Intelligent design of manufacturing systems.

The design of a manufacturing system is normally performed in two distinct stages, i.e. steady state design and dynamic state design. Within each system design stage a variety of decisions need to be made of which essential ones are the determination of the product range to be manufactured, the layout of equipment on the shopfloor, allocation of work tasks to workstations, planning of aggregate capacity requirements and determining the lot sizes to be processed. This research work has examined the individual problem areas listed above in order to identify the efficiency of current solution techniques and to determine the problems experienced with their use. It has been identified that for each design problem. although there are an assortment of solution techniques available, the majority of these techniques are unable to generate optimal or near optimal solutions to problems of a practical size. In addition, a variety of limitations have been identified that restrict the use of existing techniques. For example, existing methods are limited with respect to the external conditions over which they are applicable and/or cannot enable qualitative or subjective judgements of experienced personnel to influence solution outcomes. An investigation of optimization techniques has been carried out which indicated that genetic algorithms offer great potential in solving the variety of problem areas involved in manufacturing systems design. This research has, therefore, concentrated on testing the use of genetic algorithms to make individual manufacturing design decisions. In particular, the ability of genetic algorithms to generate better solutions than existing techniques has been examined and their ability to overcome the range of limitations that exist with current solution techniques. IIFor each problem area, a typical solution has been coded in terms of a genetic algorithm structure, a suitable objective function constructed and experiments performed to identify the most suitable operators and operator parameter values to use. The best solution generated using these parameters has then been compared with the solution derived using a traditional solution technique. In addition, from the range of experiments undertaken the underlying relationships have been identified between problem characteristics and optimality of operator types and parameter values. The results of the research have identified that genetic algorithms could provide an improved solution technique for all manufacturing design decision areas investigated. In most areas genetic algorithms identified lower cost solutions and overcame many of the limitations of existing techniques

GSE1 Postgraduate Information Literacy and Communication Skills Training-Project Orientated Delivery

Module presented by the Faculty of Science and Engineering in cooperation with the Subject Librarian from Learning Teaching and Research Development in the Library. Original format was four three hour workshops plus 18 hrs self paced course work using interdisciplinary written and verbal skills training tasks . Translate a peer reviewed Journal paper to communicate it to a interdisciplinary audience and prepare a short presentation. It was enhanced with the introduction of a peer-learning component by dividing participants into four groups of eight. A project orientated and problem based learning (POPBL) approach has been shown to work well in the delivery of educational outcomes and also in the delivery of Information Literac

It’s all in whom you know (as well as what you know). Using network analysis and health professionals own knowledge for recruitment.

Peer reviewedPublisher PD

Random number generation using spontaneous symmetry breaking in a Kerr resonator

We experimentally demonstrate an all-optical random number generator based on spontaneous symmetry breaking in a coherently-driven Kerr resonator. Random bit sequences are generated by repeatedly tuning a control parameter across a symmetry-breaking bifurcation that enacts random selection between two possible steady-states of the system. Experiments are performed in a fibre ring resonator, where the two symmetry-broken steady-states are associated with orthogonal polarization modes. Detrimental biases due to system asymmetries are completely suppressed by leveraging a recently-discovered self-symmetrization phenomenon that ensures the symmetry breaking acts as an unbiased coin toss, with a genuinely random selection between the two available steady-states. We optically generate bits at a rate of over 3~MHz without post-processing and verify their randomness using the National Institute of Standards and Technology and Dieharder statistical test suites.Comment: 5 pages, 4 figure

Nonlinear topological symmetry protection in a dissipative system

We report an experimental and theoretical investigation of a system whose dynamics is dominated by an intricate interplay between three key concepts of modern physics: topology, nonlinearity, and spontaneous symmetry breaking. The experiment is based on a two-mode coherently-driven optical resonator in which photons interact through the Kerr nonlinearity. In presence of a phase defect between the modes, a nonlinear attractor develops, which confers a synthetic M\"obius topology to the modal structure of the system. That topology is associated with an inherently protected exchange symmetry between the modes, enabling the realization of spontaneous symmetry breaking in ideal, bias-free, conditions without any fine tuning of parameters. The dynamic manifests itself by a periodic alternation of the modes from one resonator roundtrip to the next reminiscent of period-doubling. This extends to a range of localized structures in the form of domain walls, bright solitons, and breathers, which have all been observed with remarkable long term stability. A rigorous testing of the randomness of the symmetry-broken state selection statistics has also confirmed the robustness of the exchange symmetry in our experiment. Our results and conclusions are supported by an effective Hamiltonian model explaining the symmetry protection in our system. The model also shows that our work has relevance to other systems of interacting bosons and to the Floquet engineering of quantum matter. Our work could also be beneficial to the implementation of coherent Ising machines.Comment: 14 pages, 5 figure

Bioaccumulation of metals in juvenile rainbow trout 1 (oncorhynchus mykiss) via dietary exposure to blue mussels

The potential for metals to bioaccumulate in aquatic species, such as fish, via trophic level transfer was investigated. An in vivo experiment was set up in a flow-through system in which juvenile rainbow trout were fed blue mussels collected from a Class A pristine site and an effluent-impacted river estuary, over a period of 28 days. Selected elements (As, Cd, Cr, Co, Cu, Fe, Pb, Mn, Mo, Ni, Se, Sn, V, Zn) were determined in the mussels and fish tissues (muscle and skin) collected at 0, 14 and 28 days. This study reveals the occurrence of metals in mussels sampled in the Irish marine environment and highlights the bioaccumulation potential of metals in fish tissues via trophic transfer. All 14 monitored metals were determined in the mussels collected from both sites and mussels collected from the effluent-impacted site contained three times more Co, Mo, Sn and V than the mussels collected from the Class A site. Following a 28-day dietary exposure, concentrations of As and Se (fish muscle), and Pb, Se and Zn (fish skin), were significantly greater in fish feeding on contaminated mussels compared to those with a regular fish feed diet. The significance of metal detection and bioaccumulation in the mussel and fish tissues, highlights the potential for metal exposure to humans through the food chain. As fish are recommended as a healthy and nutritious food source, it is important to fully understand metal bioaccumulation in commercially important aquatic species and ensure the safety of human consumers

Relationship between immune checkpoint proteins, tumour microenvironment characteristics, and prognosis in primary operable colorectal cancer

The tumour microenvironment is an important factor for colorectal cancer prognosis, affecting the patient's immune response. Immune checkpoints, which regulate the immune functions of lymphocytes, may provide prognostic power. This study aimed to investigate the prognostic value of the immune checkpoints TIM‐3, LAG‐3 and PD‐1 in patients with stage I–III colorectal cancer. Immunohistochemistry was employed to detect TIM‐3, LAG‐3, PD‐1 and PD‐L1 in 773 patients with stage I–III colorectal cancer. Immune checkpoint protein expression was assessed in tumour cells using the weighted histoscore, and in immune cells within the stroma using point counting. Scores were analysed for associations with survival and clinical factors. High tumoural LAG‐3 (hazard ratio [HR] 1.45 95% confidence interval [CI] 1.00–2.09, p = 0.049) and PD‐1 (HR 1.34 95% CI 1.00–1.78, p = 0.047) associated with poor survival, whereas high TIM‐3 (HR 0.60 95% CI 0.42–0.84, p = 0.003), LAG‐3 (HR 0.58 95% CI 0.40–0.87, p = 0.006) and PD‐1 (HR 0.65 95% CI 0.49–0.86, p = 0.002) on immune cells within the stroma associated with improved survival, while PD‐L1 in the tumour (p = 0.487) or the immune cells within the stroma (p = 0.298) was not associated with survival. Furthermore, immune cell LAG‐3 was independently associated with survival (p = 0.017). Checkpoint expression scores on stromal immune cells were combined into a Combined Immune Checkpoint Stromal Score (CICSS), where CICSS 3 denoted all high, CICSS 2 denoted any two high, and CICSS 1 denoted other combinations. CICSS 3 was associated with improved patient survival (HR 0.57 95% CI 0.42–0.78, p = 0.001). The results suggest that individual and combined high expression of TIM‐3, LAG‐3, and PD‐1 on stromal immune cells are associated with better colorectal cancer prognosis, suggesting there is added value to investigating multiple immune checkpoints simultaneously

Identification of novel risk loci and causal insights for sporadic Creutzfeldt-Jakob disease: a genome-wide association study

Background: Human prion diseases are rare and usually rapidly fatal neurodegenerative disorders, the most common being sporadic Creutzfeldt-Jakob disease (sCJD). Variants in the PRNP gene that encodes prion protein are strong risk factors for sCJD but, although the condition has similar heritability to other neurodegenerative disorders, no other genetic risk loci have been confirmed. We aimed to discover new genetic risk factors for sCJD, and their causal mechanisms. Methods: We did a genome-wide association study of sCJD in European ancestry populations (patients diagnosed with probable or definite sCJD identified at national CJD referral centres) with a two-stage study design using genotyping arrays and exome sequencing. Conditional, transcriptional, and histological analyses of implicated genes and proteins in brain tissues, and tests of the effects of risk variants on clinical phenotypes, were done using deep longitudinal clinical cohort data. Control data from healthy individuals were obtained from publicly available datasets matched for country. Findings: Samples from 5208 cases were obtained between 1990 and 2014. We found 41 genome-wide significant single nucleotide polymorphisms (SNPs) and independently replicated findings at three loci associated with sCJD risk; within PRNP (rs1799990; additive model odds ratio [OR] 1·23 [95% CI 1·17-1·30], p=2·68 × 10-15; heterozygous model p=1·01 × 10-135), STX6 (rs3747957; OR 1·16 [1·10-1·22], p=9·74 × 10-9), and GAL3ST1 (rs2267161; OR 1·18 [1·12-1·25], p=8·60 × 10-10). Follow-up analyses showed that associations at PRNP and GAL3ST1 are likely to be caused by common variants that alter the protein sequence, whereas risk variants in STX6 are associated with increased expression of the major transcripts in disease-relevant brain regions. Interpretation: We present, to our knowledge, the first evidence of statistically robust genetic associations in sporadic human prion disease that implicate intracellular trafficking and sphingolipid metabolism as molecular causal mechanisms. Risk SNPs in STX6 are shared with progressive supranuclear palsy, a neurodegenerative disease associated with misfolding of protein tau, indicating that sCJD might share the same causal mechanisms as prion-like disorders. Funding: Medical Research Council and the UK National Institute of Health Research in part through the Biomedical Research Centre at University College London Hospitals National Health Service Foundation Trust

An ultrahot Neptune in the Neptune desert

About 1 out of 200 Sun-like stars has a planet with an orbital period shorter than one day: an ultrashort-period planet. All of the previously known ultrashort-period planets are either hot Jupiters, with sizes above 10 Earth radii (R⊕), or apparently rocky planets smaller than 2 R⊕. Such lack of planets of intermediate size (the ‘hot Neptune desert’) has been interpreted as the inability of low-mass planets to retain any hydrogen/helium (H/He) envelope in the face of strong stellar irradiation. Here we report the discovery of an ultrashort-period planet with a radius of 4.6 R⊕ and a mass of 29 M⊕, firmly in the hot Neptune desert. Data from the Transiting Exoplanet Survey Satellite revealed transits of the bright Sun-like star LTT 9779 every 0.79 days. The planet’s mean density is similar to that of Neptune, and according to thermal evolution models, it has a H/He-rich envelope constituting 9.0^(+2.7)_(−2.9)% of the total mass. With an equilibrium temperature around 2,000 K, it is unclear how this ‘ultrahot Neptune’ managed to retain such an envelope. Follow-up observations of the planet’s atmosphere to better understand its origin and physical nature will be facilitated by the star’s brightness (V_(mag) = 9.8)

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data