Miracle-dz/UniFAR-FTUs huggingface dataset:
Disruption of Basal JNK Activity Differentially Affects Key Fibroblast Functions Important for Wound Healing*

We used both a gene knockout approach and pharmacologic modulation to study the implication of the JNK pathway in regulating fibroblast motility, capacity to contract mechanically unloaded collagen gels, and type I collagen gene expression in vitro. These parameters, which are important for tissue repair, are positively regulated by transforming growth factor (TGF)-β, a cytokine viewed as playing a master role during wound healing. We demonstrate that basal JNK activity is critical for fibroblast motility because (a) mouse embryo jnk–/– fibroblasts exhibit significantly lower ability to close mechanically induced cell layer wounds than their wild-type (wt) counterparts, and (b) wound closure by human dermal fibroblasts is dramatically impaired by the specific JNK inhibitor SP600125. junAA fibroblasts, in which amino acids Ser63 and Ser73 of c-Jun are replaced by two Ala residues so that c-Jun cannot be phosphorylated by JNK, also exhibited impaired motility, suggesting that c-Jun phosphorylation by JNK is critical for fibroblast migration. In sharp contrast to their lesser motility on plastic, jnk–/– and junAA fibroblasts contracted free-floating, mechanically unloaded, collagen lattices markedly faster than wt fibroblasts. Furthermore, basal mRNA steady-state levels for types I and III collagen genes were similar in jnk–/– and wt fibroblasts. Likewise, overexpression of a dominant-negative mutant form of MKK4 in dermal fibroblasts did not affect collagen expression. We also demonstrate that basal JNK activity does not affect either TGF-β-induced collagen gene expression or lattice contraction, whereas on the other hand, the blockage of motility initiated by JNK inhibition cannot be overcome by TGF-β. Together these results demonstrate discrete, yet significant and highly specific, regulation of fibroblast functions important for wound healing by basal JNK activity.
The Streptococcus pyogenes Serotype M49 Nra-Ralp3 Transcriptional Regulatory Network and Its Control of Virulence Factor Expression from the Novel eno ralp3 epf sagA Pathogenicity Region

ABSTRACT Many Streptococcus pyogenes (group A streptococcus [GAS]) virulence factor- and transcriptional regulator-encoding genes cluster together in discrete genomic regions. Nra is a central regulator of the FCT region. Previous studies exclusively described Nra as a transcriptional repressor of adhesin and toxin genes. Here transcriptome and proteome analysis of a serotype M49 GAS strain and an isogenic Nra mutant of this strain revealed the complete Nra regulon profile. Nra is active in all growth phases tested, with the largest regulon in the transition phase. Almost exclusively, virulence factor-encoding genes are repressed by Nra; these genes include the GAS pilus operon, the capsule synthesis operon, the cytolysin-mediated translocation system genes, all Mga region core virulence genes, and genes encoding other regulators, like the Ihk/Irr system, Rgg, and two additional RofA-like protein family regulators. Surprisingly, our experiments revealed that Nra additionally acts as a positive regulator, mostly for genes encoding proteins and enzymes with metabolic functions. Epidemiological investigations revealed strong genetic linkage of one particular Nra-repressed regulator, Ralp3 (SPy0735), with a gene encoding Epf (extracellular protein factor from Streptococcus suis). In a serotype-specific fashion, this ralp3 epf gene block is integrated, most likely via transposition, into the eno sagA virulence gene block, which is present in all GAS serotypes. In GAS serotypes M1, M4, M12, M28, and M49 this novel discrete genetic region is therefore designated the eno ralp3 epf sagA (ERES) pathogenicity region. Functional experiments showed that Epf is a novel GAS plasminogen-binding protein and revealed that Ralp3 activity counteracts Nra and MsmR regulatory activity. In addition to the Mga and FCT regions, the ERES region is the third discrete chromosomal pathogenicity region. All of these regions are transcriptionally linked, adding another level of complexity to the known GAS growth phase-dependent regulatory network.
Seasonal changes of population genetic structure and relatedness in the bank vole Clethrionomys glareolus: An analysis of age cohorts

The genetic consequences of age structure were investigated in five populations of the bank vole, Clethrionomys glareolus, using 18 variable allozyme loci. Temporal samples and age cohorts were analysed to detect seasonaldifferences in population genetic structure and relatedness between individuals. Changes in allele frequencies between seasons were found in one population. While over-wintered cohorts were genetically homogenous in all study populations, there were within year differences in allele frequencies among cohorts in two of the populations. Pairwise relatedness changed throughout the year and differed between sexes in some populations. The N e /N ratio was high, presumably due to the promiscuous mating system in C. glareolus. Lack of correlation between genetic distance matrices from different seasons revealed that the pattern of interpopulation genetic structuring was not stable over time. The tendency for higher genetic differentiation among populations in autumn than in spring, as well as large differences between F 1 S and F S T in autumn indicated lower dispersal rate at the end of the breeding season than in the spring.
T cell responses to a human cartilage autoantigen in the context of rheumatoid arthritis-associated and nonassociated HLA-DR4 alleles.

OBJECTIVE To analyze the CD4+ T cell responses to the human cartilage antigen glycoprotein-39 (HCgp-39) in the context of rheumatoid arthritis (RA)-associated (DRalphabeta1*0401) and nonassociated (DRalphabeta1*0402) HLA class II molecules. METHODS Large numbers of HCgp-39-specific T cell hybridomas were generated following immunization of HLA-DR4/human CD4 transgenic, murine major histocompatibility complex class II deficient mice with native HCgp-39. Fine epitope mapping of DRalphabeta1*0401-and DRalphabeta1*0402-restricted T cell hybridomas was performed using overlapping synthetic peptides. Antigen-specific cytokine production by lymph node T cells was evaluated after immunization with native antigen. Proliferative T cell responses of healthy human subjects were compared with the T cell responses of patients with active RA using HCgp-39 epitopes defined in HLA-DR4 transgenic mice. RESULTS CD4+ T cells from DRalphabeta1*0401 and DRalphabeta1*0402 transgenic mice identified completely different immunodominant peptide epitopes of HCgp-39, and this was not explained by known DR4-binding motifs or direct peptide-binding studies. DRalphabeta1*0401-restricted, antigen-specific T cells produced significantly more interferon-gamma and tumor necrosis factor a in response to HCgp-39 than did T cells from DRalphabeta1*0402 transgenic mice. Finally, HCgp-39 peptides defined in DRalphabeta1*0401 transgenic mice stimulated T cells from HLA-DR4 positive human subjects and RA patients, but not T cells from HLA-DR4 negative individuals. CONCLUSION T cell epitopes of HCgp-39 that were defined in HLA-DR4 transgenic mice stimulated T cells from human subjects carrying RA-associated HLA-DR4 alleles. HLA-DR4 molecules may influence the disease process in RA both by presentation of selected peptide epitopes and by promoting the production of proinflammatory cytokines in synovial joints.
Increased Expression of the Receptor for Advanced Glycation End-Products (RAGE) Is Associated with Advanced Breast Cancer Stage

Background: The receptor for advanced glycation end-products (RAGE) is a multiligand transmembrane receptor that is overexpressed in various pathological conditions including cancers. However, the expression pattern of RAGE in breast cancer tumors is still not completely clear. Methods: In this study, we investigated the expression levels of RAGE in 25 fresh-frozen breast cancer samples and corresponding noncancerous tissue samples collected from breast cancer patients, by real-time polymerase chain reaction (PCR). Additionally, we performed immunohistochemistry on breast cancer specimens. Results: The results indicate a high expression of the RAGE-encoding gene in the cancerous tissues. RAGE expression at the mRNA and protein levels was statistically significantly up-regulated in advanced-stage and triple-negative breast tumors and node-positive tissues compared with other tissues (p < 0.001). A significant association between RAGE expression and tumor size was observed (p = 0.029). Conclusions: Overexpression of RAGE in advanced-stage tumors may be a useful biomarker for diagnosis and the prediction of breast cancer progression.
Nickel, cobalt and chromium in consumer products: a role in allergic contact dermatitis?

In spite of the improved awareness of the potential for nickel, cobalt and chromium to en use skin allergy, the incidence of serialization to them is generally on the increase, especially for nickel. We review data from the literature and industry on transition metal contamination of consumer products and assess the hazard to man. Consumer products are defined as personal care items and detergent/cleaning products used regularly in domestic York. The analytical data demonstrate that consumer products are a relatively minor source of contact with nickel, cobalt or chromium. The traces found in consumer products will not be the primary cause of sensitization to these metals: levels will be too low and exposure too brief. A person sensitized to these metals has many other more significant sources of daily contact such as earrings, jewellery and metal objects. It is therefore necessary to focus on decreasing the high exposure to these transition metals from other sources rather than on possible trace amounts found in consumer products. Current good manufacturing practice ensures that trace nickel, cobalt and chromium concentrations in consumer products are less than 5 ppm of each metal, it is recommended that this be accepted as a standard for maximum concentrations and that the target should be to achieve concentrations as low as 1 ppm.
Generalized Polyhedral Object Recognition and Localization Using Crossbeam Sensing

Object localization is a fundamental task in industrial automa tion. In this article, we present a recognition and localization technique based upon binary beam sensors. Binary beam sen sors, which consist of modulated LED light sources and de tectors, are appropriate for manufacturing applications due to their reliability, high accuracy, robustness, inexpensiveness, and ease of calibration. By extracting sufficient information, recognition and localization can be performed as fast (~ 0.1 s) and as accurately (~ 25 microns) as high-speed manufactur ing requires. Generalized polyhedral objects are recognized and localized by being passed through a crossbeam sensor which is a set of coplanar oriented binary light-beam sensors; robot positions are recorded when the beam sensors' outputs change. Recognition and localization share two subproblems: the correspondence problem (the problem of interpreting the sensed features in terms of the model features), and the pose- estimation problem (the problem of estimating the object's pose from the sensed data and an interpretation of the sensed fea tures in terms of model features). In Wallack and Manocha (1994), we described a pose-estimation technique for crossbeam sensor data. In this article, we present two methods for solving the correspondence problem for crossbeam sensor data: a lin ear time completely on-line method, and a constant-time on-line method that utilizes preprocessing.
Naproxen versus Acetaminophen for Therapy of Soft Tissue Injuries to the Ankle in Children

Background: Musculoskeletal (MSK) ankle injuries cause significant morbidity in ambulatory pediatric populations. No optimal pharmacotherapy is available. Objective: To conduct a randomized, double-blind trial to compare 2 drug therapies for soft tissue injury of the ankle. Methods: Patients (N = 77, aged 8–14 y, 61% male) with ankle injuries presenting to a regional pediatric emergency department were assigned to receive either acetaminophen (15 mg/kg 4 times a day) or naproxen (5 mg/kg 4 times a day) in a double-blind fashion on a routine basis for a 5 day period. On days 0 and 7, patients rated their degree of disability and pain on weight bearing using a 10 cm visual analog scale developed for this study. In addition, they were examined by a physician who rated pain, tenderness on palpation, and swelling using a 4 point scale. There were 3 follow-up telephone calls on days 3, 14, and 21. Adherence was evaluated by self-report and pill count. Results: Both the acetaminophen and naproxen groups had significant improvement in degree of disability and pain from day 0 to day 7. There was no statistically significant difference in outcome between the 2 groups by patient self-evaluation or physician assessment. There also was no significant difference in adverse event rates between the 2 groups, and the majority of patients in both groups felt that the medication was helpful. Conclusions: No significant difference in efficacy of pain control or improvement of disability between the naproxen and acetaminophen groups suggests no preferential advantage for naproxen over acetaminophen for MSK injuries when given on a regular basis, with concurrent supportive treatment. Possible differential benefit from intermittent therapy needs to be evaluated among children with ankle injury.
Music and Conceptualization

Acknowledgements 1. Introduction: hearing ascriptions 2. Musical hearing as weakly nonconceptual 3. Musical Hearing as Strongly Nonconceptual 4. Is There an Observation-Theory Distinction in Music? 5. Theoretically Informed Listening 6. Conceptions of musical structure Works cited Index.
Group B Streptococcal Infections in Adult Males

A 19-month study of group B streptococcal infection was performed to investigate the spectrum of such infections in adult males, the relation of serotypes to clinical illnesses, the effects of previous antibiotic therapy on infection and colonization, and the antibiotic susceptibility pattern of these organisms.Twenty-four patients had definite or possible infections while 41 patients were colonized with group B streptococci. The most frequent infections encountered were pneumonia (ten cases) and soft tissue infections (nine cases). Five infections (21%) were nosocomial in origin. The most frequent serotypes were la and II. No correlation of serotype and type of infection was observed. Patients receiving previous antibiotic therapy were significantly more likely to be colonized than infected with group B streptococci. Penicillin was the antibiotic to which these organisms were most susceptible; tetracycline and gentamicin showed the least activity.
Description of CoTCAT (Complement to CRISM Analysis Toolkit)

Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) hyperspectral data have a spatial resolution ranging from 12 to 36 m/pixel allowing the high-resolution mapping of minerals at the surface of Mars. However, the signal-to-noise ratio (SNR) makes the discrimination of minerals with close spectral signature such as hydrated minerals challenging. We describe here a pipeline to be used as complement to CRISM Analysis Toolkit (CAT) together with different ratioing methods used to highlight the signal. We present tests on library spectra artificially noised as well as on CRISM data. These tests show that our pipeline is efficient to improve the visualization and the qualitative analysis CRISM data with an SNR higher than 20.
An Antibody Blocking Activin Type II Receptors Induces Strong Skeletal Muscle Hypertrophy and Protects from Atrophy

ABSTRACT The myostatin/activin type II receptor (ActRII) pathway has been identified to be critical in regulating skeletal muscle size. Several other ligands, including GDF11 and the activins, signal through this pathway, suggesting that the ActRII receptors are major regulatory nodes in the regulation of muscle mass. We have developed a novel, human anti-ActRII antibody (bimagrumab, or BYM338) to prevent binding of ligands to the receptors and thus inhibit downstream signaling. BYM338 enhances differentiation of primary human skeletal myoblasts and counteracts the inhibition of differentiation induced by myostatin or activin A. BYM338 prevents myostatin- or activin A-induced atrophy through inhibition of Smad2/3 phosphorylation, thus sparing the myosin heavy chain from degradation. BYM338 dramatically increases skeletal muscle mass in mice, beyond sole inhibition of myostatin, detected by comparing the antibody with a myostatin inhibitor. A mouse version of the antibody induces enhanced muscle hypertrophy in myostatin mutant mice, further confirming a beneficial effect on muscle growth beyond myostatin inhibition alone through blockade of ActRII ligands. BYM338 protects muscles from glucocorticoid-induced atrophy and weakness via prevention of muscle and tetanic force losses. These data highlight the compelling therapeutic potential of BYM338 for the treatment of skeletal muscle atrophy and weakness in multiple settings.
On the definition of negative imaginary system for not necessarily rational symmetric transfer functions

In this paper we provide a definition and characterisation of negative imaginary systems for not necessarily rational but symmetric transfer functions along the same lines of the classic definition of positive real systems. We then derive a necessary and sufficient condition that characterises symmetric negative imaginary transfer functions in terms of a matrix sign condition on the imaginary axis.
Photoluminescence and photoinduced oxygen adsorption of colloidal zinc sulfide dispersions

Etudes de suspensions colloidales aqueuses de ZnS et de la relation entre l'intensite d'emission et la distribution spectrale, et des facteurs tels que la concentration du dopant Mn 2+ , la presence d'oxygene dissous ou d'ions sulfure en solution, la presence de lacunes dans le reseau de soufre, la photodegradation et l'extinction de la luminescence par des reactifs en solution
The representation of asymmetric grammatical gender systems in the bilingual mental lexicon

Abstract Previous research has led to conflicting notions of the representation of L1 and L2 grammatical gender systems in the mental lexicon: under the gender-integrated representation hypothesis the L1 and L2 gender nodes are shared, while these nodes are language-specific in the gender autonomous representation hypothesis. We address this debate, extending this research to L1 and L2 systems mismatched in number of gender values. In this study, Spanish–German bilinguals performed an L2 picture-naming task in which gender congruency (congruent, incongruent and neuter) between L1 and L2 nouns was manipulated. Latencies were shorter for gender-congruent than gender-incongruent nouns, and latencies for the German neuter nouns were also shorter than those for the masculine–feminine incongruent nouns. These gender congruency effects support the gender-integrated representation hypothesis and indicate a unique representation of the gender value not present in the L1 which interferes with the response significantly less than when the incongruency is between gender values present in both languages.
Isolation and Molecular Characterization of a Nelfinavir (NFV)-Resistant Human Immunodeficiency Virus Type 1 That Exhibits NFV-Dependent Enhancement of Replication

ABSTRACT During the use of a phenotypic anti-human immunodeficiency virus type 1 (HIV-1) drug resistance assay in a large set of clinical virus isolates, we found a unique variant (CL-4) that exhibited a high level of nelfinavir (NFV) resistance and rather enhanced replication under subinhibitory concentrations of NFV (0.001 to 0.1 μM). Comparison of gag-pol sequences of the CL-4 variant and its predecessor virus isolates showed a stepwise accumulation of a total of 19 amino acid substitutions in protease (PR) and Gag p17 during 32-month NFV-containing antiretroviral therapy, while other Gag regions including the cleavage sites of the p55 precursor remained highly conserved. To understand the relationship between the genetic and phenotypic changes in CL-4, we constructed chimeric viruses using pNL4-3, replacing the PR, p24PR, or p17PR gene segment of CL-4 or its predecessor. A series of tissue culture infections with the chimeras in the absence or presence of increasing concentrations of NFV demonstrated that only the p17PR segment of CL-4 could confer the NFV-dependent replication enhancement phenotype on NL4-3. Our data suggest a novel adaptation mechanism of HIV-1 to NFV, in which coevolution of Gag and PR genes generates a variant that replicates more efficiently in the cellular environment in the presence of NFV than without the drug.
Spiritual growth in cancer patients: a qualitative study

This study aimed to explain spiritual growth and explore its dimensions in patients with cancer. In t his qualitative study, conventional content analysis was used for collection and analysis of data. The 12 patients that qualified for this study were selected from among patients with different types of cancer, referred to the two large teaching cancer hos pitals in Tehran. Six main themes and 11 subthemes were extracted. The main themes included: “return to self”, “tend to spirituality”, “human perfection”, “inner peace”, “a fresh outlook on death”, and “closeness to God. ”Cancer patients dramatically turn t o spirituality, and use it as a powerful tool to adjust with the disease. The emerging new themes brought to light new aspects of consequences of cancer that can help care providers to enhance growth and improve patients’ compliance with the stressful even t of cancer.
Serum as a modulator of lipoplex‐mediated gene transfection: dependence of amphiphile, cell type and complex stability

Cationic liposomes belong to the family of non‐viral vectors for gene delivery. Despite several drawbacks, such as low efficiency compared to viruses and inactivation by serum, cationic liposomes remain a promising tool for gene therapy. Therefore further investigation of the mechanism of transfection and improvement of formulations are warranted.
Improving Medication Use in Newly Admitted Home Healthcare Patients: A Randomized Controlled Trial

OBJECTIVES: To test the efficacy of a medication use improvement program developed specifically for home health agencies. The program addressed four medication problems identified by an expert panel: unnecessary therapeutic duplication, cardiovascular medication problems, use of psychotropic drugs in patients with possible adverse psychomotor or adrenergic effects, and use of nonsteroidal antiinflammatory drugs (NSAIDs) in patients at high risk of peptic ulcer complications. It used a structured collaboration between a specially trained clinical pharmacist and the patients' home‐care nurses to improve medication use.
Current status of therapy in bacterial endocarditis.

The most dramatic effects of the use of antibiotics are demonstrable in those infections which in the past had been almost invariably fatal. This is well illustrated in cases of bacterial endocarditis, for in this disease recoveries before the antibiotic era were considered to be curiosities (the authenticity of many of them remains in doubt), whereas at present the great majority (from 60 to 80% or even more) of patients whose cases are recognized recover if treated early and properly with antibiotics. The incidence of bacterial endocarditis has probably been reduced by the general use of antibiotics in the treatment or prevention of infections, including those which predispose the body to the disease, directly or indirectly. The only reliable data in this regard, however, are the over-all reduction in the occurrence of this lesion in several large series of autopsies, from an average of about 1.5% prior to 1943 to