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Epitaxially grown semiconductor quantum dots (QDs) and quantum rings (QRs) have been demonstrated to be excellent sources of single photons and entangled photon pairs enabling applications within quantum photonics. The emerging field of QD-based nanophotonics requires the deterministic integration of single or multiple QD structures into photonic architectures. However, the natural inhomogeneity and spatial randomness of self-assembled QDs limit their potential, and the reliable formation of homogeneous and ordered QDs during epitaxy still presents a challenge. Here, we demonstrate the fabrication of regular arrays of single III–V QDs and QRs using molecular beam epitaxy assisted by in situ direct laser interference patterning. Both droplet epitaxy (DE) GaAs/AlGaAs QDs and QRs and Stranski–Krastanov (SK) InAs/GaAs QDs are presented. The resulting QD structures exhibit high uniformity and good optical quality, in which a record-narrow photoluminescence linewidth of ∼17 meV from patterned GaAs QD arrays is achieved. Such QD and QR arrays fabricated through this novel optical technique constitute a next-generation platform for functional nanophotonic devices and act as useful building blocks for the future quantum revolution.

The administration of intermittent parathyroid hormone (iPTH) is anabolic to the skeleton. Recent studies with cultured osteoblasts have revealed that the expression of PHOSPHO1, a bone-specific phosphatase essential for the initiation of mineralisation, is regulated by PTH. Therefore, this study sought to determine whether the bone anabolic response to iPTH involves modulation of expression of Phospho1 and of other enzymes critical for bone matrix mineralisation. To mimic iPTH treatment, primary murine osteoblasts were challenged with 50 nM PTH for 6 h in every 48 h period for 8 days (4 cycles), 14 days (7 cycles) and 20 days (10 cycles) in total. The expression of both Phospho1 and Smpd3 was almost completely inhibited after 4 cycles, whereas 10 cycles were required to stimulate a similar response in Alpl expression. To explore the in vivo role of PHOSPHO1 in PTH-mediated osteogenesis, the effects of 14- and 28-day iPTH (80 µg/kg/day) administration was assessed in male wild-type (WT) and Phospho1

Fracture burden has created a need to better understand bone repair processes under different pathophysiological states. Evaluation of structural and material properties of the mineralised callus, which is integral to restoring biomechanical is therefore, vital. Micro-CT can facilitate non-invasive imaging of fracture repair, however, current methods for callus segmentation are only semi-automated, restricted to defined regions, time/labour intensive and prone to user-variation. Herein, we share a new automatic method for segmenting callus in micro-CT tomograms that will allow for objective, quantitative analysis of the bone fracture microarchitecture. Fractured and non-fractured mouse femurs were scanned and processed by both manual and automated segmentation of fracture callus from cortical bone after which microarchitectural parameters were analysed. All segmentation and analysis steps were performed using CTAn (Bruker, Belgium) with automatic segmentation performed using the software's image processing plugins. Results showed automatic segmentation reliably and consistently segmented callus from cortical bone, demonstrating good agreement with manual methods with low bias: tissue volume: -0.320mm

Summary This study is the first comprehensive characterisation of the pain phenotype after fracture using both evoked and naturalistic behaviours in adult male and ovariectomised female mice. It also shows that an anti-nerve growth factor (NGF) therapy could be considered to reduce pain after fracture surgery. Introduction Bone fractures are common due to the ageing population and very painful even after healing. The phenotype of this pain is still poorly understood. We aimed to characterise it in a femoral fracture model in mice. Methods We employed both adult male, and female ovariectomised (OVX) mice to mimic osteoporotic fractures. Mice underwent a unilateral femoral fracture maintained by an external fixator or a sham surgery. Pain behaviours, including mechanical and thermal sensitivity, weight bearing and LABORAS, were measured from baseline to 6 weeks after fracture. The effect on pain of an antibody against nerve growth factor (anti-NGF) was assessed. Changes in nerve density at the fracture callus were analysed by immunohistochemistry. Results Following surgery, all groups exhibited high levels of invoked nociception. Mechanical and thermal hyperalgesia were observed from 1 week after surgery, with nociceptive sensitization in the fracture group maintained for the 6 weeks, whereas it resolved in the sham group after 3 weeks. OVX induced reduction in pain thresholds, which was maintained after fracture. The frequency of naturalistic behaviours did not change between groups. Anti-NGF administered before and weekly after surgery alleviated fracture-induced mechanical nociception. The density of nerve fibres in the fracture callus was similar in all groups 6 weeks after surgery. Conclusions Fractures in rodent models are highly painful in both sexes. This pain-like phenotype is prolonged and should be routinely considered in fracture healing studies as it can affect the study outcome. The anti-NGF alleviates fracture-induced mechanical pain.

Nanophotonics, driven by low processing power and high density integration, is appearing as the next logical step for microwave photonics. Optical frequency combs (OFCs), which play a vital role in integrated microwave photonics, have not yet generated using nano-structured devices. In this paper, we propose OFC generation based on all-optical modulation of nanophotonic structures. A theoretical model based on temporal coupled mode theory is developed to describe cascaded all-optical photonic crystal intensity and phase modulators. Using a modulation light with a sinusoidal waveform, a separate carrier light is modulated to generate an OFC. By manipulating the modulation power and device dimensions, a flat OFC that spans over a 600 GHz is delivered. The proposed system offers OFC generation with tunable comb line spacing using devices with high density integration capabilities.

InGaAs/GaAsSb type-II superlattice (T2SL) photodiodes grown on InP substrates are an alternative detector technology for applications operating in the short wavelength infrared band. Their cut-off wavelengths are heavily influenced by the thickness and material composition of InGaAs and GaAsSb used in the T2SL. We present a single band k.p. model performed using a finite difference approach in nextnano validated against two T2SL photodiode wafers and results from literature. These photodiode wafers cover both lattice matched and strained GaAs1−x Sb x compositions (x = 0.40, wafer A and 0.49, wafer B). The validation data covers temperature dependence of cut-off wavelengths (obtained from phase-sensitive photo response data) from 200 K to room temperature. The cut-off wavelengths were found to reduce at 1.32 nm K−1 for wafer A and 1.07 nm K−1 for wafer B. Good agreement was achieved between the validation data and nextnano simulations, after altering the GaAs1−x Sb x valance band offset (VBO) bowing parameter to −1.06 eV. Using this validated model, we show that the wavefunction overlap drops significantly if the GaAsSb barrier is thicker than the InGaAs well layer, hence defining the upper limit of the barrier layer. This validated model is then used to demonstrate that there is a linear dependence between the maximum achievable wavefunction overlap and cut-off wavelength of a lattice matched InGaAs/GaAsSb T2SL. We also found that the adoption of a 5 nm/3 nm InGaAs/GaAsSb T2SL structure offers an improved wavefunction overlap over the more common 5 nm/5 nm InGaAs/GaAsSb T2SL designs. The data reported in this paper is available from doi: 10.15131/shef.data.20310591.

Collagen XII, belonging to the fibril-associated collagens with interrupted triple helix (FACIT) family, assembles from three identical α-chains encoded by the COL12A1 gene. The trimeric molecule consists of three N-terminal noncollagenous NC3 domains joined by disulfide bonds followed by a short interrupted collagen triple helix at the C-terminus. Collagen XII is expressed widely in the musculoskeletal system and mutations in the COL12A1 gene cause an Ehlers-Danlos/myopathy overlap syndrome, which is associated with skeletal abnormalities and muscle weakness. Our study defines the role of collagen XII in patella development using the Col12a1-/- mouse model. Deficiency in Col12a1 expression causes malformed facies patellaris femoris grooves at an early stage, which leads to patella subluxation and growth retardation. Due to the patella subluxation, more muscle fibers with centralized nuclei occur in the quadriceps than in the gastrocnemius muscles indicating a local effect. To further understand the role of collagen XII in the skeletal tissues single cell RNAseq (scRNA-seq) was performed. Comparison of the gene expression in the tenocyte cell sub-population of wild type and Col12a1-/- mice showed that several matrix genes are altered. Finally, we reinvestigated collagen XII deficient patients and observed a patella instability.

Rheumatoid arthritis (RA) is a progressive degenerative disorder that leads to joint destruction. Available treatments only target the inflammatory component with minimal impact on joint repair. We recently uncovered a previously unappreciated family of pro-resolving mediators, the maresin conjugate in tissue regeneration (MCTR), that display both immunoregulatory and tissue-protective activities. Thus, we queried whether the production of these autacoids is disrupted in RA patients and whether they can be useful in treating joint inflammation and promoting joint repair.Using a highly phenotyped RA cohort we evaluated plasma MCTR concentrations and correlated these to clinical markers of disease activity. To evaluate the immunoregulatory and tissue reparative activities we employed both in vivo models of arthritis and organ culture models.Herein, we observed that plasma MCTR3 concentrations were negatively correlated with joint disease activity and severity in RA patients. Evaluation of the mechanisms engaged by this mediator in arthritic mice demonstrated that MCTR3 reprograms monocytes to confer enduring joint protective properties. Single cell transcriptomic profiling and flow cytometric evaluation of macrophages from mice treated with MCTR3-reprogrammed monocytes revealed a role for Arginase-1 (Arg-1) in mediating their joint reparative and pro-resolving activities. Arg-1 inhibition reversed both the anti-arthritic and tissue reparative actions of MCTR3-reprogrammed monocytes.Our findings demonstrate that circulating MCTR3 levels are negatively correlated with disease in RA. When administered to mice in vivo, MCTR3 displayed both anti-inflammatory and joint reparative activities, protecting both cartilage and bone in murine arthritis. These activities were, at least in part, mediated via the reprogramming of mononuclear phagocyte responses.This work was supported by funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant no: 677542) and the Barts Charity (grant no: MGU0343) to J.D. J.D. is also supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant 107613/Z/15/Z).

We report the fabrication of highly ordered arrays of GaAs/AlGaAs quantum dots (QDs) by droplet epitaxy using in-situ direct laser interference patterning (DLIP). Two-dimensional arrays of Ga droplets with a periodicity of ~ 300 nm are initially formed on nanoisland structured AlGaAs surfaces due to the localised surface diffusion under the influence of a thermal gradient imposed by the light pulse. After crystallisation under an arsenic flux, precisely ordered arrays of GaAs single dots are obtained. The size distribution and optical properties of the ordered GaAs QDs are shown to be optimised by careful choice of parameters for nucleation and droplet formation.

The effective manipulation of mode oscillation and competition is of fundamental importance for controlling light emission in semiconductor lasers. Here we develop a rate equation model which considers the spatially modulated gain and spontaneous emission, which are inherently governed by the ripple of the vacuum electromagnetic field in a Fabry-Pérot (FP) microcavity. By manipulating the interplay between the spatial oscillation of the vacuum field and external optical injection via dual-beam laser interference, single longitudinal mode operation is observed in a FP-type microcavity with a side mode suppression ratio exceeding 40 dB. An exploration of this extended rate equation model bridges the gap between the classical model of multimode competition in semiconductor lasers and a quantum-optics understanding of radiative processes in microcavities.

Using cascaded intensity and phase modulators to achieve frequency combs is a common technique. However, this technique has not yet been employed to achieve optical frequency combs (OFCs) at the nanoscale. A theoretical model based on temporal coupled mode theory is developed to simulate an all-optical photonic crystal modulator. The concepts used to generate an OFC based on electro-optic modulators are then extended to the nanophotonic domain. It is theoretically proven that an OFC can be generated via all optical modulation of nanophotonic devices.

Laser interference has been widely used to produce one-dimensional gratings and more recently has shown great potential for two-dimensional patterning. In this study, the authors examine by simulation, its application to in-situ patterning during materials growth. To understand the potential, it is important to study the surface processes resulting from the laser–matter interaction, which have a key influence on the resulting growth mechanisms. In this work, the intensity distribution and the laser–semiconductor interaction resulting from four-beam interference patterns are analysed by numerical simulations. In particular, the authors derive the time and spatially dependent thermal distribution along with the thermal-induced desorption and surface diffusion. The results provide a crucial understanding of the light-induced thermal profile and show that the surface temperature and the surface adatom kinetics can be controlled by multi-beam pulsed laser interference patterning due to photothermal reactions. The approach has potential as an in-situ technique for the fast and precise nanostructuring of semiconductor material surfaces.

Precisely ordered arrays of InAs quantum dots are formed on a nanoisland-structured GaAs (100) surface using in situ laser interference during self-assembled molecular beam epitaxial growth. Nanoislands induced by single-pulse four-beam laser interference act as preferential nucleation sites for InAs quantum dots and result in site occupation dependent on the size of nanoislands, the InAs coverage, and the laser parameters. By optimizing the growth and interference conditions, regular dense ordering of single dots was obtained for the first time using this in situ noninvasive approach. The photoluminescence spectra of the resulting quantum dot arrays with a period of 300 nm show good optical quality and uniformity. This technique paves the way for the rapid large-scale fabrication of arrays of single dots to enable quantum information technology device platforms.

Blood supply is essential for osteogenesis, yet its relationship to load-related increases in bone mass is poorly defined. Herein, we aim to investigate the link between load-induced osteogenesis and the blood supply (bone perfusion and vascular porosity) using an established osteogenic noninvasive model of axial loading. Accordingly, 12 N mechanical loads were applied to the right tibiae of six male C57BL6 mice at 10–12 wk of age, 3 times/wk for 2 wk. Skeletal perfusion was measured acutely (postloading) and chronically in loaded and contralateral, nonloaded hindlimbs by laser-Doppler imaging. Vascular and lacunar porosity of the cortical bone and tibia load-related changes in trabecular and cortical bone was measured by nanoCT and micro-CT, respectively. We found that the mean skeletal perfusion (loaded: nonloaded limb ratio) increased by 56% immediately following the first loading episode (vs. baseline, P < 0.01), and a similar increase was observed after all loading episodes, demonstrating that these acute responses were conserved for 2 wk of loading. Loading failed, however, to engender any significant chronic changes in mean perfusion between the beginning and the end of the experiment. In contrast, 2 wk of loading engendered an increased vascular canal number in the tibial cortical compartment (midshaft) and, as expected, also increased trabecular and cortical bone volumes and modified tibial architecture in the loaded limb. Our results indicate that each episode of loading both generates acute enhancement in skeletal blood perfusion and also stimulates chronic vascular architectural changes in the bone cortices, which coincide with load-induced increases in bone mass.NEW & NOTEWORTHY This study investigated modifications to the blood supply (bone perfusion and intracortical vascular canals) in mechanoadaptive responses in C57BL6 mice. Each episode of mechanical loading acutely increases skeletal perfusion. Two weeks of mechanical loading increased bone mass and cortical vascular canal number, while there was no chronic increase in hindlimb perfusion. Our findings suggest that the blood supply may participate in the processes that govern load-induced bone formation.

In this paper, a novel method to generate optical frequency combs (OFCs) using nanoscale structures is explored. The growing demand for on-chip photonic processing dictates the need for multi-wavelength light sources, such as OFCs, that can be densely integrated with low processing power. Photonic crystal structues provide a viable method to generate all-optical modulation with sub-femto joule switching power and high density integration potential. This method of all-optical modulation is utilised here to generate an OFC from photonic crystal nanocavities and waveguides. Very- at-topped optical frequency combs with a small intensity variation can be generated based on theoretical predictions via detailed analysis of coupled mode theory for photonic crystal nanocavities and waveguides.

Summary Objective In osteoarthritis (OA), the pain-structure relationship remains complex and poorly understood. Here, we used the mechanical joint loading (MJL) model of OA to investigate both knee pathology and nociceptive behaviour. Design MJL was used to induce OA in the right knees of 12-week-old male C57BL/6 mice (40 cycles, 9N, 3x/week for 2 weeks). Mechanical sensitivity thresholds and weight-bearing ratios were measured before loading and at weeks one, three and six post-loading. At these time points, separate groups of loaded and non-loaded mice (n = 12/group) were sacrificed, joints collected, and fur corticosterone levels measured. μCT analyses of subchondral bone integrity was performed before joint sections were prepared for nerve quantification, cartilage or synovium grading (scoring system from 0 to 6). Results Loaded mice showed increased mechanical hypersensitivity paired with altered weight-bearing. Initial ipsilateral cartilage lesions 1-week post-loading (1.8 ± 0.4) had worsened at weeks three (3.0 ± 0.6, CI = −1.8–0.6) and six (2.8 ± 0.4, CI = −1.6–0.4). This increase in lesion severity correlated with mechanical hypersensitivity development (correlation; 0.729, P = 0.0071). Loaded mice displayed increased synovitis (3.6 ± 0.5) compared to non-loaded mice (1.5 ± 0.5, CI = −2.2–0.3) 1-week post-loading which returned to normal by weeks three and six. Similarly, corticosterone levels were only increased at week one post-loading (0.21 ± 0.04 ng/mg) compared to non-loaded controls (0.14 ± 0.01 ng/mg, CI = −1.8–0.1). Subchondral bone integrity and nerve volume remained unchanged. Conclusions Our data indicates that although the loading induces an initial stress reaction and local inflammation, these processes are not directly responsible for the nociceptive phenotype observed. Instead, MJL-induced allodynia is mainly associated with OA-like progression of cartilage lesions.

We report on a novel lithographic approach for the fabrication of integrated quantum dot (QD)-photonic crystal (PhC) nanocavity systems. We exploit unique hydrogen's ability to tailor the band gap energy of dilute nitride semiconductors to fabricate isolated site-controlled QDs via a spatially selective hydrogenation at the nanometer-scale. A deterministic integration of the realized site-controlled QDs with PhC nanocavities is provided by the inherent realignment precision (~20nm) of the electron beam lithography system used for the fabrication of both QDs and PhC cavities. A detailed description of the fabrication steps leading to the realization of integrated QD-PhC cavity systems is provided, together with the experimental evidence of a weak coupling effect between the single-photon emitter and the PhC cavity. Display Omitted A fabrication strategy for quantum dot-photonic crystal integration is presented.Spatial controlled hydrogen diffusion in dilute nitrides is used.Weak coupling effect between single photon emitter and cavity are observed.

Laser interference lithography is used to directly pattern the growing surface during molecular beam epitaxy growth of self-assembled InAs quantum dots on GaAs (100) substrates. Arrays of few-monolayer high nano-islands are formed prior to InAs quantum dot growth, which we believe result from the surface diffusion promoted by transient photothermal gradients. The deposition of InAs on such a surface leads to the nucleation of quantum dots solely at the island sites. The number of dots per site is determined by the island size which varies with the laser energy intensity. We are able to achieve highly ordered dense arrays of quantum dots with a single nanosecond laser pulse exposure. InAs quantum dots formed in this fashion show bright narrow photoluminescence with a peak at 1.04 eV at 88 K.

We demonstrate broadband and wide-angle antireflective surface nanostructuring in GaAs semiconductors using variable dose electron-beam lithography (EBL). Various designed structures are written with EBL on a positive EB-resist coated GaAs and developed followed by shallow inductively coupled plasma etching. An optimized nanostructured surface shows a reduced surface reflectivity down to less than 2.5% in the visible range of 450–700 nm and an average reflectance of less than 4% over a broad near-infrared wavelength range from 900–1400 nm. The results are obtained over a wide incidence angle of 33.3°. This study shows the potential for anti-reflective structures using a simpler reverse EBL process which can provide optical absorption or extraction efficiency enhancement in semiconductors relevant to improved performance in solar photovoltaics or light-emitting diodes.

Coherence of solid state spin qubits is limited by decoherence and random fluctuations in the spin bath environment. Here we develop spin bath control sequences which simultaneously suppress the fluctuations arising from intrabath interactions and inhomogeneity. Experiments on neutral self-assembled quantum dots yield up to a five-fold increase in coherence of a bare nuclear spin bath. Numerical simulations agree with experiments and reveal emergent thermodynamic behaviour where fluctuations are ultimately caused by irreversible conversion of coherence into many-body quantum entanglement. Simulations show that for homogeneous spin baths our sequences are efficient with non-ideal control pulses, while inhomogeneous bath coherence is inherently limited even under ideal-pulse control, especially for strongly correlated spin-9/2 baths. These results highlight the limitations of self-assembled quantum dots and advantages of strain-free dots, where our sequences can be used to control the fluctuations of a homogeneous nuclear spin bath and potentially improve electron spin qubit coherence., Fluctuating nuclear spin ensembles are a significant decoherence mechanism for solid-state spin qubits. Here the authors introduce an approach to controlling and extending the coherence of a nuclear spin bath around self-assembled quantum dots and gain insight into the many-body dynamics.

We demonstrate an effective method for fabricating large area periodic two-dimensional semiconductor nanostructures by means of single-pulse laser interference. Utilizing a pulsed nanosecond laser with a wavelength of 355 nm, precisely ordered square arrays of nanoholes with a periodicity of 300 nm were successfully obtained on UV photoresist and also directly via a resist-free process onto semiconductor wafers. We show improved uniformity using a beam-shaping system consisting of cylindrical lenses with which we can demonstrate highly regular arrays over hundreds of square micrometers. We propose that our novel observation of direct pattern transfer to GaAs is due to local congruent evaporation and subsequent droplet etching of the surface. The results show that single-pulse interference can provide a rapid and highly efficient route for the realization of wide-area periodic nanostructures on semiconductors and potentially on other engineering materials.

A two- to three-dimensional (2D to 3D) transition in InAs/GaAs sub-monolayer quantum dot (SML-QD) growth was investigated, and its evolution was traced. From the AFM results, the SML-QDs disappeared gradually and plateaus around each island formed with increasing GaAs capping layer thickness (tCL) from 1.5 ML to 4.5 ML. The SML-QDs become fully covered with a GaAs capping layer, leading to a planarization process caused by strain relaxation. In addition, when the individual InAs coverage was is insufficient to cause a 3D transition, similar plateaus formed when stacking with an increasing number of stacking layers (S) from 2 to 6. On the other hand, as the InAs coverage was increased from 0.3 to 0.5 ML, 3D dots with a comparable size to typical SK-QDs were observed beyond S = 4. This means that as the total InAs deposition thickness increases above a critical thickness (~2.0 ML), 2D-small islands transform spontaneously into 3D-pyramid QDs. Such structures then show similar optical characteristics to SK-QDs. Overall, the transition from 2D to 3D in InAs/GaAs SML-QD growth could be controlled by careful choice of the parameters tcl, θ, and S.

One of the key challenges in spectroscopy is the inhomogeneous broadening that masks the homogeneous spectral lineshape and the underlying coherent dynamics. Techniques such as four-wave mixing and spectral hole-burning are used in optical spectroscopy, and spin-echo in nuclear magnetic resonance (NMR). However, the high-power pulses used in spin-echo and other sequences often create spurious dynamics obscuring the subtle spin correlations important for quantum technologies. Here we develop NMR techniques to probe the correlation times of the fluctuations in a nuclear spin bath of individual quantum dots, using frequency-comb excitation, allowing for the homogeneous NMR lineshapes to be measured without high-power pulses. We find nuclear spin correlation times exceeding one second in self-assembled InGaAs quantum dots - four orders of magnitude longer than in strain-free III-V semiconductors. This observed freezing of the nuclear spin fluctuations suggests ways of designing quantum dot spin qubits with a well-understood, highly stable nuclear spin bath.

E11/Podoplanin (Pdpn) is implicated in early osteocytogenesis and the formation of osteocyte dendrites. This dendritic network is critical for bone modelling/remodelling, through the production of receptor activator of nuclear factor κ B (RANK)-ligand (RANKL). Despite this, the role of Pdpn in the control of bone remodelling is yet to be established in vivo. Here we utilised bone-specific Pdpn conditional knockout mice (cKO) to examine the role of Pdpn in the bone loss associated with ovariectomy (OVX). MicroCT revealed that Pdpn deletion had no significant effect on OVX-induced changes in trabecular microarchitecture. Significant differences between genotypes were observed in the trabecular pattern factor (P

We demonstrate the growth and surface characterization of laterally ordered arrays of InAs quantum dot molecules (QDMs) on GaAs (100) substrates produced by a combination of in situ interferometric nanopatterning and molecular beam epitaxy growth. Four-beam ultraviolet laser interference is applied during the growth process resulting in the formation of quasi two-dimensional islands due to localized surface diffusion. With further InAs deposition, the edges of the islands are observed to act as preferential sites for the nucleation of InAs quantum dots. Well-ordered square arrays of lateral QDMs with a period of 300 nm and site occupancy ranging from single dot up to hexa-molecules are obtained by varying the InAs coverage from 1.55 ML to 1.75 ML.

A commonly used technique to generate an optical frequency comb (OFC) generation is to cascade intensity and phase electro-optical modulators [1]. Nanoscale all-optical devices can also achieve intensity and phase modulation, however the use of these modulators to generate OFCs has hitherto not been addressed. In this paper a mathematical model is introduced to simulate an all-optical modulator, based on temporal coupled mode theory. The techniques used in electro-optical modulators to generate an OFC are then extended to function on the nanoscale. Using this model, it is theoretically demonstrated that all-optical modulation of a nanophotonic device can generate an OFC.

Following the demonstration of quality factor (Q-factor) control in coupled photonic crystal nanocavities, we present our new research work on the Q-factor control in laterally coupled vertical cavities. Thermal-optic Q-tuning has been successfully observed when bringing a square-shaped vertical cavity and an adjacent Fabry-Perot-like cavity into resonance. The approach paves the way towards a few quantum optical applications using vertical cavities.

ObjectivesHuman osteoarthritis (OA) is detected only at late stages. Male STR/Ort mice develop knee OA spontaneously with known longitudinal trajectory, offering scope to identify OA predisposing factors. We exploit the lack of overt OA in female STR/Ort and in both sexes of parental, control CBA mice to explore whether early divergence in tibial bone mass or shape are linked to emergent OA.MethodWe undertook detailed micro-CT comparisons of trabecular and cortical bone, multiple structural/architectural parameters and finite element modelling (FEM) of the tibia from male and female STR/Ort and CBA mice at 8-10 (pre-OA), 18-20 (OA onset) and 40+ weeks (advanced OA) of age.ResultsWe found higher trabecular bone mass in female STR/Ort than in either OA-prone male STR/Ort or non-prone CBA mice. Cortical bone, as expected, showed greater cross-sectional area in male than female CBA, which surprisingly was reversed in STR/Ort mice. STR/Ort also exhibited higher cortical bone mass than CBA mice. Our analyses revealed similar tibial ellipticity, yet greater predicted resistance to torsion in male than female CBA mice. In contrast, male STR/Ort exhibited greater ellipticity than both female STR/Ort and CBA mice at specific cortical sites. Longitudinal analysis revealed greater tibia curvature and shape deviations in male STR/Ort mice that coincided with onset and were more pronounced in late OA.ConclusionGeneralised higher bone mass in STR/Ort mice is more marked in non OA-prone females, but pre-OA divergence in bone shape is restricted to male STR/Ort mice in which OA develops spontaneously.

The secondary dystroglycanopathies are characterized by the hypoglycosylation of alpha dystroglycan, and are associated with mutations in at least 18 genes that act on the glycosylation of this cell surface receptor rather than the Dag1 gene itself. At the severe end of the disease spectrum, there are substantial structural brain defects, the most striking of which is often cobblestone lissencephaly. The aim of this study was to determine the gene-specific aspects of the dystroglycanopathy brain phenotype through a detailed investigation of the structural brain defects present at birth in three mouse models of dystroglycanopathy-the FKRP(KD) , which has an 80% reduction in Fkrp transcript levels; the Pomgnt1null , which carries a deletion of exons 7-16 of the Pomgnt1 gene; and the Large(myd) mouse, which carries a deletion of exons 5-7 of the Large gene. We show a rostrocaudal and mediolateral gradient in the severity of brain lesions in FKRP(KD) , and to a lesser extent Pomgnt1null mice. Furthermore, the mislocalization of Cajal-Retzius cells is correlated with the gradient of these lesions and the severity of the brain phenotype in these models. Overall these observations implicate gene-specific differences in the pathogenesis of brain lesions in this group of disorders.