Probabilistic methods for drug discovery

This thesis introduces a flexible visual data exploration framework which combines advanced projection algorithms from the machine learning domain with visual representation techniques developed in the information visualisation domain to help a user to explore and understand effectively large multi-dimensional datasets. The advantage of such a framework to other techniques currently available to the domain experts is that the user is directly involved in the data mining process and advanced machine learning algorithms are employed for better projection. A hierarchical visualisation model guided by a domain expert allows them to obtain an informed segmentation of the input space. Two other components of this thesis exploit properties of these principled probabilistic projection algorithms to develop a guided mixture of local experts algorithm which provides robust prediction and a model to estimate feature saliency simultaneously with the training of a projection algorithm.Local models are useful since a single global model cannot capture the full variability of a heterogeneous data space such as the chemical space. Probabilistic hierarchical visualisation techniques provide an effective soft segmentation of an input space by a visualisation hierarchy whose leaf nodes represent different regions of the input space. We use this soft segmentation to develop a guided mixture of local experts (GME) algorithm which is appropriate for the heterogeneous datasets found in chemoinformatics problems. Moreover, in this approach the domain experts are more involved in the model development process which is suitable for an intuition and domain knowledge driven task such as drug discovery. We also derive a generative topographic mapping (GTM) based data visualisation approach which estimates feature saliency simultaneously with the training of a visualisation model.

From the physics of interacting polymers to optimizing routes on the London Underground

Optimizing paths on networks is crucial for many applications, ranging from subway traffic to Internet communication. Because global path optimization that takes account of all path choices simultaneously is computationally hard, most existing routing algorithms optimize paths individually, thus providing suboptimal solutions. We use the physics of interacting polymers and disordered systems to analyze macroscopic properties of generic path optimization problems and derive a simple, principled, generic, and distributed routing algorithm capable of considering all individual path choices simultaneously. We demonstrate the efficacy of the algorithm by applying it to: (i) random graphs resembling Internet overlay networks, (ii) travel on the London Underground network based on Oyster card data, and (iii ) the global airport network. Analytically derived macroscopic properties give rise to insightful new routing phenomena, including phase transitions and scaling laws, that facilitate better understanding of the appropriate operational regimes and their limitations, which are difficult to obtain otherwise.

Unsupervised KDD to creatively support managers' decision making with fuzzy association rules:a distribution channel application

To be competitive in contemporary turbulent environments, firms must be capable of processing huge amounts of information, and effectively convert it into actionable knowledge. This is particularly the case in the marketing context, where problems are also usually highly complex, unstructured and ill-defined. In recent years, the development of marketing management support systems has paralleled this evolution in informational problems faced by managers, leading to a growth in the study (and use) of artificial intelligence and soft computing methodologies. Here, we present and implement a novel intelligent system that incorporates fuzzy logic and genetic algorithms to operate in an unsupervised manner. This approach allows the discovery of interesting association rules, which can be linguistically interpreted, in large scale databases (KDD or Knowledge Discovery in Databases.) We then demonstrate its application to a distribution channel problem. It is shown how the proposed system is able to return a number of novel and potentially-interesting associations among variables. Thus, it is argued that our method has significant potential to improve the analysis of marketing and business databases in practice, especially in non-programmed decisional scenarios, as well as to assist scholarly researchers in their exploratory analysis. © 2013 Elsevier Inc.

Implementation of Genetic Algorithms for Transit Points Arrangement

The problem of transit points arrangement is presented in the paper. This issue is connected with accuracy of tariff distance calculation and it is the urgent problem at present. Was showed that standard method of tariff distance discovering is not optimal. The Genetic Algorithms are used in optimization problem resolution. The UML application class diagram and class content are showed. In the end the example of transit points arrangement is represented.

Comparative Analysis of Viscoelastic Models Involving Fractional Derivatives of Different Orders

Mathematics Subject Classification: 74D05, 26A33

Fractional Integration and Fractional Differentiation of the M-Series

Mathematics Subject Classification: 26A33, 33C60, 44A15

Codifferentiable Mappings with Applications to Vector Optimality

AMS subject classification: Primary 49J52; secondary: 26A27, 90C48, 47N10.

An inconsistency control system based on incomplete pairwise comparison matrices

Incomplete pairwise comparison matrix was introduced by Harker in 1987 for the case in which the decision maker does not fill in the whole matrix completely due to, e.g., time limitations. However, incomplete matrices occur in a natural way even if the decision maker provides a completely filled in matrix in the end. In each step of the total n(n–1)/2, an incomplete pairwise comparison is given, except for the last one where the matrix turns into complete. Recent results on incomplete matrices make it possible to estimate inconsistency indices CR and CM by the computation of tight lower bounds in each step of the filling in process. Additional information on ordinal inconsistency is also provided. Results can be applied in any decision support system based on pairwise comparison matrices. The decision maker gets an immediate feedback in case of mistypes, possibly causing a high level of inconsistency.

Néhány megjegyzés a kockázat, bizonytalanság, valószínűség kérdéséhez (Some remarks about uncertainty, risk and probability)

A címben említett három fogalom a közgazdasági elméletben központi szerepet foglal el. Ezek viszonya elsősorban a közgazdaságtudományi megismerés határait feszegeti. Mit tudunk a gazdasági döntésekről? Milyen információk alapján születnek a döntések? Lehet-e a gazdasági döntéseket „tudományos” alapra helyezni? A bizonytalanság kérdéséről az 1920-as években való megjelenése óta mindent elmondtak. Megvizsgálták a kérdést filozófiailag, matematikailag. Tárgyalták a kérdés számtalan elméleti és gyakorlati aspektusát. Akkor miért kell sokadszorra is foglalkozni a témával? A válasz igen egyszerű: azért, mert a kérdés minden szempontból ténylegesen alapvető, és mindenkor releváns. Úgy hírlik, hogy a római diadalmenetekben a győztes szekerén mindig volt egy rabszolga is, aki folyamatosan figyelmeztette a diadaltól megmámorosodott vezért, hogy ő is csak egy ember, ezt ne feledje el. A gazdasági döntéshozókat hasonló módon újra és újra figyelmeztetni kell arra, hogy a gazdasági döntések a bizonytalanság jegyében születnek. A gazdasági folyamatok megérthetőségének és kontrollálhatóságának van egy igen szoros korlátja. Ezt a korlátot a folyamatok inherens bizonytalansága adja. A gazdasági döntéshozók fülébe folyamatosan duruzsolni kell: ők is csak emberek, és ezért ismereteik igen korlátozottak. A „bátor” döntések során az eredmény bizonytalan, a tévedés azonban bizonyosra vehető. / === / In the article the author presents some remarks on the application of probability theory in financial decision making. From mathematical point of view the risk neutral measures used in finance are some version of separating hyperplanes used in optimization theory and in general equilibrium theory. Therefore they are just formally a probabilities. They interpretation as probabilities are misleading analogies leading to wrong decisions.

Improving the predictability of time series by chaotic parameter estimation

Limited literature regarding parameter estimation of dynamic systems has been identified as the central-most reason for not having parametric bounds in chaotic time series. However, literature suggests that a chaotic system displays a sensitive dependence on initial conditions, and our study reveals that the behavior of chaotic system: is also sensitive to changes in parameter values. Therefore, parameter estimation technique could make it possible to establish parametric bounds on a nonlinear dynamic system underlying a given time series, which in turn can improve predictability. By extracting the relationship between parametric bounds and predictability, we implemented chaos-based models for improving prediction in time series. ^ This study describes work done to establish bounds on a set of unknown parameters. Our research results reveal that by establishing parametric bounds, it is possible to improve the predictability of any time series, although the dynamics or the mathematical model of that series is not known apriori. In our attempt to improve the predictability of various time series, we have established the bounds for a set of unknown parameters. These are: (i) the embedding dimension to unfold a set of observation in the phase space, (ii) the time delay to use for a series, (iii) the number of neighborhood points to use for avoiding detection of false neighborhood and, (iv) the local polynomial to build numerical interpolation functions from one region to another. Using these bounds, we are able to get better predictability in chaotic time series than previously reported. In addition, the developments of this dissertation can establish a theoretical framework to investigate predictability in time series from the system-dynamics point of view. ^ In closing, our procedure significantly reduces the computer resource usage, as the search method is refined and efficient. Finally, the uniqueness of our method lies in its ability to extract chaotic dynamics inherent in non-linear time series by observing its values. ^

A case study of the Ellison model's use of mentoring as an approach toward inclusive community building

The Ellison Executive Mentoring Inclusive Community Building (ICB) Model is a paradigm for initiating and implementing projects utilizing executives and professionals from a variety of fields and industries, university students, and pre-college students. The model emphasizes adherence to ethical values and promotes inclusiveness in community development. It is a hierarchical model in which actors in each succeeding level of operation serve as mentors to the next. Through a three-step process—content, process, and product—participants must be trained with this mentoring and apprenticeship paradigm in conflict resolution, and they receive sensitivity and diversity training through an interactive and dramatic exposition. ^ The content phase introduces participants to the model's philosophy, ethics, values and methods of operation. The process used to teach and reinforce its precepts is the mentoring and apprenticeship activities and projects in which the participants engage and whose end product demonstrates their knowledge and understanding of the model's concepts. This study sought to ascertain from the participants' perspectives whether the model's mentoring approach is an effective means of fostering inclusiveness, based upon their own experiences in using it. The research utilized a qualitative approach and included data from field observations, individual and group interviews, and written accounts of participants' attitudes. ^ Participants complete ICB projects utilizing The Ellison Model as a method of development and implementation. They generally perceive that the model is a viable tool for dealing with diversity issues whether at work, at school, or at home. The projects are also instructional in that whether participants are mentored or serve as apprentices, they gain useful skills and knowledge about their careers. Since the model is relatively new, there is ample room for research in a variety of areas including organizational studies to determine its effectiveness in combating problems related to various kinds of discrimination. ^

Literatura femenina en el Peru decimononico. La cuestion del naturalismo y el feminismo en la obra de Mercedes Cabello de Carbonera

Women writers in the nineteenth century were often underestimated and in some cases completely ignored. At the end of that century, a considerable group of Peruvian women writers had a significant influence in the development of Lima's cultural life. Either together in the “veladas literarias” or individually in their own work, they showed a common interest in women's concerns and especially in the problems regarding women education or, better to say, the lack of it. Although frequently these writers just followed the paths men have marked for them, they often tried to find their own ways of expression in their works. ^ This dissertation examined the cultural life in Lima at the end of the century and concentrated in one of these writers, Mercedes Cabello de Carbonera (1845–1909), whose work was analyzed from a feminist point of view. American critics had been chosen for the analysis and especially the feminist theories of Sandra Gilbert, Susan Gubar and Elaine Showalter. They were applied to three of Cabello de Carbonera's novels: Sacrificio y recompensa, Las consecuencias and Blanca Sol. ^ The study attempted to prove how often women opinions were distorted by the male tradition and how they tried a different way of expression through the metaphors and symbols referring to the state of repression women were in. Beneath the surface of their work lies a determined feminine consciousness. ^

Treatment moderation and secondary outcomes: Results from a randomized clinical trial

The present study pursued two objectives in the context of a randomized clinical trial of cognitive-behavioral therapy with parent (CBT/P) and group (GCBT) involvement. The first objective was to examine the variability in treatment outcome. There were three specific aims within the first objective, to evaluate: (1) youth characteristics (age, depressive, and externalizing disorders) as moderators of treatment outcome; (2) the differential outcome of the treatment approaches as a function of youth characteristics; and (3) the relative efficacy of the treatment approaches at each level of the moderators. ^ The second objective was to evaluate the efficacy of anxiety treatments along secondary depressive symptoms and externalizing behaviors. There were five specific aims within the second objective, to evaluate: (1) whether anxiety treatment yields reductions in secondary problems, (2) the efficacy of anxiety treatments in reducing secondary problems as a function of approach and youth characteristics, (3) whether reductions in anxiety symptoms significantly mediate changes in secondary problems, (4) the directionality of change in the hypothesized mediated relations, and (5) whether the hypothesized mediated relations are moderated by treatment approach and youth characteristics. The specific aims were pursued using data collected from 183 youth and their mothers. Research questions were tested using multiple regressions and structural equation modeling. ^ Age, depressive, and externalizing disorders were significant moderators. CBT/P relative to GCBT lowered anxiety more for younger than older youth. GCBT relative to CBT/P lowered anxiety more for older than younger youth. GCBT relative to CBT/P lowered anxiety more for depressed youth than non-depressed youth. GCBT relative to CBT/P lowered anxiety less for externalizing youth than non-externalizing youth. Treatment reduced depressive symptoms and externalizing problem behaviors. Reductions in anxiety mediated changes in depressive symptoms and externalizing problem behaviors. Reversed directionality was found in the relation between social anxiety and depressive symptoms. In CBT/P the direction of change was from depressive to social anxiety. The opposite was true in GCBT. Reductions in social anxiety mediated posttreatment changes in depressive symptoms in GCBT but not CBT/P. The reverse was true at follow-up. Reductions in social anxiety mediated changes in depressive symptoms for girls but not boys.^

A Case Study of the Ellison Model's Use of Mentoring as an Approach Toward Inclusive Community Building

The Ellison Executive Mentoring Inclusive Community Building (ICB) Model is a paradigm for initiating and implementing projects utilizing executives and professionals from a variety of fields and industries, university students, and pre-college students. The model emphasizes adherence to ethical values and promotes inclusiveness in community development. It is a hierarchical model in which actors in each succeeding level of operation serve as mentors to the next. Through a three-step process--content, process, and product--participants must be trained with this mentoring and apprenticeship paradigm in conflict resolution, and they receive sensitivitiy and diversity training, through an interactive and dramatic exposition. The content phase introduces participants to the model's philosophy, ethics, values and methods of operation. The process used to teach and reinforce its precepts is the mentoring and apprenticeship activities and projects in which the participants engage and whose end product demontrates their knowledge and understanding of the model's concepts. This study sought to ascertain from the participants' perspectives whether the model's mentoring approach is an effective means of fostering inclusiveness, based upon their own experiences in using it. The research utilized a qualitative approach and included data from field observations, individual and group interviews, and written accounts of participants' attitudes. Participants complete ICB projects utilizing the Ellison Model as a method of development and implementation. They generally perceive that the model is a viable tool for dealing with diversity issues whether at work, at school, or at home. The projects are also instructional in that whether participants are mentored or seve as apprentices, they gain useful skills and knowledge about their careers. Since the model is relatively new, there is ample room for research in a variety of areas including organizational studies to dertmine its effectiveness in combating problems related to various kinds of discrimination.