Search results for "Mutation."

Darbu plānošanas optimizācijas problēmu risināšana ar binārās programmēšanas metodēm

2016

Darbā aprakstītas trīs dažādas flow shop problēmas ar uzdevumu minimizēt kopējo darbu izpildes laiku: permutation flow shop problēma, blocking flow shop problēma un no-wait flow shop problēma. Katrai no problēmām ir atrasts atbilstošais lineārās programmēšanas uzdevums ar veseliem un bināriem mainīgajiem. Problēmu risināšanai ir aprobētas divas klasiskās metodes, ko izmando diskrētās programmēšanas uzdevumiem: Gomorī apgriešanas metode un sazarošanās un robežu algoritms. Skaitliskie aprēķini tika veikti, izmantojot datorprogrammu LPSolve IDE.

Rescuing CFTR Protein Function: 1,3,4-oxadiazoles versus 1,2,4-oxadiazoles as readthrough inducing drugs

In Cystic fibrosis (CF) disease nonsense mutations in the CFTR gene cause the absence of the CFTR protein expression and a more severe form of the disease. About 10% of patient affected by CF show a nonsense mutation. A potential treatment of this alteration is to promote translational readthrough of premature termination codons (PTCs) by translational readthrough inducing drugs such as Ataluren (1). We reported a rationale for Ataluren promoted readthrough of PTCs by computational approach and GFP-reporter cell-based assay (2) and the observed enhancement of readthrough activity by some Ataluren derivatives (3, 4). In this context we aimed to compare the 1,2,4-oxadiazole core of Ataluren w…

Translational Readthrough Inducing Drugs (TRIDs): a study of biodistribution evaluation in mice models

OXADIAZOLE DERIVATIVES FOR THE TREATMENT OF GENETIC DISEASES DUE TO NONSENSE MUTATIONS

2018

Are disclosed oxadiazole derivatives, their use as medicaments and in particular for the treatment of diseases associated with the presence of a nonsense mutation in the gene or a premature stop codon in the mRNA, pharmaceutical formulation comprising said oxadiazole derivatives and prodrug or mixture thereof and the methods for the preparation of said Oxadiazole derivatives.

Intron variants of the p53 gene are associated with increased risk for ovarian cancer but not in carriers of BRCA1 or BRCA2 germline mutations

1999

Two biallelic polymorphisms in introns 3 and 6 of the p53 gene were analysed for a possible risk-modifying effect for ovarian cancer. Germline DNA was genotyped from 310 German Caucasian ovarian cancer patients and 364 healthy controls. We also typed 124 affected and 276 unaffected female carriers with known deleterious BRCA1 or BRCA2 germline mutation from high-risk breast-ovarian cancer families. Genotyping was based on PCR and high-resolution gel electrophoresis. German ovarian cancer patients who carried the rare allele of the MspI restriction fragment length polymorphism (RELP) in intron 6 were found to have an overall 1.93-fold increased risk (95% confidence internal (CI) 1.27–2.91) w…

Heterogeneity within and between primary colorectal carcinomas and matched metastases as revealed by analysis of Ki-ras and p53 mutations

2004

Analysis of the genetic status of Ki-ras and p53 in primary colorectal carcinomas and matched colorectal liver metastasis from 30 patients reveals an overall heterogeneity both within and between the two tumoral tissues. Both genes were found mutated with a similar frequency in both tissues; however, identical mutations in primary tumor and matched metastasis were found less frequently in the case of the Ki-ras than the p53 gene. Only in three cases the same p53 and Ki-ras mutations found in the primary tumor were found also in the metastasis. In several metastatic specimens the DNA bearing a mutation detected also in the primary tumor appears significantly less abundant than the wild-type …

Mutations in p53 Gene Exons in a Sample from the South of Spain in Oral Cancer

2021

[Background+ Cancer is a genetic disease caused by mutations in DNA and epigenetic alterations that control gene expression. The majority of epidermoid carcinomas develop within the fields of epithelial genetic alterations. The mechanisms underlying tumorigenesis of epidermoid carcinoma are as yet unknown; therefore, precise identification of the risk factors is needed.

Targeting HSP90 with the small molecule inhibitor AUY922 (luminespib) as a treatment strategy against hepatocellular carcinoma

2018

Hepatocellular carcinoma (HCC) is a highly malignant tumor that responds very poorly to existing therapies, most probably due to its extraordinary inter- and intra-tumor molecular heterogeneity. The modest therapeutic response to molecular targeted agents underlines the need for new therapeutic approaches for HCC. In our study, we took advantage of well-characterized human HCC cell lines, differing in transcriptomic subtypes, DNA mutation and amplification alterations, reflecting the heterogeneity of primary HCCs, to provide a preclinical evaluation of the specific heat shock protein 90 (HSP90) inhibitor AUY922 (luminespib). Indeed, HSP90 is highly expressed in different tumor types, but it…

Testing for Lynch Syndrome in Endometrial Carcinoma: From Universal to Age-Selective MLH1 Methylation Analysis

2022

Simple Summary International guidelines recommend universal screening of endometrial carcinoma patients for Lynch syndrome, a hereditary cancer predisposition syndrome. Screening is based on mismatch repair protein immunohistochemistry and reflex MLH1 methylation analysis to exclude the likely sporadic cases of MMR deficiency. As sporadic MLH1 protein loss is common in endometrial carcinoma, the ability to target methylation testing would save efforts and costs. We discovered that limiting methylation testing to patients under 65 years would have significantly reduced the testing effort while maintaining a low false negative rate for MLH1-LS detection (0% and 3% in our clinic and registry-b…

On Prefix Normal Words

2011

We present a new class of binary words: the prefix normal words. They are defined by the property that for any given length $k$, no factor of length $k$ has more $a$'s than the prefix of the same length. These words arise in the context of indexing for jumbled pattern matching (a.k.a. permutation matching or Parikh vector matching), where the aim is to decide whether a string has a factor with a given multiplicity of characters, i.e., with a given Parikh vector. Using prefix normal words, we give the first non-trivial characterization of binary words having the same set of Parikh vectors of factors. We prove that the language of prefix normal words is not context-free and is strictly contai…