Solving ill-posed bilevel programs

This paper deals with ill-posed bilevel programs, i.e., problems admitting multiple lower-level solutions for some upper-level parameters. Many publications have been devoted to the standard optimistic case of this problem, where the difficulty is essentially moved from the objective function to the feasible set. This new problem is simpler but there is no guaranty to obtain local optimal solutions for the original optimistic problem by this process. Considering the intrinsic non-convexity of bilevel programs, computing local optimal solutions is the best one can hope to get in most cases. To achieve this goal, we start by establishing an equivalence between the original optimistic problem an a certain set-valued optimization problem. Next, we develop optimality conditions for the latter problem and show that they generalize all the results currently known in the literature on optimistic bilevel optimization. Our approach is then extended to multiobjective bilevel optimization, and completely new results are derived for problems with vector-valued upper- and lower-level objective functions. Numerical implementations of the results of this paper are provided on some examples, in order to demonstrate how the original optimistic problem can be solved in practice, by means of a special set-valued optimization problem

Analysis of chronic rejection and obliterative arteriopathy: Possible contributions of donor antigen-presenting cells and lymphatic disruption

Sequential analysis of changes that lead to chronic rejection was undertaken in an animal model of chronic rejection and obliterative arteriopathy. Brown Norway rats are pretreated with a Lewis bone marrow infusion or a Lewis orthotopic liver allograft and a short course of immunosuppression. They are challenged 100 days later with a Lewis heterotopic heart graft without immunosuppression. The heart grafts in both groups undergo a transient acute rejection, but all rats are operationally tolerant; the heart grafts are accepted and remain beating for more than 100 days. Early arterial remodeling, marked by arterial bromodeoxyuridine incorporation, occurred in both groups between 5 and 30 days during the transient acute rejection. It coincided with the presence of interstitial (but not arterial intimal) inflammation and lymphatic disruption and resulted in mild intimal thickening. Significant arterial narrowing occurred only in the bone-marrow-pretreated rats between 60 and 100 days. It was associated with T lymphocyte and macrophage inflammation of the heart graft that accumulated in the endocardium and arterial intima and adventitia near draining lymphatics. There also was loss of passenger leukocytes from the heart graft, up-regulation of cytokine mRNA and major histocompatibility class II on the endothelium, and focal disruption of lymphatics. In contrast, long-surviving heart grafts from the Lewis orthotopic liver allograft pretreated group are near normal and freedom from chronic rejection in this group was associated with persistence of donor major histocompatibility class-II-positive hematolymphoid cells, including OX62+ donor dendritic cells. This study offers insights into two different aspects of chronic rejection: 1) possible mechanisms underlying the persistent immunological injury and 2) the association between immunological injury and the development of obliterative arteriopathy. Based on the findings, it is not unreasonable to raise the testable hypothesis that direct presentation of alloantigen by donor antigen-presenting cells is required for long-term, chronic-rejection-free allograft acceptance. In addition, chronic intermittent lymphatic disruption is implicated as a possible mechanism for the association between chronic interstitial allograft inflammation and the development of obliterative arteriopathy

Selective fluorescent probes for molecular imaging of ROS/RNS: Challenges and opportunities

Session-1: The Power of Technology - Key Note Speakerpublished_or_final_versio

Allometric equation for Raphia laurentii De Wild, the commonest palm in the central Congo peatlands

The world's largest tropical peatland lies in the central Congo Basin. Raphia laurentii De Wild, the most abundant palm in these peatlands, forms dominant to mono-dominant stands across approximately 45% of the peatland area. R. laurentii is a trunkless palm with fronds up to 20 m long. Owing to its morphology, there is currently no allometric equation which can be applied to R. laurentii. Therefore it is currently excluded from aboveground biomass (AGB) estimates for the Congo Basin peatlands. Here we develop allometric equations for R. laurentii, by destructively sampling 90 individuals in a peat swamp forest, in the Republic of the Congo. Prior to destructive sampling, stem base diameter, petiole mean diameter, the sum of petiole diameters, total palm height, and number of palm fronds were measured. After destructive sampling, each individual was separated into stem, sheath, petiole, rachis, and leaflet categories, then dried and weighed. We found that palm fronds represented at least 77% of the total AGB in R. laurentii and that the sum of petiole diameters was the best single predictor variable of AGB. The best overall allometric equation, however, combined the sum of petiole diameters (SDp), total palm height (H), and tissue density (TD): AGB = Exp(-2.691 + 1.425 × ln(SDp) + 0.695 × ln(H) + 0.395 × ln(TD)). We applied one of our allometric equations to data from two nearby 1-hectare forest plots, one dominated by R. laurentii, where R. laurentii accounted for 41% of the total forest AGB (with hardwood tree AGB estimated using the Chave et al. 2014 allometric equation), and one dominated by hardwood species, where R. laurentii accounted for 8% of total AGB. Across the entire region we estimate that R. laurentii stores around 2 million tonnes of carbon aboveground. The inclusion of R. laurentii in AGB estimates, will drastically improve overall AGB, and therefore carbon stock estimates for the Congo Basin peatlands

Minimizing the condition number of a Gram matrix

2010-2011 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Variable chimerism, graft - Versus - Host disease, and tolerance after different kinds of cell and whole organ transplantation from lewis to brown Norway rats

The bidirectional paradigm of tolerance involving reciprocal host vs. graft and graft vs. host reactions was examined after Lewis (LEW) → Brown Norway (BN) transplantation of different whole organs (liver, intestine, heart, and kidney) or of 2.5 × l08 LEW leukocytes obtained from bone marrow, spleen, lymph nodes, and thymus. The experiments were performed without immunosuppression or under 14 daily doses of postoperative tacrolimus, which were continued in weekly doses to 100 days in a “continuous treatment” subgroup, and to 27 days in a short treatment group. Without immunosuppression, all organs and cell suspensions failed to engraft or were acutely rejected.GVHD (usually fatal) was always caused when either the long or short treatment was used for recipients of intestinal grafts and cell suspensions of spleen and lymph nodes. In contrast, both immunosuppressive protocols allowed engraftment of bone marrow cells, liver, heart, and kidney without clinical GVHD, whereas thymus cell suspensions and small doses of whole blood neither engrafted nor caused GVHD. At 100 days, now drug-free for 73 days, the liver, bone marrow, and heart recipients were tolerant in that they accepted all challenge LEW heart and/or liver grafts for 100 more days despite in vitro evidence of donor-specific reactivity (split tolerance). At 200 days, histopathologic studies of the challenge livers were normal no matter what the priming graft. However, the still-beating challenge hearts had a spectrum from normal to severe chronic rejection that defined the tolerogenicity of the original primary grafts: liver best → bone marrow next → heart least. Both the GVHD propensity and tolerogenicity in these experiments were closely associated with recipient tissue chimer-ism 30 and 100 days after the experiments began. The tissue chimerism was invariably multilineage, but the GVHD outcome was associated with T cell over-repre-sentation. These observations provide guidelines that should be considered in devising leukocyte augmentation protocols for human whole organ recipients. The results are discussed in relation to the historical tolerance studies of Billingham, Brent, and Medawar; Good; Monaco; and Caine. © 1995 by Williams and Wilkins

Classification of time series by shapelet transformation

Time-series classification (TSC) problems present a specific challenge for classification algorithms: how to measure similarity between series. A \emph{shapelet} is a time-series subsequence that allows for TSC based on local, phase-independent similarity in shape. Shapelet-based classification uses the similarity between a shapelet and a series as a discriminatory feature. One benefit of the shapelet approach is that shapelets are comprehensible, and can offer insight into the problem domain. The original shapelet-based classifier embeds the shapelet-discovery algorithm in a decision tree, and uses information gain to assess the quality of candidates, finding a new shapelet at each node of the tree through an enumerative search. Subsequent research has focused mainly on techniques to speed up the search. We examine how best to use the shapelet primitive to construct classifiers. We propose a single-scan shapelet algorithm that finds the best $k$ shapelets, which are used to produce a transformed dataset, where each of the $k$ features represent the distance between a time series and a shapelet. The primary advantages over the embedded approach are that the transformed data can be used in conjunction with any classifier, and that there is no recursive search for shapelets. We demonstrate that the transformed data, in conjunction with more complex classifiers, gives greater accuracy than the embedded shapelet tree. We also evaluate three similarity measures that produce equivalent results to information gain in less time. Finally, we show that by conducting post-transform clustering of shapelets, we can enhance the interpretability of the transformed data. We conduct our experiments on 29 datasets: 17 from the UCR repository, and 12 we provide ourselve

Paradoxical roles of antioxidant enzymes:Basic mechanisms and health implications

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated from aerobic metabolism, as a result of accidental electron leakage as well as regulated enzymatic processes. Because ROS/RNS can induce oxidative injury and act in redox signaling, enzymes metabolizing them will inherently promote either health or disease, depending on the physiological context. It is thus misleading to consider conventionally called antioxidant enzymes to be largely, if not exclusively, health protective. Because such a notion is nonetheless common, we herein attempt to rationalize why this simplistic view should be avoided. First we give an updated summary of physiological phenotypes triggered in mouse models of overexpression or knockout of major antioxidant enzymes. Subsequently, we focus on a series of striking cases that demonstrate “paradoxical” outcomes, i.e., increased fitness upon deletion of antioxidant enzymes or disease triggered by their overexpression. We elaborate mechanisms by which these phenotypes are mediated via chemical, biological, and metabolic interactions of the antioxidant enzymes with their substrates, downstream events, and cellular context. Furthermore, we propose that novel treatments of antioxidant enzyme-related human diseases may be enabled by deliberate targeting of dual roles of the pertaining enzymes. We also discuss the potential of “antioxidant” nutrients and phytochemicals, via regulating the expression or function of antioxidant enzymes, in preventing, treating, or aggravating chronic diseases. We conclude that “paradoxical” roles of antioxidant enzymes in physiology, health, and disease derive from sophisticated molecular mechanisms of redox biology and metabolic homeostasis. Simply viewing antioxidant enzymes as always being beneficial is not only conceptually misleading but also clinically hazardous if such notions underpin medical treatment protocols based on modulation of redox pathways