Perspective Cuts for the ACOPF with Generators

International audienceThe alternating current optimal power flow problem is a fundamental problem in the management of smart grids. In this paper we consider a variant which includes activation/deactivation of generators at some of the grid sites. We formulate the problem as a mathematical program, prove its NP-hardness w.r.t. ac-tivation/deactivation, and derive two perspective reformulations

Effect of Small-Molecule-Binding Affinity on Tumor Uptake In Vivo: A Systematic Study Using a Pretargeted Bispecific Antibody

Small-molecule ligands specific for tumor-associated surface receptors have wide applications in cancer diagnosis and therapy. Achieving high-affinity binding to the desired target is important for improving detection limits and for increasing therapeutic efficacy. However, the affinity required for maximal binding and retention remains unknown. Here, we present a systematic study of the effect of small-molecule affinity on tumor uptake in vivo with affinities spanning a range of three orders of magnitude. A pretargeted bispecific antibody with different binding affinities to different DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-based small molecules is used as a receptor proxy. In this particular system targeting carcinoembryonic antigen, a small-molecule–binding affinity of 400 pmol/L was sufficient to achieve maximal tumor targeting, and an improvement in affinity to 10 pmol/L showed no significant improvement in tumor uptake at 24 hours postinjection. We derive a simple mathematical model of tumor targeting using measurable parameters that correlates well with experimental observations. We use relations derived from the model to develop design criteria for the future development of small-molecule agents for targeted cancer therapeutics.National Science Foundation (U.S.). Graduate Research Fellowship ProgramNational Institutes of Health (U.S.) (Grant R01-CA-101830

Organic Alternatives to Quantum Dots for Intraoperative Near-Infrared Fluorescent Sentinel Lymph Node Mapping:

Intraoperative near-infrared (NIR) fluorescence imaging provides the surgeon with real-time image guidance during cancer and other surgeries. We have previously reported the use of NIR fluorescent quantum dots (QDs) for sentinel lymph node (SLN) mapping. However, because of concerns over potential toxicity, organic alternatives to QDs will be required for initial clinical studies. We describe a family of 800 nm organic heptamethine indocyanine-based contrast agents for SLN mapping spanning a spectrum from 775 Da small molecules to 7 MDa nanocolloids. We provide a detailed characterization of the optical and physical properties of these contrast agents and discuss the advantages and disadvantages of each. We present robust methods for the covalent conjugation, purification, and characterization of proteins with tetra-sulfonated heptamethine indocyanines, including mass spectroscopic site mapping of highly substituted molecules. One contrast agent, NIR fluorescent human serum albumin (HSA800), emerged as the molecule with the best overall performance with respect to entry to lymphatics, flow to the SLN, retention in the SLN, fluorescence yield and reproducibility. This preclinical study, performed on large animals approaching the size of humans, should serve as a foundation for future clinical studies. Mol Imaging (2005) 4, 172 – 181

Design Considerations for Tumor-Targeted Nanoparticles

Inorganic/organic hybrid nanoparticles are potentially useful in biomedicine, but to avoid non-specific background fluorescence and long-term toxicity, they need to be cleared from the body within a reasonable timescale1. Previously, we have shown that rigid spherical nanoparticles such as quantum dots can be cleared by the kidneys if they have a hydrodynamic diameter of approximately 5.5 nm and a zwitterionic surface charge2. Here, we show that quantum dots functionalized with high-affinity small-molecule ligands that target tumours can also be cleared by the kidneys if their hydrodynamic diameter is less than this value, which sets an upper limit of 5–10 ligands per quantum dot for renal clearance. Animal models of prostate cancer and melanoma show receptor-specific imaging and renal clearance within 4 h post-injection. This study suggests a set of design rules for the clinical translation of targeted nanoparticles that can be eliminated through the kidneys.National Science Foundation (U.S.) (NSF-0070319)National Institutes of Health (U.S.) (NIH GM68762)National Institutes of Health (U.S.) (NIH grant no. R33-EB-000673)National Institutes of Health (U.S.) ( NIH grant no. R01-CA-115296)National Institutes of Health (U.S.) (MIT-Harvard NanoMedical Consortium (1U54-CA119349, a Center of Cancer Nanotechnology Excellence))Bank of AmericaMedical Foundation, inc. (Charles A. King Trust Postdoctoral Research Fellowship Program)cance

Nonlinear Integer Programming

Research efforts of the past fifty years have led to a development of linear integer programming as a mature discipline of mathematical optimization. Such a level of maturity has not been reached when one considers nonlinear systems subject to integrality requirements for the variables. This chapter is dedicated to this topic. The primary goal is a study of a simple version of general nonlinear integer problems, where all constraints are still linear. Our focus is on the computational complexity of the problem, which varies significantly with the type of nonlinear objective function in combination with the underlying combinatorial structure. Numerous boundary cases of complexity emerge, which sometimes surprisingly lead even to polynomial time algorithms. We also cover recent successful approaches for more general classes of problems. Though no positive theoretical efficiency results are available, nor are they likely to ever be available, these seem to be the currently most successful and interesting approaches for solving practical problems. It is our belief that the study of algorithms motivated by theoretical considerations and those motivated by our desire to solve practical instances should and do inform one another. So it is with this viewpoint that we present the subject, and it is in this direction that we hope to spark further research.Comment: 57 pages. To appear in: M. J\"unger, T. Liebling, D. Naddef, G. Nemhauser, W. Pulleyblank, G. Reinelt, G. Rinaldi, and L. Wolsey (eds.), 50 Years of Integer Programming 1958--2008: The Early Years and State-of-the-Art Surveys, Springer-Verlag, 2009, ISBN 354068274

The relationship between redox enzyme activity and electrochemical potential—cellular and mechanistic implications from protein film electrochemistry

In protein film electrochemistry a redox protein of interest is studied as an electroactive film adsorbed on an electrode surface. For redox enzymes this configuration allows quantification of the relationship between catalytic activity and electrochemical potential. Considered as a function of enzyme environment, i.e., pH, substrate concentration etc., the activity–potential relationship provides a fingerprint of activity unique to a given enzyme. Here we consider the nature of the activity–potential relationship in terms of both its cellular impact and its origin in the structure and catalytic mechanism of the enzyme. We propose that the activity–potential relationship of a redox enzyme is tuned to facilitate cellular function and highlight opportunities to test this hypothesis through computational, structural, biochemical and cellular studies

Adipocyte-specific protein tyrosine phosphatase 1B deletion increases lipogenesis, adipocyte cell size and is a minor regulator of glucose homeostasis

Peer reviewedPublisher PD

Network Flows Heuristics for Complementary Cell Suppression: An Empirical Evaluation and Extensions

Several network flows heuristics have been suggested in the past for the solution of the complementary suppression problem. However, a limited computational experience using them is reported in the literature, and, moreover, they were only appropriate for two-dimensional tables. The purpose of this paper is twofold. First, we perform an em-pirical comparison of two network flows heuristics. They are improved versions of already existing approaches. Second, we show that exten-sions of network flows methods (i.e., multicommodity network flows and network flows with side constraints) can model three-dimensional, hierarchical and linked tables. Exploiting this network structure can improve the performance of any solution method solely based on linear programming formulations