Miracle-dz/UniFAR-FTUs huggingface dataset:
Assembly of spaced chromatin involvement of ATP and DNA topoisomerase activity.

Undiluted extracts from eggs or oocytes of Xenopus laevis support the assembly of chromatin with physiologically spaced nucleosomes. Micrococcal nuclease and DNase I digestion experiments show that nucleosome formation as well as supercoiling of circular DNA concomitant to assembly do not require ATP or Mg2+. However these factors are essential for the stability and the physiological spacing of the assembled chromatin. gamma‐S‐ATP can substitute for ATP in this process. With topoisomers of defined linking number topological interconversions proceed by steps of unity, both in vitro as well as in vivo, indicating that topoisomerase I is dominantly acting in this process. Novobiocin sensitivity occurred only with diluted extracts and was unrelated to an inhibition of topoisomerase II. Finally, nucleosome assembly occurs efficiently on linear DNA although the assembled DNA is less stable than with circular DNA. From these results we propose that mature chromatin is formed in a two‐step reaction. In the first step, nucleosome deposition occurs independently of ATP and Mg2+. Thus, nucleosome formation can be uncoupled from their spacing. In this step, topoisomerase activity is involved in the relaxation of the topological constraints generated by chromatin assembly rather than in the process of assembly itself. The second step, requiring ATP and Mg2+, generates properly spaced chromatin.
Preparation and characterization of anti-GP73 monoclonal antibodies and development of double-antibody sandwich ELISA.

BACKGROUND Serum Golgi protein 73 (GP73) as a novel and potential marker for diagnosing hepatocellular carcinoma (HCC) have been found to be elevated in HCC patients and associated with clinical variables representing tumor growth and invasiveness. The aim of this study was to prepare a pair of monoclonal antibodys (mAbs) against GP73 and develop a newly designed double-antibody sandwich enzyme-linked immunosorbent assay (s-ELISA), which would be used in the detection of serum GP73 (sGP73) as well as in the diagnosis of HCC. MATERIALS AND METHODS Produced by prokaryotic expression, the purified recombinant GP73 (rGP73), produced by prokaryotic expression, was used to immunize the Balb/c mice. Two hybridoma cell lines against GP73 were obtained by fusing mouse Sp2/0 myeloma cells with spleen cells from the immunized mice. The titers of anti-GP73 mAb reached 1:243,000. Western blotting analysis and Immunohistochemistry staining revealed that anti-GP73 mAb could recognize GP73 protein. The double-antibody s-ELISA was successfully established and validated by 119 HCC and 103 normal serum samples. RESULTS showed that the detection limit of this method could reach 1.56 ng/ml, and sGP73 levels in HCC group (mean=190.6 ng/ml) were much higher than those of in healthy controls (mean=70.92 ng/ml). CONCLUSIONS Results of our study not only showed that sGP73 levels of HCC patients were significantly higher than those of healthy controls, but also indicated that the laboratory homemade anti-GP73 mAbs could be the optimal tool used in evaluating sGP73 levels, which would provide a solid foundation for subsequent clinical applications.
Insulin for glycaemic control in acute ischaemic stroke.

BACKGROUND Patients with hyperglycaemia concomitant with an acute stroke have greater stroke severity and greater functional impairment when compared to those with normoglycaemia at stroke presentation. OBJECTIVES To determine whether maintaining serum glucose within a specific normal range (4 to 7.5 mmol/L) in the first 24 hours of acute ischaemic stroke influences outcome. SEARCH STRATEGY We searched the Cochrane Stroke Group Trials Register (June 2010), CENTRAL (The Cochrane Library 2010, Issue 2), MEDLINE (1950 to June 2010), EMBASE (1980 to June 2010), CINAHL (1982 to June 2010), Science Citation Index (1900 to June 2010), and Web of Science (ISI Web of Knowledge) (1993 to June 2010). In an effort to identify further published, unpublished and ongoing trials we searched ongoing trials registers and SCOPUS. SELECTION CRITERIA Eligible studies were randomised controlled trials comparing intensively monitored insulin therapy versus usual care in adult patients with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS Two review authors independently extracted the study characteristics, study quality, and data to estimate the odds ratio (OR) and 95% confidence interval (CI), mean difference (MD) and standardised mean difference (SMD) of outcome measures. MAIN RESULTS We included seven trials involving 1296 participants (639 participants in the intervention group and 657 in the control group). We found that there was no difference between treatment and control groups in the outcome of death or disability and dependence (OR 1.00, 95% CI 0.78 to 1.28) or final neurological deficit (SMD -0.12, 95% CI -0.23 to 0.00). The rate of symptomatic hypoglycaemia was higher in the intervention group (OR 25.9, 95% CI 9.2 to 72.7). In the subgroup analyses of diabetes mellitus (DM) versus non-DM, we found no difference for the outcomes of death and dependency or neurological deficit. AUTHORS' CONCLUSIONS With the current evidence, we found that the administration of intravenous insulin with the objective of maintaining serum glucose within a specific range in the first hours of acute ischaemic stroke does not provide benefit in terms of functional outcome, death, or improvement in final neurological deficit and significantly increased the number of hypoglycaemic episodes. Specifically, those who were maintained within a more tight range of glycaemia with intravenous insulin experienced a greater risk of symptomatic and asymptomatic hypoglycaemia than those individuals in the control group.
A CHANGE TO RADIOLOGICAL PERITONEAL DIALYSIS CATHETER INSERTION: THREE-MONTH OUTCOMES

♦ Background: Best practices for peritoneal dialysis (PD) catheter insertion call for timely placement of catheters to reduce complications and increase the likelihood of a successful initiation of PD. The purpose of our study was to assess if a change in approach to PD catheter insertion, including a switch to radiological insertion of PD catheters and introduction of a dialysis access nurse to coordinate all patient care, was associated with more outpatient procedures and achievement of guideline-based outcomes, including timelier PD starts. ♦ Methods: We conducted a single-center retrospective chart review of all patients that had their first PD catheter inserted at our center over a 7-year period ending in 2007. ♦ Results: PD catheters were placed in 88 patients by interventional radiology and in 125 patients by surgical insertion during an earlier period. Insertion of PD catheters by interventional radiology was significantly associated with a higher rate of outpatient procedures (70% vs 32%, p < 0.0001) than surgical placement. At PD start, 82% of patients that underwent radiological insertions had an estimated glomerular filtration rate of over 8 mL/minute/1.73 m2 and their mean serum albumin level was 38.2 g/L. ♦ Conclusions: The new procedure of radiological insertion of PD catheters, coordinated by a dedicated dialysis access nurse, was associated with more outpatient procedures than the earlier surgical method and allowed patients to receive a PD catheter with timing consistent with clinical practice recommendations.
Empagliflozin, a novel selective sodium glucose cotransporter‐2 (SGLT‐2) inhibitor: characterisation and comparison with other SGLT‐2 inhibitors

Aims: Empagliflozin is a selective sodium glucose cotransporter‐2 (SGLT‐2) inhibitor in clinical development for the treatment of type 2 diabetes mellitus. This study assessed pharmacological properties of empagliflozin in vitro and pharmacokinetic properties in vivo and compared its potency and selectivity with other SGLT‐2 inhibitors.
Factors impeding the development of Oman spatial data infrastructure

Spatial Data Infrastructure (SDI) is an innovative concept introduced more than twenty years ago to allow the sharing and reuse of geospatial data. The National Spatial Data Infrastructure (NSDI), an SDI expanded to the national level, is now widely considered as an essential basic infrastructure for a country in this information era. To date countries all over the world, irrespective of their size, economic strength, political stability and population size, have developed, developing or considering developing their own SDI. A number of developed countries had successfully developed an impressive operational SDI while others are still progressively developing theirs. Yet for other countries the SDI development still remains an innovative concept. Understandably, besides the political and economic factors, many interrelated technical and non-technical factors can affect the development of SDI, the complexity of which can increase with the increase in the level of jurisdictions involved in spatial data sharing. Oman was one of the countries that had taken up the early initiative but unfortunately all that was known of the initiative was some feasibility studies conducted by non-national institution. Therefore this research has attempted to investigate the factors impeding the SDI development of Oman as an effort to revive the initiative to develop an operational Oman SDI, seen as an integral infrastructure to Oman’s future development and an important component in disaster and environmental management. Through this study, it was found that SDI is about communications between SDI participants to share spatial data. Through the thorough review of the data gathered from interviews and questionnaires, this research methodology was supported by systematic inspection and analysis of the essential data. The main stumbling block to Oman’s effort in building the SDI is the non-technical factors, including the human aspects entailing the lack of knowledge and awareness of spatial data and use of GIS, lack of knowledge on SDI concept and SDI benefits, and also the lack of cooperation, collaboration and coordination among the participants. It can be concluded that the lack of knowledge and awareness make communication between SDI participants difficult, thus almost impossible for cooperation, collaboration and coordination. This had left Oman with no option but to leave the initiative as an innovative concept, are now identified to be given the highest priority to enable Oman to pave the way forward.
Resynchronization/defibrillation for ambulatory heart failure trial: rationale and trial design

Purpose of review This paper reviews the effect of cardiac resynchronization therapy (CRT) on patients with heart failure symptoms, in particular, in patients with mild symptoms of heart failure. It provides the rationale and design of a randomized controlled trial to determine if CRT, when added to implantable cardioverter defibrillator, will be beneficial in patients with left ventricular dysfunction, ventricular conduction delay and mild heart failure symptoms. Recent findings CRT has been demonstrated to improve functional capacity, quality of life, and reduce heart failure hospitalization in patients with advanced symptomatic heart failure, and evidence of a ventricular conduction abnormality on ECG. In patients with milder heart failure symptoms, three randomized controlled trials and observational studies failed to convincingly show improvement of functional status, but demonstrated improved ventricular reverse remodelling with more advanced heart failure patients. Summary Two large randomized clinical trials are currently ongoing (RAFT and MADIT-CRT). The results of these trials will determine the efficacy of CRT in patients with systolic heart failure, ventricular conduction abnormality and milder symptoms.
Modifying the farmer field school method to support on-farm adaptation of complex rice systems

ABSTRACT Purpose: Complex rice systems (CRSs) are polycultures of plants and animals that enhance ecological processes contributing to sustainable and profitable farming systems. However, the contextual management complexity can hamper adoption, despite the large long-term benefits that CRSs offer. This paper aimed to provide a method that encourages active farmer involvement and integrates farmer’s feedback to deliver timely adaptations to CRS management. Design/methodology/approach: FFSs that are commonly used in guiding rural development processes involve a long process of preparation, weekly meetings and dissemination of new technologies with a greater knowledge flows from researchers or institutions to farmers than contrariwise. We have simplified FFS components and modified its curriculum focusing on extracting and integrating farmers’ feedback into adaptation measures. Surveys were conducted and their results were validated through focus group discussions, which provided an adequate database to simplify the steps in the FFS approach. Findings: Only four meetings for agroecosystems analysis that emphasised an analytical and reflective learning cycle generated suitable adaptation measures selected from farmers’ feedback. Repetition of the shortened FFS over several rice cropping cycles proved more effective than the frequent meetings within one cropping cycle. Practical implications: The modified FFS could be considered as a promising approach to training farmers, whilst simultaneously identifying and discovering adaptations of agricultural innovations and monitoring the evolution of complex polycultures like CRSs, under diverse conditions. Theoretical implications: The modified FFS provides participants additional time to reflect on the training topics, resulting in a significant improvement in their knowledge and the performance of the CRS. Originality/value: The modified FFS approach is focused on reflexive learning cycles and adaptation of innovations. Therefore, it is highly suitable for management of complex polycultures such as CRSs.
Relações de cooperação para competitividade e inovação no APL de TI do Vale do Rio Pardo (RS)

As abordagens sobre arranjos produtivos locais, como forma de dinamizar e explicar o dinamismo de determinados espaços geográficos, são a base do estudo sobre o Arranjo Produtivo Local (APL) da Tecnologia da Informação (TI) da Região do Vale do Rio Pardo (RS). O objetivo central foi verificar se as questões relativas à proximidade geográfica do aglomerado produtivo permitem que as relações de cooperação ocorram com maior intensidade e sejam fatores de competitividade e inovação de um arranjo produtivo local. Para alcançar o objetivo, foi realizada uma pesquisa qualitativa exploratória com empresas do APL de TI, via entrevistas semiestruturadas. Os resultados indicam que a proximidade geográfica é um fator competitivo, a partir da cooperação entre as empresas do APL e também com outros atores, como Universidade, Associações e Governo, gerando externalidades positivas para o conjunto de empresas. Essas inovações foram identificadas como oriundas de pesquisas de mercado, desenvolvimento interno e qualificação da equipe. Assim, a partir desse estudo, evidenciou-se como as empresas do APL de TI do Vale do Rio Pardo têm realizado atividades em conjunto em relação a suas competitividades individuais e coletivas para a criação de ambientes inovadores.
Activation of the unfolded protein response by Listeria monocytogenes

The endoplasmic reticulum (ER) responds to perturbation of homeostasis with stress. To maintain ER function, a signalling‐circuitry has evolved which, when engaged, attempts to reduce a surplus of unfolded proteins by triggering the unfolded protein response (UPR). Several studies have implicated UPR in viral infections, neurodegenerative disorders and metabolic diseases but UPR has not yet been widely linked to bacterial infections. Here we demonstrate that the facultative intracellular pathogen Listeria monocytogenes (Lm) induces ER expansion and UPR prior to host cell entry. Lm activated protein kinase RNA‐like ER kinase (PERK) evidenced by the phosphorylation of the α‐subunit of eukaryotic translation initiation factor‐2 (eIF2α), inositol‐requiring protein‐1 (IRE1) as shown by detection of spliced X‐box binding protein‐1 (XBP1) and activating transcription factor‐6 (ATF6) as demonstrated by depletion of its inactive form. A mutant LmΔhly strain that did not produce listeriolysin (LLO) lacked the UPR response. Conversely purified LLO activated UPR. Sustained infection with Lm resulted in apoptosis. Induction of ER stress by thapsigargin or tunicamycin reduced intracellular bacterial number. Our findings suggest that UPR plays an important role in the cell autonomous defence responses to bacterial infection.
The harmful dysfunction model of alcohol use disorder: revised criteria to improve the validity of diagnosis and prevalence estimates.

AIMS To formulate harmful dysfunction (HD) diagnostic criteria for alcohol use disorder (AUD) and test whether they increase validity relative to standard DSM criteria, as evidenced by lowered prevalence, increased validator levels including service use, severity and family history and enhanced specificity. DESIGN DSM-IV AUD, DSM-IV dependence, DSM-5 AUD and HD AUD definitions were compared on eight validity related tests using nationally representative community data. SETTING United States. PARTICIPANTS National Epidemiologic Survey of Alcoholism and Related Conditions (NESARC) respondents, aged 18-54 years (wave 1, n = 29 673; wave 2, n = 24 244). MEASURES NESARC DSM-IV and DSM-5 criteria were taken from published studies. Whereas DSM-5 diagnosis requires any two AUD symptoms, HD criteria were constructed from NESARC items to require symptoms of both impaired-control dysfunction [withdrawal, drink to prevent/stop withdrawal, cannot stop/reduce drinking, or craving (wave 2 only)] and harm (sacrificed important activities, problems caring for home/family, job/school problems, health problems, psychological problems or problems with family/friends). Validators included service use, severity and family history, among others. Specificity was tested using a teen transient drinker criterion group. FINDINGS Compared with DSM-5 AUD (DSM-IV results were similar), HD criteria yielded lower prevalence (95% confidence intervals): HD life-time 6.7% (6.2, 7.2%), 1-year 2.3% (2.0, 2.5%); and DSM-5 life-time 38.2% (36.5, 39.9%), 1-year 12.4% (11.7, 13.1%). HD AUD was higher than DSM-5 on pathology validators, including: life-time alcohol-related service use: HD 41.0% (38.1, 43.9%), DSM-5 11.5% (10.7, 12.3%); severity (number of life-time alcohol symptoms): HD 20.8 (20.4, 21.2), DSM-5 10.6 (10.4, 10.8); and family history of alcohol problems: HD 50.1% (47.3, 52.9), DSM-5 32.8% (31.6, 34.0). HD criteria eliminated 83% of a DSM-5 teen transient drinker false-positives criterion group. CONCLUSIONS Prevalence estimates of alcohol use disorder are lowered and diagnostic validity improved when using 'harmful dysfunction' diagnostic criteria compared with standard DSM criteria, partly by reducing misdiagnosis of teenage transient drinkers.
Nudge: A relevant communication tool adapted for agile innovation

This research aims to show the interest of nudges as a communication tool for organizations involved in an agile innovation approach. It describes how the flexibility, adaptability and low cost of nudges strengthen the ability of the organizations that use them to improve their agility. From a literature review on the nudges and agile innovation concepts, we propose a typology of nudges with a managerial orientation. Based on this typology we show in a last section how nudges represent a tool that is perfectly suited to innovative organizations wishing to develop their agility, whether in the context of their communications to their employees or their customers. Lastly, research perspectives are envisaged around the concept of agile communication. JEL Codes: M37, M15, M14
Novel approaches to drug design for the treatment of schizophrenia

Introduction: Schizophrenia is an important health issue affecting almost 1% of the population with significant unmet medical needs. The classical drug targets for the treatment of schizophrenia are dopamine D2 receptors. Second-generation (‘atypical') drugs block more receptors of the G-protein-coupled receptor (GPCR) class 1 (e.g., clozapine is a D(2)-5HT(2) antagonist). Areas covered: In this article, the author presents the new targets for GPCR as well as ligand-gated ion. Furthermore, the author reviews the opportunities for drug design offered by the structures solved recently. Expert opinion: For drug design, the availability of these protein structures, or the possibility to build high quality models, allows to shift the paradigm from ligand-based to target-based drug design. The analysis of the drugs, both on the market and in development, shows that numerous targets are being considered which may reveal an ambiguity on the ideal drug target. This situation may be simplified, in the future, owing to recent integrative projects: the ‘Human Brain Project' and the ‘Brain Activity Map' that aim at modeling the brain as well as the Allen Atlas.
Does heart failure exacerbation increase response to warfarin?A critical review of the literature

ABSTRACT Background: Numerous factors, such as other drugs, diet, and age, are well documented as altering response to warfarin. Less attention has been focused on the effect of disease states on the response to oral anticoagulants. Decompensated heart failure is reported to increase response to warfarin, but documentation is limited. Objective: The purpose of this review is to critically examine the evidence of a possible effect of heart failure exacerbations on response to warfarin. Research design and methods: A literature search was completed of the last 60 years using several databases, including PubMed, MEDLINE, EMBASE, and SCOPUS. Key terms in our search included ‘warfarin’ AND ‘heart failure’ and ‘heart failure exacerbation’ (or ‘decompensated heart failure’) AND ‘effect on warfarin’. When relevant citations were found, the references cited by those authors were checked. Results: Several reports from 1946–1989 suggested that decompensated heart failure increases response to oral anticoagulants. Unfortunately, these early reports have important limitations. More recent reports, since the widespread use of the international normalized ratio (INR), also suggest that heart failure exacerbations are associated with increased response to warfarin. Patient populations are small in these reports. Conclusions: Heart failure exacerbations may be associated with an increased response to warfarin and other vitamin K antagonists, but many reports are inadequate, and it appears that not all patients are susceptible to this effect. More frequent monitoring of INR in patients with decompensated heart failure is warranted. It is prudent to initiate warfarin at lower doses in patients with a history of heart failure and to monitor INR every 1–2 weeks during times of instability in ambulatory patients, and daily INRs in hospitalized patients. Given the large number of variables that impact on warfarin dose requirement, it is difficult to clearly establish the effect of decompensated heart failure on response to warfarin. Further studies must take all of these variables into account.