Search results for "mutation."
showing 10 items of 2808 documents
Gefitinib in lung cancer therapy. Clinical results, predictive markers of response and future perspectives.
2009
Over the past few years, epidermal growth factor receptor has emerged as one of the most important targets in tumorgenesis and several drugs targeting signal transduction pathways have been developed. The first among these agents to be approved for the treatment of NSCLC was gefitinib, a potent, selective and reversible inhibitor of HER1/EGFR tyrosine kinase activity. The review summarizes its clinical development and the new therapeutic options, with particular focus on predictive markers of susceptibility to this drug.
Toward a Rationale for the PTC124 (Ataluren) Promoted Readthrough of Premature Stop Codons: A Computational Approach and GFP-Reporter Cell-Based Assay
2014
The presence in the mRNA of premature stop codons (PTCs) results in protein truncation responsible for several inherited (genetic) diseases. A well-known example of these diseases is cystic fibrosis (CF), where approximately 10% (worldwide) of patients have nonsense mutations in the CF transmembrane regulator (CFTR) gene. PTC124 (3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)-benzoic acid), also known as Ataluren, is a small molecule that has been suggested to allow PTC readthrough even though its target has yet to be identified. In the lack of a general consensus about its mechanism of action, we experimentally tested the ability of PTC124 to promote the readthrough of premature termination c…
Analysis of Protected Accidental Transients in the EFIT Reactor With the RELAP5 Thermal-Hydraulic Code
2008
The European Facility for Industrial Transmutation (EFIT) is aimed at demonstrating the feasibility of transmutation process through the Accelerator Driven System (ADS) route on an industrial scale. The conceptual design of this reactor of about 400 MW thermal power is under development in the frame of the European EUROTRANS Integrated Project of the EURATOM Sixth Framework Program (FP6). EFIT is a pool-type reactor cooled by forced circulation of lead in the primary system where the heat is removed by steam generators installed inside the reactor vessel. The reactor power is sustained by a spallation neutron source supplied by a proton beam impinging on a lead target at the core centre. A …
Novel Munc13-4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis
2006
Familial haemophagocytic lymphohistiocytosis (FHL) is a genetically heterogeneous disorder characterised by constitutive defects in cellular cytotoxicity resulting in fever, hepatosplenomegaly and cytopenia, and the outcome is fatal unless treated by chemoimmunotherapy followed by haematopoietic stem‐cell transplantation. Since 1999, mutations in the perforin gene giving rise to this disease have been identified; however, these account only for 40% of cases. Lack of a genetic marker hampers the diagnosis, suitability for transplantation, selection of familial donors, identification of carriers, genetic counselling and prenatal diagnosis. Mutations in the Munc13–4 gene have recently been des…
Histopathological progression of hidradenitis suppurativa/acne inversa
2021
It is generally acknowledged that the first morphological change of hidradenitis suppurativa/acne inversa (HS/AI) consists of infundibular plugging of the folliculosebaceous apocrine apparatus, which is followed by acute and chronic inflammation, cysts with sinus formation, and fibrosis. Alternatively, it has been hypothesized that HS/AI is primarily a neutrophilic autoinflammatory disease and that the follicular plugging typical of this disease is secondary to inflammation.To review the sequence of the changes that mark the disease development, we have performed a histopathologic study on the surgical material from a series of axillary and inguinal/perineal cases.The histologic material fr…
Woc (without children) gene control of ecdysone biosynthesis in Drosophila melanogaster.
2001
Abstract The first step in ecdysteroidogenesis, i.e. the 7,8-dehydrogenation of dietary cholesterol (C) to 7-dehydrocholesterol (7dC), is blocked in Drosophila melanogaster homozygous woc (without children) third instar larval ring glands (source of ecdysone). Unlike ring glands from wild-type D. melanogaster larvae, glands from woc mutants cannot convert radiolabelled C or 25-hydroxycholesterol (25C) to 7dC or 7-dehydro-25-hydroxycholesterol (7d25C) in vitro, nor to ecdysone (E). Yet, when these same glands are incubated with synthetic tracer 7d25C, the rate of metabolism of this polar Δ5,7-sterol into E is identical to that observed with glands from comparably staged wild-type larvae. The…
Sequence variation and regulatory variation in acetylcholinesterase genes contribute to insecticide resistance in different populations of Leptinotar…
2021
Abstract Although insect herbivores are known to evolve resistance to insecticides through multiple genetic mechanisms, resistance in individual species has been assumed to follow the same mechanism. While both mutations in the target site insensitivity and increased amplification are known to contribute to insecticide resistance, little is known about the degree to which geographic populations of the same species differ at the target site in a response to insecticides. We tested structural (e.g., mutation profiles) and regulatory (e.g., the gene expression of Ldace1 and Ldace2, AChE activity) differences between two populations (Vermont, USA and Belchow, Poland) of the Colorado potato beet…
A Note on Resampling the Integration Across the Correlation Integral with Alternative Ranges
2003
Abstract This paper reconsiders the nonlinearity test proposed by Ko[cbreve]enda (Ko[cbreve]enda, E. (2001). An alternative to the BDS test: integration across the correlation integral. Econometric Reviews20:337–351). When the analyzed series is non‐Gaussian, the empirical rejection rates can be much larger than the nominal size. In this context, the necessity of tabulating the empirical distribution of the statistic each time the test is computed is stressed. To that end, simple random permutation works reasonably well. This paper also shows, through Monte Carlo experiments, that Ko[cbreve]enda's test can be more powerful than the Brock et al. (Brock, W., Dechert, D., Scheickman, J., LeBar…
The measurement of rank mobility
2009
Abstract In this paper we investigate the problem of measuring social mobility when the social status of individuals is given by their rank. In order to sensibly represent the rank mobility of subgroups within a given society, we address the problem in terms of partial permutation matrices which include standard (“global”) matrices as a special case. We first provide a characterization of a partial ordering on partial matrices which, in the standard case of global matrices, coincides with the well-known “concordance” ordering. We then provide a characterization of an index of rank mobility based on partial matrices and show that, in the standard case of comparing global matrices, it is equi…
Photo-thermal control of surface plasmon mode propagation at telecom wavelengths
2016
Surface plasmon polaritons (SPPs) is the promising versatile platform proposed for guiding electromagnetic waves at nanoscale dimensions. In this context dynamic control of SPPs prop- agation is of paramount importance. Thermo-optical (TO) effect is considered as an efficient technique for performing active control of plasmonic devices. Among the thermo-optical based plasmonic devices demonstrated so far TO coefficient is dominantly provided by a dielectric material on top of the metal sustaining the SPP mode, however, the role of TO properties of the metal has been rarely investigated for plasmonic applications especially at the telecom frequency ranges. Therefore, the aim of this thesis i…