Acetaldehyde as an underestimated risk factor for cancer development: role of genetics in ethanol metabolism

Chronic ethanol consumption is a strong risk factor for the development of certain types of cancer including those of the upper aerodigestive tract, the liver, the large intestine and the female breast. Multiple mechanisms are involved in alcohol-mediated carcinogenesis. Among those the action of acetaldehyde (AA), the first metabolite of ethanol oxidation is of particular interest. AA is toxic, mutagenic and carcinogenic in animal experiments. AA binds to DNA and forms carcinogenic adducts. Direct evidence of the role of AA in alcohol-associated carcinogenesis derived from genetic linkage studies in alcoholics. Polymorphisms or mutations of genes coding for AA generation or detoxifying enzymes resulting in elevated AA concentrations are associated with increased cancer risk. Approximately 40% of Japanese, Koreans or Chinese carry the AA dehydrogenase 2*2 (ALDH2*2) allele in its heterozygous form. This allele codes for an ALDH2 enzyme with little activity leading to high AA concentrations after the consumption of even small amounts of alcohol. When individuals with this allele consume ethanol chronically, a significant increased risk for upper alimentary tract and colorectal cancer is noted. In Caucasians, alcohol dehydrogenase 1C*1 (ADH1C*1) allele encodes for an ADH isoenzyme which produces 2.5 times more AA than the corresponding allele ADH1C*2. In studies with moderate to high alcohol intake, ADH1C*1 allele frequency and rate of homozygosity was found to be significantly associated with an increased risk for cancer of the upper aerodigestive tract, the liver, the colon and the female breast. These studies underline the important role of acetaldehyde in ethanol-mediated carcinogenesis.

Evaluation of Binocular Eye Trackers and Algorithms for 3D Gaze Interaction in Virtual Reality Environments

Tracking user’s visual attention is a fundamental aspect in novel human-computer interaction paradigms found in Virtual Reality. For example, multimodal interfaces or dialogue-based communications with virtual and real agents greatly benefit from the analysis of the user’s visual attention as a vital source for deictic references or turn-taking signals. Current approaches to determine visual attention rely primarily on monocular eye trackers. Hence they are restricted to the interpretation of two-dimensional fixations relative to a defined area of projection. The study presented in this article compares precision, accuracy and application performance of two binocular eye tracking devices. Two algorithms are compared which derive depth information as required for visual attention-based 3D interfaces. This information is further applied to an improved VR selection task in which a binocular eye tracker and an adaptive neural network algorithm is used during the disambiguation of partly occluded objects.

Algorithms For Automatic And Robust Registration Of 3D Head Scans

wo methods for registering laser-scans of human heads and transforming them to a new semantically consistent topology defined by a user-provided template mesh are described. Both algorithms are stated within the Iterative Closest Point framework. The first method is based on finding landmark correspondences by iteratively registering the vicinity of a landmark with a re-weighted error function. Thin-plate spline interpolation is then used to deform the template mesh and finally the scan is resampled in the topology of the deformed template. The second algorithm employs a morphable shape model, which can be computed from a database of laser-scans using the first algorithm. It directly optimizes pose and shape of the morphable model. The use of the algorithm with PCA mixture models, where the shape is split up into regions each described by an individual subspace, is addressed. Mixture models require either blending or regularization strategies, both of which are described in detail. For both algorithms, strategies for filling in missing geometry for incomplete laser-scans are described. While an interpolation-based approach can be used to fill in small or smooth regions, the model-driven algorithm is capable of fitting a plausible complete head mesh to arbitrarily small geometry, which is known as "shape completion". The importance of regularization in the case of extreme shape completion is shown.

Genome sequence, comparative analysis, and population genetics of the domestic horse

We report a high-quality draft sequence of the genome of the horse (Equus caballus). The genome is relatively repetitive but has little segmental duplication. Chromosomes appear to have undergone few historical rearrangements: 53% of equine chromosomes show conserved synteny to a single human chromosome. Equine chromosome 11 is shown to have an evolutionary new centromere devoid of centromeric satellite DNA, suggesting that centromeric function may arise before satellite repeat accumulation. Linkage disequilibrium, showing the influences of early domestication of large herds of female horses, is intermediate in length between dog and human, and there is long-range haplotype sharing among breeds.

A Video Database for the Development of Stereo-3D Post-Production Algorithms

This paper introduces a database of freely available stereo-3D content designed to facilitate research in stereo post-production. It describes the structure and content of the database and provides some details about how the material was gathered. The database includes examples of many of the scenarios characteristic to broadcast footage. Material was gathered at different locations including a studio with controlled lighting and both indoor and outdoor on-location sites with more restricted lighting control. The database also includes video sequences with accompanying 3D audio data recorded in an Ambisonics format. An intended consequence of gathering the material is that the database contains examples of degradations that would be commonly present in real-world scenarios. This paper describes one such artefact caused by uneven exposure in the stereo views, causing saturation in the over-exposed view. An algorithm for the restoration of this artefact is proposed in order to highlight the usefuiness of the database.

Molecular genetics and functional anomalies in a series of 248 Brugada cases with 11 mutations in the TRPM4 channel.

Brugada syndrome (BrS) is a condition defined by ST-segment alteration in right precordial leads and a risk of sudden death. Because BrS is often associated with right bundle branch block and the TRPM4 gene is involved in conduction blocks, we screened TRPM4 for anomalies in BrS cases. The DNA of 248 BrS cases with no SCN5A mutations were screened for TRPM4 mutations. Among this cohort, 20 patients had 11 TRPM4 mutations. Two mutations were previously associated with cardiac conduction blocks and 9 were new mutations (5 absent from ~14'000 control alleles and 4 statistically more prevalent in this BrS cohort than in control alleles). In addition to Brugada, three patients had a bifascicular block and 2 had a complete right bundle branch block. Functional and biochemical studies of 4 selected mutants revealed that these mutations resulted in either a decreased expression (p.Pro779Arg and p.Lys914X) or an increased expression (p.Thr873Ile and p.Leu1075Pro) of TRPM4 channel. TRPM4 mutations account for about 6% of BrS. Consequences of these mutations are diverse on channel electrophysiological and cellular expression. Because of its effect on the resting membrane potential, reduction or increase of TRPM4 channel function may both reduce the availability of sodium channel and thus lead to BrS.

Searching for the majority: algorithms of voluntary control.

Voluntary control of information processing is crucial to allocate resources and prioritize the processes that are most important under a given situation; the algorithms underlying such control, however, are often not clear. We investigated possible algorithms of control for the performance of the majority function, in which participants searched for and identified one of two alternative categories (left or right pointing arrows) as composing the majority in each stimulus set. We manipulated the amount (set size of 1, 3, and 5) and content (ratio of left and right pointing arrows within a set) of the inputs to test competing hypotheses regarding mental operations for information processing. Using a novel measure based on computational load, we found that reaction time was best predicted by a grouping search algorithm as compared to alternative algorithms (i.e., exhaustive or self-terminating search). The grouping search algorithm involves sampling and resampling of the inputs before a decision is reached. These findings highlight the importance of investigating the implications of voluntary control via algorithms of mental operations.