Induced pluripotent stem cells as an alternative to embryonic stem cells for the treatment of type 1 diabetes

Type 1 diabetes mellitus (T1DM) results from auto-immune destruction of the insulin-secreting β-cells of the pancreas. The most common treatment is injection of exogenous insulin, but this allows only partial control over blood glucose levels, so other therapies are needed. Pancreatic islet transplantation has shown proof of principle for cell replacement therapy to treat T1DM. There are several sources of cells which could be used, but much of the focus has been on pluripotent stem cells, which are able to self-renew indefinitely in culture and give rise to any cell in the body. Insulin-expressing cells have successfully been produced from embryonic stem cells (ESCs) by recapitulating embryonic development in vitro. However, problems associated with the use of ESCs mean that an alternative cell source is needed. In 2006, it was discovered that 4 transcription factors can reprogram somatic cells into induced pluripotent stem cells (iPSCs). iPSCs provide an alternative source of pluripotent stem cells and can be derived in a patient-specific manner. iPSCs have been shown to differentiate in vitro into insulin-expressing cells, but it is unknown whether iPSCs are truly equivalent to ESCs. Important differences have been shown to exist between iPSCs and ESCs which may affect the ability of iPSCs to give rise to cells of a pancreatic lineage and therefore limit their usefulness for the treatment of T1DM. The aim of this project is to identify whether iPSCs are a viable alternative to ESCs for generating β-cells in vitro for cell replacement therapy to treat type 1 diabetes. The differentiation potential of iPSCs and ESCs to give rise to first definitive endoderm (the first stage in differentiation towards a pancreatic lineage) in vitro will be compared, and the involvement of miRNAs in differentiation of ESCs and iPSCs to definitive endoderm will be investigated.Open Acces

Multi-phase semicrystalline microstructures drive exciton dissociation in neat plastic semiconductors

The optoelectronic properties of macromolecular semiconductors depend fundamentally on their solid-state microstructure. For example, the molecular-weight distribution influences polymeric- semiconductor properties via diverse microstructures; polymers of low weight-average molecular weight (Mw) form unconnected, extended-chain crystals, usually of a paraffinic structure. Because of the non-entangled nature of the relatively short-chain macromolecules, this leads to a polycrystalline, one-phase morphology. In contrast, with high-Mw materials, where average chain lengths are longer than the length between entanglements, two-phase morphologies, comprised of crystalline moieties embedded in largely unordered (amorphous) regions, are obtained. We investigate charge photogeneration processes in neat regioregular poly(3-hexylthiophene) (P3HT) of varying Mw by means of time-resolved photoluminescence (PL) spectroscopy. At 10 K, PL originating from recombination of long-lived charge pairs decays over microsecond timescales. Both the amplitude and decay rate distribution depend strongly on Mw. In films with dominant one-phase chain-extended microstructures, the delayed PL is suppressed as a result of a diminished yield of photoinduced charges, and its decay is significantly faster than in two-phase microstructures. However, independent of Mw, charge recombination regenerates singlet excitons in torsionally disordered chains forming more strongly coupled photophysical aggregates than those in the steady-state ensemble, with delayed PL lineshape reminiscent of that in paraffinic morphologies at steady state. We conclude that highly delocalized excitons in disordered regions between crystalline and amorphous phases dissociate extrinsically with yield and spatial distribution that depend intimately upon microstructure.Comment: 19 pages, 4 figure

Charge separation by photoexcitation in semicrystalline polymeric semiconductors: An intrinsic or extrinsic mechanism?

We probe charge photogeneration and subsequent recombination dynamics in neat regioregular poly(3-hexylthiophene) films over six decades in time by means of time-resolved photoluminescence spectroscopy. Exciton dissociation at 10K occurs extrinsically at interfaces between molecularly ordered and disordered domains. Polaron pairs thus produced recombine by tunnelling with distributed rates governed by the distribution of electron-hole radii. Quantum-chemical calculations suggest that hot-exciton dissociation at such interfaces results from a high charge-transfer character.Comment: 10 pages, 3 figure

FEMA's Pre-Disaster Mitigation Program: Overview and Issues

Pre-Disaster Mitigation (PDM), as federal law and a program activity, began in 1997. Congress established a pilot program, which FEMA named "Project Impact," to test the concept of investing prior to disasters to reduce the vulnerability of communities to future disasters. From its beginnings as "Project Impact" to its current state, the PDM program has grown in its level of appropriated resources and the scope of participation nationwide. Along with that growth have come issues for Congressional consideration, including the approach for awarding grant funds, the eligibility of certain applicants, the eligibility of certain projects, the degree of commitment by state and local governments, and related questions. This report discusses PDM, "Project Impact," and related legislative issues that Congress currently faces

Characterizing Sediment from Riverton, WY

Riverton, Wyoming is home to the seventh-largest Native American Reservation by area and a former uranium processing facility. Milling activities at this site have left the sediments and groundwater with elevated concentrations of uranium that occasionally disrupt water quality to the 12,000 residents of the reservation. The floodplain becomes seasonally wet and sometimes flooded from snowmelt that can be amplified by El Niño events. As a result, the sediments of this area experience periodic droughts and floods. There is concern that a decreased water stage can have major impacts on the geochemical makeup of this ecosystem as 1) a decreased water volume may result in an increase of pollutant concentrations and 2) a decreased water stage can have a significant impact the redox cycling within the subsurface and affect major biogeochemical cycles. This study addresses the need to understand current subsurface elemental distributions in Riverton, Wyoming. Overall, the project explores the sediment characteristics of several Riverton cores in response to drought and flood conditions. Samples for this study were taken over the course of twelve months - at three different time points. This summer, 105 Riverton sediment samples from August 2016 (the final time point) were geochemically characterized and compared to samples from dry conditions (August 2015) prior to the second largest flood on record at this location. We expect the sediments collected prior to the flood to vary greatly from the sediments collected after the flood because the activity of microbial communities is affected by differences in the physical structure of the soil. This data, along with an analysis of the microbial communities present in these sediments, will help the Francis Lab understand what factors shape the distribution and diversity of microbial communities present in order to better understand the subsurface biogeochemistry at Riverton

FEMA's Pre-Disaster Mitigation Program: Overview and Issues

This report discusses Pre-Disaster Mitigation (PDM), "Project Impact," and related legislative issues that Congress currently faces. PDM, as federal law and a program activity, began in 1997. Congress established a pilot program, which FEMA named "Project Impact," to test the concept of investing prior to disasters to reduce the vulnerability of communities to future disasters

Lee Silverman voice treatment versus standard NHS speech and language therapy versus control in Parkinson's disease (PD COMM pilot):study protocol for a randomized controlled trial

Background: Parkinson’s disease is a common movement disorder affecting approximately 127,000 people in the UK, with an estimated two thirds having speech-related problems. Currently there is no preferred approach to speech and language therapy within the NHS and there is little evidence for the effectiveness of standard NHS therapy or Lee Silverman voice treatment. This trial aims to investigate the feasibility and acceptability of randomizing people with Parkinson’s disease-related speech or voice problems to Lee Silverman voice treatment or standard speech and language therapy compared to a no-intervention control. Methods/Design: The PD COMM pilot is a three arm, assessor-blinded, randomized controlled trial. Randomization will be computer-generated with participants randomized at a ratio of 1:1:1. Participants randomized to intervention arms will be immediately referred to the appropriate speech and language therapist. The target population are patients with a confirmed diagnosis of idiopathic Parkinson’s disease who have problems with their speech or voice. The Lee Silverman voice treatment intervention group will receive the standard regime of 16 sessions between 50 and 60 minutes in length over four weeks, with extra home practice. The standard speech and language therapy intervention group will receive a dose determined by patients’ individual needs, but not exceeding eight weeks of treatment. The control group will receive standard care with no speech and language therapy input for at least six months post-randomization. Outcomes will be assessed at baseline (pre-randomization) and post- randomization at three, six, and 12 months. The outcome measures include patient-reported voice measures, quality of life, resource use, and assessor-rated speech recordings. The recruitment aim is at least 60 participants over 21 months from 11 sites, equating to at least 20 participants in each arm of the trial. This trial is ongoing and recruitment commenced in May 2012. Discussion: This study will provide information on the feasibility and acceptability of randomizing participants to different speech and language therapies or control/deferred treatment. The findings relating to recruitment, treatment compliance, outcome measures, and effect size will inform a future phase III randomized controlled trial