The 9p21 region in bladder cancer cell lines: large homozygous deletion inactivate the CDKN2, CDKN2B and MTAP genes

Homozygous and hemizygous deletions of 9p21 are the earliest and most common genetic alteration in bladder cancer. The identification of two cell cycle regulators, CDKN2 and CDKN2B, that map to the common region of deletion has prompted the hypothesis that they are critical tumor suppressor genes in this malignancy. However, controversy as to whether these genes are the only or even the most important target in bladder cancer oncogenesis remains. To more clearly determine the effect of these 9p21 alterations, we mapped the homozygous deletions and performed a detailed mutational and expression analysis for CDKN2, CDKN2B and a closely linked gene, methylthioadenoside phosphorylase (MTAP), in 16 established bladder cancer cell lines. Nine of the 16 lines exhibit large (30 to > 2000 kb) homozygous deletions on 9p21. All deletions include at least one exon of CDKN2, eight of nine include CDKN2B, and six of nine include MTAP. MTAP function correlates with the genomic deletions. SSCP and sequence analysis does not reveal any inactivating point mutations of CDKN2 or of CDKN2B in any of the cell lines without homozygous deletions, and all express the CDKN2 and the CDKN2B mRNA as well as the encoded p16 protein. The p16 protein levels vary widely and are correlated with absent pRb expression. We conclude that the 9p21 deletions in bladder cancer usually inactivate the CDKN2. CDKN2B, and MTAP genes but that CDKN2 is the most common target. Other mechanisms for inactivating this gene in bladder cancer appear to be uncommon.     

Hydrogen evolution during the oxidation of formaldehyde on Au:: The influence of single crystal structure and Tl-upd

Hydrogen evolution during formaldehyde oxidation in alkaline solution has been monitored by Differential Electrochemical Mass Spectrometry on Au(111) and polycrystalline gold. The current efficiency for hydrogen evolution increases with higher concentration and is in the same range on both, polycrystalline Au and Au(111) electrode. The onset potentials and half-wave potentials are higher on Au(111). Reaction orders for the faradaic current on the bare gold electrodes have been determined as 0.21 for higher and 0.76 for lower concentrations. Reaction orders for hydrogen evolution during formaldehyde oxidation are 1.4 times higher in each case. Tafel slopes in the range of 140-160 mV are found. This signifies that the first reaction step involving the formation of adsorbed hydrogen is largely determining the overall reaction rate. In the presence of thallium adlayers hydrogen evolution from formaldehyde oxidation is largely suppressed. On the thallium modified polycrystalline Au, formaldehyde oxidation is shifted for 100 mV to higher potentials where Tl is partially desorbed and hydroxide is coadsorbed on the modified surface. On thallium modified Au(111), a similar process takes place, but in the same potential region as the onset of formaldehyde oxidation on the bare surface and therefore the formaldehyde oxidation is only slightly shifted. Tafel slopes are decreased to 80 mV/dec in the presence of thallium. In the presence of adsorbed thallium, the first reaction step is in equilibrium, the coverage with adsorbed hydrogen is smaller and its recombination to H₂ is largely suppressed.     

Approximate similarity search for online multimedia services on distributed CPU–GPU platforms

Similarity search in high-dimensional spaces is a pivotal operation for several database applications, including online content-based multimedia services. With the increasing popularity of multimedia applications, these services are facing new challenges regarding (1) the very large and growing volumes of data to be indexed/searched and (2) the necessity of reducing the response times as observed by end-users. In addition, the nature of the interactions between users and online services creates fluctuating query request rates throughout execution, which requires a similarity search engine to adapt to better use the computation platform and minimize response times. In this work, we address these challenges with Hypercurves, a flexible framework for answering approximate k-nearest neighbor (kNN) queries for very large multimedia databases. Hypercurves executes in hybrid CPU–GPU environments and is able to attain massive query-processing rates through the cooperative use of these devices. Hypercurves also changes its CPU–GPU task partitioning dynamically according to the observed load, aiming for optimal response times. In our empirical evaluation, dynamic task partitioning reduced query response times by approximately 50 % compared to the best static task partition. Due to a probabilistic proof of equivalence to the sequential kNN algorithm, the CPU–GPU execution of Hypercurves in distributed (multi-node) environments can be aggressively optimized, attaining superlinear scalability while still guaranteeing, with high probability, results at least as good as those from the sequential algorithm.     

Precise selective deposition of microparticles on electrodes of microelectronic chips

We examined the high precision deposition of toner and polymer microparticles with a typical size of approximately 10 microm on electrode arrays with electrodes of 100 microm and below using custom-made microelectronic chips. Selective desorption of redundant particles was employed to obtain a given particle pattern from preadsorbed particle layers. Microparticle desorption was regulated by dielectrophoretic attracting forces generated by individual pixel electrodes, tangential detaching forces of an air flow, and adhesion forces on the microchip surface. A theoretical consideration of the acting forces showed that without pixel voltage, the tangential force applied for particle detachment exceeded the particle adhesion force. When the pixel voltage was switched on, however, the sum of attracting forces was larger than the tangential detaching force, which was crucial for desorption efficiency. In our experiments, appropriately large dielectrophoretic forces were achieved by applying high voltages of up to 100 V on the pixel electrodes. In addition, electrode geometries on the chip's surface as well as particle size influenced the desorption quality. We further demonstrated the compatibility of this procedure to complementary metal oxide semiconductor chip technology, which should allow for an easy technical implementation with respect to high-resolution microparticle deposition.     

Model predictive control of a rotary cement kiln

A first principles model of a cement kiln is used to control and optimize the burning of clinker in the cement production process. The model considers heat transfer between a gas and a feed state via convection and radiation. Furthermore, it contains effects such as chemical reactions, feed transport, energy losses and energy input. A model predictive controller is used to stabilize a temperature profile along the rotary kiln, guarantee good combustion conditions and maximize production. Moving horizon estimation was used for online estimation of selected model parameters and unmeasured states. Results from the pilot site are presented.     

Workload characterization of JVM languages

Originally developed with a single language in mind, the JVM is now targeted by numerous programming languages—its automatic memory management, just‐in‐time compilation, and adaptive optimizations—making it an attractive execution platform. However, the garbage collector, the just‐in‐time compiler, and other optimizations and heuristics were designed primarily with the performance of Java programs in mind. Consequently, many of the languages targeting the JVM, and especially the dynamically typed languages, are suffering from performance problems that cannot be simply solved at the JVM side. In this article, we aim to contribute to the understanding of the character of the workloads imposed on the JVM by both dynamically typed and statically typed JVM languages. To this end, we introduce a new set of dynamic metrics for workload characterization, along with an easy‐to‐use toolchain to collect the metrics. We apply the toolchain to applications written in six JVM languages (Java, Scala, Clojure, Jython, JRuby, and JavaScript) and discuss the findings. Given the recently identified importance of inlining for the performance of Scala programs, we also analyze the inlining behavior of the HotSpot JVM when executing bytecode originating from different JVM languages. As a result, we identify several traits in the non‐Java workloads that represent potential opportunities for optimization. © 2015 The Authors. Software: Practice and Experience Published by John Wiley & Sons Ltd.     

Quantum dot light emitting devices for photomedical applications

While OLEDs have struggled to find a niche lighting application that can fully take advantage of their unique form factors as thin, flexible, lightweight and uniformly large‐area luminaire, photomedical researchers have been in search of low‐cost, effective illumination devices with such form factors that could facilitate widespread clinical applications of photodynamic therapy (PDT) or photobiomodulation (PBM). Although existing OLEDs with either fluorescent or phosphorescent emitters cannot achieve the required high power density at the right wavelength windows for photomedicine, the recently developed ultrabright and efficient deep red quantum dot light emitting devices (QLEDs) can nicely fit into this niche. Here, we report for the first time the in‐vitro study to demonstrate that this QLED‐based photomedical approach could increase cell metabolism over control systems for PBM and kill cancerous cells efficiently for PDT. The perspective of developing wavelength‐specific, flexible QLEDs for two critical photomedical fields (wound repair and cancer treatment) will be presented with their potential impacts summarized. The work promises to generate flexible QLED‐based light sources that could enable the widespread use and clinical acceptance of photomedical strategies including PDT and PBM.     

Barrier Trees on Poset-Valued Landscapes

Fitness landscapes have proved to be a valuable concept in evolutionary biology, combinatorial optimization, and the physics of disordered systems. Usually, a fitness landscape is considered as a mapping from a configuration space equipped with some notion of adjacency, nearness, distance, or accessibility, into the real numbers. In the context of multi-objective optimization problems this concept can be extended to poset-valued landscapes. In a geometric analysis of such a structure, local Pareto points take on the role of local minima. We show that the notion of saddle points, barriers, and basins can be extended to the poset-valued case in a meaningful way and describe an algorithm that efficiently extracts these features from an exhaustive enumeration of a given generalized landscape.     

Simultaneous reconstruction of evolutionary history and epidemiological dynamics from viral sequences with the birth–death SIR model

The evolution of RNA viruses, such as human immunodeficiency virus (HIV), hepatitis C virus and influenza virus, occurs so rapidly that the viruses'' genomes contain information on past ecological dynamics. Hence, we develop a phylodynamic method that enables the joint estimation of epidemiological parameters and phylogenetic history. Based on a compartmental susceptible–infected–removed (SIR) model, this method provides separate information on incidence and prevalence of infections. Detailed information on the interaction of host population dynamics and evolutionary history can inform decisions on how to contain or entirely avoid disease outbreaks. We apply our birth–death SIR method to two viral datasets. First, five HIV type 1 clusters sampled in the UK between 1999 and 2003 are analysed. The estimated basic reproduction ratios range from 1.9 to 3.2 among the clusters. All clusters show a decline in the growth rate of the local epidemic in the middle or end of the 1990s. The analysis of a hepatitis C virus genotype 2c dataset shows that the local epidemic in the Córdoban city Cruz del Eje originated around 1906 (median), coinciding with an immigration wave from Europe to central Argentina that dates from 1880 to 1920. The estimated time of epidemic peak is around 1970.     

Comparative toxicity of nanostructured alumina and a commercial inert dust for Sitophilus oryzae (L.) and Rhyzopertha dominica (F.) at varying ambient humidity levels

The widespread concern for environmental and human health has raised the need for new reduced-risk control strategies and the search for new chemical classes of pesticides. Recently, a novel type of particulate material, nanostructured alumina (NSA) has been found to induce mortality in insects exposed to wheat treated with NSA dust. Preliminary studies have shown insecticidal activity of NSA particles on two insect species, Sitophilus oryzae (L.), and Rhyzopertha dominica, (F.), major pests of stored grain. We investigated the toxicity of NSA and Protect-It^® diatomaceous earth (DE) using dry dust applications at three different relative ambient humidity levels. Results showed that NSA was more effective in killing S. oryzae than Protect-It^® and was equally toxic to R. dominica. Treatment with both products also reduced progeny production. In addition, R. dominica was less susceptible to inert dusts than S. oryzae. Our results suggest that NSA might prove a good alternative or complement to DE based products, and encourage further testing with other insect pests and systems, plus experiments on delivery options to further enhance NSA products.