A GPU-Oriented Algorithm Design for Secant-Based Dimensionality Reduction

Dimensionality-reduction techniques are a fundamental tool for extracting useful information from high-dimensional data sets. Because secant sets encode manifold geometry, they are a useful tool for designing meaningful data-reduction algorithms. In one such approach, the goal is to construct a projection that maximally avoids secant directions and hence ensures that distinct data points are not mapped too close together in the reduced space. This type of algorithm is based on a mathematical framework inspired by the constructive proof of Whitney's embedding theorem from differential topology. Computing all (unit) secants for a set of points is by nature computationally expensive, thus opening the door for exploitation of GPU architecture for achieving fast versions of these algorithms. We present a polynomial-time data-reduction algorithm that produces a meaningful low-dimensional representation of a data set by iteratively constructing improved projections within the framework described above. Key to our algorithm design and implementation is the use of GPUs which, among other things, minimizes the computational time required for the calculation of all secant lines. One goal of this report is to share ideas with GPU experts and to discuss a class of mathematical algorithms that may be of interest to the broader GPU community.Comment: To appear in the 17th IEEE International Symposium on Parallel and Distributed Computing, Geneva, Switzerland 201

Resistance mechanisms to targeted therapy in BRAF-mutant melanoma - A mini review

Background The introduction of targeted therapies for the treatment of BRAF-mutant melanomas have improved survival rates in a significant proportion of patients. Nonetheless, the emergence of resistance to treatment remains inevitable in most patients. Scope of review Here, we review known and emerging molecular mechanisms that underlay the development of resistance to MAPK inhibition in melanoma cells and the potential strategies to overcome these mechanisms. Major conclusions Multiple genetic and non-genetic mechanisms contribute to treatment failure, commonly leading to the reactivation of the MAPK pathway. A variety of resistance mechanisms are enabled by the underlying heterogeneity and plasticity of melanoma cells. Moreover, it has become apparent that resistance to targeted therapy is underpinned by early functional adaptations involving the rewiring of cell states and metabolic pathways. General significance The evidence presented suggest that the use of a combinatorial treatment approach would delay the emergence of resistance and improve patient outcomes

Circulating tumour DNA (ctDNA) as a biomarker in metachronous melanoma and colorectal cancer- a case report

Background: Circulating tumour DNA (ctDNA) has emerged as a promising blood-based biomarker for monitoring disease status of patients with advanced cancers. The presence of ctDNA in the blood is a result of biological processes, namely tumour cell apoptosis and/or necrosis, and can be used to monitor different cancers by targeting cancer-specific mutation. Case presentation: We present the case of a 67 year old Caucasian male that was initially treated with BRAF inhibitors followed by anti-CTLA4 and then anti-PD1 immunotherapy for metastatic melanoma but later developed colorectal cancer. The kinetics of ctDNA derived from each cancer type were monitored targeting BRAF V600R (melanoma) and KRAS G13D (colon cancer), specifically reflected the status of the patient\u27s tumours. In fact, the discordant pattern of BRAF and KRAS ctDNA was significantly correlated with the clinical response of melanoma to pembrolizumab treatment and progression of colorectal cancer noted by PET and/or CT scan. Based on these results, ctDNA can be used to specifically clarify disease status of patients with metachronous cancers. Conclusions: Using cancer-specific mutational targets, we report here for the first time the efficacy of ctDNA to accurately provide a comprehensive outlook of the tumour status of two different cancers within one patient. Thus, ctDNA analysis has a potential clinical utility to delineate clinical information in patients with multiple cancer types

SOX11 expression correlates to promoter methylation and regulates tumor growth in hematopoietic malignancies

<p>Abstract</p> <p>Background</p> <p>The transcription factor SOX11 plays an important role in embryonic development of the central nervous system (CNS) and is expressed in the adult immature neuron but is normally not expressed in any other adult tissue. It has recently been reported to be implicated in various malignant neoplasms, including several lymphoproliferative diseases, by its specific expression and in some cases correlation to prognosis. SOX11 has been shown to prevent gliomagenesis <it>in vivo </it>but the causes and consequences of aberrant expression of <it>SOX11 </it>outside the CNS remain unexplained.</p> <p>Results</p> <p>We now show the first function of <it>SOX11 </it>in lymphoproliferative diseases, by demonstrating <it>in vitro </it>its direct involvement in growth regulation, as assessed by siRNA-mediated silencing and ectopic overexpression in hematopoietic malignancies. Gene Chip analysis identified cell cycle regulatory pathways, including Rb-E2F, to be associated with SOX11-induced growth reduction. Furthermore, promoter analysis revealed that <it>SOX11 </it>is silenced through DNA methylation in B cell lymphomas, suggesting that its regulation is epigenetically controlled.</p> <p>Conclusions</p> <p>The data show that SOX11 is not a bystander but an active and central regulator of cellular growth, as both siRNA-mediated knock-down and ectopic overexpression of <it>SOX11 </it>resulted in altered proliferation. Thus, these data demonstrate a tumor suppressor function for <it>SOX11 </it>in hematopoietic malignancies and revealed a potential epigenetic regulation of this developmentally involved gene.</p

The Descriptions and Attitudes of Riders and Arena Owners to 656 Equestrian Sport Surfaces in Sweden

Horses in equestrian sports are commonly trained in arenas with prepared footing. Information on the number and variants of such arenas is generally unknown. This paper provides an overview of the primary construction types of riding surfaces in Sweden including details on composition, constructions principles, usage frequency, maintenance, and cost of operation as well as to investigate rider perception of the ideal arena properties using a large population of riders. Data on 656 equestrian surfaces in Sweden obtained up to 2014 are presented, of which 373 were outdoor and 283 were indoor arenas. Dressage and show-jumping were the main disciplines conducted in the arenas. Sand-mineral arenas were most common outdoors and sand-woodchips arenas most common indoors, followed by sand-fibre arenas and even fewer synthetic arenas. Comparing the three most common arena types, dragging was most often done on sand-woodchips and sand-fibre arenas. Harrowing was less often done on sand-mineral arenas compared to sand-woodchips and sand-fibre arenas. Combining dragging, harrowing, deep harrowing, and rolling, arenas with higher usage were maintained more frequently, compared to those used less frequently. It was commonly claimed that the top-layer needs renovation every other-4th year or every 5th to 10th year. Few respondents allocated more than 10,000 SEK in yearly maintenance costs, with the exception for sand-woodchips and sand-fibre arenas followed by synthetic arenas. The shortest duration perceived between required renovations was found for sand-woodchips top-layer arenas. Ideal surface properties were evaluated by 3,158 riders. Dressage and show-jumping riders differed somewhat regarding ideal spans of functional arena properties: for impact firmness, responsiveness, and grip. The current study likely included well-utilised arenas, compared to those less well-utilised. The resources necessary to keep an arena consistent over time seemed underestimated. Knowledge of maintenance and priorities for arenas are important to users and arenas managers, be they construction companies or arena managers in order to maximise the outcome of efforts for arena improvement and optimise locomotor health for horses that use them. Further, many arenas were new and research into organic arena management is important, especially if equestrians continue to build and renew arena surfaces