Theology of the Church as Ministry to Blind People

Throughout history, people who are blind have been viewed by those in the sighted culture as limited and broken. This is true both in the church and in society in general. Our ecclesiology, however, should encourage, promote, or utilize blind people and their gifts to serve in the body of Christ. The church can, and should, accept, uplift, and utilize people who are blind and visually impaired as full members with a healthy and whole identity in Christ. To this end, our ecclesiology must not prohibit the ordination of a man who is blind solely on the basis of blindness as has been done in the past. I wrote this paper with the goal of helping the church realize that blindness is not necessarily a result of sin. Rather, it is a gift of God to be used by the church. I hope to help the church become more sensitive to people who are blind and develop more productive ways of serving and utilizing these people

Hedonistic Differences Between Mechanical Game Players And Table Game Players: An Exploratory Investigation On The Road To A Comprehensive Theory For Gambling

This exploratory research examined relationships between casino play and hedonic factors. The hedonic factors examined were emotion, sensation seeking and impulsivity, absorbing experiences, and analytical characteristics. Differences between slot players and table game players were measured. The subjects were a convenience sampling of 1,010 casino gamblers at a Las Vegas Strip casino catering to out of town visitors. All participants completed a 45- item survey. The constructs were measured using the Mehrabian and Russell (1974) pleasure, arousal, and dominance scale; the Zuckerman Kuhlman sensation seeking and impulsivity scale; the Swanson (1978) absorbing experience scale; and an analytical scale developed by the researchers. Both table game players and slot players derive pleasure from the pursuit of gambling. Table game players are more deeply involved and tend to be more aware of the intricacies of the games than slot players. Table game players are not as impulsive and tend to be more controlled than slot players. The overwhelming majority of table game players and slot players demonstrate discipline in terms of their gambling spending

Short‐term effects of smoking marijuana on balance in patients with multiple sclerosis and normal volunteers

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110106/1/cptclpt199433.pd

Alstom's Chemical Looping Combustion Prototype for CO{sub 2} Capture from Existing Pulverized Coal-Fired Power Plants: Final Report

Alstom’s Limestone Chemical Looping (LCL™) process has the potential to capture CO{sub 2} from new and existing coal-fired power plants while maintaining high plant power generation efficiency. This new power plant concept is based on a hybrid combustion- gasification process utilizing high temperature chemical and thermal looping technology. This process could also be potentially configured as a hybrid combustion-gasification process producing a syngas or hydrogen for various applications while also producing a separate stream of CO{sub 2} for use or sequestration. The targets set for this technology is to capture over 90% of the total carbon in the coal at cost of electricity which is less than 20% greater than Conventional PC or CFB units. Previous work with bench scale test and a 65 kWt Process Development Unit Development (PDU) has validated the chemistry required for the chemical looping process and provided for the investigation of the solids transport mechanisms and design requirements. The objective of this project is to continue development of the combustion option of chemical looping (LCL-C™) by designing, building and testing a 3 MWt prototype facility. The prototype includes all of the equipment that is required to operate the chemical looping plant in a fully integrated manner with all major systems in service. Data from the design, construction, and testing will be used to characterize environmental performance, identify and address technical risks, reassess commercial plant economics, and develop design information for a demonstration plant planned to follow the proposed Prototype. A cold flow model of the prototype will be used to predict operating conditions for the prototype and help in operator training. Operation of the prototype will provide operator experience with this new technology and performance data of the LCL-C™ process, which will be applied to the commercial design and economics and plan for a future demonstration plant

Global Public Health Security

National public health institutes will play a key role in implementation of the revised International Health Regulations

Epigenomic Landscapes of hESC-Derived Neural Rosettes: Modeling Neural Tube Formation and Diseases

We currently lack a comprehensive understanding of the mechanisms underlying neural tube formation and their contributions to neural tube defects (NTDs). Developing a model to study such a complex morphogenetic process, especially one that models human-specific aspects, is critical. Three-dimensional, human embryonic stem cell (hESC)-derived neural rosettes (NRs) provide a powerful resource for in vitro modeling of human neural tube formation. Epigenomic maps reveal enhancer elements unique to NRs relative to 2D systems. A master regulatory network illustrates that key NR properties are related to their epigenomic landscapes. We found that folate-associated DNA methylation changes were enriched within NR regulatory elements near genes involved in neural tube formation and metabolism. Our comprehensive regulatory maps offer insights into the mechanisms by which folate may prevent NTDs. Lastly, our distal regulatory maps provide a better understanding of the potential role of neurological-disorder-associated SNPs.</p

An Activating STAT3 Mutation Causes Neonatal Diabetes through Premature Induction of Pancreatic Differentiation

Activating germline mutations in STAT3 were recently identified as a cause of neonatal diabetes mellitus associated with beta-cell autoimmunity. We have investigated the effect of an activating mutation, STAT3(K392R,) on pancreatic development using induced pluripotent stem cells (iPSCs) derived from a patient with neonatal diabetes and pancreatic hypoplasia. Early pancreatic endoderm differentiated similarly from STAT3(K392R) and healthy-control cells, but in later stages, NEUROG3 expressionwas upregulated prematurely in STAT3(K392R) cells together with insulin (INS) and glucagon (GCG). RNA sequencing (RNA-seq) showed robust NEUROG3 downstream targets upregulation. STAT3 mutation correction with CRISPR/Cas9 reversed completely the disease phenotype. STAT3(K392R) -activating properties were not explained fully by altered DNA-binding affinity or increased phosphorylation. Instead, reporter assays demonstrated NEUROG3 promoter activation by STAT3 in pancreatic cells. Furthermore, proteomic and immunocytochemical analyses revealed increased nuclear translocation of STAT3(K392R). Collectively, our results demonstrate that the STAT3(K392R) mutation causes premature endocrine differentiation through direct induction of NEUROG3 expression.Peer reviewe

Genetic Variability Overrides the Impact of Parental Cell Type and Determines iPSC Differentiation Potential

Reports on the retention of somatic cell memory in induced pluripotent stem cells (iPSCs) have complicated the selection of the optimal cell type for the generation of iPSC biobanks. To address this issue we compared transcriptomic, epigenetic, and differentiation propensities of genetically matched human iPSCs derived from fibroblasts and blood, two tissues of the most practical relevance for biobanking. Our results show that iPSC lines derived from the same donor are highly similar to each other. However, genetic variation imparts a donor-specific expression and methylation profile in reprogrammed cells that leads to variable functional capacities of iPSC lines. Our results suggest that integration-free, bona fide iPSC lines from fibroblasts and blood can be combined in repositories to form biobanks. Due to the impact of genetic variation on iPSC differentiation, biobanks should contain cells from large numbers of donors.Peer reviewe

Methylome Analysis of Human Bone Marrow MSCs Reveals Extensive Age- and Culture-Induced Changes at Distal Regulatory Elements

Human bone marrow stromal cells, or mesenchymal stem cells (BM-MSCs), need expansion prior to use as cell-based therapies in immunological and tissue repair applications. Aging and expansion of BM-MSCs induce epigenetic changes that can impact therapeutic outcomes. By applying sequencing-based methods, we reveal that the breadth of DNA methylation dynamics associated with aging and expansion is greater than previously reported. Methylation changes are enriched at known distal transcription factor binding sites such as enhancer elements, instead of CpG-rich regions, and are associated with changes in gene expression. From this, we constructed hypo- and hypermethylation-specific regulatory networks, including a sub-network of BM-MSC master regulators and their predicted target genes, and identified putatively disrupted signaling pathways. Our genome-wide analyses provide a broader overview of age- and expansion-induced DNA methylation changes and a better understanding of the extent to which these changes alter gene expression and functionality of human BM-MSCs.</p

RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord

ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned \u3e50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG’s). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network “hub” gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF’s involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful in ALS patients