Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessment of P-glycoprotein in patients with malignant bone and soft-tissue tumors using technetium-99m-MIBI scintigraphy.

UNLABELLED Overexpression of P-glycoprotein (Pgp) has been detected in many malignant tumors including bone and soft-tissue tumors. Technetium-99m-MIBI has proved to be a transport substrate for Pgp. The purpose of our study was to explore 99mTc-MIBI as a functional imaging agent reflecting Pgp expression in malignant bone and soft-tissue tumors. METHODS Technetium-99m-MIBI scintigraphy was performed in 30 patients with malignant bone and soft-tissue tumors. Radionuclide angiography with 99mTc-MIBI was done and, at 15 min and 3 hr postinjection of the radiopharmaceutical, imaging was performed. The 99mTc-MIBI uptake ratio was calculated by dividing the lesion count by the background count. The washout rate (WR) for 99mTc-MIBI was calculated by the following formula: WR = 100 x [(Te-Be)-(Td-Bd)]/(Te-Be) (%), where Te and Td = decay-corrected count density of the tumor in the 15-min and 3-hr images, respectively. Be and Bd = decay-corrected count density of the background in the 15-min and 3-hr images, respectively. The lesions were resected by open biopsy to obtain a histopathological diagnosis, and immunohistochemical staining was performed to detect Pgp. RESULTS Twenty-four of 30 patients showed significant uptake at the 15-min image. In these 24 patients, the lesions with a high Pgp expression showed a similar 99mTc-MIBI perfusion index (3.00 +/- 1.04) and uptake ratio (2.05 +/- 0.58) at the 15-min image to those of lesions without a high Pgp expression (2.65 +/- 0.85 and 2.28 +/- 0.64, respectively). On delayed images, the 99mTc-MIBI uptake ratio was lower in patients with a high Pgp expression than in patients without a high Pgp expression (1.37 +/- 0.41 versus 1.87 +/- 0.39, p < 0.01). The washout ratio of 99mTc-MIBI was higher in patients with a high Pgp expression than in patients without a high Pgp expression (66% +/- 25% versus 29% +/- 18%, p < 0.001). None of the 6 patients without 99mTc-MIBI uptake at the 15-min imaging showed 201TI uptake, and only 2 had a high Pgp expression. CONCLUSION In malignant bone and soft-tissue tumors, perfusion and initial 99mTc-MIBI uptake were not related to the Pgp expression; however, washout of 99mTc-MIBI from the tumor was related to Pgp expression. Technetium-99m-MIBI scintigraphy with washout analysis may be a useful method for the evaluation of Pgp overexpression and its function.
Urban Form Relationships with Youth Physical Activity

This article summarizes and synthesizes empirical research on relationships between youth physical activity and urban form across several disciplines, for a planning audience. It highlights how physical activity is characterized, introduces ecological theories of physical activity behavior, provides a conceptual model of interactions between urban form and other influences on youth physical activity behavior, and discusses implications of new evidence for future research and policy. Further research is needed to address several gaps and inconsistencies across studies and to build on recent methodological developments. Despite the limitations of existing research, it is evident that urban form can either serve to constrain or promote physical activity. Urban form interventions have the potential to result in lasting influences on the behavior of large populations of youth.
Effects of Antiviral Usage on Transmission Dynamics of Herpes Simplex Virus Type 1 and on Antiviral Resistance: Predictions of Mathematical Models

ABSTRACT Herpes simplex virus type 1 (HSV-1) causes recurrent herpes labialis (RHL), a common disease afflicting up to 40% of adults worldwide. Mathematical models are used to analyze the effect of antiviral treatment on the transmission of, and the prevalence of drug resistance in, HSV-1 in the United States. Three scenarios are analyzed: no antiviral use, the current level of use, and a substantial increase in nucleoside analogue use, such as might occur if topical penciclovir were available over-the-counter for the treatment of RHL. A basic model predicts that present level of nucleoside analogue use has a negligible effect on HSV-1 transmission and that even if use of topical penciclovir for (RHL) increased substantially, the overall prevalence of infectious HSV-1 is unlikely to be reduced by more than 5%. An expanded model, which allows for acquired resistance and includes immunocompromised hosts and other more realistic features, predicts that current antiviral use is unlikely to lead to any noticeable increase in resistance. If antiviral use increases, the resulting rise in resistance in the population will depend primarily on the probability that immunocompetent hosts will acquire permanent resistance upon treatment. This probability is known to be small, but its exact value remains uncertain. If acquired resistance occurs less than once per 2,500 treated episodes, then in the community at large, the frequency of HSV-1 resistance is predicted to increase slowly, if at all (remaining below 0.5% for >50 years), even with extensive nucleoside analogue use. If acquired resistance emerges in 1 of 625 treated episodes (the maximum of an approximate 95% confidence interval derived from the results of several studies of resistance in treated hosts), then the prevalence of infection with resistant HSV-1 could rise from about 0.2% to 1.5 to 3% within 50 years. The limitations of existing data on acquired resistance and the potential impact of acquired resistance if it occurs are discussed, and strategies are suggested for enhancing information on acquired resistance. The predictions of this model contrast with the more rapid increases in antimicrobial resistance anticipated by models and observed for other pathogenic bacteria and viruses. The reasons for these contrasting predictions are discussed.
Perceptions of genetically modified crops among Danish farmers

Abstract The objective of this paper is to investigate what factors have an impact on farmers' attitude toward accepting genetically modified (GM) crops. For this purpose, a farm survey was conducted and data were subjected to a multinomial logit regression analysis. The main results indicate that approximately 45%, 28%, and 27% of the farmers are positive, negative, and neutral, respectively, toward GM technology. Farm income is the main driver for adoption of the technology. More than 25% of neutral as well as negative farmers will adopt GM crops if farm income improves. Farmers expect improved yields and reduction in the use of herbicides, insecticides, fungicides, and growth regulators. Neutral farmers are additionally concerned about the general risks and resistances that may be attributed to adopting GM crops. While positive farmers are additionally concerned about environment, health hazards, and the limitations on biological diversity within the vicinity of their farms. A significant number of negative farmers would revise their choice if the chemical plant protection inputs are reduced. The age of the farmer has a less clear impact on the attitude toward GM technology.
Translational Medicine and Reliability of Single-Nucleotide Polymorphism Studies: Can We Believe in SNP Reports or Not?

Background: The number of genetic association studies is increasing exponentially. Nonetheless, genetic association reports are prone to potential biases which may influence the reported outcome. Aim: We hypothesized that positive outcome for a determined polymorphism might be over-reported across genetic association studies analysing a small number of polymorphisms, when compared to studies analysing the same polymorphism together with a high number of other polymorphisms. Methods: We systematically reviewed published reports on the association of glutathione s-transferase (GST) single-nucleotide polymorphisms (SNPs) and cancer outcome. Result: We identified 79 eligible trials. Most of the studies examined the GSTM1, theGSTP1 Ile105Val mutation, and GSTT1polymorphisms (n = 54, 57 and 46, respectively). Studies analysing one to three polymorphisms (n = 39) were significantly more likely to present positive outcomes, compared to studies examining more than 3 polymorphisms (n=40) p = 0.004; this was particularly evident for studies analysing the GSTM1polymorphism (p =0.001). We found no significant associations between journal impact factor, number of citations, and probability of publishing positive studies or studies with 1-3 polymorphisms examined. Conclusions: We propose a new subtype of publication bias in genetic association studies. Positive results for genetic association studies analysing a small number of polymorphisms (n = 1-3) should be evaluated extremely cautiously, because a very large number of such studies are inconclusive and statistically under-powered. Indeed, publication of misleading reports may affect harmfully medical decision-making and use of resources, both in clinical and pharmacological development setting.
Determinants of profit heterogeneity at firm level: evidence from Pakistan

Purpose – The purpose of this study is to determine and investigate the relative importance of different factors that result in profit heterogeneity at firm level. Design/methodology/approach – This study uses analysis of variance (ANOVA) random effect model for a broad-based panel data of 337 listed firms for 22 years period from 1987 to 2008 to explain variation in firm profitability. Using ownership structure as a basic criterion, it develops different models to observe the impact of different independent variables on profit variation. Findings – Profitability has a strong relationship with the firm-specific variables. This study demonstrates that for the firms operating in Pakistan, having its own peculiar macroeconomic anomalies, pervasive credit risk, poor corporate governance, and inefficient legal and regulatory framework; leverage is the dominant factor in explaining total variation in profitability and adversely affecting it. Size, liquidity, market share and age have a positive impact on profit.
A vision and strategy for the virtual physiological human in 2010 and beyond

European funding under framework 7 (FP7) for the virtual physiological human (VPH) project has been in place now for nearly 2 years. The VPH network of excellence (NoE) is helping in the development of common standards, open-source software, freely accessible data and model repositories, and various training and dissemination activities for the project. It is also helping to coordinate the many clinically targeted projects that have been funded under the FP7 calls. An initial vision for the VPH was defined by framework 6 strategy for a European physiome (STEP) project in 2006. It is now time to assess the accomplishments of the last 2 years and update the STEP vision for the VPH. We consider the biomedical science, healthcare and information and communications technology challenges facing the project and we propose the VPH Institute as a means of sustaining the vision of VPH beyond the time frame of the NoE.
Evaluating the forecasting performance of linear and nonlinear monetary policy rules for South Africa

This paper compares forecast performance of linear and nonlinear monetary policy rules using South African data. Recursive forecasts values are computed for 1- to 12-steps ahead for the out-of-sample period 2006:01 to 2010:12. For the nonlinear models we use bootstrap method for multi-step ahead forecasts as opposed to point forecasts approach used for linear models. The aim of the paper is to evaluate the performance of three competing models in an out-of-sample forecasting exercise. Overall ranking reveals the superiority of the nonlinear model that distinguishes between downward and upward movements in the business cycles in closely matching the historical record. As such, forecasting performance tests reveal that the South African Reserve bank pays particular attention to business cycles movements when setting its policy rate.
A dominant-negative cyclin D1 mutant prevents nuclear import of cyclin-dependent kinase 4 (CDK4) and its phosphorylation by CDK-activating kinase

Cyclins contain two characteristic cyclin folds, each consisting of five alpha-helical bundles, which are connected to one another by a short linker peptide. The first repeat makes direct contact with cyclin-dependent kinase (CDK) subunits in assembled holoenzyme complexes, whereas the second does not contribute directly to the CDK interface. Although threonine 156 in mouse cyclin D1 is predicted to lie at the carboxyl terminus of the linker peptide that separates the two cyclin folds and is buried within the cyclin subunit, mutation of this residue to alanine has profound effects on the behavior of the derived cyclin D1-CDK4 complexes. CDK4 in complexes with mutant cyclin D1 (T156A or T156E but not T156S) is not phosphorylated by recombinant CDK-activating kinase (CAK) in vitro, fails to undergo activating T-loop phosphorylation in vivo, and remains catalytically inactive and unable to phosphorylate the retinoblastoma protein. Moreover, when it is ectopically overexpressed in mammalian cells, cyclin D1 (T156A) assembles with CDK4 in the cytoplasm but is not imported into the cell nucleus. CAK phosphorylation is not required for nuclear transport of cyclin D1-CDK4 complexes, because complexes containing wild-type cyclin D1 and a CDK4 (T172A) mutant lacking the CAK phosphorylation site are efficiently imported. In contrast, enforced overexpression of the CDK inhibitor p21Cip1 together with mutant cyclin D1 (T156A)-CDK4 complexes enhanced their nuclear localization. These results suggest that cyclin D1 (T156A or T156E) forms abortive complexes with CDK4 that prevent recognition by CAK and by other cellular factors that are required for their nuclear localization. These properties enable ectopically overexpressed cyclin D1 (T156A), or a more stable T156A/T286A double mutant that is resistant to ubiquitination, to compete with endogenous cyclin D1 in mammalian cells, thereby mobilizing CDK4 into cytoplasmic, catalytically inactive complexes and dominantly inhibiting the ability of transfected NIH 3T3 fibroblasts to enter S phase.
Does aversion to the sucker's payoff matter in public goods games?

A usual explanation to low levels of contribution to public goods is the fear of getting the sucker’s payoff (cooperation by the participant and defection by the other players). In order to disentangle the effect of this fear from other motives, we design a public good game where people have an assurance against getting the sucker’s payoff. We show that contributions to the public good under this ‘protective’ design are significantly higher and interact with expectations on other individuals' contribution to the public good. Some policy implications and extensions are suggested.
Line managers: facilitators of knowledge sharing in teams

As human resource management (HRM) and knowledge management are still new areas of research, if we assume the co‐existence of strategic integration, and devolution of HRM responsibilities to line managers, then we can see that an organisation's strategic intent could be to maximise the contribution of employee's knowledge and skills, through creating competitive advantage by utilising human capital. The challenge of “capturing” employee's tacit knowledge, to facilitate its transfer into organisational competence for today's organisations remains paramount. Competitive business pressures are leading to streamlined organisational structures, flatter management layers, adoption of team‐working processes and employee empowerment, which offers line managers a key role in contributing to strategic HRM outcomes by encouraging knowledge sharing in teams. Reviews and discusses the impact of such devolved HR responsibilities on the role of line managers. Intends to: explore the role of line managers facilitating creation and transfer of tacit knowledge in teams; summarise barriers concerning the transfer of tacit knowledge between individuals and teams; and finally outline the importance of developing line managers as facilitators. Aims to construct an agenda outlining future research in this field.
Microarray analysis of prostate cancer progression to reduced androgen dependence: Studies in unique models contrasts early and late molecular events

Three unique variants of the CWR22 human prostate cancer xenograft model (CWR22LD1, LD2, and LD3) with a decrease in dependence on androgens were selected under noncastrate conditions, i.e., by outgrowth after transplantation into male NCR (AT) nu mice without testosterone supplementation. These variants were unable to grow in castrated male mice. For comparison, a second set of variants with even less dependence on androgens (castrate‐resistant) were derived following outgrowth from CWR22 (CWR22Rv1 and RC) or CWRLD1 (CWR22RS) after transplantion in castrated male mice. The androgen receptor (AR) gene in the CWR22LD variants was transcriptionally active and was neither mutated nor significantly overexpressed compared to CWR22. Oligonucleotide microarray analysis showed distinctly different profiles of dysregulated gene expression among the CWR22LD variants. Groups of only 26–41 genes were dysregulated greater than threefold with a different proportion of up versus downregulated genes in each variant. Only one of the castrate‐resistant variants (CWR22Rv1) had a highly overexpressed AR gene but AR in this variant and the two other castrate‐resistant variants, CWR22 RS and RC, was not mutated beyond that seen in CWR22. In contrast to the CWR22LD variants, a total of 342, 295, and 222 genes were dysregulated at least threefold in CWR22Rv1, CWR22RS, and CWR22RC, respectively, differing as well in the proportion of up versus downregulated genes. Many of the genes dysregulated in CWR22LD1, LD2, and LD3 were further dysregulated in CWR22Rv1, RC, or RS. The most downregulated gene was microseminoprotein beta (MSPB). Along with cyclin D1, the most upregulated gene by an order of magnitude compared to other upregulated genes was hepatocyte growth factor (HGF) (scatter factor). These results suggest that the onset in the loss of androgen dependence in CWR22 proceeds through multiple pathways and does not require any direct change in the status of AR. However, upregulation of other survival pathways like that involving HGF in these studies could co‐activate AR signaling. The endogenous overexpression of genes regulating sterol biosynthesis also observed in castrate‐resistant CWR22 variants delineated a clinically relevant, compensatory mechanism for overcoming androgen deprivation reaffirming a central role for AR signaling in this process. © 2004 Wiley‐Liss, Inc.
Some new perfect Steiner triple systems

In a Steiner triple system STS(v)=(V,B), for each pair {a, b} ⊂ V , the cycle graph Ga,b can be defined as follows. The vertices of Ga,b are V \{a, b, c} where {a, b, c} ∈ B. {x, y} is an edge if either {a, x, y} or {b, x, y} ∈ B. The Steiner triple system is said to be perfect if the cycle graph of every pair is a single (v − 3)-cycle. Perfect STS(v) are known only for v = 7, 9, 25 and 33. We construct perfect STS(v) for v = 79, 139, 367, 811, 1531, 25771, 50923, 61339 and 69991.
Intensification of cocoa agroforestry systems as a REDD+ strategy in Cameroon: hurdles, motivations, and challenges

Tree planting and the use of inputs within cocoa agroforestry systems are key intensification pathways for enhancing the contribution of these systems to REDD+. However, scholarship on the hurdles, motivations, and challenges pertaining to intensification of these systems remains surprisingly scanty. A questionnaire addressing these knowledge gaps was administered to 461 cocoa farmers randomly selected from 10 communities in the South Region of Cameroon. The lack of technical support was identified as one of the main obstacles to tree planting and the use of inputs. The least motivating factor behind tree planting and the use of inputs was inadequate technical assistance. Limited access to credit facilities was observed as of the most important challenges to tree planting and the use of inputs. Addressing the various hurdles and challenges and promoting the least motivation factor through proper incentive mechanisms could advance REDD+ since intensification pathways within these systems increase agricultural productivity thereby enabling farmers to stay on the same land. This results in less forest being cleared and allows for the recovery of forests degaraded for the creation of these systems. In closing, we proffer incentive mechansims for promoting intensification pathways within these cocoa agroforestry systems.
An Analysis of the Performance of SSIs in the Era of Globalization

Small Scale Industries (SSIs) have a significant role to play in the socioeconomic upliftment of developing countries like India. The SSIs occupy a unique position in the Indian economy for its contribution towards value-addition, employment generation, expansion of entrepreneurial base, and also for the diversification of the industrial sector. After independence, the Indian government recognized the importance of developing SSIs and incorporated the same in its industrial policy. India initiated the economic reforms in 1991 with the objective of faster economic growth. Since, the liberalization process has been in vogue for the past 16 years, it becomes essential to analyze whether the new economic order has had a positive or negative impact on the performance of SSIs in India. The present paper is an attempt in this direction. The findings reveal that the growth in the share of exports of SSIs in total exports of India was higher in pre-liberalization period than the post-liberalization period. Compound Annual Growth Rate (CAGR), with reference to the number of units, employment level, production, and value of plant and machinery in SSIs were also comparatively higher in the pre-liberalization period. The percentage share of SSI sector in total bank credit and in total outlay of various five year plans has also declined significantly. Moreover, this sector is growing at a rate half of the total industrial growth rate. Obviously, the SSI sector could not grow to the desired level due to intense competition from large and medium sized domestic and multinational companies. Essentially, the objective of the policymakers as well as small industry associations should be to enable the sector to be vibrant and competitive. Now, it has become essential for the small and medium enterprises to focus on R&D not only to improve the overall quality, but also to deliver a superior product in the market.
New research instruments for government: measuring community engagement

Australian contemporary public administration is characterised by the re-emergence of community as a useful category across a range of policy-making and service delivery areas. The background to this introduction of social factors to balance the market oriented instruments of the New Public Management (NPM) has been the subject of considerable commentary (Smyth et al., 2005; Vinson, 2004; Considine, 2004). Less attention has been paid to the actual instruments needed to make community a practical part of policy making and public management. This chapter outlines progress to date in Victoria in establishing what could become a national measurement framework for engaging communities.