Report on BCTCS 2016: The 32nd British Colloquium for Theoretical Computer Science 22–24 March 2016, Queen’s University Belfast

Report on BCTCS 2016: The 32nd British Colloquium for Theoretical Computer Science 22–24 March 2016, Queen’s University Belfas

Prognostic and predictive value of liquid biopsy-derived androgen receptor variant 7 (AR-V7) in prostate cancer : a systematic review and meta-analysis

In advanced prostate cancer, access to recent diagnostic tissue samples is restricted and this affects the analysis of the association of evolving biomarkers such as AR-V7 with metastatic castrate resistance. Liquid biopsies are emerging as alternative analytes. To clarify clinical value of AR-V7 detection from liquid biopsies, here we performed a meta-analysis on the prognostic and predictive value of androgen receptor variant 7 (AR-V7) detected from liquid biopsy for patients with prostate cancer (PC), three databases, the Embase, Medline, and Scopus were searched up to September 2021. A total of 37 studies were included. The effects of liquid biopsy AR-V7 status on overall survival (OS), radiographic progression-free survival (PFS), and prostate-specific antigen (PSA)-PFS were calculated with RevMan 5.3 software. AR-V7 positivity detected in liquid biopsy significantly associates with worse OS, PFS, and PSA-PFS (P <0.00001). A subgroup analysis of patients treated with androgen receptor signaling inhibitors (ARSi such as abiraterone and enzalutamide) showed a significant association of AR-V7 positivity with poorer OS, PFS, and PSA-PFS. A statistically significant association with OS was also found in taxane-treated patients (P = 0.04), but not for PFS (P = 0.21) or PSA-PFS (P = 0.93). For AR-V7 positive patients, taxane treatment has better OS outcomes than ARSi (P = 0.01). Study quality, publication bias and sensitivity analysis were integrated in the assessment. Our data show that liquid biopsy AR-V7 is a clinically useful biomarker that is associated with poor outcomes of ARSi-treated castrate resistant PC (CRPC) patients and thus has the potential to guide patient management and also to stratify patients for clinical trials. More studies on chemotherapy-treated patients are warranted. Systematic Review Registration: PROSPERO, CRD42021239353

Sintesis dan Karakterisasi TiO2-Karbon Aktif Tempurung Kelapa sebagai Photocatalyst Agent dalam Pengolahan Limbah Cair Batik

Produksi industri batik banyak menggunakan bahan kimia dan pewarna sintetis dalam proses produksinya. Limbah cair yang dihasilkan, apabila tidak diolah akan menyebabkan pencemaran lingkungan. Salah satu metode alternatif dalam pengolahan limbah cair batik yaitu metode fotokatalis. Kelebihan metode fotokatalis yaitu dapat mendegradasi bahan anorganik dan bahan organik, biaya operasi yang rendah dan ramah lingkungan. Penelitihan ini bertujuan sintesis dan karakterisasi TiO2/C sebagai photocatalyst agent dalam pengolahan limbah cair batik. Karakterisasi yang digunakan meliputi pengujian kualitas arang aktif teknis, FTIR, dan XRD. Kualitas karbon aktif telah memenuhi (SNI) 06-3730-1995 tentang syarat mutu karbon aktif teknis powder. Pengujian XRD dari hasil sintesis didapatkan TiO2 tipe anatase. Hasil pengujian FTIR karbon aktif terbaca gugus fungsi O-H, C=C, C-O dan gugus C-C. FTIR TiO2 dan sintesis TiO2/C terbaca gugus Ti-O-C dan Ti-O-Ti

Analysis of AR/AR-V7signalling pathways in circulating tumour cells of prostate cancer patients

Biomarkers detected in liquid biopsy (such as circulating tumour cells, CTCs) demonstrate high concordance with biomarkers detected in conventional tissue biopsy. Prostate cancer, when metastatic, is treated with androgen deprivation therapy (ADT). However, resistance to ADT evolves into a clinical state referred to as castrate resistant prostate cancer (CRPC), in which increased, abnormal, androgen receptor (AR) signalling through changed AR structures (amplification, point mutations or variant expression) occurs. Although CRPC also facilitates development of other, complex signalling pathways that promote cell survival, our hypothesis is that the abnormal AR signalling is tightly linked to PTEN/AKT and Hippo/YAP pathways that contribute to the oncogenic driver role that confers ADT resistance. This PhD project aims to evaluate the role of AR, PTEN, and Hippo driver pathways in CRPC through analysis of CTCs, which have become important biological correlates and sources to study tumour biology in prostate cancer. The main focus was on the AR splice variant 7 (ARV7), a promising predictive and prognostic CRPC biomarker. The overall outcomes of this PhD project were to (i) investigate the role of AR, PTEN, and Hippo pathways implicated in CRPC, (ii) validate liquid-biopsy-detected AR-V7 as a CRPC biomarker, (iii) define the best antibody to detect AR-V7 CTCs in CRPC patient blood, and (iv) optimise methods that enable multiplex immunocytostaining of prostate cancer cells, including CTCs with a view to conduct ‘proteomic microscopy’ in the future. This work in this PhD puts in place basic procedures and methods that will enable CTC multiplex “proteomic microscopy” a method that could change the current paradigm of CTC analysis by allowing analysis of these rare cells for multiple markers targeting multiple biological pathways at the same time

An Evaluation of LFUCG Economic Development: Making Strides Towards Strategic, Performance-Driven Partnerships

Like many other municipal governments, Lexington utilizes a web of partnerships to support economic development. These relationships take many forms; LFUCG employs grants, tax incentives for businesses, and contracts with other organizations. Unlike some of its peers, though, LFUCG does not have a strategic plan in place to drive decision-making processes and sharpen its focus on outcomes. This report sets the foundation for future strategic management efforts by identifying opportunities and weaknesses that might be addressed by LFUCG through an environmental scan and establishing a performance management framework for existing contractual economic development partners. The key findings are as follows: There are two informal priorities that drive economic development policy. Through its efforts, LFUCG seeks to increase wages and increase jobs in Lexington. These two priorities can be leveraged to capture return on investment across programs and time. While LFUCG is not responsible for all aspects of economic development, there is an opportunity to better coordinate strategy between stakeholders, both locally and regionally. For example, while human capital is a focus of many external institutions in Lexington, there are not a great deal of municipal resources dedicated to this pillar of economic development. Furthermore, while many resources focus on business development, there is very little evident strategy that is neighborhood-based, even as there are large disparities between areas of Lexington in key economic indicators. While at least one economic development partner, Commerce Lexington, provides extensive quantitative performance metrics, there is an opportunity to align new metrics across financial partners with their respective logic models and LFUCG’s informal development priorities

Security of electric power systems : cascading outage analysis, interdiction model and resilience to natural disasters

textSecure electric power system operation is key to social warfare. However, recent years have seen numerous natural disasters and terrorist attacks that threat the grid security. This dissertation summarizes the efforts to develop a model to analyze cascading outages, an interdiction model to analyze worst-case attacks on power grids, and research on grid resilience to natural disasters. The developed cascading outage analysis model uses outage checkers to systematically simulate the system behavior after an initial disturbance, and calculate the potential cascading outage path and electric load shedding. The new interdiction model combines the previously developed medium-term attack-defense model with the short-term cascading outage analysis model to find worst-case terrorist attack. The dissertation also reviews the research on power grid resilience to natural disaster, and develops a framework to simulate the impacts of hurricanes.Electrical and Computer Engineerin

Quantifying Underspecification in Machine Learning with Explainable AI

To evaluate a trained machine learning (ML) model’s performance, it is general practice to test its performance by predicting targets from a held-out testing set. For such a dataset, various models can be constructed with different reasoning that produce near-optimal test performance. However, due to this variance in reasoning some models can generalise, whilst some perform unexpectedly on further unseen data. The existence of multiple equally performing models exhibits underspecification of the ML pipeline used for producing such models. Underspecification poses challenges towards the credibility of such test performance evaluations and has been identified as a key reason why many models that perform well in testing, exhibit poor performance in deployment.In this work, we propose identifying underspecification by estimating the variance of reasoning within a set of near-optimal models produced by a pipeline, also called a Rashomon set. We iteratively train models using the same pipeline to produce an em-pirical Rashomon set of a fixed size. In order to quantify the variation of models within this Rashomon set, we measure the variation of SHapley Additive exPlanations that the models produce using a variety of metrics. This provides us with an index representing the variation of reasoning within this Rashomon set, and thus the pipeline. This index therefore represents the extent of underspecification the pipeline exhibits.We provide an implementation for this approach, and make it publicly available on github. We validate that this implementation shows the trends we expect using evaluation techniques previously used to prove the existence of underspecification. Fur-thermore, we demonstrate our approach on multiple datasets drawn from the literature, and in a COVID-19 virus transmission case study

Agoric computation: trust and cyber-physical systems

In the past two decades advances in miniaturisation and economies of scale have led to the emergence of billions of connected components that have provided both a spur and a blueprint for the development of smart products acting in specialised environments which are uniquely identifiable, localisable, and capable of autonomy. Adopting the computational perspective of multi-agent systems (MAS) as a technological abstraction married with the engineering perspective of cyber-physical systems (CPS) has provided fertile ground for designing, developing and deploying software applications in smart automated context such as manufacturing, power grids, avionics, healthcare and logistics, capable of being decentralised, intelligent, reconfigurable, modular, flexible, robust, adaptive and responsive. Current agent technologies are, however, ill suited for information-based environments, making it difficult to formalise and implement multiagent systems based on inherently dynamical functional concepts such as trust and reliability, which present special challenges when scaling from small to large systems of agents. To overcome such challenges, it is useful to adopt a unified approach which we term agoric computation, integrating logical, mathematical and programming concepts towards the development of agent-based solutions based on recursive, compositional principles, where smaller systems feed via directed information flows into larger hierarchical systems that define their global environment. Considering information as an integral part of the environment naturally defines a web of operations where components of a systems are wired in some way and each set of inputs and outputs are allowed to carry some value. These operations are stateless abstractions and procedures that act on some stateful cells that cumulate partial information, and it is possible to compose such abstractions into higher-level ones, using a publish-and-subscribe interaction model that keeps track of update messages between abstractions and values in the data. In this thesis we review the logical and mathematical basis of such abstractions and take steps towards the software implementation of agoric modelling as a framework for simulation and verification of the reliability of increasingly complex systems, and report on experimental results related to a few select applications, such as stigmergic interaction in mobile robotics, integrating raw data into agent perceptions, trust and trustworthiness in orchestrated open systems, computing the epistemic cost of trust when reasoning in networks of agents seeded with contradictory information, and trust models for distributed ledgers in the Internet of Things (IoT); and provide a roadmap for future developments of our research

Event-B in the Institutional Framework: Defining a Semantics, Modularisation Constructs and Interoperability for a Specification Language

Event-B is an industrial-strength specification language for verifying the properties of a given system’s specification. It is supported by its Eclipse-based IDE, Rodin, and uses the process of refinement to model systems at different levels of abstraction. Although a mature formalism, Event-B has a number of limitations. In this thesis, we demonstrate that Event-B lacks formally defined modularisation constructs. Additionally, interoperability between Event-B and other formalisms has been achieved in an ad hoc manner. Moreover, although a formal language, Event-B does not have a formal semantics. We address each of these limitations in this thesis using the theory of institutions. The theory of institutions provides a category-theoretic way of representing a formalism. Formalisms that have been represented as institutions gain access to an array of generic specification-building operators that can be used to modularise specifications in a formalismindependent manner. In the theory of institutions, there are constructs (known as institution (co)morphisms) that provide us with the facility to create interoperability between formalisms in a mathematically sound way. The main contribution of this thesis is the definition of an institution for Event-B, EVT, which allows us to address its identified limitations. To this end, we formally define a translational semantics from Event- B to EVT. We show how specification-building operators can provide a unified set of modularisation constructs for Event-B. In fact, the institutional framework that we have incorporated Event-B into is more accommodating to modularisation than the current state-of-the-art for Rodin. Furthermore, we present institution morphisms that facilitate interoperability between the respective institutions for Event-B and UML. This approach is more generic than the current approach to interoperability for Event-B and in fact, allows access to any formalism or logic that has already been defined as an institution. Finally, by defining EVT, we have outlined the steps required in order to include similar formalisms into the institutional framework. Hence, this thesis acts as a template for defining an institution for a specification language