142 research outputs found
Branch-and-lift algorithm for deterministic global optimization in nonlinear optimal control
This paper presents a branch-and-lift algorithm for solving optimal control problems with smooth nonlinear dynamics and potentially nonconvex objective and constraint functionals to guaranteed global optimality. This algorithm features a direct sequential method and builds upon a generic, spatial branch-and-bound algorithm. A new operation, called lifting, is introduced, which refines the control parameterization via a Gram-Schmidt orthogonalization process, while simultaneously eliminating control subregions that are either infeasible or that provably cannot contain any global optima. Conditions are given under which the image of the control parameterization error in the state space contracts exponentially as the parameterization order is increased, thereby making the lifting operation efficient. A computational technique based on ellipsoidal calculus is also developed that satisfies these conditions. The practical applicability of branch-and-lift is illustrated in a numerical example. © 2013 Springer Science+Business Media New York
Hybrid optimization method with general switching strategy for parameter estimation
This article is available from: http://www.biomedcentral.com/1752-0509/2/26[Background] Modeling and simulation of cellular signaling and metabolic pathways as networks of
biochemical reactions yields sets of non-linear ordinary differential equations. These models usually
depend on several parameters and initial conditions. If these parameters are unknown, results from
simulation studies can be misleading. Such a scenario can be avoided by fitting the model to
experimental data before analyzing the system. This involves parameter estimation which is usually
performed by minimizing a cost function which quantifies the difference between model predictions
and measurements. Mathematically, this is formulated as a non-linear optimization problem which
often results to be multi-modal (non-convex), rendering local optimization methods detrimental.[Results] In this work we propose a new hybrid global method, based on the combination of an
evolutionary search strategy with a local multiple-shooting approach, which offers a reliable and
efficient alternative for the solution of large scale parameter estimation problems.[Conclusion] The presented new hybrid strategy offers two main advantages over previous
approaches: First, it is equipped with a switching strategy which allows the systematic
determination of the transition from the local to global search. This avoids computationally
expensive tests in advance. Second, using multiple-shooting as the local search procedure reduces
the multi-modality of the non-linear optimization problem significantly. Because multiple-shooting
avoids possible spurious solutions in the vicinity of the global optimum it often outperforms the
frequently used initial value approach (single-shooting). Thereby, the use of multiple-shooting yields
an enhanced robustness of the hybrid approach.This work was supported by the European Community as part of the FP6
COSBICS Project (STREP FP6-512060), the German Federal Ministry of
Education and Research, BMBF-project FRISYS (grant 0313921) and Xunta
de Galicia (PGIDIT05PXIC40201PM).Peer reviewe
Cytotoxic T-cell precursor frequencies to HER-2 (369 – 377) in patients with HER-2/neu-positive epithelial tumours
HER-2/neu oncoprotein contains several major histocompatibility complex class I-restricted epitopes, which are recognised by cytotoxic T lymphocyte (CTL) on autologous tumours and therefore can be used in immune-based cancer therapies. Of these, the most extensively studied is HER-2(9(369)). In the present report, we used dendritic cells pulsed with HER-2(9(369)) to stimulate, in the presence of IL-7 and IL-12, the production of IFN-gamma by patients' CTL detected by the enzyme-linked immunosorbent spot-assay. Frequencies of peptide-specific precursors were estimated in HLA-A2, HLA-A3 and HLA-A26 patients with HER-2/neu-positive (+) breast, ovarian, lung, colorectal and prostate cancers and healthy individuals. We found increased percentages of such precursors in HLA-A2 (25%) and HLA-A26 (30%) patients, which were significantly higher (60%) in HLA-A3 patients. Our results demonstrate for the first time that pre-existing immunity to HER-2(9(369)) occurs in patients with colorectal, lung and prostate cancer. They also suggest that HER-2(9(369)) can be recognised by CTL, besides HLA-A2, also in the context of HLA-A3 and HLA-A26, thus increasing the applicability of HER-2(9(369))-based vaccinations in a considerably broader patients' population.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe
Defining the Critical Hurdles in Cancer Immunotherapy
ABSTRACT: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators, others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet be overcome to improve outcomes of patients with cancer
Defining the critical hurdles in cancer immunotherapy
Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer
Unified framework for the propagation of continuous-time enclosures for parametric nonlinear ODEs
Feedback control algorithms for the dissipation of traffic waves with autonomous vehicles
International audienceThis article considers the problem of traffic control in which an autonomous vehicle is used to regulate human piloted traffic to dissipate stop and go traffic waves. We first investigate the controllability of well-known microscopic traffic flow models, namely i) the Bando model (also known as the optimal velocity model), ii) the follow-the-leader model, and iii) a combined optimal velocity follow the leader model. Based on the controllability results, we propose three control strategies for an autonomous vehicle to stabilize the other, human-piloted traffic. We subsequently simulate the control effects on the microscopic models of human drivers in numerical experiments to quantify the potential benefits of the controllers. Based on the simulations, finally we conduct a field experiment with 22 human drivers and a fully autonomous-capable vehicle, to assess the feasibility of autonomous vehicle based traffic control on real human piloted traffic. We show that both in simulation and in the field test that an autonomous vehicle is able to dampen waves generated by 22 cars, and that as a consequence, the total fuel consumption of all vehicles is reduced by up to 20%
A narrative review of health research capacity strengthening in low and middle-income countries: lessons for conflict-affected areas
Abstract Conducting health research in conflict-affected areas and other complex environments is difficult, yet vital. However, the capacity to undertake such research is often limited and with little translation into practice, particularly in poorer countries. There is therefore a need to strengthen health research capacity in conflict-affected countries and regions. In this narrative review, we draw together evidence from low and middle-income countries to highlight challenges to research capacity strengthening in conflict, as well as examples of good practice. We find that authorship trends in health research indicate global imbalances in research capacity, with implications for the type and priorities of research produced, equity within epistemic communities and the development of sustainable research capacity in low and middle-income countries. Yet, there is little evidence on what constitutes effective health research capacity strengthening in conflict-affected areas. There is more evidence on health research capacity strengthening in general, from which several key enablers emerge: adequate and sustained financing; effective stewardship and equitable research partnerships; mentorship of researchers of all levels; and effective linkages of research to policy and practice. Strengthening health research capacity in conflict-affected areas needs to occur at multiple levels to ensure sustainability and equity. Capacity strengthening interventions need to take into consideration the dynamics of conflict, power dynamics within research collaborations, the potential impact of technology, and the wider political environment in which they take place
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