Serum Complement C3 and C4 Levels in Relation to Diagnosis of Lupus Nephritis

Purpose: The main objective of this study was to measure serum complement C3 and C4 concentrations in patients of lupus nephritis to see if these simple measurements would give useful information to the clinician managing such patients.Method: A total of 52 samples were obtained from SLE patients, 17 suffering from lupus nephritis. All patients met the revised 1997 American College of Rheumatology criteria for SLE. Serum C3 and C4 concentrations were measured with single gel radioimmunodiffusion technique. Results: In lupus nephritis, C3 and C4 are generally correlated. Both C3 and C4 levels were decreased but C4 concentrations were more often and more profoundly depressed than C3 concentration. Conclusion: All patients of lupus nephritis with low C3 or C4 concentrations should have serial measurements performed and selected patients will need a full complement profile, including measurement of alternate pathway components and total hemolytic pathway. Keywords: Systemic lupus erythematosus, Auto antibodies, Lupus nephritis, C3 and C4Tropical Journal of Pharmaceutical Research Vol. 7(4) 2008: pp. 1117-112

Physico-Chemical Assessment of Drinking Water Available to the Inhabitants of Low Income and Thickly Populated Areas of Karachi City

The aim of this study was to investigate the physico-chemical properties of drinking water available to the population of low income areas of Karachi city. The study incorporated the attention towards the fluoride content in water being used for domestic and drinking purpose by the inhabitants of low income and thickly populated areas of Karachi. Samples were collected from selected locations from all the districts of Karachi city. Laboratory tests were performed to analyze both physical and chemical characteristics of drinking water. It was observed in this study that except few of the locations, fluoride content was present either in low concentration or in high concentration. Medical data of the areas under study was collected through questionnaires and survey forms. The consequence of the variation of fluoride concentration was found to be in agreement with the findings of medical data analyzed from concerned areas where both cases of Fluorosis and dental cavities were reported. Correlation of fluoride with other parameters was analyzed using principle component analysis determined PC1 & PC2 as most significant components. PC1 showed dominance of TDS with salts while PC2 indicated loadings were temperature DO & pH. Monitoring of fluoride ion concentration and other health related parameters are essential for the development of efficient water management system. Fluoride content in drinking water should be regulated by periodic assessment and elevated levels can be controlled by adsorption or membrane techniques. Keywords: Physico-chemical properties, drinking water, districts of Karachi, fluoride variation, correlation analysis, principle component analysis, water management system. DOI: 10.7176/JNSR/11-14-01 Publication date:July 31st 202

Mechanotransducive surfaces for enhanced cell osteogenesis, a review

Novel strategies employing mechano-transducing materials eliciting biological outcomes have recently emerged for controlling cellular behaviour. Targeted cellular responses are achieved by manipulating physical, chemical, or biochemical modification of material properties. Advances in techniques such as nanopatterning, chemical modification, biochemical molecule embedding, force-tuneable materials, and artificial extracellular matrices are helping understand cellular mechanotransduction. Collectively, these strategies manipulate cellular sensing and regulate signalling cascades including focal adhesions, YAP-TAZ transcription factors, and multiple osteogenic pathways. In this minireview, we are providing a summary of the influence that these materials, particularly titanium-based orthopaedic materials, have on cells. We also highlight recent complementary methodological developments including, but not limited to, the use of metabolomics for identification of active biomolecules that drive cellular differentiation

Neural Networks based Shunt Hybrid Active Power Filter for Harmonic Elimination

The growing use of nonlinear devices is introducing harmonics in the power system networks that results in distortion of current and voltage signals causing damage to the power distribution system. Therefore, in power systems, the elimination of harmonics is of great concern. This paper presents an efficient techno-economical approach to suppress harmonics and improve the power factor in the power distribution network using neural network algorithms-based Shunt Hybrid Active Power Filter (SHAPF), such as Artificial Neural Network (ANN), Adaptive Neuro-Fuzzy Inference System (ANFIS), and Recurrent Neural Network (RNN). The objective of the proposed algorithms for SHAPF is to reduce Total Harmonic Distortion (THD) within an acceptable range to improve system quality. In our filter design approach, we tested and compared conventional pq0 theory and neural networks to detect the harmonics present in the power system. Moreover, for the regulation of the DC supply to the inverter of the SHAPF, the conventional PI controller and neural networks-based controllers are used and compared. The applicability of the proposed filter is tested for three different nonlinear load cases. The simulation results show that the neural networks-based filter control techniques satisfy all international standards with minimum current THD, neutral wire current elimination, and small DC voltage fluctuations for voltage regulation current. Furthermore, all three neural network architectures are tested and compared based on accuracy and computational complexity, with RNN outperforming the rest

The IĸB protein BCL3 controls osteogenesis and bone health

Objective: IĸB protein B-cell lymphoma 3-encoded protein (BCL3) is a regulator of the NF-κB family of transcription factors. NF-κB signalling fundamentally influences the fate of bone-forming osteoblasts and bone-resorbing osteoclasts, but the role of BCL3 in bone biology has not been investigated. The objective of this study was to evaluate BCL3 in skeletal development, maintenance and osteoarthritic pathology. Methods: To assess the contribution of BCL3 to skeletal homeostasis, neonatal mice (n = 6-14) lacking BCL3 (Bcl3−/−) and WT controls were characterised for bone phenotype and density. To reveal the contribution to bone phenotype by the osteoblast compartment in Bcl3−/− mice, transcriptomic analysis of early osteogenic differentiation and cellular function (n = 3-7) were assessed. Osteoclast differentiation and function in Bcl3−/− mice (n = 3-5) was assessed. Adult 20-week Bcl3−/− and WT mice bone phenotype, strength and turnover were assessed. A destabilisation of the medial meniscus (DMM) model of osteoarthritic ostephytogenesis was utilised to understand adult bone formation in Bcl3−/− mice (n = 11-13). Results: Evaluation of Bcl3−/− mice revealed congenitally increased bone density, long bone dwarfism, increased bone biomechanical strength and altered bone turnover. Molecular and cellular characterisation of mesenchymal precursors showed that Bcl3−/− cells display an accelerated osteogenic transcriptional profile that leads to enhanced differentiation into osteoblasts with increased functional activity; which could be reversed with a mimetic peptide. In a model of osteoarthritis-induced osteophytogenesis, Bcl3−/− mice exhibit decreased pathological osteophyte formation (P < 0.05). Conclusion: Cumulatively, these findings demonstrate that BCL3 controls developmental mineralisation to enable appropriate bone formation, whilst in a pathological setting it contributes to skeletal pathology

Helical ordering of envelope‐associated proteins and glycoproteins in respiratory syncytial virus

Human respiratory syncytial virus (RSV) causes severe respiratory illness in children and the elderly. Here, using cryogenic electron microscopy and tomography combined with computational image analysis and three-dimensional reconstruction, we show that there is extensive helical ordering of the envelope-associated proteins and glycoproteins of RSV filamentous virions. We calculated a 16 Å resolution sub-tomogram average of the matrix protein (M) layer that forms an endoskeleton below the viral envelope. These data define a helical lattice of M-dimers, showing how M is oriented relative to the viral envelope. Glycoproteins that stud the viral envelope were also found to be helically ordered, a property that was coordinated by the M-layer. Furthermore, envelope glycoproteins clustered in pairs, a feature that may have implications for the conformation of fusion (F) glycoprotein epitopes that are the principal target for vaccine and monoclonal antibody development. We also report the presence, in authentic virus infections, of N-RNA rings packaged within RSV virions. These data provide molecular insight into the organisation of the virion and the mechanism of its assembly

The role of NF-κB regulator Bcl-3 in the skeleton

Bone and joint erosion and fragility fractures are associated with osteoarthritis and osteoporosis, and represent a major unmet clinical problem. In health, the balance between chondrocytes, osteoblasts and osteoclasts is a dynamic process under tight regulation. In disease, regulation is uncontrolled resulting in overt skeletal dysfunction and bone loss. NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells) is a master regulator of cellular function and is an essential element in the development and homeostasis of the skeletal system. As such it is a critical controller of chondrocyte, osteoblast and osteoclast differentiation and function. Bcl-3 (B-cell lymphoma 3-encoded protein) is an atypical IκB protein and via its selective interaction with p50 and p52 homodimers of NF-κB is a regulator of cellular function. As a regulator of NF-κB, the role of Bcl-3 was hypothesised to be critical in affecting skeletal health. With the aim of defining the role of Bcl-3 in the skeleton, mice deficient in Bcl-3 (Bcl-3-/-) were compared to wild-type (Wt) mice. Ex vivo phenotypic analysis of Bcl-3-/- mice and in vitro cellular differentiation assays of Bcl-3-/- chondrocytes, osteoblasts and osteoclasts were performed. In neonatal Bcl-3-/- mice, multiple phenotypes were discovered, including dwarfism and increased mineral density. Morphometric analysis of developing and adult mice showed that 20-week Bcl-3-/- mice had a profoundly divergent phenotype from Wt. Male 20-week Bcl-3-/- mice had increased bone density in the trabecular and cortical regions and increased biomechanical strength, compared to Wt, implicating increased bone formation. Female 20-week Bcl-3-/- mice did not differ from Wt in the trabecular region; however, they possessed decreased bone area in cortical bone. Bone turnover rates of 20-week Bcl-3-/- males were lower than in Wt, implicating an accelerated rate of bone resorption, following peak bone density. While no differences in chondrocyte differentiation were found, Bcl-3-/- osteoblasts were found to have accelerated osteogenesis. Complementarily, simulated overexpression with Bcl-3 mimetic peptide restricted osteoblast differentiation. An expression repertoire of marker genes and miRNAs reflected increased RUNX2 (Runt-related transcription factor 2) activity in early-differentiating Bcl-3-/- osteoblasts. Compared to Wt, Bcl-3-/- osteoblasts had an altered whole-transcriptomic profile in early osteogenesis, with multiple NF-κB-driven osteogenic gene clusters identified. Osteoblasts increased expression of RANKL (RANK ligand) and decreased OPG (osteoprotegerin) expression, involved in signalling cross-talk with osteoclasts. Bcl-3-/- osteoclasts had increased intrinsic osteoclastogenesis and resorption, while treatment with Bcl-3 peptide restricted osteoclast differentiation and function. The ex vivo phenotypic results were complementary to in vitro assays, showing increased bone turnover. The lack of Bcl-3 in both, osteoblasts and osteoclasts, increased their differentiation and activities. Thus, Bcl-3 functions as an inhibitor of NF-κB-driven early osteogenesis and osteoclastogenesis. These findings help identify Bcl-3 as a novel target for the treatment of diseases involving skeletal pathology

Precision Landing and Testing of Aerospace Vehicles.

Planetary precision landing in non-cooperative sites has been a major challenge. An indoor novel planetary precision landing facility known as Surrey Precision Landing Facility (SPLF) has been developed to bridge the gap between software simulations and outdoor expensive UAV based planetary precision landing testbeds. The 3D motion capture system provides real-time accurate navigation data by removing the uncertainty in the position, and thus allows the flexibility to test the planetary terminal descent based Guidance and Control algorithms on quadrotors safely, rapidly, repeatedly with very low operating cost. Quadrotors can follow the trajectory of a planetary lander during its terminal descent. Model Predictive Control (MPC) incorporates input/output constraints in the calculation of the control law and thus can be used for the planetary terminal descent scenarios. Feasibility and computation time have been a key hindrance in practical validation of MPC for quadrotor control. Therefore, a novel single stage linear MPC algorithm in a state-space framework has been developed to improve feasibility and computation time over Optimal MPC (OMPC), Laguerre OMPC (LOMPC) and Steady-State (SS) OMPC (SSOMPC) by linking reference governor, Closed-Loop Paradigm, Steady-State Target Optimization and Laguerre function techniques. The novel SSLOMPC algorithm is simulated to test its performance on a simple two state model, and then has been implemented in simulation and practically validated at SPLF on a quadrotor for the set-point tracking scenarios. Disturbance rejection and offset free tracking is achieved via a Kalman filter. Simulated and practical implementations of PID, LQR and MPC control laws on a quadrotor helicopter for the Mars terminal descent phase has been performed at SPLF, where SSOMPC/SSLOMPC successfully demonstrates the ability to respect the control input and output constraints. The conclusion is that the use of Steady-State OMPC with Laguerre functions improves feasibility and computation time. MPC can be used as a practical candidate controller for planetary precision landing scenarios. The tracking errors for PID, LQR and MPC control laws were less than 10 cm in the practical tests