Miracle-dz/UniFAR-FTUs huggingface dataset:
Connexin 47 (Cx47)-Deficient Mice with Enhanced Green Fluorescent Protein Reporter Gene Reveal Predominant Oligodendrocytic Expression of Cx47 and Display Vacuolized Myelin in the CNS

To further characterize the recently described gap junction gene connexin 47 (Cx47), we generated Cx47-null mice by replacing the Cx47 coding DNA with an enhanced green fluorescent protein (EGFP) reporter gene, which was thus placed under control of the endogenous Cx47 promoter. Homozygous mutant mice were fertile and showed no obvious morphological or behavioral abnormalities. Colocalization of EGFP fluorescence and immunofluorescence of cell marker proteins revealed that Cx47 was mainly expressed in oligodendrocytes in highly myelinated CNS tissues and in few calcium-binding protein S100β subunit-positive cells but not in neurons or peripheral sciatic nerve. This corrects our previous conclusion that Cx47 mRNA is expressed in brain and spinal cord neurons (Teubner et al., 2001). Cx47 protein was detected by Western blot analysis after immunoprecipitation in CNS tissues of wild-type mice but not in heart or Cx47-deficient tissues. Electron microscopic analysis of CNS white matter in Cx47-deficient mice revealed a conspicuous vacuolation of nerve fibers, particularly at the site of the optic nerve where axons are first contacted by oligodendrocytes and myelination starts. Initial analyses of Cx32/Cx47-double-deficient mice showed that these mice developed an action tremor and died on average at 51 d after birth. The central white matter of these double-deficient mice exhibited much more abundant vacuolation in nerve fibers than mice deficient only in Cx47.
Temporal and Spatial Melanoma Trends in Austria: An Ecological Study

Annual solar ultraviolet radiation (UVR) is mostly determined by latitude and altitude. Over the last decades, increasing UVR ground levels have been observed. Exposure to UVR is associated with a life-time risk to develop melanoma, a malign skin cancer. Thus, we hypothesized that melanoma incidence in Austria is associated with altitude of place of living and time of diagnosis. We investigated this hypothesis in an ecological study by district and year for Austrian melanoma incidence (1990–2010) and mortality (1970–2011) data. As expected, incidence rates increased with altitude (about 2% per 10 m) and year (about 2%). Additionally, melanoma incidence rates were about 50% higher in urban than in rural districts. In contrast, mortality rates decreased with altitude (for males: 0.4% per 10 m, for women: 0.7% per 10 m, respectively). The observed discrepancy between incidence and mortality data could partly be explained by melanoma diagnosis at earlier tumor stage in districts with higher altitude. Possible reasons for this finding include higher awareness of patients, better diagnostic performance of medical professionals working at higher altitudes, or slower tumor growth due to protective effects of sun light-associated vitamin D synthesis.
Federal Reserve Bank of San Francisco Working Paper Series How Much of South Korea's Growth Miracle Can Be Explained by Trade Policy? How Much of South Korea's Growth Miracle Can Be Explained by Trade Policy?

and Philadelphia Fed for very useful comments. Edith Ostapik and Mohan Anand provided excellent research assistance. The views expressed in this paper are those of the authors and are not necessarily reflective of views of the Federal Reserve Bank of Philadelphia or the Federal Reserve System. Abstract South Korea's growth miracle has been well documented. A large set of institutional and policy reforms in the early 1960s is thought to have contributed to the country's extraordinary performance. In this paper, we assess the importance of one key set of policies, the trade policy reforms in Korea, as well as the concurrent GATT tariff reductions. We develop a model of neoclassical growth and trade that highlights two forces by which lower trade barriers can lead to increased per worker GDP: comparative advantage and specialization, and capital accumulation. We calibrate the model and simulate the effects of three sets of tariff reductions that occurred between the early 1962 and 1995. Our main finding is that the model can explain up to 32 percent of South Korea's catch-up to the G7 countries in output per worker in the manufacturing sector. We find that the effects of the tariff reductions taken together are about twice as large as the sum of each reduction applied individually.
Implementation Fidelity of the National Malaria Control Program in Burkina Faso

Background Every year 40,000 people die of malaria in Burkina Faso. In 2010, the Burkinabè authorities implemented a national malaria control program that provides for the distribution of mosquito nets and the home-based treatment of children with fever by community health workers. The objective of this study was to measure the implementation fidelity of this program. Methods We conducted a case study in two comparable districts (Kaya and Zorgho). Data were collected one year after the program’s implementation through field observations (10 weeks), documentary analysis, and individual interviews with stakeholders (n = 48) working at different levels of the program. The analysis framework looked at the fidelity of (i) the intervention’s content, (ii) its coverage, and (iii) its schedule. Results The program’s implementation was relatively faithful to what was originally planned and was comparable in the two districts. It encountered certain obstacles in terms of the provision of supplies. Coverage fidelity was better in Kaya than in Zorgho, where many community health workers (CHW) experienced problems with the restocking of artemisinin-based combination therapy and with remuneration for periods of training. In both districts, the community was rarely involved in the process of selecting CHWs. The components affected by scheduling all experienced successive implementation delays that pushed nets distribution and the initial provision of artemisinin-based combination therapies to the CHWs past the 2010 malaria season. Conclusions The activities intended by the program were mostly implemented with good fidelity. However, the implementation was plagued by delays that probably postponed the expected beneficial effects.
Relationships between Growth, Growth Response to Nutrient Supply, and Ion Content Using a Recombinant Inbred Line Population in Arabidopsis1[W][OA]

Growth is an integrative trait that responds to environmental factors and is crucial for plant fitness. A major environmental factor influencing plant growth is nutrient supply. In order to explore this relationship further, we quantified growth-related traits, ion content, and other biochemical traits (protein, hexose, and chlorophyll contents) of a recombinant inbred line population of Arabidopsis (Arabidopsis thaliana) grown on different levels of potassium and phosphate. Performing an all subsets multiple regression analyses revealed a link between growth-related traits and mineral nutrient content. Based on our results, up to 85% of growth variation can be explained by variation in ion content, highlighting the importance of ionomics for a broader understanding of plant growth. In addition, quantitative trait loci (QTLs) were detected for growth-related traits, ion content, further biochemical traits, and their responses to reduced supplies of potassium or phosphate. Colocalization of these QTLs is explored, and candidate genes are discussed. A QTL for rosette weight response to reduced potassium supply was identified on the bottom of chromosome 5, and its effects were validated using selected near isogenic lines. These lines retained over 20% more rosette weight in reduced potassium supply, accompanied by an increase in potassium content in their leaves.
Changing the output: The logic of amendment success in the European Parliament’s ENVI Committee

This study tests three hypotheses on factors driving the success and failure of amendments in the European Parliament’s ENVI committee. The hypotheses, which are derived from different theories of legislative organization, are tested with an original dataset containing 550 amendments from 55 ENVI members. Contrary to existing empirical evidence on the structure of political conflict in plenary, the results suggest that a committee member’s general ideological orientation on the left-right dimension is not decisive for his prospects to change the committee output. Instead, it seems like ENVI members with ties to green interest groups play a greater role in the formulation of environmental policies than committee members without comparable affiliations. Finally, the empirical evidence indicates that rapporteurs are only rarely challenged successfully by competing amendments. However, they are often willing to accept compromises.
Forgiven But Not Forgotten: Covert Uncertainty in Overt Responses and the Paradox of Defection-Despite-Trust

Despite the widespread belief that trust is a critical determinant of loyalty, empirical and anecdotal evidence calls into question the real-world robustness of the trust–loyalty link. An important reason for the fuzzy nature of the trust–loyalty link may be the fuzzy nature of trust itself. That is, stated trust judgments embody both a magnitude dimension (i.e., the position along a favorable-unfavorable continuum) and an uncertainty dimension (i.e., the lack of conviction with which the judgment is held). We investigated this possibility using data pertaining to consumers’ reactions to a service failure and the provider's success in responding to their complaints. We found that the interplay between dissatisfaction with the complaint handling and past experience simultaneously influences trust magnitude and trust uncertainty. However, these two dimensions of trust are shaped by different underlying processes. Finally, uncertainty dampens the impact of stated trust on loyalty.
Barriers to evidence-based decision making among Polish healthcare managers

The 1999 reform of the Polish healthcare system revealed deficiencies in the research base and a lack of organized systems of information provision. Professionals who most need effective information systems are policymakers and healthcare managers. The main aim of the described study was to obtain data describing the needs, preferences and limitations of healthcare managers as information users, and to identify environmental factors influencing their information behaviour. A national postal survey was conducted and supplemented with information collected during focus groups, semi-structured interviews and through analysis of relevant policy documents. The target population included hospital chief executives, medical directors, head nurses and directors of the institutions responsible for health services planning and purchasing. Target institutions were drawn systematically from official lists, stratified by regions of the country and hospital reference level. The interviews were conducted with primary care unit managers and with Ministry of Health officials. National health strategy and directives, cost-effectiveness analyses of interventions and clinical practice guidelines emerged as information of primary importance to respondents. The main barriers to effective information behaviour were found to be: attitudes towards research activity, lack of appropriately processed data, lack of skills enabling information seeking and appraisal, inappropriate format of publications, ineffective dissemination of information and absence of services facilitating access to evidence. The current information environment of healthcare managers, together with their attitude towards information and deficiencies in information skills, appear to serve as a barrier to evidence-based practice in the Polish healthcare system.
Plaque-Associated Overexpression of Insulin-Degrading Enzyme in the Cerebral Cortex of Aged Transgenic Tg2576 Mice With Alzheimer Pathology

It was proposed that insulin-degrading enzyme (IDE) participates in the clearance of amyloid &bgr; (A&bgr;) in the brain, and its low expression or activity may be relevant for the progression of Alzheimer disease. We performed a longitudinal study of brain level, activity, and distribution of IDE in transgenic mice (Tg2576) expressing the Swedish mutation in human A&bgr; precursor protein. At 16 months of age, Tg2576 showed a significant 2-fold increment in IDE protein level as compared with 4.5- and 11-month-old animals. The peak of IDE was in synchrony with the sharp accumulation of sodium dodecyl sulfate-soluble A&bgr; and massive A&bgr; deposition into plaques. At this stage, IDE appeared surrounding A&bgr; fibrillar deposits within glial fibrillar acidic protein-positive astrocytes, suggesting that it was locally overexpressed during the A&bgr;-mediated inflammation process. When primary astrocytes were exposed to fibrillar A&bgr; in vitro, IDE protein level increased as compared with control, and this effect was reduced by the addition of U0126, a specific inhibitor of the ERK1/2 mitogen-activated protein kinase cascade. We propose that in Tg2576 mice and in contrast to its behavior in Alzheimer brains, active IDE increases with age around plaques as a component of astrocyte activation as a result of A&bgr;-triggered inflammation.
Estimation of a structural model of the determinants of neonatal mortality in Hungary, 1984–88 and 1994–98

We developed and evaluated a structural model of the determinants of neonatal mortality in Hungary that embodies the causal mechanisms by which its proximate and indirect determinants—socio-economic, behavioural, and biological—are related. The statistical model used distinguishes between endogenous and exogenous variables and allows the causal effect of each to be correctly estimated. Unobserved variables are integrated into the model, which was tested using Hungarian data for the periods 1984–88 and 1994–98. The principal findings are as follows: weight at birth and duration of gestation are the most important of the (direct) causal determinants of neonatal mortality. Mother's age has an indirect and detrimental effect: when mothers are older than 30 years of age, the risk of lower birth weight or multiple births and, in consequence, neonatal mortality is increased. Father's age has no direct or indirect causal effect on neonatal mortality.
Short and Intense Tailor-Made Notched Music Training against Tinnitus: The Tinnitus Frequency Matters

Tinnitus is one of the most common diseases in industrialized countries. Here, we developed and evaluated a short-term (5 subsequent days) and intensive (6 hours/day) tailor-made notched music training (TMNMT) for patients suffering from chronic, tonal tinnitus. We evaluated (i) the TMNMT efficacy in terms of behavioral and magnetoencephalographic outcome measures for two matched patient groups with either low (≤8 kHz, N = 10) or high (>8 kHz, N = 10) tinnitus frequencies, and the (ii) persistency of the TMNMT effects over the course of a four weeks post-training phase. The results indicated that the short-term intensive TMNMT took effect in patients with tinnitus frequencies ≤8 kHz: subjective tinnitus loudness, tinnitus-related distress, and tinnitus-related auditory cortex evoked activity were significantly reduced after TMNMT completion. However, in the patients with tinnitus frequencies >8 kHz, significant changes were not observed. Interpreted in their entirety, the results also indicated that the induced changes in auditory cortex evoked neuronal activity and tinnitus loudness were not persistent, encouraging the application of the TMNMT as a longer-term training. The findings are essential in guiding the intended transfer of this neuro-scientific treatment approach into routine clinical practice.
A machine learning approach to the identification of WH gaps

In this paper, we pursue a multi-modular, statistical approach to WH dependencies, using a feedforward network as our modeling tool. The empirical basis of this model and the availability of performance measures for our system address deficiencies in earlier computational work on WH gaps, which require richer sources of semantic and lexical information in order to run. The statistical nature of our models allows them to be simply combined with other modules of grammar, such as a syntactic parser.
Screening for Syphilis in Arrestees: Usefulness for Community-wide Syphilis Surveillance and Control

Background Syphilis screening of jail arrestees has been promoted as an effective method for both disease control and surveillance. Goals To evaluate the yield of the East Baton Rouge Parish Jail screening program in detecting previously undiagnosed syphilis, to evaluate the program as a means for monitoring community syphilis rates, and to characterize arrestees at greatest risk for syphilis infection. Study Design From July 1994 to December 1998, arrestees brought to the East Baton Rouge Parish Jail were screened for syphilis. Annual early syphilis prevalence in screened arrestees was calculated and compared with the annual period prevalence of early syphilis in the general population of East Baton Rouge Parish, as reported by laboratories and health providers. A case–control study of cases detected at the jail from 1995 to 1997 and contemporary controls was conducted. Results A total of 50,941 arrestees were booked into the East Baton Rouge Parish Jail, of whom 38,573 (76%) were screened for syphilis. Of the 38,573 arrestees screened, 494 (1.3%) were diagnosed with untreated syphilis. Of these, 299 (61%) were treated for syphilis before release. The estimated prevalence of early syphilis in arrestees decreased by 68% during the study period, from 0.79% in 1994 to 0.25% in 1998. During this time, the East Baton Rouge Parish community rates decreased by 79%, from 150 cases per 100,000 to 31 cases per 100,000. In female arrestees, a booking charge of prostitution was associated with syphilis (odds ratio [OR] 7.0; 95% CI, 1.5, 39.3). In male arrestees, a booking charge of felony theft was associated with syphilis (OR 4.8; 95% CI, 1.8, 13.8). However, only 15 (12%) of the early syphilis cases would have been detected if screening had been based on the booking charges found to be associated with syphilis in this study. Conclusions Routine syphilis screening and treatment in jail settings is feasible and identifies many persons with syphilis. Monitoring of syphilis prevalence among arrestees is a useful method for monitoring community prevalence of syphilis. Analysis of booking charges may be useful for determining factors associated with syphilis infection, but not for developing screening criteria.
Chemical enhancement of torsinA function in cell and animal models of torsion dystonia

SUMMARY Movement disorders represent a significant societal burden for which therapeutic options are limited and focused on treating disease symptomality. Early-onset torsion dystonia (EOTD) is one such disorder characterized by sustained and involuntary muscle contractions that frequently cause repetitive movements or abnormal postures. Transmitted in an autosomal dominant manner with reduced penetrance, EOTD is caused in most cases by the deletion of a glutamic acid (ΔE) in the DYT1 (also known as TOR1A) gene product, torsinA. Although some patients respond well to anticholingerics, therapy is primarily limited to either neurosurgery or chemodenervation. As mutant torsinA (ΔE) expression results in decreased torsinA function, therapeutic strategies directed toward enhancement of wild-type (WT) torsinA activity in patients who are heterozygous for mutant DYT1 may restore normal cellular functionality. Here, we report results from the first-ever screen for candidate small molecule therapeutics for EOTD, using multiple activity-based readouts for torsinA function in Caenorhabditis elegans, subsequent validation in human DYT1 patient fibroblasts, and behavioral rescue in a mouse model of DYT1 dystonia. We exploited the nematode to rapidly discern chemical effectors of torsinA and identified two classes of antibiotics, quinolones and aminopenicillins, which enhance WT torsinA activity in two separate in vivo assays. Representative molecules were assayed in EOTD patient fibroblasts for improvements in torsinA-dependent secretory function, which was improved significantly by ampicillin. Furthermore, a behavioral defect associated with an EOTD mouse knock-in model was also rescued following administration of ampicillin. These combined data indicate that specific small molecules that enhance torsinA activity represent a promising new approach toward therapeutic development for EOTD, and potentially for other diseases involving the processing of mutant proteins.
Update on prescription extended-release opioids and appropriate patient selection

Chronic pain is largely underdiagnosed, often undertreated, and expected to increase as the American population ages. Many patients with chronic pain require long-term treatment with analgesic medications, and pain management may involve use of prescription opioids for patients whose pain is inadequately controlled through other therapies. Yet because of the potential for abuse and addiction, many clinicians hesitate to treat their patients with pain with potentially beneficial agents. Finding the right opioid for the right patient is the first – often complicated – step. Ensuring that patients continue to properly use the medication while achieving therapeutic analgesic effects is the long-term goal. Combined with careful patient selection and ongoing monitoring, new formulations using extended-release technologies incorporating tamper-resistant features may help combat the growing risk of abuse or misuse, which will hopefully reduce individual suffering and the societal burden of chronic pain. The objective of this manuscript is to provide an update on extended-release opioids and to provide clinicians with a greater understanding of which patients might benefit from these new opioid formulations and how to integrate the recommended monitoring for abuse potential into clinical practice.
Effects of Buyang Huanwu Decoction on Ventricular Remodeling and Differential Protein Profile in a Rat Model of Myocardial Infarction

Buyang Huanwu decoction (BYHWD) is a well-known and canonical Chinese medicine formula from “Correction on Errors in Medical Classics” in Qing dynasty. Here, we show that BYHWD could alleviate the ventricular remodeling induced by left anterior descending (LAD) artery ligation in rats. BYHWD treatment (18 g/kg/day) decreased heart weight/body weight (HW/BW), left ventricle (LV) dimension at end diastole (LVDd) and increased LV ejection fraction (LVEF) and LV fractional shortening (LVFS) significantly compared to model group at the end of 12 weeks. The collagen volume of BYHWD group was more significantly decreased than that of model group. Proteomic analysis showed that atrial natriuretic factor (ANF) was downregulated; heat shock protein beta-6 (HSPB6) and peroxiredoxin-6 (PRDX6) were upregulated in BYHWD-treated group among successfully identified proteins. The apoptotic index (AI) was reduced by BYHWD accompanied by decreased expression of Bax and caspase 3 activity, increased Bcl-2/Bax ratio, and phosphorylation of HSPB6 compared to that of model group. Taken together, these results suggest that BYHWD can alleviate ventricular remodeling induced by LAD artery ligation. The antiremodeling effects of BYHWD are conferred by decreasing AI through affecting multiple targets including increased Bcl-2/Bax ratio and decreased caspase 3 activity that might be via upregulated PRDX6, phosphorylation of HSPB6 and subsequently reduction of ANF.