (5.7%) and trimethoprim-sulfamethoxazole (0.8%). Among 247 isolates B1 was the predominant phylogenetic group identified comprising 151 isolates (61.1%), followed by groups A (27.9%), D (7%) and B2 (4%). Out of 139 isolates investigated for AME, 130 (93.5%) isolates carried at least one AME gene. aph3″-1a and aph3″-1b (46%) were the principal genes detected, followed by aac3-IVa (34.5%). ant2″-1a was the least detected gene (2.2%). Nine (6.5%) strains carried no AME genes. Twelve (63.2%) among 19 isolates transferred an AME gene to a recipient and aph3΄-1a was the dominant transferred gene. Transferability mainly occurred via the IncFIB replicon type (52.6%). Pulsed-field gel electrophoresis typing demonstrated a higher degree of diversity with 14 distinct cluster types. This result suggests that commensal microflora from food-producing animals has a tremendous ability to harbor and transfer AME genes, and poses a potential risk by dissemination of resistance to humans through the food chain.
New Therapeutic Targets for Mood Disorders

Existing pharmacological treatments for bipolar disorder (BPD) and major depressive disorder (MDD) are often insufficient for many patients. Here we describe a number of targets/compounds that clinical and preclinical studies suggest could result in putative novel treatments for mood disorders. These include: (1) glycogen synthase kinase-3 (GSK-3) and protein kinase C (PKC), (2) the purinergic system, (3) histone deacetylases (HDACs), (4) the melatonergic system, (5) the tachykinin neuropeptides system, (6) the glutamatergic system, and (7) oxidative stress and bioenergetics. The paper reviews data on new compounds that have shown antimanic or antidepressant effects in subjects with mood disorders, or similar effects in preclinical animal models. Overall, an improved understanding of the neurobiological underpinnings of mood disorders is critical in order to develop targeted treatments that are more effective, act more rapidly, and are better tolerated than currently available therapies.
ClonalFrameML: Efficient Inference of Recombination in Whole Bacterial Genomes

Recombination is an important evolutionary force in bacteria, but it remains challenging to reconstruct the imports that occurred in the ancestry of a genomic sample. Here we present ClonalFrameML, which uses maximum likelihood inference to simultaneously detect recombination in bacterial genomes and account for it in phylogenetic reconstruction. ClonalFrameML can analyse hundreds of genomes in a matter of hours, and we demonstrate its usefulness on simulated and real datasets. We find evidence for recombination hotspots associated with mobile elements in Clostridium difficile ST6 and a previously undescribed 310kb chromosomal replacement in Staphylococcus aureus ST582. ClonalFrameML is freely available at http://clonalframeml.googlecode. com/.
Comparison of three methods of collecting nasal specimens for respiratory virus analysis.

BACKGROUND Nasopharyngeal aspiration (NPA) is used widely in the collection of nasal specimens for respiratory virus diagnosis. The method has limitations in relation to technical expertise, patient anxiety, and apparatus dependence. Nasal washing (NW) offers an alternative approach. OBJECTIVE To identify the merits of two different NW methods in comparison with NPA. DESIGN Two hundred children with acute respiratory infection (ARI) were randomised to receive one of three collection devices: (i) standard NPA, (ii) NW using a 30ml ear-syringe bulb (NWb), or (iii) NW using a 5ml syringe (NWs) with a shortened (9cm) 8FG tube. Assessment focused on ease of procedure, acceptability to parent and child, and adequacy of epithelial cell yield for immunofluorescence testing. A short questionnaire was delivered. SETTING Paediatric Ward of Kilifi District Hospital, (KDH) Kilifi, Kenya. SUBJECTS Any child admitted with ARI between 5th November 2001 and 24th January 2002. RESULTS Children recruited into NPA, NWb and NWs procedures numbered 62, 76 and 62, respectively (median age of 8 months). A higher proportion of children receiving NWb did not cry (43%) compared to those receiving NPA (13%) (OR 5.18; 95% CI 2.17-12.4). Whereas 66% of mothers were comfortable with NPA procedure, the proportion for NWs was 40% (OR 0.341; 0.163-0.714). Acceptability to the operator was marginally lower for NWs than NPA (79% vs 92%, OR 0.324, 0.107-0.974). For other observations there were no differences between the procedures; these were length of procedure (98% <5mins), the acceptable time interval for repeating a procedure (64% <1 week), comparison with blood collection (77% preferred the nasal specimen) and slides with 20 or more epithelial cells (overall 82%). CONCLUSION Nasal washing methods provide simple and effective alternatives to NPA, with the NWb being the more acceptable, and have merits for use in resource poor and home settings.
Differential expression of neuroligin genes in the nervous system of zebrafish

The establishment and maturation of appropriate synaptic connections is crucial in the development of neuronal circuits. Cellular adhesion is believed to play a central role in this process. Neuroligins are neuronal cell adhesion molecules that are hypothesized to act in the initial formation and maturation of synaptic connections. In order to establish the zebrafish as a model to investigate the in vivo role of Neuroligin proteins in nervous system development, we identified the zebrafish orthologs of neuroligin family members and characterized their expression. Zebrafish possess seven neuroligin genes. Synteny analysis and sequence comparisons show that NLGN2, NLGN3, and NLGN4X are duplicated in zebrafish, but NLGN1 has a single zebrafish ortholog. All seven zebrafish neuroligins are expressed in complex patterns in the developing nervous system and in the adult brain. The spatial and temporal expression patterns of these genes suggest that they occupy a role in nervous system development and maintenance. Developmental Dynamics 239:703–714, 2010. © 2010 Wiley‐Liss, Inc.
Molecular Insights on the Peripheral and Intratumoral Effects of Systemic High-Dose rIL-2 (Aldesleukin) Administration for the Treatment of Metastatic Melanoma

Purpose: We have previously shown that within tumors, recombinant interleukin-2 (rIL-2, aldesleukin) consistently activates tumor-associated macrophages and upregulates IFN-stimulated genes while inducing minimal migration, activation, or proliferation of T cells. These effects are independent of tumor response to treatment. Here, we prospectively evaluated transcriptional alterations induced by rIL-2 in peripheral blood mononuclear cells (PBMC) and within melanoma metastases. Experimental Design: We evaluated gene expression changes by serially comparing pre- to posttreatment samples in 13 patients and also compared transcriptional differences among lesions displaying different responsiveness to therapy, focusing on 2 lesions decreasing in size and 2 remaining stable (responding lesions) compared with nonresponding ones. Results: As previously described, the effects of rIL-2 were dramatic within PBMCs, whereas effects within the tumor microenvironment were lesion specific and limited. However, distinct signatures specific to response could be observed in responding lesions pretreatment that were amplified following rIL-2 administration. These signatures match the functional profile observed in other human or experimental models in which immune-mediated tissue-specific destruction (TSD) occurs, underscoring common pathways leading to rejection. Moreover, the signatures observed in pretreatment lesions were qualitatively similar to those associated with TSD, underlining a determinism to immune responsiveness that depends upon the genetic background of the host or the intrinsic genetic makeup of individual tumors. Conclusions: This is the first prospectively collected insight on global transcriptional events occurring during high-dose rIL-2 therapy in melanoma metastases responding to treatment. Clin Cancer Res; 17(23); 7440–50. ©2011 AACR.
Experiential Group Learning for Developing Competencies in Usability Practice

This chapter provides an overview of usability and reflects on a number of years of experience in a usability lab. Over this time, an approach to usability testing called situated co-inquiry was developed. Situated co-inquiry also became a very useful way to structure the teaching of usability. This chapter illustrates this teaching and some of the ways an experiential learning approach has been used in a group setting. I hope that some of this will be new and appealing to you and so assist you to generate fresh ideas in your teaching of the different areas of information systems (IS).
Measuring Similarities between Technical Terms Based on Wikipedia

The term similarities are utilized for measuring relatedness which is useful for semantic information processing such as content understanding, query expansion and word sense disambiguation. In our research, term similarities are used for grasping technical terms deeply related to emerging technologies. To measure term similarities, we propose a hybrid method based on both Wikipedia category and internal link information. And its performance is evaluated by comparative analysis with WLM (Wikipedia Link-based Measure), which is a state-of-the-art methodology. The performance evaluation shows that our method works better than other methods.
Attitudes, social support and environmental perceptions as predictors of active commuting behaviour in school children

Background: Environmental perceptions appear to play a role in determining behaviour in children, although their influence on active commuting remains unclear. This study examines whether attitudes, social support and environmental perceptions are associated with active commuting behaviour in school children and whether these associations are moderated by the distance to school. Methods: Data were collected as part of the SPEEDY study (Sport, Physical activity and Eating behaviour: Environmental Determinants in Young people), a cross-sectional study of 2064 children from schools in Norfolk, UK. Data regarding the usual mode of travel to school, attitudes towards and social support for active commuting, perceptions of the neighbourhood and route to school were assessed using questionnaires completed by 2012 children and their parents. Distance to school was estimated using a Geographic Information System and this was used to compare associations between personal and environmental factors and active travel, across different distance categories. Results: Forty per cent of children reported usually walking to school, with 9% cycling and the remainder using motorised travel. Parental attitudes and safety concerns, the presence of social support from parents and friends and parent-reported neighbourhood walkability were all found to be predictors of active commuting, with children receiving peer and family support and living in supportive environments being more likely to walk or cycle. There was some evidence of a moderating effect of distance whereby attitudes were more important for short distances and safety concerns long. Conclusion: Both attitudinal and environmental perceptions are associated with children’s active commuting behaviours. Given the difficulty in modifying attitudes directly, the effect on them of interventions to provide more supportive environments should be evaluated.
Datacenter net profit optimization with deadline dependent pricing

This paper considers deadline dependent pricing and its impact to datacenter net profit optimization. We formulate the problem by jointly maximizing total revenue as a function of individual job deadlines and minimizing electricity cost through job scheduling over different time and locations. These two complementary objectives-the maximization of revenue and the minimization of cost-are mutually-dependent due to the coupling of job completion time and scheduling decisions. Lever-aging a new approximation method for job completion time, we develop two low-complexity, distributed algorithms for the net profit optimization. Through numerical evaluations, we show the efficacy of the proposed algorithms as well as the net profit improvements.
In vivo measurement of T*2 and field inhomogeneity maps in the human heart at 1.5 T

Cardiac echo‐planar imaging suffers invariably from regions of severe distortion and T*2 decay in the myocardium. The purpose of this work was to perform local measurements of T*2 and field inhomogeneities in the myocardium and to identify the sources of focal signal loss and distortion. Field inhomogeneity maps and T*2 were measured in five normal volunteers in short‐axis slices spanning from base to apex. It was found that T*2 ranged from 26 ms (SD = 7 ms, n = 5) to 41 ms (SD = 11 ms, n = 5) over most of the heart, and peak‐to‐peak field inhomogeneity differences were 71 Hz (SD = 14 Hz, n = 5). In all hearts, regions of severe signal loss were consistently adjacent to the posterior vein of the left ventricle; T*2 in these regions was 12 ms (SD = 2 ms, n = 5), and the difference in resonance frequency with the surrounding myocardium was 70‐100 Hz. These effects may be caused by increased magnetic susceptibility from deoxygenated blood in these veins.
Patient‐adaptive reconstruction and acquisition in dynamic imaging with sensitivity encoding (PARADISE)

MRI of the human heart without explicit cardiac synchronization promises to extend the applicability of cardiac MR to a larger patient population and potentially expand its diagnostic capabilities. However, conventional nongated imaging techniques typically suffer from low image quality or inadequate spatio‐temporal resolution and fidelity. Patient‐Adaptive Reconstruction and Acquisition in Dynamic Imaging with Sensitivity Encoding (PARADISE) is a highly accelerated nongated dynamic imaging method that enables artifact‐free imaging with high spatio‐temporal resolutions by utilizing novel computational techniques to optimize the imaging process. In addition to using parallel imaging, the method gains acceleration from a physiologically driven spatio‐temporal support model; hence, it is doubly accelerated. The support model is patient adaptive, i.e., its geometry depends on dynamics of the imaged slice, e.g., subject's heart rate and heart location within the slice. The proposed method is also doubly adaptive as it adapts both the acquisition and reconstruction schemes. Based on the theory of time‐sequential sampling, the proposed framework explicitly accounts for speed limitations of gradient encoding and provides performance guarantees on achievable image quality. The presented in‐vivo results demonstrate the effectiveness and feasibility of the PARADISE method for high‐resolution nongated cardiac MRI during short breath‐hold. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Real-Time PCR Targeting the penA Mosaic XXXIV Type for Prediction of Extended-Spectrum-Cephalosporin Susceptibility in Clinical Neisseria gonorrhoeae Isolates

ABSTRACT Neisseria gonorrhoeae isolates with decreased susceptibility to extended-spectrum cephalosporins (ESCs) are increasing. We developed an assay to predict N. gonorrhoeae susceptibility to ESCs by targeting penA mosaic XXXIV, an allele prevalent among U.S. isolates with elevated ESC MICs. The assay was 97% sensitive and 100% specific for predicting at least one ESC MIC above the CDC alert value among clinical isolates, and it could be multiplexed with a previously validated gyrA PCR to predict ciprofloxacin susceptibility.
Adaptive from Innate: Human IFN-γ+CD4+ T Cells Can Arise Directly from CXCL8-Producing Recent Thymic Emigrants in Babies and Adults

We recently demonstrated that the major effector function of neonatal CD4+ T cells is to produce CXCL8, a prototypic cytokine of innate immune cells. In this article, we show that CXCL8 expression, prior to proliferation, is common in newly arising T cells (so-called “recent thymic emigrants”) in adults, as well as in babies. This effector potential is acquired in the human thymus, prior to TCR signaling, but rather than describing end-stage differentiation, such cells, whether isolated from neonates or adults, can further differentiate into IFN-γ–producing CD4+ T cells. Thus, the temporal transition of host defense from innate to adaptive immunity is unexpectedly mirrored at the cellular level by the capacity of human innate-like CXCL8-producing CD4+ T cells to transition directly into Th1 cells.
Contamination of the Norepinephrine Pro‐Drug Droxidopa by Dihydroxyphenylacetaldehyde

Droxidopa (3,4‐threo‐L‐dihydroxyphenylserine, L‐DOPS) is a norepinephrine (NE) pro‐drug under development to treat orthostatic hypotension. 3,4‐Dihydroxyphenylacetaldehyde (DOPAL) is a toxic catecholaldehyde.
Resting‐state functional connectivity and presynaptic monoamine signaling in Alcohol Dependence

Alcohol Dependence (AD) is a chronic relapsing disorder with high degrees of morbidity and mortality. While multiple neurotransmitter systems are involved in the complex symptomatology of AD, monoamine dysregulation and subsequent neuroadaptations have been long postulated to play an important role. Presynaptic monoamine transporters, such as the vesicular monoamine transporter 1 (VMAT1), are likely critical as they represent a key common entry point for monoamine regulation and may represent a shared pathway for susceptibility to AD. Excessive monoaminergic signaling as mediated by genetic variation in VMAT1 might affect functional brain connectivity in particular in alcoholics compared to controls. We conducted resting‐state fMRI functional connectivity (FC) analysis using the independent component analysis (ICA) approach in 68 AD subjects and 72 controls. All subjects were genotyped for the Thr136Ile (rs1390938) variant in VMAT1. Functional connectivity analyses showed a significant increase of resting‐state FC in 4 networks in alcoholics compared to controls (P < 0.05, corrected). The FC was significantly positively correlated with Alcohol Dependence Scale (ADS). The hyperfunction allele 136Ile was associated with a significantly decreased FC in the Default Mode Network, Prefrontal Cortex Network, and Executive Control Network in alcohol dependent participants (P < 0.05, corrected), but not in controls. Our data suggest that increased FC might represent a neuroadaptive mechanism relevant to AD that is furthermore mediated by genetic variation in VMAT1. The hyperfunction allele Thr136Ile might have a protective effect that is, in particular, relevant in AD by mechanism of increased monoamine transport into presynaptic storage vesicles. Hum Brain Mapp 36:4808–4818, 2015. Published 2015. This article is a U.S. Government work and is in the public domain in the USA
Rabbit olfactory stem cells. Isolation protocol and characterization.

PURPOSE To describe a new technique for isolation of a mesenchymal stem cells (MSCs) population from the olfactory mucosa in rabbits. METHODS Olfactory stem cells (OSCs) were retrieved from under the cribriform plate of the Ethmoid bone. Several assays were accomplished to characterize the cell population and attest its viability in vitro. The cells were submitted to flow cytometry with the antibodies CD34, CD45, CD73, CD79, CD90 and CD105 and also they were induced to differentiate in three lineages. Functional evaluation involved analysis of in vitro growth behavior, colony forming unit like fibroblasts (CFU-f) and cryopreservation response. Further transduction with Green Fluorescent Protein (GFP) was also performed. RESULTS The OSCs showed mesenchymal features, as positive response to CD34, CD73 and CD90 antibodies and plasticity. Additionally, these cells have high proliferated rate, and they could be cultured through many passages and kept the ability to proliferate and differentiate after cryopreservation. The positive response to the transduction signalizes the possibility of cellular tracking in vivo. This is a desirable feature in case those cells are used for pre-clinical trials. CONCLUSION The cells harvested were mesenchymal stem cells and the technique described is therefore efficient for rabbit olfactory stem cells isolation.
Patterns and Predictors of Adolescent Academic Achievement and Performance in a Sample of Children with Attention-Deficit/Hyperactivity Disorder

The current study examined predictors of academic achievement, measured by standardized test scores, and performance, measured by school grades, in adolescents (Mn age = 16.8) who met diagnostic criteria for Attention-Deficit/Hyperactivity Disorder (ADHD)–Combined type in early childhood (Mn age = 8.5; N = 579). Several mediation models were also tested to determine whether ADHD medication use, receipt of special education services, classroom performance, homework completion, or homework management mediated the relationship between symptoms of ADHD and academic outcomes. Childhood predictors of adolescent achievement differed from those for performance. Classroom performance and homework management mediated the relationship between symptoms of inattention and academic outcomes.