Fibrotic-like changes in degenerate human intervertebral discs revealed by quantitative proteomic analysis.

OBJECTIVE: Intervertebral disc degeneration (IDD) can lead to symptomatic conditions including sciatica and back pain. The purpose of this study is to understand the extracellular matrix (ECM) changes in disc biology through comparative proteomic analysis of degenerated and non-degenerated human intervertebral disc (IVD) tissues of different ages. DESIGN: Seven non-degenerated (11-46 years of age) and seven degenerated (16-53 years of age) annulus fibrosus (AF) and nucleus pulposus (NP) samples were used. Proteins were extracted using guanidine hydrochloride, separated from large proteoglycans (PGs) by caesium chloride (CsCl) density gradient ultracentrifugation, and identified using liquid chromatography (LC) coupled with tandem mass spectrometry (MS/MS). For quantitative comparison, proteins were labeled with iTRAQ reagents. Collagen fibrils in the NP were assessed using scanning electron microscopy (SEM). RESULTS: In the AF, quantitative analysis revealed increased levels of HTRA1, COMP and CILP in degeneration when compared with samples from older individuals. Fibronectin showed increment with age and degeneration. In the NP, more CILP and CILP2 were present in degenerated samples of younger individuals. Reduced protein solubility was observed in degenerated and older non-degenerated samples correlated with an accumulation of type I collagen in the insoluble fibers. Characterization of collagen fibrils in the NP revealed smaller mean fibril diameters and decreased porosity in the degenerated samples. CONCLUSIONS: Our study identified distinct matrix changes associated with aging and degeneration in the intervertebral discs (IVDs). The nature of the ECM changes, together with observed decreased in solubility and changes in fibril diameter is consistent with a fibrotic-like environment.

Development and validation of a computational model of the knee joint for the evaluation of surgical treatments for osteoarthritis.

A three-dimensional (3D) knee joint computational model was developed and validated to predict knee joint contact forces and pressures for different degrees of malalignment. A 3D computational knee model was created from high-resolution radiological images to emulate passive sagittal rotation (full-extension to 65°-flexion) and weight acceptance. A cadaveric knee mounted on a six-degree-of-freedom robot was subjected to matching boundary and loading conditions. A ligament-tuning process minimised kinematic differences between the robotically loaded cadaver specimen and the finite element (FE) model. The model was validated by measured intra-articular force and pressure measurements. Percent full scale error between FE-predicted and in vitro-measured values in the medial and lateral compartments were 6.67% and 5.94%, respectively, for normalised peak pressure values, and 7.56% and 4.48%, respectively, for normalised force values. The knee model can accurately predict normalised intra-articular pressure and forces for different loading conditions and could be further developed for subject-specific surgical planning.

Spin-enabled plasmonic metasurfaces for manipulating orbital angular momentum of light.

Here, we investigate the spin-induced manipulation of orbitals using metasurfaces constructed from geometric phase elements. By carrying the spin effects to the orbital angular momentum, we show experimentally the transverse angular splitting between the two spins in the reciprocal space with metasurface, as a direct observation of the optical spin Hall effect, and an associated global orbital rotation through the effective orientations of the geometric phase elements. Such spin-orbit interaction from a metasurface with a definite topological charge can be geometrically interpreted using the recently developed high order Poincaré sphere picture. These investigations may give rise to an extra degree of freedom in manipulating optical vortex beams and orbitals using "spin-enabled" metasurfaces.

Effects of nucleus pulposus cell-derived acellular matrix on the differentiation of mesenchymal stem cells.

Recent attempts to treat disc degeneration with mesenchymal stem cells (MSCs) showed encouraging results. Differentiating MSCs towards nucleus pulposus cell (NPC)-like lineages represents a speculative mechanism. Niche factors including hypoxia, growth factors and cell-cell interactions have been suggested but the matrix niche factor has not been studied. Our collagen microencapsulation provides a 3D model to study matrix niche as it enables the encapsulated cells to remodel the template matrix. We previously demonstrated the chondro-inductive role of of chondrocytes-derived matrix in MSCs and showed that NPCs maintained their phenotype and remodeled the template matrix of collagen microspheres into a glycosaminoglycan (GAG)-rich one. Here we aim to study the effects of NPC-derived matrix on MSC differentiation towards NPC-like lineages by firstly producing an NPC-derived matrix in collagen microspheres, secondly optimizing a decellularization protocol to discard NPCs yet retaining the matrix, thirdly repopulating the acellular NPC-derived matrix with MSCs and fourthly evaluating their phenotype. Finally, we injected these microspheres in a pilot rabbit disc degeneration model. Results showed that NPCs survived, maintained their phenotypic markers and produced GAGs. A decellularization protocol with maximal removal of the NPCs, minimal loss in major matrix components and partial retention of NPC-specific markers was identified. The resulting acellular matrix supported MSC survival and matrix production, and up-regulated the gene expression of NPC markers including type II collagen and glypican 3. Finally, injection of MSC in these microspheres in rabbit degenerative disc better maintained hydration level with more pronounced staining of GAGs and type II collagen than controls.

Efficient doping and energy transfer from ZnO to Eu3+ ions in Eu(3+)-doped ZnO nanocrystals.

Successful doping of Eu3+ ions into ZnO nanocrystals has been realized by using a low temperature wet chemical doping technique. The substitution of Eu3+ for Zn2+ is shown to be dominant in the Eu-doped ZnO nanocrystals by analyzing the X-ray diffraction patterns, transmission electron microscopy images, Raman and selectively excited photoluminescence spectra. Measurement of the luminescence from the samples shows that the excited ZnO transfers the excited energy efficiently to the doped Eu3+ ions, giving rise to efficient emission at red spectral region. The red emission quantum yield is measured to be 31% at room temperature. The temperature dependence of photoluminescence and the photoluminescence excitation spectra have also been investigated, showing strong energy coupling between the ZnO host and Eu3+ ions through free and bound excitons. The result indicates that Eu3+ ion-doped ZnO nanocrystals are promising light-conversion materials and have potential application in highly distinguishable emissive flat panel display and LED backlights.

Highly flexible near-infrared metamaterials.

Plasmonic or metamaterial nanostructures are usually fabricated on rigid substrate i.e. glass, silicon. Optical functionality of such kinds of nanostructures is limited by the planar surface and thus sensitive to the incident angle of light. In this work, we demonstrated that a tri-layer flexible metamaterials working at near infrared (NIR) regime can be fabricated on transparent PET substrate using flip chip transfer (FCT) technique. FCT technique is solution-free and can also be applied to fabricate other functional nanostructures device on flexible substrate. We demonstrated NIR metamaterial device can be transformed into various shapes by bending the PET substrate.

Narrowband plasmonic excitation on gold hole-array nanostructures observed using spectroscopic ellipsometer.

Surface plasmon polaritons (SPPs) modes on gold hole-array nanostructures were studied using spectroscopy ellipsometer in reflection mode. Using background free techniques in the optical ellipsometer, clear SPP bands on gold nanostructure/air interface were measured in UV-Visible-Near infrared (NIR) regime (300 nm-1800 nm). Plasmonic excitation with bandwidth of 13 nm (FWHM) was observed in reflection measurement, and it is much narrower than that observed in transmission measurement mode. In addition, the plasmonic excitation bands were characterized in both amplitude and phase domain. Theoretical analysis using reciprocal lattice vector method and rigorous coupled wave analysis (RCWA) agreed well with the experimental results. By measuring the TM and TE waves simultaneously, the spectroscopic ellipsometer provides an important method to analyze both amplitude and phase information in plasmonic nanostructures and metamaterials.

Near field imaging from multilayer lens.

Multilayer superlens has been reported that it had advantages over the single metal layer superlens. In this work, single silver layer and Ag-SiO2 multilayer superlens devices working at wavelength of 365 nm were fabricated using standard photolithography method. Grating objects with line/space (190 nm/190 nm) resolution could be resolved through both kinds of lens structures with working distance up to 128 nm. However, Ag-SiO2 multilayer lens shows higher transmittance and image contrast than the single silver layer device, the experimental result proves the theoretical calculation.

Near field imaging with resonant cavity lens.

We showed that a Ag-SiO(2)-Ag Fabry-Pérot cavity can be used in near-field imaging based on omnidirectional resonance tunneling. The omnidirectional resonance was experimentally demonstrated in the Ag-SiO(2)-Ag resonant cavity working at a wavelength of 365 nm. The resonant cavity lens with high transmittance and high image fidelity was fabricated using standard photolithography method. Grating source with 190 nm line resolution was imaged through the resonant cavity lens with a total thickness of 128 nm.

Stridor in Parkinson's disease: a case of 'dry drowning'?

OBJECTIVES: (1) To present a rare case of stridor secondary to prolonged laryngospasm in a patient with Parkinson's disease, and (2) to review the literature on stridor in Parkinson's disease. METHODS: We report a 73-year-old Parkinson's disease patient who developed acute stridor due to prolonged laryngospasm triggered by overspill of excessive secretions. The literature was reviewed, following a Medline search using the keywords 'Parkinson's disease' and 'stridor' or 'airway obstruction' or 'laryngospasm' or 'laryngeal dystonia' or 'bilateral vocal cord palsy'. RESULT: Only 12 previously reported cases of stridor in Parkinson's disease patients were identified. Causes included bilateral vocal fold palsy (eight cases), laryngospasm (five), and dystonia of the jaw and neck muscles (two). The mechanism of laryngospasm in our patient was similar to 'dry drowning', and has not previously been described. CONCLUSION: Laryngospasm can be triggered in Parkinson's disease by excessive secretions entering the larynx. The mechanism is similar to 'dry drowning'. Treatment focuses on reducing secretions. The use of botulinum toxin to reduce spasm is inappropriate in this situation. This case emphasises the importance of recognising different causes of stridor in Parkinson's disease patients, as this affects management.

Increased basal insulin secretion in Pdzd2-deficient mice.

Expression of the multi-PDZ protein Pdzd2 (PDZ domain-containing protein 2) is enriched in pancreatic islet beta cells, but not in exocrine or alpha cells, suggesting a role for Pdzd2 in the regulation of pancreatic beta-cell function. To explore the in vivo function of Pdzd2, Pdzd2-deficient mice were generated. Homozygous Pdzd2 mutant mice were viable and their gross morphology appeared normal. Interestingly, Pdzd2-deficient mice showed enhanced glucose tolerance in intraperitoneal glucose tolerance tests and their plasma insulin levels indicated increased basal insulin secretion after fasting. Moreover, insulin release from mutant pancreatic islets was found to be twofold higher than from normal islets. To verify the functional defect in vitro, Pdzd2 was depleted in INS-1E cells using two siRNA duplexes. Pdzd2-depleted INS-1E cells also displayed increased insulin secretion at low concentrations of glucose. Our results provide the first evidence that Pdzd2 is required for normal regulation of basal insulin secretion.

GaN/ZnO nanorod light emitting diodes with different emission spectra.

Light emitting diodes (LEDs) consisting of p-GaN epitaxial films and n-ZnO nanorods have been fabricated and characterized. The rectifying behavior and emission spectra were strongly dependent on the electronic properties of both GaN film and ZnO nanorods. Light emission under both forward and reverse bias was obtained in all cases, and emission spectra could be changed by annealing the ZnO nanorods. The emission spectra could be further tuned by using a GaN LED epiwafer as a substrate. Both forward and backward diode behavior has been observed and the emission spectra were significantly affected by both the properties of the GaN substrate and the annealing conditions for the ZnO nanorods.

Stresses in cement mantles of hip replacements: effect of femoral implant sizes, body mass index and bone quality.

The effects of femoral prosthetic heads of diameters 22 and 28 mm were investigated on the stability of reconstructed hemi-pelves with cement mantles of thicknesses 1-4 mm and different bone qualities. Materialise medical imaging package and I-Deas finite element (FE) software were used to create accurate geometry of a hemi-pelvis from CT-scan images. Our FE results show an increase in cement mantle stresses associated with the larger femoral head. When a 22 mm femoral head is used on acetabulae of diameters 56 mm and above, the probability of survivorship can be increased by creating a cement mantle of at least 1 mm thick. However, when a 28 mm femoral head is used, a cement mantle thickness of at least 4 mm is needed. Poor bone quality resulted in an average 45% increase in the tensile stresses of the cement mantles, indicating resulting poor survivorship rate.

Properties of high-oleic palm oils derived by fractional crystallization.

High-oleic palm oil (HOPO) with an oleic acid content of 59.0% and an iodine value (IV) of 78.2 was crystallized in a 200-kg De Smet crystallizer with a predetermined cooling program and appropriate agitation. The slurry was then fractionated by means of dry fractionation at 4, 8, 10, 12, and 15 degrees C. The oil and the fractionated products were subjected to physical and chemical analyses, including fatty acid composition, triacylglycerol and diacylglycerol composition, solid fat content, cloud point, slip melting point, and cold stability test. Fractionation at 15 degrees C resulted in the highest olein yield but with minimal oleic acid content. Due to the enhanced unsaturation of the oil, fractionation at relatively lower crystallization temperature showed a considerable effect on fatty acid composition as well as triacylglycerol and diacylglycerol composition of liquid fractions compared to higher crystallization temperature. The olein and stearin fractionated at 4 degrees C had the best cold stability at 0 degrees C and sharper melting profile, respectively.

Blue-shift and intensity enhancement of photoluminescence in lead-zirconate-titanate-doped silica nanocomposites.

Transparent PbZr(0.52)Ti(0.48)O(3) (PZT)-doped silica nanocomposites were fabricated via a modified sol-gel process. The nanocomposites were annealed at different temperatures between 740 and 800 °C in order to produce PZT crystallites with different particle sizes. X-ray diffraction analysis indicated that the embedded PZT nanoparticles were crystallized with a perovskite structure while the SiO(2) matrix was still in an amorphous state. Transmission electron microscopy confirmed that the PZT particles were of nanosize with perovskite structure and dispersed within the SiO(2) matrix. Photoluminescence spectra of the samples were measured between 10 and 290 K. The pure silica matrix showed an emission band at 3.20 eV and a weak emission band at 2.65 eV. They were noticeably suppressed in the PZT/SiO(2) nanocomposites. An additional emission band at ∼2.30 eV, due to transition within the PZT crystallites, was identified. This emission band showed a large blue-shift with decreasing PZT crystallite size and a substantially enhanced intensity as compared with that of bulk PZT ceramics. Our studies demonstrate the typical quantum size effect of ferroelectric-doped nanocomposites and the large influence of the silica matrix on the PL intensity of the embedded PZT particles.

Configuration of anchorage holes affects fixation of the acetabular component in cemented total hip replacement--a finite element study.

Our survey of current practice among UK orthopaedic surgeons shows wide variations in fixation techniques. The aim of this study, is to investigate the effect of drilling different configurations of anchorage holes in the acetabulum on implant stability. To avoid variables that could incur during in vitro testing, we used commercially available COSMOS finite element analysis package to investigate the stress distributions, deformations, and strains on the cement mantle when drilling three large anchorage holes and six smaller ones, with straight and rounded cement pegs. The results, which are in line with our in vitro studies on simulated reconstructed acetabulae, indicate better stability of the acetabular component when three larger holes than six smaller holes are drilled and when the necks of the anchorage holes are rounded. The longevity of total hip replacements could be improved by drilling three large anchorage holes, rather than many smaller ones, as initially proposed by Charnley.

Phenotypic and population differences in the association between CILP and lumbar disc disease.

BACKGROUND: Lumbar disc disease (LDD) is one of the leading causes of disability in the working-age population. A functional single-nucleotide polymorphism (SNP), +1184T-->C, in exon 8 of the cartilage intermediate layer protein gene (CILP) was recently identified as a risk factor for LDD in the Japanese population (odds ratio (OR) 1.61, 95% CI 1.31 to 1.98), with implications for impaired transforming growth factorbeta1 signalling. AIM: To validate this finding in two different ethnic cohorts with LDD. METHODS: This SNP and flanking SNPs were analysed in 243 Finnish patients with symptoms of LDD and 259 controls, and in 348 Chinese subjects with MRI-defined LDD and 343 controls. RESULTS AND CONCLUSION: The results showed no evidence of association in the Finnish (OR = 1.35, 95% CI 0.97 to 1.87; p = 0.14) or the Chinese (OR = 1.05, 95% CI 0.77 to 1.43; p = 0.71) samples, suggesting that cartilage intermediate layer protein gene is not a major risk factor for symptoms of LDD in Caucasians or in the general population that included individuals with or without symptoms.

The Mll-Een knockin fusion gene enhances proliferation of myeloid progenitors derived from mouse embryonic stem cells and causes myeloid leukaemia in chimeric mice.

Rearrangement of the mixed lineage leukaemia (MLL) gene with extra eleven nineteen (EEN) was previously identified in an infant with acute myeloid leukaemia. Using homologous recombination, we have created a mouse equivalent of the human MLL-EEN allele and showed that when Mll(Een/+) embryonic stem (ES) cells were induced to differentiate in vitro into haemopoietic cells, there was increased proliferation of myeloid progenitors with self-renewal property. We also generated Mll(Een/+) chimeric mice, which developed leukaemia displaying enlarged livers, spleens, thymuses and lymph nodes owing to infiltration of Mll(Een/+)-expressing leukemic cells. Immunophenotyping of cells from enlarged organs and bone marrow (BM) of the Mll(Een/+) chimeras revealed an accumulation of Mac-1+/Gr-1- immature myeloid cells and a reduction in normal B- and T-cell populations. We observed differential regulation of Hox genes between myeloid cells derived from Mll(Een/+) ES cells and mouse BM leukemic cells which suggested different waves of Hox expression may be activated by MLL fusion proteins for initiation (in ES cells) and maintenance (in leukemic cells) of the disease. We believe studies of MLL fusion proteins in ES cells combined with in vivo animal models offer new approaches to the dissection of molecular events in multistep pathogenesis of leukaemia.

ZnO nanorods on in-situ synthesized ZnSe grains.

The ZnO nanorods grown on in-situ synthesized ZnSe grains through the chemical vapour deposition method are reported here for the first time. With a suitable growth condition, single crystal ZnO nanorods grow on the well-defined bounded facets of the random shape ZnSe grains using Zn and Se powders without any metal catalyst. The growth direction of ZnSe nanorods on a facet of a ZnSe grain is quite uniform. The synthesis mechanism of the ZnO nanorods on the ZnSe grains is proposed. The effects of the Se powder usage on the ZnO-ZnSe products and the photoluminescence of the products are investigated.

Quasi-phase-matched generation of tunable blue light in a quasi-periodic structure.

We present what is to our knowledge a new approach to generating tunable blue light by cascaded nonlinear frequency conversion in a single LiTaO3 crystal. Simultaneous quasi-phase matching of an optical parametric generation process and a sum-frequency mixing process is achieved by means of structuring the crystal with a quasi-periodic optical superlattice. The spectral (wavelength tuning and bandwidth) and power characteristics of the blue-light generation are studied with a fixed-wavelength 532-nm picosecond laser and a wavelength-tunable nanosecond optical parametric oscillator (OPO) as the pump sources. By tuning the OPO wavelength, we could tune the blue output over approximately 20 nm. Temperature tuning of the blue output at a fixed pump wavelength of 532 nm was limited to approximately 1.5 nm. A maximum blue power of 15 microW was generated at a pump power of 0.5 mW, corresponding to an efficiency of 3%.