Investigation of electrophoretic loading and enhanced mechanical properties of hydrogels for delivery of therapeutic proteins

Hydrogels, which are three-dimensional crosslinked hydrophilic polymers, have been used and studied widely as vehicles for drug delivery due to their good biocompatibility. Traditional methods to load therapeutic proteins into hydrogels have some disadvantages. Biological activity of drugs or proteins can be compromised during polymerization process or the process of loading protein can be really timeconsuming. Therefore, different loading methods have been investigated. Based on the theory of electrophoresis, an electrochemical gradient can be used to transport proteins into hydrogels. Therefore, an electrophoretic method was used to load protein in this study. Chemically and radiation crosslinked polyacrylamide was used to set up the model to load protein electrophoretically into hydrogels. Different methods to prepare the polymers have been studied and have shown the effect of the crosslinker (bisacrylamide) concentration on the protein loading and release behaviour. The mechanism of protein release from the hydrogels was anomalous diffusion (i.e. the process was non-Fickian). The UV-Vis spectra of proteins before and after reduction show that the bioactivities of proteins after release from hydrogel were maintained. Due to the concern of cytotoxicity of residual monomer in polyacrylamide, poly(2-hydroxyethyl- methacrylate) (pHEMA) was used as the second tested material. In order to control the pore size, a polyethylene glycol (PEG) porogen was introduced to the pHEMA. The hydrogel disintegrated after immersion in water indicating that the swelling forces exceeded the strength of the material. In order to understand the cause of the disintegration, several different conditions of crosslinker concentration and preparation method were studied. However, the disintegration of the hydrogel still occurred after immersion in water principally due to osmotic forces. A hydrogel suitable for drug delivery needs to be biocompatible and also robust. Therefore, an approach to improving the mechanical properties of the porogen-containing pHEMA hydrogel by introduction of an inter-penetrating network (IPN) into the hydrogel system has been researched. A double network was formed by the introduction of further HEMA solution into the system by both electrophoresis and slow diffusion. Raman spectroscopy was used to observe the diffusion of HEMA into the hydrogel prior to further crosslinking by ã-irradiation. The protein loading and release behaviour from the hydrogel showing enhanced mechanical property was also studied. Biocompatibility is a very important factor for the biomedical application of hydrogels. Different hydrogels have been studied on both a three-dimensional HSE model and a HSE wound model for their biocompatibilities. They did not show any detrimental effect to the keratinocyte cells. From the results reported above, these hydrogels show good biocompatibility in both models. Due to the advantage of the hydrogels such as the ability to absorb and deliver protein or drugs, they have potential to be used as topical materials for wound healing or other biomedical applications.

Strategic dalliances as an enabler for discontinuous innovation in slow clockspeed industries: evidence from the oil and gas industry

The concept of ‘strategic dalliances’– defined as non-committal relationships that companies can ‘dip in and out of,’ or dally with, while simultaneously maintaining longer-term strategic partnerships with other firms and suppliers – has emerged as a promising strategy by which organizations can create discontinuous innovations. But does this approach work equally well for every sector? Moreover, how can these links be effectively used to foster the process of discontinuous innovation? Toward assessing the role that industry clockspeed plays in the success or failure of strategic dalliances, we provide case study evidence from Twister BV, an upstream oil and gas technology provider, and show that strategic dalliances can be an enabler for the discontinuous innovation process in slow clockspeed industries. Implications for research and practice are discussed, and conclusions from our findings are drawn.

Hypoxia-mimicking mesoporous bioactive glass scaffolds with controllable cobalt ion release for bone tissue engineering

Low oxygen pressure (hypoxia) plays an important role in stimulating angiogenesis; there are, however, few studies to prepare hypoxia-mimicking tissue engineering scaffolds. Mesoporous bioactive glass (MBG) has been developed as scaffolds with excellent osteogenic properties for bone regeneration. Ionic cobalt (Co) is established as a chemical inducer of hypoxia-inducible factor (HIF)-1α, which induces hypoxia-like response. The aim of this study was to develop hypoxia-mimicking MBG scaffolds by incorporating ionic Co2+ into MBG scaffolds and investigate if the addition of Co2+ ions would induce a cellular hypoxic response in such a tissue engineering scaffold system. The composition, microstructure and mesopore properties (specific surface area, nano-pore volume and nano-pore distribution) of Co-containing MBG (Co-MBG) scaffolds were characterized and the cellular effects of Co on the proliferation, differentiation, vascular endothelial growth factor (VEGF) secretion, HIF-1α expression and bone-related gene expression of human bone marrow stromal cells (BMSCs) in MBG scaffolds were systematically investigated. The results showed that low amounts of Co (< 5%) incorporated into MBG scaffolds had no significant cytotoxicity and that their incorporation significantly enhanced VEGF protein secretion, HIF-1α expression, and bone-related gene expression in BMSCs, and also that the Co-MBG scaffolds support BMSC attachment and proliferation. The scaffolds maintain a well-ordered mesopore channel structure and high specific surface area and have the capacity to efficiently deliver antibiotics drugs; in fact, the sustained released of ampicillin by Co-MBG scaffolds gives them excellent anti-bacterial properties. Our results indicate that incorporating cobalt ions into MBG scaffolds is a viable option for preparing hypoxia-mimicking tissue engineering scaffolds and significantly enhanced hypoxia function. The hypoxia-mimicking MBG scaffolds have great potential for bone tissue engineering applications by combining enhanced angiogenesis with already existing osteogenic properties.

Cyclin-dependent kinase-mediated phosphorylation of RBP1 and pRb promotes their dissociation to mediate release of the SAP30·mSin3·HDAC transcriptional repressor complex

Eukaryotic cell cycle progression is mediated by phosphorylation of protein substrates by cyclin-dependent kinases (CDKs). A critical substrate of CDKs is the product of the retinoblastoma tumor suppressor gene, pRb, which inhibits G1-S phase cell cycle progression by binding and repressing E2F transcription factors. CDK-mediated phosphorylation of pRb alleviates this inhibitory effect to promote G1-S phase cell cycle progression. pRb represses transcription by binding to the E2F transactivation domain and recruiting the mSin3·histone deacetylase (HDAC) transcriptional repressor complex via the retinoblastoma-binding protein 1 (RBP1). RBP1 binds to the pocket region of pRb via an LXCXE motif and to the SAP30 subunit of the mSin3·HDAC complex and, thus, acts as a bridging protein in this multisubunit complex. In the present study we identified RBP1 as a novel CDK substrate. RBP1 is phosphorylated by CDK2 on serines 864 and 1007, which are N- and C-terminal to the LXCXE motif, respectively. CDK2-mediated phosphorylation of RBP1 or pRb destabilizes their interaction in vitro, with concurrent phosphorylation of both proteins leading to their dissociation. Consistent with these findings, RBP1 phosphorylation is increased during progression from G 1 into S-phase, with a concurrent decrease in its association with pRb in MCF-7 breast cancer cells. These studies provide new mechanistic insights into CDK-mediated regulation of the pRb tumor suppressor during cell cycle progression, demonstrating that CDK-mediated phosphorylation of both RBP1 and pRb induces their dissociation to mediate release of the mSin3·HDAC transcriptional repressor complex from pRb to alleviate transcriptional repression of E2F.

Machine vision toolbox for MATLAB, release 3 [Software]

The Toolbox, combined with MATLAB ® and a modern workstation computer, is a useful and convenient environment for investigation of machine vision algorithms. For modest image sizes the processing rate can be sufficiently ``real-time'' to allow for closed-loop control. Focus of attention methods such as dynamic windowing (not provided) can be used to increase the processing rate. With input from a firewire or web camera (support provided) and output to a robot (not provided) it would be possible to implement a visual servo system entirely in MATLAB. Provides many functions that are useful in machine vision and vision-based control. Useful for photometry, photogrammetry, colorimetry. It includes over 100 functions spanning operations such as image file reading and writing, acquisition, display, filtering, blob, point and line feature extraction, mathematical morphology, homographies, visual Jacobians, camera calibration and color space conversion.

Robotics toolbox for MATLAB, release 9 [Software]

The ninth release of the Toolbox, represents over fifteen years of development and a substantial level of maturity. This version captures a large number of changes and extensions generated over the last two years which support my new book “Robotics, Vision & Control”. The Toolbox has always provided many functions that are useful for the study and simulation of classical arm-type robotics, for example such things as kinematics, dynamics, and trajectory generation. The Toolbox is based on a very general method of representing the kinematics and dynamics of serial-link manipulators. These parameters are encapsulated in MATLAB ® objects - robot objects can be created by the user for any serial-link manipulator and a number of examples are provided for well know robots such as the Puma 560 and the Stanford arm amongst others. The Toolbox also provides functions for manipulating and converting between datatypes such as vectors, homogeneous transformations and unit-quaternions which are necessary to represent 3-dimensional position and orientation. This ninth release of the Toolbox has been significantly extended to support mobile robots. For ground robots the Toolbox includes standard path planning algorithms (bug, distance transform, D*, PRM), kinodynamic planning (RRT), localization (EKF, particle filter), map building (EKF) and simultaneous localization and mapping (EKF), and a Simulink model a of non-holonomic vehicle. The Toolbox also including a detailed Simulink model for a quadcopter flying robot.

Turbulence measurements in a small subtropical estuary under king tide conditions

In natural waterways and estuaries, the understanding of turbulent mixing is critical to the knowledge of sediment transport, stormwater runoff during flood events, and release of nutrient-rich wastewater into ecosystems. In the present study, some field measurements were conducted in a small subtropical estuary with micro-tidal range and semi-diurnal tides during king tide conditions: i. e., the tidal range was the largest for both 2009 and 2010. The turbulent velocity measurements were performed continuously at high-frequency (50Hz) for 60 h. Two acoustic Doppler velocimeters (ADVs) were sampled simultaneously in the middle estuarine zone, and a third ADV was deployed in the upper estuary for 12 h only. The results provided an unique characterisation of the turbulence in both middle and upper estuarine zones under the king tide conditions. The present observations showed some marked differences between king tide and neap tide conditions. During the king tide conditions, the tidal forcing was the dominant water exchange and circulation mechanism in the estuary. In contrast, the long-term oscillations linked with internal and external resonance played a major role in the turbulent mixing during neap tides. The data set showed further that the upper estuarine zone was drastically less affected by the spring tide range: the flow motion remained slow, but the turbulent velocity data were affected by the propagation of a transient front during the very early flood tide motion at the sampling site. © 2012 Springer Science+Business Media B.V.

Effort-release public-key encryption from cryptographic puzzles

Timed-release cryptography addresses the problem of “sending messages into the future”: information is encrypted so that it can only be decrypted after a certain amount of time, either (a) with the help of a trusted third party time server, or (b) after a party performs the required number of sequential operations. We generalise the latter case to what we call effort-release public key encryption (ER-PKE), where only the party holding the private key corresponding to the public key can decrypt, and only after performing a certain amount of computation which may or may not be parallelisable. Effort-release PKE generalises both the sequential-operation-based timed-release encryption of Rivest, Shamir, and Wagner, and also the encapsulated key escrow techniques of Bellare and Goldwasser. We give a generic construction for ER-PKE based on the use of moderately hard computational problems called puzzles. Our approach extends the KEM/DEM framework for public key encryption by introducing a difficulty notion for KEMs which results in effort-release PKE. When the puzzle used in our generic construction is non-parallelisable, we recover timed-release cryptography, with the addition that only the designated receiver (in the public key setting) can decrypt.

Environmental and economic evaluation of N fertilizer rates in a maize crop in Italy : a spatial and temporal analysis using crop models

Crop simulation models have the potential to assess the risk associated with the selection of a specific N fertilizer rate, by integrating the effects of soil-crop interactions on crop growth under different pedo-climatic and management conditions. The objective of this study was to simulate the environmental and economic impact (nitrate leaching and N2O emissions) of a spatially variable N fertilizer application in an irrigated maize field in Italy. The validated SALUS model was run with 5 nitrogen rates scenarios, 50, 100, 150, 200, and 250 kg N ha−1, with the latter being the N fertilization adopted by the farmer. The long-term (25 years) simulations were performed on two previously identified spatially and temporally stable zones, a high yielding and low yielding zone. The simulation results showed that N fertilizer rate can be reduced without affecting yield and net return. The marginal net return was on average higher for the high yield zone, with values ranging from 1550 to 2650 € ha−1 for the 200 N and 1485 to 2875 € ha−1 for the 250 N. N leaching varied between 16.4 and 19.3 kg N ha−1 for the 200 N and the 250 N in the high yield zone. In the low yield zone, the 250 N had a significantly higher N leaching. N2O emissions varied between 0.28 kg N2O ha−1 for the 50 kg N ha−1 rate to a maximum of 1.41 kg N2O ha−1 for the 250 kg N ha−1 rate.

Advanced numerical characterization of silicon with defect by nanoindentation

Nano silicon is widely used as the essential element of complementary metal–oxide–semiconductor (CMOS) and solar cells. It is recognized that today, large portion of world economy is built on electronics products and related services. Due to the accessible fossil fuel running out quickly, there are increasing numbers of researches on the nano silicon solar cells. The further improvement of higher performance nano silicon components requires characterizing the material properties of nano silicon. Specially, when the manufacturing process scales down to the nano level, the advanced components become more and more sensitive to the various defects induced by the manufacturing process. It is known that defects in mono-crystalline silicon have significant influence on its properties under nanoindentation. However, the cost involved in the practical nanoindentation as well as the complexity of preparing the specimen with controlled defects slow down the further research on mechanical characterization of defected silicon by experiment. Therefore, in current study, the molecular dynamics (MD) simulations are employed to investigate the mono-crystalline silicon properties with different pre-existing defects, especially cavities, under nanoindentation. Parametric studies including specimen size and loading rate, are firstly conducted to optimize computational efficiency. The optimized testing parameters are utilized for all simulation in defects study. Based on the validated model, different pre-existing defects are introduced to the silicon substrate, and then a group of nanoindentation simulations of these defected substrates are carried out. The simulation results are carefully investigated and compared with the perfect Silicon substrate which used as benchmark. It is found that pre-existing cavities in the silicon substrate obviously influence the mechanical properties. Furthermore, pre-existing cavities can absorb part of the strain energy during loading, and then release during unloading, which possibly causes less plastic deformation to the substrate. However, when the pre-existing cavities is close enough to the deformation zone or big enough to exceed the bearable stress of the crystal structure around the spherical cavity, the larger plastic deformation occurs which leads the collapse of the structure. Meanwhile, the influence exerted on the mechanical properties of silicon substrate depends on the location and size of the cavity. Substrate with larger cavity size or closer cavity position to the top surface, usually exhibits larger reduction on Young’s modulus and hardness.