Why Fox stands ‘shoulder to shoulder’ with the USA in Afghanistan

Britain’s battered military mission in Afghanistan badly needed a shot in the arm. Morgan Roach heard Liam Fox making a clearcut case to a conservative thinktank in Washington on the rationale for continued intervention and on the trajectory for future developments

The K+ Channel KCa3.1 as a Novel Target for Idiopathic Pulmonary Fibrosis

Background\ud \ud Idiopathic pulmonary fibrosis (IPF) is a common, progressive and invariably lethal interstitial lung disease with no effective therapy. We hypothesised that KCa3.1 K+ channel-dependent cell processes contribute to IPF pathophysiology.\ud Methods\ud \ud KCa3.1 expression in primary human lung myofibroblasts was examined using RT-PCR, western blot, immunofluorescence and patch-clamp electrophysiology. The role of KCa3.1 channels in myofibroblast proliferation, wound healing, collagen secretion and contraction was examined using two specific and distinct KCa3.1 blockers (TRAM-34 and ICA-17043 [Senicapoc]).\ud Results\ud \ud Both healthy non fibrotic control and IPF-derived human lung myofibroblasts expressed KCa3.1 channel mRNA and protein. KCa3.1 ion currents were elicited more frequently and were larger in IPF-derived myofibroblasts compared to controls. KCa3.1 currents were increased in myofibroblasts by TGFβ1 and basic FGF. KCa3.1 was expressed strongly in IPF tissue. KCa3.1 pharmacological blockade attenuated human myofibroblast proliferation, wound healing, collagen secretion and contractility in vitro, and this was associated with inhibition of TGFβ1-dependent increases in intracellular free Ca2+.\ud Conclusions\ud \ud KCa3.1 activity promotes pro-fibrotic human lung myofibroblast function. Blocking KCa3.1 may offer a novel approach to treating IPF with the potential for rapid translation to the clinic

p190RhoGAP is the convergence point of adhesion signals from α5β1 integrin and syndecan-4

The fibronectin receptors α5β1 integrin and syndecan-4 cocluster in focal adhesions and coordinate cell migration by making individual contributions to the suppression of RhoA activity during matrix engagement. p190Rho–guanosine triphosphatase–activating protein (GAP) is known to inhibit RhoA during the early stages of cell spreading in an Src-dependent manner. This paper dissects the mechanisms of p190RhoGAP regulation and distinguishes the contributions of α5β1 integrin and syndecan-4. Matrix-induced tyrosine phosphorylation of p190RhoGAP is stimulated solely by engagement of α5β1 integrin and is independent of syndecan-4. Parallel engagement of syndecan-4 causes redistribution of the tyrosine-phosphorylated pool of p190RhoGAP between membrane and cytosolic fractions by a mechanism that requires direct activation of protein kinase C α by syndecan-4. Activation of both pathways is necessary for the efficient regulation of RhoA and, as a consequence, focal adhesion formation. Accordingly, we identify p190RhoGAP as the convergence point for adhesive signals mediated by α5β1 integrin and syndecan-4. This molecular mechanism explains the cooperation between extracellular matrix receptors during cell adhesion

MH-60 Seahawk / MQ-8 Fire Scout interoperability

Approved for public release; distribution is unlimitedAs part of a Naval Postgraduate School's capstone project in Systems Engineering, a project team from Cohort 311-0911 performed a Systems Engineering analysis. This Project focused on defining alternatives for enhanced Anti-Surface Warfare (ASUW) mission effectiveness through increased interoperability and integration for the Fire Scout Unmanned Air Vehicle and Seahawk helicopter. Specifically, the Project explored the available trade space for enhancing communications back to the ship for analysis and decision-making. Modeling and Simulation (MandS) was used to assess the impact of enhanced communication on specific Key performance Parameters (KPPs) and Measures of Effectiveness (MOEs) associated with the ASUW mission. Once the trade space was defined, alternatives were analyzed and a recommendation provided that supports near-, mid-, and long-term mission enhancement

Mesenchymal Stem Cell-Derived Extracellular Vesicles Reduce Disease Severity and Immune Responses in Inflammatory Arthritis

Abstract Background Novel biological therapies have revolutionised the management of Rheumatoid Arthritis (RA) but no cure currently exists. Mesenchymal stem cells (MSCs) immunomodulate inflammatory responses through paracrine signalling via growth factors, cytokines, chemokines and extracellular vesicles (EVs) in the cell secretome; however, MSCs are still not available in the clinic. We evaluated the therapeutic potential of MSCs-derived EVs in an antigen-induced model of arthritis (AIA). Methods EVs isolated from MSCs in normal (21% O 2 , 5% CO 2 ) or hypoxic (2% O 2 , 5% CO 2 ) culture or from MSCs pre-conditioned with a pro-inflammatory cytokine cocktail were applied into the AIA model. Disease pathology was assessed 3 days post arthritis induction through histopathological analysis of knee joints. Spleens and lymph nodes were collected and assessed for T cell polarisation within the immune response to AIA. Activated naïve CD4+ T cells from spleens of healthy mice were cultured with EVs or MSCs to assess deactivation capabilities. Results All EV treatments significantly reduced knee-joint swelling and histopathological signs of AIA with enhanced responses to normoxic and pro-inflammatory primed EVs. Polarisation of T cells towards CD4+ helper cells expressing IL17a (Th17) was reduced when EV treatments from MSCs cultured in hypoxia or pro-inflammatory priming conditions were applied. Conclusions Hypoxically cultured EVs present a priming methodology that is as effective in reducing swelling, IL-17a expression, Th17 polarisation and T cell proliferation as pro-inflammatory priming. EVs present an effective novel technology for cell-free therapeutic translation in treating inflammatory arthritis and autoimmune disorders such as RA

Interaction of CO2 laser-modified nylon with osteoblast cells in relation to wettability

It has been amply demonstrated previously that CO2 lasers hold the ability to surface modify various polymers. In addition, it has been observed that these surface enhancements can augment the biomimetic nature of the laser irradiated materials. This research has employed a CO2 laser marker to produce trench and hatch topographical patterns with peak heights of around 1 μm on the surface of nylon 6,6. The patterns generated have been analysed using white light interferometery, optical microscopy and X-ray photoelectron spectroscopy was employed to determine the surface oxygen content. Contact angle measurements were used to characterize each sample in terms of wettability. Generally, it was seen that as a result of laser processing the contact angle, surface roughness and surface oxygen content increased whilst the apparent polar and total surface energies decreased. The increase in contact angle and reduction in surface energy components was found to be on account of a mixed intermediate state wetting regime owing to the change in roughness due to the induced topographical patterns. To determine the biomimetic nature of the modified and as-received control samples each one was seeded with 2×104 cells/ml normal human osteoblast cells and observed after periods of 24 hours and 4 days using optical microscopy and SEM to determine mean cell cover densities and variations in cell morphology. In addition a haeymocytometer was used to show that the cell count for the laser patterned samples had increased by up to a factor of 1.5 compared to the as-received control sample after 4 days of incubation. Significantly, it was determined that all laser-induced patterns gave rise to better cell response in comparison to the as-received control sample studied due to increased preferential cell growth on those surfaces with increased surface roughness

Residual spinal cord compression following hemilaminectomy and mini-hemilaminectomy in dogs:a prospective randomized study

The aim of this study was to compare the reduction of spinal cord compression after surgical treatment of dogs with acute thoracolumbar intervertebral disc (IVD) extrusion achieved using hemilaminectomy versus mini-hemilaminectomy techniques. This was a prospective randomized study with client-owned dogs presented with acute IVD extrusion that were allocated to surgical treatment using hemilaminectomy (n = 15) or mini-hemilaminectomy (n = 15) techniques. Plain and intravenous-contrast computed tomography was performed pre- and postoperatively. The preoperative minimal cross-sectional dimension of the spinal cord (MDSC(pre)) and the postoperative minimal cross-sectional dimension of the spinal cord (MDSC(post)) were measured at the level of greatest compression. The minimal diameter of the uncompressed spinal cord was measured in a similar way both pre- (MDUSC(pre)) and postoperatively (MDUSC(post)). Dogs in the mini-hemilaminectomy group had significantly greater reduction of compression (RC) (p < 0.01) after surgery compared to dogs in the hemilaminectomy group. The mean RC in the hemilaminectomy group was 34.6% and in the mini-hemilaminectomy group 62.6%. Our results showed a significantly greater reduction of spinal cord compression for mini-hemilaminectomy compared to hemilaminectomy. Additionally, mini-hemilaminectomy could be a preferred method due to its minimal invasiveness and easier access to lateral fenestration

Development and evaluation of the Children's Experiences of Dental Anxiety Measure

Background Existing measures of children's dental anxiety have not been developed with children or based on a theoretical framework of dental anxiety. Aim To develop the children's experiences of dental anxiety measure (CEDAM) and evaluate the measure's properties. Design The measure was developed from interviews with dentally anxious children. Children recruited from a dental hospital and secondary school completed the CEDAM and Modified Child Dental Anxiety Scale (MCDAS). A subgroup of children completed the CEDAM before and after receiving an intervention to reduce dental anxiety to examine the measure's responsiveness. Rasch and Classical test analyses were undertaken. Results Children were aged between 9 and 16 years (N = 88 recruited from a dental hospital and N = 159 recruited from a school). Rasch analysis confirmed the measure's unidimensionality. The CEDAM correlated well with the MCDAS (rho = 0.67, P < 0.01) and had excellent internal consistency (Cronbach's alpha = 0.88) and test–retest reliability (ICC = 0.98). The CEDAM was also able to detect changes in dental anxiety following the intervention (baseline mean = 22.36, SD = 2.57 and follow-up mean = 18.88, SD = 2.42, t(df = 37) = 9.54, P < 0.01, Cohen's d = 1.39). Conclusions The results support the reliability, validity and responsiveness of the CEDAM. Initial findings indicate it has potential for use in future intervention trials or in clinical practice to monitor children's dental anxiety

Specific Changes in Arabidopsis thaliana Rosette Lipids during Freezing Can Be Associated with Freezing Tolerance

While the roles of a few specific lipids in plant freezing tolerance are understood, the effect of many plant lipids remains to be determined. Acclimation of plants to non-freezing cold before exposure to freezing temperatures improves the outcome of plants, compared to plants exposed to freezing without acclimation. Arabidopsis thaliana plants were subjected to one of three treatments: (1) “control”, i.e., growth at 21 °C, (2) “non-acclimated”, i.e., 3 days at 21 °C, 2 h at −8 °C, and 24 h recovery at 21 °C, and (3) “acclimated”, i.e., 3 days at 4 °C, 2 h at −8 °C, and 24 h recovery at 21 °C. Plants were harvested at seven time points during the treatments, and lipid levels were measured by direct-infusion electrospray ionization tandem mass spectrometry. Ion leakage was measured at the same time points. To examine the function of lipid species in relation to freezing tolerance, the lipid levels in plants immediately following the freezing treatment were correlated with the outcome, i.e., ion leakage 24-h post-freezing. Based on the correlations, hypotheses about the functions of specific lipids were generated. Additionally, analysis of the lipid levels in plants with mutations in genes encoding patatin-like phospholipases, lipoxygenases, and 12-oxophytodienoic acid reductase 3 (opr3), under the same treatments as the wild-type plants, identified only the opr3-2 mutant as having major lipid compositional differences compared to wild-type plants