ILP-assisted de novo drug design

The accurate and early detection of epileptic seizures in continuous electroencephalographic (EEG) data has a growing role in the management of patients with epilepsy. Early detection allows for therapy to be delivered at the start of seizures and for caregivers to be notified promptly about potentially debilitating events. The challenge to detecting epileptic seizures, however, is that seizure morphologies exhibit considerable inter-patient and intra-patient variability. While recent work has looked at addressing the issue of variations across different patients (inter-patient variability) and described patient-specific methodologies for seizure detection, there are no examples of systems that can simultaneously address the challenges of inter-patient and intra-patient variations in seizure morphology. In our study, we address this complete goal and describe a multi-task learning approach that trains a classifier to perform well across many kinds of seizures rather than potentially overfitting to the most common seizure types. Our approach increases the generalizability of seizure detection systems and improves the tradeoff between latency and sensitivity versus false positive rates. When compared against the standard approach on the CHB–MIT multi-channel scalp EEG data, our proposed method improved discrimination between seizure and non-seizure EEG for almost 83 % of the patients while reducing false positives on nearly 70 % of the patients studied.     

Intralesional Infiltrations of Arteriosclerotic Tissue Cells-Free Filtrate Reproduce Vascular Pathology in Healthy Recipient Rats

Lower-extremity arterial disease is a major health problem with increasing prevalence, often leading to non-traumatic amputation, disability and mortality. The molecular mechanisms underpinning abnormal vascular wall remodeling are not fully understood. We hypothesized on the existence of a vascular tissue memory that may be transmitted through soluble signaling messengers, transferred from humans to healthy recipient animals, and consequently drive the recapitulation of arterial wall thickening and other vascular pathologies. We examined the effects of the intralesional infiltration for 6 days of arteriosclerotic popliteal artery-derived homogenates (100 µg of protein) into rats’ full-thickness wounds granulation tissue. Animals infiltrated with normal saline solution or healthy brachial arterial tissue homogenate obtained from traumatic amputation served as controls. The significant thickening of arteriolar walls was the constant outcome in two independent experiments for animals receiving arteriosclerotic tissue homogenates. This material induced other vascular morphological changes including an endothelial cell phenotypic reprogramming that mirrored the donor’s vascular histopathology. The immunohistochemical expression pattern of relevant vascular markers appeared to match between the human tissue and the corresponding recipient rats. These changes occurred within days of administration, and with no cross-species limitation. The identification of these “vascular disease drivers” may pave novel research avenues for atherosclerosis pathobiology.     

Multiplex qualitative PCR assay for identification of genetically modified canola events and real-time event-specific PCR assay for quantification of the GT73 canola event

Genetically modified (GM) canola is the most widely grown oilseed crop in Canada. At this time, commercially produced GM canola cultivars in Canada have the events GT73/RT73 and Ms8xRf3. Commercial seed sale of canola cultivars containing the GM events such as OXY235 and T45 has been discontinued. Adventitious presence of GM seeds and grains in non-GM grains is a concern for international grain trade, and development of effective detection methods is important. A multiplex qualitative PCR procedure was established for the detection of the GM canola events OXY235, Ms8xRf3, T45 and GT73. The presence of the GM canola events was also successfully detected in ground spiked wheat and barley grain samples prepared at 0.1%, 0.5% and 1.0% levels (w/w). The GT73 real-time PCR assay was successfully used to quantify DNA extracted from spiked ground canola samples consisting of 5%, 1%, 0.5% and 0.1% GT73 (w/w).     

Thermal and mechanical behavior of copper molds during thin-slab casting (I): Plant trial and mathematical modeling

Three-dimensional (3-D) finite-element thermal-stress models have been developed to predict temperature, distortion, and residual stress in the mold of continuous casters of thin steel slabs, comparing both funnel-shaped and parallel molds. The mold shape and high casting speed leads to higher mold temperatures and shorter mold life than in conventional slab casters. This study investigates heat flux and the effects of mold shape on distortion and cracking of the thin-slab mold. In Part I of this two-part article, mold wall temperatures measured in the plant were analyzed to determine the corresponding heat-flux profiles in thin-slab molds. This data was then used in an elastic-visco-plastic analysis to investigate the deformation of the molds in service for the two different mold shapes. The model predictions of temperature and distortion during operation match plant observations. During operation, the hot-face temperature reaches 580 °C and heat flux varies from 7 to 4.5 MW/m² when casting at 3.6 m/min. The copper plates bend toward the steel, with a maximum outward distortion of about 0.3 mm. This occurs just above the center of the wide faces and is smaller than the distortion of a conventional slab mold.     

Optimality Of sequential prorability ratio tests for a class of continuous parameter stochastic processes

For a wide class of stochastic processes including processes belonging to the curved exponential families, it is proved that Wald SPRT is optimal in the sense of minimizing the expectations of increasing processes associated with the stochastic process. The increasing processes are given by the Doob-Meyer decompositions of the log-probability ratio under the two hypotheses.     

Hydroxyapatite coating on selectively passivated and sensitively polymer-protected surgical grade stainless steel

Surgical grade stainless steel (316L SS) is a widely used implant material in orthopedic surgeries. However, the release of metallic ions evidenced from the 316L SS implants in vivo conditions is a big challenge. In order to minimize the release of metallic ions, coating the 316L SS implant with a biocompatible material like hydroxyapatite [HAP, Ca₁₀(PO₄)₆(OH)₂] is one of the suitable methods. In this paper, the hydroxyapatite coating on borate passivated through poly-ortho-phenylenediamine (PoPD)-coated 316L SS by a dip coating method has been reported. The coatings were characterized by electrochemical techniques such as potentiodynamic polarization, electrochemical impedance spectroscopy, and cyclic voltammetry. Surface characterization studies of the coatings such as X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM) were also carried out. The leach out characteristics of the coatings was determined at the impressed potential. The mechanical property of the coatings was evaluated by Vicker’s microhardness test. The Cr-rich passive film formed underneath the PoPD layer showed a higher protective efficiency. The ability to form apatite on the post-passivated PoPD-coated 316L SS specimen was examined by immersing it in the simulated body fluid. The enhanced corrosion resistivity of the HAP coating on the post-passivated PoPD-coated 316L SS was due to an effective barrier of PoPD followed by the passive film underneath the PoPD.     

Motion of conducting particles causing inadvertent outages in GIS

Inadvertent failure of a HV gas-insulated system (GIS) is traced to a seemingly innocuous mechanism in particle-induced breakdown. Impending dangers from inconspicuous conducting particles in a large physical system are quite intriguing. The dynamic behavior of the particle due to electric field/particle/fluid medium interaction is a complex phenomenon. To understand this interaction a credible database has been generated for the field-induced motion of the particles on a physical prototype model. Induced surface charge acquired by the particle is calculated based on the proposed model (field calculations) and by considering it to be a prolate ellipsoid. Methods for deactivating potentially dynamic particles using dielectric coated active parts and grounded enclosures, and a novel technique called reverse polarity charging have been suggested. Performance of GIS in the presence of metallic particles has been studied with bare electrodes and with dielectric coatings of different conductivities with a view to obtain an optimal value of the conductivity     

Emerging technologies for identification of disinfection byproducts: GC/FT-ICR MS characterization of solvent artifacts

Water samples from a local water treatment plant were analyzed, using gas chromatography Fourier transform ion cyclotron resonance mass spectrometry (GC/FT-ICR MS), to identify potential disinfection byproducts (DBPs). Both liquid-liquid extraction (LLE) and solid-phase microextraction (SPME) techniques were used for sample preparation prior to GC/MS analyses. Based on the averaged mass measurement accuracy (MMA) of better than five parts-per-million (<5 ppm), multiple solvent artifacts were identified. It is shown that solventless SPME can be utilized to reduce potential interferences from solvent stabilizers. Six DBPs were detected and their molecular compositions were assigned at a high level of confidence. At the ppb concentration ranges and in the broadband mass spectral detection mode, internally calibrated mass spectra provided concurrent high resolution (resolving power M/deltaM50% > 30,000 at m/z values -110) and MMA of better than one part-per-million (MMA < 1 ppm). The use of thermochemical data, such as proton affinities, as a complementary tool to enhance analytical resolution is also demonstrated.