38,196 research outputs found
Exploring roles and relationships in the production of the built environment
Given the number of different agencies and the complexity of institutional and professional relationships in the production, management and regulation of the built environment, many students entering built environment professions leave university education to take up work placements or employment without a sufficient understanding of the different actors and the formal and informal interactions and social relationships between them. Furthermore, destructive stereotypes may form during the educational process as students construct their own professional identity, in part learnt from their teachers and peers, and naturalised by the academic and professional institutions that form the context of their education â a process of enculturation termed âprofessional socializationâ by social scientists (Cuff, 1991: 118). These stereotypes may lead ultimately to inter-professional tensions and hostilities. Innovations in practice often involve challenges to established roles or joined-up thinking which breaches institutional structures, for all of which graduates may be ill-prepared
Scanning laser source and scanning laser detection techniques for different surface crack geometries
Standard test samples typically contain simulated defects such as slots machined normal to the surface. However, real defects will not always propagate in this manner; for example, rolling contact fatigue on rails propagates at around 25Âș to the surface, and corrosion cracking can grow in a branched manner. Therefore, there is a need to understand how ultrasonic surface waves interact with different crack geometries. We present measurements of machined slots inclined at an angle to the surface normal, or with simple branched geometries, using laser ultrasound. Recently, Rayleigh wave enhancements observed when using the scanning laser source technique, where a generation laser is scanned along a sample, have been highlighted for their potential in detecting surface cracks. We show that the enhancement measured with laser detector scanning can give a more significant enhancement when different crack geometries are considered. We discuss the behaviour of an incident Rayleigh wave in the region of an angled defect, and consider mode-conversions which lead to a very large enhancement when the detector is close to the opening of a shallow defect. This process could be used in characterising defects, as well as being an excellent fingerprint of their presence
Non-contact ultrasonic detection of angled surface defects
Non-destructive testing is an important technique, and improvements are constantly needed. Surface defects in metals are not necessarily confined to orientations normal to the sample surface; however, much of the previous work investigating the interaction of ultrasonic surface waves with surface-breaking defects has assumed cracks inclined at 90° to the surface. This paper explores the interaction of Rayleigh waves with cracks which have a wide range of angles and depths relative to the surface, using a non-contact laser generation and detection system. Additional insight is acquired using a 3D model generated using finite element method software. A clear variation of the reflection and transmission coefficients with both crack angle and length is found, in both the out-of-plane and in-plane components. The 3D model is further used to understand the contributions of different wavemodes to B-Scans produced when scanning a sample, to enable understanding of the reflection and transmission behaviour, and help identify angled defects. Knowledge of these effects is essential to correctly gauge the severity of surface cracking
End to end distance on contour loops of random gaussian surfaces
A self consistent field theory that describes a part of a contour loop of a
random Gaussian surface as a trajectory interacting with itself is constructed.
The exponent \nu characterizing the end to end distance is obtained by a Flory
argument. The result is compared with different previuos derivations and is
found to agree with that of Kondev and Henley over most of the range of the
roughening exponent of the random surface.Comment: 7 page
Harnessing autophagy to overcome mitogenâactivated protein kinase kinase inhibitorâinduced resistance in metastatic melanoma
Background
Patients with malignant melanoma often relapse after treatment with BRAF and/or mitogenâactivated protein kinase kinase (MEK) inhibitors (MEKi) owing to development of drug resistance.
Objectives
To establish the temporal pattern of CD271 regulation during development of resistance by melanoma to trametinib, and determine the association between development of resistance to trametinib and induction of prosurvival autophagy.
Methods
Immunohistochemistry for CD271 and p62 was performed on human naevi and primary malignant melanoma tumours. Western blotting was used to analyse expression of CD271, p62 and LC3 in melanoma subpopulations. Flow cytometry and immunofluorescence microscopy was used to evaluate trametinibâinduced cell death and CD271 expression. MTS viability assays and zebrafish xenografts were used to evaluate the effect of CD271 and autophagy modulation on trametinibâresistant melanoma cell survival and invasion, respectively.
Results
CD271 and autophagic signalling are increased in stage III primary melanomas vs. benign naevi. In vitro studies demonstrate MEKi of BRAFâmutant melanoma induced cytotoxic autophagy, followed by the emergence of CD271âexpressing subpopulations. Trametinibâinduced CD271 reduced autophagic flux, leading to activation of prosurvival autophagy and development of MEKi resistance. Treatment of CD271âexpressing melanoma subpopulations with RNA interference and smallâmolecule inhibitors to CD271 reduced the development of MEKi resistance, while clinically applicable autophagy modulatory agents â including Î9âtetrahydrocannabinol and Vps34 â reduced survival of MEKiâresistant melanoma cells. Combined MEK/autophagy inhibition also reduced the invasive and metastatic potential of MEKiâresistant cells in an in vivo zebrafish xenograft.
Conclusions
These results highlight a novel mechanism of MEKiâinduced drug resistance and suggest that targeting autophagy may be a translatable approach to resensitize drugâresistant melanoma cells to the cytotoxic effects of MEKi
Beneficial effects of childhood selective dorsal rhizotomy in adulthood
Background: Selective dorsal rhizotomy (SDR) has been used to treat children with spastic cerebral palsy (CP) for over three decades. However, little is known about the outcomes of childhood SDR in adults. Objectives: 1) To study the effects of childhood SDR on the quality of life and ambulatory function in adult life. 2) To determine late side effects of SDR in adults.  Methods: Adults (> 17.9 years) who underwent SDR in childhood (2 - 17.9 years) between 1987 and 2013 were surveyed in 2015. Patients completed a survey, including questions on demographic information, quality of life, health, surgical outcomes, motor function, manual ability, pain, braces/orthotics, post-SDR treatment, living situation, education level, work status, and side effects of SDR. Results: In our study population of 294 patients (18.0 - 37.4 years), patients received SDR during the ages of 2.0 - 17.9 years and were followed up 2.2 to 28.3 years after surgery. Eighty-four percent had spastic diplegia, 12% had spastic quadriplegia, and 4% had spastic triplegia. The majority (88%) of patients reported improved post-SDR quality of life and 1% considered the surgery detrimental. Most (83%) would recommend the procedure to others and 3% would not. However, patients who would not recommend SDR to others ambulated with a walker or were not ambulatory at all prior to SDR. The majority (83%) of patients improved (30%) or remained stable (53%) in ambulation. Twenty-nine percent of patients reported pain, mostly in the back and lower limbs, with a mean pain level of 4.4 ± 2.4 on the Numeric Pain Rating Scale (NPRS). Decreased sensation in small areas of the lower limbs was reported by 8% of patients, though this did not affect daily life. Scoliosis was diagnosed in 28%, with 40% of these patients pursuing treatment. Whether scoliosis was related to SDR is not clear, though scoliosis is known to occur in patients with CP and also in the general population. Only 4% of patients underwent spinal fusion. Orthopedic surgeries were pursued by 59% of patients. The most common orthopedic surgeries were hamstring lengthenings (31%), Achilles tendon lengthenings (18%), adductor lengthenings (16%), and derotational osteotomies (16%). Twenty-four percent of all patients later underwent hip surgery and 8% had surgeries on their knees. Conclusion: Results of this study indicate that the beneficial effects of childhood SDR extend to adulthood quality of life and ambulatory function without late side effects of surgery
Scanning laser techniques for characterisation of different surface breaking defect geometries
Measurements using a laser scanning system consisting of a pulsed Nd:YAG laser to generate surface ultrasonic
waves and an interferometer to detect the surface displacement, are presented for different samples and defect geometries. We show, ïŹrstly, details of the interaction of Rayleigh waves in thick samples with machined slots inclined at an angle to the surface normal, or with simple branched geometries, scanning the generation source over the defect (SLLS) or scanning the detection point over the defect (SLD). Secondly, we discuss effects of Lamb waves interacting with V-shaped defects in thin samples. The results from these measurements have shown that the signal enhancement found in the near-ïŹeld in both cases can be used to position the defect and gain an idea of its geometry, and have shown this to be a suitable ïŹngerprint of the presence of the defect
Force correlations and arches formation in granular assemblies
In the context of a simple microscopic schematic scalar model we study the
effects of spatial correlations in force transmission in granular assemblies.
We show that the parameters of the normalized weights distribution function,
, strongly depend on the spatial extensions,
, of such correlations. We show, then, the connections between
measurable macroscopic quantities and microscopic mechanisms enhancing
correlations. In particular we evaluate how the exponential cut-off,
, and the small forces power law exponent, , depend
on the correlation length, . If correlations go to infinity, weights are
power law distributed.Comment: 6 page
Approach to the Continuum Limit of the Quenched Hermitian Wilson-Dirac Operator
We investigate the approach to the continuum limit of the spectrum of the
Hermitian Wilson-Dirac operator in the supercritical mass region for pure gauge
SU(2) and SU(3) backgrounds. For this we study the spectral flow of the
Hermitian Wilson-Dirac operator in the range . We find that the
spectrum has a gap for and that the spectral density at zero,
, is non-zero for . We find that and, for
(exponential in the lattice spacing) as one goes to
the continuum limit. We also compute the topological susceptibility and the
size distribution of the zero modes. The topological susceptibility scales well
in the lattice spacing for both SU(2) and SU(3). The size distribution of the
zero modes does not appear to show a peak at a physical scale.Comment: 19 pages revtex with 9 postscript figures included by eps
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