Miracle-dz/UniFAR-FTUs huggingface dataset:
Biochemical and Structural Characterization of an Essential Acyl Coenzyme A Carboxylase from Mycobacterium tuberculosis

ABSTRACT Pathogenic mycobacteria contain a variety of unique fatty acids that have methyl branches at an even-numbered position at the carboxyl end and a long n-aliphatic chain. One such group of acids, called mycocerosic acids, is found uniquely in the cell wall of pathogenic mycobacteria, and their biosynthesis is essential for growth and pathogenesis. Therefore, the biosynthetic pathway of the unique precursor of such lipids, methylmalonyl coenzyme A (CoA), represents an attractive target for developing new antituberculous drugs. Heterologous protein expression and purification of the individual subunits allowed the successful reconstitution of an essential acyl-CoA carboxylase from Mycobacterium tuberculosis, whose main role appears to be the synthesis of methylmalonyl-CoA. The enzyme complex was reconstituted from the α biotinylated subunit AccA3, the carboxyltransferase β subunit AccD5, and the ε subunit AccE5 (Rv3281). The kinetic properties of this enzyme showed a clear substrate preference for propionyl-CoA compared with acetyl-CoA (specificity constant fivefold higher), indicating that the main physiological role of this enzyme complex is to generate methylmalonyl-CoA for the biosynthesis of branched-chain fatty acids. The α and β subunits are capable of forming a stable α6-β6 subcomplex but with very low specific activity. The addition of the ε subunit, which binds tightly to the α-β subcomplex, is essential for gaining maximal enzyme activity.
The Role of Djp1 in Import of the Mitochondrial Protein Mim1 Demonstrates Specificity between a Cochaperone and Its Substrate Protein

ABSTRACT A special group of mitochondrial outer membrane proteins spans the membrane once, exposing soluble domains to both sides of the membrane. These proteins are synthesized in the cytosol and then inserted into the membrane by an unknown mechanism. To identify proteins that are involved in the biogenesis of the single-span model protein Mim1, we performed a high-throughput screen in yeast. Two interesting candidates were the cytosolic cochaperone Djp1 and the mitochondrial import receptor Tom70. Our results indeed demonstrate a direct interaction of newly synthesized Mim1 molecules with Tom70. We further observed lower steady-state levels of Mim1 in mitochondria from djp1Δ and tom70 tom71Δ cells and massive mislocalization of overexpressed GFP-Mim1 to the endoplasmic reticulum in the absence of Djp1. Importantly, these phenotypes were observed specifically for the deletion of DJP1 and were not detected in mutant cells lacking any of the other cytosolic cochaperones of the Hsp40 family. Furthermore, the djp1Δ tom70Δ tom71Δ triple deletion resulted in a severe synthetic sick/lethal growth phenotype. Taking our results together, we identified Tom70 and Djp1 as crucial players in the biogenesis of Mim1. Moreover, the involvement of Djp1 provides a unique case of specificity between a cochaperone and its substrate protein.
Accuracy of ECG interpretation in competitive athletes: the impact of using standardised ECG criteria

Background Interpretation of ECGs in athletes is complicated by physiological changes related to training. The purpose of this study was to determine the accuracy of ECG interpretation in athletes among different physician specialties, with and without use of a standised ECG criteria tool. Methods Physicians were asked to interpret 40 ECGs (28 normal ECGs from college athletes randomised with 12 abnormal ECGs from individuals with known ciovascular pathology) and classify each ECG as (1) ‘normal or variant – no further evaluation and testing needed’ or (2) ‘abnormal – further evaluation and testing needed. ’ After reading the ECGs, participants received a two-page ECG criteria tool to guide interpretation of the ECGs again. Results A total of 60 physicians participated: 22 primary care (PC) residents, 16 PC attending physicians, 12 sports medicine (SM) physicians and 10 ciologists. At baseline, the total number of ECGs correctly interpreted was PC residents 73%, PC attendings 73%, SM physicians 78% and ciologists 85%. With use of the ECG criteria tool, all physician groups significantly improved their accuracy (p<0.0001): PC residents 92%, PC attendings 90%, SM physicians 91% and ciologists 96%. With use of the ECG criteria tool, specificity improved from 70% to 91%, sensitivity improved from 89% to 94% and there was no difference comparing ciologists versus all other physicians (p=0.053). Conclusions Providing standised criteria to assist ECG interpretation in athletes significantly improves the ability to accurately distinguish normal from abnormal findings across physician specialties, even in physicians with little or no experience.
Task-specific grasping of simiiar objects by probabiiistic fusion of vision and tactiie measurements

This paper presents a probabilistic approach for task-specific grasping of novel objects from a known category. RGB-D imaging is used to establish an initial estimate of the target object's shape and pose, which is used to plan an optimal grasp over the uncertain estimate. Tactile information is then used for incrementally improving the estimate and sequentially replanning better grasps. The resulting grasp is maximally likely to be task compatible and stable taking into account shape uncertainty in a probabilistic context. Experimental results in simulation and on a real platform show that tactile information can be used for improving the stability of grasps for objects which belong to a known category even if they vary considerably in shape.
Do Politicians Use Policy to Make Politics? The Case of Public-Sector Labor Laws

Schattschneider's insight that “policies make politics” has played an influential role in the modern study of political institutions and public policy. Yet if policies do indeed make politics, rational politicians have opportunities to use policies to structure future politics to their own advantage—and this strategic dimension has gone almost entirely unexplored. Do politicians actually use policies to make politics? Under what conditions? In this article, we develop a theoretical argument about what can be expected from strategic politicians, and we carry out an empirical analysis on a policy development that is particularly instructive: the adoption of public-sector collective bargaining laws by the states during the 1960s, 1970s, and early 1980s—laws that fueled the rise of public-sector unions, and “made politics” to the advantage of Democrats over Republicans.
Intersectoral Linkage of Labor Markets of Tradeables and Nontradeables Sector

Based on a search-matching model of a small open economy with a nontradeables sector, this paper analyzes how rising job destruction rate in one sector affect the equilibrium rate of unemployment through its impacts on labor markets of each sector. If job destruction rate rises in tradeables sector, sectoral unemployment rates rise in both tradeables and nontradeables sector because the undermined bargaining position of workers in tradeables sector spills over to nontradeables sector. We can also show that when the job destruction rate in the nontradeables sector is sufficiently high, sectoral rate of unemployment is higher, and equilibrium wage is lower in nontradeables sector than in tradeables sector.
Identifying reference companies using the book-to-market ratio: a minimum spanning tree approach

There is substantial evidence to suggest that the book-to-market (BM) ratio is an important factor in explaining stock market returns. Its role has proved difficult to isolate, however, due to statistical problems in its construction and to its observational equivalence to a number of risk and behavioural explanations. In addition, now widely recognised complex behaviour in financial markets has called into question modelling approaches that are limited in their ability to uncover relationships that are possibly masked during financial crises, for example. As one response, our research explores the value of a newly applied technique which examines the topological properties of minimum spanning trees as applied to both the BM ratio and market returns. Our intention is to identify and report investment signals as determined by the BM ratio and to assess the relationships of these signals to returns outcomes. The approach enables highly nonlinear behaviour to be addressed and the relationships we set out to capture to be reported in novel ways. We motivate and evidence a previously unreported role for BM as an investment signal which is effective over varying stock market conditions, including the financial crisis that began in 2008.
Sequence Determinants of C-terminal Substrate Recognition by the Tsp Protease (*)

Cytochrome b is not cleaved by the tail-specific protease Tsp in vitro or in the periplasm of Escherichia coli but becomes a good substrate when the C-terminal sequence WVAAA is added. Following randomization of the final three residue positions of this substrate, 54 different mutants with single residue substitutions were recovered. The steady-state expression levels of cytochrome variants bearing these mutant tails were similar in an E. coli strain deleted for the tsp gene but differed markedly in a strain containing Tsp. Wild-type cytochrome b and seven variants, displaying a range of intracellular expression levels, were purified. These proteins were found to have the same T values in thermal denaturation experiments but to be cleaved by Tsp at rates differing by as much as 30-fold. Overall, the rates of Tsp cleavage of these proteins in vitro correlate with their rates of cleavage in vivo as determined by pulse-chase experiments. These results indicate that the C-terminal sequence of the cytochrome-b variants is important in determining their proteolytic fate in the cell and show that this degradation is mediated predominantly by Tsp. There are different selectivity rules at each of the three C-terminal positions. The identity of the C-terminal residue of the substrate, where small, uncharged residues (Ala, Cys, Ser, Thr, Val) are preferred, is most important in determining the rate of substrate cleavage by Tsp. Non-polar residues are also preferred at the second and third positions, but larger and more hydrophobic side chains are also acceptable at these positions in good substrates.
Complementarities between organisational strategies and innovation

The purpose of this paper is to determine whether organizational strategies in various manufacturing industries are complementary with innovation. In particular, our interest is to discover which organizational strategies are complementary with major innovations (world-first and Canada-first). Knowledge of complementarity should pave the way for creating sustainable competitive advantage because the use of a complex strategy may be difficult to imitate. In other words, competitive advantage increases as the complexity of the strategy increases (i.e. because the number of strategy combinations follows a power law), which acts as a barrier to potential imitators (Rivkin, J.W. (2000) Imitation of Complex Strategies. Management Science, 46(6), 824–844. ). Because of the static nature of our results (productivity and profit are for 1997), their interpretation can only be tentative. Thus, our research is really a first step along the road to understanding the (potential) importance of complementarities among firm strategies. Caveats aside, managers may want to compare their own firm’s emphasis on particular strategies against what is empirically determined to be complementary with innovation and high-performance within their industry. The frequency of complementary pairs that involve innovation range from 40 to 50% depending on whether we are talking about profit, productivity, or strategies. This result is important—as it means that innovation outcomes are statistically significant for both increased productivity and increased profit. Furthermore, innovation was found to be complementary with many organizational strategies. The complementary strategies across industries were quite different, but this was expected to occur.
Delayed Pituitary Adenylate Cyclase–Activating Polypeptide Delivery After Brain Stroke Improves Functional Recovery by Inducing M2 Microglia/Macrophage Polarization

Background and Purpose— Until now, except thrombolysis, the therapeutical strategies targeting the acute phase of cerebral ischemia have been proven ineffective, and no approach is available to attenuate the delayed cell death mechanisms and the resulting functional deficits in the late phase. Then, we investigated whether a targeted and delayed delivery of pituitary adenylate cyclase–activating polypeptide (PACAP), a peptide known to exert neuroprotective activities, may dampen delayed pathophysiological processes improving functional recovery. Methods— Three days after permanent focal ischemia, PACAP-producing stem cells were transplanted intracerebro ventricularly in nonimmunosuppressed mice. At 7 and 14 days post ischemia, the effects of this stem cell–based targeted delivery of PACAP on functional recovery, volume lesions, and inflammatory processes were analyzed. Results— The delivery of PACAP in the vicinity of the infarct zone 3 days post stroke promotes fast, stable, and efficient functional recovery. This was correlated with a modulation of the postischemic inflammatory response. Transcriptomic and Ingenuity Pathway Analysis–based bioinformatic analyses identified several gene networks, functions, and key transcriptional factors, such as nuclear factor-&kgr;B, C/EBP-&bgr;, and Notch/RBP-J as PACAP’s potential targets. Such PACAP-dependent immunomodulation was further confirmed by morphometric and phenotypic analyses of microglial cells showing increased number of Arginase-1+ cells in mice treated with PACAP-expressing cells specifically, demonstrating the redirection of the microglial response toward a neuroprotective M2 phenotype. Conclusions— Our results demonstrated that immunomodulatory strategies capable of redirecting the microglial response toward a neuroprotective M2 phenotype in the late phase of brain ischemia could represent attractive options for stroke treatment in a new and unexploited therapeutical window.
In situ reactivation of glycerol-inactivated coenzyme B12-dependent enzymes, glycerol dehydratase and diol dehydratase

The catalytic properties of coenzyme B12-dependent glycerol dehydratase and diol dehydratase were studied in situ with Klebsiella pneumoniae cells permeabilized by toluene treatment, since the in situ enzymes approximate the in vivo conditions of the enzymes more closely than enzymes in cell-free extracts or cell homogenates. Both dehydratases in situ underwent rapid "suicidal" inactivation by glycerol during catalysis, as they do in vitro. The inactivated dehydratases in situ, however, were rapidly and continually reactivated by adenosine 5'-triphosphate (ATP) and Mn2+ in the presence of free adenosylcobalamin, although in cell-free extracts or in cell homogenates they could not be reactivated at all under the same reaction conditions. ATP was partially replaced by cytidine 5'-triphosphate or guanosine 5'-triphosphate but not by the beta, gamma-methylene analog of ATP in the in situ reactivation. Mn2+ was fully replaced by Mg2+ but only partially by Co2+. Hydroxocoblamin could not replace adenosylcobalamin in reactivation mixtures. The ability to reactivate the glycerol-inactivated dehydratases in situ was only seen in cells grown anaerobically in glycerol-containing media. This suggests that some factor(s) required for in situ reactivation is subject to induction by glycerol. Of the two possible mechanisms of in situ reactivation, i.e., the regeneration of adenosylcobalamin by Co-adenosylation of the bound inactivated coenzyme moiety (B12-adenosylation mechanism) and the displacement of the bound inactivated coenzyme moiety by free adenosyl-cobalamin (B12-exchange mechanism), the former seems very unlikely from the experimental results.
BAYESIAN ANALYSIS FOR POLITICAL RESEARCH

▪ Abstract Bayesian data analysis relies on Bayes' Theorem, using data to update prior beliefs about parameters. In this review I introduce and contrast Bayesian analysis with conventional frequentist inference and then distinguish two types of Bayesian analysis in political science. First, Bayesian analysis is used to merge historical information with current data in an analysis of likely election outcomes in Florida in 2000; particular attention is paid to the sensitivity of the results to the choice of prior (i.e., how much confidence one places in the historical information). Second, a more “modern” style of Bayesian analysis is reviewed, relying on Markov chain Monte Carlo algorithms to generate computationally intensive “random tours” of the high dimensional posterior distributions that are the focus of many contemporary Bayesian analyses; the example used is a central problem in political science, the analysis of legislators' preferences using roll call data.
Biomedical Informatics Research Network: Building a National Collaboratory to Hasten the Derivation of New Understanding and Treatment of Disease

Through support from the National Institutes of Health's National Center for Research Resources, the Biomedical Informatics Research Network (BIRN) is pioneering the use of advanced cyberinfrastructure for medical research. By synchronizing developments in advanced wide area networking, distributed computing, distributed database federation, and other emerging capabilities of e-science, the BIRN has created a collaborative environment that is paving the way for biomedical research and clinical information management. The BIRN Coordinating Center (BIRN-CC) is orchestrating the development and deployment of key infrastructure components for immediate and long-range support of biomedical and clinical research being pursued by domain scientists in three neuroimaging test beds.
Coronary angioplasty with or without stent implantation for acute myocardial infarction. Stent Primary Angioplasty in Myocardial Infarction Study Group.

BACKGROUND Coronary-stent implantation is frequently performed for treatment of acute myocardial infarction. However, few studies have compared stent implantation with primary angioplasty alone. METHODS We designed a multicenter study to compare primary angioplasty with angioplasty accompanied by implantation of a heparin-coated Palmaz-Schatz stent. Patients with acute myocardial infarction underwent emergency catheterization and angioplasty. Those with vessels suitable for stenting were randomly assigned to undergo angioplasty with stenting (452 patients) or angioplasty alone (448 patients). RESULTS The mean (+/-SD) minimal luminal diameter was larger after stenting than after angioplasty alone (2.56+/-0.44 mm vs. 2.12+/-0.45 mm, P<0.001), although fewer patients assigned to stenting had grade 3 blood flow (according to the classification of the Thrombolysis in Myocardial Infarction trial) (89.4 percent, vs. 92.7 percent in the angioplasty group; P=0.10). After six months, fewer patients in the stent group than in the angioplasty group had angina (11.3 percent vs. 16.9 percent, P=0.02) or needed target-vessel revascularization because of ischemia (7.7 percent vs. 17.0 percent, P<0.001). In addition, the combined primary end point of death, reinfarction, disabling stroke, or target-vessel revascularization because of ischemia occurred in fewer patients in the stent group than in the angioplasty group (12.6 percent vs. 20.1 percent, P<0.01). The decrease in the combined end point was due entirely to the decreased need for target-vessel revascularization. The six-month mortality rates were 4.2 percent in the stent group and 2.7 percent in the angioplasty group (P=0.27). Angiographic follow-up at 6.5 months demonstrated a lower incidence of restenosis in the stent group than in the angioplasty group (20.3 percent vs. 33.5 percent, P<0.001). CONCLUSIONS In patients with acute myocardial infarction, routine implantation of a stent has clinical benefits beyond those of primary coronary angioplasty alone.
Evaluation of the detectability of broken rotor bars for double squirrel cage rotor induction motors

Double squirrel cage rotor design is employed in induction motor applications that require high starting torque and high efficiency operation. The outer cage of double cage rotors is vulnerable to fatigue failure since it must withstand the large thermal/mechanical stresses experienced during a loaded startup due to the high starting current and long acceleration time. However, there are only a few publications that investigate broken bar detection for double cage induction motors. In this paper, the detectability of broken outer cage bars in double cage motors for the most commonly used rotor bar test methods is evaluated. A finite element and experimental study show that the sensitivity of on-line MCSA is significantly decreased, whereas that of off-line standstill tests is not influenced for broken outer cage bars. This suggests that one should be aware of the insensitivity of MCSA for double cage rotors, and there is a need for development of new on-line monitoring methods.
The Effect of the Private Securities Litigation Reform Act on Analyst Forecast Properties: The Impact of Firm Size and Growth Opportunities

We provide evidence that the effect of the Private Securities Litigation Reform Act (the Act) of 1995 on analyst forecast properties is conditional on firm size and growth opportunities. We show that analyst coverage, frequency of forecast revisions, forecast errors and dispersion after the Act decreased for large firms and for firms with low growth opportunities but increased for small firms and for firms with high growth opportunities. These results are consistent with the hypothesis that the Act results in additional high quality disclosures in large firms, which face higher litigation risk and tighter scrutiny from investors but not in smaller firms. Our findings of increases in analyst coverage and revision but deterioration in accuracy and precision of analyst forecasts for firms with high growth opportunities after the Act suggest that in spite of increased corporate disclosures, the information environment for analysts deteriorated in those firms. Copyright 2006 The Authors Journal compilation (c) 2006 Blackwell Publishing Ltd.
Terrorism and its Impact on Economic Growth: Evidence from Pakistan and India

3 Abstract: The terrorism incidents had always been a problem in the developing countries and the last few decades had increased them exponentially. This paper tries to give the empirical evidence of terrorist activities impact on the economic growth and the results show that the terrorism activities have a negative impact on the economic growth of the country. The seven year data from the World Bank was used for the analysis. ADF test was used to find the co integration between terrorist activities of these two countries. This paper also digs into the details of the relationship between the terrorism activities and the economic growth of India and Pakistan and made a comparison between these two. India's economic growth has no impact of terrorist activities while the economic growth of Pakistan does. Results also showed that the Indian terrorist activities have an impact on the Pakistani terrorist activities in the short run, but this impact is not stable in the long run.