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The Computational Complexity of N-K Fitness Functions
- IEEE TRANS. ON EVOLUTIONARY COMPUTATION
, 1999
"... The N-K fitness landscapes have been widely used as examples and test functions in the field of evolutionary computation. Thus, the computational complexity of these landscapes as optimization problems is of interest. We investigate the computational complexity of the problem of optimizing the N-K t ..."
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The N-K fitness landscapes have been widely used as examples and test functions in the field of evolutionary computation. Thus, the computational complexity of these landscapes as optimization problems is of interest. We investigate the computational complexity of the problem of optimizing the N-K tness functions and related fitness functions. We give an algorithm to optimize adjacent-model N-K tness functions which is polynomial in N . We show that the decision problem corresponding to optimizing random-model NK fitness functions is NP-complete for K > 1 and is polynomial for K = 1. However, if the restriction that the ith component function depends on the ith bit is removed, then the problem is NP-complete even for K = 1. We also give a polynomial-time approximation algorithm for the arbitrary-model N-K optimization problem.
New insights into human nondisjunction of chromosome 21 in oocytes
- PLoS Genet
, 2008
"... Abstract Nondisjunction of chromosome 21 is the leading cause of Down syndrome. Two risk factors for maternal nondisjunction of chromosome 21 are increased maternal age and altered recombination. In order to provide further insight on mechanisms underlying nondisjunction, we examined the associatio ..."
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Abstract Nondisjunction of chromosome 21 is the leading cause of Down syndrome. Two risk factors for maternal nondisjunction of chromosome 21 are increased maternal age and altered recombination. In order to provide further insight on mechanisms underlying nondisjunction, we examined the association between these two well established risk factors for chromosome 21 nondisjunction. In our approach, short tandem repeat markers along chromosome 21 were genotyped in DNA collected from individuals with free trisomy 21 and their parents. This information was used to determine the origin of the nondisjunction error and the maternal recombination profile. We analyzed 615 maternal meiosis I and 253 maternal meiosis II cases stratified by maternal age. The examination of meiosis II errors, the first of its type, suggests that the presence of a single exchange within the pericentromeric region of 21q interacts with maternal age-related risk factors. This observation could be explained in two general ways: 1) a pericentromeric exchange initiates or exacerbates the susceptibility to maternal age risk factors or 2) a pericentromeric exchange protects the bivalent against age-related risk factors allowing proper segregation of homologues at meiosis I, but not segregation of sisters at meiosis II. In contrast, analysis of maternal meiosis I errors indicates that a single telomeric exchange imposes the same risk for nondisjunction, irrespective of the age of the oocyte. Our results emphasize the fact that human nondisjunction is a multifactorial trait that must be dissected into its component parts to identify specific associated risk factors.
Astragalus membranaceus Inhibits Inflammation via Phospho-P38 Mitogen-Activated Protein Kinase (MAPK) and Nuclear Factor (NF)-κB Pathways in Advanced Glycation End
, 2012
"... Abstract: Advanced glycation end products (AGEs) and inflammation contribute to the development of diabetic complications. Astragalus membranaceus has properties of immunological regulation in many diseases. The aim of this study was to determine the function of A. membranaceus extract (AME) on the ..."
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Abstract: Advanced glycation end products (AGEs) and inflammation contribute to the development of diabetic complications. Astragalus membranaceus has properties of immunological regulation in many diseases. The aim of this study was to determine the function of A. membranaceus extract (AME) on the AGE-induced inflammatory response in Ana-1 macrophages. The viability of cells treated with AME or AGEs was evaluated with the MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] method. The secretion and mRNA levels of IL-1β and TNF-α were measured by ELISA and RT-PCR, respectively. The activity of NF-κB was assayed by EMSA. The phosphorylation of p38 MAPK was assessed by western blotting. The results showed that AME was not toxic to macrophages. The treatment of macrophages with AME effectively inhibited AGE-induced IL-1β and TNF-α secretion and mRNA expression in macrophages. These effects may be mediated by p38 MAPK and the NF-κB pathway. The results suggest that AME can inhibit AGE-induced inflammatory cytokine production to down-regulate macrophage-mediated inflammation via p38 MAPK and NF-κB signaling pathways
Department of Biochemistry,
"... bS Supporting Information ABSTRACT: The proteomic effects of specific cancer-related mutations have not been well characterized. In colorectal cancer (CRC), a relatively small number of mutations in key signaling pathways appear to drive tumorigenesis. Mutations in adenomatous polyposis coli (APC), ..."
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bS Supporting Information ABSTRACT: The proteomic effects of specific cancer-related mutations have not been well characterized. In colorectal cancer (CRC), a relatively small number of mutations in key signaling pathways appear to drive tumorigenesis. Mutations in adenomatous polyposis coli (APC), a negative regulator of Wnt signaling, occur in up to 60 % of CRC tumors. Here we examine the proteomic consequences of a single gene mutation by using an isogenic CRC cell culture model in which wildtype APC expression has been ectopically restored. Using LC MS/MS label free shotgun proteomics, over 5000 proteins were identified in SW480Null (mutant APC) and SW480APC (APC restored). We observed 155 significantly differentially expressed proteins between the two cell lines, with 26 proteins showing opposite expression trends relative to gene expression measurements. Protein changes corresponded to previously characterized features of the APCNull phenotype: loss of cell adhesion proteins, increase in cell cycle regulators, alteration in Wnt signaling related proteins, and redistribution of β-catenin. Increased expression of RNA processing and isoprenoid biosynthetic proteins occurred in SW480Null cells. Therefore, shotgun proteomics reveals proteomic differences associated with a single gene change, including many novel differences that fall outside known target pathways. KEYWORDS: shotgun proteomics, label-free quantitation, multiple reaction monitoring (MRM), LC MS/MS, colorectal cancer, APC
Telomerase-Independent Paths to Immortality in Predictable Cancer Subtypes
"... licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. Received: 2011.12.16; Accepted: 2012.01.28; Published: 2012.01.31 The vast majority of cancers commandeer the activity of telomerase- the remarka ..."
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licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. Received: 2011.12.16; Accepted: 2012.01.28; Published: 2012.01.31 The vast majority of cancers commandeer the activity of telomerase- the remarkable enzyme responsible for prolonging cellular lifespan by maintaining the length of telomeres at the ends of chromosomes. Telomerase is only normally active in embryonic and highly proliferative somatic cells. Thus, targeting telomerase is an attractive anti-cancer therapeutic rationale currently under investigation in various phases of clinical development. However, previous reports suggest that an average of 10-15 % of all cancers lose the functional activity of telomerase and most of these turn to an Alternative Lengthening of Telomeres pathway (ALT). ALT-positive tumours will therefore not respond to anti-telomerase therapies and there is a real possibility that such drugs would be toxic to normal telomerase-utilising cells and ultimately select for resistant cells that activate an ALT mechanism. ALT exploits certain DNA damage response (DDR) components to counteract telomere shortening and rapid trimming. ALT has been reported in many cancer subtypes including sarcoma, gastric carcinoma, central
FUNCTIONAL AND MECHANISTIC STUDY OF DOT1L IN MOUSE EMBRYONIC HEMATOPOIESIS BY
"... ii The Dissertation Committee for Yi Feng certifies that this is the approved version of the following dissertation: FUNCTIONAL AND MECHANISTIC STUDY OF DOT1L IN MOUSE EMBRYONIC HEMATOPOIESIS ..."
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ii The Dissertation Committee for Yi Feng certifies that this is the approved version of the following dissertation: FUNCTIONAL AND MECHANISTIC STUDY OF DOT1L IN MOUSE EMBRYONIC HEMATOPOIESIS
Acute Lymphoblastic Leukemia: Genetic Events and Molecular Signatures
"... Abstract Childhood or pediatric acute precursor B cell lymphoblastic leukemia (B-ALL) is the most prevalent hematological malignancy in children. Previous studies have revealed relationships between genetic lesions and the disease. In this review, I discuss our current understanding of the genetic ..."
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Abstract Childhood or pediatric acute precursor B cell lymphoblastic leukemia (B-ALL) is the most prevalent hematological malignancy in children. Previous studies have revealed relationships between genetic lesions and the disease. In this review, I discuss our current understanding of the genetic lesions and molecular events in childhood B-ALL and the related therapeutic implications.
PAPER Special Section on Cryptography and Information Security Constructing Boolean Functions by Modifying
, 2005
"... SUMMARY In this study, we construct balanced Boolean functions with a high nonlinearity and an optimum algebraic degree for both odd and even dimensions. Our approach is based on modifying functions from the Maiorana-McFarland’s superclass, which has been introduced by Carlet. A drawback of Maiorana ..."
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SUMMARY In this study, we construct balanced Boolean functions with a high nonlinearity and an optimum algebraic degree for both odd and even dimensions. Our approach is based on modifying functions from the Maiorana-McFarland’s superclass, which has been introduced by Carlet. A drawback of Maiorana-McFarland’s function is that their restrictions obtained by fixing some variables in their input are affine. Affine functions are cryptographically weak functions, so there is a risk that this property will be exploited in attacks. Due to the contribution of Carlet, our constructions do not have the potential weakness that is shared by the Maiorana-McFarland construction or its modifications. key words: Boolean function, nonlinearity, algebraic degree, balancedness,
PaPer TyPe www.landesbioscience.com mabs 871
"... Calcitonin gene-related peptide (CGRP) is a neuropeptide that plays an important role in the pathophysiology of migraine.1,2 During migraine attacks, plasma CGRP levels are elevated in the external jugular vein and treatment with the acute migraine ..."
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Calcitonin gene-related peptide (CGRP) is a neuropeptide that plays an important role in the pathophysiology of migraine.1,2 During migraine attacks, plasma CGRP levels are elevated in the external jugular vein and treatment with the acute migraine
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"... www.impactjournals.com/oncotarget / Oncotarget, Vol. 5, No. 18 Identification of a DNA methylation signature to predict disease-free survival in locally advanced rectal cancer ..."
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www.impactjournals.com/oncotarget / Oncotarget, Vol. 5, No. 18 Identification of a DNA methylation signature to predict disease-free survival in locally advanced rectal cancer
