Acute phase protein levels in dogs with mast cell tumours and sarcomas

<p><b>Context:</b> The acute phase protein response is part of a non-specific and complex host response to inflammation. It occurs shortly after tissue injury and may be induced by a range of different causes, including infectious, inflammatory, neoplastic, traumatic or immunological disease. Although it was conventionally believed that APPs were exclusively hepatocyte derived, there is increasing evidence to support extra-hepatic generation in neoplastic and other disease states. In people, C-reactive protein (CRP) has been shown to be of value in identifying metastatic disease from primary renal tumours as well as showing promise for monitoring rejection of renal transplants. Serum CRP correlates with survival in colorectal cancer and oesophageal squamous cell carcinoma while serum amyloid A (SAA) concentrations correlate with cancer activity, stage and prognosis in gastric tumours. Recent immunohistochemical studies in people with oesophageal carcinoma suggest that tumour tissue may itself elaborate APP with a poorer survival and outcome associated with tumours elaborating higher levels of CRP. A similar association has been seen between alpha-1 acid glycoprotein (AGP) and colorectal tumours and ovarian carcinoma.</p> <p>As yet, studies regarding APP values in neoplastic conditions in dogs are limited, and many are non-specific. In veterinary patients, elevated levels of AGP have been identified in dogs with a range of tumours with localisation to liver and splenic tissue in one study. Another study found higher levels of AGP in dogs with non-specific tumours of grade III-IV based on the WHO Tumour Node Metastasis (TNM) scale and elevated serum AGP has been documented in non-specific tumour-bearing cats. Elevated CRP levels have been documented in both dogs and cats with lymphoma and serum CRP may be used as an indicator of complete remission status in dogs with multicentric lymphoma. Elevated levels of CRP, Haptoglobin (Hp) and SAA have been identified in dogs with mammary tumours, with significant increases over normal in the presence of metastatic disease, primary tumours greater than 5cm in diameter and those with ulceration.</p> <p>In this study we evaluated an APP profile using four APPs (CRP, Hp, SAA and AGP), in dogs with mast cell tumours (MCTs) and sarcomas to assess whether the APP profile would change in reflection of tumour presence; whether the extent of any change would correlate with tumour grade; and whether the changes would differ with tumour type.</p> <p><b>Approach:</b> Patients with naturally occurring MCTs and sarcomas presenting for staging and treatment were included if they met the study criteria. Criteria for inclusion were that the patient was not currently being treated with steroids, did not have a recent history of infectious or inflammatory disease other than the tumour, a definitive histological diagnosis was available and a full staging procedure was completed prior to surgery using standard oncological protocols to identify metastatic disease where present. Following surgical resection each tumour was submitted for full histological evaluation and grading to include assessment of the margins of excision. Cases were only enrolled in the study if blood sampling formed part of the clinical investigation and/or treatment, and where residual blood was available after diagnostic sampling which would otherwise have been disposed of as clinical waste. In brief, the CRP levels were determined by immunoturbidometric assay and Hp by means of haemoglobin binding capacity assay. SAA was measured with a commercial canine ELISA kit (TriDelta Development, Dublin, Ireland) and AGP was measured with a commercial radial immunodiffusion assay (J-Path Inc, Tokyo, Japan).</p> <p><b>Results:</b> All comparisons using continuous data were checked for normality and equality of variances and appropriate statistical tests were employed (student’s t test operationalised as a two-sample Welch’s test for samples of unequal sizes and variances, Mann-Whitney, Chi-square and Fishers exact tests as appropriate). In MCTs, the CRP and AGP were elevated above reference ranges, Hp showed no significant change and SAA dropped relative to the reference range. In sarcoma patients CRP, Hp and AGP were all elevated above reference ranges. None of the tumour grade differences were significant apart from SAA in sarcoma patients where values in grade 2 sarcoma were significantly higher than those in grade 1.</p> <p><b>Interpretation and notes of caution:</b> The numbers in our groups were small which compromises the validity of statistical evaluation so our results must be interpreted with caution. However some interesting relationships have emerged from the initial evaluation which suggests that APP profiles may have potential for screening in patients with neoplastic disease. For patients with MCTs, CRP and AGP levels would be expected to increase, with a concurrent drop in SAA levels. In sarcoma patients CRP, AGP and Hp can all be expected to increase. These initial results need to be evaluated in larger numbers of cases with naturally occurring disease to validate the findings, to assess whether the presence and extent of metastatic disease has a significant effect, and also to confirm whether the values alter after surgical resection of the primary tumour.</p> <p><b>Significance of findings:</b> If there are consistent and specific changes in APP profiles associated with different tumour types in dogs, as is the case with a wide range of cancers in humans, then there may be potential for APP profiles on routine blood samples to be used as indicators of disease, or where monitoring for recurrence. Whether they could also have potential for assessment of the presence of metastatic disease and prognosis as in people is unknown as yet.</p&gt

Ultra high molecular weight polyethylene with incorporated crystal violet and gold nanoclusters is antimicrobial in low intensity light and in the dark

Antibiotics lose their effectiveness over time due to antimicrobial resistance. The increasing risk of hospital-acquired infections from contaminated surfaces and medical interventions requires the development of new antimicrobial materials. We report the first example of a modified ultra high molecular weight polyethylene that showed good antibacterial properties on light activation. Its efficacy was due to the production of reactive oxygen species under low-intensity white light sources (ca. 375 lux). Crystal violet and cysteine capped gold nanoclusters were successfully incorporated into the polymer using a readily available solvent as a dispersing agent followed by the process of compression moulding at 200 °C, 4.5 MPa for 1 min. This modified ultra-high molecular weight polyethylene demonstrates excellent robustness with regards to dye and metal leaching as well as photostability. Despite incorporating antimicrobial agents, the modified ultra-high molecular weight polyethylene retained its mechanical properties and showed >99% reduction in bacterial numbers against Escherichia coli and. To our knowledge, this paper reports the first use of compression moulding to create a light-activated antimicrobial surface which has distinct processing advantages over the widely used “swell-encapsulation-shrink” method and is potentially scalable

X-ray emission from the double-binary OB-star system QZ Car (HD 93206)

X-ray observations of the double-binary OB-star system QZ Car (HD 93206) obtained with the Chandra X-ray Observatory over a period of roughly 2 years are presented. The orbit of systems A (O9.7 I+b2 v, PA = 21 d) and B (O8 III+o9 v, PB = 6 d) are reasonably well sampled by the observations, allowing the origin of the X-ray emission to be examined in detail. The X-ray spectra can be well fitted by an attenuated three temperature thermal plasma model, characterised by cool, moderate, and hot plasma components at kT ~ 0.2, 0.7, and 2 keV, respectively, and a circumstellar absorption of ~ 0.2 x 10^22 cm-2. Although the hot plasma component could be indicating the presence of wind-wind collision shocks in the system, the model fluxes calculated from spectral fits, with an average value of ~ 7 x 10^-13 erg s-1 cm-2, do not show a clear correlation with the orbits of the two constituent binaries. A semi-analytical model of QZ Car reveals that a stable momentum balance may not be established in either system A or B. Yet, despite this, system B is expected to produce an observed X-ray flux well in excess of the observations. If one considers the wind of the O8 III star to be disrupted by mass transfer the model and observations are in far better agreement, which lends support to the previous suggestion of mass-transfer in the O8 III + o9 v binary. We conclude that the X-ray emission from QZ Car can be reasonably well accounted for by a combination of contributions mainly from the single stars and the mutual wind-wind collision between systems A and B.Comment: 11 pages, 7 figures. Accepted for the ApJS Special Issue on the Chandra Carina Complex Project (CCCP), scheduled for publication in May 2011. All 16 CCCP Special Issue papers are available at http://cochise.astro.psu.edu/Carina_public/special_issue.html through 2011 at leas

Spin Diode Based on Fe/MgO Double Tunnel Junction

We demonstrate a spin diode consisting of a semiconductor free nano-scale Fe/MgO-based double tunnel junction. The device exhibits a near perfect spin-valve effect combined with a strong diode effect. The mechanism consistent with our data is resonant tunneling through discrete states in the middle ferromagnetic layer sandwiched by tunnel barriers of different spin-dependent transparency. The observed magneto-resistance is record high, ~4000%, essentially making the structure an on/off spin-switch. This, combined with the strong diode effect, ~100, offers a new device that should be promising for such technologies as magnetic random access memory and re-programmable logic.Comment: 14 page

Kinetics-based design of a flow platform for highly reproducible on demand synthesis of gold nanoparticles with controlled size between 50 and 150 nm and their application in SERS and PIERS sensing

Seeded-growth synthetic protocols enable precise control of particle size and shape, crucial for many sensing applications. However, scaling-up these syntheses in a reproducible way is challenging, as minimal variation in process parameters such as seed size, concentration or reaction temperature can significantly alter the final product. Flow reactors enable tight control in the process parameters and high reproducibility of the synthesis, representing a potential technology to perform seeded-growth syntheses in large scale. This work reports the design of a flow platform for the controlled synthesis of spherical gold nanoparticles with size up to 150nm through a seeded-growth approach, and their use in Surface Enhanced Raman Scattering (SERS) and Photoinduced Enhanced Raman Spectroscopy (PIERS). The particle growth kinetics were studied via in situ time-resolved UV–Vis spectroscopy. The spectroscopic data were fitted with a kinetic model, which was subsequently used for the design of the reactor. The kinetics-based design approach enabled fast translation of the growth synthesis in flow, eventually allowing the on demand flow synthesis of particles with controllable size, ranging from 50 to 150nm, with high reproducibility and full precursor conversion. The particles were tested for SERS and PIERS for different substrates, including warfare agents and biomolecules, with enhancement factors between 103 and 108 depending on the analyte, demonstrating their potential for detection of various analytes

Spin-dependent electrical transport in ion-beam sputter deposited Fe-Cr multilayers

The temperature dependence of the electrical resistivity and magnetoresistance of Xe-ion beam sputtered Fe-Cr multilayers has been investigated. The electrical resistivity between 5 and 300 K in the fully ferromagnetic state, obtained by applying a field beyond the saturation field (H_sat) necessary for the antiferromagnetic(AF)-ferromagnetic(FM) field-induced transition, shows evidence of spin-disorder resistivity as in crystalline Fe and an s-d scattering contribution (as in 3d metals and alloys). The sublattice magnetization m(T) in these multilayers has been calculated in terms of the planar and interlayer exchange energies. The additional spin-dependent scattering \Delta \rho (T) = \rho(T,H=0)_AF - \rho(T,H=H_sat)_FM in the AF state over a wide range of temperature is found to be proportional to the sublattice magnetization, both \Delta \rho(T) and m(T) reducing along with the antiferromagnetic fraction. At intermediate fields, the spin-dependent part of the electrical resistivity (\rho_s (T)) fits well to the power law \rho_s (T) = b - cT^\alpha where c is a constant and b and \alpha are functions of H. At low fields \alpha \approx 2 and the intercept b decreases with H much the same way as the decrease of \Delta \rho (T) with T. A phase diagram (T vs. H_sat) is obtained for the field- induced AF to FM transition. Comparisons are made between the present investigation and similar studies using dc magnetron sputtered and molecular beam epitaxy (MBE) grown Fe-Cr multilayers.Comment: 8 pages, 10 figures, to appear in Phys. Rev.

Rapid Synthesis of [Au₂₅(Cys)₁₈] Nanoclusters via Carbon Monoxide in Microfluidic Liquid-Liquid Segmented Flow System and their Antimicrobial Performance

Atomically precise thiolate-gold nanoclusters with well-defined structures attract attention for use in various applications. However, most of the recently reported synthetic methods rely on prolonged synthesis times (a few hours to days) in order to produce high purity materials with a single cluster size. Such extended synthesis times make these processes ill-suited for adaptation to industrial scale production with continuous flow. In this work, an improved method for the synthesis of thiolated Au25 nanoclusters is presented utilising a microfluidic system and CO-mediated reduction. The optimized system, based on a coiled flow inverter with inner diameter of 1 mm operating at 80 °C and 500 kPa took only 3 min for the synthesis of atomically precise cysteine-capped [Au25(Cys)18] nanoclusters, as characterized by ultraviolet–visible spectroscopy and electrospray ionization mass spectrometry. The productivity of the system was increased by using higher reactant concentrations which led to a throughput of 0.9 gAu per day, without changing the reaction time or affecting the product purity. The Au nanoclusters were used as photobactericidal enhancement materials. In antimicrobial testing against S. aureus, encapsulation of the Au nanoclusters into crystal violet impregnated silicone showed high photobactericidal activity (~1.7 log reduction in viable bacteria) upon 6 h illumination of white light at ~312 lx, while crystal violet did not show significant photobactericidal activity on its own

Continuous Single-Phase Synthesis of [Au₂₅(Cys)₁₈] Nanoclusters and their Photobactericidal Enhancement

Thiolate–gold nanoclusters have various applications. However, most of the synthesis methods require prolonged synthesis times from several hours to days. In the present study, we report a rapid synthesis method for [Au25(Cys)18] nanoclusters and their application for photobactericidal enhancement. For [Au25(Cys)18] synthesis, we employed a tube-in-tube membrane reactor using CO as a reducing agent at elevated temperatures. This approach allows continuous generation of high-quality [Au25(Cys)18] within 3 min. Photobactericidal tests against Staphylococcus aureus showed that crystal violet-treated polymer did not have photobactericidal activity, but addition of [Au25(Cys)18] in the treated polymer demonstrated a potent photobactericidal activity at a low white light flux, resulting in >4.29 log reduction in viable bacteria numbers. Steady-state and time-resolved photoluminescence spectroscopies demonstrated that after light irradiation, photoexcited electrons in crystal violet flowed to [Au25(Cys)18] in the silicone, suggesting that redox reaction from [Au25(Cys)18] enhanced the photobactericidal activity. Stability tests revealed that leaching of crystal violet and [Au25(Cys)18] from the treated silicone was negligible and cyclic testing showed that the silicone maintained a strong photobactericidal activity after repeated use

Tunneling in double barrier junctions with 'hot spots'

We investigate electronic transport in epitaxial Fe(100)/MgO/Fe/MgO/Fe double magnetic tunnel junctions with soft barrier breakdown (hot spots). Specificity of these junctions are continious middle layer and Nitrogen doping of the MgO barriers which provides soft breakdown at biases about 0.5V. In the junctions with hot spots we observe quasi-periodic changes in the resistance as a function of bias voltage which point out formation of quantum well states in the middle Fe continuous free layer. The room-temperature oscillations have been observed in both parallel and antiparallel magnetic configurations and for both bias polarizations. A simple model of tunneling through hot spots in the double barrier magnetic junction is proposed to explain qualitatively this effect.Comment: 11 pages, 4 figure