Miracle-dz/UniFAR-FTUs huggingface dataset:
Cyclosporine A attenuates the natriuretic action of loop diuretics by inhibition of renal COX-2 expression.

BACKGROUND It is known that inhibition of cyclooxygenase (COX) impairs the renal actions of loop diuretics. Recently, we found that cyclosporine A (CsA) inhibits renal COX-2 expression. Therefore, we examined the interferences of CsA with the renal actions of loop diuretics. METHOD We investigated the renal effects of furosemide administration (12 mg/day subcutaneously) in male Sprague-Dawley rats receiving in addition vehicle, CsA (15 mg/kg x day), rofecoxib (10 mg/kg x day), or a combination of both. RESULTS CsA, rofecoxib, and their combination lowered the furosemide-induced increase of prostaglandin E(2) (PGE(2)) and of 6-keto prostaglandin F(1 alpha) (6-keto PGF(1 alpha)) excretion by 55% and by 70%. They also lowered furosemide stimulated renal excretion of sodium and water by about 65% and 60%. Basal as well as furosemide-induced stimulation of plasma renin activity (PRA) and of renal renin mRNA was further enhanced by CsA. In contrast, rofecoxib attenuated the furosemide-induced rise of PRA and of renin mRNA, both in the absence and in the presence of CsA. In addition, the increase in plasma 6-keto PGF(1 alpha) levels by furosemide was further enhanced by CsA and was attenuated by rofecoxib. CONCLUSION Taken together, our data suggest that CsA acts as an antinatriuretic, likely by the inhibition of COX-2-mediated renal prostanoid formation. Since the furosemide-induced stimulation of the renin system is not attenuated by CsA but by COX-2 inhibition, we speculate that extrarenal COX-2-derived prostanoids may be involved in the stimulation of the renin system by CsA and by loop diuretics.
Potential and limitations of e-learning in emergency medicine

This paper describes the potential benefits, pitfalls and barriers to adopting e-learning in emergency medicine. While the benefits relating to access, engagement and quality assurance are clear, caution is urged in embracing e-learning for e-learning's sake. It is argued that, if educational strategies are to change, this must be to the benefit of learners and not just for the convenience of access or record keeping. A variety of e-learning approaches are available, but those that promote group discussion or provide feedback from an educator are more likely to lead to successful learning than stand-alone feedback-free modules. A blended approach to learning is advocated where e-learning opportunities form an important but limited part of the overall educational experience. Shop floor and workshop-based teaching should be enhanced with e-learning, not replaced by it.
Microarrays and the microscope: balancing throughput with resolution

The cellular complexity of the brain is a major issue in the planning, execution and interpretation of microarray studies. Recent technical advances allow for high‐throughput study of specific cell populations and circuits. Here we review representative examples of currently available methods that allow high resolution and specificity in brain microarray studies, while maintaining the goal of comprehensive, high‐throughput analysis.
Relationship between red cell distribution width and short-term outcomes in acute coronary syndrome in a Chinese population.

OBJECTIVE This study was undertaken to determine the relationship between red cell distribution width (RDW) and short-term outcomes in acute coronary syndrome (ACS) in a Chinese population. METHODS AND PATIENTS A total of 1,654 patients with ACS on admission were divided into four groups according to quartiles of baseline RDW. The relationships between RDW and one-month cardiac mortality as well as heart failure and recurrent infarction were assessed. RESULTS Higher RDW values were associated with increased one-month cardiac mortality (quartile 1: 0.2%; quartile 2: 0.6%; quartile 3: 3.3%; quartile 4: 8.1%; p<0.001) and one-month heart failure and recurrent infarction (quartile 1: 2.1%; quartile 2: 2.7%; quartile 3: 3.6%; quartile 4: 15.2%; p<0.001). Logistic regression analysis revealed that RDW independently predicted for cardiac mortality (OR: 2.116, 95% CI: 1.427-3.137, p<0.001) and heart failure and recurrent infarction (OR: 2.134, 95% CI: 1.602-2.844, p<0.001) during a one-month follow-up in patients with ACS. CONCLUSION The present study indicates that elevated RDW could predict an increased risk of short-term adverse outcomes in patients with ACS.
Direct laser interference technology and potential applications

Development of direct laser interference technology (DLIT) is reviewed in this paper. With the merits of being independent on the pretreatment, mask and pattern transfer processes, DLIT is demonstrated a facile and efficient method of producing sub-micro structures on various material surfaces. From a representative perspective, a number of past achievements, containing theoretical and practice aspects, attained by the nanosecond, picosecond, and femtosecond laser interference techniques are introduced. Advantages and limitations in comparison to one another are also addressed. With the progress of the emerging subwavelength structures (e.g. metasurfaces, plasmonic structures) offering the fascinating possibility of controlling the behaviour of light in an unprecedented way, the perspectives of potential applications benefited from DLIT are finally given.
Automated level set segmentation of histopathologic cells with sparse shape prior support and dynamic occlusion constraint

In this paper, we propose a novel segmentation method for cells in histopathologic images based on a sparse shape prior guided variational level set framework. We automate the cell contour initialization by detecting seeds and deform contours by minimizing a new energy functional that incorporates a shape term involving sparse shape priors, an adaptive contour occlusion penalty term, and a boundary term encouraging contours to converge to strong edges. As a result, our approach is able to accommodate mutual occlusions and detect contours of multiple intersected cells. We apply our algorithm to a set of whole-slide histopathologic images of brain tumor sections. The proposed method is compared with other popular methods, and demonstrates good accuracy for cell segmentation by quantitative measures, suggesting its promise to support biomedical image-based investigations.
Challenging a Paradigm: the Role of DNA Homology in Tyrosine Recombinase Reactions

SUMMARY A classical feature of the tyrosine recombinase family of proteins catalyzing site-specific recombination, as exemplified by the phage lambda integrase and the Cre and Flp recombinases, is the ability to recombine substrates sharing very limited DNA sequence identity. Decades of research have established the importance of this short stretch of identity within the core regions of the substrates. Since then, several new enzymes that challenge this paradigm have been discovered and require the role of sequence identity in site-specific recombination to be reconsidered. The integrases of the conjugative transposons such as Tn916, Tn1545, and CTnDOT recombine substrates with heterologous core sequences. The integrase of the mobilizable transposon NBU1 performs recombination more efficiently with certain core mismatches. The integration of CTX phage and capture of gene cassettes by integrons also occur by altered mechanisms. In these systems, recombination occurs between mismatched sequences by a single strand exchange. In this review, we discuss literature that led to the formulation of the current strand-swapping isomerization model for tyrosine recombinases. The review then focuses on recent developments on the recombinases that challenged the paradigm that was derived from the studies of early systems.
DIALLELIC POLYMORPHISM MAY EXPLAIN VARIATIONS OF THE BLOOD CONCENTRATION OF MANNAN‐BINDING PROTEIN IN ESKIMOS, BUT NOT IN BLACK AFRICANS

Mannan‐binding protein (MBP) is a lectin which, upon binding to certain carbohydrates, activates the classical pathway of complement without the involvement of antibody or C1q. Deficiency of the MBP is associated with an opsonic defect and recurrent infections during early life. An amino acid substitution in the exon 1 at codon 54 in the MBP gene (GGC [glycine] to GAC [aspartic acid]) has been shown to be closely associated with low MBP concentration in Caucasoids. The gene frequency of the mutant allele in this population has been estimated at 0.13. In the study described here, we investigated the association between the mutant allele and MBP protein concentration in Eskimos from East‐Greenland and black Africans from the Baringo District in Kenya. The frequency of the GAC allele was identical in Eskimos and Caucasoids (0.13). No overlap with regard to MBP concentration between the genotypes was found in the Eskimos. In contrast, the Africans revealed a low frequency of the GAC allele (0.009). However, the median MBP protein concentration was approximately 5 times lower among the Africans than the Eskimos. In 12.6% of the Africans and in 2.5% of the Eskimos, MBP was undetectable. Thus, MBP deficiency is the most frequent immunodeficiency so far described. The high prevalence of MBP deficiency among healthy individuals indicates that MBP deficiency also confers some selective advantages. We advance the hypothesis that MBP deficiency is maintained in populations because MBP deficiency decreases the infectivity of some intracellular micro‐organisms which are dependent on opsonization.
The Effects of Magnesium Supplementation on Exercise Performance

ObjectivesMagnesium (Mg) status, although difficult to assess, is suspected to be marginal in many individuals, especially athletes, and this has led to the common use of Mg supplements. The purpose of this article is to critique research that has addressed Mg supplementation in athletes. Data SourcesThe primary database was Medline, which was searched for English articles from 1966 to June 1999 using the words “magnesium” and “supplementation. ” Study SelectionOnly experimental studies dealing with human subjects, Mg supplementation, and exercise performance were critiqued (n = 12). Data ExtractionQuality of critiqued articles was based on 1) use of cross-over designs, 2) how and if Mg status was assessed, 3) whether treatment was solely Mg supplementation, 4) duration of supplementation, 5) subject number, and 6) degree of experimental control. Articles were classified into “no effect” and “positive effect,” and also were examined in regard to the type of performance outcome (strength, anaerobic–lactacid, and aerobic). Data SynthesisMg is a cofactor to over 325 enzymatic reactions, and a deficiency of the mineral therefore has many physiological and exercise performance implications. Low dietary intakes, as found in many female athletes, coupled with increased urinary losses with exercise, may eventually lead to an Mg deficiency. Strength of evidence favors those studies finding no effect of Mg supplementation, regardless of whether the performance outcome was strength, anaerobic–lactacid, or aerobic. Analysis was confounded due to: 1) variable exercise modes, intensities, and durations, 2) variable training states and ages of subjects, 3) subject selection favoring males and gender differences has not been probed, 4) Mg dosage has ranged from 1 day to 3 months and from 116 mg/day to 500 mg/day, 5) multivitamins/minerals have been ingested with the Mg, 6) with one exception, 1 Mg status was either not reported or reliant on total Mg (TMg), 7) lack of a cross-over design, 8) only one study 2 made note of controlling exercise prior to exercise testing and blood assay, and 9) typical Mg intake measured was only measured in three of the studies. ConclusionsMost evidence indicates no effect of Mg supplementation on performance (strength, anaerobic–lactacid, and aerobic). When only peak treadmill speed during a VO2 max test is examined, the strength of evidence is equivocal. Trained subjects appear to benefit less than untrained subjects, but this observation requires further study. Little research has focused on physically active females who may be at the highest risk for Mg deficiency. Research has been confounded by numerous factors.
Emerging principles of regulatory evolution

Understanding the genetic and molecular mechanisms governing the evolution of morphology is a major challenge in biology. Because most animals share a conserved repertoire of body-building and -patterning genes, morphological diversity appears to evolve primarily through changes in the deployment of these genes during development. The complex expression patterns of developmentally regulated genes are typically controlled by numerous independent cis-regulatory elements (CREs). It has been proposed that morphological evolution relies predominantly on changes in the architecture of gene regulatory networks and in particular on functional changes within CREs. Here, we discuss recent experimental studies that support this hypothesis and reveal some unanticipated features of how regulatory evolution occurs. From this growing body of evidence, we identify three key operating principles underlying regulatory evolution, that is, how regulatory evolution: (i) uses available genetic components in the form of preexisting and active transcription factors and CREs to generate novelty; (ii) minimizes the penalty to overall fitness by introducing discrete changes in gene expression; and (iii) allows interactions to arise among any transcription factor and downstream CRE. These principles endow regulatory evolution with a vast creative potential that accounts for both relatively modest morphological differences among closely related species and more profound anatomical divergences among groups at higher taxonomical levels.
Subject instructions and methods of target presentation in accommodation research.

PURPOSE The authors investigated the potential of subject instructions to alter the static accommodative stimulus-response function. They also investigated whether the reduced cue environment of the Badal optical system leads to accommodative responses different from those that occur for targets presented in real space. METHODS Static accommodative responses with three focusing instructions were compared to baselines obtained with minimal instruction to stabilize gaze. Static accommodative responses were recorded for targets presented in real space and in a Badal optical system. RESULTS Individuals differ widely in their responses to Instruction 1 (" . make no special effort . "), although some adopt a relatively fixed position of focus. Responses with Instruction 2 (" . look at the words naturally . ") and Instruction 3 (" . carefully focus . ") are not significantly different from each other, but differ slightly from the responses with the baseline instruction ("pick a word in the middle of the block of text and look at it"). In a sample including most subjects, mean responses for Badal and real space targets are identical. However, it appears that some subjects have difficulty accommodating for Badal targets. CONCLUSIONS The authors recommend the use of Instructions 2 and 3 for investigation of the static accommodative response, with a number of provisos. Accommodative responses to Badal and real space targets are generally equivalent, but researchers should take care to identify those persons who have difficulties accommodating for Badal targets.
The Transfer Function Bake-Off

Direct volume rendering is a key technology for visualizing large 3D data sets from scientific or medical applications. Transfer functions are particularly important to the quality of direct volume-rendered images. A transfer function assigns optical properties, such as color and opacity, to original values of the data set being visualized. Unfortunately, finding good transfer functions proves difficult. It is one of the major problems in volume visualization. The article examines four of the currently most promising approaches to transfer function design. The four approaches are: trial and error, with minimum computer aid; data-centric, with no underlying assumed model; data-centric, using an underlying data model; and image-centric, using organized sampling.
Non-specific beneficial effect of measles immunisation: analysis of mortality studies from developing countries

Abstract Objective: To examine whether the reduction in mortality after standard titre measles immunisation in developing countries can be explained simply by the prevention of acute measles and its long term consequences. Design: An analysis of all studies comparing mortality of unimmunised children and children immunised with standard titre measles vaccine in developing countries. Studies: 10 cohort and two case-control studies from Bangladesh, Benin, Burundi, Guinea-Bissau, Haiti, Senegal, and Zaire. Main outcome measures: Protective efficacy of standard titre measles immunisation against all cause mortality. Extent to which difference in mortality between immunised and unimmunised children could be explained by prevention of measles disease. Results: Protective efficacy against death after measles immunisation ranged from 30% to 86%. Efficacy was highest in the studies with short follow up and when children were immunised in infancy (range 44-100%). Vaccine efficacy against death was much greater than the proportion of deaths attributed to acute measles disease. In four studies from Guinea-Bissau, Senegal, and Burundi vaccine efficacy against death remained almost unchanged when cases of measles were excluded from the analysis. Diphtheria-tetanus-pertussis and polio vaccinations were not associated with reduction in mortality. Conclusion: These observations suggest that standard titre measles vaccine may confer a beneficial effect which is unrelated to the specific protection against measles disease.
[Expression of TLR9 in human nasal epithelial cells].

OBJECTIVE To analyze expression of TLR9 in human nasal epithelial cells by semi-quantitative reverse transcription-polymerase chain reaction, immunohistochemistry and flow cytometry. METHOD Human primary nasal epithelial cells (HNECs) were cultured, and then analyze the expression of TLR9 in primary cultured HNECs measured by semi-quantitative RT-PCR and immunohistochemistry and flow cytometry. RESULT Primary cultured HNECs were observed by 400 x optical microscopes. Round or irregular cells stick to the bottom of cell culture plates. RT-PCR showed that mRNA expressions of TLR9 were found in primary nasal epithelial cells by 1% agarose gel electrophoresis. Interestingly, by analyzing with gray level of GAPDH, expression of TLR9 mRNA in HNECs was higher than positive control PBMCs. CONCLUSION TLR9 is expressed by HNECs. Expression of TLR9 mRNA in nasal epithelial cells is higher than in PBMCs.
Diagnosis of Chlamydia trachomatis infections in men and women by testing first-void urine by ligase chain reaction

From April to September 1993, 305 men and 447 women in Hamilton, Canada, consented to the collection of a urethral or cervical swab, respectively, for culture and 20 ml of first-void urine (FVU) for testing by the enzyme immunoassay Chlamydiazyme and by ligase chain reaction (LCR) in the form of a kit from Abbott Laboratories called LCx Chlamydia trachomatis. Evaluation of test performance with each specimen was calculated on the basis of an expanded "gold standard" of a patient found to be positive by culture or by a confirmed nonculture test. By using this expanded standard, the prevalence of infection was determined to be 6% (27/447) for the women and 18.4% (56/305) for the men. LCR testing of FVU in both studies was the most sensitive approach (96%). The performance of Chlamydiazyme was as follows: cervical swab, 78.3% sensitivity; female FVU, 37% sensitivity; and male FVU, 67.9% sensitivity. Culture was the least sensitive approach to diagnosis: female cervix, 55.6%; and male urethra, 37.5%. LCR testing of FVU from men or women diagnosed the greatest number of genitourinary tract infections with no false positives.
Lytic versus stimulatory synapse in cytotoxic T lymphocyte/target cell interaction: Manifestation of a dual activation threshold

Activation of biological functions in T lymphocytes is determined by the molecular dynamics occurring at the T cell/opposing cell interface. In the present study, a central question of cytotoxic T lymphocyte (CTL) biology was studied at the single-cell level: can two distinct activation thresholds for cytotoxicity and cytokine production be explained by intercellular molecular dynamics between CTLs and targets? In this study, we combine morphological approaches with numerical analysis, which allows us to associate specific patterns of calcium mobilization with different biological responses. We show that CTLs selectively activated to cytotoxicity lack a mature immunological synapse while exhibiting a low threshold polarized secretion of lytic granules and spike-like patterns of calcium mobilization. This finding is contrasted by fully activated CTLs, which exhibit a mature immunological synapse and smooth and sustained calcium mobilization. Our results indicate that intercellular molecular dynamics and signaling characteristics allow the definition of two activation thresholds in individual CTLs: one for polarized granule secretion (lytic synapse formation) and the other for cytokine production (stimulatory synapse formation).
[Upper extremities, neck and back symptoms in office employees working at computer stations].

BACKGROUND To obtain current data on the occurrence ofwork-related symptoms of office computer users in Poland we implemented a questionnaire survey. Its goal was to assess the prevalence and intensity of symptoms of upper extremities, neck and back in office workers who use computers on a regular basis, and to find out if the occurrence of symptoms depends on the duration of computer use and other work-related factors. MATERIAL AND METHODS Office workers in two towns (Warszawa and Katowice), employed in large social services companies, were invited to fill in the Polish version of Nordic Questionnaire. The questions included work history and history of last-week symptoms of pain of hand/wrist, elbow, arm, neck and upper and lower back (occurrence and intensity measured by visual scale). Altogether 477 men and women returned the completed questionnaires. Between-group symptom differences (chi-square test) were verified by multivariate analysis (GLM). RESULTS The prevalence of symptoms in individual body parts was as follows: neck, 55.6%; arm, 26.9%; elbow, 13.3%; wrist/hand, 29.9%; upper back, 49.6%; and lower back, 50.1%. Multivariate analysis confirmed the effect of gender, age and years of computer use on the occurrence of symptoms. Among other determinants, forearm support explained pain of wrist/hand, wrist support of elbow pain, and chair adjustment of arm pain. Association was also found between low back pain and chair adjustment and keyboard position. CONCLUSIONS The findings revealed frequent occurrence of symptoms of pain in upper extremities and neck in office workers who use computers on a regular basis. Seating position could also contribute to the frequent occurrence of back pain in the examined population.