Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Compact collimators for high brightness blue LEDs using dielectric multilayers

A novel method is presented to inject the light of millimeter-sized high-brightness blue LEDs into light guides of submillimeter thickness. Use is made of an interference filter that is designed to pass only those modes that will propagate in the light guide by total internal reflection. Other modes are reflected back to the LED cavity and recycled, leading to an increased brightness. With this method a collimator has been designed and made that is only 1mm thick, with a diameter of 6.5mm. It creates a beam of 26deg Full Width at Half Maximum. Presently, collimators with these characteristics have a thickness of 10-20mm and a diameter of 20-30mm and require careful mounting and alignment. The new collimator contains a 4.5micron thick interference filter made of 54 layers of Nb2O5 and SiO2 layers. The filter is optically coupled to the LED with Silicone adhesive which makes the configuration very robust. A cylindrical lightguide, tapered from 6.5mm to 2.5mm diameter and 1mm thick captures the light that passes the filter, folds the light path and redirects the beam. Measurements on collimator prototypes show good agreement with the designed characteristics. This promising approach enables much more compact collimators optics that offer material cost savings and design freedom.Optics Research GroupApplied Science

Increasing Acceptance of Haptic Feedback on UAV Teleoperations by Visualizing Force Fields

In tele-operating an UAV human operators fully rely on cameras to control the vehicle from a distance. To increase operator situation awareness and reduce workload, a haptic feedback on the control stick has been developed which acts as an automatic collision avoidance system. A virtual force field surrounding the moving vehicle interacts with obstacles surrounding it, yielding repulsive forces on the stick that lead the vehicle away from them. Albeit successful in significantly reducing the number of collisions, the haptic interface received low user acceptance ratings. Operators do not always fully understand the collision avoidance automation intentions, and they experience the haptic forces as intrusive. This paper discusses the development and testing of several visualizations of the underlying automation intentions, primarily the artificial force field. Results of a human-in-the-loop experiment show that these visualizations indeed led to higher user acceptance ratings, without affecting the operator’s safety, performance and workload.Control & SimulationControl & Operation

Increasing Acceptance of Haptic Feedback in UAV Teleoperations by Visualizing Force Fields

Haptic interfaces have been developed to assist human operators controlling unmanned aerial vehicles (UAV) be- yond line-of-sight. These systems complement the predominantly camera-based visual interfaces and act like a collision-avoidance system: when nearing obstacles, the operator gets re-directed by the haptic force feedback. Previous research showed that, although being successful in reducing the number of collisions, these haptic interfaces also lead to lower user acceptance, as the operators do not always understand the system’s intentions. This paper discusses two novel visualizations which were developed to increase operator acceptance. Both designs were evaluated in a human-in-the-loop experiment (n=12). Results from acceptance- related questionnaires show that our subjects preferred tele- operating the UAV with the visualizations active. Acceptance ratings were higher for the same levels of safety, performance and operator workload.Control & SimulationControl & Operation

Injecting light of high-power LEDs into thin light guides

A new method using a thin-film multilayer filter is described to couple light from high-power LEDs into a thin light guide such as an LCD backlight. Light emitted below the critical angle is reflected back to the LED and recycled. Largeangle emitted light passes the filter and is transported by total internal reflection in the light guide. The light guide can be as thin as 0.3mm for an LED of 1x1mm2, and the best coupling efficiency is estimated to be around 80%. With this approach, a backlight system can be greatly simplified but also compact collimators can be realized. In this paper the optical design and testing of the filter is described, and a 1mm thick, 6.5mm diameter collimator is presented that emits in a cone of 2x13o. Measurements on prototypes show good agreement with the designed characteristicsOptics Research GroepApplied Science

Optic-flow based slope estimation for autonomous landing

Micro Air Vehicles need to have a robust landing capability, especially when they operate outside line-of-sight. Autonomous landing requires the identification of a relatively flat landing surface that does not have too large an inclination. In this article, a vision algorithm is introduced that fits a second-order approximation to the optic flow field underlying the optic flow vectors in images from a bottom camera. The flow field provides information on the ventral flow (vx/h), the time-to-contact (h/ ? vz), the flatness of the landing surface, and the surface slope. The algorithm is computationally efficient and since it regards the flow field as a whole, it is suitable for use during relatively fast maneuvers. The algorithm is subsequently tested on artificial image sequences, hand-held videos, and on the images made by a Parrot AR drone. In a preliminary robotic experiment, the AR drone uses the vision algorithm to determine when to land in a scenario where it flies off a stairs onto the flat floor.Control & OperationsAerospace Engineerin

Multi-objective optimization of laminated composite beam structures using NSGA-II algorithm

The paper deals with the multi-objective optimization problems of laminated composite beam structures. The objective function is to minimize the weight of the whole laminated composite beam and maximize the natural frequency. In particular, the simultaneous use of all the design variables such as fiber volume fractions, thickness and fiber orientation angles of layers is conducted, in which the fiber volume fractions are taken as continuous design variables with the constraint on manufacturing process while the thickness and fiber orientation angles are considered as discrete variables. The beam structure is subjected to the constraint in the natural frequency which must be greater than or equal to a predetermined frequency. For free vibration analysis of the structure, the finite element method is used with the two-node Bernoulli-Euler beam element. For solving the multi-objective optimization problem, the nondominated sorting genetic algorithm II (NSGA-II) is employed. The reliability and effectiveness of the proposed approach are demonstrated through three numerical examples by comparing the current results with those of previous studies in the literature.Aerospace Transport & Operation

Nonlinear Finite Element Analysis of Deteriorated RC Slab Bridge

Applications of nonlinear finite element analysis (NLFEA) to complete structures have been limited. The study reported in this paper examined the reliability of NLFEA to assess strength and stiffness of a three-span reinforced concrete slab bridge that was loaded to failure in the field. The researchers at the University of Cincinnati and Delft University of Technology, in The Netherlands, conducted preliminary analyses that were then compared to the measured responses. These analyses indicate a significant influence of tensile behavior of concrete in the postcracking range, and the level of slab membrane force that is directly affected by the assumed horizontal support conditions at the slab-abutment connection. Reasonable correlation of the measured responses was possible by removing the horizontal restraints at the slab-abutment connections. However, such models do not simulate the observed behavior at the abutments. The shear keys at the slab-abutment connections would not permit free horizontal movements, yet the slab can rotate about the shear keys. The resulting rotation would reduce the membrane force that can be developed. An improved model incorporating this behavior produced better results than the original model assuming full horizontal restraints at the abutments

Effects of exercise on swallowing and tongue strength in patients with oral and oropharyngeal cancer treated with primary radiotherapy with or without chemotherapy

Tongue strength is reduced in patients treated with chemoradiotherapy for oral/oropharyngeal cancer. Tongue strengthening protocols have resulted in improved lingual strength and swallowing in healthy individuals, as well as in patients following a neurological event. However, no studies have examined the efficacy of tongue strengthening exercises on tongue strength, swallowing, and quality of life (QOL; Head and Neck Cancer Inventory) in patients treated with chemoradiotherapy. A randomized clinical trial examined the effects of a tongue strengthening programme paired with traditional exercises vs. traditional exercises alone. Dependent variables included tongue strength, swallowing, and QOL in a group of patients with oral and oropharyngeal cancer treated with primary radiotherapy with or without chemotherapy. Differences with regard to tongue strength and oropharyngeal swallow efficiency (OPSE) were not observed within or between groups. QOL in the eating and speech domains improved following treatment in both groups. However, the experimental group demonstrated greater impairment in QOL in the social disruption domain following treatment, whereas the control group demonstrated a slight improvement in functioning. Tongue strengthening did not yield a statistically significant improvement in either tongue strength or swallowing measures in this patient cohort. Patient compliance and treatment timing may be factors underlying these outcomes

Refinement of the basis and impact of common 11q23.1 variation to the risk of developing colorectal cancer.

The common single-nucleotide polymorphism (SNP) rs3802842 at 11q23.1 has recently been reported to be associated with risk of colorectal cancer (CRC). To examine this association in detail we genotyped rs3802842 in eight independent case-control series comprising a total of 10 638 cases and 10 457 healthy individuals. A significant association between the C allele of rs3802842 and CRC risk was found (per allele OR = 1.17; 95% confidence interval [CI]: 1.12-1.22; P = 1.08 x 10(-12)) with the risk allele more frequent in rectal than colonic disease (P = 0.02). In combination with 8q21, 8q24, 10p14, 11q, 15q13.3 and 18q21 variants, the risk of CRC increases with an increasing numbers of variant alleles for the six loci (OR(per allele) = 1.19; 95% CI: 1.15-1.23; P(trend) = 7.4 x 10(-24)). Using the data from our genome-wide association study of CRC, LD mapping and imputation, we were able to refine the location of the causal locus to a 60 kb region and screened for coding changes. The absence of exonic mutations in any of the transcripts (FLJ45803, LOC120376, C11orf53 and POU2AF1) mapping to this region makes the association likely to be a consequence of non-coding effects on gene expression