Stochastic level-set method for shape optimisation

We present a new method for stochastic shape optimisation of engineering structures. The method generalises an existing deterministic scheme, in which the structure is represented and evolved by a level-set method coupled with mathematical programming. The stochastic element of the algorithm is built on the methods of statistical mechanics and is designed so that the system explores a Boltzmann-Gibbs distribution of structures. In non-convex optimisation problems, the deterministic algorithm can get trapped in local optima: the stochastic generalisation enables sampling of multiple local optima, which aids the search for the globally-optimal structure. The method is demonstrated for several simple geometrical problems, and a proof-of-principle calculation is shown for a simple engineering structure.Comment: 17 pages, 10 fig

Method for Obtaining Antifungal and Herbicidal Compounds that Target the First Committed Step in Shingolipid Long-Chain Base Biosynthesis

The invention provides the LCB1 and LCB2 genes of the yeast Saccharomyces cerevisiae that encode subunits of the enzyme serine palmitoyltransferase (SPT), the first enzyme leading to synthesis of the long-base component of the sphingolipids. The present specification describes the isolation of the LCB1 and LCB2 genes. The invention further relates to methods of using these genes to either inhibit SPT activity or to inhibit synthesis of the enzyme. Furthermore, the invention relates to methods for constructing strains of S. cerevisiae or other organisms that can be used to select and to test for compounds that either inhibit SPT activity or to inhibit synthesis of the enzyme

Fungal IPC Synthase Assay

The presently-disclosed IPC synthase-inhibitor assays comprise the steps of: (1) expression of the IPC1 gene in a cell; (2) introducing labeled starting substrates for ceramide conversion as well as potential inhibitor(s) of such conversion to the expressed gene product in an environment which allows time and conditions for conversion, and (3) identifying those potential inhibitors which actually inhibit conversion. The present invention also provides methods to determine the ability of a test compound to inhibit fungal growth, comprising the steps of (1) presenting active inositolphosophotidylceramide synthase in a manner such that synthesis of inositolphosphotidylceramide can occur; (2) introducing ceramide and phosphotylinositol, said ceramide or phosphatidylinositol carrying label for identification; (3) subjecting said active inositolphosophotidylceramide synthase, ceramide and phosphotylinositol to ordinary conditions necessary for ceramide conversion to phosphoinositol ceramide; and (4) identifying those test compounds which inhibit ceramide conversion to phosphoinositol ceramide

Technique for Specifying the Fatty Acid at the SN2 Position of Acylglycerol Lipids

A method for specifying a fatty acid at the sn2 position of acylglycerol lipids including (a) transfecting a vector including the SLC1 gene or a variant thereof into embryonic biological material, and (b) allowing the SLC1 gene to specify the type of fatty acid at the sn2 position of acylglycerol lipids. Also provided for is an isolated SLC1 gene and a probe for its detection

Inactivation of cloned Na channels expressed in Xenopus oocytes

This study investigates the inactivation properties of Na channels expressed in Xenopus oocytes from two rat IIA Na channel cDNA clones differing by a single amino acid residue. Although the two cDNAs encode Na channels with substantially different activation properties (Auld, V. J., A. L. Goldin, D. S. Krafte, J. Marshall, J. M. Dunn, W. A. Catterall, H. A. Lester, N. Davidson, and R. J. Dunn. 1988. Neuron. 1:449-461), their inactivation properties resemble each other strongly but differ markedly from channels induced by poly(A+) rat brain RNA. Rat IIA currents inactivate more slowly, recover from inactivation more slowly, and display a steady-state voltage dependence that is shifted to more positive potentials. The macroscopic inactivation process for poly(A+) Na channels is defined by a single exponential time course; that for rat IIA channels displays two exponential components. At the single-channel level these differences in inactivation occur because rat IIA channels reopen several times during a depolarizing pulse; poly(A+) channels do not. Repetitive stimulation (greater than 1 Hz) produces a marked decrement in the rat IIA peak current and changes the waveform of the currents. When low molecular weight RNA is coinjected with rat IIA RNA, these inactivation properties are restored to those that characterize poly(A+) channels. Slow inactivation is similar for rat IIA and poly(A+) channels, however. The data suggest that activation and inactivation involve at least partially distinct regions of the channel protein

Infections by Kudoa ciliatae (Myxozoa: Myxosporea) in Indo-Pacific whiting Sillago spp.

Infections by Kudoa ciliatae Lom, Rohde & Dykova, 1992 were detected in 141 (32%) of 444 Indo-Pacific whiting Sillago spp, caught in Moreton Bay, Australia. The parasite was detected in the type host, S. ciliata (in 14% of 73 fish), and from 2 new hosts, S, maculata (46% of 264) and S. analis (9% of 107). Prevalence of infection in S. maculata was greatest in autumn (100%) and lowest in spring (10%), the seasonal differences being positively correlated to host size (more prevalent in larger fish caught in autumn). Intensity of infection ranged from 1 to 45 cysts per fish (mean 7.6) and the cysts measured up to 2.5 mm in length. Most cysts were located on the serosal surface of the intestinal tract extending into the circular smooth muscle layer. The majority were found in the distal third of the intestine, often in groups of 2 to 5 cysts. Parasites were also found for the first time in the pyloric caeca, intestinal mesentery and liver. Calcified cysts were occasionally detected in S, ciliata and S, analis

Preparation and relaxation of very stable glassy states of a simulated liquid

We prepare metastable glassy states in a model glass-former made of Lennard-Jones particles by sampling biased ensembles of trajectories with low dynamical activity. These trajectories form an inactive dynamical phase whose `fast' vibrational degrees of freedom are maintained at thermal equilibrium by contact with a heat bath, while the `slow' structural degrees of freedom are located in deep valleys of the energy landscape. We examine the relaxation to equilibrium and the vibrational properties of these metastable states. The glassy states we prepare by our trajectory sampling method are very stable to thermal fluctuations and also more mechanically rigid than low-temperature equilibrated configurations.Comment: Minor revisions in light of referee comments. 5 pages, 4 fig

Is There a Role for Benefit-Cost Analysis in Environmental, Health, and Safety Regulation?

Benefit-cost analysis has a potentially important role to play in helping inform regulatory decision-making, although it should not be the sole basis for such decision-making. This paper offers eight principles on the appropriate use of benefit-cost analysis.Environment, Health and Safety, Regulatory Reform

Benefit-Cost Analysis in Environmental, Health, and Safety Regulation: A Statement of Principles

Benefit-cost analysis can play a very important role in legislative and regulatory policy debates on improving the environment, health, and safety. It can help illustrate the tradeoffs that are inherent in public policymaking as well as make those tradeoffs more transparent. It can also help agencies set regulatory priorities. Benefit-cost analysis should be used to help decisionmakers reach a decision. Contrary to the views of some, benefit-cost analysis is neither necessary nor sufficient for designing sensible public policy. If properly done, it can be very helpful to agencies in the decisionmaking process. Decisionmakers should not be precluded from considering the economic benefits and costs of different policies in the development of regulations. Laws that prohibit costs or other factors from being considered in administrative decisionmaking are inimical to good public policy. Currently, several of the most important regulatory statutes have been interpreted to imply such prohibitions. Benefit-cost analysis should be required for all major regulatory decisions, but agency heads should not be bound by a strict benefit-cost test. Instead, they should be required to consider available benefit-cost analyses and to justify the reasons for their decision in the event that the expected costs of a regulation far exceed the expected benefits. Agencies should be encouraged to use economic analysis to help set regulatory priorities. Economic analyses prepared in support of particularly important decisions should be subjected to peer review both inside and outside government. Benefits and costs of proposed major regulations should be quantified wherever possible. Best estimates should be presented along with a description of the uncertainties. Not all benefits or costs can be easily quantified, much less translated into dollar terms. Nevertheless, even qualitative descriptions of the pros and cons associated with a contemplated action can be helpful. Care should be taken to ensure that quantitative factors do not dominate important qualitative factors in decisionmaking. The Office of Management and Budget, or some other coordinating agency, should establish guidelines that agencies should follow in conducting benefit-cost analyses. Those guidelines should specify default values for the discount rate and certain types of benefits and costs, such as the value of a small reduction in mortality risk. In addition, agencies should present their results using a standard format, which summarizes the key results and highlights major uncertainties.