Is entrepreneurship an emerging area of research? A computational response

Objective: We aim to answer four questions. First, with the increasing number of publications, is there a concentration in specific subjects, or on the contrary, a dispersion, amplifying the span of themes related to entrepreneurship? Second, is there a hierarchy of subjects, in the sense that some of them constitute the core of entrepreneurship? Third, are they connected with other established research areas? Finally, it is possible to identify papers that are influential, acting as hubs in the clusters formation? Method: We developed an original version of the computational procedure proposed by Shibata et al (2008), which allows us to understand the diversity of the different sub-areas of the topic investigated, reducing the need for specialist supervision. Originality / Relevance: We developed and applied a method to capture the formation and evolution of research areas in entrepreneurship literature, via direct citation networks, allowing us to understand the iteration between the different research sub-areas. Results: The dispersion is a feature of entrepreneurship as field research, with a hierarchy between research areas, indicating an emergent organization in the expansion processes. We concluded that research on entrepreneurship consists of specialization, that is, by application in niches.</jats:p

Passive parametric macromodeling by using Sylvester state-space realizations

A judicious choice of the state-space realization is required in order to account for the assumed smoothness of the state-space matrices with respect to the design parameters. The direct parameterization of poles and residues may be not appropriate, due to their possible non-smooth behavior with respect to design parameters. This is avoided in the proposed technique, by converting the pole-residue description to a Sylvester description which is computed for each root macromodel. This technique is used in combination with suitable parameterizing schemes for interpolating a set of state-space matrices, and hence the poles and residues indirectly, in order to build accurate parametric macromodels. The key features of the present approach are first the choice of a proper pivot matrix and second, finding a well-conditioned solution of a Sylvester equation. Stability and passivity are guaranteed by construction over the design space of interest. Pertinent numerical examples validate the proposed Sylvester technique for parametric macromodeling

Transcribed ultraconserved noncoding RNAs (T-UCR) are involved in Barrett's esophagus carcinogenesis.

Barretts esophagus (BE) involves a metaplastic replacement of native esophageal squamous epithelium (Sq) by columnar-intestinalized mucosa, and it is the main risk factor for Barrett-related adenocarcinoma (BAc). Ultra-conserved regions (UCRs) are a class non-coding sequences that are conserved in humans, mice and rats. More than 90% of UCRs are transcribed (T-UCRs) in normal tissues, and are altered at transcriptional level in tumorigenesis. To identify the T-UCR profiles that are dysregulated in Barretts mucosa transformation, microarray analysis was performed on a discovery set of 51 macro-dissected samples obtained from 14 long-segment BE patients. Results were validated in an independent series of esophageal biopsy/surgery specimens and in two murine models of Barretts esophagus (i.e. esophagogastric-duodenal anastomosis). Progression from normal to BE to adenocarcinoma was each associated with specific and mutually exclusive T-UCR signatures that included up-regulation of uc.58-, uc.202-, uc.207-, and uc.223- and down-regulation of uc.214+. A 9 T-UCR signature characterized BE versus Sq (with the down-regulation of uc.161-, uc.165-, and uc.327-, and the up-regulation of uc.153-, uc.158-, uc.206-, uc.274-, uc.472-, and uc.473-). Analogous BE-specific T-UCR profiles were shared by human and murine lesions. This study is the first demonstration of a role for T-UCRs in the transformation of Barretts mucosa

Identification of disease-causing genes using microarray data mining and gene ontology

Background: One of the best and most accurate methods for identifying disease-causing genes is monitoring gene expression values in different samples using microarray technology. One of the shortcomings of microarray data is that they provide a small quantity of samples with respect to the number of genes. This problem reduces the classification accuracy of the methods, so gene selection is essential to improve the predictive accuracy and to identify potential marker genes for a disease. Among numerous existing methods for gene selection, support vector machine-based recursive feature elimination (SVMRFE) has become one of the leading methods, but its performance can be reduced because of the small sample size, noisy data and the fact that the method does not remove redundant genes. Methods: We propose a novel framework for gene selection which uses the advantageous features of conventional methods and addresses their weaknesses. In fact, we have combined the Fisher method and SVMRFE to utilize the advantages of a filtering method as well as an embedded method. Furthermore, we have added a redundancy reduction stage to address the weakness of the Fisher method and SVMRFE. In addition to gene expression values, the proposed method uses Gene Ontology which is a reliable source of information on genes. The use of Gene Ontology can compensate, in part, for the limitations of microarrays, such as having a small number of samples and erroneous measurement results. Results: The proposed method has been applied to colon, Diffuse Large B-Cell Lymphoma (DLBCL) and prostate cancer datasets. The empirical results show that our method has improved classification performance in terms of accuracy, sensitivity and specificity. In addition, the study of the molecular function of selected genes strengthened the hypothesis that these genes are involved in the process of cancer growth. Conclusions: The proposed method addresses the weakness of conventional methods by adding a redundancy reduction stage and utilizing Gene Ontology information. It predicts marker genes for colon, DLBCL and prostate cancer with a high accuracy. The predictions made in this study can serve as a list of candidates for subsequent wet-lab verification and might help in the search for a cure for cancers

G6PD deficiency alleles in a malaria-endemic region in the Western Brazilian Amazon.

BACKGROUND: Plasmodium vivax parasites are the predominant cause of malaria infections in the Brazilian Amazon. Infected individuals are treated with primaquine, which can induce haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals and may lead to severe and fatal complications. This X-linked disorder is distributed globally and is caused by allelic variants with a geographical distribution that closely reflects populations exposed historically to endemic malaria. In Brazil, few studies have reported the frequency of G6PD deficiency (G6PDd) present in malaria-endemic areas. This is particularly important, as G6PDd screening is not currently performed before primaquine treatment. The aim of this study was to determine the prevalence of G6PDd in the region of Alto do Juruá, in the Western Brazilian Amazon, an area characterized by a high prevalence of P. vivax infection. METHODS: Five-hundred and sixteen male volunteers were screened for G6PDd using the fluorescence spot test (Beutler test) and CareStart™ G6PD Biosensor system. Demographic and clinical-epidemiological data were acquired through an individual interview. To assess the genetic basis of G6PDd, 24 SNPs were genotyped using the Kompetitive Allele Specific PCR assay. RESULTS: Twenty-three (4.5%) individuals were G6PDd. No association was found between G6PDd and the number of malaria cases. An increased risk of reported haemolysis symptoms and blood transfusions was evident among the G6PDd individuals. Twenty-two individuals had the G6PDd A(-) variant and one the G6PD A(+) variant. The Mediterranean variant was not present. Apart from one polymorphism, almost all SNPs were monomorphic or with low frequencies (0-0.04%). No differences were detected among ethnic groups. CONCLUSIONS: The data indicates that ~1/23 males from the Alto do Juruá could be G6PD deficient and at risk of haemolytic anaemia if treated with primaquine. G6PD A(-) is the most frequent deficiency allele in this population. These results concur with reported G6PDd in other regions in Brazil. Routine G6PDd screening to personalize primaquine administration should be considered, particularly as complete treatment of patients with vivax malaria using chloroquine and primaquine, is crucial for malaria elimination

Conjugation with L, L-diphenylalanine Self-Assemblies Enhances In Vitro Antitumor Activity of Phthalocyanine Photosensitizer

We present the synthesis and characterization of new peptide conjugates obtained by hierarchical co-assembly of L,L-diphenylalanine (FF) and zinc phthalocyanine complexes (ZnPc) in water. Self-assembly capabilities under defined conditions were investigated by scanning electron microscopy, and photophysical properties were evaluated using UV-Vis and fluorescence spectroscopy. AFM observations demonstrated that these ZnPcs form different highly ordered arrays on the crystalline faces of the FF microplates and that surface roughness significantly changes with the presence of differently substituted phthalocyanine units. XRD assays showed that the overall molecular packing of the conjugates is organized according to a hexagonal symmetry, with ZnPcs hosted in the interstices of the peptide phase. In vitro photodynamic studies were conducted on human breast cancer MCF-7 cells to investigate both cellular uptake and cytotoxicity. It was shown that FF self-assemblies are not toxicity and enhance accumulation of ZnPc in MCF-7 cells, improving apoptotic cell death upon irradiation. Our findings demonstrate enhancement of ZnPc antitumor efficiency by FF conjugates and a proof-of-concept for new photosensitizer carriers based on peptide conjugates

Gene expression changes associated with Barrett's esophagus and Barrett's-associated adenocarcinoma cell lines after acid or bile salt exposure

<p>Abstract</p> <p>Background</p> <p>Esophageal reflux and Barrett's esophagus represent two major risk factors for the development of esophageal adenocarcinoma. Previous studies have shown that brief exposure of the Barrett's-associated adenocarcinoma cell line, SEG-1, or primary cultures of Barrett's esophageal tissues to acid or bile results in changes consistent with cell proliferation. In this study, we determined whether similar exposure to acid or bile salts results in gene expression changes that provide insights into malignant transformation.</p> <p>Methods</p> <p>Using previously published methods, Barrett's-associated esophageal adenocarcinoma cell lines and primary cultures of Barrett's esophageal tissue were exposed to short pulses of acid or bile salts followed by incubation in culture media at pH 7.4. A genome-wide assessment of gene expression was then determined for the samples using cDNA microarrays. Subsequent analysis evaluated for statistical differences in gene expression with and without treatment.</p> <p>Results</p> <p>The SEG-1 cell line showed changes in gene expression that was dependent on the length of exposure to pH 3.5. Further analysis using the Gene Ontology, however, showed that representation by genes associated with cell proliferation is not enhanced by acid exposure. The changes in gene expression also did not involve genes known to be differentially expressed in esophageal adenocarcinoma. Similar experiments using short-term primary cultures of Barrett's esophagus also did not result in detectable changes in gene expression with either acid or bile salt exposure.</p> <p>Conclusion</p> <p>Short-term exposure of esophageal adenocarcinoma SEG-1 cells or primary cultures of Barrett's esophagus does not result in gene expression changes that are consistent with enhanced cell proliferation. Thus other model systems are needed that may reflect the impact of acid and bile salt exposure on the esophagus <it>in vivo</it>.</p