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Libraries have begun to rethink their big deals, moving beyond traditional ‘read’ models to deals that incorporate support for publishing: read and publish deals. These transformative agreements are one pathway toward a much more open future. Yet libraries lack a framework for assessing the combined value of open publishing and comprehensive read access that these deals provide. This may lead to uncertainty at renewal time. Transformative agreements tend to carry forward historical pricing inequities based on print subscription profiles. In addition, their perceived and actual value and price vary greatly, since some institutions are major content producers (‘publish’ institutions), while others are primarily or exclusively content consumers (‘read’ institutions). This session focuses on one key question: How can libraries assess the value of transformative agreements from the differing perspectives of ‘read’ and ‘publish’ institutions?

Resonance-assisted hydrogen bonds (RAHBs) are exploited in chemical synthesis or serve as models for biologically relevant proton-transfer reactions [K. T. Mahmudov and A. J. L. Pombeiro, Chem. – Eur. J., 2016, 22, 16356–16398]. Their properties depend on the position of the hydrogen atom between donor and acceptor atoms. In the intramolecular RAHB of hydrogen maleate salts, this position is strongly influenced by the counter cation and varies from highly asymmetric to perfectly symmetric. This compound class is therefore ideally suited to investigate the factors determining geometry and electron density of intramolecular RAHBs. Here, it is shown that Hirshfeld atom refinements (HARs) of X-ray diffraction data of different hydrogen maleate salts can accurately and precisely match the hydrogen atom positions obtained from neutron diffraction and are independent of the model used for the hydrogen atom displacement parameters. Thus, the simplest, i.e. isotropic, HAR model can be used to locate hydrogen atoms also in bridging positions. In contrast, the determination of electron-density parameters with X-ray constrained wavefunction (XCW) fitting requires anisotropic, highly accurate hydrogen atom displacement parameters.

This final chapter considers Neill Blomkamp’s film District 9 for its commentary on human and non-human alien relationships. Returning to many of the issues raised in the previous chapters, this coda analyzes the overt biopolitical dimensions of the film and considers how desire works to challenge the violent machinations of the multinational security company, Multi-National United. It examines how the film’s protagonist gets caught up in logics of exclusion in his experience of becoming-alien and approaches a position of bare life, outside the protections of the community. Ultimately, the chapter concludes the project by arguing that new, creative modes of resisting neocolonial and capitalist violence will be needed in response to biopolitical regimes, and that such creativity might arise from different desires and other modes of affect.

This chapter offers a critique of animal rights approaches for their weakness in relying on the passage of laws, and in depending upon their proper administration by legal authorities to attempt the protection of animals. Where some thinkers espouse an animal rights perspective, this chapter argues that postcolonial desire is vital to protecting communities in ways that rights discourse and the law cannot in the context of the biopolitical workings of the state and globalized capitalism. Drawing from Deleuze and Guattari’s work on desire and the law in Kafka (1986), the chapter considers the potential of desire to offer creative alternatives, outside of legal discourse, toward the protection of animals and the larger community. Additionally, it recognizes how indigenous environmental knowledge and notions of desire offer ways of relating to animals that can challenge capitalist instrumentalization.

Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database ( http://ibdmdb.org ), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases.

Temperature shifts trigger genome-wide changes in Escherichia coli's gene expression. We studied if chromosome integration impacts on a gene's sensitivity to these shifts, by comparing the single-RNA production kinetics of a PLacO3O1 promoter, when chromosomally-integrated and when single-copy plasmid-borne. At suboptimal temperatures their induction range, fold change, and response to decreasing temperatures are similar. At critically low temperatures, the chromosome-integrated promoter becomes weaker and noisier. Dissection of its initiation kinetics reveals longer lasting states preceding open complex formation, suggesting enhanced supercoiling buildup. Measurements with Gyrase and Topoisomerase I inhibitors suggest hindrance to escape supercoiling buildup at low temperatures. Consistently, similar phenomena occur in energy-depleted cells by DNP at 30 °C. Transient, critically-low temperatures have no long-term consequences, as raising temperature quickly restores transcription rates. We conclude that the chromosomally-integrated PLacO3O1 has higher sensitivity to low temperatures, due to longer-lasting super-coiled states. A lesser active, chromosome-integrated native lac is shown to be insensitive to Gyrase overexpression, even at critically low temperatures, indicating that the rate of escaping positive supercoiling buildup is temperature and transcription rate dependent. A genome-wide analysis supports this, since cold-shock genes exhibit atypical supercoiling-sensitivities. This phenomenon might partially explain the temperature-sensitivity of some transcriptional programs of E. coli. publishedVersion

A proximity enforcing diarylsilane ligand is reported, which gives rise to unusual Si−H···M interactions with the d10 metal ions Cu+ and Ag+ upon complexation. These interactions are studied in detail both experimentally and computationally and can be classified to be weakly agostic in nature for the Si−H···Cu interaction. The Si−H···Ag interaction has more signatures of an electrostatic contact.

Fifty-one new and 309 published thermochronometric ages (nine systems with closure temperatures ranging from ~450 to 70°C) from the Graubünden region of the Central Alps demonstrate that a pronounced thermal mismatch between the Austroalpine allochthon (Alpine “orogenic lid”) and the Pennine zone persisted until at least 29 Ma and, allowably, until circa 18 Ma. The observed mismatch supports previous suggestions that the famous “overthrust” between the Austroalpine allochthon and the Pennine zone, historically regarded as primarily an Eocene top-north thrust fault, is in fact primarily an Oligocene-Miocene normal fault that has a minimum of 60 km of displacement with top-south or top-southeast sense of shear. Two hallmarks of Alpine geology, deposition of the foredeep Molasse and emplacement of the Helvetic nappes, appear to be coeval, peripheral manifestations of crustal thickening via the interposition of the Pennine zone as a northward intruding wedge between the Austroalpine “lid” and the European cratonic margin, with the Helvetic system (European margin) acting as the “floor” of the wedge. We presume the Penninic wedge is driven by the buoyant rise of subducted crust no longer able to remain attached to the descending slab. If so, emplacement of the Pennine wedge could have occurred mainly after Adria was juxtaposed against cratonic Europe.

I. A compilation of 362 cooling ages, including 52 newly reported in this study, from nine thermochronometric systems, 40K/39Ar amphibole, 40K/39Ar white mica, 87Rb/86Sr white mica, 40K/39Ar biotite, 87Rb/86Sr biotite, zircon and apatite fission track, zircon and apatite (U-Th)/He, indicate that the base of the Austroalpine allochthonous ‘orogenic lid’ was not in full thermal equilibrium with its Penninic substrate until at least the middle Oligocene, approximately 29-28 Ma, to allowably as late as the early Miocene, ca. 18 Ma. There is about a factor-of-five difference in cooling rates between the hanging wall (ca. 4°C/m.y.) and footwall (ca. 20°C/m.y.) during this period. In addition, there are demonstrably higher metamorphic grades, including blueschist- and eclogite-facies, in the Pennine footwall compared to lower greenschist-facies in the Austroalpine hanging wall. Together these two facts demonstrate that hot, high-pressure Penninic nappes were forced upward against the cold, low-pressure overriding Austroalpine plate in a very short time window of approximately 7-10 m.y. between the time of peak metamorphism during the Eocene and the time of thermal equilibration with the overriding plate during the Oligo-Miocene. The most likely mechanism to produce such a cold-on-hot juxtaposition is a normal fault, and therefore, we conclude that an important period of nappe emplacement in the Central Swiss Alps occurred concurrently with orogen-perpendicular normal fault motion at the base of the Austroalpine allochthon persisting well into the Oligocene and possibly into the early Miocene, post-dating the 32-30 Ma age of the Bergell intrusion. Mesoscopic structural measurements made at the top and bottom of the Pennine zone in eastern Switzerland indicate multiple, spatially heterogeneous directions of movement. At the top, in the Oberhalbstein Valley, movement directions vary from dominantly top-east to top-south-southeast a very minor top-north component within Pennine rocks of the Martegnas shear zone and no preferred movement direction within the Austroalpine hanging wall. Near Piz Toissa, a minimum of two kilometers of nearby structural section in the Err and Platta nappes have been faulted out. At the bottom of the Pennine zone in Val Lumnezia and the Chur Rhein Valley at Trimmis, we observe top-northwest, top-north, and top-northeast movements. In Val Lumnezia, the Sub-Penninic Scopi zone (Gotthard cover rocks) shows movement in a top-northwest direction; the superjacent Peidener imbricate fault zone, a relatively thin (ca. 50 to 100 m thick) structural zone consisting of Scopi zone lithologies, shows movement in a northeasterly direction; above that, the basal Penninic Bündnerschiefer shows no dominant movement direction. To the east, in the Chur Rhine Valley, movement is well defined as exclusively top-north. Therefore, movement directions in the lower Bündnerschiefer are broadly top-north but heterogeneous in direction along strike between Val Lumnezia and Chur Rhein Valley, and, as first suggested by Weh and Frotizheim (2001), it may be erroneous to regard the basal Pennine thrust as a simple through-going structure. In Val Lumnezia, the Scopi-Peidener-Pennine nappes resemble a “jelly sandwich” in which the thick Pennine mass utilized the Peidener zone to move in an oblique sinistral-normal slip sense past the southeast-dipping allochthonous Scopi zone and its east-dipping Gotthard “massif” substrate. If the Peidener zone continues northeastward beneath alluvial cover of the Chur Rhein Valley, it may serve as a late, NE-directed shear zone that separates the Pennine nappes from European units. If so, it would explain the apparent truncation and progressive omission of allochthonous elements of European affinity along the zone from southwest to northeast beneath alluvium of the Chur Rhein Valley. We therefore infer that the direct juxtaposition of Penninic units to the east with the Helvetic autochthon to the west at the latitude of Trimmis records an episode of top-northeast, orogen-parallel strike-slip and extensional movement. Zircon (U-Th)/He (ZHe) cooling ages from the Oberhalbstein Valley indicate that the Austroalpine-Pennine contact was still active at ca. 27 Ma, and that the Martegnas shear zone was active, in part, between ca. 27 and 24 Ma. It is likely that the Piz Toissa klippe formed around this time during the late Oligocene. The pattern of much younger ZHe ages at the bottom of the Pennine zone is independent of any nappe boundaries, including the Peidener imbricate fault zone, but is consistent with the rise of the Aar massif during the Miocene. Tectonic movements, as recorded by the mesostructure in the Austroalpine, Penninic, and Sub-Penninic domains, and local ZHe cooling ages generally support the conclusion drawn strictly from cooling ages that the Pennine zone was emplaced en masse as a coherent ‘piston’ or ‘mega-pip’ during Oligocene to early Miocene time (approximately 29 to 18 Ma), well after juxtaposition of Apulia with cratonic Europe (continent-continent collision) and during the development of Alpine topography and the peripheral basins (viz. Molasse and Lombardi). Additional top-north movement and late uplift and flexure of the nappe stack, along with the Aar massif, occurred primarily in middle to upper Miocene time, following the post-collisional structural interposition of the Pennine zone between Europe and Apulia. II. Nine carbonate phases at Kennecott, Alaska were measured for their clumped isotope (∆47) equilibration temperatures. The total range for carbonate temperatures spans 38-164°C. Premineral phases are relatively cool (43-71°C); synmineral phases are relatively warm (89-157°C); late postmineral phases are the most cool (38-59°C) but overlap some premineral phases. Zebra dolomite precipitated in the range 130-163°C. Dedolomite, a hallmark alteration feature of the mineralizing fluids, falls into a narrow range of 98-109°C, consistent with the stability field for the low-temperature chalcocite polymorph. Except for one sample, none of the synmineral calcites crystallized within the stability field of djurleite, a volumetrically significant component of the main-stage ore, which suggests that intergrown djurleite may have been a somewhat later recrystallization product of chalcocite rather than a coeval phase. Calculated compositions for δ18Owater vary from -4.2 to +11.0‰. The most depleted water precipitated hydrothermal baroque dolomite, whereas the most enriched water was associated with recrystallized limestone wallrock on the periphery of the orebody. Waters that precipitated calcite+copper vary from -1.1 to +9.3‰. Intriguingly, rhythmic layering in zebra dolomite can be resolved in ∆47 space, and preliminary data indicate that the coarser-grained baroque dolomite bands precipitated at temperatures 5-10°C cooler than the surrounding, finer-grained dolomite wall rock bands. The calculated values of δ18Owater support a genetic model that invokes redox changes associated with fluid mixing as the likely mechanism responsible for copper deposition. In this model a sulfidic, basinal fluid having δ18O similar to seawater mixes with a cuprous fluid having heavier δ18O (5 to 8‰) which was derived from the Nikolai Greenstone during prehnite-pumpellyite-facies metamorphism.

Many academic libraries are implementing discovery services as a way of giving their users a single comprehensive search option for all library resources. These tools are designed to change the research experience, yet very few studies have investigated the impact of discovery service implementation. This study examines one aspect of that impact by asking whether usage of publisher-hosted journal content changes after implementation of a discovery tool. Libraries that have begun using the four major discovery services have seen an increase in usage of this content, suggesting that for this particular type of material, discovery services have a positive impact on use. Though all discovery services significantly increased usage relative to a no discovery service control group, some had a greater impact than others, and there was extensive variation in usage change among libraries using the same service. Future phases of this study will look at other types of content.

In this work, we demonstrate the scale-up from an 80 L fed-batch scale to 40 m3 along with the design of a 4 m3continuous process for enzymatic biodiesel production catalysed by NS-40116 (a liquid formulation of a modified Thermomyces lanuginosus lipase). Based on the analysis of actual pilot plant data for the transesterification of used cooking oil and brown grease, we propose a method applying first order integral analysis to fed-batch data based on either the bound glycerol or free fatty acid content in the oil. This method greatly simplifies the modelling process and gives an indication of the effect of mixing at the various scales (80L to 40m3) along with the prediction of the residence time needed to reach a desired conversion in a CSTR.Suitable process metrics reflecting commercial performance such as the reaction time, enzyme efficiency and reactor productivity were evaluated for both the fed-batch and CSTR cases. Given similar operating conditions, the CSTR operation on average, has a reaction time which is 1.3 times greater than the fed-batch operation.We also showed how the process metrics can be used to quickly estimate the selling price of the enzyme. Assuming a biodiesel selling price of 0.6 USD/kg and a one-time use of the enzyme (0.1% (w/woil) enzyme dosage); the enzyme can then be sold for 30 USD/kg which ensures that that the enzyme cost is not more than 5% of the biodiesel revenue. This article is protected by copyright. All rights reserved

Many modernists in the late nineteenth century harboured a strong suspicion of the emerging mass culture produced for the working classes. Adopting a position similar to Matthew Arnold’s (2009) that culture was the speciality of a cultured few, and not the uneducated working classes, some sought to protect ‘high art’ from ‘low’ mass forms. Modernists associated with the avant-garde, however, do not appear to have held such rigid views; and for Peter Bürger (1984) this is what distinguishes it from modernism. Historical avant-garde artists tended to be more forthcoming about their connections to other cultural forms, not only acknowledging mass and popular culture, but openly co-opting and integrated it into their art. Bürger sees this not only as part of the avant-garde’s resistance to modernism, but its ‘attack on the status of art in bourgeois society’ (1984, 49). \ud \ud In this paper I will interrogate the tensions between these two modernist positions, and will consider the ways that mass and popular culture forms became an important tool for aesthetic experimentation amongst avant-garde artists. I will focus on three distinct areas in which such experimentation occurred: early Parisian cabaret, Futurism and Dada. In doing so, the paper aims to do two things: (1) to demonstrate the fundamental role that popular and mass cultural forms played in the development of avant-garde aesthetics; and (2) to show how, through such appropriation, avant-garde practices intended to critique mass culture, the belief in high and low art categories, and the capitalist system responsible for their production.

Many signaling and regulatory molecules within cells exist in very few copies per cell. Any process affecting even limited numbers of these molecules therefore has the potential to affect the dynamics of the biochemical networks of which they are a part. This sensitivity to small copy-number changes is what allows stochasticity in gene expression to introduce a degree of randomness in what cells do. While this randomness can be suppressed, it does not appear to be so in many biological systems, at least not to the maximum degree possible. This suggests that this randomness is not necessarily detrimental to cell populations, as it can produce qualitatively new behaviours in genetic networks which may be utilized by cells.In this thesis, two other mechanisms are investigated which, through their interaction with low copy-number molecules, are able to produce qualitatively different dynamics in genetic networks: the stochastic partitioning of molecules in cell division, and the direct interaction of two low copy-number molecules. For this, a novel simulator of chemical kinetics is first presented, designed to simulate the dynamics of genetic circuits inside growing populations of cells. It is then used to study a genetic switch where one repressive link is formed by direct interaction between RNA molecules. This arrangement was found to decouple the stability of the two noisy attractors of the network and the speeds of the state transitions. In other words, it allows the network to have two equally-stable noisy attractors, but differing state transition speeds.Next, the cell-to-cell diversity in RNA numbers (as quantified by the normalized variance) of a single gene over time in a growing model cell population was studied as a function of the division synchrony. In the model, synchronous cell divisions introduce transient increases in the cell-to-cell diversity in RNA numbers of the population, a prediction which was verified using single-molecule measurements of RNA numbers. Finally, the effects of the stochastic partitioning of regulatory molecules in cell division on the dynamics of two genetic circuits, a switch and a clock, were studied. Of these two circuits, the switch has the most dramatic changes in its dynamics, brought on by the inevitable negative correlation in molecule numbers that sister cells inherit. This negative correlation can allow a cell population to partition the phenotypes of the individual cells with less variance than a binomial distribution.These results advance our understanding of the different behaviours that can be produced in genetic circuits due to these two mechanisms. Since they produce unique behaviours, these mechanisms, and combinations thereof, are expected to be used for specialized purposes in natural genetic circuits. Further, since the downstream effects of these mechanisms may be more predictable than, e.g., modifying promoter sequences, they may also be useful in the design and implementation of future synthetic genetic circuits with specific behaviours.

In this first large-scale study of the effect of discovery systems on electronic resource usage, the authors present initial findings on how these systems alter online journal usage by academic library researchers. The study examines usage of content hosted by four major academic journal publishers at 24 libraries that have implemented one of the major discovery systems, EBSCO's EDS, Ex Libris’s Primo, OCLC’s Worldcat Local, or SerialsSolutions’s Summon. A statistically rigorous comparison of COUNTER-compliant journal usage at each library from the 12 months before and after implementation will determine the degree to which usage rises or falls after discovery tool implementation and address rumors that discovery tools differ in their impact on electronic resource usage.

This paper demonstrates the added benefits of using uncertainty and sensitivity analysis in the kinetics of enzymatic biodiesel production. For this study, a kinetic model by Fedosov and co-workers is used. For the uncertainty analysis the Monte Carlo procedure was used to statistically quantify the variability in the model outputs due to uncertainties in the parameter estimates; showing the model is most reliable in the start (first 5 hours) of the reaction. To understand which input parameters are responsible for the output uncertainty, two global sensitivity methods (Standardized Regression Coefficients, and Morris screening) were used. The results from both sensitivity analyses identified that only 10 of the 32 parameters are influential to the model outputs. The model was then simplified by removing the non-influential parameters. A parity plot of the simplified model vs. the full model gave a R2 value of over 0.95 for all the model outputs.

In developing sustainable industrial processes, biochemical engineering, as a part of abroader field of chemical engineering is becoming an increasingly important as a tool in thechemical engineers toolbox. Its application is driven by consumer demand for new productsand by industry wishing to increase profits while reducing operating cost, as well as meetinggovernment and regulatory pressures for processes to be environmentally friendly andsustainable. Current applications of biocatalysts, more specifically, enzymes for large scalebulk production of chemicals have been successfully applied to the production of highfructose corn syrup, upgrading of fats and oils and biodiesel production to name a few.Despite these examples of industrial enzymatic applications, it is still not “clear cut” how toimplement biocatalyst in industry and how best to optimize the processes. This is becausethe processing strategy is usually different to most traditional catalytic processes. In nature,enzymes operate at much lower substrate and product concentrations compared to mostindustrial chemical processes. What this means is that the natural conditions for biocatalystsare normally much different from conventional process-relevant conditions. Also, theoptimal process conditions can vary greatly from one biocatalyst to the next. Hence, tomaximize product yields and reactor productivity then the type of reactor operation anddownstream processing need to be able to address the aforementioned issues. One way toachieve this is through process modelling to help focus the experimental work needed forprocess understanding and to support further process development and optimization of theprocess.To address how the reactors should be operated; a strategy using mechanistic modellingby combining the biological aspects of the enzyme with reaction/reactor engineering isperformed. This strategy is applied to a case study of biodiesel production catalysed by aliquid enzyme formulation. The use of enzymes for biodiesel production is still in its infancywith non-optimized process designs. Furthermore is it unclear how the process should beoperated to ensure optimal economics given the relatively high cost of the enzyme and thelow value of the products.

Salts of the family [M(NCMe)4]+X− (M = Cu, Ag; X− = [BF4]−, [ClO4]−, [PF6]− crystallize in the space groups Pna21 or P212121 with very similar cell dimensions. This gives rise to two sets of true isomorphs (four members in Pna21, two in P212121), and a solvated species (Cu/PF6/MeCN) with a distorted P212121 lattice. Across the two space groups and regardless of the choice of metal atom or anion, the underlying basic structures are virtually identical in the six unsolvated cases, consisting of alternate sheets of cations and anions, mainly held together by C–H⋯C,N and C,N⋯C,N interactions, and a columnar cation–anion motif perpendicular to the sheets maintained by C–H⋯F,O interactions. The pair of concomitant polymorphs found with Cu/BF4 in both Pna21 and P212121 can readily be described as being quasi-isomorphous. Using a Hirshfeld surface approach and a tri-cationic structural synthon extracted from the asymmetric units, the common underlying pattern of close intercomponent approaches has been analysed and quantified. The structure of the Ag/PF6 complex is new; low-temperature redeterminations are recorded for the Ag/ClO4 and the Cu/PF6/MeCN complexes.

Stochastic chemical simulations have proven to be a powerful tool to investigate the dynamics of biological systems. Traditional simulations built upon the Stochastic Simulation Algorithm ignore the identity and spatial relationship between the molecules, and instead treat them as being in a homogeneous mixture. However, cells are not homogeneous compartments and their function requires spatial compartmentalization of processes. Space can be introduced into stochastic simulations by statically compartmentalizing the reactants with diffusion reactions between them. Here, we describe a new exact stochastic chemical kinetics simulator which is capable of simultaneously simulating the chemical kinetics within a set of interacting compartments, each of which can be created or destroyed at runtime. The simulator is constructed to be efficient, taking worst-case logarithmic time per reaction and per compartment for each reaction step performed. We then construct and perform a cursory analysis of the dynamics of two models that would not have been possible to simulate at the molecular level without this simulator: a model of a growing/shrinking population of bacteria infected by a bacteriophage, and a single-nucleotide model of coupled transcription and translation in prokaryotes.

Municipal solid waste (MSW) landfills are one of the largest human-generated sources of methane emissions in the United States and other countries globally. Methane is believed to be a very potent greenhouse gas that is a key contributor to global climate change, over 21 times stronger than CO2. Methane also has a short (10-year) atmospheric life. Because methane is both potent and short-lived, reducing methane emissions from MSW landfills is one of the best ways to achieve a near-term beneficial impact in mitigating global climate change. The United States Environmental Protection Agency estimates that a landfill gas (LFG) project will capture roughly 60-90% of the methane emitted from the landfill, depending on system design and effectiveness. The captured methane can be then purified and used for industrial applications, as in this case the production of SCP. Utilizing methane in this way decreases its demand from fossil fuels which is its traditional source.

This thesis is an attempt to analyze the strategy and tactics used in the most pivotal battles and wars waged by Alexios I Komnenos, Byzantine Emperor from 1081-1118. Alexios I is generally credited with inciting the Crusades due to his appeal to Pope Urban for assistance against the Muslims. While considering the style and effectiveness of warfare used by Alexios, I examined numerous military treatises, spanning over two thousand years. These included both Byzantine sources, especially Maurice, and non-Byzantine sources, most notably Sun-Tzu and Clausewitz, to gather a comprehensive collection of ideals of warfare. These texts formed the basis with which to judge the quality of generalship. I then compared the strategies and tactics used by Alexios I to those espoused by these authors in their respective military manuals. There were many universal concepts that were consistent in all sources used. After careful consideration of the sources and ideals of warfare presented within the research material, I have determined that Alexios I Komnenos should be considered the penultimate Byzantine general.

A multi-chromosome GA (Multi-GA) was developed, based upon concepts from the natural world, allowing improved flexibility in a number of areas including representation, genetic operators, their parameter rates and real world multi-dimensional applications. A series of experiments were conducted, comparing the performance of the Multi-GA to a traditional GA on a number of recognised and increasingly complex test optimisation surfaces, with promising results. Further experiments demonstrated the Multi-GA's flexibility through the use of non-binary chromosome representations and its applicability to dynamic parameterisation. A number of alternative and new methods of dynamic parameterisation were investigated, in addition to a new non-binary 'Quotient crossover' mechanism. Finally, the Multi-GA was applied to two real world problems, demonstrating its ability to handle mixed type chromosomes within an individual, the limited use of a chromosome level fitness function, the introduction of new genetic operators for structural self-adaptation and its viability as a serious real world analysis tool. The first problem involved optimum placement of computers within a building, allowing the Multi-GA to use multiple chromosomes with different type representations and different operators in a single individual. The second problem, commonly associated with Geographical Information Systems (GIS), required a spatial analysis location of the optimum number and distribution of retail sites over two different population grids. In applying the Multi-GA, two new genetic operators (addition and deletion) were developed and explored, resulting in the definition of a mechanism for self-modification of genetic material within the Multi-GA structure and a study of this behaviour.

Introduction: In this phase I study using a 3 + 3 dose escalation design, the safety, dose-limiting toxicity (DLT), immunogenicity and efficacy of intravenous Lipovaxin-MM—a multi-component dendritic cell-targeted liposomal vaccine against metastatic melanoma—was investigated. Methods: Twelve subjects with metastatic cutaneous melanoma were recruited in three cohorts. Patients in Cohort A (n = 3) and Cohort B (n = 3) received three doses of 0.1 and 1 mL of Lipovaxin-MM, respectively, every 4 weeks. Patients in Cohort C (n = 6) received four doses of 3 mL vaccine weekly. Immunologic assessments of peripheral blood were made at regular intervals and included leukocyte subsets, cytokine levels, and Lipovaxin-MM-specific T-cell and antibody reactivities. Tumor responses were assessed by RECIST v1.0 at screening, then 8 weekly in Cohorts A and B and 6 weekly in Cohort C. Results: Of a total of 94 adverse events (AEs) reported in ten subjects, 43 AEs in six subjects were considered to be possibly or probably vaccine-related. Most (95%) vaccine-related AEs were grade 1 or 2, two (5%) grade 3 vaccine-related AEs of anemia and lethargy were recorded, and higher grade AEs and DLTs were not observed. No consistent evidence of vaccine-specific humoral or cellular immune responses was found in post-immunization blood samples. One patient had a partial response, two patients had stable disease, and the remaining patients had progressive disease. Conclusions: Lipovaxin-MM was well tolerated and without clinically significant toxicity. Immunogenicity of Lipovaxin-MM was not detected. Partial response and stable disease were observed in one and two patients, respectively. Refereed/Peer-reviewed