The Molecular In Silico Dissection of Cancer using TCLASS and its Application in the Identification of the Tissue of Origin of Cancers of Unknown Primary Site

Traditional cancer diagnosis relies on a combination of clinical and histo-pathological data. In many cases, however, the morphology of in particular metastatic cancer is not discriminative enough for correct diagnosis. In addition, the morphology of tumor cells do not provide information on aberrant molecular pathways that may be used to specifically target the tumor like the application of Herceptin to breast cancers with amplification in the ERBB2 gene. With the completion of the human genome project, molecular pathology has dramatically increased its arsenal of novel molecular biomarkers that can be used to determine the phenotype of tumors. Gene expression profiling using high-density microarray technology is an extremely powerful tool to comprehensively characterize the tumor phenotype. We have developed TCLASS® a multi-class tumor classifier that interprets gene expression microarray data and allows the identification of the primary site of Cancers of Unknown Promary site (CUP). The classifier is implemented as a web-based tool and is an extremely simple and straightforward approach for molecular characterization of tumor samples. We are currently looking for collaborations with clinicians with access to fresh frozen CUP samples to further validate the tool in a clinical context. Alternatively, CEL files of CUP samples analyzed with Affynetrix 133 Plus 2.0 arrays can also be directly analyzed using TCLASS.
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An investigation into international business collaboration in higher education organisations: a case study of international partnerships in four UK leading universities

Purpose - The purpose of this paper is to develop a comparative analysis of the main objectives of international institutional partnerships in four UK leading universities. Based on the presented case studies, the paper outlines a model for objectives and implementation of international partnership. Design/methodology/approach - Using a multiple case study approach, the paper employs three sources of data: templates of international partnerships, actual agreements of international partnerships and interviews with senior and very senior managers concerned with internationalisation at the four universities. The analysis includes inter-university comparative analysis and templates-agreements-interviews comparative analysis for each of the four universities separately. Findings - It is found that, for the four universities, the objectives of international partnerships are related to both students and staff with relative importance given to the student dimension. While the student dimension refers to any overseas partnerships where the core topic of the partnership is the student whether it is related to student exchange, collaborative programs, student recruitment, etc.; the staff dimension refers to any overseas partnerships that are more related to the staff topic, such as joint research, collaborative teaching, staff exchange, etc

The Effect Of Organizational Culture On Turnover Intention In Private Universities In Afghanistan

This study's primary goal is to investigate the link between organizational culture and the variables that affect an employee's decision to quit their present position at Private universities. Employee turnover still is a major problem for companies since it is highly expensive from the organization's perspective and has a substantial negative impact. The majority of the explanations that are mentioned in the literature are conservative views of traditional causes, including sociological and psychological organizational behavior. Organizational culture is one of the traditional factors of voluntary turnover that has been studied but still requires attention. This paper examined how organizational culture affects professional University staff’s intentions to leave private Universities. To determine the connection and impact between the independent and dependent variables, correlation and regression analyses were used. The results demonstrate that Type B adhocracy culture predominated in private Universities. The findings showed that there is just one sort of organizational culture that affects intention to leave: Type A Clan culture, it is also shown that this type of organizational culture has a significant and positive effect on voluntary turnover intention among University staff. This discovery may be used by decision-makers and other interested parties that need to find a means to stop professional University employees from quitting on their own and create an organizational culture or policy to keep them employed in private Universities

MAP Kinases Phosphorylate SPF45 and Regulate Its Alternative Splicing Function: Insights onto Phosphorylation-Dependent and -Independent Effects in Ovarian Cancer Cells

Alternative pre-mRNA splicing increases proteome diversity and is important in the behavior of cells in health and disease. The processes that regulate alternative premRNA splicing are diverse and include regulation of splicing factors by phosphorylation. Here we report that the pre-mRNA alternative splicing factor SPF45 is a novel substrate of ERK, JNK and p38 MAP kinases in ovarian cancer cells. Using mutational analysis and phospho-specific antibodies, we demonstrate that MAP kinases phosphorylate SPF45 on Thr71 and Ser222 and that phosphorylation in cells is induced by a number of extracellular stimuli including PMA, EGF, serum, H20 2 and UV. Exon 6 of the death receptor Fas/CD95 has been shown to undergo alternative splicing in the presence of SPF45. Using a Fas minigene assay, we show that ERK2 and p38 inhibit SPF45 alternative splicing activity towards Fas, dependent upon these two phosphorylation sites. Other than Fas, no other pre-mRNA targets of SPF45 have been reported in mammalian cells. We generated SKOV3 cells stably-overexpressing wild-type SPF45 or a phosphorylation site mutant and performed an exon and gene array analysis to identify novel SPF45 splicing targets and genes whose expression is changed downstream of SPF45 splicing activity, respectively. From this analysis, 139 potential splicing targets and over 150 genes with altered expression were identified. We focus on four genes for validation with emphasis on ErbB2 and fibronectin. We show that SPF45 downregulates cellular proliferation in SKOV3 cells in a phosphorylation-dependent manner. Furthermore, we demonstrate that SPF45 regulates fibronectin alternative splicing, enhances inclusion of FN-EDIIIA region, and affects cellular adhesion to fibronectin matrix. We also assess SPF45 binding to SFl and SF3b15S, essential components of the spliceosome, as well as the impact of Thr71 and Ser222 mutations on this interaction. Finally, we determine the effect of SPF45 overexpression in SKOV3 cells on their drug resistance profile. This study provides a link between MAP kinase signaling and splicing factors and identifies the role of this interaction in regulating molecular processes in ovarian cancer cells. Additionally, it provides the basis to investigate the role of SPF45 in ovarian cancer and to produce successful therapeutic interventions targeting SPF45-mediated effects

Inclusive/exclusive talent management, responsible leadership and organizational downsizing

Purpose: The purpose of this paper is to focus on three Egyptian public business schools in an attempt to explore the effect of inclusive/exclusive talent management on the organizational downsizing of academics and the mediating role of responsible leadership. Design/methodology/approach: A total of 330 academics were contacted and given a set of questionnaires. After three follow-ups, a total of 240 responses were collected with a response rate of 72.73 percent. Multiple regressions were employed to show how much variation in organizational downsizing can be explained by inclusive/exclusive talent management and responsible leadership. Findings: The findings highlighted a very weak statistical association between academics’ inclusive talent management and organizational downsizing, whereas a strong statistical association has been discovered between exclusive talent management and organizational downsizing. Statistical analysis showed that responsible leadership has no role in mediating the relationship between inclusive/exclusive talent management of academics and their downsizing. Research limitations/implications: The authors have focused on only three Egyptian public business schools, the matter that may limit opportunities to generalize the results of this study to private business schools and other faculties in Egypt. Future research could use a double source method. Practical implications: By preparing a set of academic competences, business schools will be able to classify their academic staff into talented and non-talented, and accordingly they can initiate their tailored downsizing strategies. Furthermore, undertaking a responsible strategy of downsizing, which includes and is not limited to justifying the need to decrease academic staff numbers to guarantee post-redundancy care practices for laid-off academics may alleviate many of the negative psychological, societal and economic consequences of downsizing. Originality/value: This paper contributes by filling a gap in HR management and higher education literature, in which empirical studies on the relationship between talent management and academics’ organizational downsizing have been limited until now. This may create better research opportunities for cross-disciplinary papers that should be done by HR, higher education and leadership scholars