Construction of large signaling pathways using an adaptive perturbation approach with phosphoproteomic data.

PubMed

Melas, Ioannis N; Mitsos, Alexander; Messinis, Dimitris E; Weiss, Thomas S; Rodriguez, Julio-Saez; Alexopoulos, Leonidas G

2012-04-01

Construction of large and cell-specific signaling pathways is essential to understand information processing under normal and pathological conditions. On this front, gene-based approaches offer the advantage of large pathway exploration whereas phosphoproteomic approaches offer a more reliable view of pathway activities but are applicable to small pathway sizes. In this paper, we demonstrate an experimentally adaptive approach to construct large signaling pathways from phosphoproteomic data within a 3-day time frame. Our approach--taking advantage of the fast turnaround time of the xMAP technology--is carried out in four steps: (i) screen optimal pathway inducers, (ii) select the responsive ones, (iii) combine them in a combinatorial fashion to construct a phosphoproteomic dataset, and (iv) optimize a reduced generic pathway via an Integer Linear Programming formulation. As a case study, we uncover novel players and their corresponding pathways in primary human hepatocytes by interrogating the signal transduction downstream of 81 receptors of interest and constructing a detailed model for the responsive part of the network comprising 177 species (of which 14 are measured) and 365 interactions.

Adaptation of a RAS pathway activation signature from FF to FFPE tissues in colorectal cancer.

PubMed

Omolo, Bernard; Yang, Mingli; Lo, Fang Yin; Schell, Michael J; Austin, Sharon; Howard, Kellie; Madan, Anup; Yeatman, Timothy J

2016-10-19

The KRAS gene is mutated in about 40 % of colorectal cancer (CRC) cases, which has been clinically validated as a predictive mutational marker of intrinsic resistance to anti-EGFR inhibitor (EGFRi) therapy. Since nearly 60 % of patients with a wild type KRAS fail to respond to EGFRi combination therapies, there is a need to develop more reliable molecular signatures to better predict response. Here we address the challenge of adapting a gene expression signature predictive of RAS pathway activation, created using fresh frozen (FF) tissues, for use with more widely available formalin fixed paraffin-embedded (FFPE) tissues. In this study, we evaluated the translation of an 18-gene RAS pathway signature score from FF to FFPE in 54 CRC cases, using a head-to-head comparison of five technology platforms. FFPE-based technologies included the Affymetrix GeneChip (Affy), NanoString nCounter™ (NanoS), Illumina whole genome RNASeq (RNA-Acc), Illumina targeted RNASeq (t-RNA), and Illumina stranded Total RNA-rRNA-depletion (rRNA). Using Affy_FF as the "gold" standard, initial analysis of the 18-gene RAS scores on all 54 samples shows varying pairwise Spearman correlations, with (1) Affy_FFPE (r = 0.233, p = 0.090); (2) NanoS_FFPE (r = 0.608, p < 0.0001); (3) RNA-Acc_FFPE (r = 0.175, p = 0.21); (4) t-RNA_FFPE (r = -0.237, p = 0.085); (5) and t-RNA (r = -0.012, p = 0.93). These results suggest that only NanoString has successful FF to FFPE translation. The subsequent removal of identified "problematic" samples (n = 15) and genes (n = 2) further improves the correlations of Affy_FF with three of the five technologies: Affy_FFPE (r = 0.672, p < 0.0001); NanoS_FFPE (r = 0.738, p < 0.0001); and RNA-Acc_FFPE (r = 0.483, p = 0.002). Of the five technology platforms tested, NanoString technology provides a more faithful translation of the RAS pathway gene expression signature from FF to FFPE than the Affymetrix GeneChip and multiple RNASeq technologies. Moreover, NanoString was the most forgiving technology in the analysis of samples with presumably poor RNA quality. Using this approach, the RAS signature score may now be reasonably applied to FFPE clinical samples.

Spaces of Innovation: Experiences from Two Small High-Tech Firms

ERIC Educational Resources Information Center

Heiskanen, Tuula; Heiskanen, Hannu

2011-01-01

Purpose: By comparing two small high-tech firms specialising in medical technology this article seeks to answer the following questions: What are the key characteristics of innovation processes in the case firms? How do the mutual relationships between mental, social and physical spaces explain the different pathways in the innovation processes in…

Light Water Reactor Sustainability Program: Digital Technology Business Case Methodology Guide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomas, Ken; Lawrie, Sean; Hart, Adam

The Department of Energy’s (DOE’s) Light Water Reactor Sustainability Program aims to develop and deploy technologies that will make the existing U.S. nuclear fleet more efficient and competitive. The program has developed a standard methodology for determining the impact of new technologies in order to assist nuclear power plant (NPP) operators in building sound business cases. The Advanced Instrumentation, Information, and Control (II&C) Systems Technologies Pathway is part of the DOE’s Light Water Reactor Sustainability (LWRS) Program. It conducts targeted research and development (R&D) to address aging and reliability concerns with the legacy instrumentation and control and related information systemsmore » of the U.S. operating light water reactor (LWR) fleet. This work involves two major goals: (1) to ensure that legacy analog II&C systems are not life-limiting issues for the LWR fleet and (2) to implement digital II&C technology in a manner that enables broad innovation and business improvement in the NPP operating model. Resolving long-term operational concerns with the II&C systems contributes to the long-term sustainability of the LWR fleet, which is vital to the nation’s energy and environmental security. The II&C Pathway is conducting a series of pilot projects that enable the development and deployment of new II&C technologies in existing nuclear plants. Through the LWRS program, individual utilities and plants are able to participate in these projects or otherwise leverage the results of projects conducted at demonstration plants. Performance advantages of the new pilot project technologies are widely acknowledged, but it has proven difficult for utilities to derive business cases for justifying investment in these new capabilities. Lack of a business case is often cited by utilities as a barrier to pursuing wide-scale application of digital technologies to nuclear plant work activities. The decision to move forward with funding usually hinges on demonstrating actual cost reductions that can be credited to budgets and thereby truly reduce O&M or capital costs. Technology enhancements, while enhancing work methods and making work more efficient, often fail to eliminate workload such that it changes overall staffing and material cost requirements. It is critical to demonstrate cost reductions or impacts on non-cost performance objectives in order for the business case to justify investment by nuclear operators. The Business Case Methodology (BCM) addresses the “benefit” side of the analysis—as opposed to the cost side—and how the organization evaluates discretionary projects (net present value (NPV), accounting effects of taxes, discount rates, etc.). The cost and analysis side is not particularly difficult for the organization and can usually be determined with a fair amount of precision (not withstanding implementation project cost overruns). It is in determining the "benefits" side of the analysis that utilities have more difficulty in technology projects and that is the focus of this methodology.« less

Rare copy number variants in patients with congenital conotruncal heart defects.

PubMed

Xie, Hongbo M; Werner, Petra; Stambolian, Dwight; Bailey-Wilson, Joan E; Hakonarson, Hakon; White, Peter S; Taylor, Deanne M; Goldmuntz, Elizabeth

2017-03-01

Previous studies using different cardiac phenotypes, technologies and designs suggest a burden of large, rare or de novo copy number variants (CNVs) in subjects with congenital heart defects. We sought to identify disease-related CNVs, candidate genes, and functional pathways in a large number of cases with conotruncal and related defects that carried no known genetic syndrome. Cases and control samples were divided into two cohorts and genotyped to assess each subject's CNV content. Analyses were performed to ascertain differences in overall CNV prevalence and to identify enrichment of specific genes and functional pathways in conotruncal cases relative to healthy controls. Only findings present in both cohorts are presented. From 973 total conotruncal cases, a burden of rare CNVs was detected in both cohorts. Candidate genes from rare CNVs found in both cohorts were identified based on their association with cardiac development or disease, and/or their reported disruption in published studies. Functional and pathway analyses revealed significant enrichment of terms involved in either heart or early embryonic development. Our study tested one of the largest cohorts specifically with cardiac conotruncal and related defects. These results confirm and extend previous findings that CNVs contribute to disease risk for congenital heart defects in general and conotruncal defects in particular. As disease heterogeneity renders identification of single recurrent genes or loci difficult, functional pathway and gene regulation network analyses appear to be more informative. Birth Defects Research 109:271-295, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Identifying viable regulatory and innovation pathways for regenerative medicine: a case study of cultured red blood cells.

PubMed

Mittra, J; Tait, J; Mastroeni, M; Turner, M L; Mountford, J C; Bruce, K

2015-01-25

The creation of red blood cells for the blood transfusion markets represents a highly innovative application of regenerative medicine with a medium term (5-10 year) prospect for first clinical studies. This article describes a case study analysis of a project to derive red blood cells from human embryonic stem cells, including the systemic challenges arising from (i) the selection of appropriate and viable regulatory protocols and (ii) technological constraints related to stem cell manufacture and scale up to clinical Good Manufacturing Practice (GMP) standard. The method used for case study analysis (Analysis of Life Science Innovation Systems (ALSIS)) is also innovative, demonstrating a new approach to social and natural science collaboration to foresight product development pathways. Issues arising along the development pathway include cell manufacture and scale-up challenges, affected by regulatory demands emerging from the innovation ecosystem (preclinical testing and clinical trials). Our discussion reflects on the efforts being made by regulators to adapt the current pharmaceuticals-based regulatory model to an allogeneic regenerative medicine product and the broader lessons from this case study for successful innovation and translation of regenerative medicine therapies, including the role of methodological and regulatory innovation in future development in the field. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Trading-off emission reduction, carbon capture and geoengineering to reach the Paris agreement

NASA Astrophysics Data System (ADS)

Gasser, T.; Boucher, O.; Lecocq, F.; Obersteiner, M.

2017-12-01

We explore virtually all possible future pathways that respect the Paris agreement, with an innovative modeling framework. We show that immediate and extreme mitigation of CO2 and non-CO2 species alike, carbon dioxide removal (CDR) and/or solar radiation management (SRM) technologies are required. We analyze the tradeoffs between these solutions. We generate thousands of temperature change pathways that extend historical records, stay below 2°C, and aim at 1.5°C in the long run. Non-CO2 forcings are generated likewise. With a simple model of the Earth system, we then back-calculate anthropogenic CO2 emissions compatible with these pathways. Other key global variables such as ocean acidity, sea level and permafrost thaw are also simulated. From this large ensemble of fully consistent scenarios, we analyze subsets that meet certain criteria: physical targets, emission levels, technology use, or any combination thereof. We show that staying below 1.5°C is feasible if CO2 emissions peak before 2025 and non-CO2 forcings are also reduced to zero. In case of a positive long-term non-CO2 forcing (a mitigation floor), CDR is necessary. Alternatively, emissions can peak later and/or higher if SRM is allowed. For pathways overshooting 1.5°C, results depend on the overshoot's size and length. Because of thawing permafrost, virtually all overshoot pathways require CDR, unless non-CO2 species (possibly SRM) are cooling the system at the time of peak temperature. When considering additional physical targets, which can be relevant for preserving ecosystems, the space of allowable pathways is systematically reduced. Especially: limiting ocean acidification rules out SRM. The nationally determined contributions (NDCs) indicate that reaching even the strictest interpretation of the agreement is feasible. However, if SRM is ruled out and only a reasonable amount of CDR is allowed, NDCs are compatible with very few of our pathways (≈5%). If a mitigation floor is added on top of that, virtually no pathways remain (<1%). We conclude that, in its strictest interpretation, the Paris agreement relies heavily on currently non-existent (and potentially harmful) technologies. In a looser interpretation, these technologies may not be needed, although the window of opportunity is closing extremely fast.

Constraints on biomass energy deployment in mitigation pathways: the case of water scarcity

NASA Astrophysics Data System (ADS)

Séférian, Roland; Rocher, Matthias; Guivarch, Céline; Colin, Jeanne

2018-05-01

To limit global warming to well below 2 ° most of the IPCC-WGIII future stringent mitigation pathways feature a massive global-scale deployment of negative emissions technologies (NETs) before the end of the century. The global-scale deployment of NETs like Biomass Energy with Carbon Capture and Storage (BECCS) can be hampered by climate constraints that are not taken into account by Integrated assessment models (IAMs) used to produce those pathways. Among the various climate constraints, water scarcity appears as a potential bottleneck for future land-based mitigation strategies and remains largely unexplored. Here, we assess climate constraints relative to water scarcity in response to the global deployment of BECCS. To this end, we confront results from an Earth system model (ESM) and an IAM under an array of 25 stringent mitigation pathways. These pathways are compatible with the Paris Agreement long-term temperature goal and with cumulative carbon emissions ranging from 230 Pg C and 300 Pg C from January 1st onwards. We show that all stylized mitigation pathways studied in this work limit warming below 2 °C or even 1.5 °C by 2100 but all exhibit a temperature overshoot exceeding 2 °C after 2050. According to the IAM, a subset of 17 emission pathways are feasible when evaluated in terms of socio-economic and technological constraints. The ESM however shows that water scarcity would limit the deployment of BECCS in all the mitigation pathways assessed in this work. Our findings suggest that the evolution of the water resources under climate change can exert a significant constraint on BECCS deployment before 2050. In 2100, the BECCS water needs could represent more than 30% of the total precipitation in several regions like Europe or Asia.

Pathway to care for drug resistant tuberculosis cases identified during a retrospective study conducted in high TB burden wards in Mumbai

PubMed Central

Lobo, Eunice; Shah, Shimoni; Rangan, Sheela; Dholakia, Yatin; Mistry, Nerges

2018-01-01

Background: Mumbai is witnessing a rising incidence of all forms of drug resistant tuberculosis (DR-TB). Methods: A population-based, retrospective study was conducted between April and July 2014, in 15 high TB burden wards in Mumbai, to capture the patient pathways to TB care. A total of 23 DR-TB patients were identified and their pathways to access DR-TB care were recorded using semi-structured interviews. Results: The total DR-TB pathway time of new patients (who did not report any past episode of TB) (180 days; IQR 123,346) was found to be more than twice that of retreatment patients (who reported a past episode of TB) (69 days; IQR 42,128). Conclusions: The unacceptable delay for diagnosis and treatment of DR-TB in Mumbai advocates for consistent implementation of early screening of patients using rapid gene-based technologies. PMID:29863175

Pathway to care for drug resistant tuberculosis cases identified during a retrospective study conducted in high TB burden wards in Mumbai.

PubMed

Lobo, Eunice; Shah, Shimoni; Rangan, Sheela; Dholakia, Yatin; Mistry, Nerges

2018-05-10

Background: Mumbai is witnessing a rising incidence of all forms of drug resistant tuberculosis (DR-TB). Methods: A population-based, retrospective study was conducted between April and July 2014, in 15 high TB burden wards in Mumbai, to capture the patient pathways to TB care. A total of 23 DR-TB patients were identified and their pathways to access DR-TB care were recorded using semi-structured interviews. Results: The total DR-TB pathway time of new patients (who did not report any past episode of TB) (180 days; IQR 123,346) was found to be more than twice that of retreatment patients (who reported a past episode of TB) (69 days; IQR 42,128). Conclusions: The unacceptable delay for diagnosis and treatment of DR-TB in Mumbai advocates for consistent implementation of early screening of patients using rapid gene-based technologies.

Reactome graph database: Efficient access to complex pathway data

PubMed Central

Korninger, Florian; Viteri, Guilherme; Marin-Garcia, Pablo; Ping, Peipei; Wu, Guanming; Stein, Lincoln; D’Eustachio, Peter

2018-01-01

Reactome is a free, open-source, open-data, curated and peer-reviewed knowledgebase of biomolecular pathways. One of its main priorities is to provide easy and efficient access to its high quality curated data. At present, biological pathway databases typically store their contents in relational databases. This limits access efficiency because there are performance issues associated with queries traversing highly interconnected data. The same data in a graph database can be queried more efficiently. Here we present the rationale behind the adoption of a graph database (Neo4j) as well as the new ContentService (REST API) that provides access to these data. The Neo4j graph database and its query language, Cypher, provide efficient access to the complex Reactome data model, facilitating easy traversal and knowledge discovery. The adoption of this technology greatly improved query efficiency, reducing the average query time by 93%. The web service built on top of the graph database provides programmatic access to Reactome data by object oriented queries, but also supports more complex queries that take advantage of the new underlying graph-based data storage. By adopting graph database technology we are providing a high performance pathway data resource to the community. The Reactome graph database use case shows the power of NoSQL database engines for complex biological data types. PMID:29377902

Reactome graph database: Efficient access to complex pathway data.

PubMed

Fabregat, Antonio; Korninger, Florian; Viteri, Guilherme; Sidiropoulos, Konstantinos; Marin-Garcia, Pablo; Ping, Peipei; Wu, Guanming; Stein, Lincoln; D'Eustachio, Peter; Hermjakob, Henning

2018-01-01

Reactome is a free, open-source, open-data, curated and peer-reviewed knowledgebase of biomolecular pathways. One of its main priorities is to provide easy and efficient access to its high quality curated data. At present, biological pathway databases typically store their contents in relational databases. This limits access efficiency because there are performance issues associated with queries traversing highly interconnected data. The same data in a graph database can be queried more efficiently. Here we present the rationale behind the adoption of a graph database (Neo4j) as well as the new ContentService (REST API) that provides access to these data. The Neo4j graph database and its query language, Cypher, provide efficient access to the complex Reactome data model, facilitating easy traversal and knowledge discovery. The adoption of this technology greatly improved query efficiency, reducing the average query time by 93%. The web service built on top of the graph database provides programmatic access to Reactome data by object oriented queries, but also supports more complex queries that take advantage of the new underlying graph-based data storage. By adopting graph database technology we are providing a high performance pathway data resource to the community. The Reactome graph database use case shows the power of NoSQL database engines for complex biological data types.

Techno-economic analysis for a sugarcane biorefinery: Colombian case.

PubMed

Moncada, Jonathan; El-Halwagi, Mahmoud M; Cardona, Carlos A

2013-05-01

In this paper a techno-economic analysis for a sugarcane biorefinery is presented for the Colombian case. It is shown two scenarios for different conversion pathways as function of feedstock distribution and technologies for sugar, fuel ethanol, PHB, anthocyanins and electricity production. These scenarios are compared with the Colombian base case which simultaneously produce sugar, fuel ethanol and electricity. A simulation procedure was used in order to evaluate biorefinery schemes for all the scenarios, using Aspen Plus software, that include productivity analysis, energy calculations and economic evaluation for each process configuration. The results showed that the configuration with the best economic, environmental and social performance is the one that considers fuel ethanol and PHB production from combined cane bagasse and molasses. This result served as the basis to draw recommendations on technological and economic feasibility as well as social aspects for the implementation of such type of biorefinery in Colombia. Copyright © 2012 Elsevier Ltd. All rights reserved.

Biofuels Fuels Technology Pathway Options for Advanced Drop-in Biofuels Production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kevin L Kenney

2011-09-01

Advanced drop-in hydrocarbon biofuels require biofuel alternatives for refinery products other than gasoline. Candidate biofuels must have performance characteristics equivalent to conventional petroleum-based fuels. The technology pathways for biofuel alternatives also must be plausible, sustainable (e.g., positive energy balance, environmentally benign, etc.), and demonstrate a reasonable pathway to economic viability and end-user affordability. Viable biofuels technology pathways must address feedstock production and environmental issues through to the fuel or chemical end products. Potential end products include compatible replacement fuel products (e.g., gasoline, diesel, and JP8 and JP5 jet fuel) and other petroleum products or chemicals typically produced from a barrelmore » of crude. Considering the complexity and technology diversity of a complete biofuels supply chain, no single entity or technology provider is capable of addressing in depth all aspects of any given pathway; however, all the necessary expert entities exist. As such, we propose the assembly of a team capable of conducting an in-depth technology pathway options analysis (including sustainability indicators and complete LCA) to identify and define the domestic biofuel pathways for a Green Fleet. This team is not only capable of conducting in-depth analyses on technology pathways, but collectively they are able to trouble shoot and/or engineer solutions that would give industrial technology providers the highest potential for success. Such a team would provide the greatest possible down-side protection for high-risk advanced drop-in biofuels procurement(s).« less

T85C polymorphisms of the dihydropyrimidine dehydrogenase gene detected in gastric cancer tissues by high-resolution melting curve analysis.

PubMed

Fang, Weijia; Xu, Nong; Jin, Dazhi; Chen, Yu; Chen, Xiaogang; Zheng, Yi; Shen, Hong; Yuan, Ying; Zheng, Shusen

2012-01-01

Dihydropyrimidine dehydrogenase is a key enzyme acting on the metabolic pathway of medications for gastric cancer. High-resolution melting curve technology, which was developed recently, can distinguish the wild-type dihydropyrimidine dehydrogenase gene from multiple polymorphisms by fluorescent quantitative polymerase chain reaction products in a direct and effective manner. T85C polymorphisms of dihydropyrimidine dehydrogenase in the peripheral blood of 112 Chinese gastric cancer patients were detected by real-time polymerase chain reaction combined with high-resolution melting curve technology. Primer design, along with the reaction system and conditions, was optimized based on the GenBank sequence. Seventy nine cases of wild-type (TT, [70.5%]), 29 cases of heterozygous (TC, [25.9%]), and 4 cases of homozygous mutant (CC, [3.6%]) were observed. The result was completely consistent with the results of the sequencing. Real-time polymerase chain reaction combined with high-resolution melting curve technology is a rapid, simple, reliable, direct-viewing, and convenient method for the detection and screening of polymorphisms.

PANDA: pathway and annotation explorer for visualizing and interpreting gene-centric data.

PubMed

Hart, Steven N; Moore, Raymond M; Zimmermann, Michael T; Oliver, Gavin R; Egan, Jan B; Bryce, Alan H; Kocher, Jean-Pierre A

2015-01-01

Objective. Bringing together genomics, transcriptomics, proteomics, and other -omics technologies is an important step towards developing highly personalized medicine. However, instrumentation has advances far beyond expectations and now we are able to generate data faster than it can be interpreted. Materials and Methods. We have developed PANDA (Pathway AND Annotation) Explorer, a visualization tool that integrates gene-level annotation in the context of biological pathways to help interpret complex data from disparate sources. PANDA is a web-based application that displays data in the context of well-studied pathways like KEGG, BioCarta, and PharmGKB. PANDA represents data/annotations as icons in the graph while maintaining the other data elements (i.e., other columns for the table of annotations). Custom pathways from underrepresented diseases can be imported when existing data sources are inadequate. PANDA also allows sharing annotations among collaborators. Results. In our first use case, we show how easy it is to view supplemental data from a manuscript in the context of a user's own data. Another use-case is provided describing how PANDA was leveraged to design a treatment strategy from the somatic variants found in the tumor of a patient with metastatic sarcomatoid renal cell carcinoma. Conclusion. PANDA facilitates the interpretation of gene-centric annotations by visually integrating this information with context of biological pathways. The application can be downloaded or used directly from our website: http://bioinformaticstools.mayo.edu/research/panda-viewer/.

Wellbore Completion Systems Containment Breach Solution Experiments at a Large Scale Underground Research Laboratory : Sealant placement & scale-up from Lab to Field

NASA Astrophysics Data System (ADS)

Goodman, H.

2017-12-01

This investigation seeks to develop sealant technology that can restore containment to completed wells that suffer CO2 gas leakages currently untreatable using conventional technologies. Experimentation is performed at the Mont Terri Underground Research Laboratory (MT-URL) located in NW Switzerland. The laboratory affords investigators an intermediate-scale test site that bridges the gap between the laboratory bench and full field-scale conditions. Project focus is the development of CO2 leakage remediation capability using sealant technology. The experimental concept includes design and installation of a field scale completion package designed to mimic well systems heating-cooling conditions that may result in the development of micro-annuli detachments between the casing-cement-formation boundaries (Figure 1). Of particular interest is to test novel sealants that can be injected in to relatively narrow micro-annuli flow-paths of less than 120 microns aperture. Per a special report on CO2 storage submitted to the IPCC[1], active injection wells, along with inactive wells that have been abandoned, are identified as one of the most probable sources of leakage pathways for CO2 escape to the surface. Origins of pressure leakage common to injection well and completions architecture often occur due to tensile cracking from temperature cycles, micro-annulus by casing contraction (differential casing to cement sheath movement) and cement sheath channel development. This discussion summarizes the experiment capability and sealant testing results. The experiment concludes with overcoring of the entire mock-completion test site to assess sealant performance in 2018. [1] IPCC Special Report on Carbon Dioxide Capture and Storage (September 2005), section 5.7.2 Processes and pathways for release of CO2 from geological storage sites, page 244

Pathways to Genome-targeted Therapies in Serous Ovarian Cancer.

PubMed

Axelrod, Joshua; Delaney, Joe

2017-07-01

Genome sequencing technologies and corresponding oncology publications have generated enormous publicly available datasets for many cancer types. While this has enabled new treatments, and in some limited cases lifetime management of the disease, the treatment options for serous ovarian cancer remain dismal. This review summarizes recent advances in our understanding of ovarian cancer, with a focus on heterogeneity, functional genomics, and actionable data.

Least cost pathways to a low carbon electricity system for Australia: impacts of transmission augmentation and extension

NASA Astrophysics Data System (ADS)

Dargaville, R. J.

2016-12-01

Designing the pathway to a low carbon energy system is complex, requiring consideration of the variable nature of renewables at the hourly timescale, emission intensity and ramp rate constraints of dispatchable technologies (both fossil and renewable) and transmission and distribution network limitations. In this work, an optimization framework taking into account these considerations has been applied to find the lowest cost ways to reduce carbon emissions by either 80% or 100% in 2050 while keeping the system operating reliably along the way. Technologies included are existing and advanced coal and gas technologies (with and without carbon capture and storage), rooftop PV, utility scale PV, concentrating solar thermal, hydro with and without pumped storage, bioenergy, and nuclear. In this study we also also the optimisation to increase transmission capacity along existing lines, and to extend key trunk lines into currently unserved areas. These augementations and extensions come at a cost. The otpimisation chooses these options when the benefits of accessing high quality renewable energy resources outweights the costs. Results show that for the 80% emission reduction case, there is limited need for transmission capacity increase, and that the existing grid copes well with the increased flows due to conversion to distrubuted renewable energy resources. However, in the 100% case the increased reliance on renewables means that signficant transmission augmentation is beneficial to the overall cost. This strongly suggests that it is important to understand the long term emission target early so that infrastructure investments can be optimised.

Effect of government actions on technological innovation for SO2 control.

PubMed

Taylor, Margaret R; Rubin, Edward S; Hounshell, David A

2003-10-15

The relationship between government actions and innovation in environmental control technology is important for the design of cost-effective policies to achieve environmental goals. This paper examines such relationships for the case of sulfur dioxide control technology for U.S. coal-fired power plants. The study employs several complementary research methods, including analyses of key government actions, technology patenting activity, technology performance and cost trends, knowledge transfer activities, and expert elicitations. Our results indicate that government regulation appears to be a greater stimulus to inventive activity than government-sponsored research support alone, and that the anticipation of regulation also spurs inventive activity. Regulatory stringency focuses this activity along particular technical pathways and is a key factor in creating markets for environmental technologies. We also find that with greater technology adoption, both new and existing systems experience notable efficiency improvements and capital cost reductions. The important role of government in fostering knowledge transfer via technical conferences and other measures is also seen as an important factor in promoting environmental technology innovation.

Robotic Whipple Procedure for Pancreatic Cancer: The Moffitt Cancer Center Pathway.

PubMed

Rashid, Omar M; Mullinax, John E; Pimiento, Jose M; Meredith, Kenneth L; Malafa, Mokenge P

2015-07-01

Resection of malignancies in the head and uncinate process of the pancreas (Whipple procedure) using a robotic approach is emerging as a surgical option. Although several case series of the robotic Whipple procedure have been reported, detailed descriptions of operative techniques and a clear pathway for adopting this technology are lacking. We present a focused review of the procedure as it applies to pancreatic cancer and describe our clinical pathway for the robotic Whipple procedure used in pancreatic cancer and review the outcomes of our early experience. A systematic review of the literature is provided, focusing on the indications, variations in surgical techniques, complications, and oncological results of the robotic Whipple procedure. A clinical pathway has been defined for preoperative training of surgeons, the requirements for hospital privileges, patient selection, and surgical techniques for the robotic Whipple procedure. The robotic technique for managing malignant lesions of the pancreas head is safe when following well-established guidelines for adopting the technology. Preliminary data demonstrate that perioperative convalescence may exceed end points when compared with the open technique. The robotic Whipple procedure is a minimally invasive approach for select patients as part of multidisciplinary management of periampullary lesions in tertiary centers where clinicians have developed robotic surgical programs. Prospective trials are needed to define the short- and long-term benefits of the robotic Whipple procedure.

The first FDA marketing authorizations of next-generation sequencing technology and tests: challenges, solutions and impact for future assays.

PubMed

Bijwaard, Karen; Dickey, Jennifer S; Kelm, Kellie; Težak, Živana

2015-01-01

The rapid emergence and clinical translation of novel high-throughput sequencing technologies created a need to clarify the regulatory pathway for the evaluation and authorization of these unique technologies. Recently, the US FDA authorized for marketing four next generation sequencing (NGS)-based diagnostic devices which consisted of two heritable disease-specific assays, library preparation reagents and a NGS platform that are intended for human germline targeted sequencing from whole blood. These first authorizations can serve as a case study in how different types of NGS-based technology are reviewed by the FDA. In this manuscript we describe challenges associated with the evaluation of these novel technologies and provide an overview of what was reviewed. Besides making validated NGS-based devices available for in vitro diagnostic use, these first authorizations create a regulatory path for similar future instruments and assays.

Use of eQTL Analysis for the Discovery of Target Genes Identified by GWAS

DTIC Science & Technology

2013-04-01

the biologic pathways affected by these inherited factors, and ultimately to identify targets for disease prediction, risk stratification and...quality using an Agilent chip technology. Cases having a RIN number of 7.0 or greater were considered good quality. Once completed, the optimum set of...AD_________________ Award Number: W81XWH-11-1-0261 TITLE: Use of eQTL Analysis for the Discovery of

Development and Performance of Alternative Electricity Sector Pathways Subject to Multiple Climate and Water Projections

NASA Astrophysics Data System (ADS)

Newmark, R. L.; Vorosmarty, C. J.; Miara, A.; Cohen, S.; Macknick, J.; Sun, Y.; Corsi, F.; Fekete, B. M.; Tidwell, V. C.

2017-12-01

Climate change impacts on air temperatures and water availability have the potential to alter future electricity sector investment decisions as well as the reliability and performance of the power sector. Different electricity sector configurations are more or less vulnerable to climate-induced changes. For example, once-through cooled thermal facilities are the most cost-effective and efficient technologies under cooler and wetter conditions, but can be substantially affected by and vulnerable to warmer and drier conditions. Non-thermal renewable technologies, such as PV and wind, are essentially "drought-proof" but have other integration and reliability challenges. Prior efforts have explored the impacts of climate change on electric sector development for a limited set of climate and electricity scenarios. Here, we provide a comprehensive suite of scenarios that evaluate how different electricity sector pathways could be affected by a range of climate and water resource conditions. We use four representative concentration pathway (RCP) scenarios under five global circulation models (GCM) as climate drivers to a Water Balance Model (WBM), to provide twenty separate future climate-water conditions. These climate-water conditions influence electricity sector development from present day to 2050 as determined using the Regional Energy Deployment Systems (ReEDS) model. Four unique electricity sector pathways will be considered, including business-as-usual, carbon cap, high renewable energy technology costs, and coal reliance scenarios. The combination of climate-water and electricity sector pathway scenarios leads to 80 potential future cases resulting in different national and regional electricity infrastructure configurations. The vulnerability of these configurations in relation to climate change (including in-stream thermal pollution impacts and environmental regulations) is evaluated using the Thermoelectric Power and Thermal Pollution (TP2M) model, providing quantitative estimates of the power sector's ability to meet loads, given changes in air temperature, water temperature, and water availability.

Process Design and Economics for the Conversion of Lignocellulosic Biomass to Hydrocarbon Fuels. Thermochemical Research Pathways with In Situ and Ex Situ Upgrading of Fast Pyrolysis Vapors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dutta, Abhijit; Sahir, Asad; Tan, Eric

This report was developed as part of the U.S. Department of Energy’s Bioenergy Technologies Office’s efforts to enable the development of technologies for the production of infrastructurecompatible, cost-competitive liquid hydrocarbon fuels from biomass. Specifically, this report details two conceptual designs based on projected product yields and quality improvements via catalyst development and process integration. It is expected that these research improvements will be made within the 2022 timeframe. The two conversion pathways detailed are (1) in situ and (2) ex situ upgrading of vapors produced from the fast pyrolysis of biomass. While the base case conceptual designs and underlying assumptionsmore » outline performance metrics for feasibility, it should be noted that these are only two of many other possibilities in this area of research. Other promising process design options emerging from the research will be considered for future techno-economic analysis.« less

STEM Career Cluster Engineering and Technology Education pathway in Georgia: Perceptions of Georgia engineering and technology education high school teachers and CTAE administrators as measured by the Characteristics of Engineering and Technology Education survey

NASA Astrophysics Data System (ADS)

Crenshaw, Mark VanBuren

This study examined the perceptions held by Georgia Science, Technology, Engineering, and Mathematics (STEM) Career Cluster Engineering and Technology Education (ETE) high school pathway teachers and Georgia's Career, Technical and Agriculture Education (CTAE) administrators regarding the ETE pathway and its effect on implementation within their district and schools. It provides strategies for ETE teaching methods, curriculum content, STEM integration, and how to improve the ETE pathway program of study. Current teaching and curricular trends were examined in ETE as well as the role ETE should play as related to STEM education. The study, using the Characteristics of Engineering and Technology Education Survey, was conducted to answer the following research questions: (a) Is there a significant difference in the perception of ETE teaching methodology between Georgia ETE high school teachers and CTAE administrators as measured by the Characteristics of Engineering and Technology Education Survey? (b) Is there a significant difference in the perception of ETE curriculum content between Georgia ETE high school teachers and CTAE administrators as measured by the Characteristics of Engineering and Technology Education Survey? (c) Is there a significant difference in the perception of STEM integration in the ETE high school pathway between Georgia ETE high school teachers and CTAE administrators as measured by the Characteristics of Engineering and Technology Education Survey? and (d) Is there a significant difference in the perception of how to improve the ETE high school pathway between Georgia ETE high school teachers and CTAE administrators as measured by the Characteristics of Engineering and Technology Education Survey? Suggestions for further research also were offered.

Acquiring Data by Mining the Past: Pairing Communities with Environmental Monitoring Methods through Open Online Collaborative Replication

NASA Astrophysics Data System (ADS)

Lippincott, M.; Lewis, E. S.; Gehrke, G. E.; Wise, A.; Pyle, S.; Sinatra, V.; Bland, G.; Bydlowski, D.; Henry, A.; Gilberts, P. A.

2016-12-01

Community groups are interested in low-cost sensors to monitor their environment. However, many new commercial sensors are unknown devices without peer-reviewed evaluations of data quality or pathways to regulatory acceptance, and the time to achieve these outcomes may be beyond a community's patience and attention. Rather than developing a device from scratch or validating a new commercial product, a workflow is presented whereby existing technologies, especially those that are out of patent, are replicated through open online collaboration between communities affected by environmental pollution, volunteers, academic institutions, and existing open hardware and open source software projects. Technology case studies will be presented, focusing primarily on a passive PM monitor based on the UNC Passive Monitor. Stages of the project will be detailed moving from identifying community needs, reviewing existing technology, partnership development, technology replication, IP review and licensing, data quality assurance (in process), and field evaluation with community partners (in process), with special attention to partnership development and technology review. We have leveraged open hardware and open source software to lower the cost and access barriers of existing technologies for PM10-2.5 and other atmospheric measures that have already been validated through peer review. Existing validation of and regulatory familiarity with a technology enables a rapid pathway towards collecting data, shortening the time it takes for communities to leverage data in environmental management decisions. Online collaboration requires rigorous documentation that aids in spreading research methods and promoting deep engagement by interested community researchers outside academia. At the same time, careful choice of technology and the use of small-scale fabrication through laser cutting, 3D printing, and open, shared repositories of plans and software enables educational engagement that broadens a project's reach.

Continence technologies whitepaper: Informing new engineering science research.

PubMed

Culmer, Pete; Alazmani, Ali; Bryant, Mike; Mancuso, Elena; King, Sarah; Mapunde, Vee; Jeays-Ward, Katherine; Heron, Nicola; Pearson, Russell; Vollebregt, Paul F; Corner, Lynne; Day, Richard

2018-06-01

Advances in healthcare technology for continence have historically been limited compared to other areas of medicine, reflecting the complexities of the condition and social stigma which act as a barrier to participation. This whitepaper has been developed to inspire and direct the engineering science community towards research opportunities that exist for continence technologies that address unmet needs in diagnosis, treatment and long-term management. Our aim is to pinpoint key challenges and highlight related research opportunities for novel technological advances. To do so, we draw on experience and expertise from academics, clinicians, patients and patient groups linked to continence healthcare. This is presented in four areas of consideration: the clinical pathway, patient perspective, research challenges and effective innovation. In each we introduce seminal research, background information and demonstrative case-studies, before discussing their relevance to engineering science researchers who are interested in approaching this overlooked but vital area of healthcare.

A pathway of nanocrystallite fabrication by photo-assisted growth in pure water

NASA Astrophysics Data System (ADS)

Jeem, Melbert; Bin Julaihi, Muhammad Rafiq Mirza; Ishioka, Junya; Yatsu, Shigeo; Okamoto, Kazumasa; Shibayama, Tamaki; Iwasaki, Tomio; Kato, Takahiko; Watanabe, Seiichi

2015-06-01

We report a new production pathway for a variety of metal oxide nanocrystallites via submerged illumination in water: submerged photosynthesis of crystallites (SPSC). Similar to the growth of green plants by photosynthesis, nanocrystallites shaped as nanoflowers and nanorods are hereby shown to grow at the protruded surfaces via illumination in pure, neutral water. The process is photocatalytic, accompanied with hydroxyl radical generation via water splitting; hydrogen gas is generated in some cases, which indicates potential for application in green technologies. Together with the aid of ab initio calculation, it turns out that the nanobumped surface, as well as aqueous ambience and illumination are essential for the SPSC method. Therefore, SPSC is a surfactant-free, low-temperature technique for metal oxide nanocrystallites fabrication.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vimmerstedt, Laura; Brown, Austin; Newes, Emily

The transportation sector is changing, influenced by concurrent, ongoing, dynamic trends that could dramatically affect the future energy landscape, including effects on the potential for greenhouse gas emissions reductions. Battery cost reductions and improved performance coupled with a growing number of electric vehicle model offerings are enabling greater battery electric vehicle market penetration, and advances in fuel cell technology and decreases in hydrogen production costs are leading to initial fuel cell vehicle offerings. Radically more efficient vehicles based on both conventional and new drivetrain technologies reduce greenhouse gas emissions per vehicle-mile. Net impacts also depend on the energy sources usedmore » for propulsion, and these are changing with increased use of renewable energy and unconventional fossil fuel resources. Connected and automated vehicles are emerging for personal and freight transportation systems and could increase use of low- or non-emitting technologies and systems; however, the net effects of automation on greenhouse gas emissions are uncertain. The longstanding trend of an annual increase in transportation demand has reversed for personal vehicle miles traveled in recent years, demonstrating the possibility of lower-travel future scenarios. Finally, advanced biofuel pathways have continued to develop, highlighting low-carbon and in some cases carbon-negative fuel pathways. We discuss the potential for transformative reductions in petroleum use and greenhouse gas emissions through these emerging transportation-sector technologies and trends and present a Clean Transportation Sector Initiative scenario for such reductions, which are summarized in Table ES-1.« less

Advanced Sensors and Controls for Building Applications: Market Assessment and Potential R&D Pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brambley, Michael R.; Haves, Philip; McDonald, Sean C.

2005-04-13

Significant energy savings can be achieved in commercial building operation, along with increased comfort and control for occupants, through the implementation of advanced technologies. This document provides a market assessment of existing building sensors and controls and presents a range of technology pathways (R&D options) for pursuing advanced sensors and building control strategies. This paper is actually a synthesis of five other white papers: the first describes the market assessment including estimates of market potential and energy savings for sensors and control strategies currently on the market as well as a discussion of market barriers to these technologies. The othermore » four cover technology pathways: (1) current applications and strategies for new applications, (2) sensors and controls, (3) networking, security, and protocols and standards, and (4) automated diagnostics, performance monitoring, commissioning, optimal control and tools. Each technology pathway chapter gives an overview of the technology or application. This is followed by a discussion of needs and the current status of the technology. Finally, a series of research topics is proposed.« less

COMPUGIRLS: Stepping Stone to Future Computer-Based Technology Pathways

ERIC Educational Resources Information Center

Lee, Jieun; Husman, Jenefer; Scott, Kimberly A.; Eggum-Wilkens, Natalie D.

2015-01-01

The COMPUGIRLS: Culturally relevant technology program for adolescent girls was developed to promote underrepresented girls' future possible selves and career pathways in computer-related technology fields. We hypothesized that the COMPUGIRLS would promote academic possible selves and self-regulation to achieve these possible selves. We compared…

Deliberative public participation and hexachlorobenzene stockpiles.

PubMed

Carson, Lyn

2009-04-01

This paper is concerned with the quality of citizen involvement in relation to the governance of industrial risks. Specifically, it explores the hexachlorobenzene (HCB) case relative to best practice public participation, which is consistent with deliberative democratic theory. The case could be judged a public participation failure given that the community committee in combination with the corporate sponsor was unable to agree on a mutually acceptable technological pathway. This stalemate might have been attributable in part to the time spent on the task of review. A diligent participation working party could have created a much more effective public participation plan, grounded in the core values of professional public participation practice.

Global climate change: the quantifiable sustainability challenge.

PubMed

Princiotta, Frank T; Loughlin, Daniel H

2014-09-01

Population growth and the pressures spawned by increasing demands for energy and resource-intensive goods, foods, and services are driving unsustainable growth in greenhouse gas (GHG) emissions. Recent GHG emission trends are consistent with worst-case scenarios of the previous decade. Dramatic and near-term emission reductions likely will be needed to ameliorate the potential deleterious impacts of climate change. To achieve such reductions, fundamental changes are required in the way that energy is generated and used. New technologies must be developed and deployed at a rapid rate. Advances in carbon capture and storage, renewable, nuclear and transportation technologies are particularly important; however, global research and development efforts related to these technologies currently appear to fall short relative to needs. Even with a proactive and international mitigation effort, humanity will need to adapt to climate change, but the adaptation needs and damages will be far greater if mitigation activities are not pursued in earnest. In this review, research is highlighted that indicates increasing global and regional temperatures and ties climate changes to increasing GHG emissions. GHG mitigation targets necessary for limiting future global temperature increases are discussed, including how factors such as population growth and the growing energy intensity of the developing world will make these reduction targets more challenging. Potential technological pathways for meeting emission reduction targets are examined, barriers are discussed, and global and US. modeling results are presented that suggest that the necessary pathways will require radically transformed electric and mobile sectors. While geoengineering options have been proposed to allow more time for serious emission reductions, these measures are at the conceptual stage with many unanswered cost, environmental, and political issues. Implications: This paper lays out the case that mitigating the potential for catastrophic climate change will be a monumental challenge, requiring the global community to transform its energy system in an aggressive, coordinated, and timely manner. If this challenge is to be met, new technologies will have to be developed and deployed at a rapid rate. Advances in carbon capture and storage, renewable, nuclear, and transportation technologies are particularly important. Even with an aggressive international mitigation effort, humanity will still need to adapt to significant climate change.

Modeling Protein Expression and Protein Signaling Pathways

PubMed Central

Telesca, Donatello; Müller, Peter; Kornblau, Steven M.; Suchard, Marc A.; Ji, Yuan

2015-01-01

High-throughput functional proteomic technologies provide a way to quantify the expression of proteins of interest. Statistical inference centers on identifying the activation state of proteins and their patterns of molecular interaction formalized as dependence structure. Inference on dependence structure is particularly important when proteins are selected because they are part of a common molecular pathway. In that case, inference on dependence structure reveals properties of the underlying pathway. We propose a probability model that represents molecular interactions at the level of hidden binary latent variables that can be interpreted as indicators for active versus inactive states of the proteins. The proposed approach exploits available expert knowledge about the target pathway to define an informative prior on the hidden conditional dependence structure. An important feature of this prior is that it provides an instrument to explicitly anchor the model space to a set of interactions of interest, favoring a local search approach to model determination. We apply our model to reverse-phase protein array data from a study on acute myeloid leukemia. Our inference identifies relevant subpathways in relation to the unfolding of the biological process under study. PMID:26246646

Pathways to Success: Using Technologies To Reach Distant Learners.

ERIC Educational Resources Information Center

Annenberg/CPB Project, Washington, DC.

This report contains information on institutions that submitted proposals for integrating technology in education to the Annenberg/CPB (Corporation for Public Broadcasting) Project's New Pathways to a Degree program. It is noted that, although the 243 proposals received contained a number of innovative ideas about how to use technologies to…

Developmental Pathways and Technology: The Foundations of Enhanced Intellectual Excellence.

ERIC Educational Resources Information Center

Williamson, Edward A.; Slye, Gail L.

The combination of technology applications and an understanding of developmental pathways theory enhances intellectual growth for preservice teachers. Utilizing the theories developed by Dr. James Comer and integrating them with state of the art technological applications, this paper describes one model of preservice education that has been…

Quantifying nitrous oxide production pathways in wastewater treatment systems using isotope technology - A critical review.

PubMed

Duan, Haoran; Ye, Liu; Erler, Dirk; Ni, Bing-Jie; Yuan, Zhiguo

2017-10-01

Nitrous oxide (N 2 O) is an important greenhouse gas and an ozone-depleting substance which can be emitted from wastewater treatment systems (WWTS) causing significant environmental impacts. Understanding the N 2 O production pathways and their contribution to total emissions is the key to effective mitigation. Isotope technology is a promising method that has been applied to WWTS for quantifying the N 2 O production pathways. Within the scope of WWTS, this article reviews the current status of different isotope approaches, including both natural abundance and labelled isotope approaches, to N 2 O production pathways quantification. It identifies the limitations and potential problems with these approaches, as well as improvement opportunities. We conclude that, while the capabilities of isotope technology have been largely recognized, the quantification of N 2 O production pathways with isotope technology in WWTS require further improvement, particularly in relation to its accuracy and reliability. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mapping patient pathways and estimating resource use for point of care versus standard testing and treatment of chlamydia and gonorrhoea in genitourinary medicine clinics in the UK.

PubMed

Adams, Elisabeth J; Ehrlich, Alice; Turner, Katherine M E; Shah, Kunj; Macleod, John; Goldenberg, Simon; Meray, Robin K; Pearce, Vikki; Horner, Patrick

2014-07-23

We aimed to explore patient pathways using a chlamydia/gonorrhoea point-of-care (POC) nucleic acid amplification test (NAAT), and estimate and compare the costs of the proposed POC pathways with the current pathways using standard laboratory-based NAAT testing. Workshops were conducted with healthcare professionals at four sexual health clinics representing diverse models of care in the UK. They mapped out current pathways that used chlamydia/gonorrhoea tests, and constructed new pathways using a POC NAAT. Healthcare professionals' time was assessed in each pathway. The proposed POC pathways were then priced using a model built in Microsoft Excel, and compared to previously published costs for pathways using standard NAAT-based testing in an off-site laboratory. Pathways using a POC NAAT for asymptomatic and symptomatic patients and chlamydia/gonorrhoea-only tests were shorter and less expensive than most of the current pathways. Notably, we estimate that POC testing as part of a sexual health screen for symptomatic patients, or as stand-alone chlamydia/gonorrhoea testing, could reduce costs per patient by as much as £16 or £6, respectively. In both cases, healthcare professionals' time would be reduced by approximately 10 min per patient. POC testing for chlamydia/gonorrhoea in a clinical setting may reduce costs and clinician time, and may lead to more appropriate and quicker care for patients. Further study is warranted on how to best implement POC testing in clinics, and on the broader clinical and cost implications of this technology. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Microfluidic molecular assay platform for the detection of miRNAs, mRNAs, proteins, and posttranslational modifications at single-cell resolution.

PubMed

Wu, Meiye; Singh, Anup K

2014-12-01

Cell signaling is a dynamic and complex process. A typical signaling pathway may begin with activation of cell surface receptors, leading to activation of a kinase cascade that culminates in induction of messenger RNA (mRNA) and noncoding microRNA (miRNA) production in the nucleus, followed by modulation of mRNA expression by miRNAs in the cytosol, and end with production of proteins in response to the signaling pathway. Signaling pathways involve proteins, miRNA, and mRNAs, along with various forms of transient posttranslational modifications, and detecting each type of signaling molecule requires categorically different sample preparation methods such as Western blotting for proteins, PCR for nucleic acids, and flow cytometry for posttranslational modifications. Since we know that cells in populations behave heterogeneously,(1) especially in the cases of stem cells, cancer, and hematopoiesis, there is need for a new technology that provides capability to detect and quantify multiple categories of signaling molecules in intact single cells to provide a comprehensive view of the cell's physiological state. In this Technology Brief, we describe our automated microfluidic platform with a portfolio of customized molecular assays that can detect nucleic acids, proteins, and posttranslational modifications in single intact cells with >95% reduction in reagent requirement in under 8 h. © 2014 Society for Laboratory Automation and Screening.

Objective monitoring of mTOR inhibitor therapy by three-dimensional facial analysis.

PubMed

Baynam, Gareth S; Walters, Mark; Dawkins, Hugh; Bellgard, Matthew; Halbert, Anne R; Claes, Peter

2013-08-01

With advances in therapeutics for rare, genetic and syndromic diseases, there is an increasing need for objective assessments of phenotypic endpoints. These assessments will preferentially be high precision, non-invasive, non-irradiating, and relatively inexpensive and portable. We report a case of a child with an extensive lymphatic vascular malformation of the head and neck, treated with an mammalian target of Rapamycin (mTOR) inhibitor that was assessed using 3D facial analysis. This case illustrates that this technology is prospectively a cost-effective modality for treatment monitoring, and it supports that it may also be used for novel explorations of disease biology for conditions associated with disturbances in the mTOR, and interrelated, pathways.

Estimating environmental co-benefits of U.S. low-carbon pathways using an integrated assessment model with state-level resolution.

PubMed

Ou, Yang; Shi, Wenjing; Smith, Steven J; Ledna, Catherine M; West, J Jason; Nolte, Christopher G; Loughlin, Daniel H

2018-04-15

There are many technological pathways that can lead to reduced carbon dioxide emissions. However, these pathways can have substantially different impacts on other environmental endpoints, such as air quality and energy-related water demand. This study uses an integrated assessment model with state-level resolution of the energy system to compare environmental impacts of alternative low-carbon pathways for the United States. One set of pathways emphasizes nuclear energy and carbon capture and storage, while another set emphasizes renewable energy, including wind, solar, geothermal power, and bioenergy. These are compared with pathways in which all technologies are available. Air pollutant emissions, mortality costs attributable to particulate matter smaller than 2.5 μm in diameter, and energy-related water demands are evaluated for 50% and 80% carbon dioxide reduction targets in 2050. The renewable low-carbon pathways require less water withdrawal and consumption than the nuclear and carbon capture pathways. However, the renewable low-carbon pathways modeled in this study produce higher particulate matter-related mortality costs due to greater use of biomass in residential heating. Environmental co-benefits differ among states because of factors such as existing technology stock, resource availability, and environmental and energy policies.

The notch pathway is activated in neoplastic progression in esophageal squamous cell carcinoma.

PubMed

Lubin, Daniel J; Mick, Rosemarie; Shroff, Stuti G; Stashek, Kristen; Furth, Emma E

2018-02-01

The Notch signaling pathway is integral to normal human development and homeostasis and has a deterministic function on cell differentiation. Recent studies suggest aberrant Notch signaling may contribute to neoplastic progression by an increase in stem cell survival, chemoresistance, and the promotion of epithelial-to-mesenchymal transition. The goals of our study were to determine, utilizing quantitative technologies, the expression of activated Notch 1 in esophageal squamous cell carcinoma (SCC) and to determine the relationship between Notch 1 expression and various clinicopathologic parameters. Immunohistochemical staining for Notch intracellular domain (NICD) was performed on 60 consecutive cases of esophageal squamous cell carcinoma, 42 cases of benign esophageal squamous epithelium, and 13 cases of eosinophilic esophagitis diagnosed in our department from 2007 through 2015, and exact nuclear staining and nuclear characteristics were graded using the Vectra imaging system. Clinicopathologic data (gender, age at diagnosis, smoking status, tumor grade, tumor stage, tumor location, and survival) were collected for each SCC case and these were correlated with NICD staining. Cases of esophageal SCC demonstrated significantly higher NICD staining compared to cases of benign and reactive esophageal epithelium (P=.003 and .005, respectively). Among cases of esophageal SCC, nuclear NICD staining was significantly correlated with both tumor grade and stage. Following classification and regression tree analysis, esophageal SCC patients with increased NICD expression were found to be more likely to die from their disease than those with lower levels of expression. Taken together, the findings suggest that increased Notch 1 may contribute to the development and aggressiveness of esophageal SCC. Copyright © 2017 Elsevier Inc. All rights reserved.

The Geek Perspective: Answering the Call for Advanced Technology in Research Inquiry Related to Pediatric Brain Injury and Motor Disability.

PubMed

Wininger, Michael; Pidcoe, Peter

2017-10-01

The Academy of Pediatric Physical Therapy Research Summit IV issued a Call to Action for community-wide intensification of a research enterprise in inquiries related to pediatric brain injury and motor disability by way of technological integration. But the barriers can seem high, and the pathways to integrative clinical research can seem poorly marked. Here, we answer the Call by providing framework to 3 objectives: (1) instrumentation, (2) biometrics and study design, and (3) data analytics. We identify emergent cases where this Call has been answered and advocate for others to echo the Call both in highly visible physical therapy venues and in forums where the audience is diverse.

Current and Future United States Light-Duty Vehicle Pathways: Cradle-to-Grave Lifecycle Greenhouse Gas Emissions and Economic Assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elgowainy, Amgad; Han, Jeongwoo; Ward, Jacob

This article presents a cradle-to-grave (C2G) assessment of greenhouse gas (GHG) emissions and costs for current (2015) and future (2025-2030) light-duty vehicles. The analysis addressed both fuel cycle and vehicle manufacturing cycle for the following vehicle types: gasoline and diesel internal combustion engine vehicles (ICEVs), flex fuel vehicles, compressed natural gas (CNG) vehicles, hybrid electric vehicles (HEVs), hydrogen fuel cell electric vehicles (FCEVs), battery electric vehicles (BEVs), and plug-in hybrid electric vehicles (PHEVs). Gasoline ICEVs using current technology have C2G emissions of ~450 gCO2e/mi (grams of carbon dioxide equivalents per mile), while C2G emissions from HEVs, PHEVs, H2 FCEVs, andmore » BEVs range from 300-350 gCO2e/mi. Future vehicle efficiency gains are expected to reduce emissions to ~350 gCO2/mi for ICEVs and ~250 gCO2e/mi for HEVs, PHEVs, FCEVs, and BEVs. Utilizing low-carbon fuel pathways yields GHG reductions more than double those achieved by vehicle efficiency gains alone. Levelized costs of driving (LCDs) are in the range $0.25-$1.00/mi depending on time frame and vehicle-fuel technology. In all cases, vehicle cost represents the major (60-90%) contribution to LCDs. Currently, HEV and PHEV petroleum-fueled vehicles provide the most attractive cost in terms of avoided carbon emissions, although they offer lower potential GHG reductions. The ranges of LCD and cost of avoided carbon are narrower for the future technology pathways, reflecting the expected economic competitiveness of these alternative vehicles and fuels.« less

Current and Future United States Light-Duty Vehicle Pathways: Cradle-to-Grave Lifecycle Greenhouse Gas Emissions and Economic Assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elgowainy, Amgad; Han, Jeongwoo; Ward, Jacob

This article presents a cradle-to-grave (C2G) assessment of greenhouse gas (GHG) emissions and costs for current (2015) and future (2025–2030) light-duty vehicles. The analysis addressed both fuel cycle and vehicle manufacturing cycle for the following vehicle types: gasoline and diesel internal combustion engine vehicles (ICEVs), flex fuel vehicles, compressed natural gas (CNG) vehicles, hybrid electric vehicles (HEVs), hydrogen fuel cell electric vehicles (FCEVs), battery electric vehicles (BEVs), and plug-in hybrid electric vehicles (PHEVs). Gasoline ICEVs using current technology have C2G emissions of ~450 gCO2e/mi (grams of carbon dioxide equivalents per mile), while C2G emissions from HEVs, PHEVs, H2 FCEVs, andmore » BEVs range from 300–350 gCO2e/mi. Future vehicle efficiency gains are expected to reduce emissions to ~350 gCO2/mi for ICEVs and ~250 gCO2e/mi for HEVs, PHEVs, FCEVs and BEVs. Utilizing low-carbon fuel pathways yields GHG reductions more than double those achieved by vehicle efficiency gains alone. Levelized costs of driving (LCDs) are in the range $0.25–$1.00/mi depending on timeframe and vehicle-fuel technology. In all cases, vehicle cost represents the major (60–90%) contribution to LCDs. Currently, HEV and PHEV petroleum-fueled vehicles provide the most attractive cost in terms of avoided carbon emissions, although they offer lower potential GHG reductions The ranges of LCD and cost of avoided carbon are narrower for the future technology pathways, reflecting the expected economic competitiveness of these alternative vehicles and fuels.« less

Current and Future United States Light-Duty Vehicle Pathways: Cradle-to-Grave Lifecycle Greenhouse Gas Emissions and Economic Assessment.

PubMed

Elgowainy, Amgad; Han, Jeongwoo; Ward, Jacob; Joseck, Fred; Gohlke, David; Lindauer, Alicia; Ramsden, Todd; Biddy, Mary; Alexander, Mark; Barnhart, Steven; Sutherland, Ian; Verduzco, Laura; Wallington, Timothy J

2018-02-20

This article presents a cradle-to-grave (C2G) assessment of greenhouse gas (GHG) emissions and costs for current (2015) and future (2025-2030) light-duty vehicles. The analysis addressed both fuel cycle and vehicle manufacturing cycle for the following vehicle types: gasoline and diesel internal combustion engine vehicles (ICEVs), flex fuel vehicles, compressed natural gas (CNG) vehicles, hybrid electric vehicles (HEVs), hydrogen fuel cell electric vehicles (FCEVs), battery electric vehicles (BEVs), and plug-in hybrid electric vehicles (PHEVs). Gasoline ICEVs using current technology have C2G emissions of ∼450 gCO 2 e/mi (grams of carbon dioxide equivalents per mile), while C2G emissions from HEVs, PHEVs, H 2 FCEVs, and BEVs range from 300-350 gCO 2 e/mi. Future vehicle efficiency gains are expected to reduce emissions to ∼350 gCO 2 /mi for ICEVs and ∼250 gCO 2e /mi for HEVs, PHEVs, FCEVs, and BEVs. Utilizing low-carbon fuel pathways yields GHG reductions more than double those achieved by vehicle efficiency gains alone. Levelized costs of driving (LCDs) are in the range $0.25-$1.00/mi depending on time frame and vehicle-fuel technology. In all cases, vehicle cost represents the major (60-90%) contribution to LCDs. Currently, HEV and PHEV petroleum-fueled vehicles provide the most attractive cost in terms of avoided carbon emissions, although they offer lower potential GHG reductions. The ranges of LCD and cost of avoided carbon are narrower for the future technology pathways, reflecting the expected economic competitiveness of these alternative vehicles and fuels.

Industrial bioconversion of renewable resources as an alternative to conventional chemistry.

PubMed

Willke, Th; Vorlop, K-D

2004-12-01

There are numerous possibilities for replacing chemical techniques with biotechnological methods based on renewable resources. The potential of biotechnology (products, technologies, metabolic pathways) is for the most part well known. Often the costs are still the problem. Biotechnological advances have the best chances for replacing some fine chemicals. While the raw material costs are less of a consideration here, the environmental benefit is huge, as chemical-technical processes often produce a wide range of undesirable/harmful by-products or waste. In the case of bulk chemicals (<1 US dollar/kg) the product price is affected mainly by raw material costs. As long as fossil raw materials are still relatively inexpensive, alternatives based on renewable resources cannot establish themselves. Residues and waste, which are available even at no cost in some cases, are an exception. The introduction of new technologies for the efficient use of such raw materials is currently being promoted. The utilisation of residual wood, plant parts, waste fat, and crude glycerol, for example, provides great potential. For industrial chemicals (2-4 US dollars/kg), process and recovery costs play a greater role. Here, innovative production technologies and product recovery techniques (e.g. on-line product separation) can increase competitiveness.

Glioblastoma of the optic pathways: An Atypical case

PubMed Central

Brar, Rahat; Prasad, Abhishek; Brar, Manpreet

2009-01-01

We present a case of glioblastoma multiforme of the optic pathways in a 68 year old lady. Glioblastomas of the optic pathways are rare tumors; the predominant non enhancing component and the vast extent of involvement makes this a unique case. This case report further increases the database of knowledge available on the MRI characteristics of malignant optic glioma of adulthood. PMID:22470685

Glioblastoma of the optic pathways: An Atypical case.

PubMed

Brar, Rahat; Prasad, Abhishek; Brar, Manpreet

2009-01-01

We present a case of glioblastoma multiforme of the optic pathways in a 68 year old lady. Glioblastomas of the optic pathways are rare tumors; the predominant non enhancing component and the vast extent of involvement makes this a unique case. This case report further increases the database of knowledge available on the MRI characteristics of malignant optic glioma of adulthood.

Pathway to Deployment of Gene Drive Mosquitoes as a Potential Biocontrol Tool for Elimination of Malaria in Sub-Saharan Africa: Recommendations of a Scientific Working Group†.

PubMed

James, Stephanie; Collins, Frank H; Welkhoff, Philip A; Emerson, Claudia; Godfray, H Charles J; Gottlieb, Michael; Greenwood, Brian; Lindsay, Steve W; Mbogo, Charles M; Okumu, Fredros O; Quemada, Hector; Savadogo, Moussa; Singh, Jerome A; Tountas, Karen H; Touré, Yeya T

2018-06-01

Gene drive technology offers the promise for a high-impact, cost-effective, and durable method to control malaria transmission that would make a significant contribution to elimination. Gene drive systems, such as those based on clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein, have the potential to spread beneficial traits through interbreeding populations of malaria mosquitoes. However, the characteristics of this technology have raised concerns that necessitate careful consideration of the product development pathway. A multidisciplinary working group considered the implications of low-threshold gene drive systems on the development pathway described in the World Health Organization Guidance Framework for testing genetically modified (GM) mosquitoes , focusing on reduction of malaria transmission by Anopheles gambiae s.l. mosquitoes in Africa as a case study. The group developed recommendations for the safe and ethical testing of gene drive mosquitoes, drawing on prior experience with other vector control tools, GM organisms, and biocontrol agents. These recommendations are organized according to a testing plan that seeks to maximize safety by incrementally increasing the degree of human and environmental exposure to the investigational product. As with biocontrol agents, emphasis is placed on safety evaluation at the end of physically confined laboratory testing as a major decision point for whether to enter field testing. Progression through the testing pathway is based on fulfillment of safety and efficacy criteria, and is subject to regulatory and ethical approvals, as well as social acceptance. The working group identified several resources that were considered important to support responsible field testing of gene drive mosquitoes.

Pathway to Deployment of Gene Drive Mosquitoes as a Potential Biocontrol Tool for Elimination of Malaria in Sub-Saharan Africa: Recommendations of a Scientific Working Group†

PubMed Central

James, Stephanie; Collins, Frank H.; Welkhoff, Philip A.; Emerson, Claudia; Godfray, H. Charles J.; Gottlieb, Michael; Greenwood, Brian; Lindsay, Steve W.; Mbogo, Charles M.; Okumu, Fredros O.; Quemada, Hector; Savadogo, Moussa; Singh, Jerome A.; Tountas, Karen H.; Touré, Yeya T.

2018-01-01

Abstract. Gene drive technology offers the promise for a high-impact, cost-effective, and durable method to control malaria transmission that would make a significant contribution to elimination. Gene drive systems, such as those based on clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein, have the potential to spread beneficial traits through interbreeding populations of malaria mosquitoes. However, the characteristics of this technology have raised concerns that necessitate careful consideration of the product development pathway. A multidisciplinary working group considered the implications of low-threshold gene drive systems on the development pathway described in the World Health Organization Guidance Framework for testing genetically modified (GM) mosquitoes, focusing on reduction of malaria transmission by Anopheles gambiae s.l. mosquitoes in Africa as a case study. The group developed recommendations for the safe and ethical testing of gene drive mosquitoes, drawing on prior experience with other vector control tools, GM organisms, and biocontrol agents. These recommendations are organized according to a testing plan that seeks to maximize safety by incrementally increasing the degree of human and environmental exposure to the investigational product. As with biocontrol agents, emphasis is placed on safety evaluation at the end of physically confined laboratory testing as a major decision point for whether to enter field testing. Progression through the testing pathway is based on fulfillment of safety and efficacy criteria, and is subject to regulatory and ethical approvals, as well as social acceptance. The working group identified several resources that were considered important to support responsible field testing of gene drive mosquitoes. PMID:29882508

Electrification pathways for Kenya-linking spatial electrification analysis and medium to long term energy planning

NASA Astrophysics Data System (ADS)

Moksnes, Nandi; Korkovelos, Alexandros; Mentis, Dimitrios; Howells, Mark

2017-09-01

In September 2015 UN announced 17 Sustainable Development goals (SDG) from which goal number 7 envisions universal access to modern energy services for all by 2030. In Kenya only about 46% of the population currently has access to electricity. This paper analyses hypothetical scenarios, and selected implications, investigating pathways that would allow the country to reach its electrification targets by 2030. Two modelling tools were used for the purposes of this study, namely OnSSET and OSeMOSYS. The tools were soft-linked in order to capture both the spatial and temporal dynamics of their nature. Two electricity demand scenarios were developed representing low and high end user consumption goals respectively. Indicatively, results show that geothermal, coal, hydro and natural gas would consist the optimal energy mix for the centralized national grid. However, in the case of the low demand scenario a high penetration of stand-alone systems is evident in the country, reaching out to approximately 47% of the electrified population. Increasing end user consumption leads to a shift in the optimal technology mix, with higher penetration of mini-grid technologies and grid extension.

Impact of Next Generation District Heating Systems on Distribution Network Heat Losses: A Case Study Approach

NASA Astrophysics Data System (ADS)

Li, Yu; Rezgui, Yacine

2018-01-01

District heating (DH) is a promising energy pathway to alleviate environmental negative impacts induced by fossil fuels. Improving the performance of DH systems is one of the major challenges facing its wide adoption. This paper discusses the heat losses of the next generation DH based on the constructed Simulink model. Results show that lower distribution temperature and advanced insulation technology greatly reduce network heat losses. Also, the network heat loss can be further minimized by a reduction of heat demand in buildings.

Lifecycle analysis of renewable natural gas and hydrocarbon fuels from wastewater treatment plants’ sludge

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Uisung; Han, Jeongwoo; Urgun Demirtas, Meltem

Wastewater treatment plants (WWTPs) produce sludge as a byproduct when they treat wastewater. In the United States, over 8 million dry tons of sludge are produced annually just from publicly owned WWTPs. Sludge is commonly treated in anaerobic digesters, which generate biogas; the biogas is then largely flared to reduce emissions of methane, a potent greenhouse gas. Because sludge is quite homogeneous and has a high energy content, it is a good potential feedstock for other conversion processes that make biofuels, bioproducts, and power. For example, biogas from anaerobic digesters can be used to generate renewable natural gas (RNG), whichmore » can be further processed to produce compressed natural gas (CNG) and liquefied natural gas (LNG). Sludge can be directly converted into hydrocarbon liquid fuels via thermochemical processes such as hydrothermal liquefaction (HTL). Currently, the environmental impacts of converting sludge into energy are largely unknown, and only a few studies have focused on the environmental impacts of RNG produced from existing anaerobic digesters. As biofuels from sludge generate high interest, however, existing anaerobic digesters could be upgraded to technology with more economic potential and more environmental benefits. The environmental impacts of using a different anaerobic digestion (AD) technology to convert sludge into energy have yet to be analyzed. In addition, no studies are available about the direct conversion of sludge into liquid fuels. In order to estimate the energy consumption and greenhouse gas (GHG) emissions impacts of these alternative pathways (sludge-to-RNG and sludge-to-liquid), this study performed a lifecycle analysis (LCA) using the Greenhouse gases, Regulated Emissions, and Energy use in Transportation (GREET®) model. The energy uses and GHG emissions associated with the RNG and hydrocarbon liquid are analyzed relative to the current typical sludge management case, which consists of a single-stage mesophilic digester with biogas flaring. Along with the alternative HTL process, four types of AD technologies with fuel production—single-stage mesophilic, mesophilic 2-stage, single-stage mesophilic with thermohydrolysis treatment, and mesophilicmesophilic acid/gas phase—are studied. Results show that the sludge-to-CNG pathway via AD and the sludge-to-liquid pathway via HTL reduce GHG emissions consumptions significantly. When we compare the GHG emissions of the alternative fuel production pathways to that of the counterfactual case in terms of the amount of sludge treated, reductions in GHG emissions are 39%–80% and 87% for alternative AD and HTL, respectively. Compared to petroleum gasoline and diesel GHG emission results in terms of MJ, the renewable CNG production pathway via AD and the renewable diesel production pathway via HTL reduce GHG emissions by 193% and 46%, respectively. These large reductions are mainly due to GHG credits from avoiding GHGs under the counterfactual scenario, and/or fertilizer displacement credits. Similarly, reductions in fossil fuel use for sludge-based fuels are huge. However, well-defined counterfactual scenarios are needed because the results of the study depend on the counterfactual scenario, which might vary over time.« less

In Situ Treatment of Chlorinated Ethene-Contaminated Groundwater Using horizontal Flow Treatment Wells.

DTIC Science & Technology

2000-03-01

groundwater, Environmental Science and Technology, 30 (12): 536A-539A, 1996. Arnold, W. A. and A. L. Roberts, Pathways of chlorinated ethylene and...chlorinated acetylene reaction with Zn(0), Environmental Science and Technology, 32 (19): 3017-3025, 1998. Arnold, W. A. and A. L. Roberts, Pathways and...kinetics of chlorinated ethylene and chlorinated acetylene reaction with Fe(0) particles, Environmental Science and Technology, in press, 2000

Efficient key pathway mining: combining networks and OMICS data.

PubMed

Alcaraz, Nicolas; Friedrich, Tobias; Kötzing, Timo; Krohmer, Anton; Müller, Joachim; Pauling, Josch; Baumbach, Jan

2012-07-01

Systems biology has emerged over the last decade. Driven by the advances in sophisticated measurement technology the research community generated huge molecular biology data sets. These comprise rather static data on the interplay of biological entities, for instance protein-protein interaction network data, as well as quite dynamic data collected for studying the behavior of individual cells or tissues in accordance with changing environmental conditions, such as DNA microarrays or RNA sequencing. Here we bring the two different data types together in order to gain higher level knowledge. We introduce a significantly improved version of the KeyPathwayMiner software framework. Given a biological network modelled as a graph and a set of expression studies, KeyPathwayMiner efficiently finds and visualizes connected sub-networks where most components are expressed in most cases. It finds all maximal connected sub-networks where all nodes but k exceptions are expressed in all experimental studies but at most l exceptions. We demonstrate the power of the new approach by comparing it to similar approaches with gene expression data previously used to study Huntington's disease. In addition, we demonstrate KeyPathwayMiner's flexibility and applicability to non-array data by analyzing genome-scale DNA methylation profiles from colorectal tumor cancer patients. KeyPathwayMiner release 2 is available as a Cytoscape plugin and online at http://keypathwayminer.mpi-inf.mpg.de.

Estimating environmental co-benefits of U.S. low-carbon pathways using an integrated assessment model with state-level resolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ou, Yang; Shi, Wenjing; Smith, Steven J.

There are many technological pathways that can lead to reduced carbon dioxide (CO 2) emissions. However, these pathways can have substantially different impacts on other environmental endpoints, such as air quality and energy-related water demand. This study uses an integrated assessment model with state-level resolution of the U.S. energy system to compare environmental impacts of alternative low-carbon pathways. One set of pathways emphasizes nuclear energy and carbon capture and storage (NUC/CCS), while another set emphasizes renewable energy (RE). These are compared with pathways in which all technologies are available. Air pollutant emissions, mortality costs attributable to particulate matter less thanmore » 2.5 microns in diameter (PM2.5), and energy-related water demands are evaluated for 50% and 80% CO 2 reduction targets in the U.S. in 2050. The RE low-carbon pathways require less water withdrawal and consumption than the NUC/CCS pathways because of the large cooling demands of nuclear power and CCS. However, the NUC/CCS low-carbon pathways produce greater health benefits, mainly because the NUC/CCS assumptions result in less primary PM2.5 emissions from residential wood combustion. Environmental co-benefits differ among states because of factors such as existing technology stock, resource availability, and environmental and energy policies. An important finding is that biomass in the building sector can offset some of the health co-benefits of the low-carbon pathways even though it plays only a minor role in reducing CO 2 emissions.« less

Meta-analysis of pathway enrichment: combining independent and dependent omics data sets.

PubMed

Kaever, Alexander; Landesfeind, Manuel; Feussner, Kirstin; Morgenstern, Burkhard; Feussner, Ivo; Meinicke, Peter

2014-01-01

A major challenge in current systems biology is the combination and integrative analysis of large data sets obtained from different high-throughput omics platforms, such as mass spectrometry based Metabolomics and Proteomics or DNA microarray or RNA-seq-based Transcriptomics. Especially in the case of non-targeted Metabolomics experiments, where it is often impossible to unambiguously map ion features from mass spectrometry analysis to metabolites, the integration of more reliable omics technologies is highly desirable. A popular method for the knowledge-based interpretation of single data sets is the (Gene) Set Enrichment Analysis. In order to combine the results from different analyses, we introduce a methodical framework for the meta-analysis of p-values obtained from Pathway Enrichment Analysis (Set Enrichment Analysis based on pathways) of multiple dependent or independent data sets from different omics platforms. For dependent data sets, e.g. obtained from the same biological samples, the framework utilizes a covariance estimation procedure based on the nonsignificant pathways in single data set enrichment analysis. The framework is evaluated and applied in the joint analysis of Metabolomics mass spectrometry and Transcriptomics DNA microarray data in the context of plant wounding. In extensive studies of simulated data set dependence, the introduced correlation could be fully reconstructed by means of the covariance estimation based on pathway enrichment. By restricting the range of p-values of pathways considered in the estimation, the overestimation of correlation, which is introduced by the significant pathways, could be reduced. When applying the proposed methods to the real data sets, the meta-analysis was shown not only to be a powerful tool to investigate the correlation between different data sets and summarize the results of multiple analyses but also to distinguish experiment-specific key pathways.

Socioeconomic constraints on the technological choices in rural sewage treatment.

PubMed

Gu, Baojing; Fan, Liangcong; Ying, Zechun; Xu, Qingshan; Luo, Weidong; Ge, Ying; Scott, Steffanie; Chang, Jie

2016-10-01

Technological innovation is one of the potential engines to mitigate environmental pollution. However, the implementation of new technologies sometimes fails owing to socioeconomic constraints from different stakeholders. Thus, it is essential to analyze constraints of environmental technologies in order to build a pathway for their implementation. In this study, taking three technologies on rural sewage treatment in Hangzhou, China as a case study, i.e., wastewater treatment plant (WTP), constructed wetland (CW), and biogas system, we analyzed how socioeconomic constraints affect the technological choices. Results showed that socioeconomic constraints play a key role through changing the relative opportunity cost of inputs from government as compared to that of residents to deliver the public good-sewage treatment-under different economic levels. Economic level determines the technological choice, and the preferred sewage treatment technologies change from biogas system to CW and further to WTP along with the increase of economic level. Mismatch of technological choice and economic level results in failures of rural sewage treatment, e.g., the CW only work well in moderately developed regions in Hangzhou. This finding expands the environmental Kuznets law by introducing the coproduction theory into analysis (i.e., inputs from both government and residents are essential for the delivery of public goods and services such as good environmental quality). A match between technology and socioeconomic conditions is essential to the environmental governance.

A Glimpse into a State Technical College System's POS Pathways

ERIC Educational Resources Information Center

Frazier, Stephanie D.; Swygert, N. Maria

2012-01-01

The South Carolina Technical College System (SCTCS) has embraced POS, providing students across the state with pathways into careers ranging from nuclear systems technology to health care to industrial technology. The SCTCS has strived, over the last 50 years, to foster a bridge between business and education. The colleges coordinate and…

Climate Change Impacts on Agriculture and Food Security in 2050 under a Range of Plausible Socioeconomic and Emissions Scenarios

NASA Astrophysics Data System (ADS)

Wiebe, K.; Lotze-Campen, H.; Bodirsky, B.; Kavallari, A.; Mason-d'Croz, D.; van der Mensbrugghe, D.; Robinson, S.; Sands, R.; Tabeau, A.; Willenbockel, D.; Islam, S.; van Meijl, H.; Mueller, C.; Robertson, R.

2014-12-01

Previous studies have combined climate, crop and economic models to examine the impact of climate change on agricultural production and food security, but results have varied widely due to differences in models, scenarios and data. Recent work has examined (and narrowed) these differences through systematic model intercomparison using a high-emissions pathway to highlight the differences. New work extends that analysis to cover a range of plausible socioeconomic scenarios and emission pathways. Results from three general circulation models are combined with one crop model and five global economic models to examine the global and regional impacts of climate change on yields, area, production, prices and trade for coarse grains, rice, wheat, oilseeds and sugar to 2050. Results show that yield impacts vary with changes in population, income and technology as well as emissions, but are reduced in all cases by endogenous changes in prices and other variables.

Hedgehog signaling pathway in neuroblastoma differentiation.

PubMed

Souzaki, Ryota; Tajiri, Tatsuro; Souzaki, Masae; Kinoshita, Yoshiaki; Tanaka, Sakura; Kohashi, Kenichi; Oda, Yoshinao; Katano, Mitsuo; Taguchi, Tomoaki

2010-12-01

The hedgehog (Hh) signaling pathway is activated in some adult cancers. On the other hand, the Hh signaling pathway plays an important role in the development of the neural crest in embryos. The aim of this study is to show the activation of Hh signaling pathway in neuroblastoma (NB), a pediatric malignancy arising from neural crest cells, and to reveal the meaning of the Hh signaling pathway in NB development. This study analyzed the expression of Sonic hedgehog (Shh), GLI1, and Patched 1 (Ptch1), transactivators of Hh signaling pathway, by immunohistochemistry in 82 NB and 10 ganglioneuroblastoma cases. All 92 cases were evaluated for the status of MYCN amplification. Of the 92 cases, 67 (73%) were positive for Shh, 62 cases (67%) were positive for GLI1, and 73 cases (79%) were positive for Ptch1. Only 2 (10%) of the 20 cases with MYCN amplification were positive for Shh and GLI1, and 4 cases (20%) were positive for Ptch1 (MYCN amplification vs no MYCN amplification, P ≦ .01). The percentage of GLI1-positive cells in the cases with INSS stage 1 without MYCN amplification was significantly higher than that with INSS stage 4. Of 72 cases without MYCN amplification, 60 were GLI1-positive. Twelve cases were GLI1-negative, and the prognosis of the GLI1-positive cases was significantly better than that of the GLI1-negative cases (P = .015). Most of NBs without MYCN amplification were positive for Shh, GLI1, and Ptch1. In the cases without MYCN amplification, the high expression of GLI1 was significantly associated with early clinical stage and a good prognosis of the patients. In contrast to adult cancers, the activation of the Hh signaling pathway in NB may be associated with the differentiation of the NB. Copyright © 2010 Elsevier Inc. All rights reserved.

Application of the critical pathway and integrated case teaching method to nursing orientation.

PubMed

Goodman, D

1997-01-01

Nursing staff development programs must be responsive to current changes in healthcare. New nursing staff must be prepared to manage continuous change and to function competently in clinical practice. The orientation pathway, based on a case management model, is used as a structure for the orientation phase of staff development. The integrated case is incorporated as a teaching strategy in orientation. The integrated case method is based on discussion and analysis of patient situations with emphasis on role modeling and integration of theory and skill. The orientation pathway and integrated case teaching method provide a useful framework for orientation of new staff. Educators, preceptors and orientees find the structure provided by the orientation pathway very useful. Orientation that is developed, implemented and evaluated based on a case management model with the use of an orientation pathway and incorporation of an integrated case teaching method provides a standardized structure for orientation of new staff. This approach is designed for the adult learner, promotes conceptual reasoning, and encourages the social and contextual basis for continued learning.

Life cycle water use for electricity generation: a review and harmonization of literature estimates

NASA Astrophysics Data System (ADS)

Meldrum, J.; Nettles-Anderson, S.; Heath, G.; Macknick, J.

2013-03-01

This article provides consolidated estimates of water withdrawal and water consumption for the full life cycle of selected electricity generating technologies, which includes component manufacturing, fuel acquisition, processing, and transport, and power plant operation and decommissioning. Estimates were gathered through a broad search of publicly available sources, screened for quality and relevance, and harmonized for methodological differences. Published estimates vary substantially, due in part to differences in production pathways, in defined boundaries, and in performance parameters. Despite limitations to available data, we find that: water used for cooling of thermoelectric power plants dominates the life cycle water use in most cases; the coal, natural gas, and nuclear fuel cycles require substantial water per megawatt-hour in most cases; and, a substantial proportion of life cycle water use per megawatt-hour is required for the manufacturing and construction of concentrating solar, geothermal, photovoltaic, and wind power facilities. On the basis of the best available evidence for the evaluated technologies, total life cycle water use appears lowest for electricity generated by photovoltaics and wind, and highest for thermoelectric generation technologies. This report provides the foundation for conducting water use impact assessments of the power sector while also identifying gaps in data that could guide future research.

Using process monitor wafers to understand directed self-assembly defects

NASA Astrophysics Data System (ADS)

Cao, Yi; Her, YoungJun; Delgadillo, Paulina R.; Vandenbroeck, Nadia; Gronheid, Roel; Chan, Boon Teik; Hashimoto, Yukio; Romo, Ainhoa; Somervell, Mark; Nafus, Kathleen; Nealey, Paul F.

2013-03-01

As directed self-assembly (DSA) has gained momentum over the past few years, questions about its application to high volume manufacturing have arisen. One of the major concerns is about the fundamental limits of defectivity that can be attained with the technology. If DSA applications demonstrate defectivity that rivals of traditional lithographic technologies, the pathway to the cost benefits of the technology creates a very compelling case for its large scale implementation. To address this critical question, our team at IMEC has established a process monitor flow to track the defectivity behaviors of an exemplary chemo-epitaxy application for printing line/space patterns. Through establishing this baseline, we have been able to understand both traditional lithographic defect sources in new materials as well as new classes of assembly defects associated with DSA technology. Moreover, we have explored new materials and processing to lower the level of the defectivity baseline. The robustness of the material sets and process is investigated as well. In this paper, we will report the understandings learned from the IMEC DSA process monitor flow.

Analysis of the acceptance of autonomous planetary science data collection by field of inquiry

NASA Astrophysics Data System (ADS)

Straub, Jeremy

2015-06-01

The acceptance of autonomous control technologies in planetary science has met significant resistance. Many within this scientific community question the efficacy of autonomous technologies for making decisions regarding what data to collect, how to process it and its processing. These technologies, however, can be used to significantly increase the scientific return on mission investment by removing limitations imposed by communications bandwidth constraints and communications and human decision making delays. A fully autonomous mission, in an ideal case, could be deployed, perform most of the substantive work itself (possibly relying on human assistance for dealing with any unexpected or unexplained occurrences) and return an answer to a scientific question along with data selected to allow scientists to validate software performance. This paper presents the results of a survey of planetary scientists which attempts to identify the root causes of the impediments to the use of this type of technology and identify pathways to its acceptance. Previous work considered planetary science as a single large community. This paper contrasts the differences in acceptance between component fields of planetary science.

Ethical Considerations in Tissue Engineering Research: Case Studies in Translation

PubMed Central

Baker, Hannah B.; McQuilling, John P.

2016-01-01

Tissue engineering research is a complex process that requires investigators to focus on the relationship between their research and anticipated gains in both knowledge and treatment improvements. The ethical considerations arising from tissue engineering research are similarly complex when addressing the translational progression from bench to bedside, and investigators in the field of tissue engineering act as moral agents at each step of their research along the translational pathway, from early benchwork and preclinical studies to clinical research. This review highlights the ethical considerations and challenges at each stage of research, by comparing issues surrounding two translational tissue engineering technologies: the bioartificial pancreas and a tissue engineered skeletal muscle construct. We present relevant ethical issues and questions to consider at each step along the translational pathway, from the basic science bench to preclinical research to first-in-human clinical trials. Topics at the bench level include maintaining data integrity, appropriate reporting and dissemination of results, and ensuring that studies are designed to yield results suitable for advancing research. Topics in preclinical research include the principle of “modest translational distance” and appropriate animal models. Topics in clinical research include key issues that arise in early-stage clinical trials, including selection of patient-subjects, disclosure of uncertainty, and defining success. The comparison of these two technologies and their ethical issues brings to light many challenges for translational tissue engineering research and provides guidance for investigators engaged in development of any tissue engineering technology. PMID:26282436

Ethical considerations in tissue engineering research: Case studies in translation.

PubMed

Baker, Hannah B; McQuilling, John P; King, Nancy M P

2016-04-15

Tissue engineering research is a complex process that requires investigators to focus on the relationship between their research and anticipated gains in both knowledge and treatment improvements. The ethical considerations arising from tissue engineering research are similarly complex when addressing the translational progression from bench to bedside, and investigators in the field of tissue engineering act as moral agents at each step of their research along the translational pathway, from early benchwork and preclinical studies to clinical research. This review highlights the ethical considerations and challenges at each stage of research, by comparing issues surrounding two translational tissue engineering technologies: the bioartificial pancreas and a tissue engineered skeletal muscle construct. We present relevant ethical issues and questions to consider at each step along the translational pathway, from the basic science bench to preclinical research to first-in-human clinical trials. Topics at the bench level include maintaining data integrity, appropriate reporting and dissemination of results, and ensuring that studies are designed to yield results suitable for advancing research. Topics in preclinical research include the principle of "modest translational distance" and appropriate animal models. Topics in clinical research include key issues that arise in early-stage clinical trials, including selection of patient-subjects, disclosure of uncertainty, and defining success. The comparison of these two technologies and their ethical issues brings to light many challenges for translational tissue engineering research and provides guidance for investigators engaged in development of any tissue engineering technology. Copyright © 2015 Elsevier Inc. All rights reserved.

An evaluation of negative-emission transportation-energy systems for the US

NASA Astrophysics Data System (ADS)

Larson, E. D.; Meerman, J. C.

2017-12-01

We present technical, economic, and carbon footprint evaluations of alternative technological pathways for negative emissions transportation energy from sustainably-sourced lignocellulosic biomass in the U.S. We combine the understanding of alternative technological pathways with spatially-resolved projections of the sustainable supply of lignocellulosic biomass and with future demands for transportation services to provide insights on the extent to which biomass-based energy might be able to help meet mid-century U.S. transportation energy needs and carbon mitigation targets. Biomass conversion routes included in our evaluations are biochemical, biocatalytic, thermocatalytic hydropyrolysis, and thermochemical gasification/synthesis to produce liquid fuels fungible with petroleum-derived fuels, and thermochemical conversion to hydrogen (for fuel cell vehicles) or electricity (for battery electric vehicles). Lifecycle net negative emissions are achieved for each system via soil carbon buildup during biomass production and/or capture of CO2 at the conversion facility and underground storage. Co-processing of some fossil fuel is considered in some cases to improve economics. For self-consistency in the analysis across systems, a common set of technical, economic and carbon footprint input parameters are adopted. Capital cost estimates are harmonized by taking into account scale of facilities, level of engineering details available in generating a cost estimate, and the technology readiness level (TRL) of components and the process as a whole. Implications for economics of future commercial plants are investigated, considering alternative prospective reductions in capital and operating costs (via "learning by doing") and alternative carbon mitigation policies.

Crossing Educational Boundaries: Text, Technology, and Dialogue as a Critical Pathway

ERIC Educational Resources Information Center

Abnet, LaNae; Nichols, Joe D.; Moss, Glenda

2008-01-01

Can the perceived boundary between professor and student be crossed? Can technology be used as a pathway to cross that boundary? These questions were answered as a result of a project initiated to meet the requirements in creating an honors option for an undergraduate educational psychology course. In constructing the course requirements, the…

Clean Restructuring: Design Elements for Low Carbon Wholesale Markets and Beyond

DOE Office of Scientific and Technical Information (OSTI.GOV)

None, None

Countries around the world are in various stages of power system reform and restructuring to more effectively meet development goals and decarbonization commitments. Changes in social dynamics, technology, business models, and environmental goals are increasing pressure for countries to consider improvements to their power systems. This brochure overviews the 21st Century Power Partnerships thought leadership report that explores the clean restructuring pathway in depth, envisions an end state, and articulates three main areas of consideration for decision makers embarking on a clean restructuring process. The report also details case studies from Germany, Denmark, and Mexico.

Care pathway, towards the establishment of tailored funding: Reasons and criteria for success.

PubMed

Emery, Grégory; Le Fur, Camille; Epis-de-Fleurian, Anne-Aurélie; Josseran, Anne

2018-02-01

Care pathways are often at the forefront of political thinking about health care practices in France without ever finding a durable means for their extension. Closely linked to funding of healthcare system, they have, once again, been the object of so many economical discussions in 2017, as part of a more optimistic climate of governance which is therefore more open to change. Our changing system, the development and increasingly chronic nature of diseases, the scale of technological breakthroughs, these are all factors driving this topic forward. The object of this work, after a necessary study of the semantics of the term "pathway" and even "funding", was to identify all prerequisites and good practices for the stakeholders to develop a pilot pathway and then its relevant implementation in France. To do so, the members of the Round Table have relied on the presentation of examples of care pathways in order to identify triggers to a progressive, adapted extension to the whole territory. The group has identified key elements and priorities for the establishment of public funding beyond existing funding to incentive team work, particularly in the case of treatment rupture points and/or when they have diverging interests. Finally, creating a climate of confidence among patients, professionals, hospitals, the ARS, payers and manufacturers in handling change management will become the key challenges of the implementation of future pathways. Copyright © 2018 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Transcriptome Analysis of Orbital Adipose Tissue in Active Thyroid Eye Disease Using Next Generation RNA Sequencing Technology

PubMed Central

Lee, Bradford W.; Kumar, Virender B.; Biswas, Pooja; Ko, Audrey C.; Alameddine, Ramzi M.; Granet, David B.; Ayyagari, Radha; Kikkawa, Don O.; Korn, Bobby S.

2018-01-01

Objective: This study utilized Next Generation Sequencing (NGS) to identify differentially expressed transcripts in orbital adipose tissue from patients with active Thyroid Eye Disease (TED) versus healthy controls. Method: This prospective, case-control study enrolled three patients with severe, active thyroid eye disease undergoing orbital decompression, and three healthy controls undergoing routine eyelid surgery with removal of orbital fat. RNA Sequencing (RNA-Seq) was performed on freshly obtained orbital adipose tissue from study patients to analyze the transcriptome. Bioinformatics analysis was performed to determine pathways and processes enriched for the differential expression profile. Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) was performed to validate the differential expression of selected genes identified by RNA-Seq. Results: RNA-Seq identified 328 differentially expressed genes associated with active thyroid eye disease, many of which were responsible for mediating inflammation, cytokine signaling, adipogenesis, IGF-1 signaling, and glycosaminoglycan binding. The IL-5 and chemokine signaling pathways were highly enriched, and very-low-density-lipoprotein receptor activity and statin medications were implicated as having a potential role in TED. Conclusion: This study is the first to use RNA-Seq technology to elucidate differential gene expression associated with active, severe TED. This study suggests a transcriptional basis for the role of statins in modulating differentially expressed genes that mediate the pathogenesis of thyroid eye disease. Furthermore, the identification of genes with altered levels of expression in active, severe TED may inform the molecular pathways central to this clinical phenotype and guide the development of novel therapeutic agents. PMID:29760827

Mining pathway associations for disease-related pathway activity analysis based on gene expression and methylation data.

PubMed

Lee, Hyeonjeong; Shin, Miyoung

2017-01-01

The problem of discovering genetic markers as disease signatures is of great significance for the successful diagnosis, treatment, and prognosis of complex diseases. Even if many earlier studies worked on identifying disease markers from a variety of biological resources, they mostly focused on the markers of genes or gene-sets (i.e., pathways). However, these markers may not be enough to explain biological interactions between genetic variables that are related to diseases. Thus, in this study, our aim is to investigate distinctive associations among active pathways (i.e., pathway-sets) shown each in case and control samples which can be observed from gene expression and/or methylation data. The pathway-sets are obtained by identifying a set of associated pathways that are often active together over a significant number of class samples. For this purpose, gene expression or methylation profiles are first analyzed to identify significant (active) pathways via gene-set enrichment analysis. Then, regarding these active pathways, an association rule mining approach is applied to examine interesting pathway-sets in each class of samples (case or control). By doing so, the sets of associated pathways often working together in activity profiles are finally chosen as our distinctive signature of each class. The identified pathway-sets are aggregated into a pathway activity network (PAN), which facilitates the visualization of differential pathway associations between case and control samples. From our experiments with two publicly available datasets, we could find interesting PAN structures as the distinctive signatures of breast cancer and uterine leiomyoma cancer, respectively. Our pathway-set markers were shown to be superior or very comparable to other genetic markers (such as genes or gene-sets) in disease classification. Furthermore, the PAN structure, which can be constructed from the identified markers of pathway-sets, could provide deeper insights into distinctive associations between pathway activities in case and control samples.

Pathway-based outlier method reveals heterogeneous genomic structure of autism in blood transcriptome

PubMed Central

2013-01-01

Background Decades of research strongly suggest that the genetic etiology of autism spectrum disorders (ASDs) is heterogeneous. However, most published studies focus on group differences between cases and controls. In contrast, we hypothesized that the heterogeneity of the disorder could be characterized by identifying pathways for which individuals are outliers rather than pathways representative of shared group differences of the ASD diagnosis. Methods Two previously published blood gene expression data sets – the Translational Genetics Research Institute (TGen) dataset (70 cases and 60 unrelated controls) and the Simons Simplex Consortium (Simons) dataset (221 probands and 191 unaffected family members) – were analyzed. All individuals of each dataset were projected to biological pathways, and each sample’s Mahalanobis distance from a pooled centroid was calculated to compare the number of case and control outliers for each pathway. Results Analysis of a set of blood gene expression profiles from 70 ASD and 60 unrelated controls revealed three pathways whose outliers were significantly overrepresented in the ASD cases: neuron development including axonogenesis and neurite development (29% of ASD, 3% of control), nitric oxide signaling (29%, 3%), and skeletal development (27%, 3%). Overall, 50% of cases and 8% of controls were outliers in one of these three pathways, which could not be identified using group comparison or gene-level outlier methods. In an independently collected data set consisting of 221 ASD and 191 unaffected family members, outliers in the neurogenesis pathway were heavily biased towards cases (20.8% of ASD, 12.0% of control). Interestingly, neurogenesis outliers were more common among unaffected family members (Simons) than unrelated controls (TGen), but the statistical significance of this effect was marginal (Chi squared P < 0.09). Conclusions Unlike group difference approaches, our analysis identified the samples within the case and control groups that manifested each expression signal, and showed that outlier groups were distinct for each implicated pathway. Moreover, our results suggest that by seeking heterogeneity, pathway-based outlier analysis can reveal expression signals that are not apparent when considering only shared group differences. PMID:24063311

Biological Pathways

MedlinePlus

... Sheets A Brief Guide to Genomics About NHGRI Research About the International HapMap Project Biological Pathways Chromosome Abnormalities Chromosomes Cloning Comparative Genomics DNA Microarray Technology DNA Sequencing Deoxyribonucleic Acid ( ...

Conceptual Biorefinery Design and Research Targeted for 2022: Hydrothermal Liquefacation Processing of Wet Waste to Fuels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Snowden-Swan, Lesley J.; Zhu, Yunhua; Bearden, Mark D.

The Department of Energy Bioenergy Technologies Office (BETO) invests in research and development of new pathways for commercially viable conversion of biomass into drop-in ready transportation fuels, fuel blendstocks and products. The primary emphasis has been on terrestrial and algae feedstocks, but more recently BETO has begun to explore the potential of wet wastes for biofuel production, with focus on wastewater residuals, manure, food waste, and fats, oils and grease. A recent resource analysis estimates that 77 million dry tons per year of these wastes are generated annually, 65% of which are underutilized for any beneficial purpose. Approximately 14 millionmore » dry tons of the total resource is wastewater residuals (sludge and biosolids) generated at the nation’s wastewater treatment plants (WWTPs). Conversion of this resource into transportation fuels could significantly contribute to the creation of a new domestic bioenergy and bioproduct industry, while providing an economically and environmentally sustainable alternative for current waste disposal practices. Hydrothermal liquefaction (HTL) is a process that uses hot, pressurized water in the condensed phase to convert biomass to a thermally stable oil product, also known as “biocrude”, which can then be thermo-catalytically upgraded to hydrocarbon fuel blendstocks. HTL is conceptually simple, has a high carbon efficiency, and can be applied to a wide range of wet feedstocks at similar processing conditions. The purpose of this report is to document the conceptual design, economics and supporting data for a sludge-to-fuel pathway via HTL and biocrude upgrading. The configuration includes a HTL plant that is co-located with a WWTP and a larger scale biocrude upgrading plant for production of hydrocarbon fuel blendstocks. Experimental data from bench scale testing of a 1:1 mixture of primary:secondary sludges are used to establish the economic and technical assumptions for the analysis. The design represents a goal case for the pathway, targeting performance that is anticipated to be achievable by 2022 with further research and development. The year 2022 is BETO’s target year for verification of hydrocarbon biofuel pathways. As this analysis represents a goal case, assumed values of several design parameters represent improvements in the technology relative to what has currently been demonstrated in the laboratory. While HTL is fairly well developed and may therefore be ready for commercialization prior to 2022, there are specific advancements addressed in this analysis that are necessary to enhance performance compared to what has been demonstrated to date. In addition, an important aspect to the pathway is the upgrading of biocrude to fuel blendstock, an area that has received much less attention and requires significant research to validate the goal case performance parameters. The estimated plant gate minimum fuel selling price for fuel blendstock from sludge HTL and upgrading is $3.46/gasoline gallon equivalent (gge). This price is within the tolerance (+$0.49/gge) of BETO’s $3/gge programmatic cost target and illustrates that fuel blendstocks generated from HTL of sludge and centralized biocrude upgrading have the potential to be competitive with fossil fuels. This analysis illustrates the feasibility of HTL for point-of-generation conversion of waste feedstock at a scale 1/20th that of the standard lignocellulosic biorefinery scale typically used in BETO design cases. The relevance of this work reaches beyond wastewater treatment sludge to lay the groundwork for application to other distributed wet wastes and blends that together represent a significant resource of underutilized biomass.« less

Clinical Decision Support Systems (CDSS) for preventive management of COPD patients.

PubMed

Velickovski, Filip; Ceccaroni, Luigi; Roca, Josep; Burgos, Felip; Galdiz, Juan B; Marina, Nuria; Lluch-Ariet, Magí

2014-11-28

The use of information and communication technologies to manage chronic diseases allows the application of integrated care pathways, and the optimization and standardization of care processes. Decision support tools can assist in the adherence to best-practice medicine in critical decision points during the execution of a care pathway. The objectives are to design, develop, and assess a clinical decision support system (CDSS) offering a suite of services for the early detection and assessment of chronic obstructive pulmonary disease (COPD), which can be easily integrated into a healthcare providers' work-flow. The software architecture model for the CDSS, interoperable clinical-knowledge representation, and inference engine were designed and implemented to form a base CDSS framework. The CDSS functionalities were iteratively developed through requirement-adjustment/development/validation cycles using enterprise-grade software-engineering methodologies and technologies. Within each cycle, clinical-knowledge acquisition was performed by a health-informatics engineer and a clinical-expert team. A suite of decision-support web services for (i) COPD early detection and diagnosis, (ii) spirometry quality-control support, (iii) patient stratification, was deployed in a secured environment on-line. The CDSS diagnostic performance was assessed using a validation set of 323 cases with 90% specificity, and 96% sensitivity. Web services were integrated in existing health information system platforms. Specialized decision support can be offered as a complementary service to existing policies of integrated care for chronic-disease management. The CDSS was able to issue recommendations that have a high degree of accuracy to support COPD case-finding. Integration into healthcare providers' work-flow can be achieved seamlessly through the use of a modular design and service-oriented architecture that connect to existing health information systems.

Clinical Decision Support Systems (CDSS) for preventive management of COPD patients

PubMed Central

2014-01-01

Background The use of information and communication technologies to manage chronic diseases allows the application of integrated care pathways, and the optimization and standardization of care processes. Decision support tools can assist in the adherence to best-practice medicine in critical decision points during the execution of a care pathway. Objectives The objectives are to design, develop, and assess a clinical decision support system (CDSS) offering a suite of services for the early detection and assessment of chronic obstructive pulmonary disease (COPD), which can be easily integrated into a healthcare providers' work-flow. Methods The software architecture model for the CDSS, interoperable clinical-knowledge representation, and inference engine were designed and implemented to form a base CDSS framework. The CDSS functionalities were iteratively developed through requirement-adjustment/development/validation cycles using enterprise-grade software-engineering methodologies and technologies. Within each cycle, clinical-knowledge acquisition was performed by a health-informatics engineer and a clinical-expert team. Results A suite of decision-support web services for (i) COPD early detection and diagnosis, (ii) spirometry quality-control support, (iii) patient stratification, was deployed in a secured environment on-line. The CDSS diagnostic performance was assessed using a validation set of 323 cases with 90% specificity, and 96% sensitivity. Web services were integrated in existing health information system platforms. Conclusions Specialized decision support can be offered as a complementary service to existing policies of integrated care for chronic-disease management. The CDSS was able to issue recommendations that have a high degree of accuracy to support COPD case-finding. Integration into healthcare providers' work-flow can be achieved seamlessly through the use of a modular design and service-oriented architecture that connect to existing health information systems. PMID:25471545

EERE Wind and Hydropower Technologies Program Technology Review (Deep Dive) for Under Secretaries Johnson and Koonin

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2009-09-01

September 4, 2009 presentation highlighting the Wind and Hydropower Program, addressing program goals and objectives, budgets, technology pathways, breakthroughs, and DOE solutions to market barriers.

EERE Wind and Hydropower Technologies Program Technology Review (Deep Dive) for Under Secretaries Johnson and Koonin

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCluer, Megan

2009-09-04

September 4, 2009 presentation highlighting the Wind and Hydropower Program, addressing program goals and objectives, budgets, technology pathways, breakthroughs, and DOE solutions to market barriers.

Estimating environmental co-benefits of U.S. low-carbon pathways using an integrated assessment model with state-level resolution

EPA Science Inventory

There are many technological pathways that can lead to reduced carbon dioxide emissions. However, these pathways can have substantially different impacts on other environmental endpoints, such as air quality and energy-related water demand. This study uses an integrated assessmen...

Estimating Environmental Co-benefits of U.S. CO2 Reduction Pathways Using the GCAM-USA Integrated Assessment Model

EPA Science Inventory

Various technological pathways can lead to reduced CO2 emissions. However, different pathways can have substantially different impacts on other environmental endpoints, such as air quality and energy-related water demand. The Global Change Assessment Model (GCAM) is a high resolu...

Proton beam therapy and the convoluted pathway to incorporating emerging technology into routine medical care in the United States.

PubMed

Steinberg, Michael L; Konski, Andre

2009-01-01

The pathway that emerging medical technologies take to incorporation into routine medical care in the United States is a product of the social, economic, and political milieu. Our review explores how this milieu brought the incorporation of proton beam therapy into the healthcare delivery system to its current point. We look at how new technologies are presently accepted into this system and discuss the emerging trends--such as the use of evidence-based assessment of technology, coverage with evidence policies, and comparative effectiveness analysis--that are affecting proton beam therapy's effort to finds its place in the pantheon of available medical treatments for patients with cancer.

Real-time cell toxicity profiling of Tox21 10K compounds reveals cytotoxicity dependent toxicity pathway linkage

PubMed Central

Huang, Ruili; Lin, Ja-An; Sedykh, Alexander; Zhao, Jinghua; Tice, Raymond R.; Paules, Richard S.; Xia, Menghang; Auerbach, Scott S.

2017-01-01

Cytotoxicity is a commonly used in vitro endpoint for evaluating chemical toxicity. In support of the U.S. Tox21 screening program, the cytotoxicity of ~10K chemicals was interrogated at 0, 8, 16, 24, 32, & 40 hours of exposure in a concentration dependent fashion in two cell lines (HEK293, HepG2) using two multiplexed, real-time assay technologies. One technology measures the metabolic activity of cells (i.e., cell viability, glo) while the other evaluates cell membrane integrity (i.e., cell death, flor). Using glo technology, more actives and greater temporal variations were seen in HEK293 cells, while results for the flor technology were more similar across the two cell types. Chemicals were grouped into classes based on their cytotoxicity kinetics profiles and these classes were evaluated for their associations with activity in the Tox21 nuclear receptor and stress response pathway assays. Some pathways, such as the activation of H2AX, were associated with the fast-responding cytotoxicity classes, while others, such as activation of TP53, were associated with the slow-responding cytotoxicity classes. By clustering pathways based on their degree of association to the different cytotoxicity kinetics labels, we identified clusters of pathways where active chemicals presented similar kinetics of cytotoxicity. Such linkages could be due to shared underlying biological processes between pathways, for example, activation of H2AX and heat shock factor. Others involving nuclear receptor activity are likely due to shared chemical structures rather than pathway level interactions. Based on the linkage between androgen receptor antagonism and Nrf2 activity, we surmise that a subclass of androgen receptor antagonists cause cytotoxicity via oxidative stress that is associated with Nrf2 activation. In summary, the real-time cytotoxicity screen provides informative chemical cytotoxicity kinetics data related to their cytotoxicity mechanisms, and with our analysis, it is possible to formulate mechanism-based hypotheses on the cytotoxic properties of the tested chemicals. PMID:28531190

The practical paradox of technology: The influence of communication technology use on employee burnout and engagement.

PubMed

Ter Hoeven, Claartje L; van Zoonen, Ward; Fonner, Kathryn L

2016-04-02

Technological advancements in the workplace frequently have produced contradictory effects by facilitating accessibility and efficiency while increasing interruptions and unpredictability. We combine insights from organizational paradoxes and the job demands-resources model to construct a framework identifying positive and negative mechanisms in the relationship between communication technology use (CTU) and employee well-being, operationalized as work engagement and burnout. In this study of Dutch workers, we demonstrate that CTU increases well-being through positive pathways (accessibility and efficiency) and decreases well-being through negative pathways (interruptions and unpredictability). We highlight the importance of (1) investigating CTU resources and demands simultaneously to grasp the relationship between CTU and employee well-being, and (2) considering CTU's downsides to successfully implement new communication technologies and flexible work designs.

First-trimester emergencies: a radiologist's perspective.

PubMed

Phillips, Catherine H; Wortman, Jeremy R; Ginsburg, Elizabeth S; Sodickson, Aaron D; Doubilet, Peter M; Khurana, Bharti

2018-02-01

The purpose of this article is to help the practitioner ensure early diagnosis and response to emergencies in the first trimester by reviewing anatomy of the developing embryo, highlighting the sonographic appearance of common first-trimester emergencies, and discussing key management pathways for treating emergent cases. First-trimester fetal development is a stepwise process that can be challenging to evaluate in the emergency department (ED) setting. This is due, in part, to the complex anatomy of early pregnancy, subtlety of the sonographic findings, and the fact that fewer than half of patients with ectopic pregnancy present with the classic clinical findings of a positive pregnancy test, vaginal bleeding, pelvic pain, and tender adnexa. Ultrasound (US) has been the primary approach to diagnostic imaging of first-trimester emergencies, with magnetic resonance imaging (MRI) and computed tomography (CT) playing a supportive role in a small minority of cases. Familiarity with the sonographic findings diagnostic of and suspicious for early pregnancy failure, ectopic pregnancy, retained products of conception, gestational trophoblastic disease, failed intrauterine devices, and complications associated with assisted reproductive technology (ART) is critical for any emergency radiologist. Evaluation of first-trimester emergencies is challenging, and knowledge of key imaging findings and familiarity with management pathways are needed to ensure early diagnosis and response.

Energy at the Frontier: Low Carbon Energy System Transitions and Innovation in Four Prime Mover Countries

NASA Astrophysics Data System (ADS)

Araujo, Kathleen M.

All too often, discussion about the imperative to change national energy pathways revolves around long timescales and least cost economics of near-term energy alternatives. While both elements certainly matter, they don't fully reflect what can drive such development trajectories. This study explores national energy transitions by examining ways in which four prime mover countries of low carbon energy technology shifted away from fossil fuels, following the first global oil crisis of 1973. The research analyzes the role of readiness, sectoral contributions and adaptive policy in the scale-up and innovations of advanced, alternative energy technologies. Cases of Brazilian biofuels, Danish wind power, French nuclear power and Icelandic geothermal energy are analyzed for a period of four decades. Fundamentally, the research finds that significant change can occur in under 15 years; that technology complexity need not necessarily impede change; and that countries of different governance approaches and consumption levels can effectuate such transitions. This research also underscores that low carbon energy technologies may be adopted before they are competitive and then become competitive in the process. (Copies available exclusively from MIT Libraries, libraries.mit.edu/docs - docs mit.edu)

Using decision pathway surveys to inform climate engineering policy choices

PubMed Central

Gregory, Robin; Satterfield, Terre; Hasell, Ariel

2016-01-01

Over the coming decades citizens living in North America and Europe will be asked about a variety of new technological and behavioral initiatives intended to mitigate the worst impacts of climate change. A common approach to public input has been surveys whereby respondents’ attitudes about climate change are explained by individuals’ demographic background, values, and beliefs. In parallel, recent deliberative research seeks to more fully address the complex value tradeoffs linked to novel technologies and difficult ethical questions that characterize leading climate mitigation alternatives. New methods such as decision pathway surveys may offer important insights for policy makers by capturing much of the depth and reasoning of small-group deliberations while meeting standard survey goals including large-sample stakeholder engagement. Pathway surveys also can help participants to deepen their factual knowledge base and arrive at a more complete understanding of their own values as they apply to proposed policy alternatives. The pathway results indicate more fully the conditional and context-specific nature of support for several “upstream” climate interventions, including solar radiation management techniques and carbon dioxide removal technologies. PMID:26729883

Using decision pathway surveys to inform climate engineering policy choices.

PubMed

Gregory, Robin; Satterfield, Terre; Hasell, Ariel

2016-01-19

Over the coming decades citizens living in North America and Europe will be asked about a variety of new technological and behavioral initiatives intended to mitigate the worst impacts of climate change. A common approach to public input has been surveys whereby respondents' attitudes about climate change are explained by individuals' demographic background, values, and beliefs. In parallel, recent deliberative research seeks to more fully address the complex value tradeoffs linked to novel technologies and difficult ethical questions that characterize leading climate mitigation alternatives. New methods such as decision pathway surveys may offer important insights for policy makers by capturing much of the depth and reasoning of small-group deliberations while meeting standard survey goals including large-sample stakeholder engagement. Pathway surveys also can help participants to deepen their factual knowledge base and arrive at a more complete understanding of their own values as they apply to proposed policy alternatives. The pathway results indicate more fully the conditional and context-specific nature of support for several "upstream" climate interventions, including solar radiation management techniques and carbon dioxide removal technologies.

Emerging roles for lipids in non-apoptotic cell death

PubMed Central

Magtanong, L; Ko, P J; Dixon, S J

2016-01-01

Non-apoptotic regulated cell death (RCD) is essential to maintain organismal homeostasis and may be aberrantly activated during certain pathological states. Lipids are emerging as key components of several non-apoptotic RCD pathways. For example, a direct interaction between membrane phospholipids and the pore-forming protein mixed lineage kinase domain-like (MLKL) is needed for the execution of necroptosis, while the oxidative destruction of membrane polyunsaturated fatty acids (PUFAs), following the inactivation of glutathione peroxidase 4 (GPX4), is a requisite gateway to ferroptosis. Here, we review the roles of lipids in the initiation and execution of these and other forms of non-apoptotic cell death. We also consider new technologies that are allowing for the roles of lipids and lipid metabolism in RCD to be probed in increasingly sophisticated ways. In certain cases, this new knowledge may enable the development of therapies that target lipids and lipid metabolic processes to enhance or suppress specific non-apoptotic RCD pathways. PMID:26967968

Diagnosis and Management of Hereditary Phaeochromocytoma and Paraganglioma.

PubMed

Lalloo, Fiona

2016-01-01

About 30% of phaeochromocytomas or paragangliomas are genetic. Whilst some individuals will have clinical features or a family history of inherited cancer syndrome such as neurofibromatosis type 1 (NF1) or multiple endocrine neoplasia 2 (MEN2), the majority will present as an isolated case. To date, 14 genes have been described in which pathogenic mutations have been demonstrated to cause paraganglioma or phaeochromocytoma . Many cases with a pathogenic mutation may be at risk of developing further tumours. Therefore, identification of genetic cases is important in the long-term management of these individuals, ensuring that they are entered into a surveillance programme. Mutation testing also facilitates cascade testing within the family, allowing identification of other at-risk individuals. Many algorithms have been described to facilitate cost-effective genetic testing sequentially of these genes, with phenotypically driven pathways. New genetic technologies including next-generation sequencing and whole-exome sequencing will allow much quicker, cheaper and extensive testing of individuals in whom a genetic aetiology is suspected.

Nomad Biosensors: A New Multiplexed Technology for the Screening of GPCR Ligands.

PubMed

Mella, Rosa M; Kortazar, Danel; Roura-Ferrer, Meritxell; Salado, Clarisa; Valcárcel, María; Castilla, Amaia; Villacé, Patricia

2018-06-01

Nomad Technology (Innoprot [Innovative Technologies in Biological Systems], Derio, Spain), a novel tool for multiplexing high-throughput cell-based G protein-coupled receptor (GPCR) assays, is described in this work. This new technology comprises a family of fluorescent biosensors called Nomad Biosensors that allow for the measurement of responses mediated by G proteins through their interactions with second-messenger transduction proteins. GPCRs are one of the largest protein families of receptors in eukaryotes, and their signaling mediates important physiological processes within cells. Thus, GPCRs are associated with a wide variety of diseases, and considered major targets in therapeutic research. Nomad constitutes a novel tool for unraveling the mechanism of GPCR signal transduction by simultaneously tracing different pathways. GPCR activation changes the structural folding of the biosensor and promotes its vesicularization, as well as an increase in the fluorescence intensity. Based on this technology, the MPX Nomad cellular model was developed to discriminate between the Ca 2+ -mediated pathway and the cyclic adenosine monophosphate (cAMP)-mediated pathway. To validate this model, endothelin receptor B (ET B R) was coexpressed into the MPX Nomad cell line and assessed with a specific agonist, an antagonist, and a chemical library of compounds. Nomad Technology optimizes the identification of novel GPCR ligands and enables the testing of large numbers of compounds.

Modelling socio-environmental sensitivities: how public responses to low carbon energy technologies could shape the UK energy system.

PubMed

Moran Jay, Brighid; Howard, David; Hughes, Nick; Whitaker, Jeanette; Anandarajah, Gabrial

2014-01-01

Low carbon energy technologies are not deployed in a social vacuum; there are a variety of complex ways in which people understand and engage with these technologies and the changing energy system overall. However, the role of the public's socio-environmental sensitivities to low carbon energy technologies and their responses to energy deployments does not receive much serious attention in planning decarbonisation pathways to 2050. Resistance to certain resources and technologies based on particular socio-environmental sensitivities would alter the portfolio of options available which could shape how the energy system achieves decarbonisation (the decarbonisation pathway) as well as affecting the cost and achievability of decarbonisation. Thus, this paper presents a series of three modelled scenarios which illustrate the way that a variety of socio-environmental sensitivities could impact the development of the energy system and the decarbonisation pathway. The scenarios represent risk aversion (DREAD) which avoids deployment of potentially unsafe large-scale technology, local protectionism (NIMBY) that constrains systems to their existing spatial footprint, and environmental awareness (ECO) where protection of natural resources is paramount. Very different solutions for all three sets of constraints are identified; some seem slightly implausible (DREAD) and all show increased cost (especially in ECO).

Modelling Socio-Environmental Sensitivities: How Public Responses to Low Carbon Energy Technologies Could Shape the UK Energy System

PubMed Central

Moran Jay, Brighid

2014-01-01

Low carbon energy technologies are not deployed in a social vacuum; there are a variety of complex ways in which people understand and engage with these technologies and the changing energy system overall. However, the role of the public's socio-environmental sensitivities to low carbon energy technologies and their responses to energy deployments does not receive much serious attention in planning decarbonisation pathways to 2050. Resistance to certain resources and technologies based on particular socio-environmental sensitivities would alter the portfolio of options available which could shape how the energy system achieves decarbonisation (the decarbonisation pathway) as well as affecting the cost and achievability of decarbonisation. Thus, this paper presents a series of three modelled scenarios which illustrate the way that a variety of socio-environmental sensitivities could impact the development of the energy system and the decarbonisation pathway. The scenarios represent risk aversion (DREAD) which avoids deployment of potentially unsafe large-scale technology, local protectionism (NIMBY) that constrains systems to their existing spatial footprint, and environmental awareness (ECO) where protection of natural resources is paramount. Very different solutions for all three sets of constraints are identified; some seem slightly implausible (DREAD) and all show increased cost (especially in ECO). PMID:24587735

Application of an access technology delivery protocol to two children with cerebral palsy.

PubMed

Mumford, Leslie; Chau, Tom

2015-07-14

This study further delineates the merits and limitations of the Access Technology Delivery Protocol (ATDP) through its application to two children with severe disabilities. We conducted mixed methods case studies to demonstrate the ATDP with two children with no reliable means of access to an external device. Evaluations of response efficiency, satisfaction, goal attainment, technology use and participation were made after 8 and 16 weeks of training with custom access technologies. After 16 weeks, one child's switch offered improved response efficiency, high teacher satisfaction and increased participation. The other child's switch resulted in improved satisfaction and switch effectiveness but lower overall efficiency. The latter child was no longer using his switch by the end of the study. These contrasting findings indicate that changes to any contextual factors that may impact the user's switch performance should mandate a reassessment of the access pathway. Secondly, it is important to ensure that individuals who will be responsible for switch training be identified at the outset and engaged throughout the ATDP. Finally, the ATDP should continue to be tested with individuals with severe disabilities to build an evidence base for the delivery of response efficient access solutions. Implications for Rehabilitation A data-driven, comprehensive access technology delivery protocol for children with complex communication needs could help to mitigate technology abandonment. Successful adoption of an access technology requires personalized design, training of the technology user, the teaching staff, the caregivers and other communication partners, and integration with functional activities.

Estimating Impacts of Diesel Fuel Reformulation with Vector-based Blending

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hadder, G.R.

2003-01-23

The Oak Ridge National Laboratory Refinery Yield Model has been used to study the refining cost, investment, and operating impacts of specifications for reformulated diesel fuel (RFD) produced in refineries of the U.S. Midwest in summer of year 2010. The study evaluates different diesel fuel reformulation investment pathways. The study also determines whether there are refinery economic benefits for producing an emissions reduction RFD (with flexibility for individual property values) compared to a vehicle performance RFD (with inflexible recipe values for individual properties). Results show that refining costs are lower with early notice of requirements for RFD. While advanced desulfurizationmore » technologies (with low hydrogen consumption and little effect on cetane quality and aromatics content) reduce the cost of ultra low sulfur diesel fuel, these technologies contribute to the increased costs of a delayed notice investment pathway compared to an early notice investment pathway for diesel fuel reformulation. With challenging RFD specifications, there is little refining benefit from producing emissions reduction RFD compared to vehicle performance RFD. As specifications become tighter, processing becomes more difficult, blendstock choices become more limited, and refinery benefits vanish for emissions reduction relative to vehicle performance specifications. Conversely, the emissions reduction specifications show increasing refinery benefits over vehicle performance specifications as specifications are relaxed, and alternative processing routes and blendstocks become available. In sensitivity cases, the refinery model is also used to examine the impact of RFD specifications on the economics of using Canadian synthetic crude oil. There is a sizeable increase in synthetic crude demand as ultra low sulfur diesel fuel displaces low sulfur diesel fuel, but this demand increase would be reversed by requirements for diesel fuel reformulation.« less

Pathways for balancing CO2 emissions and sinks.

PubMed

Walsh, Brian; Ciais, Philippe; Janssens, Ivan A; Peñuelas, Josep; Riahi, Keywan; Rydzak, Felicjan; van Vuuren, Detlef P; Obersteiner, Michael

2017-04-13

In December 2015 in Paris, leaders committed to achieve global, net decarbonization of human activities before 2100. This achievement would halt and even reverse anthropogenic climate change through the net removal of carbon from the atmosphere. However, the Paris documents contain few specific prescriptions for emissions mitigation, leaving various countries to pursue their own agendas. In this analysis, we project energy and land-use emissions mitigation pathways through 2100, subject to best-available parameterization of carbon-climate feedbacks and interdependencies. We find that, barring unforeseen and transformative technological advancement, anthropogenic emissions need to peak within the next 10 years, to maintain realistic pathways to meeting the COP21 emissions and warming targets. Fossil fuel consumption will probably need to be reduced below a quarter of primary energy supply by 2100 and the allowable consumption rate drops even further if negative emissions technologies remain technologically or economically unfeasible at the global scale.

Pathways for balancing CO2 emissions and sinks

PubMed Central

Walsh, Brian; Ciais, Philippe; Janssens, Ivan A.; Peñuelas, Josep; Riahi, Keywan; Rydzak, Felicjan; van Vuuren, Detlef P.; Obersteiner, Michael

2017-01-01

In December 2015 in Paris, leaders committed to achieve global, net decarbonization of human activities before 2100. This achievement would halt and even reverse anthropogenic climate change through the net removal of carbon from the atmosphere. However, the Paris documents contain few specific prescriptions for emissions mitigation, leaving various countries to pursue their own agendas. In this analysis, we project energy and land-use emissions mitigation pathways through 2100, subject to best-available parameterization of carbon-climate feedbacks and interdependencies. We find that, barring unforeseen and transformative technological advancement, anthropogenic emissions need to peak within the next 10 years, to maintain realistic pathways to meeting the COP21 emissions and warming targets. Fossil fuel consumption will probably need to be reduced below a quarter of primary energy supply by 2100 and the allowable consumption rate drops even further if negative emissions technologies remain technologically or economically unfeasible at the global scale. PMID:28406154

Estimating environmental co-benefits of U.S. GHG reduction pathways using the GCAM-USA Integrated Assessment Model (A&WMA Presentation)

EPA Science Inventory

A variety of technological pathways lead to reduced greenhouse gas (GHG) emissions. However, different pathways can have substantially different impacts on other environmental endpoints, such as air quality and energy-related water demand. In this study we use the Global Change ...

Education and Career Pathways in Information Communication Technology: What Are Schoolgirls Saying?

ERIC Educational Resources Information Center

Lasen, Michelle

2010-01-01

This paper highlights key themes which emerged from schoolgirls' responses to focus group questions regarding perceptions of Information Communication Technology (ICT) subjects in the Queensland senior secondary curriculum, primarily, Information Processing Technology (IPT) and Information Technology Systems (ITS). The 2006 focus group interviews…

Accelerating the Integration of Distributed Water Solutions: A Conceptual Financing Model from the Electricity Sector

NASA Astrophysics Data System (ADS)

Quesnel, Kimberly J.; Ajami, Newsha K.; Wyss, Noemi

2017-11-01

Modern challenges require new approaches to urban water management. One solution in the portfolio of potential strategies is the integration of distributed water infrastructure, practices, and technologies into existing systems. However, many practical barriers have prevented the widespread adoption of these systems in the US. The objective of this paper is to address these challenges by developing a conceptual model encompassing regulatory, financial, and governance components that can be used to incorporate new distributed water solutions into our current network. To construct the model, case studies of successfully implemented distributed electricity systems, specifically energy efficiency and renewable energy technologies, were examined to determine how these solutions have become prominent in recent years and what lessons can be applied to the water sector in a similar pursuit. The proposed model includes four action-oriented elements: catalyzing change, establishing funding sources, using resource pathways, and creating innovative governance structures. As illustrated in the model, the water sector should use suite of coordinated policies to promote change, engage end users through fiscal incentives, and encourage research, development and dissemination of new technologies over time.

Accelerating the Integration of Distributed Water Solutions: A Conceptual Financing Model from the Electricity Sector.

PubMed

Quesnel, Kimberly J; Ajami, Newsha K; Wyss, Noemi

2017-11-01

Modern challenges require new approaches to urban water management. One solution in the portfolio of potential strategies is the integration of distributed water infrastructure, practices, and technologies into existing systems. However, many practical barriers have prevented the widespread adoption of these systems in the US. The objective of this paper is to address these challenges by developing a conceptual model encompassing regulatory, financial, and governance components that can be used to incorporate new distributed water solutions into our current network. To construct the model, case studies of successfully implemented distributed electricity systems, specifically energy efficiency and renewable energy technologies, were examined to determine how these solutions have become prominent in recent years and what lessons can be applied to the water sector in a similar pursuit. The proposed model includes four action-oriented elements: catalyzing change, establishing funding sources, using resource pathways, and creating innovative governance structures. As illustrated in the model, the water sector should use suite of coordinated policies to promote change, engage end users through fiscal incentives, and encourage research, development and dissemination of new technologies over time.

Adaptation Pathway of Low Impact Development Planning under Climate Change for a Sustainable Rural Community

NASA Astrophysics Data System (ADS)

Chen, P. Y.; Tung, C. P.

2016-12-01

The study focuses on developing the methodology of adaptation pathway for storm water management in a community scale. Following previous results on adaptation procedures including problem and goal setup, current risk assessment and analysis, future risk assessment and analysis, and adaptation options identification and evaluation, the study aims at analyzing adaptation pathway planning and implementation, namely the fifth step, for applying low impact development (LID). Based on the efficacy analyses of the feasible adaptation options, an adaptation pathway map can be build. Each pathway is a combination of the adaptation measures arranged in certain order. The developed adaptation pathway map visualizes the relative effectiveness and the connection of the adaptation measures. In addition, the tipping points of the system can be clearly identified and the triggers can be defined accordingly. There are multiple choices of pathways in an adaptation pathway map, which can be referred as pathway candidates. To ensure the applicability and operability, the methodology of adaptation pathway analysis is applied to a case study. Required information for developing an adaptation pathway map includes the scores of the adaptation options on the criteria, namely the effects, costs, immediacy, and side effect. Feasible adaptation options for the design case are dredging, pipeline expansion, pumping station, LID and detention pond. By ranking the options according to the criteria, LID is found dominating dredging and pumping station in this case. The information of the pathway candidates can be further used by the stakeholders to select the most suitable and promising pathway.

The Peroxide Pathway

NASA Technical Reports Server (NTRS)

McNeal, Curtis I., Jr.; Anderson, William

1999-01-01

NASA's current focus on technology roadmaps as a tool for guiding investment decisions leads naturally to a discussion of NASA's roadmap for peroxide propulsion system development. NASA's new Second Generation Space Transportation System roadmap calls for an integrated Reusable Upper-Stage (RUS) engine technology demonstration in the FY03/FY04 time period. Preceding this integrated demonstration are several years of component developments and subsystem technology demonstrations. NASA and the Air Force took the first steps at developing focused upper stage technologies with the initiation of the Upper Stage Flight Experiment with Orbital Sciences in December 1997. A review of this program's peroxide propulsion development is a useful first step in establishing the peroxide propulsion pathway that could lead to a RUS demonstration in 2004.

Fostering development of nursing practices to support integrated care when implementing integrated care pathways: what levers to use?

PubMed

Longpré, Caroline; Dubois, Carl-Ardy

2017-11-29

Care integration has been the focus of recent health system reforms. Given their functions at all levels of the care continuum, nurses have a substantial and primordial role to play in such integration processes. The aim of this study was to identify levers and strategies that organizations can use to support the development of a nursing practice aligned with the requirements of care integration in a health and social services centre (HSSC) in Quebec. The research design was a cross-sectional descriptive qualitative study based on a single case study with nested levels of analysis. The case was a public, multi-disciplinary HSSC in a semi-urban region of Quebec. Semi-structured interviews with 37 persons (nurses, professionals, managers, administrators) allowed for data saturation and ensured theoretical representation by covering four care pathways constituting different care integration contexts. Analysis involved four steps: preparing a predetermined list of codes based on the reference framework developed by Minkman (2011); coding transcript content; developing general and summary matrices to group observations for each care pathway; and creating a general model showing the overall results for the four pathways. The organization's capacity for response with regard to developing an integrated system of services resulted in two types of complementary interventions. The first involved investing in key resources and renewing organizational structures; the second involved deploying a series of organizational and clinical-administrative processes. In resource terms, integration efforts resulted in setting up new strategic services, re-arranging physical infrastructures, and deploying new technological resources. Organizational and clinical-administrative processes to promote integration involved renewing governance, improving the flow of care pathways, fostering continuous quality improvement, developing new roles, promoting clinician collaboration, and strengthening care providers' capacities. However, progress in these areas was offset by persistent constraints. The results highlight key levers organizations can use to foster the implementation and institutionalization of integrative nursing practices. They show that progress in this area requires a combination of strategies using multiple complementary levers. They also suggest that such progress calls for rethinking not only the deployment of certain organizational resources and structures, but also a series of organizational and clinical processes.

Integrated tumor and germline whole-exome sequencing identifies mutations in MAPK and PI3K pathway genes in an adolescent with rosette-forming glioneuronal tumor of the fourth ventricle

PubMed Central

Lin, Frank Y.; Bergstrom, Katie; Person, Richard; Bavle, Abhishek; Ballester, Leomar Y.; Scollon, Sarah; Raesz-Martinez, Robin; Jea, Andrew; Birchansky, Sherri; Wheeler, David A.; Berg, Stacey L.; Chintagumpala, Murali M.; Adesina, Adekunle M.; Eng, Christine; Roy, Angshumoy; Plon, Sharon E.; Parsons, D. Williams

2016-01-01

The integration of genome-scale studies such as whole-exome sequencing (WES) into the clinical care of children with cancer has the potential to provide insight into the genetic basis of an individual's cancer with implications for clinical management. This report describes the results of clinical tumor and germline WES for a patient with a rare tumor diagnosis, rosette-forming glioneuronal tumor of the fourth ventricle (RGNT). Three pathogenic gene alterations with implications for clinical care were identified: somatic activating hotspot mutations in FGFR1 (p.N546K) and PIK3CA (p.H1047R) and a germline pathogenic variant in PTPN11 (p.N308S) diagnostic for Noonan syndrome. The molecular landscape of RGNT is not well-described, but these data are consistent with prior observations regarding the importance of the interconnected MAPK and PI3K/AKT/mTOR signaling pathways in this rare tumor. The co-occurrence of FGFR1, PIK3CA, and PTPN11 alterations provides further evidence for consideration of RGNT as a distinct molecular entity from pediatric low-grade gliomas and suggests potential therapeutic strategies for this patient in the event of tumor recurrence as novel agents targeting these pathways enter pediatric clinical trials. Although RGNT has not been definitively linked with cancer predisposition syndromes, two prior cases have been reported in patients with RASopathies (Noonan syndrome and neurofibromatosis type 1 [NF1]), providing an additional link between these tumors and the mitogen-activated protein kinase (MAPK) signaling pathway. In summary, this case provides an example of the potential for genome-scale sequencing technologies to provide insight into the biology of rare tumors and yield both tumor and germline results of potential relevance to patient care. PMID:27626068

The practical paradox of technology: The influence of communication technology use on employee burnout and engagement

PubMed Central

Ter Hoeven, Claartje L.; van Zoonen, Ward; Fonner, Kathryn L.

2016-01-01

ABSTRACT Technological advancements in the workplace frequently have produced contradictory effects by facilitating accessibility and efficiency while increasing interruptions and unpredictability. We combine insights from organizational paradoxes and the job demands–resources model to construct a framework identifying positive and negative mechanisms in the relationship between communication technology use (CTU) and employee well-being, operationalized as work engagement and burnout. In this study of Dutch workers, we demonstrate that CTU increases well-being through positive pathways (accessibility and efficiency) and decreases well-being through negative pathways (interruptions and unpredictability). We highlight the importance of (1) investigating CTU resources and demands simultaneously to grasp the relationship between CTU and employee well-being, and (2) considering CTU's downsides to successfully implement new communication technologies and flexible work designs. PMID:27226694

Technological Education for the Rural Community (TERC) Project: Technical Mathematics for the Advanced Manufacturing Technician

ERIC Educational Resources Information Center

McCormack, Sherry L.; Zieman, Stuart

2017-01-01

Hopkinsville Community College's Technological Education for the Rural Community (TERC) project is funded through the National Science Foundation Advanced Technological Education (NSF ATE) division. It is advancing innovative educational pathways for technological education promoted at the community college level serving rural communities to fill…

Bi-directional gene set enrichment and canonical correlation analysis identify key diet-sensitive pathways and biomarkers of metabolic syndrome.

PubMed

Morine, Melissa J; McMonagle, Jolene; Toomey, Sinead; Reynolds, Clare M; Moloney, Aidan P; Gormley, Isobel C; Gaora, Peadar O; Roche, Helen M

2010-10-07

Currently, a number of bioinformatics methods are available to generate appropriate lists of genes from a microarray experiment. While these lists represent an accurate primary analysis of the data, fewer options exist to contextualise those lists. The development and validation of such methods is crucial to the wider application of microarray technology in the clinical setting. Two key challenges in clinical bioinformatics involve appropriate statistical modelling of dynamic transcriptomic changes, and extraction of clinically relevant meaning from very large datasets. Here, we apply an approach to gene set enrichment analysis that allows for detection of bi-directional enrichment within a gene set. Furthermore, we apply canonical correlation analysis and Fisher's exact test, using plasma marker data with known clinical relevance to aid identification of the most important gene and pathway changes in our transcriptomic dataset. After a 28-day dietary intervention with high-CLA beef, a range of plasma markers indicated a marked improvement in the metabolic health of genetically obese mice. Tissue transcriptomic profiles indicated that the effects were most dramatic in liver (1270 genes significantly changed; p < 0.05), followed by muscle (601 genes) and adipose (16 genes). Results from modified GSEA showed that the high-CLA beef diet affected diverse biological processes across the three tissues, and that the majority of pathway changes reached significance only with the bi-directional test. Combining the liver tissue microarray results with plasma marker data revealed 110 CLA-sensitive genes showing strong canonical correlation with one or more plasma markers of metabolic health, and 9 significantly overrepresented pathways among this set; each of these pathways was also significantly changed by the high-CLA diet. Closer inspection of two of these pathways--selenoamino acid metabolism and steroid biosynthesis--illustrated clear diet-sensitive changes in constituent genes, as well as strong correlations between gene expression and plasma markers of metabolic syndrome independent of the dietary effect. Bi-directional gene set enrichment analysis more accurately reflects dynamic regulatory behaviour in biochemical pathways, and as such highlighted biologically relevant changes that were not detected using a traditional approach. In such cases where transcriptomic response to treatment is exceptionally large, canonical correlation analysis in conjunction with Fisher's exact test highlights the subset of pathways showing strongest correlation with the clinical markers of interest. In this case, we have identified selenoamino acid metabolism and steroid biosynthesis as key pathways mediating the observed relationship between metabolic health and high-CLA beef. These results indicate that this type of analysis has the potential to generate novel transcriptome-based biomarkers of disease.

Bi-directional gene set enrichment and canonical correlation analysis identify key diet-sensitive pathways and biomarkers of metabolic syndrome

PubMed Central

2010-01-01

Background Currently, a number of bioinformatics methods are available to generate appropriate lists of genes from a microarray experiment. While these lists represent an accurate primary analysis of the data, fewer options exist to contextualise those lists. The development and validation of such methods is crucial to the wider application of microarray technology in the clinical setting. Two key challenges in clinical bioinformatics involve appropriate statistical modelling of dynamic transcriptomic changes, and extraction of clinically relevant meaning from very large datasets. Results Here, we apply an approach to gene set enrichment analysis that allows for detection of bi-directional enrichment within a gene set. Furthermore, we apply canonical correlation analysis and Fisher's exact test, using plasma marker data with known clinical relevance to aid identification of the most important gene and pathway changes in our transcriptomic dataset. After a 28-day dietary intervention with high-CLA beef, a range of plasma markers indicated a marked improvement in the metabolic health of genetically obese mice. Tissue transcriptomic profiles indicated that the effects were most dramatic in liver (1270 genes significantly changed; p < 0.05), followed by muscle (601 genes) and adipose (16 genes). Results from modified GSEA showed that the high-CLA beef diet affected diverse biological processes across the three tissues, and that the majority of pathway changes reached significance only with the bi-directional test. Combining the liver tissue microarray results with plasma marker data revealed 110 CLA-sensitive genes showing strong canonical correlation with one or more plasma markers of metabolic health, and 9 significantly overrepresented pathways among this set; each of these pathways was also significantly changed by the high-CLA diet. Closer inspection of two of these pathways - selenoamino acid metabolism and steroid biosynthesis - illustrated clear diet-sensitive changes in constituent genes, as well as strong correlations between gene expression and plasma markers of metabolic syndrome independent of the dietary effect. Conclusion Bi-directional gene set enrichment analysis more accurately reflects dynamic regulatory behaviour in biochemical pathways, and as such highlighted biologically relevant changes that were not detected using a traditional approach. In such cases where transcriptomic response to treatment is exceptionally large, canonical correlation analysis in conjunction with Fisher's exact test highlights the subset of pathways showing strongest correlation with the clinical markers of interest. In this case, we have identified selenoamino acid metabolism and steroid biosynthesis as key pathways mediating the observed relationship between metabolic health and high-CLA beef. These results indicate that this type of analysis has the potential to generate novel transcriptome-based biomarkers of disease. PMID:20929581

Extrahepatic portal obstruction without hepatopetal pathway associated with congenital arterioportal fistula: a case report.

PubMed

Maeda, N; Horie, Y; Koda, M; Suou, T; Andachi, H; Nakamura, K; Kawasaki, H

1997-01-01

Extrahepatic portal obstruction is one of the causes of portal hypertension, in which well-developed hepatopetal pathways are commonly recognized. Herein an extremely rare case of extrahepatic portal obstruction without hepatopetal pathway, probably caused by arterioportal fistula, is reported. The patient was a normally matured 16-year-old girl admitted for further evaluation of jaundice, presenting with the clinical manifestations of the portal hypertension associated with hypersplenism and portosystemic venous shunt. Celiac angiography clearly demonstrated an intrahepatic arterial aneurysm fed by the right hepatic artery shunting to the superior mesenteric vein, and portography disclosed complete obstruction of the portal trunk with conspicuous hepatofugal pathway but no hepatopetal collateral veins. The exact mechanism of this phenomenon is not known and whether the extrahepatic portal obstruction was primary or secondary is still obscure. However, this is the first case report in the world literature describing extrahepatic portal obstruction with absence of hepatopetal pathway.

Investigation of Future Thermal Comforts in a Tropical Megacity Using Coupling of Energy Balance Model and Large Eddy Simulation

NASA Astrophysics Data System (ADS)

Sueishi, T.; Yucel, M.; Ashie, Y.; Varquez, A. C. G.; Inagaki, A.; Darmanto, N. S.; Nakayoshi, M.; Kanda, M.

2017-12-01

Recently, temperature in urban areas continue to rise as an effect of climate change and urbanization. Specifically, Asian megacities are projected to expand rapidly resulting to serious in the future atmospheric environment. Thus, detailed analysis of urban meteorology for Asian megacities is needed to prescribe optimum against these negative climate modifications. A building-resolving large eddy simulation (LES) coupled with an energy balance model is conducted for a highly urbanized district in central Jakarta on typical daytime hours. Five cases were considered; case 1 utilizes present urban scenario and four cases representing different urban configurations in 2050. The future configurations were based on representative concentration pathways (RCP) and shared socio-economic pathways (SSP). Building height maps and land use maps of simulation domains are shown in the attached figure (top). Case 1 3 focuses on the difference of future scenarios. Case 1 represents current climatic and urban conditions, case 2 and 3 was an idealized future represented by RCP2.6/SSP1 and RCP8.5/SSP3, respectively. More complex urban morphology was applied in case 4, vegetation and building area were changed in case 5. Meteorological inputs and anthropogenic heat emission (AHE) were calculated using Weather Research and Forecasting (WRF) model (Varquez et al [2017]). Sensible and latent heat flux from surfaces were calculated using an energy balance model (Ashie et al [2011]), with considers multi-reflection, evapotranspiration and evaporation. The results of energy balance model (shown in the middle line of figure), in addition to WRF outputs, were used as input into the PArallelized LES Model (PALM) (Raasch et al [2001]). From standard new effective temperature (SET*) which included the effects of temperature, wind speed, humidity and radiation, thermal comfort in urban area was evaluated. SET* contours at 1 m height are shown in the bottom line of the figure. Extreme climate change increase average SET* as expected; however, construction of dense high-rise buildings (case 2) can minimize this effect due to increased shading throughout the district. Acknowledgement: This research was supported by the Environment Research and Technology Development Fund (S-14) of the Ministry of the Environment, Japan.

Appendix for the Final Technical Report - DE FE0009284

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duguid, Andrew

2017-05-29

Carbon capture utilization storage (CCUS) is a potential technology to store anthropogenic emissions for CO 2. Utilization often refers to CO 2-enhanced oil recovery (CO 2-EOR). An important factor in the success of CO 2 storage in saline formations or CO 2-EOR reservoirs is ensuring that the storage occurs safely and is long-term. Assessment of well integrity has become more important for CCS and CO 2-EOR as it has become apparent that wells represent the most likely migration pathway for CO 2 to leave a CCS storage unit or a CO 2-EOR reservoir. Although wells represent a migration pathway theymore » are also the best vehicle for employing technology monitoring CO 2 injection and storage. This contradiction of being a potential migration path and key monitoring technology leads to a need to understand how monitoring wells may be similar or different in comparison to other types of wells with respect to migration risk. The maturation and completion US Department of Energy sponsored research projects presents an opportunity to assess the integrity of monitoring wells that have been exposed to injected CO 2. This paper discusses an integrity assessment of two monitoring wells in an operating CO 2-EOR flood in Mississippi, USA. The CFU31F-2 and CFU31F-3 monitoring wells were constructed to test monitoring technologies in and above a commercial CO 2-EOR project. The materials selected and the design of the well were optimized for monitoring. Carbonation in CFU31-F2 was seen as high as 7900 ft, above what was considered top of cement based on the logs. Time-lapse comparison of cement bond amplitude data and acoustic impedance maps show a deterioration of signal that implies a deterioration of cement bond or cement along much of the cemented annulus in the long-string section. Analysis of sidewall cores using XRD and LA-ICP-MS validated the log interpretation by confirming the degradation of cement (carbonation) along the casing-cement interface. The ultrasonic image maps also clearly identify the control lines and monitoring technology attached to the outside of the of the long-string casing on each well studied. The control lines appear as microdebonded or fluid filled vertical features implying that they could act as leakage pathways. The sidewall core through the control line at 10380 ft confirms that CO 2 is migrating along the control line with heavily carbonated cement at the control line interface. LA-ICP-MS and XRD on formation interface of the sidewall cores collected in both wells indicates that CO 2 is also moving of the cement-formation interface. LA-ICP-MS and XRD indicate that the amount carbonation in the center of the cores was less than the carbonation at the interfaces. Indicating that CO 2 is reaching the center of the cores by diffusing in from the interfaces and not migrating up from the reservoir though the porous matrix of the cement. This agrees with Duguid et al. [5] and Carey et al. [1] who have found that the interfaces in the well are more conductive than the porous network of the cement. Both the materials used to construct the well and the decision to attach monitoring technology to the outside of the well may have contributed to the migration of CO 2 along the interfaces. Careful consideration should be given to material selection to ensure that it does not degrade when in contact with the fluids in the reservoir and overlying strata. The addition of the control line on the outside of the casing complicated the cement placement and likely caused no cement to bond to the casing adjacent to the control line leading out of the reservoir. Further study of other wells with external lines should be conducted to see of the results of the construction of CFU31-F2 and -F3 is normal or an exception.« less

Pathways from College to University: A Social Science Example from Ontario

ERIC Educational Resources Information Center

LeSage, Ann; Samis, John; Hinch, Ron; Longo, Fabiola; DiGiuseppe, Maurice; Goodman, William; Percival, Jennifer; De La Rocha, Arlene; Rodrigues, Anna; Raby, Phil; Sanchez, Otto

2014-01-01

This study evaluates the impact of a College to University Pathway Program in the Faculty of Social Science and Humanities at The University of Ontario Institute of Technology. The findings support the assertion that Pathway students perform as well as or better than students who enter university directly from secondary school. This finding is…

Technology Opportunities to Reduce U.S. Greenhouse Gas Emissions

DOE Office of Scientific and Technical Information (OSTI.GOV)

National Lab Directors, . .

2001-04-05

The rise in greenhouse gas emissions from fossil fuel combustion and industrial and agricultural activities has aroused international concern about the possible impacts of these emissions on climate. Greenhouse gases--mostly carbon dioxide, some methane, nitrous oxide and other trace gases--are emitted to the atmosphere, enhancing an effect in which heat reflected from the earth's surface is kept from escaping into space, as in a greenhouse. Thus, there is concern that the earth's surface temperature may rise enough to cause global climate change. Approximately 90% of U.S. greenhouse gas emissions from anthropogenic sources come from energy production and use, most ofmore » which are a byproduct of the combustion of fossil fuels. On a per capita basis, the United States is one of the world's largest sources of greenhouse gas emissions, comprising 4% of the world's population, yet emitting 23% of the world's greenhouse gases. Emissions in the United States are increasing at around 1.2% annually, and the Energy Information Administration forecasts that emissions levels will continue to increase at this rate in the years ahead if we proceed down the business-as-usual path. President Clinton has presented a two-part challenge for the United States: reduce greenhouse gas emissions and grow the economy. Meeting the challenge will mean that in doing tomorrow's work, we must use energy more efficiently and emit less carbon for the energy expended than we do today. To accomplish these goals, President Clinton proposed on June 26, 1997, that the United States ''invest more in the technologies of the future''. In this report to Secretary of Energy Pena, 47 technology pathways are described that have significant potential to reduce carbon dioxide emissions. The present study was completed before the December 1997 United Nations Framework Convention on Climate Change and is intended to provide a basis to evaluate technology feasibility and options to reduce greenhouse gas emissions. These technology pathways (which are described in greater detail in Appendix B, Technology Pathways) address three areas: energy efficiency, clean energy, and carbon sequestration (removing carbon from emissions and enhancing carbon storage). Based on an assessment of each of these technology pathways over a 30-year planning horizon, the directors of the Department of Energy's (DOE's) national laboratories conclude that success will require pursuit of multiple technology pathways to provide choices and flexibility for reducing greenhouse gas emissions. Advances in science and technology are necessary to reduce greenhouse gas emissions from the United States while sustaining economic growth and providing collateral benefits to the nation.« less

Concentrating Solar Power Gen3 Demonstration Roadmap

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mehos, Mark; Turchi, Craig; Vidal, Judith

Today's power-tower concentrating solar power (CSP) technology exists in large part as a result of Department of Energy (DOE) and utility industry funding of demonstration systems in the 1980s and 1990s. Today's most advanced towers are integrated with molten-salt thermal energy storage, delivering thermal energy at 565 degrees C for integration with conventional steam-Rankine cycles. The supercritical carbon dioxide power cycle has been identified as a likely successor to the steam-Rankine power cycle due to its potential for high efficiency when operating at elevated temperatures of 700 degrees C or greater. Over the course of the SunShot Initiative, DOE hasmore » supported a number of technology pathways that can operate efficiently at these temperatures and that hold promise to be reliable and cost effective. Three pathways - molten salt, particle, and gaseous - were selected for further investigation based on a two-day workshop held in August of 2016. The information contained in this roadmap identifies research and development challenges and lays out recommended research activities for each of the three pathways. DOE foresees that by successfully addressing the challenges identified in this roadmap, one or more technology pathways will be positioned for demonstration and subsequent commercialization within the next ten years. Based on current knowledge of the three power tower technologies, all three have the potential to achieve the SunShot goal of 6 cents/kilowatt-hour. Further development, modeling, and testing are now required to bring one or more of the technologies to a stage where integrated system tests and pilot demonstrations are feasible.« less

Undesirable leakage to overlying formations with horizontal and vertical injection wells

NASA Astrophysics Data System (ADS)

Mosaheb, M.; Zeidouni, M.

2017-12-01

Deep saline aquifers are considered for underground storage of carbon dioxide. Undesirable leakage of injected CO2 to adjacent layers would disturb the storage process and can pollute shallower fresh water resources as well as atmosphere. Leaky caprocks, faults, and abandoned wells are examples of leaky pathways. In addition, the overpressure can reactivate a sealing fault or damage the caprock layer. Pressure management is applicable during the storage operation to avoid these consequences and to reduce undesirable leakage.The fluids can be injected through horizontal wells with a wider interval than vertical wells. Horizontal well injection would make less overpressure by delocalizing induced pressure especially in thin formations. In this work, numerical and analytical approaches are applied to model different leaky pathways with horizontal and vertical injection wells. we compare leakage rate and overpressure for horizontal and vertical injection wells in different leaky pathway systems. Results show that the horizontal well technology would allow high injection rates with lower leakage rate for leaky well, leaky fault, and leaky caprock cases. The overpressure would reduce considerably by horizontal well comparing to vertical well injection especially in leaky fault system. The horizontal well injection is an effective method to avoid reaching to threshold pressure of fault reactivation and prevent the consequent induced seismicity.

New Insights into Sulfur Metabolism in Yeasts as Revealed by Studies of Yarrowia lipolytica

PubMed Central

Hébert, Agnès; Forquin-Gomez, Marie-Pierre; Roux, Aurélie; Aubert, Julie; Junot, Christophe; Heilier, Jean-François; Landaud, Sophie; Bonnarme, Pascal

2013-01-01

Yarrowia lipolytica, located at the frontier of hemiascomycetous yeasts and fungi, is an excellent candidate for studies of metabolism evolution. This yeast, widely recognized for its technological applications, in particular produces volatile sulfur compounds (VSCs) that fully contribute to the flavor of smear cheese. We report here a relevant global vision of sulfur metabolism in Y. lipolytica based on a comparison between high- and low-sulfur source supplies (sulfate, methionine, or cystine) by combined approaches (transcriptomics, metabolite profiling, and VSC analysis). The strongest repression of the sulfate assimilation pathway was observed in the case of high methionine supply, together with a large accumulation of sulfur intermediates. A high sulfate supply seems to provoke considerable cellular stress via sulfite production, resulting in a decrease of the availability of the glutathione pathway's sulfur intermediates. The most limited effect was observed for the cystine supply, suggesting that the intracellular cysteine level is more controlled than that of methionine and sulfate. Using a combination of metabolomic profiling and genetic experiments, we revealed taurine and hypotaurine metabolism in yeast for the first time. On the basis of a phylogenetic study, we then demonstrated that this pathway was lost by some of the hemiascomycetous yeasts during evolution. PMID:23220962

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Meiye; Singh, Anup K.

In this study, cell signaling is a dynamic and complex process. A typical signaling pathway may begin with activation of cell surface receptors, leading to activation kinase cascade that culminates in induction of mRNA and non-coding miRNA production in the nucleus, followed by modulation of mRNA expression by miRNAs in the cytosol, and end with production of proteins in response to the signaling pathway. Signaling pathways involve proteins, miRNA, and mRNAs, along with various forms of transient post-translational modifications, and detecting each type of signaling molecule requires categorically different sample preparation methods such as Western blotting for proteins, PCR formore » nucleic acids, and flow cytometry for post-translational modifications. Since we know that cells in populations behave heterogeneously1, especially in the cases of stem cells, cancer, and hematopoiesis, there is need for a new technology that provides capability to detect and quantify multiple categories of signaling molecules in intact single cells to provide a comprehensive view of the cell’s physiological state. In this technical brief, we describe our microfluidic platform with a portfolio of customized molecular assays that can detect nucleic acids, proteins, and post-translational modifications in single intact cells with >95% reduction in reagent requirement in under 8 hours.« less

Single-session Gamma Knife radiosurgery for optic pathway/hypothalamic gliomas.

PubMed

El-Shehaby, Amr M N; Reda, Wael A; Abdel Karim, Khaled M; Emad Eldin, Reem M; Nabeel, Ahmed M

2016-12-01

OBJECTIVE Because of their critical and central location, it is deemed necessary to fractionate when considering irradiating optic pathway/hypothalamic gliomas. Stereotactic fractionated radiotherapy is considered safer when dealing with gliomas in this location. In this study, the safety and efficacy of single-session stereotactic radiosurgery for optic pathway/hypothalamic gliomas were reviewed. METHODS Between December 2004 and June 2014, 22 patients with optic pathway/hypothalamic gliomas were treated by single-session Gamma Knife radiosurgery. Twenty patients were available for follow-up for a minimum of 1 year after treatment. The patients were 5 to 43 years (median 16 years) of age. The tumor volume was 0.15 to 18.2 cm 3 (median 3.1 cm 3 ). The prescription dose ranged from 8 to 14 Gy (median 11.5 Gy). RESULTS The mean follow-up period was 43 months. Five tumors involved the optic nerve only, and 15 tumors involved the chiasm/hypothalamus. Two patients died during the follow-up period. The tumors shrank in 12 cases, remained stable in 6 cases, and progressed in 2 cases, thereby making the tumor control rate 90%. Vision remained stable in 12 cases, improved in 6 cases, and worsened in 2 cases in which there was tumor progression. Progression-free survival was 83% at 3 years. CONCLUSIONS The initial results indicate that single-session Gamma Knife radiosurgery is a safe and effective treatment option for optic pathway/hypothalamic gliomas.

Genetically Engineered Crops and Certified Organic Agriculture for Improving Nutrition Security in Africa and South Asia.

PubMed

Pray, Carl; Ledermann, Samuel

2016-01-01

In Africa and South Asia, where nutrition insecurity is severe, two of the most prominent production technologies are genetically modified (GM) crops and certified organic agriculture. We analyze the potential impact pathways from agricultural production to nutrition. Our review of data and the literature reveals increasing farm-level income from cash crop production as the main pathway by which organic agriculture and GM agriculture improve nutrition. Potential secondary pathways include reduced prices of important food crops like maize due to GM maize production and increased food production using organic technology. Potential tertiary pathways are improvements in health due to reduced insecticide use. Challenges to the technologies achieving their impact include the politics of GM agriculture and the certification costs of organic agriculture. Given the importance of agricultural production in addressing nutrition security, accentuated by the post-2015 sustainable development agenda, the chapter concludes by stressing the importance of private and public sector research in improving the productivity and adoption of both GM and organic crops. In addition, the chapter reminds readers that increased farm income and productivity require complementary investments in health, education, food access and women's empowerment to actually improve nutrition security. © 2016 S. Karger AG, Basel.

Advanced Sensors and Controls for Building Applications: Market Assessment and Potential R&D Pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brambley, M. R.; Haves, P.; McDonald, S. C.

2005-04-01

This document provides a market assessment of existing building sensors and controls and presents a range of technology pathways (R&D options) for pursuing advanced sensors and building control strategies.

A Systematic Review on the Existing Screening Pathways for Lynch Syndrome Identification.

PubMed

Tognetto, Alessia; Michelazzo, Maria Benedetta; Calabró, Giovanna Elisa; Unim, Brigid; Di Marco, Marco; Ricciardi, Walter; Pastorino, Roberta; Boccia, Stefania

2017-01-01

Lynch syndrome (LS) is the most common hereditary colon cancer syndrome, accounting for 3-5% of colorectal cancer (CRC) cases, and it is associated with the development of other cancers. Early detection of individuals with LS is relevant, since they can take advantage of life-saving intensive care surveillance. The debate regarding the best screening policy, however, is far from being concluded. This prompted us to conduct a systematic review of the existing screening pathways for LS. We performed a systematic search of MEDLINE, ISI Web of Science, and SCOPUS online databases for the existing screening pathways for LS. The eligibility criteria for inclusion in this review required that the studies evaluated a structured and permanent screening pathway for the identification of LS carriers. The effectiveness of the pathways was analyzed in terms of LS detection rate. We identified five eligible studies. All the LS screening pathways started from CRC cases, of which three followed a universal screening approach. Concerning the laboratory procedures, the pathways used immunohistochemistry and/or microsatellite instability testing. If the responses of the tests indicated a risk for LS, the genetic counseling, performed by a geneticist or a genetic counselor, was mandatory to undergo DNA genetic testing. The overall LS detection rate ranged from 0 to 5.2%. This systematic review reported different existing pathways for the identification of LS patients. Although current clinical guidelines suggest to test all the CRC cases to identify LS cases, the actual implementation of pathways for LS identification has not been realized. Large-scale screening programs for LS have the potential to reduce morbidity and mortality for CRC, but coordinated efforts in educating all key stakeholders and addressing public needs are still required.

t4 Workshop Report*

PubMed Central

Kleensang, Andre; Maertens, Alexandra; Rosenberg, Michael; Fitzpatrick, Suzanne; Lamb, Justin; Auerbach, Scott; Brennan, Richard; Crofton, Kevin M.; Gordon, Ben; Fornace, Albert J.; Gaido, Kevin; Gerhold, David; Haw, Robin; Henney, Adriano; Ma’ayan, Avi; McBride, Mary; Monti, Stefano; Ochs, Michael F.; Pandey, Akhilesh; Sharan, Roded; Stierum, Rob; Tugendreich, Stuart; Willett, Catherine; Wittwehr, Clemens; Xia, Jianguo; Patton, Geoffrey W.; Arvidson, Kirk; Bouhifd, Mounir; Hogberg, Helena T.; Luechtefeld, Thomas; Smirnova, Lena; Zhao, Liang; Adeleye, Yeyejide; Kanehisa, Minoru; Carmichael, Paul; Andersen, Melvin E.; Hartung, Thomas

2014-01-01

Summary Despite wide-spread consensus on the need to transform toxicology and risk assessment in order to keep pace with technological and computational changes that have revolutionized the life sciences, there remains much work to be done to achieve the vision of toxicology based on a mechanistic foundation. A workshop was organized to explore one key aspect of this transformation – the development of Pathways of Toxicity (PoT) as a key tool for hazard identification based on systems biology. Several issues were discussed in depth in the workshop: The first was the challenge of formally defining the concept of a PoT as distinct from, but complementary to, other toxicological pathway concepts such as mode of action (MoA). The workshop came up with a preliminary definition of PoT as “A molecular definition of cellular processes shown to mediate adverse outcomes of toxicants”. It is further recognized that normal physiological pathways exist that maintain homeostasis and these, sufficiently perturbed, can become PoT. Second, the workshop sought to define the adequate public and commercial resources for PoT information, including data, visualization, analyses, tools, and use-cases, as well as the kinds of efforts that will be necessary to enable the creation of such a resource. Third, the workshop explored ways in which systems biology approaches could inform pathway annotation, and which resources are needed and available that can provide relevant PoT information to the diverse user communities. PMID:24127042

Pathways to Commercial Success: Technologies and Products Supported by the Fuel Cell Technologies Office - 2014

DOE Office of Scientific and Technical Information (OSTI.GOV)

None, None

This FY 2014 report updates the results of an effort to identify and characterize commercial and near-commercial (emerging) technologies and products that benefited from the support of the Fuel Cell Technologies Office and its predecessor programs within DOE's Office of Energy Efficiency and Renewable Energy.

Pathways to Commercial Success. Technologies and Products Supported by the Fuel Cell Technologies Program - 2012

DOE Office of Scientific and Technical Information (OSTI.GOV)

none,

This FY 2012 report updates the results of an effort to identify and characterize commercial and near-commercial (emerging) technologies and products that benefited from the support of the Fuel Cell Technologies Program and its predecessor programs within DOE's Office of Energy Efficiency and Renewable Energy.

Pathways to Commercial Success. Technologies and Products Supported by the Fuel Cell Technologies Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

none,

This FY 2011 report updates the results of an effort to identify and characterize commercial and near-commercial (emerging) technologies and products that benefited from the support of the Fuel Cell Technologies Program and its predecessor programs within DOE's Office of Energy Efficiency and Renewable Energy.

Pathways to Commercial Success: Technologies and Products Supported by the Fuel Cell Technologies Office - 2013

DOE Office of Scientific and Technical Information (OSTI.GOV)

none,

This FY 2013 report updates the results of an effort to identify and characterize commercial and near-commercial (emerging) technologies and products that benefited from the support of the Fuel Cell Technologies Office and its predecessor programs within DOE's Office of Energy Efficiency and Renewable Energy.

Why Do Health Economists Promote Technology Adoption Rather Than the Search for Efficiency? A Proposal for a Change in Our Approach to Economic Evaluation in Health Care.

PubMed

Scotland, Graham; Bryan, Stirling

2017-02-01

At a time of intense pressure on health care budgets, the technology management challenge is for disinvestment in low-value technologies and reinvestment in higher value alternatives. The aim of this article is to explore ways in which health economists might begin to redress the observed imbalance between the evaluation of new and existing in-use technologies. The argument is not against evaluating new technologies but in favor of the "search for efficiency," where the ultimate objective is to identify reallocations that improve population health in the face of resource scarcity. We explore why in-use technologies may be of low value and consider how economic evaluation analysts might embrace a broader efficiency lens, first through "technology management" (a process of analysis and evidence-informed decision making throughout a technology's life cycle) and progressing through "pathway management" (the search for efficiency gains across entire clinical care pathways). A number of model-based examples are used to illustrate the approaches.

Negative Emissions: Where Will the Carbon Come From?

NASA Astrophysics Data System (ADS)

Aines, R. D.; McCoy, S. T.

2017-12-01

The need for energy technologies that remove carbon dioxide from the air grows with each year of delay in acting to address climate change. The most commonly mentioned approach for achieving that, bioenergy with carbon capture and storage (BECCS), today is largely a modeler's concept, not a technology. Thus, in the near term how can we confidently discuss the scale of biomass for energy with a net reduction in CO2 concentrations in the absence of examples? As a first step toward achieving that research objective, this talk frames the likely ways in which net reductions in CO2 concentrations can be achieved from a lifecycle perspective, and the pathways through which biomass can be converted to fuels and materials while removing CO2 from the atmosphere. We will address questions such as: What pathways exist for converting biomass into transportation fuels, electricity, and materials? How can we capture and manage the carbon dioxide emissions from these kinds of activities? And, what are the tradeoffs between pathways? We have conducted preliminary analyses of some of the common biofuel production pathways, such as ethanol from corn with and without carbon capture. These pathways are still uniformly carbon positive, that is to say, they do not achieve the goal of reducing atmospheric CO2, even if they result in lower emissions than do petroleum-based fuels. More advanced pathways appear to have the capacity for minor atmospheric reductions, including those for drop-in replacement transportation fuels and some long-lived materials. Targets and options for improving these technologies to the point that they can, in fact, be carbon negative will be discussed, including pre-processing of the biomass near the production site to reduce transportation emissions, finding ways to manage small CO2 sources associated with processing, and uses of biochar. We will end with a summary of near-term RD&D needs to advance carbon-negative pathways and the associated technologies. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

Genes and (Common) Pathways Underlying Drug Addiction

PubMed Central

Li, Chuan-Yun; Mao, Xizeng; Wei, Liping

2008-01-01

Drug addiction is a serious worldwide problem with strong genetic and environmental influences. Different technologies have revealed a variety of genes and pathways underlying addiction; however, each individual technology can be biased and incomplete. We integrated 2,343 items of evidence from peer-reviewed publications between 1976 and 2006 linking genes and chromosome regions to addiction by single-gene strategies, microrray, proteomics, or genetic studies. We identified 1,500 human addiction-related genes and developed KARG (http://karg.cbi.pku.edu.cn), the first molecular database for addiction-related genes with extensive annotations and a friendly Web interface. We then performed a meta-analysis of 396 genes that were supported by two or more independent items of evidence to identify 18 molecular pathways that were statistically significantly enriched, covering both upstream signaling events and downstream effects. Five molecular pathways significantly enriched for all four different types of addictive drugs were identified as common pathways which may underlie shared rewarding and addictive actions, including two new ones, GnRH signaling pathway and gap junction. We connected the common pathways into a hypothetical common molecular network for addiction. We observed that fast and slow positive feedback loops were interlinked through CAMKII, which may provide clues to explain some of the irreversible features of addiction. PMID:18179280

Solutions for data integration in functional genomics: a critical assessment and case study.

PubMed

Smedley, Damian; Swertz, Morris A; Wolstencroft, Katy; Proctor, Glenn; Zouberakis, Michael; Bard, Jonathan; Hancock, John M; Schofield, Paul

2008-11-01

The torrent of data emerging from the application of new technologies to functional genomics and systems biology can no longer be contained within the traditional modes of data sharing and publication with the consequence that data is being deposited in, distributed across and disseminated through an increasing number of databases. The resulting fragmentation poses serious problems for the model organism community which increasingly rely on data mining and computational approaches that require gathering of data from a range of sources. In the light of these problems, the European Commission has funded a coordination action, CASIMIR (coordination and sustainability of international mouse informatics resources), with a remit to assess the technical and social aspects of database interoperability that currently prevent the full realization of the potential of data integration in mouse functional genomics. In this article, we assess the current problems with interoperability, with particular reference to mouse functional genomics, and critically review the technologies that can be deployed to overcome them. We describe a typical use-case where an investigator wishes to gather data on variation, genomic context and metabolic pathway involvement for genes discovered in a genome-wide screen. We go on to develop an automated approach involving an in silico experimental workflow tool, Taverna, using web services, BioMart and MOLGENIS technologies for data retrieval. Finally, we focus on the current impediments to adopting such an approach in a wider context, and strategies to overcome them.

Using Large-Scale Cooperative Control to Manage Operational Uncertainties for Aquifer Thermal Energy Storage

NASA Astrophysics Data System (ADS)

Jaxa-Rozen, M.; Rostampour, V.; Kwakkel, J. H.; Bloemendal, M.

2017-12-01

Seasonal Aquifer Thermal Energy Storage (ATES) technology can help reduce the demand of energy for heating and cooling in buildings, and has become a popular option for larger buildings in northern Europe. However, the larger-scale deployment of this technology has evidenced some issues of concern for policymakers; in particular, recent research shows that operational uncertainties contribute to inefficient outcomes under current planning methods for ATES. For instance, systems in the Netherlands typically use less than half of their permitted pumping volume on an annual basis. This overcapacity gives users more flexibility to operate their systems in response to the uncertainties which drive building energy demand; these include short-term operational factors such as weather and occupancy, and longer-term, deeply uncertain factors such as changes in climate and aquifer conditions over the lifespan of the buildings. However, as allocated subsurface volume remains unused, this situation limits the adoption of the technology in dense areas. Previous work using coupled agent-based/geohydrological simulation has shown that the cooperative operation of neighbouring ATES systems can support more efficient spatial planning, by dynamically managing thermal interactions in response to uncertain operating conditions. An idealized case study with centralized ATES control thus showed significant improvements in the energy savings which could obtained per unit of allocated subsurface volume, without degrading the recovery performance of systems. This work will extend this cooperative approach for a realistic case study of ATES planning in the city of Utrecht, in the Netherlands. This case was previously simulated under different scenarios for individual ATES operation. The poster will compare these results with a cooperative case under which neighbouring systems can coordinate their operation to manage interactions. Furthermore, a cooperative game-theoretical framework will be used to analyze the theoretical conditions under which cooperation between ATES operators could be assumed to be stable and beneficial, under a range of scenarios for climate trends and ATES adoption pathways.

Mutation of genes of the PI3K/AKT pathway in breast cancer supports their potential importance as biomarker for breast cancer aggressiveness.

PubMed

Tserga, Aggeliki; Chatziandreou, Ilenia; Michalopoulos, Nicolaos V; Patsouris, Efstratios; Saetta, Angelica A

2016-07-01

Deregulation of phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is closely associated with cancer development and cancer progression. PIK3CA, AKT1, and PTEN are the fundamental molecules of the PI3K/AKT pathway with increased mutation rates in cancer cases leading to aberrant regulation of the pathway. Even though molecular alterations of the PI3K/AKT pathway have been studied in breast cancer, correlations between specific molecular alterations and clinicopathological features remain contradictory. In this study, we examined mutations of the PI3K/AKT pathway in 75 breast carcinomas using high-resolution melting analysis and pyrosequencing, in parallel with analysis of relative expression of PIK3CA and AKT2 genes. Mutations of PIK3CA were found in our cohort in 21 cases (28 %), 10 (13 %) in exon 9 and 11(15 %) in exon 20. Mutation frequency of AKT1 and PTEN genes was 4 and 3 %, respectively. Overall, alterations in the PI3K/AKT signaling cascade were detected in 35 % of the cases. Furthermore, comparison of 50 breast carcinomas with adjacent normal tissues showed elevated PIK3CA messenger RNA (mRNA) levels in 18 % of tumor cases and elevated AKT2 mRNA levels in 14 %. Our findings, along with those of previous studies, underline the importance of the PI3K/AKT pathway components as potential biomarkers for breast carcinogenesis.

From generic pathways to ICT-supported horizontally integrated care: the SmartCare approach and convergence with future Internet assembly.

PubMed

Urošević, Vladimir; Mitić, Marko

2014-01-01

Successful service integration in policy and practice requires both technology innovation and service process innovation being pursued and implemented at the same time. The SmartCare project (partially EC-funded under CIP ICT PSP Program) aims to achieve this through development, piloting and evaluation of ICT-based services, horizontally integrating health and social care in ten pilot regions, including Kraljevo region in Serbia. The project has identified and adopted two generic highest-level common thematic pathways in joint consolidation phase - integrated support for long-term care and integrated support after hospital discharge. A common set of standard functional specifications for an open ICT platform enabling the delivery of integrated care is being defined, around the challenges of data sharing, coordination and communication in these two formalized pathways. Implementation and system integration on technology and architecture level are to be based on open standards, multivendor interoperability, and leveraging on the current evolving open specification technology foundations developed in relevant projects across the European Research Area.

A framework to analyze emissions implications of ...

EPA Pesticide Factsheets

Future year emissions depend highly on the evolution of the economy, technology and current and future regulatory drivers. A scenario framework was adopted to analyze various technology development pathways and societal change while considering existing regulations and future uncertainty in regulations and evaluate resulting emissions growth patterns. The framework integrates EPA’s energy systems model with an economic Input-Output (I/O) Life Cycle Assessment model. The EPAUS9r MARKAL database is assembled from a set of technologies to represent the U.S. energy system within MARKAL bottom-up technology rich energy modeling framework. The general state of the economy and consequent demands for goods and services from these sectors are taken exogenously in MARKAL. It is important to characterize exogenous inputs about the economy to appropriately represent the industrial sector outlook for each of the scenarios and case studies evaluated. An economic input-output (I/O) model of the US economy is constructed to link up with MARKAL. The I/O model enables user to change input requirements (e.g. energy intensity) for different sectors or the share of consumer income expended on a given good. This gives end-users a mechanism for modeling change in the two dimensions of technological progress and consumer preferences that define the future scenarios. The framework will then be extended to include environmental I/O framework to track life cycle emissions associated

Social energy: mining energy from the society

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Jun Jason; Gao, David Wenzhong; Zhang, Yingchen

The inherent nature of energy, i.e., physicality, sociality and informatization, implies the inevitable and intensive interaction between energy systems and social systems. From this perspective, we define 'social energy' as a complex sociotechnical system of energy systems, social systems and the derived artificial virtual systems which characterize the intense intersystem and intra-system interactions. The recent advancement in intelligent technology, including artificial intelligence and machine learning technologies, sensing and communication in Internet of Things technologies, and massive high performance computing and extreme-scale data analytics technologies, enables the possibility of substantial advancement in socio-technical system optimization, scheduling, control and management. In thismore » paper, we provide a discussion on the nature of energy, and then propose the concept and intention of social energy systems for electrical power. A general methodology of establishing and investigating social energy is proposed, which is based on the ACP approach, i.e., 'artificial systems' (A), 'computational experiments' (C) and 'parallel execution' (P), and parallel system methodology. A case study on the University of Denver (DU) campus grid is provided and studied to demonstrate the social energy concept. In the concluding remarks, we discuss the technical pathway, in both social and nature sciences, to social energy, and our vision on its future.« less

Technology Student Characteristics: Course Taking Patterns as a Pathway to STEM Disciplines

ERIC Educational Resources Information Center

Asunda, Paul A.; Kim, Eun Sook; Westberry, Richard

2015-01-01

Rising concern about America's ability to maintain its competitive position in the global economy has renewed interest in STEM education. The power and the promise of STEM education is based on the need for technological literacy. Technology education is a discipline devoted to the delivery of technological literacy for all. Nevertheless, a…

High Throughput Transcriptomics: From screening to pathways

EPA Science Inventory

The EPA ToxCast effort has screened thousands of chemicals across hundreds of high-throughput in vitro screening assays. The project is now leveraging high-throughput transcriptomic (HTTr) technologies to substantially expand its coverage of biological pathways. The first HTTr sc...

Sphingolipid metabolism potential in fecal microbiome and bronchiolitis in infants: a case-control study.

PubMed

Hasegawa, Kohei; Stewart, Christopher J; Mansbach, Jonathan M; Linnemann, Rachel W; Ajami, Nadim J; Petrosino, Joseph F; Camargo, Carlos A

2017-07-26

Emerging evidence demonstrated that the structure of fecal microbiome is associated with the likelihood of bronchiolitis in infants. However, no study has examined functional profiles of fecal microbiome in infants with bronchiolitis. In this context, we conducted a case-control study. As a part of multicenter prospective study, we collected stool samples from 40 infants hospitalized with bronchiolitis (cases). We concurrently enrolled 115 age-matched healthy controls. First, by applying 16S rRNA gene sequencing to these 155 fecal samples, we identified the taxonomic profiles of fecal microbiome. Next, based on the taxonomy data, we inferred the functional capabilities of fecal microbiome and tested for differences in the functional capabilities between cases and controls. Overall, the median age was 3 months and 45% were female. Among 274 metabolic pathways surveyed, there were significant differences between bronchiolitis cases and healthy controls for 37 pathways, including lipid metabolic pathways (false discovery rate [FDR] <0.05). Particularly, the fecal microbiome of bronchiolitis cases had consistently higher abundances of gene function related to the sphingolipid metabolic pathways compared to that of controls (FDR <0.05). These pathways were more abundant in infants with Bacteroides-dominant microbiome profile compared to the others (FDR <0.001). On the basis of the predicted metagenome in this case-control study, we found significant differences in the functional potential of fecal microbiome between infants with bronchiolitis and healthy controls. Although causal inferences remain premature, our data suggest a potential link between the bacteria-derived metabolites, modulations of host immune response, and development of bronchiolitis.

Promoter library-based module combination (PLMC) technology for optimization of threonine biosynthesis in Corynebacterium glutamicum.

PubMed

Wei, Liang; Xu, Ning; Wang, Yiran; Zhou, Wei; Han, Guoqiang; Ma, Yanhe; Liu, Jun

2018-05-01

Due to the lack of efficient control elements and tools, the fine-tuning of gene expression in the multi-gene metabolic pathways is still a great challenge for engineering microbial cell factories, especially for the important industrial microorganism Corynebacterium glutamicum. In this study, the promoter library-based module combination (PLMC) technology was developed to efficiently optimize the expression of genes in C. glutamicum. A random promoter library was designed to contain the putative - 10 (NNTANANT) and - 35 (NNGNCN) consensus motifs, and refined through a three-step screening procedure to achieve numerous genetic control elements with different strength levels, including fluorescence-activated cell sorting (FACS) screening, agar plate screening, and 96-well plate screening. Multiple conventional strategies were employed for further precise characterizations of the promoter library, such as real-time quantitative PCR, sodium dodecyl sulfate polyacrylamide gel electrophoresis, FACS analysis, and the lacZ reporter system. These results suggested that the established promoter elements effectively regulated gene expression and showed varying strengths over a wide range. Subsequently, a multi-module combination technology was created based on the efficient promoter elements for combination and optimization of modules in the multi-gene pathways. Using this technology, the threonine biosynthesis pathway was reconstructed and optimized by predictable tuning expression of five modules in C. glutamicum. The threonine titer of the optimized strain was significantly improved to 12.8 g/L, an approximate 6.1-fold higher than that of the control strain. Overall, the PLMC technology presented in this study provides a rapid and effective method for combination and optimization of multi-gene pathways in C. glutamicum.

Pathway Analysis and Omics Data Visualization Using Pathway Genome Databases: FragariaCyc, a Case Study.

PubMed

Naithani, Sushma; Jaiswal, Pankaj

2017-01-01

The species-specific plant Pathway Genome Databases (PGDBs) based on the BioCyc platform provide a conceptual model of the cellular metabolic network of an organism. Such frameworks allow analysis of the genome-scale expression data to understand changes in the overall metabolisms of an organism (or organs, tissues, and cells) in response to various extrinsic (e.g. developmental and differentiation) and/or extrinsic signals (e.g. pathogens and abiotic stresses) from the surrounding environment. Using FragariaCyc, a pathway database for the diploid strawberry Fragaria vesca, we show (1) the basic navigation across a PGDB; (2) a case study of pathway comparison across plant species; and (3) an example of RNA-Seq data analysis using Omics Viewer tool. The protocols described here generally apply to other Pathway Tools-based PGDBs.

A Pathway Based Classification Method for Analyzing Gene Expression for Alzheimer's Disease Diagnosis.

PubMed

Voyle, Nicola; Keohane, Aoife; Newhouse, Stephen; Lunnon, Katie; Johnston, Caroline; Soininen, Hilkka; Kloszewska, Iwona; Mecocci, Patrizia; Tsolaki, Magda; Vellas, Bruno; Lovestone, Simon; Hodges, Angela; Kiddle, Steven; Dobson, Richard Jb

2016-01-01

Recent studies indicate that gene expression levels in blood may be able to differentiate subjects with Alzheimer's disease (AD) from normal elderly controls and mild cognitively impaired (MCI) subjects. However, there is limited replicability at the single marker level. A pathway-based interpretation of gene expression may prove more robust. This study aimed to investigate whether a case/control classification model built on pathway level data was more robust than a gene level model and may consequently perform better in test data. The study used two batches of gene expression data from the AddNeuroMed (ANM) and Dementia Case Registry (DCR) cohorts. Our study used Illumina Human HT-12 Expression BeadChips to collect gene expression from blood samples. Random forest modeling with recursive feature elimination was used to predict case/control status. Age and APOE ɛ4 status were used as covariates for all analysis. Gene and pathway level models performed similarly to each other and to a model based on demographic information only. Any potential increase in concordance from the novel pathway level approach used here has not lead to a greater predictive ability in these datasets. However, we have only tested one method for creating pathway level scores. Further, we have been able to benchmark pathways against genes in datasets that had been extensively harmonized. Further work should focus on the use of alternative methods for creating pathway level scores, in particular those that incorporate pathway topology, and the use of an endophenotype based approach.

Assessment of air quality and climate co-benefits of decarbonisation of the UK energy system using remote sensing and model simulations - the case for prioritizing end uses in urban areas

NASA Astrophysics Data System (ADS)

Sobral Mourao, Zenaida; Konadu, Daniel Dennis; Damoah, Richard; Li, Pei-hao

2017-04-01

The UK has a binding obligation to reduce GHG emission by 80% (based on 1990 levels) by 2050. Meeting this target requires extensive decarbonisation of the UK energy system. Different pathways that achieve this target at the lowest system costs are being explored at different levels of policy and decisions on future energy infrastructure. Whilst benefits of decarbonisation are mainly focused on the impacts on climate change, there are other potential environmental and health impacts such as air-quality. In particular, a decrease in fossil fuel use by directly substituting current systems with low-carbon technologies could lead to significant reductions in the concentrations of SO2, NOX, CO and other atmospheric pollutants. So far, the proposed decarbonisation pathways tend to target the electricity sector first, followed by a transition in transport and heating technologies and use. However, the spatial dimension of where short term changes in the energy sector occur in relation to high density population areas is not taken into account when defining the energy transition strategies. This may lead to limited short-term improvements in air quality within urban areas, where use of fossil fuels for heating and transport is the main contribution to overall atmospheric pollutant levels. It is therefore imperative to explore decarbonisation strategies that prioritise transition in sectors of the energy system that produce immediate improvements in air quality in key regions of the UK. This study aims to use a combination of Remote Sensing observations and atmospheric chemistry/transport modelling approaches to estimate and map the impact on NOx of the traditional approach of decarbonising electricity first compared to a slower transition in the electricity sector, but faster change in the transport sector. This is done by generating a set of alternative energy system pathways with a higher share of zero emissions vehicles in 2030 than the energy system optimization model would choose if the only goal was the 80% GHG emissions reduction. Our overarching goal is to provide an additional standard to compare future energy system pathways beyond the traditional metrics of cost and GHG emissions reductions.

Capability of Virtual Environments to Meet Military Requirements

DTIC Science & Technology

2000-11-01

Hettinger, 1992). These symptoms, now called cybersickness (McCauley & Sharkey, 1992), could retard development of VE technology and limit its use as a... cybersickness may involve multiple functional pathways. The first pathway is related to ill-effects upon the autonomic nervous system or ANS (Money...avoided by obtaining a better understanding of the ANS mechanism. Another cybersickness pathway involves adaptation within the central nervous system

Point-of-care diagnostics: extending the laboratory network to reach the last mile.

PubMed

Drain, Paul K; Rousseau, Christine

2017-03-01

More point-of-care (POC) diagnostic tests are becoming available for HIV diagnosis and treatment in resource-limited settings. These novel technologies have the potential to foster decentralized HIV care and treatment for the benefit of clinical laboratories, HIV clinics, and HIV-infected patients. There continue to be many business, technological, and operational challenges that limit product development and regulatory approval, which limits products available for the required operational and cost-effectiveness studies and delays policy adoption and implementation. Although the rapid HIV diagnostic test has been widely successful, the pathways for POC CD4 cell count and HIV viral load assay analyzers have been more challenging. We describe significant hurdles for product development, approval, and implementation, which include the business case, technical development, clinical impact, and integrating laboratory and clinical networks. The objective of this review is to highlight the obstacles for developing and implementing appropriate strategies for POC HIV testing assays to improve the clinical services for HIV-infected patients in resource-limited settings.

ARC-2003-ACD03-0112-050

NASA Image and Video Library

2003-09-05

NRTC/RITA Precision Pathway Terminal Guidance: UH-60 RASCAL (#012) (National Rotocraft Technology Center/Rotorcraft Industry Technology Association) runway independent aircraft; Sikorsky Helicopter pilot Kevin Bredenbeck preparing for flight in RASCAL with Dave Arterburn

ARC-2003-ACD03-0112-046

NASA Image and Video Library

2003-09-05

NRTC/RITA Precision Pathway Terminal Guidance: UH-60 RASCAL (#012) (National Rotocraft Technology Center/Rotorcraft Industry Technology Association) runway independent aircraft - Sikorsky Helicopter pilot Kevin Bredenbeck preparing for flight in RASCAL with Dave Arterburn

ARC-2003-ACD03-0112-044

NASA Image and Video Library

2003-09-05

NRTC/RITA Precision Pathway Terminal Guidance: UH-60 RASCAL (#012) (National Rotocraft Technology Center/Rotorcraft Industry Technology Association) runway independent aircraft - Sikorsky Helicopter pilot Kevin Bredenbeck preparing for flight in RASCAL with Dave Arterburn

ARC-2003-ACD03-0112-047

NASA Image and Video Library

2003-09-05

NRTC/RITA Precision Pathway Terminal Guidance: UH-60 RASCAL (#012) (National Rotocraft Technology Center/Rotorcraft Industry Technology Association) runway independent aircraft - Sikorsky Helicopter pilot Kevin Bredenbeck with Dave Arterburn and Ernie Morales of Ames

ARC-2003-ACD03-0112-048

NASA Image and Video Library

2003-09-05

NRTC/RITA Precision Pathway Terminal Guidance: UH-60 RASCAL (#012) (National Rotocraft Technology Center/Rotorcraft Industry Technology Association) runway independent aircraft - Sikorsky Helicopter pilot Kevin Bredenbeck with Dave Arterburn and Ernie Morales of Ames

Preoperative Visualization of Cranial Nerves in Skull Base Tumor Surgery Using Diffusion Tensor Imaging Technology.

PubMed

Ma, Jun; Su, Shaobo; Yue, Shuyuan; Zhao, Yan; Li, Yonggang; Chen, Xiaochen; Ma, Hui

2016-01-01

To visualize cranial nerves (CNs) using diffusion tensor imaging (DTI) with special parameters. This study also involved the evaluation of preoperative estimates and intraoperative confirmation of the relationship between nerves and tumor by verifying the accuracy of visualization. 3T magnetic resonance imaging scans including 3D-FSPGR, FIESTA, and DTI were used to collect information from 18 patients with skull base tumor. DTI data were integrated into the 3D slicer for fiber tracking and overlapped anatomic images to determine course of nerves. 3D reconstruction of tumors was achieved to perform neighboring, encasing, and invading relationship between lesion and nerves. Optic pathway including the optic chiasm could be traced in cases of tuberculum sellae meningioma and hypophysoma (pituitary tumor). The oculomotor nerve, from the interpeduncular fossa out of the brain stem to supraorbital fissure, was clearly visible in parasellar meningioma cases. Meanwhile, cisternal parts of trigeminal nerve and abducens nerve, facial nerve were also imaged well in vestibular schwannomas and petroclival meningioma cases. The 3D-spatial relationship between CNs and skull base tumor estimated preoperatively by tumor modeling and tractography corresponded to the results determined during surgery. Supported by DTI and 3D slicer, preoperative 3D reconstruction of most CNs related to skull base tumor is feasible in pathological circumstances. We consider DTI Technology to be a useful tool for predicting the course and location of most CNs, and syntopy between them and skull base tumor.

A model of user engagement in medical device development.

PubMed

Grocott, Patricia; Weir, Heather; Ram, Mala Bridgelal

2007-01-01

The purpose of this paper is to address three topical themes: user involvement in health services research; determining the value of new medical technologies in patient care pathways, furthering knowledge related to quality in health and social care; and knowledge exchange between manufacturers, health service supply chain networks and device users. The model is being validated in a case study in progress. The latter is a "proving ground" study for a translational research company. Medical devices play a pivotal role in the management of chronic diseases, across all care settings. Failure to engage users in device development inevitably affects the quality of clinical outcomes. A model of user engagement is presented, turning unmet needs for medical devices into viable commercial propositions. A case study investigating the perceptions of individuals with Epidermolysis Bullosa (EB), their lay and professional carers into unmet needs. EB is an inherited condition affecting the skin and mucosal linings that leads to blistering and wounds. Qualitative data are being collected to generate understanding of unmet needs and wound care products. These needs are being translated into new design concepts and prototypes. Prototypes will be evaluated in an n = 1 experimental design, generating quantitative outcomes data. There are generalisations from the case study, and the model outlined. New products for managing EB wounds can logically benefit other groups. The model is transferable to other clinical problems, which can benefit from research and technological advances that are integral to clinical needs and care.

Using Technology to Provide Differentiated Instruction for Deaf Learners

ERIC Educational Resources Information Center

Shepherd, Carol M.; Alpert, Madelon

2015-01-01

Knowledge is power. Technological devices provide the new pathway to online learning and student retention. This is especially true for deaf learners, who have difficulty learning with the traditional pedagogies used in teaching. Results of studies have indicated that students using the suggested new technologies become more interested and…

Open Campus: Strategic Plan

DTIC Science & Technology

2016-05-01

The formal and informal interactions among scientists, engineers, and business and technology specialists fostered by this environment will lead...pathways for highly trained graduates of science, technology, engineering, and mathematics (STEM) academic programs, and help academic institutions...engineering and mathematics (STEM) disciplines relevant to ARL science and technology programs. Under EPAs, visiting students and professors

20180311 - High Throughput Transcriptomics: From screening to pathways (SOT 2018)

EPA Science Inventory

The EPA ToxCast effort has screened thousands of chemicals across hundreds of high-throughput in vitro screening assays. The project is now leveraging high-throughput transcriptomic (HTTr) technologies to substantially expand its coverage of biological pathways. The first HTTr sc...

PARTITION COEFFICIENTS FOR METALS IN SURFACE WATER, SOIL, AND WASTE

EPA Science Inventory

This report presents metal partition coefficients for the surface water pathway and for the source model used in the Multimedia, Multi-pathway, Multi-receptor Exposure and Risk Assessment (3MRA) technology under development by the U.S. Environmental Protection Agency. Partition ...

Feedstock Supply System Design and Economics for Conversion of Lignocellulosic Biomass to Hydrocarbon Fuels Conversion Pathway: Fast Pyrolysis and Hydrotreating Bio-Oil Pathway "The 2017 Design Case"

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kevin L. Kenney; Kara G. Cafferty; Jacob J. Jacobson

The U.S. Department of Energy promotes the production of liquid fuels from lignocellulosic biomass feedstocks by funding fundamental and applied research that advances the state of technology in biomass sustainable supply, logistics, conversion, and overall system sustainability. As part of its involvement in this program, Idaho National Laboratory (INL) investigates the feedstock logistics economics and sustainability of these fuels. Between 2000 and 2012, INL quantified and the economics and sustainability of moving biomass from the field or stand to the throat of the conversion process using conventional equipment and processes. All previous work to 2012 was designed to improve themore » efficiency and decrease costs under conventional supply systems. The 2012 programmatic target was to demonstrate a biomass logistics cost of $55/dry Ton for woody biomass delivered to fast pyrolysis conversion facility. The goal was achieved by applying field and process demonstration unit-scale data from harvest, collection, storage, preprocessing, handling, and transportation operations into INL’s biomass logistics model.« less

Process Design and Economics for the Conversion of Lignocellulosic Biomass to Hydrocarbon Fuels: Thermochemical Research Pathways with In Situ and Ex Situ Upgrading of Fast Pyrolysis Vapors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dutta, Abhijit; Sahir, A. H.; Tan, Eric

This report was developed as part of the U.S. Department of Energy’s Bioenergy Technologies Office’s efforts to enable the development of technologies for the production of infrastructure-compatible, cost-competitive liquid hydrocarbon fuels from biomass. Specifically, this report details two conceptual designs based on projected product yields and quality improvements via catalyst development and process integration. It is expected that these research improvements will be made within the 2022 timeframe. The two conversion pathways detailed are (1) in situ and (2) ex situ upgrading of vapors produced from the fast pyrolysis of biomass. While the base case conceptual designs and underlying assumptionsmore » outline performance metrics for feasibility, it should be noted that these are only two of many other possibilities in this area of research. Other promising process design options emerging from the research will be considered for future techno-economic analysis. Both the in situ and ex situ conceptual designs, using the underlying assumptions, project MFSPs of approximately $3.5/gallon gasoline equivalent (GGE). The performance assumptions for the ex situ process were more aggressive with higher distillate (diesel-range) products. This was based on an assumption that more favorable reaction chemistry (such as coupling) can be made possible in a separate reactor where, unlike in an in situ upgrading reactor, one does not have to deal with catalyst mixing with biomass char and ash, which pose challenges to catalyst performance and maintenance. Natural gas was used for hydrogen production, but only when off gases from the process was not sufficient to meet the needs; natural gas consumption is insignificant in both the in situ and ex situ base cases. Heat produced from the burning of char, coke, and off-gases allows for the production of surplus electricity which is sold to the grid allowing a reduction of approximately 5¢/GGE in the MFSP.« less

Policy making for vaccine use as a driver of vaccine innovation and development in the developed world.

PubMed

Seib, Katherine; Pollard, Andrew J; de Wals, Philippe; Andrews, Ross M; Zhou, Fangjun; Hatchett, Richard J; Pickering, Larry K; Orenstein, Walter A

2017-03-07

In the past 200years, vaccines have had unmistakable impacts on public health including declines in morbidity and mortality, most markedly in economically-developed countries. Highly engineered vaccines including vaccines for conditions other than infectious diseases are expected to dominate future vaccine development. We examine immunization vaccine policy as a driver of vaccine innovation and development. The pathways to recommendation for use of licensed vaccines in the US, UK, Canada and Australia have been similar, including: expert review of disease epidemiology, disease burden and severity; vaccine immunogenicity, efficacy and safety; programmatic feasibility; public demand; and increasingly cost-effectiveness. Other attributes particularly important in development of future vaccines are likely to include: duration of immunity for improved vaccines such as pertussis; a greater emphasis on optimizing community protection rather than direct protection only; programmatic implementation, feasibility, improvements (as in the case of development of a universal influenza vaccine); public concerns/confidence/fears related to outbreak pathogens like Ebola and Zika virus; and major societal burden for combating hard to treat diseases like HIV and antimicrobial resistant pathogens. Driving innovation and production of future vaccines faces enormous economic hurdles as available approaches, technologies and regulatory pathways become more complex. As such, cost-mitigating strategies and focused, aligned efforts (by governments, private organizations, and private-public partnerships) will likely be needed to continue to spur major advances in vaccine technologies and development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pathways to Deep Decarbonization in the United States

NASA Astrophysics Data System (ADS)

Torn, M. S.; Williams, J.

2015-12-01

Limiting anthropogenic warming to less than 2°C will require a reduction in global net greenhouse gas (GHG) emissions on the order of 80% below 1990 levels by 2050. Thus, there is a growing need to understand what would be required to achieve deep decarbonization (DD) in different economies. We examined the technical and economic feasibility of such a transition in the United States, evaluating the infrastructure and technology changes required to reduce U.S. GHG emissions in 2050 by 80% below 1990 levels. Using the PATHWAYS and GCAM models, we found that this level of decarbonization in the U.S. can be accomplished with existing commercial or near-commercial technologies, while providing the same level of energy services and economic growth as a reference case based on the U.S. DOE Annual Energy Outlook. Reductions are achieved through high levels of energy efficiency, decarbonization of electric generation, electrification of most end uses, and switching the remaining end uses to lower carbon fuels. Incremental energy system cost would be equivalent to roughly 1% of gross domestic product, not including potential non-energy benefits such as avoided human and infrastructure costs of climate change. Starting now on the deep decarbonization path would allow infrastructure stock turnover to follow natural replacement rates, which reduces costs, eases demand on manufacturing, and allows gradual consumer adoption. Energy system changes must be accompanied by reductions in non-energy and non-CO2 GHG emissions.

An evolving paradigm for the secretory pathway?

PubMed Central

Lippincott-Schwartz, Jennifer

2011-01-01

The paradigm that the secretory pathway consists of a stable endoplasmic reticulum and Golgi apparatus, using discrete transport vesicles to exchange their contents, gained important support from groundbreaking biochemical and genetic studies during the 1980s. However, the subsequent development of new imaging technologies with green fluorescent protein introduced data on dynamic processes not fully accounted for by the paradigm. As a result, we may be seeing an example of how a paradigm is evolving to account for the results of new technologies and their new ways of describing cellular processes. PMID:22039065

Independent Assessment of Technology Characterizations to Support the Biomass Program Annual State-of-Technology Assessments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yeh, B.

2011-03-01

This report discusses an investigation that addressed two thermochemical conversion pathways for the production of liquid fuels and addressed the steps to the process, the technology providers, a method for determining the state of technology and a tool to continuously assess the state of technology. This report summarizes the findings of the investigation as well as recommendations for improvements for future studies.

Webs Wires Waves: The Science & Technology of Communication. National Science and Technology Week, April 20-26, 1997.

ERIC Educational Resources Information Center

National Science Foundation, Arlington, VA.

This collection of activities revolves around the theme of National Science and Technology Week (NSTW). The six 8-page booklets that make up this package present activities that follow a pathway from natural, simple forms of communication toward increasingly complex and technological forms. They are designed to be undertaken in sequence, but can…

Redundancy control in pathway databases (ReCiPa): an application for improving gene-set enrichment analysis in Omics studies and "Big data" biology.

PubMed

Vivar, Juan C; Pemu, Priscilla; McPherson, Ruth; Ghosh, Sujoy

2013-08-01

Abstract Unparalleled technological advances have fueled an explosive growth in the scope and scale of biological data and have propelled life sciences into the realm of "Big Data" that cannot be managed or analyzed by conventional approaches. Big Data in the life sciences are driven primarily via a diverse collection of 'omics'-based technologies, including genomics, proteomics, metabolomics, transcriptomics, metagenomics, and lipidomics. Gene-set enrichment analysis is a powerful approach for interrogating large 'omics' datasets, leading to the identification of biological mechanisms associated with observed outcomes. While several factors influence the results from such analysis, the impact from the contents of pathway databases is often under-appreciated. Pathway databases often contain variously named pathways that overlap with one another to varying degrees. Ignoring such redundancies during pathway analysis can lead to the designation of several pathways as being significant due to high content-similarity, rather than truly independent biological mechanisms. Statistically, such dependencies also result in correlated p values and overdispersion, leading to biased results. We investigated the level of redundancies in multiple pathway databases and observed large discrepancies in the nature and extent of pathway overlap. This prompted us to develop the application, ReCiPa (Redundancy Control in Pathway Databases), to control redundancies in pathway databases based on user-defined thresholds. Analysis of genomic and genetic datasets, using ReCiPa-generated overlap-controlled versions of KEGG and Reactome pathways, led to a reduction in redundancy among the top-scoring gene-sets and allowed for the inclusion of additional gene-sets representing possibly novel biological mechanisms. Using obesity as an example, bioinformatic analysis further demonstrated that gene-sets identified from overlap-controlled pathway databases show stronger evidence of prior association to obesity compared to pathways identified from the original databases.

Modeling Signaling Networks to Advance New Cancer Therapies.

PubMed

Saez-Rodriguez, Julio; MacNamara, Aidan; Cook, Simon

2015-01-01

Cell signaling pathways control cells' responses to their environment through an intricate network of proteins and small molecules partitioned by intracellular structures, such as the cytoskeleton and nucleus. Our understanding of these pathways has been revised recently with the advent of more advanced experimental techniques; no longer are signaling pathways viewed as linear cascades of information flowing from membrane-bound receptors to the nucleus. Instead, such pathways must be understood in the context of networks, and studying such networks requires an integration of computational and experimental approaches. This understanding is becoming more important in designing novel therapies for diseases such as cancer. Using the MAPK (mitogen-activated protein kinase) and PI3K (class I phosphoinositide-3' kinase) pathways as case studies of cellular signaling, we give an overview of these pathways and their functions. We then describe, using a number of case studies, how computational modeling has aided in understanding these pathways' deregulation in cancer, and how such understanding can be used to optimally tailor current therapies or help design new therapies against cancer.

The role of technology and telemetry medicine in the initial management of a ST-segment elevated myocardial infarction in a rural emergency department.

PubMed

Hood, Michael L

2018-05-01

The 12-lead electrocardiogram (ECG) is an integral part of the diagnostic tools available for recognising a patient who is experiencing an ST-segment elevated myocardial infarction (STEMI). Consequently, a great emphasis is placed on the rapid acquisition and expert interpretation of the 12-lead ECG so that the appropriate reperfusion management might be commenced to optimise patient outcomes by preventing further damage to the myocardium. With the advancement of telemetric and diagnostic abilities of the modern ECG machine, the role of frontline rural emergency clinicians is as important as ever. This clinical case report describes the presentation and management of a person experiencing a STEMI in a rural Australian hospital emergency department setting. The emanating point of interest from this case report is the early clinician recognition of significant ST-segment elevation in multiple leads of the initial ECG trace, indicating a STEMI. Despite the presence of significant acute ST-segment changes throughout the trace, the ECG's diagnostic analysis of the 12-lead ECG did not identify it as meeting STEMI criteria. Subsequently, the ECG was not recommended by the ECG machine for telemetric transmission to the remote on-call cardiologist for immediate STEMI management guidance. This article focuses on the telemetric technology utilised in the management of STEMIs in the rural emergency department, the diagnostic ability of the modern ECG and the role of the frontline rural emergency clinician in the utilisation of such technology. Competent utilisation of key technologies applied to the ECG machine require the clinician to be well trained in the technical use of the equipment, have a thorough understanding of how the technology interacts within the established clinical pathway and be ready to apply its use in a timely manner in order to prevent delays in treatment. Furthermore, an over-reliance on the diagnostic ability of the modern ECG machine in the rural or remote context may potentially lead to poor patient outcomes.

Bioelectrohydrogenesis and inhibition of methanogenic activity in microbial electrolysis cells - A review.

PubMed

Karthikeyan, Rengasamy; Cheng, Ka Yu; Selvam, Ammaiyappan; Bose, Arpita; Wong, Jonathan W C

2017-11-01

Microbial electrolysis cells (MECs) are a promising technology for biological hydrogen production. Compared to abiotic water electrolysis, a much lower electrical voltage (~0.2V) is required for hydrogen production in MECs. It is also an attractive waste treatment technology as a variety of biodegradable substances can be used as the process feedstock. Underpinning this technology is a recently discovered bioelectrochemical pathway known as "bioelectrohydrogenesis". However, little is known about the mechanism of this pathway, and numerous hurdles are yet to be addressed to maximize hydrogen yield and purity. Here, we review various aspects including reactor configurations, microorganisms, substrates, electrode materials, and inhibitors of methanogenesis in order to improve hydrogen generation in MECs. Copyright © 2017 Elsevier Inc. All rights reserved.

Designing a Care Pathway Model - A Case Study of the Outpatient Total Hip Arthroplasty Care Pathway.

PubMed

Oosterholt, Robin I; Simonse, Lianne Wl; Boess, Stella U; Vehmeijer, Stephan Bw

2017-03-09

Although the clinical attributes of total hip arthroplasty (THA) care pathways have been thoroughly researched, a detailed understanding of the equally important organisational attributes is still lacking. The aim of this article is to contribute with a model of the outpatient THA care pathway that depicts how the care team should be organised to enable patient discharge on the day of surgery. The outpatient THA care pathway enables patients to be discharged on the day of surgery, shortening the length of stay and intensifying the provision and organisation of care. We utilise visual care modelling to construct a visual design of the organisation of the care pathway. An embedded case study was conducted of the outpatient THA care pathway at a teaching hospital in the Netherlands. The data were collected using a visual care modelling toolkit in 16 semi-structured interviews. Problems and inefficiencies in the care pathway were identified and addressed in the iterative design process. The results are two visual models of the most critical phases of the outpatient THA care pathway: diagnosis & preparation (1) and mobilisation & discharge (4). The results show the care team composition, critical value exchanges, and sequence that enable patient discharge on the day of surgery. The design addressed existing problems and is an optimisation of the case hospital's pathway. The network of actors consists of the patient (1), radiologist (1), anaesthetist (1), nurse specialist (1), pharmacist (1), orthopaedic surgeon (1,4), physiotherapist (1,4), nurse (4), doctor (4) and patient application (1,4). The critical value exchanges include patient preparation (mental and practical), patient education, aligned care team, efficient sequence of value exchanges, early patient mobilisation, flexible availability of the physiotherapist, functional discharge criteria, joint decision making and availability of the care team.

Materials Management: State of the Practice 2012

EPA Science Inventory

The report presents an evaluation of six materials management technologies that were assessed with respect to each technology's process, material and energy pathways, commercialization status, and associated economics. The inclusion and implementation of a materials recycling pr...

Improving Global Access to New Vaccines: Intellectual Property, Technology Transfer, and Regulatory Pathways

PubMed Central

2014-01-01

The 2012 World Health Assembly Global Vaccine Action Plan called for global access to new vaccines within 5 years of licensure. Current approaches have proven insufficient to achieve sustainable vaccine pricing within such a timeline. Paralleling the successful strategy of generic competition to bring down drug prices, a clear consensus is emerging that market entry of multiple suppliers is a critical factor in expeditiously bringing down prices of new vaccines. In this context, key target objectives for improving access to new vaccines include overcoming intellectual property obstacles, streamlining regulatory pathways for biosimilar vaccines, and reducing market entry timelines for developing-country vaccine manufacturers by transfer of technology and know-how. I propose an intellectual property, technology, and know-how bank as a new approach to facilitate widespread access to new vaccines in low- and middle-income countries by efficient transfer of patented vaccine technologies to multiple developing-country vaccine manufacturers. PMID:25211753

Improving global access to new vaccines: intellectual property, technology transfer, and regulatory pathways.

PubMed

Crager, Sara Eve

2014-11-01

The 2012 World Health Assembly Global Vaccine Action Plan called for global access to new vaccines within 5 years of licensure. Current approaches have proven insufficient to achieve sustainable vaccine pricing within such a timeline. Paralleling the successful strategy of generic competition to bring down drug prices, a clear consensus is emerging that market entry of multiple suppliers is a critical factor in expeditiously bringing down prices of new vaccines. In this context, key target objectives for improving access to new vaccines include overcoming intellectual property obstacles, streamlining regulatory pathways for biosimilar vaccines, and reducing market entry timelines for developing-country vaccine manufacturers by transfer of technology and know-how. I propose an intellectual property, technology, and know-how bank as a new approach to facilitate widespread access to new vaccines in low- and middle-income countries by efficient transfer of patented vaccine technologies to multiple developing-country vaccine manufacturers.

[Improving global access to new vaccines: intellectual property, technology transfer, and regulatory pathways].

PubMed

Crager, Sara Eve

2015-01-01

The 2012 World Health Assembly Global Vaccine Action Plan called for global access to new vaccines within 5 years of licensure. Current approaches have proven insufficient to achieve sustainable vaccine pricing within such a timeline. Paralleling the successful strategy of generic competition to bring down drug prices, a clear consensus is emerging that market entry of multiple suppliers is a critical factor in expeditiously bringing down prices of new vaccines. In this context, key target objectives for improving access to new vaccines include overcoming intellectual property obstacles, streamlining regulatory pathways for biosimilar vaccines, and reducing market entry timelines for developing-country vaccine manufacturers by transfer of technology and know-how. I propose an intellectual property, technology, and know-how bank as a new approach to facilitate widespread access to new vaccines in low- and middle-income countries by efficient transfer of patented vaccine technologies to multiple developing-country vaccine manufacturers.

Biallelic Alteration and Dysregulation of the Hippo Pathway in Mucinous Tubular and Spindle Cell Carcinoma of the Kidney.

PubMed

Mehra, Rohit; Vats, Pankaj; Cieslik, Marcin; Cao, Xuhong; Su, Fengyun; Shukla, Sudhanshu; Udager, Aaron M; Wang, Rui; Pan, Jincheng; Kasaian, Katayoon; Lonigro, Robert; Siddiqui, Javed; Premkumar, Kumpati; Palapattu, Ganesh; Weizer, Alon; Hafez, Khaled S; Wolf, J Stuart; Sangoi, Ankur R; Trpkov, Kiril; Osunkoya, Adeboye O; Zhou, Ming; Giannico, Giovanna; McKenney, Jesse K; Dhanasekaran, Saravana M; Chinnaiyan, Arul M

2016-11-01

Mucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare subtype of renal cell carcinoma (RCC) with distinctive morphologic and cytogenetic features. Here, we carry out whole-exome and transcriptome sequencing of a multi-institutional cohort of MTSCC (n = 22). We demonstrate the presence of either biallelic loss of Hippo pathway tumor suppressor genes (TSG) and/or evidence of alteration of Hippo pathway genes in 85% of samples. PTPN14 (31%) and NF2 (22%) were the most commonly implicated Hippo pathway genes, whereas other genes such as SAV1 and HIPK2 were also involved in a mutually exclusive fashion. Mutations in the context of recurrent chromosomal losses amounted to biallelic alterations in these TSGs. As a readout of Hippo pathway inactivation, a majority of cases (90%) exhibited increased nuclear YAP1 protein expression. Taken together, nearly all cases of MTSCC exhibit some evidence of Hippo pathway dysregulation. MTSCC is a rare and relatively recently described subtype of RCC. Next-generation sequencing of a multi-institutional MTSCC cohort revealed recurrent chromosomal losses and somatic mutations in the Hippo signaling pathway genes leading to potential YAP1 activation. In virtually all cases of MTSCC, there was evidence of Hippo pathway dysregulation, suggesting a common mechanistic basis for this disease. Cancer Discov; 6(11); 1258-66. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 1197. ©2016 American Association for Cancer Research.

Evaluation of additional biogeochemical impacts on mitigation pathways in an energy sytem integrated assessment model.

NASA Astrophysics Data System (ADS)

Dessens, O.

2017-12-01

Within the last IPCC AR5 a large and systematic sensitivity study around available technologies and timing of policies applied in IAMs to achieve the 2°C target has been conducted. However the simple climate representations included in IAMs are generally tuned to the results of ensemble means. This may result in hiding within the ensemble mean results possible challenging mitigation pathways for the economy or the technology future scenarios. This work provides new insights on the sensitivity of the socio-economic response to different climate factors under a 2°C climate change target in order to help guide future efforts to reduce uncertainty in the climate mitigation decisions. The main objective is to understand and bring new insights on how future global warming will affect the natural biochemical feedbacks on the climate system and what could be the consequences of these feedbacks on the anthropogenic emission pathways with a specific focus on the energy-economy system. It specifically focuses on three issues of the climate representation affecting the energy system transformation and GHG emissions pathways: 1- Impacts of the climate sensitivity (or TCR); 2- Impacts of warming on the radiative forcing (cloudiness,...); 3- Impacts of warming on the carbon cycle (carbon cycle feedback). We use the integrated assessment model TIAM-UCL to examine the mitigation pathways compatible with the 2C target depending on assumptions regarding the 3 issues of the climate representation introduced above. The following key conclusions drawn from this study are that mitigation to 2°C is still possible under strong climate sensitivity (TCR), strong carbon cycle amplification or positive radiative forcing feedback. However, this level of climate mitigation will require a significant transformation in the way we produce and consume energy. Carbon capture and sequestration on electricity generation, industry and biomass is part of the technology pool needed to achieve this level of decarbonisation. In extreme condition (positive correlation between the 3 issues discussed) the integrated assessment model TIAM-UCL creates pathways requiring additional negative emission technologies at the end of this century to keep temperature change well below 2°C.

Microfluidic molecular assay platform for the detection of miRNAs, mRNAs, proteins, and post-translational modifications at single-cell resolution

DOE PAGES

Wu, Meiye; Singh, Anup K.

2014-07-15

In this study, cell signaling is a dynamic and complex process. A typical signaling pathway may begin with activation of cell surface receptors, leading to activation kinase cascade that culminates in induction of mRNA and non-coding miRNA production in the nucleus, followed by modulation of mRNA expression by miRNAs in the cytosol, and end with production of proteins in response to the signaling pathway. Signaling pathways involve proteins, miRNA, and mRNAs, along with various forms of transient post-translational modifications, and detecting each type of signaling molecule requires categorically different sample preparation methods such as Western blotting for proteins, PCR formore » nucleic acids, and flow cytometry for post-translational modifications. Since we know that cells in populations behave heterogeneously1, especially in the cases of stem cells, cancer, and hematopoiesis, there is need for a new technology that provides capability to detect and quantify multiple categories of signaling molecules in intact single cells to provide a comprehensive view of the cell’s physiological state. In this technical brief, we describe our microfluidic platform with a portfolio of customized molecular assays that can detect nucleic acids, proteins, and post-translational modifications in single intact cells with >95% reduction in reagent requirement in under 8 hours.« less

Using Augmented Reality to Teach and Learn Biochemistry

ERIC Educational Resources Information Center

Vega Garzón, Juan Carlos; Magrini, Marcio Luiz; Galembeck, Eduardo

2017-01-01

Understanding metabolism and metabolic pathways constitutes one of the central aims for students of biological sciences. Learning metabolic pathways should be focused on the understanding of general concepts and core principles. New technologies such Augmented Reality (AR) have shown potential to improve assimilation of biochemistry abstract…

Kentucky Workforce Pathways Development

ERIC Educational Resources Information Center

Coburn, Karen L.

2017-01-01

The purpose of the study was to determine whether the advent of healthcare information technology was a viable career pathway for the people of northeastern Kentucky. The qualitative study used the Delphi Method to conduct and examine interviews with nine experts in Kentucky's workforce development, economic development, education, and healthcare…

MULTI-SENSOR REPORTER CELL TECHNOLOGY TO ASSESS HAZARD INVOLVING ENDOCRINE SIGNALING PATHWAYS

EPA Science Inventory

Results will define an experimental approach that can be used in a high-throughput format to evaluate the response of hormone signaling pathways and networks to individual chemicals or mixtures. The assay also will have application across species and would significantly reduce...

Concealed Accessory Pathways with a Single Ventricular and Two Discrete Atrial Insertion Sites.

PubMed

Kipp, Ryan T; Abu Sham'a, Raed; Hiroyuki, Ito; Han, Frederick T; Refaat, Marwan; Hsu, Jonathan C; Field, Michael E; Kopp, Douglas E; Marcus, Gregory M; Scheinman, Melvin M; Hoffmayer, Kurt S

2017-03-01

Atrioventricular reciprocating tachycardia (AVRT) utilizing a concealed accessory pathway is common. It is well appreciated that some patients may have multiple accessory pathways with separate atrial and ventricular insertion sites. We present three cases of AVRT utilizing concealed pathways with evidence that each utilizing a single ventricular insertion and two discrete atrial insertion sites. In case one, two discrete atrial insertion sites were mapped in two separate procedures, and only during the second ablation was the Kent potential identified. Ablation of the Kent potential at this site remote from the two atrial insertion sites resulted in the termination of the retrograde conduction in both pathways. Case two presented with supraventricular tachycardia (SVT) with alternating eccentric atrial activation patterns without alteration in the tachycardia cycle length. The two distinct atrial insertion sites during orthodromic AVRT and ventricular pacing were targeted and each of the two atrial insertion sites were successfully mapped and ablated. In case three, retrograde decremental conduction utilizing both atrial insertion sites was identified prior to ablation. After mapping and ablation of the first discrete atrial insertion site, tachycardia persisted utilizing the second atrial insertion site. Only after ablation of the second atrial insertion site was SVT noninducible, and VA conduction was no longer present. Concealed retrograde accessory pathways with discrete atrial insertion sites may have a common ventricular insertion site. Identification and ablation of the ventricular insertion site or the separate discrete atrial insertion sites result in successful treatment. © 2017 Wiley Periodicals, Inc.

Pathways to Commercial Success: Technologies and Products Supported by the Fuel Cell Technologies Office - 2015

DOE Office of Scientific and Technical Information (OSTI.GOV)

None, None

2016-01-08

This FY 2015 report updates the results of an effort to identify and document the commercial and emerging (projected to be commercialized within the next 3 to 5 years) hydrogen and fuel cell technologies and products that resulted from U.S. Department of Energy support through the Fuel Cell Technologies Office in the Office of Energy Efficiency and Renewable Energy.

Learning Technologies: Prospects and Pathways. Selected papers from EdTech '96 Biennial Conference of the Australian Society for Educational Technology (Melbourne, Australia, July 7-10, 1996).

ERIC Educational Resources Information Center

Hedberg, John G., Ed.; And Others

This book presents a series of conference papers dealing with educational technology. The papers are: "The Role of Educational Technology in Upgrading Teacher Education in Pakistan" (M. Hashim Abbasi and Alex C. Millar); "Report on the Teaching and Learning on the Internet Project--RMIT TAFE" (Laurie Armstrong); "A…

Tools, courses, and learning pathways offered by the National Interagency Fuels, Fire, and Vegetation Technology Transfer

Treesearch

Eva K. Strand; Kathy H. Schon; Jeff Jones

2010-01-01

Technological advances in the area of fuel and wildland fire management have created a need for effective decision support tools and technology training. The National Interagency Fuels Committee and LANDFIRE have chartered a team to develop science-based learning tools for assessment of fire and fuels and to provide online training and technology transfer to help...

Charting the Emergence of Corporate Procurement of Utility-Scale PV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heeter, Jenny S.; Cook, Jeffrey J.; Bird, Lori A.

Corporations and other institutions have contracted for more than 2300 MW of off-site solar, using power purchase agreements, green tariffs, or bilateral deals with utilities. This paper examines the benefits, challenges, and outlooks for large-scale off-site solar purchasing in the United States. Pathways differ based on where they are available, the hedge value they can provide, and their ease of implementation. The paper features case studies of an aggregate PPA (Massachusetts Institute of Technology, Boston Medical Center, and Post Office Square), a corporation exiting their incumbent utility (MGM Resorts), a utility offering large scale renewables to corporate customers (Alabama Powersmore » Renewable Procurement Program), and a company with approval to sell energy into wholesale markets (Google Energy Inc.).« less

Mutation analysis of the EGFR pathway genes, EGFR, RAS, PIK3CA, BRAF, and AKT1, in salivary gland adenoid cystic carcinoma.

PubMed

Saida, Kosuke; Murase, Takayuki; Ito, Mayuko; Fujii, Kana; Takino, Hisashi; Masaki, Ayako; Kawakita, Daisuke; Ijichi, Kei; Tada, Yuichiro; Kusafuka, Kimihide; Iida, Yoshiyuki; Onitsuka, Tetsuro; Yatabe, Yasushi; Hanai, Nobuhiro; Hasegawa, Yasuhisa; Shinomiya, Hitomi; Nibu, Ken-Ichi; Shimozato, Kazuo; Inagaki, Hiroshi

2018-03-30

Adenoid cystic carcinoma (AdCC), one of the most common salivary gland carcinomas, usually has a fatal outcome. Epidermal growth factor receptor (EGFR) pathway gene mutations are important in predicting a patient's prognosis and estimating the efficacy of molecular therapy targeting the EGFR pathway. In this study of salivary gland AdCC (SAdCC), we looked for gene mutations in EGFR, RAS family ( KRAS, HRAS, and NRAS ), PIK3CA, BRAF, and AKT1 , using a highly sensitive single-base extension multiplex assay, SNaPshot. Out of 70 cases, EGFR pathway missense mutations were found in 13 (18.6%): RAS mutations in 10 (14.3%), EGFR in one (1.4%), and PIK3CA in 5 (7.1%). None of the cases showed an EGFR deletion by direct sequencing. Concurrent gene mutations were found in three cases (4.3%). EGFR pathway mutations were significantly associated with a shorter disease-free ( p = 0.011) and overall survival ( p = 0.049) and RAS mutations were as well; ( p = 0.010) and ( p = 0.024), respectively. The gene fusion status as determined by a FISH assay had no significant association with mutations of the genes involved in the EGFR pathway. In conclusion, EGFR pathway mutations, especially RAS mutations, may be frequent in SAdCC, and associated with a poor prognosis for the patient.

Transforming exoelectrogens for biotechnology using synthetic biology.

PubMed

TerAvest, Michaela A; Ajo-Franklin, Caroline M

2016-04-01

Extracellular electron transfer pathways allow certain bacteria to transfer energy between intracellular chemical energy stores and extracellular solids through redox reactions. Microorganisms containing these pathways, exoelectrogens, are a critical part of microbial electrochemical technologies that aim to impact applications in bioenergy, biosensing, and biocomputing. However, there are not yet any examples of economically viable microbial electrochemical technologies due to the limitations of naturally occurring exoelectrogens. Here we first briefly summarize recent discoveries in understanding extracellular electron transfer pathways, then review in-depth the creation of customized and novel exoelectrogens for biotechnological applications. We analyze engineering efforts to increase current production in native exoelectrogens, which reveals that modulating certain processes within extracellular electron transfer are more effective than others. We also review efforts to create new exoelectrogens and highlight common challenges in this work. Lastly, we summarize work utilizing engineered exoelectrogens for biotechnological applications and the key obstacles to their future development. Fueled by the development of genetic tools, these approaches will continue to expand and genetically modified organisms will continue to improve the outlook for microbial electrochemical technologies. © 2015 Wiley Periodicals, Inc.

Assessment of environmental co-benefits of energy system decarbonisation - the case of UK air quality using Remote Sensing and Model simulations

NASA Astrophysics Data System (ADS)

Sobral Mourao, Z.; Konadu, D. D.; Damoah, R.

2016-12-01

The UK has a binding obligation to reduce GHG emission by 80% (based on 1990 levels) by 2050. Meeting this target requires extensive decarbonisation of the UK energy system. Different pathways that achieve this target at the lowest system costs are being explored at different levels of policy and decisions on future energy infrastructure. Whilst benefits of decarbonisation are mainly focused on the impacts on climate change, there are other potential environmental and health impacts such as air-quality. In particular, a decrease in fossil fuel use by directly substituting current systems with low-carbon technologies could lead to significant reductions in the concentrations of SO2, NOX, CO and other atmospheric pollutants. So far, the proposed decarbonisation pathways tend to target the electricity sector first, followed by a transition in transport and heating technologies and use. However, the spatial dimension of where short term changes in the energy sector occur in relation to high density population areas is not taken into account when defining the energy transition strategies. This may lead to limited short-term improvements in air quality within urban areas, where use of fossil fuels for heating and transport is the main contribution to overall atmospheric pollutant levels. It is therefore imperative to explore decarbonisation strategies that prioritise transition in sectors of the energy system that produce immediate improvements in air quality in key regions of the UK. This study aims to use a combination of Remote Sensing observations and atmospheric chemistry/transport modelling approaches to estimate and map the atmospheric pollutants impact of the traditional approach of decarbonising electricity first compared to a slower transition in the electricity sector, but faster change in end use sectors (heating and transport). This would provide an additional standard to compare future energy system pathways beyond the traditional metrics of cost and GHG emissions reductions.

Integrated RNA-Seq and sRNA-Seq Analysis Identifies Chilling and Freezing Responsive Key Molecular Players and Pathways in Tea Plant (Camellia sinensis)

PubMed Central

Zheng, Chao; Zhao, Lei; Wang, Yu; Shen, Jiazhi; Zhang, Yinfei; Jia, Sisi; Li, Yusheng; Ding, Zhaotang

2015-01-01

Tea [Camellia sinensis (L) O. Kuntze, Theaceae] is one of the most popular non-alcoholic beverages worldwide. Cold stress is one of the most severe abiotic stresses that limit tea plants’ growth, survival and geographical distribution. However, the genetic regulatory network and signaling pathways involved in cold stress responses in tea plants remain unearthed. Using RNA-Seq, DGE and sRNA-Seq technologies, we performed an integrative analysis of miRNA and mRNA expression profiling and their regulatory network of tea plants under chilling (4℃) and freezing (-5℃) stress. Differentially expressed (DE) miRNA and mRNA profiles were obtained based on fold change analysis, miRNAs and target mRNAs were found to show both coherent and incoherent relationships in the regulatory network. Furthermore, we compared several key pathways (e.g., ‘Photosynthesis’), GO terms (e.g., ‘response to karrikin’) and transcriptional factors (TFs, e.g., DREB1b/CBF1) which were identified as involved in the early chilling and/or freezing response of tea plants. Intriguingly, we found that karrikins, a new group of plant growth regulators, and β-primeverosidase (BPR), a key enzyme functionally relevant with the formation of tea aroma might play an important role in both early chilling and freezing response of tea plants. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis further confirmed the results from RNA-Seq and sRNA-Seq analysis. This is the first study to simultaneously profile the expression patterns of both miRNAs and mRNAs on a genome-wide scale to elucidate the molecular mechanisms of early responses of tea plants to cold stress. In addition to gaining a deeper insight into the cold resistant characteristics of tea plants, we provide a good case study to analyse mRNA/miRNA expression and profiling of non-model plant species using next-generation sequencing technology. PMID:25901577

Integrated RNA-Seq and sRNA-Seq Analysis Identifies Chilling and Freezing Responsive Key Molecular Players and Pathways in Tea Plant (Camellia sinensis).

PubMed

Zheng, Chao; Zhao, Lei; Wang, Yu; Shen, Jiazhi; Zhang, Yinfei; Jia, Sisi; Li, Yusheng; Ding, Zhaotang

2015-01-01

Tea [Camellia sinensis (L) O. Kuntze, Theaceae] is one of the most popular non-alcoholic beverages worldwide. Cold stress is one of the most severe abiotic stresses that limit tea plants' growth, survival and geographical distribution. However, the genetic regulatory network and signaling pathways involved in cold stress responses in tea plants remain unearthed. Using RNA-Seq, DGE and sRNA-Seq technologies, we performed an integrative analysis of miRNA and mRNA expression profiling and their regulatory network of tea plants under chilling (4℃) and freezing (-5℃) stress. Differentially expressed (DE) miRNA and mRNA profiles were obtained based on fold change analysis, miRNAs and target mRNAs were found to show both coherent and incoherent relationships in the regulatory network. Furthermore, we compared several key pathways (e.g., 'Photosynthesis'), GO terms (e.g., 'response to karrikin') and transcriptional factors (TFs, e.g., DREB1b/CBF1) which were identified as involved in the early chilling and/or freezing response of tea plants. Intriguingly, we found that karrikins, a new group of plant growth regulators, and β-primeverosidase (BPR), a key enzyme functionally relevant with the formation of tea aroma might play an important role in both early chilling and freezing response of tea plants. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis further confirmed the results from RNA-Seq and sRNA-Seq analysis. This is the first study to simultaneously profile the expression patterns of both miRNAs and mRNAs on a genome-wide scale to elucidate the molecular mechanisms of early responses of tea plants to cold stress. In addition to gaining a deeper insight into the cold resistant characteristics of tea plants, we provide a good case study to analyse mRNA/miRNA expression and profiling of non-model plant species using next-generation sequencing technology.

Thermal evolution of the metastable r8 and bc8 polymorphs of silicon

DOE PAGES

Haberl, Bianca; Guthrie, Malcolm; Sinogeikin, Stanislav V.; ...

2015-01-28

The kinetics of two metastable polymorphs of silicon under thermal annealing was investigated. These phases with body-centered cubic bc8 and rhombohedral r8 structures can be formed upon pressure release from metallic silicon.We study these metastable polymorphs were formed by two different methods, via point loading and in a diamond anvil cell (DAC). Upon thermal annealing different transition pathways were detected. In the point loading case, the previously reported Si-XIII formed and was confirmed as a new phase with an as-yet-unidentified structure. In the DAC case, bc8-Si transformed to the hexagonal-diamond structure at elevated pressure, consistent with previous studies at ambientmore » pressure. In contrast, r8-Si transformed directly to diamond-cubic Si at a temperature of 255⁰C. In conclusion, these data were used to construct diagrams of the metastability regimes of the polymorphs formed in a DAC and may prove useful for potential technological applications of these metastable polymorphs.« less

Thermal evolution of the metastable r8 and bc8 polymorphs of silicon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haberl, Bianca; Guthrie, Malcolm; Sinogeikin, Stanislav V.

The kinetics of two metastable polymorphs of silicon under thermal annealing was investigated. These phases with body-centered cubic bc8 and rhombohedral r8 structures can be formed upon pressure release from metallic silicon.We study these metastable polymorphs were formed by two different methods, via point loading and in a diamond anvil cell (DAC). Upon thermal annealing different transition pathways were detected. In the point loading case, the previously reported Si-XIII formed and was confirmed as a new phase with an as-yet-unidentified structure. In the DAC case, bc8-Si transformed to the hexagonal-diamond structure at elevated pressure, consistent with previous studies at ambientmore » pressure. In contrast, r8-Si transformed directly to diamond-cubic Si at a temperature of 255⁰C. In conclusion, these data were used to construct diagrams of the metastability regimes of the polymorphs formed in a DAC and may prove useful for potential technological applications of these metastable polymorphs.« less

Neuroethics, confidentiality, and a cultural imperative in early onset Alzheimer disease: a case study with a First Nation population

PubMed Central

2013-01-01

The meaningful consideration of cultural practices, values and beliefs is a necessary component in the effective translation of advancements in neuroscience to clinical practice and public discourse. Society’s immense investment in biomedical science and technology, in conjunction with an increasingly diverse socio-cultural landscape, necessitates the study of how potential discoveries in neurodegenerative diseases such as Alzheimer disease are perceived and utilized across cultures. Building on the work of neuroscientists, ethicists and philosophers, we argue that the growing field of neuroethics provides a pragmatic and constructive pathway to guide advancements in neuroscience in a manner that is culturally nuanced and relevant. Here we review a case study of one issue in culturally oriented neuroscience research where it is evident that traditional research ethics must be broadened and the values and needs of diverse populations considered for meaningful and relevant research practices. A global approach to neuroethics has the potential to furnish critical engagement with cultural considerations of advancements in neuroscience. PMID:24131854

Recycling potential of neodymium: the case of computer hard disk drives.

PubMed

Sprecher, Benjamin; Kleijn, Rene; Kramer, Gert Jan

2014-08-19

Neodymium, one of the more critically scarce rare earth metals, is often used in sustainable technologies. In this study, we investigate the potential contribution of neodymium recycling to reducing scarcity in supply, with a case study on computer hard disk drives (HDDs). We first review the literature on neodymium production and recycling potential. From this review, we find that recycling of computer HDDs is currently the most feasible pathway toward large-scale recycling of neodymium, even though HDDs do not represent the largest application of neodymium. We then use a combination of dynamic modeling and empirical experiments to conclude that within the application of NdFeB magnets for HDDs, the potential for loop-closing is significant: up to 57% in 2017. However, compared to the total NdFeB production capacity, the recovery potential from HDDs is relatively small (in the 1-3% range). The distributed nature of neodymium poses a significant challenge for recycling of neodymium.

Cultivating Science Identity through Sources of Self-Efficacy

ERIC Educational Resources Information Center

Flowers, Alonzo M., III; Banda, Rosa

2016-01-01

Purpose: In an attempt to understand the postsecondary and occupational pathways of minorities who choose to pursue science, technology, engineering and mathematics (STEM) pathways, what this paper offers is an examination of literature that focuses on identity. More specifically, this paper aims to present a research argument that highlights the…

Atomic layer deposition (ALD) for optical nanofabrication

NASA Astrophysics Data System (ADS)

Maula, Jarmo

2010-02-01

ALD is currently one of the most rapidly developing fields of thin film technology. Presentation gives an overview of ALD technology for optical film deposition, highlighting benefits, drawbacks and peculiarities of the ALD, especially compared to PVD. Viewpoint is practical, based on experience gained from tens of different applications over the last few decades. ALD is not competing, but enabling technology to provide coatings, which are difficult for traditional technologies. Examples of such cases are films inside of tubes; double side deposition on the substrate; large area accurate coatings; decorative coating for 3D parts; conformal coatings on high aspect ratio surfaces or inside porous structures. Novel materials can be easily engineered by making modifications on molecular level. ALD coats large surfaces effectively and fast. Opposite to common view, it actually provides high throughput (coated area/time), when used properly with a batch and/or in-line tools. It is possible to use ALD for many micrometers thick films or even produce thin parts with competitive cost. Besides optical films ALD provides large variety of features for nanofabrication. For example pin hole free films for passivation and barrier applications and best available films for conformal coatings like planarization or to improve surface smoothness. High deposition repeatability even with subnanometer film structures helps fabrication. ALD enters to production mostly through new products, not yet existing on the market and so the application IP field is reasonably open. ALD is an enabling, mature technology to fabricate novel optical materials and to open pathways for new applications.

Search Pathways: Modeling GeoData Search Behavior to Support Usable Application Development

NASA Astrophysics Data System (ADS)

Yarmey, L.; Rosati, A.; Tressel, S.

2014-12-01

Recent technical advances have enabled development of new scientific data discovery systems. Metadata brokering, linked data, and other mechanisms allow users to discover scientific data of interes across growing volumes of heterogeneous content. Matching this complex content with existing discovery technologies, people looking for scientific data are presented with an ever-growing array of features to sort, filter, subset, and scan through search returns to help them find what they are looking for. This paper examines the applicability of available technologies in connecting searchers with the data of interest. What metrics can be used to track success given shifting baselines of content and technology? How well do existing technologies map to steps in user search patterns? Taking a user-driven development approach, the team behind the Arctic Data Explorer interdisciplinary data discovery application invested heavily in usability testing and user search behavior analysis. Building on earlier library community search behavior work, models were developed to better define the diverse set of thought processes and steps users took to find data of interest, here called 'search pathways'. This research builds a deeper understanding of the user community that seeks to reuse scientific data. This approach ensures that development decisions are driven by clearly articulated user needs instead of ad hoc technology trends. Initial results from this research will be presented along with lessons learned for other discovery platform development and future directions for informatics research into search pathways.

Life cycle environmental impacts of wastewater-based algal biofuels.

PubMed

Mu, Dongyan; Min, Min; Krohn, Brian; Mullins, Kimberley A; Ruan, Roger; Hill, Jason

2014-10-07

Recent research has proposed integrating wastewater treatment with algae cultivation as a way of producing algal biofuels at a commercial scale more sustainably. This study evaluates the environmental performance of wastewater-based algal biofuels with a well-to-wheel life cycle assessment (LCA). Production pathways examined include different nutrient sources (municipal wastewater influent to the activated sludge process, centrate from the sludge drying process, swine manure, and freshwater with synthetic fertilizers) combined with emerging biomass conversion technologies (microwave pyrolysis, combustion, wet lipid extraction, and hydrothermal liquefaction). Results show that the environmental performance of wastewater-based algal biofuels is generally better than freshwater-based algal biofuels, but depends on the characteristics of the wastewater and the conversion technologies. Of 16 pathways compared, only the centrate cultivation with wet lipid extraction pathway and the centrate cultivation with combustion pathway have lower impacts than petroleum diesel in all environmental categories examined (fossil fuel use, greenhouse gas emissions, eutrophication potential, and consumptive water use). The potential for large-scale implementation of centrate-based algal biofuel, however, is limited by availability of centrate. Thus, it is unlikely that algal biofuels can provide a large-scale and environmentally preferable alternative to petroleum transportation fuels without considerable improvement in current production technologies. Additionally, the cobenefit of wastewater-based algal biofuel production as an alternate means of treating various wastewaters should be further explored.

Enabling Equal Access to Molecular Diagnostics: What Are the Implications for Policy and Health Technology Assessment?

PubMed

Plun-Favreau, Juliette; Immonen-Charalambous, Kaisa; Steuten, Lotte; Strootker, Anja; Rouzier, Roman; Horgan, Denis; Lawler, Mark

2016-01-01

Molecular diagnostics can offer important benefits to patients and are a key enabler of the integration of personalised medicine into health care systems. However, despite their promise, few molecular diagnostics are embedded into clinical practice (especially in Europe) and access to these technologies remains unequal across countries and sometimes even within individual countries. If research translation and the regulatory environments have proven to be more challenging than expected, reimbursement and value assessment remain the main barriers to providing patients with equal access to molecular diagnostics. Unclear or non-existent reimbursement pathways, together with the lack of clear evidence requirements, have led to significant delays in the assessment of molecular diagnostics technologies in certain countries. Additionally, the lack of dedicated diagnostics budgets and the siloed nature of resource allocation within certain health care systems have significantly delayed diagnostics commissioning. This article will consider the perspectives of different stakeholders (patients, health care payers, health care professionals, and manufacturers) on the provision of a research-enabled, patient-focused molecular diagnostics platform that supports optimal patient care. Through the discussion of specific case studies, and building on the experience from countries that have successfully integrated molecular diagnostics into clinical practice, this article will discuss the necessary evolutions in policy and health technology assessment to ensure that patients can have equal access to appropriate molecular diagnostics. © 2016 S. Karger AG, Basel.

Maximizing Residential Energy Savings: Net Zero Energy House (ZEH) Technology Pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, R.; Roberts, D.

To meet current U.S. Department of Energy zero-energy home performance goals, new technologies and solutions must increase whole-house efficiency savings by an additional 40% relative to those provided by best available components and systems.

2015 Accomplishments Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

None, None

This report covers selected highlights from the four research pathways in the LWRS Program: Materials Aging and Degradation; Risk-Informed Safety Margin Characterization; Advanced Instrumentation, Information, and Control Systems Technologies; and Reactor Safety Technologies, as well as a look-ahead at planned activities for 2017.

2016 Accomplishments Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

None, None

This report covers selected highlights from the four research pathways in the LWRS Program: Materials Aging and Degradation; Risk-Informed Safety Margin Characterization; Advanced Instrumentation, Information, and Control Systems Technologies; and Reactor Safety Technologies, as well as a look-ahead at planned activities for 2017.

Pathways Triple P and the Child Welfare System: A Promising Fit.

PubMed

Petra, Megan; Kohl, Patricia

2010-04-01

Parents referred to the child welfare system following maltreatment allegations are often ill-prepared to constructively address child disruptive behaviors, despite the high prevalence of these behaviors among this population. Evidence-based parent-mediated interventions are effective in improving parenting skills; however, they are rarely offered within the child welfare system. The purpose of this pilot project was to evaluate the fit and acceptability of one parent-mediated training program (Pathways Triple P) to case managers and parents within this system of care. We implemented Pathways Triple P and subsequently interviewed referring case managers and parents who had participated in the program. Case managers felt the program would work well within the existing child welfare system and would help them to better serve parents. They felt the program had potential to improve parenting skills and prevent future maltreatment. Parents appreciated the program's use of diverse methods, and the variety of parenting techniques taught. In keeping with case manager expectations, participants reported that their enhanced parenting skills and new ability to use non-physical discipline resulted in a better home life. We conclude that Pathways Triple P fits well within the child welfare system and is acceptable to both case managers and parents within this system.

Successful catheter ablation of a left anterior accessory pathway from the non-coronary cusp of the aortic valve.

PubMed

Laranjo, Sérgio; Oliveira, Mário; Trigo, Conceição

2015-08-01

Left anterior accessory pathways are considered to be rare findings. Catheter ablation of accessory pathways in this location remains a challenging target, and few reports about successful ablation of these accessory pathways are available. We describe our experience regarding a case of a manifest left anterior accessory pathway ablation using radiofrequency energy at the junction of the left coronary cusp with the non-coronary cusp.

Hydrogen Pathways: Updated Cost, Well-to-Wheels Energy Use, and Emissions for the Current Technology Status of Ten Hydrogen Production, Delivery, and Distribution Scenarios

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramsden, T.; Ruth, M.; Diakov, V.

2013-03-01

This report describes a life-cycle assessment conducted by the National Renewable Energy Laboratory (NREL) of 10 hydrogen production, delivery, dispensing, and use pathways that were evaluated for cost, energy use, and greenhouse gas (GHG) emissions. This evaluation updates and expands on a previous assessment of seven pathways conducted in 2009. This study summarizes key results, parameters, and sensitivities to those parameters for the 10 hydrogen pathways, reporting on the levelized cost of hydrogen in 2007 U.S. dollars as well as life-cycle well-to-wheels energy use and GHG emissions associated with the pathways.

CRISPRi-sRNA: Transcriptional-Translational Regulation of Extracellular Electron Transfer in Shewanella oneidensis.

PubMed

Cao, Yingxiu; Li, Xiaofei; Li, Feng; Song, Hao

2017-09-15

Extracellular electron transfer (EET) in Shewanella oneidensis MR-1, which is one of the most well-studied exoelectrogens, underlies many microbial electrocatalysis processes, including microbial fuel cells, microbial electrolysis cells, and microbial electrosynthesis. However, regulating the efficiency of EET remains challenging due to the lack of efficient genome regulation tools that regulate gene expression levels in S. oneidensis. Here, we systematically established a transcriptional regulation technology, i.e., clustered regularly interspaced short palindromic repeats interference (CRISPRi), in S. oneidensis MR-1 using green fluorescent protein (GFP) as a reporter. We used this CRISPRi technology to repress the expression levels of target genes, individually and in combination, in the EET pathways (e.g., the MtrCAB pathway and genes affecting the formation of electroactive biofilms in S. oneidensis), which in turn enabled the efficient regulation of EET efficiency. We then established a translational regulation technology, i.e., Hfq-dependent small regulatory RNA (sRNA), in S. oneidensis by repressing the GFP reporter and mtrA, which is a critical gene in the EET pathways in S. oneidensis. To achieve coordinated transcriptional and translational regulation at the genomic level, the CRISPRi and Hfq-dependent sRNA systems were incorporated into a single plasmid harbored in a recombinant S. oneidensis strain, which enabled an even higher efficiency of mtrA gene repression in the EET pathways than that achieved by the CRISPRi and Hfq-dependent sRNA system alone, as exhibited by the reduced electricity output. Overall, we developed a combined CRISPRi-sRNA method that enabled the synergistic transcriptional and translational regulation of target genes in S. oneidensis. This technology involving CRISPRi-sRNA transcriptional-translational regulation of gene expression at the genomic level could be applied to other microorganisms.

Computer Support for Knowledge Communication in Science Exhibitions: Novel Perspectives from Research on Collaborative Learning

ERIC Educational Resources Information Center

Knipfer, Kristin; Mayr, Eva; Zahn, Carmen; Schwan, Stephan; Hesse, Friedrich W.

2009-01-01

In this article, the potentials of advanced technologies for learning in science exhibitions are outlined. For this purpose, we conceptualize science exhibitions as "dynamic information space for knowledge building" which includes three pathways of knowledge communication. This article centers on the second pathway, that is, knowledge…

78 FR 65715 - Request for Comments on the Program Solicitation for the Advanced Technological Education Program...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-01

... academic institutions and industry to promote improvement in the education of science and engineering...; professional development of college faculty and secondary school teachers; career pathways to two-year colleges from secondary schools and from two-year colleges to four-year institutions; career pathways that lead...

Pathways to STEMM Professions for Students from Noncollege Homes

ERIC Educational Resources Information Center

Miller, Jon D.; Pearson, Willie, Jr.

2012-01-01

In this article we use data from the Longitudinal Study of American Youth to examine the influence of parent education on pathways to science, technology, engineering, mathematics, and medicine (STEMM) professions. Building on a general model of factors related to STEMM education and employment, we employ a two-group structural equation model to…

A Longitudinal Analysis of Young Adult Pathways to STEMH Occupations

ERIC Educational Resources Information Center

Fletcher, Edward C., Jr.; Tyson, Will

2017-01-01

In this study, we determined the educational pathways and key life course transitions of young adults who enter Science, Technology, Engineering, Mathematics, and Health (STEMH) technician and professional jobs using the 1997 National Longitudinal Survey of Youth (NLSY) dataset, tracking high school students from 1997 to adulthood in 2009. Using…

Pathways for Learning from 3D Technology

ERIC Educational Resources Information Center

Carrier, L. Mark; Rab, Saira S.; Rosen, Larry D.; Vasquez, Ludivina; Cheever, Nancy A.

2012-01-01

The purpose of this study was to find out if 3D stereoscopic presentation of information in a movie format changes a viewer's experience of the movie content. Four possible pathways from 3D presentation to memory and learning were considered: a direct connection based on cognitive neuroscience research; a connection through "immersion"…

Updating Status: Tracing College Women's Diverging Educational Pathways with Facebook

ERIC Educational Resources Information Center

Allaman, Erin

2013-01-01

As young people incorporate digital media into the ecologies of their daily lives, new technologies play an important role in how they experience higher education while simultaneously creating a digital record of their educational pathways. Little research has been conducted that explores how Millennials' forays into college life are defined…

Diversity in Pathways to Parenthood: Patterns, Implications, and Emerging Research Directions

ERIC Educational Resources Information Center

Smock, Pamela J.; Greenland, Fiona Rose

2010-01-01

This review examines and synthesizes recent research on pathways to parenthood. We begin by providing basic information about patterns, differentials, and trends and discussing adoption and new reproductive technologies. We next turn to several areas of inquiry that became particularly prominent in the last decade: the continued "decoupling" of…

Southern Pennsylvania's Industrial Pipeline: "Pathways" Program Helps Local Manufacturers Find Quality Workers

ERIC Educational Resources Information Center

Dixon, John; Girifalco, Tony; Yakabosky, Walt

2008-01-01

This article describes the Applied Engineering Technology (AET) Career and Educational Pathways Program, which helps local manufacturers find quality workers. The program features 32 high schools, three community colleges, and 10 four-year institutions offering an integrated regional system of applied engineering education. The goal is to enroll…

Advising and Progress in the Community College STEM Transfer Pathway

ERIC Educational Resources Information Center

Packard, Becky Wai-Ling; Jeffers, Kimberly C.

2013-01-01

Community college students enrolled in science and technology fields face many challenges as they pursue transfer pathways to earn a 4-year degree. Despite clear links to student persistence, advising interactions that facilitate or inhibit transfer progress are not clearly understood. In this study, 82 community college students pursuing science…

Linking social change and developmental change: shifting pathways of human development.

PubMed

Greenfield, Patricia M

2009-03-01

P. M. Greenfield's new theory of social change and human development aims to show how changing sociodemographic ecologies alter cultural values and learning environments and thereby shift developmental pathways. Worldwide sociodemographic trends include movement from rural residence, informal education at home, subsistence economy, and low-technology environments to urban residence, formal schooling, commerce, and high-technology environments. The former ecology is summarized by the German term Gemeinschaft ("community") and the latter by the German term Gesellschaft ("society"; Tönnies, 1887/1957). A review of empirical research demonstrates that, through adaptive processes, movement of any ecological variable in a Gesellschaft direction shifts cultural values in an individualistic direction and developmental pathways toward more independent social behavior and more abstract cognition--to give a few examples of the myriad behaviors that respond to these sociodemographic changes. In contrast, the (much less frequent) movement of any ecological variable in a Gemeinschaft direction is predicted to move cultural values and developmental pathways in the opposite direction. In conclusion, sociocultural environments are not static either in the developed or the developing world and therefore must be treated dynamically in developmental research.

Future Climate Prediction of Urban Atmosphere in A Tropical Megacity: Utilization of RCP/SSP Scenarios with an Urban Growth Model

NASA Astrophysics Data System (ADS)

Darmanto, N. S.; Varquez, A. C. G.; Kanda, M.; Takakuwa, S.

2016-12-01

Economic development in Southeast Asia megacities leads to rapid transformation into more complicated urban configurations. These configurations, including building geometry, enhance aerodynamic drag thus reducing near-surface wind speeds. Roughness parameters representing building geometry, along with anthropogenic heat emissions, contribute to the formation of urban heat islands (UHI). All these have been reproduced successfully in the Weather Research and Forecasting (WRF) Model coupled with an improved single-layer urban canopy model incorporating a realistic distribution of urban parameters and anthropogenic heat emission in the Jakarta Greater Area. We apply this technology to climate change studies by introducing future urbanization defined by urban sprawl, vertical rise in buildings, and increase anthropogenic heat emission (AHE) due to population changes, into futuristic climate modelling. To simulate 2050s future climate, pseudo-global warming method was used which relied on current and ensembles of 5 CMIP5 GCMs for 2 representative concentration pathways (RCP), 2.6 and 8.5. To determine future urbanization level, 2050 population growth and energy consumption were estimated from shared socioeconomic pathways (SSP). This allows the estimation of future urban sprawl, building geometry, and AHE using the SLEUTH urban growth model and spatial growth assumptions. Two cases representing combinations of RCP and SSP were simulated in WRF: RCP2.6-SSP1 and RCP8.5-SSP3. Each case corresponds to best and worst-case scenarios of implementing adaptation and mitigation strategies, respectively. It was found that 2-m temperature of Jakarta will increase by 0.62°C (RCP2.6) and 1.44°C (RCP8.5) solely from background climate change; almost on the same magnitude as the background temperature increase of RCP2.6 (0.5°C) and RCP8.5 (1.2°C). Compared with previous studies, the result indicates that the effect of climate change on UHI in tropical cities may be lesser than cities located in the mid-latitudes. However, it is expected that the combined effect of urbanization and climate change will result to significant changes on future urban temperature. ACK: This research was supported by the Environment Research and Technology Development Fund (S-14) of the Ministry of the Environment, Japan.

Global health and climate change: moving from denial and catastrophic fatalism to positive action.

PubMed

Costello, Anthony; Maslin, Mark; Montgomery, Hugh; Johnson, Anne M; Ekins, Paul

2011-05-13

The health effects of climate change have had relatively little attention from climate scientists and governments. Climate change will be a major threat to population health in the current century through its potential effects on communicable disease, heat stress, food and water security, extreme weather events, vulnerable shelter and population migration. This paper addresses three health-sector strategies to manage the health effects of climate change-promotion of mitigation, tackling the pathways that lead to ill-health and strengthening health systems. Mitigation of greenhouse gas (GHG) emissions is affordable, and low-carbon technologies are available now or will be in the near future. Pathways to ill-health can be managed through better information, poverty reduction, technological innovation, social and cultural change and greater coordination of national and international institutions. Strengthening health systems requires increased investment in order to provide effective public health responses to climate-induced threats to health, equitable treatment of illness, promotion of low-carbon lifestyles and renewable energy solutions within health facilities. Mitigation and adaptation strategies will produce substantial benefits for health, such as reductions in obesity and heart disease, diabetes, stress and depression, pneumonia and asthma, as well as potential cost savings within the health sector. The case for mitigating climate change by reducing GHGs is overwhelming. The need to build population resilience to the global health threat from already unavoidable climate change is real and urgent. Action must not be delayed by contrarians, nor by catastrophic fatalists who say it is all too late. © 2011 Royal Society

A Framework for the Next Generation of Risk Science

PubMed Central

Krewski, Daniel; Andersen, Melvin E.; Paoli, Gregory M.; Chiu, Weihsueh A.; Al-Zoughool, Mustafa; Croteau, Maxine C.; Burgoon, Lyle D.; Cote, Ila

2014-01-01

Objectives: In 2011, the U.S. Environmental Protection Agency initiated the NexGen project to develop a new paradigm for the next generation of risk science. Methods: The NexGen framework was built on three cornerstones: the availability of new data on toxicity pathways made possible by fundamental advances in basic biology and toxicological science, the incorporation of a population health perspective that recognizes that most adverse health outcomes involve multiple determinants, and a renewed focus on new risk assessment methodologies designed to better inform risk management decision making. Results: The NexGen framework has three phases. Phase I (objectives) focuses on problem formulation and scoping, taking into account the risk context and the range of available risk management decision-making options. Phase II (risk assessment) seeks to identify critical toxicity pathway perturbations using new toxicity testing tools and technologies, and to better characterize risks and uncertainties using advanced risk assessment methodologies. Phase III (risk management) involves the development of evidence-based population health risk management strategies of a regulatory, economic, advisory, community-based, or technological nature, using sound principles of risk management decision making. Conclusions: Analysis of a series of case study prototypes indicated that many aspects of the NexGen framework are already beginning to be adopted in practice. Citation: Krewski D, Westphal M, Andersen ME, Paoli GM, Chiu WA, Al-Zoughool M, Croteau MC, Burgoon LD, Cote I. 2014. A framework for the next generation of risk science. Environ Health Perspect 122:796–805; http://dx.doi.org/10.1289/ehp.1307260 PMID:24727499

Pathways to Commercial Success: Technologies and Innovations Enabled by the U.S. Department of Energy Fuel Cell Technologies Office

DOE Office of Scientific and Technical Information (OSTI.GOV)

None, None

This report published in October 2017 updates the results of an effort to identify and document the commercial and emerging (projected to be commercialized within the next 3 to 5 years) hydrogen and fuel cell technologies and products that resulted from U.S. Department of Energy support through the Fuel Cell Technologies Office in the Office of Energy Efficiency and Renewable Energy.

A proteomics study of hyperhomocysteinemia injury of the hippocampal neurons using iTRAQ.

PubMed

Fang, Min; Wang, Jing; Yan, Han; Zhao, Yan-Xin; Liu, Xue-Yuan

2014-11-01

High levels of homocysteine, caused by abnormal methionine metabolism, can induce degeneration of mouse hippocampal neurons. iTRAQ™ technology has been widely used in the field of proteomics research and through employing this technology, the present study identified that hyperhomocysteinemia induced the downregulation of 52 proteins and upregulation of 44 proteins in the mouse hippocampus. Through gene ontology and pathway analysis, the upregulation of components of the cytoskeleton, actin, regulators of focal adhesion, calcium signaling pathways, tight junctions, ErbB and gonadotrophin‑releasing hormone signaling, leukocyte, transendothelial migration, propanoate and pyruvate metabolism, valine, leucine and isoleucine biosynthesis, synthesis and degradation of ketone bodies and benzoate degradation via CoA ligation pathway, was identified. It was additionally verified that tau protein was highly expressed in the hyperhomocysteinemic neurons. Further analysis revealed that tau network proteins played functional roles in homocysteine‑induced neuronal damage.

Reflections on a Career in Second Language Studies: Promising Pathways for Future Research

ERIC Educational Resources Information Center

Cohen, Andrew D.

2018-01-01

This article highlights a series of areas deemed worthy of attention by L2 researchers. In some cases the research effort would entail following up on studies initiated some years ago and in other cases the effort would involve relatively new research thrusts. The article includes ideas about research regarding: (1) "pathways to success in…

Pathways to Death Row for America's Disabled Youth: Three Case Studies Driving Reform

ERIC Educational Resources Information Center

Schroeder, Julie; Guin, Cecile C.; Chaisson, Rebecca; Houchins, David

2004-01-01

This article uses the case study method to examine the lives of three youths with disabilities living in the southern part of the United States who have followed a pathway to death row. An empirically established developmental and theoretical framework is used to examine issues related to the influence of disabilities and race on children and…

In response to 'Can sugars be produced from fatty acids? A test case for pathway analysis tools'.

PubMed

Faust, Karoline; Croes, Didier; van Helden, Jacques

2009-12-01

In their article entitled 'Can sugars be produced from fatty acids? A test case for pathway analysis tools' de Figueiredo and co-authors assess the performance of three pathway prediction tools (METATOOL, PathFinding and Pathway Hunter Tool) using the synthesis of glucose-6-phosphate (G6P) from acetyl-CoA in humans as a test case. We think that this article is biased for three reasons: (i) the metabolic networks used as input for the respective tools were of very different sizes; (ii) the 'assessment' is restricted to two study cases; (iii) developers are inherently more skilled to use their own tools than those developed by other people. We extended the analyses led by de Figueiredo and clearly show that the apparent superior performance of their tool (METATOOL) is partly due to the differences in input network sizes. We also see a conceptual problem in the comparison of tools that serve different purposes. In our opinion, metabolic path finding and elementary mode analysis are answering different biological questions, and should be considered as complementary rather than competitive approaches. Supplementary data are available at Bioinformatics online.

Transcriptome Profiling of Chironomus kiinensis under Phenol Stress Using Solexa Sequencing Technology

PubMed Central

Cao, Chuanwang; Wang, Zhiying; Niu, Changying; Desneux, Nicolas; Gao, Xiwu

2013-01-01

Phenol is a major pollutant in aquatic ecosystems due to its chemical stability, water solubility and environmental mobility. To date, little is known about the molecular modifications of invertebrates under phenol stress. In the present study, we used Solexa sequencing technology to investigate the transcriptome and differentially expressed genes (DEGs) of midges (Chironomus kiinensis) in response to phenol stress. A total of 51,518,972 and 51,150,832 clean reads in the phenol-treated and control libraries, respectively, were obtained and assembled into 51,014 non-redundant (Nr) consensus sequences. A total of 6,032 unigenes were classified by Gene Ontology (GO), and 18,366 unigenes were categorized into 238 Kyoto Encyclopedia of Genes and Genomes (KEGG) categories. These genes included representatives from almost all functional categories. A total of 10,724 differentially expressed genes (P value <0.05) were detected in a comparative analysis of the expression profiles between phenol-treated and control C. kiinensis including 8,390 upregulated and 2,334 downregulated genes. The expression levels of 20 differentially expressed genes were confirmed by real-time RT-PCR, and the trends in gene expression that were observed matched the Solexa expression profiles, although the magnitude of the variations was different. Through pathway enrichment analysis, significantly enriched pathways were identified for the DEGs, including metabolic pathways, aryl hydrocarbon receptor (AhR), pancreatic secretion and neuroactive ligand-receptor interaction pathways, which may be associated with the phenol responses of C. kiinensis. Using Solexa sequencing technology, we identified several groups of key candidate genes as well as important biological pathways involved in the molecular modifications of chironomids under phenol stress. PMID:23527048

Hydrogen Fuel Cell Analysis: Lessons Learned from Stationary Power Generation Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scott E. Grasman; John W. Sheffield; Fatih Dogan

2010-04-30

This study considered opportunities for hydrogen in stationary applications in order to make recommendations related to RD&D strategies that incorporate lessons learned and best practices from relevant national and international stationary power efforts, as well as cost and environmental modeling of pathways. The study analyzed the different strategies utilized in power generation systems and identified the different challenges and opportunities for producing and using hydrogen as an energy carrier. Specific objectives included both a synopsis/critical analysis of lessons learned from previous stationary power programs and recommendations for a strategy for hydrogen infrastructure deployment. This strategy incorporates all hydrogen pathways andmore » a combination of distributed power generating stations, and provides an overview of stationary power markets, benefits of hydrogen-based stationary power systems, and competitive and technological challenges. The motivation for this project was to identify the lessons learned from prior stationary power programs, including the most significant obstacles, how these obstacles have been approached, outcomes of the programs, and how this information can be used by the Hydrogen, Fuel Cells & Infrastructure Technologies Program to meet program objectives primarily related to hydrogen pathway technologies (production, storage, and delivery) and implementation of fuel cell technologies for distributed stationary power. In addition, the lessons learned address environmental and safety concerns, including codes and standards, and education of key stakeholders.« less

Designing a Care Pathway Model – A Case Study of the Outpatient Total Hip Arthroplasty Care Pathway

PubMed Central

Oosterholt, Robin I; Boess, Stella U; Vehmeijer, Stephan BW

2017-01-01

Introduction: Although the clinical attributes of total hip arthroplasty (THA) care pathways have been thoroughly researched, a detailed understanding of the equally important organisational attributes is still lacking. The aim of this article is to contribute with a model of the outpatient THA care pathway that depicts how the care team should be organised to enable patient discharge on the day of surgery. Theory: The outpatient THA care pathway enables patients to be discharged on the day of surgery, shortening the length of stay and intensifying the provision and organisation of care. We utilise visual care modelling to construct a visual design of the organisation of the care pathway. Methods: An embedded case study was conducted of the outpatient THA care pathway at a teaching hospital in the Netherlands. The data were collected using a visual care modelling toolkit in 16 semi-structured interviews. Problems and inefficiencies in the care pathway were identified and addressed in the iterative design process. Results: The results are two visual models of the most critical phases of the outpatient THA care pathway: diagnosis & preparation (1) and mobilisation & discharge (4). The results show the care team composition, critical value exchanges, and sequence that enable patient discharge on the day of surgery. Conclusion: The design addressed existing problems and is an optimisation of the case hospital’s pathway. The network of actors consists of the patient (1), radiologist (1), anaesthetist (1), nurse specialist (1), pharmacist (1), orthopaedic surgeon (1,4), physiotherapist (1,4), nurse (4), doctor (4) and patient application (1,4). The critical value exchanges include patient preparation (mental and practical), patient education, aligned care team, efficient sequence of value exchanges, early patient mobilisation, flexible availability of the physiotherapist, functional discharge criteria, joint decision making and availability of the care team. PMID:29042844

Getting to the roots of it: Genetic and hormonal control of root architecture

PubMed Central

Jung, Janelle K. H.; McCouch, Susan

2013-01-01

Root system architecture (RSA) – the spatial configuration of a root system – is an important developmental and agronomic trait, with implications for overall plant architecture, growth rate and yield, abiotic stress resistance, nutrient uptake, and developmental plasticity in response to environmental changes. Root architecture is modulated by intrinsic, hormone-mediated pathways, intersecting with pathways that perceive and respond to external, environmental signals. The recent development of several non-invasive 2D and 3D root imaging systems has enhanced our ability to accurately observe and quantify architectural traits on complex whole-root systems. Coupled with the powerful marker-based genotyping and sequencing platforms currently available, these root phenotyping technologies lend themselves to large-scale genome-wide association studies, and can speed the identification and characterization of the genes and pathways involved in root system development. This capability provides the foundation for examining the contribution of root architectural traits to the performance of crop varieties in diverse environments. This review focuses on our current understanding of the genes and pathways involved in determining RSA in response to both intrinsic and extrinsic (environmental) response pathways, and provides a brief overview of the latest root system phenotyping technologies and their potential impact on elucidating the genetic control of root development in plants. PMID:23785372

Exosomes play an important role in the process of psoralen reverse multidrug resistance of breast cancer.

PubMed

Wang, Xiaohong; Xu, Chengfeng; Hua, Yitong; Sun, Leitao; Cheng, Kai; Jia, Zhongming; Han, Yong; Dong, Jianli; Cui, Yuzhen; Yang, Zhenlin

2016-12-01

Release of exosomes have been shown to play critical roles in drug resistance by delivering cargo. Targeting the transfer of exosomes from resistant cells to sensitive cells may be an approach to overcome some cases of drug resistance. In this study, we investigated the potential role of exosomes in the process of psoralen reverse multidrug resistance of MCF-7/ADR cells. Exosomes were isolated by differential centrifugation of culture media from MCF-7/ADR cells (ADR/exo) and MCF-7 parental cells (S/exo). Exosomes were characterized by morphology, exosomal markers and size distribution. The ability of ADR/exo to transfer multidrug resistance was assessed by MTT and real-time quantitative PCR. The different formation and secretion of exosomes were detected by immunofluorescence and transmission electron microscopy. Then we performed comparative transcriptomic analysis using RNA-Seq technology and real-time quantitative PCR to better understand the gene expression regulation in exosmes formation and release after psoralen treatment. Our data showed that exosomes derived from MCF-7/ADR cells were able to promote active sequestration of drugs and could induce a drug resistance phenotype by transferring drug-resistance-related gene MDR-1 and P-glycoprotein protein. Psoralen could reduce the formation and secretion of exosomes to overcome drug resistance. There were 21 differentially expressed genes. Gene ontology (GO) pathway analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the most significantly expressed genes were linked to PPAR and P53 signaling pathways which were related to exosomes formation, secretion and cargo sorting. Psoralen can affect the exosomes and induce the reduction of resistance transmission via exosomes might through PPAR and P53 signaling pathways, which might provide a novel strategy for breast cancer resistance to chemotherapy in the future.

Polymer nanocomposites for sealing microannulus cracks in wellbores cement-steel interface

NASA Astrophysics Data System (ADS)

Genedy, M.; Fernandez, S. G.; Stormont, J.; Matteo, E. N.; Dewers, T. A.; Reda Taha, M.

2017-12-01

Seal integrity of production and storage wellbores has become a critical challenge with the increasing oil and gas leakage incidents. The general consensus is that one of the potential leakage pathways is micro-annuli at the cement-steel interface. In this paper, we examine the efficiency of proposed polymer nanocomposite to seal microannulus cracks at the cement-steel interface. The repair material efficiency is defined as the ability of the repair material to reduce or eliminate the gas permeability of the cement-steel interface. The flow rate of an inert gas (Nitrogen) at the cement-steel interface was investigated for three cases: 1) repaired test samples with traditional repair material (microfine cement), 2) polymer nanocomposites, and 3) unrepaired test samples. Flow rates were measured and compared for all three cases. The experimental results show up to 99.5% seal efficiency achieved by using polymer nanocomposites compared to 20% efficiency achieved in the case of microfine cement. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology and Engineering Solutions of Sandia, LLC., a wholly owned subsidiary of Honeywell International, Inc., for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-NA-0003525. SAND2017-8094 A.

Exploring How Technology Growth Limits Impact Optimal Carbon dioxide Mitigation Pathways

EPA Science Inventory

Energy system optimization models prescribe the optimal mix of technologies and fuels for meeting energy demands over a time horizon, subject to energy supplies, demands, and other constraints. When optimizing, these models will, to the extent allowed, favor the least cost combin...

Stochastic techno-economic analysis of alcohol-to-jet fuel production.

PubMed

Yao, Guolin; Staples, Mark D; Malina, Robert; Tyner, Wallace E

2017-01-01

Alcohol-to-jet (ATJ) is one of the technical feasible biofuel technologies. It produces jet fuel from sugary, starchy, and lignocellulosic biomass, such as sugarcane, corn grain, and switchgrass, via fermentation of sugars to ethanol or other alcohols. This study assesses the ATJ biofuel production pathway for these three biomass feedstocks, and advances existing techno-economic analyses of biofuels in three ways. First, we incorporate technical uncertainty for all by-products and co-products though statistical linkages between conversion efficiencies and input and output levels. Second, future price uncertainty is based on case-by-case time-series estimation, and a local sensitivity analysis is conducted with respect to each uncertain variable. Third, breakeven price distributions are developed to communicate the inherent uncertainty in breakeven price. This research also considers uncertainties in utility input requirements, fuel and by-product outputs, as well as price uncertainties for all major inputs, products, and co-products. All analyses are done from the perspective of a private firm. The stochastic dominance results of net present values (NPV) and breakeven price distributions show that sugarcane is the lowest cost feedstock over the entire range of uncertainty with the least risks, followed by corn grain and switchgrass, with the mean breakeven jet fuel prices being $0.96/L ($3.65/gal), $1.01/L ($3.84/gal), and $1.38/L ($5.21/gal), respectively. The variation of revenues from by-products in corn grain pathway can significantly impact its profitability. Sensitivity analyses show that technical uncertainty significantly impacts breakeven price and NPV distributions. Technical uncertainty is critical in determining the economic performance of the ATJ fuel pathway. Technical uncertainty needs to be considered in future economic analyses. The variation of revenues from by-products plays a significant role in profitability. With the distribution of breakeven prices, potential investors can apply whatever risk preferences they like to determine an appropriate bid or breakeven price that matches their risk profile.

Genetic Engineering Strategies for Enhanced Biodiesel Production.

PubMed

Hegde, Krishnamoorthy; Chandra, Niharika; Sarma, Saurabh Jyoti; Brar, Satinder Kaur; Veeranki, Venkata Dasu

2015-07-01

The focus on biodiesel research has shown a tremendous growth over the last few years. Several microbial and plant sources are being explored for the sustainable biodiesel production to replace the petroleum diesel. Conventional methods of biodiesel production have several limitations related to yield and quality, which led to development of new engineering strategies to improve the biodiesel production in plants, and microorganisms. Substantial progress in utilizing algae, yeast, and Escherichia coli for the renewable production of biodiesel feedstock via genetic engineering of fatty acid metabolic pathways has been reported in the past few years. However, in most of the cases, the successful commercialization of such engineering strategies for sustainable biodiesel production is yet to be seen. This paper systematically presents the drawbacks in the conventional methods for biodiesel production and an exhaustive review on the present status of research in genetic engineering strategies for production of biodiesel in plants, and microorganisms. Further, we summarize the technical challenges need to be tackled to make genetic engineering technology economically sustainable. Finally, the need and prospects of genetic engineering technology for the sustainable biodiesel production and the recommendations for the future research are discussed.

Vehicle Integrated Prognostic Reasoner (VIPR) 2010 Annual Final Report

NASA Technical Reports Server (NTRS)

Hadden, George D.; Mylaraswamy, Dinkar; Schimmel, Craig; Biswas, Gautam; Koutsoukos, Xenofon; Mack, Daniel

2011-01-01

Honeywell's Central Maintenance Computer Function (CMCF) and Aircraft Condition Monitoring Function (ACMF) represent the state-of-the art in integrated vehicle health management (IVHM). Underlying these technologies is a fault propagation modeling system that provides nose-to-tail coverage and root cause diagnostics. The Vehicle Integrated Prognostic Reasoner (VIPR) extends this technology to interpret evidence generated by advanced diagnostic and prognostic monitors provided by component suppliers to detect, isolate, and predict adverse events that affect flight safety. This report describes year one work that included defining the architecture and communication protocols and establishing the user requirements for such a system. Based on these and a set of ConOps scenarios, we designed and implemented a demonstration of communication pathways and associated three-tiered health management architecture. A series of scripted scenarios showed how VIPR would detect adverse events before they escalate as safety incidents through a combination of advanced reasoning and additional aircraft data collected from an aircraft condition monitoring system. Demonstrating VIPR capability for cases recorded in the ASIAS database and cross linking them with historical aircraft data is planned for year two.

Experiences of high school Hispanic girls in pursuit of science, technology, engineering, and mathematics-related coursework and careers

NASA Astrophysics Data System (ADS)

Vijil, Veronica G.

2011-12-01

An overall increased awareness of the importance of science, technology, engineering, and mathematics (STEM) has prompted attention toward the continued underrepresentation of Hispanic women in this field. The purpose of this collective case study was to explore the support systems, perceived barriers, and prior experiences influencing high school Hispanic girls' decisions to pursue advanced coursework and related careers through a career pathway in science, technology, engineering, and mathematics (STEM) areas. Specifically, participants were interviewed regarding their mathematics and science experiences in elementary and middle schools, as well as perceived supports and barriers to their choices to pursue STEM careers and advanced coursework. Results indicated that the participants linked their elementary and middle school experiences with their teachers rather than specific activities. Accolades such as certificates and good grades for academic achievement contributed to the girls' strong self-efficacy at an early age. The participants possessed self-discipline and self-confidence, using intrinsic motivation to pursue their goals. Support systems included families and a few teachers. Barriers were revealed in different forms including derogatory comments by boys in class, difficult curricula with limited tutors available for higher level courses, and receipt of financial assistance to attend a university of their choice.

The use of standard operating procedures in day case anterior cruciate ligament reconstruction.

PubMed

Khan, T; Jackson, W F; Beard, D J; Marfin, A; Ahmad, M; Spacie, R; Jones, R; Howes, S; Barker, K; Price, A J

2012-08-01

The current rate of day-case anterior cruciate ligament reconstruction (ACLR) in the UK remains low. Although specialised care pathways with standard operating procedures (SOPs) have been effective in reducing length of stay following some surgical procedures, this has not been previously reported for ACLR. We evaluate the effectiveness of SOPs for establishing day-case ACLR in a specialist unit. Fifty patients undergoing ACLR between May and September 2010 were studied prospectively ("study group"). SOPs were designed for pre-operative assessment, anaesthesia, surgical procedure, mobilisation and discharge. We evaluated length of stay, readmission rates, patient satisfaction and compliance to SOPs. A retrospective analysis of 50 patients who underwent ACLR prior to implementation of the day-case pathway was performed ("standard practice group"). Eighty percent of patients in the study group were discharged on the day of surgery (mean length of stay=5.3h) compared to 16% in the standard practice group (mean length of stay=21.6h). This difference was statistically significant (p<0.05, Mann-Whitney U test). All patients were satisfied with the day case pathway. Ninety-two percent of the study group were discharged on the day of surgery when all SOPs were followed and 46% where they were not. High rates of day-case ACLR with excellent patient satisfaction can be achieved with the use of a specialised patient pathway with SOPs. Copyright © 2011 Elsevier B.V. All rights reserved.

2015 Summary Report on Industrial and Regulatory Engagement Activities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomas, Kenneth David

2015-09-01

The Advanced Instrumentation, Information, and Control (II&C) Systems Technologies pathway of the Light Water Reactor Sustainability(LWRS) Program conducts a vigorous engagement strategy with the U.S. nuclear power industry, including the nuclear operating companies, major support organizations, the Nuclear Regulatory Commission (NRC), and suppliers. The goal of this engagement strategy is to develop a shared vision and common understanding across the nuclear industry of the need for II&C modernization, the performance improvement that can be obtained, and the opportunities for collaboration to enact this vision. The primary means of engaging the nuclear operating companies is through a Utility Working Group (UWG),more » composed of utility representatives that participate in formal meetings and bi-monthly phone calls to provide input on nuclear plant needs and priorities for II&C technologies. Two working groups were initiated during FY 2015 to provide a means for UWG members to focus on particular technologies of interest. The Outage Improvement Working Group consists of eight utilities that participate in periodic conference calls and have access to a share-point web page for acccess to project materials developed in the Advanced Outage Control Center pilot project. In the area of computer-based procedures and automated work packages, the II&C Pathway has worked with the Nuclear Information Technology Strategic Leadership (NITSL) to set up a monthly conference call with interested utility members to discuss various aspects of mobile worker technologies. Twenty one technical and project reports were delivered to the UWG during FY 2015, reflecting the work of the II&C Pathway pilot projects during the year. Distribution of these reports is one of the primary means of transferring to the nuclear industry the knowledge and experience gained during the development of advanced II&C technologies in support of LWR sustainability. Site visits to discuss pilot project activities and future plans were made to Arizona Public Service, Exelon, Duke Energy, Pacific Gas & Electric, SCANA, Southern Nuclear, South Texas Project, STARS Alliance, Tennessee Valley Authority, and Xcel. Discussions were also held on the pathway goals and activities with major industry support organizations during FY 2102, including the Institute of Nuclear Power Operations (INPO), the Nuclear Information Technology Strategic Leadership (NITSL), the Nuclear Energy Institute (NEI), and the Electric Power Research Institute. The Advanced II&C Pathway work was presented at five major industry conferences and Informal discussions were held with key NRC managers at industry conferences. In addition, discussions were held with NRC senior managers on digital regulatory issues through participation on the NEI Digital I&C Working Group. Meetings were held with major industry suppliers and consultants, to explore opportunities for collaboration and to provide a means of pilot project technology transfer. In the international area, discussions were held with Electricite’ de France (EdF) concerning possible collaboration in the area NPP configuration control using intelligent wireless devices.« less

Toxicogenomics: the challenges and opportunities to identify biomarkers, signatures and thresholds to support mode-of-action.

PubMed

Currie, Richard A

2012-08-15

Toxicogenomics (TGx) can be defined as the application of "omics" techniques to toxicology and risk assessment. By identifying molecular changes associated with toxicity, TGx data might assist hazard identification and investigate causes. Early technical challenges were evaluated and addressed by consortia (e.g. ISLI/HESI and the Microarray Quality Control consortium), which demonstrated that TGx gave reliable and reproducible information. The MAQC also produced "best practice on signature generation" after conducting an extensive evaluation of different methods on common datasets. Two findings of note were the need for methods that control batch variability, and that the predictive ability of a signature changes in concert with the variability of the endpoint. The key challenge remaining is data interpretation, because TGx can identify molecular changes that are causal, associated with or incidental to toxicity. Application of Bradford Hill's tests for causation, which are used to build mode of action (MOA) arguments, can produce reasonable hypotheses linking altered pathways to phenotypic changes. However, challenges in interpretation still remain: are all pathway changes equal, which are most important and plausibly linked to toxicity? Therefore the expert judgement of the toxicologist is still needed. There are theoretical reasons why consistent alterations across a metabolic pathway are important, but similar changes in signalling pathways may not alter information flow. At the molecular level thresholds may be due to the inherent properties of the regulatory network, for example switch-like behaviours from some network motifs (e.g. positive feedback) in the perturbed pathway leading to the toxicity. The application of systems biology methods to TGx data can generate hypotheses that explain why a threshold response exists. However, are we adequately trained to make these judgments? There is a need for collaborative efforts between regulators, industry and academia to properly define how these technologies can be applied using appropriate case-studies. Copyright © 2012 Elsevier B.V. All rights reserved.

Identification of shared and unique susceptibility pathways among cancers of the lung, breast, and prostate from genome-wide association studies and tissue-specific protein interactions

PubMed Central

Qian, David C.; Byun, Jinyoung; Han, Younghun; Greene, Casey S.; Field, John K.; Hung, Rayjean J.; Brhane, Yonathan; Mclaughlin, John R.; Fehringer, Gordon; Landi, Maria Teresa; Rosenberger, Albert; Bickeböller, Heike; Malhotra, Jyoti; Risch, Angela; Heinrich, Joachim; Hunter, David J.; Henderson, Brian E.; Haiman, Christopher A.; Schumacher, Fredrick R.; Eeles, Rosalind A.; Easton, Douglas F.; Seminara, Daniela; Amos, Christopher I.

2015-01-01

Results from genome-wide association studies (GWAS) have indicated that strong single-gene effects are the exception, not the rule, for most diseases. We assessed the joint effects of germline genetic variations through a pathway-based approach that considers the tissue-specific contexts of GWAS findings. From GWAS meta-analyses of lung cancer (12 160 cases/16 838 controls), breast cancer (15 748 cases/18 084 controls) and prostate cancer (14 160 cases/12 724 controls) in individuals of European ancestry, we determined the tissue-specific interaction networks of proteins expressed from genes that are likely to be affected by disease-associated variants. Reactome pathways exhibiting enrichment of proteins from each network were compared across the cancers. Our results show that pathways associated with all three cancers tend to be broad cellular processes required for growth and survival. Significant examples include the nerve growth factor (P = 7.86 × 10−33), epidermal growth factor (P = 1.18 × 10−31) and fibroblast growth factor (P = 2.47 × 10−31) signaling pathways. However, within these shared pathways, the genes that influence risk largely differ by cancer. Pathways found to be unique for a single cancer focus on more specific cellular functions, such as interleukin signaling in lung cancer (P = 1.69 × 10−15), apoptosis initiation by Bad in breast cancer (P = 3.14 × 10−9) and cellular responses to hypoxia in prostate cancer (P = 2.14 × 10−9). We present the largest comparative cross-cancer pathway analysis of GWAS to date. Our approach can also be applied to the study of inherited mechanisms underlying risk across multiple diseases in general. PMID:26483192

Process Simulation and Techno-Economic Evaluation of Alternative Biorefinery Scenarios

NASA Astrophysics Data System (ADS)

Aizpurua Gonzalez, Carlos Ernesto

A biorefinery is a complex processing facility that uses sustainably produced biomass as feedstock to generate biofuels and chemical products using a wide variety of alternative conversion pathways. The alternative conversion pathways can be generally classified as either biochemical or thermochemical conversion. A biorefinery is commonly based on a core biomass conversion technology (pretreatment, hydrolysis, pyrolysis, etc.) followed by secondary processing stages that determine the specific product, and its recovery. In this study, techno-economic analysis of several different lignocellulosic biomass conversion pathways have been performed. First, a novel biochemical conversion, which used electron beam and steam explosion pretreatments for ethanol production was evaluated. This evaluation include both laboratory work and process modeling. Encouraging experimental results are obtained that showed the biomass had enhanced reactivity to the enzyme hydrolysis. The total sugar recovery for the hardwood species was 72% using 5 FPU/g enzyme dosage. The combination of electron beam and steam explosion provides an improvement in sugar conversion of more than 20% compared to steam explosion alone. This combination of pretreatments was modeled along with a novel ethanol dehydration process that is based on vapor permeation membranes. The economic feasibility of this novel pretreatment-dehydration technology was evaluated and compared with the dilute acid process proposed by NREL in 2011. Overall, the pretreatment-dehydration technology process produces the same ethanol yields (81 gal/bdton). However, the economics of this novel process does not look promising since the minimum ethanol selling price (MESP) to generate an internal rate of return of 10% is of 3.09 /gal, compared to 2.28 /gal for the base case. To enhance the economic potential of a biorefinery, the isolation of value-added co-products was incorporated into the base dilute acid biorefinery process. In this case the work focused on the ethanol extraction of the non-structural components of switchgrass prior to pretreatment and enzymatic hydrolysis. Promising results obtained with an Aspen PlusRTM model showed that a MESP of 2.5 /gal along with an assumed co-product selling price of 1 /Kg generated an 18% internal rate of return (IRR). In a second series of studies biomass fast pyrolysis and the bio-oil upgrading for the production of drop-in fuels was analyzed. Again, an Aspen PlusRTM based process model was used to evaluate the impacts of different biomass feedstock composition on the biofuel product. In this case the biofuel produced both a gasoline and diesel fraction. Model results showed that both the carbon and ash content of the biomass had an impact on the amount and price of the biofuel products. The highest biofuel yield were obtained with the hardwood (red maple) and perennial (switchgrass) feedstocks at about 48 gal/bdton of biomass, while the softwood (loblolly pine) provided 46 gal/bdton. Bark (acacia), the feedstock with the highest ash content, only provided 39 gal/bdton. But when the cost of these feedstocks was included the softwood is predicted to provide the lowest cost fuel, followed by the bark. As expected overall cost of the biofuel was dramatically impacted by the cost of the feedstock, and also by the use of a fraction of the intermediate bio-oil as the source of the hydrogen needed for upgrading the bio-oil to a hydrocarbon fuel product. Using hydrogen from natural gas instead of hydrogen from reforming the intermediate bio-oil reduced the estimated cost of the fuel product by $1.20/gal.

Adapting biomarker technologies to adverse outcome pathways (AOPs) research: current thoughts on using in vivo discovery for developing in vitro target methods

EPA Science Inventory

Adverse outcome pathways (AOP) research is a relatively new concept in human systems biology for assessing the molecular level linkage from an initiating (chemical) event that could lead to a disease state. Although most implementations of AOPs are based on liquids analyses, the...

Pathways to Drug and Sexual Risk Behaviors among Detained Adolescents

ERIC Educational Resources Information Center

Voisin, Dexter R.; Neilands, Torsten B.; Salazar, Laura F.; Crosby, Richard; DiClemente, Ralph J.

2008-01-01

This study recruited 559 youths from detention centers (mean age was 15.4 years; 50.1% of detainees were girls) to investigate pathways that link witnessing community violence in the 12 months before detainment to drug and sexual risk behaviors in the two months preceding detainment. Through the use of audio-computer-assisted technology, data were…

New Pathways to a Degree. Project Evaluation: First Year Report.

ERIC Educational Resources Information Center

Markwood, Richard A., Ed.; Johnstone, Sally M., Ed.

The first year's observations of projects funded by the Annenberg/Corporation for Public Broadcasting in its New Pathways to a Degree project are summarized. The project was designed to help colleges use technologies to develop academic degree programs that are accessible to the new majority of learners, those who have jobs, home responsibilities,…

An Institutional Three-Stage Framework: Elevating Academic Writing and Integrity Standards of International Pathway Students

ERIC Educational Resources Information Center

Velliaris, Donna M.; Breen, Paul

2016-01-01

In this paper, the authors explore a holistic three-stage framework currently used by the Eynesbury Institute of Business and Technology (EIBT), focused on academic staff identification and remediation processes for the prevention of (un)intentional student plagiarism. As a pre-university pathway provider--whose student body is 98%…

An enhanced functional interrogation/manipulation of intracellular signaling pathways with the peptide 'stapling' technology.

PubMed

He, Y; Chen, D; Zheng, W

2015-11-12

Specific protein-protein interactions (PPIs) constitute a key underlying mechanism for the presence of a multitude of intracellular signaling pathways, which are essential for the survival of normal and cancer cells. Specific molecular blockers for a crucial PPI would therefore be invaluable tools for an enhanced functional interrogation of the signaling pathway harboring this particular PPI. On the other hand, if a particular PPI is essential for the survival of cancer cells but is absent in or dispensable for the survival of normal cells, its specific molecular blockers could potentially be developed into effective anticancer therapeutics. Due to the flat and extended PPI interface, it would be conceivably difficult for small molecules to achieve an effective blockade, a problem which could be potentially circumvented with peptides or proteins. However, the well-documented proteolytic instability and cellular impermeability of peptides and proteins in general would make their developing into effective intracellular PPI blockers quite a challenge. With the advent of the peptide 'stapling' technology which was demonstrated to be able to stabilize the α-helical conformation of a peptide via bridging two neighboring amino-acid side chains with a 'molecular staple', a linear parent peptide could be transformed into a stronger PPI blocker with enhanced proteolytic stability and cellular permeability. This review will furnish an account on the peptide 'stapling' technology and its exploitation in efforts to achieve an enhanced functional interrogation or manipulation of intracellular signaling pathways especially those that are cancer relevant.

Case Study Approaches for Implementing the 2007 NRC Report “Toxicity Testing in the 21st Century: A Vision and A Strategy”

PubMed Central

Andersen, Melvin E.; Clewell, Harvey J.; Carmichael, Paul L.; Boekelheide, Kim

2013-01-01

The 2007 report “Toxicity Testing in the 21st Century: A Vision and A Strategy” argued for a change in toxicity testing for environmental agents and discussed federal funding mechanisms that could be used to support this transformation within the USA. The new approach would test for in vitro perturbations of toxicity pathways using human cells with high throughput testing platforms. The NRC report proposed a deliberate timeline, spanning about 20 years, to implement a wholesale replacement of current in-life toxicity test approaches focused on apical responses with in vitro assays. One approach to accelerating implementation is to focus on well-studied prototype compounds with known toxicity pathway targets. Through a series of carefully executed case studies with four or five pathway prototypes, the various steps required for implementation of an in vitro toxicity pathway approach to risk assessment could be developed and refined. In this article, we discuss alternative approaches for implementation and also outline advantages of a case study approach and the manner in which the cases studies could be pursued using current methodologies. A case study approach would be complementary to recently proposed efforts to map the human toxome, while representing a significant extension toward more formal risk assessment compared to the profiling and prioritization approaches offered by programs such as the EPA’s ToxCast effort. PMID:21993955

Time-Lapse Measurement of Wellbore Integrity

NASA Astrophysics Data System (ADS)

Duguid, A.

2017-12-01

Well integrity is becoming more important as wells are used longer or repurposed. For CO2, shale gas, and other projects it has become apparent that wells represent the most likely unintended migration pathway for fluids out of the reservoir. Comprehensive logging programs have been employed to determine the condition of legacy wells in North America. These studies provide examples of assessment technologies. Logging programs have included pulsed neutron logging, ultrasonic well mapping, and cement bond logging. While these studies provide examples of what can be measured, they have only conducted a single round of logging and cannot show if the well has changed over time. Recent experience with time-lapse logging of three monitoring wells at a US Department of Energy sponsored CO2 project has shown the full value of similar tools. Time-lapse logging has shown that well integrity changes over time can be identified. It has also shown that the inclusion of and location of monitoring technologies in the well and the choice of construction materials must be carefully considered. Two of the wells were approximately eight years old at the time of study; they were constructed with steel and fiberglass casing sections and had lines on the outside of the casing running to the surface. The third well was 68 years old when it was studied and was originally constructed as a production well. Repeat logs were collected six or eight years after initial logging. Time-lapse logging showed the evolution of the wells. The results identified locations where cement degraded over time and locations that showed little change. The ultrasonic well maps show clearly that the lines used to connect the monitoring technology to the surface are visible and have a local effect on cement isolation. Testing and sampling was conducted along with logging. It provided insight into changes identified in the time-lapse log results. Point permeability testing was used to provide an in-situ point estimate of the cement isolating capacity. Cased-hole sidewall cores in the steel and fiberglass casing sections allowed analysis of bulk cement and the cement at the casing- and formation-interface. This presentation will cover how time-lapse logging was conducted, how the results may be applicable to other wells, and how monitoring well design may affect wellbore integrity.

Predictive value of EGFR-PI3K-pAKT-mTOR-pS6 pathway in sinonasal squamous cell carcinomas.

PubMed

Muñoz-Cordero, María Gabriela; López, Fernando; García-Inclán, Cristina; López-Hernández, Alejandro; Potes-Ares, Sira; Fernández-Vañes, Laura; Llorente, José Luis; Hermsen, Mario

2018-03-21

We have previously indicated that EGFR has a role in carcinogenesis in a subgroup of sinonasal squamous cell carcinomas (SNSCC). In addition, EGFR activates 2 of the most important intracellular signalling pathways: PI3K/pAKT/mTOR/pS6 and MAP pathway kinases. The objective of this study was to evaluate the involvement of the EGFR/PI3K/pAKT/mTOR/pS6 pathway and its relationship with clinical-pathological parameters and follow-up of sinonasal squamous cell carcinoma. The immunohistochemical expression of different components of the PI3K/AKT/mTOR/pS6 pathway and its relationship with various clinical-pathological parameters was studied in a series of 54 patients with SNSCC. Loss of PTEN expression was observed in 33/54 cases (61%) and pAKT, mTOR and pS6 pre-expression was observed in 19/54 cases (35%), 8/54 cases (15%), and 47/54 cases (87%), respectively. Loss of PTEN expression was related to intracranial invasion and development of regional metastases (p=0.005). Overexpression of pS6 was associated with a decrease in survival (p=0.008), presence of local recurrences (p=0.055), and worsening of overall prognosis (p=0.007). No significant relationships were observed between pAKT and mTOR expression and the clinicopathological parameters studied. Alterations in the expression of EGFR/PI3K/pAKT/mTOR/pS6 pathway components are common in a subgroup of SNSCC. This study reveals that the absence of pS6 overexpression is associated with better clinical outcomes. Therefore, pS6 expression could be considered as an unfavourable prognostic marker. Copyright © 2018. Publicado por Elsevier España, S.L.U.

Nature's inordinate fondness for metabolic enzymes: why metabolic enzyme loci are so frequently targets of selection.

PubMed

Marden, James H

2013-12-01

Metabolic enzyme loci were some of the first genes accessible for molecular evolution and ecology research. New technologies now make the whole genome, transcriptome or proteome readily accessible, allowing unbiased scans for loci exhibiting significant differences in allele frequency or expression level and associated with phenotypes and/or responses to natural selection. With surprising frequency and in many cases in proportions greater than chance relative to other genes, glycolysis and TCA cycle enzyme loci appear among the genes with significant associations in these studies. Hence, there is an ongoing need to understand the basis for fitness effects of metabolic enzyme polymorphisms. Allele-specific effects on the binding affinity and catalytic rate of individual enzymes are well known, but often of uncertain significance because metabolic control theory and in vivo studies indicate that many individual metabolic enzymes do not affect pathway flux rate. I review research, so far little used in evolutionary biology, showing that metabolic enzyme substrates affect signalling pathways that regulate cell and organismal biology, and that these enzymes have moonlighting functions. To date there is little knowledge of how alleles in natural populations affect these phenotypes. I discuss an example in which alleles of a TCA enzyme locus associate with differences in a signalling pathway and development, organismal performance, and ecological dynamics. Ultimately, understanding how metabolic enzyme polymorphisms map to phenotypes and fitness remains a compelling and ongoing need for gaining robust knowledge of ecological and evolutionary processes. © 2013 John Wiley & Sons Ltd.

What is the mechanism effect that links social support to coping and psychological outcome within individuals affected by prostate cancer? Real time data collection using mobile technology.

PubMed

Paterson, Catherine; Jones, Martyn; Rattray, Janice; Lauder, William; Nabi, Ghulam

2016-04-01

Unmet support needs are prevalent in men affected by prostate cancer. Moreover, little is known about the optimal type of social support, or its mechanism effect between coping and emotional outcome in men affected by this disease to identify areas for clinical intervention. This study aimed to empirically test the propositions of social support theory in "real time" within individual men living with and beyond prostate cancer. Purposeful sub-sample from a larger prospective longitudinal study of prostate cancer survivors, took part in real time data collection using mobile technology. Self-reports were collected for 31 days prompted by an audio alarm 3 times per day (a total of 93 data entries) for each of the 12 case studies. Electronic data were analysed using time series analysis. Majority of response rates were >90%. Men reported a lack of satisfaction with their support over time. Testing the propositions of social support theory "within individuals" over time demonstrated different results for main effect, moderation and mediation pathways that linked coping and social support to emotional outcome. For two men, negative effects of social support were identified. For six men the propositions of social support theory did not hold considering their within-person data. This innovative study is one of the first, to demonstrate the acceptability of e-health technology in an ageing population of men affected by prostate cancer. Collectively, the case series provided mixed support for the propositions of social support theory, and demonstrates that "one size does not fit all". Copyright © 2015 Elsevier Ltd. All rights reserved.

Game Development as a Pathway to Information Technology Literacy

ERIC Educational Resources Information Center

Frydenberg, Mark

2016-01-01

Teaching game development has become an accepted methodology for introducing programming concepts and capturing the interest of beginning computer science and information technology (IT) students. This study, conducted over three consecutive semesters, explores game development using a gaming engine, rather than a traditional programming language,…

GIS tools, courses, and learning pathways offered by The National Interagency Fuels, Fire, and Vegetation Technology Transfer (NIFTT)

Treesearch

Heather Heward; Kathy H. Schon

2009-01-01

As technology continues to evolve in the area of fuel and wildland fire management so does the need to have effective tools and training on these technologies. The National Interagency Fuels Coordination Group has chartered a team of professionals to coordinate, develop, and transfer consistent, efficient, science-based fuel and fire ecology assessment GIS tools and...

Making the Case for GeoSTEM Education

NASA Astrophysics Data System (ADS)

Moore, John

2014-05-01

As the national Science-Technology-Engineering-Mathematics (STEM) education policy makers in the United States work through reports, findings, forums, workshops, etc., there emerges an opportunity to present the strong case of why and how the role of the Geosciences community can and should be at the forefront of these discussions. Currently existing within the Geosciences scientific and educational community are policies, frameworks, guidance, innovative technology, and unique interdisciplinary Earth System data sets that will establish a pathway to the role of the Geosciences in the classroom, in the 21st Century workforce, and in society. The question may be raised, "Why GeoSTEM?" But the real question should be … "Why not?" Over the past several years the Geosciences have dominated the news cycle in the United States. As we face future natural and human generated hazards and disasters such as the Gulf Oil Spill, not to mention issues confronting society such as Climate Change, Sustainability and Energy, the Geosciences have a critical role in the public awareness, safety, and national security of our nation. In the past year we have experienced volcanic eruptions, earth¬quakes, tsunamis, hurricanes, tornadoes, wildfires, severe drought and flooding, outbreaks of severe weather. Planet Earth will be monitored, observed, and studied as an Earth System, in real or near real time. Policy-makers, decision-makers, scientists, teachers, students, and citizens will not only participate in the process, but come to use such information and data routinely in their daily lives. 3-D data visualizations, virtual field trips, and interactive imagery from space all will contribute to the doing of real science in real time. Policy-Makers have linked Science, Technology, Engineering, and Mathematics (STEM) Education to United States' future economy and national security. The GeoSTEM community can deliver added value through leveraging current and future Geoscience-related resources that monitor our planet and protect the life and property of our citizens. The integration of a Geoscience and Remote Sensing Laboratory into an existing Earth Science program or a new Earth Systems Science course allows students to acquire the necessary rigorous laboratory skills as required by colleges or universities, while developing and becoming proficient in technological skills using industry standard analysis tools. With the accessibility of real-time or near real time data, students in a GeoSTEM driven course can engage in inquiry-based laboratory experiences focusing on real life applications, both local and global. Developing pathways between geoscientists, researchers, teachers, and students, will create an exchange of information, data, observations, and measurements that will lead to authentic science investigations through the monitoring of weather, water quality, sea surface temperature, coral reefs, marine wildlife, earthquakes, tsunamis, wildfires, air quality, land cover, and much more. Satellite, remote sensing, and geospatial technologies can introduce students and society to data that can inform policy makers and society both now and in the future.

Promoting the Use of Online Social Technology as a Case-Based Learning Tool

ERIC Educational Resources Information Center

Ractham, Peter; Chen, Charlie

2013-01-01

Social technology is proliferating and influencing different aspects of society. However, very few studies have examined the use of such a technology for a case-based learning pedagogy. This preliminary study investigates the use of social technology as a case-based learning tool to improve the effectiveness of case-based learning in the…

Safe and sustainable increases in day case emergency surgery.

PubMed

Hotchen, Andrew J; Coleman, Grant; O'Callaghan, John M; McWhinnie, Doug

2016-03-01

Selected patients referred to emergency general surgery departments are suitable for day case emergency surgery with no overnight hospital stay. There are no well-described sustainable pathways for these expedited operations and in many hospitals patients undergo unnecessary admissions and experience long waiting times. The authors proposed a new, sustainable, day case emergency surgery pathway which was implemented to streamline the assessment, treatment and discharge of acute surgical referrals. It requires rapid assessment of the patient by a senior clinician, and ready availability of diagnostic services and operating facilities. To assess this pathway, the authors conducted a prospective audit of general surgical referrals to a district general hospital in the UK. During the inclusion period 746 emergency referrals were assessed, 281 (37%) of these underwent an operation. Over a 5-month investigation period, the audit found that approximately 27% of all emergency general surgery patients requiring an operation could be managed with day case emergency surgery. This figure was maintained throughout the duration of the study. Operations included incision and drainage of abscesses, incarcerated hernia repairs and appendicectomies. The average length of stay of all surgical admissions decreased from 5 days to less than 3 days and the median time to senior review was 30 minutes. The authors have developed a pathway involving permanent members of the surgical assessment team that is sustainable over a 5-month period. The pathway has allowed rapid assessment of patients and reduced unnecessary inpatient stay in a sustainable and reproducible manner.

Ethylene resistance in flowering ornamental plants – improvements and future perspectives

PubMed Central

Olsen, Andreas; Lütken, Henrik; Hegelund, Josefine Nymark; Müller, Renate

2015-01-01

Various strategies of plant breeding have been attempted in order to improve the ethylene resistance of flowering ornamental plants. These approaches span from conventional techniques such as simple cross-pollination to new breeding techniques which modify the plants genetically such as precise genome-editing. The main strategies target the ethylene pathway directly; others focus on changing the ethylene pathway indirectly via pathways that are known to be antagonistic to the ethylene pathway, e.g. increasing cytokinin levels. Many of the known elements of the ethylene pathway have been addressed experimentally with the aim of modulating the overall response of the plant to ethylene. Elements of the ethylene pathway that appear particularly promising in this respect include ethylene receptors as ETR1, and transcription factors such as EIN3. Both direct and indirect approaches seem to be successful, nevertheless, although genetic transformation using recombinant DNA has the ability to save much time in the breeding process, they are not readily used by breeders yet. This is primarily due to legislative issues, economic issues, difficulties of implementing this technology in some ornamental plants, as well as how these techniques are publically perceived, particularly in Europe. Recently, newer and more precise genome-editing techniques have become available and they are already being implemented in some crops. New breeding techniques may help change the current situation and pave the way toward a legal and public acceptance if products of these technologies are indistinguishable from plants obtained by conventional techniques. PMID:26504580

Appropriateness of cases presenting in the emergency department following ambulance service secondary telephone triage: a retrospective cohort study

PubMed Central

Eastwood, Kathryn; Smith, Karen; Morgans, Amee; Stoelwinder, Johannes

2017-01-01

Objective To investigate the appropriateness of cases presenting to the emergency department (ED) following ambulance-based secondary telephone triage. Design A pragmatic retrospective cohort analysis of all the planned and unplanned ED presentations within 48 hours of a secondary telephone triage. Setting The secondary telephone triage service, called the Referral Service, and the hospitals were located in metropolitan Melbourne, Australia and operated 24 hours a day, servicing 4.25 million people. The Referral Service provides an in-depth secondary triage of cases classified as low acuity when calling the Australian emergency telephone number. Population Cases triaged by the Referral Service between September 2009 and June 2012 were linked to ED and hospital admission records (N=44,523). Planned ED presentations were cases referred to the ED following the secondary triage, unplanned ED presentations were cases that presented despite being referred to alternative care pathways. Main outcome measures Appropriateness was measured using an ED suitability definition and hospital admission rates. These were compared with mean population data which consisted of all of the ED presentations for the state (termed the ‘average Victorian ED presentation’). Results Planned ED presentations were more likely to be ED suitable than unplanned ED presentations (OR 1.62; 95% CI 1.5 to 1.7; p<0.001) and the average Victorian ED presentation (OR 1.85; 95% CI 1.01 to 3.4; p=0.046). They were also more likely to be admitted to the hospital than the unplanned ED presentation (OR 1.5; 95% CI 1.4 to 1.6; p<0.001) and the average Victorian ED presentation (OR 2.3, 95% CI 2.24 to 2.33; p<0.001). Just under 15% of cases diverted away from the emergency care pathways presented in the ED (unplanned ED attendances), and 9.5% of all the alternative care pathway cases were classified as ED suitable and 6.5% were admitted to hospital. Conclusions Secondary telephone triage was able to appropriately identify many ED suitable cases, and while most cases referred to alternative care pathways did not present in the ED. Further research is required to establish that these were not inappropriately triaged away from the emergency care pathways. PMID:29038180

Pathway modeling of microarray data: A case study of pathway activity changes in the testis following in utero exposure to dibutyl phthalate (DBP)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ovacik, Meric A.; Sen, Banalata; Euling, Susan Y.

Pathway activity level analysis, the approach pursued in this study, focuses on all genes that are known to be members of metabolic and signaling pathways as defined by the KEGG database. The pathway activity level analysis entails singular value decomposition (SVD) of the expression data of the genes constituting a given pathway. We explore an extension of the pathway activity methodology for application to time-course microarray data. We show that pathway analysis enhances our ability to detect biologically relevant changes in pathway activity using synthetic data. As a case study, we apply the pathway activity level formulation coupled with significancemore » analysis to microarray data from two different rat testes exposed in utero to Dibutyl Phthalate (DBP). In utero DBP exposure in the rat results in developmental toxicity of a number of male reproductive organs, including the testes. One well-characterized mode of action for DBP and the male reproductive developmental effects is the repression of expression of genes involved in cholesterol transport, steroid biosynthesis and testosterone synthesis that lead to a decreased fetal testicular testosterone. Previous analyses of DBP testes microarray data focused on either individual gene expression changes or changes in the expression of specific genes that are hypothesized, or known, to be important in testicular development and testosterone synthesis. However, a pathway analysis may inform whether there are additional affected pathways that could inform additional modes of action linked to DBP developmental toxicity. We show that Pathway activity analysis may be considered for a more comprehensive analysis of microarray data.« less

EDITORIAL: Commercial opportunities for neural engineers

NASA Astrophysics Data System (ADS)

Cavuoto, James

2008-03-01

Research and academic professionals in neural engineering know well the promise the field offers for advancing our understanding of basic neuroscience and devising new therapies for treating neurological diseases and disorders. But there is also considerable commercial opportunity for new start-up companies in several areas of neural engineering. The neurotechnology industry, which includes firms that manufacture neuromodulation devices, neural prostheses, neurorehabilitation systems, and neurosensing devices, is forecast to grow to grow from 3.6 billion this year to 8.8 billion in 2012, according to a recently published market research study from Neurotech Reports. In recent years, there have been several successful spinoffs of neurotechnology startup firms that originated with research at universities and clinical institutions. In many cases, the academic researchers who invented the new technology or product innovation have stayed on with their startup firms after receiving funding from venture capital firms, or after going public. Among the most successful neurotechnology industry spinoffs in recent years were: Cyberkinetics Inc., Foxborough, MA, a manufacturer of brain-computer interface devices based on research at Brown University. John Donoghue, a professor and chairman of the department of neuroscience at Brown University and executive director of the brain science program at Brown, founded the company in 2001 and remains on board as the chief scientific officer. Synapse Biomedical, Inc., Oberlin, OH, a manufacturer of diaphragm pacing systems, based on research at Case Western Reserve University. Raymond Onders, director of minimal invasive surgery and associate professor at University Hospital Case Medical Center in Cleveland, was the primary researcher. He was helped by J. Thomas Mortimer, professor emeritus of biomedical engineering at Case, and it was Mortimer who came up with the name NeuRx for the device. Onders performed his first surgical implant of the device in 2000. Anthony Ignagni, who worked with Mortimer and Onders as project director and chief biomedical engineer, became a co-founder of Synapse and is currently president and CEO. Afferent Corp., Providence, RI, a manufacturer of sensory stimulation systems based on research at Boston University, Afferent's technology is based on work by James Collins, professor of biomedical engineering at Boston University, who showed that low-level stochastic, or random, vibrations improved sense of touch. Collins went on to demonstrate that generating a subthreshold noise in the sensory pathways with a random electrical stimulation improves detectability of weak mechanical stimuli. In 1999 entrepreneur Jason Harry licensed the stochastic resonance technology from Boston University and received help from the Community Technology Fund-the university's technology transfer incubator. NeuroNexus Technologies, Inc., Ann Arbor, MI, a manufacturer of implanted neural probes, based on a program at the University of Michigan. NeuroNexus was spun out of UM's Center for Neural Communications Technology. Daryl Kipke, head of the Neural Engineering Laboratory at the university, started up NeuroNexus with several colleagues and currently serves as president and CEO. Commercialization issues were discussed recently at a preconference workshop at the 2007 meeting of the International Neuromodulation Society in Acapulco, Mexico. In the session, which was chaired by Chris Coburn of the Cleveland Clinic, neurotech entrepreneurs John Bowers from Northstar Neuroscience and Ben Pless, formerly of NeuroPace, shared their experiences bringing neuromodulation therapies to market. Coburn related his observations from the Cleveland Clinic, which has spun off 22 companies over the last five years. He cited several factors that would influence a neurotech startup's market potential, such as identifying the regulatory pathway, any predicate devices that exist, and the revenue potential for potential investors. Bowers cited several factors that would be critical for the growth of the industry, including reaching out to the 'influential implanters' and pushing reimbursement based on quality of life improvements, rather than mortality. Pless provided an overview of patent-related issues affecting neuromodulation devices. He noted that there have been 2000 issued patents for neuromodulation devices, most of them involving the peripheral nervous system. The example set by these companies and other startups in the neurotechnology industry should remind neural engineering researchers that there are plenty of opportunities for commercial success based on promising research at university and clinical research laboratories. Given the wide range of help and information that is available to potential entrepreneurs in this field, we expect to see many more examples of neurotechnology spinoffs in the years ahead.

Using Technology in Consultation: Enhancing Relationships

ERIC Educational Resources Information Center

Pease, Terrie; Copa, Annette; Proulx, Gregory A.; Boss, Jennifer

2004-01-01

Jennifer Boss, Senior Program Associate at ZERO TO THREE, spoke with three infant mental health consultants who worked with three different Early Head Start programs as part of the Pathways to Prevention (PTP) initiative. The interviews particularly focused on how to infuse technology into consultation arrangements that center around building and…

STEM - Science, Technology, Engineering, & Mathematics Career Expo

Science.gov Websites

Search STEM - Science, Technology, Engineering, & Mathematics Career Expo Come to Fermilab to meet Career Expo on April 18, 2018! Here's your guide to the event. Meet scientists, engineers, & ; technicians Ask career questions of the experts Ask experts about educational pathways leading to specific

40 CFR 80.1352 - What are the pre-compliance reporting requirements for the gasoline benzene program?

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Benzene concentration. An estimate of the average gasoline benzene concentration corresponding to the time... engineering and permitting, Procurement and Construction, and Commissioning and startup. (7) Basic information regarding the selected technology pathway for compliance (e.g., precursor re-routing or other technologies...

Building Families: Diverse Pathways to Parenthood

ERIC Educational Resources Information Center

Rosenblum, Katherine L.; Olshansky, Ellen

2007-01-01

Due to advances in reproductive technology and more progressive adoption laws, prospective parents now have many more choices and opportunities for how they form their families. This article explores the experiences of adoption, gay and lesbian families, and assisted reproductive technology to illustrate the concept that there are many legitimate…

Electronic Pathways. Adult Learning and the New Communication Technologies.

ERIC Educational Resources Information Center

Field, Jane, Ed.

This book, which is intended as a practical resource for individuals who are professionally concerned with adult learning, contains 21 papers and 3 checklists concerning the new communication and information technologies (IT) and adult learning. The following papers and checklists are included: "Introduction" (Jane Field); "The Use…

Digital Learning: Strengthening and Assessing 21st Century Skills, Grades 5-8

ERIC Educational Resources Information Center

Serim, Ferdi

2012-01-01

This comprehensive book offers a practical pathway for developing twenty-first-century skills while simultaneously strengthening content-area learning. "Digital Learning" contains a wealth of research-based practices to integrate the International Society for Technology in Education (ISTE) National Education Technology Standards (NETS) for both…

Professional Standards for Physical Education Teachers' Professional Development: Technologies for Performance?

ERIC Educational Resources Information Center

Macdonald, Doune; Mitchell, Jane; Mayer, Diane

2006-01-01

Background: The widespread and diverse models of professional standards for teaching raise questions with respect to the need to provide teachers with a pathway for continuing professional development balanced with the public nature of surveillance and accountability that may accompany standards. Ways of understanding technologies of power in…

Secondary School Technology Education in New Zealand: Does It Do What It Says on the Box?

ERIC Educational Resources Information Center

Reinsfield, Elizabeth

2014-01-01

Technology education, as mandated in the "New Zealand Curriculum" (Ministry of Education, 2007) provides an opportunity for schools and teachers to offer contextually relevant and innovative curriculum responses. Recent governmental initiatives appear to offer additional transitional pathways for "at risk" students but signpost…

Recognizing and Fostering Creativity in Technological Design Education

ERIC Educational Resources Information Center

Cropley, David; Cropley, Arthur

2010-01-01

The importance of creativity in technological design education is now clearly recognized, both in everyday understanding and also in formal curriculum guidelines. Design offers special opportunities for creativity because of the "openness" of problems (ill-defined problems, the existence of a variety of pathways to the solution, the absence of…

Pipelines and Pathways: Women of Color in Undergraduate STEM Majors and the College Experiences That Contribute to Persistence

ERIC Educational Resources Information Center

Espinosa, Lorelle L.

2011-01-01

Supporting undergraduate achievement in science, technology, engineering, and mathematics (STEM) disciplines is paramount to ensuring our nation's continued scientific and technological advancement. In this quantitative study, Lorelle Espinosa examines the effect of precollege characteristics, college experiences, and institutional setting on the…

Career Pathways of Science, Engineering and Technology Research Postgraduates

ERIC Educational Resources Information Center

Giles, Marnie; Ski, Chantal; Vrdoljak, Davorin

2009-01-01

Suitably qualified scientists and engineers are essential for research and development, innovation and, in turn, the growth of the economy. Science, engineering and technology skills are therefore necessary for Australia to remain competitive in a global market. This article reports findings from a nationwide study investigating the career…

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

PubMed

Cordell, Heather J; Han, Younghun; Mells, George F; Li, Yafang; Hirschfield, Gideon M; Greene, Casey S; Xie, Gang; Juran, Brian D; Zhu, Dakai; Qian, David C; Floyd, James A B; Morley, Katherine I; Prati, Daniele; Lleo, Ana; Cusi, Daniele; Gershwin, M Eric; Anderson, Carl A; Lazaridis, Konstantinos N; Invernizzi, Pietro; Seldin, Michael F; Sandford, Richard N; Amos, Christopher I; Siminovitch, Katherine A

2015-09-22

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

Lesions along the upper motor neuronal pathway with locked-in features after lightning strike and cardiac arrest: a case-review analysis.

PubMed

Abdulla, Susanne; Conrad, Anton; Schwemm, Karl-Peter; Stienstra, Mark P; Gorsselink, Edward L; Dengler, Reinhard; Abdulla, Walied

2014-01-01

This study describes a case of lesions of the upper motor neuronal pathway with locked-in features after lightning strike and cardiac arrest. A case-review analysis. In a 29-year-old male who was hit by a lightning strike during farming activities, cardiopulmonary resuscitation was provided first by co-workers and continued with success by the medical rescue service. After conducting advanced life support under monitoring and therapeutic hypothermia, quadriplegia with facial diplegia was recognized. A review was undertaken detailing the clinical course. MR imaging presented signs consistent with hypoxia-induced damage and diffusion-weighted MR images revealed pronounced damages along the upper motor neuronal pathway. A reactive electroencephalogram pattern, sustained eye movement and the patient communicating via eye-blinking were interpreted as locked-in features. Two weeks after admission the patient was transferred to a neurological rehabilitation centre for further professional care. Direct damage of the upper motor neuron pathway due to the current of the lightning should be considered, albeit the relative contribution of hypoxia-induced damage cannot be separated.

Are Universities Providing Non-STEM Students the Mathematics Preparation Required by Their Programs?: A Case Study of A Quantitative Literacy Pathway and Vertical Alignment from Remediation to Degree Completion

ERIC Educational Resources Information Center

Allen, Charles

2017-01-01

Informed by Gagne's belief in the necessity of prerequisite knowledge for new learning, and Bruner's Spiral Curriculum Theory, the objective of this case study was to explore the postsecondary pathway from remedial mathematics, through one gateway mathematics course, and into the quantitative literacy requirements of various non-STEM programs of…

Dynamic Transmission of Protein Allostery without Structural Change: Spatial Pathways or Global Modes?

PubMed Central

McLeish, Tom C.B.; Cann, Martin J.; Rodgers, Thomas L.

2015-01-01

We examine the contrast between mechanisms for allosteric signaling that involve structural change, and those that do not, from the perspective of allosteric pathways. In particular we treat in detail the case of fluctuation-allostery by which amplitude modulation of the thermal fluctuations of the elastic normal modes conveys the allosteric signal, and address the question of what an allosteric pathway means in this case. We find that a perturbation theory of thermal elastic solids and nonperturbative approach (by super-coarse-graining elasticity into internal bending modes) have opposite signatures in their structure of correlated pathways. We illustrate the effect from analysis of previous results from GlxR of Corynebacterium glutamicum, an example of the CRP/FNR transcription family of allosteric homodimers. We find that the visibility of both correlated pathways and disconnected sites of correlated motion in this protein suggests that mechanisms of local elastic stretch and bend are recruited for the purpose of creating and controlling allosteric cooperativity. PMID:26338443

Metabolic Complementation in Bacterial Communities: Necessary Conditions and Optimality

PubMed Central

Mori, Matteo; Ponce-de-León, Miguel; Peretó, Juli; Montero, Francisco

2016-01-01

Bacterial communities may display metabolic complementation, in which different members of the association partially contribute to the same biosynthetic pathway. In this way, the end product of the pathway is synthesized by the community as a whole. However, the emergence and the benefits of such complementation are poorly understood. Herein, we present a simple model to analyze the metabolic interactions among bacteria, including the host in the case of endosymbiotic bacteria. The model considers two cell populations, with both cell types encoding for the same linear biosynthetic pathway. We have found that, for metabolic complementation to emerge as an optimal strategy, both product inhibition and large permeabilities are needed. In the light of these results, we then consider the patterns found in the case of tryptophan biosynthesis in the endosymbiont consortium hosted by the aphid Cinara cedri. Using in-silico computed physicochemical properties of metabolites of this and other biosynthetic pathways, we verified that the splitting point of the pathway corresponds to the most permeable intermediate. PMID:27774085

The Influence of Curriculum, Instruction, Technology, and Social Interactions on Two Fifth-Grade Students' Epistemologies in Modeling Throughout a Model-Based Curriculum Unit

NASA Astrophysics Data System (ADS)

Baek, Hamin; Schwarz, Christina V.

2015-04-01

In the past decade, reform efforts in science education have increasingly attended to engaging students in scientific practices such as scientific modeling. Engaging students in scientific modeling can help them develop their epistemologies by allowing them to attend to the roles of mechanism and empirical evidence when constructing and revising models. In this article, we present our in-depth case study of how two fifth graders—Brian and Joon—who were students in a public school classroom located in a Midwestern state shifted their epistemologies in modeling as they participated in the enactment of a technologically enhanced, model-based curriculum unit on evaporation and condensation. First, analyses of Brian's and Joon's models indicate that their epistemologies in modeling related to explanation and empirical evidence shifted productively throughout the unit. Additionally, while their initial and final epistemologies in modeling were similar, the pathways in which their epistemologies in modeling shifted differed. Next, analyses of the classroom activities illustrate how various components of the learning ecology including technological tools, the teacher's scaffolding remarks, and students' collective activities and conversations, were marshaled in the service of the two students' shifting epistemologies in modeling. These findings suggest a nuanced view of individual learners' engagement in scientific modeling, their epistemological shifts in the practice, and the roles of technology and other components of a modeling-oriented learning environment for such shifts.

Pathways to STEM Initiative (PSI): Evaluation Report for an Investing in Innovation (I3) Development Grant

ERIC Educational Resources Information Center

Nakamoto, Jonathan; Bojorquez, Juan Carlos

2017-01-01

The purpose of this study was to assess the impact of the Pathways to STEM Initiative (PSI) on students and science teachers and to describe the level of PSI implementation. One group of middle schools participated in PSI, which included project-based science, technology, engineering, and math (STEM) coursework; extra-curricular STEM opportunities…

Basic Education for Adults: Pathways to College and Careers for Washington's Emerging Workforce. Washington's Community and Technical Colleges

ERIC Educational Resources Information Center

Washington State Board for Community and Technical Colleges, 2015

2015-01-01

This brief describes the Basic Education for Adults (BEdA) programs that bridge the gap between school and work, thereby creating pathways to college and careers for Washington's emerging workforce. BEdA programs teach foundational skills--reading, writing, math, technology and English language--so adults can move through college and into…

Identification of mutated driver pathways in cancer using a multi-objective optimization model.

PubMed

Zheng, Chun-Hou; Yang, Wu; Chong, Yan-Wen; Xia, Jun-Feng

2016-05-01

New-generation high-throughput technologies, including next-generation sequencing technology, have been extensively applied to solve biological problems. As a result, large cancer genomics projects such as the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium are producing large amount of rich and diverse data in multiple cancer types. The identification of mutated driver genes and driver pathways from these data is a significant challenge. Genome aberrations in cancer cells can be divided into two types: random 'passenger mutation' and functional 'driver mutation'. In this paper, we introduced a Multi-objective Optimization model based on a Genetic Algorithm (MOGA) to solve the maximum weight submatrix problem, which can be employed to identify driver genes and driver pathways promoting cancer proliferation. The maximum weight submatrix problem defined to find mutated driver pathways is based on two specific properties, i.e., high coverage and high exclusivity. The multi-objective optimization model can adjust the trade-off between high coverage and high exclusivity. We proposed an integrative model by combining gene expression data and mutation data to improve the performance of the MOGA algorithm in a biological context. Copyright © 2016 Elsevier Ltd. All rights reserved.

Using Patient Pathway Analysis to Design Patient-centered Referral Networks for Diagnosis and Treatment of Tuberculosis: The Case of the Philippines

PubMed Central

Garfin, Celine; Mantala, Mariquita; Yadav, Rajendra; Hanson, Christy L; Osberg, Mike; Hymoff, Aaron; Makayova, Julia

2017-01-01

Abstract Background Tuberculosis (TB) is the 8th leading cause of death in the Philippines. A recent prevalence survey found that there were nearly 70% more cases of tuberculosis than previously estimated. Given these new data, the National TB Program (NTP), operating through a decentralized health system, identified about 58% of the estimated new drug-sensitive (DS) TB patients in 2016. However, the NTP only identified and commenced treatment for around 17% of estimated new drug-resistant patients. In order to reach the remaining 42% of drug-sensitive patients and 83% of drug-resistant patients, it is necessary to develop a better understanding of where patients seek care. Methods National and regional patient pathway analyses (PPAs) were undertaken using existing national survey and NTP data. The PPA assessed the alignment between patient care seeking and the availability of TB diagnostic and treatment services. Results Systemic referral networks from the community-level Barangay Health Stations (BHSs) to diagnostic facilities have enabled more efficient detection of drug-sensitive tuberculosis in the public sector. Approximately 36% of patients initiated care in the private sector, where there is limited coverage of appropriate diagnostic technologies. Important differences in the alignment between care seeking patterns and diagnostic and treatment availability were found between regions. Conclusions The PPA identified opportunities for strengthening access to care for all forms of tuberculosis and for accelerating the time to diagnosis by aligning services to where patients initiate care. Geographic variations in care seeking may guide prioritization of some regions for intensified engagement with the private sector. PMID:29117352

Infertility and Its Treatments in Association with Autism Spectrum Disorders: A Review and Results from the CHARGE Study

PubMed Central

Lyall, Kristen; Baker, Alice; Hertz-Picciotto, Irva; Walker, Cheryl K.

2013-01-01

Previous findings on relationships between infertility, infertility therapies, and autism spectrum disorders (ASD) have been inconsistent. The goals of this study are first, to briefly review this evidence and second, to examine infertility and its treatments in association with having a child with ASD in newly analyzed data. In review, we identified 14 studies published as of May 2013 investigating infertility and/or its treatments and ASD. Overall, prior results showed little support for a strong association, though some increases in risk with specific treatments were found; many limitations were noted. In new analyses of the CHildhood Autism Risk from Genetics and the Environment (CHARGE) population-based study, cases with autism spectrum disorder (ASD, n = 513) and controls confirmed to have typical development (n = 388) were compared with regard to frequencies of infertility diagnoses and treatments overall and by type. Infertility diagnoses and treatments were also grouped to explore potential underlying pathways. Logistic regression was used to obtain crude and adjusted odds ratios overall and, in secondary analyses, stratified by maternal age (≥35 years) and diagnostic subgroups. No differences in infertility, infertility treatments, or hypothesized underlying pathways were found between cases and controls in crude or adjusted analyses. Numbers were small for rarer therapies and in subgroup analyses; thus the potential for modest associations in specific subsets cannot be ruled out. However, converging evidence from this and other studies suggests that assisted reproductive technology is not a strong independent risk factor for ASD. Recommendations for future studies of this topic are provided. PMID:23965925

Computational genomic identification and functional reconstitution of plant natural product biosynthetic pathways

PubMed Central

2016-01-01

Covering: 2003 to 2016 The last decade has seen the first major discoveries regarding the genomic basis of plant natural product biosynthetic pathways. Four key computationally driven strategies have been developed to identify such pathways, which make use of physical clustering, co-expression, evolutionary co-occurrence and epigenomic co-regulation of the genes involved in producing a plant natural product. Here, we discuss how these approaches can be used for the discovery of plant biosynthetic pathways encoded by both chromosomally clustered and non-clustered genes. Additionally, we will discuss opportunities to prioritize plant gene clusters for experimental characterization, and end with a forward-looking perspective on how synthetic biology technologies will allow effective functional reconstitution of candidate pathways using a variety of genetic systems. PMID:27321668

Power Systems of the Future: A 21st Century Power Partnership Thought Leadership Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zinaman, Owen; Miller, Mackay; Adil, Ali

This report summarizes key forces driving transformation in the power sector around the world, presents a framework for evaluating decisions regarding extent and pace of change, and defines pathways for transformation. Powerful trends in technology, policy environments, financing, and business models are driving change in power sectors globally. In light of these trends, the question is no longer whether power systems will be transformed, but rather how these transformations will occur. Three approaches to policy and technology decision-making can guide these transformations: adaptive, reconstructive, and evolutionary. Within these approaches, we explore the five pathways that have emerged as viable modelsmore » for power system transformation.« less

Predictive role of computer simulation in assessing signaling pathways of crizotinib-treated A549 lung cancer cells.

PubMed

Xia, Pu; Mou, Fei-Fei; Wang, Li-Wei

2012-01-01

Non-small-cell lung cancer (NSCLC) is a leading cause of cancer deaths worldwide. Crizotinib has been approved by the U.S. Food and Drug Administration for the treatment of patients with advanced NSCLC. However, understanding of mechanisms of action is still limited. In our studies, we confirmed crizotinib-induced apoptosis in A549 lung cancer cells. In order to assess mechanisms, small molecular docking technology was used as a preliminary simulation of signaling pathways. Interesting, our results of experiments were consistent with the results of computer simulation. This indicates that small molecular docking technology should find wide use for its reliability and convenience.

Novel technologies provide more engineering strategies for amino acid-producing microorganisms.

PubMed

Gu, Pengfei; Su, Tianyuan; Qi, Qingsheng

2016-03-01

Traditionally, amino acid-producing strains were obtained by random mutagenesis and subsequent selection. With the development of genetic and metabolic engineering techniques, various microorganisms with high amino acid production yields are now constructed by rational design of targeted biosynthetic pathways. Recently, novel technologies derived from systems and synthetic biology have emerged and open a new promising avenue towards the engineering of amino acid production microorganisms. In this review, these approaches, including rational engineering of rate-limiting enzymes, real-time sensing of end-products, pathway optimization on the chromosome, transcription factor-mediated strain improvement, and metabolic modeling and flux analysis, were summarized with regard to their application in microbial amino acid production.

The development and technology transfer of software engineering technology at NASA. Johnson Space Center

NASA Technical Reports Server (NTRS)

Pitman, C. L.; Erb, D. M.; Izygon, M. E.; Fridge, E. M., III; Roush, G. B.; Braley, D. M.; Savely, R. T.

1992-01-01

The United State's big space projects of the next decades, such as Space Station and the Human Exploration Initiative, will need the development of many millions of lines of mission critical software. NASA-Johnson (JSC) is identifying and developing some of the Computer Aided Software Engineering (CASE) technology that NASA will need to build these future software systems. The goal is to improve the quality and the productivity of large software development projects. New trends are outlined in CASE technology and how the Software Technology Branch (STB) at JSC is endeavoring to provide some of these CASE solutions for NASA is described. Key software technology components include knowledge-based systems, software reusability, user interface technology, reengineering environments, management systems for the software development process, software cost models, repository technology, and open, integrated CASE environment frameworks. The paper presents the status and long-term expectations for CASE products. The STB's Reengineering Application Project (REAP), Advanced Software Development Workstation (ASDW) project, and software development cost model (COSTMODL) project are then discussed. Some of the general difficulties of technology transfer are introduced, and a process developed by STB for CASE technology insertion is described.

Improving Assistive Technology Service by Using 3D Printing: Three Case Studies.

PubMed

Watanabe, Takashi; Hatakeyama, Takuro; Tomiita, Mitsuru

2015-01-01

Assistive technology services are essential for adapting assistive devices to the individual needs of users with disabilities. In this study, we attempted to apply three-dimensional (3D) printing technology to three actual cases, and to study its use, effectiveness, and future applications. We assessed the usefulness of 3D printing technology by categorizing its utilization after reviewing the outcomes of these case studies. In future work, we aim to gather additional case studies and derive information on using 3D printing technology that will enable its effective application in the process of assistive technology services.

Students' Learning Performance and Transitions in Different Learning Pathways to Higher Vocational Education

ERIC Educational Resources Information Center

Biemans, Harm; Mariën, Hans; Fleur, Erik; Tobi, Hilde; Nieuwenhuis, Loek; Runhaar, Piety

2016-01-01

To improve students' transitions between successive educational levels, continuing learning pathways are being designed and implemented in many countries. This study was carried out to examine the effects of the Green Lycea (GL) as critical cases of continuing learning pathways in vocational education in The Netherlands. The GL were compared with…

Practical aspects of NGS-based pathways analysis for personalized cancer science and medicine

PubMed Central

Paleeva, Anna; Kremenetskaya, Olga; Vinogradov, Dmitriy

2016-01-01

Nowadays, the personalized approach to health care and cancer care in particular is becoming more and more popular and is taking an important place in the translational medicine paradigm. In some cases, detection of the patient-specific individual mutations that point to a targeted therapy has already become a routine practice for clinical oncologists. Wider panels of genetic markers are also on the market which cover a greater number of possible oncogenes including those with lower reliability of resulting medical conclusions. In light of the large availability of high-throughput technologies, it is very tempting to use complete patient-specific New Generation Sequencing (NGS) or other “omics” data for cancer treatment guidance. However, there are still no gold standard methods and protocols to evaluate them. Here we will discuss the clinical utility of each of the data types and describe a systems biology approach adapted for single patient measurements. We will try to summarize the current state of the field focusing on the clinically relevant case-studies and practical aspects of data processing. PMID:27191992

Intentionally Linking Gateway-Course Transformation Efforts with Guided Pathways

ERIC Educational Resources Information Center

Rife, Martine Courant; Conner, Christine

2017-01-01

Offered as a case study, this chapter shows how Lansing Community College intentionally combined efforts to redesign eight high-risk courses with efforts to create clearer guided curricular pathways for the college's students.

Adaptive Control Model Reveals Systematic Feedback and Key Molecules in Metabolic Pathway Regulation

PubMed Central

Moffitt, Richard A.; Merrill, Alfred H.; Wang, May D.

2011-01-01

Abstract Robust behavior in metabolic pathways resembles stabilized performance in systems under autonomous control. This suggests we can apply control theory to study existing regulation in these cellular networks. Here, we use model-reference adaptive control (MRAC) to investigate the dynamics of de novo sphingolipid synthesis regulation in a combined theoretical and experimental case study. The effects of serine palmitoyltransferase over-expression on this pathway are studied in vitro using human embryonic kidney cells. We report two key results from comparing numerical simulations with observed data. First, MRAC simulations of pathway dynamics are comparable to simulations from a standard model using mass action kinetics. The root-sum-square (RSS) between data and simulations in both cases differ by less than 5%. Second, MRAC simulations suggest systematic pathway regulation in terms of adaptive feedback from individual molecules. In response to increased metabolite levels available for de novo sphingolipid synthesis, feedback from molecules along the main artery of the pathway is regulated more frequently and with greater amplitude than from other molecules along the branches. These biological insights are consistent with current knowledge while being new that they may guide future research in sphingolipid biology. In summary, we report a novel approach to study regulation in cellular networks by applying control theory in the context of robust metabolic pathways. We do this to uncover potential insight into the dynamics of regulation and the reverse engineering of cellular networks for systems biology. This new modeling approach and the implementation routines designed for this case study may be extended to other systems. Supplementary Material is available at www.liebertonline.com/cmb. PMID:21314456

Genetic variations in vitamin D-related pathways and breast cancer risk in African American women in the AMBER consortium

PubMed Central

Yao, Song; Haddad, Stephen A.; Hu, Qiang; Liu, Song; Lunetta, Kathryn L.; Ruiz-Narvaez, Edward A.; Hong, Chi-Chen; Zhu, Qianqian; Sucheston-Campbell, Lara; Cheng, Ting-Yuan David; Bensen, Jeannette T.; Johnson, Candace S.; Trump, Donald L.; Haiman, Christopher A.; Olshan, Andrew F.; Palmer, Julie R.; Ambrosone, Christine B.

2016-01-01

Studies of genetic variations in vitamin D-related pathways and breast cancer risk have been conducted mostly in populations of European ancestry, and only sparsely in African Americans (AA), who are known for a high prevalence of vitamin D deficiency. We analyzed 24,445 germline variants in 63 genes from vitamin D-related pathways in the African American Breast Cancer Epidemiology and Risk (AMBER) consortium, including 3,663 breast cancer cases and 4,687 controls. Odds ratios (OR) were derived from logistic regression models for overall breast cancer, by estrogen receptor (ER) status (1,983 ER positive and 1,098 ER negative), and for case-only analyses of ER status. None of the three vitamin D-related pathways were associated with breast cancer risk overall or by ER status. Gene-level analyses identified associations with risk for several genes at a nominal p ≤ 0.05, particularly for ER− breast cancer, including rs4647707 in DDB2. In case-only analyses, vitamin D metabolism and signaling pathways were associated with ER− cancer (pathway-level p = 0.02), driven by a single gene CASR (gene-level p = 0.001). The top SNP in CASR was rs112594756 (p = 7 × 10−5, gene-wide corrected p = 0.01), followed by a second signal from a nearby SNP rs6799828 (p = 1 × 10−4, corrected p = 0.03). In summary, several variants in vitamin D pathways were associated with breast cancer risk in AA women. In addition, CASR may be related to tumor ER status, supporting a role of vitamin D or calcium in modifying breast cancer phenotypes. PMID:26650177

Approaches to Children’s Exposure Assessment: Case Study with Diethylhexylphthalate (DEHP)

PubMed Central

Ginsberg, Gary; Ginsberg, Justine; Foos, Brenda

2016-01-01

Children’s exposure assessment is a key input into epidemiology studies, risk assessment and source apportionment. The goals of this article are to describe a methodology for children’s exposure assessment that can be used for these purposes and to apply the methodology to source apportionment for the case study chemical, diethylhexylphthalate (DEHP). A key feature is the comparison of total (aggregate) exposure calculated via a pathways approach to that derived from a biomonitoring approach. The 4-step methodology and its results for DEHP are: (1) Prioritization of life stages and exposure pathways, with pregnancy, breast-fed infants, and toddlers the focus of the case study and pathways selected that are relevant to these groups; (2) Estimation of pathway-specific exposures by life stage wherein diet was found to be the largest contributor for pregnant women, breast milk and mouthing behavior for the nursing infant and diet, house dust, and mouthing for toddlers; (3) Comparison of aggregate exposure by pathways vs biomonitoring-based approaches wherein good concordance was found for toddlers and pregnant women providing confidence in the exposure assessment; (4) Source apportionment in which DEHP presence in foods, children’s products, consumer products and the built environment are discussed with respect to early life mouthing, house dust and dietary exposure. A potential fifth step of the method involves the calculation of exposure doses for risk assessment which is described but outside the scope for the current case study. In summary, the methodology has been used to synthesize the available information to identify key sources of early life exposure to DEHP. PMID:27376320

Air Force Organizational Adoption of Remotely Piloted Vehicles

DTIC Science & Technology

2004-05-01

organization that employs them. On the other hand, disruptive technologies are consistent with RMAs, eliminating a fundamental ability that provides...the idea of sustaining and disruptive technologies . An extensive case study of the disk drive industry details some key but often overlooked...characteristics of disruptive technology. A total of 116 cases of new technologies were studied with four of the cases involving disruptive technologies . In

Locate the Lesion: A Project-Based Learning Case that Stimulates Comprehension and Application of Neuroanatomy

PubMed Central

Lemons, Michele L.

2017-01-01

A fictitious patient, Mr. Challenge, is admitted to the emergency room and displays symptoms consistent with damage to the central nervous system. In this problem-based learning case, students are challenged to determine the location of a lesion that is consistent with Mr. Challenge’s symptoms. Students discover details about Mr. Challenge’s symptoms while exploring three anatomical pathways: corticospinal tract, spinothalamic tract and medial lemniscal pathway. Students make predictions as to which of these pathways may be damaged in Mr. Challenge and defend their predictions based on their research of the function and anatomical location of these tracts. This ultimately leads the student to identifying a single lesion site that can account for Mr. Challenge’s symptoms. This case is executed in an undergraduate neuroscience course and would be useful in anatomy and physiology course, as well as other courses that serve students interested in health science related careers. PMID:28690440

Statistical and methodological issues in the evaluation of case management studies.

PubMed

Lesser, M L; Robertson, S; Kohn, N; Cooper, D J; Dlugacz, Y D

1996-01-01

For the past 3 years, the nursing case management team at North Shore University Hospital in Manhasset, NY, has been involved in a project to implement more than 50 clinical pathways, which provide a written "time line" for clinical events that should occur during a patient's hospital stay. A major objective of this project was to evaluate the efficacy of these pathways with respect to a number of important outcomes, such as length of stay, hospital costs, quality of patient care, and nursing and patient satisfaction. This article discusses several statistics-related issues in the design and evaluation of such case management studies. In particular, the role of a research approach in implementing and evaluating hospital programs, the choice of a comparison (control) group, the exclusion of selected patients from analysis, and the problems of equating pathways with diagnosis-related groups are addressed.

Locate the Lesion: A Project-Based Learning Case that Stimulates Comprehension and Application of Neuroanatomy.

PubMed

Lemons, Michele L

2017-01-01

A fictitious patient, Mr. Challenge, is admitted to the emergency room and displays symptoms consistent with damage to the central nervous system. In this problem-based learning case, students are challenged to determine the location of a lesion that is consistent with Mr. Challenge's symptoms. Students discover details about Mr. Challenge's symptoms while exploring three anatomical pathways: corticospinal tract, spinothalamic tract and medial lemniscal pathway. Students make predictions as to which of these pathways may be damaged in Mr. Challenge and defend their predictions based on their research of the function and anatomical location of these tracts. This ultimately leads the student to identifying a single lesion site that can account for Mr. Challenge's symptoms. This case is executed in an undergraduate neuroscience course and would be useful in anatomy and physiology course, as well as other courses that serve students interested in health science related careers.

Escher: A Web Application for Building, Sharing, and Embedding Data-Rich Visualizations of Biological Pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, Zachary A.; Drager, Andreas; Ebrahim, Ali

Escher is a web application for visualizing data on biological pathways. Three key features make Escher a uniquely effective tool for pathway visualization. First, users can rapidly design new pathway maps. Escher provides pathway suggestions based on user data and genome-scale models, so users can draw pathways in a semi-automated way. Second, users can visualize data related to genes or proteins on the associated reactions and pathways, using rules that define which enzymes catalyze each reaction. Thus, users can identify trends in common genomic data types (e.g. RNA-Seq, proteomics, ChIP)—in conjunction with metabolite- and reaction-oriented data types (e.g. metabolomics, fluxomics).more » Third, Escher harnesses the strengths of web technologies (SVG, D3, developer tools) so that visualizations can be rapidly adapted, extended, shared, and embedded. This paper provides examples of each of these features and explains how the development approach used for Escher can be used to guide the development of future visualization tools.« less

Escher: A Web Application for Building, Sharing, and Embedding Data-Rich Visualizations of Biological Pathways

PubMed Central

King, Zachary A.; Dräger, Andreas; Ebrahim, Ali; Sonnenschein, Nikolaus; Lewis, Nathan E.; Palsson, Bernhard O.

2015-01-01

Escher is a web application for visualizing data on biological pathways. Three key features make Escher a uniquely effective tool for pathway visualization. First, users can rapidly design new pathway maps. Escher provides pathway suggestions based on user data and genome-scale models, so users can draw pathways in a semi-automated way. Second, users can visualize data related to genes or proteins on the associated reactions and pathways, using rules that define which enzymes catalyze each reaction. Thus, users can identify trends in common genomic data types (e.g. RNA-Seq, proteomics, ChIP)—in conjunction with metabolite- and reaction-oriented data types (e.g. metabolomics, fluxomics). Third, Escher harnesses the strengths of web technologies (SVG, D3, developer tools) so that visualizations can be rapidly adapted, extended, shared, and embedded. This paper provides examples of each of these features and explains how the development approach used for Escher can be used to guide the development of future visualization tools. PMID:26313928

Escher: A Web Application for Building, Sharing, and Embedding Data-Rich Visualizations of Biological Pathways

DOE PAGES

King, Zachary A.; Drager, Andreas; Ebrahim, Ali; ...

2015-08-27

Escher is a web application for visualizing data on biological pathways. Three key features make Escher a uniquely effective tool for pathway visualization. First, users can rapidly design new pathway maps. Escher provides pathway suggestions based on user data and genome-scale models, so users can draw pathways in a semi-automated way. Second, users can visualize data related to genes or proteins on the associated reactions and pathways, using rules that define which enzymes catalyze each reaction. Thus, users can identify trends in common genomic data types (e.g. RNA-Seq, proteomics, ChIP)—in conjunction with metabolite- and reaction-oriented data types (e.g. metabolomics, fluxomics).more » Third, Escher harnesses the strengths of web technologies (SVG, D3, developer tools) so that visualizations can be rapidly adapted, extended, shared, and embedded. This paper provides examples of each of these features and explains how the development approach used for Escher can be used to guide the development of future visualization tools.« less

A guide for building biological pathways along with two case studies: hair and breast development.

PubMed

Trindade, Daniel; Orsine, Lissur A; Barbosa-Silva, Adriano; Donnard, Elisa R; Ortega, J Miguel

2015-03-01

Genomic information is being underlined in the format of biological pathways. Building these biological pathways is an ongoing demand and benefits from methods for extracting information from biomedical literature with the aid of text-mining tools. Here we hopefully guide you in the attempt of building a customized pathway or chart representation of a system. Our manual is based on a group of software designed to look at biointeractions in a set of abstracts retrieved from PubMed. However, they aim to support the work of someone with biological background, who does not need to be an expert on the subject and will play the role of manual curator while designing the representation of the system, the pathway. We therefore illustrate with two challenging case studies: hair and breast development. They were chosen for focusing on recent acquisitions of human evolution. We produced sub-pathways for each study, representing different phases of development. Differently from most charts present in current databases, we present detailed descriptions, which will additionally guide PESCADOR users along the process. The implementation as a web interface makes PESCADOR a unique tool for guiding the user along the biointeractions, which will constitute a novel pathway. Copyright © 2014 Elsevier Inc. All rights reserved.

Challenges in using electronic health record data for CER: experience of 4 learning organizations and solutions applied.

PubMed

Bayley, K Bruce; Belnap, Tom; Savitz, Lucy; Masica, Andrew L; Shah, Nilay; Fleming, Neil S

2013-08-01

To document the strengths and challenges of using electronic health records (EHRs) for comparative effectiveness research (CER). A replicated case study of comparative effectiveness in hypertension treatment was conducted across 4 health systems, with instructions to extract data and document problems encountered using a specified list of required data elements. Researchers at each health system documented successes and challenges, and suggested solutions for addressing challenges. Data challenges fell into 5 categories: missing data, erroneous data, uninterpretable data, inconsistencies among providers and over time, and data stored in noncoded text notes. Suggested strategies to address these issues include data validation steps, use of surrogate markers, natural language processing, and statistical techniques. A number of EHR issues can hamper the extraction of valid data for cross-health system comparative effectiveness studies. Our case example cautions against a blind reliance on EHR data as a single definitive data source. Nevertheless, EHR data are superior to administrative or claims data alone, and are cheaper and timelier than clinical trials or manual chart reviews. All 4 participating health systems are pursuing pathways to more effectively use EHR data for CER.A partnership between clinicians, researchers, and information technology specialists is encouraged as a way to capitalize on the wealth of information contained in the EHR. Future developments in both technology and care delivery hold promise for improvement in the ability to use EHR data for CER.

Visible Pathways: A Life Course Perspective on Technology Use and Relationship Reconnection

ERIC Educational Resources Information Center

Quinn, Kelly Ann

2012-01-01

Research on internet communication technologies by midlife and older adults has received less attention than the young, yet rapid gains in the use internet media suggest older adults have become significant users. Adoption of specific applications has emerged in patterns distinct from younger users, reflecting the different experiences and…

Designing STEM Pathways through Early College: Ohio's Metro Early College High School

ERIC Educational Resources Information Center

North, Charlotte

2011-01-01

Calls for improved outcomes in U.S. science, technology, engineering, and mathematics education are frequent and insistent. In 2009, the Commission on Mathematics and Science Education, convened by the Institute for Advanced Study and Carnegie Corporation of New York, concluded that: "Knowledge and skills from science, technology, engineering…

Using Educational Technology to Help Students Get Back on Track

ERIC Educational Resources Information Center

Bertrand, Clare

2013-01-01

Increasingly, school districts, schools, and their partners are incorporating technology into strategies that help engage young people who have fallen off track to on-time graduation get back on track and move into effective educational pathways. This is especially true in light of the continuing pressure to raise high school graduation rates and…

Drug-Path: a database for drug-induced pathways

PubMed Central

Zeng, Hui; Cui, Qinghua

2015-01-01

Some databases for drug-associated pathways have been built and are publicly available. However, the pathways curated in most of these databases are drug-action or drug-metabolism pathways. In recent years, high-throughput technologies such as microarray and RNA-sequencing have produced lots of drug-induced gene expression profiles. Interestingly, drug-induced gene expression profile frequently show distinct patterns, indicating that drugs normally induce the activation or repression of distinct pathways. Therefore, these pathways contribute to study the mechanisms of drugs and drug-repurposing. Here, we present Drug-Path, a database of drug-induced pathways, which was generated by KEGG pathway enrichment analysis for drug-induced upregulated genes and downregulated genes based on drug-induced gene expression datasets in Connectivity Map. Drug-Path provides user-friendly interfaces to retrieve, visualize and download the drug-induced pathway data in the database. In addition, the genes deregulated by a given drug are highlighted in the pathways. All data were organized using SQLite. The web site was implemented using Django, a Python web framework. Finally, we believe that this database will be useful for related researches. Database URL: http://www.cuilab.cn/drugpath PMID:26130661

Drug-Path: a database for drug-induced pathways.

PubMed

Zeng, Hui; Qiu, Chengxiang; Cui, Qinghua

2015-01-01

Some databases for drug-associated pathways have been built and are publicly available. However, the pathways curated in most of these databases are drug-action or drug-metabolism pathways. In recent years, high-throughput technologies such as microarray and RNA-sequencing have produced lots of drug-induced gene expression profiles. Interestingly, drug-induced gene expression profile frequently show distinct patterns, indicating that drugs normally induce the activation or repression of distinct pathways. Therefore, these pathways contribute to study the mechanisms of drugs and drug-repurposing. Here, we present Drug-Path, a database of drug-induced pathways, which was generated by KEGG pathway enrichment analysis for drug-induced upregulated genes and downregulated genes based on drug-induced gene expression datasets in Connectivity Map. Drug-Path provides user-friendly interfaces to retrieve, visualize and download the drug-induced pathway data in the database. In addition, the genes deregulated by a given drug are highlighted in the pathways. All data were organized using SQLite. The web site was implemented using Django, a Python web framework. Finally, we believe that this database will be useful for related researches. © The Author(s) 2015. Published by Oxford University Press.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bryant, M.; Starkey, A.H.; Dick-Peddie, W.A.

A brief overview of the present day geothermal applications for hydrothermal electrical generation and direct heat use and their environmental implications is provided. Technologies and environmental impacts are considered at all points on the pathway of development resource exploration; well field, plant and transmission line construction; and plant operation. The technologies for electrical generation-direct, dry steam conversion; separated steam conversion; single-flash conversion, separated-steam/single-flash conversion and binary cycle conversion and the technologies for direct heat use - direct use of geothermal waters, surface heat exhanger, down-the hole heat exchanger and heat pump are described. A summary of the geothermal technologies plannedmore » or in operation within New Mexico geothermal areas is provided. A review of regulations that affect geothermal development and its related environmental impact in New Mexico is presented. The regulatory pathway, both state and federal, of geothermal exploration after the securing of appropriate leases, development, and construction and implementation of a geothermal facility are described. Six categories (Geophysical, Water, Air, Noise, Biota and Socioeconomics) were selected for environmental assessment. The data available is described.« less

Open questions: The disrupted circuitry of the cancer cell

DOE PAGES

Wiley, H. Steven

2014-10-18

Every new decade of biology brings with it a change in outlook driven by new technologies and fresh perspectives. Such is the case for cancer and how we consider the disease. The advent of molecular biology led to the identification of altered signaling molecules and 'oncogenes' that were proposed to drive uncontrolled cell proliferation. The rise of cell biology and new imaging and culturing technologies led to the idea that disruptions in the extracellular environment prime cells for transformation. In the current genomics era, cancer is most commonly seen as a genetic disorder where an unstable genome gives rise tomore » a variety of different cell variants that are selected for proliferation and survival. All of these views are partially correct, of course, and are simply different ways of saying that genetic alterations in cancer cells result in a loss of growth homeostasis. They also take the view that molecular changes 'drive' a cell to grow uncontrollably, rather than tip the balance from one normal state (quiescence) to another (proliferation). Underlying this oversimplification is a profound ignorance of what controls homeostatic cell growth in the first place and how specific mutations impact it. Normal, proliferation-competent cells can accurately monitor their environment and respond appropriately to perturbation, whether it is a loss of neighbors or an inflammatory stimulus. Cancer cells either proliferate or refuse to die where and when they should not, which clearly indicates that they have problems in detecting or responding to their environment. Thus, an enormous amount of effort has gone into defining the signaling pathways that can trigger a proliferative response and the biochemical mechanisms underlying these pathways. Far less work has focused on understanding the higher-order logic of these pathways and the roles played by all of the components as part of an integrated system. In other words, we do not really understand how cells process information and make decisions and thus cannot predict how any given molecular change will alter what a cell does.« less

Eight-step method to build the clinical content of an evidence-based care pathway: the case for COPD exacerbation

PubMed Central

2012-01-01

Background Optimization of the clinical care process by integration of evidence-based knowledge is one of the active components in care pathways. When studying the impact of a care pathway by using a cluster-randomized design, standardization of the care pathway intervention is crucial. This methodology paper describes the development of the clinical content of an evidence-based care pathway for in-hospital management of chronic obstructive pulmonary disease (COPD) exacerbation in the context of a cluster-randomized controlled trial (cRCT) on care pathway effectiveness. Methods The clinical content of a care pathway for COPD exacerbation was developed based on recognized process design and guideline development methods. Subsequently, based on the COPD case study, a generalized eight-step method was designed to support the development of the clinical content of an evidence-based care pathway. Results A set of 38 evidence-based key interventions and a set of 24 process and 15 outcome indicators were developed in eight different steps. Nine Belgian multidisciplinary teams piloted both the set of key interventions and indicators. The key intervention set was judged by the teams as being valid and clinically applicable. In addition, the pilot study showed that the indicators were feasible for the involved clinicians and patients. Conclusions The set of 38 key interventions and the set of process and outcome indicators were found to be appropriate for the development and standardization of the clinical content of the COPD care pathway in the context of a cRCT on pathway effectiveness. The developed eight-step method may facilitate multidisciplinary teams caring for other patient populations in designing the clinical content of their future care pathways. PMID:23190552

Cerebral toxoplasmosis in Acquired Immunodeficiency Syndrome (AIDS) patients also provides unifying pathophysiologic hypotheses for Holmes tremor.

PubMed

Lekoubou, Alain; Njouoguep, Rodrigue; Kuate, Callixte; Kengne, André Pascal

2010-06-03

Holmes tremor is a rare symptomatic movement disorder. Currently suggested pathophysiological mechanisms of the disease are mostly derived from stroke cases. Although rare, cerebral toxoplasmosis may strengthen the pathophysiologic mechanism of disease. A case of Holmes tremor secondary to cerebral toxoplasmosis in an AIDS patient is presented. A relevant literature search was performed, using pubmed and several entries for Holmes tremor as labelled in the literature. The unifying feature of our case and those of the literature is the involvement of either the cerebello-thalamo-cortical and/or the dentato-rubro-olivary pathways. The abscess or the extension of surrounding edema beyond these two circuits may account for the superimposed dysfunction of the nigrostriatal system in some but not all cases. The short delay observed in our observation and the dramatic response to treatment may indirectly support the secondary neuronal degeneration theory in the mechanism of Holmes tremor. Cases of cerebral toxoplasmosis in AIDS patients also provide arguments for the role of the thalamo-cortical and/or the dentato-rubro-olivary pathways dysfunction in the pathogenesis of Holmes tremor. Involvement of the nigro-striatal pathway may not be crucial in the development of this syndrome. Our case also brings additional indirect arguments for the role of secondary neuronal degeneration in the mechanism of Holmes tremor.

Influence of Referral Pathway on Ebola Virus Disease Case-Fatality Rate and Effect of Survival Selection Bias.

PubMed

Rudolf, Frauke; Damkjær, Mads; Lunding, Suzanne; Dornonville de la Cour, Kenn; Young, Alyssa; Brooks, Tim; Sesay, Tom; Salam, Alex P; Mishra, Sharmistha; Storgaard, Merete

2017-04-01

Case-fatality rates in Ebola treatment centers (ETCs) varied widely during the Ebola virus disease (EVD) outbreak in West Africa. We assessed the influence of referral pathway on ETC case-fatality rates with a retrospective cohort of 126 patients treated at the Mathaska ETC in Port Loko, Sierra Leone. The patients consisted of persons who had confirmed EVD when transferred to the ETC or who had been diagnosed onsite. The case-fatality rate for transferred patients was 46% versus 67% for patients diagnosed onsite (p = 0.02). The difference was mediated by Ebola viral load at diagnosis, suggesting a survival selection bias. Comparisons of case-fatality rates across ETCs and clinical management strategies should account for potential survival selection bias.

Influence of Referral Pathway on Ebola Virus Disease Case-Fatality Rate and Effect of Survival Selection Bias

PubMed Central

Damkjær, Mads; Lunding, Suzanne; Dornonville de la Cour, Kenn; Young, Alyssa; Brooks, Tim; Sesay, Tom; Salam, Alex P.; Mishra, Sharmistha; Storgaard, Merete

2017-01-01

Case-fatality rates in Ebola treatment centers (ETCs) varied widely during the Ebola virus disease (EVD) outbreak in West Africa. We assessed the influence of referral pathway on ETC case-fatality rates with a retrospective cohort of 126 patients treated at the Mathaska ETC in Port Loko, Sierra Leone. The patients consisted of persons who had confirmed EVD when transferred to the ETC or who had been diagnosed onsite. The case-fatality rate for transferred patients was 46% versus 67% for patients diagnosed onsite (p = 0.02). The difference was mediated by Ebola viral load at diagnosis, suggesting a survival selection bias. Comparisons of case-fatality rates across ETCs and clinical management strategies should account for potential survival selection bias. PMID:28322693

A case study to illustrate the utility of the Aggregate Exposure Pathway and Adverse Outcome Pathway frameworks for integrating human health and ecological data into cumulative risk assessment

EPA Science Inventory

Cumulative risk assessment (CRA) methods, which evaluate the risk of multiple adverse outcomes (AOs) from multiple chemicals, promote the use of a conceptual site model (CSM) to integrate risk from relevant stressors. The Adverse Outcome Pathway (AOP) framework can inform these r...

Country Roads Take Me...?: An Ethnographic Case Study of College Pathways among Rural, First-Generation Students

ERIC Educational Resources Information Center

Beasley, Sarah Elizabeth

2011-01-01

The purpose of this study was to examine college pathways or college access and success of rural, first-generation students. Most research on college pathways for low- and moderate-income students focuses on those students as a whole or on urban low-socioeconomic status (SES) students. (Caution is in order when generalizing the experiences of…

Parasystole due to re-entry as the possible mechanism of ventricular parasystole with second-degree entrance block.

PubMed

Kinoshita, Shinji; Katoh, Takakazu; Yoshida, Hiroshi

2010-05-01

In 1974, Kinoshita reported a case of 'irregular parasystole' due to type I second-degree entrance block. Since then, many cases of such 'irregular' parasystole have been reported by us. To explain the mechanism of 'irregular' parasystole, two theories have been suggested, namely, 'electrotonic modulation' by Jalife and Moe, and 'type I second-degree entrance block' by us. On the contrary, in 1960, Kinoshita et al. reported a case of concealed bigeminy for the first time. The electrocardiographic findings in concealed bigeminy have suggested that there are dual re-entrant pathways with markedly long effective refractory periods in the re-entrant pathway. We have suggested that parasystole may be caused by re-entry in such re-entrant pathways. In this article, attempts are made to explain the mechanism of all the electrocardiographic findings in our cases of parasystole by 'parasystole due to re-entry'. Using 24 studies on parasystole and 21 studies on concealed extrasystoles that we have reported over 50 years, as well as three exemplary cases in this article, attempts are made to explain all electrocardiographic findings in parasystole by 'parasystole due to re-entry'. The electrocardiographic findings in our previous clinical cases of parasystole and concealed extrasystoles, as well as exemplary cases and diagrams in the present article, strongly suggest 'parasystole due to re-entry' as the mechanism of ventricular parasystole with second-degree entrance block.

Epigenomics

MedlinePlus

... Sheets A Brief Guide to Genomics About NHGRI Research About the International HapMap Project Biological Pathways Chromosome Abnormalities Chromosomes Cloning Comparative Genomics DNA Microarray Technology DNA Sequencing Deoxyribonucleic Acid ( ...

Cloning

MedlinePlus

... Sheets A Brief Guide to Genomics About NHGRI Research About the International HapMap Project Biological Pathways Chromosome Abnormalities Chromosomes Cloning Comparative Genomics DNA Microarray Technology DNA Sequencing Deoxyribonucleic Acid ( ...

Chromosomes

MedlinePlus

... Sheets A Brief Guide to Genomics About NHGRI Research About the International HapMap Project Biological Pathways Chromosome Abnormalities Chromosomes Cloning Comparative Genomics DNA Microarray Technology DNA Sequencing Deoxyribonucleic Acid ( ...

Transcriptome

MedlinePlus

... Sheets A Brief Guide to Genomics About NHGRI Research About the International HapMap Project Biological Pathways Chromosome Abnormalities Chromosomes Cloning Comparative Genomics DNA Microarray Technology DNA Sequencing Deoxyribonucleic Acid ( ...

The IgE-dependent pathway in allergic transfusion reactions: involvement of donor blood allergens other than plasma proteins.

PubMed

Matsuyama, Nobuki; Yasui, Kazuta; Amakishi, Etsuko; Hayashi, Tomoya; Kuroishi, Ayumu; Ishii, Hiroyuki; Matsukura, Harumichi; Tani, Yoshihiko; Furuta, Rika A; Hirayama, Fumiya

2015-07-01

On transfusion, several plasma proteins can cause anaphylaxis in patients deficient in the corresponding plasma proteins. However, little is known about other allergens, which are encountered much more infrequently. Although it has been speculated that an allergen-independent pathway underlying allergic transfusion reactions (ATRs) is elicited by biological response modifiers accumulated in blood components during storage, the exact mechanisms remain unresolved. Furthermore, it is difficult even to determine whether ATRs are induced via allergen-dependent or allergen-independent pathways. To distinguish these two pathways in ATR cases, we established a basophil activation test, in which the basophil-activating ability of supernatants of residual transfused blood of ATR cases to whole blood basophils was assessed in the presence or absence of dasatinib, an inhibitor of IgE-mediated basophil activation. Three of 37 supernatants from the platelet concentrates with ATRs activated panel blood basophils in the absence, but not in the presence, of dasatinib. The basophil activation was inhibited by treatment of anti-fish collagen I MoAb in one case, suggesting that the involvement of fish allergens may have been present in donor plasma. We concluded that unknown non-plasma proteins, some of which had epitopes similar to fish antigens, in blood component may be involved in ATRs via an allergen/IgE-dependent pathway.

Immunohistochemical loss of 5-hydroxymethylcytosine expression in acute myeloid leukaemia: relationship to somatic gene mutations affecting epigenetic pathways.

PubMed

Magotra, Minoti; Sakhdari, Ali; Lee, Paul J; Tomaszewicz, Keith; Dresser, Karen; Hutchinson, Lloyd M; Woda, Bruce A; Chen, Benjamin J

2016-12-01

Genes affecting epigenetic pathways are frequently mutated in myeloid malignancies, including acute myeloid leukaemia (AML). The genes encoding TET2, IDH1 and IDH2 are among the most commonly mutated genes, and cause defective conversion of 5-methylcytosine into 5-hydroxymethylcytosine (5hmC), impairing demethylation of DNA, and presumably serving as driver mutations in leukaemogenesis. The aim of this study was to correlate 5hmC immunohistochemical loss with the mutation status of genes involved in epigenetic pathways in AML. Immunohistochemical staining with an anti-5hmC antibody was performed on 41 decalcified, formalin-fixed paraffin-embedded (FFPE) bone marrow biopsies from patients with AML. Archived DNA was subjected to next-generation sequencing for analysis of a panel of genes, including TET2, IDH1, IDH2, WT1 and DNMT3A. TET2, IDH1, IDH2, WT1 and DNMT3A mutations were found in 46% (19/41) of the cases. Ten of 15 cases (67%) with TET2, IDH1, IDH2 or WT1 mutations showed deficient 5hmC staining, whereas nine of 26 cases (35%) without a mutation in these genes showed loss of 5hmC. It is of note that all four cases with TET2 mutations showed deficient 5hmC staining. Overall, somatic mutations in TET2, IDH1, IDH2, WT1 and DNMT3A were common in our cohort of AML cases. Immunohistochemical staining for 5hmC was lost in the majority of cases harbouring mutations in these genes, reflecting the proposed relationship between dysfunctional epigenetic pathways and leukaemogenesis. © 2016 John Wiley & Sons Ltd.

BRAF gene alterations and enhanced mammalian target of rapamycin signaling in gangliogliomas.

PubMed

Kakkar, Aanchal; Majumdar, Atreye; Pathak, Pankaj; Kumar, Anupam; Kumari, Kalpana; Tripathi, Manjari; Sharma, Mehar C; Suri, Vaishali; Tandon, Vivek; Chandra, Sarat P; Sarkar, Chitra

2017-01-01

Gangliogliomas (GGs) are slow-growing glioneuronal tumors seen in children and young adults. They are associated with intractable epilepsy, and have recently been found to harbor BRAF (B- rapidly accelerated fibrosarcoma) gene mutations. However, the mammalian target of rapamycin (mTOR) signaling pathway, downstream of BRAF, has not been evaluated extensively in GGs. GG cases were retrieved, clinical data obtained, and histopathological features reviewed. Sequencing for BRAF V600E mutation, analysis of BRAF copy number by quantitative real-time polymerase chain reaction, and immunohistochemistry for mTOR pathway markers p-S6 and p-4EBP1 were performed. Sixty-four cases of GG were identified (0.9% of central nervous system tumors). Of these, 28 had sufficient tumor tissue for further evaluation. Mixed glial and neuronal morphology was the commonest (64%) type. Focal cortical dysplasia was identified in the adjacent cortex (6 cases). BRAF V600E mutation was identified in 30% of GGs; BRAF copy number gain was observed in 50% of them. p-S6 and p-4EBP1 immunopositivity was seen in 57% cases each. Thus, mTOR pathway activation was seen in 81% cases, and was independent of BRAF alterations. 87% patients had Engel grade I outcome, while 13% had Engel grade II outcome. Both the Engel grade II cases analyzed showed BRAF V600E mutation. BRAF V600E mutation is frequent in GGs, as is BRAF gain; the former may serve as a target for personalized therapy in patients with residual tumors, necessitating its assessment in routine pathology reporting of these tumors. Evidence of mTOR pathway activation highlights similarities in the pathogenetic mechanisms underlying GG and focal cortical dysplasia, and suggests that mTOR inhibitors may be of utility in GG patients with persistent seizures after surgery.

Neurofibromatosis-Noonan syndrome: case report and clinicopathogenic review of the Neurofibromatosis-Noonan syndrome and RAS-MAPK pathway.

PubMed

Reig, Irela; Boixeda, Pablo; Fleta, Beatriz; Morenoc, Carmen; Gámez, Lucía; Truchuelo, Mayte

2011-04-15

Neurofibromatosis-Noonan syndrome is an entity that combines both features of Noonan syndrome and Neurofibromatosis type 1. This phenotypic overlap can be explained by the involvement of the RAS-MAPK pathway (mitogen-activated protein kinase) in both disorders. We report the case of a 17-year-old boy with Neurofibromatosis 1 with Noonan-like features, who complained of the progressive appearance of blue-gray lesions on his back.

DRUGS System Improving the Effects of Clinical Pathways: A Systematic Study.

PubMed

Wang, Shan; Zhu, Xiaohe; Zhao, Xian; Lu, Yang; Yang, Zhifu; Qian, Xiaoliang; Li, Weiwei; Ma, Lixiazi; Guo, Huning; Wang, Jingwen; Wen, Aidong

2016-03-01

The aim of the study is to assess the feasibility of Drugs Rational Usage Guideline System (DRUGS)-supported clinical pathway (CP) for breast carcinoma, cataract, inguinal hernia and 2-diabetes mellitus whether the application of such a system could improve work efficiency, medical safety, and decrease hospital cost. Four kinds of diseases which included 1773 cases (where 901 cases using paper-based clinical pathways and 872 cases using DRUGS-supported clinical pathways) were selected and their demographic and clinical data were collected. The evaluation criteria were length of stay, preoperative length of stay, hospital cost, antibiotics prescribed during hospitalization, unscheduled surgery, complications and prognosis. The median total LOS was 1 to 3 days shorter in the DRUGS-supported CP group as compared to the Paper-based CP group for all types (p < 0.05). Totel hospital cost decreased significantly in the DRUGS-supported CP group than that in Paper-based CP group. About antibiotics prescribed during hospitalization, there were no statistically differences in the time of initial dose of antibiotic and the duration of administration except the choice of antibiotic categories. The proportion of DRUGS-supported clinical pathway conditions where a broad-spectrum antibiotic was prescribed decreased from 63.6 to 34.5 % (p < 0.01) in the Paper-based group. While after the intervention, the differences were statistically not significant in unscheduled surgery, complications and prognosis. In this study, DRUGS-supported clinical pathway for breast carcinoma, cataract, inguinal hernia, 2-diabetes mellitus was smoothly shifted from a paper-based to an electronic system, and confer benefits at the hospital level.

High-throughput sequencing of mGluR signaling pathway genes reveals enrichment of rare variants in autism.

PubMed

Kelleher, Raymond J; Geigenmüller, Ute; Hovhannisyan, Hayk; Trautman, Edwin; Pinard, Robert; Rathmell, Barbara; Carpenter, Randall; Margulies, David

2012-01-01

Identification of common molecular pathways affected by genetic variation in autism is important for understanding disease pathogenesis and devising effective therapies. Here, we test the hypothesis that rare genetic variation in the metabotropic glutamate-receptor (mGluR) signaling pathway contributes to autism susceptibility. Single-nucleotide variants in genes encoding components of the mGluR signaling pathway were identified by high-throughput multiplex sequencing of pooled samples from 290 non-syndromic autism cases and 300 ethnically matched controls on two independent next-generation platforms. This analysis revealed significant enrichment of rare functional variants in the mGluR pathway in autism cases. Higher burdens of rare, potentially deleterious variants were identified in autism cases for three pathway genes previously implicated in syndromic autism spectrum disorder, TSC1, TSC2, and SHANK3, suggesting that genetic variation in these genes also contributes to risk for non-syndromic autism. In addition, our analysis identified HOMER1, which encodes a postsynaptic density-localized scaffolding protein that interacts with Shank3 to regulate mGluR activity, as a novel autism-risk gene. Rare, potentially deleterious HOMER1 variants identified uniquely in the autism population affected functionally important protein regions or regulatory sequences and co-segregated closely with autism among children of affected families. We also identified rare ASD-associated coding variants predicted to have damaging effects on components of the Ras/MAPK cascade. Collectively, these findings suggest that altered signaling downstream of mGluRs contributes to the pathogenesis of non-syndromic autism.

High-Throughput Sequencing of mGluR Signaling Pathway Genes Reveals Enrichment of Rare Variants in Autism

PubMed Central

Hovhannisyan, Hayk; Trautman, Edwin; Pinard, Robert; Rathmell, Barbara; Carpenter, Randall; Margulies, David

2012-01-01

Identification of common molecular pathways affected by genetic variation in autism is important for understanding disease pathogenesis and devising effective therapies. Here, we test the hypothesis that rare genetic variation in the metabotropic glutamate-receptor (mGluR) signaling pathway contributes to autism susceptibility. Single-nucleotide variants in genes encoding components of the mGluR signaling pathway were identified by high-throughput multiplex sequencing of pooled samples from 290 non-syndromic autism cases and 300 ethnically matched controls on two independent next-generation platforms. This analysis revealed significant enrichment of rare functional variants in the mGluR pathway in autism cases. Higher burdens of rare, potentially deleterious variants were identified in autism cases for three pathway genes previously implicated in syndromic autism spectrum disorder, TSC1, TSC2, and SHANK3, suggesting that genetic variation in these genes also contributes to risk for non-syndromic autism. In addition, our analysis identified HOMER1, which encodes a postsynaptic density-localized scaffolding protein that interacts with Shank3 to regulate mGluR activity, as a novel autism-risk gene. Rare, potentially deleterious HOMER1 variants identified uniquely in the autism population affected functionally important protein regions or regulatory sequences and co-segregated closely with autism among children of affected families. We also identified rare ASD-associated coding variants predicted to have damaging effects on components of the Ras/MAPK cascade. Collectively, these findings suggest that altered signaling downstream of mGluRs contributes to the pathogenesis of non-syndromic autism. PMID:22558107

Research and Development Needs for Building-Integrated Solar Technologies

DOE Office of Scientific and Technical Information (OSTI.GOV)

none,

2014-01-01

The Building Technologies Office (BTO) has identified Building Integrated Solar Technologies (BIST) as a potentially valuable piece of the comprehensive pathway to help achieve its goal of reducing energy consumption in residential and commercial buildings by 50% by the year 2030. This report helps to identify the key research and development (R&D) needs that will be required for BIST to make a substantial contribution toward that goal. BIST include technologies for space heating and cooling, water heating, hybrid photovoltaic-thermal systems (PV/T), active solar lighting, and building-integrated photovoltaics (BIPV).

Making big sense from big data in toxicology by read-across.

PubMed

Hartung, Thomas

2016-01-01

Modern information technologies have made big data available in safety sciences, i.e., extremely large data sets that may be analyzed only computationally to reveal patterns, trends and associations. This happens by (1) compilation of large sets of existing data, e.g., as a result of the European REACH regulation, (2) the use of omics technologies and (3) systematic robotized testing in a high-throughput manner. All three approaches and some other high-content technologies leave us with big data--the challenge is now to make big sense of these data. Read-across, i.e., the local similarity-based intrapolation of properties, is gaining momentum with increasing data availability and consensus on how to process and report it. It is predominantly applied to in vivo test data as a gap-filling approach, but can similarly complement other incomplete datasets. Big data are first of all repositories for finding similar substances and ensure that the available data is fully exploited. High-content and high-throughput approaches similarly require focusing on clusters, in this case formed by underlying mechanisms such as pathways of toxicity. The closely connected properties, i.e., structural and biological similarity, create the confidence needed for predictions of toxic properties. Here, a new web-based tool under development called REACH-across, which aims to support and automate structure-based read-across, is presented among others.

Genetic Mapping

MedlinePlus

... Sheets A Brief Guide to Genomics About NHGRI Research About the International HapMap Project Biological Pathways Chromosome Abnormalities Chromosomes Cloning Comparative Genomics DNA Microarray Technology DNA Sequencing Deoxyribonucleic Acid ( ...

Sustainable and efficient pathways for bioenergy recovery from low-value process streams via bioelectrochemical systems in biorefineries

DOE PAGES

Borole, Abhijeet P.

2015-08-25

Conversion of biomass into bioenergy is possible via multiple pathways resulting in production of biofuels, bioproducts and biopower. Efficient and sustainable conversion of biomass, however, requires consideration of many environmental and societal parameters in order to minimize negative impacts. Integration of multiple conversion technologies and inclusion of upcoming alternatives such as bioelectrochemical systems can minimize these impacts and improve conservation of resources such as hydrogen, water and nutrients via recycle and reuse. This report outlines alternate pathways integrating microbial electrolysis in biorefinery schemes to improve energy efficiency while evaluating environmental sustainability parameters.

Research and Development Opportunities for Technologies to Influence Water Consumption Behavior

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levin, Todd; Horner, Robert M.; Muehleisen, Ralph T.

In April 2015, Argonne National Laboratory hosted a two-day workshop that convened water experts and stakeholders from across industry, government, and academia to undertake three primary tasks: 1) identify technology characteristics that are favorable for motivating behavioral change, 2) identify barriers that have prevented the development and market adoption of technologies with these characteristics in the water sector, and 3) identify concrete research and development pathways that could be undertaken to overcome these barriers, increase the penetration of technologies that influence water consumption behavior, and ultimately reduce domestic water consumption. While efforts to reduce water consumption have gained momentum inmore » recent years, there are a number of key barriers that have limited the effectiveness of such efforts. Chief among these is the fact that many consumers have limited awareness of their water consumption patterns because of poor data availability, and/or are unmotivated to reduce their consumption because of low costs and split incentives. Without improved data availability and stronger price signals, it will be difficult to effect true transformative behavioral change. This report also reviews a number of technology characteristics that have successfully motivated behavioral change in other sectors, as well as several technologies that could be developed specifically for the water sector. Workshop participants discussed how technologies that provide active feedback and promote measurable goals and social accountability have successfully influenced changes in other types of behavior. A range of regulatory and policy actions that could be implemented to support such efforts are also presented. These include institutional aggregation, revenue decoupling, and price structure reforms. Finally, several R&D pathways were proposed, including efforts to identify optimal communication strategies and to better understand consumer perceptions and psychology as they relate to human behavior regarding water consumption. The findings presented here can help to inform policy makers as they develop new policies and seek to support new research to help consumers use water more efficiently. It is our hope that these findings will also be utilized to prioritize topics for additional follow-up workshops to address individual issues and barriers more directly and in more detail. The goal of such future workshops will be to develop specific solutions, research plans, and technology development pathways that can be undertaken to increase the market penetration of technologies that effect behavioral change and reduce water consumption.« less

Use of genomic data in risk assessment case study: II. Evaluation of the dibutyl phthalate toxicogenomic data set

DOE Office of Scientific and Technical Information (OSTI.GOV)

Euling, Susan Y., E-mail: euling.susan@epa.gov; White, Lori D.; Kim, Andrea S.

An evaluation of the toxicogenomic data set for dibutyl phthalate (DBP) and male reproductive developmental effects was performed as part of a larger case study to test an approach for incorporating genomic data in risk assessment. The DBP toxicogenomic data set is composed of nine in vivo studies from the published literature that exposed rats to DBP during gestation and evaluated gene expression changes in testes or Wolffian ducts of male fetuses. The exercise focused on qualitative evaluation, based on a lack of available dose–response data, of the DBP toxicogenomic data set to postulate modes and mechanisms of action formore » the male reproductive developmental outcomes, which occur in the lower dose range. A weight-of-evidence evaluation was performed on the eight DBP toxicogenomic studies of the rat testis at the gene and pathway levels. The results showed relatively strong evidence of DBP-induced downregulation of genes in the steroidogenesis pathway and lipid/sterol/cholesterol transport pathway as well as effects on immediate early gene/growth/differentiation, transcription, peroxisome proliferator-activated receptor signaling and apoptosis pathways in the testis. Since two established modes of action (MOAs), reduced fetal testicular testosterone production and Insl3 gene expression, explain some but not all of the testis effects observed in rats after in utero DBP exposure, other MOAs are likely to be operative. A reanalysis of one DBP microarray study identified additional pathways within cell signaling, metabolism, hormone, disease, and cell adhesion biological processes. These putative new pathways may be associated with DBP effects on the testes that are currently unexplained. This case study on DBP identified data gaps and research needs for the use of toxicogenomic data in risk assessment. Furthermore, this study demonstrated an approach for evaluating toxicogenomic data in human health risk assessment that could be applied to future chemicals. - Highlights: ► We evaluate the dibutyl phthalate toxicogenomic data for use in risk assessment. ► We focus on information about the mechanism of action for the developing testis. ► Multiple studies report effects on testosterone and insl3-related pathways. ► We identify additional affected pathways that may explain some testis effects. ► The case study is a template for evaluating toxicogenomic data in risk assessment.« less

Biofuel alternatives to ethanol: pumping the microbial well

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fortman, J. L.; Chhabra, Swapnil; Mukhopadhyay, Aindrila

Engineered microorganisms are currently used for the production of food products, pharmaceuticals, ethanol fuel and more. Even so, the enormous potential of this technology has yet to be fully exploited. The need for sustainable sources of transportation fuels has gener-ated a tremendous interest in technologies that enable biofuel production. Decades of work have produced a considerable knowledge-base for the physiology and pathway engineering of microbes, making microbial engineering an ideal strategy for producing biofuel. Although ethanol currently dominates the biofuel mar-ket, some of its inherent physical properties make it a less than ideal product. To highlight additional options, we reviewmore » advances in microbial engineering for the production of other potential fuel molecules, using a variety of biosynthetic pathways.« less

Biofuel alternatives to ethanol: pumping the microbial well

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fortman, J.L.; Chhabra, Swapnil; Mukhopadhyay, Aindrila

2009-08-19

Engineered microorganisms are currently used for the production of food products, pharmaceuticals, ethanol fuel and more. Even so, the enormous potential of this technology has yet to be fully exploited. The need for sustainable sources of transportation fuels has generated a tremendous interest in technologies that enable biofuel production. Decades of work have produced a considerable knowledge-base for the physiology and pathway engineering of microbes, making microbial engineering an ideal strategy for producing biofuel. Although ethanol currently dominates the biofuel market, some of its inherent physical properties make it a less than ideal product. To highlight additional options, we reviewmore » advances in microbial engineering for the production of other potential fuel molecules, using a variety of biosynthetic pathways.« less

B cell modulation strategies in autoimmunity: the SLE example.

PubMed

Rosado, M Manuela; Diamanti, Andrea Picchianti; Capolunghi, Federica; Carsetti, Rita

2011-01-01

The paradigm that T cells are the prime effectors of autoimmune diseases has been recently challenged by growing evidence that B-lymphocytes play a role in the development, re-activation and persistence of autoimmune disorders. B-cells of different subsets may play different roles in autoimmune pathologies due to their ability to secrete antibodies, produce cytokines, present antigen and form ectopic germinal centers. Thus, a given therapeutic approach or drug may have distinct outcomes depending on which specific B cell subset is targeted. Immunosuppressive therapies such as azathioprine (AZA), cyclophosphamide (CyC) or methotrexate (MTX) are conventionally used in autoimmune diseases with the aim of reducing disease activity and improving the patient's general health conditions. These treatments do not target a specific cellular type or subset and have substantial side effects, such as impairment of liver function and fertility. Moreover, autoimmune patients may be refractory to immunosuppressive therapy. In these cases finding an effective treatment becomes a challenge. The fast evolution in antibody technology is leading to the production of a wide array of humanized monoclonal antibodies, targeting specific cell types or pathways, initiating a new era in the treatment of autoimmune disorders. In addition, the recent discovery that toll like receptors (TLRs) activation can fire up autoimmunity in humans and maintain disease gives the grounds for the development of new drugs targeting the TLR/MyD88 pathway. In contrast to conventional immune-suppression, the availability of drugs interfering with B-cell specific pathogenetic pathways gives the possibility to choose therapies tailored to each disease and, possibly, to each patient.

Proof-of-Concept Demonstrations for Computation-Based Human Reliability Analysis. Modeling Operator Performance During Flooding Scenarios

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joe, Jeffrey Clark; Boring, Ronald Laurids; Herberger, Sarah Elizabeth Marie

The United States (U.S.) Department of Energy (DOE) Light Water Reactor Sustainability (LWRS) program has the overall objective to help sustain the existing commercial nuclear power plants (NPPs). To accomplish this program objective, there are multiple LWRS “pathways,” or research and development (R&D) focus areas. One LWRS focus area is called the Risk-Informed Safety Margin and Characterization (RISMC) pathway. Initial efforts under this pathway to combine probabilistic and plant multi-physics models to quantify safety margins and support business decisions also included HRA, but in a somewhat simplified manner. HRA experts at Idaho National Laboratory (INL) have been collaborating with othermore » experts to develop a computational HRA approach, called the Human Unimodel for Nuclear Technology to Enhance Reliability (HUNTER), for inclusion into the RISMC framework. The basic premise of this research is to leverage applicable computational techniques, namely simulation and modeling, to develop and then, using RAVEN as a controller, seamlessly integrate virtual operator models (HUNTER) with 1) the dynamic computational MOOSE runtime environment that includes a full-scope plant model, and 2) the RISMC framework PRA models already in use. The HUNTER computational HRA approach is a hybrid approach that leverages past work from cognitive psychology, human performance modeling, and HRA, but it is also a significant departure from existing static and even dynamic HRA methods. This report is divided into five chapters that cover the development of an external flooding event test case and associated statistical modeling considerations.« less

Applications of pathology-assisted image analysis of immunohistochemistry-based biomarkers in oncology.

PubMed

Shinde, V; Burke, K E; Chakravarty, A; Fleming, M; McDonald, A A; Berger, A; Ecsedy, J; Blakemore, S J; Tirrell, S M; Bowman, D

2014-01-01

Immunohistochemistry-based biomarkers are commonly used to understand target inhibition in key cancer pathways in preclinical models and clinical studies. Automated slide-scanning and advanced high-throughput image analysis software technologies have evolved into a routine methodology for quantitative analysis of immunohistochemistry-based biomarkers. Alongside the traditional pathology H-score based on physical slides, the pathology world is welcoming digital pathology and advanced quantitative image analysis, which have enabled tissue- and cellular-level analysis. An automated workflow was implemented that includes automated staining, slide-scanning, and image analysis methodologies to explore biomarkers involved in 2 cancer targets: Aurora A and NEDD8-activating enzyme (NAE). The 2 workflows highlight the evolution of our immunohistochemistry laboratory and the different needs and requirements of each biological assay. Skin biopsies obtained from MLN8237 (Aurora A inhibitor) phase 1 clinical trials were evaluated for mitotic and apoptotic index, while mitotic index and defects in chromosome alignment and spindles were assessed in tumor biopsies to demonstrate Aurora A inhibition. Additionally, in both preclinical xenograft models and an acute myeloid leukemia phase 1 trial of the NAE inhibitor MLN4924, development of a novel image algorithm enabled measurement of downstream pathway modulation upon NAE inhibition. In the highlighted studies, developing a biomarker strategy based on automated image analysis solutions enabled project teams to confirm target and pathway inhibition and understand downstream outcomes of target inhibition with increased throughput and quantitative accuracy. These case studies demonstrate a strategy that combines a pathologist's expertise with automated image analysis to support oncology drug discovery and development programs.

gsSKAT: Rapid gene set analysis and multiple testing correction for rare-variant association studies using weighted linear kernels.

PubMed

Larson, Nicholas B; McDonnell, Shannon; Cannon Albright, Lisa; Teerlink, Craig; Stanford, Janet; Ostrander, Elaine A; Isaacs, William B; Xu, Jianfeng; Cooney, Kathleen A; Lange, Ethan; Schleutker, Johanna; Carpten, John D; Powell, Isaac; Bailey-Wilson, Joan E; Cussenot, Olivier; Cancel-Tassin, Geraldine; Giles, Graham G; MacInnis, Robert J; Maier, Christiane; Whittemore, Alice S; Hsieh, Chih-Lin; Wiklund, Fredrik; Catalona, William J; Foulkes, William; Mandal, Diptasri; Eeles, Rosalind; Kote-Jarai, Zsofia; Ackerman, Michael J; Olson, Timothy M; Klein, Christopher J; Thibodeau, Stephen N; Schaid, Daniel J

2017-05-01

Next-generation sequencing technologies have afforded unprecedented characterization of low-frequency and rare genetic variation. Due to low power for single-variant testing, aggregative methods are commonly used to combine observed rare variation within a single gene. Causal variation may also aggregate across multiple genes within relevant biomolecular pathways. Kernel-machine regression and adaptive testing methods for aggregative rare-variant association testing have been demonstrated to be powerful approaches for pathway-level analysis, although these methods tend to be computationally intensive at high-variant dimensionality and require access to complete data. An additional analytical issue in scans of large pathway definition sets is multiple testing correction. Gene set definitions may exhibit substantial genic overlap, and the impact of the resultant correlation in test statistics on Type I error rate control for large agnostic gene set scans has not been fully explored. Herein, we first outline a statistical strategy for aggregative rare-variant analysis using component gene-level linear kernel score test summary statistics as well as derive simple estimators of the effective number of tests for family-wise error rate control. We then conduct extensive simulation studies to characterize the behavior of our approach relative to direct application of kernel and adaptive methods under a variety of conditions. We also apply our method to two case-control studies, respectively, evaluating rare variation in hereditary prostate cancer and schizophrenia. Finally, we provide open-source R code for public use to facilitate easy application of our methods to existing rare-variant analysis results. © 2017 WILEY PERIODICALS, INC.

SPV: a JavaScript Signaling Pathway Visualizer.

PubMed

Calderone, Alberto; Cesareni, Gianni

2018-03-24

The visualization of molecular interactions annotated in web resources is useful to offer to users such information in a clear intuitive layout. These interactions are frequently represented as binary interactions that are laid out in free space where, different entities, cellular compartments and interaction types are hardly distinguishable. SPV (Signaling Pathway Visualizer) is a free open source JavaScript library which offers a series of pre-defined elements, compartments and interaction types meant to facilitate the representation of signaling pathways consisting of causal interactions without neglecting simple protein-protein interaction networks. freely available under Apache version 2 license; Source code: https://github.com/Sinnefa/SPV_Signaling_Pathway_Visualizer_v1.0. Language: JavaScript; Web technology: Scalable Vector Graphics; Libraries: D3.js. sinnefa@gmail.com.

Modelling and Decision Support of Clinical Pathways

NASA Astrophysics Data System (ADS)

Gabriel, Roland; Lux, Thomas

The German health care market is under a rapid rate of change, forcing especially hospitals to provide high-quality services at low costs. Appropriate measures for more effective and efficient service provision are process orientation and decision support by information technology of clinical pathway of a patient. The essential requirements are adequate modelling of clinical pathways as well as usage of adequate systems, which are capable of assisting the complete path of a patient within a hospital, and preferably also outside of it, in a digital way. To fulfil these specifications the authors present a suitable concept, which meets the challenges of well-structured clinical pathways as well as rather poorly structured diagnostic and therapeutic decisions, by interplay of process-oriented and knowledge-based hospital information systems.

Attitudes towards the use and acceptance of eHealth technologies: a case study of older adults living with chronic pain and implications for rural healthcare.

PubMed

Currie, Margaret; Philip, Lorna J; Roberts, Anne

2015-04-16

Providing health services to an ageing population is challenging, and in rural areas even more so. It is expensive to provide high quality services to small populations who are widely dispersed; staff and patients are often required to travel considerable distances to access services, and the economic downturn has created a climate where delivery costs are under constant review. There is potential for technology to overcome some of these problems by decreasing or ceasing the need for patients and health professionals to travel to attend/deliver in-person appointments. A variety of eHealth initiatives (for example Pathways through Pain an online course aimed to aid self-help amongst those living with persistent pain) have been launched across the UK, but roll out remains at an early stage. This mixed-methods study of older adults with chronic pain examines attitudes towards, current use of and acceptance of the use of technology in healthcare. A survey (n = 168, 40% response rate) captured broad experiences of the use of technology in health and social care. Semi-structured interviews (four with technology and seven without technology participants) elicited attitudes towards technology in healthcare and explored attributes of personal and social interaction during home visits. People suffering from chronic pain access healthcare in a variety of ways. eHealth technology use was most common amongst older adults who lived alone. There was broad acceptance of eHealth being used in future care of people with chronic pain, but older adults wanted eHealth to be delivered alongside existing in-person visits from health and social care professionals. eHealth has the potential to overcome some traditional challenges of providing rural healthcare, however roll out needs to be gradual and begin by supplementing, not substituting, existing care and should be mindful of individual's circumstances, capability and preferences. Acceptance of technology may relate to existing levels of personal and social contact, and may be greater where technological help is not perceived to be replacing in-person care.

A framework to analyze emissions implications of manufacturing shifts in the industrial sector through integrating bottom-up energy models and economic input-output environmental life cycle assessment models

EPA Science Inventory

Future year emissions depend highly on the evolution of the economy, technology and current and future regulatory drivers. A scenario framework was adopted to analyze various technology development pathways and societal change while considering existing regulations and future unc...

A framework to analyze emissions implications of manufacturing shifts in the industrial sector through integrating bottom-up energy models and economic input/output environmental life cycle assessment models

EPA Science Inventory

Future year emissions depend highly on economic, technological, societal and regulatory drivers. A scenario framework was adopted to analyze technology development pathways and changes in consumer preferences, and evaluate resulting emissions growth patterns while considering fut...

Vehicle Technologies and Fuel Cell Technologies Program: Prospective Benefits Assessment Report for Fiscal Year 2016

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stephens, T. S.; Taylor, C. H.; Moore, J. S.

Under a diverse set of programs, the Vehicle Technologies and Fuel Cell Technologies offices of DOE’s Office of Energy Efficiency and Renewable Energy invest in research, development, demonstration, and deployment of advanced vehicle, hydrogen production, delivery and storage, and fuel cell technologies. This report estimates the benefits of successfully developing and deploying these technologies (a “Program Success” case) relative to a base case (the “No Program” case). The Program Success case represents the future with completely successful deployment of Vehicle Technologies Office (VTO) and Fuel Cell Technologies Office (FCTO) technologies. The No Program case represents a future in which theremore » is no contribution after FY 2016 by the VTO or FCTO to these technologies. The benefits of advanced vehicle, hydrogen production, delivery and storage, and fuel cell technologies were estimated on the basis of differences in fuel use, primary energy use, and greenhouse gas (GHG) emissions from light-, medium- and heavy-duty vehicles, including energy and emissions from fuel production, between the base case and the Program Success case. Improvements in fuel economy of various vehicle types, growth in the stock of fuel cell vehicles and other advanced technology vehicles, and decreased GHG intensity of hydrogen production and delivery in the Program Success case over the No Program case were projected to result in savings in petroleum use and GHG emissions. Benefits were disaggregated by individual program technology areas, which included the FCTO program and the VTO subprograms of batteries and electric drives; advanced combustion engines; fuels and lubricants; materials (for reduction in vehicle mass, or “lightweighting”); and, for medium- and heavy-duty vehicles, reduction in rolling and aerodynamic resistance. Projections for the Program Success case indicate that by 2035, the average fuel economy of on-road, light-duty vehicle stock could be 47% to 76% higher than in the No Program case. On-road medium- and heavy-duty vehicle stock could be as much as 39% higher. The resulting petroleum savings in 2035 were estimated to be as high as 3.1 million barrels per day, and reductions in GHG emissions were estimated to be as high as 500 million metric tons of CO2 equivalent per year. The benefits of continuing to invest government resources in advanced vehicle and fuel cell technologies would have significant economic value in the U.S. transportation sector and reduce its dependency on oil and its vulnerability to oil price shocks.« less

Approaches in studying the pharmacology of Chinese Medicine formulas: bottom-up, top-down-and meeting in the middle.

PubMed

Huang, Tao; Zhong, Linda L D; Lin, Chen-Yuan; Zhao, Ling; Ning, Zi-Wan; Hu, Dong-Dong; Zhang, Man; Tian, Ke; Cheng, Chung-Wah; Bian, Zhao-Xiang

2018-01-01

Investigating the pharmacology is key to the modernization of Chinese Medicine (CM) formulas. However, identifying which are the active compound(s) of CM formulas, which biological entities they target, and through which signaling pathway(s) they act to modify disease symptoms, are still difficult tasks for researchers, even when equipped with an arsenal of advanced modern technologies. Multiple approaches, including network pharmacology, pharmaco-genomics, -proteomics, and -metabolomics, have been developed to study the pharmacology of CM formulas. They fall into two general categories in terms of how they tackle a problem: bottom-up and top-down. In this article, we compared these two different approaches in several dimensions by using the case of MaZiRenWan (MZRW, also known as Hemp Seed Pill), a CM herbal formula for functional constipation. Multiple hypotheses are easy to be proposed in the bottom-up approach (e.g. network pharmacology); but these hypotheses are usually false positives and hard to be tested. In contrast, it is hard to suggest hypotheses in the top-down approach (e.g. pharmacometabolomics); however, once a hypothesis is proposed, it is much easier to be tested. Merging of these two approaches could results in a powerful approach, which could be the new paradigm for the pharmacological study of CM formulas.

Parameter space exploration within dynamic simulations of signaling networks.

PubMed

De Ambrosi, Cristina; Barla, Annalisa; Tortolina, Lorenzo; Castagnino, Nicoletta; Pesenti, Raffaele; Verri, Alessandro; Ballestrero, Alberto; Patrone, Franco; Parodi, Silvio

2013-02-01

We started offering an introduction to very basic aspects of molecular biology, for the reader coming from computer sciences, information technology, mathematics. Similarly we offered a minimum of information about pathways and networks in graph theory, for a reader coming from the bio-medical sector. At the crossover about the two different types of expertise, we offered some definition about Systems Biology. The core of the article deals with a Molecular Interaction Map (MIM), a network of biochemical interactions involved in a small signaling-network sub-region relevant in breast cancer. We explored robustness/sensitivity to random perturbations. It turns out that our MIM is a non-isomorphic directed graph. For non physiological directions of propagation of the signal the network is quite resistant to perturbations. The opposite happens for biologically significant directions of signal propagation. In these cases we can have no signal attenuation, and even signal amplification. Signal propagation along a given pathway is highly unidirectional, with the exception of signal-feedbacks, that again have a specific biological role and significance. In conclusion, even a relatively small network like our present MIM reveals the preponderance of specific biological functions over unspecific isomorphic behaviors. This is perhaps the consequence of hundreds of millions of years of biological evolution.

Normal Patterns of Deja Experience in a Healthy, Blind Male: Challenging Optical Pathway Delay Theory

ERIC Educational Resources Information Center

O'Connor, Akira R.; Moulin, Christopher J. A.

2006-01-01

We report the case of a 25-year-old healthy, blind male, MT, who experiences normal patterns of deja vu. The optical pathway delay theory of deja vu formation assumes that neuronal input from the optical pathways is necessary for the formation of the experience. Surprisingly, although the sensation of deja vu is known to be experienced by blind…

[The application of cortical and subcortical stimulation threshold in identifying the motor pathway and guiding the resection of gliomas in the functional areas].

PubMed

Ren, X H; Yang, X C; Huang, W; Yang, K Y; Liu, L; Qiao, H; Guo, L J; Cui, Y; Lin, S

2018-03-06

Objective: This study aimed to analyze the application of cortical and subcortical stimulation threshold in identifying the motor pathway and guiding the resection of gliomas in the functional area, and to illustrate the minimal safe threshold by ROC method. Methods: Fifty-seven patients with gliomas in the functional areas were enrolled in the study at Beijing Tiantan Hospital from 2015 to 2017. Anesthesia was maintained intravenously with propofol 10% and remifentanil. Throughout the resection process, cortical or subcortical stimulation threshold was determined along tumor border using monopolar or bipolar electrodes. The motor pathway was identified and protected from resection according to the stimulation threshold and transcranial MEPs. Minimal threshold in each case was recorded. Results: Total resection was achieved in 32 cases(56.1%), sub-total resection in 22 cases(38.6%), and partial resection in 3 cases(5.3%). Pre-operative motor disability was found in 9 cases. Compared with pre-operative motor scores, 19 exhibited impaired motor functions on day 1 after surgery, 5 had quick recovery by day 7 after surgery, and 7 had late recovery by 3 months after surgery. At 3 months, 7 still had impaired motor function. The frequency of intraoperative seizure was 1.8%(1/57). No other side effect was found during electronic monitoring in the operation. The ROC curve revealed that the minimal safe monopolar subcortical threshold was 5.70 mA for strength deterioration on day 1 and day 7 after surgery. Univariate analysis revealed that decreased transcranial MEPs and minimal subcortical threshold ≤5.7 mA were correlated with postoperative strength deterioration. Conclusions: Cortical and subcortical stimulation threshold has its merit in identifying the motor pathway and guiding the resection for tumors within the functional areas. 5.7 mA can be used as the minimal safe threshold to protect the motor pathway from injury.

The implications of renewable energy research and development: Policy scenario analysis with experience and learning effects

NASA Astrophysics Data System (ADS)

Kobos, Peter Holmes

This dissertation analyzes the current and potential future costs of renewable energy technology from an institutional perspective. The central hypothesis is that reliable technology cost forecasting can be achieved through standard and modified experience curves implemented in a dynamic simulation model. Additionally, drawing upon region-specific institutional lessons highlights the role of market, social, and political institutions throughout an economy. Socio-political influences and government policy pathways drive resource allocation decisions that may be predominately influenced by factors other than those considered in a traditional market-driven, mechanistic approach. Learning in economic systems as a research topic is an attractive complement to the notion of institutional pathways. The economic implications of learning by doing, as first outlined by Arrow (1962), highlight decreasing production costs as individuals, or more generally the firm, become more familiar with a production process. The standard approach in the literature has been to employ a common experience curve where cumulative production is the only independent variable affecting costs. This dissertation develops a two factor experience curve, adding research, development and demonstration (RD&D) expenditures as a second variable. To illustrate the concept in the context of energy planning, two factor experience curves are developed for wind energy technology and solar photovoltaic (PV) modules under different assumptions on learning rates for cumulative capacity and the knowledge stock (a function of past RD&D efforts). Additionally, a one factor experience curve and cost trajectory scenarios are developed for concentrated solar power and geothermal energy technology, respectively. Cost forecasts are then developed for all four of these technologies in a dynamic simulation model. Combining the theoretical framework of learning by doing with the fields of organizational learning and institutional economics, this dissertation argues that the current state of renewable energy technology costs is largely due to the past production efforts (learning by doing) and RD&D efforts (learning by searching) in these global industries. This cost pathway, however, may be altered through several policy process feedback mechanisms including targeted RD&D expenditures, maintenance of RD&D to promote learning effects, and financial incentive programs that support energy production from renewable energy technologies.

Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer: possibilities for therapeutic intervention

PubMed Central

Davis, Nicole M.; Sokolosky, Melissa; Stadelman, Kristin; Abrams, Stephen L.; Libra, Massimo; Candido, Saverio; Nicoletti, Ferdinando; Polesel, Jerry; Maestro, Roberta; D’Assoro, Antonino; Drobot, Lyudmyla; Rakus, Dariusz; Gizak, Agnieszka; Laidler, Piotr; Dulińska-Litewka, Joanna; Basecke, Joerg; Mijatovic, Sanja; Maksimovic-Ivanic, Danijela; Montalto, Giuseppe; Cervello, Melchiorre; Fitzgerald, Timothy L.; Demidenko, Zoya N.; Martelli, Alberto M.; Cocco, Lucio; Steelman, Linda S.; McCubrey, James A.

2014-01-01

The EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway plays prominent roles in malignant transformation, prevention of apoptosis, drug resistance and metastasis. The expression of this pathway is frequently altered in breast cancer due to mutations at or aberrant expression of: HER2, ERalpha, BRCA1, BRCA2, EGFR1, PIK3CA, PTEN, TP53, RB as well as other oncogenes and tumor suppressor genes. In some breast cancer cases, mutations at certain components of this pathway (e.g., PIK3CA) are associated with a better prognosis than breast cancers lacking these mutations. The expression of this pathway and upstream HER2 has been associated with breast cancer initiating cells (CICs) and in some cases resistance to treatment. The anti-diabetes drug metformin can suppress the growth of breast CICs and herceptin-resistant HER2+ cells. This review will discuss the importance of the EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway primarily in breast cancer but will also include relevant examples from other cancer types. The targeting of this pathway will be discussed as well as clinical trials with novel small molecule inhibitors. The targeting of the hormone receptor, HER2 and EGFR1 in breast cancer will be reviewed in association with suppression of the EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway. PMID:25051360

Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer: possibilities for therapeutic intervention.

PubMed

Davis, Nicole M; Sokolosky, Melissa; Stadelman, Kristin; Abrams, Steve L; Libra, Massimo; Candido, Saverio; Nicoletti, Ferdinando; Polesel, Jerry; Maestro, Roberta; D'Assoro, Antonino; Drobot, Lyudmyla; Rakus, Dariusz; Gizak, Agnieszka; Laidler, Piotr; Dulińska-Litewka, Joanna; Basecke, Joerg; Mijatovic, Sanja; Maksimovic-Ivanic, Danijela; Montalto, Giuseppe; Cervello, Melchiorre; Fitzgerald, Timothy L; Demidenko, Zoya; Martelli, Alberto M; Cocco, Lucio; Steelman, Linda S; McCubrey, James A

2014-07-15

The EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway plays prominent roles in malignant transformation, prevention of apoptosis, drug resistance and metastasis. The expression of this pathway is frequently altered in breast cancer due to mutations at or aberrant expression of: HER2, ERalpha, BRCA1, BRCA2, EGFR1, PIK3CA, PTEN, TP53, RB as well as other oncogenes and tumor suppressor genes. In some breast cancer cases, mutations at certain components of this pathway (e.g., PIK3CA) are associated with a better prognosis than breast cancers lacking these mutations. The expression of this pathway and upstream HER2 has been associated with breast cancer initiating cells (CICs) and in some cases resistance to treatment. The anti-diabetes drug metformin can suppress the growth of breast CICs and herceptin-resistant HER2+ cells. This review will discuss the importance of the EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway primarily in breast cancer but will also include relevant examples from other cancer types. The targeting of this pathway will be discussed as well as clinical trials with novel small molecule inhibitors. The targeting of the hormone receptor, HER2 and EGFR1 in breast cancer will be reviewed in association with suppression of the EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway.

[Arnold-Chiari malformation in Noonan syndrome and other syndromes of the RAS/MAPK pathway].

PubMed

Ejarque, Ismael; Millán-Salvador, José M; Oltra, Silvestre; Pesudo-Martínez, José V; Beneyto, Magdalena; Pérez-Aytés, Antonio

2015-05-01

Noonan syndrome (NS) and other syndromes with a similar phenotype, such as LEOPARD, cardiofaciocutaneous, Costello and Legius, are associated to mutations in genes included in the RAS/MAPK pathway (RASopathies), which is an important signalling pathway related to cell proliferation. Tonsillar descent into the upper cervical spinal canal, known as Arnold-Chiari malformation (ACM), has been reported in patients with NS and this has led some researchers to suggest that ACM could be part of the phenotypic spectrum of NS. We report two cases of NS and ACM. Case 1: 29-year-old female with Noonan phenotype who underwent surgery at the age of nine years due to pulmonary valve stenosis. At the age of 27, she presented symptomatic ACM that required surgical decompression. She presented the c.922A>G (N308D) mutation in the gene PTPN that belongs to the RAS/MAPK pathway. Case 2: a 10-year-old female with Noonan phenotype and asymptomatic ACM detected in magnetic resonance imaging of the brain. She was a carrier of the c.923A>G (N308S) mutation in gene PTPN11. Six patients with this association have been found in the literature, four with the Noonan phenotype and two with LEOPARD. Our two patients provide supplementary evidence that backs up the hypothesis by which ACM would be part of the phenotypic spectrum of NS. The small number of reported cases of patients with this association does not allow us to draw up recommendations about when and how often neuroimaging studies should be performed; a careful neurological examination, however, should be included in the anticipatory health guidelines in syndromes involving the RAS/MAPK pathway.

Emerging technologies with potential for objectively evaluating speech recognition skills.

PubMed

Rawool, Vishakha Waman

2016-01-01

Work-related exposure to noise and other ototoxins can cause damage to the cochlea, synapses between the inner hair cells, the auditory nerve fibers, and higher auditory pathways, leading to difficulties in recognizing speech. Procedures designed to determine speech recognition scores (SRS) in an objective manner can be helpful in disability compensation cases where the worker claims to have poor speech perception due to exposure to noise or ototoxins. Such measures can also be helpful in determining SRS in individuals who cannot provide reliable responses to speech stimuli, including patients with Alzheimer's disease, traumatic brain injuries, and infants with and without hearing loss. Cost-effective neural monitoring hardware and software is being rapidly refined due to the high demand for neurogaming (games involving the use of brain-computer interfaces), health, and other applications. More specifically, two related advances in neuro-technology include relative ease in recording neural activity and availability of sophisticated analysing techniques. These techniques are reviewed in the current article and their applications for developing objective SRS procedures are proposed. Issues related to neuroaudioethics (ethics related to collection of neural data evoked by auditory stimuli including speech) and neurosecurity (preservation of a person's neural mechanisms and free will) are also discussed.

State of the art discovery with tumor profiling in pediatric oncology.

PubMed

Carroll, William L; Raetz, Elizabeth; Meyer, Julia

2015-01-01

It is an exciting era in pediatric oncology with the advent of new technologies to comprehensively characterize cancer genomes in childhood tumors. Defining the genetic landscape of pediatric tumors has not only provided critical insight into tumor evolution, but it has also offered promise for more effective treatment in some cases, such as Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) and anaplastic lymphoma kinase (ALK)-mutated tumors. However, several challenges remain as the field of genomic tumor profiling emerges. This new technology is costly, and the overall impact on survival has yet to be determined. Tumor heterogeneity and clonal evolution have also presented challenges in the development of targeted therapy. In this article, we review breakthroughs in gene sequencing methodology and discuss examples where genomic discoveries have resulted in the recognition of tumor susceptibility as well as incorporation of targeted therapy. We also discuss how broad scale comprehensive tumor analyses have demonstrated the convergence of individual genetic alterations on common relevant pathways. Although the impact of tumor profiling is best studied within the context of rigorously designed clinical trials, there is promise that there will be growing opportunities for the adaption of precision medicine in pediatric oncology in the future.

Application of stochastic multiattribute analysis to assessment of single walled carbon nanotube synthesis processes.

PubMed

Canis, Laure; Linkov, Igor; Seager, Thomas P

2010-11-15

The unprecedented uncertainty associated with engineered nanomaterials greatly expands the need for research regarding their potential environmental consequences. However, decision-makers such as regulatory agencies, product developers, or other nanotechnology stakeholders may not find the results of such research directly informative of decisions intended to mitigate environmental risks. To help interpret research findings and prioritize new research needs, there is an acute need for structured decision-analytic aids that are operable in a context of extraordinary uncertainty. Whereas existing stochastic decision-analytic techniques explore uncertainty only in decision-maker preference information, this paper extends model uncertainty to technology performance. As an illustrative example, the framework is applied to the case of single-wall carbon nanotubes. Four different synthesis processes (arc, high pressure carbon monoxide, chemical vapor deposition, and laser) are compared based on five salient performance criteria. A probabilistic rank ordering of preferred processes is determined using outranking normalization and a linear-weighted sum for different weighting scenarios including completely unknown weights and four fixed-weight sets representing hypothetical stakeholder views. No single process pathway dominates under all weight scenarios, but it is likely that some inferior process technologies could be identified as low priorities for further research.

Recent advances in cancer metabolism: a technological perspective.

PubMed

Kang, Yun Pyo; Ward, Nathan P; DeNicola, Gina M

2018-04-16

Cancer cells are highly dependent on metabolic pathways to sustain both their proliferation and adaption to harsh microenvironments. Thus, understanding the metabolic reprogramming that occurs in tumors can provide critical insights for the development of therapies targeting metabolism. In this review, we will discuss recent advancements in metabolomics and other multidisciplinary techniques that have led to the discovery of novel metabolic pathways and mechanisms in diverse cancer types.

Automated and Autonomous Systems for Combat Service Support: Scoping Study and Technology Prioritisation

DTIC Science & Technology

2016-10-01

workshop, and use case development for automated and autonomous systems for CSS. The scoping study covers key concepts and trends, a technology scan, and...requirements and delimiters for the selected technologies. The report goes on to present detailed use cases for two technologies of interest: semi...selected use cases . As a result of the workshop, the large list of technologies and applications from the scoping study was narrowed down to the top

Cytosensor Microphysiometer: technology and recent applications.

PubMed

Hafner, F

2000-06-01

The Cytosensor Microphysiometer system detects functional responses from living cells in minutes and offers novel information on cell signalling that is often unobtainable with other assay methods. The principle of the system is based on the measurement of small changes in extracellular acidification, using a light addressable potentiometric sensor (LAPS). Energy metabolism in living cells is tightly coupled to cellular ATP usage, so that any event which perturbs cellular ATP levels--such as receptor activation and initiation of signal transduction--will result in a change in acid excretion. As the extrusion of protons is a very general parameter involved in the activation of nearly all kinds of membrane-bound receptors, receptors can be investigated without prior knowledge of the corresponding signalling pathway. However, by blocking certain signalling pathways inside the cell by means of signal transduction probes, specificity can be brought into the system and the corresponding receptor pathways can easily be elucidated. The aim is to give an overview about Cytosensor Microphysiometer technology and to demonstrate, with the help of some recent applications, the capability of the system to measure acidification rates from a wide variety of cell- and receptor-types coupled to different signal transduction pathways. This feature makes the cytosensor system an ideal tool for acting as a single assay system and circumventing the need for multiple assays.

Final Report: Hydrogen Production Pathways Cost Analysis (2013 – 2016)

DOE Office of Scientific and Technical Information (OSTI.GOV)

James, Brian David; DeSantis, Daniel Allan; Saur, Genevieve

This report summarizes work conducted under a three year Department of Energy (DOE) funded project to Strategic Analysis, Inc. (SA) to analyze multiple hydrogen (H 2) production technologies and project their corresponding levelized production cost of H 2. The analysis was conducted using the H2A Hydrogen Analysis Tool developed by the DOE and National Renewable Energy Laboratory (NREL). The project was led by SA but conducted in close collaboration with the NREL and Argonne National Laboratory (ANL). In-depth techno-economic analysis (TEA) of five different H 2 production methods was conducted. These TEAs developed projections for capital costs, fuel/feedstock usage, energymore » usage, indirect capital costs, land usage, labor requirements, and other parameters, for each H 2 production pathway, and use the resulting cost and system parameters as inputs into the H2A discounted cash flow model to project the production cost of H 2 ($/kgH 2). Five technologies were analyzed as part of the project and are summarized in this report: Proton Exchange Membrane technology (PEM), High temperature solid oxide electrolysis cell technology (SOEC), Dark fermentation of biomass for H 2 production, H 2 production via Monolithic Piston-Type Reactors with rapid swing reforming and regeneration reactions, and Reformer-Electrolyzer-Purifier (REP) technology developed by Fuel Cell Energy, Inc. (FCE).« less

Automated Surgical Approach Planning for Complex Skull Base Targets: Development and Validation of a Cost Function and Semantic At-las.

PubMed

Aghdasi, Nava; Whipple, Mark; Humphreys, Ian M; Moe, Kris S; Hannaford, Blake; Bly, Randall A

2018-06-01

Successful multidisciplinary treatment of skull base pathology requires precise preoperative planning. Current surgical approach (pathway) selection for these complex procedures depends on an individual surgeon's experiences and background training. Because of anatomical variation in both normal tissue and pathology (eg, tumor), a successful surgical pathway used on one patient is not necessarily the best approach on another patient. The question is how to define and obtain optimized patient-specific surgical approach pathways? In this article, we demonstrate that the surgeon's knowledge and decision making in preoperative planning can be modeled by a multiobjective cost function in a retrospective analysis of actual complex skull base cases. Two different approaches- weighted-sum approach and Pareto optimality-were used with a defined cost function to derive optimized surgical pathways based on preoperative computed tomography (CT) scans and manually designated pathology. With the first method, surgeon's preferences were input as a set of weights for each objective before the search. In the second approach, the surgeon's preferences were used to select a surgical pathway from the computed Pareto optimal set. Using preoperative CT and magnetic resonance imaging, the patient-specific surgical pathways derived by these methods were similar (85% agreement) to the actual approaches performed on patients. In one case where the actual surgical approach was different, revision surgery was required and was performed utilizing the computationally derived approach pathway.

Information technology equipment cooling method

DOEpatents

Schultz, Mark D.

2015-10-20

According to one embodiment, a system for removing heat from a rack of information technology equipment may include a sidecar indoor air to liquid heat exchanger that cools air utilized by the rack of information technology equipment to cool the rack of information technology equipment. The system may also include a liquid to liquid heat exchanger and an outdoor heat exchanger. The system may further include configurable pathways to connect and control fluid flow through the sidecar heat exchanger, the liquid to liquid heat exchanger, the rack of information technology equipment, and the outdoor heat exchanger based upon ambient temperature and/or ambient humidity to remove heat generated by the rack of information technology equipment.

Systems biology approach to developing S(2)RM-based "systems therapeutics" and naturally induced pluripotent stem cells.

PubMed

Maguire, Greg; Friedman, Peter

2015-05-26

The degree to, and the mechanisms through, which stem cells are able to build, maintain, and heal the body have only recently begun to be understood. Much of the stem cell's power resides in the release of a multitude of molecules, called stem cell released molecules (SRM). A fundamentally new type of therapeutic, namely "systems therapeutic", can be realized by reverse engineering the mechanisms of the SRM processes. Recent data demonstrates that the composition of the SRM is different for each type of stem cell, as well as for different states of each cell type. Although systems biology has been successfully used to analyze multiple pathways, the approach is often used to develop a small molecule interacting at only one pathway in the system. A new model is emerging in biology where systems biology is used to develop a new technology acting at multiple pathways called "systems therapeutics". A natural set of healing pathways in the human that uses SRM is instructive and of practical use in developing systems therapeutics. Endogenous SRM processes in the human body use a combination of SRM from two or more stem cell types, designated as S(2)RM, doing so under various state dependent conditions for each cell type. Here we describe our approach in using state-dependent SRM from two or more stem cell types, S(2)RM technology, to develop a new class of therapeutics called "systems therapeutics." Given the ubiquitous and powerful nature of innate S(2)RM-based healing in the human body, this "systems therapeutic" approach using S(2)RM technology will be important for the development of anti-cancer therapeutics, antimicrobials, wound care products and procedures, and a number of other therapeutics for many indications.

Improved Protein Arrays for Quantitative Systems Analysis of the Dynamics of Signaling Pathway Interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Chin-Rang

Astronauts and workers in nuclear plants who repeatedly exposed to low doses of ionizing radiation (IR, <10 cGy) are likely to incur specific changes in signal transduction and gene expression in various tissues of their body. Remarkable advances in high throughput genomics and proteomics technologies enable researchers to broaden their focus from examining single gene/protein kinetics to better understanding global gene/protein expression profiling and biological pathway analyses, namely Systems Biology. An ultimate goal of systems biology is to develop dynamic mathematical models of interacting biological systems capable of simulating living systems in a computer. This Glue Grant is to complementmore » Dr. Boothman’s existing DOE grant (No. DE-FG02-06ER64186) entitled “The IGF1/IGF-1R-MAPK-Secretory Clusterin (sCLU) Pathway: Mediator of a Low Dose IR-Inducible Bystander Effect” to develop sensitive and quantitative proteomic technology that suitable for low dose radiobiology researches. An improved version of quantitative protein array platform utilizing linear Quantum dot signaling for systematically measuring protein levels and phosphorylation states for systems biology modeling is presented. The signals are amplified by a confocal laser Quantum dot scanner resulting in ~1000-fold more sensitivity than traditional Western blots and show the good linearity that is impossible for the signals of HRP-amplification. Therefore this improved protein array technology is suitable to detect weak responses of low dose radiation. Software is developed to facilitate the quantitative readout of signaling network activities. Kinetics of EGFRvIII mutant signaling was analyzed to quantify cross-talks between EGFR and other signaling pathways.« less

Technology-based tools and services for people with dementia and carers: Mapping technology onto the dementia care pathway.

PubMed

Lorenz, Klara; Freddolino, Paul P; Comas-Herrera, Adelina; Knapp, Martin; Damant, Jacqueline

2017-01-01

The extent to which technology may be able to support people with dementia and their carers along the care pathway and in different care settings is of interest to policy makers and governments. In this paper we provide an overview of the role of technology in dementia care, treatment and support by mapping existing technologies - by function, target user and disease progression. Technologies identified are classified into seven functions: memory support, treatment, safety and security, training, care delivery, social interaction and other. Different groups of potential users are distinguished: people with mild cognitive impairment and early stages of dementia, people with moderate to severe dementia and unpaid carers and health- and social care professionals. We also identified the care settings, in which the technologies are used (or for which the technologies are developed): at home in the community and in institutional care settings. The evidence has been drawn from a rapid review of the literature, expert interviews and web and social media searches. The largest number of technologies identified aim to enhance the safety and security of people with dementia living in the community. These devices are often passive monitors, such as smoke detectors. Other safety interventions, such as panic buttons, require active intervention. The second largest number of interventions aims to enhance people's memory and includes global positioning systems devices and voice prompts. These technologies mostly target people in the early stages of dementia. A third group focusing on treatment and care delivery emerged from the literature. These interventions focus on technology-aided reminiscence or therapeutic aspects of care for people with dementia and their carers. While the review found a range of technologies available for people with dementia and carers there is very little evidence of widespread practical application. Instead, it appears that stakeholders frequently rely on everyday technologies re-purposed to meet their needs.

A Case Study of Technology Choices by High School Students

ERIC Educational Resources Information Center

Owens-Hartman, Amy R.

2015-01-01

The purpose of this case study was to examine student technology choices when given the freedom to choose technology devices to complete a project-based learning activity in a content area of study. The study also analyzed factors affecting technology choice as well as how technology proficiency scores aligned to technology choices. Patterns and…

An ontology-driven semantic mash-up of gene and biological pathway information: Application to the domain of nicotine dependence

PubMed Central

Sahoo, Satya S.; Bodenreider, Olivier; Rutter, Joni L.; Skinner, Karen J.; Sheth, Amit P.

2008-01-01

Objectives This paper illustrates how Semantic Web technologies (especially RDF, OWL, and SPARQL) can support information integration and make it easy to create semantic mashups (semantically integrated resources). In the context of understanding the genetic basis of nicotine dependence, we integrate gene and pathway information and show how three complex biological queries can be answered by the integrated knowledge base. Methods We use an ontology-driven approach to integrate two gene resources (Entrez Gene and HomoloGene) and three pathway resources (KEGG, Reactome and BioCyc), for five organisms, including humans. We created the Entrez Knowledge Model (EKoM), an information model in OWL for the gene resources, and integrated it with the extant BioPAX ontology designed for pathway resources. The integrated schema is populated with data from the pathway resources, publicly available in BioPAX-compatible format, and gene resources for which a population procedure was created. The SPARQL query language is used to formulate queries over the integrated knowledge base to answer the three biological queries. Results Simple SPARQL queries could easily identify hub genes, i.e., those genes whose gene products participate in many pathways or interact with many other gene products. The identification of the genes expressed in the brain turned out to be more difficult, due to the lack of a common identification scheme for proteins. Conclusion Semantic Web technologies provide a valid framework for information integration in the life sciences. Ontology-driven integration represents a flexible, sustainable and extensible solution to the integration of large volumes of information. Additional resources, which enable the creation of mappings between information sources, are required to compensate for heterogeneity across namespaces. Resource page http://knoesis.wright.edu/research/lifesci/integration/structured_data/JBI-2008/ PMID:18395495

An ontology-driven semantic mashup of gene and biological pathway information: application to the domain of nicotine dependence.

PubMed

Sahoo, Satya S; Bodenreider, Olivier; Rutter, Joni L; Skinner, Karen J; Sheth, Amit P

2008-10-01

This paper illustrates how Semantic Web technologies (especially RDF, OWL, and SPARQL) can support information integration and make it easy to create semantic mashups (semantically integrated resources). In the context of understanding the genetic basis of nicotine dependence, we integrate gene and pathway information and show how three complex biological queries can be answered by the integrated knowledge base. We use an ontology-driven approach to integrate two gene resources (Entrez Gene and HomoloGene) and three pathway resources (KEGG, Reactome and BioCyc), for five organisms, including humans. We created the Entrez Knowledge Model (EKoM), an information model in OWL for the gene resources, and integrated it with the extant BioPAX ontology designed for pathway resources. The integrated schema is populated with data from the pathway resources, publicly available in BioPAX-compatible format, and gene resources for which a population procedure was created. The SPARQL query language is used to formulate queries over the integrated knowledge base to answer the three biological queries. Simple SPARQL queries could easily identify hub genes, i.e., those genes whose gene products participate in many pathways or interact with many other gene products. The identification of the genes expressed in the brain turned out to be more difficult, due to the lack of a common identification scheme for proteins. Semantic Web technologies provide a valid framework for information integration in the life sciences. Ontology-driven integration represents a flexible, sustainable and extensible solution to the integration of large volumes of information. Additional resources, which enable the creation of mappings between information sources, are required to compensate for heterogeneity across namespaces. RESOURCE PAGE: http://knoesis.wright.edu/research/lifesci/integration/structured_data/JBI-2008/

Knockdown of RNA interference pathway genes in western corn rootworm, Diabrotica virgifera virgifera, identifies no fitness costs associated with Argonaute 2 or Dicer-2.

PubMed

Camargo, Carolina; Wu, Ke; Fishilevich, Elane; Narva, Kenneth E; Siegfried, Blair D

2018-06-01

The use of transgenic crops that induce silencing of essential genes using double-stranded RNA (dsRNA) through RNA interference (RNAi) in western corn rootworm, Diabrotica virgifera virgifera, is likely to be an important component of new technologies for the control of this important corn pest. Previous studies have demonstrated that the dsRNA response in D. v. virgifera depends on the presence of RNAi pathway genes including Dicer-2 and Argonaute 2, and that downregulation of these genes limits the lethality of environmental dsRNA. A potential resistance mechanism to lethal dsRNA may involve loss of function of RNAi pathway genes. Howver, the potential for resistance to evolve may depend on whether these pathway genes have essential functions such that the loss of function of core proteins in the RNAi pathway will have fitness costs in D. v. virgifera. Fitness costs associated with potential resistance mechanisms have a central role in determining how resistance can evolve to RNAi technologies in western corn rootworm. We evaluated the effect of dsRNA and microRNA pathway gene knockdown on the development of D. v. virgifera larvae through short-term and long-term exposures to dsRNA for Dicer and Argonaute genes. Downregulation of Argonaute 2, Dicer-2, Dicer-1 did not significantly affect larval survivorship or development through short and long-term exposure to dsRNA. However, downregulation of Argonaute 1 reduced larval survivorship and delayed development. The implications of these results as they relate to D. v. virgifera resistance to lethal dsRNA are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

Risk disparities in the globalisation of assisted reproductive technology: the case of Asia.

PubMed

Ha, Jung-Ok

2013-01-01

This paper analyses the disparities in risks associated with biomedical technology focusing on the results of assisted reproductive technology (ART). ART among biomedical technologies transferred to Asia is a representative case that reveals in its clinical use and related scientific research the global politics of technology. This study notes the global politics at work in the recognition of and reaction to such risks. While many Asian countries aggressively pursue technological development, weak legislative and administrative regulations have created various problems and controversial cases. This study asserts that risks associated with technology are characterised as social facts not natural ones or mere 'side effects', since technological development and risk are closely intertwined.

Development Challenges of Game-Changing Entry System Technologies From Concept to Mission Infusion

NASA Technical Reports Server (NTRS)

Venkatapathy, Ethiraj; Beck, Robin; Ellerby, Donald; Feldman, Jay; Gage, Peter; Munk, Michelle; Wercinski, Paul

2016-01-01

NASA's Space Technology Mission Directorate (STMD) and the Game Changing Development Program (GCDP) were created to develop new technologies. This paper describes four entry system technologies that are funded by the GCDP and summarizes the lessons learned during the development. The investments are already beginning to show success, mission infusion pathways after five years of existence. It is hoped that our experience and observations, drawn from projects supported by the GCD program/STMD, Orion and SMD can help current and future technology development projects. Observations on fostering a culture of success and on constraints that limit greater success are also provided.

Information technology equipment cooling system

DOEpatents

Schultz, Mark D.

2014-06-10

According to one embodiment, a system for removing heat from a rack of information technology equipment may include a sidecar indoor air to liquid heat exchanger that cools warm air generated by the rack of information technology equipment. The system may also include a liquid to liquid heat exchanger and an outdoor heat exchanger. The system may further include configurable pathways to connect and control fluid flow through the sidecar heat exchanger, the liquid to liquid heat exchanger, the rack of information technology equipment, and the outdoor heat exchanger based upon ambient temperature and/or ambient humidity to remove heat from the rack of information technology equipment.

Innovative Water Management Technology to Reduce Environmental Impacts of Produced Water

DOE Office of Scientific and Technical Information (OSTI.GOV)

Castle, James; Rodgers, John; Alley, Bethany

2013-05-15

Clemson University with Chevron as an industry partner developed and applied treatment technology using constructed wetland systems to decrease targeted constituents in simulated and actual produced waters to achieve reuse criteria and discharge limits. Pilot-scale and demonstration constructed wetland treatment system (CWTS) experiments led to design strategies for treating a variety of constituents of concern (COCs) in produced waters including divalent metals, metalloids, oil and grease, and ammonia. Targeted biogeochemical pathways for treatment of COCs in pilot-scale CWTS experiments included divalent metal sulfide precipitation through dissimilatory sulfate reduction, metal precipitation through oxidation, reduction of selenite to insoluble elemental selenium, aerobicmore » biodegradation of oil, nitrification of ammonia to nitrate, denitrification of nitrate to nitrogen gas, separation of oil using an oilwater separator, and sorption of ammonia to zeolite. Treatment performance results indicated that CWTSs can be designed and built to promote specific environmental and geochemical conditions in order for targeted biogeochemical pathways to operate. The demonstration system successfully achieved consistent removal extents even while inflow concentrations of COCs in the produced water differed by orders of magnitude. Design strategies used in the pilot-scale and demonstration CWTSs to promote specific conditions that can be applied to designing full-scale CWTSs include plant and soil selection, water-depth selection, addition of amendments, and hydraulic retention time (HRT). These strategies allow conditions within a CWTS to be modified to achieve ranges necessary for the preferred biogeochemical treatment pathways. In the case of renovating a produced water containing COCs that require different biogeochemical pathways for treatment, a CWTS can be designed with sequential cells that promote different conditions. For example, the pilot-scale CWTS for post-reverse osmosis produced water was designed to promote oxidizing conditions within the first wetland cell for nitrification of ammonia, and the subsequent three cells were designed to promote reducing conditions for denitrification of nitrate. By incorporating multiple wetland cells in a CWTS, the conditions within each cell can be modified for removal of specific COCs. In addition, a CWTS designed with multiple cells allows for convenient sample collection points so that biogeochemical conditions of individual cells can be monitored and performance evaluated. Removal rate coefficients determined from the pilot-scale CWTS experiments and confirmed by the demonstration system can be used to calculate HRTs required to treat COCs in full-scale CWTSs. The calculated HRTs can then be used to determine the surface area or ?footprint? of a full-size CWTS for a given inflow rate of produced water.« less

Innovative Water Management Technology to Reduce Environment Impacts of Produced Water

DOE Office of Scientific and Technical Information (OSTI.GOV)

Castle, James W.; Rodgers, John H.; Alley, Bethany

2013-08-08

Clemson University with Chevron as an industry partner developed and applied treatment technology using constructed wetland systems to decrease targeted constituents in simulated and actual produced waters to achieve reuse criteria and discharge limits. Pilot-scale and demonstration constructed wetland treatment system (CWTS) experiments led to design strategies for treating a variety of constituents of concern (COCs) in produced waters including divalent metals, metalloids, oil and grease, and ammonia. Targeted biogeochemical pathways for treatment of COCs in pilot-scale CWTS experiments included divalent metal sulfide precipitation through dissimilatory sulfate reduction, metal precipitation through oxidation, reduction of selenite to insoluble elemental selenium, aerobicmore » biodegradation of oil, nitrification of ammonia to nitrate, denitrification of nitrate to nitrogen gas, separation of oil using an oilwater separator, and sorption of ammonia to zeolite. Treatment performance results indicated that CWTSs can be designed and built to promote specific environmental and geochemical conditions in order for targeted biogeochemical pathways to operate. The demonstration system successfully achieved consistent removal extents even while inflow concentrations of COCs in the produced water differed by orders of magnitude. Design strategies used in the pilot-scale and demonstration CWTSs to promote specific conditions that can be applied to designing full-scale CWTSs include plant and soil selection, water-depth selection, addition of amendments, and hydraulic retention time (HRT). These strategies allow conditions within a CWTS to be modified to achieve ranges necessary for the preferred biogeochemical treatment pathways. In the case of renovating a produced water containing COCs that require different biogeochemical pathways for treatment, a CWTS can be designed with sequential cells that promote different conditions. For example, the pilot-scale CWTS for post-reverse osmosis produced water was designed to promote oxidizing conditions within the first wetland cell for nitrification of ammonia, and the subsequent three cells were designed to promote reducing conditions for denitrification of nitrate. By incorporating multiple wetland cells in a CWTS, the conditions within each cell can be modified for removal of specific COCs. In addition, a CWTS designed with multiple cells allows for convenient sample collection points so that biogeochemical conditions of individual cells can be monitored and performance evaluated. Removal rate coefficients determined from the pilot-scale CWTS experiments and confirmed by the demonstration system can be used to calculate HRTs required to treat COCs in full-scale CWTSs. The calculated HRTs can then be used to determine the surface area or footprint of a full-size CWTS for a given inflow rate of produced water.« less

Innovative Water Management Technology to Reduce Environment Impacts of Produced Water

DOE Office of Scientific and Technical Information (OSTI.GOV)

Castle, James; Rodgers, John; Alley, Bethany

2013-05-15

Clemson University with Chevron as an industry partner developed and applied treatment technology using constructed wetland systems to decrease targeted constituents in simulated and actual produced waters to achieve reuse criteria and discharge limits. Pilot-scale and demonstration constructed wetland treatment system (CWTS) experiments led to design strategies for treating a variety of constituents of concern (COCs) in produced waters including divalent metals, metalloids, oil and grease, and ammonia. Targeted biogeochemical pathways for treatment of COCs in pilot-scale CWTS experiments included divalent metal sulfide precipitation through dissimilatory sulfate reduction, metal precipitation through oxidation, reduction of selenite to insoluble elemental selenium, aerobicmore » biodegradation of oil, nitrification of ammonia to nitrate, denitrification of nitrate to nitrogen gas, separation of oil using an oilwater separator, and sorption of ammonia to zeolite. Treatment performance results indicated that CWTSs can be designed and built to promote specific environmental and geochemical conditions in order for targeted biogeochemical pathways to operate. The demonstration system successfully achieved consistent removal extents even while inflow concentrations of COCs in the produced water differed by orders of magnitude. Design strategies used in the pilot-scale and demonstration CWTSs to promote specific conditions that can be applied to designing full-scale CWTSs include plant and soil selection, water-depth selection, addition of amendments, and hydraulic retention time (HRT). These strategies allow conditions within a CWTS to be modified to achieve ranges necessary for the preferred biogeochemical treatment pathways. In the case of renovating a produced water containing COCs that require different biogeochemical pathways for treatment, a CWTS can be designed with sequential cells that promote different conditions. For example, the pilot-scale CWTS for post-reverse osmosis produced water was designed to promote oxidizing conditions within the first wetland cell for nitrification of ammonia, and the subsequent three cells were designed to promote reducing conditions for denitrification of nitrate. By incorporating multiple wetland cells in a CWTS, the conditions within each cell can be modified for removal of specific COCs. In addition, a CWTS designed with multiple cells allows for convenient sample collection points so that biogeochemical conditions of individual cells can be monitored and performance evaluated. Removal rate coefficients determined from the pilot-scale CWTS experiments and confirmed by the demonstration system can be used to calculate HRTs required to treat COCs in full-scale CWTSs. The calculated HRTs can then be used to determine the surface area or footprint of a full-size CWTS for a given inflow rate of produced water.« less

Spatially organizing biochemistry: choosing a strategy to translate synthetic biology to the factory.

PubMed

Jakobson, Christopher M; Tullman-Ercek, Danielle; Mangan, Niall M

2018-05-29

Natural biochemical systems are ubiquitously organized both in space and time. Engineering the spatial organization of biochemistry has emerged as a key theme of synthetic biology, with numerous technologies promising improved biosynthetic pathway performance. One strategy, however, may produce disparate results for different biosynthetic pathways. We use a spatially resolved kinetic model to explore this fundamental design choice in systems and synthetic biology. We predict that two example biosynthetic pathways have distinct optimal organization strategies that vary based on pathway-dependent and cell-extrinsic factors. Moreover, we demonstrate that the optimal design varies as a function of kinetic and biophysical properties, as well as culture conditions. Our results suggest that organizing biosynthesis has the potential to substantially improve performance, but that choosing the appropriate strategy is key. The flexible design-space analysis we propose can be adapted to diverse biosynthetic pathways, and lays a foundation to rationally choose organization strategies for biosynthesis.

Integration of Technology into the Classroom: Case Studies.

ERIC Educational Resources Information Center

Johnson, D. LaMont, Ed.; Maddux, Cleborne D., Ed.; Liu, Leping, Ed.

This book contains the following case studies on the integration of technology in education: (1) "First Steps toward a Statistically Generated Information Technology Integration Model" (D. LaMont Johnson and Leping Liu); (2) "Case Studies: Are We Rejecting Rigor or Rediscovering Richness?" (Cleborne D. Maddux); (3)…

[Strategies of elucidation of biosynthetic pathways of natural products].

PubMed

Zou, Li-Qiu; Kuang, Xue-Jun; Sun, Chao; Chen, Shi-Lin

2016-11-01

Elucidation of the biosynthetic pathways of natural products is not only the major goal of herb genomics, but also the solid foundation of synthetic biology of natural products. Here, this paper reviewed recent advance in this field and put forward strategies to elucidate the biosynthetic pathway of natural products. Firstly, a proposed biosynthetic pathway should be set up based on well-known knowledge about chemical reactions and information on the identified compounds, as well as studies with isotope tracer. Secondly, candidate genes possibly involved in the biosynthetic pathway were screened out by co-expression analysis and/or gene cluster mining. Lastly, all the candidate genes were heterologously expressed in the host and then the enzyme involved in the biosynthetic pathway was characterized by activity assay. Sometimes, the function of the enzyme in the original plant could be further studied by RNAi or VIGS technology. Understanding the biosynthetic pathways of natural products will contribute to supply of new leading compounds by synthetic biology and provide "functional marker" for herbal molecular breeding, thus but boosting the development of traditional Chinese medicine agriculture. Copyright© by the Chinese Pharmaceutical Association.

Regulating ehrlich and demethiolation pathways for alcohols production by the expression of ubiquitin-protein ligase gene HUWE1.

PubMed

Zhang, Quan; Jia, Kai-Zhi; Xia, Shi-Tao; Xu, Yang-Hua; Liu, Rui-Sang; Li, Hong-Mei; Tang, Ya-Jie

2016-02-10

Ehrlich and demethiolation pathways as two competing branches converted amino acid into alcohols. Controlling both pathways offers considerable potential for industrial applications including alcohols overproduction, flavor-quality control and developing new flavors. While how to regulate ehrlich and demethiolation pathways is still not applicable. Taking the conversion of methionine into methionol and methanethiol for example, we constructed two suppression subtractive cDNA libraries of Clonostachys rosea by using suppression subtractive hybridization (SSH) technology for screening regulators controlling the conversion. E3 ubiquitin-protein ligase gene HUWE1 screened from forward SSH library was validated to be related with the biosynthesis of end products. Overexpressing HUWE1 in C. rosea and S. cerevisiae significantly increased the biosynthesis of methanethiol and its derivatives in demethiolation pathway, while suppressed the biosynthesis of methional and methionol in ehrlich pathway. These results attained the directional regulation of both pathways by overexpressing HUWE1. Thus, HUWE1 has potential to be a key target for controlling and enhancing alcohols production by metabolic engineering.

Using Patient Pathway Analysis to Design Patient-centered Referral Networks for Diagnosis and Treatment of Tuberculosis: The Case of the Philippines.

PubMed

Garfin, Celine; Mantala, Mariquita; Yadav, Rajendra; Hanson, Christy L; Osberg, Mike; Hymoff, Aaron; Makayova, Julia

2017-11-06

Tuberculosis (TB) is the 8th leading cause of death in the Philippines. A recent prevalence survey found that there were nearly 70% more cases of tuberculosis than previously estimated. Given these new data, the National TB Program (NTP), operating through a decentralized health system, identified about 58% of the estimated new drug-sensitive (DS) TB patients in 2016. However, the NTP only identified and commenced treatment for around 17% of estimated new drug-resistant patients. In order to reach the remaining 42% of drug-sensitive patients and 83% of drug-resistant patients, it is necessary to develop a better understanding of where patients seek care. National and regional patient pathway analyses (PPAs) were undertaken using existing national survey and NTP data. The PPA assessed the alignment between patient care seeking and the availability of TB diagnostic and treatment services. Systemic referral networks from the community-level Barangay Health Stations (BHSs) to diagnostic facilities have enabled more efficient detection of drug-sensitive tuberculosis in the public sector. Approximately 36% of patients initiated care in the private sector, where there is limited coverage of appropriate diagnostic technologies. Important differences in the alignment between care seeking patterns and diagnostic and treatment availability were found between regions. The PPA identified opportunities for strengthening access to care for all forms of tuberculosis and for accelerating the time to diagnosis by aligning services to where patients initiate care. Geographic variations in care seeking may guide prioritization of some regions for intensified engagement with the private sector. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Molecular classification of gastric cancer: Towards a pathway-driven targeted therapy

PubMed Central

Espinoza, Jaime A.; Weber, Helga; García, Patricia; Nervi, Bruno; Garrido, Marcelo; Corvalán, Alejandro H.; Roa, Juan Carlos; Bizama, Carolina

2015-01-01

Gastric cancer (GC) is the third leading cause of cancer mortality worldwide. Although surgical resection is a potentially curative approach for localized cases of GC, most cases of GC are diagnosed in an advanced, non-curable stage and the response to traditional chemotherapy is limited. Fortunately, recent advances in our understanding of the molecular mechanisms that mediate GC hold great promise for the development of more effective treatment strategies. In this review, an overview of the morphological classification, current treatment approaches, and molecular alterations that have been characterized for GC are provided. In particular, the most recent molecular classification of GC and alterations identified in relevant signaling pathways, including ErbB, VEGF, PI3K/AKT/mTOR, and HGF/MET signaling pathways, are described, as well as inhibitors of these pathways. An overview of the completed and active clinical trials related to these signaling pathways are also summarized. Finally, insights regarding emerging stem cell pathways are described, and may provide additional novel markers for the development of therapeutic agents against GC. The development of more effective agents and the identification of biomarkers that can be used for the diagnosis, prognosis, and individualized therapy for GC patients, have the potential to improve the efficacy, safety, and cost-effectiveness for GC treatments. PMID:26267324

A novel analysis strategy for integrating methylation and expression data reveals core pathways for thyroid cancer aetiology

PubMed Central

2015-01-01

Background Recently, a wide range of diseases have been associated with changes in DNA methylation levels, which play a vital role in gene expression regulation. With ongoing developments in technology, attempts to understand disease mechanism have benefited greatly from epigenetics and transcriptomics studies. In this work, we have used expression and methylation data of thyroid carcinoma as a case study and explored how to optimally incorporate expression and methylation information into the disease study when both data are available. Moreover, we have also investigated whether there are important post-translational modifiers which could drive critical insights on thyroid cancer genetics. Results In this study, we have conducted a threshold analysis for varying methylation levels to identify whether setting a methylation level threshold increases the performance of functional enrichment. Moreover, in order to decide on best-performing analysis strategy, we have performed data integration analysis including comparison of 10 different analysis strategies. As a result, combining methylation with expression and using genes with more than 15% methylation change led to optimal detection rate of thyroid-cancer associated pathways in top 20 functional enrichment results. Furthermore, pooling the data from different experiments increased analysis confidence by improving the data range. Consequently, we have identified 207 transcription factors and 245 post-translational modifiers with more than 15% methylation change which may be important in understanding underlying mechanisms of thyroid cancer. Conclusion While only expression or only methylation information would not reveal both primary and secondary mechanisms involved in disease state, combining expression and methylation led to a better detection of thyroid cancer-related genes and pathways that are found in the recent literature. Moreover, focusing on genes that have certain level of methylation change improved the functional enrichment results, revealing the core pathways involved in disease development such as; endocytosis, apoptosis, glutamatergic synapse, MAPK, ErbB, TGF-beta and Toll-like receptor pathways. Overall, in addition to novel analysis framework, our study reveals important thyroid-cancer related mechanisms, secondary molecular alterations and contributes to better knowledge of thyroid cancer aetiology. PMID:26678064

The application of DNA microarrays in gene expression analysis.

PubMed

van Hal, N L; Vorst, O; van Houwelingen, A M; Kok, E J; Peijnenburg, A; Aharoni, A; van Tunen, A J; Keijer, J

2000-03-31

DNA microarray technology is a new and powerful technology that will substantially increase the speed of molecular biological research. This paper gives a survey of DNA microarray technology and its use in gene expression studies. The technical aspects and their potential improvements are discussed. These comprise array manufacturing and design, array hybridisation, scanning, and data handling. Furthermore, it is discussed how DNA microarrays can be applied in the working fields of: safety, functionality and health of food and gene discovery and pathway engineering in plants.

Racial disparity in pathophysiologic pathways of preterm birth based on genetic variants

PubMed Central

Menon, Ramkumar; Pearce, Brad; Velez, Digna R; Merialdi, Mario; Williams, Scott M; Fortunato, Stephen J; Thorsen, Poul

2009-01-01

Objective To study pathophysiologic pathways in spontaneous preterm birth and possibly the racial disparity associating with maternal and fetal genetic variations, using bioinformatics tools. Methods A large scale candidate gene association study was performed on 1442 SNPs in 130 genes in a case (preterm birth < 36 weeks) control study (term birth > 37 weeks). Both maternal and fetal DNA from Caucasians (172 cases and 198 controls) and 279 African-Americans (82 cases and 197 controls) were used. A single locus association (genotypic) analysis followed by hierarchical clustering was performed, where clustering was based on p values for significant associations within each race. Using Ingenuity Pathway Analysis (IPA) software, known pathophysiologic pathways in both races were determined. Results From all SNPs entered into the analysis, the IPA mapped genes to specific disease functions. Gene variants in Caucasians were implicated in disease functions shared with other known disorders; specifically, dermatopathy, inflammation, and hematological disorders. This may reflect abnormal cervical ripening and decidual hemorrhage. In African-Americans inflammatory pathways were the most prevalent. In Caucasians, maternal gene variants showed the most prominent role in disease functions, whereas in African Americans it was fetal variants. The IPA software was used to generate molecular interaction maps that differed between races and also between maternal and fetal genetic variants. Conclusion Differences at the genetic level revealed distinct disease functions and operational pathways in African Americans and Caucasians in spontaneous preterm birth. Differences in maternal and fetal contributions in pregnancy outcome are also different between African Americans and Caucasians. These results present a set of explicit testable hypotheses regarding genetic associations with preterm birth in African Americans and Caucasians PMID:19527514

Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma.

PubMed

Kang, J H; Loomis, S J; Yaspan, B L; Bailey, J C; Weinreb, R N; Lee, R K; Lichter, P R; Budenz, D L; Liu, Y; Realini, T; Gaasterland, D; Gaasterland, T; Friedman, D S; McCarty, C A; Moroi, S E; Olson, L; Schuman, J S; Singh, K; Vollrath, D; Wollstein, G; Zack, D J; Brilliant, M; Sit, A J; Christen, W G; Fingert, J; Forman, J P; Buys, E S; Kraft, P; Zhang, K; Allingham, R R; Pericak-Vance, M A; Richards, J E; Hauser, M A; Haines, J L; Wiggs, J L; Pasquale, L R

2014-06-01

Vascular perfusion may be impaired in primary open-angle glaucoma (POAG); thus, we evaluated a panel of markers in vascular tone-regulating genes in relation to POAG. We used Illumina 660W-Quad array genotype data and pooled P-values from 3108 POAG cases and 3430 controls from the combined National Eye Institute Glaucoma Human Genetics Collaboration consortium and Glaucoma Genes and Environment studies. Using information from previous literature and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we compiled single-nucleotide polymorphisms (SNPs) in 186 vascular tone-regulating genes. We used the 'Pathway Analysis by Randomization Incorporating Structure' analysis software, which performed 1000 permutations to compare the overall pathway and selected genes with comparable randomly generated pathways and genes in their association with POAG. The vascular tone pathway was not associated with POAG overall or POAG subtypes, defined by the type of visual field loss (early paracentral loss (n=224 cases) or only peripheral loss (n=993 cases)) (permuted P≥0.20). In gene-based analyses, eight were associated with POAG overall at permuted P<0.001: PRKAA1, CAV1, ITPR3, EDNRB, GNB2, DNM2, HFE, and MYL9. Notably, six of these eight (the first six listed) code for factors involved in the endothelial nitric oxide synthase activity, and three of these six (CAV1, ITPR3, and EDNRB) were also associated with early paracentral loss at P<0.001, whereas none of the six genes reached P<0.001 for peripheral loss only. Although the assembled vascular tone SNP set was not associated with POAG, genes that code for local factors involved in setting vascular tone were associated with POAG.

Diet and Colorectal Cancer: Analysis of a Candidate Pathway Using SNPS, Haplotypes, and Multi-Gene Assessment

PubMed Central

Slattery, Martha L.; Lundgreen, Abbie; Herrick, Jennifer S.; Caan, Bette J.; Potter, John D.; Wolff, Roger K.

2012-01-01

There is considerable biologic plausibility to the hypothesis that genetic variability in pathways involved in insulin signaling and energy homeostasis may modulate dietary risk associated with colorectal cancer. We utilized data from 2 population-based case-control studies of colon (n = 1,574 cases, 1,970 controls) and rectal (n = 791 cases, 999 controls) cancer to evaluate genetic variation in candidate SNPs identified from 9 genes in a candidate pathway: PDK1, RP6KA1, RPS6KA2, RPS6KB1, RPS6KB2, PTEN, FRAP1 (mTOR), TSC1, TSC2, Akt1, PIK3CA, and PRKAG2 with dietary intake of total energy, carbohydrates, fat, and fiber. We employed SNP, haplotype, and multiple-gene analysis to evaluate associations. PDK1 interacted with dietary fat for both colon and rectal cancer and with dietary carbohydrates for colon cancer. Statistically significant interaction with dietary carbohydrates and rectal cancer was detected by haplotype analysis of PDK1. Evaluation of dietary interactions with multiple genes in this candidate pathway showed several interactions with pairs of genes: Akt1 and PDK1, PDK1 and PTEN, PDK1 and TSC1, and PRKAG2 and PTEN. Analyses show that genetic variation influences risk of colorectal cancer associated with diet and illustrate the importance of evaluating dietary interactions beyond the level of single SNPs or haplotypes when a biologically relevant candidate pathway is examined. PMID:21999454

Tag Clouds as a Pathway to Improved Pedagogical Efficacy in Information Systems Courses: A Baseline Study Involving Web 2.0 Technologies

ERIC Educational Resources Information Center

Conn, Samuel S.; English, John; Scheffler, Fred; Hall, Simin

2011-01-01

Various Web 2.0 technologies can be used to support pedagogy. Examples include wikis, blogs, and social media including forum discussions. Online class forum discussions involving electronic text can result in robust strings of data containing meta-knowledge, inherent meaning, themes and patterns. Based on instructional design, learning outcomes…

Gender Gap in Science, Technology, Engineering, and Mathematics (STEM): Current Knowledge, Implications for Practice, Policy, and Future Directions

ERIC Educational Resources Information Center

Wang, Ming-Te; Degol, Jessica L.

2017-01-01

Although the gender gap in math course-taking and performance has narrowed in recent decades, females continue to be underrepresented in math-intensive fields of Science, Technology, Engineering, and Mathematics (STEM). Career pathways encompass the ability to pursue a career as well as the motivation to employ that ability. Individual differences…

Evaluating interactive technology for an evolving case study on learning and satisfaction of graduate nursing students.

PubMed

Vogt, Marjorie A; Schaffner, Barbara H

2016-07-01

Nursing education is challenged to prepare students for complex healthcare needs through the integration of teamwork and informatics. Technology has become an important teaching tool in the blended classroom to enhance group based learning experiences. Faculty evaluation of classroom technologies is imperative prior to adoption. Few studies have directly compared various technologies and their impact on student satisfaction and learning. The purpose of this study was to evaluate technology enhanced teaching methods on the learning and satisfaction of graduate students in an advanced pharmacology class using an unfolding case study. After IRB approval, students were randomly assigned to one of three groups: blogging group, wiki group or webinar group. Students completed the evolving case study using the assigned interactive technology. Student names were removed from the case studies. Faculty evaluated the case study using a rubric, while blinded to the assigned technology method used. No significant difference was found on case study grades, the range of grades on the assignment demonstrated little differences between the methods used. Students indicated an overall positive impact related to networking and collaboration on a satisfaction survey. Impact of technology methods needs to be explored in other areas of graduate nursing education. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comprehensive analysis of the tryptophan metabolome in urine of patients with acute intermittent porphyria.

PubMed

Gomez-Gomez, Alex; Marcos, Josep; Aguilera, Paula; To-Figueras, Jordi; Pozo, Oscar J

2017-08-15

Acute intermittent porphyria (AIP) is a rare metabolic disorder due to a deficiency of porphobilinogen deaminase, the third enzyme of the heme biosynthetic pathway. This low enzymatic activity may predispose to the appearance of acute neurological attacks. Seminal studies suggested that AIP was associated with changes in tryptophan homeostasis with inconclusive results. Therefore, the aim of this study was to analyze the urinary metabolome of AIP patients focusing on tryptophan metabolism using state-of-the-art technology. This was a case-control study including a group of 25 AIP patients with active biochemical disease and increased excretion of heme-precursors and 25 healthy controls. Tryptophan and related compounds and metabolites including: large neutral amino acids (LNAAs), serotonin, kynurenine, kynurenic acid and anthranilic acid were quantified in urine by liquid chromatography tandem-mass spectrometry (LC-MS/MS). Twenty-nine biological markers (including metabolic ratios and absolute concentrations) were compared between patients and controls. Significant differences were found in the tryptophan-kynurenine metabolic pathway. Compared to controls, AIP patients showed: (a) increased urinary excretion of kynurenine and anthranilic acid (P<0.005); (b): elevation of the kynurenine/tryptophan ratio (P<0.001) and (c): decrease of the kynurenic acid/kynurenine ratio (P=0.001). In contrast, no differences were found in the serotonin metabolic pathway independently of the markers and ratios used. The results of the study demonstrate that there is an imbalance in the kynurenine metabolic pathway in AIP patients, with an increase of the kynurenine/tryptophan ratio in urine and a reduction of the kynurenic acid/kynurenine ratio. The modified ratios suggest induction of indoleamine 2,3-deoxygenase and decreased activity of kynurenine aminotransferase in the liver. The results confirm that LC-MS/MS is useful for the characterization of the urinary metabolome of hepatic porphyrias. Copyright © 2017. Published by Elsevier B.V.

Guiding the folding pathway of DNA origami

NASA Astrophysics Data System (ADS)

Dunn, Katherine E.; Dannenberg, Frits; Ouldridge, Thomas E.; Kwiatkowska, Marta; Turberfield, Andrew J.; Bath, Jonathan

2015-09-01

DNA origami is a robust assembly technique that folds a single-stranded DNA template into a target structure by annealing it with hundreds of short `staple' strands. Its guiding design principle is that the target structure is the single most stable configuration. The folding transition is cooperative and, as in the case of proteins, is governed by information encoded in the polymer sequence. A typical origami folds primarily into the desired shape, but misfolded structures can kinetically trap the system and reduce the yield. Although adjusting assembly conditions or following empirical design rules can improve yield, well-folded origami often need to be separated from misfolded structures. The problem could in principle be avoided if assembly pathway and kinetics were fully understood and then rationally optimized. To this end, here we present a DNA origami system with the unusual property of being able to form a small set of distinguishable and well-folded shapes that represent discrete and approximately degenerate energy minima in a vast folding landscape, thus allowing us to probe the assembly process. The obtained high yield of well-folded origami structures confirms the existence of efficient folding pathways, while the shape distribution provides information about individual trajectories through the folding landscape. We find that, similarly to protein folding, the assembly of DNA origami is highly cooperative; that reversible bond formation is important in recovering from transient misfoldings; and that the early formation of long-range connections can very effectively enforce particular folds. We use these insights to inform the design of the system so as to steer assembly towards desired structures. Expanding the rational design process to include the assembly pathway should thus enable more reproducible synthesis, particularly when targeting more complex structures. We anticipate that this expansion will be essential if DNA origami is to continue its rapid development and become a reliable manufacturing technology.

Guiding the folding pathway of DNA origami.

PubMed

Dunn, Katherine E; Dannenberg, Frits; Ouldridge, Thomas E; Kwiatkowska, Marta; Turberfield, Andrew J; Bath, Jonathan

2015-09-03

DNA origami is a robust assembly technique that folds a single-stranded DNA template into a target structure by annealing it with hundreds of short 'staple' strands. Its guiding design principle is that the target structure is the single most stable configuration. The folding transition is cooperative and, as in the case of proteins, is governed by information encoded in the polymer sequence. A typical origami folds primarily into the desired shape, but misfolded structures can kinetically trap the system and reduce the yield. Although adjusting assembly conditions or following empirical design rules can improve yield, well-folded origami often need to be separated from misfolded structures. The problem could in principle be avoided if assembly pathway and kinetics were fully understood and then rationally optimized. To this end, here we present a DNA origami system with the unusual property of being able to form a small set of distinguishable and well-folded shapes that represent discrete and approximately degenerate energy minima in a vast folding landscape, thus allowing us to probe the assembly process. The obtained high yield of well-folded origami structures confirms the existence of efficient folding pathways, while the shape distribution provides information about individual trajectories through the folding landscape. We find that, similarly to protein folding, the assembly of DNA origami is highly cooperative; that reversible bond formation is important in recovering from transient misfoldings; and that the early formation of long-range connections can very effectively enforce particular folds. We use these insights to inform the design of the system so as to steer assembly towards desired structures. Expanding the rational design process to include the assembly pathway should thus enable more reproducible synthesis, particularly when targeting more complex structures. We anticipate that this expansion will be essential if DNA origami is to continue its rapid development and become a reliable manufacturing technology.

Process modeling and supply chain design for advanced biofuel production based on bio-oil gasification

NASA Astrophysics Data System (ADS)

Li, Qi

As a potential substitute for petroleum-based fuel, second generation biofuels are playing an increasingly important role due to their economic, environmental, and social benefits. With the rapid development of biofuel industry, there has been an increasing literature on the techno-economic analysis and supply chain design for biofuel production based on a variety of production pathways. A recently proposed production pathway of advanced biofuel is to convert biomass to bio-oil at widely distributed small-scale fast pyrolysis plants, then gasify the bio-oil to syngas and upgrade the syngas to transportation fuels in centralized biorefinery. This thesis aims to investigate two types of assessments on this bio-oil gasification pathway: techno-economic analysis based on process modeling and literature data; supply chain design with a focus on optimal decisions for number of facilities to build, facility capacities and logistic decisions considering uncertainties. A detailed process modeling with corn stover as feedstock and liquid fuels as the final products is presented. Techno-economic analysis of the bio-oil gasification pathway is also discussed to assess the economic feasibility. Some preliminary results show a capital investment of 438 million dollar and minimum fuel selling price (MSP) of $5.6 per gallon of gasoline equivalent. The sensitivity analysis finds that MSP is most sensitive to internal rate of return (IRR), biomass feedstock cost, and fixed capital cost. A two-stage stochastic programming is formulated to solve the supply chain design problem considering uncertainties in biomass availability, technology advancement, and biofuel price. The first-stage makes the capital investment decisions including the locations and capacities of the decentralized fast pyrolysis plants and the centralized biorefinery while the second-stage determines the biomass and biofuel flows. The numerical results and case study illustrate that considering uncertainties can be pivotal in this supply chain design and optimization problem. Also, farmers' participation has a significant effect on the decision making process.

Subpathway-GM: identification of metabolic subpathways via joint power of interesting genes and metabolites and their topologies within pathways.

PubMed

Li, Chunquan; Han, Junwei; Yao, Qianlan; Zou, Chendan; Xu, Yanjun; Zhang, Chunlong; Shang, Desi; Zhou, Lingyun; Zou, Chaoxia; Sun, Zeguo; Li, Jing; Zhang, Yunpeng; Yang, Haixiu; Gao, Xu; Li, Xia

2013-05-01

Various 'omics' technologies, including microarrays and gas chromatography mass spectrometry, can be used to identify hundreds of interesting genes, proteins and metabolites, such as differential genes, proteins and metabolites associated with diseases. Identifying metabolic pathways has become an invaluable aid to understanding the genes and metabolites associated with studying conditions. However, the classical methods used to identify pathways fail to accurately consider joint power of interesting gene/metabolite and the key regions impacted by them within metabolic pathways. In this study, we propose a powerful analytical method referred to as Subpathway-GM for the identification of metabolic subpathways. This provides a more accurate level of pathway analysis by integrating information from genes and metabolites, and their positions and cascade regions within the given pathway. We analyzed two colorectal cancer and one metastatic prostate cancer data sets and demonstrated that Subpathway-GM was able to identify disease-relevant subpathways whose corresponding entire pathways might be ignored using classical entire pathway identification methods. Further analysis indicated that the power of a joint genes/metabolites and subpathway strategy based on their topologies may play a key role in reliably recalling disease-relevant subpathways and finding novel subpathways.

Genetic and Environmental Pathways in Type 1 Diabetes Complications

DTIC Science & Technology

2008-09-01

the “Limit By Function Type” heading opens a new browser window to the online user guide describing the use of this filter when selecting SNPs for...T1D. The juxtaglomerular apparatus comprises different structures in functional and structural link: cells of the extraglomerular mesangium, which fill...27 Aug 2007-26 Aug 2008 4. TITLE AND SUBTITLE Genetic and Environmental Pathways in Type 1 Diabetes Complications New Advanced Technology to

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hill, David P.; D’Eustachio, Peter; Berardini, Tanya Z.

The concept of a biological pathway, an ordered sequence of molecular transformations, is used to collect and represent molecular knowledge for a broad span of organismal biology. Representations of biomedical pathways typically are rich but idiosyncratic presentations of organized knowledge about individual pathways. Meanwhile, biomedical ontologies and associated annotation files are powerful tools that organize molecular information in a logically rigorous form to support computational analysis. The Gene Ontology (GO), representing Molecular Functions, Biological Processes and Cellular Components, incorporates many aspects of biological pathways within its ontological representations. Here we present a methodology for extending and refining the classes inmore » the GO for more comprehensive, consistent and integrated representation of pathways, leveraging knowledge embedded in current pathway representations such as those in the Reactome Knowledgebase and MetaCyc. With carbohydrate metabolic pathways as a use case, we discuss how our representation supports the integration of variant pathway classes into a unified ontological structure that can be used for data comparison and analysis.« less

Surgical data science: The new knowledge domain

PubMed Central

Vedula, S. Swaroop; Hager, Gregory D.

2017-01-01

Healthcare in general, and surgery/interventional care in particular, is evolving through rapid advances in technology and increasing complexity of care with the goal of maximizing quality and value of care. While innovations in diagnostic and therapeutic technologies have driven past improvements in quality of surgical care, future transformation in care will be enabled by data. Conventional methodologies, such as registry studies, are limited in their scope for discovery and research, extent and complexity of data, breadth of analytic techniques, and translation or integration of research findings into patient care. We foresee the emergence of Surgical/Interventional Data Science (SDS) as a key element to addressing these limitations and creating a sustainable path toward evidence-based improvement of interventional healthcare pathways. SDS will create tools to measure, model and quantify the pathways or processes within the context of patient health states or outcomes, and use information gained to inform healthcare decisions, guidelines, best practices, policy, and training, thereby improving the safety and quality of healthcare and its value. Data is pervasive throughout the surgical care pathway; thus, SDS can impact various aspects of care including prevention, diagnosis, intervention, or post-operative recovery. Existing literature already provides preliminary results suggesting how a data science approach to surgical decision-making could more accurately predict severe complications using complex data from pre-, intra-, and post-operative contexts, how it could support intra-operative decision-making using both existing knowledge and continuous data streams throughout the surgical care pathway, and how it could enable effective collaboration between human care providers and intelligent technologies. In addition, SDS is poised to play a central role in surgical education, for example, through objective assessments, automated virtual coaching, and robot-assisted active learning of surgical skill. However, the potential for transforming surgical care and training through SDS may only be realized through a cultural shift that not only institutionalizes technology to seamlessly capture data but also assimilates individuals with expertise in data science into clinical research teams. Furthermore, collaboration with industry partners from the inception of the discovery process promotes optimal design of data products as well as their efficient translation and commercialization. As surgery continues to evolve through advances in technology that enhance delivery of care, SDS represents a new knowledge domain to engineer surgical care of the future. PMID:28936475

Surgical data science: The new knowledge domain.

PubMed

Vedula, S Swaroop; Hager, Gregory D

2017-04-01

Healthcare in general, and surgery/interventional care in particular, is evolving through rapid advances in technology and increasing complexity of care with the goal of maximizing quality and value of care. While innovations in diagnostic and therapeutic technologies have driven past improvements in quality of surgical care, future transformation in care will be enabled by data. Conventional methodologies, such as registry studies, are limited in their scope for discovery and research, extent and complexity of data, breadth of analytic techniques, and translation or integration of research findings into patient care. We foresee the emergence of Surgical/Interventional Data Science (SDS) as a key element to addressing these limitations and creating a sustainable path toward evidence-based improvement of interventional healthcare pathways. SDS will create tools to measure, model and quantify the pathways or processes within the context of patient health states or outcomes, and use information gained to inform healthcare decisions, guidelines, best practices, policy, and training, thereby improving the safety and quality of healthcare and its value. Data is pervasive throughout the surgical care pathway; thus, SDS can impact various aspects of care including prevention, diagnosis, intervention, or post-operative recovery. Existing literature already provides preliminary results suggesting how a data science approach to surgical decision-making could more accurately predict severe complications using complex data from pre-, intra-, and post-operative contexts, how it could support intra-operative decision-making using both existing knowledge and continuous data streams throughout the surgical care pathway, and how it could enable effective collaboration between human care providers and intelligent technologies. In addition, SDS is poised to play a central role in surgical education, for example, through objective assessments, automated virtual coaching, and robot-assisted active learning of surgical skill. However, the potential for transforming surgical care and training through SDS may only be realized through a cultural shift that not only institutionalizes technology to seamlessly capture data but also assimilates individuals with expertise in data science into clinical research teams. Furthermore, collaboration with industry partners from the inception of the discovery process promotes optimal design of data products as well as their efficient translation and commercialization. As surgery continues to evolve through advances in technology that enhance delivery of care, SDS represents a new knowledge domain to engineer surgical care of the future.

Customizing the genome as therapy for the β-hemoglobinopathies

PubMed Central

Canver, Matthew C.

2016-01-01

Despite nearly complete understanding of the genetics of the β-hemoglobinopathies for several decades, definitive treatment options have lagged behind. Recent developments in technologies for facile manipulation of the genome (zinc finger nucleases, transcription activator-like effector nucleases, or clustered regularly interspaced short palindromic repeats–based nucleases) raise prospects for their clinical application. The use of genome-editing technologies in autologous CD34+ hematopoietic stem and progenitor cells represents a promising therapeutic avenue for the β-globin disorders. Genetic correction strategies relying on the homology-directed repair pathway may repair genetic defects, whereas genetic disruption strategies relying on the nonhomologous end joining pathway may induce compensatory fetal hemoglobin expression. Harnessing the power of genome editing may usher in a second-generation form of gene therapy for the β-globin disorders. PMID:27053533

Metabolomic strategies to map functions of metabolic pathways

PubMed Central

Mulvihill, Melinda M.

2014-01-01

Genome sequencing efforts have revealed a strikingly large number of unannotated and uncharacterized genes that fall into metabolic enzymes classes, likely indicating that our current knowledge of biochemical pathways in normal physiology, let alone in disease states, remains largely incomplete. This realization presents a daunting challenge for post-genomic-era scientists in deciphering the biochemical and (patho)physiological roles of these enzymes and their metabolites and metabolic networks. This is further complicated by many recent studies showing a rewiring of normal metabolic networks in disease states to give rise to unique pathophysiological functions of enzymes, metabolites, and metabolic pathways. This review focuses on recent discoveries made using metabolic mapping technologies to uncover novel pathways and metabolite-mediated posttranslational modifications and epigenetic alterations and their impact on physiology and disease. PMID:24918200

[Advance in flavonoids biosynthetic pathway and synthetic biology].

PubMed

Zou, Li-Qiu; Wang, Cai-Xia; Kuang, Xue-Jun; Li, Ying; Sun, Chao

2016-11-01

Flavonoids are the valuable components in medicinal plants, which possess a variety of pharmacological activities, including anti-tumor, antioxidant and anti-inflammatory activities. There is an unambiguous understanding about flavonoids biosynthetic pathway, that is,2S-flavanones including naringenin and pinocembrin are the skeleton of other flavonoids and they can transform to other flavonoids through branched metabolic pathway. Elucidation of the flavonoids biosynthetic pathway lays a solid foundation for their synthetic biology. A few flavonoids have been produced in Escherichia coli or yeast with synthetic biological technologies, such as naringenin, pinocembrin and fisetin. Synthetic biology will provide a new way to get valuable flavonoids and promote the research and development of flavonoid drugs and health products, making flavonoids play more important roles in human diet and health. Copyright© by the Chinese Pharmaceutical Association.

Outsourcing to increase service capacity in a New Zealand hospital.

PubMed

Renner, C; Palmer, E

1999-01-01

Service firms manage variability using both demand-side tactics (levelling customer demand), and supply-side tactics (increasing available capacity). One popular way of increasing available capacity is the outsourcing of non-core services. This article uses a case study to examine the impact of an outsourced non-core service on a hospital's overall service system. Findings show that the outsourced service provides access to more sophisticated technology, increases in-house capacity and saves capital expenditure. However, the outsourcing also increases the scheduling problems that the hospital faces. These problems are largely due to communication delays from the involvement of more than one organisation. These delays decrease the response time available to match changes in demand for the outsourced service. Given the obvious benefits of such outsourcing, the article concludes that management should pay close attention to the communication pathways between organisations, in order to minimise the end effects identified in this study.

Aortic stent grafting: a new approach to a deadly diagnosis: one hospital's findings in defining new care processes.

PubMed

Kalinowski, H

2001-01-01

Ruptured abdominal aortic aneurysm (AAA) is the 13th leading cause of death in the United States. Diagnosis is the key to prevention of death from AAA. Millions of Americans harbor this silent, potentially lethal aneurysm. For over 50 years, conventional open surgical repair has been performed for ruptured aortic abdominal aneurysm. It is a major operation with an extended hospital stay and recovery period. An alternative approach to AAA repair has evolved over the past 10 years that combines advances in catheter and stent technologies. With the AAA aortic stent graft, patients usually do not require intensive care and are discharged home within 48 hours of the procedure. This article describes the AAA aortic stent graft procedure, in the formation of a case management team to develop a clinical pathway and standing orders for these patients and defines the outcomes of care.

Bringing the pregnancy test home from the hospital.

PubMed

Robinson, Joan H

2016-10-01

This paper explores the settlement process of one of the most common home diagnostic tools currently in use, the home pregnancy test. The controversial new device appeared to threaten the jurisdiction of both doctors and Food and Drug Administration regulations, while it aligned with the women's health movement's goals. But this study finds a more nuanced narrative: one of boundaries and positions that at once were blurry, later shifted, and were ultimately aligned without compromising the credibility of doctors or the legal system. To understand this process, the roles of court decisions and regulations are explained by stages of juris-technical accordance. In this case, rather than restricting technological innovation, legal innovation provided pathways for widespread acceptance of the home pregnancy test by various groups. As more tools move from expert users to layperson users, this paper demonstrates the utility of examining existing juris-technical assemblages as we consider the future of self-monitoring and self-diagnosis.

Data Reduction Approaches for Dissecting Transcriptional Effects on Metabolism

PubMed Central

Schwahn, Kevin; Nikoloski, Zoran

2018-01-01

The availability of high-throughput data from transcriptomics and metabolomics technologies provides the opportunity to characterize the transcriptional effects on metabolism. Here we propose and evaluate two computational approaches rooted in data reduction techniques to identify and categorize transcriptional effects on metabolism by combining data on gene expression and metabolite levels. The approaches determine the partial correlation between two metabolite data profiles upon control of given principal components extracted from transcriptomics data profiles. Therefore, they allow us to investigate both data types with all features simultaneously without doing preselection of genes. The proposed approaches allow us to categorize the relation between pairs of metabolites as being under transcriptional or post-transcriptional regulation. The resulting classification is compared to existing literature and accumulated evidence about regulatory mechanism of reactions and pathways in the cases of Escherichia coli, Saccharomycies cerevisiae, and Arabidopsis thaliana. PMID:29731765

National and International Security Applications of Cryogenic Detectors—Mostly Nuclear Safeguards

NASA Astrophysics Data System (ADS)

Rabin, Michael W.

2009-12-01

As with science, so with security—in both arenas, the extraordinary sensitivity of cryogenic sensors enables high-confidence detection and high-precision measurement even of the faintest signals. Science applications are more mature, but several national and international security applications have been identified where cryogenic detectors have high potential payoff. International safeguards and nuclear forensics are areas needing new technology and methods to boost speed, sensitivity, precision and accuracy. Successfully applied, improved nuclear materials analysis will help constrain nuclear materials diversion pathways and contribute to treaty verification. Cryogenic microcalorimeter detectors for X-ray, gamma-ray, neutron, and alpha-particle spectrometry are under development with these aims in mind. In each case the unsurpassed energy resolution of microcalorimeters reveals previously invisible spectral features of nuclear materials. Preliminary results of quantitative analysis indicate substantial improvements are still possible, but significant work will be required to fully understand the ultimate performance limits.

Using Adverse Outcome Pathways to Build Chemical Groups: A Case Study for Hepatic Steatosis

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework systematically documents the mechanisms underlying effects of chemicals. Ideally, the AOP traces the mechanism to the initial interaction of chemicals with the biological system. Thus, AOPs should help inform chemical grouping by identi...

Recent advances in reconstructing microbial secondary metabolites biosynthesis in Aspergillus spp.

PubMed

He, Yi; Wang, Bin; Chen, Wanping; Cox, Russell J; He, Jingren; Chen, Fusheng

High throughput genome sequencing has revealed a multitude of potential secondary metabolites biosynthetic pathways that remain cryptic. Pathway reconstruction coupled with genetic engineering via heterologous expression enables discovery of novel compounds, elucidation of biosynthetic pathways, and optimization of product yields. Apart from Escherichia coli and yeast, fungi, especially Aspergillus spp., are well known and efficient heterologous hosts. This review summarizes recent advances in heterologous expression of microbial secondary metabolite biosynthesis in Aspergillus spp. We also discuss the technological challenges and successes in regard to heterologous host selection and DNA assembly behind the reconstruction of microbial secondary metabolite biosynthesis. Copyright © 2018 Elsevier Inc. All rights reserved.

Established enteral nutrition pathway in a severe acute pancreatitis patient with duodenum fistula: a case report.

PubMed

Li, G; Shen, X; Ke, L; Tong, Z; Li, W

2015-10-01

Enteral feeding is the preferred way to provide nutritional support in patients with high nutritional risk but relatively normal gastrointestinal function; thus, establishing a safe and a reliable pathway of enteral nutrition (EN) is of great importance. There are many techniques for placing the feeding tube, such as blind placement at bedside, assisting by fluoroscopy and endoscopy, surgical and so on. Despite these variable techniques, it is still difficult to obtain the pathway for EN in some specific patients. Here, we present a recent case of infected pancreatic/peripancreatic necrosis complicated by a duodenal enteric fistula in whom we establish the feeding pathway extraordinarily. Briefly, after several failed attempts of placing the nasojejunal feeding tube, a jejunal feeding tube was placed percutaneously guided by computed tomography, and EN was successfully applied thereafter. With the implementation of EN, duodenal fistula healed without surgical intervention. As EN is pivotal for the recovery of duodenal fistula, this novel approach could be beneficial in selected patients.

The Lectin Pathway in Thrombotic Conditions-A Systematic Review.

PubMed

Larsen, Julie Brogaard; Hvas, Christine Lodberg; Hvas, Anne-Mette

2018-06-04

The lectin pathway of the complement system can activate the coagulation system in vitro, but the role of the lectin pathway in haemostatic activation and thrombosis in vivo is not clear. We performed a systematic review of the existing literature on associations between the lectin pathway and arterial and venous thrombosis, in accordance with the Assessing the Methodological Quality of Systematic Reviews guidelines. PubMed and Embase were searched from January 1990 to March 2017. We included original studies on human study populations investigating associations between the lectin pathway (protein serum levels, genotype or gene expression) and thrombotic conditions or laboratory coagulation markers. Exclusion criteria were case studies including fewer than five cases, conference abstracts or any other language than English. In total, 43 studies were included which investigated associations between the lectin pathway and cardiovascular thrombotic events (CVEs) ( n  = 22), ischaemic stroke ( n  = 9), CVE and stroke ( n  = 1) and other conditions (systemic lupus erythematosus [ n  = 6], sepsis-related coagulopathy [ n  = 3], pulmonary embolism [ n  = 1], asparaginase treatment [ n  = 1]). Studies on the lectin pathway and CVE risk reported discrepant results, as both high and low mannose-binding lectin (MBL) serum levels were found to correlate with increased CVE risk. In ischaemic stroke patients, occurrence of stroke as well as increased stroke severity and poor outcome were consistently associated with high serum MBL. For other thromboembolic conditions, only few studies were identified. In conclusion, lectin pathway activation may negatively influence outcome after ischaemic stroke and possibly contribute to CVE risk. Further research is warranted to elucidate the role of the lectin pathway in other thrombotic conditions. Schattauer GmbH Stuttgart.

Pathways to Medical Home Recognition: A Qualitative Comparative Analysis of the PCMH Transformation Process.

PubMed

Mendel, Peter; Chen, Emily K; Green, Harold D; Armstrong, Courtney; Timbie, Justin W; Kress, Amii M; Friedberg, Mark W; Kahn, Katherine L

2017-12-15

To understand the process of practice transformation by identifying pathways for attaining patient-centered medical home (PCMH) recognition. The CMS Federally Qualified Health Center (FQHC) Advanced Primary Care Practice Demonstration was designed to help FQHCs achieve NCQA Level 3 PCMH recognition and improve patient outcomes. We used a stratified random sample of 20 (out of 503) participating sites for this analysis. We developed a conceptual model of structural, cultural, and implementation factors affecting PCMH transformation based on literature and initial qualitative interview themes. We then used conventional cross-case analysis, followed by qualitative comparative analysis (QCA), a cross-case method based on Boolean logic algorithms, to systematically identify pathways (i.e., combinations of factors) associated with attaining-or not attaining-Level 3 recognition. Site-level indicators were derived from semistructured interviews with site leaders at two points in time (mid- and late-implementation) and administrative data collected prior to and during the demonstration period. The QCA results identified five distinct pathways to attaining PCMH recognition and four distinct pathways to not attaining recognition by the end of the demonstration. Across these pathways, one condition (change leader capacity) was common to all pathways for attaining recognition, and another (previous improvement or recognition experience) was absent in all pathways for not attaining recognition. In general, sites could compensate for deficiencies in one factor with capacity in others, but they needed a threshold of strengths in cultural and implementation factors to attain PCMH recognition. Future efforts at primary care transformation should take into account multiple pathways sites may pursue. Sites should be assessed on key cultural and implementation factors, in addition to structural components, in order to differentiate interventions and technical assistance. © Health Research and Educational Trust.

Axonal guidance signaling pathway interacting with smoking in modifying the risk of pancreatic cancer: a gene- and pathway-based interaction analysis of GWAS data.

PubMed

Tang, Hongwei; Wei, Peng; Duell, Eric J; Risch, Harvey A; Olson, Sara H; Bueno-de-Mesquita, H Bas; Gallinger, Steven; Holly, Elizabeth A; Petersen, Gloria; Bracci, Paige M; McWilliams, Robert R; Jenab, Mazda; Riboli, Elio; Tjønneland, Anne; Boutron-Ruault, Marie Christine; Kaaks, Rudolph; Trichopoulos, Dimitrios; Panico, Salvatore; Sund, Malin; Peeters, Petra H M; Khaw, Kay-Tee; Amos, Christopher I; Li, Donghui

2014-05-01

Cigarette smoking is the best established modifiable risk factor for pancreatic cancer. Genetic factors that underlie smoking-related pancreatic cancer have previously not been examined at the genome-wide level. Taking advantage of the existing Genome-wide association study (GWAS) genotype and risk factor data from the Pancreatic Cancer Case Control Consortium, we conducted a discovery study in 2028 cases and 2109 controls to examine gene-smoking interactions at pathway/gene/single nucleotide polymorphism (SNP) level. Using the likelihood ratio test nested in logistic regression models and ingenuity pathway analysis (IPA), we examined 172 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, 3 manually curated gene sets, 3 nicotine dependency gene ontology pathways, 17 912 genes and 468 114 SNPs. None of the individual pathway/gene/SNP showed significant interaction with smoking after adjusting for multiple comparisons. Six KEGG pathways showed nominal interactions (P < 0.05) with smoking, and the top two are the pancreatic secretion and salivary secretion pathways (major contributing genes: RAB8A, PLCB and CTRB1). Nine genes, i.e. ZBED2, EXO1, PSG2, SLC36A1, CLSTN1, MTHFSD, FAT2, IL10RB and ATXN2 had P interaction < 0.0005. Five intergenic region SNPs and two SNPs of the EVC and KCNIP4 genes had P interaction < 0.00003. In IPA analysis of genes with nominal interactions with smoking, axonal guidance signaling $$\\left(P=2.12\\times 1{0}^{-7}\\right)$$ and α-adrenergic signaling $$\\left(P=2.52\\times 1{0}^{-5}\\right)$$ genes were significantly overrepresented canonical pathways. Genes contributing to the axon guidance signaling pathway included the SLIT/ROBO signaling genes that were frequently altered in pancreatic cancer. These observations need to be confirmed in additional data set. Once confirmed, it will open a new avenue to unveiling the etiology of smoking-associated pancreatic cancer.

A Powerful Procedure for Pathway-Based Meta-analysis Using Summary Statistics Identifies 43 Pathways Associated with Type II Diabetes in European Populations.

PubMed

Zhang, Han; Wheeler, William; Hyland, Paula L; Yang, Yifan; Shi, Jianxin; Chatterjee, Nilanjan; Yu, Kai

2016-06-01

Meta-analysis of multiple genome-wide association studies (GWAS) has become an effective approach for detecting single nucleotide polymorphism (SNP) associations with complex traits. However, it is difficult to integrate the readily accessible SNP-level summary statistics from a meta-analysis into more powerful multi-marker testing procedures, which generally require individual-level genetic data. We developed a general procedure called Summary based Adaptive Rank Truncated Product (sARTP) for conducting gene and pathway meta-analysis that uses only SNP-level summary statistics in combination with genotype correlation estimated from a panel of individual-level genetic data. We demonstrated the validity and power advantage of sARTP through empirical and simulated data. We conducted a comprehensive pathway-based meta-analysis with sARTP on type 2 diabetes (T2D) by integrating SNP-level summary statistics from two large studies consisting of 19,809 T2D cases and 111,181 controls with European ancestry. Among 4,713 candidate pathways from which genes in neighborhoods of 170 GWAS established T2D loci were excluded, we detected 43 T2D globally significant pathways (with Bonferroni corrected p-values < 0.05), which included the insulin signaling pathway and T2D pathway defined by KEGG, as well as the pathways defined according to specific gene expression patterns on pancreatic adenocarcinoma, hepatocellular carcinoma, and bladder carcinoma. Using summary data from 8 eastern Asian T2D GWAS with 6,952 cases and 11,865 controls, we showed 7 out of the 43 pathways identified in European populations remained to be significant in eastern Asians at the false discovery rate of 0.1. We created an R package and a web-based tool for sARTP with the capability to analyze pathways with thousands of genes and tens of thousands of SNPs.

A Powerful Procedure for Pathway-Based Meta-analysis Using Summary Statistics Identifies 43 Pathways Associated with Type II Diabetes in European Populations

PubMed Central

Zhang, Han; Wheeler, William; Hyland, Paula L.; Yang, Yifan; Shi, Jianxin; Chatterjee, Nilanjan; Yu, Kai

2016-01-01

Meta-analysis of multiple genome-wide association studies (GWAS) has become an effective approach for detecting single nucleotide polymorphism (SNP) associations with complex traits. However, it is difficult to integrate the readily accessible SNP-level summary statistics from a meta-analysis into more powerful multi-marker testing procedures, which generally require individual-level genetic data. We developed a general procedure called Summary based Adaptive Rank Truncated Product (sARTP) for conducting gene and pathway meta-analysis that uses only SNP-level summary statistics in combination with genotype correlation estimated from a panel of individual-level genetic data. We demonstrated the validity and power advantage of sARTP through empirical and simulated data. We conducted a comprehensive pathway-based meta-analysis with sARTP on type 2 diabetes (T2D) by integrating SNP-level summary statistics from two large studies consisting of 19,809 T2D cases and 111,181 controls with European ancestry. Among 4,713 candidate pathways from which genes in neighborhoods of 170 GWAS established T2D loci were excluded, we detected 43 T2D globally significant pathways (with Bonferroni corrected p-values < 0.05), which included the insulin signaling pathway and T2D pathway defined by KEGG, as well as the pathways defined according to specific gene expression patterns on pancreatic adenocarcinoma, hepatocellular carcinoma, and bladder carcinoma. Using summary data from 8 eastern Asian T2D GWAS with 6,952 cases and 11,865 controls, we showed 7 out of the 43 pathways identified in European populations remained to be significant in eastern Asians at the false discovery rate of 0.1. We created an R package and a web-based tool for sARTP with the capability to analyze pathways with thousands of genes and tens of thousands of SNPs. PMID:27362418

40 CFR 63.55 - Maximum achievable control technology (MACT) determinations for affected sources subject to case...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 10 2013-07-01 2013-07-01 false Maximum achievable control technology (MACT) determinations for affected sources subject to case-by-case determination of equivalent emission... Requirements for Control Technology Determinations for Major Sources in Accordance With Clean Air Act Sections...

40 CFR 63.55 - Maximum achievable control technology (MACT) determinations for affected sources subject to case...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 10 2012-07-01 2012-07-01 false Maximum achievable control technology (MACT) determinations for affected sources subject to case-by-case determination of equivalent emission... Requirements for Control Technology Determinations for Major Sources in Accordance With Clean Air Act Sections...

40 CFR 63.55 - Maximum achievable control technology (MACT) determinations for affected sources subject to case...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 9 2011-07-01 2011-07-01 false Maximum achievable control technology (MACT) determinations for affected sources subject to case-by-case determination of equivalent emission... Requirements for Control Technology Determinations for Major Sources in Accordance With Clean Air Act Sections...

40 CFR 63.55 - Maximum achievable control technology (MACT) determinations for affected sources subject to case...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 10 2014-07-01 2014-07-01 false Maximum achievable control technology (MACT) determinations for affected sources subject to case-by-case determination of equivalent emission... Requirements for Control Technology Determinations for Major Sources in Accordance With Clean Air Act Sections...

Frequent germline deleterious mutations in DNA repair genes in familial prostate cancer cases are associated with advanced disease.

PubMed

Leongamornlert, D; Saunders, E; Dadaev, T; Tymrakiewicz, M; Goh, C; Jugurnauth-Little, S; Kozarewa, I; Fenwick, K; Assiotis, I; Barrowdale, D; Govindasami, K; Guy, M; Sawyer, E; Wilkinson, R; Antoniou, A C; Eeles, R; Kote-Jarai, Z

2014-03-18

Prostate cancer (PrCa) is one of the most common diseases to affect men worldwide and among the leading causes of cancer-related death. The purpose of this study was to use second-generation sequencing technology to assess the frequency of deleterious mutations in 22 tumour suppressor genes in familial PrCa and estimate the relative risk of PrCa if these genes are mutated. Germline DNA samples from 191 men with 3 or more cases of PrCa in their family were sequenced for 22 tumour suppressor genes using Agilent target enrichment and Illumina technology. Analysis for genetic variation was carried out by using a pipeline consisting of BWA, Genome Analysis Toolkit (GATK) and ANNOVAR. Clinical features were correlated with mutation status using standard statistical tests. Modified segregation analysis was used to determine the relative risk of PrCa conferred by the putative loss-of-function (LoF) mutations identified. We discovered 14 putative LoF mutations in 191 samples (7.3%) and these mutations were more frequently associated with nodal involvement, metastasis or T4 tumour stage (P=0.00164). Segregation analysis of probands with European ancestry estimated that LoF mutations in any of the studied genes confer a relative risk of PrCa of 1.94 (95% CI: 1.56-2.42). These findings show that LoF mutations in DNA repair pathway genes predispose to familial PrCa and advanced disease and therefore warrants further investigation. The clinical utility of these findings will become increasingly important as targeted screening and therapies become more widespread.

Unraveling human complexity and disease with systems biology and personalized medicine

PubMed Central

Naylor, Stephen; Chen, Jake Y

2010-01-01

We are all perplexed that current medical practice often appears maladroit in curing our individual illnesses or disease. However, as is often the case, a lack of understanding, tools and technologies are the root cause of such situations. Human individuality is an often-quoted term but, in the context of human biology, it is poorly understood. This is compounded when there is a need to consider the variability of human populations. In the case of the former, it is possible to quantify human complexity as determined by the 35,000 genes of the human genome, the 1–10 million proteins (including antibodies) and the 2000–3000 metabolites of the human metabolome. Human variability is much more difficult to assess, since many of the variables, such as the definition of race, are not even clearly agreed on. In order to accommodate human complexity, variability and its influence on health and disease, it is necessary to undertake a systematic approach. In the past decade, the emergence of analytical platforms and bioinformatics tools has led to the development of systems biology. Such an approach offers enormous potential in defining key pathways and networks involved in optimal human health, as well as disease onset, progression and treatment. The tools and technologies now available in systems biology analyses offer exciting opportunities to exploit the emerging areas of personalized medicine. In this article, we discuss the current status of human complexity, and how systems biology and personalized medicine can impact at the individual and population level. PMID:20577569

Drug reformulations and repositioning in the pharmaceutical industry and their impact on market access: regulatory implications

PubMed Central

Murteira, Susana; Millier, Aurélie; Ghezaiel, Zied; Lamure, Michel

2014-01-01

Background Repurposing has become a mainstream strategy in drug development, but it faces multiple challenges, amongst them the increasing and ever changing regulatory framework. This is the second study of a series of three-part publication project with the ultimate goal of understanding the market access rationale and conditions attributed to drug repurposing in the United States and in Europe. The aim of the current study to evaluate the regulatory path associated with each type of repurposing strategy according to the previously proposed nomenclature in the first article of this series. Methods From the cases identified, a selection process retrieved a total of 141 case studies in all countries, harmonized for data availability and common approval in the United States and in Europe. Regulatory information for each original and repurposed drug product was extracted, and several related regulatory attributes were also extracted such as, designation change and filing before or after patent expiry, among others. Descriptive analyses were conducted to determine trends and to investigate potential associations between the different regulatory paths and attributes of interest, for reformulation and repositioning cases separately. Results Within the studied European countries, most of the applications for reformulated products were filed through national applications. In contrast, for repositioned products, the centralized procedure was the most frequent regulatory pathway. Most of the repurposing cases were approved before patent expiry, and those cases have followed more complex regulatory pathways in the United States and in Europe. For new molecular entities filed in the United States, a similar number of cases were developed by serendipity and by a hypothesis-driven approach. However, for the new indication's regulatory pathway in the United States, most of the cases were developed through a hypothesis-driven approach. Conclusion The regulations in the United States and in Europe for drug repositionings and reformulations allowed confirming that repositioning strategies were usually filed under a more complex regulatory process than reformulations. Also, it seems that parameters such as patent expiry and type of repositioning approach or reformulation affect the regulatory pathways chosen for each case. PMID:27226839

Modeling biochemical pathways in the gene ontology

DOE PAGES

Hill, David P.; D’Eustachio, Peter; Berardini, Tanya Z.; ...

2016-09-01

The concept of a biological pathway, an ordered sequence of molecular transformations, is used to collect and represent molecular knowledge for a broad span of organismal biology. Representations of biomedical pathways typically are rich but idiosyncratic presentations of organized knowledge about individual pathways. Meanwhile, biomedical ontologies and associated annotation files are powerful tools that organize molecular information in a logically rigorous form to support computational analysis. The Gene Ontology (GO), representing Molecular Functions, Biological Processes and Cellular Components, incorporates many aspects of biological pathways within its ontological representations. Here we present a methodology for extending and refining the classes inmore » the GO for more comprehensive, consistent and integrated representation of pathways, leveraging knowledge embedded in current pathway representations such as those in the Reactome Knowledgebase and MetaCyc. With carbohydrate metabolic pathways as a use case, we discuss how our representation supports the integration of variant pathway classes into a unified ontological structure that can be used for data comparison and analysis.« less

More than blindsight: Case report of a child with extraordinary visual capacity following perinatal bilateral occipital lobe injury.

PubMed

Mundinano, Inaki-Carril; Chen, Juan; de Souza, Mitchell; Sarossy, Marc G; Joanisse, Marc F; Goodale, Melvyn A; Bourne, James A

2017-11-13

Injury to the primary visual cortex (V1, striate cortex) and the geniculostriate pathway in adults results in cortical blindness, abolishing conscious visual perception. Early studies by Larry Weiskrantz and colleagues demonstrated that some patients with an occipital-lobe injury exhibited a degree of unconscious vision and visually-guided behaviour within the blind field. A more recent focus has been the observed phenomenon whereby early-life injury to V1 often results in the preservation of visual perception in both monkeys and humans. These findings initiated a concerted effort on multiple fronts, including nonhuman primate studies, to uncover the neural substrate/s of the spared conscious vision. In both adult and early-life cases of V1 injury, evidence suggests the involvement of the Middle Temporal area (MT) of the extrastriate visual cortex, which is an integral component area of the dorsal stream and is also associated with visually-guided behaviors. Because of the limited number of early-life V1 injury cases for humans, the outstanding question in the field is what secondary visual pathways are responsible for this extraordinary capacity? Here we report for the first time a case of a child (B.I.) who suffered a bilateral occipital-lobe injury in the first two weeks postnatally due to medium-chain acyl-Co-A dehydrogenase deficiency. At 6 years of age, B.I. underwent a battery of neurophysiological tests, as well as structural and diffusion MRI and ophthalmic examination at 7 years. Despite the extensive bilateral occipital cortical damage, B.I. has extensive conscious visual abilities, is not blind, and can use vision to navigate his environment. Furthermore, unlike blindsight patients, he can readily and consciously identify happy and neutral faces and colors, tasks associated with ventral stream processing. These findings suggest significant re-routing of visual information. To identify the putative visual pathway/s responsible for this ability, MRI tractography of secondary visual pathways connecting MT with the lateral geniculate nucleus (LGN) and the inferior pulvinar (PI) were analysed. Results revealed an increased PI-MT pathway in the left hemisphere, suggesting that this pulvinar relay could be the neural pathway affording the preserved visual capacity following an early-life lesion of V1. These findings corroborate anatomical evidence from monkeys showing an enhanced PI-MT pathway following an early-life lesion of V1, compared to adults. Copyright © 2017 Elsevier Ltd. All rights reserved.

Benefits of Integration of Aerojet Rocketdyne and RTI Advanced Gasification Technologies for Hydrogen-Rich Syngas Production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, Vijay; Denton, David; SHarma, Pradeep

The key objective for this project was to evaluate the potential to achieve substantial reductions in the production cost of H 2-rich syngas via coal gasification with near-zero emissions due to the cumulative and synergistic benefits realized when multiple advanced technologies are integrated into the overall conversion process. In this project, Aerojet Rocketdyne’s (AR’s) advanced gasification technology (currently being offered as R-GAS™) and RTI International’s (RTI’s) advanced warm syngas cleanup technologies were evaluated via a number of comparative techno-economic case studies. AR’s advanced gasification technology consists of a dry solids pump and a compact gasifier system. Based on the uniquemore » design of this gasifier, it has been shown to reduce the capital cost of the gasification block by between 40 and 50%. At the start of this project, actual experimental work had been demonstrated through pilot plant systems for both the gasifier and dry solids pump. RTI’s advanced warm syngas cleanup technologies consist primarily of RTI’s Warm Gas Desulfurization Process (WDP) technology, which effectively allows decoupling of the sulfur and CO 2 removal allowing for more flexibility in the selection of the CO 2 removal technology, plus associated advanced technologies for direct sulfur recovery and water gas shift (WGS). WDP has been demonstrated at pre-commercial scale using an activated amine carbon dioxide recovery process which would not have been possible if a majority of the sulfur had not been removed from the syngas by WDP. This pre-commercial demonstration of RTI’s advanced warm syngas cleanup system was conducted in parallel to the activities on this project. The technical data and cost information from this pre-commercial demonstration were extensively used in this project during the techno-economic analysis. With this project, both of RTI’s advanced WGS technologies were investigated. Because RT’s advanced fixed-bed WGS (AFWGS) process was successfully implemented in the WDP pre-commercial demonstration test mentioned above, this technology was used as part of RTI’s advanced warm syngas technology package for the techno-economic analyses for this project. RTI’s advanced transport-reactor-based WGS (ATWGS) process was still conceptual at the start of this project, but one of the tasks for this project was to evaluate the technical feasibility of this technology. In each of the three application-based comparison studies conducted as part of this project, the reference case was based on an existing Department of Energy National Energy Technology Laboratory (DOE/NETL) system study. Each of these references cases used existing commercial technology and the system resulted in > 90% carbon capture. In the comparison studies for the use of the hydrogen-rich syngas generated in either an Integrated Gasification Combined Cycle (IGCC) or a Coal-to-Methanol (CTM) plant, the comparison cases consisted of the reference case, a case with the integration of each individual advanced technology (either AR or RTI), and finally a case with the integration of all the advanced technologies (AR and RTI combined). In the Coal-to-Liquids (CTL) comparison study, the comparison study consisted of only three cases, which included a reference case, a case with just RTI’s advanced syngas cleaning technology, and a case with AR’s and RTI’s advanced technologies. The results from these comparison studies showed that the integration of the advanced technologies did result in substantial benefits, and by far the greatest benefits were achieved for cases integrating all the advanced technologies. For the IGCC study, the fully integrated case resulted in a 1.4% net efficiency improvement, an 18% reduction in capital cost per kW of capacity, a 12% reduction in the operating cost per kWh, and a 75–79% reduction in sulfur emissions. For the CTM case, the fully integrated plant resulted in a 22% reduction in capital cost, a 13% reduction in operating costs, a > 99% net reduction in sulfur emissions, and a reduction of 13–15% in CO 2 emissions. Because the capital cost represents over 60% of the methanol Required Selling Price (RSP), the significant reduction in the capital cost for the advanced technology case resulted in an 18% reduction in methanol RSP. For the CTL case, the fully integrated plant resulted in a 16% reduction in capital cost, which represented a 13% reduction in diesel RSP. Finally, the technical feasibility analysis of RTI’s ATWGS process demonstrated that a fluid-bed catalyst with sufficient attrition resistance and WGS activity could be made and that the process achieved about a 24% reduction in capital cost compared to a conventional fixed-bed commercial process.« less

Innovative technologies and social inequalities in health: A scoping review of the literature

PubMed Central

Jensen, Magnus Rom; Solhaug, Solvor; Krokstad, Steinar

2018-01-01

The aim of this study was to systematically review the range, nature, and extent of current research activity exploring the influence of innovative health-related technologies on social inequalities in health, with specific focus on a deeper understanding of the variables used to measure this connection and the pathways leading to the (re)production of inequalities. A review process was conducted, based on scoping review techniques, searching literature published from January 1, 1996 to November 25, 2016 using MEDLINE, Scopus, and ISI web of science. Search, sorting, and data extraction processes were conducted by a team of researchers and experts using a dynamic, reflexive examination process. Of 4139 studies collected from the search process, a total of 33 were included in the final analysis. Results of this study include the classification of technologies based on how these technologies are accessed and used by end users. In addition to the factors and mechanisms that influence unequal access to technologies, the results of this study highlight the importance of variations in use that importantly shape social inequalities in health. Additionally, focus on health care services technologies must be accompanied by investigating emerging technologies influencing healthy lifestyle, genomics, and personalized devices in health. Findings also suggest that choosing one measure of social position over another has important implications for the interpretation of research results. Furthermore, understanding the pathways through which various innovative health technologies reduce or (re)produce social inequalities in health is context dependent. In order to better understand social inequalities in health, these contextual variations draw attention to the need for critical distinctions between technologies based on how these various technologies are accessed and used. The results of this study provide a comprehensive starting point for future research to further investigate how innovative technologies may influence the unequal distribution of health as a human right. PMID:29614114

Innovative technologies and social inequalities in health: A scoping review of the literature.

PubMed

Weiss, Daniel; Rydland, Håvard T; Øversveen, Emil; Jensen, Magnus Rom; Solhaug, Solvor; Krokstad, Steinar

2018-01-01

The aim of this study was to systematically review the range, nature, and extent of current research activity exploring the influence of innovative health-related technologies on social inequalities in health, with specific focus on a deeper understanding of the variables used to measure this connection and the pathways leading to the (re)production of inequalities. A review process was conducted, based on scoping review techniques, searching literature published from January 1, 1996 to November 25, 2016 using MEDLINE, Scopus, and ISI web of science. Search, sorting, and data extraction processes were conducted by a team of researchers and experts using a dynamic, reflexive examination process. Of 4139 studies collected from the search process, a total of 33 were included in the final analysis. Results of this study include the classification of technologies based on how these technologies are accessed and used by end users. In addition to the factors and mechanisms that influence unequal access to technologies, the results of this study highlight the importance of variations in use that importantly shape social inequalities in health. Additionally, focus on health care services technologies must be accompanied by investigating emerging technologies influencing healthy lifestyle, genomics, and personalized devices in health. Findings also suggest that choosing one measure of social position over another has important implications for the interpretation of research results. Furthermore, understanding the pathways through which various innovative health technologies reduce or (re)produce social inequalities in health is context dependent. In order to better understand social inequalities in health, these contextual variations draw attention to the need for critical distinctions between technologies based on how these various technologies are accessed and used. The results of this study provide a comprehensive starting point for future research to further investigate how innovative technologies may influence the unequal distribution of health as a human right.

Reconciling ethical and economic conceptions of value in health policy using the capabilities approach: A qualitative investigation of Non-Invasive Prenatal Testing.

PubMed

Kibel, Mia; Vanstone, Meredith

2017-12-01

When evaluating new morally complex health technologies, policy decision-makers consider a broad range of different evaluations, which may include the technology's clinical effectiveness, cost effectiveness, and social or ethical implications. This type of holistic assessment is challenging, because each of these evaluations may be grounded in different and potentially contradictory assumptions about the technology's value. One such technology where evaluations conflict is Non-Invasive Prenatal Testing (NIPT). Cost-effectiveness evaluations of NIPT often assess NIPT's ability to deliver on goals (i.e preventing the birth of children with disabilities) that social and ethical analyses suggest it should not have. Thus, cost effectiveness analyses frequently contradict social and ethical assessments of NIPT's value. We use the case of NIPT to explore how economic evaluations using a capabilities approach may be able to capture a broader, more ethical view of the value of NIPT. The capabilities approach is an evaluative framework which bases wellbeing assessments on a person's abilities, rather than their expressed preferences. It is linked to extra-welfarist approaches in health economic assessment. Beginning with Nussbaum's capability framework, we conducted a directed qualitative content analysis of interview data collected in 2014 from 27 Canadian women with personal experience of NIPT. We found that eight of Nussbaum's ten capabilities related to options, states, or choices that women valued in the context of NIPT, and identified one new capability. Our findings suggest that women value NIPT for its ability to provide more and different choices in the prenatal care pathway, and that a capabilities approach can indeed capture the value of NIPT in a way that goes beyond measuring health outcomes of ambiguous social and ethical value. More broadly, the capabilities approach may serve to resolve contradictions between ethical and economic evaluations of health technologies, and contribute to extra-welfarist approaches in the assessment of morally complex health technologies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Brief Guide to Genomics: DNA, Genes and Genomes

MedlinePlus

... Sheets A Brief Guide to Genomics About NHGRI Research About the International HapMap Project Biological Pathways Chromosome Abnormalities Chromosomes Cloning Comparative Genomics DNA Microarray Technology DNA Sequencing Deoxyribonucleic Acid ( ...

Genome-wide genetic analyses highlight mitogen-activated protein kinase (MAPK) signaling in the pathogenesis of endometriosis.

PubMed

Uimari, Outi; Rahmioglu, Nilufer; Nyholt, Dale R; Vincent, Katy; Missmer, Stacey A; Becker, Christian; Morris, Andrew P; Montgomery, Grant W; Zondervan, Krina T

2017-04-01

Do genome-wide association study (GWAS) data for endometriosis provide insight into novel biological pathways associated with its pathogenesis? GWAS analysis uncovered multiple pathways that are statistically enriched for genetic association signals, analysis of Stage A disease highlighted a novel variant in MAP3K4, while top pathways significantly associated with all endometriosis and Stage A disease included several mitogen-activated protein kinase (MAPK)-related pathways. Endometriosis is a complex disease with an estimated heritability of 50%. To date, GWAS revealed 10 genomic regions associated with endometriosis, explaining <4% of heritability, while half of the heritability is estimated to be due to common risk variants. Pathway analyses combine the evidence of single variants into gene-based measures, leveraging the aggregate effect of variants in genes and uncovering biological pathways involved in disease pathogenesis. Pathway analysis was conducted utilizing the International Endogene Consortium GWAS data, comprising 3194 surgically confirmed endometriosis cases and 7060 controls of European ancestry with genotype data imputed up to 1000 Genomes Phase three reference panel. GWAS was performed for all endometriosis cases and for Stage A (revised American Fertility Society (rAFS) I/II, n = 1686) and B (rAFS III/IV, n = 1364) cases separately. The identified significant pathways were compared with pathways previously investigated in the literature through candidate association studies. The most comprehensive biological pathway databases, MSigDB (including BioCarta, KEGG, PID, SA, SIG, ST and GO) and PANTHER were utilized to test for enrichment of genetic variants associated with endometriosis. Statistical enrichment analysis was performed using the MAGENTA (Meta-Analysis Gene-set Enrichment of variaNT Associations) software. The first genome-wide association analysis for Stage A endometriosis revealed a novel locus, rs144240142 (P = 6.45 × 10-8, OR = 1.71, 95% CI = 1.23-2.37), an intronic single-nucleotide polymorphism (SNP) within MAP3K4. This SNP was not associated with Stage B disease (P = 0.086). MAP3K4 was also shown to be differentially expressed in eutopic endometrium between Stage A endometriosis cases and controls (P = 3.8 × 10-4), but not with Stage B disease (P = 0.26). A total of 14 pathways enriched with genetic endometriosis associations were identified (false discovery rate (FDR)-P < 0.05). The pathways associated with any endometriosis were Grb2-Sos provides linkage to MAPK signaling for integrins pathway (P = 2.8 × 10-5, FDR-P = 3.0 × 10-3), Wnt signaling (P = 0.026, FDR-P = 0.026) and p130Cas linkage to MAPK signaling for integrins pathway (P = 6.0 × 10-4, FDR-P = 0.029); with Stage A endometriosis: extracellular signal-regulated kinase (ERK)1 ERK2 MAPK (P = 5.0 × 10-4, FDR-P = 5.0 × 10-4) and with Stage B endometriosis: two overlapping pathways that related to extracellular matrix biology-Core matrisome (P = 1.4 × 10-3, FDR-P = 0.013) and ECM glycoproteins (P = 1.8 × 10-3, FDR-P = 7.1 × 10-3). Genes arising from endometriosis candidate gene studies performed to date were enriched for Interleukin signaling pathway (P = 2.3 × 10-12), Apoptosis signaling pathway (P = 9.7 × 10-9) and Gonadotropin releasing hormone receptor pathway (P = 1.2 × 10-6); however, these pathways did not feature in the results based on GWAS data. Not applicable. The analysis is restricted to (i) variants in/near genes that can be assigned to pathways, excluding intergenic variants; (ii) the gene-based pathway definition as registered in the databases; (iii) women of European ancestry. The top ranked pathways associated with overall and Stage A endometriosis in particular involve integrin-mediated MAPK activation and intracellular ERK/MAPK acting downstream in the MAPK cascade, both acting in the control of cell division, gene expression, cell movement and survival. Other top enriched pathways in Stage B disease include ECM glycoprotein pathways important for extracellular structure and biochemical support. The results highlight the need for increased efforts to understand the functional role of these pathways in endometriosis pathogenesis, including the investigation of the biological effects of the genetic variants on downstream molecular processes in tissue relevant to endometriosis. Additionally, our results offer further support for the hypothesis of at least partially distinct causal pathophysiology for minimal/mild (rAFS I/II) vs. moderate/severe (rAFS III/IV) endometriosis. The genome-wide association data and Wellcome Trust Case Control Consortium (WTCCC) were generated through funding from the Wellcome Trust (WT084766/Z/08/Z, 076113 and 085475) and the National Health and Medical Research Council (NHMRC) of Australia (241944, 339462, 389927, 389875, 389891, 389892, 389938, 443036, 442915, 442981, 496610, 496739, 552485 and 552498). N.R. was funded by a grant from the Medical Research Council UK (MR/K011480/1). A.P.M. is a Wellcome Trust Senior Fellow in Basic Biomedical Science (grant WT098017). All authors declare there are no conflicts of interest. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

Genome-wide genetic analyses highlight mitogen-activated protein kinase (MAPK) signaling in the pathogenesis of endometriosis

PubMed Central

Uimari, Outi; Rahmioglu, Nilufer; Nyholt, Dale R.; Vincent, Katy; Missmer, Stacey A.; Becker, Christian; Morris, Andrew P.; Montgomery, Grant W.

2017-01-01

Abstract STUDY QUESTION Do genome-wide association study (GWAS) data for endometriosis provide insight into novel biological pathways associated with its pathogenesis? SUMMARY ANSWER GWAS analysis uncovered multiple pathways that are statistically enriched for genetic association signals, analysis of Stage A disease highlighted a novel variant in MAP3K4, while top pathways significantly associated with all endometriosis and Stage A disease included several mitogen-activated protein kinase (MAPK)-related pathways. WHAT IS KNOWN ALREADY Endometriosis is a complex disease with an estimated heritability of 50%. To date, GWAS revealed 10 genomic regions associated with endometriosis, explaining <4% of heritability, while half of the heritability is estimated to be due to common risk variants. Pathway analyses combine the evidence of single variants into gene-based measures, leveraging the aggregate effect of variants in genes and uncovering biological pathways involved in disease pathogenesis. STUDY DESIGN, SIZE, DURATION Pathway analysis was conducted utilizing the International Endogene Consortium GWAS data, comprising 3194 surgically confirmed endometriosis cases and 7060 controls of European ancestry with genotype data imputed up to 1000 Genomes Phase three reference panel. GWAS was performed for all endometriosis cases and for Stage A (revised American Fertility Society (rAFS) I/II, n = 1686) and B (rAFS III/IV, n = 1364) cases separately. The identified significant pathways were compared with pathways previously investigated in the literature through candidate association studies. PARTICIPANTS/MATERIALS, SETTING, METHODS The most comprehensive biological pathway databases, MSigDB (including BioCarta, KEGG, PID, SA, SIG, ST and GO) and PANTHER were utilized to test for enrichment of genetic variants associated with endometriosis. Statistical enrichment analysis was performed using the MAGENTA (Meta-Analysis Gene-set Enrichment of variaNT Associations) software. MAIN RESULTS AND THE ROLE OF CHANCE The first genome-wide association analysis for Stage A endometriosis revealed a novel locus, rs144240142 (P = 6.45 × 10−8, OR = 1.71, 95% CI = 1.23–2.37), an intronic single-nucleotide polymorphism (SNP) within MAP3K4. This SNP was not associated with Stage B disease (P = 0.086). MAP3K4 was also shown to be differentially expressed in eutopic endometrium between Stage A endometriosis cases and controls (P = 3.8 × 10−4), but not with Stage B disease (P = 0.26). A total of 14 pathways enriched with genetic endometriosis associations were identified (false discovery rate (FDR)-P < 0.05). The pathways associated with any endometriosis were Grb2-Sos provides linkage to MAPK signaling for integrins pathway (P = 2.8 × 10−5, FDR-P = 3.0 × 10−3), Wnt signaling (P = 0.026, FDR-P = 0.026) and p130Cas linkage to MAPK signaling for integrins pathway (P = 6.0 × 10−4, FDR-P = 0.029); with Stage A endometriosis: extracellular signal-regulated kinase (ERK)1 ERK2 MAPK (P = 5.0 × 10−4, FDR-P = 5.0 × 10−4) and with Stage B endometriosis: two overlapping pathways that related to extracellular matrix biology—Core matrisome (P = 1.4 × 10−3, FDR-P = 0.013) and ECM glycoproteins (P = 1.8 × 10−3, FDR-P = 7.1 × 10−3). Genes arising from endometriosis candidate gene studies performed to date were enriched for Interleukin signaling pathway (P = 2.3 × 10−12), Apoptosis signaling pathway (P = 9.7 × 10−9) and Gonadotropin releasing hormone receptor pathway (P = 1.2 × 10−6); however, these pathways did not feature in the results based on GWAS data. LARGE SCALE DATA Not applicable. LIMITATIONS, REASONS FOR CAUTION The analysis is restricted to (i) variants in/near genes that can be assigned to pathways, excluding intergenic variants; (ii) the gene-based pathway definition as registered in the databases; (iii) women of European ancestry. WIDER IMPLICATIONS OF THE FINDINGS The top ranked pathways associated with overall and Stage A endometriosis in particular involve integrin-mediated MAPK activation and intracellular ERK/MAPK acting downstream in the MAPK cascade, both acting in the control of cell division, gene expression, cell movement and survival. Other top enriched pathways in Stage B disease include ECM glycoprotein pathways important for extracellular structure and biochemical support. The results highlight the need for increased efforts to understand the functional role of these pathways in endometriosis pathogenesis, including the investigation of the biological effects of the genetic variants on downstream molecular processes in tissue relevant to endometriosis. Additionally, our results offer further support for the hypothesis of at least partially distinct causal pathophysiology for minimal/mild (rAFS I/II) vs. moderate/severe (rAFS III/IV) endometriosis. STUDY FUNDING/COMPETING INTEREST(S) The genome-wide association data and Wellcome Trust Case Control Consortium (WTCCC) were generated through funding from the Wellcome Trust (WT084766/Z/08/Z, 076113 and 085475) and the National Health and Medical Research Council (NHMRC) of Australia (241944, 339462, 389927, 389875, 389891, 389892, 389938, 443036, 442915, 442981, 496610, 496739, 552485 and 552498). N.R. was funded by a grant from the Medical Research Council UK (MR/K011480/1). A.P.M. is a Wellcome Trust Senior Fellow in Basic Biomedical Science (grant WT098017). All authors declare there are no conflicts of interest. PMID:28333195

Environmental Technology Verification (ETV) Program Case Studies: Demonstrating Program Outcomes, Volume III

EPA Science Inventory

This booklet, ETV Program Case Studies: Demonstrating Program Outcomes, Volume III contains two case studies, addressing verified environmental technologies for decentalized wastewater treatment and converting animal waste to energy. Each case study contains a brief description ...

Enhancing Student Interactions with the Instructor and Content Using Pen-Based Technology, YouTube Videos, and Virtual Conferencing

ERIC Educational Resources Information Center

Cox, James R.

2011-01-01

This report describes the incorporation of digital learning elements in organic chemistry and biochemistry courses. The first example is the use of pen-based technology and a large-format PowerPoint slide to construct a map that integrates various metabolic pathways and control points. Students can use this map to visualize the integrated nature…

Teaching-as-Research Internships: A Model for the Development of Future Chemistry Faculty and the Improvement of Teaching in Science, Technology, Engineering, and Math

ERIC Educational Resources Information Center

Gillian-Daniel, Donald L.; Walz, Kenneth A.

2016-01-01

Over the past decade, the University of Wisconsin-Madison (UW-Madison) and Madison Area Technical College (Madison College) partnered to create an internship pathway for graduate students pursuing careers as future science, technology, engineering and math (STEM) faculty members. Since 2003, 10 doctoral students from the university completed…

Virtual surgical planning and 3D printing in prosthetic orbital reconstruction with percutaneous implants: a technical case report

PubMed Central

Huang, Yu-Hui; Seelaus, Rosemary; Zhao, Linping; Patel, Pravin K; Cohen, Mimis

2016-01-01

Osseointegrated titanium implants to the cranial skeleton for retention of facial prostheses have proven to be a reliable replacement for adhesive systems. However, improper placement of the implants can jeopardize prosthetic outcomes, and long-term success of an implant-retained prosthesis. Three-dimensional (3D) computer imaging, virtual planning, and 3D printing have become accepted components of the preoperative planning and design phase of treatment. Computer-aided design and computer-assisted manufacture that employ cone-beam computed tomography data offer benefits to patient treatment by contributing to greater predictability and improved treatment efficiencies with more reliable outcomes in surgical and prosthetic reconstruction. 3D printing enables transfer of the virtual surgical plan to the operating room by fabrication of surgical guides. Previous studies have shown that accuracy improves considerably with guided implantation when compared to conventional template or freehand implant placement. This clinical case report demonstrates the use of a 3D technological pathway for preoperative virtual planning through prosthesis fabrication, utilizing 3D printing, for a patient with an acquired orbital defect that was restored with an implant-retained silicone orbital prosthesis. PMID:27843356

Virtual surgical planning and 3D printing in prosthetic orbital reconstruction with percutaneous implants: a technical case report.

PubMed

Huang, Yu-Hui; Seelaus, Rosemary; Zhao, Linping; Patel, Pravin K; Cohen, Mimis

2016-01-01

Osseointegrated titanium implants to the cranial skeleton for retention of facial prostheses have proven to be a reliable replacement for adhesive systems. However, improper placement of the implants can jeopardize prosthetic outcomes, and long-term success of an implant-retained prosthesis. Three-dimensional (3D) computer imaging, virtual planning, and 3D printing have become accepted components of the preoperative planning and design phase of treatment. Computer-aided design and computer-assisted manufacture that employ cone-beam computed tomography data offer benefits to patient treatment by contributing to greater predictability and improved treatment efficiencies with more reliable outcomes in surgical and prosthetic reconstruction. 3D printing enables transfer of the virtual surgical plan to the operating room by fabrication of surgical guides. Previous studies have shown that accuracy improves considerably with guided implantation when compared to conventional template or freehand implant placement. This clinical case report demonstrates the use of a 3D technological pathway for preoperative virtual planning through prosthesis fabrication, utilizing 3D printing, for a patient with an acquired orbital defect that was restored with an implant-retained silicone orbital prosthesis.

Alteration of metabolite profiling by cold atmospheric plasma treatment in human myeloma cells.

PubMed

Xu, Dehui; Xu, Yujing; Ning, Ning; Cui, Qingjie; Liu, Zhijie; Wang, Xiaohua; Liu, Dingxin; Chen, Hailan; Kong, Michael G

2018-01-01

Despite new progress of chemotherapy in multiple myeloma (MM) clinical treatment, MM is still a refractory disease and new technology is needed to improve the outcomes and prolong the survival. Cold atmospheric plasma is a rapidly developed technology in recent years, which has been widely applied in biomedicine. Although plasma could efficiently inactivate various tumor cells, the effects of plasma on tumor cell metabolism have not been studied yet. In this study, we investigated the metabolite profiling of He plasma treatment on myeloma tumor cells by gas-chromatography time-of-flight (GC-TOF) mass-spectrometry. Meanwhile, by bioinformatic analysis such as GO and KEGG analysis we try to figure out the metabolism pathway that was significantly affected by gas plasma treatment. By GC-TOF mass-spectrometry, 573 signals were detected and evaluated using PCA and OPLS-DA. By KEGG analysis we listed all the differential metabolites and further classified into different metabolic pathways. The results showed that beta-alanine metabolism pathway was the most significant change after He gas plasma treatment in myeloma cells. Besides, propanoate metabolism and linoleic acid metabolism should also be concerned during gas plasma treatment of cancer cells. Cold atmospheric plasma treatment could significantly alter the metabolite profiling of myeloma tumor cells, among which, the beta-alanine metabolism pathway is the most susceptible to He gas plasma treatment.

RCP4.5: A Pathway for Stabilization of Radiative Forcing by 2100

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomson, Allison M.; Calvin, Katherine V.; Smith, Steven J.

2011-07-29

Representative Concentration Pathway (RCP) 4.5 is a scenario that stabilizes radiative forcing at 4.5 W m{sup -2} in the year 2100 without ever exceeding that value. Simulated with the Global Change Assessment Model (GCAM), RCP4.5 includes long-term, global emissions of greenhouse gases, short-lived species, and land-use-land-cover in a global economic framework. RCP4.5 was updated from earlier GCAM scenarios to incorporate historical emissions and land cover information common to the RCP process and follows a cost-minimizing pathway to reach the target radiative forcing. The imperative to limit emissions in order to reach this target drives changes in the energy system, includingmore » shifts to electricity, to lower emissions energy technologies and to the deployment of carbon capture and geologic storage technology. In addition, the RCP4.5 emissions price also applies to land use emissions; as a result, forest lands expand from their present day extent. The simulated future emissions and land use were downscaled from the regional simulation to a grid to facilitate transfer to climate models. While there are many alternative pathways to achieve a radiative forcing level of 4.5 W m{sup -2}, the application of the RCP4.5 provides a common platform for climate models to explore the climate system response to stabilizing the anthropogenic components of radiative forcing.« less

Reducing Amputations in People with Diabetes (RAPID): Evaluation of a New Care Pathway

PubMed Central

MacRury, Sandra; Main, Fiona; Gorman, Jane; Jones, Sandra; Macfarlane, David

2018-01-01

People with diabetes are at increased risk of foot ulcers, which, if left untreated, can lead to infection, gangrene, and subsequent amputation. Management by a multidisciplinary diabetes foot team has been shown to reduce amputation rates; however, accessing specialist treatment is made particularly difficult when living in remote and rural locations, such as many individuals cared for within NHS Highland. The RAPID project was made up of two phases: firstly, to evaluate the technical feasibility of a new integrated care pathway using innovative technology, and secondly, to establish process enhancement of the pathway to justify a larger-scale study. Omni-HubTM enabled a face-to-face consultation by the community podiatrist to be enhanced by virtual consultation with members of the multidisciplinary foot team, including specialist diabetes podiatrists and a diabetes consultant. The technical feasibility study provided recommended changes focused around adaptations to the equipment used and the best means to gain successful connectivity. The process enhancement study demonstrated positive outcomes in the process with positive effects both in the service received by patients and experiences of healthcare professionals involved. The RAPID project provides evidence and justification for a larger-scale empirical study to test an embedded pathway and technology solution, which will inform policy change and a paradigm shift in the management of foot ulceration in the community. PMID:29772673

Reducing Amputations in People with Diabetes (RAPID): Evaluation of a New Care Pathway.

PubMed

MacRury, Sandra; Stephen, Kate; Main, Fiona; Gorman, Jane; Jones, Sandra; Macfarlane, David

2018-05-16

People with diabetes are at increased risk of foot ulcers, which, if left untreated, can lead to infection, gangrene, and subsequent amputation. Management by a multidisciplinary diabetes foot team has been shown to reduce amputation rates; however, accessing specialist treatment is made particularly difficult when living in remote and rural locations, such as many individuals cared for within NHS Highland. The RAPID project was made up of two phases: firstly, to evaluate the technical feasibility of a new integrated care pathway using innovative technology, and secondly, to establish process enhancement of the pathway to justify a larger-scale study. Omni-Hub TM enabled a face-to-face consultation by the community podiatrist to be enhanced by virtual consultation with members of the multidisciplinary foot team, including specialist diabetes podiatrists and a diabetes consultant. The technical feasibility study provided recommended changes focused around adaptations to the equipment used and the best means to gain successful connectivity. The process enhancement study demonstrated positive outcomes in the process with positive effects both in the service received by patients and experiences of healthcare professionals involved. The RAPID project provides evidence and justification for a larger-scale empirical study to test an embedded pathway and technology solution, which will inform policy change and a paradigm shift in the management of foot ulceration in the community.

Applications of a Case Library of Technology Integration Stories for Teachers

ERIC Educational Resources Information Center

Wang, Feng-Kwei; Jonassen, David H.; Strobel, Johannes; Cernusca, Dawn

2003-01-01

Stories are the most natural form of communication and learning among humans. In this paper, we describe how we have designed and implemented an case library of technology integration stories to support pre-service and in-service teachers learning how to integrate technologies into their teaching. The case library was built using the artificial…

Electron tunneling through covalent and noncovalent pathways in proteins

NASA Technical Reports Server (NTRS)

Beratan, David N.; Onuchic, Jose Nelson; Hopfield, J. J.

1987-01-01

A model is presented for electron tunneling in proteins which allows the donor-acceptor interaction to be mediated by the covalent bonds between amino acids and noncovalent contacts between amino acid chains. The important tunneling pathways are predicted to include mostly bonded groups with less favorable nonbonded interactions being important when the through bond pathway is prohibitively long. In some cases, vibrational motion of nonbonded groups along the tunneling pathway strongly influences the temperature dependence of the rate. Quantitative estimates for the sizes of these noncovalent interactions are made and their role in protein mediated electron transport is discussed.

Circadian pathway genetic variation and cancer risk: evidence from genome-wide association studies.

PubMed

Mocellin, Simone; Tropea, Saveria; Benna, Clara; Rossi, Carlo Riccardo

2018-02-19

Dysfunction of the circadian clock and single polymorphisms of some circadian genes have been linked to cancer susceptibility, although data are scarce and findings inconsistent. We aimed to investigate the association between circadian pathway genetic variation and risk of developing common cancers based on the findings of genome-wide association studies (GWASs). Single nucleotide polymorphisms (SNPs) of 17 circadian genes reported by three GWAS meta-analyses dedicated to breast (Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Consortium; cases, n = 15,748; controls, n = 18,084), prostate (Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) Consortium; cases, n = 14,160; controls, n = 12,724) and lung carcinoma (Transdisciplinary Research In Cancer of the Lung (TRICL) Consortium; cases, n = 12,160; controls, n = 16,838) in patients of European ancestry were utilized to perform pathway analysis by means of the adaptive rank truncated product (ARTP) method. Data were also available for the following subgroups: estrogen receptor negative breast cancer, aggressive prostate cancer, squamous lung carcinoma and lung adenocarcinoma. We found a highly significant statistical association between circadian pathway genetic variation and the risk of breast (pathway P value = 1.9 × 10 -6 ; top gene RORA, gene P value = 0.0003), prostate (pathway P value = 4.1 × 10 -6 ; top gene ARNTL, gene P value = 0.0002) and lung cancer (pathway P value = 6.9 × 10 -7 ; top gene RORA, gene P value = 2.0 × 10 -6 ), as well as all their subgroups. Out of 17 genes investigated, 15 were found to be significantly associated with the risk of cancer: four genes were shared by all three malignancies (ARNTL, CLOCK, RORA and RORB), two by breast and lung cancer (CRY1 and CRY2) and three by prostate and lung cancer (NPAS2, NR1D1 and PER3), whereas four genes were specific for lung cancer (ARNTL2, CSNK1E, NR1D2 and PER2) and two for breast cancer (PER1, RORC). Our findings, based on the largest series ever utilized for ARTP-based gene and pathway analysis, support the hypothesis that circadian pathway genetic variation is involved in cancer predisposition.

Instructional Technology Applications in Vocational Education: A Notebook of Cases.

ERIC Educational Resources Information Center

Gooler, Dennis D.; Roth, Gene L.

This resource book is one of a series of three information resources containing ideas about instructional technology applications and how certain technology applications may have particular relevance to vocational education. It contains descriptions of some instructional technology systems applications that are currently in use. The cases focus…

Why University Members Use and Resist Technology? A Structure Enactment Perspective

ERIC Educational Resources Information Center

Lin, Canchu; Singer, Ross; Ha, Louisa

2010-01-01

This case study investigated university members' use of and resistance to a communication information technology system in a higher education organization. This case study utilized the technology enactment framework to examine structure enactment in university members' technology use and resistance. We found that the following structures were…

Autoimmune-autoinflammatory rheumatoid arthritis overlaps: a rare but potentially important subgroup of diseases

PubMed Central

Savic, Sinisa; Mistry, Anoop; Wilson, Anthony G; Barcenas-Morales, Gabriela; Doffinger, Rainer; Emery, Paul; McGonagle, Dennis

2017-01-01

At the population level, rheumatoid arthritis (RA) is generally viewed as autoimmune in nature with a small subgroup of cases having a palindromic form or systemic autoinflammatory disorder (SAID) phenotype. Herein, we describe resistant cases of classical autoantibody associated RA that had clinical, genetic and therapeutic responses indicative of coexistent autoinflammatory disease. Five patients with clinically overlapping features between RA and SAID including polysynovitis and autoantibody/shared epitope positivity, and who had abrupt severe self-limiting attacks including fevers and serositis, are described. Mutations or single nucleotide polymorphisms in recognised autoinflammatory pathways were evident. Generally, these cases responded poorly to conventional Disease-modifying anti-rheumatic drugs (DMARD) treatment with some excellent responses to colchicine or interleukin 1 pathway blockade. A subgroup of RA cases have a mixed autoimmune-autoinflammatory phenotype and genotype with therapeutic implications. PMID:29177082

Autoimmune-autoinflammatory rheumatoid arthritis overlaps: a rare but potentially important subgroup of diseases.

PubMed

Savic, Sinisa; Mistry, Anoop; Wilson, Anthony G; Barcenas-Morales, Gabriela; Doffinger, Rainer; Emery, Paul; McGonagle, Dennis

2017-01-01

At the population level, rheumatoid arthritis (RA) is generally viewed as autoimmune in nature with a small subgroup of cases having a palindromic form or systemic autoinflammatory disorder (SAID) phenotype. Herein, we describe resistant cases of classical autoantibody associated RA that had clinical, genetic and therapeutic responses indicative of coexistent autoinflammatory disease. Five patients with clinically overlapping features between RA and SAID including polysynovitis and autoantibody/shared epitope positivity, and who had abrupt severe self-limiting attacks including fevers and serositis, are described. Mutations or single nucleotide polymorphisms in recognised autoinflammatory pathways were evident. Generally, these cases responded poorly to conventional Disease-modifying anti-rheumatic drugs (DMARD) treatment with some excellent responses to colchicine or interleukin 1 pathway blockade. A subgroup of RA cases have a mixed autoimmune-autoinflammatory phenotype and genotype with therapeutic implications.

Practical approaches to adverse outcome pathway development and weight‐of‐evidence evaluation as illustrated by ecotoxicological case studies

EPA Science Inventory

Adverse Outcome Pathways (AOPs) describe toxicant effects as a sequential chain of causally linked events beginning with a molecular perturbation and culminating in an adverse outcome at an individual or population level. Strategies for developing AOPs are still evolving and dep...

Development of Transcriptomic Resources for Interrogating the Biosynthesis of Monoterpene Indole Alkaloids in Medicinal Plant Species

PubMed Central

Góngora-Castillo, Elsa; Childs, Kevin L.; Fedewa, Greg; Hamilton, John P.; Liscombe, David K.; Magallanes-Lundback, Maria; Mandadi, Kranthi K.; Nims, Ezekiel; Runguphan, Weerawat; Vaillancourt, Brieanne; Varbanova-Herde, Marina; DellaPenna, Dean; McKnight, Thomas D.; O’Connor, Sarah; Buell, C. Robin

2012-01-01

The natural diversity of plant metabolism has long been a source for human medicines. One group of plant-derived compounds, the monoterpene indole alkaloids (MIAs), includes well-documented therapeutic agents used in the treatment of cancer (vinblastine, vincristine, camptothecin), hypertension (reserpine, ajmalicine), malaria (quinine), and as analgesics (7-hydroxymitragynine). Our understanding of the biochemical pathways that synthesize these commercially relevant compounds is incomplete due in part to a lack of molecular, genetic, and genomic resources for the identification of the genes involved in these specialized metabolic pathways. To address these limitations, we generated large-scale transcriptome sequence and expression profiles for three species of Asterids that produce medicinally important MIAs: Camptotheca acuminata, Catharanthus roseus, and Rauvolfia serpentina. Using next generation sequencing technology, we sampled the transcriptomes of these species across a diverse set of developmental tissues, and in the case of C. roseus, in cultured cells and roots following elicitor treatment. Through an iterative assembly process, we generated robust transcriptome assemblies for all three species with a substantial number of the assembled transcripts being full or near-full length. The majority of transcripts had a related sequence in either UniRef100, the Arabidopsis thaliana predicted proteome, or the Pfam protein domain database; however, we also identified transcripts that lacked similarity with entries in either database and thereby lack a known function. Representation of known genes within the MIA biosynthetic pathway was robust. As a diverse set of tissues and treatments were surveyed, expression abundances of transcripts in the three species could be estimated to reveal transcripts associated with development and response to elicitor treatment. Together, these transcriptomes and expression abundance matrices provide a rich resource for understanding plant specialized metabolism, and promotes realization of innovative production systems for plant-derived pharmaceuticals. PMID:23300689

Unprecedented rates of land-use transformation in modeled climate change mitigation pathways

NASA Astrophysics Data System (ADS)

Turner, P. A.; Field, C. B.; Lobell, D. B.; Sanchez, D.; Mach, K. J.

2017-12-01

Integrated assessment models (IAMs) generate climate change mitigation scenarios consistent with global temperature targets. To limit warming to 2°, stylized cost-effective mitigation pathways rely on extensive deployments of carbon dioxide (CO2) removal (CDR) technologies, including multi-gigatonne yearly carbon removal from the atmosphere through bioenergy with carbon capture and storage (BECCS) and afforestation/reforestation. These assumed CDR deployments keep ambitious temperature limits in reach, but associated rates of land-use transformation have not been evaluated. For IAM scenarios from the IPCC Fifth Assessment Report, we compare rates of modeled land-use conversion to recent observed commodity crop expansions. In scenarios with a likely chance of limiting warming to 2° in 2100, the rate of energy cropland expansion supporting BECCS exceeds past commodity crop rates by several fold. In some cases, mitigation scenarios include abrupt reversal of deforestation, paired with massive afforestation/reforestation. Specifically, energy cropland in <2° scenarios expands, on average, by 8.2 Mha yr-1 and 11.7% p.a. across scenarios. This rate exceeds, by more than 3-fold, the observed expansion of soybean, the most rapidly expanding commodity crop. If energy cropland instead increases at rates equal to recent soybean and oil palm expansions, the scale of CO2 removal possible with BECCS is 2.6 to 10-times lower, respectively, than the deployments <2° IAM scenarios rely upon in 2100. IAM mitigation pathways may favor multi-gigatonne biomass-based CDR given undervalued sociopolitical and techno-economic deployment barriers. Heroic modeled rates for land-use transformation imply that large-scale biomass-based CDR is not an easy solution to the climate challenge.

The Application of the Open Pharmacological Concepts Triple Store (Open PHACTS) to Support Drug Discovery Research

PubMed Central

Ratnam, Joseline; Zdrazil, Barbara; Digles, Daniela; Cuadrado-Rodriguez, Emiliano; Neefs, Jean-Marc; Tipney, Hannah; Siebes, Ronald; Waagmeester, Andra; Bradley, Glyn; Chau, Chau Han; Richter, Lars; Brea, Jose; Evelo, Chris T.; Jacoby, Edgar; Senger, Stefan; Loza, Maria Isabel; Ecker, Gerhard F.; Chichester, Christine

2014-01-01

Integration of open access, curated, high-quality information from multiple disciplines in the Life and Biomedical Sciences provides a holistic understanding of the domain. Additionally, the effective linking of diverse data sources can unearth hidden relationships and guide potential research strategies. However, given the lack of consistency between descriptors and identifiers used in different resources and the absence of a simple mechanism to link them, gathering and combining relevant, comprehensive information from diverse databases remains a challenge. The Open Pharmacological Concepts Triple Store (Open PHACTS) is an Innovative Medicines Initiative project that uses semantic web technology approaches to enable scientists to easily access and process data from multiple sources to solve real-world drug discovery problems. The project draws together sources of publicly-available pharmacological, physicochemical and biomolecular data, represents it in a stable infrastructure and provides well-defined information exploration and retrieval methods. Here, we highlight the utility of this platform in conjunction with workflow tools to solve pharmacological research questions that require interoperability between target, compound, and pathway data. Use cases presented herein cover 1) the comprehensive identification of chemical matter for a dopamine receptor drug discovery program 2) the identification of compounds active against all targets in the Epidermal growth factor receptor (ErbB) signaling pathway that have a relevance to disease and 3) the evaluation of established targets in the Vitamin D metabolism pathway to aid novel Vitamin D analogue design. The example workflows presented illustrate how the Open PHACTS Discovery Platform can be used to exploit existing knowledge and generate new hypotheses in the process of drug discovery. PMID:25522365

Discontinuation of dialysis with eculizumab therapy in a pediatric patient with dense deposit disease.

PubMed

Tran, Cheryl L; Sethi, Sanjeev; Murray, David; Cramer, Carl H; Sas, David J; Willrich, Maria; Smith, Richard J; Fervenza, Fernando C

2016-04-01

Dense deposit disease (DDD) is a rare glomerular disease caused by an uncontrolled activation of the alternative complement pathway leading to end-stage renal disease in 50 % of patients. As such, DDD has been classified within the spectrum of complement component 3 (C3) glomerulopathies due to its pathogenesis from alternative pathway dysregulation. Conventional immunosuppressive therapies have no proven effectiveness. Eculizumab, a terminal complement inhibitor, has been reported to mitigate disease in some cases. We report on the efficacy of eculizumab in a pediatric patient who failed to respond to cyclophosphamide, corticosteroids, and plasma exchange. Complement biomarker profiling was remarkable for low serum C3, low properdin, and elevated soluble C5b-9. Consistent with these findings, the alternative pathway functional assay was abnormally low, indicative of alternative pathway activity, although neither C3-nephritic factors nor Factor H autoantibodies were detected. Eculizumab therapy was associated with significant improvement in proteinuria and renal function allowing discontinuation of hemodialysis (HD). Repeat C3 and soluble C5b-9 levels normalized, showing that terminal complement pathway activity was successfully blocked while the patient was receiving eculizumab therapy. Repeat testing for alternative pathway activation allowed for a successful decrease in eculizumab dosing. The case reported here demonstrates the successful recovery of renal function in a pediatric patient on HD following the use of eculizumab.

Adaptive approaches to licensing, health technology assessment, and introduction of drugs and devices.

PubMed

Husereau, Don; Henshall, Chris; Jivraj, Jamil

2014-07-01

Adaptive approaches to the introduction of drugs and medical devices involve the use of an evolving evidence base rather than conventional single-point-in-time evaluations as a proposed means to promote patient access to innovation, reduce clinical uncertainty, ensure effectiveness, and improve the health technology development process. This report summarizes a Health Technology Assessment International (HTAi) Policy Forum discussion, drawing on presentations from invited experts, discussions among attendees about real-world case examples, and background paper. For adaptive approaches to be understood, accepted, and implemented, the Forum identified several key issues that must be addressed. These include the need to define the goals of and to set priorities for adaptive approaches; to examine evidence collection approaches; to clarify the roles and responsibilities of stakeholders; to understand the implications of adaptive approaches on current legal and ethical standards; to determine costs of such approaches and how they will be met; and to identify differences in applying adaptive approaches to drugs versus medical devices. The Forum also explored the different implications of adaptive approaches for various stakeholders, including patients, regulators, HTA/coverage bodies, health systems, clinicians, and industry. A key outcome of the meeting was a clearer understanding of the opportunities and challenges adaptive approaches present. Furthermore, the Forum brought to light the critical importance of recognizing and including a full range of stakeholders as contributors to a shared decision-making model implicit in adaptive pathways in future discussions on, and implementation of, adaptive approaches.

Targeting Transcriptional Regulators of CD8+ T Cell Dysfunction to Boost Anti-Tumor Immunity

PubMed Central

Waugh, Katherine A.; Leach, Sonia M.; Slansky, Jill E.

2015-01-01

Transcription is a dynamic process influenced by the cellular environment: healthy, transformed, and otherwise. Genome-wide mRNA expression profiles reflect the collective impact of pathways modulating cell function under different conditions. In this review we focus on the transcriptional pathways that control tumor infiltrating CD8+ T cell (TIL) function. Simultaneous restraint of overlapping inhibitory pathways may confer TIL resistance to multiple mechanisms of suppression traditionally referred to as exhaustion, tolerance, or anergy. Although decades of work have laid a solid foundation of altered transcriptional networks underlying various subsets of hypofunctional or “dysfunctional” CD8+ T cells, an understanding of the relevance in TIL has just begun. With recent technological advances, it is now feasible to further elucidate and utilize these pathways in immunotherapy platforms that seek to increase TIL function. PMID:26393659

Metabolomic strategies to map functions of metabolic pathways.

PubMed

Mulvihill, Melinda M; Nomura, Daniel K

2014-08-01

Genome sequencing efforts have revealed a strikingly large number of unannotated and uncharacterized genes that fall into metabolic enzymes classes, likely indicating that our current knowledge of biochemical pathways in normal physiology, let alone in disease states, remains largely incomplete. This realization presents a daunting challenge for post-genomic-era scientists in deciphering the biochemical and (patho)physiological roles of these enzymes and their metabolites and metabolic networks. This is further complicated by many recent studies showing a rewiring of normal metabolic networks in disease states to give rise to unique pathophysiological functions of enzymes, metabolites, and metabolic pathways. This review focuses on recent discoveries made using metabolic mapping technologies to uncover novel pathways and metabolite-mediated posttranslational modifications and epigenetic alterations and their impact on physiology and disease. Copyright © 2014 the American Physiological Society.

Systems Genetics Analysis of GWAS reveals Novel Associations between Key Biological Processes and Coronary Artery Disease

PubMed Central

Ghosh, Sujoy; Vivar, Juan; Nelson, Christopher P; Willenborg, Christina; Segrè, Ayellet V; Mäkinen, Ville-Petteri; Nikpay, Majid; Erdmann, Jeannette; Blankenberg, Stefan; O'Donnell, Christopher; März, Winfried; Laaksonen, Reijo; Stewart, Alexandre FR; Epstein, Stephen E; Shah, Svati H; Granger, Christopher B; Hazen, Stanley L; Kathiresan, Sekar; Reilly, Muredach P; Yang, Xia; Quertermous, Thomas; Samani, Nilesh J; Schunkert, Heribert; Assimes, Themistocles L; McPherson, Ruth

2016-01-01

Objective Genome-wide association (GWA) studies have identified multiple genetic variants affecting the risk of coronary artery disease (CAD). However, individually these explain only a small fraction of the heritability of CAD and for most, the causal biological mechanisms remain unclear. We sought to obtain further insights into potential causal processes of CAD by integrating large-scale GWA data with expertly curated databases of core human pathways and functional networks. Approaches and Results Employing pathways (gene sets) from Reactome, we carried out a two-stage gene set enrichment analysis strategy. From a meta-analyzed discovery cohort of 7 CADGWAS data sets (9,889 cases/11,089 controls), nominally significant gene-sets were tested for replication in a meta-analysis of 9 additional studies (15,502 cases/55,730 controls) from the CARDIoGRAM Consortium. A total of 32 of 639 Reactome pathways tested showed convincing association with CAD (replication p<0.05). These pathways resided in 9 of 21 core biological processes represented in Reactome, and included pathways relevant to extracellular matrix integrity, innate immunity, axon guidance, and signaling by PDRF, NOTCH, and the TGF-β/SMAD receptor complex. Many of these pathways had strengths of association comparable to those observed in lipid transport pathways. Network analysis of unique genes within the replicated pathways further revealed several interconnected functional and topologically interacting modules representing novel associations (e.g. semaphorin regulated axonal guidance pathway) besides confirming known processes (lipid metabolism). The connectivity in the observed networks was statistically significant compared to random networks (p<0.001). Network centrality analysis (‘degree’ and ‘betweenness’) further identified genes (e.g. NCAM1, FYN, FURIN etc.) likely to play critical roles in the maintenance and functioning of several of the replicated pathways. Conclusions These findings provide novel insights into how genetic variation, interpreted in the context of biological processes and functional interactions among genes, may help define the genetic architecture of CAD. PMID:25977570

A Model of an Integrated Immune System Pathway in Homo sapiens and Its Interaction with Superantigen Producing Expression Regulatory Pathway in Staphylococcus aureus: Comparing Behavior of Pathogen Perturbed and Unperturbed Pathway

PubMed Central

Tomar, Namrata; De, Rajat K.

2013-01-01

Response of an immune system to a pathogen attack depends on the balance between the host immune defense and the virulence of the pathogen. Investigation of molecular interactions between the proteins of a host and a pathogen helps in identifying the pathogenic proteins. It is necessary to understand the dynamics of a normally behaved host system to evaluate the capacity of its immune system upon pathogen attack. In this study, we have compared the behavior of an unperturbed and pathogen perturbed host system. Moreover, we have developed a formalism under Flux Balance Analysis (FBA) for the optimization of conflicting objective functions. We have constructed an integrated pathway system, which includes Staphylococcal Superantigen (SAg) expression regulatory pathway and TCR signaling pathway of Homo sapiens. We have implemented the method on this pathway system and observed the behavior of host signaling molecules upon pathogen attack. The entire study has been divided into six different cases, based on the perturbed/unperturbed conditions. In other words, we have investigated unperturbed and pathogen perturbed human TCR signaling pathway, with different combinations of optimization of concentrations of regulatory and signaling molecules. One of these cases has aimed at finding out whether minimization of the toxin production in a pathogen leads to the change in the concentration levels of the proteins coded by TCR signaling pathway genes in the infected host. Based on the computed results, we have hypothesized that the balance between TCR signaling inhibitory and stimulatory molecules can keep TCR signaling system into resting/stimulating state, depending upon the perturbation. The proposed integrated host-pathogen interaction pathway model has accurately reflected the experimental evidences, which we have used for validation purpose. The significance of this kind of investigation lies in revealing the susceptible interaction points that can take back the Staphylococcal Enterotoxin (SE)-challenged system within the range of normal behavior. PMID:24324645

Customizing the genome as therapy for the β-hemoglobinopathies.

PubMed

Canver, Matthew C; Orkin, Stuart H

2016-05-26

Despite nearly complete understanding of the genetics of the β-hemoglobinopathies for several decades, definitive treatment options have lagged behind. Recent developments in technologies for facile manipulation of the genome (zinc finger nucleases, transcription activator-like effector nucleases, or clustered regularly interspaced short palindromic repeats-based nucleases) raise prospects for their clinical application. The use of genome-editing technologies in autologous CD34(+) hematopoietic stem and progenitor cells represents a promising therapeutic avenue for the β-globin disorders. Genetic correction strategies relying on the homology-directed repair pathway may repair genetic defects, whereas genetic disruption strategies relying on the nonhomologous end joining pathway may induce compensatory fetal hemoglobin expression. Harnessing the power of genome editing may usher in a second-generation form of gene therapy for the β-globin disorders. © 2016 by The American Society of Hematology.

Advances in Gammalloy Materials-Processes-Application Technology: Successes, Dilemmas, and Future

NASA Astrophysics Data System (ADS)

Kim, Young-Won; Kim, Sang-Lan

2018-04-01

For the last several years, gamma titanium aluminide ( γ-TiAl)-based alloys, called "gammalloys," in specific alloy-microstructure forms began to be implemented in civil aero-engines as cast or wrought low-pressure turbine (LPT) blades and in select ground vehicle engines as cast turbocharger rotors and wrought exhaust valves. Their operation temperatures are approximately up to 750°C for LPT blades and around 1000°C for turbocharger rotors. This article critically assesses current engineering gammalloys and their limitations and introduces eight strengthening pathways that can be adopted immediately for the development of advanced, higher temperature gammalloys. Intelligent integration of the pathways into the emerging application-specific research and development processes is emphasized as the key to the advancement of the gammalloy technology to the next higher engineering performance levels.

A new nano-enhanced technology proposed to quantify intracellular detection of radiation-induced metabolic processes.

PubMed

Malak, Henryk; Richmond, Robert; Dicello, J F

2011-02-01

A new approach to intracellular detection and imaging of metabolic processes and pathways is presented that uses surface plasmon resonance to enhance interactions between photon-absorbing metabolites and metal nanoparticles in contact with cells in vitro or in vivo. Photon absorption in the nanoparticles creates plasmon fields, enhancing intrinsic metabolite fluorescence, thereby increasing absorption and emission rates, creating new spectral emission bands, shortening fluorescence lifetimes, becoming more photo-stable and increasing fluorescent resonance energy transfer efficiency. Because the cells remain viable, it is proposed that the method may be used to interrogate cells prior to and after irradiation, with the potential for automated analyses of intracellular interactive pathways associated with radiation exposures at lower doses than existing technologies. The design and concepts of the instrument are presented along with data for unexposed cells.

2 °C and SDGs: united they stand, divided they fall?

NASA Astrophysics Data System (ADS)

von Stechow, Christoph; Minx, Jan C.; Riahi, Keywan; Jewell, Jessica; McCollum, David L.; Callaghan, Max W.; Bertram, Christoph; Luderer, Gunnar; Baiocchi, Giovanni

2016-03-01

The adoption of the Sustainable Development Goals (SDGs) and the new international climate treaty could put 2015 into the history books as a defining year for setting human development on a more sustainable pathway. The global climate policy and SDG agendas are highly interconnected: the way that the climate problem is addressed strongly affects the prospects of meeting numerous other SDGs and vice versa. Drawing on existing scenario results from a recent energy-economy-climate model inter-comparison project, this letter analyses these synergies and (risk) trade-offs of alternative 2 °C pathways across indicators relevant for energy-related SDGs and sustainable energy objectives. We find that limiting the availability of key mitigation technologies yields some co-benefits and decreases risks specific to these technologies but greatly increases many others. Fewer synergies and substantial trade-offs across SDGs are locked into the system for weak short-term climate policies that are broadly in line with current Intended Nationally Determined Contributions (INDCs), particularly when combined with constraints on technologies. Lowering energy demand growth is key to managing these trade-offs and creating synergies across multiple energy-related SD dimensions. We argue that SD considerations are central for choosing socially acceptable 2 °C pathways: the prospects of meeting other SDGs need not dwindle and can even be enhanced for some goals if appropriate climate policy choices are made. Progress on the climate policy and SDG agendas should therefore be tracked within a unified framework.

Smart phones make smart referrals: The use of mobile phone technology in burn care - A retrospective case series.

PubMed

den Hollander, Daan; Mars, Maurice

2017-02-01

Telemedicine using cellular phones allows for real-time consultation of burn patients seen at distant hospitals. Telephonic consultations to our unit have required completion of a proforma, to ensure collection of the following information: demographics, mechanism of injury, vital signs, relevant laboratory data, management at the referring hospital and advice given by the burn team. Since December 2014 we have required referring doctors to send photographs of the burn wounds to the burns specialist before making a decision on acceptance of the referral or providing management advice. The photographs are taken and sent by smartphone using MMS or WhatsApp. The cases, with photographs, are entered into a database of telemedicine consultations which we have retrospectively reviewed. During the study period (December 2014-July 2015) we were consulted about 119 patients, in 100 of whom the telemedicine consultation was completed. Inappropriate transfer to the burns centre was avoided in 38% of cases, and in 28% a period of treatment in the referral hospital was advised before transfer. For a total of 66% of patients the telemedicine consultation changed, and either avoided an inappropriate admission, or delayed admission in late referrals until the patient was ready for definitive treatment. We conclude that telemedicine consultations using a cellular phone significantly change referral pathways in burns. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Optimizing the interaction of children with information and communication technologies.

PubMed

Straker, L; Pollock, C

2005-04-15

This paper outlines the major changes in the lives of children in industrially advanced countries associated with the increased interaction with information and communication technologies. The potential opportunities and threats to the cognitive, social, physical and visual development of children are reviewed to emphasize the importance of optimizing the interaction. The change in children's use of technology also poses opportunities and threats for ergonomics that should be noted if the profession is to continue being relevant and useful into this century. The paper ends with a pathway to the development and implementation of guidelines about child information and communication technology use for different groups of guideline users.

Targeted exome sequencing and chromosomal microarray for the molecular diagnosis of nevoid basal cell carcinoma syndrome.

PubMed

Matsudate, Yoshihiro; Naruto, Takuya; Hayashi, Yumiko; Minami, Mitsuyoshi; Tohyama, Mikiko; Yokota, Kenji; Yamada, Daisuke; Imoto, Issei; Kubo, Yoshiaki

2017-06-01

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder mainly caused by heterozygous mutations of PTCH1. In addition to characteristic clinical features, detection of a mutation in causative genes is reliable for the diagnosis of NBCCS; however, no mutations have been identified in some patients using conventional methods. To improve the method for the molecular diagnosis of NBCCS. We performed targeted exome sequencing (TES) analysis using a multi-gene panel, including PTCH1, PTCH2, SUFU, and other sonic hedgehog signaling pathway-related genes, based on next-generation sequencing (NGS) technology in 8 cases in whom possible causative mutations were not detected by previously performed conventional analysis and 2 recent cases of NBCCS. Subsequent analysis of gross deletion within or around PTCH1 detected by TES was performed using chromosomal microarray (CMA). Through TES analysis, specific single nucleotide variants or small indels of PTCH1 causing inferred amino acid changes were identified in 2 novel cases and 2 undiagnosed cases, whereas gross deletions within or around PTCH1, which are validated by CMA, were found in 3 undiagnosed cases. However, no mutations were detected even by TES in 3 cases. Among 3 cases with gross deletions of PTCH1, deletions containing the entire PTCH1 and additional neighboring genes were detected in 2 cases, one of which exhibited atypical clinical features, such as severe mental retardation, likely associated with genes located within the 4.3Mb deleted region, especially. TES-based simultaneous evaluation of sequences and copy number status in all targeted coding exons by NGS is likely to be more useful for the molecular diagnosis of NBCCS than conventional methods. CMA is recommended as a subsequent analysis for validation and detailed mapping of deleted regions, which may explain the atypical clinical features of NBCCS cases. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

[Transcriptome analysis of Dunaliella viridis].

PubMed

Zhu, Shuai-qi; Gong, Yi-fu; Hang, Yu-qing; Liu, Hao; Wang, He-yu

2015-08-01

In order to understand the gene information, function, haloduric pathway (glycerolipid metabolism) and related key genes for Dunaliella viridis, we used Illumina HiSeqTM 2000 high-throughput sequencing technology to sequence its transcriptome. Trinity soft was used to assemble the data to form transcripts. Based on the Clusters of Orthologous Groups (COG), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG ) databases, we carried out functional annotation and classification, pathway annotation, and the opening reading fragment (ORF) sequence prediction of transcripts. The key genes in the glycerolipid metabolism were analyzed. The results suggested that 81,593 transcripts were found, and 77,117 ORF sequences were predicted, accounting for 94.50% of all transcripts. COG classification results showed that 16,569 transcripts were assigned to 24 categories. GO classification annotated 76,436 transcripts. The number of transcripts for biologcial processes was 30,678, accounting for 40.14% of all transcripts. KEGG pathway analysis showed that 26,428 transcripts were annotated to 317 pathways, and 131 pathways were related to metabolism, accounting for 41.32% of all annotated pathways. Only one transcript was annotated as coding the key enzyme dihydroxyacetone kinase involved in the glycerolipid pathway. This enzyme could be related to glycerol biosynthesis under salt stress. This study further improved the gene information and laid the foundation of metabolic pathway research for Dunaliella viridis.

Subpathway-GM: identification of metabolic subpathways via joint power of interesting genes and metabolites and their topologies within pathways

PubMed Central

Li, Chunquan; Han, Junwei; Yao, Qianlan; Zou, Chendan; Xu, Yanjun; Zhang, Chunlong; Shang, Desi; Zhou, Lingyun; Zou, Chaoxia; Sun, Zeguo; Li, Jing; Zhang, Yunpeng; Yang, Haixiu; Gao, Xu; Li, Xia

2013-01-01

Various ‘omics’ technologies, including microarrays and gas chromatography mass spectrometry, can be used to identify hundreds of interesting genes, proteins and metabolites, such as differential genes, proteins and metabolites associated with diseases. Identifying metabolic pathways has become an invaluable aid to understanding the genes and metabolites associated with studying conditions. However, the classical methods used to identify pathways fail to accurately consider joint power of interesting gene/metabolite and the key regions impacted by them within metabolic pathways. In this study, we propose a powerful analytical method referred to as Subpathway-GM for the identification of metabolic subpathways. This provides a more accurate level of pathway analysis by integrating information from genes and metabolites, and their positions and cascade regions within the given pathway. We analyzed two colorectal cancer and one metastatic prostate cancer data sets and demonstrated that Subpathway-GM was able to identify disease-relevant subpathways whose corresponding entire pathways might be ignored using classical entire pathway identification methods. Further analysis indicated that the power of a joint genes/metabolites and subpathway strategy based on their topologies may play a key role in reliably recalling disease-relevant subpathways and finding novel subpathways. PMID:23482392

Addressing the Nets for Students through Constructivist Technology Use in K-12 Classrooms

ERIC Educational Resources Information Center

Niederhauser, Dale S.; Lindstrom, Denise L.

2006-01-01

The National Educational Technology Standards for Students promote constructivist technology use for K-12 students in U.S. schools. In this study, researchers reported on 716 cases in which teachers described technology-based activities they conducted with their students. Narrative analysis was used to examine case transcripts relative to the…

Molecular mechanisms associated with 46,XX disorders of sex development.

PubMed

Knarston, Ingrid; Ayers, Katie; Sinclair, Andrew

2016-03-01

In the female gonad, distinct signalling pathways activate ovarian differentiation while repressing the formation of testes. Human disorders of sex development (DSDs), such as 46,XX DSDs, can arise when this signalling is aberrant. Here we review the current understanding of the genetic mechanisms that control gonadal development, with particular emphasis on those that drive or inhibit ovarian differentiation. We discuss how disruption to these molecular pathways can lead to 46,XX disorders of ovarian development. Finally, we look at recently characterized novel genes and pathways that contribute and speculate how advances in technology will aid in further characterization of normal and disrupted human ovarian development. © 2016 Authors; published by Portland Press Limited.

Constructing phylogenetic trees using interacting pathways.

PubMed

Wan, Peng; Che, Dongsheng

2013-01-01

Phylogenetic trees are used to represent evolutionary relationships among biological species or organisms. The construction of phylogenetic trees is based on the similarities or differences of their physical or genetic features. Traditional approaches of constructing phylogenetic trees mainly focus on physical features. The recent advancement of high-throughput technologies has led to accumulation of huge amounts of biological data, which in turn changed the way of biological studies in various aspects. In this paper, we report our approach of building phylogenetic trees using the information of interacting pathways. We have applied hierarchical clustering on two domains of organisms-eukaryotes and prokaryotes. Our preliminary results have shown the effectiveness of using the interacting pathways in revealing evolutionary relationships.

The Influence of Affirming Kindness and Community on Broadening Participation in STEM Career Pathways

PubMed Central

Estrada, Mica; Eroy-Reveles, Alegra; Matsui, John

2018-01-01

The United States’ inability to achieve equitable workforce development in science, technology, engineering, and mathematics (STEM) career pathways is well-recognized and has been attributed to the poor retention of a diverse stream of students in academia. Social science theory and research provide evidence that social contextual variables—specifically kindness cues affirming social inclusion—influence chronic underrepresentation of some groups within STEM career pathways. Review of the literature suggests that the current STEM academic context does not consistently provide cues that affirm social inclusion to all members of the academic population, and that policies that address this disparity are essential to broadening STEM workforce development in the United States. PMID:29657577

Melanins and melanogenesis: from pigment cells to human health and technological applications.

PubMed

d'Ischia, Marco; Wakamatsu, Kazumasa; Cicoira, Fabio; Di Mauro, Eduardo; Garcia-Borron, Josè Carlos; Commo, Stephane; Galván, Ismael; Ghanem, Ghanem; Kenzo, Koike; Meredith, Paul; Pezzella, Alessandro; Santato, Clara; Sarna, Tadeusz; Simon, John D; Zecca, Luigi; Zucca, Fabio A; Napolitano, Alessandra; Ito, Shosuke

2015-09-01

During the past decade, melanins and melanogenesis have attracted growing interest for a broad range of biomedical and technological applications. The burst of polydopamine-based multifunctional coatings in materials science is just one example, and the list may be expanded to include melanin thin films for organic electronics and bioelectronics, drug delivery systems, functional nanoparticles and biointerfaces, sunscreens, environmental remediation devices. Despite considerable advances, applied research on melanins and melanogenesis is still far from being mature. A closer intersectoral interaction between research centers is essential to raise the interests and increase the awareness of the biomedical, biomaterials science and hi-tech sectors of the manifold opportunities offered by pigment cells and related metabolic pathways. Starting from a survey of biological roles and functions, the present review aims at providing an interdisciplinary perspective of melanin pigments and related pathway with a view to showing how it is possible to translate current knowledge about physical and chemical properties and control mechanisms into new bioinspired solutions for biomedical, dermocosmetic, and technological applications. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Epigenetics and Epigenomics of Plants.

PubMed

Yadav, Chandra Bhan; Pandey, Garima; Muthamilarasan, Mehanathan; Prasad, Manoj

2018-01-23

The genetic material DNA in association with histone proteins forms the complex structure called chromatin, which is prone to undergo modification through certain epigenetic mechanisms including cytosine DNA methylation, histone modifications, and small RNA-mediated methylation. Alterations in chromatin structure lead to inaccessibility of genomic DNA to various regulatory proteins such as transcription factors, which eventually modulates gene expression. Advancements in high-throughput sequencing technologies have provided the opportunity to study the epigenetic mechanisms at genome-wide levels. Epigenomic studies using high-throughput technologies will widen the understanding of mechanisms as well as functions of regulatory pathways in plant genomes, which will further help in manipulating these pathways using genetic and biochemical approaches. This technology could be a potential research tool for displaying the systematic associations of genetic and epigenetic variations, especially in terms of cytosine methylation onto the genomic region in a specific cell or tissue. A comprehensive study of plant populations to correlate genotype to epigenotype and to phenotype, and also the study of methyl quantitative trait loci (QTL) or epiGWAS, is possible by using high-throughput sequencing methods, which will further accelerate molecular breeding programs for crop improvement. Graphical Abstract.

Recent advance on genome editing for therapy of β-hemoglobinopathies.

PubMed

Liu, Jia-Wei; Hong, Tao; Qin, Xin; Liang, Ying-Min; Zhang, Ping

2018-02-20

β-hemoglobinopathies are one of six groups of common illnesses affecting human health. Although the genetic mechanisms have been elucidated for several decades, curable treatment options, other than allogeneic bone marrow transplantation, are still lacking. In recent years, rapid development in genome editing technologies and their clinical applications have opened up new directions for treatment of β-hemoglobinopathies. Genome editing technologies, as applied in autologous CD34 + hematopoietic stem and progenitor cells, represents a promising remedial means for the β-globin disorders. Hemoglobin gene mutations could be corrected with homologous recombination-mediated DNA repair pathway to repair the genetic defects, while the nonhomologous end-joining pathway may be used to silence the key repressor of fetal globin expression and reactivate fetal hemoglobin expression, thereby alleviating the clinical symptoms of β-hemoglobinopathies in patients. This review summarizes the recent advances on genome editing of β-hemoglobinopathies from the bench design to the establishment of clinical translational platforms, thereby providing critical insights and references on the application of genome editing technologies for the development of therapeutic strategies for β-hemoglobinopathies.

Readings in technology assessment. [in relation to social impact and the law

NASA Technical Reports Server (NTRS)

1975-01-01

Papers are presented which reflect research in the following areas: development of the concept of technology assessment; institutionalization of technology assessment; the interface between law and technology assessment; and assessment case studies. Case studies include hazards of the medical use of X-rays, environmental noise effects in transportation planning, genetic technology, impact of underground coal mining, and aircraft/airport noise abatement.

The puzzle of the Krebs citric acid cycle: assembling the pieces of chemically feasible reactions, and opportunism in the design of metabolic pathways during evolution.

PubMed

Meléndez-Hevia, E; Waddell, T G; Cascante, M

1996-09-01

The evolutionary origin of the Krebs citric acid cycle has been for a long time a model case in the understanding of the origin and evolution of metabolic pathways: How can the emergence of such a complex pathway be explained? A number of speculative studies have been carried out that have reached the conclusion that the Krebs cycle evolved from pathways for amino acid biosynthesis, but many important questions remain open: Why and how did the full pathway emerge from there? Are other alternative routes for the same purpose possible? Are they better or worse? Have they had any opportunity to be developed in cellular metabolism evolution? We have analyzed the Krebs cycle as a problem of chemical design to oxidize acetate yielding reduction equivalents to the respiratory chain to make ATP. Our analysis demonstrates that although there are several different chemical solutions to this problem, the design of this metabolic pathway as it occurs in living cells is the best chemical solution: It has the least possible number of steps and it also has the greatest ATP yielding. Study of the evolutionary possibilities of each one-taking the available material to build new pathways-demonstrates that the emergence of the Krebs cycle has been a typical case of opportunism in molecular evolution. Our analysis proves, therefore, that the role of opportunism in evolution has converted a problem of several possible chemical solutions into a single-solution problem, with the actual Krebs cycle demonstrated to be the best possible chemical design. Our results also allow us to derive the rules under which metabolic pathways emerged during the origin of life.

Polymer Uncrossing and Knotting in Protein Folding, and Their Role in Minimal Folding Pathways

PubMed Central

Mohazab, Ali R.; Plotkin, Steven S.

2013-01-01

We introduce a method for calculating the extent to which chain non-crossing is important in the most efficient, optimal trajectories or pathways for a protein to fold. This involves recording all unphysical crossing events of a ghost chain, and calculating the minimal uncrossing cost that would have been required to avoid such events. A depth-first tree search algorithm is applied to find minimal transformations to fold , , , and knotted proteins. In all cases, the extra uncrossing/non-crossing distance is a small fraction of the total distance travelled by a ghost chain. Different structural classes may be distinguished by the amount of extra uncrossing distance, and the effectiveness of such discrimination is compared with other order parameters. It was seen that non-crossing distance over chain length provided the best discrimination between structural and kinetic classes. The scaling of non-crossing distance with chain length implies an inevitable crossover to entanglement-dominated folding mechanisms for sufficiently long chains. We further quantify the minimal folding pathways by collecting the sequence of uncrossing moves, which generally involve leg, loop, and elbow-like uncrossing moves, and rendering the collection of these moves over the unfolded ensemble as a multiple-transformation “alignment”. The consensus minimal pathway is constructed and shown schematically for representative cases of an , , and knotted protein. An overlap parameter is defined between pathways; we find that proteins have minimal overlap indicating diverse folding pathways, knotted proteins are highly constrained to follow a dominant pathway, and proteins are somewhere in between. Thus we have shown how topological chain constraints can induce dominant pathway mechanisms in protein folding. PMID:23365638

Meeting the challenges of case management with remote patient monitoring technology.

PubMed

Cherry, J C; Colliflower, S J; Tsiperfal, A

2000-01-01

The article presents an overview of some of the current trends in health care and the challenges faced by nurse case managers who are providing disease management services. It discusses some of the emerging technologies available today for innovative case management. In particular, this article describes a program run by a healthcare system in Sacramento, California that uses an Internet-based technology to enhance their nurse case management model. The article demonstrates how the Health Hero platform enables interactive communication between nurse case managers and their patients, thereby meeting some of the challenges the nurse case managers are faced with in the modern disease-management world.

Metabolic Engineering for the Production of Natural Products

PubMed Central

Pickens, Lauren B.; Tang, Yi; Chooi, Yit-Heng

2014-01-01

Natural products and natural product derived compounds play an important role in modern healthcare as frontline treatments for many diseases and as inspiration for chemically synthesized therapeutics. With advances in sequencing and recombinant DNA technology, many of the biosynthetic pathways responsible for the production of these chemically complex and pharmaceutically valuable compounds have been elucidated. With an ever expanding toolkit of biosynthetic components, metabolic engineering is an increasingly powerful method to improve natural product titers and generate novel compounds. Heterologous production platforms have enabled access to pathways from difficult to culture strains; systems biology and metabolic modeling tools have resulted in increasing predictive and analytic capabilities; advances in expression systems and regulation have enabled the fine-tuning of pathways for increased efficiency, and characterization of individual pathway components has facilitated the construction of hybrid pathways for the production of new compounds. These advances in the many aspects of metabolic engineering have not only yielded fascinating scientific discoveries but also make it an increasingly viable approach for the optimization of natural product biosynthesis. PMID:22432617

Do Growth Mindsets in Math Benefit Females? Identifying Pathways between Gender, Mindset, and Motivation.

PubMed

Degol, Jessica L; Wang, Ming-Te; Zhang, Ya; Allerton, Julie

2018-05-01

Despite efforts to increase female representation in science, technology, engineering, and mathematics (STEM), females continue to be less motivated to pursue STEM careers than males. A short-term longitudinal study used a sample of 1449 high school students (grades 9-12; 49% females) to examine pathways from gender and mindset onto STEM outcomes via motivational beliefs (i.e., expectancy beliefs, task value, and cost). Mindset, motivational beliefs, and STEM career aspirations were assessed between the fall and winter months of the 2014-2015 school year and math grades were obtained at the conclusion of the same year. Student growth mindset beliefs predicted higher task values in math. Task values also mediated the pathway from a growth mindset to higher STEM career aspirations. Expectancy beliefs mediated the pathway between gender and math achievement. This mediated pathway was stronger for females than for males, such that females had higher math achievement than males when they endorsed a growth mindset. Findings suggest possible avenues for improving female's interest in STEM.

Genetic dissection of cardiac growth control pathways

NASA Technical Reports Server (NTRS)

MacLellan, W. R.; Schneider, M. D.

2000-01-01

Cardiac muscle cells exhibit two related but distinct modes of growth that are highly regulated during development and disease. Cardiac myocytes rapidly proliferate during fetal life but exit the cell cycle irreversibly soon after birth, following which the predominant form of growth shifts from hyperplastic to hypertrophic. Much research has focused on identifying the candidate mitogens, hypertrophic agonists, and signaling pathways that mediate these processes in isolated cells. What drives the proliferative growth of embryonic myocardium in vivo and the mechanisms by which adult cardiac myocytes hypertrophy in vivo are less clear. Efforts to answer these questions have benefited from rapid progress made in techniques to manipulate the murine genome. Complementary technologies for gain- and loss-of-function now permit a mutational analysis of these growth control pathways in vivo in the intact heart. These studies have confirmed the importance of suspected pathways, have implicated unexpected pathways as well, and have led to new paradigms for the control of cardiac growth.