Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA methylation predicts survival and response to therapy in patients with myelodysplastic syndromes.

PURPOSE The current classification systems of myelodysplastic syndromes (MDS), including the International Prognostic Scoring System (IPSS), do not fully reflect the molecular heterogeneity of the disease. Molecular characterization may predict clinical outcome and help stratify patients for targeted therapies. Epigenetic therapy using decitabine, a DNA hypomethylating agent, is clinically effective for the treatment of MDS. Therefore, we investigated the association between DNA methylation and clinical outcome in MDS. PATIENTS AND METHODS We screened 24 patients with MDS for promoter CpG island methylation of 24 genes and identified aberrant hypermethylation at 10 genes. We then performed quantitative methylation analyses by bisulfite pyrosequencing of the identified genes in 317 patient samples from three independent studies and assessed relations between methylation and clinical outcome. RESULTS In an initial training cohort of 89 patients with MDS, methylation frequencies of individual genes ranged from 7% to 70% and were highly concordant. Therefore, we defined a methylation z score based on all genes for each patient. We found that patients with higher levels of methylation, compared with patients with lower levels, had a shorter median overall survival (12.3 v 17.5 months, respectively; P = .04) and shorter median progression-free survival (6.4 v 14.9 months, respectively; P = .009). This methylation prognostic model was independent of age, sex, and IPSS group. Applied to two validation cohorts (228 patients), this model was confirmed as an independent prognostic predictor for survival. Although methylation at baseline did not correlate with clinical response to decitabine, we observed a significant correlation between reduced methylation over time and clinical responses. CONCLUSION DNA methylation predicts overall and progression-free survival in MDS.
Secondary school technology education in New Zealand: Does it do what it says on the box?

Technology education, as mandated in the New Zealand Curriculum (Ministry of Education, 2007) provides an opportunity for schools and teachers to offer contextually relevant and innovative curriculum responses. Recent governmental initiatives appear to offer additional transitional pathways for ‘at risk’ students but signpost new challenges for technology teachers who are already experiencing tensions between political agenda, school compliance and community expectations. The research upon which this article is based highlights that even when technology teachers feel motivated and empowered to enact curriculum change in their schools, local constraints require ongoing, negotiated responses to ensure that all of their students’ diverse learning needs are being addressed. This article asserts that the continued political shift towards vocational education through initiatives such as the introduction of the Youth Guarantee Scheme, have the potential to further undermine the position of technology teachers and technology education within the New Zealand secondary schooling system.
A dynamic innovation model for managing capabilities of continuous innovation

Businesses today, under the pressure of fierce market competition, demanding customers, and the advance of technology are required to have the capability to continuously apply new methods and ideas in improving products, internal processes, technologies, and operations in satisfying current and future customers. To be able to capture and construct business opportunities and implement innovative plans, organizations need to dynamically align operational effectiveness with strategic flexibility. This involves a variety of capabilities for organizations to be able to sustain their competitiveness. The primary objective of this study is to investigate the required capabilities for continuous innovation through analysis of the existing literature and examination of empirical cases. A dynamic innovation model (DIM) is proposed with an expectation of accelerating enterprise capabilities in building continuous innovation into the dynamic business environment. The DIM combines the concept of entrepreneurship and resource management and highlights the importance of co-evolving relationships among these capabilities. Findings of a comparison analysis of the DIM for two PC manufacturers, DigiCom and GigaCom, illustrate how the business leaders combined foresight and insight with cyclical processes of resource integration, learning, and transformation in delivering innovations continuously. We argue that DIM offers an interesting and useful analytical framework for the explanation and management of business capabilities for continuous innovation.
Epoxidation of Fatty Acid Methyl Esters derived from Jatropha oil

Fatty Acid Methyl Esters (FAMEs) from transesterification of Jatropha oil were obtained by both acid and base catalyzed transesterification reactions. These FAMEs were epoxidized in or without solvent by either peroxyformic acid or peroxyacetic acid, formed in situ by 30% hydrogen peroxide. n-hexane was used as solvent. Detailed study regarding effects of type and concentration of organic acid used in and without solvent at temperatures 50°C, 60°C and 69°C is presented here. Molar ratio of FAMEs: H2O2 was fixed at 1:3.5 and reaction time was fixed at 6 hours. The formic acid-FAMEs molar ratio was (FAMEs: Formic acid) 1:0.45, while for acetic acid molar ratio was (FAMEs: Acetic acid) 1:0.60. For formic acid, it was found that without solvent, the conversion was 79% while in solvent; it was found that the highest conversion (83%) was obtained at a temperature of 60°C. When acetic acid as oxygen carrier was used, it required 1.5% H2SO4 as catalyst for the reaction in solvent to give maximum conversion of 71%. Without solvent the conversion was 74% at 69°C. The products were analyzed by NMR, GC-MS, FT-IR and volumetric analyses for qualitative and quantitative determinations.
Developing a Culture of Performance Learning in U.K. Public Sector Project Management

The U.K. government is seeking to gain enhanced value from all public expenditure and, in particular, from capital investment activities. As part of this drive for enhanced value, a series of performance measurement and benchmarking protocols have been introduced. Such protocols were introduced into construction procurement. It was realized that if inputs, in terms of good management practices, were to be measured against outputs, these benchmarking protocols could be turned into templates that might be used to influence continual improvement in procurement of capital works and, by extension, public investment elsewhere. This article examined a pilot project to introduce such a form of benchmarking, focusing on the behavioral implications for civil servants charged with delivering on government targets and the industry suppliers with whom they interacted. A number of cultural barriers and tensions were found to exist and possible ways of resolving these are explored in the article.
Enjeux éthiques de la réalité environnementale dans un contexte d'audit financier : une étude empirique

Ethical issues related to environmental accounting present new challenges to the accounting profession. With little by way of relevant accounting and auditing standards, public accountants and statutory auditors face ethical dilemnas in discharging professional responsabilities, especially in forming professional judgements about treatment of environmental issues for the purpose of the audit report. To explore these issues, we present results of a study involving public accountants in a Montreal accounting firm. We review literature on the subject, present an analytic framework and discuss our findings.
Competitive Two-Part Tariffs as a Response to Differential Rates of Time Preference

The major focus of the nonlinear pricing literature has been to demonstrate how welfare in a monopoly can be improved through the use of a nonlinear payment schedule. However, nonlinear prices arise in many different markets. This paper explores nonlinear price equilibria in which both multiple firms and price schedules exist. These outcomes are driven by the use of a sustainability criterion for equilibrium and differential rates of discount as the motivating force for the formation of nonlinear prices. Copyright 1991 by The London School of Economics and Political Science.
Echocardiographic Findings of Patients With Retinal Ischemia or Embolism

Background and Purpose. A potential source of emboli is not detected in more than 50% of patients with retinal arterial occlusive events. Echocardiographic studies are not always included in the diagnostic workup of these patients. The authors studied the diagnostic yield of transthoracic (TTE) and/or transesophageal (TEE) echocardiography in identifying potential sources of emboli in patients with retinal ischemia or embolism. Methods. In a prospective study, 73 consecutive patients with clinically diagnosed retinal ischemia or embolism received a standardized diagnostic workup including retinal photography, echocardiography, and imaging studies of the internal carotid arteries. TTE was performed in 83.6% of patients, TEE was performed in 5.5% of patients, and both TTE and TEE were per‐formed in 11.0% of patients. Ophthalmological diagnoses consisted of amaurosis fugax (n= 28), asymptomatic cholesterol embolism to the retina (n= 34), and branch or central retinal artery occlusion (n= 11). Results. Echocardiography identified a potential cardiac or proximal aortic source for embolism in 16 of 73 (21.9%) patients, including 8 who also had either atrial fibrillation or internal carotid artery stenosis of more than 50% on the side of interest. Thus, 8 of 73 (11.0%) patients had lesions detected only by echocardiography. The most commonly identified lesions were proximal aortic plaque of more than 4 mm thickness (n= 7, 9.6%) and left ventricular ejection fraction of less than 30% (n= 6, 8.2%). TEE was particularly helpful in identifying prominent aortic plaques. Conclusion. Echocardiography frequently identifies lesions of the heart or aortic arch that can act as potential sources for retinal ischemia or embolism. Further studies are needed to evaluate the prognostic and therapeutic relevance of these findings.
[Interobserver variation in ultrasonographic scanning of carotid stenosis].

INTRODUCTION Ultrasonic carotid interna scanning is today the gold standard for diagnosing carotid stenosis in patients with stroke or transient ischemic attack. The procedure of ultrasonic carotid interna scanning is not a well-defined procedure. Knowledge of the reproducibility of the method used in own department is important in order to evaluate its usefulness. MATERIAL AND METHODS Interobserver variability of ultrasonic, duplex carotid artery scanning was examined in 68 carotid arteries in 35 patients by two experienced technologists. The two observers were compared using the kappa (kappa) statistics to analyse the agreement beyond chance. RESULTS kappa was 0.70 (CI: 0.56-0.83) when the stenoses were categorised in the intervals 0-14%, 15-49%, 50-69%, 70-79%, 80-99% and occlusion. Categorising the stenosis in the clinically relevant intervals 0-69%, 70-79% and occlusion which are used to determine if the patient is a candidate or not to carotid endarterectomy yielded a kappa = 0.92 (CI: 0.81-1.00). DISCUSSION Low level stenosis accounted for most variability. If state-of-the-art ultrasonic equipment and experienced technologists are used a high level of reproducibility can be achieved.
The role of the Central Bank in the Economic Slow-down in Russia.

This paper is looking into the causes of the GDP decline in Russia during 2008-2009 and the slow-down of the GDP growth during 2012-2013. The impact of the money supply on the GDP is discussed. Analogies are drawn with the crises in the USA: the Great Depression during 1929-1933 and the 2008-2009 crisis. Possible measures necessary for growth in Russia are investigated.
Essential APSES Transcription Factors for Mycotoxin Synthesis, Fungal Development, and Pathogenicity in Aspergillus flavus

Aflatoxins are a potent carcinogenic mycotoxin and has become a research model of fungal secondary metabolism (SM). Via systematically investigating the APSES transcription factors (TFs), two APSES proteins were identified: AfRafA and AfStuA. These play central roles in the synthesis of mycotoxins including aflatoxin and cyclopiazonic acid, and fungal development and are consequently central to the pathogenicity of the aflatoxigenic A. flavus. Loss of AfRafA not only dramatically suppressed aflatoxin cluster expression, subsequently reducing toxin synthesis both in vitro and in vivo, but also impaired conidia and sclerotia development. More importantly, aflatoxin biosynthesis as well as conidia and sclerotia development were fully blocked in ΔAfStuA. In addition, our results supported that AfStuA regulated the aflatoxin synthesis in an AflR-dependent manner. Intriguingly, it was revealed that AfRafA and AfStuA exert an antagonistic role in the regulation of biosynthesis of cyclopiazonic acid. In summary, two global transcriptional regulators for fungal development, mycotoxin production, and seed pathogenicity of the A. flavus system have been established. The two novel regulators of mycotoxins are promising targets for future plant breeding and for the development of fungicides.
Neurogenic control of renal function in response to graded nonhypotensive hemorrhage in conscious dogs.

The reflex control of plasma renin activity (PRA) and urinary sodium excretion (UNaV) was evaluated in 13 dogs instrumented for chronic study and maintained on a normal sodium intake (40 meq/day). Graded blood volume depletion of 14 (BVD1) and 21% (BVD2) of the estimated total blood volume was used to activate renal sympathetic nerve activity (RSNA), and experiments were conducted before and after bilateral renal denervation (DNX). In dogs with innervated kidneys, nonhypotensive BVD1 increased RSNA 40.9 +/- 10.9% (P < 0.05) above control. Blood volume depletion increased PRA from 1.95 +/- 0.52 to 3.5 +/- 0.57 ng.ml-1 x h-1 and decreased UNaV from 58.2 +/- 10.1 to 35.5 +/- 4.3 mu eq/min without changing renal blood flow or glomerular filtration rate. BVD2 failed to further activate RSNA (52.0 +/- 16.7%) but did increase PRA to 4.85 +/- 0.83 ng.ml-1 x h-1 and decreased UNaV to 17.9 +/- 2.7 mu eq/min. Renal DNX (n = 13) abolished both the PRA and antinatriuretic responses to BVD1 and BVD2. Thus volume-invoked reflex activation of RSNA, but not altered renal hemodynamics, mediates, activation of PRA and antinatriuresis. This neurogenic control of renal function may be critical to the rapid regulation of extracellular fluid volume, via alterations in urinary excretion.
Modification by protons of frog skeletal muscle KATP channels: effects on ion conduction and nucleotide inhibition.

1. The molecular mechanisms underlying pH regulation of skeletal muscle ATP‐sensitive K+ (KATP) channels were studied using the patch clamp technique in the inside‐out configuration. Two effects of intracellular protons were studied in detail: the decrease in magnitude of single‐channel currents and the increase in open probability (Po) of nucleotide‐inhibited channels. 2. The pH dependence of inward unit currents under different ionic conditions was in poor agreement with either a direct block of the pore by protons or an indirect proton‐induced conformational change, but was compatible with the protonation of surface charges located near the cytoplasmic entrance of the pore. This latter electrostatic mechanism was modelled using Gouy‐Chapman‐Stern theory, which predicted the data accurately with a surface charge density of about 0.1 negative elementary charges per square nanometre and a pK (pH value for 50% effect) value for protonation of these charges of 6.25. The same mechanism, i.e. neutralization of negative surface charges by cation binding, could also account for the previously reported reduction of inward unit currents by Mg2+. 3. Intracellular alkalization did not affect Po of the KATP channels. Acidification increased Po. In the presence of 0.1 mM ATP (no Mg2+), the channel activation vs. pH relationship could be fitted with a sigmoid curve with a Hill coefficient slightly above 2 and a pK value of 6. This latter value was dependent on the ATP concentration, decreasing from 6.3 in 30 microM ATP to 5.3 in 1 microM ATP. 4. Conversely, the channel inhibition vs. ATP concentration curve was shifted to the right when the pH was lowered. At pH 7.1, the ATP concentration causing half‐maximal inhibition was about 10 microM. At pH 5.4, it was about 400 microM. The Hill coefficient values remained slightly below 2. Similar effects were observed when ADP was used as the inhibitory nucleotide. 5. These results confirm that a reciprocal competitive link exists between proton and nucleotide binding sites. Quantitatively, they are in full agreement with a steady‐state model of a KATP channel possessing four identical protonation sites (microscopic pK, 6) allosterically connected to the channel open state and two identical nucleotide sites (microscopic ATP dissociation constant, approximately 30 microM) connected to the closed state.
Do Stock Prices Play a Significant Role in Formulating Monetary Policy? A Case Study

The recent fluctuations in stock prices around the world and the critical place that the demand function for money holds in the formulation of a country’s monetary policy motivated us to investigate the question as to whether real stock prices play any significant role in affecting the demand for money and hence monetary policy. Using Australia as a case study we subject the Australian money demand function (containing real money, interest rates, real income, and real stock prices) to a rigorous econometric scrutiny. The methods applied extend the well established cointegration and error-correction framework by analyzing the out of sample properties via generalized variance decompositions, generalized impulse response and persistence profile functions. We also apply the most recently developed technique of ‘long run structural modelling’ (Pesaran and Shin, Econometric Reviews, 2002) which by imposing exactly identifying and overidentifying restrictions on the cointegrating vector has taken care of a major limitation of the conventional cointegrating estimates in that they were atheoretical in nature. We investigate the positive income effects and negative substitution effects of stock prices on money by using short and long form of interest rates together with a narrow and broad definition of money. Our results tend to indicate that stock prices do play a significant role in the money demand function. A clear policy implication is that a failure to incorporate real stock prices in the money demand function may result in the function being unstable and the monetary policy being far less effective.
An innovative approach to molecularly imprinted capillaries for polar templates by grafting polymerization

Molecularly imprinted polymers have been successfully used as selective stationary phases in capillary electrophoresis. Notwithstanding, this technique suffers from several drawbacks as the loss of molecular recognition properties in aqueous media and the lack of feasibility for imprinted systems directed towards highly polar templates soluble in aqueous environments only. Thus, the preparation of imprinted polymers for highly polar, water‐soluble analytes, represents a challenge. In this work, we present an innovative approach to overcome these drawbacks. It is based on a surface molecular imprinting technique that uses preformed macromonomers as both functional recognition elements and cross‐linking agents. A poly‐2‐hydroxyethyl‐co‐methacrylic acid linear polymer was grafted from the surface of silica capillaries. The grafted polymer was exhaustively esterified with methacrylic anhydride to obtain polyethylendimethacrylate‐co‐methacrylic acid linear chains. Then, as a proof of concept, an adequate amount of a very polar template like penicillin V was added in a hydro‐organic mixture, and a thin layer of imprinted polymer was obtained by cross‐linking the polymer linear chains. The binding behaviour of the imprinted and non‐imprinted capillaries was evaluated in different separation conditions in order to assess the presence of template selectivity and molecular recognition effects. The experimental results clearly show that this innovative kind of imprinted material can be easily obtained in very polar polymerization environments and that it is characterized by enhanced molecular recognition properties in aqueous buffers and good selectivity towards the template and strictly related molecules. Copyright © 2012 John Wiley & Sons, Ltd.
Using data from respondent-driven sampling studies to estimate the number of people who inject drugs: Application to the Kohtla-Järve region of Estonia

Estimating the size of key risk populations is essential for determining the resources needed to implement effective public health intervention programs. Several standard methods for population size estimation exist, but the statistical and practical assumptions required for their use may not be met when applied to HIV risk groups. We apply three approaches to estimate the number of people who inject drugs (PWID) in the Kohtla-Järve region of Estonia using data from a respondent-driven sampling (RDS) study: the standard “multiplier” estimate gives 654 people (95% CI 509–804), the “successive sampling” method gives estimates between 600 and 2500 people, and a network-based estimate that uses the RDS recruitment chain gives between 700 and 2800 people. We critically assess the strengths and weaknesses of these statistical approaches for estimating the size of hidden or hard-to-reach HIV risk groups.
Identification of IGF2 signaling through phosphoinositide-3-kinase regulatory subunit 3 as a growth-promoting axis in glioblastoma

Amplification or overexpression of growth factor receptors is a frequent occurrence in malignant gliomas. Using both expression profiling and in situ hybridization, we identified insulin-like growth factor 2 (IGF2) as a marker for a subset of glioblastomas (GBMs) that lack amplification or overexpression of EGF receptor. Among 165 primary high-grade astrocytomas, 13% of grade IV tumors and 2% of grade III tumors expressed IGF2 mRNA levels >50-fold the sample population median. IGF2-overexpressing tumors frequently displayed PTEN loss, were highly proliferative, exhibited strong staining for phospho-Akt, and belonged to a subclass of GBMs characterized by poor survival. Using a serum-free culture system, we discovered that IGF2 can substitute for EGF to support the growth of GBM-derived neurospheres. The growth-promoting effects of IGF2 were mediated by the insulin-like growth factor receptor 1 and phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3), a regulatory subunit of phosphoinositide 3-kinase that shows genomic gains in some highly proliferative GBM cases. PIK3R3 knockdown inhibited IGF2-induced growth of GBM-derived neurospheres. The current results provide evidence that the IGF2–PIK3R3 signaling axis is involved in promoting the growth of a subclass of highly aggressive human GBMs that lack EGF receptor amplification. Our data underscore the importance of the phosphoinositide 3-kinase/Akt pathway for growth of high-grade gliomas and suggest that multiple molecular alterations that activate this signaling cascade may promote tumorigenesis. Further, these findings highlight the parallels between growth factors or receptors that are overexpressed in GBMs and those that support in vitro growth of tumor-derived stem-like cells.