To date, most lignocellulosic biorefinery strategies have focused on optimizing conversion of cellulose to ethanol, leaving lignin as an underutilized biomass constituent. Lignin is engineered by nature with the intent to protect plants from chemical and biological attack; this leaves lignin with high structural irregularity and recalcitrance, rendering conversion of the lignin macromolecule to valuable products particularly challenging. Nevertheless, given that the economics of cellulosic ethanol production are strongly dependent on the value that can be obtained for the lignin co-product, the successful valorization of lignin is a crucial step in the transition towards a bio-based economy. This thesis focuses on lignin depolymerization using oxidative methods, specifically, the oxidation and cleavage of the β-O-4 linkage. Heterogeneous catalysis in this case is more desirable than homogenous catalysis as the catalyst easily recovered, and it is better suited for industrial applications. Initially, layered double hydroxide (LDH) supported gold nanoparticles were characterized and screened in the oxidation of various lignin model compounds using molecular oxygen, leading to the discovery of an Au/Li-Al LDH heterogeneous catalyst active for oxidative cleavage of the β-O-4 linkage. The Au/Li-Al LDH catalyst was then applied to oxidatively depolymerize Indulin AT kraft lignin and γ-valerolactone (GVL) extracted lignin, high yields of monomers being observed when the oxidized lignins underwent subsequent base-catalyzed hydrolysis. Thereafter, different literature oxidative lignin depolymerization methods were tested on kraft lignin and GVL lignin, and the results compared to the Au/Li-Al LDH catalyst (coupled with hydrolysis) system to determine the most effective oxidative depolymerization method.

Ion exchange resins, commonly used in water treatment, demonstrate promise for the production of biodiesel from biomass feedstocks. The goal of this presented PhD research is to investigate novel uses of ion exchange resins for processing biodiesel feedstocks. Specifically, this research explored using ion exchange resins to remove free fatty acids (FFA) from soybean and waste cooking oils, catalyze transesterification of soybean oil, and catalyze in-situ conversion of dried algal biomass to biodiesel and other recoverable organics. The effect of temperature, moisture content, mixing rate, and resin drying on deacidification of soybean oil with 5% oleic acid feedstock was explored using Dowex Monosphere MR-450 UPW within a batch reactor. The resins were observed to remove up to 83 +/- 1.3% of FFA from soybean oil with less than 5% moisture content while operated at a 20% resin loading at 50 degrees C while mixing at 550 rpm. Once operation characteristics impacting deacidification were evaluated, a series of experiments were carried out to demonstrate the use of mixed bed resin to remove FFA from waste cooking oils. An investigation of wash solutions capable of regenerating the resins was also carried out. Using methanol to regenerate the resins resulted in more than 40% FFA removal over three regeneration cycles, highlighting the utility of resin regeneration as a cost saving measure. Transesterification of soybean oil on Amberlyst A26-OH, a basic ion exchange resin, in the presence of excess methanol was carried out to determine the mechanism of the reaction occurring on the surface. A batch reactor approach was used and reactions were carried out with and without FFA present in the soybean oil feed stock at a 20% resin loading at 50 degrees C while mixing at 550 rpm. When FFA was present in the feedstock and methanol is present in excess, the rate constant for methanol consumption increased. Based upon model fitting, the rate constant of methanol consumption was determined to be 2.08 x 10^-7 /sec with FFA absent and 5.39 x 10^-4/sec when FFA is present when the Eley-Rideal model was used to fit the data. In-situ conversion of dried algal biomass to biodiesel and other recoverable organics was investigated using a batch reaction system with 1 gram of algae. The system was operated with 40:60 methanol:hexane as the solvent system operated at 50 degrees C while mixing at 550 rpm over a range of catalyst loadings. The highest observed ester yield, approximately 60% yield (37 mg_ester/g_algae), was observed when air dried algae was reacted with a 20% resin. An evaluation of the reaction products showed a mixture of esters, phytol, alcohols, and ketones; highlighting the complexity of the reactions occurring during in-situ biomass conversion.

We present a dynamic asset pricing model based on a heterogenous class of traders. These traders are homogenous in the sense that they are fundamentalists who base their investment decisions on an exogenoulsy given fundamental value. They are heterogenous in the sense that each trader is working with a different frequency of the underlying price data. As a result we have a system of interacting investors who together influence the market price. We derive a system that characterizes out-of-equilibrium dynamics of prices in this market which is structurally equivalent to the Nosé-Hoover thermostat equation in non-equilibrium thermodynamics. We explore the time series properties of these prices and find that they exhibit fat tails of returns distributions, volatility clustering and power laws. (author's abstract) / Series: Working Papers SFB "Adaptive Information Systems and Modelling in Economics and Management Science"

Unmanned aerial vehicles (UAVs) are becoming increasingly popular for surveillance in civil and military applications. Vehicles built for this purpose vary in their sensing capabilities, speed and maneuverability. It is therefore natural to assume that a team of UAVs given the mission of visiting a set of targets would include vehicles with differing capabilities. This paper addresses the problem of assigning each vehicle a sequence of targets to visit such that the mission is completed with the least "cost" possible given that the team of vehicles is heterogeneous. In order to simplify the problem the capabilities of each vehicle are modeled as cost to travel from one target to another. In other words, if a vehicle is particularly suited to visit a certain target, the cost for that vehicle to visit that target is low compared to the other vehicles in the team. After applying this simplification, the problem can be posed as an instance of the combinatorial problem called the Heterogeneous Travelling Salesman Problem (HTSP). This paper presents a transformation of a Heterogenous, Multiple Depot, Multiple Traveling Salesman Problem (HMDMTSP) into a single, Asymmetric, Traveling Salesman Problem (ATSP). As a result, algorithms available for the single salesman problem can be used to solve the HMDMTSP. To show the effectiveness of the transformation, the well known Lin-Kernighan-Helsgaun heuristic was applied to the transformed ATSP. Computational results show that good quality solutions can be obtained for the HMDMTSP relatively fast. Additional complications to the sequencing problem come in the form of precedence constraints which prescribe a partial order in which nodes must be visited. In this context the sequencing problem was studied seperately using the Linear Program (LP) relaxation of a Mixed Integer Linear Program (MILP) formulation of the combinatorial problem known as the "Precedence Constrained Asymmetric Travelling Salesman Problem" (PCATSP).

Transition metal nanoclusters are more active and selective catalysts than their bulk counterparts as the fraction of surface atoms increases with the decreasing particle size. When stabilized in organic or aqueous solutions, they can catalyze many reactions. The catalytic activity of metal nanoclusters depends on the particle size and size distribution. Particle size can be controlled by encapsulating the nanoclusters in the cavities of highly ordered porous materials such as zeolites. In this project, osmium(0) nanoclusters were formed within the void spaces of zeolite. Thus, nanoclusters of certain size were prepared as supported catalyst. Osmium(III) cations were introduced into the cavities of zeolite by ion exchange and were reduced partially or completely to form intrazeolite osmium(0) nanoclusters. The intrazeolite osmium(0) nanocusters were characterized by HRTEM, TEM, EDX, XPS, XRD, ICP-OES spectroscopic methods and N2 adsorption-desorption technique. Intrazeolite osmium(0) nanoclusters were employed as catalyst in the aerobic oxidation of alcohols in organic solution.

Molecular simulation is an indispensable tool in many different disciplines such as physics, biology, chemical engineering, materials science, drug design, and others. Performing large-scale molecular simulation is of great interest to biologists and chemists, because many important biological and pharmaceutical phenomena can only be observed in very large molecule systems and after sufficiently long time dynamics. On the other hand, molecular simulation methods usually have very steep computational costs, which limits current molecular simulation studies to relatively small systems. The gap between the scale of molecular simulation that existing techniques can handle and the scale of interest has become a major barrier for applying molecular simulation to study real-world problems. In order to study large-scale molecular systems using molecular simulation, it requires developing highly parallel simulation algorithms and constantly adapting the algorithms to rapidly changing high performance computing architectures. However, many existing algorithms and codes for molecular simulation are from more than a decade ago, which were designed for sequential computers or early parallel architectures. They may not scale efficiently and do not fully exploit features of today's hardware. Given the rapid evolution in computer architectures, the time has come to revisit these molecular simulation algorithms and codes. In this thesis, we demonstrate our approach to addressing the computational challenges of large-scale molecular simulation by presenting both the high-performance algorithms and software for two important molecular simulation applications: Hartree-Fock (HF) calculations and hydrodynamics simulations, on highly parallel computer architectures. The algorithms and software presented in this thesis have been used by biologists and chemists to study some problems that were unable to solve using existing codes. The parallel techniques and methods developed in this work can be also applied to other molecular simulation applications.

Multilevel modeling represents a potentially viable method for meta-analyzing single-subject research, but questions remain concerning its methodological properties with regard to characteristics of single-subject data. For this dissertation, Monte Carlo methods were used to investigate the properties of a 3 level model (i.e., with a quadratic equation at level 1), and three different level 1 error specifications (i.e., different variance components and covariances of 0, lag-1 autoregressive covariance structures, and separate error terms for each phase, with different variance components and covariances of 0). Data for simulated subjects were generated to have characteristics typical of published single-subject data (e.g., typical variances and magnitudes of effect). Samples were simulated for conditions which varied in number of data points per phase, number of subjects per study, number of studies meta-analyzed, level of autocorrelation in residuals, and continuity of variance across phases. Outcome variables examined included rates of convergence of analyses, power for statistical tests of fixed effects, and relative parameter bias of estimates of fixed effects, random effects’ variance components, and autocorrelation estimates. Convergence rates were found to be 100% for all level 1 error specifications and data conditions. Power for statistical tests of fixed effects was observed to be adequate when 10 or more data points were generated per phase and 60 or more total subjects were included in meta-analyses. The relative biases of estimates of fixed effects were found to have limited associations with numbers of data points per phase, levels of autocorrelation, and the continuity/discontinuity of variance across phases. Random effects’ variance components were observed to be frequently biased. Associations between relative bias and data conditions were found to vary by random effect. Finally, autocorrelation estimates were found to be biased in all conditions for which autocorrelation was generated. Results are discussed with regard to study strengths and limitations, and their implications for the meta-analysis of single subject data and primary single subject research. / text

Το αντικείμενο που πραγματεύεται είναι η χρήση τεχνικών και τεχνολογιών υπηρεσιοστραφούς αρχιτεκτονικής και σημασιολογικού ιστού περιλαμβάνοντας κανόνες σημασιολογίας και κατανεμημένου λογισμικού για την κάθετη ολοκλήρωση και ανάπτυξη προσβάσιμων επιχειρησιακών συστημάτων. Επομένως, η παρούσα διατριβή εστιάζει αφενός με την ολοκλήρωση ετερογενών συστημάτων μέσω της χρήσης μεθόδων και τεχνικών σημασιολογικής ολοκλήρωσης και υπηρεσιοστραφούς αρχιτεκτονικής και αφετέρου με την εισαγωγή μιας πρωτότυπης μεθοδολογίας για την ολοκλήρωση προτύπων και τεχνικών προσβασιμότητας προκειμένου να παραχθούν προσβάσιμα διαδικτυακά συστήματα για άτομα με κάθε μορφής αναπηρία. Μέρος της διατριβής αυτή έγινε στα πλαίσια του FP7 Ερευνητικού Προγράμματος με τίτλο ‘Accessibility Assessment Simulation Environment for New Applications Design and Development (ACCESSIBLE) καθώς και στα πλαίσια σχετικών συμβάσεων με την Νομαρχιακή Αυτοδιοίκηση Αχαΐας. / This Phd Thesis presents the usage of Service Oriented Technologies and techniques for the development of an hybrid top-down integrated framework that can be utilized for the integration of heterogeneous systems and the introduction of accessibility features. Taking into account the requirements of the successful deployment of semantic Web technologies regarding off-the-shelf and easy to use semantic SWRL and SPARQL rules and querry tools, the proposed muti-dimensional Framework should be capable of meeting the demands of different users. With the presented Framework, which allows for the selection of suitable matching approaches between well known tools and methodologies, we intend to contribute to the tackling of real world challenges and scenarios, with the aim of ensuring seamless interoperability and integration of different systems. Furthermore, the presented framework facilitates, for the first time, the development of an innovative methodology for the integration of international standards and appropriate techniques, in order to create accessible Web applications and systems. This thesis was partially supported by the European FP7 Research project ACCESSIBLE - Accessibility Assessment Simulation Environment for New Applications Design and Development as well as different contracts with prefecture of Achaia.

Cette thèse a pour objet de contribuer au développement du procédé de dépollution des eaux usées industrielles par ozonation catalytique hétérogène mettant en oeuvre un catalyseur poudre breveté, déposé sur des mousses de différents matériaux. Pour cela, une molécule modèle réfractaire, l'acide succinique a été ozonée en présence de catalyseur dans un réacteur lors d'expériences au cours desquelles plusieurs paramètres d'importance pour l'efficacité du procédé ont été modifiés (localisation du catalyseur, configuration du réacteur, introduction d'ozone...).Dans un premier temps la cinétique réactionnelle a été déterminée en faisant varier les concentrations initiales en acide succinique et en catalyseur.Par la suite, l'influence de la localisation du catalyseur supporté au sein du système réactionnel et du mode d'introduction de l'ozone gaz a été étudiée.La variation du temps de séjour de la solution par variation d'une part du débit d'entrée et d'autre part du volume de solution dans le système a permis (i) la confirmation de la loi cinétique et (ii) la détermination d'un volume limite à partir duquel l'efficacité de la réaction est affectée.Les résultats obtenus ont aboutis à la proposition d'un mécanisme d'ozonation catalytique hétérogène en plusieurs étapes et à la définition de paramètres de dimensionnement en vue d'une application industrielle. / This study aims at developing an industrial wastewater treatment process based on heterogeneous catalytic ozonation implementing a patented powder catalyst stuck on stainless steel and ceramic foam. A refractory model compound, succinic acid, was chosen to be ozonated in the presence of the catalyst while different operating parameters were varied.Kinetic of the catalytic reaction was determined varying initial concentrations of succinic acid and catalyst.The influence of solid catalyst within the reaction system and of the way of introduction of ozone gas was also investigated.The variation of the solution Hydraulic Retention Time through (i) inlet flow rate variation and (ii) volume of solution in the reaction system variation, allowed the confirmation of the kinetic law and the determination of a threshold volume below which the reaction efficiency decreased.The results obtained allowed the proposition of heterogeneous catalytic ozonation mechanism comprising several steps and the definition of design parameters.

Exonic sequences of eukaryotic genes are interspersed with introns which when accurately removed from the primary transcript (pre-mRNA) results in a functional transcript. These splicing reactions are carried out by the spliceosome, consisting of U1, U2, U4, U5, U6 snRNAs and 150 non-snRNP proteins, which assemble onto the pre-mRNA and catalyzes the two invariant transesterification reactions (Will and Luhrmann, 2006). The flexibility in choice of splice sites allows for alternative splicing which has immensely contributed to eukaryotic genome evolution and in diversifying the metazoan proteome (Nilesen and Graveley, 2010). Dynamic yet ordered interactions between U2, U5 and U6 snRNAs and Prp8, Prp16, Prp17, Prp18, Slu7 and Prp22 splicing factors are required in vitro for second-step of splicing of budding yeast and human model transcripts (Umen and Guthrie, 1995a; Horowitz, 2012). ScSlu7 aids 3’ss selection while its strongly associated partner ScPrp18 stabilises U5 snRNA-exonic interactions (James et al., 2002; Aronova et al., 2007). These factors are dispensable in vitro, for the splicing of introns with short branch nucleotide to 3’ss distances (Brys and Schwer, 1996; Zhang and Schwer, 1997). Nearly 43% of fission yeast genes have short introns, with degenerate splice-signals and unconventional Py(n) tracts (Kuhn and Kaufer, 2003). As these features differ extensively from budding yeast and are interestingly more representative of fungal and other eukaryotic introns, fission yeast is an attractive unicellular model to investigate alternate splice-site recognition and assembly mechanisms. Mechanistic details of the second catalytic step are poorly understood in fission yeast. Strikingly, mutations in 3’ss and Py(n) tract intronic cis elements, known to block second step splicing in budding yeast, cause pre-catalytic arrest with unspliced pre-mRNA accumulation in fission yeast (Romfo and Wise, 1997). Studies in our laboratory focussed on understanding the functions for fission yeast SpPrp18 and SpSlu7 predicted to be second-step factors, revealed remarkable differences as compared to their budding yeast counterparts. Unexpectedly, SpPrp18 and SpSlu7 were found by our lab to be required before catalysis and these proteins do not directly associate with each other. Genome-wide splicing studies in a missense slu7-2 mutant indicated widespread yet intron-specific splicing functions for SpSlu7 (Banerjee et al., 2013). Crucial functions were attributed to helix-5 and conserved region loop of SpPrp18 and in vivo splicing analysis in selected cellular transcripts in a missense mutant (V194R) also revealed intron-specific functions (Thesis, N Vijaykrishna). In this study, we have advanced our understanding of SpPrp18 functions by identifying its global substrates and correlating with its intron-specific roles. Through molecular and genetic approaches, we have probed its role in splicing/spliceosome assembly. We identified intronic features within substrates that increase the propensity for the requirement of SpSlu7 for efficient splicing. Further, using findings from the genome-wide alternative splicing patterns in SpSlu7 and SpPrp18 mutants, we have attempted to understand their role in splice-site choice and thus alternative splicing. Ia. Understanding global splicing functions and spliceosomal interactions of fission yeast splicing factor SpPrp18 Since SpPrp18 is an essential gene, our lab generated the strains (prp18-5int [V194R] and WTint), where the thiamine-repressible promoter allowed conditional expression of wild-type or mutant allele integrated at the heterologous leu1 locus. Splicing efficiency of certain cellular transcripts with differing intron characteristics was assessed by semi-quantitative RT-PCR studies and the data suggested intron-specific SpPrp18 roles (in collaboration with Vijaykrishna N). This prompted us to investigate the global splicing role for SpPrp18 for which we used splicing-sensitive microarrays having custom-designed probes to distinguish unspliced pre-mRNA and spliced mRNA for every individual pombe intron. RNA from prp18-5int (V194R) and WTint cells was used in these experiments. We derived a stringent dataset of 258 introns which were statistically significant and correlated in two biological replicate RNA samples, for various probes. Hierarchical clustering of this dataset showed that the depletion of wild-type SpPrp18 triggered a range of splicing phenotypes like (A) pre-mRNA accumulation with mRNA reduction (B) pre-mRNA accumulation (C) spliced mRNA reduction and (D) unchanged pre-mRNA and mRNA levels. Statistical analysis of cis motifs that may correlate with the substrate-specific SpPrp18 splicing functions was done, but the data showed a lack of a global discriminatory primary sequence feature. However, a subtle intron-specific role for Py(n) tracts located between 5’ss and BrP was deduced for SpPrp18. This lead was validated by examining the in vivo splicing efficiency of minitranscripts with wild-type or an altered Py tract length, carried out for a SpPrp18 dependent and an independent intron. To specifically address if SpPrp18 activity was required for second-step splicing we investigated, using primer extension analyses, for lariat intron-3’exon species, an intermediate formed after step 1. We observed that even in prp18-5int dbr1∆ double mutants (where lariat molecules are not degraded) the cells accumulate only unspliced pre-mRNA and not lariat intermediates, a signature of an early arrest prior to the first transesterification reaction. Strengthening these findings, positive genetic interactions were noted between prp18-5int and ts mutants in two factors (U2AF59 and SpPrp1) involved in precatalytic spliceosome assembly and activation. On the whole, our genome-wide studies indicate intron-specific pre-catalytic functions for SpPrp18 supported by genetic interactions with early acting splicing factors involved in spliceosomal assembly and activation. Ib. Identification of intronic features that determine substrate-specific splicing functions for SpSlu7 In vitro studies with ScSlu7 and hSlu7 show their influence in 3’ss selection when BrP to 3’ss distance is greater than 7 nts and 23 nts respectively; but the global substrates are not known in either species (Brys and Schwer, 1996; Chua and Reed, 1999b). Genome-wide analysis of the splicing efficiency changes in cells with the mis-sense spslu7+ mutant (slu7-2), previously carried out in our lab, revealed a spectrum of splicing defects (Banerjee et al., 2013). To further understand the intron context-specific roles for SpSlu7, we examined intronic cis features that may correlate with SpSlu7 dependence. Statistical analyses of the affected (422 introns) and unaffected categories (90 introns) revealed that intron length, BrP to 3’ss distance and AU content are multiple discriminatory cis features that govern SpSlu7 splicing functions. To assess the contribution of these intronic features we tested whether altering these cis elements changes a transcript’s dependency (or otherwise) on SpSlu7 by RT-PCR analyses. For these studies, we generated plasmid expressed mini-genes containing the respective wild-type intron or intron with altered BrP-3’ss distances. We used nab2+ I2 as a case of an intron spliced independent of SpSlu7 and rhb1+ I1 as a representative for SpSlu7 dependent intron. Experiments testing their in vivo splicing status proved that BrP-3’ss distance is a cis feature that dictates SpSlu7 splicing functions in a context-dependent manner. The intronic AU content particularly between the 5’ss and the BrP was assessed in minigene constructs where a chimeric intron was generated by swapping the low AU containing sequences in the 5’ss to BrP stretch of cdc2+ I2 with AU rich bpb1+ I1 5’ end sequences. The results reaffirmed that low intronic AU content particularly at the 5’ end co-relates with SpSlu7 dependency. Hence, we have deduced novel intronic elements, which perhaps in combination, create a contextual dependence for SpSlu7 to facilitate efficient splicing. II. Alternative splice-site selection in fission yeast and studies on the role of splicing factors SpSlu7 and SpPrp18 Budding yeast second-step splicing factors ScSlu7 and ScPrp18 mediate 3’ss choice in the single intron containing transcripts. Fission yeast genome encodes cis and trans factors that promote alternative splicing similar to higher eukaryotes. In this study, we have devised a data analysis pipeline to identify alternative splice events in multi-intronic transcripts of fission yeast. Further, we utilised this information to interrogate the global role for SpSlu7 and SpPrp18 in alternate splice site selection. We mapped the microarray probe sequences corresponding to all theoretically possible non-consecutive splice junctions of S. pombe transcripts onto two independent experimental next-generation (NGS) transcriptomes from wild-type samples and identified 104 exon skipping events with NGS reads more than 3 (Wilhelm et al., 2008; Rhind et al., 2011). We further generated a stringent list of ten exon skipping events having high sequence reads as well as raw intensity value in our microarray experiments with wild-type cells. Two representative events from this list, an abundant rps13+ exon 2 skipped alternative mRNA and less abundant ats1+ exon 3 skipped alternative mRNA were then taken up for experimental analyses by semi-quantitative RT-PCR assays. We confirmed these events and further noted that SpSlu7 and SpPrp18 were required for the constitutive splicing of ats1+ E2-I2-E3-I3-E4 cassette. On the other hand, SpSlu7, and not SpPrp18, exerted a subtle influence on the skipping of exon 3. In addition to exon 3 skipped mRNA, we detected an intron 3 retained ats1+ alternative mRNA (E2-E3-I3-E4) in wild-type cells. Assessment of this event in cells metabolically depleted of SpSlu7 and SpPrp18 showed a reduced abundance of this species in both instances. This suggests a role for functional SpSlu7 and SpPrp18 in retaining intron 3 in ats1+ transcripts in vivo. Among the ten microarray probes, custom-designed to detect specifically the mRNA isoforms arising from altered use of donor 5’ splice sites, we were able to detect in wild-type cells the utilisation of a downstream alternate 5’ss in intron 1 of D-Tyr-tRNA deacylase. Comparative assessment of this splicing event in prp18-5int and slu7-2 mutant cells revealed that SpPrp18 is preferentially required for the utilisation of its alternative 5’ss and such a role has not yet been attributed to its budding yeast and human homologs. On the other hand, SpSlu7 was required equally for utilisation of canonical and non-canonical 5’ss. Differential requirement for SpSlu7 for the utilisation of an upstream non-canonical 3’ss and the canonical 3’ss in DUF3074 intron 1, was noted. This role of SpSlu7 in 3’ss selection is similar to that known from in vitro studies of its budding yeast and human counterparts. Overall, we identified and experimentally validated novel alternate splice events in fission yeast and we infer an important role for SpSlu7 and SpPrp18 in both 5’ss and 3’ss selection.