Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment of major depressive disorder using botulinum toxin A: a 24-week randomized, double-blind, placebo-controlled study.

OBJECTIVE To determine whether a single treatment of botulinum toxin A in the forehead (glabellar) region can improve symptoms of depression in patients with major depressive disorder (MDD), as defined by DSM-IV criteria. METHOD Thirty participants were randomly assigned to receive either placebo or botulinum toxin A (BTA; onabotulinumtoxinA) injections in the forehead. Female participants received 29 units; male participants received 39 units. At week 12, the groups were crossed over. Participants were evaluated at weeks 0, 3, 6, 12, 15, 18, and 24 for improvement in MDD symptoms using the Patient Health Care Questionnaire-9, Beck Depression Inventory (BDI), and 21-Item Hamilton Depression Rating Scale (HDRS-21) objective measurement scales. The primary outcome was the rate of HDRS-21 response, defined as ≥ 50% score reduction from baseline. The study occurred from July 2011 to November 2012. RESULTS Patients who received BTA at week 0 (BTA-first group) and at week 12 (BTA-second group) had a statistically significant reduction in MDD symptoms as compared to placebo. Improvement in MDD continued over 24 weeks in the group that received BTA first even though the cosmetic effects of BTA wore off at 12 to 16 weeks. HDRS-21 response rates were 55% (6/11) in the BTA-first group, 24% (4/17) in the BTA-second group, and 0% (0/19) in the placebo group (P < .0001). HDRS-21 remission rates (score ≤ 7) were 18% (2/11), 18% (3/17), and 0% (0/19), respectively (P = .057). HDRS-21 scores dropped -46% and -35% in the BTA-first and -second groups versus -2% in the placebo group (P < .0001). The BDI response rate (≥ 50% reduction from baseline) was 45% (5/11) in the BTA-first group, 33% (6/18) in the BTA-second group, and 5% (1/19) in the placebo group (P = .0067). BDI remission rates (score ≤ 9) were 27% (3/11), 33% (6/18), and 5% (1/19), respectively (P = .09). BDI scores dropped -42% and -35% in the BTA-first and -second groups versus -15% in the placebo group (P < .0001). CONCLUSIONS Botulinum toxin A injection in the glabellar region was associated with significant improvement in depressive symptoms and may be a safe and sustainable intervention in the treatment of MDD. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01392963.
An Uncertain Tale: Alternative Conceptualizations of Pedagogical Leadership

This article draws on the experiences of two educators to reimagine traditional framings of pedagogical leadership. In the field of early childhood education, pedagogical leadership carries conflicting conceptualizations and is often associated with an “expert” who will dictate indicators of quality, suggesting certainty and fixed ways of practicing. Educators are often reluctant to take on leadership roles that seem antithetical to their collaborative caring practices. In our work together in the Investigating Quality Project and in using pedagogical narration as a tool for generating critical dialogue, we explore alternative images of pedagogical leadership. Through sharing our stories, we offer a mode of thinking about pedagogical leadership that embraces relationality and uncertainty and invites a culture of dialogue.
Forecasting Bond Risk Premia with Unspanned Macroeconomic Information

I provide evidence on the existence of unspanned macro risk. I investigate the usefulness of unspanned macro information for forecasting bond risk premia in a macro-finance term structure model from the perspective of a bond investor. I account for model uncertainty by combining forecasts with and without unspanned output and inflation risks optimally from the forecaster’s objective. Incorporating macro information generates significant gains in forecasting bond risk premia relative to yield curve information at long forecast horizons, especially when allowing for time-varying combination weight. These gains in predictive accuracy significantly improve investor utility.
Microarray-Based Detection and Typing of the Rhizobium Nodulation Gene nodC: Potential of DNA Arrays To Diagnose Biological Functions of Interest

ABSTRACT Environmental screening of bacteria for the presence of genes of interest is a challenging problem, due to the high variability of the nucleotide sequence of a given gene between species. Here, we tackle this general issue using a particularly well-suited model system that consists of the nodulation gene nodC, which is shared by phylogenetically distant rhizobia. 41mer and 50mer oligonucleotides featuring the nucleotide diversity of two highly conserved regions of the NodC protein were spotted on glass slides and cross hybridized with the radioactive-labeled target genomic DNA under low-stringency conditions. Statistical analysis of the hybridization patterns allowed the detection of known, as well as new, nodC sequences and classified the rhizobial strains accordingly. The microarray was successfully used to type the nodC gene directly from legume nodules, thus eliminating the need of cultivation of the endosymbiont. This approach could be extended to a panel of diagnostic genes and constitute a powerful tool for studying the distribution of genes of interest in the environment, as well as for bacteria identification.
Political Contributions and the Price of Credit Risk: Evidence from Credit Default Swaps

Firm political contributions are associated with lower credit default swap spreads for contributing firms. To address endogeneity, we employ novel instruments and use a set of exogenous events on campaign contribution restrictions: (a) the passage of the Bipartisan Campaign Reform Act (BCRA) that banned soft money contributions, (b) the Federal Election Commission decision to interpret the BCRA less strictly, (c) the partial reversal of the BCRA and, (d) the McConnell v. FEC Supreme Court decision, which upheld the BCRA. Overall, the evidence suggests that political contributions are valued by credit market participants.
Hyper-parameter optimization based on soft actor critic and hierarchical mixture regularization

Hyper-parameter optimization is a crucial problem in machine learning as it aims to achieve the state-of-the-art performance in any model. Great efforts have been made in this field, such as random search, grid search, Bayesian optimization. In this paper, we model hyper-parameter optimization process as a Markov decision process, and tackle it with reinforcement learning. A novel hyper-parameter optimization method based on soft actor critic and hierarchical mixture regularization has been proposed. Experiments show that the proposed method can obtain better hyper-parameters in a shorter time.
Meta‐analysis: the influence of pre‐treatment with a proton pump inhibitor on Helicobacter pylori eradication

Background : There is much debate about the influence of pre‐treatment with a proton pump inhibitor on Helicobacter pylori eradication. The few studies investigating the influence of pre‐treatment on triple and quadruple therapies did not find differences in eradication rates. However, the high eradication rates make it difficult to study factors associated with therapy failure in small populations. In order to overcome this problem we performed a meta‐analysis.
Oil Production as a Leading Indicator for Tanker Freight Market

The aim of this study is to determine the causality between oil production and freight rates in the seaborne oil transportation in the world. The causality with oil prices has been studied more in the literature, but the studies that examine the causality with oil production have been limited. However, the effect of the crude oil production amount on the market is also great. The methods that can detect delayed causality have been utilized unlike the existing literature. While the Baltic Dirty Tanker Index (BDTI) and Baltic Clean Tanker Index (BCTI) variables are used as the measurement for the tanker freight rates, the Bloomberg oil production index variable is used as the production measurement. The data set used in the study consists of 239 monthly observations covering between August 1998 and June 2018. Standard causality analysis developed by Granger (1969) is used for linear causality, and nonparametric tests developed by Hiemstra and Jones (1996) and Diks and Panchenko (2006) are used for nonlinear causality analysis. While linear causality cannot be spotted in the obtained results, nonlinear causality is determined. As a result of the four lagged nonlinear causality analyzes made, the causality is found from the second to the fourth lag for BDTI and from the first to the fourth lag for BCTI. According to these results, while the effect of changes in production is directly reflected in the product tanker market, it is reflected on the dirty tanker market with a delay. It is hoped that these results may be beneficial to developing business strategies and reducing risks for shipowners and charterers in the tanker market.
Early career development in the public sector: Lessons from a social constructionist perspective

This article explores the contribution a social constructionist paradigm can make to the study of career, through a small-scale empirical study of recent graduates employed in New Zealand’s state sector. A social constructionist lens denies the possibility of an individualised, generalised understanding of ‘career’, highlighting instead its local, contingent character as the product of social interaction. Our respondents’ collective construction of career was heavily shaped by a range of context-specific interactions and influences, such as the perception of a distinctive national identity, as well as by their young age and state sector location. It was also shaped by the research process, with us as researchers implicated in these meaning-making processes. Social constructionism shines a light on aspects of the field that are underplayed by mainstream, scientific approaches to the study of career, and therefore has valuable implications for practitioners, as well as scholars.
Comparison of Modern and Historical Fish Catches (AD 750–1400) to Inform Goals for Marine Protected Areas and Sustainable Fisheries

Abstract: We tested the unsustainable fishing hypothesis that species in assemblages of fish differ in relative abundance as a function of their size, growth rates, vagility, trophic level, and diet by comparing species composition in historical bone middens, modern fisheries, and areas closed to fishing. Historical data came from one of the earliest and most enduring Swahili coastal settlements (approximately AD 750–1400). Modern data came from fisheries near the archeological site and intensively harvested fishing grounds in southern Kenya. The areas we sampled that were closed to fishing (closures) were small (<28 km2) and permanent. The midden data indicated changes in the fish assemblage that are consistent with a weak expansion of fishing intensity and the unsustainable fishing hypothesis. Fishes represented in the early midden assemblages from AD 750 to 950 had longer life spans, older age at maturity, and longer generation times than fish assemblages after AD 950, when the abundance of species with longer maximum body lengths increased. Changes in fish life histories during the historical period were, however, one‐third smaller than differences between the historical and modern assemblages. Fishes in the modern assemblage had smaller mean body sizes, higher growth and mortality rates, a higher proportion of microinvertivores, omnivores, and herbivores, and higher rates of food consumption, whereas the historical assemblage had a greater proportion of piscivores and macroinvertivores. Differences in fish life histories between modern closures and modern fishing grounds were also small, but the life histories of fishes in modern closures were more similar to those in the midden before AD 950 because they had longer life spans, older age at maturity, and a higher proportion of piscivores and macroinvertivores than the modern fisheries. Modern closures and historical fish assemblages were considerably different, although both contained species with longer life spans.
Transient Receptor Potential Channels Function as a Coincidence Signal Detector Mediating Phosphatidylserine Exposure

Platelets use the ion channels TRPC3 and TRPC6 to detect simultaneous exposure to two prothrombotic signals. Clotting Takes Two Signals Blood platelets can aggregate to form thrombi to stop blood flow, a necessary physiological process that prevents excessive blood loss but one that can also contribute to blood vessel occlusion and ischemia. Positive feedback loops and integration of multiple signals are mechanisms for regulating biological processes. Harper et al. found that the nonselective cation channels TRPC3 (transient receptor potential C3) and TRPC6 were necessary to enable mouse platelets to expose phosphatidylserine in response to both thrombin and another prothrombotic signal, collagen-related peptide. Sustained calcium influx, which is necessary for phosphatidylserine exposure and thrombin generation, occurred in platelets activated by both thrombin and collagen-related peptide but not in those activated by either signal alone. Understanding how the signaling pathways trigger thrombosis could guide the development of therapies to control blood clotting. Blood platelet aggregation must be tightly controlled to promote clotting at injury sites but avoid inappropriate occlusion of blood vessels. Thrombin, which cleaves and activates Gq-coupled protease-activated receptors, and collagen-related peptide, which activates the receptor glycoprotein VI, stimulate platelets to aggregate and form thrombi. Coincident activation by these two agonists synergizes, causing the exposure of phosphatidylserine on the cell surface, which is a marker of cell death in many cell types. Phosphatidylserine exposure is also essential to produce additional thrombin on platelet surfaces, which contributes to thrombosis. We found that activation of either thrombin receptors or glycoprotein VI alone produced a calcium signal that was largely dependent only on store-operated Ca2+ entry. In contrast, experiments with platelets from knockout mice showed that the presence of both ligands activated nonselective cation channels of the transient receptor potential C (TRPC) family, TRPC3 and TRPC6. These channels principally allowed entry of Na+, which coupled to reverse-mode Na+/Ca2+ exchange to allow calcium influx and thereby contribute to Ca2+ signaling and phosphatidylserine exposure. Thus, TRPC channels act as coincidence detectors to coordinate responses to multiple signals in cells, thereby indirectly mediating in platelets an increase in intracellular calcium concentrations and exposure of prothrombotic phosphatidylserine.
Involvement of multiple DNA elements in iron‐inducible transcription of the ap65‐1 gene in the protozoan parasite Trichomonas vaginalis

A reputed iron‐responsive region, which contains multiple nuclear protein‐binding DNA sequences, was shown previously to regulate iron‐inducible transcription of the ap65‐1 gene in the protozoan pathogen, Trichomonas vaginalis. These DNA sequences include two overlapping MYB recognition elements (MRE‐1/MRE‐2r) and three abutted T‐tract elements. Additional nuclear protein‐binding DNA sequences flanking the 5′ (AGTGAAGTGA) and 3′ (MRE‐2f) of the iron‐responsive region were identified in the present study. A stable promoter assay and primer extension revealed that transcriptional activity of the ap65‐1 promoter is iron inducible as well as growth related, being lowest in the early logarithmic phase and highest in the mid‐logarithmic phase. Subsequent mutational analysis of individual DNA elements of the ap65‐1 promoter suggests that closely spaced T‐tract elements together with an intervening GAAGGAAG sequence within the iron‐responsive region are most critical for regulation of overall transcriptional activity, whereas an additional AGTGAAGTGA and MRE‐2f together with an upstream T‐rich region are required for optimal iron‐inducible activity, and the MRE‐1/MRE‐2r overlap is only involved in growth‐related activity. These observations suggest that expression of the ap65‐1 gene is dynamically regulated under various growth conditions via interactions among multiple DNA regulatory elements.
Case Studies as Unconventional Meanings

The critical exegesis of the epistemology of educational science illustrates various narratives: postmodernist views on educational sciences, links between pedagogy and the politics, dialogs between education and culture, counternarratives, critical pedagogies, etc. These reflect an intellectual space that incorporates various constructions of knowledge: different experiences, fragmentation, transcultural changes, divided borders of educational sciences, conflicts, and unifying themes. This chapter is focused on the Romanian case study in the schools playing a role in developing recent pedagogy. The qualitative research presented in this chapter is based on an investigation conducted from 2014 to 2017 at the University of Bucharest. The target population consists of 300 students in teachers training, and 446 teachers, psychologists, and school counselors who were invited to report case studies on learning topics in accordance with their personal experience. The empirical research aims to explore the Romanian possible identity of case study about learning issues and to discriminate the qualitative features of the data collected. The results are considered mentalistic structures of a case study. In these structures are included learning strategies, life styles, learning styles, teaching styles, communication styles, level of rationale involved in case studies as storytelling, and remarkable’ patterns of social network from the classroom.
The 5' noncoding sequences from a less virulent Theiler's virus dramatically attenuate GDVII neurovirulence

RNA transcripts derived from recombinant chimeras between the highly virulent GDVII virus and the less virulent BeAn virus were constructed to study the molecular pathogenesis of Theiler's murine encephalomyelitis virus infection. The presence of the BeAn 5' noncoding sequences in chimera 2 (BeAn 5' noncoding sequences joined with the GDVII nucleotides encoding the polyprotein and present in the 3' end) resulted in dramatic attenuation of GDVII neurovirulence and development of poliomyelitis in mice. This reduced neurovirulence was associated with slower virus growth and lower peak titers in the brain and spinal cord than with parental GDVII virus replication. On the other hand, the sites of replication following chimera 2 infection were the same as those seen in GDVII-infected mice; the distribution of virus antigen and histopathological changes indicated that chimera 2 replicates in neurons in the brain, e.g., in the neocortex, hippocampus, caudate putamen, and brain stem, as well as in anterior-horn cells in the spinal cord. Chimera 2 was efficiently cleared from the mouse central nervous system by day 30 postinfection, in marked contrast to the persistence of the BeAn parent in the central nervous system. This suggests that elements in the BeAn sequences that encode the polyprotein or are present in the 3' noncoding region are necessary for viral persistence. It is of interest that chimera 2-infected mice developed localized inflammatory, demyelinating lesions which were detected at day 28 postinfection but these lesions did not become larger with time. Thus, virus persistence appears to be required for maintenance and progression of immune-mediated demyelination. If the demyelinating lesions become sufficiently large, clinical signs and disease may develop.
Astrocyte and Macrophage Regulation of YKL‐40 Expression and Cellular Response in Neuroinflammation

Numerous inflammatory conditions are associated with elevated YKL‐40 expression by infiltrating macrophages. Thus, we were surprised to observe minimal macrophage and abundant astrocyte expression of YKL‐40 in neuroinflammatory conditions. The aims of the current study were to better delineate this discrepancy, characterize the factors that regulate YKL‐40 expression in macrophages and astrocytes and study whether YKL‐40 expression correlates with cell morphology and/or activation state. In vitro, macrophages expressed high levels of YKL‐40 that was induced by classical activation and inhibited by alternative activation. Cytokines released from macrophages induced YKL‐40 transcription in astrocytes that was accompanied by morphological changes and altered astrocytic motility. Because coculturing of astrocytes and macrophages did not reverse this in vitro expression pattern, additional components of the in vivo central nervous system (CNS) milieu must be required to suppress macrophage and induce astrocyte expression of YKL‐40.
Using electronic neutron generators in active interrogation to detect shielded fissionable material

Experiments have been performed at Idaho National Laboratory to study methodology and instrumentation for performing neutron active interrogation die-away analyses for the purpose of detecting shielded fissionable material. Here we report initial work using a portable DT electronic neutron generator with a He-3 fast neutron detector to detect shielded fissionable material including enriched uranium and reactor grade plutonium. Measurements have been taken of bare material as well as of material hidden within a large plywood cube. Results from this work have demonstrated the efficacy of the die-away neutron measurement technique for quickly detecting the presence of special nuclear material hidden within plywood shields by analyzing the time dependent neutron signals in-between neutron generator pulses. Using a DT electronic neutron generator operating at 300 Hz with a yield of approximately 0.36 x 108 neutrons per second, 2.2 kg of enriched uranium hidden within a 0.60 m x 0.60 m x 0.70 m volume of plywood was positively detected with a measurement signal 2-sigma above the passive background within 1 second. Similarly, for a 500 second measurement period a lower detection limit of approaching the gram level could be expected with the same simple set-up.
Inhibition of apoptosis of a PARP(-)/(-)cell line transfected with PARP DNA-binding domain mutants.

We have investigated the possibility of the involvement of PARP in apoptosis, independently of its enzymatic activity. We thus transfected PARP(-)/(-)A11 cells with a DNA construct encoding the PARP DNA-binding domain (DBD) fragment or mutants DBDbd(-), defective in DNA binding to DNA strand breaks, and DBDcl(-), resistant to caspase-3 cleavage. We found that in the absence of PARP, while expression of DBD has only a marginal effect, expression of the mutants strongly inhibits the apoptosis induced by staurosporine, as measured by the binding of annexin V. Moreover, the mutants, but not DBD, inhibit the cleavage of DNA PKcs, suggesting inhibition of activation of caspase-3. In addition, the mutant transfectants are fractionally less susceptible to low doses of an alkylating agent than the DBD transfectant or the original A11 line. The results suggest that the DBD fragment of PARP, apart from its classical role of nick detection and DNA binding, participates in complexes involved in upstream events leading to activation of the caspase cascade.