An Implicit-Function Theorem for B-Differentiable Functions

A function from one normed linear space to another is said to be Bouligand differentiable (B-differentiable) at a point if it is directionally differentiable there in every direction, and if the directional derivative has a certain uniformity property. This is a weakening of the classical idea of Frechet (F-) differentiability, and it is useful in dealing with optimization problems and in other situations in which F-differentiability may be too strong. In this paper we introduce a concept of strong B-derivative, and we employ this idea to prove an implicit-function theorem for B-differentiable functions. This theorem provides the same kinds of information as does the classical implicit-function theorem, but with B-differentiability in place of F-differentiability. Therefore it is applicable to a considerably wider class of functions than is the classical theorem

Local Structure of Feasible Sets in Nonlinear Programming - Part II. Nondegeneracy

In this paper we examine the local structure of the feasible set of a nonlinear programming problem under the condition of nondegeneracy. We introduce this condition, examine its relationships to known properties of optimization problems, and show that when it holds at a given point the portion of the feasible set near that point is diffeomorphic to a simple convex set (often polyhedral). Moreover, this diffeomorphic relation is stable under small changes in the problem functions

Persistence and Continuity of Local Minimizers

A fundamental question in nonlinear optimization is that of how optimization problems behave when the functions defining them are changed (e.g., by continuous deformation). Many authors have contributed to our knowledge in this area. This paper presents a very simple and general approach to the continuity analysis of the marginal function and the set of minimizers of such a problem. Two abstract properties are identified as being crucial to good behavior of a problem, and these are then shown to ensure persistence and stability of local optimizers of general nonlinear optimization problems

Bundle-Based Decomposition: Conditions for Convergence

Bundle-based decomposition is a recently proposed method for decentralized convex optimization. Computational tests indicate that it is very fast. In this paper we exhibit conditions for convergence of the method. In the process we study conditions for linearly-constrained approximate minimization of a convex function

Sample-path solutions for simulation optimization problems and stochastic variational inequalities

inequality;simulation;optimization

Sample-Path Optimization in Simulation

This paper summarizes information about a method, called sample-path optimization, for optimizing performance functions in certain stochastic systems that can be modeled by simulation. We explain the method, give conditions under which it converges, and display some sample calculations that indicate how it performs. We also describe briefly some more extensive numerical experiments on large systems (PERT networks with up to 110 stochastic arcs, and tandem production lines with up to 50 machines). Details of these experiments are reported elsewhere; we give references to this and other related work. We conclude with some currently unanswered questions

First measurement of low intensity fast neutron background from rock at the Boulby Underground Laboratory

A technique to measure low intensity fast neutron flux has been developed. The design, calibrations, procedure for data analysis and interpretation of the results are discussed in detail. The technique has been applied to measure the neutron background from rock at the Boulby Underground Laboratory, a site used for dark matter and other experiments, requiring shielding from cosmic ray muons. The experiment was performed using a liquid scintillation detector. A 6.1 litre volume stainless steel cell was filled with an in-house made liquid scintillator loaded with Gd to enhance neutron capture. A two-pulse signature (proton recoils followed by gammas from neutron capture) was used to identify the neutron events from much larger gamma background from PMTs. Suppression of gammas from the rock was achieved by surrounding the detector with high-purity lead and copper. Calibrations of the detector were performed with various gamma and neutron sources. Special care was taken to eliminate PMT afterpulses and correlated background events from the delayed coincidences of two pulses in the Bi-Po decay chain. A four month run revealed a neutron-induced event rate of 1.84 +- 0.65 (stat.) events/day. Monte Carlo simulations based on the GEANT4 toolkit were carried out to estimate the efficiency of the detector and the energy spectra of the expected proton recoils. From comparison of the measured rate with Monte Carlo simulations the flux of fast neutrons from rock was estimated as (1.72 +- 0.61 (stat.) +- 0.38 (syst.))*10^(-6) cm^(-2) s^(-1) above 0.5 MeV.Comment: 37 pages, 24 figures, to be published in Astroparticle Physic

Update of the management strategy for Oak Ridge National Laboratory Liquid Low-Level Waste

The strategy for management of the Oak Ridge National Laboratory`s (ORNL) radioactively contaminated liquid waste was reviewed in 1991. The latest information available through the end of 1990 on waste characterization, regulations, US Department of Energy (DOE) budget guidance, and research and development programs was evaluated to determine how the strategy should be revised. Few changes are needed to update the strategy to reflect new waste characterization, research, and regulatory information. However, recent budget guidance from DOE indicates that minimum funding will not be sufficient to accomplish original objectives to upgrade the liquid low-level waste (LLLW) system to comply with the Federal Facilities Agreement, provide long-term LLLW treatment capability, and minimize environmental, safety, and health risks. Options are presented that might allow the ORNL LLLW system to continue operations temporarily, but they would significantly reduce its capabilities to handle emergency situations, provide treatment for new waste streams, and accommodate waste from the Environmental Restoration Program and from decontamination and decommissioning of surplus facilities. These options are also likely to increase worker radiation exposure, risk of environmental insult, and generation of solid waste for on-site and off-site disposal/storage beyond existing facility capacities. The strategy will be fully developed after receipt of additional guidance. The proposed budget limitations are too severe to allow ORNL to meet regulatory requirements or continue operations long term

Antiviral screening identifies adenosine analogs targeting the endogenous dsRNA Leishmania RNA virus 1 (LRV1) pathogenicity factor.

The endogenous double-stranded RNA (dsRNA) virus Leishmaniavirus (LRV1) has been implicated as a pathogenicity factor for leishmaniasis in rodent models and human disease, and associated with drug-treatment failures in Leishmania braziliensis and Leishmania guyanensis infections. Thus, methods targeting LRV1 could have therapeutic benefit. Here we screened a panel of antivirals for parasite and LRV1 inhibition, focusing on nucleoside analogs to capitalize on the highly active salvage pathways of Leishmania, which are purine auxotrophs. Applying a capsid flow cytometry assay, we identified two 2'-C-methyladenosine analogs showing selective inhibition of LRV1. Treatment resulted in loss of LRV1 with first-order kinetics, as expected for random virus segregation, and elimination within six cell doublings, consistent with a measured LRV1 copy number of about 15. Viral loss was specific to antiviral nucleoside treatment and not induced by growth inhibitors, in contrast to fungal dsRNA viruses. Comparisons of drug-treated LRV1 <sup>+</sup> and LRV1 <sup>-</sup> lines recapitulated LRV1-dependent pathology and parasite replication in mouse infections, and cytokine secretion in macrophage infections. Agents targeting Totiviridae have not been described previously, nor are there many examples of inhibitors acting against dsRNA viruses more generally. The compounds identified here provide a key proof-of-principle in support of further studies identifying efficacious antivirals for use in in vivo studies of LRV1-mediated virulence