Transforming traditional mechanical and electrical construction to a modern process of assembly

This thesis presents the findings of a research project to develop and implement a Lean and agile Construction System on a case study project. The aim of the research project, for the sponsor company, was to improve its projects site operations, making them safer for the worker and improving effectiveness and productivity. The findings have shown that the Construction System has proved to be a successful set of countermeasures that act as an antidote to the health, safety and productivity problems that exist in UK construction and that face the sponsor company. The System has been implemented on a large and complex mechanical and electrical case study project in the healthcare sector of UK construction. The outcome of this case study project shows that 37% less onsite labour was needed, meaning fewer workers were exposed to health and safety risks from site operations, leading to zero reportable accidents. Good ergonomics was achieved by focussing on workplace design, thus improving workers wellbeing, together with an improved quality of work for those required on site carrying out simpler assembly tasks. Productivity gains resulted by eliminating process waste, therefore reducing the risk of labour cost escalation that could otherwise have occurred. A 7% direct labour cost reduction was made meaning the labour budget allocation was maintained. Significantly, an overall productivity of 116% was achieved using the Construction System, which compares favourably to BSRIA’s findings of an average overall productivity of only 37% when compared to observed best practice for the projects in that case study research. The results include the benefits found from the use of an innovative method to assemble, transport, and install frameless, preassembled mechanical and electrical services modules, where a 93% reduction in onsite labour was achieved together with an 8.62% cost benefit. No time slippage was experienced during onsite assembly to delay or disrupt other trades and the commissioning programme was not compressed that could otherwise have caused problems in handing over the facility to the customer. From a customer’s perspective, the built facilities were handed over on-time, to their satisfaction and to budget. The research has achieved two levels of innovation, one at a process level and one at a product level. The process innovation is the development and successful implementation of the Construction System, which is a combination of methods acting together as an antidote to the research problem. The product innovation is the development of the innovative method for assembling, transporting and installing frameless mechanical and electrical corridor modules, whereby modularisation can be achieved with or without an offsite manufacturing capability. The System is built on Lean principles and has been shown to standardise the work, process and products to create flow, pull and value delivery. It is transferable across the sponsor company’s business as well as the wider industry itself. The transformation that has occurred is the creation of a step-change in undertaking mechanical and electrical construction work, which has realised a significant improvement in performance for CHt that has “Transformed Traditional Mechanical and Electrical Construction into a Modern Process of Assembly”

Microsecond resolution of quasiparticle tunneling in the single-Cooper-pair-transistor

We present radio-frequency measurements on a single-Cooper-pair-transistor in which individual quasiparticle poisoning events were observed with microsecond temporal resolution. Thermal activation of the quasiparticle dynamics is investigated, and consequently, we are able to determine energetics of the poisoning and un-poisoning processes. In particular, we are able to assign an effective quasiparticle temperature to parameterize the poisoning rate.Comment: 4 pages, 4 fig

Computer-Aided Detection of Pathologically Enlarged Lymph Nodes On Non-Contrast CT In Cervical Cancer Patients For Low-Resource Settings

The mortality rate of cervical cancer is approximately 266,000 people each year, and 70% of the burden occurs in Low- and Middle- Income Countries (LMICs). Radiation therapy is the primary modality for treatment of locally advanced cervical cancer cases. In the absence of high quality diagnostic imaging needed to identify nodal metastasis, many LMIC sites treat standard pelvic fields, failing to include node metastasis outside of the field and/or to boost lymph nodes in the abdomen and pelvis. The first goal of this project was to create a program which automatically identifies positive cervical cancer lymph nodes on non-contrast daily CT images, which are widely available in LMICs(1). A region of interest which is likely to contain the nodal volumes relevant for cervical cancer was defined on a single patient CT(2). This region was deformed onto new patients using an in-house, demons-based deformation software. Edge detection and erosion filtering were used to distinguish potential positive nodes from normal structures. Regions on adjacent slices were then connected into a potential nodal 3D-structure. To differentiate these 3D structures from normal tissues, eighty-six features were generated based on the shape and mean pixel values of the structures, and four classification ensemble methods were tested to differentiate the positive nodes from normal tissues. A cohort of fifty-eight MD Anderson cervical cancer patients with pathologically enlarged lymph nodes were used as a training-test set. Similarly, twenty MD Anderson cervical cancer patients were obtained as a validation set. They contained 154 and 35 pathologically enlarged lymph nodes, respectively. Model comparison led to the selection of the Adaboost ensemble model, utilizing 17 features. In the validation set, 60% of the clinically significant positive cervical cancer nodes were identified along with a false/true positive ratio of ~4:1. The entire process takes approximately 10/number-of-cores-minutes. Our findings demonstrated that our computer-aided detection model can assist in the identification of metastatic nodal disease where high quality diagnostic imaging is not readily available. By identifying these nodes, radiation treatment fields can be modified to include pathologically enlarged lymph nodes, which is an essential element to providing potentially curative radiotherapy for cervical cancer

Calibration strategies for use of the nanoDot OSLD in CT applications.

Aluminum oxide based optically stimulated luminescent dosimeters (OSLD) have been recognized as a useful dosimeter for measuring CT dose, particularly for patient dose measurements. Despite the increasing use of this dosimeter, appropriate dosimeter calibration techniques have not been established in the literature; while the manufacturer offers a calibration procedure, it is known to have relatively large uncertainties. The purpose of this work was to evaluate two clinical approaches for calibrating these dosimeters for CT applications, and to determine the uncertainty associated with measurements using these techniques. Three unique calibration procedures were used to calculate dose for a range of CT conditions using a commercially available OSLD and reader. The three calibration procedures included calibration (a) using the vendor-provided method, (b) relative to a 120 kVp CT spectrum in air, and (c) relative to a megavoltage beam (implemented with 60 Co). The dose measured using each of these approaches was compared to dose measured using a calibrated farmer-type ion chamber. Finally, the uncertainty in the dose measured using each approach was determined. For the CT and megavoltage calibration methods, the dose measured using the OSLD nanoDot was within 5% of the dose measured using an ion chamber for a wide range of different CT scan parameters (80-140 kVp, and with measurements at a range of positions). When calibrated using the vendor-recommended protocol, the OSLD measured doses were on average 15.5% lower than ion chamber doses. Two clinical calibration techniques have been evaluated and are presented in this work as alternatives to the vendor-provided calibration approach. These techniques provide high precision for OSLD-based measurements in a CT environment

A cyclic peptide inhibitor of HIF-1 heterodimerization that inhibits hypoxia signaling in cancer cells

Hypoxia inducible factor-1 (HIF-1) is a heterodimeric transcription factor that acts as the master regulator of cellular response to reduced oxygen levels, thus playing a key role in the adaptation, survival and progression of tumors. Here we report cyclo-CLLFVY, identified from a library of 3.2 million cyclic hexapeptides using a genetically encoded high-throughput screening platform, as an inhibitor of the HIF-1α/HIF-1β protein-protein interaction in vitro and in cells. The identified compound inhibits HIF-1 dimerization and transcription activity by binding to the PAS-B domain of HIF-1α, reducing HIF-1-mediated hypoxia response signaling in a variety of cell lines, without affecting the function of the closely related HIF-2 isoform. The reported cyclic peptide demonstrates the utility of our high-throughput screening platform for the identification of protein-protein interaction inhibitors, and forms the starting point for the development of HIF-1 targeted cancer therapeutics

Activation of the Unfolded Protein Response Enhances Motor Recovery after Spinal Cord Injury

Spinal cord injury (SCI) is a major cause of paralysis, and involves multiple cellular and tissular responses including demyelination, inflammation, cell death and axonal degeneration. Recent evidence suggests that perturbation on the homeostasis of the endoplasmic reticulum (ER) is observed in different SCI models; however, the functional contribution of this pathway to this pathology is not known. Here we demonstrate that SCI triggers a fast ER stress reaction (1–3 h) involving the upregulation of key components of the unfolded protein response (UPR), a process that propagates through the spinal cord. Ablation of X-box-binding protein 1 (XBP1) or activating transcription factor 4 (ATF4) expression, two major UPR transcription factors, leads to a reduced locomotor recovery after experimental SCI. The effects of UPR inactivation were associated with a significant increase in the number of damaged axons and reduced amount of oligodendrocytes surrounding the injury zone. In addition, altered microglial activation and pro-inflammatory cytokine expression were observed in ATF4 deficient mice after SCI. Local expression of active XBP1 into the spinal cord using adeno-associated viruses enhanced locomotor recovery after SCI, and was associated with an increased number of oligodendrocytes. Altogether, our results demonstrate a functional role of the UPR in SCI, offering novel therapeutic targets to treat this invalidating condition

Axonal degeneration induced by glutamate-excitotoxicity is mediated by necroptosis

Neuronal excitotoxicity induced by glutamate leads to cell death and functional impairment in a variety of central nervous system pathologies. Glutamate-mediated excitotoxicity triggers neuronal apoptosis in the cell soma as well as degeneration of axons and dendrites by a process associated to calcium increase and mitochondrial dysfunction. Importantly, degeneration of axons initiated by diverse stimuli, including excitotoxicity, has been proposed as an important pathological event leading to functional impairment in neurodegenerative conditions. Here we demonstrate that excitotoxicity-induced axonal degeneration proceeds by a mechanism dependent on the necroptotic kinases RIPK1, RIPK3 and the necroptotic mediator MLKL. Inhibition of RIPK1, RIPK3 or MLKL prevent key steps in the axonal degeneration cascade including mitochondrial depolarization, the opening of the permeability transition pore and calcium dysregulation in the axon. Interestingly, the same excitotoxic stimuli lead to apoptosis in the cell soma, demonstrating the co-activation of two independent degenerative mechanisms in different compartments of the same cell. The identification of necroptosis as a key mechanism of axonal degeneration after excitotoxicity is an important initial step to develop novel therapeutic strategies for nervous system disorders

Modular assembly with postponement to improve health, safety, and productivity in construction

This paper presents the outcome of an engineering study as part of the design and development of a lean and agile construction system and in particular its supply chain component. This combines modular assembly with a postponement function to be tested on a case study project (not reported here), the objective of which is to improve health, safety, and productivity for the company sponsoring the research. The contribution to research is the combination of countermeasures described in this paper that have been developed and incorporated into a wider construction system, in the same way that manufacturing has used this strategy with great success. A further output is the development and use of an innovative method for assembling, transporting, and installing mechanical and electrical modules, whereby modularization can be achieved with or without offsite manufacturing capability. The research forecasts a reduction of onsite labor of 35% compared to using traditional methods of construction, with less onsite operatives at risk of injury carrying out simpler assembly tasks within ergonomic mobile work cells. Further research is proposed to measure the benefits of the construction system following its implementation on a case study project

The Soviet Union in Southeast Asia

In this monograph Dr Fedor Mediansky and Ms Dianne Court examine Soviet interests in Southeast Asia. Their principle focus is on the contemporary (post-1975) period and the discussion in centred more on Indochina than in the rest of the region. While the Soviet Union's involvement in the region goes back to its Comintern links with local communist movements in the 1920s, the region has been, and remains, of secondary interest to Moscow. The authors find that Moscow's considerable involvement with communist Vietnam stands in contrast to its more discontinuous and rather marginal involvement with the ASEAN states. The close relations that now prevail between Moscow and Hanoi are based on a complex of factors. Parallel strategic concerns and a measure of regional strategic interdependence, long standing ideological links and the isolation of both in Southeast Asia play a large part in the current relationship. So far as the future is concerned, the authors argue that Soviet-Vietnamese relations are bound to remain close while the two continue to regard China as endangering their security and so long as Vietnam remains isolated. As far as the non-communist states of the region are concerned, the authors see little prospect for a substantial convergence of Soviet and ASEAN interests