Miracle-dz/UniFAR-FTUs huggingface dataset:
Fibroblast Growth Factor Receptor 3 Is a Rational Therapeutic Target in Bladder Cancer

Activating mutations of fibroblast growth factor receptor-3 (FGFR3) have been described in approximately 75% of low-grade papillary bladder tumors. In muscle-invasive disease, FGFR3 mutations are found in 20% of tumors, but overexpression of FGFR3 is observed in about half of cases. Therefore, FGFR3 is a particularly promising target for therapy in bladder cancer. Up to now, most drugs tested for inhibition of FGFR3 have been small molecule, multityrosine kinase inhibitors. More recently, a specific inhibitory monoclonal antibody targeting FGFR3 (R3Mab) has been described and tested preclinically. In this study, we have evaluated mutation and expression status of FGFR3 in 19 urothelial cancer cell lines and a cohort of 170 American patients with bladder cancer. We have shown inhibitory activity of R3Mab on tumor growth and corresponding cell signaling in three different orthotopic xenografts of bladder cancer. Our results provide the preclinical proof of principle necessary to translate FGFR3 inhibition with R3Mab into clinical trials in patients with bladder cancer. Mol Cancer Ther; 12(7); 1245–54. ©2013 AACR.
TQM PRACTICES: CONTINUOUS IMPROVEMENT AND PROBLEM PREVENTION

This study focus on the impact of continuous improvement and problem prevention on workers of public and private organizations that have implemented TQM practices. The results of the study show that organizations that implement some degree of continuous improvement and problem prevention, their employees experience some positive impact on job satisfaction and organizational commitment. On the other hand, continuous improvement and problem prevention lack of significant relationship with job involvement and career satisfaction. Thus, top management should pay more attention to continuous improvement and problem prevention, and constantly look ahead on how can they correct and prevent problems and make improvements.
Blood oxygenation level‐dependent (BOLD)‐based techniques for the quantification of brain hemodynamic and metabolic properties – theoretical models and experimental approaches

The quantitative evaluation of brain hemodynamics and metabolism, particularly the relationship between brain function and oxygen utilization, is important for the understanding of normal human brain operation, as well as the pathophysiology of neurological disorders. It can also be of great importance for the evaluation of hypoxia within tumors of the brain and other organs. A fundamental discovery by Ogawa and coworkers of the blood oxygenation level‐dependent (BOLD) contrast opened up the possibility to use this effect to study brain hemodynamic and metabolic properties by means of MRI measurements. Such measurements require the development of theoretical models connecting the MRI signal to brain structure and function, and the design of experimental techniques allowing MR measurements to be made of the salient features of theoretical models. In this review, we discuss several such theoretical models and experimental methods for the quantification of brain hemodynamic and metabolic properties. The review's main focus is on methods for the evaluation of the oxygen extraction fraction (OEF) based on the measurement of the blood oxygenation level. A combination of the measurement of OEF and the cerebral blood flow (CBF) allows an evaluation to be made of the cerebral metabolic rate of oxygen consumption (CMRO2). We first consider in detail the magnetic properties of blood – magnetic susceptibility, MR relaxation and theoretical models of the intravascular contribution to the MR signal under different experimental conditions. We then describe a ‘through‐space’ effect – the influence of inhomogeneous magnetic fields, created in the extravascular space by intravascular deoxygenated blood, on the formation of the MR signal. Further, we describe several experimental techniques taking advantage of these theoretical models. Some of these techniques – MR susceptometry and T2‐based quantification of OEF – utilize the intravascular MR signal. Another technique – quantitative BOLD – evaluates OEF by making use of through‐space effects. In this review, we target both scientists just entering the MR field and more experienced MR researchers interested in the application of advanced BOLD‐based techniques to the study of the brain in health and disease. Copyright © 2012 John Wiley & Sons, Ltd.
Double bottom lines in microfinance: are they mutually exclusive?

Microfinance institutions (MFIs) are generally constrained by double bottom lines: keep the original social mission intact by serving the poor soutenue (the first bottom line) and attain financial sustainability (the second bottom line). However, these two bottom lines can be mutually exclusive in effect. This paper demonstrates how factor analysis, a multivariate statistical tool, can be utilized to examine this conjecture. First, factor analysis is used to construct two simulated performance indicators combining original variables, each one representing a distinct dimension of performance. Then, individual scores ascribed to MFIs on each factor are used as the dependent variables of two simultaneous-equations models that present new evidence on the determinants of MFIs’ performance and mission drift.
Transient, Phorbol Ester-induced DOC2-Munc13 Interactions in Vivo *

Munc13-1 and DOC2 have been implicated in the regulation of exocytosis. Here we demonstrate in vivo that these two proteins undergo a transient phorbol ester-mediated and protein kinase C-independent interaction, resulting in the translocation of DOC2 from a vesicular localization to the plasma membrane. The translocation of DOC2 is dependent upon the DOC2 Munc interacting domain that binds specifically to Munc13-1, whereas the association of DOC2 with intracellular membranes is dependent on its C2 domains. This is the first direct in vivo demonstration of a protein-protein interaction between two presynaptic proteins and may represent a molecular basis for phorbol ester-dependent enhancement of exocytosis.
Challenges in optimizing chemoradiation in locally advanced non small-cell lung cancers in India

Abstract Data supporting use of concurrent chemoradiation in locally advanced lung cancers comes from clinical trials from developed countries. Applicability and outcomes of such schedules in developing countries is not widely reported. There are various challenges in delivering chemoradiation in locally advanced non small cell lung cancer in developing countries which is highlighted by an audit of patients treated with chemoradiation in our center. This article deals with the challenges in the context of a developing country. We conclude that sequential chemoradiotherapy is better tolerated than concurrent chemoradiation in Indian patients with locally advanced non-small cell lung cancers. Patients with stage IIIa, normal weight or overweight, and adequate baseline pulmonary function should be offered concurrent chemoradiation.
Principles and Applications of Capillary Electrophoresis in New Drug Discovery

This review article focuses on the use of capillary electrophoresis (CE) techniques for performing high throughput drug discovery and development applications. The various examples using CE systems for performing physicochemical profiling, chiral separations, enzyme and inhibitor activity screening, metabolomic analysis, immunoassay, protein analysis and genetic analysis were presented.
Service elimination decision making: preliminary empirical evidence from the UK financial services sector

Reports on part of the findings of a broader exploratory investigation into the service elimination decision making behaviour in the UK financial services sector. The issues tackled in this paper are: the degree of planning for the service elimination decision‐making process; the formality of service elimination procedures; the place of service elimination within the broader range of service range management activities; and the relative importance of the process of service elimination compared to the process of new service development (NSD). The empirical evidence from 20 in‐depth interviews with marketing directors and managers suggests that UK financial institutions: do not always follow a planned service elimination decision‐making process; have largely informal service elimination procedures; tend to see service elimination activities as ad hoc rather than as a part of service range management activities; and favour the process of NSD considerably more than the process of service elimination. Concludes by discussing the theoretical and practical implications of the findings and by suggesting future research directions.
Laboratory Diagnosis of Dengue Infection: Current Techniques and Future Strategies

Dengue is an increasingly significant vector-borne infectious disease, with over 50 million cases reported in more than half the world’s recognised independent states. Dengue fever, dengue haemorrhagic fever and dengue shock syndrome are distinct clinical forms of an infection that is caused by Dengue Virus, a member of the Flaviviridae family. All four well characterized serotypes of the virus can cause the full spectrum of disease from asymptomatic infection to life-threatening symptoms. For effective prevention and/or treatment of disease symptoms, early and rapid detection of virus in specimens collected from clinically suspected persons is a requirement that remains challenging. A positive laboratory diagnosis is essential to confirm dengue virus infection and hence to inform patient therapy. Here, we consider the pros and cons of currently available methods for identification, ranging from conventional to sophisticated tests. Reports indicate the use of a variety of diagnostic methods of varying sensitivity, highlighting the necessity for standardisation and quality control. Several novel approaches are in development and demand further evaluation.
Acute diarrhoea associated with Cryptosporidium sp in Belém, Brazil (preliminary report).

Cryptosporidium sp was detected in faeces from three children suffering from acute diarrhoea. In two cases no other concomitant agents were detected and in a 3rd. this agent was associated with Entamoeba histolytic, Entamoeba coli, Endolimax nana, Chilomastix mesnili and Pentatricbomonas hominis.
SURF: Subject-Adaptive Unsupervised ECG Signal Compression for Wearable Fitness Monitors

Recent advances in wearable devices allow non-invasive and inexpensive collection of biomedical signals including electrocardiogram (ECG), blood pressure, respiration, among others. Collection and processing of various biomarkers are expected to facilitate preventive healthcare through personalized medical applications. Since wearables are based on size- and resource-constrained hardware, and are battery operated, they need to run lightweight algorithms to efficiently manage energy and memory. To accomplish this goal, this paper proposes SURF, a subject-adaptive unsupervised signal compressor for wearable fitness monitors. The core idea is to perform a specialized lossy compression algorithm on the ECG signal at the source (wearable device), to decrease the energy consumption required for wireless transmission and thus prolong the battery lifetime. SURF leverages unsupervised learning techniques to build and maintain, at runtime, a subject-adaptive dictionary without requiring any prior information on the signal. Dictionaries are constructed within a suitable feature space, allowing the addition and removal of code words according to the signal’s dynamics (for given target fidelity and energy consumption objectives). Extensive performance evaluation results, obtained with reference ECG traces and with our own measurements from a commercial wearable wireless monitor, show the superiority of SURF against state-of-the-art techniques, including: 1) compression ratios up to 90-times; 2) reconstruction errors between 2% and 7% of the signal’s range (depending on the amount of compression sought); and 3) reduction in energy consumption of up to two orders of magnitude with respect to sending the signal uncompressed, while preserving its morphology. SURF, with artifact prone ECG signals, allows for typical compression efficiencies (CE) in the range $\text {CE} \in [{40,50}]$ , which means that the data rate of 3 kbit/s that would be required to send the uncompressed ECG trace is lowered to 60 and 75 bit/s for CE = 40 and CE = 50, respectively.
Aspergillus section Nigri as contributor of fumonisin B2 contamination in maize

Fumonisins (FBs), which are carcinogenic mycotoxins, are known to be typically produced by several phytopathogenic fungal species belonging to the genus Fusarium. F. proliferatum and F. verticillioides, two important pathogens of maize worldwide, are the most common species that produce FBs. The main FBs produced by these species are FB1, FB2 and FB3. Moreover, recently, fungal strains belonging to Aspergillus niger have been also reported to produce FBs (in particular, FB2 and FB4). In a survey on maize carried out in Central Italy, 17 maize kernel samples were collected at harvest and analysed for FB1, FB2 and FB3, as well as fungal contamination, with a particular attention to the species-producing FBs. All 17 samples were contaminated by F. verticillioides and/or F. proliferatum at a level ranging from 13% to 100% of kernels. However, 10 out of 17 samples were also contaminated by Aspergillus section Nigri with a range from 6% to 68% of kernels. There was a significant inverse logarithmic relationship between levels of Fusarium and Aspergillus contamination. All samples were contaminated by FBs; FB1 ranged from 0.09 to 30.2 μg g–1, whereas FB2 ranged from 0.04 to 13.2 μg g–1. The ratio of FB2/FB1 contamination in the maize samples was evaluated and the highest values occurred in samples contaminated with Aspergillus section Nigri. Thirty strains of Aspergillus section Nigri isolated from these samples were molecularly identified (based on sequences of two housekeeping genes) and analysed for their capability to produce FB2. Among the 30 strains isolated, 12 were identified as Aspergillus welwitschiae (syn. A. awamori) and 18 as A. tubingensis. FB2 was produced by five out of 12 strains of A. welwitschiae within a range of 0.20–5 μg g–1. This is the first report showing the capability of Aspergillus section Nigri from maize to produce FB2 and its possibility to contribute to FB accumulation in kernels.
The (Un)Predictable Equity Risk Premium

The equity risk premium (ERP) remains one of the most hotly contested ideas in finance. The disagreement, in practical and theoretical terms, centres on how best to measure the risk of an investment, how to convert this risk measure into an expected return that compensates the investor for holding that risk, and its degree of predictability. This paper provides Australian evidence for the period 1900 through 2014 and forward looking estimates.
Dominant Designs and the Survival of Firms

The economic, population ecology and strategic perspectives on firm survival are here complemented by viewing the same phenomenon from the viewpoint of technology evolution as well. The hypothesis tested is that the competitive environment of an industry, and therefore the survival of firms in it, is substantially affected by the evolution of the technology on which it is based. Survival analysis is applied to data from six industries. The results show that by explicitly including technology as a dynamic and strategic variable our understanding of firms' survival potential and success can be enhanced.
The optimal activation of cytotoxic T lymphocytes requires metabolically intact stimulator cells not only for the activation of the interleukin 2-producing helper cells.

Primary cytotoxic responses in macrocultures against UV-treated stimulator cells or glutaraldehyde-fixed stimulator cells in the presence of third party stimulator cells were studied to investigate whether metabolically active stimulator cells are only required for the activation of interleukin 2-producing helper cells. Cultures containing splenic responder cells in a mixture with allogeneic UVtreated stimulator cells of a mouse strain X plus conventional (i.e., only ? -irradiated) stimulator cells of a third strain Y were found to generate strong cytotoxic activity against cells of strain Y but not strain X. Macrocultures with conventional stimulator cells of strain Y plus UVtreated stimulator cells of (X x Y)Fl hybrid mice also failed to generate substantial CTL activity against cells of strain X. The response against antigens of strain X was not reconstituted by interleukin 2- (IL 2) containing factors. UV-treated stimulator cells did not suppress the response against conventional stimulator cells of the same H-2 haplotype. These results provide suggestive evidence that CTL precursor cells are optimally activated in primary cytotoxic responses when their receptors interact with antigen on metabolically active stimulator cells. The experiments excluded the possibility that the metabolically active stimulator cells were on/y required for the activation of an unlinked helper effect (i.e., for the stimulation of interleukin 2 production) because the response against the third party stimulator cell proceeded in the same culture at normal magnitude. Our experiments with the (X x Y)F1 stimulator cells also excluded the possibility that the metabolically active (i.e., UV-sensitive) stimulator cells were only required for the stimulation of a type of helper cell (or for the production of an antigen-specific helper factor) that interacts with the CTL precursor cell through a cellular antigen bridge (antigenically linked helper effect). A antigenically linked helper effect through a molecular antigen bridge was not formally excluded. Cold target competition experiments revealed that the antigenic structures were not detectably destroyed by the UV-irradiation procedure. Cultures that received UV-treated stimulator cells on day 0 and an optimal dose of corresponding conventional stimulator cells on day 2 generated still weaker cytotoxicity than control cultures with conventional stimulator cells on day 0, indicating that the metabolically active (UVsensitive) stimulator cells were required in the early phase of the culture to achieve optimal cytotoxic responses.
On 3-colorable non-4-choosable planar graphs

An L-list coloring of a graph G is a proper vertex coloring in which every vertex v gets a color from a list L(v) of allowed colors. G is called k-choosable if all lists L(v) have exactly k elements and if G is L-list colorable for all possible assignments of such lists. Verifying conjectures of Erdos, Rubin and Taylor it was shown during the last years that every planar graph is 5-choosable and that there are planar graphs which are not 4-choosable. The question whether there are 3-colorable planar graphs which are not 4-choosable remained unsolved. The smallest known example far a non-4-choosable planar graph has 75 vertices and is described by Gutner. In fact, this graph is also 3 colorable and answers the above question. In addition, we give a list assignment for this graph using 5 colors only in all of the lists together such that the graph is not List-colorable. © 1997 John Wiley & Sons, Inc.
Short and Long Term Strategies for Household Water Insecurity in Ngamiland, Botswana

The paper analyses coping (short-term) and adaptation (long-term) strategies by households to address water insecurity in Ngamiland, Botswana, a middle income and semi-arid country. Quantitative (i.e. structured household questionnaires) and qualitative (i.e. key informant and informal interviews, focus group discussions and participant observation) approaches were used. The concept of water security and the actor-oriented approach inform the paper. Households in Ngamiland are experiencing water insecurity and they mainly employ coping (i.e. accessing untreated water, traditional rainwater harvesting, bulk water hauling and buying, use prioritization, and buying bottled water) as opposed to adaptation (i.e. abstracting groundwater, connecting storage tanks to main water systems and modern rainwater harvesting) strategies to deal with water insecurity. More scientific research for informing water policies and implementation of sustainable water supply strategies is required in order to enhance water security in countries like Botswana.
Corporate Governance Practices' Implementation in Romania - Achievements, Deficiencies, Action Items

This paper aims at highlighting the institutional and legislative progress made in Romania during the last years concerning corporate governance issues, the deterring factors of this process and at proposing action items for improving the corporations' administration practices. Our paper shows that the improvement of the corporate governance standards in Romania is crucial, considering the integration into the European Union.Our research indicates that most of the companies consider the adoption of corporate governance principles as being complicated, because it implies the change in the company memorandum of association and huge expenses on legal and financial-accounting consultancy. In addition, in the emerging economies, similar to Romania, the corporate governance standard of a company is not so important to the funds suppliers, whether they are banks, investment funds or individual investors and that is why companies do not feel rewarded in any way for making efforts to improve their administration practices. Unfortunately, despite the institutional efforts, inside the business environment and even among companies listed on the capital market, there still is no real concern for these issues.
Two New S‐Phase‐Specific Genes from Saccharomyces cerevisiae

Two new yeast genes, ASF1 (Anti‐Silencing Function) and ASF2, as well as a C‐terminal fragment of SIR3, were identified as genes that derepressed the silent mating type loci when overexpressed. ASF2 overexpression caused a greater derepression than did ASF1. ASF1 overexpression also weakened repression of genes near telomeres, but, interestingly, ASF2 had no effect on telomeric silencing. Sequences of these two genes revealed open reading frames of 279 and 525 amino acids for ASF1 and ASF2, respectively. The ASF1 protein was evolutionarily conserved. MCB motifs, sequences commonly present upstream of genes transcribed specifically in S phase, were found in front of both genes, and, indeed, both genes were transcribed specifically in the S phase of the cell cycle. While an asf2 mutant was viable and had no obvious phenotypes, an asf1 mutant grew poorly. Neither mutant exhibited derepression of the silent mating type loci. The asf1 mutant was sensitive to methyl methane sulfonate, slightly UV‐sensitive and somewhat deficient in minichromosome maintenance. It also lowered the restrictive temperature of a cdc13ts mutant. These phenotypes suggested a role for ASF1 in DNA repair and chromosome maintenance. The GenBank accession numbers for the ASF1 and ASF2 sequences are L07593 and L07649, respectively. © 1997 by John Wiley & Sons, Ltd.