Rhabdomyosarcoma of the tongue in a dog

A lingual rhabdomyosarcoma was diagnosed in a six-year-old Staffordshire bull terrier with clinical signs of dysphagia. The unsuccessful response to initial chemotherapy, to surgical resection and subsequent surgical resection and radiation therapy is documented. The accurate diagnosis and prognosis of such tumours is also discussed. Lingual rhabdomyosarcoma has not previously been reported in the dog.     

Non-contrast MRI methods as a tool for the pre-operative assessment and surveillance of the arterio-venous fistula for haemodialysis

Objective

To compare non-contrast enhanced MRI with ultrasound (US) for measurement of arm blood vessel geometries and flow velocities in volunteers and patients with end-stage renal disease.

Materials and methods

Subjects were scanned using US (reference standard), and MRI 2D time-of-flight (ToF), 2D phase contrast (PC), and 3D multi-echo data image combination (MEDIC). Patients were also scanned after arteriovenous fistula (AVF) surgery.

Results

For mean vessel diameters (radial and brachial arteries; cephalic vein) MEDIC measurements were similar to US (p?>?0.05). However, ToF underestimated the mean diameter of the cephalic vein relative to US (p?<?0.05). For arterial velocity measurements, the mean values derived by PC-MR and US were similar (p?>?0.05). Post-operatively, the intra-luminal signal intensity was hypo-intense at the anastomosis site using ToF and MEDIC. At the same site the outer boundary of the vessel was consistently lost on ToF, but remained clearly delineated on the MEDIC images.

Discussion

With the exception of ToF, the MRI data demonstrated excellent agreement with US for measurements of vessel geometry and flow velocity. Further, the ability to clearly delineate the post-surgery vessel edges with MEDIC MRI suggests that the technique may be useful for surveillance after AVF creation or for patient-specific modelling studies.

     

A thixotropic nanocomposite gel for three-dimensional cell culture

Thixotropic materials, which become less viscous under stress and return to their original state when stress is removed, have been used to deliver gel-cell constructs and therapeutic agents. Here we show that a polymer-silica nanocomposite thixotropic gel can be used as a three-dimensional cell culture material. The gel liquefies when vortexed--allowing cells and biological components to be added--and resolidifies to trap the components when the shear force from spinning is removed. Good permeability of nutrients and gases through the gel allows various cell types to proliferate and be viable for up to three weeks. Human mesenchymal stem cells cultured in stiffer gels developed bone-like behaviour, showing that the rheological properties of the gel can control cell differentiation. No enzymatic, chemical, or photo-crosslinking, changes in ionic strength or temperature are required to form or liquefy the gel, offering a way to sub-culture cells without using trypsin-a protease commonly used in traditional cell culture techniques.     

Trajectory optimization of a mining dragline using the method of Lagrange multipliers

The nonlinear coupled dynamic behaviour of a mining dragline is optimized to increase productivity and reduce metal fatigue on the boom. Draglines are very large crane‐like robots used in open cut mining, primarily for the removal of overburden that covers a coal seam. The dynamic behaviour of the machine is a key determinant of productivity and fatigue‐based maintenance. The Newton–Lagrange method is applied to a field‐validated model to optimize slew torque under nonlinear constraints. Two scenarios are analysed: the minimization of cycle time with a time penalty for duty (estimated fatigue damage) and fixed rope lengths, and the minimization of duty under a fixed cycle time and measured rope lengths. The results from the second scenario compare favourably with earlier efforts to optimize slew torque using intuitive manual techniques. In particular, the numerical optimization procedure achieved a 50–60% reduction in duty, improving upon manual optimization results by 10–30%. Techniques are presented for solving convergence issues related to the high degree of nonlinearity of the model and constraints, actuator limitations and noise introduced by measured data. Copyright © 2010 John Wiley & Sons, Ltd.     

Studying bacterial metabolic states using Raman spectroscopy

Natural metabolic variability expected during characteristic growth phases in batch cultures of Escherichia coli and Staphylococcus epidermidis were studied by Raman spectroscopy. Spectral changes induced by metabolic changes found in the growth phases (i.e., lag, exponential, stationary, and decay) were identified. Maximum intensity of bands assigned to DNA and RNA bases are seen at the beginning of the exponential phase, when cells are metabolically active, and minimum intensities are seen when cells are decaying. High agreement in spectral variation due to growth phases was seen for all the trials that were performed, four growth cycles for E. coli and two for S. epidermidis. Batch cultures were monitored by standard plate counts to identify all growth phases, including decay. Spectral data were analyzed by principal component analysis (PCA) and discriminant analysis to identify similarities and differences and to estimate a classification performance based on growth phases. For the species evaluated, spectra during decay are grouped closer to each other and separated from lag, exponential, and stationary cells. These results suggest that Raman spectroscopy can be used to study metabolic states in bacteria and in particular cell viability.     

Surprising shrinkage of expanding gels under an external load

Hydrogels are fascinating and useful in that they can show large volume changes in response to various stimuli, such as temperature or chemical environment. Here we report the peculiar observation that chemically crosslinked hydrogels that normally expand owing to a change in electrolyte pH can be made to shrink in certain circumstances. Specifically, these hydrogels contract when tested at a constant compressive force and subjected to a pH change that causes expansion in the absence of the applied load. When tested under tension, the gels always expand. Although the effects of external stress on the swelling of gels is known, the concomitant change in gel mechanical properties during pH switching was found to be a more dominant effect in our studies. However, existing mechanical models used to predict dimensional changes in actuator materials could not explain both the tensile and compression results. In addition, we show that the friction between metal plates of the apparatus and the gel is a key factor in explaining the contractile actuation under compressive loads. The observations reported in this paper are important for the successful design and use of hydrogel actuators in devices such as valves for microfluidics.     

Detection of inflammation in vivo by surface-enhanced Raman scattering provides higher sensitivity than conventional fluorescence imaging

The detection of inflammatory changes is a key aim for the early diagnosis and treatment of several autoimmune, infectious, and metastatic diseases. While surface-enhanced Raman scattering (SERS) has the capability to provide noninvasive, in vivo imaging at sufficient depth to achieve this goal, this approach has not been exploited in the study of inflammation. SERS-active nanoparticles were coded with a unique Raman signal that was protected under a wide range of conditions and stimuli. To detect early-stage inflammation, gold nanoparticle clusters containing Raman-active molecules were conjugated to intercellular adhesion molecule 1- (ICAM-1-) specific monoclonal antibodies. SERS allowed noninvasive measurement of ICAM-1 expression in vivo with twice the sensitivity of two-photon fluorescence. This is the first time SERS has been used for in vivo detection of inflammation and is a major advance in the ever-growing toolkit of approaches for use in noninvasive, next-generation in vivo imaging.     

A Pro504 --> Ser substitution in the beta-subunit of beta-hexosaminidase A inhibits alpha-subunit hydrolysis of GM2 ganglioside, resulting in chronic Sandhoff disease

The GM2 gangliosidoses are caused by mutations in the genes encoding the alpha- (Tay-Sachs) or beta- (Sandhoff) subunits of heterodimeric beta-hexosaminidase A (Hex A), or the GM2 activator protein (AB variant), a substrate-specific co-factor for Hex A. Although the active site associated with the hydrolysis of GM2 ganglioside, as well as part of the binding site for the ganglioside-activator complex, is associated with the alpha-subunit, elements of the beta-subunit are also involved. Missense mutations in these genes normally result in the mutant protein being retained in the endoplasmic reticulum and degraded. The mutations associated with the B1-variant of Tay-Sachs are rare exceptions that directly affect residues in the alpha-active site. We have previously reported two sisters with chronic Sandhoff disease who were heterozygous for the common HEXB deletion allele. Cells from these patients had higher than expected levels of mature beta-protein and residual Hex A activity, approximately 20%. We now identify these patients' second mutant allele as a C1510T transition encoding a beta-Pro504 --> Ser substitution. Biochemical characterization of Hex A from both patient cells and cotransfected CHO cells demonstrated that this substitution (a) decreases the level of heterodimer transport out of the endoplasmic reticulum by approximately 45%, (b) lowers its heat stability, (c) does not affect its Km for neutral or charged artificial substrates, and (d) lowers the ratio of units of ganglioside/units of artificial substrate hydrolyzed by a factor of 3. We concluded that the beta-Pro504 --> Ser mutation directly affects the ability of Hex A to hydrolyze its natural substrate but not its artificial substrates. The effect of the mutation on ganglioside hydrolysis, combined with its effect on intracellular transport, produces chronic Sandhoff disease.