28 resultados para variant genotypes

em Deakin Research Online - Australia


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The transformation texture of α/β brass with a diffusional Widmanstätten α growth morphology has been investigated. Electron micrographs and electron backscattered diffraction was used to determine that the orientation relationship between the β phase and the α associated with nucleation at β grain boundaries was (44.3°) left angle bracket1 1 6right-pointing angle bracket. Crystallographic variant selection was observed across those prior β/β grain boundaries, but this has little effect on the transformation texture due to the crystal symmetry. The effect of the crystallographic variant selection on texture is further weakened by nucleation of diffusional transformed α in the grain interior.

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Transformation textures in the two-phase alloy Ti–6Al–4V have been studied. Samples were heated into the fully β phase condition and then slow cooled to allow diffusional transformation to α. This produced a microstructure of grain boundary α encircling colonies of Widmanstätten α. Electron backscattered diffraction (EBSD) texture measurements showed that the α texture was markedly sharper than that calculated on a basis of equal variant probability, indicating that significant variant selection was occurring during diffusional transformation. Investigation of the α variants produced across prior β grain boundaries has shown that the selection of variants during transformation is highly dependant on the crystallography of those boundaries. The effect of this crystallographic variant selection on the transformation texture has been modelled.

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Aims
Cyclophosphamide (CTX) is an established treatment of severe systemic lupus erythematosus (SLE). Cytotoxic CTX metabolites are mainly detoxified by multiple glutathione S-transferases (GSTs). However, data are lacking on the relationship between the short-term side-effects of CTX therapy and GST genotypes. In the present study, the effects of common GSTM1, GSTT1, and GSTP1 genetic mutations on the severity of myelosuppression, gastrointestinal (GI) toxicity, and infection incidences induced by pulsed CTX therapy were evaluated in patients SLE.
Methods
DNA was extracted from peripheral leucocytes in patients with confirmed SLE diagnosis (n = 102). GSTM1 and GSTT1 null mutations were analyzed by a polymerase chain reaction (PCR)-multiplex procedure, whereas the GSTP1 codon 105 polymorphism (Ile→Val) was analyzed by a PCR-restriction fragment length polymorphism (RFLP) assay.
Results
Our study demonstrated that SLE patients carrying the genotypes with GSTP1 codon 105 mutation [GSTP1*-105I/V (heterozygote) and GSTP1*-105 V/V (homozygote)] had an increased risk of myelotoxicity when treated with pulsed high-dose CTX therapy (Odds ratio (OR) 5.00, 95% confidence interval (CI) 1.96, 12.76); especially in patients younger than 30 years (OR 7.50, 95% CI 2.14, 26.24), or in patients treated with a total CTX dose greater than 1.0 g (OR 12.88, 95% CI 3.16, 52.57). Similarly, patients with these genotypes (GSTP1*I/V and GSTP1*V/V) also had an increased risk of GI toxicity when treated with an initial pulsed high-dose CTX regimen (OR 3.33, 95% CI 1.03, 10.79). However, GSTM1 and GSTT1 null mutations did not significantly alter the risks of these short-term side-effects of pulsed high-dose CTX therapy in SLE patients.
Conclusions
The GSTP1 codon 105 polymorphism, but not GSTM1 or GSTT1 null mutations, significantly increased the risks of short-term side-effects of pulsed high-dose CTX therapy in SLE patients. Because of the lack of selective substrates for a GST enzyme phenotyping study, timely detection of this mutation on codon 105 may assist in optimizing pulsed high-dose CTX therapy in SLE patients.

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This paper will examine how qualitative research into bereaved young adults’ experiences of social isolation can constitute a qualitative variant on the study of social isolation to Hawthorne’s quantitative ‘Friendship Scale’ (FS). As an instrument for measuring social isolation, the FS derives primarily from a particular dimension of social support; that is, the individual’s sense of connection to other people. This sense of connection to others is similarly a principal concern in the author’s study of bereaved young siblings (aged 18-30). The death of a close family member is commonly identified by researchers as the most debilitating stressor in everyday life. How then does this major life stressor impact on the individual’s sense of social connectedness?

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In a recent paper, we demonstrated that male-female genetic relatedness determines male probability of paternity in experimental sperm competition in the Peron's tree frog (Litoria peronii), with a more closely related male out-competing his rival. Here, we test the hypothesis that a male-male difference in siring success with one female significantly predicts the corresponding difference in siring success with another female. With male sperm concentration held constant, and the proportion of viable sperm controlled statistically, the male-male difference in siring success with one female strongly predicted the corresponding difference in siring success with another female, and alone explained more than 62 per cent of the variance in male-male siring differences. This study demonstrates that male siring success is primarily dictated by among-male differences in innate siring success with less influence of male-female relatedness.

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Various statistical methods have been proposed to evaluate associations between measured genetic variants and disease, including some using family designs. For breast cancer and rare variants, we applied a modified segregation analysis method that uses the population cancer incidence and population-based case families in which a mutation is known to be segregating. Here we extend the method to a common polymorphism, and use a regressive logistic approach to model familial aggregation by conditioning each individual on their mother's breast cancer history. We considered three models: 1) class A regressive logistic model; 2) age-of-onset regressive logistic model; and 3) proportional hazards familial model. Maximum likelihood estimates were calculated using the software MENDEL. We applied these methods to data from the Australian Breast Cancer Family Study on the CYP17 5UTR TC MspA1 polymorphism measured for 1,447 case probands, 787 controls, and 213 relatives of case probands found to have the CC genotype. Breast cancer data for first- and second-degree relatives of case probands were used. The three methods gave consistent estimates. The best-fitting model involved a recessive inheritance, with homozygotes being at an increased risk of 47% (95% CI, 28-68%). The cumulative risk of the disease up to age 70 years was estimated to be 10% or 22% for a CYP17 homozygote whose mother was unaffected or affected, respectively. This analytical approach is well-suited to the data that arise from population-based case-control-family studies, in which cases, controls and relatives are studied, and genotype is measured for some but not all subjects.

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The variant selection phenomenon during the austenite to bainite phase transformation in hot-rolled TRIP-aided steels was quantitatively characterized at the level of individual austenite grains. The reconstruction of the electron backscatter diffraction maps provided evidence that bainite grows by packets of laths sharing a common {1 1 1}y plane in the austenite. The affect of hot deformation is to reduce the number of packets that form. It is suggested that slip activity is important in understanding this effect.

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The serotonin transporter gene (5-HTT) encodes a transmembrane protein that plays an important role in regulating serotonergic neurotransmission and related aspects of mood and behaviour. The short allele of a 44 bp insertion/deletion polymorphism (S-allele) within the promoter region of the 5-HTT gene (5-HTTLPR) confers lower transcriptional activity relative to the long allele (L-allele) and may act to modify the risk of serotonin-mediated outcomes such as anxiety and substance use behaviours. The purpose of this study was to determine whether (or not) 5-HTTLPR genotypes moderate known associations between attachment style and adolescent anxiety and alcohol use outcomes. Participants were drawn from an eight-wave study of the mental and behavioural health of a cohort of young Australians followed from 14 to 24 years of age (Victorian Adolescent Health Cohort Study, 1992 - present). No association was observed within low-risk attachment settings. However, within risk settings for heightened anxiety (ie, insecurely attached young people), the odds of persisting ruminative anxiety (worry) decreased with each additional copy of the S-allele (B30% per allele: OR 0.77, 95% CI 0.62–0.97, P¼0.029). Within risk settings for binge drinking (ie, securely attached young people), the odds of reporting persisting high-dose alcohol consumption (bingeing) decreased with each additional copy of the S-allele (B35% per allele: OR 0.74, 95% CI 0.64–0.86, Po0.001). Our data suggest that the S-allele is likely to be important in psychosocial development, particularly in those settings that increase risk of anxiety and alcohol use problems.

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Static detection of polymorphic malware variants plays an important role to improve system security. Control flow has shown to be an effective characteristic that represents polymorphic malware instances. In our research, we propose a similarity search of malware using novel distance metrics of malware signatures. We describe a malware signature by the set of control flow graphs the malware contains. We propose two approaches and use the first to perform pre-filtering. Firstly, we use a distance metric based on the distance between feature vectors. The feature vector is a decomposition of the set of graphs into either fixed size k-sub graphs, or q-gram strings of the high-level source after decompilation. We also propose a more effective but less computationally efficient distance metric based on the minimum matching distance. The minimum matching distance uses the string edit distances between programs' decompiled flow graphs, and the linear sum assignment problem to construct a minimum sum weight matching between two sets of graphs. We implement the distance metrics in a complete malware variant detection system. The evaluation shows that our approach is highly effective in terms of a limited false positive rate and our system detects more malware variants when compared to the detection rates of other algorithms.

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Log polar transformations for space variant systems have been proposed and used in active vision research. The idea is to generate an image with a varying resolution over a wide angle field of view. The fovea is of high resolution and the periphery is of exponentially reduced resolution. The justifications for such a sensor are: (i) it provides high resolution and a wide viewing angle, (ii) feature invariance in the fovea simplifies foveation, and (iii) it allows multiresolution analysis. The receptor density of the human retina is very high, i.e. of the order of 106 receptors at the fovea. The question is, what resolution should space variant active vision systems have? Real visual sensors have been implemented but is the resolution produced high enough? This paper investigates the resolution requirements of a space variant sensor by simulation for a tracking system using raytracing

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Without the ability to foveate on and maintain foveation, active vision for applications such as surveillance, object recognition and object tracking are difficult to build. Although foveation in cartesian coordinates is being actively pursued by many, multi-resolution high accuracy foveation in log polar space has not been given much attention. This paper addresses the use of foveation to track a single object as well as multiple objects for a simulated space variant active vision system. Complex logarithmic mapping is chosen firstly because it provides high resolution and wide angle viewing. Secondly, the spatially variant structure of log polar space leads to an object increasing in size as it moves towards the fovea. This is important as we know which object is closer to the fovea at any instant in time.