Gene transfer into genomes of human cells by the sleeping beauty transposon system

The Sleeping Beauty (SB) transposon system, derived from teleost fish sequences, is extremely effective at delivering DNA to vertebrate genomes, including those of humans. We have examined several parameters of the SB system to improve it as a potential, nonviral vector for gene therapy. Our investigation centered on three features: the carrying capacity of the transposon for efficient integration into chromosomes of HeLa cells, the effects of overexpression of the SB transposase gene on transposition rates, and improvements in the activity of SB transposase to increase insertion rates of transgenes into cellular chromosomes. We found that SB transposons of about 6 kb retained 50% of the maximal efficiency of transposition, which is sufficient to deliver 70-80% of identified human cDNAs with appropriate transcriptional regulatory sequences. Overexpression inhibition studies revealed that there are optimal ratios of SB transposase to transposon for maximal rates of transposition, suggesting that conditions of delivery of the two-part transposon system are important for the best gene-transfer efficiencies. We further refined the SB transposase to incorporate several amino acid substitutions, the result of which led to an improved transposase called SB11. With SB11 we are able to achieve transposition rates that are about 100-fold above those achieved with plasmids that insert into chromosomes by random recombination. With the recently described improvements to the transposon itself, the SB system appears to be a potential gene-transfer tool for human gene therapy.

Physical design of the new extraction system for SFC

The HIRFL (Heavy Ion Research Facility at Lanzhou) is a cyclotron complex. Its injector is a cector focusing cyclotron with K=69. Since the HIRFL started the operation in 1989, two bigger items of improvements have been finished, the species and intensity of the accelerated particles are increased obviously. But due to the lower extraction efficiency of the SFC, on one hand, a lot of beam lost, and on other hand, outgas from the surface of the electrostatic deflector is serious because of beam hitting. Even sometimes the vacuum press is destroyed. In the paper a new physical design is made to get an extraction system of the SFC with a higher efficiency.

Exact analytical expressions for the potential of electrical double layer interactions for a sphere-plate system.

Exact, closed-form analytical expressions are presented for evaluating the potential energy of electrical double layer (EDL) interactions between a sphere and an infinite flat plate for three different types of interactions: constant potential, constant charge, and an intermediate case as given by the linear superposition approximation (LSA). By taking advantage of the simpler sphere-plate geometry, simplifying assumptions used in the original Derjaguin approximation (DA) for sphere-sphere interaction are avoided, yielding expressions that are more accurate and applicable over the full range of κa. These analytical expressions are significant improvements over the existing equations in the literature that are valid only for large κa because the new equations facilitate the modeling of EDL interactions between nanoscale particles and surfaces over a wide range of ionic strength.

EMG Biofeedback Videogame System for the Gait Rehabilitation of Hemiparetic Individuals

Gemstone Team CHIP

The impact of powder flowing properties on dosator filling system operation

Purpose: To study the impact of powder flow properties on dosator filling systems, with particular focus on improvements in dose weight accuracy and repeatability. Method: This study evaluates a range of critical powder flow properties such as: flow function, cohesion, wall friction, adhesion to wall surfaces, density/compressibility data, stress ratio “K” and gas permeability. The characterisations of the powders considered in this study were undertaken using an annular shear cell using a sample size of 0.5 litres. This tester also incorporated the facility to measure bed expansion during shear in addition to contraction under consolidation forces. A modified Jenike type linear wall friction tester was used to develop the failure loci for the powder sample in conjunction with multiple wall samples (representing a variety of material types and surface finishes). Measurements of the ratio of applied normal stress versus lateral stress were determined using a piece of test equipment specifically designed for the purpose. Results: The correct characterisation of powders and the incorporation of this data into the design of process equipment are recognised as critical for reliable and accurate operation. An example of one aspect of this work is the stress ratio “K”. This characteristic is not well understood or correctly interpreted in many cases – despite its importance. Fig 1 [Omitted] (illustrates a sample of test data. The slope of the line gives the stress ratio in a uniaxial compaction system – indicating the behaviour of the material under compaction during dosing processes. Conclusions: A correct assessment of the bulk powder properties for a given formulation can allow prediction of: cavity filling behaviour (and hence dosage), efficiency of release from dosator, and strength and stability of extruded dose en route to capsule filling Influences over the effectiveness of dosator systems have been shown to be impacted upon by: bed pre-compaction history, gas permeability in the bed (with respect to local density effects), and friction effects for materials of construction for dosators

Design, construction and testing of an air-cycle refrigeration system for road transport

The environmental attractions of air-cycle refrigeration are considerable. Following a thermodynamic design analysis, an air-cycle demonstrator plant was constructed within the restricted physical envelope of an existing Thermo King SL200 trailer refrigeration unit. This unique plant operated satisfactorily, delivering sustainable cooling for refrigerated trailers using a completely natural and safe working fluid. The full load capacity of the air-cycle unit at -20 °C was 7,8 kW, 8% greater than the equivalent vapour-cycle unit, but the fuel consumption of the air-cycle plant was excessively high. However, at part load operation the disparity in fuel consumption dropped from approximately 200% to around 80%. The components used in the air-cycle demonstrator were not optimised and considerable potential exists for efficiency improvements, possibly to the point where the air-cycle system could rival the efficiency of the standard vapour-cycle system at part-load operation, which represents the biggest proportion of operating time for most units.

Co-melt fluidised bed granulation of pharmaceutical powders: Improvements in drug bioavailability

This study investigates the use of co-melt fluidised bed granulation for the agglomeration of model pharmaceutical powders, namely, lactose mono-hydrate, PEG 10000, poly-vinyl pyrolidone and ibuprofen as a model drug. Granulation within the co-melt system was found to follow a nucleationâ??steady growthâ??coating regime profile. Using high molecular weight PEG binder, the granulation mechanism and thus the extent of granulation was found to be significantly influenced by binder viscosity. The compression properties of the granulate within the hot fluidised bed were correlated using a novel high temperature experimental procedure. It was found that the fracture stress and fractural modulus of the materials under hot processing conditions were orders of magnitude lower than those measured under ambient conditions. A range of particle velocities within the granulator were considered based on theoretical models. After an initial period of nucleation, the Stokes deformation number analysis indicated that only velocities within the high shear region of the fluidised bed were sufficient to promote significant granule deformation and therefore, coalescence. The data also indicated that larger granules de-fluidised preventing agglomeration by coalescence. Furthermore, experimental data indicated that dissipation of the viscous molten binder to the surface was the most important factor in the latter stages of the granulation process. From a pharmaceutical perspective the inclusion of the model drug, ibuprofen, combined with PVP in the co-melt process proved to be highly significant. It was found that using DSC analysis on the formulations that the decrease in the heat of fusion associated with the melting of ibuprofen within the FHMG systems may be attributed to interaction between PVP and ibuprofen through inter-molecular hydrogen bonding. This interaction decreases the crystallinity of ibuprofen and facilitates solubilisation and bioavailability within the solid matrix.

Does the Child Health Computing System adequately identify children with cerebral palsy?

Background This paper assesses the usefulness of the Child Health Computing System as a source of information about children with cerebral palsy.

Methods A comparative survey of information held on the Child Health Computing System (CHCS) and the Northern Ireland Cerebral Palsy Register (NICPR) in one Health and Social Services Board in Northern Ireland was carried out. The sample comprised children with cerebral palsy aged 5–9 years.

Results Of the 135 cases recorded on the NICPR, 47 per cent were not found on the CHCS; the majority of these children had no computer record of any medical diagnosis. Of the 82 cases recorded on the CHCS, 10(12 per cent) were not found on the NICPR; five of these cases (6 per cent) were found on follow–up not to have CP.

Conclusions Unless improvements are made in case ascertainment, case validation and recording activities, the evidence suggests that the CHCS will not be able to provide the same quality of information for needs assessment and surveillance of very low birthweight infants in relation to cerebral palsy as is provided by a specialist case register.

Treatment of estrogens and androgens in dairy wastewater by a constructed wetland system.

Constructed wetland systems (CWS) have been used as a low cost bio-filtration system to treat farm wastewater. While studies have shown that CWS are efficient in removing organic compounds and pathogens, there is limited data on the presence of hormones in this type of treatment system. The objective of this study was to evaluate the ability of the CWS to reduce estrogenic and androgenic hormone concentration in dairy wastewater. This was achieved through a year long study on dairy wastewater samples obtained froma surface flow CWS. Analysis of hormonal levels was performed using a solid phase extraction (SPE) sample clean-up method, combined with reporter gene assays (RGAs) which incorporate relevant receptors capable of measuring total estrogenic or androgenic concentrations as low as 0.24 ng L1 and 6.9 ng L1 respectively. Monthly analysis showed a mean removal efficiency for estrogens of 95.2%, corresponding to an average residual concentration of 3.2 ng L1 17b-estradiol equivalent (EEQ), below the proposed lowest observable effect concentration (LOEC) of 10 ng L1. However, for one month a peak EEQ concentration of 115 ng L1 was only reduced to 18.8 ng L1. The mean androgenic activity peaked at 360 ng L1 and a removal efficiency of 92.1% left an average residual concentration of 32.3 ng L1 testosterone equivalent (TEQ). The results obtained demonstrate that this type of CWS is an efficient system for the treatment of hormones in dairy wastewater. However, additional design improvements may be required to further enhance removal efficiency of peak hormone concentrations.

Dynamic global security-aware synthesis using System-C

A dynamic global security-aware synthesis flow using the SystemC language is presented. SystemC security models are first specified at the system or behavioural level using a library of SystemC behavioural descriptions which provide for the reuse and extension of security modules. At the core of the system is incorporated a global security-aware scheduling algorithm which allows for scheduling to a mixture of components of varying security level. The output from the scheduler is translated into annotated nets which are subsequently passed to allocation, optimisation and mapping tools for mapping into circuits. The synthesised circuits incorporate asynchronous secure power-balanced and fault-protected components. Results show that the approach offers robust implementations and efficient security/area trade-offs leading to significant improvements in turnover.

Tobramycin Inhalation Powder™:a novel drug delivery system for treating chronic Pseudomonas aeruginosa infection in cystic fibrosis

Lung disease in cystic fibrosis (CF) is typified by the development of chronic airways infection culminating in bronchiectasis and progression to end-stage respiratory disease. Pseudomonas aeruginosa, a ubiquitous gram-negative bacteria, is the archetypical CF pathogen and is associated with an accelerated clinical decline. The development and widespread use of chronic suppressive aerosolized antibacterial therapies, in particular Tobramycin Inhalation Solution (TIS), in CF has contributed to reduced lung function decline and improved survival. However, the requirement for the aerosolization of these agents through nebulizers has been associated with increased treatment burden, reduced quality of life and remain a barrier to broader uptake. Tobramycin Inhalation Powder (TIP™) has been developed by Novartis with the express purpose of delivering the same benefits as TIS in a time-effective manner. Administered via the T-326™ (Novartis) Inhaler in four individual 28-mg capsules, TIP can be administered in a quarter of the time of traditional nebulizers and is inherently portable. In clinical studies, TIP has been shown to be safe, result in equivalent or superior reductions in P. aeruginosa sputum density and produce similar improvements in pulmonary function. TIP offers significant advantages in time saving, portability and convenience over traditional nebulized TIS with comparable clinical outcomes for individuals with CF.

Modelling the cycling of persistent organic pollutants (POPs) in the North Sea system: Fluxes, loading, seasonality, trends

The fate and cycling of two selected POPs is investigated for the North Sea system with an improved version of a fate and transport ocean model (FANTOM). The model uses atmospheric data from the EMEP MSC East POP model (Gusev et al., 2009), giving reasonable concentrations and seasonal distributions for the entire region, as opposed to the three observation stations that Ilyina et al. (2006) were limited to. Other model improvements include changes in the calculation of POP exchange between the water column and sediment.

We chose to simulate the fate of two POPs with very different properties, ?-HCH and PCB 153. Since the fate and cycling of POPs are strongly affected by hydrodynamic processes, a high resolution version of the Hamburg Shelf Ocean Model (HAMSOM) was developed and utilised. Simulations were made for the period 1996–2005. Both models were validated by comparing results with available data, which showed that the simulations were of very satisfactory quality.

Model results show that the North Sea is a net sink for ?-HCH and a net source to the atmosphere of PCB 153. Total masses of ?-HCH and PCB 153 in 2005 are reduced to 30% and 50%, respectively, of 1996 values.

Storms resuspending bottom sediments into the water column mobilise POPs into the atmosphere and have the potential to deliver substantial loads of these POPs into Europe.

A case study on the eco-efficiency performance of a composite processing industry: evaluation and quantification of potential improvements

In this study, an attempt was made in order to measure and evaluate the eco-efficiency performance of a pultruded composite processing company. For this purpose the recommendations of World Business Council for Sustainable Development (WCSD) and the directives of ISO 14301 standard were followed and applied. The main general indicators of eco-efficiency, as well as the specific indicators, were defined and determined. With basis on indicators’ figures, the value profile, the environmental profile, and the pertinent eco-efficiency ratios were established and analyzed. In order to evaluate potential improvements on company eco-performance, new indicators values and eco-efficiency ratios were estimated taking into account the implementation of new proceedings and procedures, at both upstream and downstream of the production process, namely: i) Adoption of a new heating system for pultrusion die-tool in the manufacturing process, more effective and with minor heat losses; ii) Recycling approach, with partial waste reuse of scrap material derived from manufacturing, cutting and assembly processes of GFRP profiles. These features lead to significant improvements on the sequent assessed eco-efficiency ratios of the present case study, yielding to a more sustainable product and manufacturing process of pultruded GFRP profiles.

Assessing the eco-efficiency of a composite processing industry: evaluation and quantification of potential improvements’

In this study, an attempt was made in order to measure and evaluate the eco-efficiency performance of a pultruded composite processing company. For this purpose the recommendations of World Business Council for Sustainable Development (WCSD) and the directives of ISO 14301 standard were followed and applied. The main general indicators of eco-efficiency, as well as the specific indicators, were defined and determined. With basis on indicators’ figures, the value profile, the environmental profile, and the pertinent ecoefficiency’s ratios were established and analyzed. In order to evaluate potential improvements on company eco-performance, new indicators values and eco-efficiency ratios were estimated taking into account the implementation of new proceedings and procedures, both in upstream and downstream of the production process, namely: a) Adoption of new heating system for pultrusion die in the manufacturing process, more effective and with minor heat losses; c) Recycling approach, with partial waste reuse of scrap material derived from manufacturing, cutting and assembly processes of GFRP profiles. These features lead to significant improvements on the sequent assessed eco-efficiency ratios of the present case study, yielding to a more sustainable product and manufacturing process of pultruded GFRP profiles.

Localization system for pedestrians based on sensor and information fusion

Nowadays there is an increase of location-aware mobile applications. However, these applications only retrieve location with a mobile device's GPS chip. This means that in indoor or in more dense environments these applications don't work properly. To provide location information everywhere a pedestrian Inertial Navigation System (INS) is typically used, but these systems can have a large estimation error since, in order to turn the system wearable, they use low-cost and low-power sensors. In this work a pedestrian INS is proposed, where force sensors were included to combine with the accelerometer data in order to have a better detection of the stance phase of the human gait cycle, which leads to improvements in location estimation. Besides sensor fusion an information fusion architecture is proposed, based on the information from GPS and several inertial units placed on the pedestrian body, that will be used to learn the pedestrian gait behavior to correct, in real-time, the inertial sensors errors, thus improving location estimation.