Configurational optimizer of combined cycle propulsion using genetic programming

In most engineering applications the optimization is employed after the conceptual design is already frozen with the only purpose of perfecting it. Although optimization algorithms capable of optimizing the configuration exist, their application is limited to electronics or control design, while for complex systems the conceptual design is often performed with manual trade off analyses among few options

Vehicle and mission design of a future small payload launcher

This paper presents the conceptual design and performance analysis of a partially reusable space launch vehicle for small payloads. The system uses a multi-stage vehicle with rocket engines, with a reusable first stage capable of glided or powered flight, and expendable upper stage(s) to inject a 500 kg payload in different low Earth orbits. The space access vehicle is designed to be air-launched from a modified aircraft carrier. The aim of the system design is to develop a commercially viable launch system for near-term operation, thus emphasis is placed on the efficient use of high TRL technologies. The vehicle design are analysed using a multi-disciplinary design optimisation approach to evaluate the performance, operational capabilities and design trade-offs

A commercially driven design approach to UK future small payload launch systems

Miniaturisation of satellite componentry, increasingly capable small sensors and substantial increases in processing capacity and transmission bandwidth are driving rapid growth in small payload development and consequential launch demand. The advent of horizontal take-off spaceports opens the door for a new generation of small payload launch systems that will fulfil this demand. However, the key to a launch system's success is its ability to provide a return on the substantial costs of development while delivering pricing levels commensurate with the needs of launch customers. Therefore, commercially led design approaches are needed to refine and optimise the design of the new small payload launch systems required. This approach was embodied in an ongoing UKSA funded NSTP2 project titled Future UK Small Payload Launcher (FSPLUK). The approach is first founded upon a bespoke and specific market assessment. This characterises, segments and quantifies the commercial opportunity and establishes principal desired system performance requirements. An assessment of available technologies at differing TRLs permits initial vehicle configuration options to be developed and technically assessed. Technically viable options are then assessed in terms of commercial viability with the best advanced into more detailed technical assessment and system optimisation. The resultant vehicles are again tested for commercial viability and, if successful, emerge as recommended development avenues. Using these methods, it has been possible to iterate design concepts from apparently simple yet economically sub-optimised stacked launcher systems through several design iterations to a resultant highly flexible and economically efficient conceptual design. The key finding relates to the inter-relationship between payload flexibility, in permitting maximised flight rates from a reasonably complex but highly reusable first stage design, and low disposable upper stage unit cost. This has driven the resultant system to feature an air launched integrated re-usable first stage vehicle, configured with a flexible internal payload bay from which one or more upper stages are deployed. This configuration maximises commercial utility and reusability. The resultant high flight rate allows development costs to be efficiently amortised with minimised direct launch costs. The configuration therefore meets low cost per kg price targets while delivering a positive return on development expenditure over life. It also provides a flight proven vehicle platform with available internal real-estate for application as a hypersonic air test platform for new propulsion systems, such as SABRE. The commercially led approach has created the foundation for viable and economically justifiable development

How to launch small payloads? Evaluation of current and future small payload launch systems

This paper describes a preferable vehicle classification alongside a brief description of key technologies available on the shelf or under development to address the demand of the small payload market. This is followed by a discussion on the investigation of the current market and the future forecast; regarding the delivery of small payloads into orbit

Bevacizumab plus XELOX as first-line treatment of metastatic colorectal cancer: The OBELIX study

AIM: To confirm the efficacy and safety of bevacizumab/XELOX combination for the treatment of locally advanced or metastatic colorectal cancer (CRC) in Italy. METHODS: This multicentric, prospective, open-label study included patients with CRC previously untreated with chemotherapy. Patients were administered bevacizumab in combination with XELOX. The primary efficacy end-point was progression-free survival (PFS). Secondary end-points included time to overall response (TOR), duration of response (DOR), time to treatment failure (TTF) and overall survival (OS). The incidence and type of adverse events AEs and severe AEs were evaluated. Also, the mutational status of BRAF and KRAS was assessed by high resolution melting and direct sequencing, and quality of life (QoL) was measured by the EuroQoL EQ-5D questionnaire at baseline and at the last visit. RESULTS: The intention-to-treat population included 197 patients (mean age: 62.3 ± 9.9 years, 56.4% males). At baseline, 16/34 evaluable subjects (47.1%) harbored a KRAS and/or a BRAF mutation; the mean QoL index was 80.2 ± 14.3. First-line therapy was given for 223.7 ± 175.9 d, and after a mean follow-up of 387.7 ± 238.8 d all patients discontinued from the study mainly for disease progression (PD, 45.4%) and AEs (25.4%). Median PFS was 9.7 mo (95%CI: 8.4-10.5) and the median values for secondary end-points were: TOR = 3.9 mo (95%CI: 2.6-4.7), DOR = 8.5 mo (95%CI: 7.3-10.3), TTF = 6.7 mo (95%CI: 6.0-7.7) and OS = 23.2 mo (95%CI: 20.1-27.2). Patients carrying at least one lesion had a lower overall response rate (66.7% vs 88.9%) and a lower probability of achieving complete or partial response than those without mutations, but the difference in relative risk was not statistically significant (P = 0.2). Mean EQ-5D-3L raw index score significantly decreased to 74.9 ± 19.1 at the last visit (signed-rank test, P = 0.0076), but in general the evaluation on QoL perceived by patients was good. CONCLUSION: The efficacy of bevacizumab in combination with XELOX in terms of PFS in patients with aCRC or mCRC in Italy was confirmed, with acceptable toxicity

Social brain, social dysfunction and social withdrawal

The human social brain is complex. Current knowledge fails to define the neurobiological processes underlying social behaviour involving the (patho-) physiological mechanisms that link system-level phenomena to the multiple hierarchies of brain function. Unfortunately, such a high complexity may also be associated with a high susceptibility to several pathogenic interventions. Consistently, social deficits sometimes represent the first signs of a number of neuropsychiatric disorders including schizophrenia (SCZ), Alzheimer's disease (AD) and major depressive disorder (MDD) which leads to a progressive social dysfunction. In the present review we summarize present knowledge linking neurobiological substrates sustaining social functioning, social dysfunction and social withdrawal in major psychiatric disorders. Interestingly, AD, SCZ, and MDD affect the social brain in similar ways. Thus, social dysfunction and its most evident clinical expression (i.e., social withdrawal) may represent an innovative transdiagnostic domain, with the potential of being an independent entity in terms of biological roots, with the perspective of targeted interventions

Social brain, social dysfunction and social withdrawal

The human social brain is complex. Current knowledge fails to define the neurobiological processes underlying social behaviour involving the (patho-) physiological mechanisms that link system-level phenomena to the multiple hierarchies of brain function. Unfortunately, such a high complexity may also be associated with a high susceptibility to several pathogenic interventions. Consistently, social deficits sometimes represent the first signs of a number of neuropsychiatric disorders including schizophrenia (SCZ), Alzheimer's disease (AD) and major depressive disorder (MDD) which leads to a progressive social dysfunction. In the present review we summarize present knowledge linking neurobiological substrates sustaining social functioning, social dysfunction and social withdrawal in major psychiatric disorders. Interestingly, AD, SCZ, and MDD affect the social brain in similar ways. Thus, social dysfunction and its most evident clinical expression (i.e., social withdrawal) may represent an innovative transdiagnostic domain, with the potential of being an independent entity in terms of biological roots, with the perspective of targeted interventions

Toward automated design of Combined Cycle Propulsion

One means to reduce both the cost and the risk associated with space missions is to employ a vehicle designed within the re-usable, airliner-like 'space plane' paradigm. Key to the practicality of such vehicles is the further development of Combined Cycle Propulsion technology. In this thesis, a new engineering tool called the HYbrid PRopulsion Optimizer (HyPro) is presented, with the aim of analysing the performance of diverse engine concepts. The tool is conceived to be modular and flexible, and makes use of parsimonious modelling, in order to describe the engine at an high level of abstraction and to be fast in execution.A configurational optimizer has also been developed in order to automatically generate new design concepts, optimizing the engine cycle structure. It is conceived to be used at the beginning of development in order to perform an automatic and objective trade-off of possible propulsion solutions.In this work the model has been implemented for Rocket-Based Combined Cycle, and it has been verified and validated against analytical models, computational fluid dyanamic analyses and experimental data. The design proposed by the optimizer in these conditions was coherent with manually designed Combined Cycle Propulsion engines, demonstrating the HyPro's capability to converge on good solutions.The results, although preliminary, are very promising and represent a novelty in the field, since a configurational optimization, in the field of propulsion concepts, has never been attempted before.The results presented here demonstrate that the configurational optimization of engine design is viable.The next steps to produce a practical optimizer, which delivers robust and innovative engine solutions, are the addition of modelling capabilities beyond the Rocket-Based Combined Cycle and analysis discipline beyond the pure performances.One means to reduce both the cost and the risk associated with space missions is to employ a vehicle designed within the re-usable, airliner-like 'space plane' paradigm. Key to the practicality of such vehicles is the further development of Combined Cycle Propulsion technology. In this thesis, a new engineering tool called the HYbrid PRopulsion Optimizer (HyPro) is presented, with the aim of analysing the performance of diverse engine concepts. The tool is conceived to be modular and flexible, and makes use of parsimonious modelling, in order to describe the engine at an high level of abstraction and to be fast in execution.A configurational optimizer has also been developed in order to automatically generate new design concepts, optimizing the engine cycle structure. It is conceived to be used at the beginning of development in order to perform an automatic and objective trade-off of possible propulsion solutions.In this work the model has been implemented for Rocket-Based Combined Cycle, and it has been verified and validated against analytical models, computational fluid dyanamic analyses and experimental data. The design proposed by the optimizer in these conditions was coherent with manually designed Combined Cycle Propulsion engines, demonstrating the HyPro's capability to converge on good solutions.The results, although preliminary, are very promising and represent a novelty in the field, since a configurational optimization, in the field of propulsion concepts, has never been attempted before.The results presented here demonstrate that the configurational optimization of engine design is viable.The next steps to produce a practical optimizer, which delivers robust and innovative engine solutions, are the addition of modelling capabilities beyond the Rocket-Based Combined Cycle and analysis discipline beyond the pure performances

Legacy Media: A Case for Creative Destruction?

Digital media have transformed the journalistic profession in decisive ways, so much so that journalism has become fuzzy and its borders and standards have been blurred. In this theoretical, narrative paper, we look at some implications of the process for media management, as organizations try to cope with a new kind of media ecology. The digital transformation has brought to light concerns about responsibility and standards that spark a healthy debate about the future of “legacy media,” with interesting precedents in the past