Prevention of vascular dysfunction and arterial hypertension in mice generated by assisted reproductive technologies by addition of melatonin to culture media.

Assisted reproductive technologies (ART) induce vascular dysfunction in humans and mice. In mice, ART-induced vascular dysfunction is related to epigenetic alteration of the endothelial nitric oxide synthase (eNOS) gene, resulting in decreased vascular eNOS expression and nitrite/nitrate synthesis. Melatonin is involved in epigenetic regulation, and its administration to sterile women improves the success rate of ART. We hypothesized that addition of melatonin to culture media may prevent ART-induced epigenetic and cardiovascular alterations in mice. We, therefore, assessed mesenteric-artery responses to acetylcholine and arterial blood pressure, together with DNA methylation of the eNOS gene promoter in vascular tissue and nitric oxide plasma concentration in 12-wk-old ART mice generated with and without addition of melatonin to culture media and in control mice. As expected, acetylcholine-induced mesenteric-artery dilation was impaired (P = 0.008 vs. control) and mean arterial blood pressure increased (109.5 ± 3.8 vs. 104.0 ± 4.7 mmHg, P = 0.002, ART vs. control) in ART compared with control mice. These alterations were associated with altered DNA methylation of the eNOS gene promoter (P < 0.001 vs. control) and decreased plasma nitric oxide concentration (10.1 ± 11.1 vs. 29.5 ± 8.0 μM) (P < 0.001 ART vs. control). Addition of melatonin (10(-6) M) to culture media prevented eNOS dysmethylation (P = 0.005, vs. ART + vehicle), normalized nitric oxide plasma concentration (23.1 ± 14.6 μM, P = 0.002 vs. ART + vehicle) and mesentery-artery responsiveness to acetylcholine (P < 0.008 vs. ART + vehicle), and prevented arterial hypertension (104.6 ± 3.4 mmHg, P < 0.003 vs. ART + vehicle). These findings provide proof of principle that modification of culture media prevents ART-induced vascular dysfunction. We speculate that this approach will also allow preventing ART-induced premature atherosclerosis in humans.

Evaluation of promising technologies for soil salinity amelioration in Timpaki (Crete): A participatory approach

Soil salinity management can be complex, expensive, and time demanding, especially in arid and semi-arid regions. Besides taking no action, possible management strategies include amelioration and adaptation measures. Here we apply the World Overview of Conservation Approaches and Technologies (WOCAT) framework for the systematic analysis and evaluation and selection of soil salinisation amelioration technologies in close collaboration with stakeholders. The participatory approach is applied in the RECARE (Preventing and Remediating degradation of soils in Europe through Land Care) project case study of Timpaki, a semiarid region in south-central Crete (Greece) where the main land use is horticulture in greenhouses irrigated by groundwater. Excessive groundwater abstractions have resulted in a drop of the groundwater level in the coastal part of the aquifer, thus leading to seawater intrusion and in turn to soil salinisation. The documented technologies are evaluated for their impacts on ecosystem services, cost, and input requirements using a participatory approach and field evaluations. Results show that technologies which promote maintaining existing crop types while enhancing productivity and decreasing soil salinity are preferred by the stakeholders. The evaluation concludes that rainwater harvesting is the optimal solution for direct soil salinity mitigation, as it addresses a wider range of ecosystem and human well-being benefits. Nevertheless, this merit is offset by poor financial motivation making agronomic measures more attractive to users.

Use of minimal invasive extracorporeal circulation in cardiac surgery: principles, definitions and potential benefits. A position paper from the Minimal invasive Extra-Corporeal Technologies international Society (MiECTiS).

Minimal invasive extracorporeal circulation (MiECC) systems have initiated important efforts within science and technology to further improve the biocompatibility of cardiopulmonary bypass components to minimize the adverse effects and improve end-organ protection. The Minimal invasive Extra-Corporeal Technologies international Society was founded to create an international forum for the exchange of ideas on clinical application and research of minimal invasive extracorporeal circulation technology. The present work is a consensus document developed to standardize the terminology and the definition of minimal invasive extracorporeal circulation technology as well as to provide recommendations for the clinical practice. The goal of this manuscript is to promote the use of MiECC systems into clinical practice as a multidisciplinary strategy involving cardiac surgeons, anaesthesiologists and perfusionists.

WOCAT - World Overview of Conservation Approaches and Technologies - Preliminary results from Eastern and Southern Africa

The World Overview of Conservation Approaches and Technologies (WOCAT) is a program of the World Association of Soil and Water Conservation (WASWC), organized as a consortium of several international institutions. The overall goal of WOCAT is to contribute to sustainable utilization of soil and water. WOCAT collects and analyzes information on soil and water conservation (SWC) technologies and approaches world-wide, and presents the collected information in computer databases and decision support systems, and in the form of handbooks, reports and maps readily accessible to SWC specialists and policy-makers world-wide. WOCAT has prepared a framework for the evaluation of soil and water conservation and has started data collection. The paper presents preliminary results with promising SWC technologies and approaches used in Eastern and Southern Africa. The first finding is that hardly any promising SWC activities could be found on common grazing lands. Analysis of the cropland shows some of the bio-physical and socioeconomic conditions under which certain SWC technologies and approaches are used, including land use types, climatic zones and land tenure, and looks at issues such as participation and costs. Furthermore, classification criteria for SWC technologies and approaches are discussed.

Public Commons for Geospatial Data: A Conceptual Model

A wide variety of spatial data collection efforts are ongoing throughout local, state and federal agencies, private firms and non-profit organizations. Each effort is established for a different purpose but organizations and individuals often collect and maintain the same or similar information. The United States federal government has undertaken many initiatives such as the National Spatial Data Infrastructure, the National Map and Geospatial One-Stop to reduce duplicative spatial data collection and promote the coordinated use, sharing, and dissemination of spatial data nationwide. A key premise in most of these initiatives is that no national government will be able to gather and maintain more than a small percentage of the geographic data that users want and desire. Thus, national initiatives depend typically on the cooperation of those already gathering spatial data and those using GIs to meet specific needs to help construct and maintain these spatial data infrastructures and geo-libraries for their nations (Onsrud 2001). Some of the impediments to widespread spatial data sharing are well known from directly asking GIs data producers why they are not currently involved in creating datasets that are of common or compatible formats, documenting their datasets in a standardized metadata format or making their datasets more readily available to others through Data Clearinghouses or geo-libraries. The research described in this thesis addresses the impediments to wide-scale spatial data sharing faced by GIs data producers and explores a new conceptual data-sharing approach, the Public Commons for Geospatial Data, that supports user-friendly metadata creation, open access licenses, archival services and documentation of parent lineage of the contributors and value- adders of digital spatial data sets.

Effects of congressional modernization laws on public access to innovative medical device technologies

The Federal Food and Drug Administration (FDA) and the Centers for Medicare and Medicaid (CMS) play key roles in making Class III, medical devices available to the public, and they are required by law to meet statutory deadlines for applications under review. Historically, both agencies have failed to meet their respective statutory requirements. Since these failures affect patient access and may adversely impact public health, Congress has enacted several “modernization” laws. However, the effectiveness of these modernization laws has not been adequately studied or established for Class III medical devices. ^ The aim of this research study was, therefore, to analyze how these modernization laws may have affected public access to medical devices. Two questions were addressed: (1) How have the FDA modernization laws affected the time to approval for medical device premarket approval applications (PMAs)? (2) How has the CMS modernization law affected the time to approval for national coverage decisions (NCDs)? The data for this research study were collected from publicly available databases for the period January 1, 1995, through December 31, 2008. These dates were selected to ensure that a sufficient period of time was captured to measure pre- and post-modernization effects on time to approval. All records containing original PMAs were obtained from the FDA database, and all records containing NCDs were obtained from the CMS database. Source documents, including FDA premarket approval letters and CMS national coverage decision memoranda, were reviewed to obtain additional data not found in the search results. Analyses were conducted to determine the effects of the pre- and post-modernization laws on time to approval. Secondary analyses of FDA subcategories were conducted to uncover any causal factors that might explain differences in time to approval and to compare with the primary trends. The primary analysis showed that the FDA modernization laws of 1997 and 2002 initially reduced PMA time to approval; after the 2002 modernization law, the time to approval began increasing and continued to increase through December 2008. The non-combined, subcategory approval trends were similar to the primary analysis trends. The combined, subcategory analysis showed no clear trends with the exception of non-implantable devices, for which time to approval trended down after 1997. The CMS modernization law of 2003 reduced NCD time to approval, a trend that continued through December 2008. This study also showed that approximately 86% of PMA devices do not receive NCDs. ^ As a result of this research study, recommendations are offered to help resolve statutory non-compliance and access issues, as follows: (1) Authorities should examine underlying causal factors for the observed trends; (2) Process improvements should be made to better coordinate FDA and CMS activities to include sharing data, reducing duplication, and establishing clear criteria for “safe and effective” and “reasonable and necessary”; (3) A common identifier should be established to allow tracking and trending of applications between FDA and CMS databases; (4) Statutory requirements may need to be revised; and (5) An investigation should be undertaken to determine why NCDs are not issued for the majority of PMAs. Any process improvements should be made without creating additional safety risks and adversely impacting public health. Finally, additional studies are needed to fully characterize and better understand the trends identified in this research study.^

Perchlorate remediation technologies: A systematic review of solely biodegradation versus a combination of ion-exchange and biodegradation technologies

A systematic review was performed in order to evaluate perchlorate remediation technologies. The two included technologies were ion-exchange concerted with biodegradation and solely biodegradation. A meta-analysis was completed and subsequently, a regression model was formed to conduct a degradation rate analysis and to depict the association between rate and various dependent variables (salinity/sali, nitrate concentration/nitc and carbon source concentration/csou). The outcome of the model analysis suggested that salt concentration did have an effect on the degradation rate in the ion-exchange process and that with a salt concentration greater than or equal to 18.6 g/L, the biodegradation process will produce a greater reduction of perchlorate than ion-exchange concerted with biodegradation. However, when a t-test examined the difference in perchlorate degradation rate between the two cleanup methods, there was no significant difference seen (p=0.7351, α = 0.05).^

NOVEL THERAPEUTIC TARGETS IDENTIFIED BY HIGH-THROUGHPUT TECHNOLOGIES FOR TRIPLE-NEGATIVE BREAST CANCER

Triple-negative breast cancers (TNBC) are characterized by the lack of or reduced expression of the estrogen and progesterone receptors, and normal expression of the human epidermal growth factor receptor 2. The lack of a well-characterized target for treatment leaves only systemic chemotherapy as the mainstay of treatment. Approximately 60-70% of patients are chemosensitive, while the remaining majority does not respond. Targeted therapies that take advantage of the unique molecular perturbations found in triple-negative breast cancer are needed. The genes that are frequently amplified or overexpressed represent potential therapeutic targets for triple-negative breast cancer. The purpose of this study was to identify and validate novel therapeutic targets for triple-negative breast cancers. 681 genes showed consistent and highly significant overexpression in TNBC compared to receptor-positive cancers in 2 data sets. For two genes, 3 of the 4 siRNAs showed preferential growth inhibition in TNBC cells. These two genes were the low density lipoprotein receptor-related protein 8 (LRP8) and very low-density lipoprotein receptor (VLDLR). Exposure to their cognate ligands, reelin and apolipoprotein E isoform 4 (ApoE4), stimulated the growth of TNBC cells in vitro. Suppression of the expression of either LRP8 or VLDLR or exposure to RAP (an inhibitor of ligand binding to LRP8 and VLDLR) abolished this ligand-induced proliferation. High-throughput protein and metabolic arrays revealed that ApoE4 stimulation rescued TNBC cells from serum-starvation induced up-regulation of genes involved in lipid biosynthesis, increased protein expression of oncogenes involved in the MAPK/ERK and DNA repair pathways, and reduced the serum-starvation induction of biochemicals involved in oxidative stress response and glycolytic metabolism. shLRP8 MDA-MB-231 xenografts had reduced tumor volume, in comparison to parental and shCON xenografts. These results indicate that LRP8-APOE signaling confers survival advantages to TNBC tumors under reduced nutrient conditions and during cellular environmental stress. We revealed that the LRP8-APOE receptor-ligand system is overexpressed in human TNBC. We also demonstrated that this receptor system mediates a strong growth promoting and survival function in TNBC cells in vitro and helps to sustain the growth of MDA-MD-231 xenografts. We propose that inhibitors of LRP8-APOE signaling may be clinically useful therapeutic agents for triple-negative breast cancer.

Geospatial analysis of groundwater depth for manual well drilling suitability in the Zinder Region, Niger

Manual and low-tech well drilling techniques have potential to assist in reaching the United Nations' millennium development goal for water in sub-Saharan Africa. This study used publicly available geospatial data in a regression tree analysis to predict groundwater depth in the Zinder region of Niger to identify suitable areas for manual well drilling. Regression trees were developed and tested on a database for 3681 wells in the Zinder region. A tree with 17 terminal leaves provided a range of ground water depth estimates that were appropriate for manual drilling, though much of the tree's complexity was associated with depths that were beyond manual methods. A natural log transformation of groundwater depth was tested to see if rescaling dataset variance would result in finer distinctions for regions of shallow groundwater. The RMSE for a log-transformed tree with only 10 terminal leaves was almost half that of the untransformed 17 leaf tree for groundwater depths less than 10 m. This analysis indicated important groundwater relationships for commonly available maps of geology, soils, elevation, and enhanced vegetation index from the MODIS satellite imaging system.

International Regulation of Emerging Technologies: Global Ideologies and Local Headaches

This paper begins to address the international regulation of emerging technologies taking an approach that includes the co-production of technologies and the nature of wicked problems. Both the development of technologies over time, the role of science in regulation, and results from case studies in the regulation of biotechnologies are discusses. Biotechnology, nanotechnology and synthetic biology receive the most attention.

Sharing Human-Generated Observations by Integrating HMI and the Semantic Sensor Web

Current “Internet of Things” concepts point to a future where connected objects gather meaningful information about their environment and share it with other objects and people. In particular, objects embedding Human Machine Interaction (HMI), such as mobile devices and, increasingly, connected vehicles, home appliances, urban interactive infrastructures, etc., may not only be conceived as sources of sensor information, but, through interaction with their users, they can also produce highly valuable context-aware human-generated observations. We believe that the great promise offered by combining and sharing all of the different sources of information available can be realized through the integration of HMI and Semantic Sensor Web technologies. This paper presents a technological framework that harmonizes two of the most influential HMI and Sensor Web initiatives: the W3C’s Multimodal Architecture and Interfaces (MMI) and the Open Geospatial Consortium (OGC) Sensor Web Enablement (SWE) with its semantic extension, respectively. Although the proposed framework is general enough to be applied in a variety of connected objects integrating HMI, a particular development is presented for a connected car scenario where drivers’ observations about the traffic or their environment are shared across the Semantic Sensor Web. For implementation and evaluation purposes an on-board OSGi (Open Services Gateway Initiative) architecture was built, integrating several available HMI, Sensor Web and Semantic Web technologies. A technical performance test and a conceptual validation of the scenario with potential users are reported, with results suggesting the approach is sound

Learning&Information Technologies Cartography

Nowadays, many researches focus their efforts in studies and applications on the Learning area. However, there is a lack of a reference system that permits to know the positioning and the existing links between Learning and Information Technologies. This paper proposes a Cartography where explains the relationships between the elements that compose the Learning Theories and Information Technologies, considering the own features of the learner and the Information Technologies Properties. This intersection will allow us to know what Information Technologies Properties promote Learning Futures.