WorldWideScience

Sample records for graphing current drug

  1. SemaTyP: a knowledge graph based literature mining method for drug discovery.

    Science.gov (United States)

    Sang, Shengtian; Yang, Zhihao; Wang, Lei; Liu, Xiaoxia; Lin, Hongfei; Wang, Jian

    2018-05-30

    Drug discovery is the process through which potential new medicines are identified. High-throughput screening and computer-aided drug discovery/design are the two main drug discovery methods for now, which have successfully discovered a series of drugs. However, development of new drugs is still an extremely time-consuming and expensive process. Biomedical literature contains important clues for the identification of potential treatments. It could support experts in biomedicine on their way towards new discoveries. Here, we propose a biomedical knowledge graph-based drug discovery method called SemaTyP, which discovers candidate drugs for diseases by mining published biomedical literature. We first construct a biomedical knowledge graph with the relations extracted from biomedical abstracts, then a logistic regression model is trained by learning the semantic types of paths of known drug therapies' existing in the biomedical knowledge graph, finally the learned model is used to discover drug therapies for new diseases. The experimental results show that our method could not only effectively discover new drug therapies for new diseases, but also could provide the potential mechanism of action of the candidate drugs. In this paper we propose a novel knowledge graph based literature mining method for drug discovery. It could be a supplementary method for current drug discovery methods.

  2. Drug-Target Interaction Prediction with Graph Regularized Matrix Factorization.

    Science.gov (United States)

    Ezzat, Ali; Zhao, Peilin; Wu, Min; Li, Xiao-Li; Kwoh, Chee-Keong

    2017-01-01

    Experimental determination of drug-target interactions is expensive and time-consuming. Therefore, there is a continuous demand for more accurate predictions of interactions using computational techniques. Algorithms have been devised to infer novel interactions on a global scale where the input to these algorithms is a drug-target network (i.e., a bipartite graph where edges connect pairs of drugs and targets that are known to interact). However, these algorithms had difficulty predicting interactions involving new drugs or targets for which there are no known interactions (i.e., "orphan" nodes in the network). Since data usually lie on or near to low-dimensional non-linear manifolds, we propose two matrix factorization methods that use graph regularization in order to learn such manifolds. In addition, considering that many of the non-occurring edges in the network are actually unknown or missing cases, we developed a preprocessing step to enhance predictions in the "new drug" and "new target" cases by adding edges with intermediate interaction likelihood scores. In our cross validation experiments, our methods achieved better results than three other state-of-the-art methods in most cases. Finally, we simulated some "new drug" and "new target" cases and found that GRMF predicted the left-out interactions reasonably well.

  3. Drug Establishments Current Registration Site

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Drug Establishments Current Registration Site (DECRS) is a database of current information submitted by drug firms to register establishments (facilities) which...

  4. Current obesity drug treatment

    Directory of Open Access Journals (Sweden)

    Marcio C. Mancini

    2006-03-01

    Full Text Available Pharmacological treatment of obesity is an area of sudden changes,development of new drugs and treatment propositions. This articlepresents information on physiological agents that are currentlybeing used as well as drugs that were widely used but are nomore available.

  5. Antiretroviral therapy: current drugs.

    Science.gov (United States)

    Pau, Alice K; George, Jomy M

    2014-09-01

    The rapid advances in drug discovery and the development of antiretroviral therapy is unprecedented in the history of modern medicine. The administration of chronic combination antiretroviral therapy targeting different stages of the human immunodeficiency virus' replicative life cycle allows for durable and maximal suppression of plasma viremia. This suppression has resulted in dramatic improvement of patient survival. This article reviews the history of antiretroviral drug development and discusses the clinical pharmacology, efficacy, and toxicities of the antiretroviral agents most commonly used in clinical practice to date. Published by Elsevier Inc.

  6. Biosimilar drugs: Current status.

    Science.gov (United States)

    Kumar, Rajiv; Singh, Jagjit

    2014-07-01

    Biologic products are being developed over the past three decades. The expiry of patent protection for many biological medicines has led to the development of biosimilars in UK or follow on biologics in USA. This article reviews the literature on biosimilar drugs that covers the therapeutic status and regulatory guidelines. Appraisal of published articles from peer reviewed journals for English language publications, search from PubMed, and guidelines from European Medicines Agency, US Food Drug Administration (FDA) and India were used to identify data for review. Literature suggest that biosimilars are similar biological products, i.e., comparable but not identical to the reference product, are not generic version of innovator product and do not ensure therapeutic equivalence. Biosimilars present more challenges than conventional generics and marketing approval is also more complicated. To improve access, US Congress passed the Biologics Price Competition and Innovation act 2009 and US FDA allowed "abbreviated pathway" for their approval. U.S law has defined new standards and terms and EMA scientific guidelines have also set detailed approval standards. India being one of the most preferred manufacturing destinations of biosimilars, there is a need for stringent safety and regulatory guidelines. The New India Guidelines "Draft Guidelines on Similar Biologics were announced in June 2012, by Department of Biotechnology at Boston bio and available online.

  7. Novel Methods for Drug-Target Interaction Prediction using Graph Mining

    KAUST Repository

    Ba Alawi, Wail

    2016-01-01

    -target interactions (DTIs) before any experiments are done. However, many of these approaches suffer from unacceptable levels of false positives. We developed two novel methods based on graph mining networks of drugs and targets. The first method (DASPfind) finds all

  8. [A retrieval method of drug molecules based on graph collapsing].

    Science.gov (United States)

    Qu, J W; Lv, X Q; Liu, Z M; Liao, Y; Sun, P H; Wang, B; Tang, Z

    2018-04-18

    To establish a compact and efficient hypergraph representation and a graph-similarity-based retrieval method of molecules to achieve effective and efficient medicine information retrieval. Chemical structural formula (CSF) was a primary search target as a unique and precise identifier for each compound at the molecular level in the research field of medicine information retrieval. To retrieve medicine information effectively and efficiently, a complete workflow of the graph-based CSF retrieval system was introduced. This system accepted the photos taken from smartphones and the sketches drawn on tablet personal computers as CSF inputs, and formalized the CSFs with the corresponding graphs. Then this paper proposed a compact and efficient hypergraph representation for molecules on the basis of analyzing factors that directly affected the efficiency of graph matching. According to the characteristics of CSFs, a hierarchical collapsing method combining graph isomorphism and frequent subgraph mining was adopted. There was yet a fundamental challenge, subgraph overlapping during the collapsing procedure, which hindered the method from establishing the correct compact hypergraph of an original CSF graph. Therefore, a graph-isomorphism-based algorithm was proposed to select dominant acyclic subgraphs on the basis of overlapping analysis. Finally, the spatial similarity among graphical CSFs was evaluated by multi-dimensional measures of similarity. To evaluate the performance of the proposed method, the proposed system was firstly compared with Wikipedia Chemical Structure Explorer (WCSE), the state-of-the-art system that allowed CSF similarity searching within Wikipedia molecules dataset, on retrieval accuracy. The system achieved higher values on mean average precision, discounted cumulative gain, rank-biased precision, and expected reciprocal rank than WCSE from the top-2 to the top-10 retrieved results. Specifically, the system achieved 10%, 1.41, 6.42%, and 1

  9. Novel Methods for Drug-Target Interaction Prediction using Graph Mining

    KAUST Repository

    Ba Alawi, Wail

    2016-08-31

    The problem of developing drugs that can be used to cure diseases is important and requires a careful approach. Since pursuing the wrong candidate drug for a particular disease could be very costly in terms of time and money, there is a strong interest in minimizing such risks. Drug repositioning has become a hot topic of research, as it helps reduce these risks significantly at the early stages of drug development by reusing an approved drug for the treatment of a different disease. Still, finding new usage for a drug is non-trivial, as it is necessary to find out strong supporting evidence that the proposed new uses of drugs are plausible. Many computational approaches were developed to narrow the list of possible candidate drug-target interactions (DTIs) before any experiments are done. However, many of these approaches suffer from unacceptable levels of false positives. We developed two novel methods based on graph mining networks of drugs and targets. The first method (DASPfind) finds all non-cyclic paths that connect a drug and a target, and using a function that we define, calculates a score from all the paths. This score describes our confidence that DTI is correct. We show that DASPfind significantly outperforms other state-of-the-art methods in predicting the top ranked target for each drug. We demonstrate the utility of DASPfind by predicting 15 novel DTIs over a set of ion channel proteins, and confirming 12 out of these 15 DTIs through experimental evidence reported in literature and online drug databases. The second method (DASPfind+) modifies DASPfind in order to increase the confidence and reliability of the resultant predictions. Based on the structure of the drug-target interaction (DTI) networks, we introduced an optimization scheme that incrementally alters the network structure locally for each drug to achieve more robust top 1 ranked predictions. Moreover, we explored effects of several similarity measures between the targets on the prediction

  10. Large-scale structural and textual similarity-based mining of knowledge graph to predict drug-drug interactions

    KAUST Repository

    Abdelaziz, Ibrahim; Fokoue, Achille; Hassanzadeh, Oktie; Zhang, Ping; Sadoghi, Mohammad

    2017-01-01

    Drug-Drug Interactions (DDIs) are a major cause of preventable Adverse Drug Reactions (ADRs), causing a significant burden on the patients’ health and the healthcare system. It is widely known that clinical studies cannot sufficiently and accurately identify DDIs for new drugs before they are made available on the market. In addition, existing public and proprietary sources of DDI information are known to be incomplete and/or inaccurate and so not reliable. As a result, there is an emerging body of research on in-silico prediction of drug-drug interactions. In this paper, we present Tiresias, a large-scale similarity-based framework that predicts DDIs through link prediction. Tiresias takes in various sources of drug-related data and knowledge as inputs, and provides DDI predictions as outputs. The process starts with semantic integration of the input data that results in a knowledge graph describing drug attributes and relationships with various related entities such as enzymes, chemical structures, and pathways. The knowledge graph is then used to compute several similarity measures between all the drugs in a scalable and distributed framework. In particular, Tiresias utilizes two classes of features in a knowledge graph: local and global features. Local features are derived from the information directly associated to each drug (i.e., one hop away) while global features are learnt by minimizing a global loss function that considers the complete structure of the knowledge graph. The resulting similarity metrics are used to build features for a large-scale logistic regression model to predict potential DDIs. We highlight the novelty of our proposed Tiresias and perform thorough evaluation of the quality of the predictions. The results show the effectiveness of Tiresias in both predicting new interactions among existing drugs as well as newly developed drugs.

  11. Large-scale structural and textual similarity-based mining of knowledge graph to predict drug-drug interactions

    KAUST Repository

    Abdelaziz, Ibrahim

    2017-06-12

    Drug-Drug Interactions (DDIs) are a major cause of preventable Adverse Drug Reactions (ADRs), causing a significant burden on the patients’ health and the healthcare system. It is widely known that clinical studies cannot sufficiently and accurately identify DDIs for new drugs before they are made available on the market. In addition, existing public and proprietary sources of DDI information are known to be incomplete and/or inaccurate and so not reliable. As a result, there is an emerging body of research on in-silico prediction of drug-drug interactions. In this paper, we present Tiresias, a large-scale similarity-based framework that predicts DDIs through link prediction. Tiresias takes in various sources of drug-related data and knowledge as inputs, and provides DDI predictions as outputs. The process starts with semantic integration of the input data that results in a knowledge graph describing drug attributes and relationships with various related entities such as enzymes, chemical structures, and pathways. The knowledge graph is then used to compute several similarity measures between all the drugs in a scalable and distributed framework. In particular, Tiresias utilizes two classes of features in a knowledge graph: local and global features. Local features are derived from the information directly associated to each drug (i.e., one hop away) while global features are learnt by minimizing a global loss function that considers the complete structure of the knowledge graph. The resulting similarity metrics are used to build features for a large-scale logistic regression model to predict potential DDIs. We highlight the novelty of our proposed Tiresias and perform thorough evaluation of the quality of the predictions. The results show the effectiveness of Tiresias in both predicting new interactions among existing drugs as well as newly developed drugs.

  12. A graph theoretical perspective of a drug abuse epidemic model

    Science.gov (United States)

    Nyabadza, F.; Mukwembi, S.; Rodrigues, B. G.

    2011-05-01

    A drug use epidemic can be represented by a finite number of states and transition rules that govern the dynamics of drug use in each discrete time step. This paper investigates the spread of drug use in a community where some users are in treatment and others are not in treatment, citing South Africa as an example. In our analysis, we consider the neighbourhood prevalence of each individual, i.e., the proportion of the individual’s drug user contacts who are not in treatment amongst all of his or her contacts. We introduce parameters α∗, β∗ and γ∗, depending on the neighbourhood prevalence, which govern the spread of drug use. We examine how changes in α∗, β∗ and γ∗ affect the system dynamics. Simulations presented support the theoretical results.

  13. Brain Graph Topology Changes Associated with Anti-Epileptic Drug Use

    Science.gov (United States)

    Levin, Harvey S.; Chiang, Sharon

    2015-01-01

    Abstract Neuroimaging studies of functional connectivity using graph theory have furthered our understanding of the network structure in temporal lobe epilepsy (TLE). Brain network effects of anti-epileptic drugs could influence such studies, but have not been systematically studied. Resting-state functional MRI was analyzed in 25 patients with TLE using graph theory analysis. Patients were divided into two groups based on anti-epileptic medication use: those taking carbamazepine/oxcarbazepine (CBZ/OXC) (n=9) and those not taking CBZ/OXC (n=16) as a part of their medication regimen. The following graph topology metrics were analyzed: global efficiency, betweenness centrality (BC), clustering coefficient, and small-world index. Multiple linear regression was used to examine the association of CBZ/OXC with graph topology. The two groups did not differ from each other based on epilepsy characteristics. Use of CBZ/OXC was associated with a lower BC. Longer epilepsy duration was also associated with a lower BC. These findings can inform graph theory-based studies in patients with TLE. The changes observed are discussed in relation to the anti-epileptic mechanism of action and adverse effects of CBZ/OXC. PMID:25492633

  14. Adaptive Graph Convolutional Neural Networks

    OpenAIRE

    Li, Ruoyu; Wang, Sheng; Zhu, Feiyun; Huang, Junzhou

    2018-01-01

    Graph Convolutional Neural Networks (Graph CNNs) are generalizations of classical CNNs to handle graph data such as molecular data, point could and social networks. Current filters in graph CNNs are built for fixed and shared graph structure. However, for most real data, the graph structures varies in both size and connectivity. The paper proposes a generalized and flexible graph CNN taking data of arbitrary graph structure as input. In that way a task-driven adaptive graph is learned for eac...

  15. Graph theory enables drug repurposing--how a mathematical model can drive the discovery of hidden mechanisms of action.

    Directory of Open Access Journals (Sweden)

    Ruggero Gramatica

    Full Text Available We introduce a methodology to efficiently exploit natural-language expressed biomedical knowledge for repurposing existing drugs towards diseases for which they were not initially intended. Leveraging on developments in Computational Linguistics and Graph Theory, a methodology is defined to build a graph representation of knowledge, which is automatically analysed to discover hidden relations between any drug and any disease: these relations are specific paths among the biomedical entities of the graph, representing possible Modes of Action for any given pharmacological compound. We propose a measure for the likeliness of these paths based on a stochastic process on the graph. This measure depends on the abundance of indirect paths between a peptide and a disease, rather than solely on the strength of the shortest path connecting them. We provide real-world examples, showing how the method successfully retrieves known pathophysiological Mode of Action and finds new ones by meaningfully selecting and aggregating contributions from known bio-molecular interactions. Applications of this methodology are presented, and prove the efficacy of the method for selecting drugs as treatment options for rare diseases.

  16. Graph theory enables drug repurposing--how a mathematical model can drive the discovery of hidden mechanisms of action.

    Science.gov (United States)

    Gramatica, Ruggero; Di Matteo, T; Giorgetti, Stefano; Barbiani, Massimo; Bevec, Dorian; Aste, Tomaso

    2014-01-01

    We introduce a methodology to efficiently exploit natural-language expressed biomedical knowledge for repurposing existing drugs towards diseases for which they were not initially intended. Leveraging on developments in Computational Linguistics and Graph Theory, a methodology is defined to build a graph representation of knowledge, which is automatically analysed to discover hidden relations between any drug and any disease: these relations are specific paths among the biomedical entities of the graph, representing possible Modes of Action for any given pharmacological compound. We propose a measure for the likeliness of these paths based on a stochastic process on the graph. This measure depends on the abundance of indirect paths between a peptide and a disease, rather than solely on the strength of the shortest path connecting them. We provide real-world examples, showing how the method successfully retrieves known pathophysiological Mode of Action and finds new ones by meaningfully selecting and aggregating contributions from known bio-molecular interactions. Applications of this methodology are presented, and prove the efficacy of the method for selecting drugs as treatment options for rare diseases.

  17. A graph rewriting programming language for graph drawing

    OpenAIRE

    Rodgers, Peter

    1998-01-01

    This paper describes Grrr, a prototype visual graph drawing tool. Previously there were no visual languages for programming graph drawing algorithms despite the inherently visual nature of the process. The languages which gave a diagrammatic view of graphs were not computationally complete and so could not be used to implement complex graph drawing algorithms. Hence current graph drawing tools are all text based. Recent developments in graph rewriting systems have produced computationally com...

  18. Graph Aggregation

    NARCIS (Netherlands)

    Endriss, U.; Grandi, U.

    Graph aggregation is the process of computing a single output graph that constitutes a good compromise between several input graphs, each provided by a different source. One needs to perform graph aggregation in a wide variety of situations, e.g., when applying a voting rule (graphs as preference

  19. Transcranial direct current stimulation generates a transient increase of small-world in brain connectivity: an EEG graph theoretical analysis.

    Science.gov (United States)

    Vecchio, Fabrizio; Di Iorio, Riccardo; Miraglia, Francesca; Granata, Giuseppe; Romanello, Roberto; Bramanti, Placido; Rossini, Paolo Maria

    2018-04-01

    Transcranial direct current stimulation (tDCS) is a non-invasive technique able to modulate cortical excitability in a polarity-dependent way. At present, only few studies investigated the effects of tDCS on the modulation of functional connectivity between remote cortical areas. The aim of this study was to investigate-through graph theory analysis-how bipolar tDCS modulate cortical networks high-density EEG recordings were acquired before and after bipolar cathodal, anodal and sham tDCS involving the primary motor and pre-motor cortices of the dominant hemispherein 14 healthy subjects. Results showed that, after bipolar anodal tDCS stimulation, brain networks presented a less evident "small world" organization with a global tendency to be more random in its functional connections with respect to prestimulus condition in both hemispheres. Results suggest that tDCS globally modulates the cortical connectivity of the brain, modifying the underlying functional organization of the stimulated networks, which might be related to changes in synaptic efficiency of the motor network and related brain areas. This study demonstrated that graph analysis approach to EEG recordings is able to intercept changes in cortical functions mediated by bipolar anodal tDCS mainly involving the dominant M1 and related motor areas. Concluding, tDCS could be an useful technique to help understanding brain rhythms and their topographic functional organization and specificity.

  20. Drug repositioning for non-small cell lung cancer by using machine learning algorithms and topological graph theory.

    Science.gov (United States)

    Huang, Chien-Hung; Chang, Peter Mu-Hsin; Hsu, Chia-Wei; Huang, Chi-Ying F; Ng, Ka-Lok

    2016-01-11

    Non-small cell lung cancer (NSCLC) is one of the leading causes of death globally, and research into NSCLC has been accumulating steadily over several years. Drug repositioning is the current trend in the pharmaceutical industry for identifying potential new uses for existing drugs and accelerating the development process of drugs, as well as reducing side effects. This work integrates two approaches--machine learning algorithms and topological parameter-based classification--to develop a novel pipeline of drug repositioning to analyze four lung cancer microarray datasets, enriched biological processes, potential therapeutic drugs and targeted genes for NSCLC treatments. A total of 7 (8) and 11 (12) promising drugs (targeted genes) were discovered for treating early- and late-stage NSCLC, respectively. The effectiveness of these drugs is supported by the literature, experimentally determined in-vitro IC50 and clinical trials. This work provides better drug prediction accuracy than competitive research according to IC50 measurements. With the novel pipeline of drug repositioning, the discovery of enriched pathways and potential drugs related to NSCLC can provide insight into the key regulators of tumorigenesis and the treatment of NSCLC. Based on the verified effectiveness of the targeted drugs predicted by this pipeline, we suggest that our drug-finding pipeline is effective for repositioning drugs.

  1. Graphs & digraphs

    CERN Document Server

    Chartrand, Gary; Zhang, Ping

    2010-01-01

    Gary Chartrand has influenced the world of Graph Theory for almost half a century. He has supervised more than a score of Ph.D. dissertations and written several books on the subject. The most widely known of these texts, Graphs and Digraphs, … has much to recommend it, with clear exposition, and numerous challenging examples [that] make it an ideal textbook for the advanced undergraduate or beginning graduate course. The authors have updated their notation to reflect the current practice in this still-growing area of study. By the authors' estimation, the 5th edition is approximately 50% longer than the 4th edition. … the legendary Frank Harary, author of the second graph theory text ever produced, is one of the figures profiled. His book was the standard in the discipline for several decades. Chartrand, Lesniak and Zhang have produced a worthy successor.-John T. Saccoman, MAA Reviews, June 2012 (This book is in the MAA's basic library list.)As with the earlier editions, the current text emphasizes clear...

  2. Introduction to quantum graphs

    CERN Document Server

    Berkolaiko, Gregory

    2012-01-01

    A "quantum graph" is a graph considered as a one-dimensional complex and equipped with a differential operator ("Hamiltonian"). Quantum graphs arise naturally as simplified models in mathematics, physics, chemistry, and engineering when one considers propagation of waves of various nature through a quasi-one-dimensional (e.g., "meso-" or "nano-scale") system that looks like a thin neighborhood of a graph. Works that currently would be classified as discussing quantum graphs have been appearing since at least the 1930s, and since then, quantum graphs techniques have been applied successfully in various areas of mathematical physics, mathematics in general and its applications. One can mention, for instance, dynamical systems theory, control theory, quantum chaos, Anderson localization, microelectronics, photonic crystals, physical chemistry, nano-sciences, superconductivity theory, etc. Quantum graphs present many non-trivial mathematical challenges, which makes them dear to a mathematician's heart. Work on qu...

  3. Current trends in microsponge drug delivery system.

    Science.gov (United States)

    Gangadharappa, H V; Gupta, N Vishal; Prasad M, Sarat Chandra; Shivakumar, H G

    2013-08-01

    Microsponge is a microscopic sphere capable of absorbing skin secretions, therefore reducing the oiliness of the skin. Microsponge having particle size of 10-25 microns in diameter, have wide range of entrapment of various ingredients in a single microsponges system and release them at desired rates. Conventional topical preparations have various disadvantages due to irritancy, odour, greasiness and patient compliance. In many topical dosage forms fail to reach the systemic circulation in sufficient amounts in few cases. These problems overcome by the usage of formulation as microsponge in the areas of research. Drug release in microsponge is done by the external stimuli like pH, temperature and rubbing. It has several advantageous over the other topical preparations in being non-allergenic, non-toxic, non-irritant and non- mutagenic. These microsponges are used in the sun screens, creams, ointments, over-the-counter skin care preparations, recently nanosponge were reported in literature used in delivery of drug by the use of cyclodextrins to enhance the solubility of poorly water soluble drugs, which are meant for topical application.

  4. Graph sampling

    OpenAIRE

    Zhang, L.-C.; Patone, M.

    2017-01-01

    We synthesise the existing theory of graph sampling. We propose a formal definition of sampling in finite graphs, and provide a classification of potential graph parameters. We develop a general approach of Horvitz–Thompson estimation to T-stage snowball sampling, and present various reformulations of some common network sampling methods in the literature in terms of the outlined graph sampling theory.

  5. Introducing graph theory to track for neuroplastic alterations in the resting human brain: a transcranial direct current stimulation study.

    Science.gov (United States)

    Polanía, Rafael; Paulus, Walter; Antal, Andrea; Nitsche, Michael A

    2011-02-01

    Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that alters cortical excitability and activity in a polarity-dependent way. Stimulation for a few minutes has been shown to induce plastic alterations of cortical excitability and to improve cognitive performance. These effects might be related to stimulation-induced alterations of functional cortical network connectivity. We aimed to investigate the impact of tDCS on cortical network function by functional connectivity and graph theoretical analysis of the BOLD fMRI spontaneous activity. fMRI resting-state datasets were acquired immediately before and after 10-min bipolar tDCS during rest, with the anode placed over the left primary motor cortex (M1) and the cathode over the contralateral frontopolar cortex. For each dataset, grey matter voxel-based synchronization matrices were calculated and thresholded to construct undirected graphs. Nodal connectivity degree and minimum path length maps were calculated and compared before and after tDCS. Nodal minimum path lengths significantly increased in the left somatomotor (SM1) cortex after anodal tDCS, which means that the number of direct functional connections from the left SM1 to topologically distant grey matter voxels significantly decreased. In contrast, functional coupling between premotor and superior parietal areas with the left SM1 significantly increased. Additionally, the nodal connectivity degree in the left posterior cingulate cortex (PCC) area as well as in the right dorsolateral prefrontal cortex (right DLPFC) significantly increased. In summary, we provide initial support that tDCS-induced neuroplastic alterations might be related to functional connectivity changes in the human brain. Additionally, we propose our approach as a powerful method to track for neuroplastic changes in the human brain. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Current manufacturing processes of drug-eluting sutures.

    Science.gov (United States)

    Champeau, Mathilde; Thomassin, Jean-Michel; Tassaing, Thierry; Jérôme, Christine

    2017-11-01

    Drug-eluting sutures represent the next generation of surgical sutures since they fulfill their mechanical functions but also deliver the drug in their vicinity after implantation. These implants are produced by a variety of manufacturing processes. Drug-eluting sutures represent the next generation of surgical sutures since they fulfill their mechanical functions but also deliver the drug in their vicinity after implantation. These implants are produced by a variety of manufacturing processes. Two general approaches can be followed: (i) the ones that add the API into the material during the manufacturing process of the suture and (ii) the ones that load the API to an already manufactured suture. Areas covered: This review provides an overview of the current manufacturing processes for drug-eluting suture production and discusses their benefits and drawbacks depending on the type of drugs. The mechanical properties and the drug delivery profile of drug-eluting sutures are highlighted since these implants must fulfill both criteria. Expert opinion: For limited drug contents, melt extrusion and electrospinning are the emerging processes since the drug is added during the suture manufacture process. Advantageously, the drug release profile can be tuned by controlling the processing parameters specific to each process and the composition of the drug-containing polymer. If high drug content is targeted, the coating or grafting of a drug layer on a pre-manufactured suture allows for preservation of the tensile strength requirements of the suture.

  7. Current situation and future usage of anticancer drug databases.

    Science.gov (United States)

    Wang, Hongzhi; Yin, Yuanyuan; Wang, Peiqi; Xiong, Chenyu; Huang, Lingyu; Li, Sijia; Li, Xinyi; Fu, Leilei

    2016-07-01

    Cancer is a deadly disease with increasing incidence and mortality rates and affects the life quality of millions of people per year. The past 15 years have witnessed the rapid development of targeted therapy for cancer treatment, with numerous anticancer drugs, drug targets and related gene mutations been identified. The demand for better anticancer drugs and the advances in database technologies have propelled the development of databases related to anticancer drugs. These databases provide systematic collections of integrative information either directly on anticancer drugs or on a specific type of anticancer drugs with their own emphases on different aspects, such as drug-target interactions, the relationship between mutations in drug targets and drug resistance/sensitivity, drug-drug interactions, natural products with anticancer activity, anticancer peptides, synthetic lethality pairs and histone deacetylase inhibitors. We focus on a holistic view of the current situation and future usage of databases related to anticancer drugs and further discuss their strengths and weaknesses, in the hope of facilitating the discovery of new anticancer drugs with better clinical outcomes.

  8. Graphing trillions of triangles.

    Science.gov (United States)

    Burkhardt, Paul

    2017-07-01

    The increasing size of Big Data is often heralded but how data are transformed and represented is also profoundly important to knowledge discovery, and this is exemplified in Big Graph analytics. Much attention has been placed on the scale of the input graph but the product of a graph algorithm can be many times larger than the input. This is true for many graph problems, such as listing all triangles in a graph. Enabling scalable graph exploration for Big Graphs requires new approaches to algorithms, architectures, and visual analytics. A brief tutorial is given to aid the argument for thoughtful representation of data in the context of graph analysis. Then a new algebraic method to reduce the arithmetic operations in counting and listing triangles in graphs is introduced. Additionally, a scalable triangle listing algorithm in the MapReduce model will be presented followed by a description of the experiments with that algorithm that led to the current largest and fastest triangle listing benchmarks to date. Finally, a method for identifying triangles in new visual graph exploration technologies is proposed.

  9. Graph spectrum

    NARCIS (Netherlands)

    Brouwer, A.E.; Haemers, W.H.; Brouwer, A.E.; Haemers, W.H.

    2012-01-01

    This chapter presents some simple results on graph spectra.We assume the reader is familiar with elementary linear algebra and graph theory. Throughout, J will denote the all-1 matrix, and 1 is the all-1 vector.

  10. Drug resistance in leishmaniasis: current drug-delivery systems and future perspectives.

    Science.gov (United States)

    Yasinzai, Masoom; Khan, Momin; Nadhman, Akhtar; Shahnaz, Gul

    2013-10-01

    Leishmaniasis is a complex of diseases with numerous clinical manifestations for instance harshness from skin lesions to severe disfigurement and chronic systemic infection in the liver and spleen. So far, the most classical leishmaniasis therapy, despite its documented toxicities, remains pentavalent antimonial compounds. The arvailable therapeutic modalities for leishmaniasis are overwhelmed with resistance to leishmaniasis therapy. Mechanisms of classical drug resistance are often related with the lower drug uptake, increased efflux, the faster drug metabolism, drug target modifications and over-expression of drug transporters. The high prevalence of leishmaniasis and the appearance of resistance to classical drugs reveal the demand to develop and explore novel, less toxic, low cost and more promising therapeutic modalities. The review describes the mechanisms of classical drug resistance and potential drug targets in Leishmania infection. Moreover, current drug-delivery systems and future perspectives towards Leishmaniasis treatment are also covered.

  11. From chemical graphs in computer-aided drug design to general Markov-Galvez indices of drug-target, proteome, drug-parasitic disease, technological, and social-legal networks.

    Science.gov (United States)

    Riera-Fernández, Pablo; Munteanu, Cristian R; Dorado, Julian; Martin-Romalde, Raquel; Duardo-Sanchez, Aliuska; González-Diaz, Humberto

    2011-12-01

    Complex Networks are useful in solving problems in drug research and industry, developing mathematical representations of different systems. These systems move in a wide range from relatively simple graph representations of drug molecular structures to large systems. We can cite for instance, drug-target protein interaction networks, drug policy legislation networks, or drug treatment in large geographical disease spreading networks. In any case, all these networks have essentially the same components: nodes (atoms, drugs, proteins, microorganisms and/or parasites, geographical areas, drug policy legislations, etc.) and edges (chemical bonds, drug-target interactions, drug-parasite treatment, drug use, etc.). Consequently, we can use the same type of numeric parameters called Topological Indices (TIs) to describe the connectivity patterns in all these kinds of Complex Networks despite the nature of the object they represent. The main reason for this success of TIs is the high flexibility of this theory to solve in a fast but rigorous way many apparently unrelated problems in all these disciplines. Another important reason for the success of TIs is that using these parameters as inputs we can find Quantitative Structure-Property Relationships (QSPR) models for different kind of problems in Computer-Aided Drug Design (CADD). Taking into account all the above-mentioned aspects, the present work is aimed at offering a common background to all the manuscripts presented in this special issue. In so doing, we make a review of the most common types of complex networks involving drugs or their targets. In addition, we review both classic TIs that have been used to describe the molecular structure of drugs and/or larger complex networks. Next, we use for the first time a Markov chain model to generalize Galvez TIs to higher order analogues coined here as the Markov-Galvez TIs of order k (MGk). Lastly, we illustrate the calculation of MGk values for different classes of

  12. Oral transmucosal drug delivery--current status and future prospects.

    Science.gov (United States)

    Sattar, Mohammed; Sayed, Ossama M; Lane, Majella E

    2014-08-25

    Oral transmucosal drug delivery (OTDD) dosage forms have been available since the 1980s. In contrast to the number of actives currently delivered locally to the oral cavity, the number delivered as buccal or sublingual formulations remains relatively low. This is surprising in view of the advantages associated with OTDD, compared with conventional oral drug delivery. This review examines a number of aspects related to OTDD including the anatomy of the oral cavity, models currently used to study OTDD, as well as commercially available formulations and emerging technologies. The limitations of current methodologies to study OTDD are considered as well as recent publications and new approaches which have advanced our understanding of this route of drug delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Equipackable graphs

    DEFF Research Database (Denmark)

    Vestergaard, Preben Dahl; Hartnell, Bert L.

    2006-01-01

    There are many results dealing with the problem of decomposing a fixed graph into isomorphic subgraphs. There has also been work on characterizing graphs with the property that one can delete the edges of a number of edge disjoint copies of the subgraph and, regardless of how that is done, the gr...

  14. A faithful functor among algebras and graphs

    OpenAIRE

    Falcón Ganfornina, Óscar Jesús; Falcón Ganfornina, Raúl Manuel; Núñez Valdés, Juan; Pacheco Martínez, Ana María; Villar Liñán, María Trinidad; Vigo Aguiar, Jesús (Coordinador)

    2016-01-01

    The problem of identifying a functor between the categories of algebras and graphs is currently open. Based on a known algorithm that identifies isomorphisms of Latin squares with isomorphism of vertex-colored graphs, we describe here a pair of graphs that enable us to find a faithful functor between finite-dimensional algebras over finite fields and these graphs.

  15. Topic Model for Graph Mining.

    Science.gov (United States)

    Xuan, Junyu; Lu, Jie; Zhang, Guangquan; Luo, Xiangfeng

    2015-12-01

    Graph mining has been a popular research area because of its numerous application scenarios. Many unstructured and structured data can be represented as graphs, such as, documents, chemical molecular structures, and images. However, an issue in relation to current research on graphs is that they cannot adequately discover the topics hidden in graph-structured data which can be beneficial for both the unsupervised learning and supervised learning of the graphs. Although topic models have proved to be very successful in discovering latent topics, the standard topic models cannot be directly applied to graph-structured data due to the "bag-of-word" assumption. In this paper, an innovative graph topic model (GTM) is proposed to address this issue, which uses Bernoulli distributions to model the edges between nodes in a graph. It can, therefore, make the edges in a graph contribute to latent topic discovery and further improve the accuracy of the supervised and unsupervised learning of graphs. The experimental results on two different types of graph datasets show that the proposed GTM outperforms the latent Dirichlet allocation on classification by using the unveiled topics of these two models to represent graphs.

  16. [Development of antituberculous drugs: current status and future prospects].

    Science.gov (United States)

    Tomioka, Haruaki; Namba, Kenji

    2006-12-01

    Worldwide, tuberculosis (TB) remains the most frequent and important infectious disease causing morbidity and death. One-third of the world's population is infected with Mycobacterium tuberculosis (MTB), the etiologic agent of TB. The World Health Organization estimates that about eight to ten million new TB cases occur annually worldwide and the incidence of TB is currently increasing. In this context, TB is in the top three, with malaria and HIV being the leading causes of death from a single infectious agent, and approximately two million deaths are attributable to TB annually. In particular, pulmonary TB, the most common form of TB, is a highly contagious and life-threatening infection. Moreover, enhanced susceptibility to TB in HIV-infected populations is another serious health problem throughout the world. In addition, multidrug-resistant TB (MDR-TB) has been increasing in incidence in many areas, not only in developing countries but industrialized countries as well, during the past decade. These situations, particularly the global resurgence of TB and the rapid emergence of MDR-TB, underscore the importance of the development of new antituberculous drugs and new protocols for efficacious clinical control of TB patients using ordinary antimycobacterial drugs. Concerning the development of new antituberculous drugs, the following points are of particular importance. (1) Development of drugs which display lasting antimycobacterial activity in vivo is desirable, since they can be administered with long intervals and consequently facilitate directly observed therapy and enhance patient compliance. (2) Development of novel antituberculosis compounds to combat MDR-TB is urgently needed. (3) The eradication of slowly metabolizing and, if possible, dormant populations of MTB organisms that cause relapse, using new classes of anti-TB drugs is very promising for prevention of TB incidence, because it will markedly reduce the incidence of active TB from persons who are

  17. Inhibition of cardiac inward rectifier currents by cationic amphiphilic drugs.

    Science.gov (United States)

    van der Heyden, M A G; Stary-Weinzinger, A; Sanchez-Chapula, J A

    2013-09-01

    Cardiac inward rectifier channels belong to three different classes of the KIR channel protein family. The KIR2.x proteins generate the classical inward rectifier current, IK1, while KIR3 and KIR6 members are responsible for the acetylcholine responsive and ATP sensitive inward rectifier currents IKAch and IKATP, respectively. Aberrant function of these channels has been correlated with severe cardiac arrhythmias, indicating their significant contribution to normal cardiac electrophysiology. A common feature of inward rectifier channels is their dependence on the lipid phosphatidyl-4,5-bisphospate (PIP2) interaction for functional activity. Cationic amphiphilic drugs (CADs) are one of the largest classes of pharmaceutical compounds. Several widely used CADs have been associated with inward rectifier current disturbances, and recent evidence points to interference of the channel-PIP2 interaction as the underlying mechanism of action. Here, we will review how six of these well known drugs, used for treatment in various different conditions, interfere in cardiac inward rectifier functioning. In contrast, KIR channel inhibition by the anionic anesthetic thiopental is achieved by a different mechanism of channel-PIP2 interference. We will discuss the latest basic science insights of functional inward rectifier current characteristics, recently derived KIR channel structures and specific PIP2-receptor interactions at the molecular level and provide insight in how these drugs interfere in the structure-function relationships.

  18. Comparison of antimalarial activity of Artemisia turanica extract with current drugs in vivo.

    Science.gov (United States)

    Taherkhani, Mahboubeh; Rustaiyan, Abdolhossein; Nahrevanian, Hossein; Naeimi, Sabah; Taherkhani, Tofigh

    2013-03-01

    The purpose of this study was to compare antimalarial activity of Artemisia turanica Krasch as Iranian flora with current antimalarial drugs against Plasmodium berghei in vivo in mice. Air-dried aerial parts of Iranian flora A. turanica were collected from Khorasan, northeastern Iran, extracted with Et2O/MeOH/Petrol and defatted. Toxicity of herbal extracts was assessed on male NMRI mice, and their antimalarial efficacy was compared with antimalarial drugs [artemether, chloroquine and sulfadoxinepyrimethamine (Fansidar)] on infected P. berghei animals. All the groups were investigated for parasitaemia, body weight, hepatomegaly, splenomegaly and anemia. The significance of differences was determined by Analysis of Variances (ANOVA) and Student's t-test using Graph Pad Prism software. The inhibitory effects of A. turanica extract on early decline of P. berghei parasitaemia highlights its antimalarial activity, however, this effect no longer can be observed in the late infection. This may be due to the metabolic process of A. turanica crude extract by mice and reduction of its concentration in the body. Crude extract of A. turanica represented its antisymptomatic effects by stabilization of body, liver and spleen weights. This study confirmed antimalarial effects of A. turanica extracts against murine malaria in vivo during early infection, however, there are more benefits on pathophysiological symptoms by this medication.

  19. Effectiveness of multiple sclerosis treatment with current immunomodulatory drugs.

    Science.gov (United States)

    Milo, Ron

    2015-04-01

    Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS of a putative autoimmune origin characterized by neurologic dysfunction disseminated in space and time due to demyelination and axonal loss that results in progressive disability. Recent advances in understanding the immune pathogenesis of the disease resulted in the introduction of numerous effective immunomodulatoty drugs having diverse mechanisms of action, modes of administration and risk-benefit profiles. This results in more complex albeit more promising treatment selection and choices. The epidemiology, clinical features, pathogenesis and diagnosis of the disease are discussed. The mode of action and main characteristics of current immunomodulatory drugs for MS and their place in the therapeutic algorithm of the disease based on evidence from clinical trials are described. Speculation on new paradigms, treatment goals and outcome measures aimed at improving the landscape of MS treatment is presented. Multiple disease, drug and patient-related factors should be taken into consideration when selecting the appropriate drug and treatment strategy to the appropriate patient, thus paving the road for personalized medicine in MS.

  20. Current advances in transdermal delivery of drugs for Alzheimer's disease

    Science.gov (United States)

    Nguyen, Thuy Trang; Giau, Vo Van; Vo, Tuong Kha

    2017-01-01

    Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the disadvantages of current pharmaceutical dosage options for this chronic disorder. They could have different strengths, such as offering a stable diffusion of active substance, avoiding the first pass metabolism, and reducing system adverse reactions. This article reviews the technical principles, novel techniques of transdermal delivery drug, and prospects for future development for the management of cognitive and behavioral dysfunctions in AD patients. PMID:28706327

  1. Current advances in transdermal delivery of drugs for Alzheimer's disease.

    Science.gov (United States)

    Nguyen, Thuy Trang; Giau, Vo Van; Vo, Tuong Kha

    2017-01-01

    Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the disadvantages of current pharmaceutical dosage options for this chronic disorder. They could have different strengths, such as offering a stable diffusion of active substance, avoiding the first pass metabolism, and reducing system adverse reactions. This article reviews the technical principles, novel techniques of transdermal delivery drug, and prospects for future development for the management of cognitive and behavioral dysfunctions in AD patients.

  2. Emerging drugs of abuse: current perspectives on synthetic cannabinoids

    Directory of Open Access Journals (Sweden)

    Debruyne D

    2015-10-01

    Full Text Available Danièle Debruyne,1,2 Reynald Le Boisselier1 1Centre for Evaluation and Information on Pharmacodependence - Addictovigilance (CEIP-A, 2Toxicology and Pharmacology Laboratory, Department of Pharmacology, University Hospital Centre Côte de Nacre, Caen, France Abstract: New psychoactive drugs that have appeared over the last decade are typically dominated by cathinones and synthetic cannabinoids (SCs. SCs have been emerging as recreational drugs because they mimic the euphoria effect of cannabis while still being legal. Sprayed on natural herb mixtures, SCs have been primarily sold as “herbal smoking blends” or “herbal incense” under brand names like “Spice” or “K2”. Currently, SCs pure compounds are available from websites for the combination with herbal materials or for the use in e-cigarettes. For the past 5 years, an ever increasing number of compounds, representative of different chemical classes, have been promoted and now represent a large assortment of new popular drugs of abuse, which are difficult to properly identify. Their legal status varies by country with many government institutions currently pushing for their control. The in vitro binding to CB1/CB2 receptors is usually well-known and considerable differences have been found in the CB1 versus CB2 selectivity and potency within the different SCs, with several structure-activity relations being evident. Desired effects by CB1 agonist users are relaxation/recreative, however, cardiovascular, gastrointestinal, or psychiatric/neurological side effects are commonly reported. At present there is no specific antidote existing if an overdose of designer drugs was to occur, and no curative treatment has been approved by health authorities. Management of acute toxic effects is mainly symptomatic and extrapolated from experience with cannabis. Keywords: synthetic cannabinoids, chemistry, analysis, pharmacology, toxicology, dependence, medical care

  3. Modern graph theory

    CERN Document Server

    Bollobás, Béla

    1998-01-01

    The time has now come when graph theory should be part of the education of every serious student of mathematics and computer science, both for its own sake and to enhance the appreciation of mathematics as a whole. This book is an in-depth account of graph theory, written with such a student in mind; it reflects the current state of the subject and emphasizes connections with other branches of pure mathematics. The volume grew out of the author's earlier book, Graph Theory -- An Introductory Course, but its length is well over twice that of its predecessor, allowing it to reveal many exciting new developments in the subject. Recognizing that graph theory is one of several courses competing for the attention of a student, the book contains extensive descriptive passages designed to convey the flavor of the subject and to arouse interest. In addition to a modern treatment of the classical areas of graph theory such as coloring, matching, extremal theory, and algebraic graph theory, the book presents a detailed ...

  4. Current status of accreditation for drug testing in hair.

    Science.gov (United States)

    Cooper, Gail; Moeller, Manfred; Kronstrand, Robert

    2008-03-21

    At the annual meeting of the Society of Hair Testing in Vadstena, Sweden in 2006, a committee was appointed to address the issue of guidelines for hair testing and to assess the current status of accreditation amongst laboratories offering drug testing in hair. A short questionnaire was circulated amongst the membership and interested parties. Fifty-two responses were received from hair testing laboratories providing details on the amount and type of hair tests they offered and the status of accreditation within their facilities. Although the vast majority of laboratories follow current guidelines (83%), only nine laboratories were accredited to ISO/IEC 17025 for hair testing. A significant number of laboratories reporting that they were in the process of developing quality systems with a view to accrediting their methods within 2-3 years. This study provides an insight into the status of accreditation in hair testing laboratories and supports the need for guidelines to encourage best practice.

  5. Interaction graphs

    DEFF Research Database (Denmark)

    Seiller, Thomas

    2016-01-01

    Interaction graphs were introduced as a general, uniform, construction of dynamic models of linear logic, encompassing all Geometry of Interaction (GoI) constructions introduced so far. This series of work was inspired from Girard's hyperfinite GoI, and develops a quantitative approach that should...... be understood as a dynamic version of weighted relational models. Until now, the interaction graphs framework has been shown to deal with exponentials for the constrained system ELL (Elementary Linear Logic) while keeping its quantitative aspect. Adapting older constructions by Girard, one can clearly define...... "full" exponentials, but at the cost of these quantitative features. We show here that allowing interpretations of proofs to use continuous (yet finite in a measure-theoretic sense) sets of states, as opposed to earlier Interaction Graphs constructions were these sets of states were discrete (and finite...

  6. Introduction to graph theory

    CERN Document Server

    Trudeau, Richard J

    1994-01-01

    Preface1. Pure Mathematics Introduction; Euclidean Geometry as Pure Mathematics; Games; Why Study Pure Mathematics?; What's Coming; Suggested Reading2. Graphs Introduction; Sets; Paradox; Graphs; Graph diagrams; Cautions; Common Graphs; Discovery; Complements and Subgraphs; Isomorphism; Recognizing Isomorphic Graphs; Semantics The Number of Graphs Having a Given nu; Exercises; Suggested Reading3. Planar Graphs Introduction; UG, K subscript 5, and the Jordan Curve Theorem; Are there More Nonplanar Graphs?; Expansions; Kuratowski's Theorem; Determining Whether a Graph is Planar or

  7. Drugs in development for toxoplasmosis: advances, challenges, and current status.

    Science.gov (United States)

    Alday, P Holland; Doggett, Joseph Stone

    2017-01-01

    Toxoplasma gondii causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against T. gondii tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis.

  8. Graph theory

    CERN Document Server

    Diestel, Reinhard

    2017-01-01

    This standard textbook of modern graph theory, now in its fifth edition, combines the authority of a classic with the engaging freshness of style that is the hallmark of active mathematics. It covers the core material of the subject with concise yet reliably complete proofs, while offering glimpses of more advanced methods in each field by one or two deeper results, again with proofs given in full detail. The book can be used as a reliable text for an introductory course, as a graduate text, and for self-study. From the reviews: “This outstanding book cannot be substituted with any other book on the present textbook market. It has every chance of becoming the standard textbook for graph theory.”Acta Scientiarum Mathematiciarum “Deep, clear, wonderful. This is a serious book about the heart of graph theory. It has depth and integrity. ”Persi Diaconis & Ron Graham, SIAM Review “The book has received a very enthusiastic reception, which it amply deserves. A masterly elucidation of modern graph theo...

  9. ANN multiscale model of anti-HIV drugs activity vs AIDS prevalence in the US at county level based on information indices of molecular graphs and social networks.

    Science.gov (United States)

    González-Díaz, Humberto; Herrera-Ibatá, Diana María; Duardo-Sánchez, Aliuska; Munteanu, Cristian R; Orbegozo-Medina, Ricardo Alfredo; Pazos, Alejandro

    2014-03-24

    This work is aimed at describing the workflow for a methodology that combines chemoinformatics and pharmacoepidemiology methods and at reporting the first predictive model developed with this methodology. The new model is able to predict complex networks of AIDS prevalence in the US counties, taking into consideration the social determinants and activity/structure of anti-HIV drugs in preclinical assays. We trained different Artificial Neural Networks (ANNs) using as input information indices of social networks and molecular graphs. We used a Shannon information index based on the Gini coefficient to quantify the effect of income inequality in the social network. We obtained the data on AIDS prevalence and the Gini coefficient from the AIDSVu database of Emory University. We also used the Balaban information indices to quantify changes in the chemical structure of anti-HIV drugs. We obtained the data on anti-HIV drug activity and structure (SMILE codes) from the ChEMBL database. Last, we used Box-Jenkins moving average operators to quantify information about the deviations of drugs with respect to data subsets of reference (targets, organisms, experimental parameters, protocols). The best model found was a Linear Neural Network (LNN) with values of Accuracy, Specificity, and Sensitivity above 0.76 and AUROC > 0.80 in training and external validation series. This model generates a complex network of AIDS prevalence in the US at county level with respect to the preclinical activity of anti-HIV drugs in preclinical assays. To train/validate the model and predict the complex network we needed to analyze 43,249 data points including values of AIDS prevalence in 2,310 counties in the US vs ChEMBL results for 21,582 unique drugs, 9 viral or human protein targets, 4,856 protocols, and 10 possible experimental measures.

  10. Graph Query Portal

    OpenAIRE

    Dayal, Amit; Brock, David

    2018-01-01

    Prashant Chandrasekar, a lead developer for the Social Interactome project, has tasked the team with creating a graph representation of the data collected from the social networks involved in that project. The data is currently stored in a MySQL database. The client requested that the graph database be Cayley, but after a literature review, Neo4j was chosen. The reasons for this shift will be explained in the design section. Secondarily, the team was tasked with coming up with three scena...

  11. Reimbursed Price of Orphan Drugs: Current Strategies and Potential Improvements.

    Science.gov (United States)

    Mincarone, Pierpaolo; Leo, Carlo Giacomo; Sabina, Saverio; Sarriá-Santamera, Antonio; Taruscio, Domenica; Serrano-Aguilar, Pedro Guillermo; Kanavos, Panos

    2017-01-01

    The pricing and reimbursement policies for pharmaceuticals are relevant to balance timely and equitable access for all patients, financial sustainability, and reward for valuable innovation. The proliferation of high-cost specialty medicines is particularly true in rare diseases (RDs) where the pricing mechanism is characterised by a lack of transparency. This work provides an overall picture of current strategies for the definition of the reimbursed prices of orphan drugs (ODs) and highlights some potential improvements. Current strategies and suggestions are presented along 4 dimensions: (1) comprehensive value assessment, (2) early dialogs among relevant stakeholders, (3) innovative reimbursement approaches, and (4) societal participation in producing ODs. Comprehensive value assessment could be achieved by clarifying the approach of distributive justice to adopt, ensuring a representative participation of stakeholders, and with a broad consideration of value-bearing factors. With respect to early dialogs, cross-border cooperation can be determinant to companies and agencies. The cost-benefit ratio of early dialogs needs to be demonstrated and the "regulatory capture" effect should be monitored. Innovative reimbursement approaches were developed to balance the need for evidence-based decisions with the timely access to innovative drugs. The societal participation in producing ODs needs to be recognised in a collaborating framework where adaptive agreements can be developed with mutual satisfaction. Such agreements could also impact on coverage and reimbursement decisions as additional elements for the determination of a comprehensive societal value of ODs. Further research is needed to investigate the highlighted open challenges so that RDs will not remain, in practical terms, orphan diseases. © 2017 S. Karger AG, Basel.

  12. Orphan drugs in development for urea cycle disorders: current perspectives

    Directory of Open Access Journals (Sweden)

    Häberle J

    2014-09-01

    Full Text Available Johannes Häberle,1 Shawn E McCandless2 1Division of Metabolism and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland; 2Center for Human Genetics, University Hospitals Case Medical Center, and Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA Abstract: The urea cycle disorders are caused by deficiency of one of the six hepatic enzymes or two transporters involved in detoxification of ammonia. The resulting hyperammonemia causes severe brain injury unless aggressive steps are taken to reduce the accumulation of ammonia, which is thought to be the most toxic metabolite. This review describes the current state of chronic management of urea cycle disorders, focusing on new and emerging therapies. Management strategies include the mainstay of treatment, namely dietary protein restriction and supplementation with l-arginine or l-citrulline. Several currently approved medications utilize and enhance alternative pathways of waste nitrogen excretion (sodium benzoate, sodium phenylacetate, sodium phenylbutyrate in several formulations, and glycerol phenylbutyrate, working through conjugation of the drug to either glycine (in the case of benzoate or glutamine, the products of which are excreted in the urine. Carglumic acid activates the first committed step of conversion of ammonia to urea, carbamoylphosphate synthetase, and thus effectively treats defective synthesis of the endogenous activator, N-acetylglutamate, whether due to genetic defects or biochemical inhibition of the N-acetylglutamate synthase enzyme. Approaches to neuroprotection during episodes of hyperammonemia are discussed, including the use of controlled hypothermia (brain cooling, as well as proposed, but as yet untested, pharmacologic therapies. Finally, cell-based therapies, including liver transplantation, infusion of fresh or cryopreserved hepatocytes, use of stem cells, and new approaches to gene

  13. Graph theory

    CERN Document Server

    Gould, Ronald

    2012-01-01

    This introduction to graph theory focuses on well-established topics, covering primary techniques and including both algorithmic and theoretical problems. The algorithms are presented with a minimum of advanced data structures and programming details. This thoroughly corrected 1988 edition provides insights to computer scientists as well as advanced undergraduates and graduate students of topology, algebra, and matrix theory. Fundamental concepts and notation and elementary properties and operations are the first subjects, followed by examinations of paths and searching, trees, and networks. S

  14. 21 CFR 212.2 - What is current good manufacturing practice for PET drugs?

    Science.gov (United States)

    2010-04-01

    ..., holding, or distribution of PET drugs intended for human use. Current good manufacturing practice is... 21 Food and Drugs 4 2010-04-01 2010-04-01 false What is current good manufacturing practice for... HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR POSITRON EMISSION...

  15. The groupies of random multipartite graphs

    OpenAIRE

    Portmann, Marius; Wang, Hongyun

    2012-01-01

    If a vertex $v$ in a graph $G$ has degree larger than the average of the degrees of its neighbors, we call it a groupie in $G$. In the current work, we study the behavior of groupie in random multipartite graphs with the link probability between sets of nodes fixed. Our results extend the previous ones on random (bipartite) graphs.

  16. Planar graphs theory and algorithms

    CERN Document Server

    Nishizeki, T

    1988-01-01

    Collected in this volume are most of the important theorems and algorithms currently known for planar graphs, together with constructive proofs for the theorems. Many of the algorithms are written in Pidgin PASCAL, and are the best-known ones; the complexities are linear or 0(nlogn). The first two chapters provide the foundations of graph theoretic notions and algorithmic techniques. The remaining chapters discuss the topics of planarity testing, embedding, drawing, vertex- or edge-coloring, maximum independence set, subgraph listing, planar separator theorem, Hamiltonian cycles, and single- or multicommodity flows. Suitable for a course on algorithms, graph theory, or planar graphs, the volume will also be useful for computer scientists and graph theorists at the research level. An extensive reference section is included.

  17. Current status of the New Antiepileptic drugs in chronic pain.

    Directory of Open Access Journals (Sweden)

    Harpreet Singh Sidhu

    2016-08-01

    Full Text Available Antiepileptic drugs (AEDs are extensively used worldwide to treat a wide range of disorders other than epilepsy, such as neuropathic pain, migraine and bipolar disorder. Due to this situation more than 20 new third-generation AEDs have been introduced in the market recently. The future design of new AEDs must also have potential to help in the non-epileptic disorders. The wide acceptance of second generation AEDs for the management of various Non-epileptic disorders has caused the emergence of generics in the market. The wide use of approved AEDs outside epilepsy is based on both economic and scientific reasons. Bipolar disorders, migraine prophylaxis, fibromyalgia and neuropathic pain represent the most attractive indication expansion opportunities for anticonvulsant developers, providing blockbuster revenues. Strong growth in non-epilepsy conditions will see Pfizer’s Lyrica become the market leading brand by 2018. In this review we mainly focus on the current status of new AEDs in the treatment of chronic pain and migraine prophylaxis. AEDs have a strong analgesic potential and this is demonstrated by the wide use of carbamazepine in trigeminal neuralgia and sodium valproate in migraine prophylaxis. At present, data on the new AEDs for non-epileptic conditions are inconclusive. Not all AEDs are effective in the management of neuropathic pain and migraine. Only those AEDs whose mechanisms of action are match with pathophysiology of the disease, have potential to show efficacy in non-epileptic disorder. For this better understanding of the pathophysiology of the disease and mechanisms of action of new AEDs are essential requirement before initiating pre-clinical and clinical trials. Many new AEDs show good results in the animal model and open-label studies but fail to provide strong evidence at randomized, placebo-controlled trials. The final decision regarding the clinical efficacy of the particular AEDs in a specific non-epileptic disorder

  18. Vaginal drug delivery systems: A Review of Current Status | Dobaria ...

    African Journals Online (AJOL)

    Among the various routes of drug delivery, the vaginal route offers many advantages due to its large permeation area, rich vascularization, avoidance of first pass metabolism and relatively low enzymatic activity. Several studies have shown that the vaginal cavity is an effective route for drug administration intended mainly ...

  19. [The costs of new drugs compared to current standard treatment].

    Science.gov (United States)

    Ujeyl, Mariam; Schlegel, Claudia; Gundert-Remy, Ursula

    2013-01-01

    Until AMNOG came into effect Germany had free pricing of new drugs. Our exemplary work investigates the costs of new drugs that were licensed in the two years prior to AMNOG, and compares them to the costs of standard treatment that has been used in pivotal trials. Also, the important components of pharmaceutical prices will be illustrated. We retrospectively analysed the European Public Assessment Reports of proprietary medicinal products that the European Medicinal Agency initially approved in 2009 and 2010 and that were tested against an active control in at least one pivotal trial. If the standard treatment was a generic, the average pharmacy retail price of new drugs was 7.4 times (median 7.1) higher than that of standard treatment. If the standard treatment was an originator drug the average price was 1.4 times (median 1.2) higher than that of the new drug. There was no clear correlation of an increase in costs for new drugs and their "grade of innovation" as rated according to the criteria of Fricke. Our study shows that prices of new drugs must be linked to the evidence of comparative benefit; since German drug pricing is complex, cost saving effects obtained thereby will depend on a range of other rules and decisions. Copyright © 2013. Published by Elsevier GmbH.

  20. Access to orphan drugs in Europe: current and future issues.

    Science.gov (United States)

    Michel, Morgane; Toumi, Mondher

    2012-02-01

    Orphan drugs target small populations of patients. In order to make the field more attractive to pharmaceutical companies and encourage R&D in rare diseases, incentives were put forward by the EU, which are discussed in this article. Because they often are the only available option to treat a disease, some orphan drugs are considered to have high value and as such benefit from high prices on national markets. This has made orphan drugs an attractive market for pharmaceutical companies, with approximately 40 approved orphan drugs generating over $200 million each in yearly sales. The resulting burden this puts on national health insurances may lead to a change in regulation and will certainly lead to new national pricing and reimbursement strategies. They will need to be coherent, fair, effective and sustainable so as to be predictable for companies. Reflection on the subject needs to be initiated.

  1. NONSTEROIDAL ANTI-INFLAMMATORY DRUGS: CURRENT ASPECTS OF THEIR USE

    Directory of Open Access Journals (Sweden)

    N. A. Shostak

    2014-07-01

    Full Text Available The paper shows the basic mechanisms of action of nonsteroidal antinflammatory drugs (NSAID and their classification. It considers riskfactors for NSAID gastropathy and the possibilities of its treatment, prevention in the context of modern medicine.

  2. NONSTEROIDAL ANTI-INFLAMMATORY DRUGS: CURRENT ASPECTS OF THEIR USE

    Directory of Open Access Journals (Sweden)

    N. A. Shostak

    2013-01-01

    Full Text Available The paper shows the basic mechanisms of action of nonsteroidal antinflammatory drugs (NSAID and their classification. It considers riskfactors for NSAID gastropathy and the possibilities of its treatment, prevention in the context of modern medicine.

  3. Chromatic graph theory

    CERN Document Server

    Chartrand, Gary; Rosen, Kenneth H

    2008-01-01

    Beginning with the origin of the four color problem in 1852, the field of graph colorings has developed into one of the most popular areas of graph theory. Introducing graph theory with a coloring theme, Chromatic Graph Theory explores connections between major topics in graph theory and graph colorings as well as emerging topics. This self-contained book first presents various fundamentals of graph theory that lie outside of graph colorings, including basic terminology and results, trees and connectivity, Eulerian and Hamiltonian graphs, matchings and factorizations, and graph embeddings. The remainder of the text deals exclusively with graph colorings. It covers vertex colorings and bounds for the chromatic number, vertex colorings of graphs embedded on surfaces, and a variety of restricted vertex colorings. The authors also describe edge colorings, monochromatic and rainbow edge colorings, complete vertex colorings, several distinguishing vertex and edge colorings, and many distance-related vertex coloring...

  4. A survey of current trends in computational drug repositioning.

    Science.gov (United States)

    Li, Jiao; Zheng, Si; Chen, Bin; Butte, Atul J; Swamidass, S Joshua; Lu, Zhiyong

    2016-01-01

    Computational drug repositioning or repurposing is a promising and efficient tool for discovering new uses from existing drugs and holds the great potential for precision medicine in the age of big data. The explosive growth of large-scale genomic and phenotypic data, as well as data of small molecular compounds with granted regulatory approval, is enabling new developments for computational repositioning. To achieve the shortest path toward new drug indications, advanced data processing and analysis strategies are critical for making sense of these heterogeneous molecular measurements. In this review, we show recent advancements in the critical areas of computational drug repositioning from multiple aspects. First, we summarize available data sources and the corresponding computational repositioning strategies. Second, we characterize the commonly used computational techniques. Third, we discuss validation strategies for repositioning studies, including both computational and experimental methods. Finally, we highlight potential opportunities and use-cases, including a few target areas such as cancers. We conclude with a brief discussion of the remaining challenges in computational drug repositioning. Published by Oxford University Press 2015. This work is written by US Government employees and is in the public domain in the US.

  5. Current trend of drug sensitivity in bovine mastitis

    Directory of Open Access Journals (Sweden)

    Rajeev Ranjan

    2010-02-01

    Full Text Available The study was conducted on 190 milk samples of bovine mastitis and 138 samples were confirmed positives for microorganisms. All the 138 samples were subjected to drug sensitivity test. The most effective antibiotic was enrofloxacin (91.67% followed by ciprofloxacin (90.15%, amikacin (87.12%, ceftriaxone (84.10%, chloramphenicol (80.31%, cefotaxime (79.55% and gentamicin (77.27%. Microorganisms were mostly resistant to drugs like streptomycin, penicillinG, ampicillin, cloxacillin, amoxycillin and neomycin in increasing order of resistance. Hence, it is suggested that the line of treatment should be based on antibiogram study of various isolates from bovine mastitis. Further, the selection of drugs after culture and sensitivity test should be based on their ability to cross blood tissue barrier or mammary parenchyma, lipophilicity and ability to work in alkaline pH. [Vet. World 2010; 3(1.000: 17-20

  6. Role of Urine Drug Testing in the Current Opioid Epidemic.

    Science.gov (United States)

    Mahajan, Gagan

    2017-12-01

    While the evidence for urine drug testing for patients on chronic opioid therapy is weak, the guidelines created by numerous medical societies and state and federal regulatory agencies recommend that it be included as one of the tools used to monitor patients for compliance with chronic opioid therapy. To get the most comprehensive results, clinicians should order both an immunoassay screen and confirmatory urine drug test. The immunoassay screen, which can be performed as an in-office point-of-care test or as a laboratory-based test, is a cheap and convenient study to order. Limitations of an immunoassay screen, however, include having a high threshold of detectability and only providing qualitative information about a select number of drug classes. Because of these restrictions, clinicians should understand that immunoassay screens have high false-positive and false-negative rates. Despite these limitations, though, the results can assist the clinician with making preliminary treatment decisions. In comparison, a confirmatory urine drug test, which can only be performed as a laboratory-based test, has a lower threshold of detectability and provides both qualitative and quantitative information. A urine drug test's greater degree of specificity allows for a relatively low false-negative and false-positive rate in contrast to an immunoassay screen. Like any other diagnostic test, an immunoassay screen and a confirmatory urine drug test both possess limitations. Clinicians must keep this in mind when interpreting an unexpected test result and consult with their laboratory when in doubt about the meaning of the test result to avoid making erroneous decisions that negatively impact both the patient and clinician.

  7. [Harm reduction interventions in drug users: current situation and recommendations].

    Science.gov (United States)

    Bosque-Prous, Marina; Brugal, María Teresa

    2016-11-01

    Harm reduction encompasses interventions, programmes and policies that seek to reduce the negative consequences of the consumption of both legal and illegal drugs on the individual and public health. Harm reduction looks to mitigate the harm suffered by drug users through drug use monitoring and prevention, and promotes initiatives that respect and protect the human rights of this population. The harm reduction policies that have proven effective and efficient are: opioid substitution maintenance therapy (methadone); needle and syringe exchange programmes; supervised drug consumption rooms; and overdose prevention through peer-based naloxone distribution. In order to be effective, these policies must have comprehensive coverage and be implemented in areas where the target population is prevalent. Resident-based opposition to the implementation of these policies is known as the NIMBY (Not In My Back Yard) phenomenon, which is characterised by being against the implementation of new measures in a particular place, but does not question their usefulness. Given that any NIMBY phenomenon is a complex social, cultural and political phenomenon, it is important to conduct a thorough analysis of the situation prior to implementing any of these measures. Harm reduction policies must be extended to other substances such as alcohol and tobacco, as well as to other conditions beyond infectious/contagious diseases and overdose. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Current and future drug targets in weight management

    NARCIS (Netherlands)

    Witkamp, R.F.

    2011-01-01

    Obesity will continue to be one of the leading causes of chronic disease unless the ongoing rise in the prevalence of this condition is reversed. Accumulating morbidity figures and a shortage of effective drugs have generated substantial research activity with several molecular targets being

  9. Graph anomalies in cyber communications

    Energy Technology Data Exchange (ETDEWEB)

    Vander Wiel, Scott A [Los Alamos National Laboratory; Storlie, Curtis B [Los Alamos National Laboratory; Sandine, Gary [Los Alamos National Laboratory; Hagberg, Aric A [Los Alamos National Laboratory; Fisk, Michael [Los Alamos National Laboratory

    2011-01-11

    Enterprises monitor cyber traffic for viruses, intruders and stolen information. Detection methods look for known signatures of malicious traffic or search for anomalies with respect to a nominal reference model. Traditional anomaly detection focuses on aggregate traffic at central nodes or on user-level monitoring. More recently, however, traffic is being viewed more holistically as a dynamic communication graph. Attention to the graph nature of the traffic has expanded the types of anomalies that are being sought. We give an overview of several cyber data streams collected at Los Alamos National Laboratory and discuss current work in modeling the graph dynamics of traffic over the network. We consider global properties and local properties within the communication graph. A method for monitoring relative entropy on multiple correlated properties is discussed in detail.

  10. Fluorescence lifetime assays: current advances and applications in drug discovery.

    Science.gov (United States)

    Pritz, Stephan; Doering, Klaus; Woelcke, Julian; Hassiepen, Ulrich

    2011-06-01

    Fluorescence lifetime assays complement the portfolio of established assay formats available in drug discovery, particularly with the recent advances in microplate readers and the commercial availability of novel fluorescent labels. Fluorescence lifetime assists in lowering complexity of compound screening assays, affording a modular, toolbox-like approach to assay development and yielding robust homogeneous assays. To date, materials and procedures have been reported for biochemical assays on proteases, as well as on protein kinases and phosphatases. This article gives an overview of two assay families, distinguished by the origin of the fluorescence signal modulation. The pharmaceutical industry demands techniques with a robust, integrated compound profiling process and short turnaround times. Fluorescence lifetime assays have already helped the drug discovery field, in this sense, by enhancing productivity during the hit-to-lead and lead optimization phases. Future work will focus on covering other biochemical molecular modifications by investigating the detailed photo-physical mechanisms underlying the fluorescence signal.

  11. Current French system of post-marketing drug surveillance.

    Science.gov (United States)

    Albengres, E; Gauthier, F; Tillement, J P

    1990-07-01

    The French system of drug surveillance is characterized by several original features: thirty regional centres are selected to cover all of France to collect, analyze and enter the adverse drug events in the national data bank. The system is based on a bank of well documented files submitted to a decision of imputation; the report of severe events by prescribers is mandatory; cases are collected either by spontaneous reporting (routine) or by direct request (intensive validation study); the system is being involved in studies of epidemiological type as carried out by the national system of health or a few societies of medicine as well as by the centres themselves in cooperative works on defined populations.

  12. Current advances in transdermal delivery of drugs for alzheimer's disease

    OpenAIRE

    Thuy Trang Nguyen; Vo Van Giau; Tuong Kha Vo

    2017-01-01

    Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the...

  13. Regulatory aspects of oncology drug safety evaluation: Past practice, current issues, and the challenge of new drugs

    International Nuclear Information System (INIS)

    Rosenfeldt, Hans; Kropp, Timothy; Benson, Kimberly; Ricci, M. Stacey; McGuinn, W. David; Verbois, S. Leigh

    2010-01-01

    The drug development of new anti-cancer agents is streamlined in response to the urgency of bringing effective drugs to market for patients with limited life expectancy. FDA's regulation of oncology drugs has evolved from the practices set forth in Arnold Lehman's seminal work published in the 1950s through the current drafting of a new International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) safety guidance for anti-cancer drug nonclinical evaluations. The ICH combines the efforts of the regulatory authorities of Europe, Japan, and the United States and the pharmaceutical industry from these three regions to streamline the scientific and technical aspects of drug development. The recent development of new oncology drug classes with novel mechanisms of action has improved survival rates for some cancers but also brings new challenges for safety evaluation. Here we present the legacy of Lehman and colleagues in the context of past and present oncology drug development practices and focus on some of the current issues at the center of an evolving harmonization process that will generate a new safety guidance for oncology drugs, ICH S9. The purpose of this new guidance will be to facilitate oncology drug development on a global scale by standardizing regional safety requirements.

  14. Drugs currently under investigation for the treatment of invasive candidiasis.

    Science.gov (United States)

    McCarthy, Matthew W; Walsh, Thomas J

    2017-07-01

    The widespread implementation of immunosuppressants, immunomodulators, hematopoietic stem cell transplantation and solid organ transplantation in clinical practice has led to an expanding population of patients who are at risk for invasive candidiasis, which is the most common form of fungal disease among hospitalized patients in the developed world. The emergence of drug-resistant Candida spp. has added to the morbidity associated with invasive candidiasis and novel therapeutic strategies are urgently needed. Areas covered: In this paper, we explore investigational agents for the treatment of invasive candidiasis, with particular attention paid to compounds that have recently entered phase I or phase II clinical trials. Expert opinion: The antifungal drug development pipeline has been severely limited due to regulatory hurdles and a systemic lack of investment in novel compounds. However, several promising drug development strategies have recently emerged, including chemical screens involving Pathogen Box compounds, combination antifungal therapy, and repurposing of existing agents that were initially developed to treat other conditions, all of which have the potential to redefine the treatment of invasive candidiasis.

  15. Strongyloidiasis Current Status with Emphasis in Diagnosis and Drug Research

    Directory of Open Access Journals (Sweden)

    Tiago Mendes

    2017-01-01

    Full Text Available Strongyloidiasis is a parasitic neglected disease caused by the nematode Strongyloides stercoralis affecting 30 to 100 million people worldwide. Complications, strongly associated with alcoholism, organ transplants, and HTLV-1 virus, often arise due to late diagnosis, frequently leading to patient death. Lack of preemptive diagnosis is not the only difficulty when dealing with this parasite, since there are no gold standard diagnostic techniques, and the ones used have problems associated with sensitivity, resulting in false negatives. Treatment is also an issue as ivermectin and benzimidazoles administration leads to inconsistent cure rates and several side effects. Researching new anti-Strongyloides drugs is a difficult task since S. stercoralis does not develop until the adult stages in Mus musculus (with the exception of SCID mice, the main experimental host model. Fortunately, alternative parasite models can be used, namely, Strongyloides ratti and S. venezuelensis. However, even with these models, there are other complications in finding new drugs, which are associated with specific in vitro assay protocol steps, such as larvae decontamination. In this review, we highlight the challenges associated with new drug search, the compounds tested, and a list of published in vitro assay methodologies. We also point out advances being made in strongyloidiasis diagnosis so far.

  16. Liposomal Drug Product Development and Quality: Current US Experience and Perspective.

    Science.gov (United States)

    Kapoor, Mamta; Lee, Sau L; Tyner, Katherine M

    2017-05-01

    Research in the area of liposomes has grown substantially in the past few decades. Liposomes are lipid bilayer structures that can incorporate drug substances to modify the drug's pharmacokinetic profile thereby improving drug delivery. The agency has received over 400 liposomal drug product submissions (excluding combination therapies), and there are currently eight approved liposomal drug products on the US market. In order to identify the pain points in development and manufacturing of liposomal drug products, a retrospective analysis was performed from a quality perspective on submissions for new and generic liposomal drug products. General analysis on liposomal drug product submissions was also performed. Results indicated that 96% of the submissions were Investigational New Drug (IND) applications, 3% were New Drug Applications (NDAs), and the remaining 1% was Abbreviated New Drug Applications (ANDAs). Doxorubicin hydrochloride was the most commonly used drug substance incorporated into the liposomes (31%). The majority of the liposomal products were administered via intravenous route (84%) with cancer (various types) being the most common indication (63%). From a quality perspective, major challenges during the development of liposomal drug products included identification and (appropriate) characterization of critical quality attributes of liposomal drug products and suitable control strategies during product development. By focusing on these areas, a faster and more efficient development of liposomal drug products may be achieved. Additionally, in this way, the drug review process for such products can be streamlined.

  17. Graph visualization (Invited talk)

    NARCIS (Netherlands)

    Wijk, van J.J.; Kreveld, van M.J.; Speckmann, B.

    2012-01-01

    Black and white node link diagrams are the classic method to depict graphs, but these often fall short to give insight in large graphs or when attributes of nodes and edges play an important role. Graph visualization aims obtaining insight in such graphs using interactive graphical representations.

  18. Current approaches for the discovery of drugs that deter substance and drug abuse.

    Science.gov (United States)

    Yasgar, Adam; Simeonov, Anton

    2014-11-01

    Much has been presented and debated on the topic of drug abuse and its multidimensional nature, including the role of society and its customs and laws, economical factors, and the magnitude and nature of the burden. Given the complex nature of the receptors and pathways implicated in regulation of the cognitive and behavioral processes associated with addiction, a large number of molecular targets have been interrogated during recent years to discover starting points for development of small-molecule interventions. This review describes recent developments in the field of early drug discovery for drug abuse interventions with an emphasis on the advances published during the 2012 - 2014 period. Technologically, the processes/platforms utilized in drug abuse drug discovery are nearly identical to those used in the other disease areas. A key complicating factor in drug abuse research is the enormous biological complexity surrounding the brain processes involved and the associated difficulty in finding 'good' targets and achieving exquisite selectivity of treatment agents. While tremendous progress has been made during recent years to use the power of high-throughput technologies to discover proof-of-principle molecules for many new targets, next-generation models will be especially important in this field. Examples include: seeking advantageous drug-drug combinations, the use of automated whole-animal behavioral screening systems, advancing our understanding of the role of epigenetics in drug addiction and the employment of organoid-level 3D test platforms (also referred to as tissue-chip or organs-on-chip).

  19. Cardiovascular effects of current and future anti-obesity drugs

    DEFF Research Database (Denmark)

    Comerma Steffensen, Simon Gabriel; Grann, Martin; Andersen, Charlotte U

    2014-01-01

    cardiovascular risk, while an inverse agonist at cannabinoid type 1 (CB1) receptors, rimonobant was withdrawn due to serious psychiatric problems. At present there are only few treatments available including orlistat and, phentermine alone or in combination with topiramate and lorcaserin, although cardiovascular...... side effects need to be clarified regarding phentermine and lorcaserin. Drugs approved for type 2 diabetes including glucagon like peptide (GLP-1) analogues and metformin also cause moderate weight losses and have a favourable cardiovascular profile, while the anti-obesity potential of nebivolol...

  20. Characterization of Direct Current-Electrical Penetration Graph Waveforms and Correlation With the Probing Behavior of Matsumuratettix hiroglyphicus (Hemiptera: Cicadellidae), the Insect Vector of Sugarcane White Leaf Phytoplasma.

    Science.gov (United States)

    Roddee, J; Kobori, Y; Yorozuya, H; Hanboonsong, Y

    2017-06-01

    The leafhopper Matsumuratettix hiroglyphicus (Matsumura) (Hemiptera: Cicadellidae) is an important vector of phytoplasma causing white leaf disease in sugarcane. Thus, the aim of our study was to understand and describe the stylet-probing activities of this vector while feeding on sugarcane plants, by using direct current (DC) electrical penetration graph (EPG) monitoring. The EPG signals were classified into six distinct waveforms, according to amplitude, frequency, voltage level, and electrical origin of the observed traces during stylet penetration into the host plant tissues (probing). These six EPG waveforms of probing behavior comprise no stylet penetration (NP); stylet pathway through epidermis, mesophyll, and parenchymal cells (waveform A); contact at the bundle sheath layer (waveform B); salivation into phloem sieve elements (waveform C); phloem sap ingestion (waveform D); and short ingestion time of xylem sap (waveform E). The above waveform patterns were correlated with histological data of salivary sheath termini in plant tissue generated from insect stylet tips. The key findings of this study were that M. hiroglyphicus ingests the phloem sap at a relatively higher rate and for longer duration from any other cell type, suggesting that M. hiroglyphicus is mainly a phloem-feeder. Quantitative comparison of probing behavior revealed that females typically probe more frequently and longer in the phloem than males. Thus, females may acquire and inoculate greater amounts of phytoplasma than males, enhancing the efficiency of phytoplasma transmission and potentially exacerbating disease spreading. Overall, our study provides basic information on the probing behavior and transmission mechanism of M. hiroglyphicus. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Current knowledge on biodegradable microspheres in drug delivery.

    Science.gov (United States)

    Prajapati, Vipul D; Jani, Girish K; Kapadia, Jinita R

    2015-08-01

    Biodegradable microspheres have gained popularity for delivering a wide variety of molecules via various routes. These types of products have been prepared using various natural and synthetic biodegradable polymers through suitable techniques for desired delivery of various challenging molecules. Selection of biodegradable polymers and technique play a key role in desired drug delivery. This review describes an overview of the fundamental knowledge and status of biodegradable microspheres in effective delivery of various molecules via desired routes with consideration of outlines of various compendial and non-compendial biodegradable polymers, formulation techniques and release mechanism of microspheres, patents and commercial biodegradable microspheres. There are various advantages of using biodegradable polymers including promise of development with different types of molecules. Biocompatibility, low dosage and reduced side effects are some reasons why usage biodegradable microspheres have gained in popularity. Selection of biodegradable polymers and formulation techniques to create microspheres is the biggest challenge in research. In the near future, biodegradable microspheres will become the eco-friendly product for drug delivery of various genes, hormones, proteins and peptides at specific site of body for desired periods of time.

  2. Pragmatic Graph Rewriting Modifications

    OpenAIRE

    Rodgers, Peter; Vidal, Natalia

    1999-01-01

    We present new pragmatic constructs for easing programming in visual graph rewriting programming languages. The first is a modification to the rewriting process for nodes the host graph, where nodes specified as 'Once Only' in the LHS of a rewrite match at most once with a corresponding node in the host graph. This reduces the previously common use of tags to indicate the progress of matching in the graph. The second modification controls the application of LHS graphs, where those specified a...

  3. The current status of community drug testing via the analysis of drugs and drug metabolites in sewage

    Directory of Open Access Journals (Sweden)

    Malcolm J. Reid

    2011-12-01

    Full Text Available Over the past few years the analysis of drug residues in sewage has been promoted as a means of estimating the level of drug use in communities. Measured drug residue concentrations in the sewage are used to determine the load (total mass of the drug being used by the entire community. Knowledge of the size or population of the community then allows for the calculation of drug-use relative to population (typically drug-mass/day/1000 inhabitants which facilitates comparisons between differing communities or populations. Studies have been performed in many European countries, including Norway, as well as in the US and Australia. The approach has successfully estimated the use of cocaine, amphetamine, methamphetamine, MDMA, cannabis, nicotine and alcohol. The analysis of biomarkers of drug use in sewage has great potential to support and complement existing techniques for estimating levels of drug use, and as such has been identified as a promising development by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA; www.emcdda.europa.eu/wastewater-analysis. The approach is not without its challenges, and ongoing collaboration across Europe aims at agreeing upon best-practice and harmonising the methods being used. In Norway development is being performed through the NFR RUSMIDDEL funded DrugMon (www.niva.no/drugmon project that has led to the development of many new techniques, significantly improved our understanding of the uncertainties associated with the approach and allowed the coordination of Europe wide collaboration which has included all important intercalibration exercises. Application of the technique can provide evidence-based and real-time estimates of collective drug use with the resulting data used to improve the much needed estimates of drug use and dependency.

  4. Emerging drugs of abuse: current perspectives on substituted cathinones

    Directory of Open Access Journals (Sweden)

    Paillet-Loilier M

    2014-05-01

    Full Text Available Magalie Paillet-Loilier,1 Alexandre Cesbron,1 Reynald Le Boisselier,2 Joanna Bourgine,1 Danièle Debruyne1,2 1Toxicology and Pharmacology Laboratory, 2Centre d'Evaluation et d'Information sur la Pharmacodépendance – Addictovigilance (CEIP-A, Department of Pharmacology, University Hospital Centre, Caen, France Abstract: Substituted cathinones are synthetic analogs of cathinone that can be considered as derivatives of phenethylamines with a beta-keto group on the side chain. They appeared in the recreational drug market in the mid-2000s and now represent a large class of new popular drugs of abuse. Initially considered as legal highs, their legal status is variable by country and is rapidly changing, with government institutions encouraging their control. Some cathinones (such as diethylpropion or pyrovalerone have been used in a medical setting and bupropion is actually indicated for smoking cessation. Substituted cathinones are widely available from internet websites, retail shops, and street dealers. They can be sold under chemical, evocative or generic names, making their identification difficult. Fortunately, analytical methods have been developed in recent years to solve this problem. Available as powders, substituted cathinones are self-administered by snorting, oral injestion, or intravenous injection. They act as central nervous system stimulants by causing the release of catecholamines (dopamine, noradrenaline, and serotonin and blocking their reuptake in the central and peripheral nervous system. They may also decrease dopamine and serotonin transporter function as nonselective substrates or potent blockers and may inhibit monoamine oxidase effects. Nevertheless, considerable differences have been found in the potencies of the different substituted cathinones in vitro. Desired effects reported by users include increased energy, empathy, and improved libido. Cardiovascular (tachycardia, hypertension and psychiatric

  5. Total colourings of graphs

    CERN Document Server

    Yap, Hian-Poh

    1996-01-01

    This book provides an up-to-date and rapid introduction to an important and currently active topic in graph theory. The author leads the reader to the forefront of research in this area. Complete and easily readable proofs of all the main theorems, together with numerous examples, exercises and open problems are given. The book is suitable for use as a textbook or as seminar material for advanced undergraduate and graduate students. The references are comprehensive and so it will also be useful for researchers as a handbook.

  6. Graphs and matrices

    CERN Document Server

    Bapat, Ravindra B

    2014-01-01

    This new edition illustrates the power of linear algebra in the study of graphs. The emphasis on matrix techniques is greater than in other texts on algebraic graph theory. Important matrices associated with graphs (for example, incidence, adjacency and Laplacian matrices) are treated in detail. Presenting a useful overview of selected topics in algebraic graph theory, early chapters of the text focus on regular graphs, algebraic connectivity, the distance matrix of a tree, and its generalized version for arbitrary graphs, known as the resistance matrix. Coverage of later topics include Laplacian eigenvalues of threshold graphs, the positive definite completion problem and matrix games based on a graph. Such an extensive coverage of the subject area provides a welcome prompt for further exploration. The inclusion of exercises enables practical learning throughout the book. In the new edition, a new chapter is added on the line graph of a tree, while some results in Chapter 6 on Perron-Frobenius theory are reo...

  7. On middle cube graphs

    Directory of Open Access Journals (Sweden)

    C. Dalfo

    2015-10-01

    Full Text Available We study a family of graphs related to the $n$-cube. The middle cube graph of parameter k is the subgraph of $Q_{2k-1}$ induced by the set of vertices whose binary representation has either $k-1$ or $k$ number of ones. The middle cube graphs can be obtained from the well-known odd graphs by doubling their vertex set. Here we study some of the properties of the middle cube graphs in the light of the theory of distance-regular graphs. In particular, we completely determine their spectra (eigenvalues and their multiplicities, and associated eigenvectors.

  8. The current status of orphan drug development in Europe and the US

    OpenAIRE

    Hall, Anthony K; Carlson, Marilyn R

    2014-01-01

    Orphan drug legislation has been introduced in a number of countries in order to stimulate the development of treatments for rare diseases by introducing commercial incentives for companies wishing to undertake that development. In order to navigate the maze of regulatory regulations and procedures so that companies can make proper use of the orphan drug incentives, specialist knowledge is required. This article will review the current status of orphan drug development in the EU and the US, e...

  9. Purification of drugs from biological fluids by counter-current chromatography.

    Science.gov (United States)

    Hochlowski, Jill E; Pan, Jeffrey Y; Searle, Philip A; Buck, Wayne R; Spanton, Stephen G

    2009-08-21

    Experiments were performed to demonstrate the potential of counter-current chromatography (CCC) for the isolation of drugs and their metabolites from biological matrices relevant to the metabolism studies of pharmaceutical research. Examples of typical drugs are spiked into biological media ex vivo to provide test samples for analysis. A mass spectrometer hyphenated to a CCC allows for the detection of small molecule drugs within the matrix through selected ion monitoring, and fraction collection can provide material for further structural elucidation by NMR.

  10. Price competition on graphs

    NARCIS (Netherlands)

    Soetevent, A.R.

    2010-01-01

    This paper extends Hotelling's model of price competition with quadratic transportation costs from a line to graphs. I propose an algorithm to calculate firm-level demand for any given graph, conditional on prices and firm locations. One feature of graph models of price competition is that spatial

  11. Graphing Inequalities, Connecting Meaning

    Science.gov (United States)

    Switzer, J. Matt

    2014-01-01

    Students often have difficulty with graphing inequalities (see Filloy, Rojano, and Rubio 2002; Drijvers 2002), and J. Matt Switzer's students were no exception. Although students can produce graphs for simple inequalities, they often struggle when the format of the inequality is unfamiliar. Even when producing a correct graph of an…

  12. Similarity Measure of Graphs

    Directory of Open Access Journals (Sweden)

    Amine Labriji

    2017-07-01

    Full Text Available The topic of identifying the similarity of graphs was considered as highly recommended research field in the Web semantic, artificial intelligence, the shape recognition and information research. One of the fundamental problems of graph databases is finding similar graphs to a graph query. Existing approaches dealing with this problem are usually based on the nodes and arcs of the two graphs, regardless of parental semantic links. For instance, a common connection is not identified as being part of the similarity of two graphs in cases like two graphs without common concepts, the measure of similarity based on the union of two graphs, or the one based on the notion of maximum common sub-graph (SCM, or the distance of edition of graphs. This leads to an inadequate situation in the context of information research. To overcome this problem, we suggest a new measure of similarity between graphs, based on the similarity measure of Wu and Palmer. We have shown that this new measure satisfies the properties of a measure of similarities and we applied this new measure on examples. The results show that our measure provides a run time with a gain of time compared to existing approaches. In addition, we compared the relevance of the similarity values obtained, it appears that this new graphs measure is advantageous and  offers a contribution to solving the problem mentioned above.

  13. Distance-regular graphs

    NARCIS (Netherlands)

    van Dam, Edwin R.; Koolen, Jack H.; Tanaka, Hajime

    2016-01-01

    This is a survey of distance-regular graphs. We present an introduction to distance-regular graphs for the reader who is unfamiliar with the subject, and then give an overview of some developments in the area of distance-regular graphs since the monograph 'BCN'[Brouwer, A.E., Cohen, A.M., Neumaier,

  14. Fuzzy Graph Language Recognizability

    OpenAIRE

    Kalampakas , Antonios; Spartalis , Stefanos; Iliadis , Lazaros

    2012-01-01

    Part 5: Fuzzy Logic; International audience; Fuzzy graph language recognizability is introduced along the lines of the established theory of syntactic graph language recognizability by virtue of the algebraic structure of magmoids. The main closure properties of the corresponding class are investigated and several interesting examples of fuzzy graph languages are examined.

  15. Spectra of Graphs

    NARCIS (Netherlands)

    Brouwer, A.E.; Haemers, W.H.

    2012-01-01

    This book gives an elementary treatment of the basic material about graph spectra, both for ordinary, and Laplace and Seidel spectra. The text progresses systematically, by covering standard topics before presenting some new material on trees, strongly regular graphs, two-graphs, association

  16. Graphs and Homomorphisms

    CERN Document Server

    Hell, Pavol

    2004-01-01

    This is a book about graph homomorphisms. Graph theory is now an established discipline but the study of graph homomorphisms has only recently begun to gain wide acceptance and interest. The subject gives a useful perspective in areas such as graph reconstruction, products, fractional and circular colourings, and has applications in complexity theory, artificial intelligence, telecommunication, and, most recently, statistical physics.Based on the authors' lecture notes for graduate courses, this book can be used as a textbook for a second course in graph theory at 4th year or master's level an

  17. Detecting peptidic drugs, drug candidates and analogs in sports doping: current status and future directions.

    Science.gov (United States)

    Thevis, Mario; Thomas, Andreas; Schänzer, Wilhelm

    2014-12-01

    With the growing availability of mature systems and strategies in biotechnology and the continuously expanding knowledge of cellular processes and involved biomolecules, human sports drug testing has become a considerably complex field in the arena of analytical chemistry. Proving the exogenous origin of peptidic drugs and respective analogs at lowest concentration levels in biological specimens (commonly blood, serum and urine) of rather limited volume is required to pursue an action against cheating athletes. Therefore, approaches employing chromatographic-mass spectrometric, electrophoretic, immunological and combined test methods have been required and developed. These allow detecting the misuse of peptidic compounds of lower (such as growth hormone-releasing peptides, ARA-290, TB-500, AOD-9604, CJC-1295, desmopressin, luteinizing hormone-releasing hormones, synacthen, etc.), intermediate (e.g., insulins, IGF-1 and analogs, 'full-length' mechano growth factor, growth hormone, chorionic gonadotropin, erythropoietin, etc.) and higher (e.g., stamulumab) molecular mass with desired specificity and sensitivity. A gap between the technically possible detection and the day-to-day analytical practice, however, still needs to be closed.

  18. Simplicial complexes of graphs

    CERN Document Server

    Jonsson, Jakob

    2008-01-01

    A graph complex is a finite family of graphs closed under deletion of edges. Graph complexes show up naturally in many different areas of mathematics, including commutative algebra, geometry, and knot theory. Identifying each graph with its edge set, one may view a graph complex as a simplicial complex and hence interpret it as a geometric object. This volume examines topological properties of graph complexes, focusing on homotopy type and homology. Many of the proofs are based on Robin Forman's discrete version of Morse theory. As a byproduct, this volume also provides a loosely defined toolbox for attacking problems in topological combinatorics via discrete Morse theory. In terms of simplicity and power, arguably the most efficient tool is Forman's divide and conquer approach via decision trees; it is successfully applied to a large number of graph and digraph complexes.

  19. Current Situation, Determinants, and Solutions to Drug Shortages in Shaanxi Province, China: A Qualitative Study.

    Science.gov (United States)

    Yang, Caijun; Wu, Lina; Cai, Wenfang; Zhu, Wenwen; Shen, Qian; Li, Zongjie; Fang, Yu

    2016-01-01

    Drug shortages were a complex global problem. The aim of this study was to analyze, characterize, and assess the drug shortages, and identify possible solutions in Shaanxi Province, western China. A qualitative methodological approach was conducted during May-June 2015 and December 2015-January 2016. Semi-structured interviews were performed to gather information from representatives of hospital pharmacists, wholesalers, pharmaceutical producers, and local health authorities. Thirty participants took part in the study. Eight traditional Chinese medicines and 87 types of biologicals and chemicals were reported to be in short supply. Most were essential medicines. Five main determinants of drug shortages were detected: too low prices, too low market demands, Good Manufacturing Practice (GMP) issues, materials issues, and approval issues for imported drugs. Five different solutions were proposed by the participants: 1) let the market decide the drug price; 2) establish an information platform; 3) establish a reserve system; 4) enhance the communication among the three parties in the supply chain; and 5) improve hospital inventory management. Western China was currently experiencing a serious drug shortage. Numerous reasons for the shortage were identified. Most drug shortages in China were currently because of "too low prices." To solve this problem, all of the stakeholders, especially the government, needed to participate in managing the drug shortages.

  20. Fed-state gastric media and drug analysis techniques: Current status and points to consider.

    Science.gov (United States)

    Baxevanis, Fotios; Kuiper, Jesse; Fotaki, Nikoletta

    2016-10-01

    Gastric fed state conditions can have a significant effect on drug dissolution and absorption. In vitro dissolution tests with simple aqueous media cannot usually predict drugs' in vivo response, as several factors such as the meal content, the gastric emptying and possible interactions between food and drug formulations can affect drug's pharmacokinetics. Good understanding of the effect of the in vivo fed gastric conditions on the drug is essential for the development of biorelevant dissolution media simulating the gastric environment after the administration of the standard high fat meal proposed by the FDA and the EMA in bioavailability/bioequivalence (BA/BE) studies. The analysis of drugs in fed state media can be quite challenging as most analytical protocols currently employed are time consuming and labour intensive. In this review, an overview of the in vivo gastric conditions and the biorelevant media used for their in vitro simulation are described. Furthermore an analysis of the physicochemical properties of the drugs and the formulations related to food effect is given. In terms of drug analysis, the protocols currently used for the fed state media sample treatment and analysis and the analytical challenges and needs emerging for more efficient and time saving techniques for a broad spectrum of compounds are being discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Current trends in the use of vitamin E-based micellar nanocarriers for anticancer drug delivery.

    Science.gov (United States)

    Muddineti, Omkara Swami; Ghosh, Balaram; Biswas, Swati

    2017-06-01

    Owing to the complexity of cancer pathogenesis, conventional chemotherapy can be an inadequate method of killing cancer cells effectively. Nanoparticle-based drug delivery systems have been widely exploited pre-clinically in recent years. Areas covered: Incorporation of vitamin-E in nanocarriers have the advantage of (1) improving the hydrophobicity of the drug delivery system, thereby improving the solubility of the loaded poorly soluble anticancer drugs, (2) enhancing the biocompatibility of the polymeric drug carriers, and (3) improving the anticancer potential of the chemotherapeutic agents by reversing the cellular drug resistance via simultaneous administration. In addition to being a powerful antioxidant, vitamin E demonstrated its anticancer potential by inducing apoptosis in various cancer cell lines. Various vitamin E analogs have proven their ability to cause marked inhibition of drug efflux transporters. Expert opinion: The review discusses the potential of incorporating vitamin E in the polymeric micelles which are designed to carry poorly water-soluble anticancer drugs. Current applications of various vitamin E-based polymeric micelles with emphasis on the use of α-tocopherol, D-α-tocopheryl succinate (α-TOS) and its conjugates such as D-α-tocopheryl polyethylene glycol-succinate (TPGS) in micellar system is delineated. Advantages of utilizing polymeric micelles for drug delivery and the challenges to treat cancer, including multiple drug resistance have been discussed.

  2. Measurement of Drug Craving in Persian Speaking Subjects; a Review on Current Experiences and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Masoomeh Maarefvand

    2012-09-01

    Full Text Available Background: Drug craving is considered as one of the main cores of drug dependency and addiction. Multidimensionality of drug craving, its cultural-bounded features and its intra individual rapidly changing nature makes it difficult to be measured. Nowadays, regarding different psychometric approaches, there are various instruments available for measurement of different aspects of drug craving but mainly for Latin-based languages in North America and European countries. High prevalence and special conditions, and unique subcultures in substance abuse and addiction in many countries, like Iran, make the design of culturally validated instruments for drug craving assessment priority. Materials and Methods: Comprehensive review on drug craving measurement instruments for Persian speaking subjects have been performed by searching in databases (ELSEVIER, Science Direct and Scientific Information Database (SID and investigating of related documents on regional experiences. Results: In this article seven main categories of drug craving instruments have been reviewed focusing on validated versions in Persian language including: self-reports, reinforcement “proxies”, drug self administration, psycho physiological responding, neurobiological responding, cognitive processing and expressive methods. Conclusion: Reviewing on weak and strength points of each instrument group and national and regional experiences shows that designing and validating a new series of ecologically-validated instruments for multidimensional measurement of drug craving in different addiction subcultures should be prioritized to cover current methodological gaps in substance abuse studies in Iran.

  3. Current good manufacturing practice and investigational new drugs intended for use in clinical trials. Final rule.

    Science.gov (United States)

    2008-07-15

    The Food and Drug Administration (FDA) is amending the current good manufacturing practice (CGMP) regulations for human drugs, including biological products, to exempt most phase 1 investigational drugs from complying with the regulatory CGMP requirements. FDA will continue to exercise oversight of the manufacture of these drugs under FDA's general statutory CGMP authority and through review of the investigational new drug applications (IND). In addition, elsewhere in this issue of the Federal Register, FDA is announcing the availability of a guidance document entitled "Guidance for Industry: CGMP for Phase 1 Investigational Drugs" dated November 2007 (the companion guidance). This guidance document sets forth recommendations on approaches to compliance with statutory CGMP for the exempted phase 1 investigational drugs. FDA is taking this action to focus a manufacturer's effort on applying CGMP that is appropriate and meaningful for the manufacture of the earliest stage investigational drug products intended for use in phase 1 clinical trials while ensuring safety and quality. This action will also streamline and promote the drug development process.

  4. Current and emerging lipid-based systems for transdermal drug delivery.

    Science.gov (United States)

    Singla, Sumeet K; Sachdeva, Vishal

    2015-01-01

    Developing a transdermal drug delivery system is a challenging task considering the selective permeability of the skin and the physicochemical properties the drug must possess to permeate through the skin. Lipid-based drug delivery systems have contributed a great deal in this direction in the last few decades, and thereby have helped to expand the range of therapeutic molecules that can be delivered through the skin in a safe and effective manner. Additionally, vesicular delivery systems such as nanoparticles and emulsions have also played important roles in providing alternative novel approaches for drug delivery. In this article, we will discuss some of the current and future lipid-based systems for transdermal drug delivery along with the associated challenges.

  5. Indexing molecules with chemical graph identifiers.

    Science.gov (United States)

    Gregori-Puigjané, Elisabet; Garriga-Sust, Rut; Mestres, Jordi

    2011-09-01

    Fast and robust algorithms for indexing molecules have been historically considered strategic tools for the management and storage of large chemical libraries. This work introduces a modified and further extended version of the molecular equivalence number naming adaptation of the Morgan algorithm (J Chem Inf Comput Sci 2001, 41, 181-185) for the generation of a chemical graph identifier (CGI). This new version corrects for the collisions recognized in the original adaptation and includes the ability to deal with graph canonicalization, ensembles (salts), and isomerism (tautomerism, regioisomerism, optical isomerism, and geometrical isomerism) in a flexible manner. Validation of the current CGI implementation was performed on the open NCI database and the drug-like subset of the ZINC database containing 260,071 and 5,348,089 structures, respectively. The results were compared with those obtained with some of the most widely used indexing codes, such as the CACTVS hash code and the new InChIKey. The analyses emphasize the fact that compound management activities, like duplicate analysis of chemical libraries, are sensitive to the exact definition of compound uniqueness and thus still depend, to a minor extent, on the type and flexibility of the molecular index being used. Copyright © 2011 Wiley Periodicals, Inc.

  6. The current status of orphan drug development in Europe and the US.

    Science.gov (United States)

    Hall, Anthony K; Carlson, Marilyn R

    2014-02-01

    Orphan drug legislation has been introduced in a number of countries in order to stimulate the development of treatments for rare diseases by introducing commercial incentives for companies wishing to undertake that development. In order to navigate the maze of regulatory regulations and procedures so that companies can make proper use of the orphan drug incentives, specialist knowledge is required. This article will review the current status of orphan drug development in the EU and the US, explain the incentives and procedures, and touch on the role of patient organisations in the process.

  7. Disease management research using event graphs.

    Science.gov (United States)

    Allore, H G; Schruben, L W

    2000-08-01

    Event Graphs, conditional representations of stochastic relationships between discrete events, simulate disease dynamics. In this paper, we demonstrate how Event Graphs, at an appropriate abstraction level, also extend and organize scientific knowledge about diseases. They can identify promising treatment strategies and directions for further research and provide enough detail for testing combinations of new medicines and interventions. Event Graphs can be enriched to incorporate and validate data and test new theories to reflect an expanding dynamic scientific knowledge base and establish performance criteria for the economic viability of new treatments. To illustrate, an Event Graph is developed for mastitis, a costly dairy cattle disease, for which extensive scientific literature exists. With only a modest amount of imagination, the methodology presented here can be seen to apply modeling to any disease, human, plant, or animal. The Event Graph simulation presented here is currently being used in research and in a new veterinary epidemiology course. Copyright 2000 Academic Press.

  8. Introductory graph theory

    CERN Document Server

    Chartrand, Gary

    1984-01-01

    Graph theory is used today in the physical sciences, social sciences, computer science, and other areas. Introductory Graph Theory presents a nontechnical introduction to this exciting field in a clear, lively, and informative style. Author Gary Chartrand covers the important elementary topics of graph theory and its applications. In addition, he presents a large variety of proofs designed to strengthen mathematical techniques and offers challenging opportunities to have fun with mathematics. Ten major topics - profusely illustrated - include: Mathematical Models, Elementary Concepts of Grap

  9. Price Competition on Graphs

    OpenAIRE

    Adriaan R. Soetevent

    2010-01-01

    This paper extends Hotelling's model of price competition with quadratic transportation costs from a line to graphs. I propose an algorithm to calculate firm-level demand for any given graph, conditional on prices and firm locations. One feature of graph models of price competition is that spatial discontinuities in firm-level demand may occur. I show that the existence result of D'Aspremont et al. (1979) does not extend to simple star graphs. I conjecture that this non-existence result holds...

  10. Price Competition on Graphs

    OpenAIRE

    Pim Heijnen; Adriaan Soetevent

    2014-01-01

    This paper extends Hotelling's model of price competition with quadratic transportation costs from a line to graphs. We derive an algorithm to calculate firm-level demand for any given graph, conditional on prices and firm locations. These graph models of price competition may lead to spatial discontinuities in firm-level demand. We show that the existence result of D'Aspremont et al. (1979) does not extend to simple star graphs and conjecture that this non-existence result holds more general...

  11. Pattern graph rewrite systems

    Directory of Open Access Journals (Sweden)

    Aleks Kissinger

    2014-03-01

    Full Text Available String diagrams are a powerful tool for reasoning about physical processes, logic circuits, tensor networks, and many other compositional structures. Dixon, Duncan and Kissinger introduced string graphs, which are a combinatoric representations of string diagrams, amenable to automated reasoning about diagrammatic theories via graph rewrite systems. In this extended abstract, we show how the power of such rewrite systems can be greatly extended by introducing pattern graphs, which provide a means of expressing infinite families of rewrite rules where certain marked subgraphs, called !-boxes ("bang boxes", on both sides of a rule can be copied any number of times or removed. After reviewing the string graph formalism, we show how string graphs can be extended to pattern graphs and how pattern graphs and pattern rewrite rules can be instantiated to concrete string graphs and rewrite rules. We then provide examples demonstrating the expressive power of pattern graphs and how they can be applied to study interacting algebraic structures that are central to categorical quantum mechanics.

  12. Functions and graphs

    CERN Document Server

    Gelfand, I M; Shnol, E E

    1969-01-01

    The second in a series of systematic studies by a celebrated mathematician I. M. Gelfand and colleagues, this volume presents students with a well-illustrated sequence of problems and exercises designed to illuminate the properties of functions and graphs. Since readers do not have the benefit of a blackboard on which a teacher constructs a graph, the authors abandoned the customary use of diagrams in which only the final form of the graph appears; instead, the book's margins feature step-by-step diagrams for the complete construction of each graph. The first part of the book employs simple fu

  13. Creating more effective graphs

    CERN Document Server

    Robbins, Naomi B

    2012-01-01

    A succinct and highly readable guide to creating effective graphs The right graph can be a powerful tool for communicating information, improving a presentation, or conveying your point in print. If your professional endeavors call for you to present data graphically, here's a book that can help you do it more effectively. Creating More Effective Graphs gives you the basic knowledge and techniques required to choose and create appropriate graphs for a broad range of applications. Using real-world examples everyone can relate to, the author draws on her years of experience in gr

  14. Graph Generator Survey

    Energy Technology Data Exchange (ETDEWEB)

    Lothian, Joshua [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Powers, Sarah S. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Sullivan, Blair D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Baker, Matthew B. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Schrock, Jonathan [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Poole, Stephen W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2013-10-01

    The benchmarking effort within the Extreme Scale Systems Center at Oak Ridge National Laboratory seeks to provide High Performance Computing benchmarks and test suites of interest to the DoD sponsor. The work described in this report is a part of the effort focusing on graph generation. A previously developed benchmark, SystemBurn, allowed the emulation of different application behavior profiles within a single framework. To complement this effort, similar capabilities are desired for graph-centric problems. This report examines existing synthetic graph generator implementations in preparation for further study on the properties of their generated synthetic graphs.

  15. Loose Graph Simulations

    DEFF Research Database (Denmark)

    Mansutti, Alessio; Miculan, Marino; Peressotti, Marco

    2017-01-01

    We introduce loose graph simulations (LGS), a new notion about labelled graphs which subsumes in an intuitive and natural way subgraph isomorphism (SGI), regular language pattern matching (RLPM) and graph simulation (GS). Being a unification of all these notions, LGS allows us to express directly...... also problems which are “mixed” instances of previous ones, and hence which would not fit easily in any of them. After the definition and some examples, we show that the problem of finding loose graph simulations is NP-complete, we provide formal translation of SGI, RLPM, and GS into LGSs, and we give...

  16. Graph Compression by BFS

    Directory of Open Access Journals (Sweden)

    Alberto Apostolico

    2009-08-01

    Full Text Available The Web Graph is a large-scale graph that does not fit in main memory, so that lossless compression methods have been proposed for it. This paper introduces a compression scheme that combines efficient storage with fast retrieval for the information in a node. The scheme exploits the properties of the Web Graph without assuming an ordering of the URLs, so that it may be applied to more general graphs. Tests on some datasets of use achieve space savings of about 10% over existing methods.

  17. 21 CFR 1404.135 - May the Office of National Drug Control Policy exclude a person who is not currently...

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false May the Office of National Drug Control Policy exclude a person who is not currently participating in a nonprocurement transaction? 1404.135 Section 1404.135 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) General § 1404.135 May the...

  18. Structural basis of drugs that increase cardiac inward rectifier Kir2.1 currents.

    Science.gov (United States)

    Gómez, Ricardo; Caballero, Ricardo; Barana, Adriana; Amorós, Irene; De Palm, Sue-Haida; Matamoros, Marcos; Núñez, Mercedes; Pérez-Hernández, Marta; Iriepa, Isabel; Tamargo, Juan; Delpón, Eva

    2014-11-01

    We hypothesize that some drugs, besides flecainide, increase the inward rectifier current (IK1) generated by Kir2.1 homotetramers (IKir2.1) and thus, exhibit pro- and/or antiarrhythmic effects particularly at the ventricular level. To test this hypothesis, we analysed the effects of propafenone, atenolol, dronedarone, and timolol on Kir2.x channels. Currents were recorded with the patch-clamp technique using whole-cell, inside-out, and cell-attached configurations. Propafenone (0.1 nM-1 µM) did not modify either IK1 recorded in human right atrial myocytes or the current generated by homo- or heterotetramers of Kir2.2 and 2.3 channels recorded in transiently transfected Chinese hamster ovary cells. On the other hand, propafenone increased IKir2.1 (EC50 = 12.0 ± 3.0 nM) as a consequence of its interaction with Cys311, an effect which decreased inward rectification of the current. Propafenone significantly increased mean open time and opening frequency at all the voltages tested, resulting in a significant increase of the mean open probability of the channel. Timolol, which interacted with Cys311, was also able to increase IKir2.1. On the contrary, neither atenolol nor dronedarone modified IKir2.1. Molecular modelling of the Kir2.1-drugs interaction allowed identification of the pharmacophore of drugs that increase IKir2.1. Kir2.1 channels exhibit a binding site determined by Cys311 that is responsible for drug-induced IKir2.1 increase. Drug binding decreases channel affinity for polyamines and current rectification, and can be a mechanism of drug-induced pro- and antiarrhythmic effects not considered until now. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  19. Graph Theory. 1. Fragmentation of Structural Graphs

    Directory of Open Access Journals (Sweden)

    Lorentz JÄNTSCHI

    2002-12-01

    Full Text Available The investigation of structural graphs has many fields of applications in engineering, especially in applied sciences like as applied chemistry and physics, computer sciences and automation, electronics and telecommunication. The main subject of the paper is to express fragmentation criteria in graph using a new method of investigation: terminal paths. Using terminal paths are defined most of the fragmentation criteria that are in use in molecular topology, but the fields of applications are more generally than that, as I mentioned before. Graphical examples of fragmentation are given for every fragmentation criteria. Note that all fragmentation is made with a computer program that implements a routine for every criterion.[1] A web routine for tracing all terminal paths in graph can be found at the address: http://vl.academicdirect.ro/molecular_topology/tpaths/ [1] M. V. Diudea, I. Gutman, L. Jäntschi, Molecular Topology, Nova Science, Commack, New York, 2001, 2002.

  20. Graph Transforming Java Data

    NARCIS (Netherlands)

    de Mol, M.J.; Rensink, Arend; Hunt, James J.

    This paper introduces an approach for adding graph transformation-based functionality to existing JAVA programs. The approach relies on a set of annotations to identify the intended graph structure, as well as on user methods to manipulate that structure, within the user’s own JAVA class

  1. Distance-transitive graphs

    NARCIS (Netherlands)

    Cohen, A.M.; Beineke, L.W.; Wilson, R.J.; Cameron, P.J.

    2004-01-01

    In this chapter we investigate the classification of distance-transitive graphs: these are graphs whose automorphism groups are transitive on each of the sets of pairs of vertices at distance i, for i = 0, 1,.... We provide an introduction into the field. By use of the classification of finite

  2. Adventures in graph theory

    CERN Document Server

    Joyner, W David

    2017-01-01

    This textbook acts as a pathway to higher mathematics by seeking and illuminating the connections between graph theory and diverse fields of mathematics, such as calculus on manifolds, group theory, algebraic curves, Fourier analysis, cryptography and other areas of combinatorics. An overview of graph theory definitions and polynomial invariants for graphs prepares the reader for the subsequent dive into the applications of graph theory. To pique the reader’s interest in areas of possible exploration, recent results in mathematics appear throughout the book, accompanied with examples of related graphs, how they arise, and what their valuable uses are. The consequences of graph theory covered by the authors are complicated and far-reaching, so topics are always exhibited in a user-friendly manner with copious graphs, exercises, and Sage code for the computation of equations. Samples of the book’s source code can be found at github.com/springer-math/adventures-in-graph-theory. The text is geared towards ad...

  3. Recognition of fractal graphs

    NARCIS (Netherlands)

    Perepelitsa, VA; Sergienko, [No Value; Kochkarov, AM

    1999-01-01

    Definitions of prefractal and fractal graphs are introduced, and they are used to formulate mathematical models in different fields of knowledge. The topicality of fractal-graph recognition from the point of view, of fundamental improvement in the efficiency of the solution of algorithmic problems

  4. Graph Colouring Algorithms

    DEFF Research Database (Denmark)

    Husfeldt, Thore

    2015-01-01

    This chapter presents an introduction to graph colouring algorithms. The focus is on vertex-colouring algorithms that work for general classes of graphs with worst-case performance guarantees in a sequential model of computation. The presentation aims to demonstrate the breadth of available...

  5. Packing Degenerate Graphs Greedily

    Czech Academy of Sciences Publication Activity Database

    Allen, P.; Böttcher, J.; Hladký, J.; Piguet, Diana

    2017-01-01

    Roč. 61, August (2017), s. 45-51 ISSN 1571-0653 R&D Projects: GA ČR GJ16-07822Y Institutional support: RVO:67985807 Keywords : tree packing conjecture * graph packing * graph processes Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics

  6. Generalized connectivity of graphs

    CERN Document Server

    Li, Xueliang

    2016-01-01

    Noteworthy results, proof techniques, open problems and conjectures in generalized (edge-) connectivity are discussed in this book. Both theoretical and practical analyses for generalized (edge-) connectivity of graphs are provided. Topics covered in this book include: generalized (edge-) connectivity of graph classes, algorithms, computational complexity, sharp bounds, Nordhaus-Gaddum-type results, maximum generalized local connectivity, extremal problems, random graphs, multigraphs, relations with the Steiner tree packing problem and generalizations of connectivity. This book enables graduate students to understand and master a segment of graph theory and combinatorial optimization. Researchers in graph theory, combinatorics, combinatorial optimization, probability, computer science, discrete algorithms, complexity analysis, network design, and the information transferring models will find this book useful in their studies.

  7. Current advances in mathematical modeling of anti-cancer drug penetration into tumor tissues.

    Science.gov (United States)

    Kim, Munju; Gillies, Robert J; Rejniak, Katarzyna A

    2013-11-18

    Delivery of anti-cancer drugs to tumor tissues, including their interstitial transport and cellular uptake, is a complex process involving various biochemical, mechanical, and biophysical factors. Mathematical modeling provides a means through which to understand this complexity better, as well as to examine interactions between contributing components in a systematic way via computational simulations and quantitative analyses. In this review, we present the current state of mathematical modeling approaches that address phenomena related to drug delivery. We describe how various types of models were used to predict spatio-temporal distributions of drugs within the tumor tissue, to simulate different ways to overcome barriers to drug transport, or to optimize treatment schedules. Finally, we discuss how integration of mathematical modeling with experimental or clinical data can provide better tools to understand the drug delivery process, in particular to examine the specific tissue- or compound-related factors that limit drug penetration through tumors. Such tools will be important in designing new chemotherapy targets and optimal treatment strategies, as well as in developing non-invasive diagnosis to monitor treatment response and detect tumor recurrence.

  8. pH-Responsive carriers for oral drug delivery: challenges and opportunities of current platforms.

    Science.gov (United States)

    Liu, Lin; Yao, WenDong; Rao, YueFeng; Lu, XiaoYang; Gao, JianQing

    2017-11-01

    Oral administration is a desirable alternative of parenteral administration due to the convenience and increased compliance to patients, especially for chronic diseases that require frequent administration. The oral drug delivery is a dynamic research field despite the numerous challenges limiting their effective delivery, such as enzyme degradation, hydrolysis and low permeability of intestinal epithelium in the gastrointestinal (GI) tract. pH-Responsive carriers offer excellent potential as oral therapeutic systems due to enhancing the stability of drug delivery in stomach and achieving controlled release in intestines. This review provides a wide perspective on current status of pH-responsive oral drug delivery systems prepared mainly with organic polymers or inorganic materials, including the strategies used to overcome GI barriers, the challenges in their development and future prospects, with focus on technology trends to improve the bioavailability of orally delivered drugs, the mechanisms of drug release from pH-responsive oral formulations, and their application for drug delivery, such as protein and peptide therapeutics, vaccination, inflammatory bowel disease (IBD) and bacterial infections.

  9. Current prescription status of antihypertensive drugs with special reference to the use of diuretics in Japan.

    Science.gov (United States)

    Ibaraki, Ai; Goto, Wataru; Iura, Rie; Tominaga, Mitsuhiro; Tsuchihashi, Takuya

    2017-02-01

    The guidelines for the management of hypertension recommend the inclusion of diuretics, especially when three or more antihypertensive drugs are used. The present study investigated the current prescription status of antihypertensive drugs with a particular focus on the use of diuretics in a local district in Japan. Prescriptions, including antihypertensive drugs, were collected from a dispensing pharmacy of the Yahata Pharmacist Association, located in Kitakyushu City, in October 2014. Of the 10 585 prescriptions, calcium channel blockers (CCBs) were prescribed in 73.5%, followed by angiotensin II receptor blockers (ARB, 62.7%), diuretics (16.5%) and β-blockers (13.6%). The average number of drugs used was 1.80. The rates of prescription of diuretics for patients with one, two, three and four drugs were 0.6%, 13.1%, 55.2% and 82.6%, respectively. Diuretics were more frequently prescribed in elderly patients, and the prescription rate of doctors in hospitals was significantly higher than that of general practitioners (19.1% vs. 15.7%, Pdiuretics were prescribed combination tablets of hydrochlorothiazide with ARB, whereas trichlormethiazide (34.9%) and indapamide (19.8%) were used in other patients. Based on these findings, the use of diuretics remains limited, even among patients taking multiple antihypertensive drugs.

  10. Current knowledge of microRNA-mediated regulation of drug metabolism in humans.

    Science.gov (United States)

    Nakano, Masataka; Nakajima, Miki

    2018-05-01

    Understanding the factors causing inter- and intra-individual differences in drug metabolism potencies is required for the practice of personalized or precision medicine, as well as for the promotion of efficient drug development. The expression of drug-metabolizing enzymes is controlled by transcriptional regulation by nuclear receptors and transcriptional factors, epigenetic regulation, such as DNA methylation and histone acetylation, and post-translational modification. In addition to such regulation mechanisms, recent studies revealed that microRNAs (miRNAs), endogenous ~22-nucleotide non-coding RNAs that regulate gene expression through the translational repression and degradation of mRNAs, significantly contribute to post-transcriptional regulation of drug-metabolizing enzymes. Areas covered: This review summarizes the current knowledge regarding miRNAs-dependent regulation of drug-metabolizing enzymes and transcriptional factors and its physiological and clinical significance. We also describe recent advances in miRNA-dependent regulation research, showing that the presence of pseudogenes, single-nucleotide polymorphisms, and RNA editing affects miRNA targeting. Expert opinion: It is unwavering fact that miRNAs are critical factors causing inter- and intra-individual differences in the expression of drug-metabolizing enzymes. Consideration of miRNA-dependent regulation would be a helpful tool for optimizing personalized and precision medicine.

  11. Autoregressive Moving Average Graph Filtering

    OpenAIRE

    Isufi, Elvin; Loukas, Andreas; Simonetto, Andrea; Leus, Geert

    2016-01-01

    One of the cornerstones of the field of signal processing on graphs are graph filters, direct analogues of classical filters, but intended for signals defined on graphs. This work brings forth new insights on the distributed graph filtering problem. We design a family of autoregressive moving average (ARMA) recursions, which (i) are able to approximate any desired graph frequency response, and (ii) give exact solutions for tasks such as graph signal denoising and interpolation. The design phi...

  12. Subgraph detection using graph signals

    KAUST Repository

    Chepuri, Sundeep Prabhakar

    2017-03-06

    In this paper we develop statistical detection theory for graph signals. In particular, given two graphs, namely, a background graph that represents an usual activity and an alternative graph that represents some unusual activity, we are interested in answering the following question: To which of the two graphs does the observed graph signal fit the best? To begin with, we assume both the graphs are known, and derive an optimal Neyman-Pearson detector. Next, we derive a suboptimal detector for the case when the alternative graph is not known. The developed theory is illustrated with numerical experiments.

  13. Subgraph detection using graph signals

    KAUST Repository

    Chepuri, Sundeep Prabhakar; Leus, Geert

    2017-01-01

    In this paper we develop statistical detection theory for graph signals. In particular, given two graphs, namely, a background graph that represents an usual activity and an alternative graph that represents some unusual activity, we are interested in answering the following question: To which of the two graphs does the observed graph signal fit the best? To begin with, we assume both the graphs are known, and derive an optimal Neyman-Pearson detector. Next, we derive a suboptimal detector for the case when the alternative graph is not known. The developed theory is illustrated with numerical experiments.

  14. The current state of GPCR-based drug discovery to treat metabolic disease.

    Science.gov (United States)

    Sloop, Kyle W; Emmerson, Paul J; Statnick, Michael A; Willard, Francis S

    2018-02-02

    One approach of modern drug discovery is to identify agents that enhance or diminish signal transduction cascades in various cell types and tissues by modulating the activity of GPCRs. This strategy has resulted in the development of new medicines to treat many conditions, including cardiovascular disease, psychiatric disorders, HIV/AIDS, certain forms of cancer and Type 2 diabetes mellitus (T2DM). These successes justify further pursuit of GPCRs as disease targets and provide key learning that should help guide identifying future therapeutic agents. This report reviews the current landscape of GPCR drug discovery with emphasis on efforts aimed at developing new molecules for treating T2DM and obesity. We analyse historical efforts to generate GPCR-based drugs to treat metabolic disease in terms of causal factors leading to success and failure in this endeavour. © 2018 The British Pharmacological Society.

  15. Groups, graphs and random walks

    CERN Document Server

    Salvatori, Maura; Sava-Huss, Ecaterina

    2017-01-01

    An accessible and panoramic account of the theory of random walks on groups and graphs, stressing the strong connections of the theory with other branches of mathematics, including geometric and combinatorial group theory, potential analysis, and theoretical computer science. This volume brings together original surveys and research-expository papers from renowned and leading experts, many of whom spoke at the workshop 'Groups, Graphs and Random Walks' celebrating the sixtieth birthday of Wolfgang Woess in Cortona, Italy. Topics include: growth and amenability of groups; Schrödinger operators and symbolic dynamics; ergodic theorems; Thompson's group F; Poisson boundaries; probability theory on buildings and groups of Lie type; structure trees for edge cuts in networks; and mathematical crystallography. In what is currently a fast-growing area of mathematics, this book provides an up-to-date and valuable reference for both researchers and graduate students, from which future research activities will undoubted...

  16. Extremal graph theory

    CERN Document Server

    Bollobas, Bela

    2004-01-01

    The ever-expanding field of extremal graph theory encompasses a diverse array of problem-solving methods, including applications to economics, computer science, and optimization theory. This volume, based on a series of lectures delivered to graduate students at the University of Cambridge, presents a concise yet comprehensive treatment of extremal graph theory.Unlike most graph theory treatises, this text features complete proofs for almost all of its results. Further insights into theory are provided by the numerous exercises of varying degrees of difficulty that accompany each chapter. A

  17. PREVALENCE OF MULTIPLE ADDICTIONS AND CURRENT TREATMENT BY DRUG TREATMENT CENTRES IN DURBAN, SOUTH AFRICA

    Directory of Open Access Journals (Sweden)

    Keen, Helen

    2015-09-01

    Full Text Available Substance-use disorders (SUD cause severe problems both globally and locally. Research suggests that multiple addictions create a more complex illness. This study investigated whether in-patients admitted for SUD at three drug treatment centres in Durban, South Africa had other, undiagnosed addictions. It utilised a three-phase concurrent mixed-methods design and initially screened for gambling and sex addiction. Results showed that, of the sample of 123 participants, 54% had either sex or gambling and 24% had both addictions which current treatment programmes neither assessed for nor treated. Recommendations include suggestions to update current assessment and treatment approaches and the need to train professional staff at drug treatment centres.

  18. Quantum Graphs And Their Resonance Properties

    International Nuclear Information System (INIS)

    Lipovsky, J.

    2016-01-01

    In the current review, we study the model of quantum graphs. We focus mainly on the resonance properties of quantum graphs. We define resolvent and scattering resonances and show their equivalence. We present various results on the asymptotics of the number of resolvent resonances in both non-magnetic and magnetic quantum graphs and find bounds on the coefficient by the leading term of the asymptotics. We explain methods how to find the spectral and resonance condition. Most of the notions and theorems are illustrated in examples. We show how to find resonances numerically and, in a simple example, we find trajectories of resonances in the complex plane. We discuss Fermi’s golden rule for quantum graphs and distribution of the mean intensity for the topological resonances. (author)

  19. Use of Attack Graphs in Security Systems

    Directory of Open Access Journals (Sweden)

    Vivek Shandilya

    2014-01-01

    Full Text Available Attack graphs have been used to model the vulnerabilities of the systems and their potential exploits. The successful exploits leading to the partial/total failure of the systems are subject of keen security interest. Considerable effort has been expended in exhaustive modeling, analyses, detection, and mitigation of attacks. One prominent methodology involves constructing attack graphs of the pertinent system for analysis and response strategies. This not only gives the simplified representation of the system, but also allows prioritizing the security properties whose violations are of greater concern, for both detection and repair. We present a survey and critical study of state-of-the-art technologies in attack graph generation and use in security system. Based on our research, we identify the potential, challenges, and direction of the current research in using attack graphs.

  20. Strategies of bringing drug product marketing applications to meet current regulatory standards.

    Science.gov (United States)

    Wu, Yan; Freed, Anita; Lavrich, David; Raghavachari, Ramesh; Huynh-Ba, Kim; Shah, Ketan; Alasandro, Mark

    2015-08-01

    In the past decade, many guidance documents have been issued through collaboration of global organizations and regulatory authorities. Most of these are applicable to new products, but there is a risk that currently marketed products will not meet the new compliance standards during audits and inspections while companies continue to make changes through the product life cycle for continuous improvement or market demands. This discussion presents different strategies to bringing drug product marketing applications to meet current and emerging standards. It also discusses stability and method designs to meet process validation and global development efforts.

  1. Downhill Domination in Graphs

    Directory of Open Access Journals (Sweden)

    Haynes Teresa W.

    2014-08-01

    Full Text Available A path π = (v1, v2, . . . , vk+1 in a graph G = (V,E is a downhill path if for every i, 1 ≤ i ≤ k, deg(vi ≥ deg(vi+1, where deg(vi denotes the degree of vertex vi ∈ V. The downhill domination number equals the minimum cardinality of a set S ⊆ V having the property that every vertex v ∈ V lies on a downhill path originating from some vertex in S. We investigate downhill domination numbers of graphs and give upper bounds. In particular, we show that the downhill domination number of a graph is at most half its order, and that the downhill domination number of a tree is at most one third its order. We characterize the graphs obtaining each of these bounds

  2. Tailored Random Graph Ensembles

    International Nuclear Information System (INIS)

    Roberts, E S; Annibale, A; Coolen, A C C

    2013-01-01

    Tailored graph ensembles are a developing bridge between biological networks and statistical mechanics. The aim is to use this concept to generate a suite of rigorous tools that can be used to quantify and compare the topology of cellular signalling networks, such as protein-protein interaction networks and gene regulation networks. We calculate exact and explicit formulae for the leading orders in the system size of the Shannon entropies of random graph ensembles constrained with degree distribution and degree-degree correlation. We also construct an ergodic detailed balance Markov chain with non-trivial acceptance probabilities which converges to a strictly uniform measure and is based on edge swaps that conserve all degrees. The acceptance probabilities can be generalized to define Markov chains that target any alternative desired measure on the space of directed or undirected graphs, in order to generate graphs with more sophisticated topological features.

  3. Cycles in graphs

    CERN Document Server

    Alspach, BR

    1985-01-01

    This volume deals with a variety of problems involving cycles in graphs and circuits in digraphs. Leading researchers in this area present here 3 survey papers and 42 papers containing new results. There is also a collection of unsolved problems.

  4. Introduction to graph theory

    CERN Document Server

    Wilson, Robin J

    1985-01-01

    Graph Theory has recently emerged as a subject in its own right, as well as being an important mathematical tool in such diverse subjects as operational research, chemistry, sociology and genetics. This book provides a comprehensive introduction to the subject.

  5. Hyperbolicity in median graphs

    Indian Academy of Sciences (India)

    mic problems in hyperbolic spaces and hyperbolic graphs have been .... that in general the main obstacle is that we do not know the location of ...... [25] Jonckheere E and Lohsoonthorn P, A hyperbolic geometry approach to multipath routing,.

  6. Uniform Single Valued Neutrosophic Graphs

    Directory of Open Access Journals (Sweden)

    S. Broumi

    2017-09-01

    Full Text Available In this paper, we propose a new concept named the uniform single valued neutrosophic graph. An illustrative example and some properties are examined. Next, we develop an algorithmic approach for computing the complement of the single valued neutrosophic graph. A numerical example is demonstrated for computing the complement of single valued neutrosophic graphs and uniform single valued neutrosophic graph.

  7. Collective Rationality in Graph Aggregation

    NARCIS (Netherlands)

    Endriss, U.; Grandi, U.; Schaub, T.; Friedrich, G.; O'Sullivan, B.

    2014-01-01

    Suppose a number of agents each provide us with a directed graph over a common set of vertices. Graph aggregation is the problem of computing a single “collective” graph that best represents the information inherent in this profile of individual graphs. We consider this aggregation problem from the

  8. Classical dynamics on graphs

    International Nuclear Information System (INIS)

    Barra, F.; Gaspard, P.

    2001-01-01

    We consider the classical evolution of a particle on a graph by using a time-continuous Frobenius-Perron operator that generalizes previous propositions. In this way, the relaxation rates as well as the chaotic properties can be defined for the time-continuous classical dynamics on graphs. These properties are given as the zeros of some periodic-orbit zeta functions. We consider in detail the case of infinite periodic graphs where the particle undergoes a diffusion process. The infinite spatial extension is taken into account by Fourier transforms that decompose the observables and probability densities into sectors corresponding to different values of the wave number. The hydrodynamic modes of diffusion are studied by an eigenvalue problem of a Frobenius-Perron operator corresponding to a given sector. The diffusion coefficient is obtained from the hydrodynamic modes of diffusion and has the Green-Kubo form. Moreover, we study finite but large open graphs that converge to the infinite periodic graph when their size goes to infinity. The lifetime of the particle on the open graph is shown to correspond to the lifetime of a system that undergoes a diffusion process before it escapes

  9. Drug-resistant tuberculosis--current dilemmas, unanswered questions, challenges, and priority needs.

    Science.gov (United States)

    Zumla, Alimuddin; Abubakar, Ibrahim; Raviglione, Mario; Hoelscher, Michael; Ditiu, Lucica; McHugh, Timothy D; Squire, S Bertel; Cox, Helen; Ford, Nathan; McNerney, Ruth; Marais, Ben; Grobusch, Martin; Lawn, Stephen D; Migliori, Giovanni-Battista; Mwaba, Peter; O'Grady, Justin; Pletschette, Michel; Ramsay, Andrew; Chakaya, Jeremiah; Schito, Marco; Swaminathan, Soumya; Memish, Ziad; Maeurer, Markus; Atun, Rifat

    2012-05-15

    Tuberculosis was declared a global emergency by the World Health Organization (WHO) in 1993. Following the declaration and the promotion in 1995 of directly observed treatment short course (DOTS), a cost-effective strategy to contain the tuberculosis epidemic, nearly 7 million lives have been saved compared with the pre-DOTS era, high cure rates have been achieved in most countries worldwide, and the global incidence of tuberculosis has been in a slow decline since the early 2000s. However, the emergence and spread of multidrug-resistant (MDR) tuberculosis, extensively drug-resistant (XDR) tuberculosis, and more recently, totally drug-resistant tuberculosis pose a threat to global tuberculosis control. Multidrug-resistant tuberculosis is a man-made problem. Laboratory facilities for drug susceptibility testing are inadequate in most tuberculosis-endemic countries, especially in Africa; thus diagnosis is missed, routine surveillance is not implemented, and the actual numbers of global drug-resistant tuberculosis cases have yet to be estimated. This exposes an ominous situation and reveals an urgent need for commitment by national programs to health system improvement because the response to MDR tuberculosis requires strong health services in general. Multidrug-resistant tuberculosis and XDR tuberculosis greatly complicate patient management within resource-poor national tuberculosis programs, reducing treatment efficacy and increasing the cost of treatment to the extent that it could bankrupt healthcare financing in tuberculosis-endemic areas. Why, despite nearly 20 years of WHO-promoted activity and >12 years of MDR tuberculosis-specific activity, has the country response to the drug-resistant tuberculosis epidemic been so ineffectual? The current dilemmas, unanswered questions, operational issues, challenges, and priority needs for global drug resistance screening and surveillance, improved treatment regimens, and management of outcomes and prevention of DR

  10. A Similarity Search Using Molecular Topological Graphs

    Directory of Open Access Journals (Sweden)

    Yoshifumi Fukunishi

    2009-01-01

    Full Text Available A molecular similarity measure has been developed using molecular topological graphs and atomic partial charges. Two kinds of topological graphs were used. One is the ordinary adjacency matrix and the other is a matrix which represents the minimum path length between two atoms of the molecule. The ordinary adjacency matrix is suitable to compare the local structures of molecules such as functional groups, and the other matrix is suitable to compare the global structures of molecules. The combination of these two matrices gave a similarity measure. This method was applied to in silico drug screening, and the results showed that it was effective as a similarity measure.

  11. Direct-to-consumer marketing of prescription drugs: a current perspective for neurologists and psychiatrists.

    Science.gov (United States)

    Hollon, Matthew F

    2004-01-01

    In the US and New Zealand, the past decade has seen tremendous growth in the marketing of prescription drugs directly to patients. The pharmaceutical industry has applied pressure in other countries to relax regulations governing such marketing although this has not yet been successful. While we still have much to learn about the potential impact on the public's health of direct-to-consumer (DTC) marketing, some data are available. This article summarises the current literature on the benefits and risks of DTC marketing. This marketing strategy has grown substantially in the US, but only select drugs are advertised. Whether there is net benefit or harm to the public's health as a result of DTC marketing depends critically on which drugs are advertised and the quality of the information provided in promotional material. Critical reviews of this promotional material suggest the information is of poor quality. Notably, 18% of the 50 drugs advertised most intensively in the US were medications used to treat psychiatric and neurological disorders. The impairments in decisional capacity often seen in psychiatric and neurological illness leave patients vunerable to the controlling influence of DTC marketing and, thus, undermine the patient autonomy that is said to be promoted by this marketing strategy. If there is any benefit from DTC marketing it is for significantly undertreated conditions. International restrictions on DTC marketing should remain in place until further evidence of net benefit or harm emerges from the DTC marketing experiment that is taking place in the US and New Zealand.

  12. Therapeutic drug monitoring in pediatric IBD: current application and future perspectives.

    Science.gov (United States)

    Lega, Sara; Bramuzzo, Matteo; Dubinsky, Marla

    2017-09-11

    As the paradigm for IBD management is evolving from symptom control to the more ambitious goal of complete deep remission, the concept of personalized medicine, as a mean to deliver individualized treatment with the best effectiveness and safety profile, is becoming paramount. Therapeutic drug monitoring (TDM) is an essential part of personalized medicine wherein serum drug concentrations are used to guide drug dosing on an individual basis. The concept of TDM has been introduced in the field of IBD along with thiopurines, over a decade ago, and evolved around anti-TNFs therapies. In the era of biologics, TDM entered the clinical field to assist clinicians managing anti-TNF failure and its role is now moving toward the concept of "proactive" TDM with the goal to optimize drug exposure and prevent loss of response. Research in TDM is rapidly expanding: while the role of TDM with new biologics is under investigation, preliminary data suggest that software-systems support tools could be an opportunity to guide dosing choices and maximize the cost-benefit profile of therapies in the near future. The review discusses the current knowledge that poses the rationale for the use of TDM and the present and future role of TDM-based approaches in the management of pediatric IBD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Current challenges and emerging drug delivery strategies for the treatment of psoriasis.

    Science.gov (United States)

    Hoffman, Melissa B; Hill, Dane; Feldman, Steven R

    2016-10-01

    Psoriasis is a common skin disorder associated with physical, social, psychological and financial burden. Over the past two decades, advances in our understanding of pathogenesis and increased appreciation for the multifaceted burden of psoriasis has led to new treatment development and better patient outcomes. Yet, surveys demonstrate that many psoriasis patients are either undertreated or are dissatisfied with treatment. There are many barriers that need be overcome to optimize patient outcomes and satisfaction. This review covers the current challenges associated with each major psoriasis treatment strategy (topical, phototherapy, oral medications and biologics). It also reviews the challenges associated with the psychosocial aspects of the disease and how they affect treatment outcomes. Patient adherence, inconvenience, high costs, and drug toxicities are all discussed. Then, we review the emerging drug delivery strategies in topical, oral, and biologic therapy. By outlining current treatment challenges and emerging drug delivery strategies, we hope to highlight the deficits in psoriasis treatment and strategies for how to overcome them. Regardless of disease severity, clinicians should use a patient-centered approach. In all cases, we need to balance patients' psychosocial needs, treatment costs, convenience, and effectiveness with patients' preferences in order to optimize treatment outcomes.

  14. Application of thermally stimulated current measurement to the polymorphic characterization of drug substances

    International Nuclear Information System (INIS)

    Ikeda, Y.; Hirayama, T.; Terada, K.

    2005-01-01

    The thermal stimulated current measurement was used as an innovative analytical equipment to evaluate the polymorphic properties of terfenadine and Compound A, being developed by Takeda Pharmaceutical Company, Limited. At first, terfenadine, which is known to have polymorphs, was used as a model sample for thermally stimulated current (TSC) analyses. The TSC curves of amorphous and two polymorphs were distinctly different from each other. Therefore, it was considered that TSC measurement could be a useful technique to evaluate the crystalline properties of drug substances. The polymorphs of compound A were difficult to distinguish the characteristics of polymorphs from conventional powder X-ray diffractometry and also differential scanning calorimetry. Forms A and B of compound A were clearly differentiated by the thermal stimulated current properties that were adequate to characterize each form. Thus, it was shown that TSC was extremely useful and powerful tool for identification of complicated polymorphs, which were not distinguished by conventional methods

  15. Proxy Graph: Visual Quality Metrics of Big Graph Sampling.

    Science.gov (United States)

    Nguyen, Quan Hoang; Hong, Seok-Hee; Eades, Peter; Meidiana, Amyra

    2017-06-01

    Data sampling has been extensively studied for large scale graph mining. Many analyses and tasks become more efficient when performed on graph samples of much smaller size. The use of proxy objects is common in software engineering for analysis and interaction with heavy objects or systems. In this paper, we coin the term 'proxy graph' and empirically investigate how well a proxy graph visualization can represent a big graph. Our investigation focuses on proxy graphs obtained by sampling; this is one of the most common proxy approaches. Despite the plethora of data sampling studies, this is the first evaluation of sampling in the context of graph visualization. For an objective evaluation, we propose a new family of quality metrics for visual quality of proxy graphs. Our experiments cover popular sampling techniques. Our experimental results lead to guidelines for using sampling-based proxy graphs in visualization.

  16. On some covering graphs of a graph

    Directory of Open Access Journals (Sweden)

    Shariefuddin Pirzada

    2016-10-01

    Full Text Available For a graph $G$ with vertex set $V(G=\\{v_1, v_2, \\dots, v_n\\}$, let $S$ be the covering set of $G$ having the maximum degree over all the minimum covering sets of $G$. Let $N_S[v]=\\{u\\in S : uv \\in E(G \\}\\cup \\{v\\}$ be the closed neighbourhood of the vertex $v$ with respect to $S.$ We define a square matrix $A_S(G= (a_{ij},$ by $a_{ij}=1,$ if $\\left |N_S[v_i]\\cap N_S[v_j] \\right| \\geq 1, i\

  17. Potential effects of current drug therapies on cognitive impairment in patients with type 2 diabetes.

    Science.gov (United States)

    Palleria, Caterina; Leporini, Christian; Maida, Francesca; Succurro, Elena; De Sarro, Giovambattista; Arturi, Franco; Russo, Emilio

    2016-07-01

    Type 2 diabetes mellitus is a complex metabolic disease that can cause serious damage to various organs. Among the best-known complications, an important role is played by cognitive impairment. Impairment of cognitive functioning has been reported both in type 1 and 2 diabetes mellitus. While this comorbidity has long been known, no major advances have been achieved in clinical research; it is clear that appropriate control of blood glucose levels represents the best current (although unsatisfactory) approach in the prevention of cognitive impairment. We have focused our attention on the possible effect on the brain of antidiabetic drugs, despite their effects on blood glucose levels, giving a brief rationale on the mechanisms (e.g. GLP-1, BDNF, ghrelin) that might be involved. Indeed, GLP-1 agonists are currently clinically studied in other neurodegenerative diseases (i.e. Parkinson's and Alzheimer's disease); furthermore, also other antidiabetic drugs have proven efficacy in preclinical studies. Overall, promising results are already available and finding new intervention strategies represents a current need in this field of research. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Fundamentals of algebraic graph transformation

    CERN Document Server

    Ehrig, Hartmut; Prange, Ulrike; Taentzer, Gabriele

    2006-01-01

    Graphs are widely used to represent structural information in the form of objects and connections between them. Graph transformation is the rule-based manipulation of graphs, an increasingly important concept in computer science and related fields. This is the first textbook treatment of the algebraic approach to graph transformation, based on algebraic structures and category theory. Part I is an introduction to the classical case of graph and typed graph transformation. In Part II basic and advanced results are first shown for an abstract form of replacement systems, so-called adhesive high-level replacement systems based on category theory, and are then instantiated to several forms of graph and Petri net transformation systems. Part III develops typed attributed graph transformation, a technique of key relevance in the modeling of visual languages and in model transformation. Part IV contains a practical case study on model transformation and a presentation of the AGG (attributed graph grammar) tool envir...

  19. The STAPL Parallel Graph Library

    KAUST Repository

    Harshvardhan,

    2013-01-01

    This paper describes the stapl Parallel Graph Library, a high-level framework that abstracts the user from data-distribution and parallelism details and allows them to concentrate on parallel graph algorithm development. It includes a customizable distributed graph container and a collection of commonly used parallel graph algorithms. The library introduces pGraph pViews that separate algorithm design from the container implementation. It supports three graph processing algorithmic paradigms, level-synchronous, asynchronous and coarse-grained, and provides common graph algorithms based on them. Experimental results demonstrate improved scalability in performance and data size over existing graph libraries on more than 16,000 cores and on internet-scale graphs containing over 16 billion vertices and 250 billion edges. © Springer-Verlag Berlin Heidelberg 2013.

  20. Graphs, groups and surfaces

    CERN Document Server

    White, AT

    1985-01-01

    The field of topological graph theory has expanded greatly in the ten years since the first edition of this book appeared. The original nine chapters of this classic work have therefore been revised and updated. Six new chapters have been added, dealing with: voltage graphs, non-orientable imbeddings, block designs associated with graph imbeddings, hypergraph imbeddings, map automorphism groups and change ringing.Thirty-two new problems have been added to this new edition, so that there are now 181 in all; 22 of these have been designated as ``difficult'''' and 9 as ``unsolved''''. Three of the four unsolved problems from the first edition have been solved in the ten years between editions; they are now marked as ``difficult''''.

  1. Profinite graphs and groups

    CERN Document Server

    Ribes, Luis

    2017-01-01

    This book offers a detailed introduction to graph theoretic methods in profinite groups and applications to abstract groups. It is the first to provide a comprehensive treatment of the subject. The author begins by carefully developing relevant notions in topology, profinite groups and homology, including free products of profinite groups, cohomological methods in profinite groups, and fixed points of automorphisms of free pro-p groups. The final part of the book is dedicated to applications of the profinite theory to abstract groups, with sections on finitely generated subgroups of free groups, separability conditions in free and amalgamated products, and algorithms in free groups and finite monoids. Profinite Graphs and Groups will appeal to students and researchers interested in profinite groups, geometric group theory, graphs and connections with the theory of formal languages. A complete reference on the subject, the book includes historical and bibliographical notes as well as a discussion of open quest...

  2. Subdominant pseudoultrametric on graphs

    Energy Technology Data Exchange (ETDEWEB)

    Dovgoshei, A A; Petrov, E A [Institute of Applied Mathematics and Mechanics, National Academy of Sciences of Ukraine, Donetsk (Ukraine)

    2013-08-31

    Let (G,w) be a weighted graph. We find necessary and sufficient conditions under which the weight w:E(G)→R{sup +} can be extended to a pseudoultrametric on V(G), and establish a criterion for the uniqueness of such an extension. We demonstrate that (G,w) is a complete k-partite graph, for k≥2, if and only if for any weight that can be extended to a pseudoultrametric, among all such extensions one can find the least pseudoultrametric consistent with w. We give a structural characterization of graphs for which the subdominant pseudoultrametric is an ultrametric for any strictly positive weight that can be extended to a pseudoultrametric. Bibliography: 14 titles.

  3. Quantitative graph theory mathematical foundations and applications

    CERN Document Server

    Dehmer, Matthias

    2014-01-01

    The first book devoted exclusively to quantitative graph theory, Quantitative Graph Theory: Mathematical Foundations and Applications presents and demonstrates existing and novel methods for analyzing graphs quantitatively. Incorporating interdisciplinary knowledge from graph theory, information theory, measurement theory, and statistical techniques, this book covers a wide range of quantitative-graph theoretical concepts and methods, including those pertaining to real and random graphs such as:Comparative approaches (graph similarity or distance)Graph measures to characterize graphs quantitat

  4. Prediction of Nucleotide Binding Peptides Using Star Graph Topological Indices.

    Science.gov (United States)

    Liu, Yong; Munteanu, Cristian R; Fernández Blanco, Enrique; Tan, Zhiliang; Santos Del Riego, Antonino; Pazos, Alejandro

    2015-11-01

    The nucleotide binding proteins are involved in many important cellular processes, such as transmission of genetic information or energy transfer and storage. Therefore, the screening of new peptides for this biological function is an important research topic. The current study proposes a mixed methodology to obtain the first classification model that is able to predict new nucleotide binding peptides, using only the amino acid sequence. Thus, the methodology uses a Star graph molecular descriptor of the peptide sequences and the Machine Learning technique for the best classifier. The best model represents a Random Forest classifier based on two features of the embedded and non-embedded graphs. The performance of the model is excellent, considering similar models in the field, with an Area Under the Receiver Operating Characteristic Curve (AUROC) value of 0.938 and true positive rate (TPR) of 0.886 (test subset). The prediction of new nucleotide binding peptides with this model could be useful for drug target studies in drug development. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. ORAL COLON TARGETED DRUG DELIVERY SYSTEM: A REVIEW ON CURRENT AND NOVEL PERSPECTIVES

    OpenAIRE

    Asija Rajesh; Chaudhari Bharat; Asija Sangeeta

    2012-01-01

    Small intestine is mostly the site for drug absorption but in some cases the drug needs to be targeted to colon due to some factors like local colonic disease, degradation related conditions, delayed release of drugs, systemic delivery of protein and peptide drugs etc. Colon targeted drug delivery is important and relatively new concept for the absorption of drugs because it offers almost neutral pH and long residence time, thereby increasing the drug absorption. Colon has proved to be a site...

  6. Current Landscape of Antiviral Drug Discovery [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Wade Blair

    2016-02-01

    Full Text Available Continued discovery and development of new antiviral medications are paramount for global human health, particularly as new pathogens emerge and old ones evolve to evade current therapeutic agents. Great success has been achieved in developing effective therapies to suppress human immunodeficiency virus (HIV and hepatitis B virus (HBV; however, the therapies are not curative and therefore current efforts in HIV and HBV drug discovery are directed toward longer-acting therapies and/or developing new mechanisms of action that could potentially lead to cure, or eradication, of the virus. Recently, exciting early clinical data have been reported for novel antivirals targeting respiratory syncytial virus (RSV and influenza (flu. Preclinical data suggest that these new approaches may be effective in treating high-risk patients afflicted with serious RSV or flu infections. In this review, we highlight new directions in antiviral approaches for HIV, HBV, and acute respiratory virus infections.

  7. Augmented marked graphs

    CERN Document Server

    Cheung, King Sing

    2014-01-01

    Petri nets are a formal and theoretically rich model for the modelling and analysis of systems. A subclass of Petri nets, augmented marked graphs possess a structure that is especially desirable for the modelling and analysis of systems with concurrent processes and shared resources.This monograph consists of three parts: Part I provides the conceptual background for readers who have no prior knowledge on Petri nets; Part II elaborates the theory of augmented marked graphs; finally, Part III discusses the application to system integration. The book is suitable as a first self-contained volume

  8. Spectral radius of graphs

    CERN Document Server

    Stevanovic, Dragan

    2015-01-01

    Spectral Radius of Graphs provides a thorough overview of important results on the spectral radius of adjacency matrix of graphs that have appeared in the literature in the preceding ten years, most of them with proofs, and including some previously unpublished results of the author. The primer begins with a brief classical review, in order to provide the reader with a foundation for the subsequent chapters. Topics covered include spectral decomposition, the Perron-Frobenius theorem, the Rayleigh quotient, the Weyl inequalities, and the Interlacing theorem. From this introduction, the

  9. Alternatives to currently used antimalarial drugs: in search of a magic bullet.

    Science.gov (United States)

    Bhagavathula, Akshaya Srikanth; Elnour, Asim Ahmed; Shehab, Abdulla

    2016-11-04

    bullet against malaria. Future studies should focus on effective single-dose molecules that can act against all stages of malaria in order to prevent transmission. Newer medicines have also raised concerns in terms of efficacy and safety. Overall, more evidence is needed to effectively reduce the current malaria burden. Treatment strategies that target the blood stage with transmission-blocking properties are needed to prevent future drug resistance.

  10. Graph embedding with rich information through heterogeneous graph

    KAUST Repository

    Sun, Guolei

    2017-01-01

    Graph embedding, aiming to learn low-dimensional representations for nodes in graphs, has attracted increasing attention due to its critical application including node classification, link prediction and clustering in social network analysis. Most

  11. Current therapeutic molecules and targets in neurodegenerative diseases based on in silico drug design.

    Science.gov (United States)

    Sehgal, Sheikh Arslan; Hammad, Mirza A; Tahir, Rana Adnan; Akram, Hafiza Nisha; Ahmad, Faheem

    2018-03-15

    As the number of elderly persons increases, neurodegenerative diseases are becoming ubiquitous. There is currently a great need for knowledge concerning management of old-age neurodegenerative diseases; the most important of which are: Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, and Huntington's disease. To summarize the potential of computationally predicted molecules and targets against neurodegenerative diseases. Review of literature published since 1997 against neurodegenerative diseases, utilizing as keywords: in silico, Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis ALS, and Huntington's disease. Due to the costs associated with experimentation and current ethical law, performing experiments directly on living organisms has become much more difficult. In this scenario, in silico techniques have been successful and have become powerful tools in the search to cure disease. Researchers use the Computer Aided Drug Design pipeline which: 1) generates 3-dimensional structures of target proteins through homology modeling 2) achieves stabilization through molecular dynamics simulation, and 3) exploits molecular docking through large compound libraries. Next generation sequencing is continually producing enormous amounts of raw sequence data while neuroimaging is producing a multitude of raw image data. To solve such pressing problems, these new tools and algorithms are required. This review elaborates precise in silico tools and techniques for drug targets, active molecules, and molecular docking studies, together with future prospects and challenges concerning possible breakthroughs in Alzheimer's, Parkinson's, Amyotrophic Lateral Sclerosis, and Huntington's disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Using Graph and Vertex Entropy to Compare Empirical Graphs with Theoretical Graph Models

    Directory of Open Access Journals (Sweden)

    Tomasz Kajdanowicz

    2016-09-01

    Full Text Available Over the years, several theoretical graph generation models have been proposed. Among the most prominent are: the Erdős–Renyi random graph model, Watts–Strogatz small world model, Albert–Barabási preferential attachment model, Price citation model, and many more. Often, researchers working with real-world data are interested in understanding the generative phenomena underlying their empirical graphs. They want to know which of the theoretical graph generation models would most probably generate a particular empirical graph. In other words, they expect some similarity assessment between the empirical graph and graphs artificially created from theoretical graph generation models. Usually, in order to assess the similarity of two graphs, centrality measure distributions are compared. For a theoretical graph model this means comparing the empirical graph to a single realization of a theoretical graph model, where the realization is generated from the given model using an arbitrary set of parameters. The similarity between centrality measure distributions can be measured using standard statistical tests, e.g., the Kolmogorov–Smirnov test of distances between cumulative distributions. However, this approach is both error-prone and leads to incorrect conclusions, as we show in our experiments. Therefore, we propose a new method for graph comparison and type classification by comparing the entropies of centrality measure distributions (degree centrality, betweenness centrality, closeness centrality. We demonstrate that our approach can help assign the empirical graph to the most similar theoretical model using a simple unsupervised learning method.

  13. Handbook of graph grammars and computing by graph transformation

    CERN Document Server

    Engels, G; Kreowski, H J; Rozenberg, G

    1999-01-01

    Graph grammars originated in the late 60s, motivated by considerations about pattern recognition and compiler construction. Since then, the list of areas which have interacted with the development of graph grammars has grown quite impressively. Besides the aforementioned areas, it includes software specification and development, VLSI layout schemes, database design, modeling of concurrent systems, massively parallel computer architectures, logic programming, computer animation, developmental biology, music composition, visual languages, and many others.The area of graph grammars and graph tran

  14. Topics in graph theory graphs and their Cartesian product

    CERN Document Server

    Imrich, Wilfried; Rall, Douglas F

    2008-01-01

    From specialists in the field, you will learn about interesting connections and recent developments in the field of graph theory by looking in particular at Cartesian products-arguably the most important of the four standard graph products. Many new results in this area appear for the first time in print in this book. Written in an accessible way, this book can be used for personal study in advanced applications of graph theory or for an advanced graph theory course.

  15. Graph mining for next generation sequencing: leveraging the assembly graph for biological insights.

    Science.gov (United States)

    Warnke-Sommer, Julia; Ali, Hesham

    2016-05-06

    The assembly of Next Generation Sequencing (NGS) reads remains a challenging task. This is especially true for the assembly of metagenomics data that originate from environmental samples potentially containing hundreds to thousands of unique species. The principle objective of current assembly tools is to assemble NGS reads into contiguous stretches of sequence called contigs while maximizing for both accuracy and contig length. The end goal of this process is to produce longer contigs with the major focus being on assembly only. Sequence read assembly is an aggregative process, during which read overlap relationship information is lost as reads are merged into longer sequences or contigs. The assembly graph is information rich and capable of capturing the genomic architecture of an input read data set. We have developed a novel hybrid graph in which nodes represent sequence regions at different levels of granularity. This model, utilized in the assembly and analysis pipeline Focus, presents a concise yet feature rich view of a given input data set, allowing for the extraction of biologically relevant graph structures for graph mining purposes. Focus was used to create hybrid graphs to model metagenomics data sets obtained from the gut microbiomes of five individuals with Crohn's disease and eight healthy individuals. Repetitive and mobile genetic elements are found to be associated with hybrid graph structure. Using graph mining techniques, a comparative study of the Crohn's disease and healthy data sets was conducted with focus on antibiotics resistance genes associated with transposase genes. Results demonstrated significant differences in the phylogenetic distribution of categories of antibiotics resistance genes in the healthy and diseased patients. Focus was also evaluated as a pure assembly tool and produced excellent results when compared against the Meta-velvet, Omega, and UD-IDBA assemblers. Mining the hybrid graph can reveal biological phenomena captured

  16. Partitioning a call graph

    NARCIS (Netherlands)

    Bisseling, R.H.; Byrka, J.; Cerav-Erbas, S.; Gvozdenovic, N.; Lorenz, M.; Pendavingh, R.A.; Reeves, C.; Röger, M.; Verhoeven, A.; Berg, van den J.B.; Bhulai, S.; Hulshof, J.; Koole, G.; Quant, C.; Williams, J.F.

    2006-01-01

    Splitting a large software system into smaller and more manageable units has become an important problem for many organizations. The basic structure of a software system is given by a directed graph with vertices representing the programs of the system and arcs representing calls from one program to

  17. Coloring geographical threshold graphs

    Energy Technology Data Exchange (ETDEWEB)

    Bradonjic, Milan [Los Alamos National Laboratory; Percus, Allon [Los Alamos National Laboratory; Muller, Tobias [EINDHOVEN UNIV. OF TECH

    2008-01-01

    We propose a coloring algorithm for sparse random graphs generated by the geographical threshold graph (GTG) model, a generalization of random geometric graphs (RGG). In a GTG, nodes are distributed in a Euclidean space, and edges are assigned according to a threshold function involving the distance between nodes as well as randomly chosen node weights. The motivation for analyzing this model is that many real networks (e.g., wireless networks, the Internet, etc.) need to be studied by using a 'richer' stochastic model (which in this case includes both a distance between nodes and weights on the nodes). Here, we analyze the GTG coloring algorithm together with the graph's clique number, showing formally that in spite of the differences in structure between GTG and RGG, the asymptotic behavior of the chromatic number is identical: {chi}1n 1n n / 1n n (1 + {omicron}(1)). Finally, we consider the leading corrections to this expression, again using the coloring algorithm and clique number to provide bounds on the chromatic number. We show that the gap between the lower and upper bound is within C 1n n / (1n 1n n){sup 2}, and specify the constant C.

  18. Supermarket model on graphs

    NARCIS (Netherlands)

    Budhiraja, A.S.; Mukherjee, D.; Wu, R.

    2017-01-01

    We consider a variation of the supermarket model in which the servers can communicate with their neighbors and where the neighborhood relationships are described in terms of a suitable graph. Tasks with unit-exponential service time distributions arrive at each vertex as independent Poisson

  19. Basin Hopping Graph

    DEFF Research Database (Denmark)

    Kucharik, Marcel; Hofacker, Ivo; Stadler, Peter

    2014-01-01

    of the folding free energy landscape, however, can provide the relevant information. Results We introduce the basin hopping graph (BHG) as a novel coarse-grained model of folding landscapes. Each vertex of the BHG is a local minimum, which represents the corresponding basin in the landscape. Its edges connect...

  20. The STAPL Parallel Graph Library

    KAUST Repository

    Harshvardhan,; Fidel, Adam; Amato, Nancy M.; Rauchwerger, Lawrence

    2013-01-01

    This paper describes the stapl Parallel Graph Library, a high-level framework that abstracts the user from data-distribution and parallelism details and allows them to concentrate on parallel graph algorithm development. It includes a customizable

  1. Prediction of Human Drug Targets and Their Interactions Using Machine Learning Methods: Current and Future Perspectives.

    Science.gov (United States)

    Nath, Abhigyan; Kumari, Priyanka; Chaube, Radha

    2018-01-01

    Identification of drug targets and drug target interactions are important steps in the drug-discovery pipeline. Successful computational prediction methods can reduce the cost and time demanded by the experimental methods. Knowledge of putative drug targets and their interactions can be very useful for drug repurposing. Supervised machine learning methods have been very useful in drug target prediction and in prediction of drug target interactions. Here, we describe the details for developing prediction models using supervised learning techniques for human drug target prediction and their interactions.

  2. A Clustering Graph Generator

    Energy Technology Data Exchange (ETDEWEB)

    Winlaw, Manda [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); De Sterck, Hans [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Sanders, Geoffrey [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-10-26

    In very simple terms a network can be de ned as a collection of points joined together by lines. Thus, networks can be used to represent connections between entities in a wide variety of elds including engi- neering, science, medicine, and sociology. Many large real-world networks share a surprising number of properties, leading to a strong interest in model development research and techniques for building synthetic networks have been developed, that capture these similarities and replicate real-world graphs. Modeling these real-world networks serves two purposes. First, building models that mimic the patterns and prop- erties of real networks helps to understand the implications of these patterns and helps determine which patterns are important. If we develop a generative process to synthesize real networks we can also examine which growth processes are plausible and which are not. Secondly, high-quality, large-scale network data is often not available, because of economic, legal, technological, or other obstacles [7]. Thus, there are many instances where the systems of interest cannot be represented by a single exemplar network. As one example, consider the eld of cybersecurity, where systems require testing across diverse threat scenarios and validation across diverse network structures. In these cases, where there is no single exemplar network, the systems must instead be modeled as a collection of networks in which the variation among them may be just as important as their common features. By developing processes to build synthetic models, so-called graph generators, we can build synthetic networks that capture both the essential features of a system and realistic variability. Then we can use such synthetic graphs to perform tasks such as simulations, analysis, and decision making. We can also use synthetic graphs to performance test graph analysis algorithms, including clustering algorithms and anomaly detection algorithms.

  3. Groupies in multitype random graphs

    OpenAIRE

    Shang, Yilun

    2016-01-01

    A groupie in a graph is a vertex whose degree is not less than the average degree of its neighbors. Under some mild conditions, we show that the proportion of groupies is very close to 1/2 in multitype random graphs (such as stochastic block models), which include Erd?s-R?nyi random graphs, random bipartite, and multipartite graphs as special examples. Numerical examples are provided to illustrate the theoretical results.

  4. Groupies in multitype random graphs.

    Science.gov (United States)

    Shang, Yilun

    2016-01-01

    A groupie in a graph is a vertex whose degree is not less than the average degree of its neighbors. Under some mild conditions, we show that the proportion of groupies is very close to 1/2 in multitype random graphs (such as stochastic block models), which include Erdős-Rényi random graphs, random bipartite, and multipartite graphs as special examples. Numerical examples are provided to illustrate the theoretical results.

  5. Temporal Representation in Semantic Graphs

    Energy Technology Data Exchange (ETDEWEB)

    Levandoski, J J; Abdulla, G M

    2007-08-07

    A wide range of knowledge discovery and analysis applications, ranging from business to biological, make use of semantic graphs when modeling relationships and concepts. Most of the semantic graphs used in these applications are assumed to be static pieces of information, meaning temporal evolution of concepts and relationships are not taken into account. Guided by the need for more advanced semantic graph queries involving temporal concepts, this paper surveys the existing work involving temporal representations in semantic graphs.

  6. Quantum walks on quotient graphs

    International Nuclear Information System (INIS)

    Krovi, Hari; Brun, Todd A.

    2007-01-01

    A discrete-time quantum walk on a graph Γ is the repeated application of a unitary evolution operator to a Hilbert space corresponding to the graph. If this unitary evolution operator has an associated group of symmetries, then for certain initial states the walk will be confined to a subspace of the original Hilbert space. Symmetries of the original graph, given by its automorphism group, can be inherited by the evolution operator. We show that a quantum walk confined to the subspace corresponding to this symmetry group can be seen as a different quantum walk on a smaller quotient graph. We give an explicit construction of the quotient graph for any subgroup H of the automorphism group and illustrate it with examples. The automorphisms of the quotient graph which are inherited from the original graph are the original automorphism group modulo the subgroup H used to construct it. The quotient graph is constructed by removing the symmetries of the subgroup H from the original graph. We then analyze the behavior of hitting times on quotient graphs. Hitting time is the average time it takes a walk to reach a given final vertex from a given initial vertex. It has been shown in earlier work [Phys. Rev. A 74, 042334 (2006)] that the hitting time for certain initial states of a quantum walks can be infinite, in contrast to classical random walks. We give a condition which determines whether the quotient graph has infinite hitting times given that they exist in the original graph. We apply this condition for the examples discussed and determine which quotient graphs have infinite hitting times. All known examples of quantum walks with hitting times which are short compared to classical random walks correspond to systems with quotient graphs much smaller than the original graph; we conjecture that the existence of a small quotient graph with finite hitting times is necessary for a walk to exhibit a quantum speedup

  7. A generalization of total graphs

    Indian Academy of Sciences (India)

    M Afkhami

    2018-04-12

    Apr 12, 2018 ... product of any lower triangular matrix with the transpose of any element of U belongs to U. The ... total graph of R, which is denoted by T( (R)), is a simple graph with all elements of R as vertices, and ...... [9] Badawi A, On dot-product graph of a commutative ring, Communications in Algebra 43 (2015). 43–50.

  8. Graph transformation tool contest 2008

    NARCIS (Netherlands)

    Rensink, Arend; van Gorp, Pieter

    This special section is the outcome of the graph transformation tool contest organised during the Graph-Based Tools (GraBaTs) 2008 workshop, which took place as a satellite event of the International Conference on Graph Transformation (ICGT) 2008. The contest involved two parts: three “off-line case

  9. On dominator colorings in graphs

    Indian Academy of Sciences (India)

    colors required for a dominator coloring of G is called the dominator .... Theorem 1.3 shows that the complete graph Kn is the only connected graph of order n ... Conversely, if a graph G satisfies condition (i) or (ii), it is easy to see that χd(G) =.

  10. Efficient Graph Computation for Node2Vec

    OpenAIRE

    Zhou, Dongyan; Niu, Songjie; Chen, Shimin

    2018-01-01

    Node2Vec is a state-of-the-art general-purpose feature learning method for network analysis. However, current solutions cannot run Node2Vec on large-scale graphs with billions of vertices and edges, which are common in real-world applications. The existing distributed Node2Vec on Spark incurs significant space and time overhead. It runs out of memory even for mid-sized graphs with millions of vertices. Moreover, it considers at most 30 edges for every vertex in generating random walks, causin...

  11. Current approaches to enhance CNS delivery of drugs across the brain barriers

    Directory of Open Access Journals (Sweden)

    Lu CT

    2014-05-01

    Full Text Available Cui-Tao Lu,1 Ying-Zheng Zhao,2,3 Ho Lun Wong,4 Jun Cai,5 Lei Peng,2 Xin-Qiao Tian1 1The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of China; 2Hainan Medical College, Haikou City, Hainan Province, People’s Republic of China; 3College of Pharmaceutical Sciences, Wenzhou Medical University, Zhejiang Province, People’s Republic of China; 4School of Pharmacy, Temple University, Philadelphia, PA, USA; 5Departments of Pediatrics and Anatomical Sciences and Neurobiology, University of Louisville School of Medicine Louisville, KY, USA Abstract: Although many agents have therapeutic potentials for central nervous system (CNS diseases, few of these agents have been clinically used because of the brain barriers. As the protective barrier of the CNS, the blood–brain barrier and the blood–cerebrospinal fluid barrier maintain the brain microenvironment, neuronal activity, and proper functioning of the CNS. Different strategies for efficient CNS delivery have been studied. This article reviews the current approaches to open or facilitate penetration across these barriers for enhanced drug delivery to the CNS. These approaches are summarized into three broad categories: noninvasive, invasive, and miscellaneous techniques. The progresses made using these approaches are reviewed, and the associated mechanisms and problems are discussed. Keywords: drug delivery system, blood–brain barrier (BBB, central nervous system, brain-targeted therapy, cerebrospinal fluid (CSF

  12. Algorithms for Planar Graphs and Graphs in Metric Spaces

    DEFF Research Database (Denmark)

    Wulff-Nilsen, Christian

    structural properties that can be exploited. For instance, a road network or a wire layout on a microchip is typically (near-)planar and distances in the network are often defined w.r.t. the Euclidean or the rectilinear metric. Specialized algorithms that take advantage of such properties are often orders...... of magnitude faster than the corresponding algorithms for general graphs. The first and main part of this thesis focuses on the development of efficient planar graph algorithms. The most important contributions include a faster single-source shortest path algorithm, a distance oracle with subquadratic...... for geometric graphs and graphs embedded in metric spaces. Roughly speaking, the stretch factor is a real value expressing how well a (geo-)metric graph approximates the underlying complete graph w.r.t. distances. We give improved algorithms for computing the stretch factor of a given graph and for augmenting...

  13. Hierarchical graphs for rule-based modeling of biochemical systems

    Directory of Open Access Journals (Sweden)

    Hu Bin

    2011-02-01

    Full Text Available Abstract Background In rule-based modeling, graphs are used to represent molecules: a colored vertex represents a component of a molecule, a vertex attribute represents the internal state of a component, and an edge represents a bond between components. Components of a molecule share the same color. Furthermore, graph-rewriting rules are used to represent molecular interactions. A rule that specifies addition (removal of an edge represents a class of association (dissociation reactions, and a rule that specifies a change of a vertex attribute represents a class of reactions that affect the internal state of a molecular component. A set of rules comprises an executable model that can be used to determine, through various means, the system-level dynamics of molecular interactions in a biochemical system. Results For purposes of model annotation, we propose the use of hierarchical graphs to represent structural relationships among components and subcomponents of molecules. We illustrate how hierarchical graphs can be used to naturally document the structural organization of the functional components and subcomponents of two proteins: the protein tyrosine kinase Lck and the T cell receptor (TCR complex. We also show that computational methods developed for regular graphs can be applied to hierarchical graphs. In particular, we describe a generalization of Nauty, a graph isomorphism and canonical labeling algorithm. The generalized version of the Nauty procedure, which we call HNauty, can be used to assign canonical labels to hierarchical graphs or more generally to graphs with multiple edge types. The difference between the Nauty and HNauty procedures is minor, but for completeness, we provide an explanation of the entire HNauty algorithm. Conclusions Hierarchical graphs provide more intuitive formal representations of proteins and other structured molecules with multiple functional components than do the regular graphs of current languages for

  14. Evaluation of transporters in drug development: Current status and contemporary issues.

    Science.gov (United States)

    Lee, Sue-Chih; Arya, Vikram; Yang, Xinning; Volpe, Donna A; Zhang, Lei

    2017-07-01

    Transporters govern the access of molecules to cells or their exit from cells, thereby controlling the overall distribution of drugs to their intracellular site of action. Clinically relevant drug-drug interactions mediated by transporters are of increasing interest in drug development. Drug transporters, acting alone or in concert with drug metabolizing enzymes, can play an important role in modulating drug absorption, distribution, metabolism and excretion, thus affecting the pharmacokinetics and/or pharmacodynamics of a drug. The drug interaction guidance documents from regulatory agencies include various decision criteria that may be used to predict the need for in vivo assessment of transporter-mediated drug-drug interactions. Regulatory science research continues to assess the prediction performances of various criteria as well as to examine the strength and limitations of each prediction criterion to foster discussions related to harmonized decision criteria that may be used to facilitate global drug development. This review discusses the role of transporters in drug development with a focus on methodologies in assessing transporter-mediated drug-drug interactions, challenges in both in vitro and in vivo assessments of transporters, and emerging transporter research areas including biomarkers, assessment of tissue concentrations, and effect of diseases on transporters. Published by Elsevier B.V.

  15. A seminar on graph theory

    CERN Document Server

    Harary, Frank

    2015-01-01

    Presented in 1962-63 by experts at University College, London, these lectures offer a variety of perspectives on graph theory. Although the opening chapters form a coherent body of graph theoretic concepts, this volume is not a text on the subject but rather an introduction to the extensive literature of graph theory. The seminar's topics are geared toward advanced undergraduate students of mathematics.Lectures by this volume's editor, Frank Harary, include ""Some Theorems and Concepts of Graph Theory,"" ""Topological Concepts in Graph Theory,"" ""Graphical Reconstruction,"" and other introduc

  16. Spectral fluctuations of quantum graphs

    International Nuclear Information System (INIS)

    Pluhař, Z.; Weidenmüller, H. A.

    2014-01-01

    We prove the Bohigas-Giannoni-Schmit conjecture in its most general form for completely connected simple graphs with incommensurate bond lengths. We show that for graphs that are classically mixing (i.e., graphs for which the spectrum of the classical Perron-Frobenius operator possesses a finite gap), the generating functions for all (P,Q) correlation functions for both closed and open graphs coincide (in the limit of infinite graph size) with the corresponding expressions of random-matrix theory, both for orthogonal and for unitary symmetry

  17. Dynamic Representations of Sparse Graphs

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting; Fagerberg, Rolf

    1999-01-01

    We present a linear space data structure for maintaining graphs with bounded arboricity—a large class of sparse graphs containing e.g. planar graphs and graphs of bounded treewidth—under edge insertions, edge deletions, and adjacency queries. The data structure supports adjacency queries in worst...... case O(c) time, and edge insertions and edge deletions in amortized O(1) and O(c+log n) time, respectively, where n is the number of nodes in the graph, and c is the bound on the arboricity....

  18. Domination criticality in product graphs

    Directory of Open Access Journals (Sweden)

    M.R. Chithra

    2015-07-01

    Full Text Available A connected dominating set is an important notion and has many applications in routing and management of networks. Graph products have turned out to be a good model of interconnection networks. This motivated us to study the Cartesian product of graphs G with connected domination number, γc(G=2,3 and characterize such graphs. Also, we characterize the k−γ-vertex (edge critical graphs and k−γc-vertex (edge critical graphs for k=2,3 where γ denotes the domination number of G. We also discuss the vertex criticality in grids.

  19. Graph Creation, Visualisation and Transformation

    Directory of Open Access Journals (Sweden)

    Maribel Fernández

    2010-03-01

    Full Text Available We describe a tool to create, edit, visualise and compute with interaction nets - a form of graph rewriting systems. The editor, called GraphPaper, allows users to create and edit graphs and their transformation rules using an intuitive user interface. The editor uses the functionalities of the TULIP system, which gives us access to a wealth of visualisation algorithms. Interaction nets are not only a formalism for the specification of graphs, but also a rewrite-based computation model. We discuss graph rewriting strategies and a language to express them in order to perform strategic interaction net rewriting.

  20. Study of Chromatic parameters of Line, Total, Middle graphs and Graph operators of Bipartite graph

    Science.gov (United States)

    Nagarathinam, R.; Parvathi, N.

    2018-04-01

    Chromatic parameters have been explored on the basis of graph coloring process in which a couple of adjacent nodes receives different colors. But the Grundy and b-coloring executes maximum colors under certain restrictions. In this paper, Chromatic, b-chromatic and Grundy number of some graph operators of bipartite graph has been investigat

  1. Categorization of psychoactive substances into "hard drugs" and "soft drugs": a critical review of terminology used in current scientific literature.

    Science.gov (United States)

    Janik, Peter; Kosticova, Michaela; Pecenak, Jan; Turcek, Michal

    2017-11-01

    Precise terminology and definitions are important components of scientific language. Although the terms "hard drugs" and "soft drugs" are used widely by professionals, neither the International Classification of Diseases nor the Diagnostic and Statistical Manual classify psychoactive substances into the categories "hard" and "soft." To analyze the occurrence of the terms "hard drugs" and "soft drugs" in recent scientific literature and to establish the degree of consensus in labeling psychoactive substances as "hard" or "soft." A critical review of scientific papers listed in PubMed and Scopus between 2011 and 2015. Three hundred thirty-four articles were initially identified as potentially relevant for review, 132 of which were included in the final analysis. One hundred twenty-four articles used the term "hard drugs" and 84.7% provided examples of substances considered "hard." Forty-four articles used the term "soft drugs" and 90.9% provided examples of substances considered "soft." Citations of relevant articles supporting categorization as "hard" or "soft" were not given in 90% of the articles. The authors often provided no or only very sparse information on their reasons for considering specific drugs as "hard" or "soft." Although it initially appeared that there is substantial agreement as to which psychoactive substances should be regarded as "hard" and "soft," closer inspection shows that the dividing line is blurred without clear criteria for categorization. At this time, it remains uncertain whether these terms should persist in the scientific literature. We therefore recommend these terms should be avoided or, if used, be clearly and precisely defined.

  2. Graph Sampling for Covariance Estimation

    KAUST Repository

    Chepuri, Sundeep Prabhakar

    2017-04-25

    In this paper the focus is on subsampling as well as reconstructing the second-order statistics of signals residing on nodes of arbitrary undirected graphs. Second-order stationary graph signals may be obtained by graph filtering zero-mean white noise and they admit a well-defined power spectrum whose shape is determined by the frequency response of the graph filter. Estimating the graph power spectrum forms an important component of stationary graph signal processing and related inference tasks such as Wiener prediction or inpainting on graphs. The central result of this paper is that by sampling a significantly smaller subset of vertices and using simple least squares, we can reconstruct the second-order statistics of the graph signal from the subsampled observations, and more importantly, without any spectral priors. To this end, both a nonparametric approach as well as parametric approaches including moving average and autoregressive models for the graph power spectrum are considered. The results specialize for undirected circulant graphs in that the graph nodes leading to the best compression rates are given by the so-called minimal sparse rulers. A near-optimal greedy algorithm is developed to design the subsampling scheme for the non-parametric and the moving average models, whereas a particular subsampling scheme that allows linear estimation for the autoregressive model is proposed. Numerical experiments on synthetic as well as real datasets related to climatology and processing handwritten digits are provided to demonstrate the developed theory.

  3. Practical graph mining with R

    CERN Document Server

    Hendrix, William; Jenkins, John; Padmanabhan, Kanchana; Chakraborty, Arpan

    2014-01-01

    Practical Graph Mining with R presents a "do-it-yourself" approach to extracting interesting patterns from graph data. It covers many basic and advanced techniques for the identification of anomalous or frequently recurring patterns in a graph, the discovery of groups or clusters of nodes that share common patterns of attributes and relationships, the extraction of patterns that distinguish one category of graphs from another, and the use of those patterns to predict the category of new graphs. Hands-On Application of Graph Data Mining Each chapter in the book focuses on a graph mining task, such as link analysis, cluster analysis, and classification. Through applications using real data sets, the book demonstrates how computational techniques can help solve real-world problems. The applications covered include network intrusion detection, tumor cell diagnostics, face recognition, predictive toxicology, mining metabolic and protein-protein interaction networks, and community detection in social networks. De...

  4. Canonical Labelling of Site Graphs

    Directory of Open Access Journals (Sweden)

    Nicolas Oury

    2013-06-01

    Full Text Available We investigate algorithms for canonical labelling of site graphs, i.e. graphs in which edges bind vertices on sites with locally unique names. We first show that the problem of canonical labelling of site graphs reduces to the problem of canonical labelling of graphs with edge colourings. We then present two canonical labelling algorithms based on edge enumeration, and a third based on an extension of Hopcroft's partition refinement algorithm. All run in quadratic worst case time individually. However, one of the edge enumeration algorithms runs in sub-quadratic time for graphs with "many" automorphisms, and the partition refinement algorithm runs in sub-quadratic time for graphs with "few" bisimulation equivalences. This suite of algorithms was chosen based on the expectation that graphs fall in one of those two categories. If that is the case, a combined algorithm runs in sub-quadratic worst case time. Whether this expectation is reasonable remains an interesting open problem.

  5. [Drug supply chain safety in hospitals: current data and experience of the Grenoble university hospital].

    Science.gov (United States)

    Bedouch, P; Baudrant, M; Detavernier, M; Rey, C; Brudieu, E; Foroni, L; Allenet, B; Calop, J

    2009-01-01

    Drug supply chain safety has become a priority for public health which implies a collective process. This process associates all health professionals including the pharmacist who plays a major role. The objective of this present paper is to describe the several approaches proven effective in the reduction of drug-related problem in hospital, illustrated by the Grenoble University Hospital experience. The pharmacist gets involved first in the general strategy of hospital drug supply chain, second by his direct implication in clinical activities. The general strategy of drug supply chain combines risk management, coordination of the Pharmacy and Therapeutics Committee, selection and purchase of drugs and organisation of drug supply chain. Computer management of drug supply chain is a major evolution. Nominative drug delivering has to be a prior objective and its implementation modalities have to be defined: centralized or decentralized in wards, manual or automated. Also, new technologies allow the automation of overall drug distribution from central pharmacy and the implementation of automated drug dispensing systems into wards. The development of centralised drug preparation allows a safe compounding of high risk drugs, like cytotoxic drugs. The pharmacist should develop his clinical activities with patients and other health care professionals in order to optimise clinical decisions (medication review, drug order analysis) and patients follow-up (therapeutic monitoring, patient education, discharge consultation).

  6. Learning heat diffusion graphs

    OpenAIRE

    Thanou, Dorina; Dong, Xiaowen; Kressner, Daniel; Frossard, Pascal

    2016-01-01

    Effective information analysis generally boils down to properly identifying the structure or geometry of the data, which is often represented by a graph. In some applications, this structure may be partly determined by design constraints or pre-determined sensing arrangements, like in road transportation networks for example. In general though, the data structure is not readily available and becomes pretty difficult to define. In particular, the global smoothness assumptions, that most of the...

  7. An Unusual Exponential Graph

    Science.gov (United States)

    Syed, M. Qasim; Lovatt, Ian

    2014-01-01

    This paper is an addition to the series of papers on the exponential function begun by Albert Bartlett. In particular, we ask how the graph of the exponential function y = e[superscript -t/t] would appear if y were plotted versus ln t rather than the normal practice of plotting ln y versus t. In answering this question, we find a new way to…

  8. Understanding Charts and Graphs.

    Science.gov (United States)

    1987-07-28

    Farenheit degrees, which have no Onaturalo zero ); finally, ratio scales have numbers that are ordered so that the magnitudes of differences are important and...system. They have to do with the very nature of how marks serve as meaningful symbols. In the ideal case, a chart or graph will be absolutely unambiguous...and these laws comprise this principle (see Stevens, 1974). Absolute discriminability: A minimal magnitude of a mark is necessary for it to be detected

  9. Liposheres as a Novel Carrier for Lipid Based Drug Delivery: Current and Future Directions.

    Science.gov (United States)

    Swain, Suryakanta; Beg, Sarwar; Babu, Sitty M

    2016-01-01

    Researchers are facing challenges to develop robust formulation and to enhance the bioavailability of poorly water-soluble drugs towards clinical applications. The development of new drug molecule alone is not adequate to assure ample pharmacotherapy of various diseases. Considerable results obtained from in vitro studies are not supported by in vivo data due to inadequate plasma drug concentrations. This may occur due to limited drug solubility and absorption. To resolve these problems, development of new drug delivery systems will be a promising approach. One of the promising pharmaceutical strategies is the use of lipospheres drug delivery system to deliver the poorly water-soluble drugs. Therefore, the present review described the methodology for manufacturing of lipospheres and factors influencing the formulation to deliver the drugs to the targeted site. Apart from that, this review also enlisted briefly the various applications of liposphers in medical and biomedical fields and critically discussed the recent patent system.

  10. Neighborhood-level LGBT hate crimes and current illicit drug use among sexual minority youth.

    Science.gov (United States)

    Duncan, Dustin T; Hatzenbuehler, Mark L; Johnson, Renee M

    2014-02-01

    To investigate whether past-30 day illicit drug use among sexual minority youth was more common in neighborhoods with a greater prevalence of hate crimes targeting lesbian, gay, bisexual, and transgender (LGBT, or sexual minority) individuals. We used a population-based survey of public school youth in Boston, Massachusetts, consisting of 1292 9th-12th grade students from the 2008 Boston Youth Survey Geospatial Dataset (sexual minority n=108). Data on LGBT hate crimes involving assaults or assaults and battery between 2005 and 2008 were obtained from the Boston Police Department and linked to youths' residential address. Youth reported past-30 day use of marijuana and other illicit drugs. Wilcoxon-Mann-Whitney tests and corresponding p-values were computed to assess differences in substance use by neighborhood-level LGBT assault hate crime rate among sexual minority youth (n=103). The LGBT assault hate crime rate in the neighborhoods of sexual minority youth who reported current marijuana use was 23.7 per 100,000, compared to 12.9 per 100,000 for sexual minority youth who reported no marijuana use (p=0.04). No associations between LGBT assault hate crimes and marijuana use among heterosexual youth (p>0.05) or between sexual minority marijuana use and overall neighborhood-level violent and property crimes (p>0.05) were detected, providing evidence for result specificity. We found a significantly greater prevalence of marijuana use among sexual minority youth in neighborhoods with a higher prevalence of LGBT assault hate crimes. These results suggest that neighborhood context (i.e., LGBT hate crimes) may contribute to sexual orientation disparities in marijuana use. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. "Current Good Manufacturing Practices" and the Federal Food, Drug and Cosmetic Act

    OpenAIRE

    Goldstein, Beth F.

    1995-01-01

    The Food and Drug Administration (hereinafter, FDA) regulates food, drugs, and cosmetics in order to ensure that these products are safe and truthfully labelled. As part of its responsibilities under the Federal Food, Drug, and Cosmetic Act (hereinafter, Act), the FDA monitors the manufacturing practices of companies involved in the production of food, drugs, and medical devices. The manufacturing practices used by these companies must comply with certain standards, identified in the Act as "...

  12. Graphs cospectral with a friendship graph or its complement

    Directory of Open Access Journals (Sweden)

    Alireza Abdollahi

    2013-12-01

    Full Text Available Let $n$ be any positive integer and let $F_n$ be the friendship (or Dutch windmill graph with $2n+1$ vertices and $3n$ edges. Here we study graphs with the same adjacency spectrum as the $F_n$. Two graphs are called cospectral if the eigenvalues multiset of their adjacency matrices are the same. Let $G$ be a graph cospectral with $F_n$. Here we prove that if $G$ has no cycle of length $4$ or $5$, then $Gcong F_n$. Moreover if $G$ is connected and planar then $Gcong F_n$.All but one of connected components of $G$ are isomorphic to $K_2$.The complement $overline{F_n}$ of the friendship graph is determined by its adjacency eigenvalues, that is, if $overline{F_n}$ is cospectral with a graph $H$, then $Hcong overline{F_n}$.

  13. Decomposing Oriented Graphs into Six Locally Irregular Oriented Graphs

    DEFF Research Database (Denmark)

    Bensmail, Julien; Renault, Gabriel

    2016-01-01

    An undirected graph G is locally irregular if every two of its adjacent vertices have distinct degrees. We say that G is decomposable into k locally irregular graphs if there exists a partition E1∪E2∪⋯∪Ek of the edge set E(G) such that each Ei induces a locally irregular graph. It was recently co...

  14. X-Graphs: Language and Algorithms for Heterogeneous Graph Streams

    Science.gov (United States)

    2017-09-01

    are widely used by academia and industry. 15. SUBJECT TERMS Data Analytics, Graph Analytics, High-Performance Computing 16. SECURITY CLASSIFICATION...form the core of the DeepDive Knowledge Construction System. 2 INTRODUCTION The goal of the X-Graphs project was to develop computational techniques...memory multicore machine. Ringo is based on Snap.py and SNAP, and uses Python . Ringo now allows the integration of Delite DSL Framework Graph

  15. [The Necessity and the Current Status of Safe Handling of Anticancer Drugs].

    Science.gov (United States)

    Kanda, Kiyoko

    2017-07-01

    Number of people who handle anticancer drugs in their profession is increasing. Anticancer drugs, which are hazardous drugs(HD), exert cytocidal effects on cancer cells, but many have also been shown to have mutagenicity, teratogenicity and carcinogenicity; therefore, safe handling of anticancer drugs is necessary. In July 2015, the first Japanese guidelines for exposure control measures, namely, the "Joint Guidelines for Safe Handling of Cancer Chemotherapy Drugs", were published jointly by 3 societies. Our guideline is the creation of the Japanese Society of Cancer Nursing(JSCN), Japanese Society of Medical Oncology(JSMO)and Japanese Society of Pharmaceutical Oncology(JASPO)and has a historical significance. This paper states the necessity of safe handling of anticancer drugs, Japan's recent movement of safe handling, the introduction of joint guidelines of safe handling of anticancer drugs, and new movement of safe handling of USP chapter 800 in the United States.

  16. Could a revision of the current guidelines for cancer drug use improve the quality of cancer treatment?

    Directory of Open Access Journals (Sweden)

    Lippert TH

    2014-01-01

    Full Text Available Theodor H Lippert,1 Hans-Jörg Ruoff,1 Manfred Volm2 1Medical Faculty, University of Tübingen, Tübingen, Germany; 2Medical Faculty, University of Heidelberg, Heidelberg, Germany Abstract: Clinical practice guidelines are indispensable for such a variable disease as malignant solid tumors, with the complex possibilities of drug treatment. The current guidelines may be criticized on several points, however. First, there is a lack of information on the outcome of treatment, such as the expected success and failure rates. Treating not only drug responders but also nonresponders, that is, patients with drug resistance, must result in failures. There is no mention of the possibility of excluding the drug nonresponders, identifiable by special laboratory tests and no consideration is given to the different side effects of the recommended drug regimens. Nor are there any instructions concerning tumor cases for which anticancer drug treatment is futile. In such cases, early palliative care may lead to significant improvements in both life quality and life expectancy. Not least, there is no transparency concerning the preparation of the guidelines: persons cannot be identified who could give a statement of conflicts of interest, and responsibility is assumed only by anonymous medical associations. A revision of the current guidelines could considerably improve cancer treatment. Keywords: anticancer drugs, quality of guidelines, critical remarks

  17. Use of toxicogenomics in drug safety evaluation: Current status and an industry perspective.

    Science.gov (United States)

    Vahle, John L; Anderson, Ulf; Blomme, Eric A G; Hoflack, Jean-Christophe; Stiehl, Daniel P

    2018-04-18

    Toxicogenomics held great promise as an approach to enable early detection of toxicities induced by xenobiotics; however, there remain questions regarding the impact of the discipline on pharmaceutical nonclinical safety assessment. To understand the current state of toxicogenomics in the sector, an industry group surveyed companies to determine the frequency of toxicogenomics use in in vivo studies at various stages of drug discovery and development and to assess how toxicogenomics use has evolved over time. Survey data were compiled during 2016 from thirteen pharmaceutical companies. Toxicogenomic analyses were infrequently conducted in the development phase and when performed were done to address specific mechanistic questions. Prior to development, toxicogenomics use was more frequent; however, there were significant differences in approaches among companies. Across all phases, gaining mechanistic insight was the most frequent reason cited for pursing toxicogenomics with few companies using toxicogenomics to predict toxicities. These data were consistent with the commentary submitted in response to survey questions asking companies to describe the evolution of their toxicogenomics strategy. Overall, these survey data indicate that toxicogenomics is not widely used as a predictive tool in the pharmaceutical industry but is used regularly by some companies and serves a broader role in mechanistic investigations and as a complement to other technologies. Copyright © 2018. Published by Elsevier Inc.

  18. Currently used and investigational drugs for Cushing´s disease.

    Science.gov (United States)

    Ciato, Denis; Mumbach, Aizhar G; Paez-Pereda, Marcelo; Stalla, Günter K

    2017-01-01

    Cushing's disease (CD) is caused by a corticotroph adenoma of the pituitary gland that secretes excess adrenocorticotropic hormone (ACTH) causing increased morbidity and mortality. Surgery is the treatment of choice, but is not always successful. Alternatives include radiotherapy, adrenal surgery, and pharmaceutical therapy. The latter is increasingly gaining momentum due to the recent development of compounds that reduce hypercortisolaemia or its symptoms, acting through different mechanisms. Areas covered: In this article, the authors provide a complete overview of the treatment options for Cushing´s disease, including adrenal-directed, tumor-targeted, and peripheral therapies that are currently used or in development, and discuss their potential advantages and limitations. Expert opinion: Considering the lack of long-term remission in up to half of the patients after surgery, and the delayed response to radiotherapy along with potential side effects, there is a strong need for an effective pharmaceutical treatment. Pasireotide, mifepristone, ketoconazole and metyrapone have been approved by regulatory authorities but their use remains limited due to considerable costs and side effects. Research in this field has focused recently on the improvement of pre-existing drugs and the development of safe new ones. However, few approaches aim at targeting the source of the disease, the ACTH-secreting adenoma.

  19. Endomorphisms of graph algebras

    DEFF Research Database (Denmark)

    Conti, Roberto; Hong, Jeong Hee; Szymanski, Wojciech

    2012-01-01

    We initiate a systematic investigation of endomorphisms of graph C*-algebras C*(E), extending several known results on endomorphisms of the Cuntz algebras O_n. Most but not all of this study is focused on endomorphisms which permute the vertex projections and globally preserve the diagonal MASA D...... that the restriction to the diagonal MASA of an automorphism which globally preserves both D_E and the core AF-subalgebra eventually commutes with the corresponding one-sided shift. Secondly, we exhibit several properties of proper endomorphisms, investigate invertibility of localized endomorphisms both on C...

  20. DDR: Efficient computational method to predict drug–target interactions using graph mining and machine learning approaches

    KAUST Repository

    Olayan, Rawan S.

    2017-11-23

    Motivation Finding computationally drug-target interactions (DTIs) is a convenient strategy to identify new DTIs at low cost with reasonable accuracy. However, the current DTI prediction methods suffer the high false positive prediction rate. Results We developed DDR, a novel method that improves the DTI prediction accuracy. DDR is based on the use of a heterogeneous graph that contains known DTIs with multiple similarities between drugs and multiple similarities between target proteins. DDR applies non-linear similarity fusion method to combine different similarities. Before fusion, DDR performs a pre-processing step where a subset of similarities is selected in a heuristic process to obtain an optimized combination of similarities. Then, DDR applies a random forest model using different graph-based features extracted from the DTI heterogeneous graph. Using five repeats of 10-fold cross-validation, three testing setups, and the weighted average of area under the precision-recall curve (AUPR) scores, we show that DDR significantly reduces the AUPR score error relative to the next best start-of-the-art method for predicting DTIs by 34% when the drugs are new, by 23% when targets are new, and by 34% when the drugs and the targets are known but not all DTIs between them are not known. Using independent sources of evidence, we verify as correct 22 out of the top 25 DDR novel predictions. This suggests that DDR can be used as an efficient method to identify correct DTIs.

  1. Graph Algorithm Animation with Grrr

    OpenAIRE

    Rodgers, Peter; Vidal, Natalia

    2000-01-01

    We discuss geometric positioning, highlighting of visited nodes and user defined highlighting that form the algorithm animation facilities in the Grrr graph rewriting programming language. The main purpose of animation was initially for the debugging and profiling of Grrr code, but recently it has been extended for the purpose of teaching algorithms to undergraduate students. The animation is restricted to graph based algorithms such as graph drawing, list manipulation or more traditional gra...

  2. Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: A study to assess the drug's cardiac ion channel profile

    International Nuclear Information System (INIS)

    Koenig, Xaver; Kovar, Michael; Rubi, Lena; Mike, Agnes K.; Lukacs, Peter; Gawali, Vaibhavkumar S.; Todt, Hannes; Hilber, Karlheinz; Sandtner, Walter

    2013-01-01

    The plant alkaloid ibogaine has promising anti-addictive properties. Albeit not licenced as a therapeutic drug, and despite hints that ibogaine may perturb the heart rhythm, this alkaloid is used to treat drug addicts. We have recently reported that ibogaine inhibits human ERG (hERG) potassium channels at concentrations similar to the drugs affinity for several of its known brain targets. Thereby the drug may disturb the heart's electrophysiology. Here, to assess the drug's cardiac ion channel profile in more detail, we studied the effects of ibogaine and its congener 18-Methoxycoronaridine (18-MC) on various cardiac voltage-gated ion channels. We confirmed that heterologously expressed hERG currents are reduced by ibogaine in low micromolar concentrations. Moreover, at higher concentrations, the drug also reduced human Na v 1.5 sodium and Ca v 1.2 calcium currents. Ion currents were as well reduced by 18-MC, yet with diminished potency. Unexpectedly, although blocking hERG channels, ibogaine did not prolong the action potential (AP) in guinea pig cardiomyocytes at low micromolar concentrations. Higher concentrations (≥ 10 μM) even shortened the AP. These findings can be explained by the drug's calcium channel inhibition, which counteracts the AP-prolonging effect generated by hERG blockade. Implementation of ibogaine's inhibitory effects on human ion channels in a computer model of a ventricular cardiomyocyte, on the other hand, suggested that ibogaine does prolong the AP in the human heart. We conclude that therapeutic concentrations of ibogaine have the propensity to prolong the QT interval of the electrocardiogram in humans. In some cases this may lead to cardiac arrhythmias. - Highlights: • We study effects of anti-addiction drug ibogaine on ionic currents in cardiomyocytes. • We assess the cardiac ion channel profile of ibogaine. • Ibogaine inhibits hERG potassium, sodium and calcium channels. • Ibogaine’s effects on ion channels are a potential

  3. Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: A study to assess the drug's cardiac ion channel profile

    Energy Technology Data Exchange (ETDEWEB)

    Koenig, Xaver; Kovar, Michael; Rubi, Lena; Mike, Agnes K.; Lukacs, Peter; Gawali, Vaibhavkumar S.; Todt, Hannes [Center for Physiology and Pharmacology, Department of Neurophysiology and -pharmacology, Medical University of Vienna, 1090 Vienna (Austria); Hilber, Karlheinz, E-mail: karlheinz.hilber@meduniwien.ac.at [Center for Physiology and Pharmacology, Department of Neurophysiology and -pharmacology, Medical University of Vienna, 1090 Vienna (Austria); Sandtner, Walter [Center for Physiology and Pharmacology, Institute of Pharmacology, Medical University of Vienna, 1090 Vienna (Austria)

    2013-12-01

    The plant alkaloid ibogaine has promising anti-addictive properties. Albeit not licenced as a therapeutic drug, and despite hints that ibogaine may perturb the heart rhythm, this alkaloid is used to treat drug addicts. We have recently reported that ibogaine inhibits human ERG (hERG) potassium channels at concentrations similar to the drugs affinity for several of its known brain targets. Thereby the drug may disturb the heart's electrophysiology. Here, to assess the drug's cardiac ion channel profile in more detail, we studied the effects of ibogaine and its congener 18-Methoxycoronaridine (18-MC) on various cardiac voltage-gated ion channels. We confirmed that heterologously expressed hERG currents are reduced by ibogaine in low micromolar concentrations. Moreover, at higher concentrations, the drug also reduced human Na{sub v}1.5 sodium and Ca{sub v}1.2 calcium currents. Ion currents were as well reduced by 18-MC, yet with diminished potency. Unexpectedly, although blocking hERG channels, ibogaine did not prolong the action potential (AP) in guinea pig cardiomyocytes at low micromolar concentrations. Higher concentrations (≥ 10 μM) even shortened the AP. These findings can be explained by the drug's calcium channel inhibition, which counteracts the AP-prolonging effect generated by hERG blockade. Implementation of ibogaine's inhibitory effects on human ion channels in a computer model of a ventricular cardiomyocyte, on the other hand, suggested that ibogaine does prolong the AP in the human heart. We conclude that therapeutic concentrations of ibogaine have the propensity to prolong the QT interval of the electrocardiogram in humans. In some cases this may lead to cardiac arrhythmias. - Highlights: • We study effects of anti-addiction drug ibogaine on ionic currents in cardiomyocytes. • We assess the cardiac ion channel profile of ibogaine. • Ibogaine inhibits hERG potassium, sodium and calcium channels. • Ibogaine’s effects on

  4. Current status and future prospects for enabling chemistry technology in the drug discovery process.

    Science.gov (United States)

    Djuric, Stevan W; Hutchins, Charles W; Talaty, Nari N

    2016-01-01

    This review covers recent advances in the implementation of enabling chemistry technologies into the drug discovery process. Areas covered include parallel synthesis chemistry, high-throughput experimentation, automated synthesis and purification methods, flow chemistry methodology including photochemistry, electrochemistry, and the handling of "dangerous" reagents. Also featured are advances in the "computer-assisted drug design" area and the expanding application of novel mass spectrometry-based techniques to a wide range of drug discovery activities.

  5. Current status and future prospects for enabling chemistry technology in the drug discovery process

    Science.gov (United States)

    Djuric, Stevan W.; Hutchins, Charles W.; Talaty, Nari N.

    2016-01-01

    This review covers recent advances in the implementation of enabling chemistry technologies into the drug discovery process. Areas covered include parallel synthesis chemistry, high-throughput experimentation, automated synthesis and purification methods, flow chemistry methodology including photochemistry, electrochemistry, and the handling of “dangerous” reagents. Also featured are advances in the “computer-assisted drug design” area and the expanding application of novel mass spectrometry-based techniques to a wide range of drug discovery activities. PMID:27781094

  6. Classification of prophylactic antiradiation drugs as the consistency of conceptual basis of current radiation pharmacology

    International Nuclear Information System (INIS)

    Vasin, M.F

    1999-01-01

    The consistency of the classification of prophylactic antiradiation drugs have been given consideration as history of their discovery, theory of the radioprotection mechanisms and their use in applied medicine. Prophylactic drugs consists of radioprotectors with short-term of long-term action, drugs stimulating radioresistance, the ones suppressing symptoms of primary radiation reaction, the ones of early detoxication, the ones for adsorption and elimination of radionuclides from an organism [ru

  7. Optimization Problems on Threshold Graphs

    Directory of Open Access Journals (Sweden)

    Elena Nechita

    2010-06-01

    Full Text Available During the last three decades, different types of decompositions have been processed in the field of graph theory. Among these we mention: decompositions based on the additivity of some characteristics of the graph, decompositions where the adjacency law between the subsets of the partition is known, decompositions where the subgraph induced by every subset of the partition must have predeterminate properties, as well as combinations of such decompositions. In this paper we characterize threshold graphs using the weakly decomposition, determine: density and stability number, Wiener index and Wiener polynomial for threshold graphs.

  8. Eulerian Graphs and Related Topics

    CERN Document Server

    Fleischner, Herbert

    1990-01-01

    The two volumes comprising Part 1 of this work embrace the theme of Eulerian trails and covering walks. They should appeal both to researchers and students, as they contain enough material for an undergraduate or graduate graph theory course which emphasizes Eulerian graphs, and thus can be read by any mathematician not yet familiar with graph theory. But they are also of interest to researchers in graph theory because they contain many recent results, some of which are only partial solutions to more general problems. A number of conjectures have been included as well. Various problems (such a

  9. Quantum Graph Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Maunz, Peter Lukas Wilhelm [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Sterk, Jonathan David [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Lobser, Daniel [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Parekh, Ojas D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Ryan-Anderson, Ciaran [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2016-01-01

    In recent years, advanced network analytics have become increasingly important to na- tional security with applications ranging from cyber security to detection and disruption of ter- rorist networks. While classical computing solutions have received considerable investment, the development of quantum algorithms to address problems, such as data mining of attributed relational graphs, is a largely unexplored space. Recent theoretical work has shown that quan- tum algorithms for graph analysis can be more efficient than their classical counterparts. Here, we have implemented a trapped-ion-based two-qubit quantum information proces- sor to address these goals. Building on Sandia's microfabricated silicon surface ion traps, we have designed, realized and characterized a quantum information processor using the hyperfine qubits encoded in two 171 Yb + ions. We have implemented single qubit gates using resonant microwave radiation and have employed Gate set tomography (GST) to characterize the quan- tum process. For the first time, we were able to prove that the quantum process surpasses the fault tolerance thresholds of some quantum codes by demonstrating a diamond norm distance of less than 1 . 9 x 10 [?] 4 . We used Raman transitions in order to manipulate the trapped ions' motion and realize two-qubit gates. We characterized the implemented motion sensitive and insensitive single qubit processes and achieved a maximal process infidelity of 6 . 5 x 10 [?] 5 . We implemented the two-qubit gate proposed by Molmer and Sorensen and achieved a fidelity of more than 97 . 7%.

  10. Building Scalable Knowledge Graphs for Earth Science

    Science.gov (United States)

    Ramachandran, R.; Maskey, M.; Gatlin, P. N.; Zhang, J.; Duan, X.; Bugbee, K.; Christopher, S. A.; Miller, J. J.

    2017-12-01

    Estimates indicate that the world's information will grow by 800% in the next five years. In any given field, a single researcher or a team of researchers cannot keep up with this rate of knowledge expansion without the help of cognitive systems. Cognitive computing, defined as the use of information technology to augment human cognition, can help tackle large systemic problems. Knowledge graphs, one of the foundational components of cognitive systems, link key entities in a specific domain with other entities via relationships. Researchers could mine these graphs to make probabilistic recommendations and to infer new knowledge. At this point, however, there is a dearth of tools to generate scalable Knowledge graphs using existing corpus of scientific literature for Earth science research. Our project is currently developing an end-to-end automated methodology for incrementally constructing Knowledge graphs for Earth Science. Semantic Entity Recognition (SER) is one of the key steps in this methodology. SER for Earth Science uses external resources (including metadata catalogs and controlled vocabulary) as references to guide entity extraction and recognition (i.e., labeling) from unstructured text, in order to build a large training set to seed the subsequent auto-learning component in our algorithm. Results from several SER experiments will be presented as well as lessons learned.

  11. Asymptote Misconception on Graphing Functions: Does Graphing Software Resolve It?

    Directory of Open Access Journals (Sweden)

    Mehmet Fatih Öçal

    2017-01-01

    Full Text Available Graphing function is an important issue in mathematics education due to its use in various areas of mathematics and its potential roles for students to enhance learning mathematics. The use of some graphing software assists students’ learning during graphing functions. However, the display of graphs of functions that students sketched by hand may be relatively different when compared to the correct forms sketched using graphing software. The possible misleading effects of this situation brought a discussion of a misconception (asymptote misconception on graphing functions. The purpose of this study is two- fold. First of all, this study investigated whether using graphing software (GeoGebra in this case helps students to determine and resolve this misconception in calculus classrooms. Second, the reasons for this misconception are sought. The multiple case study was utilized in this study. University students in two calculus classrooms who received instructions with (35 students or without GeoGebra assisted instructions (32 students were compared according to whether they fell into this misconception on graphing basic functions (1/x, lnx, ex. In addition, students were interviewed to reveal the reasons behind this misconception. Data were analyzed by means of descriptive and content analysis methods. The findings indicated that those who received GeoGebra assisted instruction were better in resolving it. In addition, the reasons behind this misconception were found to be teacher-based, exam-based and some other factors.

  12. Could a revision of the current guidelines for cancer drug use improve the quality of cancer treatment?

    Science.gov (United States)

    Lippert, Theodor H; Ruoff, Hans-Jörg; Volm, Manfred

    2014-01-01

    Clinical practice guidelines are indispensable for such a variable disease as malignant solid tumors, with the complex possibilities of drug treatment. The current guidelines may be criticized on several points, however. First, there is a lack of information on the outcome of treatment, such as the expected success and failure rates. Treating not only drug responders but also nonresponders, that is, patients with drug resistance, must result in failures. There is no mention of the possibility of excluding the drug nonresponders, identifiable by special laboratory tests and no consideration is given to the different side effects of the recommended drug regimens. Nor are there any instructions concerning tumor cases for which anticancer drug treatment is futile. In such cases, early palliative care may lead to significant improvements in both life quality and life expectancy. Not least, there is no transparency concerning the preparation of the guidelines: persons cannot be identified who could give a statement of conflicts of interest, and responsibility is assumed only by anonymous medical associations. A revision of the current guidelines could considerably improve cancer treatment.

  13. ON BIPOLAR SINGLE VALUED NEUTROSOPHIC GRAPHS

    OpenAIRE

    Said Broumi; Mohamed Talea; Assia Bakali; Florentin Smarandache

    2016-01-01

    In this article, we combine the concept of bipolar neutrosophic set and graph theory. We introduce the notions of bipolar single valued neutrosophic graphs, strong bipolar single valued neutrosophic graphs, complete bipolar single valued neutrosophic graphs, regular bipolar single valued neutrosophic graphs and investigate some of their related properties.

  14. Disease-modifying antirheumatic drugs in pregnancy - Current status and implications for the future

    NARCIS (Netherlands)

    Vroom, Fokaline; de Walle, Hermien E. K.; van de Laar, Mart A. J. F.; Brouwers, Jacobus R. B. J.; de Jong-van den Berg, Lolkje T. W.

    2006-01-01

    Drug use during pregnancy is sometimes unavoidable, especially in chronic inflammatory diseases such as rheumatoid arthritis (RA). The use of disease-modifying antirheumatic drugs (DMARDs) often starts in the early stage of RA; therefore, women of reproductive age are at risk for exposure to a DMARD

  15. Valuation of Drug Abuse: A Review of Current Methodologies and Implications for Policy Making

    Science.gov (United States)

    Schori, Maayan

    2011-01-01

    This article reviews the use of several valuation methods as they relate to drug abuse and places them within the context of U.S. policy. First, cost-of-illness (COI) studies are reviewed and their limitations discussed. Second, three additional economic methods of valuing drug abuse are reviewed, including cost-effectiveness analysis (CEA),…

  16. What the History of Drugs Can Teach Us About the Current Cannabis Legalization Process: Unfinished Business.

    Science.gov (United States)

    Adrian, Manuella

    2015-01-01

    Over time, there have been considerable changes in the variety, availability, production, distribution, and use and user(s) of psychoactive substances, the meaning of substance use and its impact on users and their social or physical environment(s). This article reviews the mechanisms of introduction of psychoactive substances such as alcohol, tobacco, coffee, tea and cannabis to populations and communities that did not have them before. It considers the historical tension between early adopters who greet new substances with various levels of enthusiasm in their eagerness to enjoy what they believe to be the benefits of using these substances, and those focused on what they believe to be the negative aspects of use, who decry these new substances with horror. With more nonusers than users in the population, social policies tend to be directed at preventing, restricting, or punishing selected use, users and .drugs., using controls and interventions such regulation, incarceration, death sentence, treatment, prevention, legalization, taxation, among others. Whatever their intent or wished-for impact, all had consequences that produced additional, unplanned for, and (often) negative effects. This paper will consider some of these sequences as they occurred historically with other substances in light of the current shift to legalization and normalization of cannabis, noting the mechanisms of use, controls, and consequences of some types of formal interventions and give some attention to how and what we can learn from our experiences in order to plan ahead and become better prepared to successfully deal with the 'unexpecteds' of that well-known 'hell' paved with good intentions.

  17. Drugs for Neglected Diseases initiative model of drug development for neglected diseases: current status and future challenges.

    Science.gov (United States)

    Ioset, Jean-Robert; Chang, Shing

    2011-09-01

    The Drugs for Neglected Diseases initiative (DNDi) is a patients' needs-driven organization committed to the development of new treatments for neglected diseases. Created in 2003, DNDi has delivered four improved treatments for malaria, sleeping sickness and visceral leishmaniasis. A main DNDi challenge is to build a solid R&D portfolio for neglected diseases and to deliver preclinical candidates in a timely manner using an original model based on partnership. To address this challenge DNDi has remodeled its discovery activities from a project-based academic-bound network to a fully integrated process-oriented platform in close collaboration with pharmaceutical companies. This discovery platform relies on dedicated screening capacity and lead-optimization consortia supported by a pragmatic, structured and pharmaceutical-focused compound sourcing strategy.

  18. Graph Theory. 2. Vertex Descriptors and Graph Coloring

    Directory of Open Access Journals (Sweden)

    Lorentz JÄNTSCHI

    2002-12-01

    Full Text Available This original work presents the construction of a set of ten sequence matrices and their applications for ordering vertices in graphs. For every sequence matrix three ordering criteria are applied: lexicographic ordering, based on strings of numbers, corresponding to every vertex, extracted as rows from sequence matrices; ordering by the sum of path lengths from a given vertex; and ordering by the sum of paths, starting from a given vertex. We also examine a graph that has different orderings for the above criteria. We then proceed to demonstrate that every criterion induced its own partition of graph vertex. We propose the following theoretical result: both LAVS and LVDS criteria generate identical partitioning of vertices in any graph. Finally, a coloring of graph vertices according to introduced ordering criteria was proposed.

  19. Can Brazil play a more important role in global tuberculosis drug production? An assessment of current capacity and challenges.

    Science.gov (United States)

    Gemal, Andre; Keravec, Joel; Menezes, Alexandre; Trajman, Anete

    2013-03-27

    Despite the existence of effective treatment, tuberculosis is still a global public health issue. The World Health Organization recommends a six-month four-drug regimen in fixed-dose combination formulation to treat drug sensitive tuberculosis, and long course regimens with several second-line drugs to treat multi-drug resistant tuberculosis. To achieve the projected tuberculosis elimination goal by 2050, it will be essential to ensure a non-interrupted supply of quality-assured tuberculosis drugs. However, quality and affordable tuberculosis drug supply is still a significant challenge for National Tuberculosis Programs. Quality drug production requires a combination of complex steps. The first challenge is to guarantee the quality of tuberculosis active pharmaceutical ingredients, then ensure an adequate manufacturing process, according to international standards, to guarantee final product's safety, efficacy and quality. Good practices for storage, transport, distribution and quality control procedures must follow. In contrast to other high-burden countries, Brazil produces tuberculosis drugs through a strong network of public sector drug manufacturers regulated by a World Health Organization-certified national sanitary authority. The installed capacity for production surpasses the 71,000 needed treatments in the country. However, in order to be prepared to act as a global supplier, important bottlenecks are to be overcome. This article presents an in-depth analysis of the current status of production of tuberculosis drugs in Brazil and the bottlenecks and opportunities for the country to sustain national demand and play a role as a potential global supplier. Raw material and drug production, quality control, international certification and pre-qualification, political commitment and regulatory aspects are discussed, as well recommendations for tackling these bottlenecks. This discussion becomes more important as new drugs and regimens to treat tuberculosis are

  20. The One Universal Graph — a free and open graph database

    International Nuclear Information System (INIS)

    Ng, Liang S.; Champion, Corbin

    2016-01-01

    Recent developments in graph database mostly are huge projects involving big organizations, big operations and big capital, as the name Big Data attests. We proposed the concept of One Universal Graph (OUG) which states that all observable and known objects and concepts (physical, conceptual or digitally represented) can be connected with only one single graph; furthermore the OUG can be implemented with a very simple text file format with free software, capable of being executed on Android or smaller devices. As such the One Universal Graph Data Exchange (GOUDEX) modules can potentially be installed on hundreds of millions of Android devices and Intel compatible computers shipped annually. Coupled with its open nature and ability to connect to existing leading search engines and databases currently in operation, GOUDEX has the potential to become the largest and a better interface for users and programmers to interact with the data on the Internet. With a Web User Interface for users to use and program in native Linux environment, Free Crowdware implemented in GOUDEX can help inexperienced users learn programming with better organized documentation for free software, and is able to manage programmer's contribution down to a single line of code or a single variable in software projects. It can become the first practically realizable “Internet brain” on which a global artificial intelligence system can be implemented. Being practically free and open, One Universal Graph can have significant applications in robotics, artificial intelligence as well as social networks. (paper)

  1. The One Universal Graph — a free and open graph database

    Science.gov (United States)

    Ng, Liang S.; Champion, Corbin

    2016-02-01

    Recent developments in graph database mostly are huge projects involving big organizations, big operations and big capital, as the name Big Data attests. We proposed the concept of One Universal Graph (OUG) which states that all observable and known objects and concepts (physical, conceptual or digitally represented) can be connected with only one single graph; furthermore the OUG can be implemented with a very simple text file format with free software, capable of being executed on Android or smaller devices. As such the One Universal Graph Data Exchange (GOUDEX) modules can potentially be installed on hundreds of millions of Android devices and Intel compatible computers shipped annually. Coupled with its open nature and ability to connect to existing leading search engines and databases currently in operation, GOUDEX has the potential to become the largest and a better interface for users and programmers to interact with the data on the Internet. With a Web User Interface for users to use and program in native Linux environment, Free Crowdware implemented in GOUDEX can help inexperienced users learn programming with better organized documentation for free software, and is able to manage programmer's contribution down to a single line of code or a single variable in software projects. It can become the first practically realizable “Internet brain” on which a global artificial intelligence system can be implemented. Being practically free and open, One Universal Graph can have significant applications in robotics, artificial intelligence as well as social networks.

  2. On an edge partition and root graphs of some classes of line graphs

    Directory of Open Access Journals (Sweden)

    K Pravas

    2017-04-01

    Full Text Available The Gallai and the anti-Gallai graphs of a graph $G$ are complementary pairs of spanning subgraphs of the line graph of $G$. In this paper we find some structural relations between these graph classes by finding a partition of the edge set of the line graph of a graph $G$ into the edge sets of the Gallai and anti-Gallai graphs of $G$. Based on this, an optimal algorithm to find the root graph of a line graph is obtained. Moreover, root graphs of diameter-maximal, distance-hereditary, Ptolemaic and chordal graphs are also discussed.

  3. Current status of prediction of drug disposition and toxicity in humans using chimeric mice with humanized liver.

    Science.gov (United States)

    Kitamura, Shigeyuki; Sugihara, Kazumi

    2014-01-01

    1. Human-chimeric mice with humanized liver have been constructed by transplantation of human hepatocytes into several types of mice having genetic modifications that injure endogenous liver cells. Here, we focus on liver urokinase-type plasminogen activator-transgenic severe combined immunodeficiency (uPA/SCID) mice, which are the most widely used human-chimeric mice. Studies so far indicate that drug metabolism, drug transport, pharmacological effects and toxicological action in these mice are broadly similar to those in humans. 2. Expression of various drug-metabolizing enzymes is known to be different between humans and rodents. However, the expression pattern of cytochrome P450, aldehyde oxidase and phase II enzymes in the liver of human-chimeric mice resembles that in humans, not that in the host mice. 3. Metabolism of various drugs, including S-warfarin, zaleplon, ibuprofen, naproxen, coumarin, troglitazone and midazolam, in human-chimeric mice is mediated by human drug-metabolizing enzymes, not by host mouse enzymes, and thus resembles that in humans. 4. Pharmacological and toxicological effects of various drugs in human-chimeric mice are also similar to those in humans. 5. The current consensus is that chimeric mice with humanized liver are useful to predict drug metabolism catalyzed by cytochrome P450, aldehyde oxidase and phase II enzymes in humans in vivo and in vitro. Some remaining issues are discussed in this review.

  4. A searching and reporting system for relational databases using a graph-based metadata representation.

    Science.gov (United States)

    Hewitt, Robin; Gobbi, Alberto; Lee, Man-Ling

    2005-01-01

    Relational databases are the current standard for storing and retrieving data in the pharmaceutical and biotech industries. However, retrieving data from a relational database requires specialized knowledge of the database schema and of the SQL query language. At Anadys, we have developed an easy-to-use system for searching and reporting data in a relational database to support our drug discovery project teams. This system is fast and flexible and allows users to access all data without having to write SQL queries. This paper presents the hierarchical, graph-based metadata representation and SQL-construction methods that, together, are the basis of this system's capabilities.

  5. Equivalence of complex drug products: advances in and challenges for current regulatory frameworks.

    Science.gov (United States)

    Hussaarts, Leonie; Mühlebach, Stefan; Shah, Vinod P; McNeil, Scott; Borchard, Gerrit; Flühmann, Beat; Weinstein, Vera; Neervannan, Sesha; Griffiths, Elwyn; Jiang, Wenlei; Wolff-Holz, Elena; Crommelin, Daan J A; de Vlieger, Jon S B

    2017-11-01

    Biotechnology and nanotechnology provide a growing number of innovator-driven complex drug products and their copy versions. Biologics exemplify one category of complex drugs, but there are also nonbiological complex drug products, including many nanomedicines, such as iron-carbohydrate complexes, drug-carrying liposomes or emulsions, and glatiramoids. In this white paper, which stems from a 1-day conference at the New York Academy of Sciences, we discuss regulatory frameworks in use worldwide (e.g., the U.S. Food and Drug Administration, the European Medicines Agency, the World Health Organization) to approve these complex drug products and their follow-on versions. One of the key questions remains how to assess equivalence of these complex products. We identify a number of points for which consensus was found among the stakeholders who were present: scientists from innovator and generic/follow-on companies, academia, and regulatory bodies from different parts of the world. A number of topics requiring follow-up were identified: (1) assessment of critical attributes to establish equivalence for follow-on versions, (2) the need to publish scientific findings in the public domain to further progress in the field, (3) the necessity to develop worldwide consensus regarding nomenclature and labeling of these complex products, and (4) regulatory actions when substandard complex drug products are identified. © 2017 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.

  6. The planar cubic Cayley graphs

    CERN Document Server

    Georgakopoulos, Agelos

    2018-01-01

    The author obtains a complete description of the planar cubic Cayley graphs, providing an explicit presentation and embedding for each of them. This turns out to be a rich class, comprising several infinite families. He obtains counterexamples to conjectures of Mohar, Bonnington and Watkins. The author's analysis makes the involved graphs accessible to computation, corroborating a conjecture of Droms.

  7. Groupies in random bipartite graphs

    OpenAIRE

    Yilun Shang

    2010-01-01

    A vertex $v$ of a graph $G$ is called a groupie if its degree is notless than the average of the degrees of its neighbors. In thispaper we study the influence of bipartition $(B_1,B_2)$ on groupiesin random bipartite graphs $G(B_1,B_2,p)$ with both fixed $p$ and$p$ tending to zero.

  8. Nested Dynamic Condition Response Graphs

    DEFF Research Database (Denmark)

    Hildebrandt, Thomas; Mukkamala, Raghava Rao; Slaats, Tijs

    2012-01-01

    We present an extension of the recently introduced declarative process model Dynamic Condition Response Graphs ( DCR Graphs) to allow nested subgraphs and a new milestone relation between events. The extension was developed during a case study carried out jointly with our industrial partner...

  9. Bell inequalities for graph states

    International Nuclear Information System (INIS)

    Toth, G.; Hyllus, P.; Briegel, H.J.; Guehne, O.

    2005-01-01

    Full text: In the last years graph states have attracted an increasing interest in the field of quantum information theory. Graph states form a family of multi-qubit states which comprises many popular states such as the GHZ states and the cluster states. They also play an important role in applications. For instance, measurement based quantum computation uses graph states as resources. From a theoretical point of view, it is remarkable that graph states allow for a simple description in terms of stabilizing operators. In this contribution, we investigate the non-local properties of graph states. We derive a family of Bell inequalities which require three measurement settings for each party and are maximally violated by graph states. In turn, any graph state violates at least one of the inequalities. We show that for certain types of graph states the violation of these inequalities increases exponentially with the number of qubits. We also discuss connections to other entanglement properties such as the positively of the partial transpose or the geometric measure of entanglement. (author)

  10. Graph Sampling for Covariance Estimation

    KAUST Repository

    Chepuri, Sundeep Prabhakar; Leus, Geert

    2017-01-01

    specialize for undirected circulant graphs in that the graph nodes leading to the best compression rates are given by the so-called minimal sparse rulers. A near-optimal greedy algorithm is developed to design the subsampling scheme for the non

  11. Network reconstruction via graph blending

    Science.gov (United States)

    Estrada, Rolando

    2016-05-01

    Graphs estimated from empirical data are often noisy and incomplete due to the difficulty of faithfully observing all the components (nodes and edges) of the true graph. This problem is particularly acute for large networks where the number of components may far exceed available surveillance capabilities. Errors in the observed graph can render subsequent analyses invalid, so it is vital to develop robust methods that can minimize these observational errors. Errors in the observed graph may include missing and spurious components, as well fused (multiple nodes are merged into one) and split (a single node is misinterpreted as many) nodes. Traditional graph reconstruction methods are only able to identify missing or spurious components (primarily edges, and to a lesser degree nodes), so we developed a novel graph blending framework that allows us to cast the full estimation problem as a simple edge addition/deletion problem. Armed with this framework, we systematically investigate the viability of various topological graph features, such as the degree distribution or the clustering coefficients, and existing graph reconstruction methods for tackling the full estimation problem. Our experimental results suggest that incorporating any topological feature as a source of information actually hinders reconstruction accuracy. We provide a theoretical analysis of this phenomenon and suggest several avenues for improving this estimation problem.

  12. A cluster algorithm for graphs

    NARCIS (Netherlands)

    S. van Dongen

    2000-01-01

    textabstractA cluster algorithm for graphs called the emph{Markov Cluster algorithm (MCL~algorithm) is introduced. The algorithm provides basically an interface to an algebraic process defined on stochastic matrices, called the MCL~process. The graphs may be both weighted (with nonnegative weight)

  13. Quantum chaos on discrete graphs

    International Nuclear Information System (INIS)

    Smilansky, Uzy

    2007-01-01

    Adapting a method developed for the study of quantum chaos on quantum (metric) graphs (Kottos and Smilansky 1997 Phys. Rev. Lett. 79 4794, Kottos and Smilansky 1999 Ann. Phys., NY 274 76), spectral ζ functions and trace formulae for discrete Laplacians on graphs are derived. This is achieved by expressing the spectral secular equation in terms of the periodic orbits of the graph and obtaining functions which belong to the class of ζ functions proposed originally by Ihara (1966 J. Mat. Soc. Japan 18 219) and expanded by subsequent authors (Stark and Terras 1996 Adv. Math. 121 124, Kotani and Sunada 2000 J. Math. Sci. Univ. Tokyo 7 7). Finally, a model of 'classical dynamics' on the discrete graph is proposed. It is analogous to the corresponding classical dynamics derived for quantum graphs (Kottos and Smilansky 1997 Phys. Rev. Lett. 79 4794, Kottos and Smilansky 1999 Ann. Phys., NY 274 76). (fast track communication)

  14. RJSplot: Interactive Graphs with R.

    Science.gov (United States)

    Barrios, David; Prieto, Carlos

    2018-03-01

    Data visualization techniques provide new methods for the generation of interactive graphs. These graphs allow a better exploration and interpretation of data but their creation requires advanced knowledge of graphical libraries. Recent packages have enabled the integration of interactive graphs in R. However, R provides limited graphical packages that allow the generation of interactive graphs for computational biology applications. The present project has joined the analytical power of R with the interactive graphical features of JavaScript in a new R package (RJSplot). It enables the easy generation of interactive graphs in R, provides new visualization capabilities, and contributes to the advance of computational biology analytical methods. At present, 16 interactive graphics are available in RJSplot, such as the genome viewer, Manhattan plots, 3D plots, heatmaps, dendrograms, networks, and so on. The RJSplot package is freely available online at http://rjsplot.net. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Computational Fragment-Based Drug Design: Current Trends, Strategies, and Applications.

    Science.gov (United States)

    Bian, Yuemin; Xie, Xiang-Qun Sean

    2018-04-09

    Fragment-based drug design (FBDD) has become an effective methodology for drug development for decades. Successful applications of this strategy brought both opportunities and challenges to the field of Pharmaceutical Science. Recent progress in the computational fragment-based drug design provide an additional approach for future research in a time- and labor-efficient manner. Combining multiple in silico methodologies, computational FBDD possesses flexibilities on fragment library selection, protein model generation, and fragments/compounds docking mode prediction. These characteristics provide computational FBDD superiority in designing novel and potential compounds for a certain target. The purpose of this review is to discuss the latest advances, ranging from commonly used strategies to novel concepts and technologies in computational fragment-based drug design. Particularly, in this review, specifications and advantages are compared between experimental and computational FBDD, and additionally, limitations and future prospective are discussed and emphasized.

  16. Current position of high-resolution MS for drug quantification in clinical & forensic toxicology.

    Science.gov (United States)

    Meyer, Markus R; Helfer, Andreas G; Maurer, Hans H

    2014-08-01

    This paper reviews high-resolution MS approaches published from January 2011 until March 2014 for the quantification of drugs (of abuse) and/or their metabolites in biosamples using LC-MS with time-of-flight or Orbitrap™ mass analyzers. Corresponding approaches are discussed including sample preparation and mass spectral settings. The advantages and limitations of high-resolution MS for drug quantification, as well as the demand for a certain resolution or a specific mass accuracy are also explored.

  17. On characterizing terrain visibility graphs

    Directory of Open Access Journals (Sweden)

    William Evans

    2015-06-01

    Full Text Available A terrain is an $x$-monotone polygonal line in the $xy$-plane. Two vertices of a terrain are mutually visible if and only if there is no terrain vertex on or above the open line segment connecting them. A graph whose vertices represent terrain vertices and whose edges represent mutually visible pairs of terrain vertices is called a terrain visibility graph. We would like to find properties that are both necessary and sufficient for a graph to be a terrain visibility graph; that is, we would like to characterize terrain visibility graphs.Abello et al. [Discrete and Computational Geometry, 14(3:331--358, 1995] showed that all terrain visibility graphs are “persistent”. They showed that the visibility information of a terrain point set implies some ordering requirements on the slopes of the lines connecting pairs of points in any realization, and as a step towards showing sufficiency, they proved that for any persistent graph $M$ there is a total order on the slopes of the (pseudo lines in a generalized configuration of points whose visibility graph is $M$.We give a much simpler proof of this result by establishing an orientation to every triple of vertices, reflecting some slope ordering requirements that are consistent with $M$ being the visibility graph, and prove that these requirements form a partial order. We give a faster algorithm to construct a total order on the slopes. Our approach attempts to clarify the implications of the graph theoretic properties on the ordering of the slopes, and may be interpreted as defining properties on an underlying oriented matroid that we show is a restricted type of $3$-signotope.

  18. Graph embedding with rich information through heterogeneous graph

    KAUST Repository

    Sun, Guolei

    2017-11-12

    Graph embedding, aiming to learn low-dimensional representations for nodes in graphs, has attracted increasing attention due to its critical application including node classification, link prediction and clustering in social network analysis. Most existing algorithms for graph embedding only rely on the topology information and fail to use the copious information in nodes as well as edges. As a result, their performance for many tasks may not be satisfactory. In this thesis, we proposed a novel and general framework for graph embedding with rich text information (GERI) through constructing a heterogeneous network, in which we integrate node and edge content information with graph topology. Specially, we designed a novel biased random walk to explore the constructed heterogeneous network with the notion of flexible neighborhood. Our sampling strategy can compromise between BFS and DFS local search on heterogeneous graph. To further improve our algorithm, we proposed semi-supervised GERI (SGERI), which learns graph embedding in an discriminative manner through heterogeneous network with label information. The efficacy of our method is demonstrated by extensive comparison experiments with 9 baselines over multi-label and multi-class classification on various datasets including Citeseer, Cora, DBLP and Wiki. It shows that GERI improves the Micro-F1 and Macro-F1 of node classification up to 10%, and SGERI improves GERI by 5% in Wiki.

  19. Summary report of PQRI Workshop on Nanomaterial in Drug Products: current experience and management of potential risks.

    Science.gov (United States)

    Bartlett, Jeremy A; Brewster, Marcus; Brown, Paul; Cabral-Lilly, Donna; Cruz, Celia N; David, Raymond; Eickhoff, W Mark; Haubenreisser, Sabine; Jacobs, Abigail; Malinoski, Frank; Morefield, Elaine; Nalubola, Ritu; Prud'homme, Robert K; Sadrieh, Nakissa; Sayes, Christie M; Shahbazian, Hripsime; Subbarao, Nanda; Tamarkin, Lawrence; Tyner, Katherine; Uppoor, Rajendra; Whittaker-Caulk, Margaret; Zamboni, William

    2015-01-01

    At the Product Quality Research Institute (PQRI) Workshop held last January 14-15, 2014, participants from academia, industry, and governmental agencies involved in the development and regulation of nanomedicines discussed the current state of characterization, formulation development, manufacturing, and nonclinical safety evaluation of nanomaterial-containing drug products for human use. The workshop discussions identified areas where additional understanding of material attributes, absorption, biodistribution, cellular and tissue uptake, and disposition of nanosized particles would continue to inform their safe use in drug products. Analytical techniques and methods used for in vitro characterization and stability testing of formulations containing nanomaterials were discussed, along with their advantages and limitations. Areas where additional regulatory guidance and material characterization standards would help in the development and approval of nanomedicines were explored. Representatives from the US Food and Drug Administration (USFDA), Health Canada, and European Medicines Agency (EMA) presented information about the diversity of nanomaterials in approved and newly developed drug products. USFDA, Health Canada, and EMA regulators discussed the applicability of current regulatory policies in presentations and open discussion. Information contained in several of the recent EMA reflection papers was discussed in detail, along with their scope and intent to enhance scientific understanding about disposition, efficacy, and safety of nanomaterials introduced in vivo and regulatory requirements for testing and market authorization. Opportunities for interaction with regulatory agencies during the lifecycle of nanomedicines were also addressed at the meeting. This is a summary of the workshop presentations and discussions, including considerations for future regulatory guidance on drug products containing nanomaterials.

  20. CORECLUSTER: A Degeneracy Based Graph Clustering Framework

    OpenAIRE

    Giatsidis , Christos; Malliaros , Fragkiskos; Thilikos , Dimitrios M. ,; Vazirgiannis , Michalis

    2014-01-01

    International audience; Graph clustering or community detection constitutes an important task forinvestigating the internal structure of graphs, with a plethora of applications in several domains. Traditional tools for graph clustering, such asspectral methods, typically suffer from high time and space complexity. In thisarticle, we present \\textsc{CoreCluster}, an efficient graph clusteringframework based on the concept of graph degeneracy, that can be used along withany known graph clusteri...

  1. Hormonal and antimicrobial therapy in theriogenology practice: currently approved drugs in the USA and possible future directions.

    Science.gov (United States)

    Modric, T; Momcilovic, D; Gwin, W E; Peter, A T

    2011-08-01

    Hormonal and antimicrobial therapies are essential to regulate and maintain healthy reproduction in domestic animals. The appropriate and legal use of these compounds is ultimately the responsibility of the veterinarian and other users, with a primary mission to directly protect and promote the health of animals, and indirectly the health of people. The appropriate use of these products is defined by the Federal Food, Drug, and Cosmetic Act, 21 United States of America § 301 et seq and implementing regulations in the Code of Federal Regulations. In the past, use of a drug in an animal for an unapproved use violated this Act. However, passage of the Animal Medicinal Drug Use Clarification Act 1994 legalized the extra-label use of certain animal and human drugs in veterinary practice for treating diseases. This manuscript reviews currently approved hormonal and antimicrobial drugs for use in theriogenology. Considering the ever increasing knowledge in the area of veterinary reproduction, particularly in the treatment and control of reproduction using antimicrobials and hormones, it would be beneficial to widen the therapeutic options in these categories. The potential for widening the therapeutic options is also discussed in this review, by providing a non-exhaustive but essential list of potential new drugs for use in clinical animal reproduction (theriogenology). Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Multigraph: Interactive Data Graphs on the Web

    Science.gov (United States)

    Phillips, M. B.

    2010-12-01

    " through large data sets, downloading only those the parts of the data that are needed for display. Multigraph is currently in use on several web sites including the US Drought Portal (www.drought.gov), the NOAA Climate Services Portal (www.climate.gov), the Climate Reference Network (www.ncdc.noaa.gov/crn), NCDC's State of the Climate Report (www.ncdc.noaa.gov/sotc), and the US Forest Service's Forest Change Assessment Viewer (ews.forestthreats.org/NPDE/NPDE.html). More information about Multigraph is available from the web site www.multigraph.org. Interactive Graph of Global Temperature Anomalies from ClimateWatch Magazine (http://www.climatewatch.noaa.gov/2009/articles/climate-change-global-temperature)

  3. Current applications of miniaturized chromatographic and electrophoretic techniques in drug analysis.

    Science.gov (United States)

    Aturki, Zeineb; Rocco, Anna; Rocchi, Silvia; Fanali, Salvatore

    2014-12-01

    In the last decade, miniaturized separation techniques have become greatly popular in pharmaceutical analysis. Miniaturized separation methods are increasingly utilized in all processes of drug discovery as well as quality control of pharmaceutical preparation. The great advantages presented by the analytical miniaturized techniques, including high separation efficiency and resolution, rapid analysis and minimal consumption of reagents and samples, make them an attractive alternative to the conventional chromatographic methods for drug analysis. The purpose of this review is to give a general overview of the applicability of capillary electrophoresis (CE), capillary electrochromatography (CEC) and micro/capillary/nano-liquid chromatography (micro-LC/CLC/nano-LC) for the analysis of pharmaceutical formulations, active pharmaceutical ingredients (API), drug impurity testing, chiral drug separation, determination of drugs and metabolites in biological fluids. The results concerning the use of CEC, micro-LC, CLC, and nano-LC in the period 2009-2013, while for CE, those from 2012 up to the review draft are here summarized and some specific examples are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Hierarchy of modular graph identities

    International Nuclear Information System (INIS)

    D’Hoker, Eric; Kaidi, Justin

    2016-01-01

    The low energy expansion of Type II superstring amplitudes at genus one is organized in terms of modular graph functions associated with Feynman graphs of a conformal scalar field on the torus. In earlier work, surprising identities between two-loop graphs at all weights, and between higher-loop graphs of weights four and five were constructed. In the present paper, these results are generalized in two complementary directions. First, all identities at weight six and all dihedral identities at weight seven are obtained and proven. Whenever the Laurent polynomial at the cusp is available, the form of these identities confirms the pattern by which the vanishing of the Laurent polynomial governs the full modular identity. Second, the family of modular graph functions is extended to include all graphs with derivative couplings and worldsheet fermions. These extended families of modular graph functions are shown to obey a hierarchy of inhomogeneous Laplace eigenvalue equations. The eigenvalues are calculated analytically for the simplest infinite sub-families and obtained by Maple for successively more complicated sub-families. The spectrum is shown to consist solely of eigenvalues s(s−1) for positive integers s bounded by the weight, with multiplicities which exhibit rich representation-theoretic patterns.

  5. Semantic graphs and associative memories

    Science.gov (United States)

    Pomi, Andrés; Mizraji, Eduardo

    2004-12-01

    Graphs have been increasingly utilized in the characterization of complex networks from diverse origins, including different kinds of semantic networks. Human memories are associative and are known to support complex semantic nets; these nets are represented by graphs. However, it is not known how the brain can sustain these semantic graphs. The vision of cognitive brain activities, shown by modern functional imaging techniques, assigns renewed value to classical distributed associative memory models. Here we show that these neural network models, also known as correlation matrix memories, naturally support a graph representation of the stored semantic structure. We demonstrate that the adjacency matrix of this graph of associations is just the memory coded with the standard basis of the concept vector space, and that the spectrum of the graph is a code invariant of the memory. As long as the assumptions of the model remain valid this result provides a practical method to predict and modify the evolution of the cognitive dynamics. Also, it could provide us with a way to comprehend how individual brains that map the external reality, almost surely with different particular vector representations, are nevertheless able to communicate and share a common knowledge of the world. We finish presenting adaptive association graphs, an extension of the model that makes use of the tensor product, which provides a solution to the known problem of branching in semantic nets.

  6. Hierarchy of modular graph identities

    Energy Technology Data Exchange (ETDEWEB)

    D’Hoker, Eric; Kaidi, Justin [Mani L. Bhaumik Institute for Theoretical Physics, Department of Physics and Astronomy,University of California,Los Angeles, CA 90095 (United States)

    2016-11-09

    The low energy expansion of Type II superstring amplitudes at genus one is organized in terms of modular graph functions associated with Feynman graphs of a conformal scalar field on the torus. In earlier work, surprising identities between two-loop graphs at all weights, and between higher-loop graphs of weights four and five were constructed. In the present paper, these results are generalized in two complementary directions. First, all identities at weight six and all dihedral identities at weight seven are obtained and proven. Whenever the Laurent polynomial at the cusp is available, the form of these identities confirms the pattern by which the vanishing of the Laurent polynomial governs the full modular identity. Second, the family of modular graph functions is extended to include all graphs with derivative couplings and worldsheet fermions. These extended families of modular graph functions are shown to obey a hierarchy of inhomogeneous Laplace eigenvalue equations. The eigenvalues are calculated analytically for the simplest infinite sub-families and obtained by Maple for successively more complicated sub-families. The spectrum is shown to consist solely of eigenvalues s(s−1) for positive integers s bounded by the weight, with multiplicities which exhibit rich representation-theoretic patterns.

  7. Neuro-symbolic representation learning on biological knowledge graphs.

    Science.gov (United States)

    Alshahrani, Mona; Khan, Mohammad Asif; Maddouri, Omar; Kinjo, Akira R; Queralt-Rosinach, Núria; Hoehndorf, Robert

    2017-09-01

    Biological data and knowledge bases increasingly rely on Semantic Web technologies and the use of knowledge graphs for data integration, retrieval and federated queries. In the past years, feature learning methods that are applicable to graph-structured data are becoming available, but have not yet widely been applied and evaluated on structured biological knowledge. Results: We develop a novel method for feature learning on biological knowledge graphs. Our method combines symbolic methods, in particular knowledge representation using symbolic logic and automated reasoning, with neural networks to generate embeddings of nodes that encode for related information within knowledge graphs. Through the use of symbolic logic, these embeddings contain both explicit and implicit information. We apply these embeddings to the prediction of edges in the knowledge graph representing problems of function prediction, finding candidate genes of diseases, protein-protein interactions, or drug target relations, and demonstrate performance that matches and sometimes outperforms traditional approaches based on manually crafted features. Our method can be applied to any biological knowledge graph, and will thereby open up the increasing amount of Semantic Web based knowledge bases in biology to use in machine learning and data analytics. https://github.com/bio-ontology-research-group/walking-rdf-and-owl. robert.hoehndorf@kaust.edu.sa. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

  8. Neuro-symbolic representation learning on biological knowledge graphs

    KAUST Repository

    Alshahrani, Mona

    2017-04-21

    Biological data and knowledge bases increasingly rely on Semantic Web technologies and the use of knowledge graphs for data integration, retrieval and federated queries. In the past years, feature learning methods that are applicable to graph-structured data are becoming available, but have not yet widely been applied and evaluated on structured biological knowledge.We develop a novel method for feature learning on biological knowledge graphs. Our method combines symbolic methods, in particular knowledge representation using symbolic logic and automated reasoning, with neural networks to generate embeddings of nodes that encode for related information within knowledge graphs. Through the use of symbolic logic, these embeddings contain both explicit and implicit information. We apply these embeddings to the prediction of edges in the knowledge graph representing problems of function prediction, finding candidate genes of diseases, protein-protein interactions, or drug target relations, and demonstrate performance that matches and sometimes outperforms traditional approaches based on manually crafted features. Our method can be applied to any biological knowledge graph, and will thereby open up the increasing amount of SemanticWeb based knowledge bases in biology to use in machine learning and data analytics.https://github.com/bio-ontology-research-group/walking-rdf-and-owl.robert.hoehndorf@kaust.edu.sa.Supplementary data are available at Bioinformatics online.

  9. Citation graph based ranking in Invenio

    CERN Document Server

    Marian, Ludmila; Rajman, Martin; Vesely, Martin

    2010-01-01

    Invenio is the web-based integrated digital library system developed at CERN. Within this framework, we present four types of ranking models based on the citation graph that complement the simple approach based on citation counts: time-dependent citation counts, a relevancy ranking which extends the PageRank model, a time-dependent ranking which combines the freshness of citations with PageRank and a ranking that takes into consideration the external citations. We present our analysis and results obtained on two main data sets: Inspire and CERN Document Server. Our main contributions are: (i) a study of the currently available ranking methods based on the citation graph; (ii) the development of new ranking methods that correct some of the identified limitations of the current methods such as treating all citations of equal importance, not taking time into account or considering the citation graph complete; (iii) a detailed study of the key parameters for these ranking methods. (The original publication is ava...

  10. Gems of combinatorial optimization and graph algorithms

    CERN Document Server

    Skutella, Martin; Stiller, Sebastian; Wagner, Dorothea

    2015-01-01

    Are you looking for new lectures for your course on algorithms, combinatorial optimization, or algorithmic game theory?  Maybe you need a convenient source of relevant, current topics for a graduate student or advanced undergraduate student seminar?  Or perhaps you just want an enjoyable look at some beautiful mathematical and algorithmic results, ideas, proofs, concepts, and techniques in discrete mathematics and theoretical computer science?   Gems of Combinatorial Optimization and Graph Algorithms is a handpicked collection of up-to-date articles, carefully prepared by a select group of international experts, who have contributed some of their most mathematically or algorithmically elegant ideas.  Topics include longest tours and Steiner trees in geometric spaces, cartograms, resource buying games, congestion games, selfish routing, revenue equivalence and shortest paths, scheduling, linear structures in graphs, contraction hierarchies, budgeted matching problems, and motifs in networks.   This ...

  11. Document organization by means of graphs

    Directory of Open Access Journals (Sweden)

    Santa Vallejo Figueroa

    2016-12-01

    Full Text Available Nowadays documents are the main way to represent information and knowledge in several domains. Continuously users store documents in hard disk or online media according to some personal organization based on topics, but such documents can contain one or more topics. This situation makes hard to access documents when is required. The current search engines are based on the name of file or content, but where the desired term or terms must match exactly as are in the content. In this paper, a method for organize documents by means of graphs is proposed, taking into account the topics of the documents. For this a graph for each document is generated taking into account synonyms, semantic related terms, hyponyms, and hypernyms of nouns and verbs contained in documents. The proposal have been compares against Google Desktop and LogicalDoc with interesting results.

  12. Dynamic graphs, community detection, and Riemannian geometry

    Energy Technology Data Exchange (ETDEWEB)

    Bakker, Craig; Halappanavar, Mahantesh; Visweswara Sathanur, Arun

    2018-03-29

    A community is a subset of a wider network where the members of that subset are more strongly connected to each other than they are to the rest of the network. In this paper, we consider the problem of identifying and tracking communities in graphs that change over time {dynamic community detection} and present a framework based on Riemannian geometry to aid in this task. Our framework currently supports several important operations such as interpolating between and averaging over graph snapshots. We compare these Riemannian methods with entry-wise linear interpolation and that the Riemannian methods are generally better suited to dynamic community detection. Next steps with the Riemannian framework include developing higher-order interpolation methods (e.g. the analogues of polynomial and spline interpolation) and a Riemannian least-squares regression method for working with noisy data.

  13. XML Graphs in Program Analysis

    DEFF Research Database (Denmark)

    Møller, Anders; Schwartzbach, Michael I.

    2011-01-01

    of XML graphs against different XML schema languages, and provide a software package that enables others to make use of these ideas. We also survey the use of XML graphs for program analysis with four very different languages: XACT (XML in Java), Java Servlets (Web application programming), XSugar......XML graphs have shown to be a simple and effective formalism for representing sets of XML documents in program analysis. It has evolved through a six year period with variants tailored for a range of applications. We present a unified definition, outline the key properties including validation...

  14. Coloring and The Lonely Graph

    OpenAIRE

    Rabern, Landon

    2007-01-01

    We improve upper bounds on the chromatic number proven independently in \\cite{reedNote} and \\cite{ingo}. Our main lemma gives a sufficient condition for two paths in graph to be completely joined. Using this, we prove that if a graph has an optimal coloring with more than $\\frac{\\omega}{2}$ singleton color classes, then it satisfies $\\chi \\leq \\frac{\\omega + \\Delta + 1}{2}$. It follows that a graph satisfying $n - \\Delta < \\alpha + \\frac{\\omega - 1}{2}$ must also satisfy $\\chi \\leq \\frac{\\ome...

  15. Graphs with Eulerian unit spheres

    OpenAIRE

    Knill, Oliver

    2015-01-01

    d-spheres in graph theory are inductively defined as graphs for which all unit spheres S(x) are (d-1)-spheres and that the removal of one vertex renders the graph contractible. Eulerian d-spheres are geometric d-spheres which are d+1 colorable. We prove here that G is an Eulerian sphere if and only if the degrees of all the (d-2)-dimensional sub-simplices in G are even. This generalizes a Kempe-Heawood result for d=2 and is work related to the conjecture that all d-spheres have chromatic numb...

  16. Surface Modified Multifunctional and Stimuli Responsive Nanoparticles for Drug Targeting: Current Status and Uses

    Directory of Open Access Journals (Sweden)

    Panoraia I. Siafaka

    2016-08-01

    Full Text Available Nanocarriers, due to their unique features, are of increased interest among researchers working with pharmaceutical formulations. Polymeric nanoparticles and nanocapsules, involving non-toxic biodegradable polymers, liposomes, solid lipid nanoparticles, and inorganic–organic nanomaterials, are among the most used carriers for drugs for a broad spectrum of targeted diseases. In fact, oral, injectable, transdermal-dermal and ocular formulations mainly consist of the aforementioned nanomaterials demonstrating promising characteristics such as long circulation, specific targeting, high drug loading capacity, enhanced intracellular penetration, and so on. Over the last decade, huge advances in the development of novel, safer and less toxic nanocarriers with amended properties have been made. In addition, multifunctional nanocarriers combining chemical substances, vitamins and peptides via coupling chemistry, inorganic particles coated by biocompatible materials seem to play a key role considering that functionalization can enhance characteristics such as biocompatibility, targetability, environmental friendliness, and intracellular penetration while also have limited side effects. This review aims to summarize the “state of the art” of drug delivery carriers in nanosize, paying attention to their surface functionalization with ligands and other small or polymeric compounds so as to upgrade active and passive targeting, different release patterns as well as cell targeting and stimuli responsibility. Lastly, future aspects and potential uses of nanoparticulated drug systems are outlined.

  17. [Current movements of four serious adverse events induced by medicinal drugs based on spontaneous reports in Japan].

    Science.gov (United States)

    Sudo, Chie; Azuma, Yu-ichiro; Maekawa, Keiko; Kaniwa, Nahoko; Sai, Kimie; Saito, Yoshiro

    2011-01-01

    Spontaneous reports on suspected serious adverse events caused by medicines from manufacturing/distributing pharmaceutical companies or medical institutions/pharmacies are regulated by the Pharmaceutical Affairs Law of Japan, and this system is important for post-marketing safety features. Although causal relationship between the medicine and the adverse event is not evaluated, and one incidence may be redundantly reported, this information would be useful to roughly grasp the current movements of drug-related serious adverse events, We searched open-source data of the spontaneous reports publicized by Pharmaceutical and Medical Devices Agency for 4 serious adverse events (interstitial lung disease, rhabdomyolysis, anaphylaxis, and Stevens-Johnson syndrome/toxic epidermal necrolysis) from 2004 to 2010 fiscal year (for 2010, from April 1 st to January 31th). Major drug-classes suspected to the adverse events were antineoplastics for interstitial lung disease, hyperlipidemia agents and psychotropics for rhabdomyolysis, antibiotics/chemotherapeutics, antineoplastics and intracorporeal diagnostic agents for anaphylaxis (anaphylactic shock, anaphylactic reactions, anaphylactoid shock and anaphylactoid reactions), and antibiotics/chemotherapeutics, antipyretics and analgesics, anti-inflammatory agents/common cold drugs, and antiepileptics for Stevens-Johnson syndrome/toxic epidermal necrolysis. These results would help understanding of current situations of the 4 drug-related serious adverse events in Japan.

  18. The Current Landscape of 3D In Vitro Tumor Models: What Cancer Hallmarks Are Accessible for Drug Discovery?

    Science.gov (United States)

    Rodenhizer, Darren; Dean, Teresa; D'Arcangelo, Elisa; McGuigan, Alison P

    2018-04-01

    Cancer prognosis remains a lottery dependent on cancer type, disease stage at diagnosis, and personal genetics. While investment in research is at an all-time high, new drugs are more likely to fail in clinical trials today than in the 1970s. In this review, a summary of current survival statistics in North America is provided, followed by an overview of the modern drug discovery process, classes of models used throughout different stages, and challenges associated with drug development efficiency are highlighted. Then, an overview of the cancer hallmarks that drive clinical progression is provided, and the range of available clinical therapies within the context of these hallmarks is categorized. Specifically, it is found that historically, the development of therapies is limited to a subset of possible targets. This provides evidence for the opportunities offered by novel disease-relevant in vitro models that enable identification of novel targets that facilitate interactions between the tumor cells and their surrounding microenvironment. Next, an overview of the models currently reported in literature is provided, and the cancer biology they have been used to explore is highlighted. Finally, four priority areas are suggested for the field to accelerate adoption of in vitro tumour models for cancer drug discovery. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Evolutionary games on graphs

    Science.gov (United States)

    Szabó, György; Fáth, Gábor

    2007-07-01

    Game theory is one of the key paradigms behind many scientific disciplines from biology to behavioral sciences to economics. In its evolutionary form and especially when the interacting agents are linked in a specific social network the underlying solution concepts and methods are very similar to those applied in non-equilibrium statistical physics. This review gives a tutorial-type overview of the field for physicists. The first four sections introduce the necessary background in classical and evolutionary game theory from the basic definitions to the most important results. The fifth section surveys the topological complications implied by non-mean-field-type social network structures in general. The next three sections discuss in detail the dynamic behavior of three prominent classes of models: the Prisoner's Dilemma, the Rock-Scissors-Paper game, and Competing Associations. The major theme of the review is in what sense and how the graph structure of interactions can modify and enrich the picture of long term behavioral patterns emerging in evolutionary games.

  20. Current good manufacturing practice in manufacturing, processing, packing, or holding of drugs; revision of certain labeling controls. Final rule.

    Science.gov (United States)

    2012-03-20

    The Food and Drug Administration (FDA) is amending the packaging and labeling control provisions of the current good manufacturing practice (CGMP) regulations for human and veterinary drug products by limiting the application of special control procedures for the use of cut labeling to immediate container labels, individual unit cartons, or multiunit cartons containing immediate containers that are not packaged in individual unit cartons. FDA is also permitting the use of any automated technique, including differentiation by labeling size and shape, that physically prevents incorrect labeling from being processed by labeling and packaging equipment when cut labeling is used. This action is intended to protect consumers from labeling errors more likely to cause adverse health consequences, while eliminating the regulatory burden of applying the rule to labeling unlikely to reach or adversely affect consumers. This action is also intended to permit manufacturers to use a broader range of error prevention and labeling control techniques than permitted by current CGMPs.

  1. Estimating the effect of current, previous and never use of drugs in studies based on prescription registries

    DEFF Research Database (Denmark)

    Nielsen, Lars Hougaard; Løkkegaard, Ellen; Andreasen, Anne Helms

    2009-01-01

    of this misclassification for analysing the risk of breast cancer. MATERIALS AND METHODS: Prescription data were obtained from Danish Registry of Medicinal Products Statistics and we applied various methods to approximate treatment episodes. We analysed the duration of HT episodes to study the ability to identify......PURPOSE: Many studies which investigate the effect of drugs categorize the exposure variable into never, current, and previous use of the study drug. When prescription registries are used to make this categorization, the exposure variable possibly gets misclassified since the registries do...... not carry any information on the time of discontinuation of treatment.In this study, we investigated the amount of misclassification of exposure (never, current, previous use) to hormone therapy (HT) when the exposure variable was based on prescription data. Furthermore, we evaluated the significance...

  2. Properly colored connectivity of graphs

    CERN Document Server

    Li, Xueliang; Qin, Zhongmei

    2018-01-01

    A comprehensive survey of proper connection of graphs is discussed in this book with real world applications in computer science and network security. Beginning with a brief introduction, comprising relevant definitions and preliminary results, this book moves on to consider a variety of properties of graphs that imply bounds on the proper connection number. Detailed proofs of significant advancements toward open problems and conjectures are presented with complete references. Researchers and graduate students with an interest in graph connectivity and colorings will find this book useful as it builds upon fundamental definitions towards modern innovations, strategies, and techniques. The detailed presentation lends to use as an introduction to proper connection of graphs for new and advanced researchers, a solid book for a graduate level topics course, or as a reference for those interested in expanding and further developing research in the area.

  3. Open Graphs and Computational Reasoning

    Directory of Open Access Journals (Sweden)

    Lucas Dixon

    2010-06-01

    Full Text Available We present a form of algebraic reasoning for computational objects which are expressed as graphs. Edges describe the flow of data between primitive operations which are represented by vertices. These graphs have an interface made of half-edges (edges which are drawn with an unconnected end and enjoy rich compositional principles by connecting graphs along these half-edges. In particular, this allows equations and rewrite rules to be specified between graphs. Particular computational models can then be encoded as an axiomatic set of such rules. Further rules can be derived graphically and rewriting can be used to simulate the dynamics of a computational system, e.g. evaluating a program on an input. Examples of models which can be formalised in this way include traditional electronic circuits as well as recent categorical accounts of quantum information.

  4. The toughness of split graphs

    NARCIS (Netherlands)

    Woeginger, G.J.

    1998-01-01

    In this short note we argue that the toughness of split graphs can be computed in polynomial time. This solves an open problem from a recent paper by Kratsch et al. (Discrete Math. 150 (1996) 231–245).

  5. Generating random networks and graphs

    CERN Document Server

    Coolen, Ton; Roberts, Ekaterina

    2017-01-01

    This book supports researchers who need to generate random networks, or who are interested in the theoretical study of random graphs. The coverage includes exponential random graphs (where the targeted probability of each network appearing in the ensemble is specified), growth algorithms (i.e. preferential attachment and the stub-joining configuration model), special constructions (e.g. geometric graphs and Watts Strogatz models) and graphs on structured spaces (e.g. multiplex networks). The presentation aims to be a complete starting point, including details of both theory and implementation, as well as discussions of the main strengths and weaknesses of each approach. It includes extensive references for readers wishing to go further. The material is carefully structured to be accessible to researchers from all disciplines while also containing rigorous mathematical analysis (largely based on the techniques of statistical mechanics) to support those wishing to further develop or implement the theory of rand...

  6. [Treatment of typical trigeminus neuralgias. Overview of the current state of drug and surgical therapy].

    Science.gov (United States)

    Möbius, E; Leopold, H C; Paulus, W M

    1984-10-11

    Carbamazepine continues to be the most useful drug in the treatment of trigeminal neuralgia. Diphenylhydantoin may be given in addition to or instead of Carbamazepine. Refractory cases may benefit from combination with Baclofen or Chlorphenesin. In cases of persistent pain the concomitant use of tricyclic antidepressant drugs is recommended. If pain continues in spite of multiple medical therapies or if serious side effects develop, then surgical procedures such as percutaneous controlled thermocoagulation or microvascular decompression are indicated. Percutaneous thermocoagulation is associated with the lowest mortality and morbidity rate and can easily be repeated. Microvascular decompression should especially be offered to young patients, who want to avoid any sensory disturbance of the face, and recommended for other patients for whom all other forms of therapy including percutaneous thermocoagulation have failed.

  7. Graph theory and its applications

    CERN Document Server

    Gross, Jonathan L

    2006-01-01

    Gross and Yellen take a comprehensive approach to graph theory that integrates careful exposition of classical developments with emerging methods, models, and practical needs. Their unparalleled treatment provides a text ideal for a two-semester course and a variety of one-semester classes, from an introductory one-semester course to courses slanted toward classical graph theory, operations research, data structures and algorithms, or algebra and topology.

  8. Drug-Loaded Microspheres for the Treatment of Liver Cancer: Review of Current Results

    International Nuclear Information System (INIS)

    Kettenbach, Joachim; Stadler, Alfred; Katzler, Isabella v.; Schernthaner, Ruediger; Blum, Melanie; Lammer, Johannes; Rand, Thomas

    2008-01-01

    Transarterial chemoembolization (TACE) involves the emulsification of a chemotherapeutic agent in a viscous drug carrier, delivered intra-arterially to liver tumor for maximum effect. TACE reduces arterial inflow, diminishes washout of the chemotherapeutic agent, and decreases systemic exposure. Despite evidence of some clinical success with TACE, a new type of microspheres with drug-eluting capabilities may offer a precisely controlled and sustainable release of the chemotherapeutic agent into the tumor bed. In animal trials tumor necrosis (approaching 100%) was greatest at 7 days, with significantly lower plasma concentrations of doxorubicin than in control animals treated with doxorubicin intra-arterially. Clinically, drug-eluting microspheres loaded with doxorubicin, either at 75 mg/m 2 or at a fixed dose of 150 mg, were used recently and no severe disorders of the hepatic function were observed postprocedure, while a substantial reduction of the fetoprotein levels occurred. An interim analysis of the first 15 patients from the Hong Kong group at 3 months showed an objective response rate of 61.54% and 53.84% according to EASL criteria and RECIST criteria, respectively, and a survival rate of 93.3%. In this paper we present how to use microspheres loaded with doxorubicin and review their clinical value and preliminary performance for treatment of unresectable liver cancer

  9. Graphs with branchwidth at most three

    NARCIS (Netherlands)

    Bodlaender, H.L.; Thilikos, D.M.

    1997-01-01

    In this paper we investigate both the structure of graphs with branchwidth at most three, as well as algorithms to recognise such graphs. We show that a graph has branchwidth at most three, if and only if it has treewidth at most three and does not contain the three-dimensional binary cube graph

  10. A Modal-Logic Based Graph Abstraction

    NARCIS (Netherlands)

    Bauer, J.; Boneva, I.B.; Kurban, M.E.; Rensink, Arend; Ehrig, H; Heckel, R.; Rozenberg, G.; Taentzer, G.

    2008-01-01

    Infinite or very large state spaces often prohibit the successful verification of graph transformation systems. Abstract graph transformation is an approach that tackles this problem by abstracting graphs to abstract graphs of bounded size and by lifting application of productions to abstract

  11. Graphs whose complement and square are isomorphic

    DEFF Research Database (Denmark)

    Pedersen, Anders Sune

    2014-01-01

    We study square-complementary graphs, that is, graphs whose complement and square are isomorphic. We prove several necessary conditions for a graph to be square-complementary, describe ways of building new square-complementary graphs from existing ones, construct infinite families of square-compl...

  12. Acyclicity in edge-colored graphs

    DEFF Research Database (Denmark)

    Gutin, Gregory; Jones, Mark; Sheng, Bin

    2017-01-01

    A walk W in edge-colored graphs is called properly colored (PC) if every pair of consecutive edges in W is of different color. We introduce and study five types of PC acyclicity in edge-colored graphs such that graphs of PC acyclicity of type i is a proper superset of graphs of acyclicity of type...

  13. Building Scalable Knowledge Graphs for Earth Science

    Science.gov (United States)

    Ramachandran, Rahul; Maskey, Manil; Gatlin, Patrick; Zhang, Jia; Duan, Xiaoyi; Miller, J. J.; Bugbee, Kaylin; Christopher, Sundar; Freitag, Brian

    2017-01-01

    Knowledge Graphs link key entities in a specific domain with other entities via relationships. From these relationships, researchers can query knowledge graphs for probabilistic recommendations to infer new knowledge. Scientific papers are an untapped resource which knowledge graphs could leverage to accelerate research discovery. Goal: Develop an end-to-end (semi) automated methodology for constructing Knowledge Graphs for Earth Science.

  14. Port-Hamiltonian Systems on Open Graphs

    NARCIS (Netherlands)

    Schaft, A.J. van der; Maschke, B.M.

    2010-01-01

    In this talk we discuss how to define in an intrinsic manner port-Hamiltonian dynamics on open graphs. Open graphs are graphs where some of the vertices are boundary vertices (terminals), which allow interconnection with other systems. We show that a directed graph carries two natural Dirac

  15. Constructing Dense Graphs with Unique Hamiltonian Cycles

    Science.gov (United States)

    Lynch, Mark A. M.

    2012-01-01

    It is not difficult to construct dense graphs containing Hamiltonian cycles, but it is difficult to generate dense graphs that are guaranteed to contain a unique Hamiltonian cycle. This article presents an algorithm for generating arbitrarily large simple graphs containing "unique" Hamiltonian cycles. These graphs can be turned into dense graphs…

  16. Skew-adjacency matrices of graphs

    NARCIS (Netherlands)

    Cavers, M.; Cioaba, S.M.; Fallat, S.; Gregory, D.A.; Haemers, W.H.; Kirkland, S.J.; McDonald, J.J.; Tsatsomeros, M.

    2012-01-01

    The spectra of the skew-adjacency matrices of a graph are considered as a possible way to distinguish adjacency cospectral graphs. This leads to the following topics: graphs whose skew-adjacency matrices are all cospectral; relations between the matchings polynomial of a graph and the characteristic

  17. Chromatic polynomials of random graphs

    International Nuclear Information System (INIS)

    Van Bussel, Frank; Fliegner, Denny; Timme, Marc; Ehrlich, Christoph; Stolzenberg, Sebastian

    2010-01-01

    Chromatic polynomials and related graph invariants are central objects in both graph theory and statistical physics. Computational difficulties, however, have so far restricted studies of such polynomials to graphs that were either very small, very sparse or highly structured. Recent algorithmic advances (Timme et al 2009 New J. Phys. 11 023001) now make it possible to compute chromatic polynomials for moderately sized graphs of arbitrary structure and number of edges. Here we present chromatic polynomials of ensembles of random graphs with up to 30 vertices, over the entire range of edge density. We specifically focus on the locations of the zeros of the polynomial in the complex plane. The results indicate that the chromatic zeros of random graphs have a very consistent layout. In particular, the crossing point, the point at which the chromatic zeros with non-zero imaginary part approach the real axis, scales linearly with the average degree over most of the density range. While the scaling laws obtained are purely empirical, if they continue to hold in general there are significant implications: the crossing points of chromatic zeros in the thermodynamic limit separate systems with zero ground state entropy from systems with positive ground state entropy, the latter an exception to the third law of thermodynamics.

  18. Commuting graphs of matrix algebras

    International Nuclear Information System (INIS)

    Akbari, S.; Bidkhori, H.; Mohammadian, A.

    2006-08-01

    The commuting graph of a ring R, denoted by Γ(R), is a graph whose vertices are all non- central elements of R and two distinct vertices x and y are adjacent if and only if xy = yx. The commuting graph of a group G, denoted by Γ(G), is similarly defined. In this paper we investigate some graph theoretic properties of Γ(M n (F)), where F is a field and n ≥ 2. Also we study the commuting graphs of some classical groups such as GL n (F) and SL n (F). We show that Γ(M n (F)) is a connected graph if and only if every field extension of F of degree n contains a proper intermediate field. We prove that apart from finitely many fields, a similar result is true for Γ(GL n (F)) and Γ(SL n (F)). Also we show that for two fields E and F and integers m, n ≥> 2, if Γ(M m (E)) ≅ Γ(M n (F)), then m = n and vertical bar E vertical bar = vertical bar F vertical bar. (author)

  19. 77 FR 16158 - Current Good Manufacturing Practice in Manufacturing, Processing, Packing, or Holding of Drugs...

    Science.gov (United States)

    2012-03-20

    .... FDA-1997-N-0518] (formerly 97N-0300) Current Good Manufacturing Practice in Manufacturing, Processing... labeling control provisions of the current good manufacturing practice (CGMP) regulations for human and... GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS 0 1. The authority citation for 21 CFR part...

  20. Graph Quasicontinuous Functions and Densely Continuous Forms

    Directory of Open Access Journals (Sweden)

    Lubica Hola

    2017-07-01

    Full Text Available Let $X, Y$ be topological spaces. A function $f: X \\to Y$ is said to be graph quasicontinuous if there is a quasicontinuous function $g: X \\to Y$ with the graph of $g$ contained in the closure of the graph of $f$. There is a close relation between the notions of graph quasicontinuous functions and minimal usco maps as well as the notions of graph quasicontinuous functions and densely continuous forms. Every function with values in a compact Hausdorff space is graph quasicontinuous; more generally every locally compact function is graph quasicontinuous.

  1. Drug-induced GABA transporter currents enhance GABA release to induce opioid withdrawal behaviors.

    Science.gov (United States)

    Bagley, Elena E; Hacker, Jennifer; Chefer, Vladimir I; Mallet, Christophe; McNally, Gavan P; Chieng, Billy C H; Perroud, Julie; Shippenberg, Toni S; Christie, MacDonald J

    2011-10-30

    Neurotransmitter transporters can affect neuronal excitability indirectly via modulation of neurotransmitter concentrations or directly via transporter currents. A physiological or pathophysiological role for transporter currents has not been described. We found that GABA transporter 1 (GAT-1) cation currents directly increased GABAergic neuronal excitability and synaptic GABA release in the periaqueductal gray (PAG) during opioid withdrawal in rodents. In contrast, GAT-1 did not indirectly alter GABA receptor responses via modulation of extracellular GABA concentrations. Notably, we found that GAT-1-induced increases in GABAergic activity contributed to many PAG-mediated signs of opioid withdrawal. Together, these data support the hypothesis that GAT-1 activity directly produces opioid withdrawal signs through direct hyperexcitation of GABAergic PAG neurons and nerve terminals, which presumably enhances GABAergic inhibition of PAG output neurons. These data provide, to the best of our knowledge, the first evidence that dysregulation of a neurotransmitter transporter current is important for the maladaptive plasticity that underlies opiate withdrawal.

  2. Interactive Graph Layout of a Million Nodes

    OpenAIRE

    Peng Mi; Maoyuan Sun; Moeti Masiane; Yong Cao; Chris North

    2016-01-01

    Sensemaking of large graphs, specifically those with millions of nodes, is a crucial task in many fields. Automatic graph layout algorithms, augmented with real-time human-in-the-loop interaction, can potentially support sensemaking of large graphs. However, designing interactive algorithms to achieve this is challenging. In this paper, we tackle the scalability problem of interactive layout of large graphs, and contribute a new GPU-based force-directed layout algorithm that exploits graph to...

  3. Khovanov homology of graph-links

    Energy Technology Data Exchange (ETDEWEB)

    Nikonov, Igor M [M. V. Lomonosov Moscow State University, Faculty of Mechanics and Mathematics, Moscow (Russian Federation)

    2012-08-31

    Graph-links arise as the intersection graphs of turning chord diagrams of links. Speaking informally, graph-links provide a combinatorial description of links up to mutations. Many link invariants can be reformulated in the language of graph-links. Khovanov homology, a well-known and useful knot invariant, is defined for graph-links in this paper (in the case of the ground field of characteristic two). Bibliography: 14 titles.

  4. PRIVATE GRAPHS – ACCESS RIGHTS ON GRAPHS FOR SEAMLESS NAVIGATION

    Directory of Open Access Journals (Sweden)

    W. Dorner

    2016-06-01

    Full Text Available After the success of GNSS (Global Navigational Satellite Systems and navigation services for public streets, indoor seems to be the next big development in navigational services, relying on RTLS – Real Time Locating Services (e.g. WIFI and allowing seamless navigation. In contrast to navigation and routing services on public streets, seamless navigation will cause an additional challenge: how to make routing data accessible to defined users or restrict access rights for defined areas or only to parts of the graph to a defined user group? The paper will present case studies and data from literature, where seamless and especially indoor navigation solutions are presented (hospitals, industrial complexes, building sites, but the problem of restricted access rights was only touched from a real world, but not a technical perspective. The analysis of case studies will show, that the objective of navigation and the different target groups for navigation solutions will demand well defined access rights and require solutions, how to make only parts of a graph to a user or application available to solve a navigational task. The paper will therefore introduce the concept of private graphs, which is defined as a graph for navigational purposes covering the street, road or floor network of an area behind a public street and suggest different approaches how to make graph data for navigational purposes available considering access rights and data protection, privacy and security issues as well.

  5. Current Trends of Drug Resistance Patterns of Acinetobacter baumannii Infection in Blood Transfusion-dependent Thalassemia Patients.

    Science.gov (United States)

    Almani, Suhail Ahmed; Naseer, Ali; Maheshwari, Sanjay Kumar; Maroof, Pir; Naseer, Raza; Khoharo, Haji Khan

    2017-01-01

    The present study aimed to evaluate the current trends of drug resistance patterns of Acinetobacter baumannii infection in blood transfusion-dependent thalassemia patients. This study was a cross sectional study, conducted at the Liaquat University of Medical and Health Sciences, Jamshoro/Hyderabad, Sindh, Pakistan from October 2014 to January 2016. Of 921 blood samples, A. baumannii strains were isolated from 100 blood samples. Blood samples were processed for the isolation, identification, and drugs sensitivity as per the Clinical and Laboratory Standards Institute. A. baumannii strains were identified by microbiological methods and Gram's staining. API 20 E kit (Biomeriuex, USA) was also used for identification. Data were analyzed on Statisti × 8.1 (USA). Mean ± standard deviation age was 11.5 ± 2.8 years. Nearly 70% were male and 30% were female ( P = 0.0001). Of 921 blood transfusion-dependent thalassemia patients, 100 (10.8%) patients showed growth of A. baumannii . Drug resistance was observed against the ceftazidime, cefixime, cefepime, imipenem, meropenem, amikacin, minocycline, tigecycline, and tazocin except for the colistin. The present study reports drug-resistant A. baumannii in blood transfusion-dependent thalassemia patients. National multicenter studies are recommended to estimate the size of the problem.

  6. The impact of currently used oral antihyperglycemic drugs on dysfunctional adipose tissue

    Directory of Open Access Journals (Sweden)

    Tomić-Naglić Dragana

    2017-01-01

    Full Text Available Obesity is a disease with pandemic frequency, often accompanied by chronic metabolic and organic complications. Type 2 diabetes mellitus (T2DM is among the most common metabolic complications of obesity. The first step in the treatment of T2DM is medical nutrition therapy combined with moderate physical activity and with advice to patients to reduce their body weight. Pharmacotherapy starts with metformin, and in the case of inadequate therapeutic response, another antihyperglycemic agent should be added. The most clinical experience exists with sulfonylurea agents, but their use is limited due to high incidence of hypoglycemia and increase in body weight. Based on the fact that dysfunction of adipose tissue can lead to the development of chronic degenerative complications, precise use of drugs with a favorable effect on the functionality of adipose tissue represents an imperative of modern T2DM treatment. Antihyperglycemic drugs of choice in obese individuals are those which cause maturation of adipocytes, improvement of secretion of protective adipokines, and redistribution of fat mass from visceral to subcutaneous depots. Oral antihyperglycemic agents that can affect the functionality of adipose tissue are metformin, SGLT-2 inhibitors, DPP-4 inhibitors, and thiazolidinediones.

  7. Current drug therapies for rosacea: a chronic vascular and inflammatory skin disease.

    Science.gov (United States)

    Feldman, Steven R; Huang, William W; Huynh, Tu T

    2014-06-01

    Rosacea is a chronic skin disorder that presents with abnormal vascular and inflammatory conditions. Clinical manifestations include flushing, facial erythema, inflammatory papules and pustules, telangiectasias, edema, and watery or irritated eyes. To discuss the evolving pathophysiology of rosacea, factors involved in promoting the chronic vascular and inflammatory abnormalities seen in rosacea, and the available drug therapies for the condition. Chronic inflammation and vascular changes are believed to be underlying factors in the pathophysiology of rosacea. Aberrant cathelicidin expression, elevated kallikrein 5 (KLK5) proteolytic activity, and altered toll-like receptor 2 (TLR2) expression have been reported in rosacea skin leading to the production of proinflammatory cytokines. Until recently, drug therapies only targeted the inflammatory lesions (papules and pustules) and transient erythema associated with these inflammatory lesions of rosacea. Brimonidine tartrate gel 0.5% was recently approved for the treatment of persistent (nontransient) facial erythema of rosacea, acting primarily on the cutaneous vascular component of the disease. Rosacea is a chronic vascular and inflammatory skin disease. Understanding the role of factors that trigger the onset of rosacea symptoms and exacerbate the condition is crucial in treating this skin disease.

  8. Nonclinical safety biomarkers of drug-induced vascular injury: current status and blueprint for the future.

    Science.gov (United States)

    Mikaelian, Igor; Cameron, Mark; Dalmas, Deidre A; Enerson, Bradley E; Gonzalez, Raymond J; Guionaud, Silvia; Hoffmann, Peter K; King, Nicholas M P; Lawton, Michael P; Scicchitano, Marshall S; Smith, Holly W; Thomas, Roberta A; Weaver, James L; Zabka, Tanja S

    2014-06-01

    Better biomarkers are needed to identify, characterize, and/or monitor drug-induced vascular injury (DIVI) in nonclinical species and patients. The Predictive Safety Testing Consortium (PSTC), a precompetitive collaboration of pharmaceutical companies and the U.S. Food and Drug Administration (FDA), formed the Vascular Injury Working Group (VIWG) to develop and qualify translatable biomarkers of DIVI. The VIWG focused its research on acute DIVI because early detection for clinical and nonclinical safety monitoring is desirable. The VIWG developed a strategy based on the premise that biomarkers of DIVI in rat would be translatable to humans due to the morphologic similarity of vascular injury between species regardless of mechanism. The histomorphologic lexicon for DIVI in rat defines degenerative and adaptive findings of the vascular endothelium and smooth muscles, and characterizes inflammatory components. We describe the mechanisms of these changes and their associations with candidate biomarkers for which advanced analytical method validation was completed. Further development is recommended for circulating microRNAs, endothelial microparticles, and imaging techniques. Recommendations for sample collection and processing, analytical methods, and confirmation of target localization using immunohistochemistry and in situ hybridization are described. The methods described are anticipated to aid in the identification and qualification of translational biomarkers for DIVI. © 2014 by The Author(s).

  9. Matching of renewable source of energy generation graphs and electrical load in local energy system

    Science.gov (United States)

    Lezhniuk, Petro; Komar, Vyacheslav; Sobchuk, Dmytro; Kravchuk, Sergiy; Kacejko, Piotr; Zavidsky, Vladislav

    2017-08-01

    The paper contains the method of matching generation graph of photovoltaic electric stations and consumers. Characteristic feature of this method is the application of morphometric analysis for assessment of non-uniformity of the integrated graph of energy supply, optimal coefficients of current distribution, that enables by mean of refining the powers, transferring in accordance with the graph , to provide the decrease of electric energy losses in the grid and transport task, as the optimization tool.

  10. Eigenfunction statistics on quantum graphs

    International Nuclear Information System (INIS)

    Gnutzmann, S.; Keating, J.P.; Piotet, F.

    2010-01-01

    We investigate the spatial statistics of the energy eigenfunctions on large quantum graphs. It has previously been conjectured that these should be described by a Gaussian Random Wave Model, by analogy with quantum chaotic systems, for which such a model was proposed by Berry in 1977. The autocorrelation functions we calculate for an individual quantum graph exhibit a universal component, which completely determines a Gaussian Random Wave Model, and a system-dependent deviation. This deviation depends on the graph only through its underlying classical dynamics. Classical criteria for quantum universality to be met asymptotically in the large graph limit (i.e. for the non-universal deviation to vanish) are then extracted. We use an exact field theoretic expression in terms of a variant of a supersymmetric σ model. A saddle-point analysis of this expression leads to the estimates. In particular, intensity correlations are used to discuss the possible equidistribution of the energy eigenfunctions in the large graph limit. When equidistribution is asymptotically realized, our theory predicts a rate of convergence that is a significant refinement of previous estimates. The universal and system-dependent components of intensity correlation functions are recovered by means of an exact trace formula which we analyse in the diagonal approximation, drawing in this way a parallel between the field theory and semiclassics. Our results provide the first instance where an asymptotic Gaussian Random Wave Model has been established microscopically for eigenfunctions in a system with no disorder.

  11. Box graphs and resolutions I

    Directory of Open Access Journals (Sweden)

    Andreas P. Braun

    2016-04-01

    Full Text Available Box graphs succinctly and comprehensively characterize singular fibers of elliptic fibrations in codimension two and three, as well as flop transitions connecting these, in terms of representation theoretic data. We develop a framework that provides a systematic map between a box graph and a crepant algebraic resolution of the singular elliptic fibration, thus allowing an explicit construction of the fibers from a singular Weierstrass or Tate model. The key tool is what we call a fiber face diagram, which shows the relevant information of a (partial toric triangulation and allows the inclusion of more general algebraic blowups. We shown that each such diagram defines a sequence of weighted algebraic blowups, thus providing a realization of the fiber defined by the box graph in terms of an explicit resolution. We show this correspondence explicitly for the case of SU(5 by providing a map between box graphs and fiber faces, and thereby a sequence of algebraic resolutions of the Tate model, which realizes each of the box graphs.

  12. Degree-based graph construction

    International Nuclear Information System (INIS)

    Kim, Hyunju; Toroczkai, Zoltan; Erdos, Peter L; Miklos, Istvan; Szekely, Laszlo A

    2009-01-01

    Degree-based graph construction is a ubiquitous problem in network modelling (Newman et al 2006 The Structure and Dynamics of Networks (Princeton Studies in Complexity) (Princeton, NJ: Princeton University Press), Boccaletti et al 2006 Phys. Rep. 424 175), ranging from social sciences to chemical compounds and biochemical reaction networks in the cell. This problem includes existence, enumeration, exhaustive construction and sampling questions with aspects that are still open today. Here we give necessary and sufficient conditions for a sequence of nonnegative integers to be realized as a simple graph's degree sequence, such that a given (but otherwise arbitrary) set of connections from an arbitrarily given node is avoided. We then use this result to present a swap-free algorithm that builds all simple graphs realizing a given degree sequence. In a wider context, we show that our result provides a greedy construction method to build all the f-factor subgraphs (Tutte 1952 Can. J. Math. 4 314) embedded within K n setmn S k , where K n is the complete graph and S k is a star graph centred on one of the nodes. (fast track communication)

  13. Hierarchical organisation of causal graphs

    International Nuclear Information System (INIS)

    Dziopa, P.

    1993-01-01

    This paper deals with the design of a supervision system using a hierarchy of models formed by graphs, in which the variables are the nodes and the causal relations between the variables of the arcs. To obtain a representation of the variables evolutions which contains only the relevant features of their real evolutions, the causal relations are completed with qualitative transfer functions (QTFs) which produce roughly the behaviour of the classical transfer functions. Major improvements have been made in the building of the hierarchical organization. First, the basic variables of the uppermost level and the causal relations between them are chosen. The next graph is built by adding intermediary variables to the upper graph. When the undermost graph has been built, the transfer functions parameters corresponding to its causal relations are identified. The second task consists in the upwelling of the information from the undermost graph to the uppermost one. A fusion procedure of the causal relations has been designed to compute the QFTs relevant for each level. This procedure aims to reduce the number of parameters needed to represent an evolution at a high level of abstraction. These techniques have been applied to the hierarchical modelling of nuclear process. (authors). 8 refs., 12 figs

  14. HIV risk-taking behaviour among injecting drug users currently, previously and never enrolled in methadone treatment.

    Science.gov (United States)

    Baker, A; Kochan, N; Dixon, J; Wodak, A; Heather, N

    1995-04-01

    This study compares the injecting and sexual risk-taking behaviour among injecting drug users (IDUs) currently, previously and never enrolled in methadone maintenance treatment (MMT). All subjects had injected during the 6 months prior to the day of interview. The current MMT group showed significantly lower injecting risk-taking behaviour subscale scores on the HIV Risk-taking Behaviour Scale (HRBS) of the Opiate Treatment Index than the previous MMT and non-MMT groups together. The current MMT group differed from the other two groups in the frequency of injecting and cleaning of injection equipment with bleach. There was no difference between the current MMT group and the other two groups combined in sexual risk-taking behaviour scores on the HRBS. There were no differences between the previous MMT and non-MMT groups in injecting and sexual risk-taking behaviour. HIV seroprevalence was low and there was no difference in seroprevalence between groups. Thus, IDUs currently enrolled in MMT are at reduced risk for HIV infection when compared with IDUs who have previously or never been enrolled in MMT. However, the absence of a difference between the current MMT and other two groups in frequency of sharing behaviours suggests the need for additional strategies among MMT clients to reduce needle-sharing. Possible strategies include the application of relapse prevention interventions and the availability of sterile injecting equipment in MMT clinics. Further research is needed to identify factors which increase attraction and retention of IDUs to MMT.

  15. Integer Flows and Circuit Covers of Graphs and Signed Graphs

    Science.gov (United States)

    Cheng, Jian

    The work in Chapter 2 is motivated by Tutte and Jaeger's pioneering work on converting modulo flows into integer-valued flows for ordinary graphs. For a signed graphs (G, sigma), we first prove that for each k ∈ {2, 3}, if (G, sigma) is (k - 1)-edge-connected and contains an even number of negative edges when k = 2, then every modulo k-flow of (G, sigma) can be converted into an integer-valued ( k + 1)-ow with a larger or the same support. We also prove that if (G, sigma) is odd-(2p+1)-edge-connected, then (G, sigma) admits a modulo circular (2 + 1/ p)-flows if and only if it admits an integer-valued circular (2 + 1/p)-flows, which improves all previous result by Xu and Zhang (DM2005), Schubert and Steffen (EJC2015), and Zhu (JCTB2015). Shortest circuit cover conjecture is one of the major open problems in graph theory. It states that every bridgeless graph G contains a set of circuits F such that each edge is contained in at least one member of F and the length of F is at most 7/5∥E(G)∥. This concept was recently generalized to signed graphs by Macajova et al. (JGT2015). In Chapter 3, we improve their upper bound from 11∥E( G)∥ to 14/3 ∥E(G)∥, and if G is 2-edgeconnected and has even negativeness, then it can be further reduced to 11/3 ∥E(G)∥. Tutte's 3-flow conjecture has been studied by many graph theorists in the last several decades. As a new approach to this conjecture, DeVos and Thomassen considered the vectors as ow values and found that there is a close relation between vector S1-flows and integer 3-NZFs. Motivated by their observation, in Chapter 4, we prove that if a graph G admits a vector S1-flow with rank at most two, then G admits an integer 3-NZF. The concept of even factors is highly related to the famous Four Color Theorem. We conclude this dissertation in Chapter 5 with an improvement of a recent result by Chen and Fan (JCTB2016) on the upperbound of even factors. We show that if a graph G contains an even factor, then it

  16. A linear graph for digoxin radioimmunoassay

    International Nuclear Information System (INIS)

    Smith, S.E.; Richter, A.

    1975-01-01

    The determination of drug or hormone concentrations by radio-immunoassay involves interpolation of values for radioisotope counts within standard curves, a technique which requires some dexterity in curve drawing and which results in some inaccuracy in practice. Most of the procedures designed to overcome these difficulties are complex and time-consuming. In radioimmunoassays involving saturation of the antibody-binding sites a special case exists in that the bound radioactivity is directly proportional to the specific activity of the ligand in the system. Thus a graph of the ratio of radioactivity bound in the absence to that in the presence of added non-radioactive ligand is linear against the concentration of added ligand (Hales,C.N., and Randle, P.J., 1963, Biochem. J., vol. 88, 137). A description is given of a simple and convenient modification of their method, and its application to the routine clinical determination of digoxin using a commercial kit (Lanoxitest β digoxin radioimmunoassay kit, Wellcome Reagents Ltd.). Specially constructed graph paper, which yields linearity with standard solutions, was designed so that it could be used directly without data transmission. The specific activity function appears as the upper arithmetical horizontal scale; corresponding values of the concentration of non-radioactive ligand in the solution added were individually calculated and appear on the lower scale opposite the appropriate values of the upper scale. The linearity of the graphs obtained confirmed that binding of digoxin was approximately constant through the range of clinical concentrations tested (0.5 to 8ng/ml), although binding declined slightly at higher concentrations. (U.K.)

  17. New insights into the use of currently available non-steroidal anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Brune K

    2015-02-01

    Full Text Available Kay Brune,1 Paola Patrignani2 1Department of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany; 2Department of Neuroscience, Imaging and Clinical Sciences, Center of Excellence on Aging, G d’Annunzio University, Chieti, Italy Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs, which act via inhibition of the cyclooxygenase (COX isozymes, were discovered more than 100 years ago. They remain a key component of the pharmacological management of acute and chronic pain. The COX-1 and COX-2 isozymes have different biological functions; analgesic activity is primarily (although not exclusively associated with inhibition of COX-2, while different side effects result from the inhibition of COX-1 and COX-2. All available NSAIDs, including acetaminophen and aspirin, are associated with potential side effects, particularly gastrointestinal and cardiovascular effects, related to their relative selectivity for COX-1 and COX-2. Since all NSAIDs exert their therapeutic activity through inhibition of the COX isozymes, strategies are needed to reduce the risks associated with NSAIDs while achieving sufficient pain relief. A better understanding of the inhibitory activity and COX-1/COX-2 selectivity of an NSAID at therapeutic doses, based on pharmacokinetic and pharmacodynamic properties (eg, inhibitory dose, absorption, plasma versus tissue distribution, and elimination, and the impact on drug tolerability and safety can guide the selection of appropriate NSAIDs for pain management. For example, many NSAIDs with moderate to high selectivity for COX-2 versus COX-1 can be administered at doses that maximize efficacy (~80% inhibition of COX-2 while minimizing COX-1 inhibition and associated side effects, such as gastrointestinal toxicity. Acidic NSAIDs with favorable tissue distribution and short plasma half-lives can additionally be dosed to provide near-constant analgesia while

  18. Graph modeling systems and methods

    Science.gov (United States)

    Neergaard, Mike

    2015-10-13

    An apparatus and a method for vulnerability and reliability modeling are provided. The method generally includes constructing a graph model of a physical network using a computer, the graph model including a plurality of terminating vertices to represent nodes in the physical network, a plurality of edges to represent transmission paths in the physical network, and a non-terminating vertex to represent a non-nodal vulnerability along a transmission path in the physical network. The method additionally includes evaluating the vulnerability and reliability of the physical network using the constructed graph model, wherein the vulnerability and reliability evaluation includes a determination of whether each terminating and non-terminating vertex represents a critical point of failure. The method can be utilized to evaluate wide variety of networks, including power grid infrastructures, communication network topologies, and fluid distribution systems.

  19. On the graph turnpike problem

    KAUST Repository

    Feder, Tomá s; Motwani, Rajeev

    2009-01-01

    Results on graph turnpike problem without distinctness, including its NP-completeness, and an O(m+n log n) algorithm, is presented. The usual turnpike problem has all pairwise distances given, but does not specify which pair of vertices w e corresponds to. There are two other problems that can be viewed as special cases of the graph turnpike problem, including the bandwidth problem and the low-distortion graph embedding problem. The aim for the turnpike problem in the NP-complete is to orient the edges with weights w i in either direction so that when the whole cycle is transversed in the real line, it returns to a chosen starting point for the cycle. An instance of the turnpike problem with or without distinctness is uniquely mappable if there exists at most one solution up to translation and choice of orientation.

  20. On the graph turnpike problem

    KAUST Repository

    Feder, Tomás

    2009-06-01

    Results on graph turnpike problem without distinctness, including its NP-completeness, and an O(m+n log n) algorithm, is presented. The usual turnpike problem has all pairwise distances given, but does not specify which pair of vertices w e corresponds to. There are two other problems that can be viewed as special cases of the graph turnpike problem, including the bandwidth problem and the low-distortion graph embedding problem. The aim for the turnpike problem in the NP-complete is to orient the edges with weights w i in either direction so that when the whole cycle is transversed in the real line, it returns to a chosen starting point for the cycle. An instance of the turnpike problem with or without distinctness is uniquely mappable if there exists at most one solution up to translation and choice of orientation.

  1. Negation switching invariant signed graphs

    Directory of Open Access Journals (Sweden)

    Deepa Sinha

    2014-04-01

    Full Text Available A signed graph (or, $sigraph$ in short is a graph G in which each edge x carries a value $\\sigma(x \\in \\{-, +\\}$ called its sign. Given a sigraph S, the negation $\\eta(S$ of the sigraph S is a sigraph obtained from S by reversing the sign of every edge of S. Two sigraphs $S_{1}$ and $S_{2}$ on the same underlying graph are switching equivalent if it is possible to assign signs `+' (`plus' or `-' (`minus' to vertices of $S_{1}$ such that by reversing the sign of each of its edges that has received opposite signs at its ends, one obtains $S_{2}$. In this paper, we characterize sigraphs which are negation switching invariant and also see for what sigraphs, S and $\\eta (S$ are signed isomorphic.

  2. Quantum snake walk on graphs

    International Nuclear Information System (INIS)

    Rosmanis, Ansis

    2011-01-01

    I introduce a continuous-time quantum walk on graphs called the quantum snake walk, the basis states of which are fixed-length paths (snakes) in the underlying graph. First, I analyze the quantum snake walk on the line, and I show that, even though most states stay localized throughout the evolution, there are specific states that most likely move on the line as wave packets with momentum inversely proportional to the length of the snake. Next, I discuss how an algorithm based on the quantum snake walk might potentially be able to solve an extended version of the glued trees problem, which asks to find a path connecting both roots of the glued trees graph. To the best of my knowledge, no efficient quantum algorithm solving this problem is known yet.

  3. Current status of muscarinic M1 and M4 receptors as drug targets for neurodegenerative diseases.

    Science.gov (United States)

    Felder, Christian C; Goldsmith, Paul J; Jackson, Kimberley; Sanger, Helen E; Evans, David A; Mogg, Adrian J; Broad, Lisa M

    2018-01-25

    The cholinergic signalling system has been an attractive pathway to seek targets for modulation of arousal, cognition, and attention which are compromised in neurodegenerative and neuropsychiatric diseases. The acetylcholine muscarinic receptor M1 and M4 subtypes which are highly expressed in the central nervous system, in cortex, hippocampus and striatum, key areas of cognitive and neuropsychiatric control, have received particular attention. Historical muscarinic drug development yielded first generation agonists with modest selectivity for these two receptor targets over M2 and M3 receptors, the major peripheral sub-types hypothesised to underlie the dose-limiting clinical side effects. More recent compound screening and medicinal chemistry optimization of orthosteric and allosteric agonists, and positive allosteric modulators binding to sites distinct from the highly homologous acetylcholine binding pocket have yielded a collection of highly selective tool compounds for preclinical validation studies. Several M1 selective ligands have progressed to early clinical development and in time will hopefully lead to useful therapeutics for treating symptoms of Alzheimer's disease and related disorders. Copyright © 2018. Published by Elsevier Ltd.

  4. On Graph Rewriting, Reduction and Evaluation

    DEFF Research Database (Denmark)

    Zerny, Ian

    2010-01-01

    We inter-derive two prototypical styles of graph reduction: reduction machines à la Turner and graph rewriting systems à la Barendregt et al. To this end, we adapt Danvy et al.'s mechanical program derivations from the world of terms to the world of graphs. We also outline how to inter-derive a t......We inter-derive two prototypical styles of graph reduction: reduction machines à la Turner and graph rewriting systems à la Barendregt et al. To this end, we adapt Danvy et al.'s mechanical program derivations from the world of terms to the world of graphs. We also outline how to inter...

  5. The fascinating world of graph theory

    CERN Document Server

    Benjamin, Arthur; Zhang, Ping

    2015-01-01

    Graph theory goes back several centuries and revolves around the study of graphs-mathematical structures showing relations between objects. With applications in biology, computer science, transportation science, and other areas, graph theory encompasses some of the most beautiful formulas in mathematics-and some of its most famous problems. The Fascinating World of Graph Theory explores the questions and puzzles that have been studied, and often solved, through graph theory. This book looks at graph theory's development and the vibrant individuals responsible for the field's growth. Introducin

  6. Graph-based modelling in engineering

    CERN Document Server

    Rysiński, Jacek

    2017-01-01

    This book presents versatile, modern and creative applications of graph theory in mechanical engineering, robotics and computer networks. Topics related to mechanical engineering include e.g. machine and mechanism science, mechatronics, robotics, gearing and transmissions, design theory and production processes. The graphs treated are simple graphs, weighted and mixed graphs, bond graphs, Petri nets, logical trees etc. The authors represent several countries in Europe and America, and their contributions show how different, elegant, useful and fruitful the utilization of graphs in modelling of engineering systems can be. .

  7. XML Graphs in Program Analysis

    DEFF Research Database (Denmark)

    Møller, Anders; Schwartzbach, Michael Ignatieff

    2007-01-01

    XML graphs have shown to be a simple and effective formalism for representing sets of XML documents in program analysis. It has evolved through a six year period with variants tailored for a range of applications. We present a unified definition, outline the key properties including validation...... of XML graphs against different XML schema languages, and provide a software package that enables others to make use of these ideas. We also survey four very different applications: XML in Java, Java Servlets and JSP, transformations between XML and non-XML data, and XSLT....

  8. Graph topologies on closed multifunctions

    Directory of Open Access Journals (Sweden)

    Giuseppe Di Maio

    2003-10-01

    Full Text Available In this paper we study function space topologies on closed multifunctions, i.e. closed relations on X x Y using various hypertopologies. The hypertopologies are in essence, graph topologies i.e topologies on functions considered as graphs which are subsets of X x Y . We also study several topologies, including one that is derived from the Attouch-Wets filter on the range. We state embedding theorems which enable us to generalize and prove some recent results in the literature with the use of known results in the hyperspace of the range space and in the function space topologies of ordinary functions.

  9. Cyclic graphs and Apery's theorem

    International Nuclear Information System (INIS)

    Sorokin, V N

    2002-01-01

    This is a survey of results about the behaviour of Hermite-Pade approximants for graphs of Markov functions, and a survey of interpolation problems leading to Apery's result about the irrationality of the value ζ(3) of the Riemann zeta function. The first example is given of a cyclic graph for which the Hermite-Pade problem leads to Apery's theorem. Explicit formulae for solutions are obtained, namely, Rodrigues' formulae and integral representations. The asymptotic behaviour of the approximants is studied, and recurrence formulae are found

  10. Interacting particle systems on graphs

    Science.gov (United States)

    Sood, Vishal

    In this dissertation, the dynamics of socially or biologically interacting populations are investigated. The individual members of the population are treated as particles that interact via links on a social or biological network represented as a graph. The effect of the structure of the graph on the properties of the interacting particle system is studied using statistical physics techniques. In the first chapter, the central concepts of graph theory and social and biological networks are presented. Next, interacting particle systems that are drawn from physics, mathematics and biology are discussed in the second chapter. In the third chapter, the random walk on a graph is studied. The mean time for a random walk to traverse between two arbitrary sites of a random graph is evaluated. Using an effective medium approximation it is found that the mean first-passage time between pairs of sites, as well as all moments of this first-passage time, are insensitive to the density of links in the graph. The inverse of the mean-first passage time varies non-monotonically with the density of links near the percolation transition of the random graph. Much of the behavior can be understood by simple heuristic arguments. Evolutionary dynamics, by which mutants overspread an otherwise uniform population on heterogeneous graphs, are studied in the fourth chapter. Such a process underlies' epidemic propagation, emergence of fads, social cooperation or invasion of an ecological niche by a new species. The first part of this chapter is devoted to neutral dynamics, in which the mutant genotype does not have a selective advantage over the resident genotype. The time to extinction of one of the two genotypes is derived. In the second part of this chapter, selective advantage or fitness is introduced such that the mutant genotype has a higher birth rate or a lower death rate. This selective advantage leads to a dynamical competition in which selection dominates for large populations

  11. Stress Mediates the Relationship Between Past Drug Addiction and Current Risky Sexual Behaviour Among Low-income Women.

    Science.gov (United States)

    Wu, Z Helen; Tennen, Howard; Hosain, G M Monawar; Coman, Emil; Cullum, Jerry; Berenson, Abbey B

    2016-04-01

    This study examined the role of stress as a mediator of the relationship between prior drug addiction and current high-risk sexual behaviour. Eight hundred twenty women aged 18 to 30 years, who received care at community-based family planning clinics, were interviewed using the Composite International Diagnostic Interview and the Sexual Risk Behavior Assessment Schedule. They also completed the brief version of the Self-Control Scale as a measure of problem-solving strategies and measures of recent stressful events, daily hassles and ongoing chronic stress. Regardless of addiction history, stress exposure during the previous 12 months was associated with risky sexual behaviour during the previous 12 months. Structural equation modelling revealed that 12-month stress levels mediated the relationship between past drug addiction and 12-month high-risk sexual behaviours, as well as the negative relationship between problem-solving strategies and high-risk sexual behaviours. Problem-solving strategies did not moderate the relationship between drug addiction and high-risk sexual behaviours. These findings suggest that stress management training may help reduce risky behaviour among young, low-income women. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Current Trends of Using Antimicrobial Drugs in the ICU at a Tertiary Level Teaching Hospital in Mymensingh.

    Science.gov (United States)

    Saha, S K; Shaha, K C; Haque, M F; Khatun, S; Akhter, S M; Akhter, H

    2016-10-01

    The aim of the present study was to investigate the current trends of using antimicrobial drugs in the ICU at a tertiary level teaching hospital in Mymensingh. The study of prescribing patterns seeks to monitor, evaluate and suggest modifications in clinicians prescribing habits so as to make medical care rational. It was an observational type of descriptive study, conducted in the Mymensingh medical college hospital, Mymensingh, during the study period of June 2016 to September 2016.The study was approved by the institutional ethical committee. Most patients in the ICU belonged to the older age group >60 years. Male patients were more than the female patients in ICU. Average duration of stay in ICU was 4.35 days. Admissions in ICU were common due to respiratory system related diseases and the present study showed that 31.68% of the reported cases belong to the respiratory system. Average number of drugs per prescription was 6.46. Average number of anti-microbial drugs per prescription was 1.38. Cephalosporin group and individually ceftriaxone was the most frequently prescribed antimicrobial group and agent respectively in the ICU. Most commonly used antimicrobial combination was Cephalosporin and Metronidazole (43.33%) followed by Carbapenem (Meropenem) and Metronidazole (13.33%). Most antimicrobial agents were prescribed without bacteriological culture and sensivity testing evidence. There is a need for motivating the physicians to prescribe antimicrobial agents with supportive bacteriological evidences.

  13. From Medicinal Chemistry to Human Health: Current Approaches to Drug Discovery for Cancer and Neglected Tropical Diseases

    Directory of Open Access Journals (Sweden)

    LEONARDO G. FERREIRA

    2018-02-01

    Full Text Available ABSTRACT Scientific and technological breakthroughs have compelled the current players in drug discovery to increasingly incorporate knowledge-based approaches. This evolving paradigm, which has its roots attached to the recent advances in medicinal chemistry, molecular and structural biology, has unprecedentedly demanded the development of up-to-date computational approaches, such as bio- and chemo-informatics. These tools have been pivotal to catalyzing the ever-increasing amount of data generated by the molecular sciences, and to converting the data into insightful guidelines for use in the research pipeline. As a result, ligand- and structure-based drug design have emerged as key pathways to address the pharmaceutical industry’s striking demands for innovation. These approaches depend on a keen integration of experimental and molecular modeling methods to surmount the main challenges faced by drug candidates - in vivo efficacy, pharmacodynamics, metabolism, pharmacokinetics and safety. To that end, the Laboratório de Química Medicinal e Computacional (LQMC of the Universidade de São Paulo has developed forefront research on highly prevalent and life-threatening neglected tropical diseases and cancer. By taking part in global initiatives for pharmaceutical innovation, the laboratory has contributed to the advance of these critical therapeutic areas through the use of cutting-edge strategies in medicinal chemistry.

  14. Bio-AIMS Collection of Chemoinformatics Web Tools based on Molecular Graph Information and Artificial Intelligence Models.

    Science.gov (United States)

    Munteanu, Cristian R; Gonzalez-Diaz, Humberto; Garcia, Rafael; Loza, Mabel; Pazos, Alejandro

    2015-01-01

    The molecular information encoding into molecular descriptors is the first step into in silico Chemoinformatics methods in Drug Design. The Machine Learning methods are a complex solution to find prediction models for specific biological properties of molecules. These models connect the molecular structure information such as atom connectivity (molecular graphs) or physical-chemical properties of an atom/group of atoms to the molecular activity (Quantitative Structure - Activity Relationship, QSAR). Due to the complexity of the proteins, the prediction of their activity is a complicated task and the interpretation of the models is more difficult. The current review presents a series of 11 prediction models for proteins, implemented as free Web tools on an Artificial Intelligence Model Server in Biosciences, Bio-AIMS (http://bio-aims.udc.es/TargetPred.php). Six tools predict protein activity, two models evaluate drug - protein target interactions and the other three calculate protein - protein interactions. The input information is based on the protein 3D structure for nine models, 1D peptide amino acid sequence for three tools and drug SMILES formulas for two servers. The molecular graph descriptor-based Machine Learning models could be useful tools for in silico screening of new peptides/proteins as future drug targets for specific treatments.

  15. The "high solubility" definition of the current FDA Guidance on Biopharmaceutical Classification System may be too strict for acidic drugs.

    Science.gov (United States)

    Yazdanian, Mehran; Briggs, Katherine; Jankovsky, Corinne; Hawi, Amale

    2004-02-01

    The purpose of this study was to assess if the definition of high solubility as proposed in the FDA Guidance on Biopharmaceutical Classification System (BCS) is too strict for highly permeable acidic drugs. The solubility and permeability values of 20 (18 acidic and 2 non-acidic) nonsteroidal anti-inflammatory drugs (NSAID) were determined. The NSAIDs were grouped into three different sets having acetic acid, propionic acid, or other acidic moieties such as fenamate, oxicam, and salicylate. Two nonacidic NSAIDs (celecoxib and rofecoxib) were also included for comparison purposes. Equilibrium solubility values were determined at pH 1.2, 5.0, 7.4, and in biorelevant media simulating fed intestinal fluid at pH 5.0. For a select number of acids, we also measured solubility values in media simulating gastric and fasted intestinal fluids. Permeability classification was established relative to that of reference drugs in the Caco-2 cell permeability model. Permeability coefficients for all drugs were measured at concentrations corresponding to the lowest and highest marketed dose strengths dissolved in 250 ml volume, and their potential interaction with cellular efflux pumps was investigated. All NSAIDs with different acidic functional groups were classified as highly permeable based on their Caco-2 cell permeability. Only ketorolac appeared to have a potential for interaction with cellular efflux pumps. Solubility classification was based on comparison of equilibrium solubility at pH 1.2, 5.0. and 7.4 relative to marketed dose strengths in 250 ml. The pKa values for the acidic NSAIDs studied were between 3.5 and 5.1. and, as expected, their solubility increased dramatically at pH 7.4 compared to pH 1.2. Only three NSAIDs, ketorolac, ketoprofen. and acetyl salicylic acid, meet the current criteria for high solubility over the entire pH range. However, with the exception of ibuprofen, oxaprozin, and mefenamic acid, the remaining compounds can be classified as Class I drugs

  16. Phase II drugs currently being investigated for the treatment of hypogonadism.

    Science.gov (United States)

    Udedibia, Emeka; Kaminetsky, Jed

    2014-12-01

    Hypogonadism is the most common endocrine disorder, which affects men of all age groups. Recent shifts in public awareness, increased screening and recognition of symptoms and updated diagnostic criteria have led to an increase in men diagnosed as hypogonadal, including middle-aged and older men who previously would have been considered eugonadal. The increase in testosterone replacement therapy (TRT) has paralleled an increase in advancements of treatment options. Although current therapies are highly efficacious for many men, there remains a need for newer therapies that are more cost-effective, preserve ease of use and administration, mitigate undesirable effects and closely mimic physiological levels of testosterone. In this review, the authors discuss current TRTs and therapies in development for the treatment of hypogonadism. The focus is on therapies under Phase II investigation or those who have recently completed Phase II study. With several new therapies in development, the authors expect advancements in achieving treatment benchmarks that meet the needs of the individual symptomatic hypogonadal male. Increased public awareness of hypogonadism and TRT has led to a welcomed expansion in the choice of TRT options. These include new delivery systems, formulations, routes of administration and non-testosterone modalities.

  17. Current antiviral drugs and their analysis in biological materials - Part II: Antivirals against hepatitis and HIV viruses.

    Science.gov (United States)

    Nováková, Lucie; Pavlík, Jakub; Chrenková, Lucia; Martinec, Ondřej; Červený, Lukáš

    2018-01-05

    This review is a Part II of the series aiming to provide comprehensive overview of currently used antiviral drugs and to show modern approaches to their analysis. While in the Part I antivirals against herpes viruses and antivirals against respiratory viruses were addressed, this part concerns antivirals against hepatitis viruses (B and C) and human immunodeficiency virus (HIV). Many novel antivirals against hepatitis C virus (HCV) and HIV have been introduced into the clinical practice over the last decade. The recent broadening portfolio of these groups of antivirals is reflected in increasing number of developed analytical methods required to meet the needs of clinical terrain. Part II summarizes the mechanisms of action of antivirals against hepatitis B virus (HBV), HCV, and HIV, their use in clinical practice, and analytical methods for individual classes. It also provides expert opinion on state of art in the field of bioanalysis of these drugs. Analytical methods reflect novelty of these chemical structures and use by far the most current approaches, such as simple and high-throughput sample preparation and fast separation, often by means of UHPLC-MS/MS. Proper method validation based on requirements of bioanalytical guidelines is an inherent part of the developed methods. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Current drug therapy of patients with BPH-LUTS with the special emphasis on PDE5 inhibitors.

    Science.gov (United States)

    Kolontarev, Konstantin; Govorov, Alexander; Kasyan, George; Priymak, Diana; Pushkar, Dmitry

    2016-01-01

    Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptom (LUTS) development in men [1]. The intensity of the symptoms may vary from mild to severe, significantly affecting the quality of life. Erectile dysfunction (ED) is one of the most challenging issues in modern urology that significantly influences the quality of life in men worldwide. The objective of this literature review was to analyze the current drug therapies of patients with BPH-LUTS, with the special emphasis on PDE5 inhibitors. The authors searched the literature for the period from 2000 until 2015 in MEDLINE and PubMed. Twenty-three articles were selected based on their reliability. A detailed analysis of the selected papers was performed. Primary attention was given to articles describing the use of PDE5. Works describing the use of different groups of drugs in patients with BPH-LUTS were also selected. The current literature analysis suggests that the introduction of PDE5 inhibitors in clinical practice for the treatment of patients with BPH-LUTS will allow for significant expansion of the therapeutic options for the treatment of this disease.

  19. Multiple graph regularized protein domain ranking

    KAUST Repository

    Wang, Jim Jing-Yan

    2012-11-19

    Background: Protein domain ranking is a fundamental task in structural biology. Most protein domain ranking methods rely on the pairwise comparison of protein domains while neglecting the global manifold structure of the protein domain database. Recently, graph regularized ranking that exploits the global structure of the graph defined by the pairwise similarities has been proposed. However, the existing graph regularized ranking methods are very sensitive to the choice of the graph model and parameters, and this remains a difficult problem for most of the protein domain ranking methods.Results: To tackle this problem, we have developed the Multiple Graph regularized Ranking algorithm, MultiG-Rank. Instead of using a single graph to regularize the ranking scores, MultiG-Rank approximates the intrinsic manifold of protein domain distribution by combining multiple initial graphs for the regularization. Graph weights are learned with ranking scores jointly and automatically, by alternately minimizing an objective function in an iterative algorithm. Experimental results on a subset of the ASTRAL SCOP protein domain database demonstrate that MultiG-Rank achieves a better ranking performance than single graph regularized ranking methods and pairwise similarity based ranking methods.Conclusion: The problem of graph model and parameter selection in graph regularized protein domain ranking can be solved effectively by combining multiple graphs. This aspect of generalization introduces a new frontier in applying multiple graphs to solving protein domain ranking applications. 2012 Wang et al; licensee BioMed Central Ltd.

  20. Multiple graph regularized protein domain ranking

    KAUST Repository

    Wang, Jim Jing-Yan; Bensmail, Halima; Gao, Xin

    2012-01-01

    Background: Protein domain ranking is a fundamental task in structural biology. Most protein domain ranking methods rely on the pairwise comparison of protein domains while neglecting the global manifold structure of the protein domain database. Recently, graph regularized ranking that exploits the global structure of the graph defined by the pairwise similarities has been proposed. However, the existing graph regularized ranking methods are very sensitive to the choice of the graph model and parameters, and this remains a difficult problem for most of the protein domain ranking methods.Results: To tackle this problem, we have developed the Multiple Graph regularized Ranking algorithm, MultiG-Rank. Instead of using a single graph to regularize the ranking scores, MultiG-Rank approximates the intrinsic manifold of protein domain distribution by combining multiple initial graphs for the regularization. Graph weights are learned with ranking scores jointly and automatically, by alternately minimizing an objective function in an iterative algorithm. Experimental results on a subset of the ASTRAL SCOP protein domain database demonstrate that MultiG-Rank achieves a better ranking performance than single graph regularized ranking methods and pairwise similarity based ranking methods.Conclusion: The problem of graph model and parameter selection in graph regularized protein domain ranking can be solved effectively by combining multiple graphs. This aspect of generalization introduces a new frontier in applying multiple graphs to solving protein domain ranking applications. 2012 Wang et al; licensee BioMed Central Ltd.

  1. Multiple graph regularized protein domain ranking.

    Science.gov (United States)

    Wang, Jim Jing-Yan; Bensmail, Halima; Gao, Xin

    2012-11-19

    Protein domain ranking is a fundamental task in structural biology. Most protein domain ranking methods rely on the pairwise comparison of protein domains while neglecting the global manifold structure of the protein domain database. Recently, graph regularized ranking that exploits the global structure of the graph defined by the pairwise similarities has been proposed. However, the existing graph regularized ranking methods are very sensitive to the choice of the graph model and parameters, and this remains a difficult problem for most of the protein domain ranking methods. To tackle this problem, we have developed the Multiple Graph regularized Ranking algorithm, MultiG-Rank. Instead of using a single graph to regularize the ranking scores, MultiG-Rank approximates the intrinsic manifold of protein domain distribution by combining multiple initial graphs for the regularization. Graph weights are learned with ranking scores jointly and automatically, by alternately minimizing an objective function in an iterative algorithm. Experimental results on a subset of the ASTRAL SCOP protein domain database demonstrate that MultiG-Rank achieves a better ranking performance than single graph regularized ranking methods and pairwise similarity based ranking methods. The problem of graph model and parameter selection in graph regularized protein domain ranking can be solved effectively by combining multiple graphs. This aspect of generalization introduces a new frontier in applying multiple graphs to solving protein domain ranking applications.

  2. Multiple graph regularized protein domain ranking

    Directory of Open Access Journals (Sweden)

    Wang Jim

    2012-11-01

    Full Text Available Abstract Background Protein domain ranking is a fundamental task in structural biology. Most protein domain ranking methods rely on the pairwise comparison of protein domains while neglecting the global manifold structure of the protein domain database. Recently, graph regularized ranking that exploits the global structure of the graph defined by the pairwise similarities has been proposed. However, the existing graph regularized ranking methods are very sensitive to the choice of the graph model and parameters, and this remains a difficult problem for most of the protein domain ranking methods. Results To tackle this problem, we have developed the Multiple Graph regularized Ranking algorithm, MultiG-Rank. Instead of using a single graph to regularize the ranking scores, MultiG-Rank approximates the intrinsic manifold of protein domain distribution by combining multiple initial graphs for the regularization. Graph weights are learned with ranking scores jointly and automatically, by alternately minimizing an objective function in an iterative algorithm. Experimental results on a subset of the ASTRAL SCOP protein domain database demonstrate that MultiG-Rank achieves a better ranking performance than single graph regularized ranking methods and pairwise similarity based ranking methods. Conclusion The problem of graph model and parameter selection in graph regularized protein domain ranking can be solved effectively by combining multiple graphs. This aspect of generalization introduces a new frontier in applying multiple graphs to solving protein domain ranking applications.

  3. Effectiveness of Vertex Nomination via Seeded Graph Matching to Find Bijections Between Similar Networks

    Science.gov (United States)

    2018-02-01

    Information Directorate This report is published in the interest of scientific and technical information exchange, and its publication does not...the current prototype. 15. SUBJECT TERMS Vertex Nomination via Seeded Graph Matching (VN via SGM), Seeded Graph Matching (SGM), Vertex of Interest (VOI...Author’s Example ................................................................................................................. 4 4.2.2 Simple

  4. Transformation of UML models to CSP : a case study for graph transformation tools

    NARCIS (Netherlands)

    Varró, D.; Asztalos, M.; Bisztray, D.; Boronat, A.; Dang, D.; Geiß, R.; Greenyer, J.; Van Gorp, P.M.E.; Kniemeyer, O.; Narayanan, A.; Rencis, E.; Weinell, E.; Schürr, A.; Nagl, M.; Zündorf, A.

    2008-01-01

    Graph transformation provides an intuitive mechanism for capturing model transformations. In the current paper, we investigate and compare various graph transformation tools using a compact practical model transformation case study carried out as part of the AGTIVE 2007 Tool Contest [22]. The aim of

  5. Precalculus Teachers' Perspectives on Using Graphing Calculators: An Example from One Curriculum

    Science.gov (United States)

    Karadeniz, Ilyas; Thompson, Denisse R.

    2018-01-01

    Graphing calculators are hand-held technological tools currently used in mathematics classrooms. Teachers' perspectives on using graphing calculators are important in terms of exploring what teachers think about using such technology in advanced mathematics courses, particularly precalculus courses. A descriptive intrinsic case study was conducted…

  6. Constructing Knowledge Graphs of Depression

    NARCIS (Netherlands)

    Huang, Zhisheng; Yang, Jie; van Harmelen, Frank; Hu, Qing

    2017-01-01

    Knowledge Graphs have been shown to be useful tools for integrating multiple medical knowledge sources, and to support such tasks as medical decision making, literature retrieval, determining healthcare quality indicators, co-morbodity analysis and many others. A large number of medical knowledge

  7. Partitioning graphs into connected parts

    NARCIS (Netherlands)

    Hof, van 't P.; Paulusma, D.; Woeginger, G.J.; Frid, A.; Morozov, A.S.; Rybalchenko, A.; Wagner, K.W.

    2009-01-01

    The 2-DISJOINT CONNECTED SUBGRAPHS problem asks if a given graph has two vertex-disjoint connected subgraphs containing pre-specified sets of vertices. We show that this problem is NP-complete even if one of the sets has cardinality 2. The LONGEST PATH CONTRACTIBILITY problem asks for the largest

  8. Isoperimetric inequalities for minimal graphs

    International Nuclear Information System (INIS)

    Pacelli Bessa, G.; Montenegro, J.F.

    2007-09-01

    Based on Markvorsen and Palmer's work on mean time exit and isoperimetric inequalities we establish slightly better isoperimetric inequalities and mean time exit estimates for minimal graphs in N x R. We also prove isoperimetric inequalities for submanifolds of Hadamard spaces with tamed second fundamental form. (author)

  9. Ancestral Genres of Mathematical Graphs

    Science.gov (United States)

    Gerofsky, Susan

    2011-01-01

    Drawing from sources in gesture studies, cognitive science, the anthropology of religion and art/architecture history, this article explores cultural, bodily and cosmological resonances carried (unintentionally) by mathematical graphs on Cartesian coordinates. Concepts of asymmetric bodily spaces, grids, orthogonality, mapping and sacred spaces…

  10. Humidity Graphs for All Seasons.

    Science.gov (United States)

    Esmael, F.

    1982-01-01

    In a previous article in this journal (Vol. 17, p358, 1979), a wet-bulb depression table was recommended for two simple experiments to determine relative humidity. However, the use of a graph is suggested because it gives the relative humidity directly from the wet and dry bulb readings. (JN)

  11. Contracting a planar graph efficiently

    DEFF Research Database (Denmark)

    Holm, Jacob; Italiano, Giuseppe F.; Karczmarz, Adam

    2017-01-01

    the data structure, we can achieve optimal running times for decremental bridge detection, 2-edge connectivity, maximal 3-edge connected components, and the problem of finding a unique perfect matching for a static planar graph. Furthermore, we improve the running times of algorithms for several planar...

  12. Graph Model Based Indoor Tracking

    DEFF Research Database (Denmark)

    Jensen, Christian Søndergaard; Lu, Hua; Yang, Bin

    2009-01-01

    The tracking of the locations of moving objects in large indoor spaces is important, as it enables a range of applications related to, e.g., security and indoor navigation and guidance. This paper presents a graph model based approach to indoor tracking that offers a uniform data management...

  13. A graph with fractional revival

    Science.gov (United States)

    Bernard, Pierre-Antoine; Chan, Ada; Loranger, Érika; Tamon, Christino; Vinet, Luc

    2018-02-01

    An example of a graph that admits balanced fractional revival between antipodes is presented. It is obtained by establishing the correspondence between the quantum walk on a hypercube where the opposite vertices across the diagonals of each face are connected and, the coherent transport of single excitations in the extension of the Krawtchouk spin chain with next-to-nearest neighbour interactions.

  14. Fixation Time for Evolutionary Graphs

    Science.gov (United States)

    Nie, Pu-Yan; Zhang, Pei-Ai

    Evolutionary graph theory (EGT) is recently proposed by Lieberman et al. in 2005. EGT is successful for explaining biological evolution and some social phenomena. It is extremely important to consider the time of fixation for EGT in many practical problems, including evolutionary theory and the evolution of cooperation. This study characterizes the time to asymptotically reach fixation.

  15. Current globalization of drug interventional clinical trials: characteristics and associated factors, 2011-2013.

    Science.gov (United States)

    Jeong, Sohyun; Sohn, Minji; Kim, Jae Hyun; Ko, Minoh; Seo, Hee-Won; Song, Yun-Kyoung; Choi, Boyoon; Han, Nayoung; Na, Han-Sung; Lee, Jong Gu; Kim, In-Wha; Oh, Jung Mi; Lee, Euni

    2017-06-21

    Clinical trial globalization is a major trend for industry-sponsored clinical trials. There has been a shift in clinical trial sites towards emerging regions of Eastern Europe, Latin America, Asia, the Middle East, and Africa. Our study objectives were to evaluate the current characteristics of clinical trials and to find out the associated multiple factors which could explain clinical trial globalization and its implications for clinical trial globalization in 2011-2013. The data elements of "phase," "recruitment status," "type of sponsor," "age groups," and "design of trial" from 30 countries were extracted from the ClinicalTrials.gov website. Ten continental representative countries including the USA were selected and the design elements were compared to those of the USA. Factors associated with trial site distribution were chosen for a multilinear regression analysis. The USA, Germany, France, Canada, and United Kingdom were the "top five" countries which frequently held clinical trials. The design elements from nine continental representative countries were quite different from those of the USA; phase 1 trials were more prevalent in India (OR 1.517, p globalization of clinical trials in the emerging regions of Asia, South Africa, and Eastern Europe developed in parallel with the factors of economic drive, population for recruitment, and regulatory constraints.

  16. Ayurveda and botanical drugs for epilepsy: Current evidence and future prospects.

    Science.gov (United States)

    Sriranjini, Sitaram Jaideep; Sandhya, Kumar; Mamta, Vernekar Sanjeeva

    2015-11-01

    The understanding of epilepsy has progressed since its earliest impression as a disease associated with paranormal and superstitious beliefs. Landmark advances have been made in deciphering the pathophysiological substrates involved in the disease process, and treatment advances have contributed significantly to ameliorating the seizures. However, disease-modifying agents are yet to be discovered. Ayurveda is a system of medicine that stresses a holistic approach to disease, and treatment is focused on disease modification and symptom management. Herbs form the core of Ayurveda medicine; though many of them have been studied for their anticonvulsant activity, very few actually mention the reference of these herbs in Ayurveda literature. Other therapeutic interventions used in Ayurveda are relatively unexplored, and future research will need to focus on this. The current manuscript briefly discusses the understanding of epilepsy as per Ayurveda and reviews herbs that have been studied for their anticonvulsant activity mentioned in Ayurveda literature. This article is part of a Special Issue entitled "Botanicals for Epilepsy". Copyright © 2015 Elsevier Inc. All rights reserved.

  17. African medicinal plants and their derivatives: Current efforts towards potential anti-cancer drugs.

    Science.gov (United States)

    Mbele, Mzwandile; Hull, Rodney; Dlamini, Zodwa

    2017-10-01

    Cancer is a leading cause of mortality and morbidity worldwide and second only to cardiovascular diseases. Cancer is a challenge in African countries because generally there is limited funding available to deal with the cancer epidemic and awareness and this should be prioritised and all possible resources should be utilized to prevent and treat cancer. The current review reports on the role of African medicinal plants in the treatment of cancer, and also outlines methodologies that can also be used to achieve better outcomes for cancer treatment. This review outlines African medicinal plants, isolated compounds and technologies that can be used to advance cancer research. Chemical structures of isolated compounds have an important role in anti-cancer treatments; new technologies and methods may assist to identify more properties of African medicinal plants and the treatment of cancer. In conclusion, African medicinal plants have shown their potential as enormous resources for novel cytotoxicity compounds. Finally it has been noted that the cytotoxicity depends on the chemical structural arrangements of African medicinal plants compounds. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Coloring sums of extensions of certain graphs

    Directory of Open Access Journals (Sweden)

    Johan Kok

    2017-12-01

    Full Text Available We recall that the minimum number of colors that allow a proper coloring of graph $G$ is called the chromatic number of $G$ and denoted $\\chi(G$. Motivated by the introduction of the concept of the $b$-chromatic sum of a graph the concept of $\\chi'$-chromatic sum and $\\chi^+$-chromatic sum are introduced in this paper. The extended graph $G^x$ of a graph $G$ was recently introduced for certain regular graphs. This paper furthers the concepts of $\\chi'$-chromatic sum and $\\chi^+$-chromatic sum to extended paths and cycles. Bipartite graphs also receive some attention. The paper concludes with patterned structured graphs. These last said graphs are typically found in chemical and biological structures.

  19. Mathematical Minute: Rotating a Function Graph

    Science.gov (United States)

    Bravo, Daniel; Fera, Joseph

    2013-01-01

    Using calculus only, we find the angles you can rotate the graph of a differentiable function about the origin and still obtain a function graph. We then apply the solution to odd and even degree polynomials.

  20. Towards a theory of geometric graphs

    CERN Document Server

    Pach, Janos

    2004-01-01

    The early development of graph theory was heavily motivated and influenced by topological and geometric themes, such as the Konigsberg Bridge Problem, Euler's Polyhedral Formula, or Kuratowski's characterization of planar graphs. In 1936, when Denes Konig published his classical Theory of Finite and Infinite Graphs, the first book ever written on the subject, he stressed this connection by adding the subtitle Combinatorial Topology of Systems of Segments. He wanted to emphasize that the subject of his investigations was very concrete: planar figures consisting of points connected by straight-line segments. However, in the second half of the twentieth century, graph theoretical research took an interesting turn. In the most popular and most rapidly growing areas (the theory of random graphs, Ramsey theory, extremal graph theory, algebraic graph theory, etc.), graphs were considered as abstract binary relations rather than geometric objects. Many of the powerful techniques developed in these fields have been su...

  1. Bounds on Gromov hyperbolicity constant in graphs

    Indian Academy of Sciences (India)

    Infinite graphs; Cartesian product graphs; independence number; domin- ation number; geodesics ... the secure transmission of information through the internet (see [15, 16]). In particular, ..... In particular, δ(G) is an integer multiple of 1/4.

  2. Summary: beyond fault trees to fault graphs

    International Nuclear Information System (INIS)

    Alesso, H.P.; Prassinos, P.; Smith, C.F.

    1984-09-01

    Fault Graphs are the natural evolutionary step over a traditional fault-tree model. A Fault Graph is a failure-oriented directed graph with logic connectives that allows cycles. We intentionally construct the Fault Graph to trace the piping and instrumentation drawing (P and ID) of the system, but with logical AND and OR conditions added. Then we evaluate the Fault Graph with computer codes based on graph-theoretic methods. Fault Graph computer codes are based on graph concepts, such as path set (a set of nodes traveled on a path from one node to another) and reachability (the complete set of all possible paths between any two nodes). These codes are used to find the cut-sets (any minimal set of component failures that will fail the system) and to evaluate the system reliability

  3. Torsional rigidity, isospectrality and quantum graphs

    International Nuclear Information System (INIS)

    Colladay, Don; McDonald, Patrick; Kaganovskiy, Leon

    2017-01-01

    We study torsional rigidity for graph and quantum graph analogs of well-known pairs of isospectral non-isometric planar domains. We prove that such isospectral pairs are distinguished by torsional rigidity. (paper)

  4. Bond graph modeling of centrifugal compression systems

    OpenAIRE

    Uddin, Nur; Gravdahl, Jan Tommy

    2015-01-01

    A novel approach to model unsteady fluid dynamics in a compressor network by using a bond graph is presented. The model is intended in particular for compressor control system development. First, we develop a bond graph model of a single compression system. Bond graph modeling offers a different perspective to previous work by modeling the compression system based on energy flow instead of fluid dynamics. Analyzing the bond graph model explains the energy flow during compressor surge. Two pri...

  5. A Graph Calculus for Predicate Logic

    Directory of Open Access Journals (Sweden)

    Paulo A. S. Veloso

    2013-03-01

    Full Text Available We introduce a refutation graph calculus for classical first-order predicate logic, which is an extension of previous ones for binary relations. One reduces logical consequence to establishing that a constructed graph has empty extension, i. e. it represents bottom. Our calculus establishes that a graph has empty extension by converting it to a normal form, which is expanded to other graphs until we can recognize conflicting situations (equivalent to a formula and its negation.

  6. Sphere and dot product representations of graphs

    NARCIS (Netherlands)

    R.J. Kang (Ross); T. Müller (Tobias)

    2012-01-01

    textabstractA graph $G$ is a $k$-sphere graph if there are $k$-dimensional real vectors $v_1,\\dots,v_n$ such that $ij\\in E(G)$ if and only if the distance between $v_i$ and $v_j$ is at most $1$. A graph $G$ is a $k$-dot product graph if there are $k$-dimensional real vectors $v_1,\\dots,v_n$ such

  7. Deep Learning with Dynamic Computation Graphs

    OpenAIRE

    Looks, Moshe; Herreshoff, Marcello; Hutchins, DeLesley; Norvig, Peter

    2017-01-01

    Neural networks that compute over graph structures are a natural fit for problems in a variety of domains, including natural language (parse trees) and cheminformatics (molecular graphs). However, since the computation graph has a different shape and size for every input, such networks do not directly support batched training or inference. They are also difficult to implement in popular deep learning libraries, which are based on static data-flow graphs. We introduce a technique called dynami...

  8. Constructs for Programming with Graph Rewrites

    OpenAIRE

    Rodgers, Peter

    2000-01-01

    Graph rewriting is becoming increasingly popular as a method for programming with graph based data structures. We present several modifications to a basic serial graph rewriting paradigm and discuss how they improve coding programs in the Grrr graph rewriting programming language. The constructs we present are once only nodes, attractor nodes and single match rewrites. We illustrate the operation of the constructs by example. The advantages of adding these new rewrite modifiers is to reduce t...

  9. Searches for Randomized Controlled Trials of Drugs in MEDLINE and EMBASE Using Only Generic Drug Names Compared with Searches Applied in Current Practice in Systematic Reviews

    Science.gov (United States)

    Waffenschmidt, Siw; Guddat, Charlotte

    2015-01-01

    Background: It is unclear which terms should be included in bibliographic searches for randomized controlled trials (RCTs) of drugs, and identifying relevant drug terms can be extremely laborious. The aim of our analysis was to determine whether a bibliographic search using only the generic drug name produces sufficient results for the generation…

  10. On the sizes of expander graphs and minimum distances of graph codes

    DEFF Research Database (Denmark)

    Høholdt, Tom; Justesen, Jørn

    2014-01-01

    We give lower bounds for the minimum distances of graph codes based on expander graphs. The bounds depend only on the second eigenvalue of the graph and the parameters of the component codes. We also give an upper bound on the size of a degree regular graph with given second eigenvalue....

  11. My Bar Graph Tells a Story

    Science.gov (United States)

    McMillen, Sue; McMillen, Beth

    2010-01-01

    Connecting stories to qualitative coordinate graphs has been suggested as an effective instructional strategy. Even students who are able to "create" bar graphs may struggle to correctly "interpret" them. Giving children opportunities to work with qualitative graphs can help them develop the skills to interpret, describe, and compare information…

  12. Modeling Software Evolution using Algebraic Graph Rewriting

    NARCIS (Netherlands)

    Ciraci, Selim; van den Broek, Pim

    We show how evolution requests can be formalized using algebraic graph rewriting. In particular, we present a way to convert the UML class diagrams to colored graphs. Since changes in software may effect the relation between the methods of classes, our colored graph representation also employs the

  13. A Type Graph Model for Java Programs

    NARCIS (Netherlands)

    Rensink, Arend; Zambon, Eduardo

    2009-01-01

    In this report we present a type graph that models all executable constructs of the Java programming language. Such a model is useful for any graph-based technique that relies on a representation of Java programs as graphs. The model can be regarded as a common representation to which all Java

  14. An intersection graph of straight lines

    DEFF Research Database (Denmark)

    Thomassen, Carsten

    2002-01-01

    G. Ehrlich, S. Even, and R.E. Tarjan conjectured that the graph obtained from a complete 3 partite graph K4,4,4 by deleting the edges of four disjoint triangles is not the intersection graph of straight line segments in the plane. We show that it is....

  15. Girth 5 graphs from relative difference sets

    DEFF Research Database (Denmark)

    Jørgensen, Leif Kjær

    2005-01-01

    We consider the problem of construction of graphs with given degree $k$ and girth 5 and as few vertices as possible. We give a construction of a family of girth 5 graphs based on relative difference sets. This family contains the smallest known graph of degree 8 and girth 5 which was constructed ...

  16. Cycles in weighted graphs and related topics

    NARCIS (Netherlands)

    Zhang, Shenggui

    2002-01-01

    This thesis contains results on paths andcycles in graphs andon a more or less relatedtopic, the vulnerability of graphs. In the first part of the thesis, Chapters 2 through 5, we concentrate on paths andcycles in weightedgraphs. A number of sufficient conditions are presentedfor graphs to contain

  17. Graph Transformation Semantics for a QVT Language

    NARCIS (Netherlands)

    Rensink, Arend; Nederpel, Ronald; Bruni, Roberto; Varró, Dániel

    It has been claimed by many in the graph transformation community that model transformation, as understood in the context of Model Driven Architecture, can be seen as an application of graph transformation. In this paper we substantiate this claim by giving a graph transformation-based semantics to

  18. Girth 5 graphs from relative difference sets

    DEFF Research Database (Denmark)

    Jørgensen, Leif Kjær

    We consider the problem of construction of graphs with given degree and girth 5 and as few vertices as possible. We give a construction of a family of girth 5 graphs based on relative difference sets. This family contains the smallest known graph of degree 8 and girth 5 which was constructed by G...

  19. Improper colouring of (random) unit disk graphs

    NARCIS (Netherlands)

    Kang, R.J.; Müller, T.; Sereni, J.S.

    2008-01-01

    For any graph G, the k-improper chromatic number ¿k(G) is the smallest number of colours used in a colouring of G such that each colour class induces a subgraph of maximum degree k. We investigate ¿k for unit disk graphs and random unit disk graphs to generalise results of McDiarmid and Reed

  20. Alliances and Bisection Width for Planar Graphs

    DEFF Research Database (Denmark)

    Olsen, Martin; Revsbæk, Morten

    2013-01-01

    An alliance in a graph is a set of vertices (allies) such that each vertex in the alliance has at least as many allies (counting the vertex itself) as non-allies in its neighborhood of the graph. We show that any planar graph with minimum degree at least 4 can be split into two alliances in polyn...

  1. A Type Graph Model for Java Programs

    NARCIS (Netherlands)

    Rensink, Arend; Zambon, Eduardo; Lee, D.; Lopes, A.; Poetzsch-Heffter, A.

    2009-01-01

    In this work we present a type graph that models all executable constructs of the Java programming language. Such a model is useful for any graph-based technique that relies on a representation of Java programs as graphs. The model can be regarded as a common representation to which all Java syntax

  2. RATGRAPH: Computer Graphing of Rational Functions.

    Science.gov (United States)

    Minch, Bradley A.

    1987-01-01

    Presents an easy-to-use Applesoft BASIC program that graphs rational functions and any asymptotes that the functions might have. Discusses the nature of rational functions, graphing them manually, employing a computer to graph rational functions, and describes how the program works. (TW)

  3. A new cluster algorithm for graphs

    NARCIS (Netherlands)

    S. van Dongen

    1998-01-01

    textabstractA new cluster algorithm for graphs called the emph{Markov Cluster algorithm ($MCL$ algorithm) is introduced. The graphs may be both weighted (with nonnegative weight) and directed. Let~$G$~be such a graph. The $MCL$ algorithm simulates flow in $G$ by first identifying $G$ in a

  4. Well-covered graphs and factors

    DEFF Research Database (Denmark)

    Randerath, Bert; Vestergaard, Preben D.

    2006-01-01

    A maximum independent set of vertices in a graph is a set of pairwise nonadjacent vertices of largest cardinality α. Plummer defined a graph to be well-covered, if every independent set is contained in a maximum independent set of G. Every well-covered graph G without isolated vertices has a perf...

  5. A new characterization of trivially perfect graphs

    Directory of Open Access Journals (Sweden)

    Christian Rubio Montiel

    2015-03-01

    Full Text Available A graph $G$ is \\emph{trivially perfect} if for every induced subgraph the cardinality of the largest set of pairwise nonadjacent vertices (the stability number $\\alpha(G$ equals the number of (maximal cliques $m(G$. We characterize the trivially perfect graphs in terms of vertex-coloring and we extend some definitions to infinite graphs.

  6. 47 CFR 80.761 - Conversion graphs.

    Science.gov (United States)

    2010-10-01

    ... MARITIME SERVICES Standards for Computing Public Coast Station VHF Coverage § 80.761 Conversion graphs. The following graphs must be employed where conversion from one to the other of the indicated types of units is... 47 Telecommunication 5 2010-10-01 2010-10-01 false Conversion graphs. 80.761 Section 80.761...

  7. Reconfiguring Independent Sets in Claw-Free Graphs

    NARCIS (Netherlands)

    Bonsma, P.S.; Kamiński, Marcin; Wrochna, Marcin; Ravi, R.; Gørtz, Inge Li

    We present a polynomial-time algorithm that, given two independent sets in a claw-free graph G, decides whether one can be transformed into the other by a sequence of elementary steps. Each elementary step is to remove a vertex v from the current independent set S and to add a new vertex w (not in

  8. Changes in the sensitivity of GABAA current rundown to drug treatments in a model of temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    Pierangelo eCifelli

    2013-07-01

    Full Text Available The pharmacological treatment of mesial temporal lobe epilepsy (mTLE, the most common epileptic syndrome in adults, is still unsatisfactory, as one third of the patients are or become refractory to antiepileptic agents. Refractoriness may depend upon drug-induced alterations, but the disease per se may also undergo a progressive evolution that affects the sensitivity to drugs. mTLE has been shown to be associated with a dysfunction of the inhibitory signaling mediated by GABAA receptors. In particular, the repetitive activation of GABAA receptors produces a use-dependent decrease (rundown of the evoked currents (IGABA, which is markedly enhanced in the hippocampus and cortex of drug-resistant mTLE patients. This phenomenon has been also observed in the pilocarpine model, where the increased IGABA rundown is observed in the hippocampus at the time of the first spontaneous seizure, then extends to the cortex and remains constant in the chronic phase of the disease. Here, we examined the sensitivity of IGABA to pharmacological modulation. We focused on the antiepileptic agent levetiracetam and on the neurotrophin BDNF, which were previously reported to attenuate mTLE-induced increased rundown in the chronic human tissue. In the pilocarpine model, BDNF displayed a paramount effect, decreasing rundown in the hippocampus at the time of the first seizure, as well as in the hippocampus and cortex in the chronic period. In contrast, levetiracetam did not affect rundown in the hippocampus, but attenuated it in the cortex. Interestingly, this effect of levetiracetam was also observed on the still unaltered rundown observed in the cortex at the time of the first spontaneous seizure. These data suggest that the sensitivity of GABAA receptors to pharmacological interventions undergoes changes during the natural history of mTLE, implicating that the site of seizure initiation and the timing of treatment may highly affect the therapeutic outcome.

  9. Interactive exploration of large-scale time-varying data using dynamic tracking graphs

    KAUST Repository

    Widanagamaachchi, W.

    2012-10-01

    Exploring and analyzing the temporal evolution of features in large-scale time-varying datasets is a common problem in many areas of science and engineering. One natural representation of such data is tracking graphs, i.e., constrained graph layouts that use one spatial dimension to indicate time and show the "tracks" of each feature as it evolves, merges or disappears. However, for practical data sets creating the corresponding optimal graph layouts that minimize the number of intersections can take hours to compute with existing techniques. Furthermore, the resulting graphs are often unmanageably large and complex even with an ideal layout. Finally, due to the cost of the layout, changing the feature definition, e.g. by changing an iso-value, or analyzing properly adjusted sub-graphs is infeasible. To address these challenges, this paper presents a new framework that couples hierarchical feature definitions with progressive graph layout algorithms to provide an interactive exploration of dynamically constructed tracking graphs. Our system enables users to change feature definitions on-the-fly and filter features using arbitrary attributes while providing an interactive view of the resulting tracking graphs. Furthermore, the graph display is integrated into a linked view system that provides a traditional 3D view of the current set of features and allows a cross-linked selection to enable a fully flexible spatio-temporal exploration of data. We demonstrate the utility of our approach with several large-scale scientific simulations from combustion science. © 2012 IEEE.

  10. Metastatic castration-resistant prostate cancer: a current view on drug therapy and alternative tumor cell regulation

    Directory of Open Access Journals (Sweden)

    R. A. Gafanov

    2018-01-01

    Full Text Available Prostate cancer (PC is one of the most common causes of death from malignant neoplasms in men in many countries around the world. Transmission of the signal in the androgenic axis of regulation is crucial for the development and progression of PC. Despite the constant dependence on androgen receptor signals in castration resistance, the use of new anti-androgenic drugs invariably leads to the stability  of the ongoing treatment. The interaction of androgen receptor and alternative (phosphoinositide-3-kinases, PI3K pathways in the regulation of cells can be one of the mechanisms of resistance to treatment. In this article, we describe current treatments for metastatic castration-resistant PC and the possible role of the PI3K pathway in the pathogenesis and progression of PC.

  11. Successful Treatment of a Drug-Resistant Epilepsy by Long-term Transcranial Direct Current Stimulation: A Case Report.

    Science.gov (United States)

    San-Juan, Daniel; Sarmiento, Carlos Ignacio; González, Katia Márquez; Orenday Barraza, José Manuel

    2018-01-01

    Transcranial direct current stimulation (tDCS) is a reemerged noninvasive cerebral therapy used to treat patients with epilepsy, including focal cortical dysplasia, with controversial results. We present a case of a 28-year-old female with left frontal cortical dysplasia refractory to antiepileptic drugs, characterized by 10-15 daily right tonic hemi-body seizures. The patient received a total of seven sessions of cathodal tDCS (2 mA, 30 min). The first three sessions were applied over three consecutive days, and the remaining four sessions of tDCS were given each at 2-week intervals. At the 1-year follow-up, the patient reported to have a single seizure per month and only mild adverse events.

  12. On a conjecture concerning helly circle graphs

    Directory of Open Access Journals (Sweden)

    Durán Guillermo

    2003-01-01

    Full Text Available We say that G is an e-circle graph if there is a bijection between its vertices and straight lines on the cartesian plane such that two vertices are adjacent in G if and only if the corresponding lines intersect inside the circle of radius one. This definition suggests a method for deciding whether a given graph G is an e-circle graph, by constructing a convenient system S of equations and inequations which represents the structure of G, in such a way that G is an e-circle graph if and only if S has a solution. In fact, e-circle graphs are exactly the circle graphs (intersection graphs of chords in a circle, and thus this method provides an analytic way for recognizing circle graphs. A graph G is a Helly circle graph if G is a circle graph and there exists a model of G by chords such that every three pairwise intersecting chords intersect at the same point. A conjecture by Durán (2000 states that G is a Helly circle graph if and only if G is a circle graph and contains no induced diamonds (a diamond is a graph formed by four vertices and five edges. Many unsuccessful efforts - mainly based on combinatorial and geometrical approaches - have been done in order to validate this conjecture. In this work, we utilize the ideas behind the definition of e-circle graphs and restate this conjecture in terms of an equivalence between two systems of equations and inequations, providing a new, analytic tool to deal with it.

  13. Centrosymmetric Graphs And A Lower Bound For Graph Energy Of Fullerenes

    Directory of Open Access Journals (Sweden)

    Katona Gyula Y.

    2014-11-01

    Full Text Available The energy of a molecular graph G is defined as the summation of the absolute values of the eigenvalues of adjacency matrix of a graph G. In this paper, an infinite class of fullerene graphs with 10n vertices, n ≥ 2, is considered. By proving centrosymmetricity of the adjacency matrix of these fullerene graphs, a lower bound for its energy is given. Our method is general and can be extended to other class of fullerene graphs.

  14. Subsampling for graph power spectrum estimation

    KAUST Repository

    Chepuri, Sundeep Prabhakar; Leus, Geert

    2016-01-01

    In this paper we focus on subsampling stationary random signals that reside on the vertices of undirected graphs. Second-order stationary graph signals are obtained by filtering white noise and they admit a well-defined power spectrum. Estimating the graph power spectrum forms a central component of stationary graph signal processing and related inference tasks. We show that by sampling a significantly smaller subset of vertices and using simple least squares, we can reconstruct the power spectrum of the graph signal from the subsampled observations, without any spectral priors. In addition, a near-optimal greedy algorithm is developed to design the subsampling scheme.

  15. On 4-critical t-perfect graphs

    OpenAIRE

    Benchetrit, Yohann

    2016-01-01

    It is an open question whether the chromatic number of $t$-perfect graphs is bounded by a constant. The largest known value for this parameter is 4, and the only example of a 4-critical $t$-perfect graph, due to Laurent and Seymour, is the complement of the line graph of the prism $\\Pi$ (a graph is 4-critical if it has chromatic number 4 and all its proper induced subgraphs are 3-colorable). In this paper, we show a new example of a 4-critical $t$-perfect graph: the complement of the line gra...

  16. Subsampling for graph power spectrum estimation

    KAUST Repository

    Chepuri, Sundeep Prabhakar

    2016-10-06

    In this paper we focus on subsampling stationary random signals that reside on the vertices of undirected graphs. Second-order stationary graph signals are obtained by filtering white noise and they admit a well-defined power spectrum. Estimating the graph power spectrum forms a central component of stationary graph signal processing and related inference tasks. We show that by sampling a significantly smaller subset of vertices and using simple least squares, we can reconstruct the power spectrum of the graph signal from the subsampled observations, without any spectral priors. In addition, a near-optimal greedy algorithm is developed to design the subsampling scheme.

  17. Proving relations between modular graph functions

    International Nuclear Information System (INIS)

    Basu, Anirban

    2016-01-01

    We consider modular graph functions that arise in the low energy expansion of the four graviton amplitude in type II string theory. The vertices of these graphs are the positions of insertions of vertex operators on the toroidal worldsheet, while the links are the scalar Green functions connecting the vertices. Graphs with four and five links satisfy several non-trivial relations, which have been proved recently. We prove these relations by using elementary properties of Green functions and the details of the graphs. We also prove a relation between modular graph functions with six links. (paper)

  18. A graph edit dictionary for correcting errors in roof topology graphs reconstructed from point clouds

    Science.gov (United States)

    Xiong, B.; Oude Elberink, S.; Vosselman, G.

    2014-07-01

    In the task of 3D building model reconstruction from point clouds we face the problem of recovering a roof topology graph in the presence of noise, small roof faces and low point densities. Errors in roof topology graphs will seriously affect the final modelling results. The aim of this research is to automatically correct these errors. We define the graph correction as a graph-to-graph problem, similar to the spelling correction problem (also called the string-to-string problem). The graph correction is more complex than string correction, as the graphs are 2D while strings are only 1D. We design a strategy based on a dictionary of graph edit operations to automatically identify and correct the errors in the input graph. For each type of error the graph edit dictionary stores a representative erroneous subgraph as well as the corrected version. As an erroneous roof topology graph may contain several errors, a heuristic search is applied to find the optimum sequence of graph edits to correct the errors one by one. The graph edit dictionary can be expanded to include entries needed to cope with errors that were previously not encountered. Experiments show that the dictionary with only fifteen entries already properly corrects one quarter of erroneous graphs in about 4500 buildings, and even half of the erroneous graphs in one test area, achieving as high as a 95% acceptance rate of the reconstructed models.

  19. Significance evaluation in factor graphs

    DEFF Research Database (Denmark)

    Madsen, Tobias; Hobolth, Asger; Jensen, Jens Ledet

    2017-01-01

    in genomics and the multiple-testing issues accompanying them, accurate significance evaluation is of great importance. We here address the problem of evaluating statistical significance of observations from factor graph models. Results Two novel numerical approximations for evaluation of statistical...... significance are presented. First a method using importance sampling. Second a saddlepoint approximation based method. We develop algorithms to efficiently compute the approximations and compare them to naive sampling and the normal approximation. The individual merits of the methods are analysed both from....... Conclusions The applicability of saddlepoint approximation and importance sampling is demonstrated on known models in the factor graph framework. Using the two methods we can substantially improve computational cost without compromising accuracy. This contribution allows analyses of large datasets...

  20. Flux networks in metabolic graphs

    International Nuclear Information System (INIS)

    Warren, P B; Queiros, S M Duarte; Jones, J L

    2009-01-01

    A metabolic model can be represented as a bipartite graph comprising linked reaction and metabolite nodes. Here it is shown how a network of conserved fluxes can be assigned to the edges of such a graph by combining the reaction fluxes with a conserved metabolite property such as molecular weight. A similar flux network can be constructed by combining the primal and dual solutions to the linear programming problem that typically arises in constraint-based modelling. Such constructions may help with the visualization of flux distributions in complex metabolic networks. The analysis also explains the strong correlation observed between metabolite shadow prices (the dual linear programming variables) and conserved metabolite properties. The methods were applied to recent metabolic models for Escherichia coli, Saccharomyces cerevisiae and Methanosarcina barkeri. Detailed results are reported for E. coli; similar results were found for other organisms

  1. 3-biplacement of bipartite graphs

    Directory of Open Access Journals (Sweden)

    Lech Adamus

    2008-01-01

    Full Text Available Let \\(G=(L,R;E\\ be a bipartite graph with color classes \\(L\\ and \\(R\\ and edge set \\(E\\. A set of two bijections \\(\\{\\varphi_1 , \\varphi_2\\}\\, \\(\\varphi_1 , \\varphi_2 :L \\cup R \\to L \\cup R\\, is said to be a \\(3\\-biplacement of \\(G\\ if \\(\\varphi_1(L= \\varphi_2(L = L\\ and \\(E \\cap \\varphi_1^*(E=\\emptyset\\, \\(E \\cap \\varphi_2^*(E=\\emptyset\\, \\(\\varphi_1^*(E \\cap \\varphi_2^*(E=\\emptyset\\, where \\(\\varphi_1^*\\, \\(\\varphi_2^*\\ are the maps defined on \\(E\\, induced by \\(\\varphi_1\\, \\(\\varphi_2\\, respectively. We prove that if \\(|L| = p\\, \\(|R| = q\\, \\(3 \\leq p \\leq q\\, then every graph \\(G=(L,R;E\\ of size at most \\(p\\ has a \\(3\\-biplacement.

  2. On the centrality of some graphs

    Directory of Open Access Journals (Sweden)

    Vecdi Aytac

    2017-10-01

    Full Text Available A central issue in the analysis of complex networks is the assessment of their stability and vulnerability. A variety of measures have been proposed in the literature to quantify the stability of networks and a number of graph-theoretic parameters have been used to derive formulas for calculating network reliability. Different measures for graph vulnerability have been introduced so far to study different aspects of the graph behavior after removal of vertices or links such as connectivity, toughness, scattering number, binding number, residual closeness and integrity. In this paper, we consider betweenness centrality of a graph. Betweenness centrality of a vertex of a graph is portion of the shortest paths all pairs of vertices passing through a given vertex. In this paper, we obtain exact values for betweenness centrality for some wheel related graphs namely gear, helm, sunflower and friendship graphs.

  3. Quantum walk on a chimera graph

    Science.gov (United States)

    Xu, Shu; Sun, Xiangxiang; Wu, Jizhou; Zhang, Wei-Wei; Arshed, Nigum; Sanders, Barry C.

    2018-05-01

    We analyse a continuous-time quantum walk on a chimera graph, which is a graph of choice for designing quantum annealers, and we discover beautiful quantum walk features such as localization that starkly distinguishes classical from quantum behaviour. Motivated by technological thrusts, we study continuous-time quantum walk on enhanced variants of the chimera graph and on diminished chimera graph with a random removal of vertices. We explain the quantum walk by constructing a generating set for a suitable subgroup of graph isomorphisms and corresponding symmetry operators that commute with the quantum walk Hamiltonian; the Hamiltonian and these symmetry operators provide a complete set of labels for the spectrum and the stationary states. Our quantum walk characterization of the chimera graph and its variants yields valuable insights into graphs used for designing quantum-annealers.

  4. Fibonacci number of the tadpole graph

    Directory of Open Access Journals (Sweden)

    Joe DeMaio

    2014-10-01

    Full Text Available In 1982, Prodinger and Tichy defined the Fibonacci number of a graph G to be the number of independent sets of the graph G. They did so since the Fibonacci number of the path graph Pn is the Fibonacci number F(n+2 and the Fibonacci number of the cycle graph Cn is the Lucas number Ln. The tadpole graph Tn,k is the graph created by concatenating Cn and Pk with an edge from any vertex of Cn to a pendant of Pk for integers n=3 and k=0. This paper establishes formulae and identities for the Fibonacci number of the tadpole graph via algebraic and combinatorial methods.

  5. Software for Graph Analysis and Visualization

    Directory of Open Access Journals (Sweden)

    M. I. Kolomeychenko

    2014-01-01

    Full Text Available This paper describes the software for graph storage, analysis and visualization. The article presents a comparative analysis of existing software for analysis and visualization of graphs, describes the overall architecture of application and basic principles of construction and operation of the main modules. Furthermore, a description of the developed graph storage oriented to storage and processing of large-scale graphs is presented. The developed algorithm for finding communities and implemented algorithms of autolayouts of graphs are the main functionality of the product. The main advantage of the developed software is high speed processing of large size networks (up to millions of nodes and links. Moreover, the proposed graph storage architecture is unique and has no analogues. The developed approaches and algorithms are optimized for operating with big graphs and have high productivity.

  6. Parallel External Memory Graph Algorithms

    DEFF Research Database (Denmark)

    Arge, Lars Allan; Goodrich, Michael T.; Sitchinava, Nodari

    2010-01-01

    In this paper, we study parallel I/O efficient graph algorithms in the Parallel External Memory (PEM) model, one o f the private-cache chip multiprocessor (CMP) models. We study the fundamental problem of list ranking which leads to efficient solutions to problems on trees, such as computing lowest...... an optimal speedup of ¿(P) in parallel I/O complexity and parallel computation time, compared to the single-processor external memory counterparts....

  7. Submanifolds weakly associated with graphs

    Indian Academy of Sciences (India)

    A CARRIAZO, L M FERN ´ANDEZ and A RODRÍGUEZ-HIDALGO. Department of Geometry and Topology, ..... by means of trees (connected graphs without cycles) and forests (disjoint unions of trees, see [6]) given in [3], by extending it to weak ... CR-submanifold. In this case, every tree is a K2. Finally, Theorem 3.8 of [3] can ...

  8. Topological structure of dictionary graphs

    International Nuclear Information System (INIS)

    Fuks, Henryk; Krzeminski, Mark

    2009-01-01

    We investigate the topological structure of the subgraphs of dictionary graphs constructed from WordNet and Moby thesaurus data. In the process of learning a foreign language, the learner knows only a subset of all words of the language, corresponding to a subgraph of a dictionary graph. When this subgraph grows with time, its topological properties change. We introduce the notion of the pseudocore and argue that the growth of the vocabulary roughly follows decreasing pseudocore numbers-that is, one first learns words with a high pseudocore number followed by smaller pseudocores. We also propose an alternative strategy for vocabulary growth, involving decreasing core numbers as opposed to pseudocore numbers. We find that as the core or pseudocore grows in size, the clustering coefficient first decreases, then reaches a minimum and starts increasing again. The minimum occurs when the vocabulary reaches a size between 10 3 and 10 4 . A simple model exhibiting similar behavior is proposed. The model is based on a generalized geometric random graph. Possible implications for language learning are discussed.

  9. Quantum information processing with graph states

    International Nuclear Information System (INIS)

    Schlingemann, Dirk-Michael

    2005-04-01

    Graph states are multiparticle states which are associated with graphs. Each vertex of the graph corresponds to a single system or particle. The links describe quantum correlations (entanglement) between pairs of connected particles. Graph states were initiated independently by two research groups: On the one hand, graph states were introduced by Briegel and Raussendorf as a resource for a new model of one-way quantum computing, where algorithms are implemented by a sequence of measurements at single particles. On the other hand, graph states were developed by the author of this thesis and ReinhardWerner in Braunschweig, as a tool to build quantum error correcting codes, called graph codes. The connection between the two approaches was fully realized in close cooperation of both research groups. This habilitation thesis provides a survey of the theory of graph codes, focussing mainly, but not exclusively on the author's own research work. We present the theoretical and mathematical background for the analysis of graph codes. The concept of one-way quantum computing for general graph states is discussed. We explicitly show how to realize the encoding and decoding device of a graph code on a one-way quantum computer. This kind of implementation is to be seen as a mathematical description of a quantum memory device. In addition to that, we investigate interaction processes, which enable the creation of graph states on very large systems. Particular graph states can be created, for instance, by an Ising type interaction between next neighbor particles which sits at the points of an infinitely extended cubic lattice. Based on the theory of quantum cellular automata, we give a constructive characterization of general interactions which create a translationally invariant graph state. (orig.)

  10. Efforts Aimed To Reduce Attrition in Antimalarial Drug Discovery: A Systematic Evaluation of the Current Antimalarial Targets Portfolio.

    Science.gov (United States)

    Chaparro, María Jesús; Calderón, Félix; Castañeda, Pablo; Fernández-Alvaro, Elena; Gabarró, Raquel; Gamo, Francisco Javier; Gómez-Lorenzo, María G; Martín, Julio; Fernández, Esther

    2018-04-13

    Malaria remains a major global health problem. In 2015 alone, more than 200 million cases of malaria were reported, and more than 400,000 deaths occurred. Since 2010, emerging resistance to current front-line ACTs (artemisinin combination therapies) has been detected in endemic countries. Therefore, there is an urgency for new therapies based on novel modes of action, able to relieve symptoms as fast as the artemisinins and/or block malaria transmission. During the past few years, the antimalarial community has focused their efforts on phenotypic screening as a pragmatic approach to identify new hits. Optimization efforts on several chemical series have been successful, and clinical candidates have been identified. In addition, recent advances in genetics and proteomics have led to the target deconvolution of phenotypic clinical candidates. New mechanisms of action will also be critical to overcome resistance and reduce attrition. Therefore, a complementary strategy focused on identifying well-validated targets to start hit identification programs is essential to reinforce the clinical pipeline. Leveraging published data, we have assessed the status quo of the current antimalarial target portfolio with a focus on the blood stage clinical disease. From an extensive list of reported Plasmodium targets, we have defined triage criteria. These criteria consider genetic, pharmacological, and chemical validation, as well as tractability/doability, and safety implications. These criteria have provided a quantitative score that has led us to prioritize those targets with the highest probability to deliver successful and differentiated new drugs.

  11. Differences in sociodemographic, drug use and health characteristics between never, former and current injecting, problematic hard-drug users in the Netherlands

    NARCIS (Netherlands)

    Havinga, Petra; van der Velden, Claudia; de Gee, Anouk; van der Poel, Agnes; Yin, Huifang

    2014-01-01

    Background: Injecting drug users are at increased risk for harmful effects compared to non-injecting drug users. Some studies have focused on differences in characteristics between these two groups (e. g., housing, overall health). However, no study has investigated the specific Dutch situation

  12. Degree Associated Edge Reconstruction Number of Graphs with Regular Pruned Graph

    Directory of Open Access Journals (Sweden)

    P. Anusha Devi

    2015-10-01

    Full Text Available An ecard of a graph $G$ is a subgraph formed by deleting an edge. A da-ecard specifies the degree of the deleted edge along with the ecard. The degree associated edge reconstruction number of a graph $G,~dern(G,$ is the minimum number of da-ecards that uniquely determines $G.$  The adversary degree associated edge reconstruction number of a graph $G, adern(G,$ is the minimum number $k$ such that every collection of $k$ da-ecards of $G$ uniquely determines $G.$ The maximal subgraph without end vertices of a graph $G$ which is not a tree is the pruned graph of $G.$ It is shown that $dern$ of complete multipartite graphs and some connected graphs with regular pruned graph is $1$ or $2.$ We also determine $dern$ and $adern$ of corona product of standard graphs.

  13. Drug Impact Index.

    Science.gov (United States)

    Western Center for Drug-Free Schools and Communities.

    The Drug Impact Index provides a set of indicators designed to determine the extent of the local drug problem in a community. Each indicator includes a technical note on the data sources, a graph showing comparative statistics on that indicator for the Portland area and for the State of Oregon, and brief remarks on the implications of the data.…

  14. Transmission of HIV drug resistance and the predicted effect on current first-line regimens in Europe

    NARCIS (Netherlands)

    Hofstra, L. Marije; Sauvageot, Nicolas; Albert, Jan; Alexiev, Ivailo; Garcia, Federico; Struck, Daniel; Van De Vijver, David A M C; Åsjö, Birgitta; Beshkov, Danail; Coughlan, Suzie; Descamps, Diane; Griskevicius, Algirdas; Hamouda, Osamah; Horban, Andrzej; Van Kasteren, Marjo; Kolupajeva, Tatjana; Kostrikis, Leontios G.; Liitsola, Kirsi; Linka, Marek; Mor, Orna; Nielsen, Claus; Otelea, Dan; Paraskevis, Dimitrios; Paredes, Roger; Poljak, Mario; Puchhammer-Stöckl, Elisabeth; Sönnerborg, Anders; Staneková, Danica; Stanojevic, Maja; Van Laethem, Kristel; Zazzi, Maurizio; Lepej, Snjezana Zidovec; Boucher, Charles A B; Schmit, Jean Claude; Wensing, Annemarie M J; Puchhammer-Stockl, E.; Sarcletti, M.; Schmied, B.; Geit, M.; Balluch, G.; Vandamme, A. M.; Vercauteren, J.; Derdelinckx, I.; Sasse, A.; Bogaert, M.; Ceunen, H.; De Roo, A.; De Wit, S.; Echahidi, F.; Fransen, K.; Goffard, J. C.; Goubau, P.; Goudeseune, E.; Yombi, J. C.; Lacor, P.; Liesnard, C.; Moutschen, M.; Pierard, D.; Rens, R.; Schrooten, Y.; Vaira, D.; Vandekerckhove, L. P R; Van Den Heuvel, A.; Van Der Gucht, B.; Van Ranst, M.; Van Wijngaerden, E.; Vandercam, B.; Vekemans, M.; Verhofstede, C.; Clumeck, N.; Van Laethem, K.; Beshkov, D.; Alexiev, I.; Lepej, S. Zidovec; Begovac, J.; Kostrikis, Leontios G.; Demetriades, I.; Kousiappa, I.; Demetriou, V.; Hezka, J.; Linka, M.; Maly, M.; Machala, L.; Nielsen, C.; Jørgensen, L. B.; Gerstoft, J.; Mathiesen, L.; Pedersen, C.; Nielsen, H.; Laursen, A.; Kvinesdal, B.; Liitsola, K.; Ristola, M.; Suni, J.; Sutinen, J.; Descamps, D.; Assoumou, L.; Castor, G.; Grude, M.; Flandre, P.; Storto, A.; Hamouda, O.; Kücherer, C.; Berg, T.; Braun, P.; Poggensee, G.; Däumer, M.; Eberle, J.; Heiken, H.; Kaiser, R.; Knechten, H.; Korn, K.; Müller, H.; Neifer, S.; Schmidt, B.; Walter, H.; Gunsenheimer-Bartmeyer, B.; Harrer, T.; Paraskevis, D.; Hatzakis, A.; Zavitsanou, A.; Vassilakis, A.; Lazanas, M.; Chini, M.; Lioni, A.; Sakka, V.; Kourkounti, S.; Paparizos, V.; Antoniadou, A.; Papadopoulos, A.; Poulakou, G.; Katsarolis, I.; Protopapas, K.; Chryssos, G.; Drimis, S.; Gargalianos, P.; Xylomenos, G.; Lourida, G.; Psichogiou, M.; Daikos, G. L.; Sipsas, N. V.; Kontos, A.; Gamaletsou, M. N.; Koratzanis, G.; Sambatakou, E.; Mariolis, H.; Skoutelis, A.; Papastamopoulos, V.; Georgiou, O.; Panagopoulos, P.; Maltezos, E.; Coughlan, S.; De Gascun, C.; Byrne, C.; Duffy, M.; Bergin, C.; Reidy, D.; Farrell, G.; Lambert, J.; O'Connor, E.; Rochford, A.; Low, J.; Coakely, P.; O'Dea, S.; Hall, W.; Mor, O.; Levi, I.; Chemtob, D.; Grossman, Z.; Zazzi, M.; De Luca, A.; Balotta, C.; Riva, C.; Mussini, C.; Caramma, I.; Capetti, A.; Colombo, M. C.; Rossi, C.; Prati, F.; Tramuto, F.; Vitale, F.; Ciccozzi, M.; Angarano, G.; Rezza, G.; Kolupajeva, T.; Kolupajeva, T.; Vasins, O.; Griskevicius, A.; Lipnickiene, V.; Schmit, J. C.; Struck, D.; Sauvageot, N.; Hemmer, R.; Arendt, V.; Michaux, C.; Staub, T.; Sequin-Devaux, C.; Wensing, A. M J; Boucher, C. A B; Van Kessel, A.; Van Bentum, P. H M; Brinkman, K.; Connell, B. J.; Van Der Ende, M. E.; Hoepelman, I. M.; Van Kasteren, M.; Kuipers, M.; Langebeek, N.; Richter, C.; Santegoets, R. M W J; Schrijnders-Gudde, L.; Schuurman, R.; Van De Ven, B. J M; Åsjö, B.; Kran, A. M Bakken; Ormaasen, V.; Aavitsland, P.; Horban, A.; Stanczak, J. J.; Stanczak, G. P.; Firlag-Burkacka, E.; Wiercinska-Drapalo, A.; Jablonowska, E.; Maolepsza, E.; Leszczyszyn-Pynka, M.; Szata, W.; Camacho, R.; Palma, C.; Borges, F.; Paixão, T.; Duque, V.; Araújo, F.; Otelea, D.; Paraschiv, S.; Tudor, A. M.; Cernat, R.; Chiriac, C.; Dumitrescu, F.; Prisecariu, L. J.; Stanojevic, M.; Jevtovic, Dj; Salemovic, D.; Stanekova, D.; Habekova, M.; Chabadová, Z.; Drobkova, T.; Bukovinova, P.; Shunnar, A.; Truska, P.; Poljak, M.; Lunar, M.; Babic, D.; Tomazic, J.; Vidmar, L.; Vovko, T.; Karner, P.; Garcia, F.; Paredes, R.; Monge, S.; Moreno, S.; Del Amo, J.; Asensi, V.; Sirvent, J. L.; De Mendoza, C.; Delgado, R.; Gutiérrez, F.; Berenguer, J.; Garcia-Bujalance, S.; Stella, N.; De Los Santos, I.; Blanco, J. R.; Dalmau, D.; Rivero, M.; Segura, F.; Elías, M. J Pérez; Alvarez, M.; Chueca, N.; Rodríguez-Martín, C.; Vidal, C.; Palomares, J. C.; Viciana, I.; Viciana, P.; Cordoba, J.; Aguilera, A.; Domingo, P.; Galindo, M. J.; Miralles, C.; Del Pozo, M. A.; Ribera, E.; Iribarren, J. A.; Ruiz, L.; De La Torre, J.; Vidal, F.; Clotet, B.; Albert, J.; Heidarian, A.; Aperia-Peipke, K.; Axelsson, M.; Mild, M.; Karlsson, A.; Sönnerborg, A.; Thalme, A.; Navér, L.; Bratt, G.; Karlsson, A.; Blaxhult, A.; Gisslén, M.; Svennerholm, B.; Bergbrant, I.; Björkman, P.; Säll, C.; Lindholm, A.; Kuylenstierna, N.; Montelius, R.; Azimi, F.; Johansson, B.; Carlsson, M.; Johansson, E.; Ljungberg, B.; Ekvall, H.; Strand, A.; Mäkitalo, S.; Öberg, S.; Holmblad, P.; Höfer, M.; Holmberg, H.; Josefson, P.; Ryding, U.

    2016-01-01

    Background. Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline

  15. Graph Theory and Ion and Molecular Aggregation in Aqueous Solutions

    Science.gov (United States)

    Choi, Jun-Ho; Lee, Hochan; Choi, Hyung Ran; Cho, Minhaeng

    2018-04-01

    In molecular and cellular biology, dissolved ions and molecules have decisive effects on chemical and biological reactions, conformational stabilities, and functions of small to large biomolecules. Despite major efforts, the current state of understanding of the effects of specific ions, osmolytes, and bioprotecting sugars on the structure and dynamics of water H-bonding networks and proteins is not yet satisfactory. Recently, to gain deeper insight into this subject, we studied various aggregation processes of ions and molecules in high-concentration salt, osmolyte, and sugar solutions with time-resolved vibrational spectroscopy and molecular dynamics simulation methods. It turns out that ions (or solute molecules) have a strong propensity to self-assemble into large and polydisperse aggregates that affect both local and long-range water H-bonding structures. In particular, we have shown that graph-theoretical approaches can be used to elucidate morphological characteristics of large aggregates in various aqueous salt, osmolyte, and sugar solutions. When ion and molecular aggregates in such aqueous solutions are treated as graphs, a variety of graph-theoretical properties, such as graph spectrum, degree distribution, clustering coefficient, minimum path length, and graph entropy, can be directly calculated by considering an ensemble of configurations taken from molecular dynamics trajectories. Here we show percolating behavior exhibited by ion and molecular aggregates upon increase in solute concentration in high solute concentrations and discuss compelling evidence of the isomorphic relation between percolation transitions of ion and molecular aggregates and water H-bonding networks. We anticipate that the combination of graph theory and molecular dynamics simulation methods will be of exceptional use in achieving a deeper understanding of the fundamental physical chemistry of dissolution and in describing the interplay between the self-aggregation of solute

  16. Graph Theory and Ion and Molecular Aggregation in Aqueous Solutions.

    Science.gov (United States)

    Choi, Jun-Ho; Lee, Hochan; Choi, Hyung Ran; Cho, Minhaeng

    2018-04-20

    In molecular and cellular biology, dissolved ions and molecules have decisive effects on chemical and biological reactions, conformational stabilities, and functions of small to large biomolecules. Despite major efforts, the current state of understanding of the effects of specific ions, osmolytes, and bioprotecting sugars on the structure and dynamics of water H-bonding networks and proteins is not yet satisfactory. Recently, to gain deeper insight into this subject, we studied various aggregation processes of ions and molecules in high-concentration salt, osmolyte, and sugar solutions with time-resolved vibrational spectroscopy and molecular dynamics simulation methods. It turns out that ions (or solute molecules) have a strong propensity to self-assemble into large and polydisperse aggregates that affect both local and long-range water H-bonding structures. In particular, we have shown that graph-theoretical approaches can be used to elucidate morphological characteristics of large aggregates in various aqueous salt, osmolyte, and sugar solutions. When ion and molecular aggregates in such aqueous solutions are treated as graphs, a variety of graph-theoretical properties, such as graph spectrum, degree distribution, clustering coefficient, minimum path length, and graph entropy, can be directly calculated by considering an ensemble of configurations taken from molecular dynamics trajectories. Here we show percolating behavior exhibited by ion and molecular aggregates upon increase in solute concentration in high solute concentrations and discuss compelling evidence of the isomorphic relation between percolation transitions of ion and molecular aggregates and water H-bonding networks. We anticipate that the combination of graph theory and molecular dynamics simulation methods will be of exceptional use in achieving a deeper understanding of the fundamental physical chemistry of dissolution and in describing the interplay between the self-aggregation of solute

  17. Multiscale weighted colored graphs for protein flexibility and rigidity analysis

    Science.gov (United States)

    Bramer, David; Wei, Guo-Wei

    2018-02-01

    Protein structural fluctuation, measured by Debye-Waller factors or B-factors, is known to correlate to protein flexibility and function. A variety of methods has been developed for protein Debye-Waller factor prediction and related applications to domain separation, docking pose ranking, entropy calculation, hinge detection, stability analysis, etc. Nevertheless, none of the current methodologies are able to deliver an accuracy of 0.7 in terms of the Pearson correlation coefficients averaged over a large set of proteins. In this work, we introduce a paradigm-shifting geometric graph model, multiscale weighted colored graph (MWCG), to provide a new generation of computational algorithms to significantly change the current status of protein structural fluctuation analysis. Our MWCG model divides a protein graph into multiple subgraphs based on interaction types between graph nodes and represents the protein rigidity by generalized centralities of subgraphs. MWCGs not only predict the B-factors of protein residues but also accurately analyze the flexibility of all atoms in a protein. The MWCG model is validated over a number of protein test sets and compared with many standard methods. An extensive numerical study indicates that the proposed MWCG offers an accuracy of over 0.8 and thus provides perhaps the first reliable method for estimating protein flexibility and B-factors. It also simultaneously predicts all-atom flexibility in a molecule.

  18. Replica methods for loopy sparse random graphs

    International Nuclear Information System (INIS)

    Coolen, ACC

    2016-01-01

    I report on the development of a novel statistical mechanical formalism for the analysis of random graphs with many short loops, and processes on such graphs. The graphs are defined via maximum entropy ensembles, in which both the degrees (via hard constraints) and the adjacency matrix spectrum (via a soft constraint) are prescribed. The sum over graphs can be done analytically, using a replica formalism with complex replica dimensions. All known results for tree-like graphs are recovered in a suitable limit. For loopy graphs, the emerging theory has an appealing and intuitive structure, suggests how message passing algorithms should be adapted, and what is the structure of theories describing spin systems on loopy architectures. However, the formalism is still largely untested, and may require further adjustment and refinement. (paper)

  19. Chemical Graph Transformation with Stereo-Information

    DEFF Research Database (Denmark)

    Andersen, Jakob Lykke; Flamm, Christoph; Merkle, Daniel

    2017-01-01

    Double Pushout graph transformation naturally facilitates the modelling of chemical reactions: labelled undirected graphs model molecules and direct derivations model chemical reactions. However, the most straightforward modelling approach ignores the relative placement of atoms and their neighbo......Double Pushout graph transformation naturally facilitates the modelling of chemical reactions: labelled undirected graphs model molecules and direct derivations model chemical reactions. However, the most straightforward modelling approach ignores the relative placement of atoms...... and their neighbours in space. Stereoisomers of chemical compounds thus cannot be distinguished, even though their chemical activity may differ substantially. In this contribution we propose an extended chemical graph transformation system with attributes that encode information about local geometry. The modelling...... of graph transformation, but we here propose a framework that also allows for partially specified stereoinformation. While there are several stereochemical configurations to be considered, we focus here on the tetrahedral molecular shape, and suggest general principles for how to treat all other chemically...

  20. GRAPES: a software for parallel searching on biological graphs targeting multi-core architectures.

    Directory of Open Access Journals (Sweden)

    Rosalba Giugno

    Full Text Available Biological applications, from genomics to ecology, deal with graphs that represents the structure of interactions. Analyzing such data requires searching for subgraphs in collections of graphs. This task is computationally expensive. Even though multicore architectures, from commodity computers to more advanced symmetric multiprocessing (SMP, offer scalable computing power, currently published software implementations for indexing and graph matching are fundamentally sequential. As a consequence, such software implementations (i do not fully exploit available parallel computing power and (ii they do not scale with respect to the size of graphs in the database. We present GRAPES, software for parallel searching on databases of large biological graphs. GRAPES implements a parallel version of well-established graph searching algorithms, and introduces new strategies which naturally lead to a faster parallel searching system especially for large graphs. GRAPES decomposes graphs into subcomponents that can be efficiently searched in parallel. We show the performance of GRAPES on representative biological datasets containing antiviral chemical compounds, DNA, RNA, proteins, protein contact maps and protein interactions networks.

  1. Short- and long-term inhibition of cardiac inward-rectifier potassium channel current by an antiarrhythmic drug bepridil.

    Science.gov (United States)

    Ma, Fangfang; Takanari, Hiroki; Masuda, Kimiko; Morishima, Masaki; Ono, Katsushige

    2016-07-01

    Bepridil is an effective antiarrhythmic drug on supraventricular and ventricular arrhythmias, and inhibitor of calmodulin. Recent investigations have been elucidating that bepridil exerts antiarrhythmic effects through its acute and chronic application for patients. The aim of this study was to identify the efficacy and the potential mechanism of bepridil on the inward-rectifier potassium channel in neonatal rat cardiomyocytes in acute- and long-term conditions. Bepridil inhibited inward-rectifier potassium current (I K1) as a short-term effect with IC50 of 17 μM. Bepridil also reduced I K1 of neonatal cardiomyocytes when applied for 24 h in the culture medium with IC50 of 2.7 μM. Both a calmodulin inhibitor (W-7) and an inhibitor of calmodulin-kinase II (KN93) reduced I K1 when applied for 24 h as a long-term effect in the same fashion, suggesting that the long-term application of bepridil inhibits I K1 more potently than that of the short-term application through the inhibition of calmodulin kinase II pathway in cardiomyocytes.

  2. A European regulatory perspective on cystic fibrosis: current treatments, trends in drug development and translational challenges for CFTR modulators.

    Science.gov (United States)

    Ponzano, Stefano; Nigrelli, Giulia; Fregonese, Laura; Eichler, Irmgard; Bertozzi, Fabio; Bandiera, Tiziano; Galietta, Luis J V; Papaluca, Marisa

    2018-06-30

    In this article we analyse the current authorised treatments and trends in early drug development for cystic fibrosis (CF) in the European Union for the time period 2000-2016. The analysis indicates a significant improvement in the innovation and development of new potential medicines for CF, shifting from products that act on the symptoms of the disease towards new therapies targeting the cause of CF. However, within these new innovative medicines, results for CF transmembrane conductance regulator (CFTR) modulators indicate that one major challenge for turning a CF concept product into an actual medicine for the benefit of patients resides in the fact that, although pre-clinical models have shown good predictability for certain mutations, a good correlation to clinical end-points or biomarkers ( e.g. forced expiratory volume in 1 s and sweat chloride) for all mutations has not yet been achieved. In this respect, the use of alternative end-points and innovative nonclinical models could be helpful for the understanding of those translational discrepancies. Collaborative endeavours to promote further research and development in these areas as well as early dialogue with the regulatory bodies available at the European competent authorities are recommended. Copyright ©ERS 2018.

  3. Reconstructing Topological Graphs and Continua

    OpenAIRE

    Gartside, Paul; Pitz, Max F.; Suabedissen, Rolf

    2015-01-01

    The deck of a topological space $X$ is the set $\\mathcal{D}(X)=\\{[X \\setminus \\{x\\}] \\colon x \\in X\\}$, where $[Z]$ denotes the homeomorphism class of $Z$. A space $X$ is topologically reconstructible if whenever $\\mathcal{D}(X)=\\mathcal{D}(Y)$ then $X$ is homeomorphic to $Y$. It is shown that all metrizable compact connected spaces are reconstructible. It follows that all finite graphs, when viewed as a 1-dimensional cell-complex, are reconstructible in the topological sense, and more genera...

  4. Decomposing a graph into bistars

    DEFF Research Database (Denmark)

    Thomassen, Carsten

    2013-01-01

    Bárat and the present author conjectured that, for each tree T, there exists a natural number kT such that the following holds: If G is a kT-edge-connected graph such that |E(T)| divides |E(G)|, then G has a T-decomposition, that is, a decomposition of the edge set into trees each of which...... is isomorphic to T. The conjecture has been verified for infinitely many paths and for each star. In this paper we verify the conjecture for an infinite family of trees that are neither paths nor stars, namely all the bistars S(k,k+1)....

  5. Combining Vertex-centric Graph Processing with SPARQL for Large-scale RDF Data Analytics

    KAUST Repository

    Abdelaziz, Ibrahim

    2017-06-27

    Modern applications, such as drug repositioning, require sophisticated analytics on RDF graphs that combine structural queries with generic graph computations. Existing systems support either declarative SPARQL queries, or generic graph processing, but not both. We bridge the gap by introducing Spartex, a versatile framework for complex RDF analytics. Spartex extends SPARQL to support programs that combine seamlessly generic graph algorithms (e.g., PageRank, Shortest Paths, etc.) with SPARQL queries. Spartex builds on existing vertex-centric graph processing frameworks, such as Graphlab or Pregel. It implements a generic SPARQL operator as a vertex-centric program that interprets SPARQL queries and executes them efficiently using a built-in optimizer. In addition, any graph algorithm implemented in the underlying vertex-centric framework, can be executed in Spartex. We present various scenarios where our framework simplifies significantly the implementation of complex RDF data analytics programs. We demonstrate that Spartex scales to datasets with billions of edges, and show that our core SPARQL engine is at least as fast as the state-of-the-art specialized RDF engines. For complex analytical tasks that combine generic graph processing with SPARQL, Spartex is at least an order of magnitude faster than existing alternatives.

  6. On path hypercompositions in graphs and automata

    Directory of Open Access Journals (Sweden)

    Massouros Christos G.

    2016-01-01

    Full Text Available The paths in graphs define hypercompositions in the set of their vertices and therefore it is feasible to associate hypercompositional structures to each graph. Similarly, the strings of letters from their alphabet, define hypercompositions in the automata, which in turn define the associated hypergroups to the automata. The study of the associated hypercompositional structures gives results in both, graphs and automata theory.

  7. Attack Graph Construction for Security Events Analysis

    Directory of Open Access Journals (Sweden)

    Andrey Alexeevich Chechulin

    2014-09-01

    Full Text Available The paper is devoted to investigation of the attack graphs construction and analysis task for a network security evaluation and real-time security event processing. Main object of this research is the attack modeling process. The paper contains the description of attack graphs building, modifying and analysis technique as well as overview of implemented prototype for network security analysis based on attack graph approach.

  8. Steiner Distance in Graphs--A Survey

    OpenAIRE

    Mao, Yaping

    2017-01-01

    For a connected graph $G$ of order at least $2$ and $S\\subseteq V(G)$, the \\emph{Steiner distance} $d_G(S)$ among the vertices of $S$ is the minimum size among all connected subgraphs whose vertex sets contain $S$. In this paper, we summarize the known results on the Steiner distance parameters, including Steiner distance, Steiner diameter, Steiner center, Steiner median, Steiner interval, Steiner distance hereditary graph, Steiner distance stable graph, average Steiner distance, and Steiner ...

  9. Density conditions for triangles in multipartite graphs

    DEFF Research Database (Denmark)

    Bondy, Adrian; Shen, Jin; Thomassé, Stephan

    2006-01-01

    subgraphs in G. We investigate in particular the case where G is a complete multipartite graph. We prove that a finite tripartite graph with all edge densities greater than the golden ratio has a triangle and that this bound is best possible. Also we show that an infinite-partite graph with finite parts has...... a triangle, provided that the edge density between any two parts is greater than 1/2....

  10. Efficient Algorithmic Frameworks via Structural Graph Theory

    Science.gov (United States)

    2016-10-28

    constant. For example, they measured that, on large samples of the entire network, the Amazon graph has average degree 17.7, the Facebook graph has average...department heads’ opinions of departments, and generally lack transparency and well-defined measures . On the other hand, the National Research Council (the...Efficient and practical resource block allocation for LTE -based D2D network via graph coloring. Wireless Networks 20(4): 611-624 (2014) 50. Hossein

  11. Decomposing a planar graph into an independent set and a 3-degenerate graph

    DEFF Research Database (Denmark)

    Thomassen, Carsten

    2001-01-01

    We prove the conjecture made by O. V. Borodin in 1976 that the vertex set of every planar graph can be decomposed into an independent set and a set inducing a 3-degenerate graph. (C) 2001 Academic Press....

  12. Graph algorithms in the titan toolkit.

    Energy Technology Data Exchange (ETDEWEB)

    McLendon, William Clarence, III; Wylie, Brian Neil

    2009-10-01

    Graph algorithms are a key component in a wide variety of intelligence analysis activities. The Graph-Based Informatics for Non-Proliferation and Counter-Terrorism project addresses the critical need of making these graph algorithms accessible to Sandia analysts in a manner that is both intuitive and effective. Specifically we describe the design and implementation of an open source toolkit for doing graph analysis, informatics, and visualization that provides Sandia with novel analysis capability for non-proliferation and counter-terrorism.

  13. The Harary index of a graph

    CERN Document Server

    Xu, Kexiang; Trinajstić, Nenad

    2015-01-01

    This is the first book to focus on the topological index, the Harary index, of a graph, including its mathematical properties, chemical applications and some related and attractive open problems. This book is dedicated to Professor Frank Harary (1921—2005), the grandmaster of graph theory and its applications. It has be written by experts in the field of graph theory and its applications. For a connected graph G, as an important distance-based topological index, the Harary index H(G) is defined as the sum of the reciprocals of the distance between any two unordered vertices of the graph G. In this book, the authors report on the newest results on the Harary index of a graph. These results mainly concern external graphs with respect to the Harary index; the relations to other topological indices; its properties and applications to pure graph theory and chemical graph theory; and two significant variants, i.e., additively and multiplicatively weighted Harary indices. In the last chapter, we present a number o...

  14. Mechatronic modeling and simulation using bond graphs

    CERN Document Server

    Das, Shuvra

    2009-01-01

    Introduction to Mechatronics and System ModelingWhat Is Mechatronics?What Is a System and Why Model Systems?Mathematical Modeling Techniques Used in PracticeSoftwareBond Graphs: What Are They?Engineering SystemsPortsGeneralized VariablesBond GraphsBasic Components in SystemsA Brief Note about Bond Graph Power DirectionsSummary of Bond Direction RulesDrawing Bond Graphs for Simple Systems: Electrical and MechanicalSimplification Rules for Junction StructureDrawing Bond Graphs for Electrical SystemsDrawing Bond Graphs for Mechanical SystemsCausalityDrawing Bond Graphs for Hydraulic and Electronic Components and SystemsSome Basic Properties and Concepts for FluidsBond Graph Model of Hydraulic SystemsElectronic SystemsDeriving System Equations from Bond GraphsSystem VariablesDeriving System EquationsTackling Differential CausalityAlgebraic LoopsSolution of Model Equations and Their InterpretationZeroth Order SystemsFirst Order SystemsSecond Order SystemTransfer Functions and Frequency ResponsesNumerical Solution ...

  15. An algebraic approach to graph codes

    DEFF Research Database (Denmark)

    Pinero, Fernando

    This thesis consists of six chapters. The first chapter, contains a short introduction to coding theory in which we explain the coding theory concepts we use. In the second chapter, we present the required theory for evaluation codes and also give an example of some fundamental codes in coding...... theory as evaluation codes. Chapter three consists of the introduction to graph based codes, such as Tanner codes and graph codes. In Chapter four, we compute the dimension of some graph based codes with a result combining graph based codes and subfield subcodes. Moreover, some codes in chapter four...

  16. The color space of a graph

    DEFF Research Database (Denmark)

    Jensen, T.R.; Thomassen, Carsten

    2000-01-01

    If k is a prime power, and G is a graph with n vertices, then a k-coloring of G may be considered as a vector in GF(k)(n). We prove that the subspace of GF(3)(n) spanned by all 3-colorings of a planar triangle-free graph with n vertices has dimension n. In particular, any such graph has at least n...... - 1 nonequivalent 3-colorings, and the addition of any edge or any vertex of degree 3 results in a 3-colorable graph. (C) 2000 John Wiley & Sons, Inc....

  17. Interactive Graph Layout of a Million Nodes

    Directory of Open Access Journals (Sweden)

    Peng Mi

    2016-12-01

    Full Text Available Sensemaking of large graphs, specifically those with millions of nodes, is a crucial task in many fields. Automatic graph layout algorithms, augmented with real-time human-in-the-loop interaction, can potentially support sensemaking of large graphs. However, designing interactive algorithms to achieve this is challenging. In this paper, we tackle the scalability problem of interactive layout of large graphs, and contribute a new GPU-based force-directed layout algorithm that exploits graph topology. This algorithm can interactively layout graphs with millions of nodes, and support real-time interaction to explore alternative graph layouts. Users can directly manipulate the layout of vertices in a force-directed fashion. The complexity of traditional repulsive force computation is reduced by approximating calculations based on the hierarchical structure of multi-level clustered graphs. We evaluate the algorithm performance, and demonstrate human-in-the-loop layout in two sensemaking case studies. Moreover, we summarize lessons learned for designing interactive large graph layout algorithms on the GPU.

  18. Text-Filled Stacked Area Graphs

    DEFF Research Database (Denmark)

    Kraus, Martin

    2011-01-01

    -filled stacked area graphs; i.e., graphs that feature stacked areas that are filled with small-typed text. Since these graphs allow for computing the text layout automatically, it is possible to include large amounts of textual detail with very little effort. We discuss the most important challenges and some...... solutions for the design of text-filled stacked area graphs with the help of an exemplary visualization of the genres, publication years, and titles of a database of several thousand PC games....

  19. Reconstructing Nearly Simple Polytopes from their Graph

    OpenAIRE

    Doolittle, Joseph

    2017-01-01

    We present a partial description of which polytopes are reconstructible from their graphs. This is an extension of work by Blind and Mani (1987) and Kalai (1988), which showed that simple polytopes can be reconstructed from their graphs. In particular, we introduce a notion of $h$-nearly simple and prove that 1-nearly simple and 2-nearly simple polytopes are reconstructible from their graphs. We also give an example of a 3-nearly simple polytope which is not reconstructible from its graph. Fu...

  20. A Reduction of the Graph Reconstruction Conjecture

    Directory of Open Access Journals (Sweden)

    Monikandan S.

    2014-08-01

    Full Text Available A graph is said to be reconstructible if it is determined up to isomor- phism from the collection of all its one-vertex deleted unlabeled subgraphs. Reconstruction Conjecture (RC asserts that all graphs on at least three vertices are reconstructible. In this paper, we prove that interval-regular graphs and some new classes of graphs are reconstructible and show that RC is true if and only if all non-geodetic and non-interval-regular blocks G with diam(G = 2 or diam(Ḡ = diam(G = 3 are reconstructible

  1. Total dominator chromatic number of a graph

    Directory of Open Access Journals (Sweden)

    Adel P. Kazemi

    2015-06-01

    Full Text Available Given a graph $G$, the total dominator coloring problem seeks a proper coloring of $G$ with the additional property that every vertex in the graph is adjacent to all vertices of a color class. We seek to minimize the number of color classes. We initiate to study this problem on several classes of graphs, as well as finding general bounds and characterizations. We also compare the total dominator chromatic number of a graph with the chromatic number and the total domination number of it.

  2. Equitable Colorings Of Corona Multiproducts Of Graphs

    Directory of Open Access Journals (Sweden)

    Furmánczyk Hanna

    2017-11-01

    Full Text Available A graph is equitably k-colorable if its vertices can be partitioned into k independent sets in such a way that the numbers of vertices in any two sets differ by at most one. The smallest k for which such a coloring exists is known as the equitable chromatic number of G and denoted by =(G. It is known that the problem of computation of =(G is NP-hard in general and remains so for corona graphs. In this paper we consider the same model of coloring in the case of corona multiproducts of graphs. In particular, we obtain some results regarding the equitable chromatic number for the l-corona product G ◦l H, where G is an equitably 3- or 4-colorable graph and H is an r-partite graph, a cycle or a complete graph. Our proofs are mostly constructive in that they lead to polynomial algorithms for equitable coloring of such graph products provided that there is given an equitable coloring of G. Moreover, we confirm the Equitable Coloring Conjecture for corona products of such graphs. This paper extends the results from [H. Furmánczyk, K. Kaliraj, M. Kubale and V.J. Vivin, Equitable coloring of corona products of graphs, Adv. Appl. Discrete Math. 11 (2013 103–120].

  3. VT Digital Line Graph Miscellaneous Transmission Lines

    Data.gov (United States)

    Vermont Center for Geographic Information — (Link to Metadata) This datalayer is comprised of Miscellaineous Transmission Lines. Digital line graph (DLG) data are digital representations of cartographic...

  4. Current status and future prospects for enabling chemistry technology in the drug discovery process [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Stevan W. Djuric

    2016-09-01

    Full Text Available This review covers recent advances in the implementation of enabling chemistry technologies into the drug discovery process. Areas covered include parallel synthesis chemistry, high-throughput experimentation, automated synthesis and purification methods, flow chemistry methodology including photochemistry, electrochemistry, and the handling of “dangerous” reagents. Also featured are advances in the “computer-assisted drug design” area and the expanding application of novel mass spectrometry-based techniques to a wide range of drug discovery activities.

  5. Improving the Communication Pattern in Matrix-Vector Operations for Large Scale-Free Graphs by Disaggregation

    Energy Technology Data Exchange (ETDEWEB)

    Kuhlemann, Verena [Emory Univ., Atlanta, GA (United States); Vassilevski, Panayot S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2013-10-28

    Matrix-vector multiplication is the key operation in any Krylov-subspace iteration method. We are interested in Krylov methods applied to problems associated with the graph Laplacian arising from large scale-free graphs. Furthermore, computations with graphs of this type on parallel distributed-memory computers are challenging. This is due to the fact that scale-free graphs have a degree distribution that follows a power law, and currently available graph partitioners are not efficient for such an irregular degree distribution. The lack of a good partitioning leads to excessive interprocessor communication requirements during every matrix-vector product. Here, we present an approach to alleviate this problem based on embedding the original irregular graph into a more regular one by disaggregating (splitting up) vertices in the original graph. The matrix-vector operations for the original graph are performed via a factored triple matrix-vector product involving the embedding graph. And even though the latter graph is larger, we are able to decrease the communication requirements considerably and improve the performance of the matrix-vector product.

  6. On cyclic orthogonal double covers of circulant graphs by special infinite graphs

    Directory of Open Access Journals (Sweden)

    R. El-Shanawany

    2017-12-01

    Full Text Available In this article, a technique to construct cyclic orthogonal double covers (CODCs of regular circulant graphs by certain infinite graph classes such as complete bipartite and tripartite graphs and disjoint union of butterfly and K1,2n−10 is introduced.

  7. The complexity of the matching-cut problem for planar graphs and other graph classes

    NARCIS (Netherlands)

    Bonsma, P.S.

    2009-01-01

    The Matching-Cut problem is the problem to decide whether a graph has an edge cut that is also a matching. Previously this problem was studied under the name of the Decomposable Graph Recognition problem, and proved to be -complete when restricted to graphs with maximum degree four. In this paper it

  8. Improving pharmacokinetic-pharmacodynamic modeling to investigate anti-infective chemotherapy with application to the current generation of antimalarial drugs.

    Directory of Open Access Journals (Sweden)

    Katherine Kay

    Full Text Available Mechanism-based pharmacokinetic-pharmacodynamic (PK/PD modelling is the standard computational technique for simulating drug treatment of infectious diseases with the potential to enhance our understanding of drug treatment outcomes, drug deployment strategies, and dosing regimens. Standard methodologies assume only a single drug is used, it acts only in its unconverted form, and that oral drugs are instantaneously absorbed across the gut wall to their site of action. For drugs with short half-lives, this absorption period accounts for a significant period of their time in the body. Treatment of infectious diseases often uses combination therapies, so we refined and substantially extended the PK/PD methodologies to incorporate (i time lags and drug concentration profiles resulting from absorption across the gut wall and, if required, conversion to another active form; (ii multiple drugs within a treatment combination; (iii differing modes of action of drugs in the combination: additive, synergistic, antagonistic; (iv drugs converted to an active metabolite with a similar mode of action. This methodology was applied to a case study of two first-line malaria treatments based on artemisinin combination therapies (ACTs, artemether-lumefantrine and artesunate-mefloquine where the likelihood of increased artemisinin tolerance/resistance has led to speculation on their continued long-term effectiveness. We note previous estimates of artemisinin kill rate were underestimated by a factor of seven, both the unconverted and converted form of the artemisinins kill parasites and the extended PK/PD methodology produced results consistent with field observations. The simulations predict that a potentially rapid decline in ACT effectiveness is likely to occur as artemisinin resistance spreads, emphasising the importance of containing the spread of artemisinin resistance before it results in widespread drug failure. We found that PK/PD data is generally very

  9. Equilibrium statistical mechanics on correlated random graphs

    Science.gov (United States)

    Barra, Adriano; Agliari, Elena

    2011-02-01

    Biological and social networks have recently attracted great attention from physicists. Among several aspects, two main ones may be stressed: a non-trivial topology of the graph describing the mutual interactions between agents and, typically, imitative, weighted, interactions. Despite such aspects being widely accepted and empirically confirmed, the schemes currently exploited in order to generate the expected topology are based on a priori assumptions and, in most cases, implement constant intensities for links. Here we propose a simple shift [-1,+1]\\to [0,+1] in the definition of patterns in a Hopfield model: a straightforward effect is the conversion of frustration into dilution. In fact, we show that by varying the bias of pattern distribution, the network topology (generated by the reciprocal affinities among agents, i.e. the Hebbian rule) crosses various well-known regimes, ranging from fully connected, to an extreme dilution scenario, then to completely disconnected. These features, as well as small-world properties, are, in this context, emergent and no longer imposed a priori. The model is throughout investigated also from a thermodynamics perspective: the Ising model defined on the resulting graph is analytically solved (at a replica symmetric level) by extending the double stochastic stability technique, and presented together with its fluctuation theory for a picture of criticality. Overall, our findings show that, at least at equilibrium, dilution (of whatever kind) simply decreases the strength of the coupling felt by the spins, but leaves the paramagnetic/ferromagnetic flavors unchanged. The main difference with respect to previous investigations is that, within our approach, replicas do not appear: instead of (multi)-overlaps as order parameters, we introduce a class of magnetizations on all the possible subgraphs belonging to the main one investigated: as a consequence, for these objects a closure for a self-consistent relation is achieved.

  10. Equilibrium statistical mechanics on correlated random graphs

    International Nuclear Information System (INIS)

    Barra, Adriano; Agliari, Elena

    2011-01-01

    Biological and social networks have recently attracted great attention from physicists. Among several aspects, two main ones may be stressed: a non-trivial topology of the graph describing the mutual interactions between agents and, typically, imitative, weighted, interactions. Despite such aspects being widely accepted and empirically confirmed, the schemes currently exploited in order to generate the expected topology are based on a priori assumptions and, in most cases, implement constant intensities for links. Here we propose a simple shift [-1,+1]→[0,+1] in the definition of patterns in a Hopfield model: a straightforward effect is the conversion of frustration into dilution. In fact, we show that by varying the bias of pattern distribution, the network topology (generated by the reciprocal affinities among agents, i.e. the Hebbian rule) crosses various well-known regimes, ranging from fully connected, to an extreme dilution scenario, then to completely disconnected. These features, as well as small-world properties, are, in this context, emergent and no longer imposed a priori. The model is throughout investigated also from a thermodynamics perspective: the Ising model defined on the resulting graph is analytically solved (at a replica symmetric level) by extending the double stochastic stability technique, and presented together with its fluctuation theory for a picture of criticality. Overall, our findings show that, at least at equilibrium, dilution (of whatever kind) simply decreases the strength of the coupling felt by the spins, but leaves the paramagnetic/ferromagnetic flavors unchanged. The main difference with respect to previous investigations is that, within our approach, replicas do not appear: instead of (multi)-overlaps as order parameters, we introduce a class of magnetizations on all the possible subgraphs belonging to the main one investigated: as a consequence, for these objects a closure for a self-consistent relation is achieved

  11. Probability on graphs random processes on graphs and lattices

    CERN Document Server

    Grimmett, Geoffrey

    2018-01-01

    This introduction to some of the principal models in the theory of disordered systems leads the reader through the basics, to the very edge of contemporary research, with the minimum of technical fuss. Topics covered include random walk, percolation, self-avoiding walk, interacting particle systems, uniform spanning tree, random graphs, as well as the Ising, Potts, and random-cluster models for ferromagnetism, and the Lorentz model for motion in a random medium. This new edition features accounts of major recent progress, including the exact value of the connective constant of the hexagonal lattice, and the critical point of the random-cluster model on the square lattice. The choice of topics is strongly motivated by modern applications, and focuses on areas that merit further research. Accessible to a wide audience of mathematicians and physicists, this book can be used as a graduate course text. Each chapter ends with a range of exercises.

  12. Enabling Graph Appliance for Genome Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Rina [ORNL; Graves, Jeffrey A [ORNL; Lee, Sangkeun (Matt) [ORNL; Sukumar, Sreenivas R [ORNL; Shankar, Mallikarjun [ORNL

    2015-01-01

    In recent years, there has been a huge growth in the amount of genomic data available as reads generated from various genome sequencers. The number of reads generated can be huge, ranging from hundreds to billions of nucleotide, each varying in size. Assembling such large amounts of data is one of the challenging computational problems for both biomedical and data scientists. Most of the genome assemblers developed have used de Bruijn graph techniques. A de Bruijn graph represents a collection of read sequences by billions of vertices and edges, which require large amounts of memory and computational power to store and process. This is the major drawback to de Bruijn graph assembly. Massively parallel, multi-threaded, shared memory systems can be leveraged to overcome some of these issues. The objective of our research is to investigate the feasibility and scalability issues of de Bruijn graph assembly on Cray s Urika-GD system; Urika-GD is a high performance graph appliance with a large shared memory and massively multithreaded custom processor designed for executing SPARQL queries over large-scale RDF data sets. However, to the best of our knowledge, there is no research on representing a de Bruijn graph as an RDF graph or finding Eulerian paths in RDF graphs using SPARQL for potential genome discovery. In this paper, we address the issues involved in representing a de Bruin graphs as RDF graphs and propose an iterative querying approach for finding Eulerian paths in large RDF graphs. We evaluate the performance of our implementation on real world ebola genome datasets and illustrate how genome assembly can be accomplished with Urika-GD using iterative SPARQL queries.

  13. Model-based drug administration : current status of target-controlled infusion and closed-loop control

    NARCIS (Netherlands)

    Kuizenga, Merel H.; Vereecke, Hugo E. M.; Struys, Michel M. R. F.

    Purpose of review Drug administration might be optimized by incorporating pharmacokinetic-dynamic (PK/PD) principles and control engineering theories. This review gives an update of the actual status of target-controlled infusion (TCI) and closed-loop computer-controlled drug administration and the

  14. 78 FR 22887 - Guidance for Industry on Non-Penicillin Beta-Lactam Drugs: A Current Good Manufacturing Practices...

    Science.gov (United States)

    2013-04-17

    ... for Preventing Cross- Contamination; Availability AGENCY: Food and Drug Administration, HHS. ACTION... require separation of manufacturing facilities to avoid cross-contamination, the only class of products... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0104...

  15. Multi-channel counter-current chromatography for high-throughput fractionation of natural products for drug discovery.

    Science.gov (United States)

    Wu, Shihua; Yang, Lu; Gao, Yuan; Liu, Xiaoyue; Liu, Feiyan

    2008-02-08

    A multi-channel counter-current chromatography (CCC) method has been designed and fabricated for the high-throughput fractionation of natural products without complications sometimes encountered with other conventional chromatographic systems, such as irreversible adsorptive constituent losses and deactivation, tailing of solute peaks and contamination. It has multiple independent CCC channels and each channel connects independent separation column(s) by parallel flow tubes, and thus the multi-channel CCC apparatus can achieve simultaneously two or more independent chromatographic processes. Furthermore, a high-throughput CCC fractionation method for natural products has been developed by a combination of a new three-channel CCC apparatus and conventional parallel chromatographic devices including pumps, sample injectors, effluent detectors and collectors, and its performance has been displayed on the fractionation of ethyl acetate extracts of three natural materials Solidago canadensis, Suillus placidus, and Trichosanthes kirilowii, which are found to be potent cytotoxic to tumor cell lines in the course of screening the antitumor candidates. By combination of biological screening programs and preparative high-performance liquid chromatography (HPLC) purification, 22.8 mg 6 beta-angeloyloxykolavenic acid and 29.4 mg 6 beta-tigloyloxykolavenic acid for S. canadensis, 25.3mg suillin for S. placidus, and 6.8 mg 23,24-dihydrocucurbitacin B for T. Kirilowii as their major cytotoxic principles were isolated from each 1000 mg crude ethyl acetate extract. Their chemical structures were characterized by electrospray ionization mass spectrometry, one- and two-dimensional nuclear magnetic resonance. The overall results indicate the multi-channel CCC is very useful for high-throughput fractionation of natural products for drug discovery in spite of the solvent balancing requirement and the lower resolution of the shorter CCC columns.

  16. Infection control, genetic assessment of drug resistance and drug susceptibility testing in the current management of multidrug/extensively-resistant tuberculosis (M/XDR-TB) in Europe

    DEFF Research Database (Denmark)

    Bothamley, Graham H.; Lange, Christoph; Albrecht, Dirk

    2017-01-01

    AIM: Europe has the highest documented caseload and greatest increase in multidrug and extensively drug-resistant tuberculosis (M/XDR-TB) of all World Health Organization (WHO) regions. This survey examines how recommendations for M/XDR-TB management are being implemented. METHODS: TBNET is a pan...

  17. Polynomial-time computability of the edge-reliability of graphs using Gilbert's formula

    Directory of Open Access Journals (Sweden)

    Thomas J. Marlowe

    1998-01-01

    Full Text Available Reliability is an important consideration in analyzing computer and other communication networks, but current techniques are extremely limited in the classes of graphs which can be analyzed efficiently. While Gilbert's formula establishes a theoretically elegant recursive relationship between the edge reliability of a graph and the reliability of its subgraphs, naive evaluation requires consideration of all sequences of deletions of individual vertices, and for many graphs has time complexity essentially Θ (N!. We discuss a general approach which significantly reduces complexity, encoding subgraph isomorphism in a finer partition by invariants, and recursing through the set of invariants.

  18. Isospectral graphs with identical nodal counts

    International Nuclear Information System (INIS)

    Oren, Idan; Band, Ram

    2012-01-01

    According to a recent conjecture, isospectral objects have different nodal count sequences (Gnutzmann et al 2005 J. Phys. A: Math. Gen. 38 8921–33). We study generalized Laplacians on discrete graphs, and use them to construct the first non-trivial counterexamples to this conjecture. In addition, these examples demonstrate a surprising connection between isospectral discrete and quantum graphs. (paper)

  19. Compression-based inference on graph data

    NARCIS (Netherlands)

    Bloem, P.; van den Bosch, A.; Heskes, T.; van Leeuwen, D.

    2013-01-01

    We investigate the use of compression-based learning on graph data. General purpose compressors operate on bitstrings or other sequential representations. A single graph can be represented sequentially in many ways, which may in uence the performance of sequential compressors. Using Normalized

  20. On minimum degree conditions for supereulerian graphs

    NARCIS (Netherlands)

    Broersma, Haitze J.; Xiong, L.

    1999-01-01

    A graph is called supereulerian if it has a spanning closed trail. Let $G$ be a 2-edge-connected graph of order $n$ such that each minimal edge cut $E \\subseteq E (G)$ with $|E| \\le 3$ satisfies the property that each component of $G-E$ has order at least $(n-2)/5$. We prove that either $G$ is

  1. On the exterior structure of graphs

    International Nuclear Information System (INIS)

    Kastler, Daniel

    2004-01-01

    After a detailed ab initio description of the exterior structure of graphs as handled by Connes and Kreimer in their work on renormalization (illustrated by the example of the φ 3 model in six dimensions) we spell out in detail their study of the Lie algebra of infinitesimal characters and of the group of characters of the Hopf algebra of Feynman graphs

  2. The Minimum Distance of Graph Codes

    DEFF Research Database (Denmark)

    Høholdt, Tom; Justesen, Jørn

    2011-01-01

    We study codes constructed from graphs where the code symbols are associated with the edges and the symbols connected to a given vertex are restricted to be codewords in a component code. In particular we treat such codes from bipartite expander graphs coming from Euclidean planes and other...... geometries. We give results on the minimum distances of the codes....

  3. Domination versus disjunctive domination in graphs | Henning ...

    African Journals Online (AJOL)

    Domination versus disjunctive domination in graphs. Michael A Henning, Sinclair A Marcon. Abstract. A dominating set in a graph G is a set S of vertices of G such that every vertex not in S is adjacent to a vertex of S. The domination number of G is the minimum cardinality of a dominating set of G. For a positive integer b, ...

  4. Eigenvalues and expansion of bipartite graphs

    DEFF Research Database (Denmark)

    Høholdt, Tom; Janwa, Heeralal

    2012-01-01

    We prove lower bounds on the largest and second largest eigenvalue of the adjacency matrix of bipartite graphs and give necessary and sufficient conditions for equality. We give several examples of classes that are optimal with respect to the bouns. We prove that BIBD-graphs are characterized by ...

  5. Co-Roman domination in graphs

    Indian Academy of Sciences (India)

    1National Centre for Advanced Research in Discrete Mathematics ... 3Department of Computer Science, Ball State University, Muncie, IN, USA .... The corona of two disjoint graphs G1 and G2 is defined to be the graph G = G1 ◦ G2,.

  6. Trajectories entropy in dynamical graphs with memory

    Directory of Open Access Journals (Sweden)

    Francesco eCaravelli

    2016-04-01

    Full Text Available In this paper we investigate the application of non-local graph entropy to evolving and dynamical graphs. The measure is based upon the notion of Markov diffusion on a graph, and relies on the entropy applied to trajectories originating at a specific node. In particular, we study the model of reinforcement-decay graph dynamics, which leads to scale free graphs. We find that the node entropy characterizes the structure of the network in the two parameter phase-space describing the dynamical evolution of the weighted graph. We then apply an adapted version of the entropy measure to purely memristive circuits. We provide evidence that meanwhile in the case of DC voltage the entropy based on the forward probability is enough to characterize the graph properties, in the case of AC voltage generators one needs to consider both forward and backward based transition probabilities. We provide also evidence that the entropy highlights the self-organizing properties of memristive circuits, which re-organizes itself to satisfy the symmetries of the underlying graph.

  7. Graphs, Ideal Flow, and the Transportation Network

    OpenAIRE

    Teknomo, Kardi

    2016-01-01

    This lecture discusses the mathematical relationship between network structure and network utilization of transportation network. Network structure means the graph itself. Network utilization represent the aggregation of trajectories of agents in using the network graph. I show the similarity and relationship between the structural pattern of the network and network utilization.

  8. Supplantation of Mental Operations on Graphs

    Science.gov (United States)

    Vogel, Markus; Girwidz, Raimund; Engel, Joachim

    2007-01-01

    Research findings show the difficulties younger students have in working with graphs. Higher mental operations are necessary for a skilled interpretation of abstract representations. We suggest connecting a concrete representation of the modeled problem with the related graph. The idea is to illustrate essential mental operations externally. This…

  9. Some remarks on definability of process graphs

    NARCIS (Netherlands)

    Grabmayer, C.A.; Klop, J.W.; Luttik, B.; Baier, C.; Hermanns, H.

    2006-01-01

    We propose the notions of "density" and "connectivity" of infinite process graphs and investigate them in the context of the wellknown process algebras BPA and BPP. For a process graph G, the density function in a state s maps a natural number n to the number of states of G with distance less or

  10. On revealing graph cycles via boundary measurements

    International Nuclear Information System (INIS)

    Belishev, M I; Wada, N

    2009-01-01

    This paper deals with boundary value inverse problems on a metric graph, the structure of the graph being assumed unknown. The question under consideration is how to detect from the dynamical and/or spectral inverse data whether the graph contains cycles (is not a tree). For any graph Ω, the dynamical as well as spectral boundary inverse data determine the so-called wave diameter d w : H -1 (Ω) → R defined on functionals supported in the graph. The known fact is that if Ω is a tree then d w ≥ 0 holds and, in this case, the inverse data determine Ω up to isometry. A graph Ω is said to be coordinate if the functions {dist Ω (., γ)} γin∂Ω constitute a coordinate system on Ω. For such graphs, we propose a procedure, which reveals the presence/absence of cycles. The hypothesis is that Ω contains cycles if and only if d w takes negative values. We do not justify this hypothesis in the general case but reduce it to a certain special class of graphs (suns)

  11. Declarative Process Mining for DCR Graphs

    DEFF Research Database (Denmark)

    Debois, Søren; Hildebrandt, Thomas T.; Laursen, Paw Høvsgaard

    2017-01-01

    We investigate process mining for the declarative Dynamic Condition Response (DCR) graphs process modelling language. We contribute (a) a process mining algorithm for DCR graphs, (b) a proposal for a set of metrics quantifying output model quality, and (c) a preliminary example-based comparison...

  12. A Graph Library Extension of SVG

    DEFF Research Database (Denmark)

    Nørmark, Kurt

    2007-01-01

    be aggregated as a single node, and an entire graph can be embedded in a single node. In addition, a number of different graph animations are described. The starting point of the SVG extension is a library that provides an exact of mirror of SVG 1.1 in the functional programming language Scheme. Each element...

  13. Acyclicity in edge-colored graphs

    DEFF Research Database (Denmark)

    Gutin, Gregory; Jones, Mark; Sheng, Bin

    2017-01-01

    A walk W in edge-colored graphs is called properly colored (PC) if every pair of consecutive edges in W is of different color. We introduce and study five types of PC acyclicity in edge-colored graphs such that graphs of PC acyclicity of type i is a proper superset of graphs of acyclicity of type i......+1, i=1,2,3,4. The first three types are equivalent to the absence of PC cycles, PC closed trails, and PC closed walks, respectively. While graphs of types 1, 2 and 3 can be recognized in polynomial time, the problem of recognizing graphs of type 4 is, somewhat surprisingly, NP-hard even for 2-edge-colored...... graphs (i.e., when only two colors are used). The same problem with respect to type 5 is polynomial-time solvable for all edge-colored graphs. Using the five types, we investigate the border between intractability and tractability for the problems of finding the maximum number of internally vertex...

  14. From concatenated codes to graph codes

    DEFF Research Database (Denmark)

    Justesen, Jørn; Høholdt, Tom

    2004-01-01

    We consider codes based on simple bipartite expander graphs. These codes may be seen as the first step leading from product type concatenated codes to more complex graph codes. We emphasize constructions of specific codes of realistic lengths, and study the details of decoding by message passing...

  15. Graph coarsening and clustering on the GPU

    NARCIS (Netherlands)

    Fagginger Auer, B.O.; Bisseling, R.H.

    2013-01-01

    Agglomerative clustering is an effective greedy way to quickly generate graph clusterings of high modularity in a small amount of time. In an effort to use the power offered by multi-core CPU and GPU hardware to solve the clustering problem, we introduce a fine-grained sharedmemory parallel graph

  16. Pixels to Graphs by Associative Embedding

    KAUST Repository

    Newell, Alejandro; Deng, Jia

    2017-01-01

    network such that it takes in an input image and produces a full graph. This is done end-to-end in a single stage with the use of associative embeddings. The network learns to simultaneously identify all of the elements that make up a graph and piece them

  17. Isomorphisms and traversability of directed path graphs

    NARCIS (Netherlands)

    Broersma, Haitze J.; Li, Xueliang; Li, X.

    1998-01-01

    The concept of a line digraph is generalized to that of a directed path graph. The directed path graph $\\forw P_k(D)$ of a digraph $D$ is obtained by representing the directed paths on $k$ vertices of $D$ by vertices. Two vertices are joined by an arc whenever the corresponding directed paths in $D$

  18. Perfect secure domination in graphs

    Directory of Open Access Journals (Sweden)

    S.V. Divya Rashmi

    2017-07-01

    Full Text Available Let $G=(V,E$ be a graph. A subset $S$ of $V$ is a dominating set of $G$ if every vertex in $Vsetminus  S$ is adjacent to a vertex in $S.$ A dominating set $S$ is called a secure dominating set if for each $vin Vsetminus S$ there exists $uin S$ such that $v$ is adjacent to $u$ and $S_1=(Ssetminus{u}cup {v}$ is a dominating set. If further the vertex $uin S$ is unique, then $S$ is called a perfect secure dominating set. The minimum cardinality of a perfect secure dominating set of $G$ is called the perfect  secure domination number of $G$ and is denoted by $gamma_{ps}(G.$ In this paper we initiate a study of this parameter and present several basic results.

  19. Graph Mining Meets the Semantic Web

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sangkeun (Matt) [ORNL; Sukumar, Sreenivas R [ORNL; Lim, Seung-Hwan [ORNL

    2015-01-01

    The Resource Description Framework (RDF) and SPARQL Protocol and RDF Query Language (SPARQL) were introduced about a decade ago to enable flexible schema-free data interchange on the Semantic Web. Today, data scientists use the framework as a scalable graph representation for integrating, querying, exploring and analyzing data sets hosted at different sources. With increasing adoption, the need for graph mining capabilities for the Semantic Web has emerged. We address that need through implementation of three popular iterative Graph Mining algorithms (Triangle count, Connected component analysis, and PageRank). We implement these algorithms as SPARQL queries, wrapped within Python scripts. We evaluate the performance of our implementation on 6 real world data sets and show graph mining algorithms (that have a linear-algebra formulation) can indeed be unleashed on data represented as RDF graphs using the SPARQL query interface.

  20. On the nullity number of graphs

    Directory of Open Access Journals (Sweden)

    Mustapha Aouchiche

    2017-10-01

    Full Text Available The paper discusses bounds on the nullity number of graphs. It is proved in [B. Cheng and B. Liu, On the nullity of graphs. Electron. J. Linear Algebra 16 (2007 60--67] that $\\eta \\le n - D$, where $\\eta$, n and D denote the nullity number, the order and the diameter of a connected graph, respectively. We first give a necessary condition on the extremal graphs corresponding to that bound, and then we strengthen the bound itself using the maximum clique number. In addition, we prove bounds on the nullity using the number of pendant neighbors in a graph. One of those bounds is an improvement of a known bound involving the domination number.

  1. Three Syntactic Theories for Combinatory Graph Reduction

    DEFF Research Database (Denmark)

    Danvy, Olivier; Zerny, Ian

    2011-01-01

    in a third syntactic theory. The structure of the store-based abstract machine corresponding to this third syntactic theory oincides with that of Turner's original reduction machine. The three syntactic theories presented here The three syntactic heories presented here therefore have the following......We present a purely syntactic theory of graph reduction for the canonical combinators S, K, and I, where graph vertices are represented with evaluation contexts and let expressions. We express this syntactic theory as a reduction semantics, which we refocus into the first storeless abstract machine...... for combinatory graph reduction, which we refunctionalize into the first storeless natural semantics for combinatory graph reduction.We then factor out the introduction of let expressions to denote as many graph vertices as possible upfront instead of on demand, resulting in a second syntactic theory, this one...

  2. Three Syntactic Theories for Combinatory Graph Reduction

    DEFF Research Database (Denmark)

    Danvy, Olivier; Zerny, Ian

    2013-01-01

    , as a store-based reduction semantics of combinatory term graphs. We then refocus this store-based reduction semantics into a store-based abstract machine. The architecture of this store-based abstract machine coincides with that of Turner's original reduction machine. The three syntactic theories presented......We present a purely syntactic theory of graph reduction for the canonical combinators S, K, and I, where graph vertices are represented with evaluation contexts and let expressions. We express this rst syntactic theory as a storeless reduction semantics of combinatory terms. We then factor out...... the introduction of let expressions to denote as many graph vertices as possible upfront instead of on demand . The factored terms can be interpreted as term graphs in the sense of Barendregt et al. We express this second syntactic theory, which we prove equivalent to the rst, as a storeless reduction semantics...

  3. Algorithms and Data Structures for Graphs

    DEFF Research Database (Denmark)

    Rotenberg, Eva

    are planar graphs, which are those that can be drawn on a piece of paper without any pair of edges crossing. For planar graphs where each edge can only be traversed in one direction, a fundamental question is whether there is a route from vertex A to vertex B in the graph. We show how such a graph can...... of the form: "Is there an edge such that all paths between A and B go via that edge?" and which can quickly be updated when edges are inserted or deleted. We further show how to represent a planar graph such that we can quickly update our representation when an edge is deleted, and such that questions...

  4. OPEX: Optimized Eccentricity Computation in Graphs

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, Keith [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2011-11-14

    Real-world graphs have many properties of interest, but often these properties are expensive to compute. We focus on eccentricity, radius and diameter in this work. These properties are useful measures of the global connectivity patterns in a graph. Unfortunately, computing eccentricity for all nodes is O(n2) for a graph with n nodes. We present OPEX, a novel combination of optimizations which improves computation time of these properties by orders of magnitude in real-world experiments on graphs of many different sizes. We run OPEX on graphs with up to millions of links. OPEX gives either exact results or bounded approximations, unlike its competitors which give probabilistic approximations or sacrifice node-level information (eccentricity) to compute graphlevel information (diameter).

  5. On The Roman Domination Stable Graphs

    Directory of Open Access Journals (Sweden)

    Hajian Majid

    2017-11-01

    Full Text Available A Roman dominating function (or just RDF on a graph G = (V,E is a function f : V → {0, 1, 2} satisfying the condition that every vertex u for which f(u = 0 is adjacent to at least one vertex v for which f(v = 2. The weight of an RDF f is the value f(V (G = Pu2V (G f(u. The Roman domination number of a graph G, denoted by R(G, is the minimum weight of a Roman dominating function on G. A graph G is Roman domination stable if the Roman domination number of G remains unchanged under removal of any vertex. In this paper we present upper bounds for the Roman domination number in the class of Roman domination stable graphs, improving bounds posed in [V. Samodivkin, Roman domination in graphs: the class RUV R, Discrete Math. Algorithms Appl. 8 (2016 1650049].

  6. Pristine transfinite graphs and permissive electrical networks

    CERN Document Server

    Zemanian, Armen H

    2001-01-01

    A transfinite graph or electrical network of the first rank is obtained conceptually by connecting conventionally infinite graphs and networks together at their infinite extremities. This process can be repeated to obtain a hierarchy of transfiniteness whose ranks increase through the countable ordinals. This idea, which is of recent origin, has enriched the theories of graphs and networks with radically new constructs and research problems. The book provides a more accessible introduction to the subject that, though sacrificing some generality, captures the essential ideas of transfiniteness for graphs and networks. Thus, for example, some results concerning discrete potentials and random walks on transfinite networks can now be presented more concisely. Conversely, the simplifications enable the development of many new results that were previously unavailable. Topics and features: *A simplified exposition provides an introduction to transfiniteness for graphs and networks.*Various results for conventional g...

  7. A model of language inflection graphs

    Science.gov (United States)

    Fukś, Henryk; Farzad, Babak; Cao, Yi

    2014-01-01

    Inflection graphs are highly complex networks representing relationships between inflectional forms of words in human languages. For so-called synthetic languages, such as Latin or Polish, they have particularly interesting structure due to the abundance of inflectional forms. We construct the simplest form of inflection graphs, namely a bipartite graph in which one group of vertices corresponds to dictionary headwords and the other group to inflected forms encountered in a given text. We, then, study projection of this graph on the set of headwords. The projection decomposes into a large number of connected components, to be called word groups. Distribution of sizes of word group exhibits some remarkable properties, resembling cluster distribution in a lattice percolation near the critical point. We propose a simple model which produces graphs of this type, reproducing the desired component distribution and other topological features.

  8. Pixels to Graphs by Associative Embedding

    KAUST Repository

    Newell, Alejandro

    2017-06-22

    Graphs are a useful abstraction of image content. Not only can graphs represent details about individual objects in a scene but they can capture the interactions between pairs of objects. We present a method for training a convolutional neural network such that it takes in an input image and produces a full graph. This is done end-to-end in a single stage with the use of associative embeddings. The network learns to simultaneously identify all of the elements that make up a graph and piece them together. We benchmark on the Visual Genome dataset, and report a Recall@50 of 9.7% compared to the prior state-of-the-art at 3.4%, a nearly threefold improvement on the challenging task of scene graph generation.

  9. Approximate Computing Techniques for Iterative Graph Algorithms

    Energy Technology Data Exchange (ETDEWEB)

    Panyala, Ajay R.; Subasi, Omer; Halappanavar, Mahantesh; Kalyanaraman, Anantharaman; Chavarria Miranda, Daniel G.; Krishnamoorthy, Sriram

    2017-12-18

    Approximate computing enables processing of large-scale graphs by trading off quality for performance. Approximate computing techniques have become critical not only due to the emergence of parallel architectures but also the availability of large scale datasets enabling data-driven discovery. Using two prototypical graph algorithms, PageRank and community detection, we present several approximate computing heuristics to scale the performance with minimal loss of accuracy. We present several heuristics including loop perforation, data caching, incomplete graph coloring and synchronization, and evaluate their efficiency. We demonstrate performance improvements of up to 83% for PageRank and up to 450x for community detection, with low impact of accuracy for both the algorithms. We expect the proposed approximate techniques will enable scalable graph analytics on data of importance to several applications in science and their subsequent adoption to scale similar graph algorithms.

  10. Inferring ontology graph structures using OWL reasoning

    KAUST Repository

    Rodriguez-Garcia, Miguel Angel

    2018-01-05

    Ontologies are representations of a conceptualization of a domain. Traditionally, ontologies in biology were represented as directed acyclic graphs (DAG) which represent the backbone taxonomy and additional relations between classes. These graphs are widely exploited for data analysis in the form of ontology enrichment or computation of semantic similarity. More recently, ontologies are developed in a formal language such as the Web Ontology Language (OWL) and consist of a set of axioms through which classes are defined or constrained. While the taxonomy of an ontology can be inferred directly from the axioms of an ontology as one of the standard OWL reasoning tasks, creating general graph structures from OWL ontologies that exploit the ontologies\\' semantic content remains a challenge.We developed a method to transform ontologies into graphs using an automated reasoner while taking into account all relations between classes. Searching for (existential) patterns in the deductive closure of ontologies, we can identify relations between classes that are implied but not asserted and generate graph structures that encode for a large part of the ontologies\\' semantic content. We demonstrate the advantages of our method by applying it to inference of protein-protein interactions through semantic similarity over the Gene Ontology and demonstrate that performance is increased when graph structures are inferred using deductive inference according to our method. Our software and experiment results are available at http://github.com/bio-ontology-research-group/Onto2Graph .Onto2Graph is a method to generate graph structures from OWL ontologies using automated reasoning. The resulting graphs can be used for improved ontology visualization and ontology-based data analysis.

  11. Inferring ontology graph structures using OWL reasoning.

    Science.gov (United States)

    Rodríguez-García, Miguel Ángel; Hoehndorf, Robert

    2018-01-05

    Ontologies are representations of a conceptualization of a domain. Traditionally, ontologies in biology were represented as directed acyclic graphs (DAG) which represent the backbone taxonomy and additional relations between classes. These graphs are widely exploited for data analysis in the form of ontology enrichment or computation of semantic similarity. More recently, ontologies are developed in a formal language such as the Web Ontology Language (OWL) and consist of a set of axioms through which classes are defined or constrained. While the taxonomy of an ontology can be inferred directly from the axioms of an ontology as one of the standard OWL reasoning tasks, creating general graph structures from OWL ontologies that exploit the ontologies' semantic content remains a challenge. We developed a method to transform ontologies into graphs using an automated reasoner while taking into account all relations between classes. Searching for (existential) patterns in the deductive closure of ontologies, we can identify relations between classes that are implied but not asserted and generate graph structures that encode for a large part of the ontologies' semantic content. We demonstrate the advantages of our method by applying it to inference of protein-protein interactions through semantic similarity over the Gene Ontology and demonstrate that performance is increased when graph structures are inferred using deductive inference according to our method. Our software and experiment results are available at http://github.com/bio-ontology-research-group/Onto2Graph . Onto2Graph is a method to generate graph structures from OWL ontologies using automated reasoning. The resulting graphs can be used for improved ontology visualization and ontology-based data analysis.

  12. The H0 function, a new index for detecting structural/topological complexity information in undirected graphs

    Science.gov (United States)

    Buscema, Massimo; Asadi-Zeydabadi, Masoud; Lodwick, Weldon; Breda, Marco

    2016-04-01

    Significant applications such as the analysis of Alzheimer's disease differentiated from dementia, or in data mining of social media, or in extracting information of drug cartel structural composition, are often modeled as graphs. The structural or topological complexity or lack of it in a graph is quite often useful in understanding and more importantly, resolving the problem. We are proposing a new index we call the H0function to measure the structural/topological complexity of a graph. To do this, we introduce the concept of graph pruning and its associated algorithm that is used in the development of our measure. We illustrate the behavior of our measure, the H0 function, through different examples found in the appendix. These examples indicate that the H0 function contains information that is useful and important characteristics of a graph. Here, we restrict ourselves to undirected.

  13. Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe

    DEFF Research Database (Denmark)

    Hofstra, L Marije; Sauvageot, Nicolas; Albert, Jan

    2016-01-01

    BACKGROUND:  Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management......, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. METHODS:  Demographic, clinical, and virological data from 4140 antiretroviral-naive human...... immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002...

  14. Ultrasonic Vocalizations as a Measure of Affect in Preclinical Models of Drug Abuse: A Review of Current Findings.

    Science.gov (United States)

    Barker, David J; Simmons, Steven J; West, Mark O

    2015-01-01

    The present review describes ways in which ultrasonic vocalizations (USVs) have been used in studies of substance abuse. Accordingly, studies are reviewed which demonstrate roles for affective processing in response to the presentation of drug-related cues, experimenter- and self-administered drug, drug withdrawal, and during tests of relapse/reinstatement. The review focuses on data collected from studies using cocaine and amphetamine, where a large body of evidence has been collected. Data suggest that USVs capture animals' initial positive reactions to psychostimulant administration and are capable of identifying individual differences in affective responding. Moreover, USVs have been used to demonstrate that positive affect becomes sensitized to psychostimulants over acute exposure before eventually exhibiting signs of tolerance. In the drug-dependent animal, a mixture of USVs suggesting positive and negative affect is observed, illustrating mixed responses to psychostimulants. This mixture is predominantly characterized by an initial bout of positive affect followed by an opponent negative emotional state, mirroring affective responses observed in human addicts. During drug withdrawal, USVs demonstrate the presence of negative affective withdrawal symptoms. Finally, it has been shown that drug-paired cues produce a learned, positive anticipatory response during training, and that presentation of drug-paired cues following abstinence produces both positive affect and reinstatement behavior. Thus, USVs are a useful tool for obtaining an objective measurement of affective states in animal models of substance abuse and can increase the information extracted from drug administration studies. USVs enable detection of subtle differences in a behavioral response that might otherwise be missed using traditional measures.

  15. An update discussion on the current assessment of the safety of veterinary antimicrobial drug residues in food with regard to their impact on the human intestinal microbiome.

    Science.gov (United States)

    Cerniglia, Carl E; Pineiro, Silvia A; Kotarski, Susan F

    2016-05-01

    The human gastrointestinal tract ecosystem consists of complex and diverse microbial communities that have now been collectively termed the intestinal microbiome. Recent scientific breakthroughs and research endeavours have increased our understanding of the important role the intestinal microbiome plays in human health and disease. The use of antimicrobial new animal drugs in food-producing animals may result in the presence of low levels of drug residues in edible foodstuffs. There is concern that antimicrobial new animal drugs in or on animal-derived food products at residue-level concentrations could disrupt the colonization barrier and/or modify the antimicrobial resistance profile of human intestinal bacteria. Therapeutic doses of antimicrobial drugs have been shown to promote shifts in the intestinal microbiome, and these disruptions promote the emergence of antimicrobial-resistant bacteria. To assess the effects of antimicrobial new animal drug residues in food on human intestinal bacteria, many national regulatory agencies and international committees follow a harmonized process, VICH GL36(R), which was issued by a trilateral organization of the European Union, the USA, and Japan called the International Cooperation on Harmonization of Technical Requirements for Veterinary Medicinal Products (VICH). The guidance describes a general approach currently used by national regulatory agencies and international committees to assess the effects of antimicrobial new animal drug residues in animal-derived food on human intestinal bacteria. The purpose of this review is to provide an overview of this current approach as part of the antimicrobial new animal drug approval process in participating countries, give insights on the microbiological endpoints used in this safety evaluation, and discuss the availability of new information. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Graph-based Operational Semantics of a Lazy Functional Languages

    DEFF Research Database (Denmark)

    Rose, Kristoffer Høgsbro

    1992-01-01

    Presents Graph Operational Semantics (GOS): a semantic specification formalism based on structural operational semantics and term graph rewriting. Demonstrates the method by specifying the dynamic ...

  17. Current scenario

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Current scenario. India , like other parts of the world, is also facing the problem of increase in the incidence of drug resistance in tuberculosis. Multi-drug resistance (MDR, resistance to RIF & INH) and extensively drug resistant strains (X-DR, resistance to RIF, INH, FQs ...

  18. Twin edge colorings of certain square graphs and product graphs

    Directory of Open Access Journals (Sweden)

    R Rajarajachozhan

    2016-04-01

    Full Text Available A twin edge $k\\!$-coloring of a graph $G$ is a proper edge $k$-coloring of $G$ with the elements of $\\mathbb{Z}_k$ so that the induced vertex $k$-coloring, in which the color of a vertex $v$ in $G$ is the sum in $\\mathbb{Z}_k$ of the colors of the edges incident with $v,$ is a proper vertex $k\\!$-coloring. The minimum $k$ for which $G$ has a twin edge $k\\!$-coloring is called the twin chromatic index of $G.$ Twin chromatic index of the square $P_n^2,$ $n\\ge 4,$ and the square $C_n^2,$ $n\\ge 6,$ are determined. In fact, the twin chromatic index of the square $C_7^2$ is $\\Delta+2,$ where $\\Delta$ is the maximum degree. Twin chromatic index of $C_m\\,\\Box\\,P_n$ is determined, where $\\Box$ denotes the Cartesian product. $C_r$ and $P_r$ are, respectively, the cycle, and the path on $r$ vertices each.

  19. Ventral medial prefrontal cortex (vmPFC) as a target of the dorsolateral prefrontal modulation by transcranial direct current stimulation (tDCS) in drug addiction.

    Science.gov (United States)

    Nakamura-Palacios, Ester Miyuki; Lopes, Isabela Bittencourt Coutinho; Souza, Rodolpho Albuquerque; Klauss, Jaisa; Batista, Edson Kruger; Conti, Catarine Lima; Moscon, Janine Andrade; de Souza, Rodrigo Stênio Moll

    2016-10-01

    Here, we report some electrophysiologic and imaging effects of the transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) in drug addiction, notably in alcohol and crack-cocaine dependence. The low resolution electromagnetic tomography (LORETA) analysis obtained through event-related potentials (ERPs) under drug-related cues, more specifically in its P3 segment (300-500 ms) in both, alcoholics and crack-cocaine users, showed that the ventral medial prefrontal cortex (vmPFC) was the brain area with the largest change towards increasing activation under drug-related cues in those subjects that kept abstinence during and after the treatment with bilateral tDCS (2 mA, 35 cm(2), cathodal left and anodal right) over dlPFC, applied repetitively (five daily sessions). In an additional study in crack-cocaine, which showed craving decreases after repetitive bilateral tDCS, we examined data originating from diffusion tensor imaging (DTI), and we found increased DTI parameters in the left connection between vmPFC and nucleus accumbens (NAcc), such as the number of voxels, fractional anisotropy (FA) and apparent diffusion coefficient (ADC), in tDCS-treated crack-cocaine users when compared to the sham-tDCS group. This increasing of DTI parameters was significantly correlated with craving decreasing after the repetitive tDCS. The vmPFC relates to the control of drug seeking, possibly by extinguishing this behavior. In our studies, the bilateral dlPFC tDCS reduced relapses and craving to the drug use, and increased the vmPFC activation under drug cues, which may be of a great importance in the control of drug use in drug addiction.

  20. Graph-theoretical concepts and physicochemical data

    Directory of Open Access Journals (Sweden)

    Lionello Pogliani

    2003-02-01

    Full Text Available Graph theoretical concepts have been used to model the molecular polarizabilities of fifty-four organic derivatives, and the induced dipole moment of a set of fifty-seven organic compounds divided into three subsets. The starting point of these modeling strategies is the hydrogen-suppressed chemical graph and pseudograph of a molecule, which works very well for second row atoms. From these types of graphs a set of graph-theoretical basis indices, the molecular connectivity indices, can be derived and used to model properties and activities of molecules. With the aid of the molecular connectivity basis indices it is then possible to build higher-order descriptors. The problem of 'graph' encoding the contribution of the inner-core electrons of heteroatoms can here be solved with the aid of odd complete graphs, Kp-(p-odd. The use of these graph tools allow to draw an optimal modeling of the molecular polarizabilities and a satisfactory modeling of the induced dipole moment of a wide set of organic derivatives.