401 research outputs found
Anti-aliasing with stratified B-spline filters of arbitrary degree
A simple and elegant method is presented to perform anti-aliasing in raytraced images. The method uses stratified
sampling to reduce the occurrence of artefacts in an image and features a B-spline filter to compute the final
luminous intensity at each pixel. The method is scalable through the specification of the filter degree. A B-spline
filter of degree one amounts to a simple anti-aliasing scheme with box filtering. Increasing the degree of the B-spline generates progressively smoother filters. Computation of the filter values is done in a recursive way, as part of a sequence of Newton-Raphson iterations, to obtain the optimal sample positions in screen space. The proposed method can perform both anti-aliasing in space and in time, the latter being more commonly known as motion blur. We show an application of the method to the ray casting of implicit procedural surfaces
A Temporal Image-Based Approach to Motion Reconstruction for Globally Illuminated Animated Environments
CXCR6 marks a novel subset of T-bet(lo)Eomes(hi) natural killer cells residing in human liver
This work was funded by a Wellcome Trust Investigator Award to MKM funding KS and LP, MRC Career Development Award to CD, MRC Clinical Research Training Fellowship to DP, Wellcome Trust Henry Dale Fellowship to VM
O6-methylguanine-DNA-methyltransferase expression and gene polymorphisms in relation to chemotherapeutic response in metastatic melanoma
In a retrospective study, O6-methylguanine-DNA-methyltransferase (MGMT) expression was analysed by immunohistochemistry using monoclonal human anti-MGMT antibody in melanoma metastases in patients receiving dacarbazine (DTIC) as single-drug therapy or as part of combination chemotherapy with DTIC–vindesine or DTIC–vindesine–cisplatin. The correlation of MGMT expression levels with clinical response to chemotherapy was investigated in 79 patients with metastatic melanoma. There was an inverse relationship between MGMT expression and clinical response to DTIC-based chemotherapy (P=0.05). Polymorphisms in the coding region of the MGMT gene were also investigated in tumours from 52 melanoma patients by PCR/SSCP and nucleotide sequence analyses. Single-nucleotide polymorphisms (SNPs) in exon 3 (L53L and L84F) and in exon 5 (I143V/K178R) were identified. There were no differences in the frequencies of these polymorphisms between these melanoma patients and patients with familial melanoma or healthy Swedish individuals. Functional analysis of variants MGMT-I143V and -I143V/K178R was performed by in vitro mutagenesis in Escherichia coli. There was no evidence that these variants decreased the MGMT DNA repair activity compared to the wild-type protein. All melanoma patients with the MGMT 53/84 polymorphism except one had tumours with high MGMT expression. There was no significant correlation between any of the MGMT polymorphisms and clinical response to chemotherapy, although an indication of a lower response rate in patients with SNPs in exon 5 was obtained. Thus, MGMT expression appears to be more related to response to chemotherapy than MGMT polymorphisms in patients with metastatic melanoma
Contributions of DNA repair and damage response pathways to the non-linear genotoxic responses of alkylating agents
Gastrointestinal Hyperplasia with Altered Expression of DNA Polymerase β
Background: Altered expression of DNA polymerase β (Pol β) has been documented in a large percentage of human tumors. However, tumor prevalence or predisposition resulting from Pol β over-expression has not yet been evaluated in a mouse model. Methodology/Principal Findings: We have recently developed a novel transgenic mouse model that over-expresses Pol β. These mice present with an elevated incidence of spontaneous histologic lesions, including cataracts, hyperplasia of Brunner's gland and mucosal hyperplasia in the duodenum. In addition, osteogenic tumors in mice tails, such as osteoma and osteosarcoma were detected. This is the first report of elevated tumor incidence in a mouse model of Pol β over-expression. These findings prompted an evaluation of human gastrointestinal tumors with regard to Pol β expression. We observed elevated expression of Pol β in stomach adenomas and thyroid follicular carcinomas, but reduced Pol β expression in esophageal adenocarcinomas and squamous carcinomas. Conclusions/Significance: These data support the hypothesis that balanced and proficient base excision repair protein expression and base excision repair capacity is required for genome stability and protection from hyperplasia and tumor formation
Balancing repair and tolerance of DNA damage caused by alkylating agents
Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity
- …