Miracle-dz/UniFAR-FTUs huggingface dataset:
Cortisol Increases Interstitial Collagenase Expression in Osteoblasts by Post-transcriptional Mechanisms (*)

Glucocorticoids regulate both bone formation and bone resorption. In osteoblasts, they inhibit type I collagen synthesis; however, there is limited information about their effects on interstitial collagenase, the enzyme that degrades type I collagen. We used primary cultures of osteoblast-enriched cells from fetal rat calvariae (Ob cells) to study the effects of cortisol on collagenase expression. Northern blot analysis showed that cortisol increased collagenase transcript levels in a dose- and time-dependent manner, which was paralleled by an increase in immunoreactive metalloproteinase in the culture medium. Cortisol increased the half-life of collagenase mRNA from 6 to 12 h in transcription-arrested Ob cells. In contrast, cortisol modestly decreased collagenase gene transcription after 24 h of treatment. The up-regulation of collagenase by cortisol is osteoblast-specific, since the glucocorticoid decreased phorbol 12-myristate 13-acetate-induced collagenase mRNA expression in rat fibroblasts, a result that agrees with other studies of collagenase gene regulation in fibroblastic cells. In conclusion, cortisol increases interstitial collagenase transcript levels by post-transcriptional mechanisms in osteoblastic cells. Our data demonstrate that glucocorticoids regulate collagenase gene expression in a novel tissue-specific manner, further highlighting the differences in gene regulation between osteoblastic and fibroblastic cells.
Evaluation of effects of JPEG2000 compression on a computer-aided detection system for prostate cancer on digitized histopathology

A single digital pathology image can occupy over 10 gigabytes of hard disk space, rendering it difficult to store, analyze, and transmit. Though image compression provides a means of reducing the storage requirement, its effects on CAD (and pathologist) performance are not yet clear. In this work we assess the impact of compression on the ability of a CAD system to detect carcinoma of the prostate (CaP) in histological sections. The CAD algorithm proceeds as follows: Glands in the tissue are segmented using a region-growing algorithm. The size of each gland is then extracted and modeled using a mixture of Gamma distributions. A Markov prior (specifically, a probabilistic pairwise Markov model) is employed to encourage nearby glands to share the same class (i.e. cancerous or non-cancerous). Finally, cancerous glands are aggregated into continuous regions using a distance-hull algorithm. We evaluate CAD performance over 12 images compressed at 14 different compression ratios using JPEG2000. Algorithm performance (measured using the under the receiver operating characteristic curves) remains relatively constant for compression ratios up to 1:256. After this point performance degrades precipitously. We also have an expert pathologist view the compressed images and assign a confidence measure as to their diagnostic fidelity.
Positive Youth Development and Participation in an Urban Debate League: Results from Chicago Public Schools, 1997-2007

Abstract:Research suggests that participation in co-curricular and extracurricular activities improves students’ academic outcomes, but less is known about the mechanisms by which these programs impact students’ educational trajectories. This study examines psychosocial factors linking participation in an urban debate league (UDL) and academic performance in a large prospective study of students in the Chicago Public Schools (N = 12,197) over a nine-year period. School, social, and civic engagement were higher among debaters than non-debaters, but mediation analysis indicated these indicators of engagement only partially explained the academic effects of UDL participation. This article discusses study implications for co-curricular programming, in particular as they relate to efforts to close racial/ethnic and socioeconomic disparities in educational attainment.
Examining the effects of the flipped model of instruction on student engagement and performance in the secondary mathematics classroom: An action research study

In many of the secondary classrooms across the country, including the research site for this study, students are passively engaged in the mathematics content, and academic performance can be described, at best, as mediocre. This action research study sought to bring about improvements in student engagement and performance in the secondary mathematics classroom through the implementation of the flipped model of instruction and compared student interaction in the flipped classroom to that of a traditional format. The flipped model of instruction is a relatively new teaching strategy attempting to improve student engagement and performance by moving the lecture outside the classroom via technology and moving homework and exercises with concepts inside the classroom via learning activities. Changes in the student participants’ perceptions and attitudes were evidenced and evaluated through the completion of a preand post-survey, a teacher-created unit test, random interviews, and a focus group session. In addition, the researcher documented observations, experiences, thoughts, and insights regarding the intervention in a journal on a daily basis. Quantitative results and qualitative findings revealed the student participants responded favorably to the flipped model of instruction and experienced an increase in their engagement and communication when compared to the traditional classroom experience. The student participants also recognized improvements in the quality of instruction and use of class of time with the flipped model of instruction. In terms of academic performance, no significant changes were demonstrated between the flipped model of instruction students and those taught in a traditional classroom environment.
Fun with Filtering French

Early use of corpora for language learning has included analysis of word usage via concordancing. In addition, some attempts have been made to use readability criteria for recommending reading to learners. In this paper we discuss various tools and approaches for enhanced language learning support, including different methods of filtering text based on vocabulary and grammatical criteria. We demonstrate the effects of various criteria on the retrieval of text, assuming the user is English-speaking and learning French. Filtering text based on a small vocabulary of frequently occurring words, a set of English-French cognates and named entities, and high coverage criteria, results in the retrieval of short readable extracts from French literature. We expect that text available from the web may yield many more documents of appropriate readability.
Physical and functional analyses of the syrA and syrB genes involved in syringomycin production by Pseudomonas syringae pv. syringae

The syrA and syrB genes involved in syringomycin production in Pseudomonas syringae pv. syringae B301D were identified from an EcoRI-pLAFR3 cosmid library and then physically and functionally analyzed in relation to plant pathogenicity. Homologous recombination of the genes required for syringomycin production from cosmids pGX183 (syrA) and pGX56 (syrB), respectively, introduced into nontoxigenic (Tox-) Tn5 mutants W4S2545 and W4S770 resulted in the concomitant restoration of toxin production and full virulence. The disease indices of the Tox+ strains obtained by recombination of the cloned, homologous DNA into the corresponding Tn5 mutant were essentially equivalent to that of strain B301D-R and significantly higher than those of W4S2545 and W4S770. A 12-kilobase (kb) EcoRI fragment from pGX183 was subcloned (i.e., pGX15) and found to contain the sequences necessary for syringomycin production. A map of pGX15 prepared by a combination of restriction endonuclease digestions and Tn5 mutagenesis showed that the syrA sequence was 2.3 to 2.8 kb. Marker exchange of syrA::Tn5 from pGX15 into B301D-R yielded nonpathogenic phenotypes, indicating that syrA is a regulatory gene since it is necessary for both syringomycin production and pathogenicity. The 4.9-kb EcoRI fragment from pGX56 was subcloned (i.e., pGX4) and shown to carry the syrB sequence which was 2.4 to 3.3 kb. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of protein extracts from B301D-R associated five proteins, ranging from approximately 130,000 to approximately 470,000 in molecular weight, with syringomycin production. The syrA and syrB genes were required for the formation of proteins SR4 (approximately 350,000) and SR5 (approximately 130,000), which are believed to be components of the syringomycin synthetase complex.
Affinity for phosphatidylinositol 4,5-bisphosphate determines muscarinic agonist sensitivity of Kv7 K+ channels

Kv7 K+-channel subunits differ in their apparent affinity for PIP2 and are differentially expressed in nerve, muscle, and epithelia in accord with their physiological roles in those tissues. To investigate how PIP2 affinity affects the response to physiological stimuli such as receptor stimulation, we exposed homomeric and heteromeric Kv7.2, 7.3, and 7.4 channels to a range of concentrations of the muscarinic receptor agonist oxotremorine-M (oxo-M) in a heterologous expression system. Activation of M1 receptors by oxo-M leads to PIP2 depletion through Gq and phospholipase C (PLC). Chinese hamster ovary cells were transiently transfected with Kv7 subunits and M1 receptors and studied under perforated-patch voltage clamp. For Kv7.2/7.3 heteromers, the EC50 for current suppression was 0.44 ± 0.08 µM, and the maximal inhibition (Inhibmax) was 74 ± 3% (n = 5–7). When tonic PIP2 abundance was increased by overexpression of PIP 5-kinase, the EC50 was shifted threefold to the right (1.2 ± 0.1 µM), but without a significant change in Inhibmax (73 ± 4%, n = 5). To investigate the muscarinic sensitivity of Kv7.3 homomers, we used the A315T pore mutant (Kv7.3T) that increases whole-cell currents by 30-fold without any change in apparent PIP2 affinity. Kv7.3T currents had a slightly right-shifted EC50 as compared with Kv7.2/7.3 heteromers (1.0 ± 0.8 µM) and a strongly reduced Inhibmax (39 ± 3%). In contrast, the dose–response curve of homomeric Kv7.4 channels was shifted considerably to the left (66 ± 8 nM), and Inhibmax was slightly increased (81 ± 6%, n = 3–4). We then studied several Kv7.2 mutants with altered apparent affinities for PIP2 by coexpressing them with Kv7.3T subunits to boost current amplitudes. For the lower affinity (Kv7.2 (R463Q)/Kv7.3T) or higher affinity (Kv7.2 (R463E)/Kv7.3T) channels, the EC50 and Inhibmax were similar to Kv7.4 or Kv7.3T homomers (0.12 ± 0.08 µM and 79 ± 6% [n = 3–4] and 0.58 ± 0.07 µM and 27 ± 3% [n = 3–4], respectively). The very low-affinity Kv7.2 (R452E, R459E, and R461E) triple mutant was also coexpressed with Kv7.3T. The resulting heteromer displayed a very low EC50 for inhibition (32 ± 8 nM) and a slightly increased Inhibmax (83 ± 3%, n = 3–4). We then constructed a cellular model that incorporates PLC activation by oxo-M, PIP2 hydrolysis, PIP2 binding to Kv7-channel subunits, and K+ current through Kv7 tetramers. We were able to fully reproduce our data and extract a consistent set of PIP2 affinities.
The processing of sounds in auditory cortex during sleep

II ACKNOWLEDGEMENTS IV TABLE OF CONTENTS VI LIST OF FIGURES X LIST OF TABLES XII CHAPTER 1: INTRODUCTION 1 1.1 BASICS OF SLEEP 2 1.1.1 Physiology of sleep 2 1.1.2 Theories of sleep 3 1.1.3 Functional role of sleep in the brain 5 1.2 HEARING DURING SLEEP 6 1.2.1 Auditory performance during sleep 6 1.2.2 Incorporation of sounds into dreams 8 1.3 STATE DEPENDENCE OF NEURAL MEASURES 9 1.3. 1 Sleep modulation of single neurons in the visual and somatosensory system: thalamus and cortex 9 1.3. 2 Imaging studies 11 1.3. 3 Evoked potential studies 13 1.3. 4 Anesthetic effects in the auditory system 15 1.3. 5 Attentional modulation of neural responses: visual and somatosensory system 16 1.3. 6 Sleep modulation in the auditory system: brainstem 18 1.3. 7 Sleep modulation in the auditory system: thalamus and cortex 18 1.4 OUTLINE 20 1.4. 1 Hypotheses 20 1.4. 2 Specific aims 22 CHAPTER 2: GENERAL METHODS 25 2.1 ANIMAL PREPARATION 25 2.2 PHYSIOLOGICAL RECORDINGS 26 2.2.1 Neural recordings 26 2.2.2 EEG and LFP recordings 27 2.3 BEHAVIORAL ASSESSMENT 28 2.3. 1 Video monitoring 28 2.3. 2 Behavioral measures 29 2.3. 3 Sleep scoring 32 2.4 EVENT WINDOWING ALGORITHM 33 2.4. 1 Algorithms attempted 34 2.4. 2 Algorithm: driven responses 37
The 5 g. d-xylose absorption test

The 5 g. d-xylose absorption test has been studied in 50 normal subjects. The five-hour urinary xylose content was 1·75 ± 0·43 g. Xylose absorption was more rapid and more complete with the 5 g. than with the 25 g. test. Comparative studies showed the results of the two tests to be significantly related, but the 5 g. test was a less sensitive indicator of malabsorption than the 25 g. test. The 25 g. test is considered the more suitable for routine use in temperate climates.
Aurora-B Regulates the Cleavage Furrow-specific Vimentin Phosphorylation in the Cytokinetic Process*

Aurora-B is an evolutionally conserved protein kinase that regulates several mitotic events including cytokinesis. We previously demonstrated the possible existence of a protein kinase that phosphorylates at least Ser-72 on vimentin, the most widely expressed intermediate filament protein, in the cleavage furrow-specific manner. Here we showed that vimentin-Ser-72 phosphorylation occurred specifically at the border of the Aurora-B-localized area from anaphase to telophase. Expression of a dominant-negative mutant of Aurora-B led to a reduction of this vimentin-Ser-72 phosphorylation. In vitro analyses revealed that Aurora-B phosphorylates vimentin at ∼2 mol phosphate/mol of substrate for 30 min and that this phosphorylation dramatically inhibits vimentin filament formation. We further identified eight Aurora-B phosphorylation sites, including Ser-72 on vimentin, and then constructed the mutant vimentin in which these identified sites are changed into Ala. Cells expressing this mutant formed an unusually long bridge-like intermediate filament structure between unseparated daughter cells. We then identified important phosphorylation sites for the bridge phenotype. Our findings indicate that Aurora-B regulates the cleavage furrow-specific vimentin phosphorylation and controls vimentin filament segregation in cytokinetic process.
Amino Acid Residue 149 of Lecithin:Cholesterol Acyltransferase Determines Phospholipase A2 and Transacylase Fatty Acyl Specificity*

Human LCAT prefers phosphatidylcholine (PC) with sn-1-palmitoyl-2-oleoyl PC (POPC) as substrate for cholesteryl ester synthesis, whereas rat LCAT (which is 92% similar in amino acid sequence) prefers sn-1-palmitoyl-2-arachidonoyl PC (PAPC). Six recombinant human LCAT cDNA clones were constructed with unique clusters of rat sequence substitutions in the human background spanning the region encoding amino acids 121-296. Media from transfected COS cells expressing each of the constructs were assayed for LCAT cholesterol esterification (CE) or phospholipase A2 (PLA2) activity using substrate particles containing POPC or PAPC. The PAPC/POPC CE activity ratio of the cluster 1 construct (amino acids 149-158) was 1.3, resembling rat LCAT, whereas cluster 2-5 clones produced CE activity ratios <0.3, unchanged from human LCAT. The cluster 6 clone (Y292H/W294F) had an intermediate ratio (0.6). Similar results were observed for LCAT PLA2 activity. In additional studies, position 149 of human LCAT was changed to the rat sequence (hE149A) and compared to a triple mutation containing the remainder of the cluster 1 changes (G151R/E154D/R158Q). CE and PLA2 activity ratio for the hE149A construct was >1.7, similar to rat LCAT, whereas the triple mutation construct retained a ratio similar to human LCAT (<0.6). Thus, a single amino acid substitution (E149A) was sufficient to alter the fatty acyl specificity of human LCAT to that of rat LCAT, with an increase in activity toward PAPC. This is the first example of a point mutation in an enzyme with PLA2 activity that results in an increase in activity toward arachidonic acid.
Output-Based Error Estimation and Mesh Adaptation in Computational Fluid Dynamics: Overview and Recent Results

This article reviews recent work in output-based error estimation and mesh adaptation for Computational Fluid Dynamics (CFD) applications in aerospace engineering. Output adjoint solutions, which play a central role in the error estimation, are introduced both in fully-discrete and in variational formulations. The adjoint-weighted residual method for error estimation is then presented in both formulations. Assumptions and approximations made in the calculations are discussed. Presentation of the discrete and variational formulations enables a side-by-side comparison of recent work in output error estimation using the finite volume method and the finite element method. Various mesh adaptation techniques for reducing output error are then discussed. Recent adaptive results using different implementations are presented for a variety of applications. These results show the power of output-based adaptive methods for improving the robustness of CFD computations. However, challenges and areas of additional future research, such as computable error bounds and robust mesh adaptation mechanics, exist, and these are discussed following the results.
Entrenchment and Severance Pay in Optimal Governance Structures

This paper explores how motivating an incumbent CEO to undertake actions that improve the effectiveness of his management interacts with the firm's policy on CEO replacement. Such policy depends on the presence and the size of severance pay in the CEO's compensation package and on the CEO's influence on the board of directors regarding his own replacement (i.e., entrenchment). We explain when and why the combination of some degree of entrenchment and a sizeable severance package is desirable. The analysis offers predictions about the correlation between entrenchment, severance pay, and incentive compensation.
Public Mental Health – Using the Mental Health Gap Action Program to Put all Hands to the Pumps

Although mental ill health constitutes a huge portion of the Global Burden of Disease (GBD), the majority of people with mental health problems do not receive any treatment, a scenario much worse in developing countries where mental health personnel are in gross short supply. The mhGAP was launched to address this gap, especially by training non-mental health professionals to deliver effective services for selected priority mental health problems. Especially in developing countries, many people with mental health problems consult traditional healers either as a first step in the pathway to biomedical mental health care or as the sole mental health service providers. Bridging the gap between mental health needs and available services in developing countries needs to incorporate traditional healers, who are ubiquitously available, easily accessible, and acceptable to the natives. Even though there are barriers in forging collaborations between traditional and biomedical mental health care providers, with mutual respect, understanding, and adapted training using the mhGAP intervention guide, it should be possible to get some traditional healers to understand the core principles of some priority mental health problems identification, treatment, and referral.
Dyspnea is a better predictor of 5-year survival than airway obstruction in patients with COPD.

BACKGROUND FEV(1) is regarded as the most significant correlate of survival in COPD and is used as a measure of disease severity in the staging of COPD. Recently, however, the categorization of patients with COPD on the basis of the level of dyspnea has similarly been reported to be useful in the prediction of health-related quality of life and improvement in exercise performance after pulmonary rehabilitation. STUDY OBJECTIVES We compared the effects of the level of dyspnea and disease severity, as evaluated by airway obstruction, on the 5-year survival rate of patients with COPD. DESIGN AND METHODS A total of 227 patients with COPD were enrolled in a 5-year, prospective, multicenter study in the Kansai area of Japan, involving 20 divisions of respiratory medicine from various university and city hospitals. RESULTS After 5 years, 183 patients were available for the follow-up examination (follow-up rate, 81%). The 5-year cumulative survival rate among patients with COPD was 73%. The effect of disease staging, based on the American Thoracic Society (ATS) guideline as evaluated by the percentage of predicted FEV(1), on the 5-year survival rate was not significant (p = 0.08). However, the level of dyspnea was significantly correlated to the 5-year survival rate (p < 0.001). The Cox proportional hazards model revealed that the level of dyspnea had a more significant effect on survival than disease severity based on FEV(1). CONCLUSIONS The categorization of patients with COPD on the basis of the level of dyspnea was more discriminating than staging of disease severity using the ATS guideline with respect to 5-year survival. Dyspnea should be included as one of the variables, in addition to airway obstruction, for evaluating patients with COPD in terms of mortality.
The degree to which students and teachers are involved in second-level school processes and participation in decision-making: an Irish Case Study

The Education Act (1998) is a key policy document in Irish education, emphasising the rights, roles and responsibilities of key stakeholders, including parents, teachers and pupils in schools. Since 1998 the Department of Education and Skills (DES) has stressed the need to introduce an increased role for teachers and pupils in decision-making. It is therefore timely to explore the response of teachers and students to such a collaborative school environment in a rural second-level school of approximately 600 students. Transition year (TY) students (ages about 15–16) and their teachers were surveyed by questionnaire and interviewed. It finds that while the school is proactive in involving students and teachers in decision-making, a source of social, personal and professional empowerment, experienced teachers, and students in particular, want a more substantial voice. For example, most students want more say. They want class discussions or a vote, not just Student Council (SC) representation, on important and not just trivial issues. They want involvement before decisions are taken, with more feedback. Overall, participation is considered important by all stakeholders.