Reconfigurable modelling of physically based systems: Dynamic modelling and optimisation for product design and development applied to the automotive drivetrain system.

The work of this thesis is concerned with the aggregation and advancement of modelling practise as used within modern day product development and optimisation environments making use of Model Based Design (¿MBD¿) and similar procedures. A review of model development and use forms the foundation of the work, with the findings being aggregated into two unique approaches for rapid model development and reconfiguration; the Plug-and-Simulate (¿PaS¿) approach and the Paradigm for Large Model Creation (¿PLMC¿); each shown to posses its own advantages. To support the MBD process a model optimisation algorithm that seeks to eliminate parameters that are of little or no significance to a simulation is developed. Eliminations are made on the basis of an energy analysis which determines the activity of a number of energy elements. Low activity elements are said to be of less significance to the global dynamics of a model and thus become targets for elimination. A model configuration tool is presented that brings together the PLMC and parameter elimination algorithm. The tool is shown to be useful for rapid configuration and reconfiguration of models and is capable of automatically running the optimisation algorithms thus producing a simulation model that is parametrically and computationally optimised. The response of the plug-and-simulate drivetrain submodels, assembled to represent a front wheel drive drivetrain, is examined. The resulting model is subjected to a torque step-input and an empirically obtained torque curve that characterises the input to a drivetrain undergoing steady acceleration. The model displays the expected response in both its full parameter and parameter reduced versions with simulation efficiency gains observed in the parameter reduced version.EPSR

Simulating the Influence of Injection Timing, Premixed Ratio, and Inlet Temperature on Natural Gas / Diesel Dual-Fuel HCCI Combustion in a Diesel Engine

YesDual-fuel HCCI engines allow a relatively small quantity of diesel fuel to be used to ignite a variety of fuels such as natural gas or methane in HCCI mode. The gaseous fuel is mixed with the incoming air, and diesel fuel is sprayed into the cylinder by direct injection. Mathematical modelling is used to investigate the effects of parameters such as premixed ratio (fuel ratio) and pilot fuel injection timing on combustion of a dual-fuel HCCI engines. A CFD package is used with AVL FIRE software to simulate dual-fuel HCCI combustion in detail. The results establish a suitable range of premixed ratio and liquid fuel injection timing for low levels of NOx, CO and HC emissions along with a reliable and efficient combustion. Dual-fuel HCCI mode can increase NOx emission with lower premixed ratios in comparison to normal HCCI engines, but it is shown that the NOx emission reduces above a certain level of the premixed ratio. Due to the requirement of homogenous mixing of liquid fuel with air, the liquid fuel injection is earlier than for diesel engines. It is shown that, with careful control of parameters, dual-fuel HCCI engines have lower emissions in comparison with conventional engines

Bi-fuel SI Engine Model for Analysis and Optimization

YesThe natural gas as an alternative fuel has economical and environmental benefits. Bi-fuel engines powered by gasoline and compressed natural gas (CNG) are an intermediate and alternative step to dedicated CNG engines. The conversion to bi-fuel CNG engine could be a short-term solution to air pollution problem in many developing countries. In this paper a mathematical model of a bi-fuel four-stroke spark ignition (SI) engine is presented for comparative studies and analysis. It is based on the two-zone combustion model, and it has the ability to simulate turbulent combustion. The model is capable of predicting the cylinder temperature and pressure, heat transfer, brake work , brake thermal and volumetric efficiency, brake torque, brake specific fuel consumption (BSFC), brake mean effective pressure (BMEP), concentration of CO2, brake specific CO (BSCO) and brake specific NOx (BSNOx). The effect of engine speed, equivalence ratio and performance parameters using gasoline and CNG fuels are analysed. The model has been validated by experimental data using the results obtained from a bi-fuel engine. The results show the capability of the model in terms of engine performance optimization and minimization of the emissions. The engine used in this study is a typical example of a modified bi-fuel engine conversion, which could benefit the researchers in the field

Niraparib in patients with metastatic castration-resistant prostate cancer and DNA repair gene defects (GALAHAD):a multicentre, open-label, phase 2 trial

Background: Metastatic castration-resistant prostate cancers are enriched for DNA repair gene defects (DRDs) that can be susceptible to synthetic lethality through inhibition of PARP proteins. We evaluated the anti-tumour activity and safety of the PARP inhibitor niraparib in patients with metastatic castration-resistant prostate cancers and DRDs who progressed on previous treatment with an androgen signalling inhibitor and a taxane. Methods: In this multicentre, open-label, single-arm, phase 2 study, patients aged at least 18 years with histologically confirmed metastatic castration-resistant prostate cancer (mixed histology accepted, with the exception of the small cell pure phenotype) and DRDs (assessed in blood, tumour tissue, or saliva), with progression on a previous next-generation androgen signalling inhibitor and a taxane per Response Evaluation Criteria in Solid Tumors 1.1 or Prostate Cancer Working Group 3 criteria and an Eastern Cooperative Oncology Group performance status of 0–2, were eligible. Enrolled patients received niraparib 300 mg orally once daily until treatment discontinuation, death, or study termination. For the final study analysis, all patients who received at least one dose of study drug were included in the safety analysis population; patients with germline pathogenic or somatic biallelic pathogenic alterations in BRCA1 or BRCA2 (BRCA cohort) or biallelic alterations in other prespecified DRDs (non-BRCA cohort) were included in the efficacy analysis population. The primary endpoint was objective response rate in patients with BRCA alterations and measurable disease (measurable BRCA cohort). This study is registered with ClinicalTrials.gov, NCT02854436. Findings: Between Sept 28, 2016, and June 26, 2020, 289 patients were enrolled, of whom 182 (63%) had received three or more systemic therapies for prostate cancer. 223 (77%) of 289 patients were included in the overall efficacy analysis population, which included BRCA (n=142) and non-BRCA (n=81) cohorts. At final analysis, with a median follow-up of 10·0 months (IQR 6·6–13·3), the objective response rate in the measurable BRCA cohort (n=76) was 34·2% (95% CI 23·7–46·0). In the safety analysis population, the most common treatment-emergent adverse events of any grade were nausea (169 [58%] of 289), anaemia (156 [54%]), and vomiting (111 [38%]); the most common grade 3 or worse events were haematological (anaemia in 95 [33%] of 289; thrombocytopenia in 47 [16%]; and neutropenia in 28 [10%]). Of 134 (46%) of 289 patients with at least one serious treatment-emergent adverse event, the most common were also haematological (thrombocytopenia in 17 [6%] and anaemia in 13 [4%]). Two adverse events with fatal outcome (one patient with urosepsis in the BRCA cohort and one patient with sepsis in the non-BRCA cohort) were deemed possibly related to niraparib treatment. Interpretation: Niraparib is tolerable and shows anti-tumour activity in heavily pretreated patients with metastatic castration-resistant prostate cancer and DRDs, particularly in those with BRCA alterations. Funding: Janssen Research & Development

Assessing Natural Resource Use by Forest-Reliant Communities in Madagascar Using Functional Diversity and Functional Redundancy Metrics

Biodiversity plays an integral role in the livelihoods of subsistence-based forest-dwelling communities and as a consequence it is increasingly important to develop quantitative approaches that capture not only changes in taxonomic diversity, but also variation in natural resources and provisioning services. We apply a functional diversity metric originally developed for addressing questions in community ecology to assess utilitarian diversity of 56 forest plots in Madagascar. The use categories for utilitarian plants were determined using expert knowledge and household questionnaires. We used a null model approach to examine the utilitarian (functional) diversity and utilitarian redundancy present within ecological communities. Additionally, variables that might influence fluctuations in utilitarian diversity and redundancy—specifically number of felled trees, number of trails, basal area, canopy height, elevation, distance from village—were analyzed using Generalized Linear Models (GLMs). Eighteen of the 56 plots showed utilitarian diversity values significantly higher than expected. This result indicates that these habitats exhibited a low degree of utilitarian redundancy and were therefore comprised of plants with relatively distinct utilitarian properties. One implication of this finding is that minor losses in species richness may result in reductions in utilitarian diversity and redundancy, which may limit local residents' ability to switch between alternative choices. The GLM analysis showed that the most predictive model included basal area, canopy height and distance from village, which suggests that variation in utilitarian redundancy may be a result of local residents harvesting resources from the protected area. Our approach permits an assessment of the diversity of provisioning services available to local communities, offering unique insights that would not be possible using traditional taxonomic diversity measures. These analyses introduce another tool available to conservation biologists for assessing how future losses in biodiversity will lead to a reduction in natural resources and provisioning services from forests

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion