Stem cells as a therapeutic tool for the blind: biology and future prospects

Retinal degeneration due to genetic, diabetic and age-related disease is the most common cause of blindness in the developed world. Blindness occurs through the loss of the light-sensing photoreceptors; to restore vision, it would be necessary to introduce alternative photosensitive components into the eye. The recent development of an electronic prosthesis placed beneath the severely diseased retina has shown that subretinal stimulation may restore some visual function in blind patients. This proves that residual retinal circuits can be reawakened after photoreceptor loss and defines a goal for stem-cell-based therapy to replace photoreceptors. Advances in reprogramming adult cells have shown how it may be possible to generate autologous stem cells for transplantation without the need for an embryo donor. The recent success in culturing a whole optic cup in vitro has shown how large numbers of photoreceptors might be generated from embryonic stem cells. Taken together, these threads of discovery provide the basis for optimism for the development of a stem-cell-based strategy for the treatment of retinal blindness

Crystallinity reduction and enhancement in the chemical reactivity of cellulose by non-dissolving pre-treatment with tetrabutylphosphonium acetate

Herein, we demonstrate the activation of commercial chemical cellulose pulps towards chemical modification by a pre-treatment step with tetrabutylphosphonium acetate ([P-4444][OAc]). A heterogeneous (non-dissolving) pre-treatment was applied allowing for a significant reduction in crystallinity, without concomitant formation of the thermodynamically stable cellulose II. An increase in chemical reactivity was demonstrated using two model reactions; (1) acetylation (organic swelling conditions), where high degrees of substitution (DS) were obtained without the need for a catalyst, and (2) 4-acetamido-TEMPO oxidation (aqueous swelling conditions), where significant degrees of oxidation (DO) were obtained, beyond those for the untreated pulps. In both tests a notable improvement in cellulose reactivity was observed. Regioselectivity of acetylation was assessed using 2D NMR for one low and one high DS sample. The low DS showed a small degree of acetylation of the 6-OH, whereas, the high DS from the pre-treated sample showed mainly mixtures of triacetate and diacetates. Important mechanistic information is attained for future development of aqueous and organic-based reactions involving this ionic liquid pre-treatment.Peer reviewe

All Weather Calibration of Wide Field Optical and NIR Surveys

The science goals for ground-based large-area surveys, such as the Dark Energy Survey, Pan-STARRS, and the Large Synoptic Survey Telescope, require calibration of broadband photometry that is stable in time and uniform over the sky to precisions of a per cent or better. This performance will need to be achieved with data taken over the course of many years, and often in less than ideal conditions. This paper describes a strategy to achieve precise internal calibration of imaging survey data taken in less than photometric conditions, and reports results of an observational study of the techniques needed to implement this strategy. We find that images of celestial fields used in this case study with stellar densities of order one per arcmin-squared and taken through cloudless skies can be calibrated with relative precision of 0.5 per cent (reproducibility). We report measurements of spatial structure functions of cloud absorption observed over a range of atmospheric conditions, and find it possible to achieve photometric measurements that are reproducible to 1 per cent in images that were taken through cloud layers that transmit as little as 25 per cent of the incident optical flux (1.5 magnitudes of extinction). We find, however, that photometric precision below 1 per cent is impeded by the thinnest detectable cloud layers. We comment on implications of these results for the observing strategies of future surveys.Comment: Accepted for publication in The Astronomical Journal (AJ

A study of facilities and fixtures for testing of a high speed civil transport wing component

A study was performed to determine the feasibility of testing a large-scale High Speed Civil Transport wing component in the Structures and Materials Testing Laboratory in Building 1148 at NASA Langley Research Center. The report includes a survey of the electrical and hydraulic resources and identifies the backing structure and floor hard points which would be available for reacting the test loads. The backing structure analysis uses a new finite element model of the floor and backstop support system in the Structures Laboratory. Information on the data acquisition system and the thermal power requirements is also presented. The study identified the hardware that would be required to test a typical component, including the number and arrangement of hydraulic actuators required to simulate expected flight loads. Load introduction and reaction structure concepts were analyzed to investigate the effects of experimentally induced boundary conditions

ENTRAP and its potential interaction with European networks

AbstractENTRAP comprises a pan-European cooperation of leading scientific institutions and regulatory bodies in the field of nuclear-waste characterization and its quality assurance for the safe disposal of radioactive waste. Here, the scope of this cooperation is presented and explained and links or interfaces for a potential collaboration with partners fulfilling tasks of IDG-TP are pursued

WtF-Nano : One-Pot Dewatering and Water-Free Topochemical Modification of Nanocellulose in Ionic Liquids or gamma-Valerolactone

Ionic liquids are used to dewater a suspension of birch Kraft pulp cellulose nanofibrils (CNF) and as a medium for water-free topochemical modification of the nanocellulose (a process denoted as "WtF-Nano"). Acetylation was applied as a model reaction to investigate the degree of modification and scope of effective ionic liquid structures. Little difference in reactivity was observed when water was removed, after introduction of an ionic liquid or molecular co-solvent. However, the viscoelastic properties of the CNF suspended in two ionic liquids show that the more basic, but non-dissolving ionic liquid, allows for better solvation of the CNF. Vibrio fischeri bacterial tests show that all ionic liquids in this study were harmless. Scanning electron microscopy and wide-angle X-ray scattering on regenerated samples show that the acetylated CNF is still in a fibrillar form. 1D and 2D NMR analyses, after direct dissolution in a novel ionic liquid electrolyte solution, indicate that both cellulose and residual xylan on the surface of the nanofibrils reacts to give acetate esters.Peer reviewe

Using A Model-Based Systems Engineering Approach for Exploration Medical System Development

No abstract availabl

Pulmonary-to-Systemic Arterial Shunt to Treat Children With Severe Pulmonary Hypertension

BACKGROUND: The placement of a pulmonary-to-systemic arterial shunt in children with severe pulmonary hypertension (PH) has been demonstrated, in relatively small studies, to be an effective palliation for their disease. OBJECTIVES: The aim of this study was to expand upon these earlier findings using an international registry for children with PH who have undergone a shunt procedure. METHODS: Retrospective data were obtained from 110 children with PH who underwent a shunt procedure collected from 13 institutions in Europe and the United States. RESULTS: Seventeen children died in-hospital postprocedure (15%). Of the 93 children successfully discharged home, 18 subsequently died or underwent lung transplantation (20%); the mean follow-up was 3.1 years (range: 25 days to 17 years). The overall 1- and 5-year freedom from death or transplant rates were 77% and 58%, respectively, and 92% and 68% for those discharged home, respectively. Children discharged home had significantly improved World Health Organization functional class (P < 0.001), 6-minute walk distances (P = 0.047) and lower brain natriuretic peptide levels (P < 0.001). Postprocedure, 59% of children were weaned completely from their prostacyclin infusion (P < 0.001). Preprocedural risk factors for dying in-hospital postprocedure included intensive care unit admission (hazard ratio [HR]: 3.2; P = 0.02), mechanical ventilation (HR: 8.3; P < 0.001) and extracorporeal membrane oxygenation (HR: 10.7; P < 0.001). CONCLUSIONS: A pulmonary-to-systemic arterial shunt can provide a child with severe PH significant clinical improvement that is both durable and potentially free from continuous prostacyclin infusion. Five-year survival is comparable to children undergoing lung transplantation for PH. Children with severely decompensated disease requiring aggressive intensive care are not good candidates for the shunt procedure

On the Mechanism of the Reactivity of 1,3-Dialkylimidazolium Salts under Basic to Acidic Conditions : A Combined Kinetic and Computational Study

Comprehensive spectroscopic kinetic studies illustrate an alternative mechanism for the traditional free-carbene intermediated H/D exchange reaction of 1,3-dialkylimidazolium salts under neutral (D2O) and acidic conditions (DCl/D2O 35wt% solution). The deuteration of high purity [bmim]Cl in D2O is studied at different temperatures, in absence of catalyst or impurities, to yield an activation energy. DFT transition-state modelling, of a small water cluster and [bmim] cation, also yields an activation energy which strongly supports the proposed mechanism. The presence of basic impurities are shown to significantly enhance the exchange reaction, which brings into question the need for further analysis of technical purities of ionic liquids and the implications for a wide range of chemical reactions in such media.Peer reviewe

Logics of knowledge and action: critical analysis and challenges

International audienceWe overview the most prominent logics of knowledge and action that were proposed and studied in the multiagent systems literature. We classify them according to these two dimensions, knowledge and action, and moreover introduce a distinction between individual knowledge and group knowledge, and between a nonstrategic an a strategic interpretation of action operators. For each of the logics in our classification we highlight problematic properties. They indicate weaknesses in the design of these logics and call into question their suitability to represent knowledge and reason about it. This leads to a list of research challenges