Travelling on Graphs with Small Highway Dimension

We study the Travelling Salesperson (TSP) and the Steiner Tree problem (STP) in graphs of low highway dimension. This graph parameter was introduced by Abraham et al. [SODA 2010] as a model for transportation networks, on which TSP and STP naturally occur for various applications in logistics. It was previously shown [Feldmann et al. ICALP 2015] that these problems admit a quasi-polynomial time approximation scheme (QPTAS) on graphs of constant highway dimension. We demonstrate that a significant improvement is possible in the special case when the highway dimension is 1, for which we present a fully-polynomial time approximation scheme (FPTAS). We also prove that STP is weakly NP-hard for these restricted graphs. For TSP we show NP-hardness for graphs of highway dimension 6, which answers an open problem posed in [Feldmann et al. ICALP 2015]

Linking Proteomic and Transcriptional Data through the Interactome and Epigenome Reveals a Map of Oncogene-induced Signaling

Cellular signal transduction generally involves cascades of post-translational protein modifications that rapidly catalyze changes in protein-DNA interactions and gene expression. High-throughput measurements are improving our ability to study each of these stages individually, but do not capture the connections between them. Here we present an approach for building a network of physical links among these data that can be used to prioritize targets for pharmacological intervention. Our method recovers the critical missing links between proteomic and transcriptional data by relating changes in chromatin accessibility to changes in expression and then uses these links to connect proteomic and transcriptome data. We applied our approach to integrate epigenomic, phosphoproteomic and transcriptome changes induced by the variant III mutation of the epidermal growth factor receptor (EGFRvIII) in a cell line model of glioblastoma multiforme (GBM). To test the relevance of the network, we used small molecules to target highly connected nodes implicated by the network model that were not detected by the experimental data in isolation and we found that a large fraction of these agents alter cell viability. Among these are two compounds, ICG-001, targeting CREB binding protein (CREBBP), and PKF118–310, targeting β-catenin (CTNNB1), which have not been tested previously for effectiveness against GBM. At the level of transcriptional regulation, we used chromatin immunoprecipitation sequencing (ChIP-Seq) to experimentally determine the genome-wide binding locations of p300, a transcriptional co-regulator highly connected in the network. Analysis of p300 target genes suggested its role in tumorigenesis. We propose that this general method, in which experimental measurements are used as constraints for building regulatory networks from the interactome while taking into account noise and missing data, should be applicable to a wide range of high-throughput datasets.National Science Foundation (U.S.) (DB1-0821391)National Institutes of Health (U.S.) (Grant U54-CA112967)National Institutes of Health (U.S.) (Grant R01-GM089903)National Institutes of Health (U.S.) (P30-ES002109

Operational Research: methods and applications

This is the final version. Available on open access from Taylor & Francis via the DOI in this recordThroughout its history, Operational Research has evolved to include methods, models and algorithms that have been applied to a wide range of contexts. This encyclopedic article consists of two main sections: methods and applications. The first summarises the up-to-date knowledge and provides an overview of the state-of-the-art methods and key developments in the various subdomains of the field. The second offers a wide-ranging list of areas where Operational Research has been applied. The article is meant to be read in a nonlinear fashion and used as a point of reference by a diverse pool of readers: academics, researchers, students, and practitioners. The entries within the methods and applications sections are presented in alphabetical order. The authors dedicate this paper to the 2023 Turkey/Syria earthquake victims. We sincerely hope that advances in OR will play a role towards minimising the pain and suffering caused by this and future catastrophes

Quasiclassical trajectory calculations of hydrogen absorption in the (NaAlH4)2Ti system on a model analytical potential energy surface.

We performed a quasiclassical trajectory dynamics study on a model analytical 21-dimensional (7 active atoms) potential energy surface (PES) to examine in detail the mechanism of the hydrogen absorption in a simple (NaAlH(4))(2)Ti model system. The reaction involves a capture of H(2) by the Ti centre and formation of the (η(2)-H(2))Ti(NaAlH(3))(2) coordination complex containing the side-on bonded dihydrogen ligand. The calculated rate constant corresponds to a very fast capture of H(2) by the Ti coordination sphere without a demonstrable barrier. This implies that this step is not the rate-determining step in the complex multi-step process of the NaAlH(4) recovery. The model analytical PES captures the essence of this reaction well and the corresponding energy contours compare favourably to those based on the all-atom hybrid density functional theory calculations

Towards understanding a mechanism for reversible hydrogen storage: theoretical study of transition metal catalysed dehydrogenation of sodium alanate.

On the basis of density functional theory and coupled-cluster CCSD(T) calculations we propose a mechanism of the dehydrogenation of transition metal doped sodium alanate. Insertion of two early 3d-transition metals, scandium and titanium, both of which are promising catalysts for reversible hydrogen storage in light metal hydrides, is compared. The mechanism is deduced from studies on the decomposition of a model system consisting of one transition metal atom and two NaAlH(4) units. Subsequently, the significance of such minimal cluster model systems to the real materials is tested by embedding the systems into the surface of the NaAlH(4) crystal. It is found that the dehydrogenation proceeds via breaking of the bridge H-Al bond and consequent formation of intermediate coordination compounds in which the H(2) molecule is side-on (eta(2)-) bonded to the transition metal centre. The total barrier to the H(2) release is thus dependent upon both the strength of the Al-H bond to be broken and the depth of the coordinative potential. The analogous mechanism applies for the recognized three successive dehydrogenation steps. The gas-phase model structures embedded into the surface of the NaAlH(4) crystal exhibit an unambiguous kinetic stability and their general geometric features remain largely unchanged

Towards understanding a mechanism for reversible hydrogen storage: theoretical study of transition metal catalysed dehydrogenation of sodium alanate.

On the basis of density functional theory and coupled-cluster CCSD(T) calculations we propose a mechanism of the dehydrogenation of transition metal doped sodium alanate. Insertion of two early 3d-transition metals, scandium and titanium, both of which are promising catalysts for reversible hydrogen storage in light metal hydrides, is compared. The mechanism is deduced from studies on the decomposition of a model system consisting of one transition metal atom and two NaAlH(4) units. Subsequently, the significance of such minimal cluster model systems to the real materials is tested by embedding the systems into the surface of the NaAlH(4) crystal. It is found that the dehydrogenation proceeds via breaking of the bridge H-Al bond and consequent formation of intermediate coordination compounds in which the H(2) molecule is side-on (eta(2)-) bonded to the transition metal centre. The total barrier to the H(2) release is thus dependent upon both the strength of the Al-H bond to be broken and the depth of the coordinative potential. The analogous mechanism applies for the recognized three successive dehydrogenation steps. The gas-phase model structures embedded into the surface of the NaAlH(4) crystal exhibit an unambiguous kinetic stability and their general geometric features remain largely unchanged

Core-shell excitation of isoxazole at the C, N, and O K-edges - an experimental NEXAFS and theoretical TD-DFT study

The near-edge X-ray absorption fine structure (NEXAFS) spectra of the gas-phase isoxazole molecule have been measured by collecting total ion yields at the C, N, and O K-edges. The spectral structures have been interpreted using time-dependent density functional theory (TD-DFT) with the short-range corrected SRC2-BLYP exchange-correlation functional. Experimental and calculated energies of core excitations are generally in good agreement, and the nature of observed core-excitation transitions has been elucidated. The experimental C 1s, N 1s, and O 1s core electron binding energies (CEBEs) have additionally been estimated from another yield measurement where the neutral fragments in high-Rydberg (HR) states were ionized by the electric field. For comparison, theoretical CEBEs have been calculated at the ΔM06-2X//mixed basis set level. We have also calculated the vibrationally resolved spectra pertaining to the lowest C 1s and N 1s core-excited roots in the Franck-Condon-Herzberg-Teller (FCHT) approximation. These spectra correlate well with the observed spectral features and have proven useful in resolving certain ambiguities in the assignment of the low-lying C 1s NEXAFS bands