Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolomics study of flavonoid-induced metabolic reprogramming in human macrophages

The ability of macrophages to change between pro-inflammatory (M1-like) and anti-inflammatory (M2-like) phenotypes makes their modulation an attractive therapeutic strategy to mitigate excessive and/or chronic inflammation. Bioflavonoids are natural compounds with well documented anti-inflammatory activity. However, little is known about their molecular and metabolic effects on human macrophages. In this thesis, NMR metabolomics has been used to assess how different bioflavonoids (Quercetin, Naringenin and Naringin) modulate the metabolism of human macrophages, with a view to better understand their modes of action. In vitro-cultured macrophages differentiated from human THP-1 monocytes were treated with each flavonoid, both in the uncommitted state (M0) or after pre-polarization with LPS/IFN-γ (M1). Treatment with IL-4/IL-13 (M2) was also carried out for comparison. Cells were solvent-extracted to obtain the polar fractions and subsequently analysed by H NMR spectroscopy. Near 50 intracellular metabolites were detected (endometabolome), whereas analysis of cells-conditioned culture medium (exometabolome) was useful to assess consumption and excretion patterns. Multivariate analysis and discrete quantitative assessments of metabolic profiles revealed consistent variations upon macrophage exposure to the different stimuli. The three flavonoids produced pronounced metabolic alterations, with the strongest impact being observed for Quercetin and the mildest for Naringin. The main effects shared by all flavonoids, especially in M1 pre-polarized macrophages, comprised downregulation of glucose uptake and decreased energetic pools (ATP, UTP, phosphocreatine). Other effects were highly flavonoid-specific, namely TCA cycle modulation and amino acid metabolism, antioxidant response and variations in membrane-related metabolites. Overall, this work has shown that, although sharing similar ability to attenuate pro-inflammatory activity of macrophages, the three flavonoids affect macrophage metabolism in distinct ways. Future studies should entail assessment of key metabolic enzymes to further advance current understanding on flavonoid-mediated modulation of macrophage metabolism. This knowledge is expected to support the development of flavonoids as immunomodulatory drugs, especially aimed at attenuating and/or resolving inflammation, for instance, in the context of chronic inflammatory diseases or the rejection of biomaterial implants.
Ultraconserved non-coding DNA within insect phyla

Presence of ultra-conserved sequence elements in vertebrate enhancers suggest that transcription factor regulatory interactions are shared across phylogenetically diverse species. To date evidence for similarly conserved elements among evolutionarily distant insects such as flies, mosquitos, ants and bees, has been elusive. This study has taken advantage of the availability of the assembled genomic sequence of these insects to explore the presence of ultraconserved sequence elements in these phylogenetic groups. To investigate the integrity of fly regulatory sequences across ~100 million years of evolutionary divergence from the fruitfly Drosophila melanogaster, we compared Drosophila non-coding sequences to those of Ceratitis capitata, the Mediterranean fruit fly and Musca domestica, the domestic housefly. Using various alignment techniques, Blastn, Clustal, Blat, EvoPrinter and Needle, we show that many of the conserved sequence blocks (CSBs) that constitute Drosophila cis-regulatory DNA, recognized by EvoPrinter alignment protocols, are also conserved in Ceratitis and Musca. We term the sequence elements shared among these species ultraconserved CSBs (uCSBs). The position of the uCSBs with respect to flanking genes is also conserved. The results suggest that CSBs represent the point of interaction of multiple trans-regulators whose functions and interactions are conserved across divergent genera. Blastn alignments also detect putative cis-regulatory sequences shared among evolutionarily distant mosquitos Anopheles gambiae and Culex pipiens and Aedes aegypti. We have also identified conserved sequences shared among bee species. Side by side comparison of bee and ant EvoPrints identify uCSBs shared between the two taxa, as well as more poorly conserved CSBs in either one or the other taxon but not in both. Analysis of uCSBs in dipterans, mosquitos and bees will lead to a greater understanding of their evolutionary origin and the function of their conserved sequences.
Planning and adaptation of virtual human character motion

is thesis covers some work on planning and adapting motions for a virtual 3d human character. emotivation is to use the physical features of themotion to drive both the planning ofmotion sequences and the subsequent editing of themotions to twith necessary adaptations to the placement of contacts between the character and the geometric environment. We present a scheme for planning sequences of motion in real time based on unrolling a graph of motions and testing availability of support for contacts. e contact model uses raycasts into the geometric scene to check for locations that approximately conform to predened hand grip and foot contacts. Short-horizon planning (on the order of a few seconds of animation) can be done in real-time given a static geometry pre-process, though with a high memory cost. Since the foot and hand placement for these motions is allowed to vary somewhat, we look at physically-based adaptation of animations to accommodate altered contact locations and mass-centre positioning. In the context of a vertex-based character representation, with constraints dening the character skeleton at each animation frame, we introduce some novel constraints to describe dynamic quantities by nite dierences over several frames. e method gives visually acceptable results for smaller adaptations to external constraints, resulting in more realistic motion than with inverse kinematics (IK) constraints and acceleration smoothing alone. However, the solver is not guaranteed to converge and tends to become unstable for larger deformations. We also explore an existingmethod for data-driven IK using principal geodesics analysis of an input set of motion capture data. We give full implementation details, and introduce an idea to improve the performance of the technique as a general full-body IK solver. e novel idea is to split the character skeleton into regions, extract the principal geodesics for each region and then recombine them in the IK solution. is gives more stable poses and allows a greater range of novel poses to be produced from the same input data set.
Visual Exploration of Diffierences Among DTI Fiber Models

In-vivo studies of fibrous structures require non-invasive tools, of which one is fiber tracking based on Diffiusion tensor imaging (DTI) datasets. Different fiber models can be produced from diffierent DTI images, which may vary from subject to subject due to variations in anatomy, motions in scanning, and signal noises. Additionally, parameters of the tracking method also have a great influence on resulting models. Illustrating, exploring, and analyzing diffierences among DTI fiber models are crucial for the purposes of group comparison, atlas construction, and uncertainty analysis. Conventional approaches illustrate fiber models in 3D space and explore diffierences either voxel-wisely or fiber-based. However, these approaches rely on accurate alignment processes and may easily be disturbed by visual clutters. We introduce a two-phase projection technique to illustrate a complex 3D fiber model with a unique 2D map to characterize features for further exploration and analysis. Moreover, regions of significant diffierences among the maps are marked out. In these 2D maps, diffierences can be easily distinguished without occlusions that often occur in 3D spaces. To facilitate comparative analysis from multiple perspectives, we design an interface for interactive exploration. The effiectiveness of our approach is evaluated with two datasets.
Forest Structure, Wood Standing Stock, and Tree Biomass in Different Restoration Systems in the Brazilian Atlantic Forest

Reliable estimates of tree growth and wood yield are fundamental to support the management of restored forests and better reconcile the objectives of recovering biodiversity with the provision of ecosystem services. In this study, wood standing volumes and tree biomass stocks were estimated in different ecological restoration systems and at two sites with contrasting soil fertility, in order to evaluate the potential trade-offs between biodiversity and forest production. At each site, a complete randomized block design, with three replications of six treatments, was established in 1997–1998: direct seeding (DIRS), high-diversity tree plantation (HDIV), modified “Taungya” agroforestry system (AFS), mixed plantation with timber and firewood species (MIX), managed agroforestry system (AFSm) and managed mixed plantation (MIXm). We inventoried all trees with diameter at breast height (DBH) ≥ 5 cm in 450 m2 per treatment per plot, 19–20 years after establishment, using site-specific allometric models. Significant site effects were found for tree height, tree density and wood volume. Restoration systems (treatments) affected forest structure and forest productivity. Higher wood stock and biomass tree were observed in the less complex system (DIRS), while AFSm and HDIV reconciled higher species richness and diversity with good wood volume yields and tree biomass.
Novel immobilization techniques of Acinetobacter (V2) and Paenibacillus (D9) bacterial strains for waste oil degradation

Abstract Bacterial isolates used for the degradation of waste oils has gained greater interest in recent times since these isolates can be immobilized. However, it’s their lack of reproducibility and continual usage that hinders its applicability. The aim of this work is to identify, purify, cultivate and immobilize bacterial isolates that are potential candidates to effectively and selectively degrade waste oils and waste oil blends and reuse them. In an attempt to render bacterium isolates applicable to degradation of lubricating and insulating oil in industrial processes this work investigates the immobilization (through support material, glutaldehyde activated amberlite, polyvinyl alcohol-sodium alginate and chitosan-sodium alginate matrix beads) of bacterial isolates. The data and observed trends show that developed immobilization techniques were successful in immobilizing bacterial isolate strains V2 and D9, with free cell degradation being most efficient (14.7–31.6%) followed by polyvinyl alcohol-sodium alginate (5.3–26.7%), chitosan-sodium alginate (8.8–0.3%) and amberlite-glutaldehyde (2.2–7.0%). The entrapment technique for immobilization of polyvinyl alcohol-sodium alginate and chitosan-sodium alginate proved to be more efficient than adsorption technique used for immobilization of amberlite-glutaldehyde. Free cell degradation was effective in degrading waste oil, but did so upon a single cycle with deterioration. Polyvinyl alcohol-sodium alginate bead matrix can be applied for degradative processes over a wide pH range and short incubation times while chitosan-sodium alginate is best suited for continuous long incubation periods. Reusability of both polyvinyl alcohol-sodium alginate and chitosan-sodium alginate beads are applicable up to a 10-cycle period.
Multivariate drivers of diversity in temperate Australian native grasslands

Disturbance has been considered essential for maintaining biodiversity in temperate grassy ecosystems in Australia. This has been particularly well demonstrated for inter-tussock plant species in C4 Themeda-dominated grasslands in mesic environments. Disturbance is also thought crucial to maintain the structure of preferred habitat for some animals. Relationships between disturbance and diversity may be contingent on ecosystem productivity, but little is known about the generality of the disturbance-promoting-diversity paradigm across the range of temperate grasslands. To date, the disturbance-promoting-diversity paradigm has taken a univariate approach to the drivers of biodiversity; rainfall is seen as a key driver of productivity, which then drives diversity, mediated by disturbance. We argue that this framework is too simplistic as biodiversity drivers are multivariate. We suggest that the accumulation of phytomass (live and dead plant material) is an important determinant of diversity in grassy ecosystems and that phytomass accumulation is governed by multiple drivers (of which disturbance is just one). For fauna, it is structure – not biomass – that determines habitat suitability, and this can be moderated by both abiotic and biotic drivers. The assumption that there is a consistent effect of disturbance on diversity through the range of temperate grassland settings in southern Australia ignores the likelihood that biodiversity also responds to other factors such as spatial heterogeneity in the environment, resource availability and climatic variation. We developed a conceptual model of the multivariate drivers of grassland diversity that explores mechanisms underpinning patterns of species richness. Despite four decades of research, it is clear that our understanding of the multivariate drivers of diversity across the range of temperate grasslands in Australia is still incomplete. Further research into the conditions under which disturbance is required to maintain biodiversity in grasslands is integral to conservation planning in these endangered systems.
A flexible tool to prioritize areas for conservation combining landscape units, measures of biodiversity, and threats

Expanding the reserve system is a key strategy to enhance biodiversity protection. Yet, conservation outcomes can be undermined by underrepresentation of some habitats and opportunistic placement of protected areas. Irreplaceability and vulnerability, the key principles of conservation, should thus be combined within a bioregionalization framework to implement protection in the habitats that most need it. We proposed a simple and flexible method to prioritize bioregions for conservation based on these principles and used it to rank the 85 bioregions of the Australian continent. To do so, we quantified biodiversity values and threats in each bioregion by gathering open‐access data on species, landscapes, and land use. Bioregions were then ranked using a set of customizable scenarios, including ecologically meaningful combinations of measures of irreplaceability and vulnerability. To identify biodiverse areas under threat but potentially overlooked, we compared our results with the location of already established biodiversity hotspots (i.e., areas identified as important for biodiversity and under threat). We found that bioregions with the highest biodiversity values are predominantly located in the southwest, east, and north of the continent. Similarly, threats, particularly land clearance, are concentrated along the east coast and in the southwest. When ranking bioregions using scenarios including both threats and biodiversity values, the majority (75%) of the highest‐ranking bioregions were already included in biodiversity hotspots. For five of these bioregions, the proportion of protected land to date still falls below the 17% recommended by the Convention on Biological Diversity and thus they likely require prompt prioritization and intervention. The method proposed can support ongoing monitoring and prioritization of land units for conservation. Its simplicity and flexibility mean it can be easily adopted for different areas and adjusted to local priorities.
Trends in Dairy Herd Genetic, Production and Reproductive Performance and Impact on Farm Profit

There is little sound information about the impact of cow genetic selection programs on whole farm profit. In this paper aggregate industry data about dairy herds are analysed to identify trends in dairy herd genetic, production and reproductive performance. The genetic distribution within herds that would result over time from a long-term genetic selection program is simulated, and a representative whole-farm bioeconomic model is used to explore the impact of genetic change in a dairy herd on the profit of a representative case farm. Analysis of an industry herd recording database revealed an average annual rate of increase in the Balanced Production Index (BPI) of 7 units for the herd (2.9 and 10.1 for the bottom and top BPI quartiles) and 10.8 units for artificial insemination sires used within herds. Modelling these trends for herds, with an age-cohort range average of 43 units of BPI and 20 per cent cohort attrition rates, shows that the natural range between bottom and top BPI quartiles expands gradually but remains between 75–100 units in most herds across 50 years of selection. This finding of persistence in the distribution of genetic merit around the herd mean indicates that the common application of comparing performance of BPI quartiles within herds provides almost no insight into impacts of genetic selection on farm profit. Bioeconomic modelling revealed that the genetic gain of a herd achieving an annual rate of increase in herd BPI of around 10 units per year contributed an average of around $2,500 extra to farm profit per annum for a 250-cow herd representative farm. Applying more widely the findings and insights from modelling genetic gain in a representative pasture-based dairy farm suggests it is likely that that, on many, or even most, dairy farms, the gains in profit from cow genetic selection is likely to be modest in light of other investment opportunities and is thus not something to be focussed on to the effective exclusion of other more profitable resource uses. ‘Ignore the principle of equi-marginal returns to all inputs at your peril’ is sage farm management economics advice to those who believe that all animal farmers need do is to improve the genetic potential of their animals. Good advice to dairy farmers would be to: (i) have realistic expectations about the role of genetic gain in their business; (ii) evaluate returns from investment in herd genetics; and (iii) compare expected returns from investments into all limiting factors present on the farm.
Verification of Concurrent Data Structures with TLA

Concurrent systems have critical applications such as aviation. Due to their inherent complexity, mechanised verification is well suited for reasoning about the safety and liveness properties of such systems. Temporal logics, such as TLA and LTL, have been used to verify distributed systems and protocols. However, it is not clear whether these logics are good fits for modelling and verifying concurrent data structures. This work describes how Temporal Logic of Actions (TLA) can be adapted to handle concurrent data structures and weak memory models. It also shows how the TLA toolchain, especially the model checker, can aid in cleanly applying the logical machinery to concrete programs. I used litmus tests to validate my encoding of memory models against prior work. These models enabled me to formalize various concurrent data structures, including the Chase-Lev queue. Then, I am able to check the behaviours of these data structures against abstract specification of their operations. In particular, my modelling can successfully find bugs in a faulty implementation of the Chase-Lev queue. The results suggest that TLA is appropriate for modelling concurrent data structures. The formal models I designed and the related modelling techniques can be used by the wider research community in their verification work.
OPTIMIZATION OF MULTI PERIOD - MULTI LOCATION CONSTRUCTION PROJECTS CONSIDERING RESOURCE POOL AND BATCH ORDERING

During the past two decades, some industries have been moving towards project-centered systems in many modern countries. Therefore, managing simultaneous projects with considering the limitations in resources, equipment and manpower is very crucial. In the real world, project-based organizations are always facing with two main important features. First, the construction projects are decentralized and their distances are long, and second, there are several construction projects undertaken at different time periods. Therefore, appropriate selection of projects with regard to the capabilities of the organization may lead with increasing an expected profitability. This paper investigates the multi-period decentralized multi construction-project and scheduling problem subject to resource constraints, optimal resource pool location, deterioration and batch ordering of nonrenewable resources altogether, for the first time in the literature. In order to describe the problem under consideration in this paper and obtaining the optimal solutions, a mixed integer linear programming model is developed. Finally, the impact of decision integration on the profit profile of an organization is comprehensively investigated by solving numerical examples and through developing some heuristic methods.
Discovery and characterization of a Gram-positive Pel polysaccharide biosynthetic gene cluster

Our understanding of the biofilm matrix components utilized by Gram-positive bacteria, and the signalling pathways that regulate their production are largely unknown. In a companion study, we developed a computational pipeline for the unbiased identification of homologous bacterial operons and applied this algorithm to the analysis of synthase-dependent exopolysaccharide biosynthetic systems (https://doi.org/10.1101/769745). Here, we explore the finding that many species of Gram-positive bacteria have operons with similarity to the Pseudomonas aeruginosa pel locus. Our characterization of the pelDEADAFG operon from Bacillus cereus ATCC 10987, presented herein, demonstrates that this locus is required for biofilm formation and produces a polysaccharide structurally similar to Pel. We show that the degenerate GGDEF domain of the B. cereus PelD ortholog binds cyclic-3’,5’-dimeric guanosine monophosphate (c-di-GMP), and that this binding is required for biofilm formation. Finally, we identify a diguanylate cyclase, CdgF, and a c-di-GMP phosphodiesterase, CdgE, that reciprocally regulate the production of Pel. The discovery of this novel c-di-GMP regulatory circuit significantly contributes to our limited understanding of c-di-GMP signalling in Gram-positive organisms. Furthermore, conservation of the core pelDEADAFG locus amongst many species of Bacilli, Clostridia, Streptococci, and Actinobacteria suggests that Pel may be a common biofilm matrix component in many Gram-positive bacteria. Author summary The Pel polysaccharide is required for biofilm formation in P. aeruginosa and we have previously found that the genes necessary for biosynthesis of this polymer are broadly distributed across Gram-negative bacteria. Herein, we show that many species of Gram-positive bacteria also possess Pel biosynthetic genes and demonstrate that these genes are used Bacillus cereus for biofilm formation. We show that Pel production in B. cereus is regulated by c-di-GMP and have identified two enzymes, a diguanylate cyclase, CdgF, and a phosphodiesterase, CdgE, that control the levels of this bacterial signalling molecule. While Pel production in B. cereus also requires the binding of c-di-GMP to the receptor PelD, the divergence of this protein in Streptococci suggests a c-di-GMP independent mechanism of regulation is used in this species. The discovery of a Pel biosynthetic gene cluster in Gram-positive bacteria and our characterization of the pel operon in B. cereus suggests that Pel is a widespread biofilm component across all bacteria.