Miracle-dz/UniFAR-FTUs huggingface dataset:
Synoviocyte Innate Immune Responses: I. Differential Regulation of Interferon Responses and the JNK Pathway by MAPK Kinases1

JNK is a key regulator of matrix metalloproteinase production in rheumatoid arthritis. It is regulated by two upstream kinases known as MKK4 and MKK7. Previous studies demonstrated that only MKK7 is required for cytokine-mediated JNK activation and matrix metalloproteinase expression in cultured fibroblast-like synoviocytes (FLS). However, the functions of MKK4 and MKK7 in synoviocyte innate immune responses have not been determined. TNF, peptidoglycan (PGN), and LPS stimulation led to higher and more prolonged MKK7 phosphorylation compared with MKK4 in FLS. However, this pattern was reversed in poly(I-C) stimulated cells. siRNA knockdown studies showed that TNF, PGN, and LPS-induced JNK and c-Jun phosphorylation are MKK7 dependent, while poly(I-C) responses require both MKK4 and MKK7. Poly(I-C)-induced expression of IP-10, RANTES, and IFN-β mRNA was decreased in MKK4- or MKK7-deficient FLS. However, MKK4 and MKK7 deficiency did not affect phosphorylation of IκB kinase-related kinases in the TLR3 signaling pathway. MKK7, but not MKK4 deficiency, significantly decreased poly(I-C)-mediated IRF3 dimerization, DNA binding, and IFN-sensitive response element-mediated gene transcription. These results were mimicked by the JNK inhibitor SP600125, indicating that JNK can directly phosphorylate IRF3. In contrast, deficiency of either MKK4 or MKK7 decreased AP-1 transcriptional activity. Therefore, JNK is differentially regulated by MKK4 and MKK7 depending on the stimulus. MKK7 is the primary activator of JNK in TNF, LPS, and PGN responses. However, TLR3 requires both MKK4 and MKK7, with the former activating c-Jun and the latter activating both c-Jun and IRF3 through JNK-dependent mechanisms.
Protective effect of melatonin on neural cells against the cytotoxicity of oxyradicals.

OBJECTIVE To investigate the exact mechanism of melatonin to prohibit the apoptosis of neural cells induced by various kinds of cytotoxic agents. METHODS We used the methods of phase contrast microscopy, MTT assay and hoechst dye staining to check this mechanism in SKNSH and U251 cell lines. RESULTS Both 2 mmol/L H2O2 and 0.5 micromol/L amyloid beta-protein (Abeta) induce these two cell lines die via apoptosis. Either melatonin or glutathione can significantly protect both cell lines. The protective effect of 10 micromol/L melatonin is as same as that of 60 micromol/L glutathione. CONCLUSION Melatonin can partly inhibit the cytotoxicity of H2O2 and Abeta through its role as a free radical scavenger.
Uncalibrated Eye-to-Hand Visual Servoing Using Inverse Fuzzy Models

A new uncalibrated eye-to-hand visual servoing based on inverse fuzzy modeling is proposed in this paper. In classical visual servoing, the Jacobian plays a decisive role in the convergence of the controller, as its analytical model depends on the selected image features. This Jacobian must also be inverted online. Fuzzy modeling is applied to obtain an inverse model of the mapping between image feature variations and joint velocities. This approach is independent from the robot's kinematic model or camera calibration and also avoids the necessity of inverting the Jacobian online. An inverse model is identified for the robot workspace, using measurement data of a robotic manipulator. This inverse model is directly used as a controller. The inverse fuzzy control scheme is applied to a robotic manipulator performing visual servoing for random positioning in the robot workspace. The obtained experimental results show the effectiveness of the proposed control scheme. The fuzzy controller can position the robotic manipulator at any point in the workspace with better accuracy than the classic visual servoing approach.
Characterization of proteinases in extracts of adult Haemonchus contortus, the ovine abomasal nematode

SUMMARY The degradation of several protein substrates, including the blood proteins haemoglobin, albumin and fibrinogen, by proteinases present in extracts of adult Haemonchus contortus was examined over a broad pH range. These proteinases were further characterized on the basis of substrate specificity, inhibitor sensitivity and molecular size by spectrophotometric and substrate gel analysis. The majority of the proteinases capable of degrading the blood proteins tested were active at acidic pH and could be ascribed to the cysteine proteinase class. In addition, evidence is presented that these proteinases are differentially recognized and inhibited by immune sera and that parasites capable of withstanding protective host immune responses exhibit modified expression of proteinases.
Differential Gene Expression and Aging

It has been established that an intricate program of gene expression controls progression through the different stages in development. The equally complex biological phenomenon known as aging is genetically determined and environmentally modulated. This review focuses on the genetic component of aging, with a special emphasis on differential gene expression. At least two genetic pathways regulating organism longevity act by modifying gene expression. Many genes are also subjected to age-dependent transcriptional regulation. Some age-related gene expression changes are prevented by caloric restriction, the most robust intervention that slows down the aging process. Manipulating the expression of some age-regulated genes can extend an organism's life span. Remarkably, the activity of many transcription regulatory elements is linked to physiological age as opposed to chronological age, indicating that orderly and tightly controlled regulatory pathways are active during aging.
The prevalence of nonadherence in difficult asthma.

RATIONALE With the advent of new and expensive therapies for severe refractory asthma, targeting the appropriate patients is important. An important issue is identifying nonadherence with current therapies. The extent of nonadherence in a population with difficult asthma has not been previously reported. OBJECTIVES To examine the prevalence of nonadherence to corticosteroid medication in a population with difficult asthma referred to a Specialist Clinic and to examine the relationship of poor adherence to asthma outcome. METHODS General practitioner prescription refill records for the previous 6 months for inhaled combination therapy and short-acting beta-agonists were compared with initial prescriptions and expressed as a percentage. Blood plasma prednisolone and cortisol assay levels were used to examine the utility of these measures in assessing adherence to oral prednisolone. Patient demographics, hospital admissions, lung function, oral prednisolone courses, and quality of life data were analyzed to indentify the variables associated with reduced medication adherence. MEASUREMENTS AND MAIN RESULTS A total of 182 patients were assessed. Sixty-three patients (35%) filled 50% or fewer inhaled medication prescriptions; 88% admitted poor adherence with inhaled therapy after initial denial. Twenty-one percent of patients filled more than 100% of presciptions, and 45% of subjects filled between 51 and 100% of prescriptions. Twenty-three of 51 patients (45%) prescribed oral steroids were found to be nonadherent. CONCLUSIONS A significant proportion of patients with difficult-to-control asthma remained nonadherent to corticosteroid therapy. Objective surrogate and direct measures of adherence should be performed as part of a difficult asthma assessment and are important before prescibing expensive novel biological therapies.
Somatic action potentials are sufficient for late-phase LTP-related cell signaling

A question of critical importance confronting neuroscientists today is how biochemical signals initiated at a synapse are conveyed to the nucleus. This problem is particularly relevant to the generation of the late phases of long-term potentiation (LTP). Here we provide evidence that some signaling pathways previously associated with late-LTP can be activated in hippocampal CA1 neurons without synaptic activity; somatic action potentials, induced by backfiring the cells, were found to be sufficient for phosphorylation of extracellular signal-regulated kinase-1/2 and cAMP response element-binding protein, as well as for induction of zif268. Furthermore, such antidromic stimulation was adequate to rescue “tagged” synapses (early-LTP) from decay. These results show that a synapse-to-nucleus signal is not necessary for late-phase LTP-associated signaling cascades in the regulation of gene expression.
Ciprofloxacin concentrations in lung tissue following a single 400 mg intravenous dose.

Intravenous ciprofloxacin is frequently prescribed for the treatment of infections due to nosocomially acquired gram-negative organisms, including those originating in the respiratory tract. In this study, the concentrations of ciprofloxacin in serum and lung tissue were determined by HPLC in patients undergoing lung surgery. A total of 22 patients scheduled for lung surgery received a single 400 mg i.v. dose of ciprofloxacin administered as a 1 h infusion. A specimen of healthy lung tissue was obtained from resected lung from 18 of the patients for analysis of ciprofloxacin concentration during the following time intervals after infusion (one sample/patient): 0-2, 2-4, 4-8 and 8-12 h. Corresponding mean serum and tissue concentrations were 2.37 mg/L and 3.84 mg/kg (0-2 h), 1.18 mg/L and 1.92 mg/kg (2-4 h), 0.69 mg/L and 1.77 mg/kg (4-8 h), and 0.13 mg/L and 0.67 mg/kg (8-12 h). Ciprofloxacin distributed rapidly to lung tissue, as seen by the high concentrations in the lung tissue as early as 2 h after infusion. Concentrations in lung tissue were generally higher than those in serum (tissue:serum ratios ranged from 1.7 to 7.1). The mean tissue concentrations found in this study remained above the MIC for most susceptible organisms.
Production and characterization of two immunotoxins specific for M5b ANLL leukaemia

We describe the production and functional characterization of 2 monocytic‐cell‐lineage‐specific immunotoxins constructed with saporin emitoxin (SAP) from Saponaria officinalis. Interest in the production of these immunotoxins, of possible clinical relevance, has been raised by the availability of 2 MAbs of high specificity for circulating monocytes and M5b ANLL, thus envisaging their potential use in bone‐marrow purging. SAP emitoxin was selected on the basis of the low cytotoxicity in unconjugated form, as opposed to highly specific cytotoxicity and favourable pharmacokinetical properties in the conjugated form. SPDP conjugation produced immunotoxins which retained serological specificity and protein‐synthesis‐inhibitory activity. The 2 immunotoxins did not interfere with bone‐marrow progenitor‐cell growth in a CFU‐GM colony assay. On the contrary, they were capable of killing monocytic cells selectively, as demonstrated in phenotypical and functional assays. Thus these 2 novel immunotoxins appear to be promising reagents in purging autologous bone marrow prior to transplantation in patients suffering from monocytic leukaemia.
Comparative Quantification of Endothelin Receptor mRNA in Human Kidney: New Tools for Direct Investigation of Human Tissue

Summary: By virtue of its exquisite sensitivity to the effects of endothelin-1 (ET-1), the kidney has been a consistent candidate for a pathophysiologic role for the endo-thelins. However, observed species differences in both receptor distribution and the subtypes mediating vasoconstriction have necessitated the development of a novel quantitative RT-PCR assay suitable for the direct investigation of human tissue, which is usually available only in very small amounts (i.e., biopsy specimens). In this study we quantified ETA and ETB receptor mRNA in normal renal cortex and medulla. For seven samples, cortex contained 0.19 ± 0.10 amol ETA mRNA and 1.09 ± 0.38 amol ETB mRNAVg total RNA (mean ± SEM). In medulla these values were 0.47 ± 0.25 and 2.17 ± 1.90, respectively. The ratios of ETA to ETB were about 20:80, which correlates closely with previous studies of expressed receptor protein. This fluorescent nested quantitative RT-PCR assay provides a tool for further investigation of the human ET system at the molecular level in tissue from living individuals, and is of general applicability to the study of endogenous ligand-receptor systems.
Regrouper des résultats SPARQL par comparaison de leurs contenus tels qu'ils sont agencés dans la base RDF interrogée

This paper proposes a novel approach to group SPARQL query results according to their similarities. In order to compare results, the originality of our approach is to consider for each result the data constituting this result such as they are present and arranged in the queryed RDF dataset. We therefore do not limit ourselves to comparing the results between them, but we recontextualize them in the dataset where they were selected in order to take into account not only the resources of results but also their links with others resources in the dataset, i.e. their neighborhoods. From the results and their neighborhoods, we define common descriptive patterns to hierarchically group results in order of similarity, thus providing the user with easier navigation and understanding of the results. MOTS-CLÉS : SPARQL, clustering query results, motif de description, hierarchical clustering.
Reduced risk of atopy among school-age children infected with geohelminth parasites in a rural area of the tropics.

BACKGROUND Childhood infections might protect against the expression of atopy. Geohelminths are among the most prevalent infections of childhood and might contribute to the low prevalence of allergic disease reported from rural areas of the tropics. OBJECTIVE We sought to establish whether geohelminth infections protect against atopy and to explore whether this protection is dependent on infection chronicity. METHODS The risk of atopy (measured by means of allergen skin test reactivity) associated with active geohelminth infections (measured by means of the presence of eggs in stool samples) or with chronic geohelminth infections (measured by means of high levels [>/=3564 IU/mL] of total serum IgE or the presence of detectable anti-Ascaris lumbricoides IgG4 antibodies) was investigated in an analytic cross-sectional study conducted among school-age children attending rural schools in Pichincha Province in Ecuador. RESULTS A total of 2865 children aged 5 to 19 years from 55 schools was examined. Active infection with any geohelminth and infections with A lumbricoides or Ancylostoma duodenale were associated with significant protective effects against allergen skin test reactivity. Children with the highest levels of total IgE or with anti-A lumbricoides IgG4 antibodies were protected against skin test reactivity also, and the protective effects of high IgE or anti-A lumbricoides IgG4 and or active geohelminth infections were statistically independent. CONCLUSION Active infections with geohelminth parasites and the presence of serologic markers of chronic infections (high levels of total serum IgE or anti-A lumbricoides IgG4) are independent protective factors against allergen skin test reactivity among school-age children living in an endemic region of the rural tropics.
Probing Spatial Working Memory with the Corsi Blocks Task

The Corsi Blocks task (CBT) measures spatial memory span, but methodological differences across previous studies prevent a clear appreciation of perceptual, memory, and motor contributions to spatial span. CBT performance in a standard condition was compared to performance with longer encoding intervals (3 vs 1 s), longer memory intervals (9 vs 1 s), or fewer response alternatives (all nine vs only the relevant positions). All experiments also contrasted ascending vs descending order of item difficulty and recorded response-initiation times. Performance improved with longer encoding and maintenance intervals and with fewer response alternatives. Item order had no reliable effects. Response-initiation times were a useful additional measure of spatial span. Implications of these findings for research using the CBT are discussed.
Coupled effects of nonlinear, rate‐limited sorption and biodegradation on transport of 2,4‐dichlorophenoxyacetic acid in soil

The transport and fate of many contaminants in subsurface systems can be influenced by several coupled processes, such as nonlinear, rate‐limited sorption and biodegradation. We investigated the transport in soil of a model organic compound, 2,4‐dichlorophenoxyacetic acid (2,4‐D), influenced by nonlinear, rate‐limited sorption and biodegradation. Miscible displacement and batch sorption experiments were conducted using a wide range of solute concentrations to investigate the impact of concentration‐dependent behavior on transport. The sorption isotherm was approximately linear at a low concentration, and nonlinear over the extended range of concentrations. Results from the transport experiments, with the fitted N values approaching 1 at low input concentrations, were consistent with the batch sorption study. Nonlinear sorption significantly influenced the position of the breakthrough curves because of concentration‐dependent retardation. However, although both nonlinear and rate‐limited sorption influenced the shape of the breakthrough curves, the impact of rate‐limited sorption was greater. The effective travel time of 2,4‐D transport is influenced by synergistic interactions between sorption and biodegradation. For example, the sequential rightward shift of the breakthrough curves with decreasing input concentration, due to nonlinear sorption of 2,4‐D, is enhanced by biodegradation.
A Mechanical Comparison of the Dynamic Compression Plate, Limited Contact-Dynamic Compression Plate, and Point Contact Fixator

Summary: Cortical bone porosis associated with the dynamic compression plate (DCP) prompted the development of the limited-contact dynamic compression plate (LC-DCP) and the point-contact fixator (PC-Fix) to increase bone vascularity. However, the comparative fixation characteristics of the three designs are unknown. Transverse fractures were physiologically created in paired cadaveric sheep tibiae, which were plated before torsion testing and four-point bending to failure. The tibiae were grouped randomly and compared as follows: DCP versus LC-DCP, DCP versus PC-Fix, and LC-DCP versus PC-Fix. Mean torque to failure demonstrated no significant difference between the three plates (p < 0.33). Mean bending stiffness, gap opening, and moment to failure also demonstrated no significant difference between the three designs withp < 0.29,< 0.13, and < 0.16, respectively. The LC-DCP and PC-Fix have torsion and bending properties comparable with the DCP in the fixation of simple transverse diaphyseal fractures
Oxidative Stress Responses in the Human Fungal Pathogen, Candida albicans

Candida albicans is a major fungal pathogen of humans, causing approximately 400,000 life-threatening systemic infections world-wide each year in severely immunocompromised patients. An important fungicidal mechanism employed by innate immune cells involves the generation of toxic reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. Consequently, there is much interest in the strategies employed by C. albicans to evade the oxidative killing by macrophages and neutrophils. Our understanding of how C. albicans senses and responds to ROS has significantly increased in recent years. Key findings include the observations that hydrogen peroxide triggers the filamentation of this polymorphic fungus and that a superoxide dismutase enzyme with a novel mode of action is expressed at the cell surface of C. albicans. Furthermore, recent studies have indicated that combinations of the chemical stresses generated by phagocytes can actively prevent C. albicans oxidative stress responses through a mechanism termed the stress pathway interference. In this review, we present an up-date of our current understanding of the role and regulation of oxidative stress responses in this important human fungal pathogen.
Natural Vertical Transmission of Ndumu Virus in Culex pipiens (Diptera: Culicidae) Mosquitoes Collected as Larvae

ABSTRACT Ndumu virus (NDUV) is a member of the family Togaviridae and genus Alphavirus. In Kenya, the virus has been isolated from a range of mosquito species but has not been associated with human or animal morbidity. Little is know about the transmission dynamics or vertebrate reservoirs of this virus. NDUV was isolated from two pools of female Culex pipiens mosquitoes, IJR37 (n = 18) and IJR73 (n = 3), which were collected as larvae on 15 April 2013 from two dambos near the village of Marey, Ijara District, Garissa County, Kenya, and reared to adults and identified to species. These results represent the first field evidence of vertical transmission of NDUV among mosquitoes.
Anglo American College in Prague: Positioning for Growth

The Case Study section of the International Journal of Entrepreneurship and Innovation serves two purposes. First, the case studies presented are concerned with problematical issues that are pertinent to students of entrepreneurship. Thus they constitute appropriate teaching and learning vehicles on a variety of postgraduate and undergraduate programmes. Each case study is accompanied by a set of guidelines for the use of tutors. Second, it is envisaged that those engaged in entrepreneurial activities will find the cases both interesting and useful. A major theme of the case study in this issue is the strategic positioning and stages of growth of a young organization in a changing economy. The Anglo American College in Prague (AAC) was started in 1991, shortly after the Velvet Revolution ushered in the Czech Republic’s new era of independence and market-driven competitiveness. The underfunded state universities’ inability to supply multinational companies’ demands for English-speaking managers and employees provided the opportunity for new providers of university-level education. AAC attracted transient American and British expatriates as faculty and non-traditional and foreign students. Sparse funding kept its administrative staff lean and facilities and student support services poor. In 1994, AAC found a permanent building and began establishing systems and procedures. After ousting its administrative director in 1996, Dr Richard Jones took the helm and built AAC’s programmes and prestige. By the end of the summer of 1998, Jones was set to leave, along with some of the more competent managers who had started with him in 1996. The case ends as Roger Cole, a retired American professor, attempts to bring AAC ‘to the next level’, following Jones’s legacy of academic rigour, open management and community connectedness.
The efficacy of individualized computerized testing in nursing education.

This study examined the effects of an individualized computerized testing system for baccalaureate nursing students enrolled in health assessment and obstetrics/women's health during a 3-year period. One hundred twenty-seven students participated in the study. The testing software, Pedagogue, was used to generate the computer tests, and the students took all quizzes on-line. The mean scores on computer tests in both courses were as good as, or better than, previous scores on paper-pencil forms of the tests (P < .05).