Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of the actin-binding domain of alpha-actinin by mutagenesis and demonstration that dystrophin contains a functionally homologous domain

To define the actin-binding site within the NH2-terminal domain (residues 1-245) of chick smooth muscle alpha-actinin, we expressed a series of alpha-actinin deletion mutants in monkey Cos cells. Mutant alpha-actinins in which residues 2-19, 217-242, and 196-242 were deleted still retained the ability to target to actin filaments and filament ends, suggesting that the actin-binding site is located within residues 20-195. When a truncated alpha-actinin (residues 1-290) was expressed in Cos cells, the protein localized exclusively to filament ends. This activity was retained by a deletion mutant lacking residues 196-242, confirming that these are not essential for actin binding. The actin-binding site in alpha-actinin was further defined by expressing both wild-type and mutant actin-binding domains as fusion proteins in E. coli. Analysis of the ability of such proteins to bind to F-actin in vitro showed that the binding site was located between residues 108 and 189. Using both in vivo and in vitro assays, we have also shown that the sequence KTFT, which is conserved in several members of the alpha- actinin family of actin-binding proteins (residues 36-39 in the chick smooth muscle protein) is not essential for actin binding. Finally, we have established that the NH2-terminal domain of dystrophin is functionally as well as structurally homologous to that in alpha- actinin. Thus, a chimeric protein containing the NH2-terminal region of dystrophin (residues 1-233) fused to alpha-actinin residues 244-888 localized to actin-containing structures when expressed in Cos cells. Furthermore, an E. coli-expressed fusion protein containing dystrophin residues 1-233 was able to bind to F-actin in vitro.
Functional analysis of third ventriculostomy patency by quantification of CSF stroke volume by using cine phase-contrast MR imaging.

OBJECTIVE Endoscopic third ventriculostomy (ETV) is increasingly used as alternative treatment for obstructive hydrocephalus. The aim of this study was to determine the utility of quantitative and qualitative examinations with cine phase-contrast MR imaging to determine the efficacy of ventriculostomy across time and whether CSF pulsation is restored after ETV. METHODS Thirty-eight patients treated with ETV were evaluated with cine phase-contrast MR within 1 month after surgery. Follow-up studies were performed after 1 year in 25 patients and after 2 years in 12. We evaluated flow void changes in the floor of the third ventricle and quantified the stroke volume at the site of the ventriculostomy. We also recorded changes in ventricular size and clinical outcome. To determine the restoration of CSF pulsation, we compared the CSF waveform at the ventriculostomy with the CSF waveform at the aqueduct in a healthy control group. RESULTS After ventriculostomy, restoration of pulsate motion characteristics of CSF circulation was observed. The stroke volume registered at ventriculostomy was maintained with time. There was a statistically significant relationship between clinical outcome and stroke volume. Overall flow magnitude was the most effective variable to determine which patients would improve after surgery. Values >75 mm3 showed a sensitivity of 76.7% and a specificity of 87.5% There was no relationship between ventricular size changes and clinical outcome. Patients with primary aqueduct stenosis had the best response to surgery, whereas patients with Arnold Chiari malformation or communicating hydrocephalus had the worst response. CONCLUSION Quantitative analysis with phase-contrast MR imaging indicates that ETV is an efficient technique for restoring CSF pulsation, with efficacy being maintained during the follow-up controls. Quantification of stroke volume at ventriculostomy is a good indicator of the functional status of ETV, and a high stroke volume in the ventriculostomy appears to be a positive predictor of favorable clinical outcome.
A literature review on sick leave determinants (1984-2004).

OBJECTIVES A literature review for the years 1984-2004 was performed to identify the determinants of the sick leave frequency and duration over that period and to establish the continuity in the character of those determinants. MATERIALS AND METHODS The review referred to national and international studies on the determinants of the frequency and duration of sick leave. RESULTS The review presented a highly consistent picture of the factors determining sick leave frequency and duration. CONCLUSION Over the study period, the frequency and duration of sick leave were determined by a broad range of factors, a substantial number of which had a similar influence on both the study parameters.
miR-486-3p, miR-139-5p, and miR-21 as Biomarkers for the Detection of Oral Tongue Squamous Cell Carcinoma

Oral tongue squamous cell carcinoma (TSCC) is a complex disease with extensive genetic and epigenetic defects, including microRNA deregulation. The aims of the present study were to test the feasibility of performing the microRNA profiling analysis on archived TSCC specimens and to assess the potential diagnostic utility of the identified microRNA biomarkers for the detection of TSCC. TaqMan array-based microRNA profiling analysis was performed on 10 archived TSCC samples and their matching normal tissues. A panel of 12 differentially expressed microRNAs was identified. Eight of these differentially expressed microRNAs were validated in an independent sample set. A random forest (RF) classification model was built with miR-486-3p, miR-139-5p, and miR-21, and it was able to detect TSCC with a sensitivity of 100% and a specificity of 86.7% (overall error rate = 6.7%). As such, this study demonstrated the utility of the archived clinical specimens for microRNA biomarker discovery. The feasibility of using microRNA biomarkers (miR-486-3p, miR-139-5p, and miR-21) for the detection of TSCC was confirmed.
Thematic review series: Skin Lipids. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism Published, JLR Papers in Press, February 2, 2008.

Many of the ichthyoses are associated with inherited disorders of lipid metabolism. These disorders have provided unique models to dissect physiologic processes in normal epidermis and the pathophysiology of more common scaling conditions. In most of these disorders, a permeability barrier abnormality “drives” pathophysiology through stimulation of epidermal hyperplasia. Among primary abnormalities of nonpolar lipid metabolism, triglyceride accumulation in neutral lipid storage disease as a result of a lipase mutation provokes a barrier abnormality via lamellar/nonlamellar phase separation within the extracellular matrix of the stratum corneum (SC). Similar mechanisms account for the barrier abnormalities (and subsequent ichthyosis) in inherited disorders of polar lipid metabolism. For example, in recessive X-linked ichthyosis (RXLI), cholesterol sulfate (CSO4) accumulation also produces a permeability barrier defect through lamellar/nonlamellar phase separation. However, in RXLI, the desquamation abnormality is in part attributable to the plurifunctional roles of CSO4 as a regulator of both epidermal differentiation and corneodesmosome degradation. Phase separation also occurs in type II Gaucher disease (GD; from accumulation of glucosylceramides as a result of to β-glucocerebrosidase deficiency). Finally, failure to assemble both lipids and desquamatory enzymes into nascent epidermal lamellar bodies (LBs) accounts for both the permeability barrier and desquamation abnormalities in Harlequin ichthyosis (HI). The barrier abnormality provokes the clinical phenotype in these disorders not only by stimulating epidermal proliferation, but also by inducing inflammation.
c-Src-Mediated Epithelial Cell Migration and Invasion Regulated by PDZ Binding Site

ABSTRACT c-Src tyrosine kinase controls proliferation, cell adhesion, and cell migration and is highly regulated. A novel regulatory mechanism to control c-Src function that has recently been identified involves the C-terminal amino acid sequence Gly-Glu-Asn-Leu (GENL) of c-Src as ligand for PDZ domains. Herein, we determined the biological relevance of this c-Src regulation in human breast epithelial cells. The intact GENL sequence maintained c-Src in an inactive state in starved cells and restricted c-Src functions that might lead to metastatic transformation under normal growth conditions. c-Src with a C-terminal Leu/Ala mutation in GENL (Src-A) promoted the activation and translocation of cortactin and focal adhesion kinase and increased the motility and persistence of cell migration on the basement membrane. Src-A promoted increased extracellular proteolytic activity, and in acinar cultures, it led to the escape of cells through the basement membrane into the surrounding matrix. We ascribe the regulatory function of C-terminal Leu to the role of GENL in modulating c-Src activity downstream of cell matrix adhesion. We propose that the C terminus of c-Src via its GENL sequence presents a mechanism that restricts c-Src in epithelia and prevents progression toward an invasive phenotype.
Magnetoconvection and dynamo coefficients: Dependence of the alpha-effect on rotation and magnetic field

We present numerical simulations of three-dimensional compressible magnetoconvection in a rotating rectangular box that represents a section of the solar convection zone. The box contains a convectively unstable layer, surrounded by stably stratified layers with overshooting convection. The magnetic Reynolds number, Rm, is chosen subcritical, thus excluding spontaneous growth of the magnetic field through dynamo action, and the magnetic energy is maintained by introducing a constant magnetic field into the box, once convection has attained a statistically stationary state. Under the influence of the Coriolis force, the advection of the magnetic field results in a non-vanishing contribution to the mean electric field, given by uxb. From this electric field, we calculate the alpha-effect, separately for the stably and the unstably stratified layers, by averaging over time and over suitably defined volumes. From the variation of alpha we derive an error estimate, and the dependence of alpha on rotation and magnetic field strength is studied. Evidence is found for rotational quenching of the vertical alpha-effect, and for a monotonic increase of the horizontal alpha-effect with increasing rotation. For Rm~30, our results for both vertical and horizontal alpha-effect are consistent with magnetic quenching by a factor 1/[1+Rm(B_0/B_eq)^2]. The signs of the small-scale current helicity and of the vertical component of alpha are found to be opposite to those for isotropic turbulence.
Rapid assessment of the HIV/AIDS crisis in racial and ethnic minority communities: an approach for timely community interventions.

OBJECTIVES The US Department of Health and Human Services, in collaboration with the Congressional Black Caucus, created a new initiative to address the disproportionate ongoing HIV/AIDS crisis in racial/ethnic minority populations. METHODS This initiative included deploying technical assistance teams through the Office of HIV/AIDS Policy. The teams introduced rapid assessment and response methodologies and trained minority communities in their use. RESULTS The first 3 eligible cities (Detroit, Miami, and Philadelphia) focused assessments in small geographic areas, using multiple methodologies to obtain data. CONCLUSIONS Data from the first 3 eligible cities provided critical information about changing the dynamics of the HIV/AIDS epidemic at the local level, including program and policy changes and infrastructure redeployment targeted at the most serious social and environmental conditions.
Moving object detection and background enhancement for thalamic visual prostheses

Visual prostheses open the door of hope to restore functional vision for the blind. One of the main challenges facing their development is the limited number of electrodes used in the stimulation process which limits the resolution of the perceived images. To improve the perception, the useful features in the scene need to be enhanced while the other features should be suppressed to achieve better resolution. This paper introduces an image processing method to enhance three main features detectable by the natural visual pathway; namely the contrast, the motion and the edges. It then reduces the size of the image into an activity matrix used to generate the electric stimulation for the electrodes array. We compared the proposed method to four other image processing strategies in terms of the quality of the resulting image in addition to the perceived image using a simulation of prosthetic vision. Results demonstrate that the proposed method outperforms the other techniques in both aspects.
Adjacent visual representations of self-motion in different reference frames

Recent investigations indicate that retinal motion is not directly available for perception when moving around [Souman JL, et al. (2010) J Vis 10:14], possibly pointing to suppression of retinal speed sensitivity in motion areas. Here, we investigated the distribution of retinocentric and head-centric representations of self-rotation in human lower-tier visual motion areas. Functional MRI responses were measured to a set of visual self-motion stimuli with different levels of simulated gaze and simulated head rotation. A parametric generalized linear model analysis of the blood oxygen level-dependent responses revealed subregions of accessory V3 area, V6+ area, middle temporal area, and medial superior temporal area that were specifically modulated by the speed of the rotational flow relative to the eye and head. Pursuit signals, which link the two reference frames, were also identified in these areas. To our knowledge, these results are the first demonstration of multiple visual representations of self-motion in these areas. The existence of such adjacent representations points to early transformations of the reference frame for visual self-motion signals and a topography by visual reference frame in lower-order motion-sensitive areas. This suggests that visual decisions for action and perception may take into account retinal and head-centric motion signals according to task requirements.
Pathogenesis of systemic lupus erythematosus

The exact patho-aetiology of systemic lupus erythematosus (SLE) remains elusive. An extremely complicated and multifactorial interaction among various genetic and environmental factors is probably involved. Multiple genes contribute to disease susceptibility. The interaction of sex, hormonal milieu, and the hypothalamo–pituitary–adrenal axis modifies this susceptibility and the clinical expression of the disease. Defective immune regulatory mechanisms, such as the clearance of apoptotic cells and immune complexes, are important contributors to the development of SLE. The loss of immune tolerance, increased antigenic load, excess T cell help, defective B cell suppression, and the shifting of T helper 1 (Th1) to Th2 immune responses leads to B cell hyperactivity and the production of pathogenic autoantibodies. Finally, certain environmental factors are probably required to trigger the disease.
COMBINING ICA AND CORTICAL SURFACE RECONSTRUCTION IN FUNCTIONAL MRI INVESTIGATIONS OF HUMAN BRAIN FUNCTIONS

The cerebral cortex is the main target of analysis in many functional magnetic resonance imaging (fMRI) studies. Since only about 20% of the voxels of a typical functional data set lie within the cortex, statistical analysis can be restricted to a subset of the voxels obtained after cortex segmentation. Here, we describe a novel approach for datadriven analysis of single-subject fMRI time-series that combines techniques for reconstruction of the cortical surface of the subject’s brain and spatial independent component analysis (ICA) of functional time-courses (cortex-based ICA or cbICA). Compared to conventional, anatomically unconstrained ICA, besides reducing computational demand (20,000 vs 100,000 voxels time-courses), our approach improves detection of cortical components and estimation of their time-courses, particularly in the case of event-related designs.
Analysis for stress environment in the alveolar sac model

Better understanding of alveolar mechanics is very important in order to avoid lung injuries for patients undergoing mechanical ventilation for treatment of respiratory problems. The objective of this study was to investigate the alveolar mechanics for two different alveolar sac models, one based on actual geometry and the other an idealized spherical geometry using coupled fluid-solid computational analysis. Both the models were analyzed through coupled fluid-solid analysis to estimate the parameters such as pressures/velocities and displacements/stresses under mechanical ventilation conditions. The results obtained from the fluid analysis indicate that both the alveolar geometries give similar results for pressures and velocities. However, the results obtained from coupled fluid-solid analysis indicate that the actual alveolar geometry results in smaller displacements in comparison to a spherical alveolar model. This trend is also true for stress/strain between the two models. The results presented indicate that alveolar geometry greatly affects the pressure/velocities as well as displacements and stresses/strains.
Mapping Multiple Quantitative Trait Loci by Bayesian Classification

We developed a classification approach to multiple quantitative trait loci (QTL) mapping built upon a Bayesian framework that incorporates the important prior information that most genotypic markers are not cotransmitted with a QTL or their QTL effects are negligible. The genetic effect of each marker is modeled using a three-component mixture prior with a class for markers having negligible effects and separate classes for markers having positive or negative effects on the trait. The posterior probability of a marker's classification provides a natural statistic for evaluating credibility of identified QTL. This approach performs well, especially with a large number of markers but a relatively small sample size. A heat map to visualize the results is proposed so as to allow investigators to be more or less conservative when identifying QTL. We validated the method using a well-characterized data set for barley heading values from the North American Barley Genome Mapping Project. Application of the method to a new data set revealed sex-specific QTL underlying differences in glucose-6-phosphate dehydrogenase enzyme activity between two Drosophila species. A simulation study demonstrated the power of this approach across levels of trait heritability and when marker data were sparse.
A macrocyclic calpain inhibitor slows the development of inherited cortical cataracts in a sheep model.

PURPOSE We used sheep with an autosomal dominant gene for cortical cataract as an animal model to evaluate novel macrocyclic calpain inhibitors with potential for the medical treatment of human cataract. METHODS The macrocyclic aldehyde, CAT811, identified previously as a calpain inhibitor that prevents calcium-induced opacification in cultured sheep lenses, was tested for its ability to protect cytoskeletal proteins from calpain proteolysis. CAT811 and its alcohol analogue, CAT505, were formulated separately into ointments, and each was applied twice daily to the right eye of sheep with early cataracts for five months. Progress of cataracts in the sheep was determined by ophthalmologic examination and comparison with a matched sample of sheep treated similarly with ointment that did not contain the active ingredient. RESULTS The novel macrocyclic aldehyde, CAT811, was able to inhibit calpain proteolysis of lens cytoskeletal proteins at micromolar concentrations. When applied topically to the eyes of sheep, CAT811 was able to slow cataract development by 27% in the initial three months of treatment (P < 0.05). Its alcohol analogue, CAT505, was not able to slow cataractogenesis significantly. CONCLUSIONS The inherited sheep cataract provides a reproducible model of cortical cataract over a time scale of several months. The data reported here, using this model, demonstrated the potential of the macrocyclic calpain inhibitor, CAT811, to act as a therapeutic for treatment of cortical cataract.
A review of The Permeability, Fluid Flow, and Anatomy of Spruce ( Picea SPP.)

This paper reviews the literature discussing some of the qualities and properties of spruce that characterize its refractory nature and influence its treatability. Topics discussed include a review of the permeability of spruce, fluid flow through wood, and the anatomy of spruce. Permeability and liquid flow through wood are discussed, with an emphasis on differences in flow between sapwood and heartwood and between earlywood and latewood. Literature covering the effects of reversing the direction of flow and decreases in flow with time are also reviewed. Permeability through earlywood and latewood was variable, with neither being more or less treatable than the other. Reversing the direction of flow through wood was shown to increase the rate of flow, which normally tapers off over time. Discussion of wood anatomy and the path of flow includes a review of longitudinal flow and transverse flow. Pit aspiration and the effects of surface tension, the rigidity of pit membrane, and the adhesion of the torus to pit border are also addressed.
Predictors of Drop-Out in an Internet Study of Men Who Have Sex with Men

Researchers have suggested the rising use of Internet to look for sexual partners is an important contributor to the resurgence in the incidence of sexually transmitted diseases (STDs) and HIV among men who have sex with men (MSM). Web-based samples of this population reflect good geographical diversity for research, but a high drop-out rate creates a significant potential for bias, misrepresentation of population, and misinterpretation of data. This study aims to describe the demographics of an Internet sample of MSM and the differences between the completers and drop-outs. We analyzed data obtained from a cross-sectional study using an online self-administered questionnaire for males, 18 years or older, who were current U.S. residents, and who had sex with men. Of 850 eligible participants, 404 (47.5%) were labeled as drop-outs. The completers and drop-outs differed significantly in age, education, country of birth, health insurance, time spent on Internet, location of computer access, types of sites visited, profile information, last homosexual experience, methods used to determine safety of partners, and type of sexual activities on real meets. Almost half of the participants dropped out before completion. Although the two groups did not differ in many of the items, high drop-out rates are a threat to the validity of such data. Drop-out constitutes a significant bias in Internet sexuality research and must be considered while interpreting the results of such studies.