Isomerism as Manifestation of Intrinsic Symmetry of Molecules: Lunn–Senior’s Theory

This article presents the principal results of the doctoral thesis “Isomerism as internal symmetry of molecules” by Valentin Vankov Iliev (Institute of Mathematics and Informatics), successfully defended before the Specialised Academic Council for Informatics and Mathematical Modelling on 15 December, 2008.

Learning Technology in Scheduling Based on the Mixed Graphs

We propose the adaptive algorithm for solving a set of similar scheduling problems using learning technology. It is devised to combine the merits of an exact algorithm based on the mixed graph model and heuristics oriented on the real-world scheduling problems. The former may ensure high quality of the solution by means of an implicit exhausting enumeration of the feasible schedules. The latter may be developed for certain type of problems using their peculiarities. The main idea of the learning technology is to produce effective (in performance measure) and efficient (in computational time) heuristics by adapting local decisions for the scheduling problems under consideration. Adaptation is realized at the stage of learning while solving a set of sample scheduling problems using a branch-and-bound algorithm and structuring knowledge using pattern recognition apparatus.

On Solving the Maximum Betweenness Problem Using Genetic Algorithms

In this paper a genetic algorithm (GA) is applied on Maximum Betweennes Problem (MBP). The maximum of the objective function is obtained by finding a permutation which satisfies a maximal number of betweenness constraints. Every permutation considered is genetically coded with an integer representation. Standard operators are used in the GA. Instances in the experimental results are randomly generated. For smaller dimensions, optimal solutions of MBP are obtained by total enumeration. For those instances, the GA reached all optimal solutions except one. The GA also obtained results for larger instances of up to 50 elements and 1000 triples. The running time of execution and finding optimal results is quite short.

Variable Neighborhood Search for the File Transfer Scheduling Problem

ACM Computing Classification System (1998): I.2.8, G.1.6.

Fraction Space Revisited

Бойко Бл. Банчев - Знае се, че рационалните числа образуват интересни и богати на изчислителни възможности структури като редици на Фарей (Феъри) и безкрайни дървета. Малко внимание се обръща на по-общо, систематично излагане на основните свойства на дробите като множество. Понятия биват въвеждани без обосноваване, някои доказателства са ненужно изкуствени, а почти винаги и едните, и другите като че биват отнесени към една или друга особена структура, вместо към множеството на дробите изобщо. Изненадващо е, че някои същностни твърдения изглежда дори не са формулирани в литературата по теория на числата. Тази статия има за цел да подобри състоянието на нещата в това отношение, като предлага общо, подходящо подредено изложение на понятия и свързани с тях твърдения. Като допълнение са представени бележки върху пораждането на множеството от всички дроби – откритие значително по-старо, отколкото е прието да се смята.

Constructing 7-Clusters

ACM Computing Classification System (1998): G.2, G.4.

Quantifying protein folding pathways

A deep understanding of the proteins folding dynamics can be get quantifying folding landscape by calculating how the number of microscopic configurations (entropy) varies with the energy of the chain, Ω=Ω(E). Because of the incredibly large number of microstates available to a protein, direct enumeration of Ω(E) is not possible on realistic computer simulations. An estimate of Ω(E) can be obtained by use of a combination of statistical mechanics and thermodynamics. By combining different definitions of entropy that are valid for a system whose probability for occupying a state is given by the canonical Boltzmann probability, computers allow the determination of Ω(E). ^ The energy landscapes of two similar, but not identical model proteins were studied. One protein contains no kinetic tracks. Results show a smooth funnel for the folding landscape. That allows the contour determination of the folding funnel. Also it was presented results for the folding landscape for a modified protein with kinetic traps. Final results show that the computational approach is able to distinguish and explore regions of the folding landscape that are due to kinetic traps from the native state folding funnel.^

Impact of mash feeding versus pellets on propionic/butyric acid levels and on total Escherichia coli load in the gastrointestinal tract of growing pigs

Feed characteristics may influence the bacterial community composition and metabolic activities in the pig gastrointestinal tract, known to be associated with positive effects on the gut. Use of mash feed is associated with reduced Salmonella excretion, but little is known of its effect on the Escherichia coli population or of the mechanism of action. Our objectives were to assess the effect of feed texture combined with feed particle size on VFA profiles and levels, total E. coli count, and the presence of genes encoding virulence factors of pathogenic E. coli strains in the digestive tract along with their impact on pig performance of fattening pigs. Pigs (n = 840) on a commercial farm received mash or pellet diets of different particle sizes during the fattening period. Caecal and colon contents from 164 pigs were sampled at the slaughterhouse for enumeration of E. coli by quantitative PCR (qPCR) and for VFA quantification by capillary gas chromatography. The yccT gene was used to enumerate total E. coli. Improved pig performances associated with pellet texture and a 500-μm size were observed. Caecal (P = 0.02) and colon (P < 0.01) propionic acid concentrations were lower for pigs receiving pellet rather than mash feed. Similarly, caecal (P = 0.01) and colon (P < 0.001) butyric acid concentrations were also lower for pigs receiving pellet rather than mash feed, as determined by capillary gas chromatography. Moreover, caecal (P = 0.03) and colon (P < 0.001) butyric acid concentrations were higher for pigs receiving a feed with a 1,250-μm particle size rather than a 500-μm particle size. On the other hand, total caecal and colon E. coli levels were higher for pigs receiving pellet feed than for those receiving mash feed. For total E. coli enumeration, caecal (P < 0.01) and colon (P < 0.01) yccT gene copies were higher for pigs receiving pellet rather than mash feed. No effect of particle size on fatty acid concentrations or on E. coli numbers was observed. Virulence gene quantification revealed no trend. Taken together, results showed that mash feed is associated with lower growth performance but with favorable intestinal changes linked to VFA levels and E. coli reduction in the intestine.

Acoustic and Magnetic Techniques for the Isolation and Analysis of Cells in Microfluidic Platforms

Cancer comprises a collection of diseases, all of which begin with abnormal tissue growth from various stimuli, including (but not limited to): heredity, genetic mutation, exposure to harmful substances, radiation as well as poor dieting and lack of exercise. The early detection of cancer is vital to providing life-saving, therapeutic intervention. However, current methods for detection (e.g., tissue biopsy, endoscopy and medical imaging) often suffer from low patient compliance and an elevated risk of complications in elderly patients. As such, many are looking to “liquid biopsies” for clues into presence and status of cancer due to its minimal invasiveness and ability to provide rich information about the native tumor. In such liquid biopsies, peripheral blood is drawn from patients and is screened for key biomarkers, chiefly circulating tumor cells (CTCs). Capturing, enumerating and analyzing the genetic and metabolomic characteristics of these CTCs may hold the key for guiding doctors to better understand the source of cancer at an earlier stage for more efficacious disease management.

The isolation of CTCs from whole blood, however, remains a significant challenge due to their (i) low abundance, (ii) lack of a universal surface marker and (iii) epithelial-mesenchymal transition that down-regulates common surface markers (e.g., EpCAM), reducing their likelihood of detection via positive selection assays. These factors potentiate the need for an improved cell isolation strategy that can collect CTCs via both positive and negative selection modalities as to avoid the reliance on a single marker, or set of markers, for more accurate enumeration and diagnosis.

The technologies proposed herein offer a unique set of strategies to focus, sort and template cells in three independent microfluidic modules. The first module exploits ultrasonic standing waves and a class of elastomeric particles for the rapid and discriminate sequestration of cells. This type of cell handling holds promise not only in sorting, but also in the isolation of soluble markers from biofluids. The second module contains components to focus (i.e., arrange) cells via forces from acoustic standing waves and separate cells in a high throughput fashion via free-flow magnetophoresis. The third module uses a printed array of micromagnets to capture magnetically labeled cells into well-defined compartments, enabling on-chip staining and single cell analysis. These technologies can operate in standalone formats, or can be adapted to operate with established analytical technologies, such as flow cytometry. A key advantage of these innovations is their ability to process erythrocyte-lysed blood in a rapid (and thus high throughput) fashion. They can process fluids at a variety of concentrations and flow rates, target cells with various immunophenotypes and sort cells via positive (and potentially negative) selection. These technologies are chip-based, fabricated using standard clean room equipment, towards a disposable clinical tool. With further optimization in design and performance, these technologies might aid in the early detection, and potentially treatment, of cancer and various other physical ailments.

Using Helix-coil Models to Study Protein Unfolded States

An abstract of a thesis devoted to using helix-coil models to study unfolded states.\\

Research on polypeptide unfolded states has received much more attention in the last decade or so than it has in the past. Unfolded states are thought to be implicated in various

misfolding diseases and likely play crucial roles in protein folding equilibria and folding rates. Structural characterization of unfolded states has proven to be

much more difficult than the now well established practice of determining the structures of folded proteins. This is largely because many core assumptions underlying

folded structure determination methods are invalid for unfolded states. This has led to a dearth of knowledge concerning the nature of unfolded state conformational

distributions. While many aspects of unfolded state structure are not well known, there does exist a significant body of work stretching back half a century that

has been focused on structural characterization of marginally stable polypeptide systems. This body of work represents an extensive collection of experimental

data and biophysical models associated with describing helix-coil equilibria in polypeptide systems. Much of the work on unfolded states in the last decade has not been devoted

specifically to the improvement of our understanding of helix-coil equilibria, which arguably is the most well characterized of the various conformational equilibria

that likely contribute to unfolded state conformational distributions. This thesis seeks to provide a deeper investigation of helix-coil equilibria using modern

statistical data analysis and biophysical modeling techniques. The studies contained within seek to provide deeper insights and new perspectives on what we presumably

know very well about protein unfolded states. \\

Chapter 1 gives an overview of recent and historical work on studying protein unfolded states. The study of helix-coil equilibria is placed in the context

of the general field of unfolded state research and the basics of helix-coil models are introduced.\\

Chapter 2 introduces the newest incarnation of a sophisticated helix-coil model. State of the art modern statistical techniques are employed to estimate the energies

of various physical interactions that serve to influence helix-coil equilibria. A new Bayesian model selection approach is utilized to test many long-standing

hypotheses concerning the physical nature of the helix-coil transition. Some assumptions made in previous models are shown to be invalid and the new model

exhibits greatly improved predictive performance relative to its predecessor. \\

Chapter 3 introduces a new statistical model that can be used to interpret amide exchange measurements. As amide exchange can serve as a probe for residue-specific

properties of helix-coil ensembles, the new model provides a novel and robust method to use these types of measurements to characterize helix-coil ensembles experimentally

and test the position-specific predictions of helix-coil models. The statistical model is shown to perform exceedingly better than the most commonly used

method for interpreting amide exchange data. The estimates of the model obtained from amide exchange measurements on an example helical peptide

also show a remarkable consistency with the predictions of the helix-coil model. \\

Chapter 4 involves a study of helix-coil ensembles through the enumeration of helix-coil configurations. Aside from providing new insights into helix-coil ensembles,

this chapter also introduces a new method by which helix-coil models can be extended to calculate new types of observables. Future work on this approach could potentially

allow helix-coil models to move into use domains that were previously inaccessible and reserved for other types of unfolded state models that were introduced in chapter 1.

Impact of mash feeding versus pellets on propionic/butyric acid levels and on total Escherichia coli load in the gastrointestinal tract of growing pigs

Feed characteristics may influence the bacterial community composition and metabolic activities in the pig gastrointestinal tract, known to be associated with positive effects on the gut. Use of mash feed is associated with reduced Salmonella excretion, but little is known of its effect on the Escherichia coli population or of the mechanism of action. Our objectives were to assess the effect of feed texture combined with feed particle size on VFA profiles and levels, total E. coli count, and the presence of genes encoding virulence factors of pathogenic E. coli strains in the digestive tract along with their impact on pig performance of fattening pigs. Pigs (n = 840) on a commercial farm received mash or pellet diets of different particle sizes during the fattening period. Caecal and colon contents from 164 pigs were sampled at the slaughterhouse for enumeration of E. coli by quantitative PCR (qPCR) and for VFA quantification by capillary gas chromatography. The yccT gene was used to enumerate total E. coli. Improved pig performances associated with pellet texture and a 500-μm size were observed. Caecal (P = 0.02) and colon (P < 0.01) propionic acid concentrations were lower for pigs receiving pellet rather than mash feed. Similarly, caecal (P = 0.01) and colon (P < 0.001) butyric acid concentrations were also lower for pigs receiving pellet rather than mash feed, as determined by capillary gas chromatography. Moreover, caecal (P = 0.03) and colon (P < 0.001) butyric acid concentrations were higher for pigs receiving a feed with a 1,250-μm particle size rather than a 500-μm particle size. On the other hand, total caecal and colon E. coli levels were higher for pigs receiving pellet feed than for those receiving mash feed. For total E. coli enumeration, caecal (P < 0.01) and colon (P < 0.01) yccT gene copies were higher for pigs receiving pellet rather than mash feed. No effect of particle size on fatty acid concentrations or on E. coli numbers was observed. Virulence gene quantification revealed no trend. Taken together, results showed that mash feed is associated with lower growth performance but with favorable intestinal changes linked to VFA levels and E. coli reduction in the intestine.

ENERGETIC BIOCIDAL MATERIALS AND SPORE NEUTRALIZATION

The objective of this dissertation is to explore a more accurate and versatile approach to investigating the neutralization of spores suffered from ultrafast heating and biocide based stresses, and further to explore and understand novel methods to supply ultrafast heating and biocides through nanostructured energetic materials A surface heating method was developed to apply accurate (± 25 ˚C), high heating rate thermal energy (200 - 800 ˚C, ~103 - ~105 ˚C/s). Uniform attachment of bacterial spores was achieved electrophoretically onto fine wires in liquids, which could be quantitatively detached into suspension for spore enumeration. The spore inactivation increased with temperature and heating rate, and fit a sigmoid response. The neutralization mechanisms of peak temperature and heating rate were correlated to the DNA damage at ~104 ˚C/s, and to the coat rupture by ultrafast vapor pressurization inside spores at ~105 ˚C/s. Humidity was found to have a synergistic effect of rapid heating and chlorine gas to neutralization efficiency. The primary neutralization mechanism of Cl2 and rapid heat is proposed to be chlorine reacting with the spore surface. The stress-kill correlation above provides guidance to explore new biocidal thermites, and to probe mechanisms. Results show that nano-Al/K2S2O8 released more gas at a lower temperature and generated a higher maximum pressure than the other nano-Al/oxysalts. Given that this thermite formulation generates the similar amount of SO2 as O2, it can be considered as a potential candidate for use in energetic biocidal applications. The reaction mechanisms of persulfate and other oxysalts containing thermites can be divided into two groups, with the reactive thermites (e.g. Al/K2S2O8) that generate ~10× higher of pressure and ~10× shorter of burn time ignited via a solid-gas Al/O2 reaction, while the less reactive thermites (e.g. Al/K2SO4) following a condensed phase Al/O reaction mechanism. These different ignition mechanisms were further re-evaluated by investigating the roles of free and bound oxygen. A constant critical reaction rate for ignition was found which is independent to ignition temperature, heating rate and free vs. bound oxygen.

FRAMEWORK SYNTHESIS FOR SYMBOLIC EXECUTION OF EVENT-DRIVEN FRAMEWORKS

Symbolic execution is a powerful program analysis technique, but it is very challenging to apply to programs built using event-driven frameworks, such as Android. The main reason is that the framework code itself is too complex to symbolically execute. The standard solution is to manually create a framework model that is simpler and more amenable to symbolic execution. However, developing and maintaining such a model by hand is difficult and error-prone. We claim that we can leverage program synthesis to introduce a high-degree of automation to the process of framework modeling. To support this thesis, we present three pieces of work. First, we introduced SymDroid, a symbolic executor for Android. While Android apps are written in Java, they are compiled to Dalvik bytecode format. Instead of analyzing an app’s Java source, which may not be available, or decompiling from Dalvik back to Java, which requires significant engineering effort and introduces yet another source of potential bugs in an analysis, SymDroid works directly on Dalvik bytecode. Second, we introduced Pasket, a new system that takes a first step toward automatically generating Java framework models to support symbolic execution. Pasket takes as input the framework API and tutorial programs that exercise the framework. From these artifacts and Pasket's internal knowledge of design patterns, Pasket synthesizes an executable framework model by instantiating design patterns, such that the behavior of a synthesized model on the tutorial programs matches that of the original framework. Lastly, in order to scale program synthesis to framework models, we devised adaptive concretization, a novel program synthesis algorithm that combines the best of the two major synthesis strategies: symbolic search, i.e., using SAT or SMT solvers, and explicit search, e.g., stochastic enumeration of possible solutions. Adaptive concretization parallelizes multiple sub-synthesis problems by partially concretizing highly influential unknowns in the original synthesis problem. Thanks to adaptive concretization, Pasket can generate a large-scale model, e.g., thousands lines of code. In addition, we have used an Android model synthesized by Pasket and found that the model is sufficient to allow SymDroid to execute a range of apps.

Privileged Words and Sturmian Words

This dissertation has two almost unrelated themes: privileged words and Sturmian words. Privileged words are a new class of words introduced recently. A word is privileged if it is a complete first return to a shorter privileged word, the shortest privileged words being letters and the empty word. Here we give and prove almost all results on privileged words known to date. On the other hand, the study of Sturmian words is a well-established topic in combinatorics on words. In this dissertation, we focus on questions concerning repetitions in Sturmian words, reproving old results and giving new ones, and on establishing completely new research directions. The study of privileged words presented in this dissertation aims to derive their basic properties and to answer basic questions regarding them. We explore a connection between privileged words and palindromes and seek out answers to questions on context-freeness, computability, and enumeration. It turns out that the language of privileged words is not context-free, but privileged words are recognizable by a linear-time algorithm. A lower bound on the number of binary privileged words of given length is proven. The main interest, however, lies in the privileged complexity functions of the Thue-Morse word and Sturmian words. We derive recurrences for computing the privileged complexity function of the Thue-Morse word, and we prove that Sturmian words are characterized by their privileged complexity function. As a slightly separate topic, we give an overview of a certain method of automated theorem-proving and show how it can be applied to study privileged factors of automatic words. The second part of this dissertation is devoted to Sturmian words. We extensively exploit the interpretation of Sturmian words as irrational rotation words. The essential tools are continued fractions and elementary, but powerful, results of Diophantine approximation theory. With these tools at our disposal, we reprove old results on powers occurring in Sturmian words with emphasis on the fractional index of a Sturmian word. Further, we consider abelian powers and abelian repetitions and characterize the maximum exponents of abelian powers with given period occurring in a Sturmian word in terms of the continued fraction expansion of its slope. We define the notion of abelian critical exponent for Sturmian words and explore its connection to the Lagrange spectrum of irrational numbers. The results obtained are often specialized for the Fibonacci word; for instance, we show that the minimum abelian period of a factor of the Fibonacci word is a Fibonacci number. In addition, we propose a completely new research topic: the square root map. We prove that the square root map preserves the language of any Sturmian word. Moreover, we construct a family of non-Sturmian optimal squareful words whose language the square root map also preserves.This construction yields examples of aperiodic infinite words whose square roots are periodic.

Does spatial distribution of fauna depend on algal belts on intertidal boulder fields of the French Basque coast ?

To determine good ecological status and conservation of the Sub-Marine area of the Bay of Biscay, the implementation of a new rocky intertidal habitats monitoring is needed. A protocol has been adapted from the Brittany protocol for the water body FRFC11 "Basque coast" for the two indicators "intertidal macroalgae" and "subtidal macroalgae" under the Water Framework Directive to qualify the ecological. However no protocol has been validated for fauna in front of meridional characters of the benthic communities. Investigations carried out on macroalgae communities on intertidal area in WFD framework, since 2008, constitute an important working basis. This is the aim of the Bigorno project (Intertidal Biodiversity of the south of the Bay of Biscay and Observation for New search and Monitoring for decision support), financed by the Agency of Marine Protected Areas and the Departmental Council. To implement knowledge, a sampling protocol has been used in 2015 on the boulder fields of Guéthary. This site is part of Natura 2000 area "rocky Basque coast and offshore extension "It constitutes also a Znieff site and restricted fishing area. The sampling strategy considers the heterogeneity of substrates and the presence of intertidal microhabitats. Two main habitats are present: "mediolittoral rock in exposed area habitat" and "boulder fields". Habitat "intertidal pools and permanent ponds" is also present but, it is not investigated. Sampling effort is of 353 quadrats of 0.1 m², drawn randomly according to a spatially stratified sampling plan, defined by habitat and algal belts. Taxa identification and enumeration are done on each quadrat. The objective of this work is to expose results from data collected during 2015 sampling program. The importance of characterizing benthic fauna communities spatial distribution belonging to the Basque coast according to algal belts defines during the WDF survey was highlighted. Concurrently, indicators of biodiversity were studied.