Why do demand responsive transport systems fail?

In developed countries, Demand Responsive Transport (DRT) (loosely termed 'paratransit' in US parlance) emerged in the 1970s to serve the specialist niche market of people with mobility difficulties. DRT systems are starting become a mainstream public transport mode and this paper examines mainstream public transport DRT schemes from around the world that have failed, in order to identify the reasons for failure, and draw lessons to help prevent similar outcomes occurring. Research for the Intermode study developed detailed cases of 72 DRT projects. A number of key failed cases are reported together with a note of the lessons that each provides. This is followed by a generic analysis of failure factors based on a marketing approach. It is concluded that DRT projects are often not realistically costed or designed with a full understanding of the market they are to serve. There is a very dangerous temptation to offer too flexible a service and to include costly technological systems, when they may not be needed. An incremental approach, if possible, appears sensible. DRT also requires more marketing effort and skills than is traditional in conventional bus operations, but above all, it requires new skills in working in partnership. It is concluded that the latter area is where the root of DRT failure is often to be found

Building Information Modelling and Standardised Construction Contracts: a Content Analysis of the GC21 Contract

Building Information Modelling (BIM) is seen as a panacea to many of the ills confronting the Architectural, Engineering and Construction (AEC) sector. In spite of its well documented benefits the widespread integration of BIM into the project lifecycle is yet to occur. One commonly identified barrier to BIM adoption is the perceived legal risks associated with its integration, coupled with the need for implementation in a collaborative environment. Many existing standardised contracts used in the Australian AEC industry were drafted before the emergence of BIM. As BIM continues to become ingrained in the delivery process the shortcomings of these existing contracts have become apparent. This paper reports on a study that reviewed and consolidated the contractual and legal concerns associated with BIM implementation. The findings of the review were used to conduct a qualitative content analysis of the GC21 2nd edition, an Australian standardised construction contract, to identify possible changes to facilitate the implementation of BIM in a collaborative environment. The findings identified a number of changes including the need to adopt a collaborative contract structure with equitable risk and reward mechanisms, recognition of the model as a contract document and the need for standardisation of communication/information exchange.

A Study of Two Protein Kinases from Trypanosoma brucei

The protozoan parasite Trypanosoma brucei undergoes major differentiation events during its complex life cycle which involves the tsetse fly and mammal as obligate hosts. At the same time it alternates between proliferative and non-proliferative forms. In higher eukaryotes differentiation and the cell cycle are controlled by complex signalling networks many of which involve protein kinases as components and, by analogy, this would be expected to be the situation in T. brucei. However, very little is known about cellular signalling m this parasite and the work presented in this thesis is a study of two T. brucei protein kinases as an approach to the identification of pathways regulating differentiation and the cell cycle. Two approaches were followed: firstly, the characterisation and purification of a 60 kDa autophosphorylating protein kinase from T. brucei that was found to be expressed in a stage-specific manner (Hide et al., 1994). This protein kinase activity was found to localise in the 100 000 g supernatant of total extracts of bloodstream forms and this supernatant was used as the starting material for purification. Using anion-exchange chromatography as the first purification step, the autophosphorylating protein kinase was detected in two peaks of activity eluting at slightly different salt concentrations. A number of different chromatography matrices were then tested for their suitability in the further purification of the protein kinase and a further level of purification was achieved using a Sepharose to which the protein kinase inhibitor H-9 had been immobilised. In addition new assays for measuring activity were developed, one of which, based on autophosphorylation in solution was found to be robust and informative. The second approach taken was to isolate and sequence a full length cDNA corresponding to an amplified cDNA fragment (Hua and Wang, 1994) for which the predicted peptide sequence showed homology to catalytic domain sequences of a rat protein kinase C family member and the Drosophila protein kinase polo. Isolation and sequencing of genes encoding T. brucei protein kinase C family members would provide valuable evidence for cell signalling in this parasite and provide tools to complement earlier studies on protein kinase C like activities in T. brucei (Keith et al., 1990). A clone was isolated in a screen of a lambdagt 11 cDNA library using a probe homologous to the original amplified cDNA fragment. Partial sequencing of the insert has shown that it is a chimaera of cDNAs for a ribosomal protein S4 homologue and for a protein kinase (this part of the chimaera includes a section identical to the probe). Hybridisation of Southern blots of T. brucei genomic DNA to probes from the ribosomal protein and protein kinase coding regions, under high stringency conditions, shows that both sequences are of T. brucei origin but that the two sequences are not co-linear in the genome. Comparisons of the two predicted peptide sequences with protein sequences in the databases show that the open reading frames for both proteins are incomplete. The open reading frame for the protein kinase homologue is probably almost complete but there is no 3' stop codon. The 5' coding sequence could be complete but there could be an upstream start codon not contained within the clone isolated. The putative protein kinase has all the defining features of a member of the polo-like kinase family and is clearly not a protein kinase C. Polo-like kinases are implicated in regulation of mitotic spindle formation and therefore mitosis, and the T. brucei enzyme would be worthy of further study given that mitosis and spindle formation are very different in T. brucei compared to higher eukaryotes

The evolution of bits and bottlenecks in a scientific workflow trying to keep up with technology: Accelerating 4D image segmentation applied to nasa data

In 2016, a team of earth scientists directly engaged a team of computer scientists to identify cyberinfrastructure (CI) approaches that would speed up an earth science workflow. This paper describes the evolution of that workflow as the two teams bridged CI and an image segmentation algorithm to do large scale earth science research. The Pacific Research Platform (PRP) and The Cognitive Hardware and Software Ecosystem Community Infrastructure (CHASE-CI) resources were used to significantly decreased the earth science workflow's wall-clock time from 19.5 days to 53 minutes. The improvement in wall-clock time comes from the use of network appliances, improved image segmentation, deployment of a containerized workflow, and the increase in CI experience and training for the earth scientists. This paper presents a description of the evolving innovations used to improve the workflow, bottlenecks identified within each workflow version, and improvements made within each version of the workflow, over a three-year time period

Rapid quantification of underivatized alloisoleucine and argininosuccinate using mixed-mode chromatography with tandem mass spectrometry

Plasma elevations of the amino acids alloisoleucine and argininosuccinic acid (ASA) are pathognomonic for maple syrup urine disease and argininosuccinate lyase deficiency, respectively. Reliable detection of these biomarkers is typically achieved using methods with tedious sample preparations or long chromatographic separations, and many published amino acid assays report poor specificity and/or sensitivity for one or both of these compounds. This report describes a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method that provides rapid quantification of alloisoleucine and ASA in human plasma. The basis of this method is a mixed-mode solid phase separation that achieves baseline resolution of alloisoleucine from isobaric interferents without the use of derivatization or ion pairing agents. The inject-to-inject time is 6 min including elution, column washing and re-equilibration. Validation studies demonstrate excellent limits of quantification (1 μmol/L), linearity (r = 0.999 from 1 to 250 μmol/L), accuracy (bias = −3.8% and −10.1%), and inter-assay imprecision (CV < 8.06%) for plasma analyses. Data from long-term clinical application confirms chromatographic consistency equivalent to more traditional reversed-phase or HILIC based columns. Additional matrix studies indicate low suppression (<10%) for a wide range of amino acids and compatibility with other matrixes such as blood spot analyses. Finally, analysis of our first 257 clinical specimens demonstrates high analytic specificity and sensitivity, allowing the detection of subtle but clinically relevant elevations of alloisoleucine and ASA that may be missed by other less sensitive methods. In conclusion, the novel LC-MS/MS method reported here overcomes a number of the challenges associated with alloisoleucine and ASA quantification. Combining this approach with published incomplete amino acid quantification methods allows, for the first time, a rapid and comprehensive LC-MS/MS analysis of underivatized amino acids without the use of ion pairing agents

On the multiphoton ionisation photoelectron spectra of phenol

The phenol molecule is a prototype for non-adiabatic dynamics and the excited-state photochemistry of biomolecules. In this article, we report a joint theoretical and experimental investigation on the resonance enhanced multiphoton ionisation photoelectron (REMPI) spectra of the two lowest ionisation bands of phenol. The focus is on the theoretical interpretation of the measured spectra using quantum dynamics simulations. These were performed by numerically solving the time-dependent Schrödinger equation using the multi-layer variant of the multiconfiguration time-dependent Hartree algorithm together with a vibronic coupling Hamiltonian model. The ionising laser pulse is modelled explicitly within the ionisation continuum model to simulate experimental femtosecond 1+1 REMPI photoelectron spectra. These measured spectra are sensitive to very short lived electronically excited states, providing a rigorous benchmark for our theoretical methods. The match between experiment and theory allows for an interpretation of the features of the spectra at different wavelengths and shows that there are features due to both 'direct' and 'indirect' ionisation, resulting from non-resonant and resonant excitation by the pump pulse

Estimation of bladder contractility from intravesical pressure–volume measurements

© 2016 Wiley Periodicals, Inc. Aims: To describe parameters from urodynamic pressure recordings that describe urinary bladder contractility through the use of principles of muscle mechanics. Methods: Subtracted detrusor pressure and voided flow were recorded from patients undergoing filling cystometry. The isovolumetric increase of detrusor pressure, P, of a voluntary bladder contraction before voiding was used to generate a plot of (dP/dt)/P versus P. Extrapolation of the plot to the y-axis and the x-axis generated a contractility parameter, vCE (the maximum rate of pressure development) and the maximum isovolumetric pressure, P0, respectively. Similar curves were obtained in ex vivo pig bladders with different concentrations of the inotropic agent carbachol and shown in a supplement. Results: Values of vCE, but not P0, diminished with age in female subjects. vCE was most significantly associated with the 20–80% duration of isovolumetric contraction t20–80; and a weaker association with maximum flow rate and BCI in women. P0 was not associated with any urodynamic variable in women, but in men was with t20–80 and isovolumetric pressure indices. Conclusions: The rate of isovolumetric subtracted detrusor pressure (t20–80) increase shows a very significant association with indices of bladder contractility as derived from a derived force–velocity curve. We propose that t20–80 is a detrusor contractility parameter (DCP). Neurourol. Urodynam. 36:1009–1014, 2017. © 2016 Wiley Periodicals, Inc

Taxation futures for sustainable mobility

Taxation futures for sustainable mobilit