Miracle-dz/UniFAR-FTUs huggingface dataset:
A rapid fluorometric assay for the S-malonyltransacylase FabD and other sulfhydryl utilizing enzymes

The development of biorenewable chemicals will support green chemistry initiatives and supplement the catalog of starting materials available to the chemical industry. Bacterial fatty acid biosynthesis is being pursued as a source of protein catalysts to synthesize novel reduced carbon molecules in fermentation systems. The availability of methods to measure enzyme catalysis for native and engineered enzymes from this pathway remains a bottleneck because a simple quantitative enzyme assay for numerous enzymes does not exist. Here we present two variations of a fluorescence assay that is readily extendable to high-throughput screening and is appropriate for thiol consuming and generating enzymes including the E. coli enzymes malonyl-coenzyme A transacylase (FabD) and keto-acylsynthase III (FabH). We measured KM values of 60 ± 20 µM (acetyl-CoA) and 20 ± 10 µM (malonyl-ACP) and a kcat of 7.4–9.0 s-1 with FabH. Assays of FabD included a precipitation step to remove the thiol-containing substrate holo-ACP from the reaction product coenzyme-A to estimate reaction rates. Analysis of initial velocity measurements revealed KM values of 60 ± 20 µM (malonyl-CoA) and 40 ± 10 µM (holo-ACP) and a kcat of 2100–2600 s-1 for the FabD enzyme. Our data show similar results when compared to existing radioactive and continuous coupled assays in terms of sensitivity while providing the benefit of simplicity, scalability and repeatability. Fluorescence detection also eliminates the need for radioactive substrates traditionally used to assay these enzymes.
Development of an internet-based intervention for parents of infants.

AIM This paper reports on a study to describe the development of an internet-based intervention for parents with infants and to compare the participants and hospitals at baseline. BACKGROUND There is a need for interventions to support parenting and for more research into the use of information technology as an intervention strategy. The design and development of healthcare interventions is a complex task, but these are rarely discussed in research reports. METHODS A quasi-experimental study was conducted. The data (N = 1300 families) were collected using a structured questionnaire at the hospital or no later than 1 week after discharge during the winter of 2006. The results were used to develop the intervention and to compare the participants at baseline. Statistically significant differences were determined by chi-squared or Fisher's exact tests for percentages and one-way anova for means. The internal consistency relialibility of the scales was analysed using Cronbach's alpha coefficients. FINDINGS Participants in the intervention (n = 469 mothers, n = 307 fathers) and control (n = 394 mothers, n = 218 fathers) hospitals were comparable in respect of parent and infant attributes. There were statistically significant differences between the hospitals in fathers' overnight stays and their access to social support from professionals on the maternity ward. Exclusive breastfeeding was more common in the intervention hospital. More support for infants' cues and behaviour, and day-rhythm and sleep were needed in the intervention hospital. CONCLUSION More research is needed to gain a clearer understanding of the effect size of the differences for a reliable evaluation of the effectiveness of the proposed intervention.
Comparison of biological target volume metrics based on FDG PET-CT and 4DCT for primary non-small-cell lung cancer

Fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) and four-dimensional CT (4DCT) are used in several methods for defining the biological target volume (BTV) in primary non-small cell lung cancer (NSCLC). Disagreements between the assessments using these methodologies make the use of BTV for radiotherapy planning controversial. In this study, we compared existing methods with our proposed internal biological target volume (IBTV) metric, derived by combining internal target volume (ITV) and BTV metrics. We defined the IBTV from ITV (IBTVi) or BTV (IBTVb) based on ITV or BTV with symmetrical margin expansion. We detected large differences between IBTV, IBTVi and IBTVb (p < 0.001), but no difference between ITV and BTV. A margin expansion of about 13 mm was necessary for ITV or BTV to encompass > 95% IBTV. The conformity index correlated negatively with IBTV/ITV, IBTV/BTV, IBTVi/ITV, and IBTVb/BTV volume ratios (p < 0.05). VR also increased the margins of IBTVi and IBTVb. Indeed, IBTV was much smaller than IBTVi or IBTVb, suggesting that using IBTV for radiotherapy planning could improve treatment by minimizing the radiation exposure of healthy tissue and organs surrounding tumors.
Capital Controls and Foreign Currency Denomination

This paper studies the effectiveness of capital controls with foreign currency denomination and its welfare implications. To do this, we develop a general equilibrium model with financial frictions and banking, in which assets and liabilities are denominated in both domestic and foreign currencies. We propose a non-pecuniary capital-control policy that limits the gap between foreign-currency denominated loans and deposits to the amount of foreign funds that bankers can borrow from the international credit market. We show that capital controls have a critical impact on the dynamics of assets and liabilities that are denominated in foreign currency. This critical impact works through the capital control constraint on quantitative nancial variables directly, not through the spreads. The non-pecuniary capital controls help to stabilize the nancial sector and, hence, reduces the negative spillovers to the real economy. A more restrictive capital-control policy signicantly attenuates the welfare effect of the foreign monetary policy and exchange rate shocks.
Rates of hospitalization among patients with deep vein thrombosis before and after the introduction of rivaroxaban

Abstract Background. Compared to warfarin, the non-vitamin K antagonist oral anticoagulant rivaroxaban may have advantages in treating patients with venous thromboembolism, because injectable bridging therapy and routine laboratory monitoring are not required. The objective of this study was to compare the rate of hospitalization in patients treated with rivaroxaban after its introduction with what it would have been before the introduction of rivaroxaban. Methods. A retrospective claims analysis was conducted using the MarketScan Hospital Drug Database from January 2011 to December 2013. Adult patients with a primary diagnosis of deep vein thrombosis (DVT) treated with rivaroxaban or low-molecular-weight heparin (LMWH) bridged to warfarin during the first day of an evaluation at a hospital were identified. Based on propensity-score methods, historical LMWH/warfarin patients (i.e., patients who received LMWH/warfarin before the approval of rivaroxaban) were matched 4:1 to rivaroxaban patients, and the rates of hospitalization were compared. Results. All rivaroxaban-treated patients (n = 134) in the database were well matched with four historical LMWH/warfarin-treated patients (n = 536). Among the rivaroxaban cohort, 60% of the patients were admitted to the hospital, compared to 82% of the historical patients treated with LMWH/warfarin in the matched cohort. The difference was statistically significant and corresponded to a 27% reduction in hospital admissions (rate ratio [95% confidence interval]: 0.73 [0.62–0.84]). Hospital admission rates adjusted for time-trend analyses also led to similar results. Conclusion. The availability of rivaroxaban significantly reduced the hospitalization rate in patients with DVT treated with rivaroxaban compared to what it would have been if only LMWH/warfarin were available.
Effects of insulin and glucocorticoids on the leptin system are mediated through free leptin

OBJECTIVE Insulin and glucocorticoids are known to increase total leptin levels. However, the effects of insulin and glucocorticoids on the components of the leptin system – free leptin (FL), bound leptin (BL) and soluble leptin receptor (SR) – have not been elucidated. The aim of this study was to determine if there is a differential effect of insulin and glucocorticoids on the leptin system.
Drivers of growth: the case of French academic spin-off

Academic spin-offs (ASOs) have developed considerably in France since the 2000s. However, despite a strong increase in the number of new ventures, little is known about their ability to experience and sustain growth beyond the first five years. Based on a sample of 118 French ASOs from the same generation, this article analyses the factors that determine their growth during the development phase. These factors are derived from a resource-based view (RBV) and a dynamic capabilities approach (DCA). The results of our quantitative study show that four factors determine the growth of ASOs: entrepreneurial orientation (and broader cognitive resources), the acquisition of skills in the entrepreneurial process, the amount of public and private financing, technological capabilities and support programs.
Lack of an association between hydatid disease and autoimmunity

The prolonged survival of Echinococcus granulosus within the human host indicates that some mechanism is operating to permit parasite evasion of the host immune response. Several publications have described autoimmune phenomena in patients infected with hydatid cysts. The aim of this study was to test the postulate that there is a higher prevalence of autoantibodies in serum from patients with hydatid disease than in control samples, and this may provide some evidence of an association between autoimmunity andE. granulosus infection. Sera from 70 patients with hydatid disease and 45 control subjects were assayed for the presence of antinuclear antibodies (ANA), tissue specific autoantibodies and rheumatoid factor. All patients were aged between 20 and 80 years of age with no known history of autoimmune disease. Hydatid patients were surgically confirmed cases. Control subjects were chosen on the basis that they were age and sex matched to the test sera and had no known illness at the time blood samples were obtained. On the basis of an ANA autoantibody litre of > 1:40 being regarded as positive, 19 (27%) of the hydatid patients, 13 (28%) of the controls were positive. Low levels of tissue specific autoantibodies and rheumatoid factor were detected in sera from 5 (7%) and 2 (11%) hydatid patients and 4 (8%) and 3 (16%) of control subjects respectively. No significant differences (P > 0–05) were found between autoantibody levels in the hydatid patient sera and the controls. These findings suggest that there is no association between hydatid infection and the level of autoantibodies to a broad range of self antigens.
Long-term ophthalmic outcome of low birth weight children with and without retinopathy of prematurity.

OBJECTIVE A prospective study of retinopathy of prematurity (ROP) of 505 infants who weighed <1701 g at birth was undertaken in the mid-1980s. This cohort was traced at 10 to 12 years of age to determine how low birth weight alone and ROP might influence their ophthalmic outcome. METHODS Outcome measures were 1) visual functions (visual acuity, contrast sensitivity, stereoacuity, perimetry, and color vision), 2) presence of strabismus, and 3), measurements of eye size and the dimensions of its components including refractive state. A total of 169 11-year-olds who were born at term were recruited as control subjects and examined under the same conditions. RESULTS A total of 448 of the original cohort were traced, and 254 consented to a further examination. Compared with the control group, the follow-up cohort differed significantly with reduced visual functions and increased incidence of both myopia and strabismus. Compared with published data, eye size was smaller in the low birth weight cohort. To summarize the ophthalmic data, we defined ophthalmic morbidity as visual acuity below 0.0 log units or the presence of strabismus, myopia, color vision defect, or visual field defect. The rate of ophthalmic morbidity was 50.8% (n = 129/254) in the study cohort compared with 19.5% (n = 33/169) in the control group. The highest rate of ophthalmic morbidity was associated with severe ROP (stages 3/4), although those with no ROP had a less favorable outcome than the control group. CONCLUSION This study shows that low birth weight children are at increased risk of visual impairments compared with children who are born at full term. Visual impairments are associated with low birth weight per se and severe ROP. Regressed mild ROP is only a risk factor for strabismus. The functional significance of these deficits is largely unknown.
Pathophysiological and pharmacological mechanisms of acute cocaine toxicity in conscious rats.

In conscious rats, continuous i.v. infusion of cocaine (2 mg/kg/min) produced a marked increase in blood pressure, an initial moderate increase followed by a decrease in heart rate, tonic-clonic convulsions and, finally, a lethal episode of status epilepticus. No change in rectal temperature was observed. Infusion of cocaine methiodide (2 mg/kg/min), a quaternary derivative of cocaine, also produced a lethal episode of status epilepticus, but it was 6 times less potent than cocaine on a molar basis. In pentobarbital-anesthetized, spontaneously breathing rats, cocaine produced death by respiratory failure. Artificial ventilation of pentobarbital-anesthetized rats elevated the lethal dose of cocaine by 15-fold and these animals died of marked hypotension. In conscious rats, pretreatment with dl-, d- or l-propranolol or the alpha 2-selective adrenoceptor antagonist yohimbine enhanced the convulsive and lethal effects of cocaine. In contrast, the alpha 2-selective adrenoceptor agonist clonidine or the alpha 1-selective adrenoceptor antagonist prazosin attenuated these effects. Yohimbine antagonized the protective effect of clonidine. The nonselective alpha adrenoceptor antagonist phentolamine, the autonomic ganglionic blocker chlorisondamine and various calcium channel blockers had no effect on the convulsive or lethal doses of cocaine. The pressor response to cocaine was attenuated by calcium channel blockers, clonidine, phentolamine and dl- or l-propranolol, but not by d-propranolol. The pressor response to cocaine was abolished by chlorisondamine, reversed to a depressor response by prazosin and enhanced by yohimbine. The initial tachycardiac response to cocaine was reversed to bradycardia by dl- and l-propranolol, prazosin, yohimbine or high doses of the calcium channel blockers, but was unaffected by phentolamine, d-propranolol, clonidine or chlorisondamine. These results indicate that in spontaneously breathing animals, acute i.v. infusions of lethal doses of cocaine produce death primarily by central effects, namely by status epilepticus in conscious rats and by respiratory arrest in pentobarbital-anesthetized rats. In artificially ventilated, pentobarbital-anesthetized rats, however, cocaine produces death by effects on the cardiovascular system. In conscious rats, endogenous alpha 1 adrenoceptors exert a deleterious influence on cocaine-induced convulsive and lethal effects, whereas alpha 2 adrenoceptors provide protective influence. Propranolol appears to enhance cocaine-induced acute lethality through a mechanism independent of beta adrenoceptors. Calcium channel blockers appear ineffective in antagonizing cocaine's lethality.
Chemical Exposures in the Synthetic Rubber Industry and Lymphohematopoietic Cancer Mortality

Objective: This study evaluated the association between exposure to several chemicals and mortality from lymphohematopoietic cancer (LHC) among 16,579 synthetic rubber industry workers who were followed up from 1943 to 1998. Methods: Poisson regression analyses examined LHC rates in relation to butadiene, styrene, and DMDTC exposure. Models provided maximum likelihood estimates of the relative rate for the contrast between categories of one agent, adjusting for other agents and for additional potential confounders. Results: Cumulative exposure to 1,3-butadiene was associated positively with all leukemia (relative rates of 1.0, 1.4, 1.2, 2.9, and 3.7, respectively, for exposures of 0, >0 to <33.7, 33.7 to <184.7, 184.7 to <425.0, and 425.0+ ppm-years), chronic myelogenous leukemia and to a lesser extent with chronic lymphocytic leukemia. Adjusting for styrene and DMDTC attenuated these associations. After controlling for butadiene, neither styrene nor DMDTC displayed a consistent exposure–response trend with all leukemia, chronic myelogenous leukemia, or chronic lymphocytic leukemia. Conclusions: This study found a positive association between butadiene and leukemia that was not explained by exposure to other agents examined.
Insulin Action in the Human Brain: Evidence from Neuroimaging Studies

Thus far, little is known about the action of insulin in the human brain. Nonetheless, recent advances in modern neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) or magnetoencephalography (MEG), have made it possible to investigate the action of insulin in the brain in humans, providing new insights into the pathogenesis of brain insulin resistance and obesity. Using MEG, the clinical relevance of the action of insulin in the brain was first identified, linking cerebral insulin resistance with peripheral insulin resistance, genetic predisposition and weight loss success in obese adults. Although MEG is a suitable tool for measuring brain activity mainly in cortical areas, fMRI provides high spatial resolution for cortical as well as subcortical regions. Thus, the action of insulin can be detected within all eating behaviour relevant regions, which include regions deeply located within the brain, such as the hypothalamus, midbrain and brainstem, as well as regions within the striatum. In this review, we outline recent advances in the field of neuroimaging aiming to investigate the action of insulin in the human brain using different routes of insulin administration. fMRI studies have shown a significant insulin‐induced attenuation predominantly in the occipital and prefrontal cortical regions and the hypothalamus, successfully localising insulin‐sensitive brain regions in healthy, mostly normal‐weight individuals. However, further studies are needed to localise brain areas affected by insulin resistance in obese individuals, which is an important prerequisite for selectively targeting brain insulin resistance in obesity.
The Singularity of Social Entrepreneurship: Untangling its Uniqueness and Market Function

Social entrepreneurship is an activity that is receiving intense scrutiny from scholars, practitioners and policymakers. However, research is only beginning to explore the unique function social entrepreneurs fill in the marketplace. This conceptual article examines if social entrepreneurs indeed represent a novel category of market actor. Building on prior work claiming that the unique function of social entrepreneurs is the creation of positive externalities and generation of spillover benefits for society, we compare social entrepreneurs with conventional entrepreneurs and other entities that seek to increase social welfare, including governments and traditional nonprofit organisations. Specifically, we contend that the strengths of social entrepreneurship are its reliance on voluntary exchange, promotion of dignity and self-sufficiency in beneficiaries, attunement to the signals of the marketplace and ability to tap into consumer spending. We also uncover the limitations of social entrepreneurship, which include the challenge of combining multiple institutional logics, the existence of social issues around which viable businesses cannot be built, dependence on consumer demand and competitive disadvantages relative to conventional businesses. We discuss the implications of our conceptualisation of social entrepreneurship for practitioners, policymakers and future research.
Acute Thymic Involution in Unexplained Third Trimester Stillbirth: Frequency, Grade, and Correlation with Neuropathologic Injury

Many 3rd-trimester stillbirths are unexplained, including the time course of the illness. Histologic acute thymic involution (ATI), when graded, correlates with duration of acute illness (grade 0, <12 hours; grade 4, >72 hours). Histologic brain injury is also common in stillbirth. We investigated ATI in unexplained stillbirth and correlated it with neuropathologic injury by identifying 58 autopsies of unexplained, 3rd-trimester stillborns (preterm, n = 24; term, n = 34) that included brain examination and graded ATI from 0 (resting state) to 4 (pronounced lymphodepletion). Gray matter injury (GMI) and white matter injury (WMI) were classified as older, recent, or absent, and ATI was correlated with GMI, WMI, thymic weight, and clinical data. Nine cases (16%) had ATI grade 0–1; 19 (33%), grade 2; 24 (41%), grade 3; and 6 (10%), grade 4. Older GMI and WMI were present in 39 (67%) and 10 (17%) stillborns, respectively. Higher ATI grade correlated significantly with older GMI (P < 0.001) and WMI (P = 0.014). The ATI grade was higher in the small-for-gestational stillborns compared with the appropriate- or large-for-gestational stillborns (P = 0.017) but did not correlate significantly with gestational age or other clinical or demographic factors evaluated. The ATI grades 2–4 were found in 84% of the stillborns, consistent with onset of acute illness between 24 and >72 hours before demise. Higher ATI grade correlated significantly with older brain injury, suggesting similar time of onset and shared underlying pathophysiologic events, the specific nature of which remains unclear.
Informal division of labour in EU foreign policy-making

ABSTRACT On many issues in European Union (EU) foreign policy-making, political steering and operational action are provided by an informal, self-selected group of actors. Although this informal division of labour is an important phenomenon, it has largely escaped the radar of EU foreign policy scholars. This article aims to fill that gap. Applying an inductive approach, it presents empirical observations from the fields of crisis management and external climate policy, illustrating the occurrence of informal division of labour. It subsequently provides an analytical framework to map the key dimensions of its different manifestations: the enabling factors, starting point, subject, institutional embeddedness, exclusiveness and durability of informal division of labour. Four possible effects on EU foreign policy-making are then discussed: an increased internal and external effectiveness; and a strengthened internal and external legitimacy. The article concludes by presenting suggestions for further empirical research on this phenomenon, as well as for theorizing it.
Protein-Protein and Protein-DNA Interactions at the Bacteriophage T4 DNA Replication Fork

The T4 DNA polymerase holoenzyme is composed of the polymerase enzyme complexed to the sliding clamp (the 45 protein), which is loaded onto DNA by an ATP-dependent clamp loader (the 44/62 complex). This paper describes a new method to directly investigate the mechanism of holoenzyme assembly using a fluorescently labeled cysteine mutant of the 45 protein. This protein possessed unaltered function yet produced substantial changes in probe fluorescence intensity upon interacting with other components of the holoenzyme. These fluorescence changes provide insight into the role of ATP hydrolysis in holoenzyme assembly. Using either ATP or the non-hydrolyzable ATP analog, adenosine 5′-O-(3-thiophosphate), events in holoenzyme assembly were assigned as either dependent or independent of ATP hydrolysis. A holoenzyme assembly mechanism is proposed in which the 44/62 complex mediates the association of the 45 protein with DNA in an ATP-dependent manner not requiring ATP hydrolysis. Upon ATP hydrolysis, the 44/62 complex triggers a conformational change in the 45 protein that may be attributed to the clamp loading onto DNA.