High-Performance Algorithm Engineering for Computational Phylogenetics

A phylogeny is the evolutionary history of a group of organisms; systematists (and other biologists) attempt to reconstruct this history from various forms of data about contemporary organisms. Phylogeny reconstruction is a crucial step in the understanding of evolution as well as an important tool in biological, pharmaceutical, and medical research. Phylogeny reconstruction from molecular data is very difficult: almost all optimization models give rise to NP-hard (and thus computationally intractable) problems. Yet approximations must be of very high quality in order to avoid outright biological nonsense. Thus many biologists have been willing to run farms of processors for many months in order to analyze just one dataset. High-performance algorithm engineering offers a battery of tools that can reduce, sometimes spectacularly, the running time of existing phylogenetic algorithms, as well as help designers produce better algorithms. We present an overview of algorithm engineering techniques, illustrating them with an application to the breakpoint analysis method of Sankoff et al., which resulted in the GRAPPA software suite. GRAPPA demonstrated a speedup in running time by over eight orders of magnitude over the original implementation on a variety of real and simulated datasets. We show how these algorithmic engineering techniques are directly applicable to a large variety of challenging combinatorial problems in computational biology.     

Performance characteristics of soot primary particle size measurements by time-resolved laser-induced incandescence

A detailed analysis of various factors that influence the accuracy of time-resolved laser-induced incandescence for the determination of primary soot particles is given. As the technique relies on the measurement of the signal ratio at two detection times of the enhanced thermal radiation after an intense laser pulse, guidelines are presented for a suitable choice of detection times to minimize statistical uncertainty. An error analysis is presented for the issues of laser energy absorption, vaporization, heat conduction, and signal detection. Results are shown for a laminar ethene diffusion flame that demonstrate that concurring results are obtained for various laser irradiances, detection characteristics, and times of observation.     

Results of a computer assisted screening program for gynecologic mass examinations (author''s transl)

The E. A. D. is a genodermatosis characterised by absence or important diminuation of sweat glands. The study of 3 children of different families allows us to identify the diagnostic elements: typical facial signs, anhidrosis, rarity of teeth "buds", abnormalities of dermatoglyphes. This diagnosis must be established early, to protect the newborn from accidents of overheating caused by perspiration insufficiency. The sweat glands are not affected alone: exocrine glands also, explaining the fragility of the upper respiratory tract in such patients. The teeth abnormalities are important and need replacement by false teeth, carefully done at an early date and continued later on. Genetic investigation is indispensable to discover women who carry the disease, with a high risk of transmission to their children.     

HiL simulation in biomechanics: a new approach for testing total joint replacements

Instability of artificial joints is still one of the most prevalent reasons for revision surgery caused by various influencing factors. In order to investigate instability mechanisms such as dislocation under reproducible, physiologically realistic boundary conditions, a novel test approach is introduced by means of a hardware-in-the-loop (HiL) simulation involving a highly flexible mechatronic test system. In this work, the underlying concept and implementation of all required units is presented enabling comparable investigations of different total hip and knee replacements, respectively. The HiL joint simulator consists of two units: a physical setup composed of a six-axes industrial robot and a numerical multibody model running in real-time. Within the multibody model, the anatomical environment of the considered joint is represented such that the soft tissue response is accounted for during an instability event. Hence, the robot loads and moves the real implant components according to the information provided by the multibody model while transferring back the position and resisting moment recorded. Functionality of the simulator is proved by testing the underlying control principles, and verified by reproducing the dislocation process of a standard total hip replacement. HiL simulations provide a new biomechanical testing tool for analyzing different joint replacement systems with respect to their instability behavior under realistic movements and physiological load conditions.     

Discovery of Halogenated Benzothiadiazine Derivatives with Anticancer Activity**

Mitochondrial respiratory complex II (CII), also known as succinate dehydrogenase, plays a critical role in mitochondrial metabolism. Known but low potency CII inhibitors are selectively cytotoxic to cancer cells including the benzothiadiazine-based anti-hypoglycemic diazoxide. Herein, we study the structure-activity relationship of benzothiadiazine derivatives for CII inhibition and their effect on cancer cells for the first time. A 15-fold increase in CII inhibition was achieved over diazoxide, albeit with micromolar IC₅₀ values. Cytotoxicity evaluation of the novel derivatives resulted in the identification of compounds with much greater antineoplastic effect than diazoxide, the most potent of which possesses an IC₅₀ of 2.93±0.07 μM in a cellular model of triple-negative breast cancer, with high selectivity over nonmalignant cells and more than double the potency of the clinical agent 5-fluorouracil. No correlation between cytotoxicity and CII inhibition was found, thus indicating an as-yet-undefined mechanism of action of this scaffold. The derivatives described herein represent valuable hit compounds for therapeutic discovery in triple-negative breast cancer.     

Modeling infinite dilution activity coefficients of organic-aqueous systems using a modified regular solution equation and cubic equations-of-state

Expressions derived from the regular solution equation and the generalized cubic equations-of-state (EOS) were employed to model the infinite dilute activity coefficient (γ^∞) of organic-aqueous systems. A database of 119 organic species in aqueous systems, divided into six classes, was gathered for models evaluations. The use of the molar density, the first order molecular connectivity, and the dipole moment appear to be adequate correlating variables for describing the structural dependence of the residual part in the modified regular solution equation (MRS). The Soave-Redlich-Kwong (SRK) and Peng-Robinson (PR) were specified and employed in the generalized cubic EOS form. The excess activity coefficient concept was used in the SRK and PR EOS models to account for the deficiency of EOS in dealing with highly non-ideal or polar systems. The abilities of two existing correlation models along with two modified versions of the UNIFAC model were also assessed. The proposed models provide creditable equations for correlating γ^∞ of organic-aqueous systems.     

Economy and risk of cleaning brushes for heat exchangers

Heat exchangers should work for many years satisfying and by low lifecycle costs. Equipping the tubes with brushes for cleaning inside can help to reduce corrosion and costs. But an additional risk of corrosion arises by running a heat exchanger at low velocity of water, causing brushes being blocked. The minimum velocity of water required depends on thickness, number and oversize length of the bristles, temperature of water, inside diameter, surface and on the total length of the tubes. For example in tubes of 4 m length, ID 16 mm, 480 bristles D 0.15 mm at 16°C, the water velocity should be minimum 0.8 m/s. Shorter tubes, thicker bristles, more bristles, lower temperature or lower water velocity are a higher risk.     

White Bass (<Emphasis Type="Italic">Morone chrysops</Emphasis>) Preferentially Retain n-3 PUFA in Ova When Fed Prepared Diets with Varying FA Content

We evaluated the fatty acid (FA) composition of broodstock white bass ova fed one of six commercial diets with increasing polyunsaturated FA content (n‐6/n‐3 ratio; 0.36, 0.39, 0.46, 0.83, 1.07, 1.12) eight weeks prior to sampling. Fatty acid profiles of ova from brooders fed each of the six diets were significantly altered according to canonical discriminant analysis. Ova FA profiles resulting from the 0.39 diet separated those from the 0.36 diet based on lower 18:2n‐6 (LNA) and higher 20:1n‐9 concentrations from the 0.36 diet. Ova profiles were further separated based on lower concentrations of 22:5n‐3 (DPA) from the 0.46 diet, lower concentrations of 20:5n‐3 (EPA) in the 1.12 and 0.83 diets, and lower concentrations of 22:6n‐3 (DHA) in all other diets relative to the 0.46 diet. Changes in ova FA profile at four and eight weeks were consistent with dietary intake with an approximate 2% increase in any given FA class with increasing time on individual diet. There was no correlation between dietary ARA concentrations (0.7–1.1 mol%), or dietary EPA/ARA ratios (7–15), and the concentrations (1.4–1.7 mol%) or ratios (3.3–4.4) found in the ova by diet. Our results suggest that white bass females have the ability to preferentially incorporate n‐3 PUFA, particularly DHA, suggesting mobilization of this FA from other tissues for ova deposition or preferential dietary incorporation of PUFA into ova. These results will add to the limited FA information available in white bass and enable nutritionists to formulate broodstock diets that maximize reproductive potential in this species.     

Rate constants of reactions of ozone with organic and inorganic compounds in water—I: Non-dissociating organic compounds

Rate constants of reactions of ozone with non-ionized solutes, such as aliphatic alcohols, olefins, chlorosubstituted ethylenes, substituted benzenes and carbohydrates, have been determined from the absolute rates with which ozone reacts in the presence of various concentrations of these compounds in water. They have been tested by comparison with the relative rates by which pairs of these solutes are transformed by ozone. Different experimental methods have been developed to determine such rate constants in the range from 10^?2 to 10⁵ M^?1 s^?1. Interferences between the direct reactions of ozone and reactions due to its preliminary decomposition to secondary oxidants could be eliminated. The kinetics of all the reactions studied are first order with respect to ozone and solute concentration. The rate constants of many types of organic compounds in water are of the same order of magnitude as in organic solvents. Substituted benzenes, however, react in water about 100 times faster. They obey a linear free energy relationship with p = ?3.1 when based on δ_p⁺ values. Comparisons of rate constants with chemical structures of the reacting groups show that all reactions of ozone are highly selective and electrophilic. The kinetic data allow explanation of the chemical effects of ozone observed in water treatment practice.