Probabilistic sensitivity analysis of biochemical reaction systems

Sensitivity analysis is an indispensable tool for studying the robustness and fragility properties of biochemical reaction systems as well as for designing optimal approaches for selective perturbation and intervention. Deterministic sensitivity analysis techniques, using derivatives of the system response, have been extensively used in the literature. However, these techniques suffer from several drawbacks, which must be carefully considered before using them in problems of systems biology. We develop here a probabilistic approach to sensitivity analysis of biochemical reaction systems. The proposed technique employs a biophysically derived model for parameter fluctuations and, by using a recently suggested variance-based approach to sensitivity analysis [Saltelli et al., Chem. Rev. (Washington, D.C.) 105, 2811 (2005)], it leads to a powerful sensitivity analysis methodology for biochemical reaction systems. The approach presented in this paper addresses many problems associated with derivative-based sensitivity analysis techniques. Most importantly, it produces thermodynamically consistent sensitivity analysis results, can easily accommodate appreciable parameter variations, and allows for systematic investigation of high-order interaction effects. By employing a computational model of the mitogen-activated protein kinase signaling cascade, we demonstrate that our approach is well suited for sensitivity analysis of biochemical reaction systems and can produce a wealth of information about the sensitivity properties of such systems. The price to be paid, however, is a substantial increase in computational complexity over derivative-based techniques, which must be effectively addressed in order to make the proposed approach to sensitivity analysis more practical

A New Time-Dependent Finite Difference Method for Relativistic Shock Acceleration

We present a new approach to calculate the particle distribution function about relativistic shocks including synchrotron losses using the method of lines with an explicit finite difference scheme. A steady, continuous, one dimensional plasma flow is considered to model thick (modified) shocks, leading to a calculation in three dimensions plus time, the former three being momentum, pitch angle and position. The method accurately reproduces the expected power law behaviour in momentum at the shock for upstream flow speeds ranging from 0.1c to 0.995c (1 < \Gamma < 10). It also reproduces approximate analytical results for the synchrotron cutoff shape for a non-relativistic shock, demonstrating that the loss process is accurately represented. The algorithm has been implemented as a hybrid OpenMP--MPI parallel algorithm to make efficient use of SMP cluster architectures and scales well up to many hundreds of CPUs.Comment: Accepted for publication in MNRA

In-Space technology experiments program. A high efficiency thermal interface (using condensation heat transfer) between a 2-phase fluid loop and heatpipe radiator: Experiment definition phase

Space Station elements and advanced military spacecraft will require rejection of tens of kilowatts of waste heat. Large space radiators and two-phase heat transport loops will be required. To minimize radiator size and weight, it is critical to minimize the temperature drop between the heat source and sink. Under an Air Force contract, a unique, high-performance heat exchanger is developed for coupling the radiator to the transport loop. Since fluid flow through the heat exchanger is driven by capillary forces which are easily dominated by gravity forces in ground testing, it is necessary to perform microgravity thermal testing to verify the design. This contract consists of an experiment definition phase leading to a preliminary design and cost estimate for a shuttle-based flight experiment of this heat exchanger design. This program will utilize modified hardware from a ground test program for the heat exchanger

Survey of Dust Issues for Lunar Seals and the RESOLVE Project

Lunar dust poses a technical challenge for sealing applications on the moon. A survey of seals used in Apollo lunar missions is presented as well as lunar soil characteristics and a description of the lunar environment. Seal requirements and technical challenges for the volatiles characterization oven and hydrogen reduction reaction chamber of the RESOLVE project are discussed. The purpose of the RESOLVE project is to find water or ice in lunar soil and demonstrate the ability to produce water, and hence oxygen and hydrogen, from lunar regolith for life support and propellants

Metabolism of Nonessential N15-Labeled Amino Acids and the Measurement of Human Whole-Body Protein Synthesis Rates

Eight N-15 labeled nonessential amino acids plus (15)NH4Cl were administered over a 10 h period to four healthy adult males using a primed-constant dosage regimen. The amount of N-15 excreted in the urine and the urinary ammonia, hippuric acid, and plasma alanine N-15 enrichments were measured. There was a high degree of consistency across subjects in the ordering of the nine compounds based on the fraction of N-15 excreted (Kendall coefficient of concordance W = 0.83, P is less than 0.01). Protein synthesis rates were calculated from the urinary ammonia plateau enrichment and the cumulative excretion of N-15. Glycine was one of the few amino acids that gave similar values by both methods

Effect of vibration in combined axes on subjective evaluation of ride quality

The effects of simultaneous sinusoidal vibration in the vertical and lateral axes on ratings of discomfort were investigated. The first experiment concentrated on the effects of variation of frequency in the two axes, and the second study concentrated on the effects of amplitude variation in the two axes

Residents' annoyance responses to aircraft noise events

In a study conducted in the vicinity of Salt Lake City International Airport, community residents reported their annoyance with individual aircraft flyovers during rating sessions conducted in their homes. Annoyance ratings were obtained at different times of the day. Aircraft noise levels were measured, and other characteristics of the aircraft were noted by trained observers. Metrics commonly used for assessing aircraft noise were compared, but none performed significantly better than A-weighted sound pressure level. A significant difference was found between the ratings of commercial jet aircraft and general aviation propeller aircraft, with the latter being judged less annoying. After the effects of noise level were accounted for, no significant differences were found between the ratings of landings and takeoffs. Aircraft noise annoyance reactions are stronger in lowered ambient noise conditions. This is consistent with the theory that reduced nighttime and evening ambient levels could create different reactions at different times of day. After controlling for ambient noise in a multiple regression analysis, no significant differences were found between the ratings of single events obtained during the three time periods: morning, afternoon, and evenings

Visit complexity, diagnostic uncertainty, and antibiotic prescribing for acute cough in primary care: a retrospective study

Background: Guidelines and performance measures recommend avoiding antibiotics for acute cough/acute bronchitis and presume visits are straightforward with simple diagnostic decision-making. We evaluated clinician-assigned diagnoses, diagnostic uncertainty, and antibiotic prescribing for acute cough visits in primary care. Methods: We conducted a retrospective analysis of acute cough visits – cough lasting ≤21 days in adults 18–64 years old without chronic lung disease – in a primary care practice from March 2011 through June 2012. Results: Of 56,301 visits, 962 (2%) were for acute cough. Clinicians diagnosed patients with 1, 2, or ≥ 3 cough-related diagnoses in 54%, 35%, and 11% of visits, respectively. The most common principal diagnoses were upper respiratory infection (46%), sinusitis (10%), acute bronchitis (9%), and pneumonia (8%). Clinicians prescribed antibiotics in 22% of all visits: 65% of visits with antibiotic-appropriate diagnoses and 4% of visits with non-antibiotic-appropriate diagnoses. Clinicians expressed diagnostic uncertainty in 16% of all visits: 43% of visits with antibiotic-appropriate diagnoses and 5% of visits with non-antibiotic-appropriate diagnoses. Clinicians expressed uncertainty more often when prescribing antibiotics than when not prescribing antibiotics (30% vs. 12%; p < 0.001). As the number of visit diagnoses increased from 1 to 2 to ≥ 3, clinicians were more likely to express diagnostic uncertainty (5%, 25%, 40%, respectively; p < 0.001) and prescribe antibiotics (16%, 25%, 41%, respectively; p < 0.001). Conclusions: Acute cough may be more complex and have more diagnostic uncertainty than guidelines and performance measures presume. Efforts to reduce antibiotic prescribing for acute cough should address diagnostic complexity and uncertainty that clinicians face

A Search for Propylene Oxide and Glycine in Sagittarius B2 (LMH) and Orion

We have used the Mopra Telescope to search for glycine and the simple chiral molecule propylene oxide in the Sgr B2 (LMH) and Orion KL, in the 3-mm band. We have not detected either species, but have been able to put sensitive upper limits on the abundances of both molecules. The 3-sigma upper limits derived for glycine conformer I are 3.7 x 10^{14} cm^{-2} in both Orion-KL and Sgr B2 (LMH), comparable to the reported detections of conformer I by Kuan et al. However, as our values are 3-sigma upper limits rather than detections we conclude that this weighs against confirming the detection of Kuan et al. We find upper limits for the glycine II column density of 7.7 x 10^{12} cm^{-2} in both Orion-KL and Sgr B2 (LMH), in agreement with the results of Combes et al. The results presented here show that glycine conformer II is not present in the extended gas at the levels detected by Kuan et al. for conformer I. Our ATCA results (Jones et al.) have ruled out the detection of glycine (both conformers I and II) in the compact hot core of the LMH at the levels reported, so we conclude that it is unlikely that Kuan et al. have detected glycine in either Sgr B2 or Orion-KL. We find upper limits for propylene oxide abundance of 3.0 x 10^{14} cm^{-2} in Orion-KL and 6.7 x 10^{14} cm^{-2} in Sgr B2 (LMH). We have detected fourteen features in Sgr B2 and four features in Orion-KL which have not previously been reported in the ISM, but have not be able to plausibly assign these transitions to any carrier.Comment: 12 pages, 3 figures. Accepted by MNRAS 12th January 200