Miracle-dz/UniFAR-FTUs huggingface dataset:
Early versus delayed invasive intervention in acute coronary syndromes.

BACKGROUND Earlier trials have shown that a routine invasive strategy improves outcomes in patients with acute coronary syndromes without ST-segment elevation. However, the optimal timing of such intervention remains uncertain. METHODS We randomly assigned 3031 patients with acute coronary syndromes to undergo either routine early intervention (coronary angiography < or = 24 hours after randomization) or delayed intervention (coronary angiography > or = 36 hours after randomization). The primary outcome was a composite of death, myocardial infarction, or stroke at 6 months. A prespecified secondary outcome was death, myocardial infarction, or refractory ischemia at 6 months. RESULTS Coronary angiography was performed in 97.6% of patients in the early-intervention group (median time, 14 hours) and in 95.7% of patients in the delayed-intervention group (median time, 50 hours). At 6 months, the primary outcome occurred in 9.6% of patients in the early-intervention group, as compared with 11.3% in the delayed-intervention group (hazard ratio in the early-intervention group, 0.85; 95% confidence interval [CI], 0.68 to 1.06; P=0.15). There was a relative reduction of 28% in the secondary outcome of death, myocardial infarction, or refractory ischemia in the early-intervention group (9.5%), as compared with the delayed-intervention group (12.9%) (hazard ratio, 0.72; 95% CI, 0.58 to 0.89; P=0.003). Prespecified analyses showed that early intervention improved the primary outcome in the third of patients who were at highest risk (hazard ratio, 0.65; 95% CI, 0.48 to 0.89) but not in the two thirds at low-to-intermediate risk (hazard ratio, 1.12; 95% CI, 0.81 to 1.56; P=0.01 for heterogeneity). CONCLUSIONS Early intervention did not differ greatly from delayed intervention in preventing the primary outcome, but it did reduce the rate of the composite secondary outcome of death, myocardial infarction, or refractory ischemia and was superior to delayed intervention in high-risk patients. (ClinicalTrials.gov number, NCT00552513.)
A Simplified Space Vector Modulation Scheme for Multilevel Converters

This paper proposes a simplified space vector modulation (SVM) scheme for multilevel converters. Compared with earlier SVM methods, the proposed scheme simplifies the detection of the nearest three vectors and the generation of switching sequences, and therefore is computationally more efficient. Particularly, for the first time, the proposed scheme achieves the same easy implementation as phase-voltage modulation techniques. Another superior characteristic of the proposed scheme over earlier methods is its potential for multiphase multilevel applications. The proposed scheme also offers the following significant advantages: 1) independence of the level number of the converter; 2) more degrees of freedom, i.e., redundant switching sequences and adjustable duty cycles, to optimize the switching patterns; and 3) no need for lookup tables or coordinate transformations. These advantages make the proposed scheme well suited to large level-number applications, such as modular multilevel converters and high voltage direct current systems. Simulation and experimental results verify this new concept.
Exoplasmic cysteine Cys384 of the HDL receptor SR-BI is critical for its sensitivity to a small-molecule inhibitor and normal lipid transport activity

The HDL receptor, scavenger receptor, class B, type I (SR-BI), is a homooligomeric cell surface glycoprotein that controls HDL structure and metabolism by mediating the cellular selective uptake of lipids, mainly cholesteryl esters, from HDL. The mechanism underlying SR-BI-mediated lipid transfer, which differs from classic receptor-mediated endocytosis, involves a two-step process (binding followed by lipid transport) that is poorly understood. Our previous structure/activity analysis of the small-molecule inhibitor blocker of lipid transport 1 (BLT-1), which potently (IC50 ∼ 50 nM) blocks SR-BI-mediated lipid transport, established that the sulfur in BLT-1’s thiosemicarbazone moiety was essential for activity. Here we show that BLT-1 is an irreversible inhibitor of SR-BI, raising the possibility that cysteine(s) in SR-BI interact with BLT-1. Mass spectrometric analysis of purified SR-BI showed two of its six exoplasmic cysteines have free thiol groups (Cys251 and Cys384). Converting Cys384 (but not Cys251) to serine resulted in complete BLT-1 insensitivity, establishing that the unique molecular target of BLT-1 inhibition of cellular SR-BI dependent lipid transport is SR-BI itself. The C384S substitution reduced the receptor’s intrinsic lipid uptake activity by approximately 60% without dramatically altering its surface expression, homooligomerization, or HDL binding. Thus, a small-molecule screening approach identified a key residue in SR-BI involved in lipid transport, providing a powerful springboard into the analyses of the structure and mechanism of SR-BI, and highlighting the power of this approach for such analyses.
Critical Conflicts between First-Wave and Feminist Critical Approaches to Alternative Dispute Resolution

This paper examines the contradictory responses of critical legal theory to alternative dispute resolution (ADR) mechanisms. By tracking the changing character of the responses that response, the paper identifies significant developments over the last twenty-five years in the methodology and conclusions of critical legal scholarship. The analysis finds that feminist critical approaches to ADR differ markedly from the first-wave (from the mid-1970s until the mid-1980s) critical accounts. They are not only more pragmatic than earlier critical theorists; feminist accounts advocate solutions that are in direct conflict with those of first-wave theorists. Where feminists embrace ADR, first-wave critical theorists express grave concern. Yet this divergence remains largely unacknowledged.The paper argues that this discontinuity in critical scholarship serves to indicate just how successful and total the attack on formality, championed by first-wave scholars, was. Furthermore, the shift in critical scholarship may be explained by critical feminist scholarship’s adoption of the individual as its unit of analysis, while retaining the critiques of formality it had inherited from first-wave scholarship. The result is a more personalized conception of conflict, rights and remedies.
Primary Cutaneous Mucinous Carcinoma Treated with Narrow Surgical Margin

Primary cutaneous mucinous carcinoma (PCMC) is a rare malignant tumor of eccrine origin. Clinically, the carcinoma presents as a solitary, slow growing, and painless nodule. For this reason, this tumor is often considered to be a benign mass in the preoperative setting. The lesion is, however, malignant in nature and has a tendency for local recurrence and infrequent metastasis. Wide local excision is the treatment of choice. However, few reports exist with information regarding surgical margins and clinical outcomes. Herein, we report a case of PCMC excised with a narrow surgical margin and review the relevant literature. A 49-year-old man presented with a small cutaneous nodule of the right cheek. The mass was excised without any margin, but pathologic examination revealed histology of mucinous carcinoma. Because of this, the operative site was re-excised with a 5-mm margin, and the wound was closed using a V-Y advancement flap. Systemic work-up did not reveal other potential metastatic primary, for a final diagnosis of PCMC. We report this case of PCMC, treated with relatively narrow margin in a patient with good prognostic factors.
False Positivity of Non-Targeted Infections in Malaria Rapid Diagnostic Tests: The Case of Human African Trypanosomiasis

Background In endemic settings, diagnosis of malaria increasingly relies on the use of rapid diagnostic tests (RDTs). False positivity of such RDTs is poorly documented, although it is especially relevant in those infections that resemble malaria, such as human African trypanosomiasis (HAT). We therefore examined specificity of malaria RDT products among patients infected with Trypanosoma brucei gambiense. Methodology/Principal Findings Blood samples of 117 HAT patients and 117 matched non-HAT controls were prospectively collected in the Democratic Republic of the Congo. Reference malaria diagnosis was based on real-time PCR. Ten commonly used malaria RDT products were assessed including three two-band and seven three-band products, targeting HRP-2, Pf-pLDH and/or pan-pLDH antigens. Rheumatoid factor was determined in PCR negative subjects. Specificity of the 10 malaria RDT products varied between 79.5 and 100% in HAT-negative controls and between 11.3 and 98.8% in HAT patients. For seven RDT products, specificity was significantly lower in HAT patients compared to controls. False positive reactions in HAT were mainly observed for pan-pLDH test lines (specificities between 13.8 and 97.5%), but also occurred frequently for the HRP-2 test line (specificities between 67.9 and 98.8%). The Pf-pLDH test line was not affected by false-positive lines in HAT patients (specificities between 97.5 and 100%). False positivity was not associated to rheumatoid factor, detected in 7.6% of controls and 1.2% of HAT patients. Conclusions/Significance Specificity of some malaria RDT products in HAT was surprisingly low, and constitutes a risk for misdiagnosis of a fatal but treatable infection. Our results show the importance to assess RDT specificity in non-targeted infections when evaluating diagnostic tests.
Management interventions in dairy herds: Exploring within herd uncertainty using an integrated Bayesian model

Knowledge of the efficacy of an intervention for disease control on an individual farm is essential to make good decisions on preventive healthcare, but the uncertainty in outcome associated with undertaking a specific control strategy has rarely been considered in veterinary medicine. The purpose of this research was to explore the uncertainty in change in disease incidence and financial benefit that could occur on different farms, when two effective farm management interventions are undertaken. Bovine mastitis was used as an example disease and the research was conducted using data from an intervention study as prior information within an integrated Bayesian simulation model. Predictions were made of the reduction in clinical mastitis within 30 days of calving on 52 farms, attributable to the application of two herd interventions previously reported as effective; rotation of dry cow pasture and differential dry cow therapy. Results indicated that there were important degrees of uncertainty in the predicted reduction in clinical mastitis for individual farms when either intervention was undertaken; the magnitude of the 95% credible intervals for reduced clinical mastitis incidence were substantial and of clinical relevance. The large uncertainty associated with the predicted reduction in clinical mastitis attributable to the interventions resulted in important variability in possible financial outcomes for each farm. The uncertainty in outcome associated with farm control measures illustrates the difficulty facing a veterinary clinician when making an on-farm decision and highlights the importance of iterative herd health procedures (continual evaluation, reassessment and adjusted interventions) to optimise health in an individual herd.
Dynamic and static mechanical compression affects akt phosphorylation in porcine patellofemoral joint cartilage

Protein kinase B (Akt)–dependent signaling pathways induced by mechanical loading have been identified in a variety of tissue. However, there is no evidence for a potential regulation of Akt in cartilage mechanotransduction. This study was conducted in order to determine whether or not the Akt in chondrocytes is regulated by mechanical loading. Porcine patellofemoral joints were loaded in compression at 500 N for 150 s either dynamically at 12 Hz or 1 Hz or statically using a custom‐designed loading frame. Left‐sided knees served as intervention, right‐sided as unloaded control. Cartilage samples were harvested at different time points after mechanical loading and the phosphorylation of Akt was analyzed immunohistochemically. A downregulation of Akt phosphorylation was seen in cartilage 300 s after mechanical loading whereas Akt phosphorylation remained unchanged in unloaded specimens. In addition, regulation of Akt appeared to change with the frequency of loading, presenting different patterns in Akt phosphorylation with static and dynamic loading. Variations in Akt phosphorylation were detected through different zones of cartilage. Overall, our findings indicate that Akt signaling in porcine patellofemoral joint cartilage is dependent upon frequency of loading, cartilage zone, and the time interval between loading and cartilage harvest. It may be concluded that Akt plays a role in cartilage mechanotransduction. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:616–623, 2008
Governing Through Early Childhood Curriculum, "the Child," and "Community"

This article examines the role of state ideology in the formation of kindergarten curriculum documents in socialist Hungary during the 1970s and in contemporary neoliberal Australia. The study explores two landmark curriculum documents, of Hungary and Australia, respectively, comparing the ways in which "the child" is conceptualized in relation to each one's particular ideas of community. Departing from earlier studies that examine images of the child as they move through history, this study uses Foucauldian genealogy for analysis and constructs a vertical case study to compare ideas of "the child" and "community" embedded in the curriculum documents' respective discursive contexts of socialist and neoliberal political ideologies. Through examination of these case studies this paper also illustrates some of the ways curriculum documents written for the early years regulate children. Sometimes, such as in socialist curriculum, this occurs in explicit and ideologically explicit ways; at other times, such as in the neoliberal curriculum, a more covert and seemingly "apolitical" regulation takes place that is nonetheless equally powerful.
The determinants of forward‐looking information in annual reports of UAE companies

Purpose – This paper aims to empirically explore the underlying factors that may affect the extent to which forward‐looking information is disclosed.Design/methodology/approach – This study uses a list of forward‐looking keywords to demonstrate the differences, if any, in the level of disclosure among firms and between sectors. The sample includes 46 companies listed in either the Dubai financial market or the Abu Dubai securities market. Statistical analysis is performed using a backward regression.Findings – Debt ratio and profitability are found to be significant; however, sector type, firm size, and auditor size are found to have insignificant association with the level of forward‐looking information disclosed in UAE annual reports.Practical implications – A number of users, such as investors, lenders, and auditors, may find these results beneficial. These users may consider the results of this study when they are dealing with firms that have low profitability and high financial risk. Accordingly, the.
The Sinorhizobium meliloti Essential Porin RopA1 Is a Target for Numerous Bacteriophages

ABSTRACT The symbiotic nitrogen-fixing bacterium Sinorhizobium meliloti harbors a gene, SMc02396, which encodes a predicted outer membrane porin that is conserved in many symbiotic and pathogenic bacteria in the order Rhizobiales. Here, this gene (renamed ropA1) is shown to be required for infection by two commonly utilized transducing bacteriophages (ΦM12 and N3). Mapping of S. meliloti mutations conferring resistance to ΦM12, N3, or both phages simultaneously revealed diverse mutations mapping within the ropA1 open reading frame. Subsequent tests determined that RopA1, lipopolysaccharide, or both are required for infection by all of a larger collection of Sinorhizobium-specific phages. Failed attempts to disrupt or delete ropA1 suggest that this gene is essential for viability. Phylogenetic analysis reveals that ropA1 homologs in many Rhizobiales species are often found as two genetically linked copies and that the intraspecies duplicates are always more closely related to each other than to homologs in other species, suggesting multiple independent duplication events.
Unroll-and-jam using uniformly generated sets

Modern architectural trends in instruction-level parallelism (ILP) are to increase the computational power of microprocessors significantly. As a result the demands on memory have increased. Unfortunately, memory systems have not kept pace. Even hierarchical cache structures are ineffective if programs do not exhibit cache locality. Because of this compilers need to be concerned not only with finding ILP to utilize machine resources effectively, but also with ensuring that the resulting code has a high degree of cache locality. One compiler transformation that is essential for a compiler to meet the above objectives is unroll-and-jam, or outer-loop unrolling. Previous work either has used a dependence-based model to compute unroll amounts, significantly increasing the size of the dependence graph, or has applied a more brute force technique. In this paper, we present an algorithm that uses a linear-algebra-based technique to compute unroll amounts. This technique results in an 84% reduction over dependence-based techniques in the total number of dependences needed in our benchmark suite. Additionally, there is no loss in optimization performance over previous techniques and a more elegant solution is utilized.
Indotecan (LMP400) and AM13-55: Two Novel Indenoisoquinolines Show Potential for Treating Visceral Leishmaniasis

ABSTRACT Visceral leishmaniasis is an emerging neglected tropical disease (NTD) caused by the protozoan Leishmania infantum in the countries bordering the Mediterranean Basin. Currently there is no effective vaccine against this disease, and the therapeutic approach is based on toxic derivatives of SbV. Therefore, the discovery of new therapeutic targets and the development of drugs designed to inhibit them comprise an extremely important approach to fighting this disease. DNA topoisomerases (Top) have been identified as promising targets for therapy against leishmaniasis. These enzymes are involved in solving topological problems generated during replication, transcription, and recombination of DNA. Being unlike that of the mammalian host, type IB DNA topoisomerase (TopIB) from Leishmania spp. is a unique bisubunit protein, which makes it very interesting as a selective drug target. In the present investigation, we studied the effect of two TopIB poisons with indenoisoquinoline structure, indotecan and AM13-55, on a murine BALB/c model of infected splenocytes with L. infantum, comparing their effectiveness with that of the clinically tested leishmanicidal drug paromomycin. Both compounds have high selectivity indexes compared with uninfected splenocytes. SDS-KCl-precipitable DNA-protein complexes in Leishmania promastigotes and in vitro cleaving assays confirmed that these drugs are Top poisons. The inhibitory potency of both indenoisoquinolines on L. infantum recombinant TopIB was assessed in vitro, with results showing that indotecan was the most active compound, preventing the relaxation of supercoiled DNA. Experimental infections in susceptible BALB/c mice treated with 2.5 mg/kg body weight/day once every other day for a total of 15 days showed that indotecan cleared more than 80% of the parasite burden of the spleen and liver, indicating promising activity against visceral leishmaniasis.
Extracellular neuraminidase production by a Pasteurella multocida A:3 strain associated with bovine pneumonia

The properties of an extracellular neuraminidase produced by a Pasteurella multocida A:3 strain that was isolated in a case of bovine pneumonia were examined during growth in a defined medium. This enzyme (isolated from concentrated culture supernatants of P. multocida A:3) was active against N-acetylneuramin lactose, human alpha-1-acid glycoprotein, fetuin, colominic acid, and bovine submaxillary mucin. Enzyme elaboration was correlated with the growth of the organism in a defined medium, with maximum quantities produced in the stationary phase. The enzyme was purified by a combination of ammonium sulfate fractionation, ion exchange on DEAE-Sephacel, and gel filtration on Sephadex G-200. The purified neuraminidase possessed a specific activity of 9.36 mumol of sialic acid released per min per mg of protein against fetuin. The enzyme possessed a pH optimum of 6.0 and a Km of 0.03 mg/ml. The P. multocida A:3 neuraminidase had a molecular weight of approximately 500,000 as estimated by gel filtration. The enzyme was stable at 4 and 37 degrees C for 3 h. Approximately 75% of the neuraminidase activity was lost within 30 min at 50 degrees C. Greater than 90% of the enzyme activity was destroyed within 10 min at temperatures of > or = 65 degrees C. The P. multocida neuraminidase does not appear to be serologically related to the Pasteurella haemolytica A1 neuraminidase since antiserum prepared against the purified P. haemolytica enzyme did not neutralize the P. multocida enzyme.
Steering the solar panel: plastids influence development.

As if they were industrial factories, plant cells reveal a multitude of interactions between compartments, with many activities requiring the traffic of components and products between them. Thirty years ago researchers made what seemed, at first, a surprising observation: a mutant of barley that, through maternal inheritance of ribosome-deficient plastids, possessed contiguous stripes of green and white tissue, showed, in the white tissue, not only very low levels of plastid-based enzymatic activities but also very low levels of synthesis template for them in the cytoplasm (Bradbeer et al., 1979). The deficient state of the plastids was providing information to the nucleus of those cells, leading to low mRNA levels of the nuclear-encoded genes for those enzymes in the cytoplasm where they were synthesized. The compartments were sharing information, including commands from seemingly subordinate organelles (namely the chloroplasts), to control expression of genes in the nucleus. This specific flow of interorganellar information is known as plastid–nuclear communication or plastid retrograde signalling. In this issue of New Phytologist, Ruckle & Larkin (pp. 367–379) provide evidence showing that this retrograde signalling controls not just the nuclear processes involved in the biogenesis and function of the organelle, but also aspects of the differentiation of cells and the development of the plant overall in its response to light, at least at its crucial seedling stage. Light is a key environmental cue without whose presence neither chloroplast biogenesis nor normal (photomorphogenic) seedling development take place. Ruckle et al. (2007) recently showed that plastid signals are capable of ‘rewiring’ the light signalling network controlling a gene (Lhcb1) for a major chloroplast protein; the cryptochrome1 (cry1*) photoreceptor and a bZIP downstream transcription factor, HY5, seemed to reverse their roles in the expression of this gene if plastids were damaged. In this issue, Ruckle & Larkin show that this reversal, as judged by the consequences of the absence of cry1, applies also to several other aspects of seedling photomorphogenesis: for example, the expansion of the first photosynthetic organs (the cotyledons) and, under some conditions, the elongation of the seedling stem (the hypocotyl), although it does not affect responses related to the production of sunscreens in nonphotosynthetic cells.