Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeted gene expression in the zebrafish prechordal plate

Targeted gene expression is a powerful tool for understanding gene function in vivo. In zebrafish, overexpression of gene products is typically accomplished ubiquitously, without temporal and spatial specificity. However, the yeast Gal4/UAS system can be used for targeted gene expression in zebrafish. Here we describe the generation and characterization of Tg[gsc: Gal4‐VP16] transgenic zebrafish lines that harbor a construct encoding Gal4‐VP16 transcriptional activator under the control of a fragment of the goosecoid gene promoter. Tg[gsc:Gal4‐VP16] embryos express Gal4‐VP16 RNA in presumptive prechordal plate mesendoderm during late blastula and throughout gastrulation. By crossing these fish to Tg[UAS‐GFP] transgenic fish, we show that the gsc:Gal4‐VP16 transgene is capable of driving strong expression of a target gene in the prechordal plate and its derivatives during gastrulation and segmentation. Thus, the use of Tg[gsc:Gal4‐VP16] fish can help in understanding gene function in the prechordal plate, an embryonic structure that is crucial for normal neural patterning. genesis 44:584–588, 2006. Published 2006 Wiley‐Liss, Inc.
Endovascular stenting as an emergency treatment for neonatal coarctation

Abstract We describe a neonate with critical coarctation of the aorta. Since treatment with Prostaglandin El had failed to reopen the arterial duct, and surgery was deemed to be associated with an unacceptably high risk in this unstable neonate, it was decided to perform balloon dilation of the coarctation as a palliative procedure to stabilize the patient. Balloon angioplasty failed to reduce the pressure gradient across the coarctation, so a stent was implanted retrogradely as an emergency procedure. Subsequently, the stented segment was resected surgically and end-to-end anastomosis created without complications at seven months of age.
Fund Flows and Performance in Brazil

This study analyzes how fund flows react to past performance in the dynamic Brazilian equity fund market over the period from 2001 to 2012. The study also tests for a “smart money” effect (Zheng, 1999), or whether funds that receive more money subsequently outperform those that receive less money. We find that investor flows chase past performance, and document some differences in the flow–performance relationship between retail and institutional funds. We do not find evidence of a “smart money” effect for the entire sample of funds. Nonetheless, flows in small and retail funds, which are often seen as populated by less sophisticated investors, do anticipate future fund performance.
Aspirin Prevention of Colorectal Cancer: Focus on NF-κB Signalling and the Nucleolus

Overwhelming evidence indicates that aspirin and related non-steroidal anti-inflammatory drugs (NSAIDs) have anti-tumour activity and the potential to prevent cancer, particularly colorectal cancer. However, the mechanisms underlying this effect remain hypothetical. Dysregulation of the nuclear factor-kappaB (NF-κB) transcription factor is a common event in many cancer types which contributes to tumour initiation and progression by driving expression of pro-proliferative/anti-apoptotic genes. In this review, we will focus on the current knowledge regarding NSAID effects on the NF-κB signalling pathway in pre-cancerous and cancerous lesions, and the evidence that these effects contribute to the anti-tumour activity of the agents. The nuclear organelle, the nucleolus, is emerging as a central regulator of transcription factor activity and cell growth and death. Nucleolar function is dysregulated in the majority of cancers which promotes cancer growth through direct and indirect mechanisms. Hence, this organelle is emerging as a promising target for novel therapeutic agents. Here, we will also discuss evidence for crosstalk between the NF-κB pathway and nucleoli, the role that this cross-talk has in the anti-tumour effects of NSAIDs and ways forward to exploit this crosstalk for therapeutic purpose.
Validation of Skeletal Muscle Volume as a Nutritional Assessment in Patients With Gastric or Colorectal Cancer Before Radical Surgery

Background Recently, some studies have reported the importance of sarcopenia as a prognostic factor in patients with gastrointestinal cancer who have undergone surgery. We aimed to examine skeletal muscle volume for use in nutritional assessment of preoperative patients, and to compare the results with those of other conventional methods of nutritional assessment, such as biochemical or body composition values. Methods This was an open cohort study which examined skeletal muscle volume for use in nutritional assessment of preoperative patients. A total of 121 patients with gastrointestinal cancer who underwent radical surgery were enrolled in this study between June 1, 2008 and December 31, 2012. There were 39 and 82 patients with gastric and colorectal cancer, respectively. The primary outcome of this study was postoperative overall survival. The secondary outcomes were postoperative survival from cancer-related deaths, recurrences of cancer after surgery, postoperative complications, and postoperative hospital inpatient stay (measured in days). Univariate and multivariate analyses were used to identify the relevant factors for postoperative outcomes mentioned above. Results Skeletal muscle volume was a significant (hazard ratio (HR): 3.34, 95% confidence interval (CI): 1.21 - 9.17, P = 0.020) independent prognostic factor for cancer-related deaths in patients with gastric or colorectal cancer who had undergone surgery, and a marginally independent (HR: 2.48, 95% CI: 0.91 - 6.81, P = 0.077) factor that negatively contributed to overall survival in these patients. In contrast, the preoperative skeletal muscle volume was not correlated with the recurrence of cancer, and was not significantly correlated with the occurrence of severe complications after surgery or prolongation of hospitalization. Conclusions The preoperative skeletal muscle volume was a significant prognostic factor in patients with gastric or colorectal cancers. Therefore, the estimation of skeletal muscle volume may be important for stable, long-term nutritional assessment in patients with gastrointestinal cancers.
Projecting Debt Servicing Capacity of Developing Countries

Analysis of the growth record of many economies indicates that foreign capital is an important factor in the process of economic development. For many developing countries, a continuing flow of foreign funds is necessary if desired growth targets are to be achieved. These funds are most likely to be in the form of loans rather than grants. This link between economicdevelopment and debt accumulation manifested itself in the enormous growth of less developed countries’ (LDCs) external indebtedness in recent years, especially after the oil crisis of 1973.
Multi-Source Performance Appraisals

Performance appraisal is crucial to effective human resource management, but there is evidence that current processes are not very effective This study reports on experience with a relatively new appraisal system in the operations office of a large federal agency The method, multi-source assessment (MSA, or "360° Feedback") utilizes ratings from peers, direct-reports, the supervisor, and the employee Comparison of survey results from before and after implementation of MSA found significant improvement in employee perceptions of the fairness and effectiveness of appraisals, particularly among protected classes The implications of these findings and suggestions for future research are discussed.
A Permanent Change in the Route to Owner Occupation?

This paper attempts to explain why home ownership rates among young adults fell in the early 1990s when various indicators suggested it had become more affordable. As a potential explanation, we focus on the relatively slower growth in their incomes and argue that this could signal a fundamental change in behaviour, a change in route adopted into owner occupation, induced by structural economic change. In examining the implications for housing tenure, we use a conditional fixed effects multinomial logit model to exploit the information on the tenure choice and the timing of transitions in the British Household Panel Survey. Our results reveal that relatively slower income growth contributed significantly to this decline and that ignoring the intertemporal correlation in micro-panels generates inconsistent results.
Can we automatically choose best uncertainty heuristics for large margin active learning?

Active learning (AL) has shown a great potential in the field of remote sensing to improve the efficiency of the classification process while keeping a limited training dataset. Active learning uses heuristics to select the most informative pixels in each iteration. In literature, there are several metrics and selection criteria. In this paper, we focus on the uncertainty heuristics for large margin active learning. Existing uncertainty metrics are presented and combined to new ones using support vector machine learning algorithm. Besides, a new methodology is proposed, which automates a priori the choice of the best uncertainty heuristic. This contribution is evaluated on hyperspectral datasets while varying two parameters: class mixing and class balance. Finally discussion and conclusion are drawn.
Northern Ireland’s property market bubble: a preliminary analysis

This article applies a recursive regression technique developed by Phillips and Yu (2011) to examine recent property market movements in both the Republic of Ireland and Northern Ireland in the context of an asset market bubble. This technique, which interprets explosiveness in the price series as evidence of the existence of a bubble, provides a method for identifying not only bubble behaviour but also a dating mechanism. Statistically significant bubble characteristics are identified in both series. For the Republic of Ireland, a prolonged period of explosiveness is detected ranging from 1996Q2 to 2007Q2. Interestingly, the explosiveness is stronger in the late 1990s and early 2000s. For Northern Ireland, the analysis identifies a short yet intense bubble when the market in the Republic had matured, extending from 2005Q3 to 2009Q1 and reaching a peak in 2007Q2. These results taken together indicate the possibility of a spillover effect between the two regions; however, further research to investigate this possibility is necessary.
Angiotensin-converting enzyme gene DD genotype neither increases susceptibility to acute pancreatitis nor influences disease severity.

BACKGROUND The renin-angiotensin system (RAS) has been implied in the pathogenesis of various diseases including acute and chronic pancreatitis. Angiotensin-converting enzyme (ACE) is the key enzyme in activating the RAS. Deletion (D)-type polymorphism in the 16th intron of the ACE gene has been associated with higher serum levels of the enzyme. Inhibition of ACE was found to ameliorate acute pancreatitis in animal models suggesting that ACE plays a role in pathogenesis and progression of acute pancreatitis. Objectives were to investigate the occurrence of the ACE insertion/deletion (I/D) polymorphism in acute pancreatitis patients and its association with the severity of the disease. MATERIAL AND METHODS Seventy-nine acute pancreatitis patients and 95 healthy controls were evaluated. Acute pancreatitis cases were grouped as mild or severe according to the Atlanta criteria. MAIN OUTCOME MEASURE The presence of the ACE I/D polymorphism. RESULTS ACE gene I and D allele frequency of patients (44% and 56%) were similar to controls (45% and 55%, respectively). There were no significant differences in severity of pancreatitis between patients with the ACE-insertion or ACE-insertion/deletion versus ACE-deletion genotypes. CONCLUSIONS The ACE gene deletion polymorphism is neither a risk factor for development of acute pancreatitis nor contributes to the severity of disease or development of complications.
A brief review on offshore wind turbine fault detection and recent development in condition monitoring based maintenance system

Offshore wind turbine requires more systematized operation and maintenance strategies to ensure systems are harmless, profitable and cost-effective. Condition monitoring and fault diagnostic systems ominously plays an important role in offshore wind turbine in order to cut down maintenance and operational costs. Condition monitoring techniques which describing complex faults and failure mode types and their generated traceable signs to provide cost-effective condition monitoring and predictive maintenance and their diagnostic schemes. Continuously monitor the condition of critical parts are the most efficient way to improve reliability of wind turbine. Implementation of Condition Based Maintenance (CBM) strategy provides right time maintenance decisions and Predictive Health Monitoring (PHM) data to overcome breakdown and machine downtime. Fault detection and CBM implementation is challenging for off shore wind farm due to the complexity of remote sensing, components health and predictive assessment, data collection, data analysis, data handling, state recognition, and advisory decision. The rapid expansion of wind farms, advanced technological development and harsh installation sites needs a successful CM approach. This paper aims to review brief status of recent development of CM techniques and focusing with major faults takes place in gear box and bearing, rotor and blade, pitch, yaw and tower system and generator and control system.
Examining the link between coronary heart disease and the elimination of chronic dental infections.

BACKGROUND While it has been suggested that periodontal disease may be associated with coronary heart disease, or CHD, there are no data to suggest that the elimination of chronic dental infections actually lowers the risk of developing chronic CHD. The goal of this study was to determine whether people with a definitive elimination of all potential dental infections--edentulous people, who are at the optimum endpoint of dental infection elimination from a CHD perspective--lower their CHD risk over time when compared with people who have a specific dental infection, periodontitis. METHODS The authors examined data from a prospective cohort of 4,027 people who participated in the First National Health and Nutrition Examination Survey, or NHANES I, Epidemiologic Follow-up Study. The primary outcome measure was the first CHD event. RESULTS During a mean follow-up of 17 years, there were 1,238 CHD events (538 fatal). The confirmed elimination of chronic dental infections did not lead to a decreased risk of experiencing a CHD event (relative risk, 1.02; 95 percent confidence interval, 0.86-1.21). The CHD risk among people with and without chronic dental infections remained constant over time with respect to each other (test for increasing or decreasing trend over time: not significant, chi2(1) = 0.48; P = . 93). CONCLUSIONS People who had a complete, definitive and long-term elimination of all potential dental infections through extraction of all teeth did not have lower CHD risk when compared with people with diagnosed periodontitis. CLINICAL IMPLICATIONS Until evidence is found to the contrary, the authors suggest that prevention of CHD should not be used as the basis for recommending treatment to eliminate chronic dental infections.
Renin Enhancer Is Critical for Control of Renin Gene Expression and Cardiovascular Function*

The important cardiovascular regulator renin contains a strong in vitro enhancer 2.7 kb upstream of its gene. Here we tested the in vivo role of the mouse Ren-1c enhancer. In renin-expressing As4.1 cells stably transfected with Ren-1c promoter with or without enhancer, expression of linked β-geo reporter, stable expression, and colony formation were dependent on the presence of the enhancer. We then generated mice carrying a targeted deletion of the enhancer (REKO mice) and found marked depletion of renin in renal juxtaglomerular and submandibular ductal cells, as well as hyperplasia of macula densa cells. Plasma creatinine was increased, but electrolytes were normal. Male REKO mice implanted with telemetry devices had 9 ± 1 mm Hg lower mean arterial pressure (p < 0.001), which was partly normalized by a high NaCl diet. Locomotor activity was lower, and baroreflex sensitivity was normal. Markedly reduced mean arterial pressure variability in the midfrequency band indicated a contribution of reduced sympathetic vasomotor tone to the hypotension. In conclusion, the renin enhancer is critical for renin gene expression and physiological sequelae, including response to alteration in salt intake. The REKO mouse may be useful as a low renin expression model.
Randomized comparison of a novel anticoagulant, vasoflux, and heparin as adjunctive therapy to streptokinase for acute myocardial infarction: results of the VITAL study (Vasoflux International Trial for Acute Myocardial Infarction Lysis).

BACKGROUND Vasoflux is a low-molecular-weight heparin derivative that inhibits factor IXa activation of factor X and catalyzes fibrin-bound thrombin inactivation by heparin cofactor II. We studied whether vasoflux improves the results of thrombolysis with streptokinase for acute myocardial infarction. METHODS AND RESULTS We randomized 277 patients with acute myocardial infarction to standard intravenous unfractionated heparin (UFH) or intravenous vasoflux 1, 4, 8, or 16 mg/kg as a bolus followed by 1, 4, 8, or 16 mg/kg per hour infusion, on top of streptokinase and aspirin, until angiography at 90 minutes. Patency and corrected Thrombolysis in Myocardial Infarction (TIMI) frame count were studied at 60 and 90 minutes. Rates of TIMI grade 3 flow with vasoflux at any dose (35% to 42%) were not different from UFH (41%) at either time point, nor was the corrected TIMI frame count. However, there was an excess of bleeding in the patients randomized to vasoflux 8 or 16 mg/kg: 78% and 71%, compared with 53% for UFH (P =.004 and.043, respectively). Major bleeding was observed in 13% and 28% at these vasoflux doses compared with 8% with UFH (P =.558 and.01, respectively). CONCLUSION At doses that increase the risk of bleeding, the addition of vasoflux to streptokinase and aspirin did not lead to improved patency rates compared with UFH. Targeting factor IXa and heparin cofactor II may not be a useful adjunct to thrombolysis.
Thyroid Dysfunction States and Incident Cardiovascular Events: The Tehran Thyroid Study

Abstract The objective of the study was to investigate the relation of different thyroid function states with the incidence of cardiovascular disease (CVD)/coronary heart disease (CHD) among a Middle-Eastern population with a high incidence of CVD/CHD. A total of 3975 participants entered the study (43.6% men). According to their thyroid stimulating hormone (TSH) and free thyroxin (FT4) levels, the participants were categorized into 5 groups: euthyroid, subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism, and overt hyperthyroidism. Multivariable Cox proportional hazard models were used to assess the relation of different thyroid function states with incident CVD/CHD, with euthyroid state as reference. The mean age (SD) of the participants was 46.5 (12.0) years. At baseline, no significant difference was observed in the frequency of prevalent CVD cases (n=201) between all groups. No significant interaction was found between prevalent CVD and different thyroid function states with outcomes, hence, we did not exclude participants with prevalent CVD from data analysis. A total of 400 CVD events (358 CHD cases) during a median follow-up of 11.2 years (inter-quartile range: 1.96) occurred. During the follow-up, even in the age and sex adjusted model, no association was observed between different states of thyroid dysfunction and incidence of CVD/CHD. The multivariable hazard ratios (95% CI) of subclinical hypothyroidism, hypothyroidism, subclinical hyperthyroidism, and hyperthyroidism for CVD events were 1.21 (0.77–1.88), 0.76 (0.33–1.69), 0.81 (0.46–1.41) and 1.48 (0.70–3.16), respectively. Both at baseline and during follow-up, no relation was observed between different states of thyroid function with prevalence and incidence of CVD/CHD.
Intrapulmonary Penetration of Voriconazole in Patients Receiving an Oral Prophylactic Regimen

ABSTRACT Voriconazole penetrated well into the pulmonary epithelial lining fluid (ELF) in lung transplant patients receiving oral prophylaxis. The ELF concentrations exceeded those of the plasma, with an average ELF-to-plasma ratio of 11 (±8). A strong association between plasma and ELF concentrations (r2 = 0.95) was noted.
Conformational drift and cryoinactivation of lactate dehydrogenase.

Solutions of porcine lactate dehydrogenase of micromolar concentration kept at 4 degrees C for several days lose the greater part of their enzymic activity but recover it when returned to room temperature. The rate of spoiling decreases and the rate of recovery increases with the concentration of the solutions. The decrease in tetramer stability in the cold is shown by experiments of pressure dissociation at various temperatures and confirmed because isozyme hybridization occurs in parallel with the inactivation at low temperature but is absent at room temperature. Cold-inactivated solutions contain tetramers that dissociate much more readily than those of the fully active solutions. It is postulated that cryoinactivation, like pressure inactivation, takes place through a cycle of dissociation, conformational drift [King, L. , & Weber, G. (1986) Biochemistry (second paper of three in this issue)] and reassociation into inactive tetramers.
Escherichia coli Cytotoxic Necrotizing Factor 1 (CNF1), a Toxin That Activates the Rho GTPase*

Cytotoxic necrotizing factor 1 (CNF1), a 110-kDa protein toxin from pathogenic Escherichia coli induces actin reorganization into stress fibers and retraction fibers in human epithelial cultured cells allowing them to spread. CNF1 is acting in the cytosol since microinjection of the toxin into HEp-2 cells mimics the effects of the externally applied CNF1. Incubation in vitro of CNF1 with recombinant small GTPases induces a modification of Rho (but not of Rac, Cdc42, Ras, or Rab6) as demonstrated by a discrete increase in the apparent molecular weight of the molecule. Preincubation of cells with CNF1 impairs the cytotoxic effects of Clostridium difficile toxin B, which inactivates Rho but not those of Clostridium sordellii LT toxin, which inhibits Ras and Rac. As shown for Rho-GTP, CNF1 activates, in a time- and dose-dependent manner, a cytoskeleton-associated phosphatidylinositol 4-phosphate 5-kinase. However, neither the phosphatidylinositol 4,5-bisphosphate (PIP2) nor the phosphatidylinositol 3,4-bisphosphate (PI 3,4-P2) or 3,4,5-trisphosphate (PIP3) cellular content were found increased in CNF1 treated HEp-2 cells. Cellular effects of CNF1 were not blocked by LY294002, a stable inhibitor of the phosphoinositide 3-kinase. Incubation of HEp-2 cells with CNF1 induces relocalization of myosin 2 in stress fibers but not in retraction fibers. Altogether, our data indicate that CNF1 is a toxin that selectively activates the Rho GTP-binding protein, thus inducing contractility and cell spreading.