Transmembrane/cytoplasmic domain-mediated membrane type 1-matrix metalloprotease docking to invadopodia is required for cellinvasion

The invasion of human malignant melanoma cells into the extracellular matrix (ECM) involves the accumulation of proteases at sites of ECM degradation where activation of matrix metalloproteases (MMP) occurs. Here, we show that when membrane type 1 MMP (MT-MMP) was overexpressed in RPMI7951 human melanoma cells, the cells made contact with the ECM, activated soluble and ECM-bound MMP-2, and degraded and invaded the ECM. Further experiments demonstrated the importance of localization of the MT-MMP to invadopodia. Overexpression of MT-MMP without invadopodial localization caused activation of soluble MMP-2, but did not facilitate ECM degradation or cell invasiveness. Up-regulation of endogenous MT-MMP with concanavalin A caused activation of MMP-2. However, concanavalin A treatment prevented invadopodial localization of MT-MMP and ECM degradation. Neither a truncated MT-MMP mutant lacking transmembrane (TM) and cytoplasmic domains (ΔTM(MT-MMP)), nor a chimeric MT-MMP containing the interleukin 2 receptor α chain (IL-2R) TM and cytoplasmic domains (ΔTM(MT-MMP)/TM(IL-2R)) were localized to invadopodia or exhibited ECM degradation. Furthermore, a chimera of the TM/cytoplasmic domain of MT-MMP (TM(MT-MMP)) with tissue inhibitor of MMP 1 (TIMP-1/TM(MT- MMP)) directed the TIMP-1 molecule to invadopodia. Thus, the MT-MMP TM/cytoplasmic domain mediates the spatial organization of MT-MMP into invadopodia and subsequent degradation of the ECM.

Failure of discontinuous railhead edges due to plastic strain accumulation

Railhead is perhaps the highest stressed civil infrastructure due to the passage of heavily loaded wheels through a very small contact patch. The stresses at the contact patch cause yielding of the railhead material and wear. Many theories exist for the prediction of these mechanisms of continuous rails; this process in the discontinuous rails is relatively sparingly researched. Discontinuous railhead edges fail due to accumulating excessive plastic strains. Significant safety concern is widely reported as these edges form part of Insulated Rail Joints (IRJs) in the signalling track circuitry. Since Hertzian contact is not valid at a discontinuous edge, 3D finite element (3DFE) models of wheel contact at a railhead edge have been used in this research. Elastic–plastic material properties of the head hardened rail steel have been experimentally determined through uniaxial monotonic tension tests and incorporated into a FE model of a cylindrical specimen subject to cyclic tension load- ing. The parameters required for the Chaboche kinematic hardening model have been determined from the stabilised hysteresis loops of the cyclic load simulation and imple- mented into the 3DFE model. The 3DFE predictions of the plastic strain accumulation in the vicinity of the wheel contact at discontinuous railhead edges are shown to be affected by the contact due to passage of wheels rather than the magnitude of the loads the wheels carry. Therefore to eliminate this failure mechanism, modification to the contact patch is essential; reduction in wheel load cannot solve this problem.

Hydrodynamic theory of liquid slippage on a solid substrate near a moving contact line

In this Letter a hydrodynamic theory of liquid slippage on a solid substrate near a moving contact line is proposed. A family of spatially varying slip lengths in the Navier slip law recovers the results of past formulations for slip in continuum theories and molecular dynamics simulations and is consistent with well-established experimental observations of complete wetting. This formulation gives a general approach for continuum hydrodynamic theories. New fluid flow behaviors are also predicted yet to be seen in experiment. © 2013 American Physical Society.

Nanopore processing in dielectric materials and dielectric template-assisted nanoarray synthesis : using pulsed bias to enhance process throughput and precision

An effective technique to improve the precision and throughput of energetic ion condensation through dielectric nanoporous templates and reduce nanopore clogging by using finely tuned pulsed bias is proposed. Multiscale numerical simulations of ion deposition show the possibility of controlling the dynamic charge balance on the upper template's surface to minimize ion deposition on nanopore sidewalls and to deposit ions selectively on the substrate surface in contact with the pore opening. In this way, the shapes of nanodots in template-assisted nanoarray fabrication can be effectively controlled. The results are applicable to various processes involving porous dielectric nanomaterials and dense nanoarrays.

Measurement of contact voltage drop and resistance in organic solar cells

Bulk heterojunction organic solar cells based on poly[4,7-bis(3- dodecylthiophene-2-yl) benzothiadiazole-co-benzothiadiazole] and [6,6]-phenyl C71-butyric acid methyl ester are investigated. A prominent kink is observed in the fourth quadrant of the current density-voltage (J-V) response. Annealing the active layer prior to cathode deposition eliminates the kink. The kink is attributed to an extraction barrier. The J-V response in these devices is well described by a power law. This behavior is attributed to an imbalance in charge carrier mobility. An expected photocurrent for the device displaying a kink in the J-V response is determined by fitting to a power law. The difference between the expected and measured photocurrent allows for the determination of a voltage drop within the device. Under simulated 1 sun irradiance, the peak voltage drop and contact resistance at short circuit are 0.14 V and 90 Ω, respectively. © 2012 American Institute of Physics.

Extending building information models to specifications and cost planning

This digital poster (which was on display at "The Cube", Queensland University of Technology) demonstrates how specification parameters can be extracted from a product library repository for use in augmenting the information contents of the objects in a local BIM tool (Revit in this instance).

Nephrotoxicity and nephrocarcinogenicity of dinitrotoluene : new aspects to be considered

Technical dinitrotoluene (DNT) is a mixture of 2,4- and 2,6-DNT. In humans, industrial or environmental exposure can occur orally, by inhalation, or by skin contact. The classification of DNT as an 'animal carcinogen' is based on the formation of malignant tumors in kidneys, liver, and mammary glands of rats and mice. Clear signs of toxic nephropathy were found in rats dosed with DNT, and the concept was derived of an interrelation between renal toxicity and carcinogenicity. Recent data point to the carcinogenicity of DNT on the urinary tract of exposed humans. Between 1984 and 1997, 6 cases of urothelial cancer and 14 cases of renal cell cancer were diagnosed in a group of 500 underground mining workers in the copper mining industry of the former GDR and having high exposures to explosives containing technical DNT. The incidences of both urothelial and renal cell tumors in this group were 4.5 and 14.3 times higher, respectively, than anticipated on the basis of the cancer registers of the GDR. The genotyping of all identified tumor patients for the polymorphic enzymes NAT2, GSTM1, and GSTT1 identified the urothelial tumor cases as exclusively 'slow acetylates'. A group of 161 miners highly exposed to DNT was investigated for signs of subclinical renal damage. The exposures were categorized semi-quantitatively into 'low', 'medium', 'high', and 'very high'. A straight dose-dependence of the excretion of urinary biomarker proteins with the ranking of exposure was seen. Biomarker excretion (alpha1-microglobulin, glutathione S-transferases alpha and pi) indicated that DNT-induced damage was directed toward the tubular system. New data on DNT-exposed humans appear consistent with the concept of cancer initiation by DNT isomers and the subsequent promotion of renal carcinogenesis by selective damage to the proximal tubule. The differential pathways of metabolic activation of DNT appear to apply to the proximal tubule of the kidney and to the urothelium of the renal pelvis and lower urinary tract as target tissues of carcinogenicity.

Pathological excretion patterns of urinary proteins in miners highly exposed to dinitrotoluene

A cohort of 161 underground miners who had been highly exposed to dinitrotoluene (DNT) in the copper-mining industry of the former German Democratic Republic was reinvestigated for signs of subclinical renal damage. The study included a screening of urinary proteins excreted by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and quantitations of the specific urinary proteins α 1-microglobulin and glutathione-S-transferase α (GST α) as biomarkers for damage of the proximal tubule and glutathione-S-transferase π (GST π) for damage of the distal tubule. The exposures were categorized semiquantitatively (low, medium, high, and very high), according to the type and duration of professional contact with DNT. A straight dose-dependence of pathological protein excretion patterns with the semiquantitative ranking of DNT exposure was seen. Most of the previously reported cancer cases of the urinary tract, especially those in the higher exposed groups, were confined to pathological urinary protein excretion patterns. The damage from DNT was directed toward the tubular system. In many cases, the appearance of Tamm-Horsfall protein, a 105-kD protein marker, was noted. Data on the biomarkers α 1-microglobulin, GST α, and GST π consistently demonstrated a dose-dependent increase in tubular damage, which confirmed the results of screening by SDS-PAGE and clearly indicated a nephrotoxic effect of DNT under the given conditions of exposure. Within the cluster of cancer patients observed among the DNT-exposed workers, only in exceptional cases were normal biomarker excretions found.

Corneal changes following short-term miniscleral contact lens wear

Purpose To examine the influence of short-term miniscleral contact lens wear on corneal shape, thickness and anterior surface aberrations. Methods Scheimpflug imaging was captured before, immediately following and 3 hours after a short period (3 hours) of miniscleral contact lens wear for 10 young (mean 27 ± 5 years), healthy participants. Natural diurnal variations were considered by measuring baseline diurnal changes obtained on a separate control day without contact lens wear. Results Small but significant anterior corneal flattening was observed immediately following lens removal (overall mean 0.02 ± 0.03 mm, p < 0.001) which returned to baseline levels three hours after lens removal. During the three hour recovery period significant corneal thinning (-13.4 ± 10.5 μm) and posterior surface flattening (0.03 ± 0.02 mm) were also observed (both p < 0.01). The magnitude of posterior corneal flattening during recovery correlated with the amount of corneal thinning (r = 0.69, p = 0.03). Central corneal clearance (maximum tear reservoir depth) was not associated with corneal swelling following lens removal (r = -0.24, p > 0.05). An increase in lower-order corneal astigmatism Z(2,2) was also observed following lens wear (mean -0.144 ± 0.075 μm, p = 0.02). Conclusions Flattening of the anterior corneal surface was observed immediately following lens wear, while ‘rebound’ thinning and flattening of the posterior surface was evident following the recovery period. Modern miniscleral contact lenses that vault the cornea may slightly influence corneal shape and power but do not induce clinically significant corneal oedema during short-term wear.

Why are we still fitting reusable soft contact lenses?

Whether the first daily disposable soft contact lens to enter the market in 1994 was the Premier lens (Award Technology, Scotland, UK; subsequently purchased by Bausch & Lomb, Rochester New York, USA) or the 1-Day Acuvue lens (Johnson and Johnson Vision Care, Jacksonville, Florida, USA) has long been a matter of bitter dispute1 but whatever the answer, this year marks the 20th anniversary of the launch of this modality of lens wear...

Donald Ezekiel AM : passionate and innovative contact lens practitioner and manufacturer

Donald Ezekiel (known to all as ‘Don’) was born in Singapore on September 12, 1936, to a German mother and Iraqi father. His parents were Jewish refugees, who met in Batavia,1 married and alternately lived in Batavia and Singapore. The family established their primary residence in Singapore after Don’s older brother Eric (later to become a haematologist) was born in 1934. The Ezekiel family was forced to flee in 1941 when the Japanese bombed Singapore and were fortunate to obtain passage on a hospital ship to Perth. They returned to Singapore after the war but left again on their own accord in 1951 due to race riots. The Ezekiels sold up everything in Singapore and decided to settle in Perth...

Influence of practice setting on contact lens prescribing in the United Kingdom

We sought to determine the impact of optometric practice setting on contact lens prescribing by analysing annual survey data of lens fits collected between 2009 and 2013 from independent and national group practices throughout the United Kingdom. Compared to national group practices, independent practices fit contact lenses to older patients and more females. Independent practices also undertake a lower proportion of soft lens fits overall (and thus a higher proportion of rigid lens fits), soft toric lens fits and daily disposable lens fits. There is a higher proportion of soft extended wear and multifocal lens fits in independent practices. We conclude that contact lens fitting behaviour is influenced by optometric practice setting.

The influence of injury cause, contact-sport participation, and personal knowledge on expectation of outcome from mild traumatic brain injury

Objective: This study investigated the influence of injury cause, contact-sport participation, and prior knowledge of mild traumatic brain injury (mTBI) on injury beliefs and chronic symptom expectations of mTBI. Method: A total of 185 non-contact-sport players (non-CSPs) and 59 contact-sport players (CSPs) with no history of mTBI were randomly allocated to one of two conditions in which they read either a vignette depicting a sport-related mTBI (mTBIsport) or a motor-vehicle-accident-related mTBI (mTBIMVA). The vignettes were otherwise standardized to convey the same injury parameters (e.g., duration of loss of consciousness). After reading a vignette, participants reported their injury beliefs (i.e., perceptions of injury undesirability, chronicity, and consequences) and their expectations of chronic postconcussion syndrome (PCS) and posttraumatic stress disorder (PTSD) symptoms. Results: Non-CSPs held significantly more negative beliefs and expected greater PTSD symptomatology and greater PCS affective symptomatology from an mTBIMVA vignette thann mTBIsport vignette, but this difference was not found for CSPs. Unlike CSPs, non-CSPs who personally knew someone who had sustained an mTBI expected significantly less PCS symptomatology than those who did not. Despite these different results for non-CSPs and CSPs, overall, contact-sport participation did not significantly affect injury beliefs and symptom expectations from an mTBIsport. Conclusions: Expectations of persistent problems after an mTBI are influenced by factors such as injury cause even when injury parameters are held constant. Personal knowledge of mTBI, but not contact sport participation, may account for some variability in mTBI beliefs and expectations. These factors require consideration when assessing mTBI outcome.

Using the WWW to teach undergraduate nurses clinical communication

On-line learning is increasingly being used in nursing education. Nevertheless, there is still insufficient evidence to demonstrate: whether students respond positively when this form of learning is used to teach relatively practical or clinical subjects; whether it is effective; and whether it is fair to students with less access to, or familiarity with, computers and the internet. In 2003, an on-line Unit on clinical communication was developed for Australian undergraduate nurses in partnership between an Australian School of Nursing and the a Department of Clinical Psychology. Students were overwhelmingly positive in their evaluation of the Unit although some regretted the lack of face-to-face contact with tutors and peers. The best aspects of the Unit included the content and structure being perceived as interesting, fun and informative, the relevance of the material for them as nurses, flexibility to work independently, promotion of critical thinking and gaining an understanding of client issues. Neither their evaluation nor their final grades were related to students’ age or whether they preferred on-line or traditional learning. Students who had readily available computer access, however, had better final grades. Also, students’ grades were correlated with how often they accessed the Unit.

Scheimpflug imaging of the post lens tear film during contact lens wear

A new imaging methodology is described to visualise the post lens tear film (PLTF) during contact lens wear. A rotating-Scheimpflug camera in combination with sodium fluorescein allows evaluation of the PLTF for different contact lens modalities, including mini-scleral, rigid gas permeable (RGP) and soft contact lenses. This imaging technique provides an extension of the instrument’s current functionality. The potential advantages and limitations of the technique are discussed.