A Study of High-Chroma Inks for Expanding CMYK Color Gamut

The number of possible reproducible colors in a printing method is called the color gamut. The need to satisfy the growing quality demands and produce color match has given rise to the use of expanded color gamuts. There are many ways to achieve an expanded color gamut, including printing with Cyan, Magenta, Yellow, Black (CMYK) plus additional inks, printing with higher ink film thickness (IFT), and printing with high-chroma inks. The purpose of this research is to study the relationship between color gamut volume, metric chroma (C*), IFT, and solid ink density (SID) for regular and high-chroma inks in offset printing process. This is done by performing ink drawdowns to understand the behavior of high-chroma and regular inks in order to determine IFT and corresponding ink saturation densities using the Tollenaar and Ernst equation. Subsequently, the research compares color gamut volume between regular and high-chroma inks using Presstek 52DI offset printing process. The measurement is carried out with i1 Pro 2 spectrophotometer and X-Rite i1 Isis2

Expression, activity and pharmacokinetic impact of ocular transporters

The eye is protected by several tissues that limit the permeability and entry of potentially harmful substances, but also hamper the delivery of drugs in the treatment of ocular diseases. Active transport across the ocular barriers may affect drug distribution, but the impact of drug transporters on ocular drug delivery is not well known. We have collected and critically reviewed the literature for ocular expression and activity of known drug transporters. The review concentrates on drug transporters that have been functionally characterized in ocular tissues or primary cells and on transporters for which there is available expression data at the protein level. Species differences are highlighted, since these may explain observed inconsistencies in the influence of specific transporters on drug disposition. There is variable evidence about the pharmacokinetic role of transporters in ocular tissues. The strongest evidence for the role of active transport is available for the blood-retinal barrier. We explored the role of active transport in the cornea and blood retinal barrier with pharmacokinetic simulations. The simulations show that the active transport is important only in the case of specific parameter combinations. (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe

A model microfluidics-based system for the human and mouse retina.

The application of microfluidics technologies to the study of retinal function and response holds great promise for development of new and improved treatments for patients with degenerative retinal diseases. Restoration of vision via retinal transplantation therapy has been severely limited by the low numbers of motile cells observed post transplantation. Using modern soft lithographic techniques, we have developed the μRetina, a novel and convenient biomimetic microfluidics device capable of examing the migratory behavior of retinal lineage cells within biomimetic geometries of the human and mouse retina. Coupled computer simulations and experimental validations were used to characterize and confirm the formation of chemical concentration gradients within the μRetina, while real-time images within the device captured radial and theta cell migration in response to concentration gradients of stromal derived factor (SDF-1), a known chemoattractant. Our data underscore how the μRetina can be used to examine the concentration-dependent migration of retinal progenitors in order to enhance current therapies, as well as develop novel migration-targeted treatments

Photonics simulation and modelling of skin for design of spectrocutometer

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Optimisation of Substrate and Growth Conditions of Retinal Pigment Epithelial Cells Destined for Transplantation

Retinal Pigment Epithelium (RPE) transplantation efforts have been ongoing for three decades . To this day no feasible cure exists for diseases such as age-related macular degeneration (AMD). The key to treatment of AMD is to replenish the RPE. Establishing cells that accurately represent their native tissue is a considerable challenge. RPE cells undergo de-differentiation in culture losing important characteristics after repeated passage. Furthermore, RPE cells are anchorage-dependant and require a substrate for survival. Attempts at replenishing the RPE using suspensions have been met with scepticism due to the high degree of apoptosis. ARPE-19, a human RPE line, retains several phenotypic characteristics of primary RPE although current passages have lost some established features. A variety of polymers with diverse chemistries, specialised coatings, and optimised media were tested to optimally grow ARPE-19 cells. Using information gathered from these experiments, optimal conditions were selected for Human Embryonic Stem Cell (HESC)-derived RPE cells. Cell/substrate composites were transplanted in pigs to validate their efficacy. Differentiation of ARPE-19 cells was enhanced by utilising a superior substrate, polyester filter, together with an optimal growth medium containing pyruvate. HESCderived RPE grown in optimal conditions developed differentiation characteristics identical to native RPE. This was assessed by morphology, immunohistochemical profile, trans-epithelial resistance, electron-microscopy, and growth factor secretion. A higher porosity version of this filter supported growth and differentiation of HESC-RPE and this was chosen as the basis for a transplantation project due to its good permeability. Transplanted HESC-RPE/polyester composites survived surgical delivery in a pig model and were eventually chosen for a phase I clinical trial. Conclusion: This thesis investigated optimal conditions for the human RPE line ARPE- 19. Optimal growth conditions were then applied to HESC-RPE cells which achieved a high level of differentiation. Composites were transplanted in pigs and led to their selection for use in clinical trials

The potential of human adipose tissue derived mesenchymal stem cells in cell therapy for retinal degenerative diseases

Este trabajo se propone la utilización del potencial de diferenciación hacia células con fenotipo EPR que poseen las hAD‐MSCs, simultáneamente con sus beneficiosos efectos paracrinos sobre el EPR y la degeneración retiniana in vitro. Este estudio intenta crear un microambiente compuesto por diferentes biomoléculas con la capacidad de guiar la vía de diferenciación de las MSCs hacia fenotipos de EPR y al mismo tiempo, de proteger la neurorretina (especialmente los PRs), mediante la utilización de sistemas de co‐cultivo indirectos. Los resultados derivados podrían proporcionar importantes avances en campos que permitirían continuar en la línea de investigación hacia experimentos in vivo antes de iniciar futuros ensayos clínicos en la DM

Microglial implication in Parkinson's Disease: studying functional and morphological changes occurring in LRRK2 microglia during PD pathophysiology using a stem cell derived human model

[eng] Parkinson’s disease (PD) is an incurable neurodegenerative disease characterized by the loss of neuromelanin (NM)-containing dopamine neurons in Substantia Nigra pars compacta (SNpc) and accumulation of insoluble cytoplasmic protein inclusions known as Lewy bodies. Microglial activation, astrocyte reactivity and lymphocyte infiltration also occur in PD. Here, we hypothesize that PD is initiated years before the emergence of motor dysfunction in response to several mechanisms some of which triggered following microglia activation that impact negatively in neuronal survival. Taking advantage of our human iPSC-based model of PD, we first generated human Microglia-like cells (hMG) from LRRK2-PD and Control iPSCs and confirmed their identity by using specific microglial markers. We then carried out functional studies with pro-inflammatory stimuli such as LPS or NM, which revealed a higher motility, cytokine release and phagocytic activity of LRRK2-PD hMG compared to control hMG. In addition, we found that extracellular NM particles induced microglial activation and increases ROS production in LRRK2-PD microglia. The use of a corrected isogenic PD hMG reverted all previous phenotypes, confirming a LRRK2-dependent activation of hMG. Upon co-culture with LRRK2-PD hMG and in the presence of NM particles, Control Dopaminergic neurons (DAn) displayed morphological signs of neurodegeneration, such as short and few neurites as well as beaded necklace-like neurites, as well as increased neuronal loss. Thus, our findings indicate a critical role for neuromelanin-activated microglia in LRRK2-PD and may serve as a valid human cellular model to test compounds that can lower risk for PD or disease progression

Autosomal recessive retinitis pigmentosa, identification and partial characterisation of a novel gene implicated in RP25

The purpose of this project is to identify the causative gene for one type of autosomal recessive retinitis pigmentosa, RP25. Through CGH (comparative genome hybridisation) and mutation screening, independent mutations were identified in arRP affected Spanish families mapping to RP25. These mutations were identified within a cluster of uncharacterised gene transcripts all which have EGF-like repeat domains; Q5T669, Q5T1H1, Q9H557_human, Q5TEL3_human, Q5TEL4_human, Q5VVG4_human, and Q5T3C8. Through 5` and 3` RACE PCR analysis, the full length gene was revealed to incorporate the EGFL11 gene. On assembling all available data we noted that RP25 gene encompasses 30 exons belonging to nine previously predicted genes and 13 newly identified exons, totaling 43 exons and spanning the interval between 64,487,835 and 66,473,839 on chromosome 6q12. The RP25 full length gene transcript is retinal specific. The genomic length covers over 2.0 MB in size and is therefore the largest eye specific gene identified to date. It is also the fifth largest gene in the human genome to date. Homologs of the RP25 gene to Drosophila eys/eys-shut (Spacemaker) were identified, leading to the annotation of the name EYS (SPAM). An apparently intact eys gene is found across the mammalian clade, including monotremes (platypus) and marsupials (opossum). However, despite the mutations and the presumed loss of function associated with human disease, this gene has been dispensed with on at least four separate occasions in the last 100 million years of mammalian evolution including in the armadillo (Dasypus novemcinctus), little brown bat (Myotis lucifugus) and ruminant (cattle and sheep) lineages. EYS has acquired several (<3) reading-frame disruptions in three rodents (mouse, rat and guinea pig) representing two of the three major rodent clades. Through immunohistochemical and electron microscopy analysis, a signal for SPAM was identified in the outer segments of photoreceptor cells

Expression Level of Kita, Kitb, Kitla, and Kitlb in Zebrafish Gastrointestional Tract

Gastrointestinal (GI) motility is the muscular contractions that move intestinal contents in an anterograde (mouth to anus) direction and is necessary for nutrient absorption and elimination of waste. GI motility is highly coordinated and rhythmic contraction patterns. Interstitial cells of Cajal (ICC), enteric neurons, and smooth muscle cells all regulate GI motility. ICC function as pacemaker cells and determine contraction frequency. ICC growth and development is influenced by Kit, a tyrosine kinase receptor located on the plasma membrane of ICC. TMEM16A is a calcium activated chloride channel which contributes to the slow wave in the GI tract. Constipation, delayed gastric emptying, and bloating have been correlated with deficits of ICC in GI tissues. A functional Kit receptor and stimulation of Kit with Kit ligand is necessary for ICC growth and development. However, little is known about ICC development in adults or in developing GI tissue. The objective for this project is to determine the relative and temporal expression levels of Kita, Kitb, Kitla, and Kitlb in the zebrafish model system at several developmental time points. Understanding the temporal and relative expression pattern of these genes is the first step towards a more complete understanding of ICC development and turnover. The zebrafish model system is anatomically similar to the human GI tract and at early time points the zebrafish is transparent. One advantage to this model system is that GI motility may be examined in the intact larvae. RNA was isolated from dissected zebrafish GI tissues and used as template for reverse transcriptase reactions to make eDNA. Relative and temporal expression levels of Kita, Kitb, Kitla, and Kitlb was determined at 5 days post fertilization (dpf), 7 dpf, 11 dpf, 28dpf, and in adult gut tissues using eDNA as template for real time PCR. Kita and Kitla were confirmed as a functional receptor/ligand pair which was first identified in melanocyte migration19. The relative expression data suggests that Kitb and Kitlb are also a functional receptor/ligand pair. Temporal expression data shows high expression of Kitb early in development (5dpf). Besides the early high expression of Kitb, gene expression for all genes of interest peak at 11 dpf. TMEM16A (also called ANOI) was identified as a more accurate marker for gastrointestinal stromal tumors (GIST) than Kit24. RNA isolated from dissected zebrafish GI tract was used to make eDNA which became the template for reverse transcriptase (RT)-PCR and real-tin1e PCR (q-PCR). Anti-ANOI antibodies were used to identify TMEM16A in dissected, fixed zebrafish GI tract. RT-PCR showed that TMEM16A, B, and Care expressed in the zebrafish GI tract. Immunohistochemistry identifies a network of cells in the zebrafish GI tract that is similar in morphology and location to ICC stained by Kit antibodies. Relative and temporal expression was determined using samples isolated at 5, 7, 11, 28dpf, and adult time points. Expression of TMEM16B dominates TMEM16A and B at 28dpf and adult time points

ENVIRONMENTALLY FRIENDLY TECHNOLOGY: THE BEHAVIOUR OF NATURAL AND SYNTHETIC BINDER SYSTEMS WITHIN PAPER COATINGS

Coating shrinkage upon drying is a phenomenon well known to the paper coating industry, where it often causes changes in the final structure of the coating layer leading to poor results in terms of gloss, light scattering, surface strength, coverage, uniformity and printability. Such shrinkage has in previous studies been wrongly associated with shrinkage of the polymeric binders used in the coating formulation, by making erroneous comparison with solvent-based paint systems. Natural binders, as starch or proteins, which come from renewable resources and are therefore environmentally friendly, suffer more from this shrinkage phenomenon than synthetic binders. The aim of this research project was to improve the understanding of the processes involved in the drying of a coating layer and to create a model able to describe them. Shrinkage while the coating layer dries has been successfully measured by observing the deflection of coated strips of a synthetic elastically-deformable substrate. Ground calcium carbonate was used as the coating pigment, together with latex binders of both low and high glass transition temperature, Tg, respectively, and also with starch which is a natural film-forming water soluble binder. The final dry coatings were studied with mercury porosimetry and by scanning electron microscopy in order to characterise their porous structure. The flow and rheological properties of the coating colour formulations were measured in order to probe the particle-particle interaction between the different species in the wet coating colour. The void space of the dry coating layers was modelled using Pore-Cor, a software which generates simulated porous networks. A new algorithm was developed to model, within the simulated void space, the effective particles or "skeletal elements" representative of the solid phase of the dried porous system. The water-filled porous structures at the beginning of the shrinkage process (first critical concentration, FCC) were subsequently modelled by creating Pore-Cor structures with the same solid skeletal elements distribution as at the second critical concentration (at which the particles lock their positions), but with higher given porosity to account for the water present The capillary forces acting on the surface of the simulated coating were calculated, and found to be several orders of magnitude larger than the measured shrinkage forces. The shrinkage process was thus described as resulting from the effect of capillary forces in the plane of the coating layer resisted by a stick-slip process, where the capillary forces yield shrinkage only if a resistance force within the drying coating layer holds the structure in place and allows the menisci to form. The stick-slip theory was strongly supported by quantitative comparisons between the experimental forces required to intrude mercury, and the capillary forces within the simulated void structure.Omya AG, Oftringen, Switzerlan