Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative Analysis of Estrogen Receptor Expression Shows SP1 Antibody Is More Sensitive Than 1D5

Studies comparing rabbit monoclonal SP1 antibody with 1D5 for estrogen receptor (ER) immunohistochemical testing show conflicting results. Here we use a standardized quantitative immunofluorescent (QIF) ER assay to determine the level and significance of discordance between the antibodies. Both antibodies were assessed by QIF on our Index TMA of cell lines and case controls, followed by QIF and immunohistochemical analysis on 2 retrospective cohorts from Yale. On the Index TMA, SP1 displayed stronger signal-to-noise ratio compared with 1D5. On the patient cohorts, the range of discrepancy between the 2 antibodies was 8% to 16.9%, with the majority of discrepant cases being SP1 positive/1D5 negative. Kaplan-Meier analysis of the discrepant cases showed outcomes comparable to those of double-positive cases, suggesting that SP1 is more sensitive than 1D5. A series of cases with high levels of ER-&bgr; shows that neither antibody cross-reacts, suggesting equivalent specificity. Future efforts are needed to determine whether response to endocrine therapies show superiority of either antibody as a companion diagnostic test.
Temperature-Dependence of Glyphosate-Based Herbicide's Effects on Egg and Tadpole Growth of Common Toads

Glyphosate-based herbicide formulations are broadly used in agriculture, silviculture, horticulture as well as in private gardens all over the world, thus posing the risk of potential contamination of nearby aquatic bodies inhabited by amphibians. Concurrently, climate change can be expected to alter the temperature of amphibian breeding sites. However, while either glyphosate-based herbicides or temperature have been shown to separately affect the development of amphibians, very little is known on possible interactive effects. We studied the impact of herbicide concentrations and temperature on growth and development of eggs and tadpoles of the Common toad (Bufo bufo L.). We hypothesized that (i) eggs would be better protected against herbicides than tadpoles because of their jelly coating, (ii) that higher temperatures would reduce potential herbicide effects because of an accelerated growth and a lower sensitivity of larger specimens. We conducted one experiment starting with eggs (Gosner stage, GS 9) and another experiment starting with tadpoles (GS 21-24) using a full factorial design with 5 concentrations of the herbicide formulation Roundup® LB Plus (0 mg acid equivalent L-1, 0.5 mg a.e. L-1, 1.0 mg a.e. L-1 or 1.5 mg a.e. L-1 and a pulse treatment with 3-4 times addition of 0.5 a.e. mg L-1 over the course of several weeks) and two temperature levels (15°C and 20°C). Contrary to our expectation, our results showed that toad eggs are more sensitive to herbicides than tadpoles leading to an averaged 31% increase in total length, tail length and body length compared to the herbicide-free control. Tadpole morphology, development or mortality was not influenced by herbicides. Higher temperature accelerated growth of both eggs and tadpoles. This is among the first study showing interactive effects between herbicides and temperature especially for egg development resulting in more pronounced herbicide effects at lower temperatures than at higher temperatures.
The Loyalties of Top Public Administrators

Images of the modern public administrator clash with yesteryear's neutral public servants obediently carrying out the orders of elected politicians. Partly influenced by the literature on New Public Management, people often argue that public administrators today should ensure quality services, give value for public funds, be responsive, operate strategically, uphold organizations' reputations, and the like. They thus seem to serve many masters, not just politicians, but do the various masters' interests harmonize or contradict? The research question of this article is: Where do the loyalties of public administrators lie? The answer involves all the potential objects of their loyalties: colleagues, the public good, moral imperatives, the law, their organizations, the organizations' clients, and elected officials. What is the composition of loyalty for top public administrators? What are their conceptions of loyalty? With the use of Q-methodology, we identify and describe four distinct types of public administrators within the context of loyalty: (a) by-the-book professionals, (b) society's neutral servants, (c) the personally grounded, and (d) open and principled independents. These conceptions matter because they indicate how administrators behave and make decisions. © The Author 2010. Published by Oxford University Press on behalf of the Journal of Public Administration Research and Theory, Inc. All rights reserved.
Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: case-control analysis within a UK primary care cohort

Objective To examine the hypothesis that risk of oesophageal, but not of gastric or colorectal, cancer is increased in users of oral bisphosphonates. Design Nested case-control analysis within a primary care cohort of about 6 million people in the UK, with prospectively recorded information on prescribing of bisphosphonates. Setting UK General Practice Research Database cohort. Participants Men and women aged 40 years or over—2954 with oesophageal cancer, 2018 with gastric cancer, and 10 641 with colorectal cancer, diagnosed in 1995-2005; five controls per case matched for age, sex, general practice, and observation time. Main outcome measures Relative risks for incident invasive cancers of the oesophagus, stomach, and colorectum, adjusted for smoking, alcohol, and body mass index. Results The incidence of oesophageal cancer was increased in people with one or more previous prescriptions for oral bisphosphonates compared with those with no such prescriptions (relative risk 1.30, 95% confidence interval 1.02 to1.66; P=0.02). Risk of oesophageal cancer was significantly higher for 10 or more prescriptions (1.93, 1.37 to 2.70) than for one to nine prescriptions (0.93, 0.66 to 1.31) (P for heterogeneity=0.002), and for use for over 3 years (on average, about 5 years: relative risk v no prescription, 2.24, 1.47 to 3.43). Risk of oesophageal cancer did not differ significantly by bisphosphonate type, and risk in those with 10 or more bisphosphonate prescriptions did not vary by age, sex, smoking, alcohol intake, or body mass index; by diagnosis of osteoporosis, fracture, or upper gastrointestinal disease; or by prescription of acid suppressants, non-steroidal anti-inflammatory drugs, or corticosteroids. Cancers of the stomach and colorectum were not associated with prescription of bisphosphonate: relative risks for one or more versus no prescriptions were 0.87 (0.64 to 1.19) and 0.87 (0.77 to 1.00). The specificity of the association for oesophageal cancer argues against methodological problems in the selection of cases and controls or in the analysis. Conclusions The risk of oesophageal cancer increased with 10 or more prescriptions for oral bisphosphonates and with prescriptions over about a five year period. In Europe and North America, the incidence of oesophageal cancer at age 60-79 is typically 1 per 1000 population over five years, and this is estimated to increase to about 2 per 1000 with five years’ use of oral bisphosphonates.
Distributed asynchronous controllers for clock management in low power systems

In digital electronic systems, the power consumption is nowadays a standard non-functional specification. Therefore the design of such complex SoCs in the nanoscale technologies is now constrained by many parameters such as the energy consumption and the robustness to process variability. Basically the implementation of a gated clock structure is a good way to limit the dynamic power consumption. Nevertheless, this needs extra computation to determine which part of the circuit has to be switched off. Moreover, the insertion of asynchronous interfaces instead of synthezising gated clock in an existing system is one way to quickly provide a robust framework for power reduction. In this paper, we introduced a novel methodology-based on a set of simple distributed asynchronous controllers - to efficiently implement gated clock at the system level. This approach has been successfully applied to an AXI bus-based system with a negligible hardware cost compared to the equivalent fully-synchronous system. The obtained results indicate that the proposed technique can have a significant impact on the power consumption with a low redesign cost.
Regulation of DOPA Decarboxylase Activity in Brain of Living Rat

Abstract: To test the hypothesis that l‐DOPA decarboxylase (DDC) is a regulated enzyme in the synthesis of dopamine (DA), we developed a model of the cerebral uptake and metabolism of [3H]DOPA. The unidirectional blood‐brain clearance of [3H]DOPA (KD1) was 0.049 ml g−1 min−1. The relative DDC activity (kD3) was 0.26 min−1 in striatum, 0.04 min−1 in hypothalamus, and 0.02 min−1 in hippocampus. In striatum, 3,4‐[3H]dihydroxyphenylacetic acid ([3H]DOPAC) was formed from [3H]DA with a rate constant of 0.013 min−1, [3H]homovanillic acid ([3H]HVA) was formed from [3H]DOPAC at a rate constant of 0.020 min−1, and [3H]HVA was eliminated from brain at a rate constant of 0.037 min−1. Together, these rate constants predicted the ratios of endogenous DOPAC and HVA to DA in rat striatum. Pargyline, an inhibitor of DA catabolism, substantially reduced the contrast between striatum and cortex, in comparison with the contrast seen in autoradiograms of control rats. At 30 min and at 4 h after pargyline, kD3 was reduced by 50% in striatum and olfactory tubercle but was unaffected in hypothalamus, indicating that DDC activity is reduced in specific brain regions after monoamine oxidase inhibition. Thus, DDC activity may be a regulated step in the synthesis of DA.
Political manoeuvrings as sources of measurement errors in forecasts

We test the extent to which political manoeuvrings can be the sources of measurement errors in forecasts. Our objective is to examine the forecast error based on a simple model in which we attempt to explain deviations between the March budget forecast and the November forecast, and deviations between the outcome and the March budget forecast in the UK. The analysis is based on forecasts made by the general government. We use the forecasts of the variables as alternatives to the outcomes. We also test for political spins in the GDP forecast updates and the GDP forecast errors. We find evidence of partisan and electoral effects in forecast updates and forecast errors. Copyright © 2005 John Wiley & Sons, Ltd.
Community Benefits Agreements: Opportunities and Traps for Developers, Municipalities, and Community Organizations

Abstract A Community Benefits Agreement (CBA) is a private contract negotiated between a prospective developer and community representatives. In essence, the CBA specifies the benefits that the developer will provide to the community in exchange for the community's support of its proposed development. A promise of community support may be especially useful to a developer seeking government subsidies or project approvals.
Cytogenetic and molecular mechanisms of resistance to imatinib.

Selective inhibition of the BCR-ABL tyrosine kinase by imatinib (Gleevec) (formerly STI571) is a promising new therapeutic strategy in patients with chronic myelogenous leukemia (CML). Despite significant hematologic and cytogenetic responses, resistance occurs in patients with chronic phase (CP) and advanced disease. A cohort of 72 patients with CML in myeloid blast crisis (BC) (n = 34), lymphoid BC (n = 2), accelerated phase (AP) (n = 16), CP (n = 18), and BCR-ABL(+) acute lymphoblastic leukemia (ALL) (n = 2) resistant to imatinib were investigated. Median levels of BCR-ABL transcripts, determined by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR), were not significantly changed at the time of resistance, but seven of 55 patients showed a greater than 10-fold increase in BCR-ABL levels. Genomic amplification of BCR-ABL was found in two of 32 patients evaluated by fluorescence in situ hybridization (FISH). Additional chromosomal aberrations were observed in 19 of 36 patients and point mutations of the ABL tyrosine kinase domain resulting in reactivation of the BCR-ABL tyrosine kinase were detected in 29 of 72 patients. Resistance may be caused by BCR-ABL-independent or BCR-ABL-dependent mechanisms. A thorough evaluation of resistant cases is required to suggest therapeutic measures in the individual case. Clonal selection of resistant cells harboring a BCR-ABL mutation might be reversed by stopping imatinib therapy and switching to chemotherapy. Combination therapy from the start of treatment to reduce the frequency of resistance is currently being evaluated with several drugs.
Stem cell factor and leukemia inhibitory factor promote primordial germ cell survival by suppressing programmed cell death (apoptosis).

Proliferating primordial germ cells (PGCs) isolated from mouse embryos soon after their arrival in the genital ridges would only survive in vitro at temperature of less than 30 degrees C (De Felici, M. and McLaren, A. (1983). Exp. Cell. Res. 144, 417-427; Wabik-Sliz, B. and McLaren, A. (1984). Exp. Cell. Res. 154, 530-536) or when co-cultured on cell feeder layers (Donovan, P. J., Stott, D., Godin, I., Heasman, J. and Wylie, C. C. (1986). Cell 44, 831-838; De Felici, M. and Dolci, S. (1991). Dev. Biol. 147, 281-284). In the present paper we report that mouse PGC death in vitro occurs with all the hallmarks of programmed cell death or apoptosis. We found that after 4-5 hours in culture many PGCs isolated from 12.5 dpc fetal gonads assumed a nuclear morphology and produced membrane bound fragments (apoptotic bodies) typical of apoptotic cells. In addition, PGCs in culture accumulated high level of tissue transglutaminase (tTGase; an enzyme that is induced and activated during apoptosis) and showed extensive degradation of DNA to oligonucleosomal fragments, which is characteristic of apoptosis. The physiological relevance of this mechanism of PGC death is supported by the finding that some PGCs undergoing apoptosis, as revealed by the high level of tTGase expression, were detected in the embryo. Most importantly, we show that the addition of stem cell factor (SCF) or leukemia inhibitory factor (LIF) to the culture medium, two cytokines known to favour PGC survival and/or proliferation in vitro, markedly reduced the occurrence of apoptosis in PGCs during the first hours in culture. (ABSTRACT TRUNCATED AT 250 WORDS)
Vascular failure and recent anti-diabetic drugs

Type 2 diabetes mellitus (T2DM) is highly prevalent and is a critical risk factor for cardiovascular (CV) disease, increasing both morbidity and mortality. T2DM is one of the most important classical CV risk factors that promote atherosclerosis. Therefore, it is important for both patients with T2DM and their doctors to identify vascular dysfunction at an early stage of atherosclerosis. Recently, new therapies based on the actions of the incretin hormones and blockade of sodium glucose transporter (SGLT) 2 have become widely used, because they offer advantages over conventional treatments by achieving glycemic control and/or possible reducing CV risks. Many experimental studies have suggested that glucagon-like peptide (GLP)-1 and dipeptidyl peptidase (DPP)-4 inhibitors exert cardioprotective effects on atherosclerosis and cardiac dysfunction both in vitro and in vivo. However, thus far, there is little clinical evidence supporting the efficacy of incretin therapy in patients with CV disease. In contrast, the SGLT2 inhibitor empagliflozin achieved a remarkable reduction in CV-related mortality in a large clinical study. The present review focuses on the effects of GLP-1-related therapies and SGLT2 inhibitors on clinical indices of endothelial function.
Price Promotions and Trade Deals with Multiproduct Retailers

In this paper we study retail price promotions and manufacturer trade deals in markets with multiproduct retailers. We find that in situations where retailers carry more than one competing brand, the promotions across brands can be positively or negatively correlated depending on the structure of the market: the relative sizes of the various market segments (in terms of loyalty to manufacturer, retailer, or the pair manufacturer-retailer). We show that sometimes retailers offer the same discount on different products, but at other times they offer a smaller discount on a brand supported by a bigger trade deal. We also present results on the effects of changes in the sizes of the different market segments on the depth of price promotions and trade deals and on pass through.
Information and Knowledge Management at South African Law Firms

Global and national law firms alike operate in a challenging business environment and managing the firm's information and knowledge assets is increasingly viewed as a key factor in efficient legal service delivery. In legal practice, information management technologies, for example intranets, portals, workflow management systems, document and content management systems, case and project management systems and online dispute resolution systems are becoming important means of legal service delivery. The reason for applying information management technologies and implementing knowledge management strategies in law firms is not only to satisfy clients' growing need for a trusted online platform to interact with legal service providers, but for law firms to capitalise on their intellectual assets, to continuously modernise legal practice management, to empower lawyers, to increase productivity, to use time efficiently, to transfer skills and knowledge from senior to junior professionals, to improve service delivery and to gain competitive advantage. This article firstly reviews the role of information and knowledge management in providing an effective legal service to clients and compares foreign and South African law firms' information management related contexts, challenges and benefits. Secondly, it presents the findings of a survey conducted at South African law firms based on their knowledge management practices. The aim of the article is to provide insights into law firm knowledge management and its effect on providing legal services in an online business environment.
Polar Bear Viewers as Deep Ecotourists: How Specialised Are They?

Individuals visiting natural areas, such as national parks, or engaging in certain outdoor recreation activities like birdwatching, are often assumed to be ecotourists and also concomitantly assumed to be highly specialised by virtue of their behaviour. In this study, tourists visiting the Churchill Wildlife Management Area in Canada to view polar bears are examined using a comprehensive index of specialisation and compared to selected demographic variables and indicators of environmental concern. The results suggest that these visitors reflect a wide range of levels of specialisation, and that the majority of visitors are novices who might not share the same degree of concern for the environment or the same motives for visiting as their more specialised counterparts. Concerns for management of natural areas for wildlife viewing are raised based on these findings.
Brand marketing management in China cigarette enterprises

With the competition environment of economic globalization and market internationalization, this paper systematically analyzes some important points of brand and competitiveness, attempts to generalize the main sources of cigarette brand competitiveness from both intrinsic and extrinsic aspects. At the initial phase of brand development, cigarette brand image and impression are of great importance, so as to intensify the awareness and recognition of potential cigarette customers. Then, cigarette enterprises must focus on brand relations and loyalty. At the end of product life cycle, the restoration of cigarette brand value cannot be over stressed to retain consumers. The conclusion indicates major brand factors must be constantly stressed to achieve cigarette brand competitiveness, and then generate marketing strategies for the prospective cigarette markets.
Cyclic Scheduling via Integer Programs with Circular Ones

A fundamental problem of cyclic staffing is to size and schedule a minimum-cost workforce so that sufficient workers are on duty during each time period. This may be modeled as an integer linear program with a cyclically structured 0-1 constraint matrix. We identify a large class of such problems for which special structure permits the ILP to be solved parametrically as a bounded series of network flow problems. Moreover, an alternative solution technique is shown in which the continuous-valued LP is solved and the result rounded in a special way to yield an optimum solution to the ILP.
“Concave islands”: Habitat heterogeneity of parafluvial ponds in a gravel-bed river

Floodplain pond distribution, density, and diversity were investigated along the active river corridor of the Tagliamento River in northeastern Italy, the last major semi-natural river in Central Europe. Along the corridor, ponds peaked in bar- and island-braided floodplains but were absent in constrained sections. Within the main study area, a 1.0-km2 large braided floodplain, the number of ponds containing water-level fluctuations were the most important variables determining pond characteristics and heterogeneity. Results from a PCA on environmental variables distinguished four groups of ponds distributed along a hydrologic and thermal gradient. Parafluvial ponds are short-lived, discrete, aquatic “islands” within the floodplain matrix. They are expected to contribute disproportionately to aquatic biodiversity; however, they are very sensitive landscape elements that disappear as a consequence of river regulation, wood removal, and flow control.
Imported Inflation: The Evidence from India

In the backdrop of recent developments in global commodity prices, this study provides analytical and empirical perspectives on imported inflation in the Indian context. Sources and commodity-wise trends in imported inflation are analysed during the last four decades. Empirical analysis suggests that at the global level, export of inflation from oil exporting countries is significantly higher than that of industrial and non-oil developing countries including Asia. At the same time, despite low domestic inflation, export of inflation from industrial countries is significantly higher than that of non-oil developing countries. Inflation in India is positively influenced by import price, capital flows and exchange rate. Based on a non-parametric approach, import price inflation on an average accounts for about 1 to 2 percentage points increase in domestic inflation. Within the framework of the vector error correction and cointegration model, about 5 percentage points increase in import prices contribute to 1 to 1.5 percentage points increase in domestic prices. In terms of variance decomposition analysis, capital flows have a greater impact on domestic inflation, deriving from the former’s association with exchange rate and import prices.