625 research outputs found
A Dynamic Spreadsheet Model for Determining the Portfolio Frontier for BSE30 Stocks
Introductory investments courses revolve around Harry Markowitz’s modern portfolio theory and William Sharpe’s Index for the performance measurement of those portfolios. This paper presents a simplified perspective of Markowitz’s contributions to Modern Portfolio Theory. It is to see the effect of duration of historical data on the risk and return of the portfolio and to see the applicability of risk-reward logic. The empirical results also show that short selling may increase the risk of the portfolio when the investor is instability preferred
A UML MODEL FOR AUTOMATION OF COUNSELING SYSTEM USING PURE OBJECT ORIENTED APPROCH
ABSTRACT In present, most institutes and universities facing the counseling problem to allocate the course and college (combination) to student from three choice preferences by entrance exam marks. Currently this is carried out by manually by the institutes/universities, the current need to get an automation model that automatically allocates the combination to the each student according to their given preferences by gained entrance exam marks. Using this paper authors proposed the automation system by UML model to solve the above problem, that automation system automatically allocates the course combination to the student by student's given three preferences and gained entrance marks and average rank. Using this automation system, seats automatically allocated. As well as UML based counseling automation system also supports to administrator to allocate (inserted) the payment seats into automation system, then automation counseling system manipulates payments seats students also with ranked students. The automation is designed Using Unified Modeling Language (UML) model. To design the automation system, authors proposed the UML Automation Process Diagram, Class Diagram, State Diagram and Sequence Diagram to acquire automation process because the UML models are directly supported to pure object oriented application development. We assume three courses and three institutes as nine combinations, for allocation
A note on anti-coordination and social interactions
This note confirms a conjecture of [Bramoull\'{e}, Anti-coordination and
social interactions, Games and Economic Behavior, 58, 2007: 30-49]. The
problem, which we name the maximum independent cut problem, is a restricted
version of the MAX-CUT problem, requiring one side of the cut to be an
independent set. We show that the maximum independent cut problem does not
admit any polynomial time algorithm with approximation ratio better than
, where is the number of nodes, and arbitrarily
small, unless P=NP. For the rather special case where each node has a degree of
at most four, the problem is still MAXSNP-hard.Comment: 7 page
Are estrogen receptor-positive breast cancers in BRCA1 mutation carriers sporadic?
There is a strong association between BRCA1 mutation carrier status and estrogen receptor-negative breast cancer. This has led to the idea that estrogen receptor-positive breast cancers in BRCA1 mutation carriers may be incidental or sporadic in nature and not as a direct result of BRCA1 dysfunction. A recent paper in Breast Cancer Research challenges this view
No evidence for association of ataxia-telangiectasia mutated gene T2119C and C3161G amino acid substitution variants with risk of breast cancer
BACKGROUND: There is evidence that certain mutations in the double-strand break repair pathway ataxia-telangiectasia mutated gene act in a dominant-negative manner to increase the risk of breast cancer. There are also some reports to suggest that the amino acid substitution variants T2119C Ser707Pro and C3161G Pro1054Arg may be associated with breast cancer risk. We investigate the breast cancer risk associated with these two nonconservative amino acid substitution variants using a large Australian population-based case–control study. METHODS: The polymorphisms were genotyped in more than 1300 cases and 600 controls using 5' exonuclease assays. Case–control analyses and genotype distributions were compared by logistic regression. RESULTS: The 2119C variant was rare, occurring at frequencies of 1.4 and 1.3% in cases and controls, respectively (P = 0.8). There was no difference in genotype distribution between cases and controls (P = 0.8), and the TC genotype was not associated with increased risk of breast cancer (adjusted odds ratio = 1.08, 95% confidence interval = 0.59–1.97, P = 0.8). Similarly, the 3161G variant was no more common in cases than in controls (2.9% versus 2.2%, P = 0.2), there was no difference in genotype distribution between cases and controls (P = 0.1), and the CG genotype was not associated with an increased risk of breast cancer (adjusted odds ratio = 1.30, 95% confidence interval = 0.85–1.98, P = 0.2). This lack of evidence for an association persisted within groups defined by the family history of breast cancer or by age. CONCLUSION: The 2119C and 3161G amino acid substitution variants are not associated with moderate or high risks of breast cancer in Australian women
CIP2A expression is increased in prostate cancer
Abstract Background The CIP2A protein is a recently characterized oncoprotein which inhibits protein phosphatase 2A activity. Expression of CIP2A has been detected in several carcinomas, but its expression and significance in prostate cancer has not been examined so far. Methods Expression of the CIP2A protein was studied using immunohistochemistry in prostate cancer (n = 59) and in benign prostatic hyperplasia (n = 20) specimens. The CIP2A staining scores were compared with several clinicopathological parameters. Results Expression of CIP2A was increased in prostate cancer epithelium as compared with the benign hyperplastic epithelium (p Conclusions Expression of the CIP2A protein is increased in prostate cancer specimens and its expression is associated with poorly differentiated and high-risk tumors.</p
Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage.
Colibactin is an assumed human gut bacterial genotoxin, whose biosynthesis is linked to the clb genomic island that has a widespread distribution in pathogenic and commensal human enterobacteria. Colibactin-producing gut microbes promote colon tumour formation and enhance the progression of colorectal cancer via cellular senescence and death induced by DNA double-strand breaks (DSBs); however, the chemical basis that contributes to the pathogenesis at the molecular level has not been fully characterized. Here, we report the discovery of colibactin-645, a macrocyclic colibactin metabolite that recapitulates the previously assumed genotoxicity and cytotoxicity. Colibactin-645 shows strong DNA DSB activity in vitro and in human cell cultures via a unique copper-mediated oxidative mechanism. We also delineate a complete biosynthetic model for colibactin-645, which highlights a unique fate of the aminomalonate-building monomer in forming the C-terminal 5-hydroxy-4-oxazolecarboxylic acid moiety through the activities of both the polyketide synthase ClbO and the amidase ClbL. This work thus provides a molecular basis for colibactin's DNA DSB activity and facilitates further mechanistic study of colibactin-related colorectal cancer incidence and prevention
ETS1 Mediates MEK1/2-Dependent Overexpression of Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A) in Human Cancer Cells
EGFR-MEK-ERK signaling pathway has an established role in promoting malignant growth and disease progression in human cancers. Therefore identification of transcriptional targets mediating the oncogenic effects of the EGFR-MEK-ERK pathway would be highly relevant. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently characterized human oncoprotein. CIP2A promotes malignant cell growth and is over expressed at high frequency (40–80%) in most of the human cancer types. However, the mechanisms inducing its expression in cancer still remain largely unexplored. Here we present systematic analysis of contribution of potential gene regulatory mechanisms for high CIP2A expression in cancer. Our data shows that evolutionary conserved CpG islands at the proximal CIP2A promoter are not methylated both in normal and cancer cells. Furthermore, sequencing of the active CIP2A promoter region from altogether seven normal and malignant cell types did not reveal any sequence alterations that would increase CIP2A expression specifically in cancer cells. However, treatment of cancer cells with various signaling pathway inhibitors revealed that CIP2A mRNA expression was sensitive to inhibition of EGFR activity as well as inhibition or activation of MEK-ERK pathway. Moreover, MEK1/2-specific siRNAs decreased CIP2A protein expression. Series of CIP2A promoter-luciferase constructs were created to identify proximal −27 to −107 promoter region responsible for MEK-dependent stimulation of CIP2A expression. Additional mutagenesis and chromatin immunoprecipitation experiments revealed ETS1 as the transcription factor mediating stimulation of CIP2A expression through EGFR-MEK pathway. Thus, ETS1 is probably mediating high CIP2A expression in human cancers with increased EGFR-MEK1/2-ERK pathway activity. These results also suggest that in addition to its established role in invasion and angiogenesis, ETS1 may support malignant cellular growth via regulation of CIP2A expression and protein phosphatase 2A inhibition
A unique strain of community-acquired Clostridium difficile in severe complicated infection and death of a young adult
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