Provably good solutions for the traveling salesman problem

The determination of true optimum solutions of combinatorial optimization problems is seldomly required in practical applications. The majority of users of optimization software would be satisfied with solutions of guaranteed quality in the sense that it can be proven that the given solution is at most a few percent off an optimum solution. This paper presents a general framework for practical problem solving with emphasis on this aspect. A detailed discussion along with a report about extensive computational experiments is given for the traveling salesman problem

Only Connect: How an Investment in Relationships Among Social Change Leaders Is Changing Them, Their Organizations, and Their City

· After years of leading social-sector organizations in an environment where competition is more the norm than collaboration, many gifted leaders are near burnout, unable to maximize their gifts. Since 2005, the Barr Fellowship has been changing that in Boston. · This network of leaders, created by the Barr Foundation, is based on the hypothesis that recognizing talented leaders and investing in their personal growth and connections with one another will result in individual, collective, and city transformation. · A longtime funder of networks, Barr designed the fellowship as a “connectivity” network, where collective actions and shared agendas might emerge but would not be imposed. In this way, the fellowship exemplifies what has been described as “ambidextrous philanthropy” – rooted in strategy yet also in values; focused on outcomes, yet also responsive. · This article describes the theory of change; strategy; evaluation methodology (including network mapping); results – for Barr Fellows, their organizations, and Boston; and how the program fits within an approach to philanthropy that embraces the long view. It discusses implications for funders interested in supporting connectivity networks

Analyzing the regulation of metabolic pathways in human breast cancer

<p>Abstract</p> <p>Background</p> <p>Tumor therapy mainly attacks the metabolism to interfere the tumor's anabolism and signaling of proliferative second messengers. However, the metabolic demands of different cancers are very heterogeneous and depend on their origin of tissue, age, gender and other clinical parameters. We investigated tumor specific regulation in the metabolism of breast cancer.</p> <p>Methods</p> <p>For this, we mapped gene expression data from microarrays onto the corresponding enzymes and their metabolic reaction network. We used Haar Wavelet transforms on optimally arranged grid representations of metabolic pathways as a pattern recognition method to detect orchestrated regulation of neighboring enzymes in the network. Significant combined expression patterns were used to select metabolic pathways showing shifted regulation of the aggressive tumors.</p> <p>Results</p> <p>Besides up-regulation for energy production and nucleotide anabolism, we found an interesting cellular switch in the interplay of biosynthesis of steroids and bile acids. The biosynthesis of steroids was up-regulated for estrogen synthesis which is needed for proliferative signaling in breast cancer. In turn, the decomposition of steroid precursors was blocked by down-regulation of the bile acid pathway.</p> <p>Conclusion</p> <p>We applied an intelligent pattern recognition method for analyzing the regulation of metabolism and elucidated substantial regulation of human breast cancer at the interplay of cholesterol biosynthesis and bile acid metabolism pointing to specific breast cancer treatment.</p

Cortical thickness and resting-state cardiac function across the lifespan: a cross-sectional pooled mega analysis

Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS – or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between cortical thickness and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research

Provably good solutions for the traveling salesman problem

The determination of true optimum solutions of combinatorial optimization problems is seldomly required in practical applications. The majority of users of optimization software would be satisfied with solutions of guaranteed quality in the sense that it can be proven that the given solution is at most a few percent off an optimum solution. This paper presents a general framework for practical problem solving with emphasis on this aspect. A detailed discussion along with a report about extensive computational experiments is given for the traveling salesman problem. Recent research in algorithm design for hard combinatorial optimization problems follows two trends. One aims at a continuously better understanding of structural properties of a given problem in the pursuit of solving larger instances to optimality. For a few prominent hard combinatorial optimization problems such as the traveling salesman problem (TSP), the linear ordering problem or the max-cut problem, branch &amp; cut alg..

Provably good solutions for the traveling salesman problem

The determination of true optimum solutions of combinatorial optimization problems is seldomly required in practical applications. The majority of users of optimization software would be satisfied with solutions of guaranteed quality in the sense that it can be proven that the given solution is at most a few percent off an optimum solution. This paper presents a general framework for practical problem solving with emphasis on this aspect. A detailed discussion along with a report about extensive computational experiments is given for the traveling salesman problem

Practical Problem Solving with Cutting Plane Algorithms in Combinatorial Optimization

Cutting plane algorithms have turned out to be practically successful computational tools in combinatorial optimization, in particular, when they are embedded in a branch and bound framework. Implementations of such &quot;branch and cut&quot; algorithms are rather complicated in comparison to many purely combinatorial algorithms. The purpose of this article is to give an introduction to cutting plane algorithms from an implementor&apos;s point of view. Special emphasis is given to control and data structures used in practically successful implementations of branch and cut algorithms. We also address the issue of parallelization. Finally, we point out that in important applications branch and cut algorithms are not only able to produce optimal solutions but also approximations to the optimum with certified good quality in moderate computation times. We close with an overview of successful practical applications in the literature

Provably Good Solutions for the Traveling Salesman Problem

The determination of true optimum solutions of combinatorial optimization problems is seldomly required in practical applications. The majority of users of optimization software would be satisfied with solutions of guaranteed quality in the sense that it can be proven that the given solution is at most a few percent off an optimum solution. This paper presents a general framework for practical problem solving with emphasis on this aspect. A detailed discussion along with a report about extensive computational experiments is given for the traveling salesman problem

Synergistic Use of Virtual Screening and Biophysical Methods for the Protein-Based Design of Peptidomimetics

Combining virtual screening with biophysical studies of protein-ligand complexes is an effective tool for designing new peptidomimetics. When a three-dimensional structure of the target protein is known, automated docking of chemical databases can be used as a powerful filter to reduce the number of molecules that will be further tested. Easy screening of potential hits can then be performed using fluorescence polarization techniques, if a fluorescent-labeled ligand already exists for the target. In addition, thermodynamic properties of protein-ligand complexes can be measured by circular dichroism spectroscopy