Effects of Cathode Configuration on Hall Thruster Cluster Plume Properties

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76620/1/AIAA-24636-518.pd

Studies of non-conventional configuration closed electron drift thrusters

In this paper, we review recent results obtained for segmented electrode and cylindrical Hall thrusters. A low sputtering graphite segmented electrode, placed at the exit of the annular thruster, is shown to affect the plasma potential distribution in the ceramic channel. This effect appears to be correlated with an observed plume reduction compared to a conventional, nonsegmented thruster. In preliminary experiments a 3-cm thruster was operated in the 50-200 W power range. Two operating regimes, stable and oscillating, were observed and investigated

Mindfulness-Based Cognitive Therapy (MBCT) For Health Anxiety (Hypochondriasis): Rationale, Implementation and Case Illustration.

Recent research has shown that mindfulness-based cognitive therapy (MBCT) could be a useful alternative approach to the treatment of health anxiety and deserves further investigation. In this paper, we outline the rationale for using MBCT in the treatment of this condition, namely its hypothesised impact on the underlying mechanisms which maintain health anxiety, such as rumination and avoidance, hypervigilance to body sensations and misinterpretation of such sensations. We also describe some of the adaptations which were made to the MBCT protocol for recurrent depression in this trial and discuss the rationale for these adaptations. We use a case example from the trial to illustrate how MBCT was implemented and outline the experience of one of the participants who took part in an 8-week MBCT course. Finally, we detail some of the more general experiences of participants and discuss the advantages and possible limitations of this approach for this population, as well as considering what might be useful avenues to explore in future research

Effects of Mindfulness-Based Cognitive Therapy on Specificity of Life Goals

This study explored the immediate effects of a course of Mindfulness-Based Cognitive Therapy (MBCT) for chronically depressed participants with a history of suicidality on the specificity of important goals for the future. Participants were randomly allocated to immediate treatment with MBCT or to a waitlist condition and life goals were assessed both before and after the treatment or waiting period. Results showed that participants receiving MBCT reported significantly more specific goals post-treatment whereas those allocated to the waitlist condition showed no significant change. Similarly, participants allocated to MBCT regarded themselves as significantly more likely to achieve their important goals post-treatment, whilst again there was no significant change in the waitlist group. Increases in goal specificity were associated with parallel increases in autobiographical memory specificity whereas increases in goal likelihood were associated with reductions in depressed mood. These results suggest that MBCT may enable participants to clarify their important goals and in doing so increase their confidence in their capacity to move in valued life directions

Methodological issues associated with collecting sensitive information over the telephone - experience from an Australian non-suicidal self-injury (NSSI) prevalence study

<p>Abstract</p> <p>Background</p> <p>Collecting population data on sensitive issues such as non-suicidal self-injury (NSSI) is problematic. Case note audits or hospital/clinic based presentations only record severe cases and do not distinguish between suicidal and non-suicidal intent. Community surveys have largely been limited to school and university students, resulting in little much needed population-based data on NSSI. Collecting these data via a large scale population survey presents challenges to survey methodologists. This paper addresses the methodological issues associated with collecting this type of data via CATI.</p> <p>Methods</p> <p>An Australia-wide population survey was funded by the Australian Government to determine prevalence estimates of NSSI and associations, predictors, relationships to suicide attempts and suicide ideation, and outcomes. Computer assisted telephone interviewing (CATI) on a random sample of the Australian population aged 10+ years of age from randomly selected households, was undertaken.</p> <p>Results</p> <p>Overall, from 31,216 eligible households, 12,006 interviews were undertaken (response rate 38.5%). The 4-week prevalence of NSSI was 1.1% (95% ci 0.9-1.3%) and lifetime prevalence was 8.1% (95% ci 7.6-8.6).</p> <p>Methodological concerns and challenges in regard to collection of these data included extensive interviewer training and post interview counselling. Ethical considerations, especially with children as young as 10 years of age being asked sensitive questions, were addressed prior to data collection. The solution required a large amount of information to be sent to each selected household prior to the telephone interview which contributed to a lower than expected response rate. Non-coverage error caused by the population of interest being highly mobile, homeless or institutionalised was also a suspected issue in this low prevalence condition. In many circumstances the numbers missing from the sampling frame are small enough to not cause worry, especially when compared with the population as a whole, but within the population of interest to us, we believe that the most likely direction of bias is towards an underestimation of our prevalence estimates.</p> <p>Conclusion</p> <p>Collecting valid and reliable data is a paramount concern of health researchers and survey research methodologists. The challenge is to design cost-effective studies especially those associated with low-prevalence issues, and to balance time and convenience against validity, reliability, sampling, coverage, non-response and measurement error issues.</p

Generation of Healthy Mice from Gene-Corrected Disease-Specific Induced Pluripotent Stem Cells

Using the murine model of tyrosinemia type 1 (fumarylacetoacetate hydrolase [FAH] deficiency; FAH−/− mice) as a paradigm for orphan disorders, such as hereditary metabolic liver diseases, we evaluated fibroblast-derived FAH−/−-induced pluripotent stem cells (iPS cells) as targets for gene correction in combination with the tetraploid embryo complementation method. First, after characterizing the FAH−/− iPS cell lines, we aggregated FAH−/−-iPS cells with tetraploid embryos and obtained entirely FAH−/−-iPS cell–derived mice that were viable and exhibited the phenotype of the founding FAH−/− mice. Then, we transduced FAH cDNA into the FAH−/−-iPS cells using a third-generation lentiviral vector to generate gene-corrected iPS cells. We could not detect any chromosomal alterations in these cells by high-resolution array CGH analysis, and after their aggregation with tetraploid embryos, we obtained fully iPS cell–derived healthy mice with an astonishing high efficiency for full-term development of up to 63.3%. The gene correction was validated functionally by the long-term survival and expansion of FAH-positive cells of these mice after withdrawal of the rescuing drug NTBC (2-(2-nitro-4-fluoromethylbenzoyl)-1,3-cyclohexanedione). Furthermore, our results demonstrate that both a liver-specific promoter (transthyretin, TTR)-driven FAH transgene and a strong viral promoter (from spleen focus-forming virus, SFFV)-driven FAH transgene rescued the FAH-deficiency phenotypes in the mice derived from the respective gene-corrected iPS cells. In conclusion, our data demonstrate that a lentiviral gene repair strategy does not abrogate the full pluripotent potential of fibroblast-derived iPS cells, and genetic manipulation of iPS cells in combination with tetraploid embryo aggregation provides a practical and rapid approach to evaluate the efficacy of gene correction of human diseases in mouse models

Transgene Excision Has No Impact on In Vivo Integration of Human iPS Derived Neural Precursors

The derivation of induced human pluripotent stem cells (hiPS) has generated significant enthusiasm particularly for the prospects of cell-based therapy. But there are concerns about the suitability of iPS cells for in vivo applications due in part to the introduction of potentially oncogenic transcription factors via viral vectors. Recently developed lentiviral vectors allow the excision of viral reprogramming factors and the development of transgene-free iPS lines. However it is unclear if reprogramming strategy has an impact on the differentiation potential and the in vivo behavior of hiPS progeny. Here we subject viral factor-free, c-myc-free and conventionally reprogrammed four-factor human iPS lines to a further challenge, by analyzing their differentiation potential along the 3 neural lineages and over extended periods of time in vitro, as well as by interrogating their ability to respond to local environmental cues by grafting into the striatum. We demonstrate similar and efficient differentiation into neurons, astrocytes and oligodendrocytes among all hiPS and human ES line controls. Upon intracranial grafting in the normal rat (Sprague Dawley), precursors derived from all hiPS lines exhibited good survival and response to environmental cues by integrating into the subventricular zone, acquiring phenotypes typical of type A, B or C cells and migrating along the rostral migratory stream into the olfactory bulb. There was no teratoma or other tumor formation 12 weeks after grafting in any of the 26 animals used in the study. Thus neither factor excision nor persistence of c-myc impact the behavior of hiPS lines in vivo.United States. National Institutes of HealthNew York State Stem Cell ScienceNational Institute of Neurological Disorders and Stroke (U.S.)Starr Foundation (Tri-Institutional Starr Stem Cell Scholars Fellowship

Clinical application of stem cell therapy in Parkinson's disease

Cell replacement therapies in Parkinson's disease (PD) aim to provide long-lasting relief of patients' symptoms. Previous clinical trials using transplantation of human fetal ventral mesencephalic (hfVM) tissue in the striata of PD patients have provided proof-of-principle that such grafts can restore striatal dopaminergic (DA-ergic) function. The transplants survive, reinnervate the striatum, and generate adequate symptomatic relief in some patients for more than a decade following operation. However, the initial clinical trials lacked homogeneity of outcomes and were hindered by the development of troublesome graft-induced dyskinesias in a subgroup of patients. Although recent knowledge has provided insights for overcoming these obstacles, it is unlikely that transplantation of hfVM tissue will become routine treatment for PD owing to problems with tissue availability and standardization of the grafts. The main focus now is on producing DA-ergic neuroblasts for transplantation from stem cells (SCs). There is a range of emerging sources of SCs for generating a DA-ergic fate in vitro. However, the translation of these efforts in vivo currently lacks efficacy and sustainability. A successful, clinically competitive SC therapy in PD needs to produce long-lasting symptomatic relief without side effects while counteracting PD progression

2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there are no therapeutic cures available. Even though animal and histological models have been of great aid in understanding disease mechanisms and identifying possible therapeutic strategies, in order to find disease-modifying solutions there is still a critical need for systems that can provide more predictive and physiologically relevant results. One possible avenue is the development of patient-derived models, e.g. by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), which can then be differentiated into any cell type for modelling. These systems contain key genetic information from the donors, and therefore have enormous potential as tools in the investigation of pathological mechanisms underlying disease phenotype, and progression, as well as in drug testing platforms. hiPSCs have been widely cultured in 2D systems, but in order to mimic human brain complexity, 3D models have been proposed as a more advanced alternative. This review will focus on the use of patient-derived hiPSCs to model AD, PD, HD and ALS. In brief, we will cover the available stem cells, types of 2D and 3D culture systems, existing models for neurodegenerative diseases, obstacles to model these diseases in vitro, and current perspectives in the field