A rapid computational filter for predicting the rate of human renal clearance

In silico models that predict the rate of human renal clearance for a diverse set of drugs, that exhibit both active secretion and net re-absorption, have been produced using three statistical approaches. Partial Least Squares (PLS) and Random Forests (RF) have been used to produce continuous models whereas Classification And Regression Trees (CART) has only been used for a classification model. The best models generated from either PLS or RF produce significant models that can predict acids/zwitterions, bases and neutrals with approximate average fold errors of 3, 3 and 4, respectively, for an independent test set that covers oral drug-like property space. These models contain additional information on top of any influence arising from plasma protein binding on the rate of renal clearance. Classification And Regression Trees (CART) has been used to generate a classification tree leading to a simple set of Renal Clearance Rules (RCR) that can be applied to man. The rules are influenced by lipophilicity and ion class and can correctly predict 60% of an independent test set. These percentages increase to 71% and 79% for drugs with renal clearances of < 0.1 ml/min/kg and > 1 ml/min/kg, respectively. As far as the authors are aware these are the first set of models to appear in the literature that predict the rate of human renal clearance and can be used to manipulate molecular properties leading to new drugs that are less likely to fail due to renal clearance.     

Walk-up VR: virtual reality beyond projection screens

Today, VR research and development efforts often focus on the continual innovation of interaction styles and metaphors for virtual environments (VEs). New tools and interaction devices aim to increase the immersive experience rather than support seamless integration with real work scenarios. Even though users may soon perceive odours within VEs, real, task-oriented interaction within these environments will continue to lag behind. Combining these efforts can result in new user interfaces that reduce the cumbersome barriers prevalent in VEs today, finally unleashing the latent impact of this technology in everyday life. Implementing this vision requires an interdisciplinary and applied approach to integrate VR into the workplace. Mixed-reality display capabilities, useful multimodal interaction and perceptual, intuitive interfaces are major components of such an application-oriented and human-centered approach, for which we coined the term walk-up VR. The paper discusses augmented and virtual reality as contributing technologies     

Prophylactic efficacy of tilmicosin for bovine respiratory tract disease

The prophylactic administration of injectable tilmicosin for pneumonia in weaned beef calves was investigated in 1,806 animals. Comparisons were made among calves receiving an "on-arrival" injection of tilmicosin, calves receiving a single injection of long-acting oxytetracycline, and calves receiving no prophylaxis. Morbidity and mortality attributable to pneumonia, morbidity and mortality attributable to all causes, and case fatality were significantly lower in the group of calves that received tilmicosin, compared with calves that received long-acting oxytetracycline and calves that received no prophylactic antibiotic. Mean time to initial pneumonia treatment was significantly extended in calves that received prophylaxis, compared with those that received no antibiotic on arrival at the feedlot. Calves that received tilmicosin gained significantly more weight than calves that received oxytetracycline. Calves that were not treated for pneumonia during the trial period gained significantly more weight than did those calves that were treated for pneumonia regardless of experimental group. The majority of mortalities were attributable to fibrinous pneumonia (31/34). Important bacterial isolates (Pasteurella spp, Haemophilus somnus, Actinomyces pyogenes) obtained at necropsy did not have resistance to tilmicosin in association with administration of tilmicosin as prophylaxis for pneumonia. However, bacterial resistance to trimethoprim/sulfonamide and to oxytetracycline were commonly found in these postmortem isolates.     

Radiopharmacology of inhaled 133Xe in skeletal sites containing deposits of Gaucher cells

Gaucher's disease is a lysosomal storage disease in which cells of the reticuloendothelial system accumulate the lipid glucocerebroside. It is characterized by slowly progressive visceral and osseous involvement. One of the latter manifestations includes lipid infiltration of bone marrow. We monitored the rate of inhaled 133Xe uptake and wash-out over diseased and normal metaphyseal and epiphyseal areas of the knee. Twenty-two patients (15 adults, 7 children) with various degrees of previously diagnosed Gaucher's disease were positioned supine under a gamma-camera interfaced to a computer system. All patients rebreathed 133Xe gas from a closed system for 10 min followed by 14 min of wash-out. Digitized images of the lung, liver, spleen, bony sites and soft tissue were obtained at 1 min intervals during the wash-in and wash-out phases. Counts for each ROI were normalized per 100 pixels and plotted as a function (time). Maximum uptake was also calculated by relating the counts/ROI/100 pixels to the 10 min integrated lung count during equilibrium (the administered "dose"). There was essentially no 133Xe uptake in liver and spleen involved with Gaucher's disease. Monophasic uptake and biphasic wash-out curves were observed in the limited investigative population. Skeletal Gaucher deposits released the 133Xe at a greater rate relative to soft tissue.     

University/corporate research agreements

The author examines the evolving university-industry relationships in the biotechnology area, addressing the conceptual basis for such arrangements and the resultant contract issues. He examines the need for development of policies in academia that will accommodate the needs of both government and industry without harming the integrity or institutional objectives of the university. The author then recommends a number of directives for written rules to help achieve these objectives, especially ones relating to patenting and licensing of inventions developed under industrial support.     

Integrable multimode interference distributed Bragg reflector laser all-optical flip-flops

A novel fully integrable all-optical flip-flop has been created using distributed Bragg reflector multimode interference bistable laser diodes. The single metal-organic vapor phase epitaxy regrowth offset quantum well structure active/passive integrated flip-flop lases in single mode at 1554 nm and is compatible with standard fabrication methods of InP photonic integrated circuits (PICs). All-optical reset switching through cross-gain saturation was demonstrated over a 52-nm range, at 1522-1574 nm. An optical set has been achieved with -3 dBm and optical reset with less than -5-dBm external light injection. The flip-flop will be useful for integration in PICs of future photonic systems for self-routing and optical memories or buffers.     

A single regrowth integration platform for photonic circuits incorporating tunable SGDBR lasers and quantum-well EAMs

A monolithic integration platform is demonstrated for high functionality photonic circuits that include quantum-well electroabsorption modulators, semiconductor optical amplifiers, and widely tunable lasers. The platform is based on the selective removal of a set of active quantum wells located above an optical waveguide layer. The waveguide layer contains a second set of quantum wells to be used in modulator regions. Fabrication requires only a single blanket InP regrowth.     

Two-phase flow patterns in turbulent flow through a dose diffusion pipe

A numerical investigation is carried out for turbulent particle-laden flow through a dose diffusion pipe for a model reactor system. A Lagrangian stochastic Monte-Carlo particle-tracking approach and the averaged Reynolds equations with a k– turbulence model, with a two-layer zonal method in the boundary layer, are used for the disperse and continuous phases. The flow patterns coupled with the particle dynamics are predicted. It is observed that the coupling of the continuous phase with the particle dynamics is important in this case. It was found that the geometry of the throat significantly influences the particle distribution, flow patterns and length of the recirculation region. The accuracy of the simulations depends on the numerical prediction and correction of the fluid phase velocity during a characteristic time interval of the particles. A numerical solution strategy for the computation of two-way momentum coupled flow is discussed. The three test cases show different flow features in the formation of a recirculation region behind the throat. The method will be useful for the qualitative analysis of conceptual designs and their optimisation.     

Bad and good news about using software assurance tools

Software assurance tools – tools that scan the source or binary code of a program to find weaknesses – are the first line of defense in assessing the security of a software project. Even though there are a plethora of such tools available, with multiple tools for almost every programming language, adoption of these tools is spotty at best. And even though different tools have distinct abilities to find different kinds of weaknesses, the use of multiple tools is even less common. And when the tools are used (or attempted to be used), they are often used in ways that reduce their effectiveness. We present a step‐by‐step discussion of how to use a software assurance tool, describing the challenges that can occur in this process. We also present quantitative evidence about the effects that can occur when assurance tools are applied in a simplistic or naive way. We base this presentation on our direct experiences with using a wide variety of assurance tools. We then present the US Department of Homeland Security funded Software Assurance Marketplace (SWAMP), an open facility where users can upload their software to have it automatically and continually assessed by a variety of tools. The goal of the SWAMP is to simplify the task of the programmer in using assurance tools, thereby removing many of the obstacles to their adoption. Copyright © 2016 The Authors. Software: Practice and Experience Published by John Wiley & Sons, Ltd.