Coarse grained force field for the molecular simulation of natural gases and condensates

AbstractThe atomistically-detailed molecular modelling of petroleum fluids is challenging, amongst other aspects, due to the very diverse multicomponent and asymmetric nature of the mixtures in question. Complicating matters further, the time scales for many important processes can be much larger than the current and foreseeable capacity of modern computers running fully-atomistic models. To overcome these limitations, a coarse grained (CG) model is proposed where some of the less-important degrees of freedom are safely integrated out, leaving as key parameters the average energy levels, the molecular conformations and the range of the Mie intermolecular potentials employed as the basis of the model. The parametrization is performed by using an analytical equation of state of the statistical associating fluid theory (SAFT) family to link the potential parameters to macroscopically observed thermophysical properties. The parameters found through this top-down approach are used directly in molecular dynamics simulations of multi-component multi-phase systems. The procedure is exemplified by calculating the phase envelope of the methane–decane binary and of two synthetic light condensate mixtures. A methodology based on the discrete expansion of a mixture is used to determine the bubble points of these latter mixtures, with an excellent agreement to experimental data. The model presented is entirely predictive and an abridged table of parameters for some fluids of interest is provided

The growth and carcass and meat characteristics of pigs raised in a free-range or conventional housing system

The growth performance and the carcass and physical and chemical characteristics of the meat of 24 Landrace X Large White pigs were compared when reared under a free-range or a conventional housing system. The free-range pigs had lower feed intakes and slower growth rates than the conventionally housed pigs. The free-range pigs also had a lower P2 fat depth and therefore yielded a carcass with a higher percentage lean meat. Housing systems had no effect on the weight distribution of the commercial cuts (as a percentage of cold carcass weight). The meat from the free-range pigs was slightly more reddish in colour, but apart from that housing systems had no effect on the water-holding capacity (WHC) of the meat, its initial pH (pH45) or its final pH (pH24). The meat from the free-range pigs had the same shear force (WBS) values as those of the conventionally housed pigs. Housing systems had an influence on the fatty acid composition. Stearic acid (C18:0) was significantly lower in the meat of the free-range pigs than that of the conventionally housed pigs while linoleic acid (C18:2n-6) and polyunsaturated fatty acid (PUFA) concentrations were significantly higher. However, the moisture, fat, protein and ash contents as well as the mineral composition in the meat were unaffected by housing systems. It could be concluded that pigs raised in a conventional housing system produced meat with similar quality characteristics to that of pigs raised in a free-range housing system. Keywords: Free-range, Housing systems, Growth performance, Carcass yield, Physical quality, Chemical composition South African Journal of Animal Science Vol.33(3) 2003:166-17

The Typical Flight Performance of Blowflies: Measuring the Normal Performance Envelope of Calliphora vicina Using a Novel Corner-Cube Arena

Despite a wealth of evidence demonstrating extraordinary maximal performance, little is known about the routine flight performance of insects. We present a set of techniques for benchmarking performance characteristics of insects in free flight, demonstrated using a model species, and comment on the significance of the performance observed. Free-flying blowflies (Calliphora vicina) were filmed inside a novel mirrored arena comprising a large (1.6 m1.6 m1.6 m) corner-cube reflector using a single high-speed digital video camera (250 or 500 fps). This arrangement permitted accurate reconstruction of the flies' 3-dimensional trajectories without the need for synchronisation hardware, by virtue of the multiple reflections of a subject within the arena. Image sequences were analysed using custom-written automated tracking software, and processed using a self-calibrating bundle adjustment procedure to determine the subject's instantaneous 3-dimensional position. We illustrate our method by using these trajectory data to benchmark the routine flight performance envelope of our flies. Flight speeds were most commonly observed between 1.2 ms−1 and 2.3 ms−1, with a maximum of 2.5 ms−1. Our flies tended to dive faster than they climbed, with a maximum descent rate (−2.4 ms−1) almost double the maximum climb rate (1.2 ms−1). Modal turn rate was around 240°s−1, with maximal rates in excess of 1700°s−1. We used the maximal flight performance we observed during normal flight to construct notional physical limits on the blowfly flight envelope, and used the distribution of observations within that notional envelope to postulate behavioural preferences or physiological and anatomical constraints. The flight trajectories we recorded were never steady: rather they were constantly accelerating or decelerating, with maximum tangential accelerations and maximum centripetal accelerations on the order of 3 g

Resection in the popliteal fossa for metastatic melanoma

BACKGROUND: Traditionally metastatic melanoma of the distal leg and the foot metastasize to the lymph nodes of the groin. Sometimes the first site of nodal disease can be the popliteal fossa. This is an infrequent event, with rare reports in literature and when it occurs, radical popliteal node dissection must be performed. CASE PRESENTATION: We report a case of a 36-year old man presented with diagnosis of 2 mm thick, Clark's level II-III, non ulcerated melanoma of the left heel, which developed during the course of the disease popliteal node metastases, after a superficial and deep groin dissection for inguinal node involvement. Five months after popliteal lymph node dissection he developed systemic disease, therefore he received nine cycles of dacarbazine plus fotemustine. To date (56 months after prior surgery and 11 months after chemotherapy) he is alive with no evidence of disease. CONCLUSION: In case of groin metastases from melanoma of distal lower extremities, clinical and ultrasound examination of ipsilateral popliteal fossa is essential. When metastatic disease is found, radical popliteal dissection is the standard of care. Therefore knowledge of anatomy and surgical technique about popliteal lymphadenectomy are required to make preservation of structures that if injured, can produce a permanent, considerable disability

Bridging topological and functional information in protein interaction networks by short loops profiling

Protein-protein interaction networks (PPINs) have been employed to identify potential novel interconnections between proteins as well as crucial cellular functions. In this study we identify fundamental principles of PPIN topologies by analysing network motifs of short loops, which are small cyclic interactions of between 3 and 6 proteins. We compared 30 PPINs with corresponding randomised null models and examined the occurrence of common biological functions in loops extracted from a cross-validated high-confidence dataset of 622 human protein complexes. We demonstrate that loops are an intrinsic feature of PPINs and that specific cell functions are predominantly performed by loops of different lengths. Topologically, we find that loops are strongly related to the accuracy of PPINs and define a core of interactions with high resilience. The identification of this core and the analysis of loop composition are promising tools to assess PPIN quality and to uncover possible biases from experimental detection methods. More than 96% of loops share at least one biological function, with enrichment of cellular functions related to mRNA metabolic processing and the cell cycle. Our analyses suggest that these motifs can be used in the design of targeted experiments for functional phenotype detection.This research was supported by the Biotechnology and Biological Sciences Research Council (BB/H018409/1 to AP, ACCC and FF, and BB/J016284/1 to NSBT) and by the Leukaemia & Lymphoma Research (to NSBT and FF). SSC is funded by a Leukaemia & Lymphoma Research Gordon Piller PhD Studentship

Principles of meiotic chromosome assembly revealed in S. cerevisiae

During meiotic prophase, chromosomes organise into a series of chromatin loops emanating from a proteinaceous axis, but the mechanisms of assembly remain unclear. Here we use Saccharomyces cerevisiae to explore how this elaborate three-dimensional chromosome organisation is linked to genomic sequence. As cells enter meiosis, we observe that strong cohesin-dependent grid-like Hi-C interaction patterns emerge, reminiscent of mammalian interphase organisation, but with distinct regulation. Meiotic patterns agree with simulations of loop extrusion with growth limited by barriers, in which a heterogeneous population of expanding loops develop along the chromosome. Importantly, CTCF, the factor that imposes similar features in mammalian interphase, is absent in S. cerevisiae, suggesting alternative mechanisms of barrier formation. While grid-like interactions emerge independently of meiotic chromosome synapsis, synapsis itself generates additional compaction that matures differentially according to telomere proximity and chromosome size. Collectively, our results elucidate fundamental principles of chromosome assembly and demonstrate the essential role of cohesin within this evolutionarily conserved process

Cost minimization analysis of different growth hormone pen devices based on time-and-motion simulations

<p>Abstract</p> <p>Background</p> <p>Numerous pen devices are available to administer recombinant Human Growth Hormone (rhGH), and both patients and health plans have varying issues to consider when selecting a particular product and device for daily use. Therefore, the present study utilized multi-dimensional product analysis to assess potential time involvement, required weekly administration steps, and utilization costs relative to daily rhGH administration.</p> <p>Methods</p> <p>Study objectives were to conduct 1) Time-and-Motion (TM) simulations in a randomized block design that allowed time and steps comparisons related to rhGH preparation, administration and storage, and 2) a Cost Minimization Analysis (CMA) relative to opportunity and supply costs. Nurses naïve to rhGH administration and devices were recruited to evaluate four rhGH pen devices (2 in liquid form, 2 requiring reconstitution) via TM simulations. Five videotaped and timed trials for each product were evaluated based on: 1) Learning (initial use instructions), 2) Preparation (arrange device for use), 3) Administration (actual simulation manikin injection), and 4) Storage (maintain product viability between doses), in addition to assessment of steps required for weekly use. The CMA applied micro-costing techniques related to opportunity costs for caregivers (categorized as wages), non-drug medical supplies, and drug product costs.</p> <p>Results</p> <p>Norditropin^®NordiFlex and Norditropin^®NordiPen (NNF and NNP, Novo Nordisk, Inc., Bagsværd, Denmark) took less weekly Total Time (p < 0.05) to use than either of the comparator products, Genotropin^®Pen (GTP, Pfizer, Inc, New York, New York) or HumatroPen^®(HTP, Eli Lilly and Company, Indianapolis, Indiana). Time savings were directly related to differences in new package Preparation times (NNF (1.35 minutes), NNP (2.48 minutes) GTP (4.11 minutes), HTP (8.64 minutes), p < 0.05)). Administration and Storage times were not statistically different. NNF (15.8 minutes) and NNP (16.2 minutes) also took less time to Learn than HTP (24.0 minutes) and GTP (26.0 minutes), p < 0.05). The number of weekly required administration steps was also least with NNF and NNP. Opportunity cost savings were greater in devices that were easier to prepare for use; GTP represented an 11.8% drug product savings over NNF, NNP and HTP at time of study. Overall supply costs represented <1% of drug costs for all devices.</p> <p>Conclusions</p> <p>Time-and-motion simulation data used to support a micro-cost analysis demonstrated that the pen device with the greater time demand has highest net costs.</p

Effect of promoter architecture on the cell-to-cell variability in gene expression

According to recent experimental evidence, the architecture of a promoter, defined as the number, strength and regulatory role of the operators that control the promoter, plays a major role in determining the level of cell-to-cell variability in gene expression. These quantitative experiments call for a corresponding modeling effort that addresses the question of how changes in promoter architecture affect noise in gene expression in a systematic rather than case-by-case fashion. In this article, we make such a systematic investigation, based on a simple microscopic model of gene regulation that incorporates stochastic effects. In particular, we show how operator strength and operator multiplicity affect this variability. We examine different modes of transcription factor binding to complex promoters (cooperative, independent, simultaneous) and how each of these affects the level of variability in transcription product from cell-to-cell. We propose that direct comparison between in vivo single-cell experiments and theoretical predictions for the moments of the probability distribution of mRNA number per cell can discriminate between different kinetic models of gene regulation.Comment: 35 pages, 6 figures, Submitte

A Dominated Coupling From The Past algorithm for the stochastic simulation of networks of biochemical reactions

<p>Abstract</p> <p>Background</p> <p>In recent years, stochastic descriptions of biochemical reactions based on the Master Equation (ME) have become widespread. These are especially relevant for models involving gene regulation. Gillespie’s Stochastic Simulation Algorithm (SSA) is the most widely used method for the numerical evaluation of these models. The SSA produces exact samples from the distribution of the ME for finite times. However, if the stationary distribution is of interest, the SSA provides no information about convergence or how long the algorithm needs to be run to sample from the stationary distribution with given accuracy. </p> <p>Results</p> <p>We present a proof and numerical characterization of a Perfect Sampling algorithm for the ME of networks of biochemical reactions prevalent in gene regulation and enzymatic catalysis. Our algorithm combines the SSA with Dominated Coupling From The Past (DCFTP) techniques to provide guaranteed sampling from the stationary distribution. The resulting DCFTP-SSA is applicable to networks of reactions with uni-molecular stoichiometries and sub-linear, (anti-) monotone propensity functions. We showcase its applicability studying steady-state properties of stochastic regulatory networks of relevance in synthetic and systems biology.</p> <p>Conclusion</p> <p>The DCFTP-SSA provides an extension to Gillespie’s SSA with guaranteed sampling from the stationary solution of the ME for a broad class of stochastic biochemical networks.</p