Avoiding epigenetic variations in transgene expression with genetic insulators

Gene transfer that relies on integrating vectors often suffers from epigenetic or regulatory effects that influence the expression of the therapeutic gene and=or of cellular genes located near the vector integration site in the chromosome. Insulator elements act to block gene activation by enhancers, while chromatin domain boundary or barrier sequences prevent gene-silencing effects. At present, the modes of action of insulator and barriers are poorly understood, and their use in the context of gene therapies remains to be documented. Using combinations of reporter genes coding for indicator fluorescent proteins, we constructed assay systems that allow the quantification of the insulator or of the barrier activities of genetic elements in individual cells. This presentation will illustrate how these assay systems were used to identify short DNA elements that can insulate nearby genes from activation by viral vector enhancer elements, and=or that can block the propagation of a silent chromatin structure that leads to gene silencing. We will show that small elements of the order of 100-400 nucleotides can be designed to achieve both insulator and boundary function, as needed for safer integrating viral vectors.

2010 Iowa Medicaid – Birth Certificate – Barriers to Prenatal Care Project Match Report Summary of Findings for Medicaid Reimbursed Births

The purpose of the fact sheet is to summarize the Iowa Barriers to Prenatal Care Project’s survey results for women with Medicaid reimbursed births during 2010. This information will be used to guide decision makers in implementing programs that improve the health outcomes of the women and infants who rely on Medicaid coverage.

MAR-mediated integration of plasmid vectors for in vivo gene transfer and regulation.

BACKGROUND: The in vivo transfer of naked plasmid DNA into organs such as muscles is commonly used to assess the expression of prophylactic or therapeutic genes in animal disease models. RESULTS: In this study, we devised vectors allowing a tight regulation of transgene expression in mice from such non-viral vectors using a doxycycline-controlled network of activator and repressor proteins. Using these vectors, we demonstrate proper physiological response as consequence of the induced expression of two therapeutically relevant proteins, namely erythropoietin and utrophin. Kinetic studies showed that the induction of transgene expression was only transient, unless epigenetic regulatory elements termed Matrix Attachment Regions, or MAR, were inserted upstream of the regulated promoters. Using episomal plasmid rescue and quantitative PCR assays, we observed that similar amounts of plasmids remained in muscles after electrotransfer with or without MAR elements, but that a significant portion had integrated into the muscle fiber chromosomes. Interestingly, the MAR elements were found to promote plasmid genomic integration but to oppose silencing effects in vivo, thereby mediating long-term expression. CONCLUSIONS: This study thus elucidates some of the determinants of transient or sustained expression from the use of non-viral regulated vectors in vivo.

Integration of Bridge Damage Detection Concepts and Components (3 volumes), TR-636, 2013

This work is divided into three volumes: Volume I: Strain-Based Damage Detection; Volume II: Acceleration-Based Damage Detection; Volume III: Wireless Bridge Monitoring Hardware. Volume I: In this work, a previously-developed structural health monitoring (SHM) system was advanced toward a ready-for-implementation system. Improvements were made with respect to automated data reduction/analysis, data acquisition hardware, sensor types, and communication network architecture. The statistical damage-detection tool, control-chart-based damage-detection methodologies, were further investigated and advanced. For the validation of the damage-detection approaches, strain data were obtained from a sacrificial specimen attached to the previously-utilized US 30 Bridge over the South Skunk River (in Ames, Iowa), which had simulated damage,. To provide for an enhanced ability to detect changes in the behavior of the structural system, various control chart rules were evaluated. False indications and true indications were studied to compare the damage detection ability in regard to each methodology and each control chart rule. An autonomous software program called Bridge Engineering Center Assessment Software (BECAS) was developed to control all aspects of the damage detection processes. BECAS requires no user intervention after initial configuration and training. Volume II: In this work, a previously developed structural health monitoring (SHM) system was advanced toward a ready-for-implementation system. Improvements were made with respect to automated data reduction/analysis, data acquisition hardware, sensor types, and communication network architecture. The objective of this part of the project was to validate/integrate a vibration-based damage-detection algorithm with the strain-based methodology formulated by the Iowa State University Bridge Engineering Center. This report volume (Volume II) presents the use of vibration-based damage-detection approaches as local methods to quantify damage at critical areas in structures. Acceleration data were collected and analyzed to evaluate the relationships between sensors and with changes in environmental conditions. A sacrificial specimen was investigated to verify the damage-detection capabilities and this volume presents a transmissibility concept and damage-detection algorithm that show potential to sense local changes in the dynamic stiffness between points across a joint of a real structure. The validation and integration of the vibration-based and strain-based damage-detection methodologies will add significant value to Iowa’s current and future bridge maintenance, planning, and management Volume III: In this work, a previously developed structural health monitoring (SHM) system was advanced toward a ready-for-implementation system. Improvements were made with respect to automated data reduction/analysis, data acquisition hardware, sensor types, and communication network architecture. This report volume (Volume III) summarizes the energy harvesting techniques and prototype development for a bridge monitoring system that uses wireless sensors. The wireless sensor nodes are used to collect strain measurements at critical locations on a bridge. The bridge monitoring hardware system consists of a base station and multiple self-powered wireless sensor nodes. The base station is responsible for the synchronization of data sampling on all nodes and data aggregation. Each wireless sensor node include a sensing element, a processing and wireless communication module, and an energy harvesting module. The hardware prototype for a wireless bridge monitoring system was developed and tested on the US 30 Bridge over the South Skunk River in Ames, Iowa. The functions and performance of the developed system, including strain data, energy harvesting capacity, and wireless transmission quality, were studied and are covered in this volume.

Neuroscience robotics to investigate multisensory integration and bodily awareness.

Humans experience the self as localized within their body. This aspect of bodily self-consciousness can be experimentally manipulated by exposing individuals to conflicting multisensory input, or can be abnormal following focal brain injury. Recent technological developments helped to unravel some of the mechanisms underlying multisensory integration and self-location, but the neural underpinnings are still under investigation, and the manual application of stimuli resulted in large variability difficult to control. This paper presents the development and evaluation of an MR-compatible stroking device capable of presenting moving tactile stimuli to both legs and the back of participants lying on a scanner bed while acquiring functional neuroimaging data. The platform consists of four independent stroking devices with a travel of 16-20 cm and a maximum stroking velocity of 15 cm/s, actuated over non-magnetic ultrasonic motors. Complemented with virtual reality, this setup provides a unique research platform allowing to investigate multisensory integration and its effects on self-location under well-controlled experimental conditions. The MR-compatibility of the system was evaluated in both a 3 and a 7 Tesla scanner and showed negligible interference with brain imaging. In a preliminary study using a prototype device with only one tactile stimulator, fMRI data acquired on 12 healthy participants showed visuo-tactile synchrony-related and body-specific modulations of the brain activity in bilateral temporoparietal cortex.

Integration of local-scale hydrological and regional-scale geophysical based on a nonlinear Bayesian sequential simulation approach

Significant progress has been made with regard to the quantitative integration of geophysical and hydrological data at the local scale. However, extending the corresponding approaches to the regional scale represents a major, and as-of-yet largely unresolved, challenge. To address this problem, we have developed a downscaling procedure based on a non-linear Bayesian sequential simulation approach. The basic objective of this algorithm is to estimate the value of the sparsely sampled hydraulic conductivity at non-sampled locations based on its relation to the electrical conductivity, which is available throughout the model space. The in situ relationship between the hydraulic and electrical conductivities is described through a non-parametric multivariate kernel density function. This method is then applied to the stochastic integration of low-resolution, re- gional-scale electrical resistivity tomography (ERT) data in combination with high-resolution, local-scale downhole measurements of the hydraulic and electrical conductivities. Finally, the overall viability of this downscaling approach is tested and verified by performing and comparing flow and transport simulation through the original and the downscaled hydraulic conductivity fields. Our results indicate that the proposed procedure does indeed allow for obtaining remarkably faithful estimates of the regional-scale hydraulic conductivity structure and correspondingly reliable predictions of the transport characteristics over relatively long distances.

Migrations sans frontières mais...barrières des représentations [Migration without borders, but...barriers of meaning].

Immigration, a political, economic, demographic, social and ethic, as well as a medical issue, continues. Among migrants, asylum seekers, refugees and undocumented immigrants are characterised by their vulnerability, particularly related to their health status. Western physicians are more and more frequently confronted to "colorful" and often vulnerable patients. They face diseases related to international migrations; and at the same time have to integrate the differences in representations and meanings given to illness by patients of diverse origins. A bio-psychosocial and spiritual approach coupled with an evaluation of pre-migration, migration and post-migration trajectories is therefore useful for the clinician; these complementary approaches have all been integrated in the learning of cultural competencies.

Estudio sobre los procesos de integración laboral de los inmigrantes. Study of immigrants' labour integration process

El presente trabajo pretende mostrar los resultados de un estudio cuya intención era identificar posibles variables que afectan a los procesos y estrategias de integración laboral de personas procedentes de otros países; las necesidades formativas en relación al colectivo de referencia y ampliar el conocimiento del fenómeno en aras de la intervención psicoeducativa y social. A partir de una metodología de investigación de orientación cualitativa se ha concluido que las diferencias en cuanto a las estrategias de integración y sus logros están más determinadas por los niveles de cualificación en el país de origen que por las propias diferencias culturales. The article shows the results of a study carried out by the authors to identify possible variables that affect the processes and strategies of occupational integration of people coming from other countries, to establish training needs in relation to the reference group and to extend the knowledge of the phenomenon for the sake of the educational and social intervention. Using a qualitative research methodology, it was concluded that the differences in integration strategies and their accomplishments are better explained by the levels of qualification attained in the country of origin than by cultural differences.

Estudio sobre los procesos de integración laboral de los inmigrantes. Study of immigrants' labour integration process

El presente trabajo pretende mostrar los resultados de un estudio cuya intención era identificar posibles variables que afectan a los procesos y estrategias de integración laboral de personas procedentes de otros países; las necesidades formativas en relación al colectivo de referencia y ampliar el conocimiento del fenómeno en aras de la intervención psicoeducativa y social. A partir de una metodología de investigación de orientación cualitativa se ha concluido que las diferencias en cuanto a las estrategias de integración y sus logros están más determinadas por los niveles de cualificación en el país de origen que por las propias diferencias culturales. The article shows the results of a study carried out by the authors to identify possible variables that affect the processes and strategies of occupational integration of people coming from other countries, to establish training needs in relation to the reference group and to extend the knowledge of the phenomenon for the sake of the educational and social intervention. Using a qualitative research methodology, it was concluded that the differences in integration strategies and their accomplishments are better explained by the levels of qualification attained in the country of origin than by cultural differences.

Effectiveness of Parallel Noise Barriers - An Iowa Study, HR-540, 1987

Traffic noise monitoring using FHWA's Demonstration Projects Division Mobile Noise Laboratory at free field, single wall and parallel barrier site on I-380 in Evansdale, Iowa is described. Access to I-380 prior to its being open to traffic afforded a controlled pass-by monitoring phase involving different vehicle types. A subsequent second phase entailed identical measurement methodology to monitor "real world" I-380 traffic noise. Phase I data indicated increases in noise were significant under the parallel barrier conditions for light duty vehicles operating in the far lane. Phase II results showed that the actual I-380 traffic mix largely offset the earlier observed effect, but minor increases in traffic noise under the parallel system were noted. These differences in noise barrier system effectiveness are judged to be insignificant at this particular study location.