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.     

Molecular basis of agonicity and antagonicity in the androgen receptor studied by molecular dynamics simulations

Treatment of prostate cancer patients with antiandrogens is initially successful, though the therapy often becomes refractory over the time. This mechanism is not fully understood, but the presence of androgen receptor (AR) mutant forms which are activated by antiandrogens and other endogenous ligands, and overexpression of the receptor have been suggested. In an attempt to explain the molecular basis for agonicity and antagonicity in the androgen receptor, and the changes on biological activity of subtle modifications at the ligand and receptor (mutations) level, molecular dynamics simulations were performed on the androgen receptor wild type (WT), and T877A and W741 mutant forms, complexed with several non-steroidal androgens. The stabilizing role of residues from helices 3, 5, 11 and 12 was observed in non-steroidal androgens R-3, S-1, and R-bicalutamide and hydroxyflutamide in resistant mutations. In the AR WT antiandrogen R-bicalutamide complex, destabilization of M895 by both W741 and the sulfonyl linkage of the ligand may be responsible for reported antagonism. Changes in the ligand or mutations alleviating this effect were observed to stabilize the receptor in the active conformation, thus developing resistance to R-bicalutamide. The results presented provide a plausible explanation for the molecular basis of agonicity and antagonicity in the androgen receptor, and complement previous studies using static crystal structures, incorporating for the first time protein dynamics into the analysis. Thus, our results provide a valuable framework for the structure-based design of improved antiandrogens.     

Programmable logic construction kits for hyper-real-time neuronal modeling

Programmable logic designs are presented that achieve exact integration of leaky integrate-and-fire soma and dynamical synapse neuronal models and incorporate spike-time dependent plasticity and axonal delays. Highly accurate numerical performance has been achieved by modifying simpler forward-Euler-based circuitry requiring minimal circuit allocation, which, as we show, behaves equivalently to exact integration. These designs have been implemented and simulated at the behavioral and physical device levels, demonstrating close agreement with both numerical and analytical results. By exploiting finely grained parallelism and single clock cycle numerical iteration, these designs achieve simulation speeds at least five orders of magnitude faster than the nervous system, termed here hyper-real-time operation, when deployed on commercially available field-programmable gate array (FPGA) devices. Taken together, our designs form a programmable logic construction kit of commonly used neuronal model elements that supports the building of large and complex architectures of spiking neuron networks for real-time neuromorphic implementation, neurophysiological interfacing, or efficient parameter space investigations.     

On the formation of the diamond grain configuration during high temperature creep and fatigue

A study has been made of the influence of test variables on the formation of the diamond grain configuration during high temperature creep and fatigue deformation of a wide variety of metals. The proposed mechanisms for the formation of this interesting grain morphology are reviewed. It is concluded that the diamond grain configuration arises from a balance between grain-boundary sliding, grain-boundary mobility, intragranular deformation and defect imbalance across the grain boundaries and that it tends to be stabilized by intergranular cavitation. While the phenomenon occurs during high temperature fatigue in a variety of metals irrespective of their crystal structure, during creep it has been observed only in to h c p metals. It is surmised that the occurrence of the diamond array of grain boundaries during creep deformation in h c p metals is aided by the limited number of slip systems which leads to high defect imbalances in adjacent grains and consequently high driving forces for grain-boundary migration. On the basis of quantitative metallography involving measurements of the number of edges per grain section, the number of grains meeting at vertices, angular distribution histograms and grain-boundary lengths in different angular orientations with respect to the stress axis in "annealed" and "diamond" microstructures, it is concluded that the shape of the "diamond" grain is essentially the same as that of the "annealed" grain but in a distorted form.     

Output feedback trajectory stabilization of the uncertainty DC servomechanism system

This work proposes a solution for the output feedback trajectory-tracking problem in the case of an uncertain DC servomechanism system. The system consists of a pendulum actuated by a DC motor and subject to a time-varying bounded disturbance. The control law consists of a Proportional Derivative controller and an uncertain estimator that allows compensating the effects of the unknown bounded perturbation. Because the motor velocity state is not available from measurements, a second-order sliding-mode observer permits the estimation of this variable in finite time. This last feature allows applying the Separation Principle. The convergence analysis is carried out by means of the Lyapunov method. Results obtained from numerical simulations and experiments in a laboratory prototype show the performance of the closed loop system.     

A blur-robust descriptor with applications to face recognition

Understanding the effect of blur is an important problem in unconstrained visual analysis. We address this problem in the context of image-based recognition by a fusion of image-formation models and differential geometric tools. First, we discuss the space spanned by blurred versions of an image and then, under certain assumptions, provide a differential geometric analysis of that space. More specifically, we create a subspace resulting from convolution of an image with a complete set of orthonormal basis functions of a prespecified maximum size (that can represent an arbitrary blur kernel within that size), and show that the corresponding subspaces created from a clean image and its blurred versions are equal under the ideal case of zero noise and some assumptions on the properties of blur kernels. We then study the practical utility of this subspace representation for the problem of direct recognition of blurred faces by viewing the subspaces as points on the Grassmann manifold and present methods to perform recognition for cases where the blur is both homogenous and spatially varying. We empirically analyze the effect of noise, as well as the presence of other facial variations between the gallery and probe images, and provide comparisons with existing approaches on standard data sets.     

Neutral shift [five years of continuous operation with adjustable frequency drives]

The combined efforts of the AFD supplier and end-user have resulted in an extremely reliable electrical adjustable speed drive system. Almost three years into the run of the first unit, all parties are confident of the ability to meet the five-year run target that was identified at the outset. The redundancy of the power cells in this particular design, together with the neutral shift control has practically eliminated the power components as a source of operational failure. Future development efforts will include applying redundancy and fault tolerance to the drive control processor to further enhance system reliability.     

Teaching Macroeconomics with GAMS

Our general goal in this paper is to show how to implement in GAMS standard deterministic nonlinear macro models, and stochastic linear macro models with rational expectations. We will also present basic concepts on solution methods and policy analysis for these kinds of models. As a practical illustration, we will use some well known teaching and experimental models in the macroeconomic literature.     

Alzheimer paired helical filaments (PHFs) studied by high-resolution TEM: what can vertical Pt-C replication tell us about the organization of the pronase-digested PHF core?

Untreated paired helical filaments (PHFs) and pronase-digested PHF-core filaments were stereoscopically imaged with a freeze-drying vertical platinum-carbon replication preparation method for TEM. The untreated PHF have an average wide region (W) = 22.8 +/- 2.4 nm, a narrow region (T) = 10.6 +/- 1.7 nm, and a helical turn period (L) = 78.6 +/- 13.4. The surfaces of the untreated PHF's fuzzy coat appears disorganized. The widths of the pronase-treated PHF-core filaments were significantly reduced (W(d) = 14.8 +/- 1.2 nm, T(d) = 5.7 +/- 1.0 nm, and L(d) = 75.4 +/- 17 nm). The surfaces of the untreated PHF contained approximately 1.1 nm strands, the same size as tau monomer ( approximately 1.0 nm). The pronase-digested PHF cores mostly contained approximately 1.6 +/- 0.3 nm strands although strand diameters ranged from 0.6-2.5 nm. The strands sometimes appear to be wrapped around the filament axis; less often, they appear to be roughly parallel to the PHF axis, and otherwise appear to be randomly oriented. Images of pronase-digested PHF core images are discussed in relation to the core's biochemical composition, its proposed beta structure, and structural subunit models. Images of the untreated and the pronase-digested PHF support a helical ribbon morphology.     

Improving post irradiation stability of high density polyethylene by multi walled carbon nanotubes

Sterilization of implants and other clinical accessories is an integral part of any medical application. Although many materials are used as implants, polyethylene stands unique owing to its versatility. Carbon nanotubes are being used as a filler material to enhance the properties of polyethylene. However, the role of multi walled carbon nanotubes (MWCNTs) as an effective antioxidant and radical scavenger in resisting the deteriorating effects of sterilization is yet to be studied in detail. The present work is aimed to investigate the mechanical properties and oxidation stability of irradiated high density polyethylene (HDPE) reinforced by MWCNTs with various concentrations such as 0.25%, 0.50%, 0.75% and 1.00 wt.%. The composites were exposed to ⁶⁰Co source in air and irradiated at different dosage level starting from 25 to 100 kGy and then shelf aged for a period of 120 days prior to investigation. The loss in toughness, Young’s modulus and ultimate strength at 100 kGy for 1 wt.% MWCNTs composite were found to be 21.5%, 20.3% and 19.2%, respectively compared to that of unirradiated composite. FTIR and ESR studies confirmed the antioxidant and radical scavenging potentialities of MWCNTs with increased concentration and irradiation dosage. It was found that by the addition of 1 wt.% MWCNTs into virgin HDPE, the oxidation index of the composite at 100 kGy was decreased by 56.2%. It is concluded that the addition of MWCNTs into polyethylene not only limits the loss of mechanical properties but also improves its post irradiation oxidative stability.