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International Outsourcing in the Information Technology Industry: Trends and Implications
This paper reviews trends in the use of international outsourcing in the Information Technology (IT) industry and explores implications for the U.S. workforce. Workforce employment projections and the trend for globalization in the IT industry are analyzed. An analogy is developed between current trends in IT workforce and the globalization of the auto industry during the latter part of the 20th century. The conclusion is that recent dips in U.S. IT employment may represent more than a transitory reflection of current economic conditions. International IT providers may be capturing a permanent share of U.S. IT expenditures and thus reducing the long term need for U.S. IT employment. IT industry and educational institutions need to plan accordingly for these new global workforce realities
WaveCNV: allele-specific copy number alterations in primary tumors and xenograft models from next-generation sequencing.
MotivationCopy number variations (CNVs) are a major source of genomic variability and are especially significant in cancer. Until recently microarray technologies have been used to characterize CNVs in genomes. However, advances in next-generation sequencing technology offer significant opportunities to deduce copy number directly from genome sequencing data. Unfortunately cancer genomes differ from normal genomes in several aspects that make them far less amenable to copy number detection. For example, cancer genomes are often aneuploid and an admixture of diploid/non-tumor cell fractions. Also patient-derived xenograft models can be laden with mouse contamination that strongly affects accurate assignment of copy number. Hence, there is a need to develop analytical tools that can take into account cancer-specific parameters for detecting CNVs directly from genome sequencing data.ResultsWe have developed WaveCNV, a software package to identify copy number alterations by detecting breakpoints of CNVs using translation-invariant discrete wavelet transforms and assign digitized copy numbers to each event using next-generation sequencing data. We also assign alleles specifying the chromosomal ratio following duplication/loss. We verified copy number calls using both microarray (correlation coefficient 0.97) and quantitative polymerase chain reaction (correlation coefficient 0.94) and found them to be highly concordant. We demonstrate its utility in pancreatic primary and xenograft sequencing data.Availability and implementationSource code and executables are available at https://github.com/WaveCNV. The segmentation algorithm is implemented in MATLAB, and copy number assignment is implemented [email protected] informationSupplementary data are available at Bioinformatics online
A novel role for 14-3-3σ in regulating epithelial cell polarity
The loss of epithelial polarity is thought to play an important role during mammary tumor progression. Using a unique transgenic mouse model of ErbB2-induced mammary tumorigenesis, we demonstrated previously that amplification of ErbB2 is frequently accompanied by loss of the 14-3-3σ gene. Here, we demonstrate that ectopic expression of 14-3-3σ results in restoration of epithelial polarity in ErbB2-transformed mammary tumor cells. We further demonstrate that targeted deletion of 14-3-3σ within primary mammary epithelial cells increases their proliferative capacity and adversely affects their ability to form polarized structures. Finally, we show that 14-3-3σ can specifically form complexes with Par3, a protein that is essential for the maintenance of a polarized epithelial state. Taken together, these observations suggest that 14-3-3σ plays a critical role in retaining epithelial polarity. © 2010 by Cold Spring Harbor Laboratory Press
G-protein-coupled receptor GPR161 is overexpressed in breast cancer and is a promoter of cell proliferation and invasion
Triple-negative breast cancer (TNBC) accounts for 20% of breast cancer in women and lacks an effective targeted therapy. Therefore, finding common vulnerabilities in these tumors represents an opportunity for more effective treatment. Despite the growing appreciation of G-protein-coupled receptor (GPCR)-mediated signaling in cancer pathogenesis, very little is known about the role GPCRs play in TNBC. Using genomic information of human breast cancer, we have discovered that the orphan GPCR, G-protein-coupled receptor 161 (GPR161) is overexpressed specifically in TNBC and correlates with poor prognosis. Knockdown of GPR161 impairs proliferation of human basal breast cancer cell lines. Overexpression of GPR161 in human mammary epithelial cells increases cell proliferation, migration, intracellular accumulation of E-cadherin, and formation of multiacinar structures in 3D culture. GPR161 forms a signaling complex with the scaffold proteins beta-arrestin 2 and Ile Gln motif containing GTPase Activating Protein 1, a regulator of mammalian target of rapamycin complex 1 and E-cadherin. Consistently, GPR161 amplified breast tumors and cells overexpressing GPR161 activate mammalian target of rapamycin signaling and decrease Ile Gln motif containing GTPase Activating Protein 1 phosphorylation. Thus, we identify the orphan GPCR, GPR161, as an important regulator and a potential drug target for TNBC
Rotational motion during three-dimensional morphogenesis of mammary epithelial acini relates to laminin matrix assembly
Our understanding of the mechanisms by which ducts and lobules develop is derived from model organisms and three-dimensional (3D) cell culture models wherein mammalian epithelial cells undergo morphogenesis to form multicellular spheres with a hollow central lumen. However, the mechanophysical properties associated with epithelial morphogenesis are poorly understood. We performed multidimensional live-cell imaging analysis to track the morphogenetic process starting from a single cell to the development of a multicellular, spherical structure composed of polarized epithelial cells surrounding a hollow lumen. We report that in addition to actively maintaining apicobasal polarity, the structures underwent rotational motions at rates of 15-20 μm/h and the structures rotated 360° every 4 h during the early phase of morphogenesis. Rotational motion was independent of the cell cycle, but was blocked by loss of the epithelial polarity proteins Scribble or Pard3, or by inhibition of dynein-based microtubule motors. Interestingly, none of the structures derived from human cancer underwent rotational motion. We found a direct relationship between rotational motion and assembly of endogenous basement membrane matrix around the 3D structures, and that structures that failed to rotate were defective in weaving exogenous laminin matrix. Dissolution of basement membrane around mature, nonrotating acini restored rotational movement and the ability to assemble exogenous laminin. Thus, coordinated rotational movement is a unique mechanophysical process observed during normal 3D morphogenesis that regulates laminin matrix assembly and is lost in cancer-derived epithelial cells
Financial correlations at ultra-high frequency: theoretical models and empirical estimation
A detailed analysis of correlation between stock returns at high frequency is
compared with simple models of random walks. We focus in particular on the
dependence of correlations on time scales - the so-called Epps effect. This
provides a characterization of stochastic models of stock price returns which
is appropriate at very high frequency.Comment: 22 pages, 8 figures, 1 table, version to appear in EPJ
Optimization Based Liver Contour Extraction of Abdominal CT Images
This paper introduces computer aided analysis system for diagnosis of liver abnormality in abdominal CT images. Segmenting the liver and visualizing the region of interest is a most challenging task in the field of cancer imaging, due to small observable changes between healthy and unhealthy liver. In this paper, hybrid approach for automatic extraction of liver contour is proposed. To obtain optimal threshold, the proposed work integrates segmentation method with optimization technique in order to provide better accuracy. This method uses bilateral filter for preprocessing and Fuzzy C means clustering (FCM) for segmentation. Mean Grey Wolf Optimization technique (mGWO) has been used to get the optimal threshold. This threshold is used for segmenting the region of interest. From the segmented output, largest connected region are identified using Label Connected Component (LCC) algorithm. The effectiveness of proposed method is quantitatively evaluated by comparing with ground truth obtained from radiologists. The performance criteria like dice coefficient, true positive error and misclassification rate are taken for evaluation
Navigating nanotechnology : unveiling the role of government pressure and organizational culture in enhancing environmental performance in printing and coatings industry
This research aims to explore the existing relationship of nanotechnology innovation with organizational culture and the environmental performance of organizations. Moreover this research used organizational culture as a mediating variable and government pressure as a moderating variable among the relationship of nanotechnology innovation and environmental performances of organizations. This research was conducted in Kingdom of Saudi Arabia and collected data from 187 employees working in different organizations of printing and coatings industry. To achieve the aim of this research this study has employed the STATA software with structural equation modeling approach. Findings of this research have shown a significant association among direct relationships of nanotechnology innovation and environmental performances of organizations. Moreover, a significant relationship was also found among nanotechnology innovation and organizational culture. The findings also confirmed that the relationship between nanotechnology innovation and environmental performance is also moderated by government pressure and mediated by organizational culture. This study demonstrates that nanotechnology possesses the capability to completely transform organizations. This study highlights the importance of a conducive business culture and environmentally conscious regulatory requirements with the aim of enhancing environmental sustainability.Vimala Venugopal Muthuswamy (Department of Management, College of Business Administration, King Faisal University), B. Sudhakar (Director -MBA, Hindusthan College of Arts and Science)Includes bibliographical reference
Quantification of depth of anesthesia by nonlinear time series analysis of brain electrical activity
We investigate several quantifiers of the electroencephalogram (EEG) signal
with respect to their ability to indicate depth of anesthesia. For 17 patients
anesthetized with Sevoflurane, three established measures (two spectral and one
based on the bispectrum), as well as a phase space based nonlinear correlation
index were computed from consecutive EEG epochs. In absence of an independent
way to determine anesthesia depth, the standard was derived from measured blood
plasma concentrations of the anesthetic via a pharmacokinetic/pharmacodynamic
model for the estimated effective brain concentration of Sevoflurane. In most
patients, the highest correlation is observed for the nonlinear correlation
index D*. In contrast to spectral measures, D* is found to decrease
monotonically with increasing (estimated) depth of anesthesia, even when a
"burst-suppression" pattern occurs in the EEG. The findings show the potential
for applications of concepts derived from the theory of nonlinear dynamics,
even if little can be assumed about the process under investigation.Comment: 7 pages, 5 figure
IRX-2, a Novel Immunotherapeutic, Enhances Functions of Human Dendritic Cells
Background: In a recent phase II clinical trial for HNSCC patients, IRX-2, a cell-derived biologic, promoted T-cell infiltration into the tumor and prolonged overall survival. Mechanisms responsible for these IRX-2-mediated effects are unknown. We hypothesized that IRX-2 enhanced tumor antigen-(TA)-specific immunity by up-regulating functions of dendritic cells (DC). Methodology/Principal Findings: Monocyte-derived DC obtained from 18 HNSCC patients and 12 healthy donors were matured using IRX-2 or a mix of TNF-α, IL-1β and IL-6 ("conv. mix"). Multicolor flow cytometry was used to study the DC phenotype and antigen processing machinery (APM) component expression. ELISPOT and cytotoxicity assays were used to evaluate tumor-reactive cytotoxic T lymphocytes (CTL). IL-12p70 and IL-10 production by DC was measured by Luminex® and DC migration toward CCL21 was tested in transwell migration assays. IRX-2-matured DC functions were compared with those of conv. mix-matured DC. IRX-2-matured DC expressed higher levels (p<0.05) of CD11c, CD40, CCR7 as well as LMP2, TAP1, TAP2 and tapasin than conv. mix-matured DC. IRX-2-matured DC migrated significantly better towards CCL21, produced more IL-12p70 and had a higher IL12p70/IL-10 ratio than conv. mix-matured DC (p<0.05 for all). IRX-2-matured DC carried a higher density of tumor antigen-derived peptides, and CTL primed with these DC mediated higher cytotoxicity against tumor targets (p<0.05) compared to the conv. mix-matured DC. Conclusion: Excellent ability of IRX-2 to induce ex vivo DC maturation in HNSCC patients explains, in part, its clinical benefits and emphasizes its utility in ex vivo maturation of DC generated for therapy. © 2013 Schilling et al
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