How Low Can You Go? Feature Selection for Drug Discovery

The cost of bringing a drug to market depends on how quickly a candidate drug can be “discovered” and evaluated to ensure safety and effectiveness. In this work we develop a method for predicting whether a given drug and protein compound will “bind.” Our aim is to select a set of features to predict drug-protein interactions. This study focuses on kinases. Kinase inhibitors are the largest class of new cancer therapies. Selective inhibition is difficult due to high sequence similarity, leading to off-target interactions and side-effects. Pictured here human c-SRC

Serial MR diffusion to predict treatment response in high-grade pediatric brain tumors: a comparison of regional and voxel-based diffusion change metrics

Background Assessment of treatment response by measuring tumor size is known to be a late and potentially confounded response index. Serial diffusion MRI has shown potential for allowing earlier and possibly more reliable response assessment in adult patients, with limited experience in clinical settings and in pediatric brain cancer. We present a retrospective study of clinical MRI data in children with high-grade brain tumors to assess and compare the values of several diffusion change metrics to predict treatment response. Methods Eighteen patients (age range, 1.9–20.6 years) with high-grade brain tumors and serial diffusion MRI (pre- and posttreatment interval range, 1–16 weeks posttreatment) were identified after obtaining parental consent. The following diffusion change metrics were compared with the clinical response status assessed at 6 months: (1) regional change in absolute and normalized apparent diffusivity coefficient (ADC), (2) voxel-based fractional volume of increased (fiADC) and decreased ADC (fdADC), and (3) a new metric based on the slope of the first principal component of functional diffusion maps (fDM). Results Responders (n = 12) differed significantly from nonresponders (n = 6) in all 3 diffusional change metrics demonstrating higher regional ADC increase, larger fiADC, and steeper slopes (P < .05). The slope method allowed the best response prediction (P < .01, η2 = 0.78) with a classification accuracy of 83% for a slope of 58° using receiver operating characteristic (ROC) analysis. Conclusions We demonstrate that diffusion change metrics are suitable response predictors for high-grade pediatric tumors, even in the presence of variable clinical diffusion imaging protocols

Insects of Western North America. 2. The cicadas of Colorado (Homoptera: Cicadidae, Tibicinidae)

May 15, 2002

Towards a Better Understanding of On and Off Target Effects of the Lymphocyte-Specific Kinase LCK for the Development of Novel and Safer Pharmaceuticals

In this work we have developed a multi-tiered computational platform to study protein-drug interactions. At the beginning of the workflow more efficient and less accurate methods are used to enable large libraries of proteins in many conformations and massive chemical libraries to be screened. At each subsequent step in the workflow a subset of input data is investigated with increased accuracy and more computationally expensive methods. We demonstrate the developed workflow with the investigation of the lymphocyte-specific kinase LCK, which is implicated as a drug target in many cancers and also known to have toxic effects when unintentionally targeted. Several LCK states and conformations are investigated using molecular docking and generalized Born and surface area continuum solvation (MM/GBSA). Different variations in the drug screening process provide unique results that may elucidate the biological mechanisms underlying the drug interactions

Characterization of Melt Infiltrated SiC/SiC Composite Combustor Liners Using Meso- and Micro-NDE Techniques

Melt-infiltrated ceramic matrix composite SiC/SiC material systems are under development for use in combustor liners for low-emission advanced gas turbines. Uncertainty in repeatability of processing methods for these large components (33--76 cm diameter), and hence possible reduced reliability for the end user. This requires that appropriate test methods, at both meso- and micro-scale, be used to ensure that the liners are acceptable for use. Nondestructive evaluation (NDE) methods, if demonstrated to reliably detect changes caused by processing, would be of significant benefit to both manufacturer and end user. This paper describes the NDE methods and their applications in detecting a process upset in a melt-infiltrated 33 cm combustor liner and how high-resolution scanning electron microscopy was used to verify the NDE data

GBTrans: A commensal search for radio pulses with the Green Bank twenty metre telescope

We describe GBTrans, a real-time search system designed to find fast radio bursts (FRBs) using the 20-m radio telescope at the Green Bank Observatory. The telescope has been part of the Skynet educational program since 2015. We give details of the observing system and report on the non-detection of FRBs from a total observing time of 503 days. Single pulses from four known pulsars were detected as part of the commensal observing. The system is sensitive enough to detect approximately half of all currently known FRBs and we estimate that our survey probed redshifts out to about 0.3 corresponding to an effective survey volume of around 124,000~Mpc$^3$. Modeling the FRB rate as a function of fluence, $F$, as a power law with $F^{-\alpha}$, we constrain the index $\alpha < 2.5$ at the 90% confidence level. We discuss the implications of this result in the context of constraints from other FRB surveys.Comment: 7 pages, 6 figure

Quantitative MRI Measurement of Binder Distributions in Green-State Ceramics

Development of reliable and improved structural ceramics for advanced heat engines and other applications requires process diagnostics and materials evaluation from powder preparation to green-body forming to final sintering. Injection molding is a promising processing method being developed for mass production of complex-shaped heat engine components such as turbochargers (rotors and stator vanes) and engine valves. Major processing steps in injection-molded ceramic manufacturing include preparation of ceramic powders and organic binders, mixing, molding, binder removal, sintering, and finishing [1]. While materials evaluation and diagnostics are needed throughout the process, it is particularly important to evaluate the distributions of binders/plasticizers in as-molded green bodies [2]. Poor distribution of these organics in a green body can lead to a final part that is defective or that has poor mechanical properties after it is sintered

The X-ray Size-Temperature Relation for Intermediate Redshift Galaxy Clusters

We present the first measurements of the X-ray size-temperature (ST) relation in intermediate redshift (z~0.30) galaxy clusters. We interpret the local ST relation (z~0.06) in terms of underlying scaling relations in the cluster dark matter properties, and then we use standard models for the redshift evolution of those dark matter properties to show that the ST relation does not evolve with redshift. We then use ROSAT HRI observations of 11 clusters to examine the intermediate redshift ST relation; for currently favored cosmological parameters, the intermediate redshift ST relation is consistent with that of local clusters. Finally, we use the ST relation and our evolution model to measure angular diameter distances; with these 11 distances we evaluate constraints on Omega_M and Omega_L which are consistent with those derived from studies of Type Ia supernovae. The data rule out a model with Omega_M=1 and Omega_L=0 with 2.5 sigma confidence. When limited to models where Omega_M+Omega_L=1, these data are inconsistent with Omega_M=1 with 3 sigma confidence.Comment: ApJ: submitted April 7, accepted June 28, to appear Dec 1 (vol 544

A morphological algorithm for improving radio-frequency interference detection

A technique is described that is used to improve the detection of radio-frequency interference in astronomical radio observatories. It is applied on a two-dimensional interference mask after regular detection in the time-frequency domain with existing techniques. The scale-invariant rank (SIR) operator is defined, which is a one-dimensional mathematical morphology technique that can be used to find adjacent intervals in the time or frequency domain that are likely to be affected by RFI. The technique might also be applicable in other areas in which morphological scale-invariant behaviour is desired, such as source detection. A new algorithm is described, that is shown to perform quite well, has linear time complexity and is fast enough to be applied in modern high resolution observatories. It is used in the default pipeline of the LOFAR observatory.Comment: Accepted for publication in A&

Star Formation in Cluster Galaxies at 0.2<z<0.55

The rest frame equivalent width of the [OII]3727 emission line, W(OII), has been measured for cluster and field galaxies in the CNOC redshift survey of rich clusters at 0.2<z<0.55. Emission lines of any strength in cluster galaxies at all distances from the cluster centre, out to 2R_{200}, are less common than in field galaxies. The mean W(OII) in cluster galaxies more luminous than M_r^k<-18.5 + 5\log h (q_o=0.1) is 3.8 \pm 0.3 A (where the uncertainty is the 1 sigma error in the mean), significantly less than the field galaxy mean of 11.2 \pm 0.3 A. For the innermost cluster members (R<0.3R_{200}), the mean W(OII) is only 0.3 \pm 0.4 A. Thus, it appears that neither the infall process nor internal tides in the cluster induce detectable excess star formation in cluster galaxies relative to the field. The colour-radius relation of the sample is unable to fully account for the lack of cluster galaxies with W(OII)>10 A, as expected in a model of cluster formation in which star formation is truncated upon infall. Evidence of supressed star formation relative to the field is present in the whole cluster sample, out to 2 R_{200}, so the mechanism responsible for the differential evolution must be acting at a large distance from the cluster centre, and not just in the core. The mean star formation rate in the cluster galaxies with the strongest emission corresponds to an increase in the total stellar mass of less than about 4% if the star formation is due to a secondary burst lasting 0.1 Gyr.Comment: aasms4 latex, 3 postscript figures, accepted for publication in ApJ Letters. Also available at http://astrowww.phys.uvic.ca/~balogh