Accident Analysis and Prevention: Course Notes 1987/88

This report consists of the notes from a series of lectures given by the authors for a course entitled Accident Analysis and Prevention. The course took place during the second term of a one year Masters degree course in Transport Planning and Engineering run by the Institute for Transport Studies and the Department of Civil Engineering at the University of Leeds. The course consisted of 18 lectures of which 16 are reported on in this document (the remaining two, on Human Factors, are not reported on in this document as no notes were provided). Each lecture represents one chapter of this document, except in two instances where two lectures are covered in one chapter (Chapters 10 and 14). The course first took place in 1988, and at the date of publication has been run for a second time. This report contains the notes for the initial version of the course. A number of changes were made in the content and emphasis of the course during its second run, mainly due to a change of personnel, with different ideas and experiences in the field of accident analysis and prevention. It is likely that each time the course is run, there will be significant changes, but that the notes provided in this document can be considered to contain a number of the core elements of any future version of the course

Optimal Control of the Argon Oxygen Decarburizing Steelmaking Process

The argon oxygen decarburizing process is an increasingly important method of stainless steel manufacture. In the present paper, a nonlinear dynamic model is presented which represents approximately, the refining process. Finite dimensional optimisation techniques are used to calculate an optimal switched control and infinite dimensional gradient methods are applied to to discover an optimal continuous strategy. Control is achieved by varying the ratio of argon and oxygen in the supplied gas. Results with a realistic cost function indicate that substantial improvements in operating practice may be achieved. The feasibility of implementing the suggested control schemes is discussed

Characterizing the metabolic effects of the selective inhibition of gut microbial β-glucuronidases in mice

The hydrolysis of xenobiotic glucuronides by gut bacterial glucuronidases reactivates previously detoxified compounds resulting in severe gut toxicity for the host. Selective bacterial β-glucuronidase inhibitors can mitigate this toxicity but their impact on wider host metabolic processes has not been studied. To investigate this the inhibitor 4-(8-(piperazin-1-yl)-1,2,3,4-tetrahydro-[1,2,3]triazino[4′,5′:4,5]thieno[2,3-c]isoquinolin-5-yl)morpholine (UNC10201652, Inh 9) was administered to mice to selectively inhibit a narrow range of bacterial β-glucuronidases in the gut. The metabolomic profiles of the intestinal contents, biofluids, and several tissues involved in the enterohepatic circulation were measured and compared to control animals. No biochemical perturbations were observed in the plasma, liver or gall bladder. In contrast, the metabolite profiles of urine, colon contents, feces and gut wall were altered compared to the controls. Changes were largely restricted to compounds derived from gut microbial metabolism. This work establishes that inhibitors targeted towards bacterial β-glucuronidases modulate the functionality of the intestinal microbiota without adversely impacting the host metabolic system

The Christiansen Effect in Saturn's narrow dusty rings and the spectral identification of clumps in the F ring

Stellar occultations by Saturn's rings observed with the Visual and Infrared Mapping Spectrometer (VIMS) onboard the Cassini spacecraft reveal that dusty features such as the F ring and the ringlets in the Encke and the Laplace Gaps have distinctive infrared transmission spectra. These spectra show a narrow optical depth minimum at wavelengths around 2.87 microns. This minimum is likely due to the Christiansen Effect, a reduction in the extinction of small particles when their (complex) refractive index is close to that of the surrounding medium. Simple Mie-scattering models demonstrate that the strength of this opacity dip is sensitive to the size distribution of particles between 1 and 100 microns across. Furthermore, the spatial resolution of the occultation data is sufficient to reveal variations in the transmission spectra within and among these rings. For example, in both the Encke Gap ringlets and F ring, the opacity dip weakens with increasing local optical depth, which is consistent with the larger particles being concentrated near the cores of these rings. The strength of the opacity dip varies most dramatically within the F ring; certain compact regions of enhanced optical depth lack an opacity dip and therefore appear to have a greatly reduced fraction of grains in the few-micron size range.Such spectrally-identifiable structures probably represent a subset of the compact optically-thick clumps observed by other Cassini instruments. These variations in the ring's particle size distribution can provide new insights into the processes of grain aggregation, disruption and transport within dusty rings. For example, the unusual spectral properties of the F-ring clumps could perhaps be ascribed to small grains adhering onto the surface of larger particles in regions of anomalously low velocity dispersion.Comment: 42 pages, 15 figures, accepted for publication in Icarus. A few small typographical errors fixed to match correction in proof

Longitudinal metabolic and gut bacterial profiling of pregnant women with previous bariatric surgery

Objective Due to the global increase in obesity rates and success of bariatric surgery in weight reduction, an increasing number of women now present pregnant with a previous bariatric procedure. This study investigates the extent of bariatric-associated metabolic and gut microbial alterations during pregnancy and their impact on fetal development. Design A parallel metabonomic (molecular phenotyping based on proton nuclear magnetic resonance spectroscopy) and gut bacterial (16S ribosomal RNA gene amplicon sequencing) profiling approach was used to determine maternal longitudinal phenotypes associated with malabsorptive/mixed (n=25) or restrictive (n=16) procedures, compared with women with similar early pregnancy body mass index but without bariatric surgery (n=70). Metabolic profiles of offspring at birth were also analysed. Results Previous malabsorptive, but not restrictive, procedures induced significant changes in maternal metabolic pathways involving branched-chain and aromatic amino acids with decreased circulation of leucine, isoleucine and isobutyrate, increased excretion of microbial-associated metabolites of protein putrefaction (phenylacetlyglutamine, p-cresol sulfate, indoxyl sulfate and p-hydroxyphenylacetate), and a shift in the gut microbiota. The urinary concentration of phenylacetylglutamine was significantly elevated in malabsorptive patients relative to controls (p=0.001) and was also elevated in urine of neonates born from these mothers (p=0.021). Furthermore, the maternal metabolic changes induced by malabsorptive surgery were associated with reduced maternal insulin resistance and fetal/birth weight. Conclusion Metabolism is altered in pregnant women with a previous malabsorptive bariatric surgery. These alterations may be beneficial for maternal outcomes, but the effect of elevated levels of phenolic and indolic compounds on fetal and infant health should be investigated further

The three-dimensional structure of Saturn's E ring

Saturn's diffuse E ring consists of many tiny (micron and sub-micron) grains of water ice distributed between the orbits of Mimas and Titan. Various gravitational and non-gravitational forces perturb these particles' orbits, causing the ring's local particle density to vary noticeably with distance from the planet, height above the ring-plane, hour angle and time. Using remote-sensing data obtained by the Cassini spacecraft in 2005 and 2006, we investigate the E-ring's three-dimensional structure during a time when the Sun illuminated the rings from the south at high elevation angles (> 15 degrees). These observations show that the ring's vertical thickness grows with distance from Enceladus' orbit and its peak brightness density shifts from south to north of Saturn's equator plane with increasing distance from the planet. These data also reveal a localized depletion in particle density near Saturn's equatorial plane around Enceladus' semi-major axis. Finally, variations are detected in the radial brightness profile and the vertical thickness of the ring as a function of longitude relative to the Sun. Possible physical mechanisms and processes that may be responsible for some of these structures include solar radiation pressure, variations in the ambient plasma, and electromagnetic perturbations associated with Saturn's shadow.Comment: 42 Pages, 13 Figures, modified to include minor proof correction

Fixed Linear Crossing Minimization by Reduction to the Maximum Cut Problem

Many real-life scheduling, routing and locating problems can be formulated as combinatorial optimization problems whose goal is to find a linear layout of an input graph in such a way that the number of edge crossings is minimized. In this paper, we study a restricted version of the linear layout problem where the order of vertices on the line is fixed, the so-called fixed linear crossing number problem (FLCNP). We show that this NP-hard problem can be reduced to the well-known maximum cut problem. The latter problem was intensively studied in the literature; practically efficient exact algorithms based on the branch-and-cut technique have been developed. By an experimental evaluation on a variety of graphs, we prove that using this reduction for solving FLCNP compares favorably to earlier branch-and-bound algorithms

Block bond-order potential as a convergent moments-based method

The theory of a novel bond-order potential, which is based on the block Lanczos algorithm, is presented within an orthogonal tight-binding representation. The block scheme handles automatically the very different character of sigma and pi bonds by introducing block elements, which produces rapid convergence of the energies and forces within insulators, semiconductors, metals, and molecules. The method gives the first convergent results for vacancies in semiconductors using a moments-based method with a low number of moments. Our use of the Lanczos basis simplifies the calculations of the band energy and forces, which allows the application of the method to the molecular dynamics simulations of large systems. As an illustration of this convergent O(N) method we apply the block bond-order potential to the large scale simulation of the deformation of a carbon nanotube.Comment: revtex, 43 pages, 11 figures, submitted to Phys. Rev.

Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma

Controversies and priorities in amyotrophic lateral sclerosis

Two decades after the discovery that 20% of familial amyotrophic lateral sclerosis (ALS) cases were linked to mutations in the superoxide dismutase-1 (SOD1) gene, a substantial proportion of the remainder of cases of familial ALS have now been traced to an expansion of the intronic hexanucleotide repeat sequence in C9orf72. This breakthrough provides an opportunity to re-evaluate longstanding concepts regarding the cause and natural history of ALS, coming soon after the pathological unification of ALS with frontotemporal dementia through a shared pathological signature of cytoplasmic inclusions of the ubiquitinated protein TDP-43. However, with profound clinical, prognostic, neuropathological, and now genetic heterogeneity, the concept of ALS as one disease appears increasingly untenable. This background calls for the development of a more sophisticated taxonomy, and an appreciation of ALS as the breakdown of a wider network rather than a discrete vulnerable population of specialised motor neurons. Identification of C9orf72 repeat expansions in patients without a family history of ALS challenges the traditional division between familial and sporadic disease. By contrast, the 90% of apparently sporadic cases and incomplete penetrance of several genes linked to familial cases suggest that at least some forms of ALS arise from the interplay of multiple genes, poorly understood developmental, environmental, and age-related factors, as well as stochastic events