Clinical features of a novel TIMP-3 mutation causing Sorsby's fundus dystrophy: implications for disease mechanism

AIMS: To describe the phenotype in three family members affected by a novel mutation in the gene coding for the enzyme tissue inhibitor of metalloproteinase-3 (TIMP-3). METHODS: Three members of the same family were seen with a history of nyctalopia and visual loss due to maculopathy. Clinical features were consistent with Sorsby's fundus dystrophy. Exon 5 of the gene coding for TIMP-3 was amplified by the polymerase chain reaction, single strand conformation polymorphism analysis undertaken and exon 5 amplicons were directly sequenced. RESULTS: Onset of symptoms was in the third to fourth decade. Five of six eyes had geographic macular atrophy rather than neovascularisation as a cause for central visual loss. Peripheral retinal pigmentary disturbances were present. Scotopic ERGs were abnormal in all three. Mutation analysis showed a GT transversion in all three resulting in a premature termination codon, E139X, deleting most of the carboxy terminal domain of TIMP-3. CONCLUSIONS: The patients described had a form of Sorsby's fundus dystrophy which fell at the severe end of the spectrum of this disease. Postulated disease mechanisms include deposition of dimerised TIMP-3 protein

Building in multifunctionality in plastic components : complexity, cost and sustainability

Multifunctionality can be embedded into material systems by three distinct design processes. These are: firstly multifunction can be embedded at a material level such as the use of nanomaterials within a polymer. In the second instance, discrete material systems can be added together. Examples are laminate systems in food pouches consisting of thin layers of metal and polymer. In the third process this can be achieved by integrating these materials systems together to form one holistically behaving component with multifunctionality. An example is an embedded antenna in an automotive windscreen.Drivers for multifunctionality include the increased push towards intelligent objects, such as the creation of the internet of things. Here, the embedding of communication and electronic function into daily consumer objects, such as milk cartons and food packaging are demanded. This must be offset by consideration of the related rise of a new wave of short-lifetime waste electronic and electronic equipment, incapable with current plastic recycling infrastructure, for disposal systems to adapt too. Designing integrated and multifunctional plastic components however, is complicated by the sheer number of material choices, multiple processing platforms, cost implications and environmental legislation. Considering just the processes of injection moulding, compression moulding and additive manufacturing, a designer is confronted with considerable complexity and numerous engineering design and stakeholder issues to consider. This paper presents examples of current state of art in multifunctional systems and discusses the barriers and potential solutions to creating fully realized multifunctional systems within a polymeric manufacturing environment. Impacts on material lifecycles and disposal infrastructures must be considered, as is the necessity to retain diversity with new integrated and advanced manufacturing processes suitable for the demands of mass customization, automation and Industry 4.0

Inkjet printed TiO2 nanoparticles from aqueous solutions for dye sensitized solar cells (DSSCs)

This is the accepted version of the following article: Cherrington, R., Hughes, D. J., Senthilarasu, S. and Goodship, V. (2015), Inkjet-Printed TiO2 Nanoparticles from Aqueous Solutions for Dye-Sensitized Solar Cells (DSSCs). Energy Technology., which has been published in final form at http://dx.doi.org/10.1002/ente.201500096This work reports on the formulation of suitable ink for inkjet printing of TiO2 by investigating the critical parame- ters of particle size, pH, viscosity, and stability. Aqueous sus- pensions of TiO2 nanoparticles (Degussa, P25) were pre- pared with the addition of 25 wt % polyethylene glycol 400 as a humectant to minimize drying at the printer nozzles and reduce the likelihood of nozzle blockage. The inkjet-printed TiO2 layers were assembled into dye-sensitized solar cells. The current–voltage (I–V) characteristics were measured under one sun (air mass 1.5, 100 mW cm 2) using a source meter (Model 2400, Keithley Instrument, Inc.), and the active area of the cell was 0.25 cm2. The inkjet-printed TiO2 photoanode produced a device with a short-circuit current (Isc) of 9.42 mA cm 2, an open-circuit voltage (Voc) of 0.76 V, and a fill factor (FF) of 0.49, resulting in a power conversion efficiency (PCE) of 3.50 %.Engineering and Physical Sciences Research Council (EPSRC

Disassembly of Li Ion cells—characterization and safety considerations of a recycling scheme

It is predicted there will be a rapid increase in the number of lithium ion batteries reaching end of life. However, recently only 5% of lithium ion batteries (LIBs) were recycled in the European Union. This paper explores why and how this can be improved by controlled dismantling, characterization and recycling. Currently, the favored disposal route for batteries is shredding of complete systems and then separation of individual fractions. This can be effective for the partial recovery of some materials, producing impure, mixed or contaminated waste streams. For an effective circular economy it would be beneficial to produce greater purity waste streams and be able to re-use (as well as recycle) some components; thus, a dismantling system could have advantages over shredding. This paper presents an alternative complete system disassembly process route for lithium ion batteries and examines the various processes required to enable material or component recovery. A schematic is presented of the entire process for all material components along with a materials recovery assay. Health and safety considerations and options for each stage of the process are also reported. This is with an aim of encouraging future battery dismantling operations

Multilayer manufacturing method utilising mould

Manufacturing method A method of manufacturing a moulded part (10) with one or more integral electronic components (10a). The method includes forming one or more layers (11) in a mould of a moulding apparatus, the one or more layers including the one or electronic components, and introducing material into the mould to form the moulded part with the one or more integral electronic components

Fast plasma sintering delivers functional graded materials components with macroporous structures and osseointegration properties

We explored the osseointegration potential of two macroporous titanium surfaces obtained using fast plasma sintering (FPS): Ti macroporous structures with 400-600 µmØ pores (TiMac400) and 850-1000 µmØ pores (TiMac850). They were compared against two surfaces currently in clinical use: Ti-Growth® and air plasma spray (Ti-Y367). Each surface was tested, once placed over a Ti-alloy and once onto a CoCr bulk substrate. Implants were placed in medial femoral condyles in 24 sheep. Samples were explanted at four and eight weeks after surgery. Push-out loads were measured using a material-testing system. Bone contact and ingrowth were assessed by histomorphometry and SEM and EDX analyses. Histology showed early osseointegration for all the surfaces tested. At 8 weeks, TiMac400, TiMac850 and Ti-Growth® showed deep bone ingrowth and extended colonisation with newly formed bone. The mechanical push-out force was equal in all tested surfaces. Plasma spray surfaces showed greater bone-implant contact and higher level of pores colonisation with new bone than FPS produced surfaces. However, the void pore area in FPS specimens was significantly higher, yet the FPS porous surfaces allowed a deeper osseointegration of bone to implant. FPS manufactured specimens showed similar osseointegration potential to the plasma spray surfaces for orthopaedic implants. FPS is a useful technology for manufacturing macroporous titanium surfaces. Furthermore, its capability to combine two implantable materials, using bulk CoCr with macroporous titanium surfaces, could be of interest as it enables designers to conceive and manufacture innovative components. FPS delivers functional graded materials components with macroporous structures optimised for osseointegration

Increased Power for Detection of Parent-of-Origin Effects via the Use of Haplotype Estimation

Parent-of-origin (or imprinting) effects relate to the situation in which traits are influenced by the allele inherited from only one parent and the allele from the other parent has little or no effect. Given SNP genotype data from case-parent trios, the parent of origin of each allele in the offspring can often be deduced unambiguously; however, this is not true when all three individuals are heterozygous. Most existing methods for investigating parent-of-origin effects operate on a SNP-by-SNP basis and either perform some sort of averaging over the possible parental transmissions or else discard ambiguous trios. If the correct parent of origin at a SNP could be determined, this would provide extra information and increase the power for detecting the effects of imprinting. We propose making use of the surrounding SNP information, via haplotype estimation, to improve estimation of parent of origin at a test SNP for case-parent trios, case-mother duos, and case-father duos. This extra information is then used in a multinomial modeling approach for estimating parent-of-origin effects at the test SNP. We show through computer simulations that our approach has increased power over previous approaches, particularly when the data consist only of duos. We apply our method to two real datasets and find a decrease in significance of p values in genomic regions previously thought to possibly harbor imprinting effects, thus weakening the evidence that such effects actually exist in these regions, although some regions retain evidence of significant effects

Is the collagen primed for mineralization in specific regions of the Turkey tendon?:an investigation of the protein-mineral interface using Raman spectroscopy

The tendons in the turkey leg have specific well-defined areas which become mineralized as the animal ages and they are a thoroughly characterized model system for studying the mineralization process of bone. In this study, nondestructive Raman spectroscopic analysis was used to explore the hypothesis that regions of the turkey tendon that are associated with mineralization exhibit distinct and observable chemical modifications of the collagen prior to the onset of mineralization. The Raman spectroscopy features associated with mineralization were identified by probing (on the micrometer scale) the transition zone between mineralized and nonmineralized regions of turkey leg tendons. These features were then measured in whole tendons and identified in regions of tendon which are destined to become rapidly mineralized around 14 weeks of age. The data show there is a site-specific difference in collagen prior to the deposition of mineral, specifically the amide III band at 1270 cm(-1) increases as the collagen becomes more ordered (increased amide III:amide I ratio) in regions that become mineralized compared to collagen destined to remain nonmineralized. If this mechanism were present in materials of different mineral fraction (and thus material properties), it could provide a target for controlling mineralization in metabolic bone disease