Response of peripheral nerve to cyclic compression in a laboratory rat model

Repetitive cyclic loading of a nerve has been proposed as a pathogenic factor in the development of occupational compression neuropathies. Little is known about the basic response of peripheral nerve to cyclic compression. We investigated the hypothesis that cyclic compression is more detrimental to nerve function than constant compression. We measured the amplitudes and velocities of distally evoked action potentials in the presence of constant or cyclic compression of the tibial nerve in rats. Seven groups were subjected to constant or cyclic compression for 6 h by a computer controlled, hydraulically activated compression chamber. Nerves were compressed with 0 (control group), 30, 60, or 90 mm Hg of constant pressure or 0-30, 20-50, or 30-60 mm Hg of cyclic compression for approximately 20,000 compression cycles. Action potentials were recorded every 15 min. The effects of cyclic compression on nerve conduction were equivalent to the effects of constant compression at the average applied pressure. Cyclic loading itself does not appear to be an important pathogenic factor in the development of nerve conduction block.     

A high proportion of novel mutations in BRCA1 with strong founder effects among Dutch and Belgian hereditary breast and ovarian cancer families

We have identified 79 mutations in BRCA1 in a set of 643 Dutch and 23 Belgian hereditary breast and ovarian cancer families collected either for research or for clinical diagnostic purposes. Twenty-eight distinct mutations have been observed, 18 of them not previously reported and 12 of them occurring more than once. Most conspicuously, a 2804delAA mutation has been found 19 times and has never been reported outside the Netherlands. A common haplotype spanning > or = 375 kb could be identified for each of the nine examined recurrent mutations, indicating the presence of multiple BRCA1 founder mutations in the Dutch population. The 2804delAA mutation has been estimated to have originated approximately 32 generations ago. No specific breast or ovarian cancer phenotype could be assigned to any of the common mutations, and the ovarian cancer incidence among 18 families with the 2804delAA mutation was heterogeneous.     

Evolutionary multiobjective optimization for base station transmitter placement with frequency assignment

We propose a new solution to the problem of positioning base station transmitters of a mobile phone network and assigning frequencies to the transmitters, both in an optimal way. Since an exact solution cannot be expected to run in polynomial time for all interesting versions of this problem (they are all NP-hard), our algorithm follows a heuristic approach based on the evolutionary paradigm. For this evolution to be efficient, i.e., goal-oriented and sufficiently random at the same time, problem-specific knowledge is embedded in the operators. The problem requires both the minimization of the cost and of the channel interference. We examine and compare two standard multiobjective techniques and a new algorithm - the steady-state evolutionary algorithm with Pareto tournaments. One major finding of the empirical investigation is a strong influence of the choice of the multiobjective selection method on the utility of the problem-specific recombination leading to a significant difference in the solution quality.     

Performance enhancement of an induction motor by secondaryimpedance control

The paper demonstrates the use of nonresistive secondary control of an induction motor to improve efficiency, power factor and torque. A mathematical algorithm is presented to predict the control requirements in terms of secondary capacitance. The required secondary capacitance is implemented by a novel electronic switching technique that effectively increases the value of the used capacitor. This overcomes the high-capacitance demand and provides a feasible solution. Experimental verification is presented in the results obtained from a small induction motor drive     

Novel (Phenothiazinyl)Vinyl-Pyridinium Dyes and Their Potential Applications as Cellular Staining Agents

We report here the synthesis and structural characterization of novel cationic (phenothiazinyl)vinyl-pyridinium (PVP) dyes, together with optical (absorption/emission) properties and their potential applicability as fluorescent labels. Convective heating, ultrasound irradiation and mechanochemical synthesis were considered as alternative synthetic methodologies proficient for overcoming drawbacks such as long reaction time, nonsatisfactory yields or solvent requirements in the synthesis of novel dye (E)-1-(3-chloropropyl)-4-(2-(10-methyl-10H-phenothiazin-3-yl)vinyl)pyridin-1-ium bromide 3d and its N-alkyl-2-methylpyridinium precursor 1c. The trans geometry of the newly synthesized (E)-4-(2-(7-bromo-10-ethyl-10H-phenothiazin-3-yl)vinyl)-1-methylpyridin-1-ium iodide 3b and (E)-1-methyl-4-(2-(10-methyl-10H-phenothiazin-3-yl)vinyl)pyridin-1-ium tetrafluoroborate 3a′ was confirmed by single crystal X-ray diffraction. A negative solvatochromism of the dyes in polar solvents was highlighted by UV-Vis spectroscopy and explanatory insights were supported by molecular modeling which suggested a better stabilization of the lowest unoccupied molecular orbitals (LUMO). The photostability of the dye 3b was investigated by irradiation at 365 nm in different solvents, while the steady-state and time-resolved fluorescence properties of dye 3b and 3a′ in solid state were evaluated under one-photon excitation at 485 nm. The in vitro cytotoxicity of the new PVP dyes on B16-F10 melanoma cells was evaluated by WST-1 assay, while their intracellular localization was assessed by epi-fluorescence conventional microscopy imaging as well as one- and two-photon excited confocal fluorescence lifetime imaging microscopy (FLIM). PVP dyes displayed low cytotoxicity, good internalization inside melanoma cells and intense fluorescence emission inside the B16-F10 murine melanoma cells, making them suitable staining agents for imaging applications.     

PACAP-38 in Acute ST-Segment Elevation Myocardial Infarction in Humans and Pigs: A Translational Study

Acute myocardial infarction (MI) is one of the most common causes of death worldwide. Pituitary adenylate cyclase activating polypeptide (PACAP) is a cardioprotective neuropeptide expressing its receptors in the cardiovascular system. The aim of our study was to examine tissue PACAP-38 in a translational porcine MI model and plasma PACAP-38 levels in patients with ST-segment elevation myocardial infarction (STEMI). Significantly lower PACAP-38 levels were detected in the non-ischemic region of the left ventricle (LV) in MI heart compared to the ischemic region of MI-LV and also to the Sham-operated LV in porcine MI model. In STEMI patients, plasma PACAP-38 level was significantly higher before percutaneous coronary intervention (PCI) compared to controls, and decreased after PCI. Significant negative correlation was found between plasma PACAP-38 and troponin levels. Furthermore, a significant effect was revealed between plasma PACAP-38, hypertension and HbA1c levels. This was the first study showing significant changes in cardiac tissue PACAP levels in a porcine MI model and plasma PACAP levels in STEMI patients. These results suggest that PACAP, due to its cardioprotective effects, may play a regulatory role in MI and could be a potential biomarker or drug target in MI.     

Integration of Data from Liquid–Liquid Phase Separation Databases Highlights Concentration and Dosage Sensitivity of LLPS Drivers

Liquid–liquid phase separation (LLPS) is a molecular process that leads to the formation of membraneless organelles, representing functionally specialized liquid-like cellular condensates formed by proteins and nucleic acids. Integrating the data on LLPS-associated proteins from dedicated databases revealed only modest agreement between them and yielded a high-confidence dataset of 89 human LLPS drivers. Analysis of the supporting evidence for our dataset uncovered a systematic and potentially concerning difference between protein concentrations used in a good fraction of the in vitro LLPS experiments, a key parameter that governs the phase behavior, and the proteomics-derived cellular abundance levels of the corresponding proteins. Closer scrutiny of the underlying experimental data enabled us to offer a sound rationale for this systematic difference, which draws on our current understanding of the cellular organization of the proteome and the LLPS process. In support of this rationale, we find that genes coding for our human LLPS drivers tend to be dosage-sensitive, suggesting that their cellular availability is tightly regulated to preserve their functional role in direct or indirect relation to condensate formation. Our analysis offers guideposts for increasing agreement between in vitro and in vivo studies, probing the roles of proteins in LLPS.     

Science in the Cloud: Allocation and Execution of Data-Intensive Scientific Workflows

An important challenge for the adoption of cloud computing in the scientific community remains the efficient allocation and execution of data-intensive scientific workflows to reduce execution time and the size of transferred data. The transferred data overhead is becoming significant with emerging scientific workflows that have input/output files and intermediate data products ranging in the hundreds of gigabytes. The allocation of scientific workflows on public clouds can be described through a variety of perspectives and parameters, and has been proved to be NP-complete. This paper proposes an evolutionary approach for task allocation on public clouds considering data transfer and execution time. In our framework, a solution is represented using an allocation chromosome that encodes the allocation of tasks to nodes, and an ordering chromosome that defines the execution order according to the scientific workflow representation. We propose a multi-objective optimization that relies on a cloud cost model and employs tailored evolution operators. Starting from a population of possible solutions, we employ crossover and mutation operators on both chromosomes aiming at optimizing the data transferred between nodes as well as the total workflow runtime. The crossover operators combine parts of solutions to reduce data overhead, whereas the mutation operators swamp between parts of the same chromosome according to pre-defined rules. Our experimental study compares between the proposed approach and current state-of-the art approaches using synthetic and real-life workflows. Our algorithm performs similarly to existing heuristics for small workflows and shows up to 80 % improvements for larger synthetic workflows. To further validate our approach we compare between the allocation and scheduling obtained by our approach with that obtained by popular scientific workflow managers, when real workflows with hundreds of tasks are executed on a public cloud. The results show a 10 % improvement in runtime over existing schedulers, caused by a 80 % reduction in transferred data and optimized allocation and ordering of tasks. This improved data locality has greater impact as it can be employed to improve and study data provenance and facilitate data persistence for scientific workflows.