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

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

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

Bankruptcy Reform: An Orderly Development of Public Policy

In legislating the pending bankruptcy reform, Congress has made many of the key decisions behind closed doors. In fact, the process has been characterized as a congressional effort to pass a stealth bankruptcy bill. This secrecy brings into question the democratic nature of congressional deliberation. When the Framers designed the legislative branch, open debate was envisioned as the rule, not the exception. Unfortunately, Congress has adopted a secretive, approach to pushing through recent bankruptcy legislation. In a sharp departure from the decades-long congressional approach to bankruptcy legislation, Congress stopped seeking expert advice and instead turned to special interest lobbyists…” Thus, Congress utilized the cover of secrecy to boldly tailor the bankruptcy laws to serve special interests. Consequently, theuse of the term \u27bankruptcy reform\u27 is considered an oxymoron to most organizations of bankruptcy professionals .... Virtually every group of bankruptcy professionals, regardless of the constituency represented, opposed both the substance of the legislation and the process ... taken by Congress. Recent efforts to alter the bankruptcy system under the cover of secrecy have received harsh criticism. Proponents of bankruptcy reform are so intent upon enacting legislation favoring special interests that they have taken the unprecedented step of attempting to enact the legislation under the guise of a completely unrelated, already-enacted bill. These tactics of congressional secrecy are contrary to the process of open, reasoned, and deliberate decision making that is a cornerstone of American democracy. This secrecy is wholly inconsistent with the process of public deliberation which the Founders envisioned

Bankruptcy Reform: An Orderly Development of Public Policy

In legislating the pending bankruptcy reform, Congress has made many of the key decisions behind closed doors. In fact, the process has been characterized as a congressional effort to pass a stealth bankruptcy bill. This secrecy brings into question the democratic nature of congressional deliberation. When the Framers designed the legislative branch, open debate was envisioned as the rule, not the exception. Unfortunately, Congress has adopted a secretive, approach to pushing through recent bankruptcy legislation. In a sharp departure from the decades-long congressional approach to bankruptcy legislation, Congress stopped seeking expert advice and instead turned to special interest lobbyists…” Thus, Congress utilized the cover of secrecy to boldly tailor the bankruptcy laws to serve special interests. Consequently, theuse of the term \u27bankruptcy reform\u27 is considered an oxymoron to most organizations of bankruptcy professionals .... Virtually every group of bankruptcy professionals, regardless of the constituency represented, opposed both the substance of the legislation and the process ... taken by Congress. Recent efforts to alter the bankruptcy system under the cover of secrecy have received harsh criticism. Proponents of bankruptcy reform are so intent upon enacting legislation favoring special interests that they have taken the unprecedented step of attempting to enact the legislation under the guise of a completely unrelated, already-enacted bill. These tactics of congressional secrecy are contrary to the process of open, reasoned, and deliberate decision making that is a cornerstone of American democracy. This secrecy is wholly inconsistent with the process of public deliberation which the Founders envisioned

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