Miracle-dz/UniFAR-FTUs huggingface dataset:
Cyclooxygenase-2-Derived E Prostaglandins Down-Regulate Matrix Metalloproteinase-1 Expression in Fibroblast-Like Synoviocytes via Inhibition of Extracellular Signal-Regulated Kinase Activation 1

We examined the regulation of matrix metalloproteinase (MMP) production by mitogen-activated protein kinases and cyclooxygenases (COXs) in fibroblast-like synoviocytes (FLSCs). IL-1β and TNF-α stimulated FLSC extracellular signal-regulated kinase (ERK) activation as well as MMP-1 and -13 release. Pharmacologic inhibitors of ERK inhibited MMP-1, but not MMP-13 expression. Whereas millimolar salicylates inhibited both ERK and MMP-1, nonsalicylate COX and selective COX-2 inhibitors enhanced stimulated MMP-1 release. Addition of exogenous PGE1 or PGE2 inhibited MMP-1, reversed the effects of COX inhibitors, and inhibited ERK activation, suggesting that COX-2 activity tonically inhibits MMP-1 production via ERK inhibition by E PGs. Exposure of FLSCs to nonselective COX and selective COX-2 inhibitors in the absence of stimulation resulted in up-regulation of MMP-1 expression in an ERK-dependent manner. Moreover, COX inhibition sufficient to reduce PGE levels increased ERK activity. Our data indicate that: 1) ERK activation mediates MMP-1 but not MMP-13 release from FLSCs, 2) COX-2-derived E PGs inhibit MMP-1 release from FLSCs via inhibition of ERK, and 3) COX inhibitors, by attenuating PGE inhibition of ERK, enhance the release of MMP-1 by FLSC.
Use of nitroxides for assessing perfusion, oxygenation, and viability of tissues: In vivo EPR and MRI studies

Relative perfusion, pO2, and bioreduction were measured simultaneously in wVo in tissues in mice by following changes in the intensity and shape of the EPR spectra of nitroxides injected directly into the tissues, using low frequency (1.1 GHz) localized EPR spectroscopy. Using normal and blood flow restricted gastrocnemius muscles it was shown that the decrease of the EPR signals of the nitroxides in tissues was due principally to perfusion, which redistributed the nitroxides. Changes in pO2 were reflected by changes of the linewidth; only a perdeuterated nttroxide with a narrow line was an adequate indicator for this parameter. This technique was applied experimental murine tumors (MTG‐B and RIF‐1) to determine the perfusion and pO2 in these relatively hypoxic model tumor systems. Using the paramagnetic properties of the nitroxides to enhance T1‐weighted MR images, heterogeneity in perfusion in individual tumors was demonstrated.
A Study of Iranian EFL University Lecturers’ Practice of Code Switching in English as Foreign Language Instruction

This study aimed at investigating where and the purposes for which code-switching is used by Iranian EFL lecturers in universities as foreign languageinstruction.The data of this study were gathered from two sources: six EFL university lecturers from three local universities where they taught English as EFL instruction.Theywere interviewed individually regarding the use of code-switching in their classrooms in order to reveal their purposes of using this strategy as well as their participants’ understandings of code-switching as a language teaching strategy. The interviews took 30-40 minutes each. The interviews were finally transcribed and the main themes were coded to answer the research questions; the second group of participants was students as native speakers of Persian. Ninety undergraduates from the three universities were randomly chosen from among those students majoring in TEFL. They were majoring in the first grade of the academic program. To this end, an eleven-item questionnaire was given to them to elicit their responses for the contexts and the reasons for which code-switching was preferred.The data from interview with EFL lecturers as well those of the students’ responses were analyzed qualitatively and quantitatively using SPSS, respectively, to determine where and for what purposes codes-switching were applied or practiced in EFL classrooms. The findings of the study indicated that their code-switching habits were connected to what was being taught. Their code-switching had to do with efficiency in their teaching and how to make it easier for the students to understand what they were teaching.
Ist die Tagesbetreuung in Krippen ein Risiko? Eine kritische Beurteilung der internationalen Krippenforschung

Die Betreuungsfrage fur Kleinstkinder unter drei Jahren ist bislang unbeantwortet. Ein Ausbau der Krippenbetreuung wird haufig mit Hinweis auf positive Forschungsbefunde aus dem Ausland favorisiert. In einer Ubersicht wurden die Vorbedingungen fur eine solche Ubertragung gepruft: methodische Zuverlassigkeit der Krippenstudien, Konsistenz der Ergebnisse sowie eindeutige Kenntnisse uber die Rahmenbedingungen der international untersuchten Krippen. Diese Minimalvoraussetzungen fur eine Ubertragung erwiesen sich als nicht gegeben. Der Verfasser pladiert fur individuellere Betreuungsformen, solange die Qualitatsstandards deutscher Krippen nicht auf einem Niveau sind, auf dem Entwicklungsrisiken ausgeschlossen werden konnen. (DIPF/Orig.) Good enough care for infants and toddlers is still an unresolved issue. Many experts are in favour of installing more infant daycare facilities, often claiming positive research results from foreign countries. In a review the preconditions for transferring these results are proved: Methodological reliability of the studies quoted, consistency of the results, and explicit knowledge about the framework conditions of the infant daycare centres studied abroad. The minimal conditions for such a transfer did not turn out to be met. The author makes a statement for forms of childcare allowing more individual attention to a child, as long as the quality standards of German infant daycare centres do not reach a level that is necessary to prevent developmental risks. (DIPF/Orig.)
The participation of scientists in public understanding of science activities: The policy and practice of the U.K. Research Councils

Participation of scientists in public understanding of science (PUS) activity has frequently been encouraged by appeals to the notion of duty. This paper reviews the schemes of five of the U.K. Scientific Research Councils that encourage their scientists to get involved in PUS activity. The success of such schemes is measured by the number of scientists participating and the way in which this activity is monitored. This paper compares and contrasts the different strategies used and gives comparative data on the Councils' expenditure on PUS activity. The results suggest an uncomfortable gap between the formal policy of the Research Councils and their practices on the ground. While the involvement of practicing scientists is an important element of the Research Councils' PUS program, the work reported here raises questions about the desirability and feasibility of the notion that PUS involvement should be an obligation for all research scientists.
How Do the Young Suicide Survivors Wish to Be Met by Psychologists? A User Study

Little user-knowledge has been documented on the experiences of young suicide bereaved with psychosocial assistance and therapy. Thirty-two adolescents who had lost a close family member or friend by suicide participated in a research project by filling in questionnaires and participating in focus group interviews. The article explores the young people's experiences with and wishes for help from psychologists, and shows that the young bereaved do not receive the psychological assistance they wish for and need. The shortcomings are discussed in relation to the organization, form, and contents of the help. In order to reach youth with adequate assistance in an extreme life situation, it is worth listening to their opinions about how they want to be approached in the wake of a suicide.
Sample size determination for studies of gene-environment interaction.

BACKGROUND The search for interaction effects is common in epidemiological studies, but the power of such studies is a major concern. This is a practical issue as many future studies will wish to investigate potential gene-gene and gene-environment interactions and therefore need to be planned on the basis of appropriate sample size calculations. METHODS The underlying model considered in this paper is a simple linear regression and relating a continuous outcome to a continuously distributed exposure variable. RESULTS The slope of the regression line is taken to be dependent on genotype, and the ratio of the slopes for each genotype is considered as the interaction parameter. Sample size is affected by the allele frequency and whether the genetic model is dominant or recessive. It is also critically dependent upon the size of the association between exposure and outcome, and the strength of the interaction term. The link between these determinants is graphically displayed to allow sample size and power to be estimated. An example of the analysis of the association between physical activity and glucose intolerance demonstrates how information from previous studies can be used to determine the sample size required to examine gene-environment interactions. CONCLUSIONS The formulae allowing the computation of the sample size required to study the interaction between a continuous environmental exposure and a genetic factor on a continuous outcome variable should have a practical utility in assisting the design of studies of appropriate power.
Upregulation of Heme Oxygenase-1 in Response to Wild Thyme Treatment Protects against Hypertension and Oxidative Stress

High blood pressure is the most powerful contributor to the cardiovascular morbidity and mortality, and inverse correlation between consumption of polyphenol-rich foods or beverages and incidence of cardiovascular diseases gains more importance. Reactive oxygen species plays an important role in the development of hypertension. We found that wild thyme (a spice plant, rich in polyphenolic compounds) induced a significant decrease of blood pressure and vascular resistance in hypertensive rats. The inverse correlation between vascular resistance and plasma heme oxygenase-1 suggests that endogenous vasodilator carbon monoxide generated by heme oxidation could account for this normalization of blood pressure. Next product of heme oxidation, bilirubin (a chain-breaking antioxidant that acts as a lipid peroxyl radical scavenger), becomes significantly increased after wild thyme treatment and induces the reduction of plasma lipid peroxidation in hypertensive, but not in normotensive rats. The obtained results promote wild thyme as useful supplement for cardiovascular interventions.
Arabidopsis SNAREs SYP61 and SYP121 Coordinate the Trafficking of Plasma Membrane Aquaporin PIP2;7 to Modulate the Cell Membrane Water Permeability[W]

This work shows that the post-Golgi trafficking of PIP2;7 involves an interaction with SYP61 and SYP121 and that SYP61 and SYP121 colocalize and are physically associated in a SNARE complex. These findings suggest that SNAREs, and possibly a SYP61/SYP121 SNARE complex, play an important role in the regulation of the transport of the plasma membrane aquaporin. Plant plasma membrane intrinsic proteins (PIPs) are aquaporins that facilitate the passive movement of water and small neutral solutes through biological membranes. Here, we report that post-Golgi trafficking of PIP2;7 in Arabidopsis thaliana involves specific interactions with two syntaxin proteins, namely, the Qc-SNARE SYP61 and the Qa-SNARE SYP121, that the proper delivery of PIP2;7 to the plasma membrane depends on the activity of the two SNAREs, and that the SNAREs colocalize and physically interact. These findings are indicative of an important role for SYP61 and SYP121, possibly forming a SNARE complex. Our data support a model in which direct interactions between specific SNARE proteins and PIP aquaporins modulate their post-Golgi trafficking and thus contribute to the fine-tuning of the water permeability of the plasma membrane.
COST OPTIMIZATION OF A COMPOSITE FLOOR SYSTEM USING ANT COLONY SYSTEM

This paper presents an ant colony system model for cost optimization of a composite floor system based on the load and resistance factor design (LRFD) specification of the AISC. The model formulation includes the cost of concrete, steel beam, and shear studs. The objective function is considered as the cost of the structure, which is minimized subjected to serviceability and strength requirements. Examples of composite floor systems are presented to illustrate the performance of the present algorithm. A parametric study is also included to investigate the effects of beam spans and loadings on the cost optimization of composite beams. Keywords– Ant colony system (ACS), cost optimization, composite floor systems, structural optimization, load and resistance factor design
Alpha-synuclein aggregation involves a bafilomycin A1-sensitive autophagy pathway

Synucleinopathies like Parkinson disease and dementia with Lewy bodies (DLB) are characterized by α-synuclein aggregates within neurons (Lewy bodies) and their processes (Lewy neurites). Whereas α-synuclein has been genetically linked to the disease process, the pathological relevance of α-synuclein aggregates is still debated. Impaired degradation is considered to result in aggregation of α-synuclein. In addition to the ubiquitin-proteasome degradation, the autophagy-lysosomal pathway (ALP) is involved in intracellular degradation processes for α-synuclein. Here, we asked if modulation of ALP affects α-synuclein aggregation and toxicity. We have identified an induction of the ALP markers LAMP-2A and LC3-II in human brain tissue from DLB patients, in a transgenic mouse model of synucleinopathy, and in a cell culture model for α-synuclein aggregation. ALP inhibition using bafilomycin A1 (BafA1) significantly potentiates toxicity of aggregated α-synuclein species in transgenic mice and in cell culture. Surprisingly, increased toxicity is paralleled by reduced aggregation in both in vivo and in vitro models. The dichotomy of effects on aggregating and nonaggregating species of α-synuclein was specifically sensitive to BafA1 and could not be reproduced by other ALP inhibitors. The present study expands on the accumulating evidence regarding the function of ALP for α-synuclein degradation by isolating an aggregation specific, BafA1-sensitive, ALP-related pathway. Our data also suggest that protein aggregation may represent a detoxifying event rather than being causal for cellular toxicity.
Partial purification of HLAMP‐1 provides direct evidence for the multicomponent nature of the particulate matrix associated with cardiac mesenchyme formation

H‐LAMP‐1 is a 283 kDa protein that is involved in the transformation of endothelial cells into mesenchyme within the AV canal and proximal outflow tract of the heart. This protein is part of the particulate matrix that has been suggested to be composed of multicomponent complexes that have been termed cardiac adherons. However, to date no direct evidence has been provided that these proteins are complexed into an adheron‐like particle. This report provides the first such evidence by showing that purification of hLAMP‐1, under gentle conditions, results in the isolation of multiple bands of similar molecular weight within the fractions that contain anti‐hLAMP‐1 activity. J. Cell. Biochem. 66:112–122, 1997. © 1997 Wiley‐Liss, Inc.
Involvement of Plasmalogens in Post-Natal Retinal Vascular Development

Objective Proper development of retinal blood vessels is essential to ensure sufficient oxygen and nutrient supplies to the retina. It was shown that polyunsaturated fatty acids (PUFAs) could modulate factors involved in tissue vascularization. A congenital deficiency in ether-phospholipids, also termed “plasmalogens”, was shown to lead to abnormal ocular vascularization. Because plasmalogens are considered to be reservoirs of PUFAs, we wished to improve our understanding of the mechanisms by which plasmalogens regulate retinal vascular development and whether the release of PUFAs by calcium-independent phospholipase A2 (iPLA2) could be involved. Methods and Results By characterizing the cellular and molecular steps of retinal vascular development in a mouse model of plasmalogen deficiency, we demonstrated that plasmalogens modulate angiogenic processes during the early phases of retinal vascularization. They influence glial activity and primary astrocyte template formation, endothelial cell proliferation and retinal vessel outgrowth, and impact the expression of the genes involved in angiogenesis in the retina. These early defects led to a disorganized and dysfunctional retinal vascular network at adult age. By comparing these data to those obtained on a mouse model of retinal iPLA2 inhibition, we suggest that these processes may be mediated by PUFAs released from plasmalogens and further signalling through the angiopoietin/tie pathways. Conclusions These data suggest that plasmalogens play a crucial role in retinal vascularization processes.
An Interdisciplinary Experience focused on Pharmacogenetics: Engaging pharmacy and physician assistant students in conversations about antiplatelet therapy with respect to CYP2C19 genotype

Objective: The goals of the interdisciplinary laboratory were to educate and engage pharmacy and physician assistant (PA) students in a discussion focused on the collection, interpretation, and application of pharmacogenetic data. Design: Interdisciplinary teams participated in a one-hour, case-based discussion and provided a therapeutic recommendation using the Clinical Pharmacogenetics Implementation Consortium guidelines. Assessment: All students were surveyed before and after the laboratory on knowledge and application of pharmacogenetics and working in interdisciplinary teams. The interdisciplinary laboratory successfully enhanced the student’s knowledge about sample collection and interpretation of pharmacogenetic information. Additionally, the laboratory improved student confidence in working in interdisciplinary teams to apply pharmacogenetic information to clinical decision making. Furthermore, the majority of students indicated that the interdisciplinary laboratory is valuable and useful in healthcare curriculums. Conclusion: The laboratory highlighted the differences between pharmacy and PA education regarding PGt, and brought to light several important uncertainties: (1) What is the depth of PGt knowledge that healthcare practitioners need? (2) What are best practices for conveying PGt information? Type: Case Study
An Unexpected Sequence of Events: Mismatch Detection in the Human Hippocampus

The ability to identify and react to novelty within the environment is fundamental to survival. Computational models emphasize the potential role of the hippocampus in novelty detection, its unique anatomical circuitry making it ideally suited to act as a comparator between past and present experience. The hippocampus, therefore, is viewed to detect associative mismatches between what is expected based on retrieval of past experience and current sensory input. However, direct evidence that the human hippocampus performs such operations is lacking. We explored brain responses to novel sequences of objects using functional magnetic resonance imaging (fMRI), while subjects performed an incidental target detection task. Our results demonstrate that hippocampal activation was maximal when prior predictions concerning which object would appear next in a sequence were violated by sensory reality. In so doing, we establish the biological reality of associative match-mismatch computations within the human hippocampus, a process widely held to play a cardinal role in novelty detection. Our results also suggest that the hippocampus may generate predictions about how future events will unfold, and critically detect when these expectancies are violated, even when task demands do not require it. The present study also offers broader insights into the nature of essential computations carried out by the hippocampus, which may also underpin its unique contribution to episodic memory.
Autopsy Prevalence of Intracranial Atherosclerosis in Patients With Fatal Stroke

Background and Purpose— The objective of this study was to determine the prevalence of intracranial plaques and stenoses and their causal role in patients with fatal stroke. Intracranial atherosclerosis is considered to be a rare condition with a severe prognosis. However, disease prevalence may be underestimated due to lack of appropriate diagnostic procedures. Methods— We performed a systematic analysis of intra- and extracranial arteries, the aortic arch, and the heart in 339 consecutive autopsies of patients with stroke. Clinical history, risk factors, imaging data, and general autopsy reports were analyzed. Patients with brain hemorrhage (n=80) were used as control subjects. Results— Intracranial plaques and stenoses occurred in 62.2% (95% CI, 56.3 to 68.1) and 43.2% (95% CI, 37.2 to 49.3) of patients with brain infarction, respectively, compared with 48.8% (P<0.05) and 17.5% (P<0.001) of patients with brain hemorrhage, respectively. In the 43% of patients with brain infarction with at least one intracranial plaque-inducing luminal stenosis graded >30%, the stenosis was considered to be causal in 5.8% of cases (n=15) because of superimposed clot on ulcerated plaques; 27% of these patients had stenoses graded 30% to 75%. In multivariate analyses, diabetes and male sex were significantly associated with intracranial plaques and stenosis. History of myocardial infarction was significantly associated with intracranial plaques and previous stroke was associated with intracranial stenosis. Conclusions— Intracranial plaques and stenoses are highly prevalent in fatal stroke, and stenoses graded 30% to 75% may be causal. New arterial wall imaging techniques should be used to reevaluate the frequency and role of intracranial artery plaques in living patients with stroke.
Current status and opportunities for therapeutic drug monitoring in the treatment of tuberculosis

ABSTRACT Introduction: Tuberculosis remains a global health problem and pharmacokinetic variability has been postulated as one of the causes of treatment failure and acquired drug resistance. New developments enable implementation of therapeutic drug monitoring, a strategy to evaluate drug exposure in order to tailor the dose to the individual patient, in tuberculosis treatment. Areas covered: Literature on pharmacokinetics and pharmacodynamics of anti-tuberculosis drugs was explored to evaluate the effect of drug exposure in relation to drug susceptibility, toxicity and efficacy. New, down-sized strategies, like dried blood spot analysis and limited sampling strategies are reviewed. In addition, molecular resistance testing of Mycobacteria tuberculosis, combining a short turn-around time with relevant information on drug susceptibility of the causative pathogen was explored. Newly emerging host biomarkers provide information on the response to treatment. Expert opinion: Therapeutic drug monitoring can minimize toxicity and increase efficacy of tuberculosis treatment and prevent the development of resistance. Dried blood spot analysis and limited sampling strategies, can be combined to provide us with a more patient friendly approach. Furthermore, rapid information on drug susceptibility by molecular testing, and information from host biomarkers on the bacteriological response, can be used to further optimize tuberculosis treatment.