Adaptation of the quality by design concept in early pharmaceutical development of an intranasal nanosized formulation.

PubMed

Pallagi, Edina; Ambrus, Rita; Szabó-Révész, Piroska; Csóka, Ildikó

2015-08-01

Regulatory science based pharmaceutical development and product manufacturing is highly recommended by the authorities nowadays. The aim of this study was to adapt regulatory science even in the nano-pharmaceutical early development. Authors applied the quality by design (QbD) concept in the early development phase of nano-systems, where the illustration material was meloxicam. The meloxicam nanoparticles produced by co-grinding method for nasal administration were studied according to the QbD policy and the QbD based risk assessment (RA) was performed. The steps were implemented according to the relevant regulatory guidelines (quality target product profile (QTPP) determination, selection of critical quality attributes (CQAs) and critical process parameters (CPPs)) and a special software (Lean QbD Software(®)) was used for the RA, which represents a novelty in this field. The RA was able to predict and identify theoretically the factors (e.g. sample composition, production method parameters, etc.) which have the highest impact on the desired meloxicam-product quality. The results of the practical research justified the theoretical prediction. This method can improve pharmaceutical nano-developments by achieving shorter development time, lower cost, saving human resource efforts and more effective target-orientation. It makes possible focusing the resources on the selected parameters and area during the practical product development. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Childers, M.; Barnes, J.

The phased field development of the Lion and Panthere fields, offshore the Ivory Coast, includes a small floating production, storage, and offloading (FPSO) tanker with minimal processing capability as an early oil production system (EPS). For the long-term production scheme, the FPSO will be replaced by a converted jack up mobile offshore production system (MOPS) with full process equipment. The development also includes guyed-caisson well platforms, pipeline export for natural gas to fuel an onshore power plant, and a floating storage and offloading (FSO) tanker for oil export. Pipeline export for oil is a future possibility. This array of innovativemore » strategies and techniques seldom has been brought together in a single project. The paper describes the development plan, early oil, jack up MOPS, and transport and installation.« less

Promoting equity through integrated early child development and nutrition interventions.

PubMed

Black, Maureen M; Dewey, Kathryn G

2014-01-01

Sustainable development, a foundation of the post-2015 global agenda, depends on healthy and productive citizens. The origins of adult health begin early in life, stemming from genetic-environmental interactions that include adequate nutrition and opportunities for responsive learning. Inequities associated with inadequate nutrition and early learning opportunities can undermine children's health and development, thereby compromising their productivity and societal contributions. Transactional theory serves as a useful framework for examining the associations that link early child development and nutrition because it emphasizes the interplay that occurs between children and the environment, mediated through caregiver interactions. Although single interventions targeting early child development or nutrition can be effective, there is limited evidence on the development, implementation, evaluation, and scaling up of integrated interventions. This manuscript introduces a special edition of papers on six topics central to integrated child development/nutrition interventions: (1) review of integrated interventions; (2) methods and topics in designing integrated interventions; (3) economic considerations related to integrated interventions; (4) capacity-building considerations; (5) examples of integrated interventions; and (6) policy implications of integrated interventions. Ensuring the health and development of infants and young children through integrated child development/nutrition interventions promotes equity, a critical component of sustainable development. © 2014 New York Academy of Sciences.

The National Heart, Lung, and Blood Institute Small Business Program

PubMed Central

Marek, Kurt W.

2016-01-01

SUMMARY Small companies working to develop products in the cardiovascular space face numerous challenges, from regulatory, intellectual property, and reimbursement barriers to securing funds to keep the lights on and reach the next development milestone. Most small companies that spin out from universities have the scientific knowledge, but product development expertise and business acumen are also needed to be successful. Other challenges include reduced interest in early stage technologies (Pharma & Biotech 2015 in Review, EP Vantage) and limited deal flow for cardiovascular products (Gormley B., Wall Street Journal, September 15, 2014). The NHLBI small business program is a comprehensive ecosystem designed to address these critical challenges and to provide resources and expertise to assist early stage companies developing cardiovascular and other products within the institute’s mission. This article describes steps that NHLBI has taken to enhance our small business program to more effectively translate basic discoveries into commercial products to benefit patients and public health, including enhancing internal expertise and developing non-financial resources to assist small businesses as they develop their products and seek private sector investment and partnership. PMID:28580435

Early-stage valuation of medical devices: the role of developmental uncertainty.

PubMed

Girling, Alan; Young, Terry; Brown, Celia; Lilford, Richard

2010-08-01

At the concept stage, many uncertainties surround the commercial viability of a new medical device. These include the ultimate functionality of the device, the cost of producing it and whether, and at what price, it can be sold to a health-care provider (HCP). Simple assessments of value can be made by estimating such unknowns, but the levels of uncertainty may mean that their operational value for investment decisions is unclear. However, many decisions taken at the concept stage are reversible and will be reconsidered later before the product is brought to market. This flexibility can be exploited to enhance early-stage valuations. To develop a framework for valuing a new medical device at the concept stage that balances benefit to the HCP against commercial costs. This is done within a simplified stage-gated model of the development cycle for new products. The approach is intended to complement existing proposals for the evaluation of the commercial headroom available to new medical products. A model based on two decision gates can lead to lower bounds (underestimates) for product value that can serve to support a decision to develop the product. Quantifiable uncertainty that can be resolved before the device is brought to market will generally enhance early-stage valuations of the device, and this remains true even when some components of uncertainty cannot be fully described. Clinical trials and other evidence-gathering activities undertaken as part of the development process can contribute to early-stage estimates of value.

A Framework for Evaluating R&D Impacts and Supply Chain Dynamics Early in a Product Life Cycle. Looking inside the black box of innovation

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

Jordan, Gretchen; Mote, Jonathan; Ruegg, Rosalie

This report provides a framework for evaluation of R&D investments aimed at speeding up the pace of innovation and strengthening domestic manufacturing and supply chains, which make up a portion of the investments of the U.S. Department of Energy's (DOEs) Office of Energy Efficiency and Renewable Energy (EERE). These investments focus on early phases of the product life cycle, characterized as extending from pre-product, late stage R&D, to initial product introduction and through to early market growth. The investments aim to provide support for additional technology, supply-chain, manufacturing, and early market development to enhance or create markets for clean energymore » technologies and strengthen the U.S. industry base.« less

Validation of the second version of the LittlEARS® Early Speech Production Questionnaire (LEESPQ) in German-speaking children with normal hearing.

PubMed

Keilmann, Annerose; Friese, Barbara; Lässig, Anne; Hoffmann, Vanessa

2018-04-01

The introduction of neonatal hearing screening and the increasingly early age at which children can receive a cochlear implant has intensified the need for a validated questionnaire to assess the speech production of children aged 0‒18. Such a questionnaire has been created, the LittlEARS ® Early Speech Production Questionnaire (LEESPQ). This study aimed to validate a second, revised edition of the LEESPQ. Questionnaires were returned for 362 children with normal hearing. Completed questionnaires were analysed to determine if the LEESPQ is reliable, prognostically accurate, internally consistent, and if gender or multilingualism affects total scores. Total scores correlated positively with age. The LEESPQ is reliable, accurate, and consistent, and independent of gender or lingual status. A norm curve was created. This second version of the LEESPQ is a valid tool to assess the speech production development of children with normal hearing, aged 0‒18, regardless of their gender. As such, the LEESPQ may be a useful tool to monitor the development of paediatric hearing device users. The second version of the LEESPQ is a valid instrument for assessing early speech production of children aged 0‒18 months.

Auditory Perception, Suprasegmental Speech Processing, and Vocabulary Development in Chinese Preschoolers.

PubMed

Wang, Hsiao-Lan S; Chen, I-Chen; Chiang, Chun-Han; Lai, Ying-Hui; Tsao, Yu

2016-10-01

The current study examined the associations between basic auditory perception, speech prosodic processing, and vocabulary development in Chinese kindergartners, specifically, whether early basic auditory perception may be related to linguistic prosodic processing in Chinese Mandarin vocabulary acquisition. A series of language, auditory, and linguistic prosodic tests were given to 100 preschool children who had not yet learned how to read Chinese characters. The results suggested that lexical tone sensitivity and intonation production were significantly correlated with children's general vocabulary abilities. In particular, tone awareness was associated with comprehensive language development, whereas intonation production was associated with both comprehensive and expressive language development. Regression analyses revealed that tone sensitivity accounted for 36% of the unique variance in vocabulary development, whereas intonation production accounted for 6% of the variance in vocabulary development. Moreover, auditory frequency discrimination was significantly correlated with lexical tone sensitivity, syllable duration discrimination, and intonation production in Mandarin Chinese. Also it provided significant contributions to tone sensitivity and intonation production. Auditory frequency discrimination may indirectly affect early vocabulary development through Chinese speech prosody. © The Author(s) 2016.

Early Action and Gesture "Vocabulary" and Its Relation with Word Comprehension and Production

ERIC Educational Resources Information Center

Caselli, Maria Cristina; Rinaldi, Pasquale; Stefanini, Silvia; Volterra, Virginia

2012-01-01

Data from 492 Italian infants (8-18 months) were collected with the parental questionnaire MacArthur Bates Communicative Development Inventories to describe early actions and gestures (A-G) "vocabulary" and its relation with spoken vocabulary in both comprehension and production. A-G were more strongly correlated with word comprehension…

CD8+ gamma-delta TCR+ and CD4+ T cells produce IFN-γ at 5-7 days after yellow fever vaccination in Indian rhesus macaques, before the induction of classical antigen-specific T cell responses.

PubMed

Neves, Patrícia C C; Rudersdorf, Richard A; Galler, Ricardo; Bonaldo, Myrna C; de Santana, Marlon Gilsepp Veloso; Mudd, Philip A; Martins, Maurício A; Rakasz, Eva G; Wilson, Nancy A; Watkins, David I

2010-11-29

The yellow fever 17D (YF-17D) vaccine is one of the most efficacious vaccines developed to date. Interestingly, vaccination with YF-17D induces IFN-γ production early after vaccination (days 5-7) before the development of classical antigen-specific CD8(+) and CD4(+) T cell responses. Here we investigated the cellular source of this early IFN-γ production. At days 5 and 7 post-vaccination activated CD8(+) gamma-delta TCR T cells produced IFN-γ and TNF-α. Activated CD4(+) T cells produced IFN-γ and TNF-α at day 7 post-vaccination. This early IFN-γ production was also induced after vaccination with recombinant YF-17D (rYF-17D), but was not observed after recombinant Adenovirus type 5 (rAd5) vaccination. Early IFN-γ production, therefore, might be an important aspect of yellow fever vaccination. Copyright © 2010 Elsevier Ltd. All rights reserved.

An Evolutionary History of Oriented Strandboard (OSB)

Treesearch

John I. Zerbe; Zhiyong Cai; George B. Harpole

2015-01-01

To improve wood utilization efficiency, oriented strandboard (OSB) was developed; 80% of the wood removed from the forest can now be processed into marketable products. This manuscript describes the history of developing this most profitable wood product, OSB, and the early FPL contribution in development.

Exploiting mAb structure characteristics for a directed QbD implementation in early process development.

PubMed

Karlberg, Micael; von Stosch, Moritz; Glassey, Jarka

2018-03-07

In today's biopharmaceutical industries, the lead time to develop and produce a new monoclonal antibody takes years before it can be launched commercially. The reasons lie in the complexity of the monoclonal antibodies and the need for high product quality to ensure clinical safety which has a significant impact on the process development time. Frameworks such as quality by design are becoming widely used by the pharmaceutical industries as they introduce a systematic approach for building quality into the product. However, full implementation of quality by design has still not been achieved due to attrition mainly from limited risk assessment of product properties as well as the large number of process factors affecting product quality that needs to be investigated during the process development. This has introduced a need for better methods and tools that can be used for early risk assessment and predictions of critical product properties and process factors to enhance process development and reduce costs. In this review, we investigate how the quantitative structure-activity relationships framework can be applied to an existing process development framework such as quality by design in order to increase product understanding based on the protein structure of monoclonal antibodies. Compared to quality by design, where the effect of process parameters on the drug product are explored, quantitative structure-activity relationships gives a reversed perspective which investigates how the protein structure can affect the performance in different unit operations. This provides valuable information that can be used during the early process development of new drug products where limited process understanding is available. Thus, quantitative structure-activity relationships methodology is explored and explained in detail and we investigate the means of directly linking the structural properties of monoclonal antibodies to process data. The resulting information as a decision tool can help to enhance the risk assessment to better aid process development and thereby overcome some of the limitations and challenges present in QbD implementation today.

The chlorinated AHR ligand 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) promotes reactive oxygen species (ROS) production during embryonic development in the killifish (Fundulus heteroclitus)

USGS Publications Warehouse

Arzuaga, Xabier; Wassenberg, Deena; Giulio, Richard D.; Elskus, Adria

2006-01-01

Exposure to dioxin-like chemicals that activate the aryl hydrocarbon receptor (AHR) can result in increased cellular and tissue production of reactive oxygen species (ROS). Little is known of these effects during early fish development. We used the fish model, Fundulus heteroclitus, to determine if the AHR ligand and pro-oxidant 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) can increase ROS production during killifish development, and to test a novel method for measuring ROS non-invasively in a living organism. The superoxide-sensitive fluorescent dye, dihydroethidium (DHE), was used to detect in ovo ROS production microscopically in developing killifish exposed to PCB126 or vehicle. Both in ovo CYP1A activity (ethoxyresorufin-o-deethylase, EROD) and in ovo ROS were induced by PCB126. In ovo CYP1A activity was inducible by PCB126 concentrations as low as 0.003 nM, with maximal induction occurring at 0.3 nM PCB126. These PCB126 concentrations also significantly increased in ovo ROS production in embryonic liver, ROS being detectable as early as 5 days post-fertilization. These data demonstrate that the pro-oxidant and CYP1A inducer, PCB126, increases both CYP1A activity and ROS production in developing killifish embryos. The superoxide detection assay (SoDA) described in this paper provides a semi-quantitative, easily measured, early indicator of altered ROS production that can be used in conjunction with simultaneous in ovo measurements of CYP1A activity and embryo development to explore functional relationships among biochemical, physiological and developmental responses to AHR ligands.

Development of a Consensus Standard for School Equipment: NSF/NSSEA 380

ERIC Educational Resources Information Center

Breitner, Ashlee

2011-01-01

For many years, the school supplies and equipment industry has investigated methods to ensure product safety and compliance across all its product categories. In early 2010, NSF International and the National School Supply and Equipment Association (NSSEA) came together to develop quality standards for products and equipment designed for use in…

Advancing Early Childhood Development: from Science to Scale 1

PubMed Central

Black, Maureen M; Walker, Susan P; Fernald, Lia C H; Andersen, Christopher T; DiGirolamo, Ann M; Lu, Chunling; McCoy, Dana C; Fink, Günther; Shawar, Yusra R; Shiffman, Prof Jeremy; Devercelli, Amanda E; Wodon, Quentin T; Vargas-Barón, Emily; Grantham-McGregor, Sally

2018-01-01

Early childhood development programmes vary in coordination and quality, with inadequate and inequitable access, especially for children younger than 3 years. New estimates, based on proxy measures of stunting and poverty, indicate that 250 million children (43%) younger than 5 years in low-income and middle-income countries are at risk of not reaching their developmental potential. There is therefore an urgent need to increase multisectoral coverage of quality programming that incorporates health, nutrition, security and safety, responsive caregiving, and early learning. Equitable early childhood policies and programmes are crucial for meeting Sustainable Development Goals, and for children to develop the intellectual skills, creativity, and wellbeing required to become healthy and productive adults. In this paper, the first in a three part Series on early childhood development, we examine recent scientific progress and global commitments to early childhood development. Research, programmes, and policies have advanced substantially since 2000, with new neuroscientific evidence linking early adversity and nurturing care with brain development and function throughout the life course. PMID:27717614

Improving product introduction through effective design reviews.

PubMed

Pelnik, Tammy M

2003-01-01

The design review process is a part of the manufacturer's due diligence in developing a safe and effective product. Design review provides early and on-going independent feedback to developers. By adopting a proactive review process, design improvements can be pursued at an optimum time in the product development effort, i.e., when it will cost less to implement changes and when these changes may have the greatest impact. Effective implementation of the design review requirement will lead to better medical products and improved product introduction results.

The Economics and Psychology of Inequality and Human Development*

PubMed Central

Cunha, Flavio; Heckman, James J.

2009-01-01

Recent research on the economics of human development deepens understanding of the origins of inequality and excellence. It draws on and contributes to personality psychology and the psychology of human development. Inequalities in family environments and investments in children are substantial. They causally affect the development of capabilities. Both cognitive and noncognitive capabilities determine success in life but to varying degrees for different outcomes. An empirically determined technology of capability formation reveals that capabilities are self-productive and cross-fertilizing and can be enhanced by investment. Investments in capabilities are relatively more productive at some stages of a child’s life cycle than others. Optimal child investment strategies differ depending on target outcomes of interest and on the nature of adversity in a child’s early years. For some configurations of early disadvantage and for some desired outcomes, it is efficient to invest relatively more in the later years of childhood than in the early years. PMID:20209045

Early Benchmarks of Product Generation Capabilities of the GOES-R Ground System for Operational Weather Prediction

NASA Astrophysics Data System (ADS)

Kalluri, S. N.; Haman, B.; Vititoe, D.

2014-12-01

The ground system under development for Geostationary Operational Environmental Satellite-R (GOES-R) series of weather satellite has completed a key milestone in implementing the science algorithms that process raw sensor data to higher level products in preparation for launch. Real time observations from GOES-R are expected to make significant contributions to Earth and space weather prediction, and there are stringent requirements to product weather products at very low latency to meet NOAA's operational needs. Simulated test data from all the six GOES-R sensors are being processed by the system to test and verify performance of the fielded system. Early results show that the system development is on track to meet functional and performance requirements to process science data. Comparison of science products generated by the ground system from simulated data with those generated by the algorithm developers show close agreement among data sets which demonstrates that the algorithms are implemented correctly. Successful delivery of products to AWIPS and the Product Distribution and Access (PDA) system from the core system demonstrate that the external interfaces are working.

Bridging the gap

PubMed Central

Mahler, Stephen M; Huang, Edwin P; Chin, David Y; Gray, Peter P

2011-01-01

Therapeutic monoclonal antibodies (mAbs) currently dominate the biologics marketplace. Development of a new therapeutic mAb candidate is a complex, multistep process and early stages of development typically begin in an academic research environment. Recently, a number of facilities and initiatives have been launched to aid researchers along this difficult path and facilitate progression of the next mAb blockbuster. Complementing this, there has been a renewed interest from the pharmaceutical industry to reconnect with academia in order to boost dwindling pipelines and encourage innovation. In this review, we examine the steps required to take a therapeutic mAb from discovery through early stage preclinical development and toward becoming a feasible clinical candidate. Discussion of the technologies used for mAb discovery, production in mammalian cells and innovations in single-use bioprocessing is included. We also examine regulatory requirements for product quality and characterization that should be considered at the earliest stages of mAb development. We provide details on the facilities available to help researchers and small-biotech build value into early stage product development, and include examples from within our own facility of how technologies are utilized and an analysis of our client base. PMID:21822050

Early Implementation of QbD in Biopharmaceutical Development: A Practical Example

PubMed Central

Zurdo, Jesús; Arnell, Andreas; Obrezanova, Olga; Smith, Noel; Gómez de la Cuesta, Ramón; Gallagher, Thomas R. A.; Michael, Rebecca; Stallwood, Yvette; Ekblad, Caroline; Abrahmsén, Lars; Höidén-Guthenberg, Ingmarie

2015-01-01

In drug development, the “onus” of the low R&D efficiency has been put traditionally onto the drug discovery process (i.e., finding the right target or “binding” functionality). Here, we show that manufacturing is not only a central component of product success, but also that, by integrating manufacturing and discovery activities in a “holistic” interpretation of QbD methodologies, we could expect to increase the efficiency of the drug discovery process as a whole. In this new context, early risk assessment, using developability methodologies and computational methods in particular, can assist in reducing risks during development in a cost-effective way. We define specific areas of risk and how they can impact product quality in a broad sense, including essential aspects such as product efficacy and patient safety. Emerging industry practices around developability are introduced, including some specific examples of applications to biotherapeutics. Furthermore, we suggest some potential workflows to illustrate how developability strategies can be introduced in practical terms during early drug development in order to mitigate risks, reduce drug attrition and ultimately increase the robustness of the biopharmaceutical supply chain. Finally, we also discuss how the implementation of such methodologies could accelerate the access of new therapeutic treatments to patients in the clinic. PMID:26075248

Fetal programming in meat production.

PubMed

Du, Min; Wang, Bo; Fu, Xing; Yang, Qiyuan; Zhu, Mei-Jun

2015-11-01

Nutrient fluctuations during the fetal stage affects fetal development, which has long-term impacts on the production efficiency and quality of meat. During the early development, a pool of mesenchymal progenitor cells proliferate and then diverge into either myogenic or adipogenic/fibrogenic lineages. Myogenic progenitor cells further develop into muscle fibers and satellite cells, while adipogenic/fibrogenic lineage cells develop into adipocytes, fibroblasts and resident fibro-adipogenic progenitor cells. Enhancing the proliferation and myogenic commitment of progenitor cells during fetal development enhances muscle growth and lean production in offspring. On the other hand, promoting the adipogenic differentiation of adipogenic/fibrogenic progenitor cells inside the muscle increases intramuscular adipocytes and reduces connective tissue, which improves meat marbling and tenderness. Available studies in mammalian livestock, including cattle, sheep and pigs, clearly show the link between maternal nutrition and the quantity and quality of meat production. Similarly, chicken muscle fibers develop before hatching and, thus, egg and yolk sizes and hatching temperature affect long-term growth performance and meat production of chicken. On the contrary, because fishes are able to generate new muscle fibers lifelong, the impact of early nutrition on fish growth performance is expected to be minor, which requires further studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Direct Capture Technologies for Genomics-Guided Discovery of Natural Products.

PubMed

Chan, Andrew N; Santa Maria, Kevin C; Li, Bo

2016-01-01

Microbes are important producers of natural products, which have played key roles in understanding biology and treating disease. However, the full potential of microbes to produce natural products has yet to be realized; the overwhelming majority of natural product gene clusters encoded in microbial genomes remain "cryptic", and have not been expressed or characterized. In contrast to the fast-growing number of genomic sequences and bioinformatic tools, methods to connect these genes to natural product molecules are still limited, creating a bottleneck in genome-mining efforts to discover novel natural products. Here we review developing technologies that leverage the power of homologous recombination to directly capture natural product gene clusters and express them in model hosts for isolation and structural characterization. Although direct capture is still in its early stages of development, it has been successfully utilized in several different classes of natural products. These early successes will be reviewed, and the methods will be compared and contrasted with existing traditional technologies. Lastly, we will discuss the opportunities for the development of direct capture in other organisms, and possibilities to integrate direct capture with emerging genome-editing techniques to accelerate future study of natural products.

Guidelines for Making a Video Presentation on Early Development.

ERIC Educational Resources Information Center

Cooper, Carolyn S.; And Others

This paper discusses the production of videotape recordings illustrating developmental milestones of early childhood to serve as a reference point in working with parents or staff caring for young children who have disabilities. Procedures for making a video presentation include the following steps: select a topic (such as motor development,…

Effects of microclimate, cropping systems, and irrigation management on early and late blight potential on Russet Burbank potato

USDA-ARS?s Scientific Manuscript database

Soil and irrigation management have been used to optimize crop production. However,their effects on microclimate, development, and controls of potato diseases have not been adequately quantified. The effects of soil, crop, and water management on development of potato early blight and late blight we...

Eco-Efficient Process Improvement at the Early Development Stage: Identifying Environmental and Economic Process Hotspots for Synergetic Improvement Potential.

PubMed

Piccinno, Fabiano; Hischier, Roland; Seeger, Stefan; Som, Claudia

2018-05-15

We present here a new eco-efficiency process-improvement method to highlight combined environmental and costs hotspots of the production process of new material at a very early development stage. Production-specific and scaled-up results for life cycle assessment (LCA) and production costs are combined in a new analysis to identify synergetic improvement potentials and trade-offs, setting goals for the eco-design of new processes. The identified hotspots and bottlenecks will help users to focus on the relevant steps for improvements from an eco-efficiency perspective and potentially reduce their associated environmental impacts and production costs. Our method is illustrated with a case study of nanocellulose. The results indicate that the production route should start with carrot pomace, use heat and solvent recovery, and deactivate the enzymes with bleach instead of heat. To further improve the process, the results show that focus should be laid on the carrier polymer, sodium alginate, and the production of the GripX coating. Overall, the method shows that the underlying LCA scale-up framework is valuable for purposes beyond conventional LCA studies and is applicable at a very early stage to provide researchers with a better understanding of their production process.

Automated Analysis of Child Phonetic Production Using Naturalistic Recordings

ERIC Educational Resources Information Center

Xu, Dongxin; Richards, Jeffrey A.; Gilkerson, Jill

2014-01-01

Purpose: Conventional resource-intensive methods for child phonetic development studies are often impractical for sampling and analyzing child vocalizations in sufficient quantity. The purpose of this study was to provide new information on early language development by an automated analysis of child phonetic production using naturalistic…

Regulatory structures for gene therapy medicinal products in the European Union.

PubMed

Klug, Bettina; Celis, Patrick; Carr, Melanie; Reinhardt, Jens

2012-01-01

Taking into account the complexity and technical specificity of advanced therapy medicinal products: (gene and cell therapy medicinal products and tissue engineered products), a dedicated European regulatory framework was needed. Regulation (EC) No. 1394/2007, the "ATMP Regulation" provides tailored regulatory principles for the evaluation and authorization of these innovative medicines. The majority of gene or cell therapy product development is carried out by academia, hospitals, and small- and medium-sized enterprises (SMEs). Thus, acknowledging the particular needs of these types of sponsors, the legislation also provides incentives for product development tailored to them. The European Medicines Agency (EMA) and, in particular, its Committee for Advanced Therapies (CAT) provide a variety of opportunities for early interaction with developers of ATMPs to enable them to have early regulatory and scientific input. An important tool to promote innovation and the development of new medicinal products by micro-, small-, and medium-sized enterprises is the EMA's SME initiative launched in December 2005 to offer financial and administrative assistance to smaller companies. The European legislation also foresees the involvement of stakeholders, such as patient organizations, in the development of new medicines. Considering that gene therapy medicinal products are developed in many cases for treatment of rare diseases often of monogenic origin, the involvement of patient organizations, which focus on rare diseases and genetic and congenital disorders, is fruitful. Two such organizations are represented in the CAT. Research networks play another important role in the development of gene therapy medicinal products. The European Commission is funding such networks through the EU Sixth Framework Program. Copyright © 2012 Elsevier Inc. All rights reserved.

Early and late blight potential on Russet Burbank potato as affected by microclimate, cropping systems and irrigation management in North-eastern United States

USDA-ARS?s Scientific Manuscript database

Soil and irrigation management have been used to optimize crop production; however,their effects on microclimate, development, and potato diseases have not been adequately quantified. The effects of soil, crop, and water management on development of potato early blight and late blight were quantifie...

Estimating millet production for famine early warning: An application of crop simulation modelling using satellite and ground-based data in Burkina Faso

USGS Publications Warehouse

Thornton, P. K.; Bowen, W. T.; Ravelo, A.C.; Wilkens, P. W.; Farmer, G.; Brock, J.; Brink, J. E.

1997-01-01

Early warning of impending poor crop harvests in highly variable environments can allow policy makers the time they need to take appropriate action to ameliorate the effects of regional food shortages on vulnerable rural and urban populations. Crop production estimates for the current season can be obtained using crop simulation models and remotely sensed estimates of rainfall in real time, embedded in a geographic information system that allows simple analysis of simulation results. A prototype yield estimation system was developed for the thirty provinces of Burkina Faso. It is based on CERES-Millet, a crop simulation model of the growth and development of millet (Pennisetum spp.). The prototype was used to estimate millet production in contrasting seasons and to derive production anomaly estimates for the 1986 season. Provincial yields simulated halfway through the growing season were generally within 15% of their final (end-of-season) values. Although more work is required to produce an operational early warning system of reasonable credibility, the methodology has considerable potential for providing timely estimates of regional production of the major food crops in countries of sub-Saharan Africa.

EARLY FLOWERING3 Regulates Flowering in Spring Barley by Mediating Gibberellin Production and FLOWERING LOCUS T Expression[C][W

PubMed Central

Boden, Scott A.; Weiss, David; Ross, John J.; Davies, Noel W.; Trevaskis, Ben; Chandler, Peter M.; Swain, Steve M.

2014-01-01

EARLY FLOWERING3 (ELF3) is a circadian clock gene that contributes to photoperiod-dependent flowering in plants, with loss-of-function mutants in barley (Hordeum vulgare), legumes, and Arabidopsis thaliana flowering early under noninductive short-day (SD) photoperiods. The barley elf3 mutant displays increased expression of FLOWERING LOCUS T1 (FT1); however, it remains unclear whether this is the only factor responsible for the early flowering phenotype. We show that the early flowering and vegetative growth phenotypes of the barley elf3 mutant are strongly dependent on gibberellin (GA) biosynthesis. Expression of the central GA biosynthesis gene, GA20oxidase2, and production of the bioactive GA, GA1, were significantly increased in elf3 leaves under SDs, relative to the wild type. Inhibition of GA biosynthesis suppressed the early flowering of elf3 under SDs independently of FT1 and was associated with altered expression of floral identity genes at the developing apex. GA is also required for normal flowering of spring barley under inductive photoperiods, with chemical and genetic attenuation of the GA biosynthesis and signaling pathways suppressing inflorescence development under long-day conditions. These findings illustrate that GA is an important floral promoting signal in barley and that ELF3 suppresses flowering under noninductive photoperiods by blocking GA production and FT1 expression. PMID:24781117

Early Vocal Development in Autism Spectrum Disorder, Rett Syndrome, and Fragile X Syndrome: Insights from Studies using Retrospective Video Analysis.

PubMed

Roche, Laura; Zhang, Dajie; Bartl-Pokorny, Katrin D; Pokorny, Florian B; Schuller, Björn W; Esposito, Gianluca; Bölte, Sven; Roeyers, Herbert; Poustka, Luise; Gugatschka, Markus; Waddington, Hannah; Vollmann, Ralf; Einspieler, Christa; Marschik, Peter B

2018-03-01

This article provides an overview of studies assessing the early vocalisations of children with autism spectrum disorder (ASD), Rett syndrome (RTT), and fragile X syndrome (FXS) using retrospective video analysis (RVA) during the first two years of life. Electronic databases were systematically searched and a total of 23 studies were selected. These studies were then categorised according to whether children were later diagnosed with ASD (13 studies), RTT (8 studies), or FXS (2 studies), and then described in terms of (a) participant characteristics, (b) control group characteristics, (c) video footage, (d) behaviours analysed, and (e) main findings. This overview supports the use of RVA in analysing the early development of vocalisations in children later diagnosed with ASD, RTT or FXS, and provides an in-depth analysis of vocalisation presentation, complex vocalisation production, and the rate and/or frequency of vocalisation production across the three disorders. Implications are discussed in terms of extending crude vocal analyses to more precise methods that might provide more powerful means by which to discriminate between disorders during early development. A greater understanding of the early manifestation of these disorders may then lead to improvements in earlier detection.

Exercise training improves in vivo endothelial repair capacity of early endothelial progenitor cells in subjects with metabolic syndrome.

PubMed

Sonnenschein, Kristina; Horváth, Tibor; Mueller, Maja; Markowski, Andrea; Siegmund, Tina; Jacob, Christian; Drexler, Helmut; Landmesser, Ulf

2011-06-01

Endothelial dysfunction and injury are considered to contribute considerably to the development and progression of atherosclerosis. It has been suggested that intense exercise training can increase the number and angiogenic properties of early endothelial progenitor cells (EPCs). However, whether exercise training stimulates the capacity of early EPCs to promote repair of endothelial damage and potential underlying mechanisms remain to be determined. The present study was designed to evaluate the effects of moderate exercise training on in vivo endothelial repair capacity of early EPCs, and their nitric oxide and superoxide production as characterized by electron spin resonance spectroscopy analysis in subjects with metabolic syndrome. Twenty-four subjects with metabolic syndrome were randomized to an 8 weeks exercise training or a control group. Superoxide production and nitric oxide (NO) availability of early EPCs were characterized by using electron spin resonance (ESR) spectroscopy analysis. In vivo endothelial repair capacity of EPCs was examined by transplantation into nude mice with defined carotid endothelial injury. Endothelium-dependent, flow-mediated vasodilation was analysed using high-resolution ultrasound. Importantly, exercise training resulted in a substantially improved in vivo endothelial repair capacity of early EPCs (24.0 vs 12.7%; p < 0.05) and improved endothelium-dependent vasodilation. Nitric oxide production of EPCs was substantially increased after exercise training, but not in the control group. Moreover, exercise training reduced superoxide production of EPCs, which was not observed in the control group. The present study suggests for the first time that moderate exercise training increases nitric oxide production of early endothelial progenitor cells and reduces their superoxide production. Importantly, this is associated with a marked beneficial effect on the in vivo endothelial repair capacity of early EPCs in subjects with metabolic syndrome.

The Introduction and Early Use of Lithography in the United States.

ERIC Educational Resources Information Center

Barnhill, Georgia B.

This paper discusses the use of lithography in the United States in the early 1800s. Highlights include: the development of lithography in Germany between 1796 and 1798; early expectations for lithography; competition against the existing technology for the production of images--relief prints and copper-plate engravings; examples of 18th-century…

Mandibular Motor Control during the Early Development of Speech and Nonspeech Behaviors

ERIC Educational Resources Information Center

Steeve, Roger W.; Moore, Christopher A.

2009-01-01

Purpose: The mandible is often portrayed as a primary structure of early babble production, but empiricists still need to specify (a) how mandibular motor control and kinematics vary among different types of multisyllabic babble, (b) whether chewing or jaw oscillation relies on a coordinative infrastructure that can be exploited for early types of…

Miami Valley ITS : early deployment plan : final user service plan

DOT National Transportation Integrated Search

1997-07-01

This User Service Plan is the first major product of the process to develop an Intelligent Transportation System (ITS) Early Deployment Plan (EDP) for the Miami Valley. This User Service Plan documents the travel environment, growth trends and transp...

Constructing the 'Best' Reliability Data for the Job - Developing Generic Reliability Data from Alternative Sources Early in a Product's Development Phase

NASA Technical Reports Server (NTRS)

Kleinhammer, Roger K.; Graber, Robert R.; DeMott, D. L.

2016-01-01

Reliability practitioners advocate getting reliability involved early in a product development process. However, when assigned to estimate or assess the (potential) reliability of a product or system early in the design and development phase, they are faced with lack of reasonable models or methods for useful reliability estimation. Developing specific data is costly and time consuming. Instead, analysts rely on available data to assess reliability. Finding data relevant to the specific use and environment for any project is difficult, if not impossible. Instead, analysts attempt to develop the "best" or composite analog data to support the assessments. Industries, consortia and vendors across many areas have spent decades collecting, analyzing and tabulating fielded item and component reliability performance in terms of observed failures and operational use. This data resource provides a huge compendium of information for potential use, but can also be compartmented by industry, difficult to find out about, access, or manipulate. One method used incorporates processes for reviewing these existing data sources and identifying the available information based on similar equipment, then using that generic data to derive an analog composite. Dissimilarities in equipment descriptions, environment of intended use, quality and even failure modes impact the "best" data incorporated in an analog composite. Once developed, this composite analog data provides a "better" representation of the reliability of the equipment or component. It can be used to support early risk or reliability trade studies, or analytical models to establish the predicted reliability data points. It also establishes a baseline prior that may updated based on test data or observed operational constraints and failures, i.e., using Bayesian techniques. This tutorial presents a descriptive compilation of historical data sources across numerous industries and disciplines, along with examples of contents and data characteristics. It then presents methods for combining failure information from different sources and mathematical use of this data in early reliability estimation and analyses.

Mass spectrometry-driven drug discovery for development of herbal medicine.

PubMed

Zhang, Aihua; Sun, Hui; Wang, Xijun

2018-05-01

Herbal medicine (HM) has made a major contribution to the drug discovery process with regard to identifying products compounds. Currently, more attention has been focused on drug discovery from natural compounds of HM. Despite the rapid advancement of modern analytical techniques, drug discovery is still a difficult and lengthy process. Fortunately, mass spectrometry (MS) can provide us with useful structural information for drug discovery, has been recognized as a sensitive, rapid, and high-throughput technology for advancing drug discovery from HM in the post-genomic era. It is essential to develop an efficient, high-quality, high-throughput screening method integrated with an MS platform for early screening of candidate drug molecules from natural products. We have developed a new chinmedomics strategy reliant on MS that is capable of capturing the candidate molecules, facilitating their identification of novel chemical structures in the early phase; chinmedomics-guided natural product discovery based on MS may provide an effective tool that addresses challenges in early screening of effective constituents of herbs against disease. This critical review covers the use of MS with related techniques and methodologies for natural product discovery, biomarker identification, and determination of mechanisms of action. It also highlights high-throughput chinmedomics screening methods suitable for lead compound discovery illustrated by recent successes. © 2016 Wiley Periodicals, Inc.

Characteristics of rare disease marketing applications associated with FDA product approvals 2006-2010.

PubMed

Pariser, Anne R; Slack, Daniel J; Bauer, Larry J; Warner, Catherine A; Tracy, LaRee A

2012-08-01

New drug and biologic product marketing applications submitted to FDA's Center for Drug Evaluation and Research (CDER) between 2006 and 2010 were analyzed to identify rare disease application characteristics associated with higher approval rates. The results show that approval rates were similar for rare and common disease applications. Larger company size, prior regulatory experience and priority review designation were associated with higher approval rates. The study findings show that rare disease product development is feasible, and increased interactions between product developers and FDA in early investigational phases can facilitate product development. Published by Elsevier Ltd.

Early identification systems for emerging foodborne hazards.

PubMed

Marvin, H J P; Kleter, G A; Prandini, A; Dekkers, S; Bolton, D J

2009-05-01

This paper provides a non-exhausting overview of early warning systems for emerging foodborne hazards that are operating in the various places in the world. Special attention is given to endpoint-focussed early warning systems (i.e. ECDC, ISIS and GPHIN) and hazard-focussed early warning systems (i.e. FVO, RASFF and OIE) and their merit to successfully identify a food safety problem in an early stage is discussed. Besides these early warning systems which are based on monitoring of either disease symptoms or hazards, also early warning systems and/or activities that intend to predict the occurrence of a food safety hazard in its very beginning of development or before that are described. Examples are trend analysis, horizon scanning, early warning systems for mycotoxins in maize and/or wheat and information exchange networks (e.g. OIE and GIEWS). Furthermore, recent initiatives that aim to develop predictive early warning systems based on the holistic principle are discussed. The assumption of the researchers applying this principle is that developments outside the food production chain that are either directly or indirectly related to the development of a particular food safety hazard may also provide valuable information to predict the development of this hazard.

RADC (Rome Air Development Center) Guide to Environmental Stress Screening

DTIC Science & Technology

1986-08-01

and the processes which are used in their manufacture. ESS is the vehicle by which latent defects are accelerated to early failure in the factory. ESS...structured as part of a production 2 reliability assurance program, is the vehicle through which product reliability in manufacture can be maintained...mechanical, electrical and/or thermal stresses to an equipment item for the purpose of precipitating latent part and workmanship defects to early failure

Multiclausal Utterances Aren't Just for Big Kids: A Framework for Analysis of Complex Syntax Production in Spoken Language of Preschool- and Early School-Age Children

ERIC Educational Resources Information Center

Arndt, Karen Barako; Schuele, C. Melanie

2013-01-01

Complex syntax production emerges shortly after the emergence of two-word combinations in oral language and continues to develop through the school-age years. This article defines a framework for the analysis of complex syntax in the spontaneous language of preschool- and early school-age children. The purpose of this article is to provide…

A Multilevel Study of Partnership Building to Support Early Childhood Development across Different Education Contexts

ERIC Educational Resources Information Center

Wang, Jianjun; Ortiz, Theresa; Maier, Roland; Navarro, Diana

2015-01-01

First five years are identified as a critical period of child growth in scientific literature. In 1998, California voters passed Proposition 10 that appropriated a 50 cent per pack tax on cigarettes and other tobacco products to support early childhood development. As a result, Kern County Children and Families Commission administered over $10…

Connecting Neurons, Concepts, and People: Brain Development and Its Implications. Preschool Policy Brief. Issue 17

ERIC Educational Resources Information Center

Thompson, Ross A.

2008-01-01

The past decade has seen an upsurge in public understanding of early brain development. News reports, statements by policymakers, and commercial marketing of products for infants and young children have all contributed to a widespread understanding of the explosive growth of the brain in the early years and that stimulation acts as a catalyst to…

A regional study of loblolly pine plantation development through 15 years after early complete woody and herbaceous plant control (COMP)

Treesearch

James H. Miller; B.R. Zutter; S.M Zedaker; M.B. Edwards; R.A. Newbold

2002-01-01

Pine plantations are increasingly cultured using early woody and/or herbaceous plant control. Developments in sustainable cultural practices are hindered by the absence of long-term data on productivity gains relative to competition levels, crop-competition dynamics, and compositional succession. To gain baseline data, this study examined loblolly pine (Pinus...

Early assessment of medical technologies to inform product development and market access: a review of methods and applications.

PubMed

Ijzerman, Maarten J; Steuten, Lotte M G

2011-09-01

Worldwide, billions of dollars are invested in medical product development and there is an increasing pressure to maximize the revenues of these investments. That is, governments need to be informed about the benefits of spending public resources, companies need more information to manage their product development portfolios and even universities may need to direct their research programmes in order to maximize societal benefits. Assuming that all medical products need to be adopted by the heavily regulated healthcare market at one point in time, it is worthwhile to look at the logic behind healthcare decision making, specifically, decisions on the coverage of medical products and decisions on the use of these products under competing and uncertain conditions. With the growing tension between leveraging economic growth through R&D spending on the one hand and stricter control of healthcare budgets on the other, several attempts have been made to apply the health technology assessment (HTA) methodology to earlier stages of technology development and implementation. For instance, horizon scanning was introduced to systematically assess emerging technologies in order to inform health policy. Others have introduced iterative economic evaluation, e.g. economic evaluations in earlier stages of clinical research. However, most of these methods are primarily intended to support governments in making decisions regarding potentially expensive new medical products. They do not really inform biomedical product developers on the probability of return on investment, nor do they inform about the market needs and specific requirements of technologies in development. It is precisely this aspect that increasingly receives attention, i.e. is it possible to use HTA tools and methods to inform biomedical product development and to anticipate further development and market access. Several methods have been used in previous decades, but have never been compiled in a comprehensive review. The main objective of this article was to provide an overview of previous work and methods in the field of early HTA, and to put these approaches in perspective through a conceptual framework introduced in this paper. A particular goal of the review was to familiarize decision makers with available techniques that can be employed in early-stage decision making, and to identify opportunities for further methodological growth in this emerging field of HTA.

Buffering boys and boosting girls: The protective and promotive effects of Early Head Start for children’s expressive language in the context of parenting stress

PubMed Central

Vallotton, C. D.; Harewood, T.; Ayoub, C. A.; Pan, B.; Mastergeorge, A. M.; Brophy-Herb, H.

2011-01-01

Children’s characteristics, including gender, influence their development by eliciting differential responses from their environments, and by influencing differential responses to their environments. Parenting-related stress, associated with poverty environments, negatively influences children’s language, likely through its impact on parent-child interactions, but may impact boys’ and girls’ development differently. Early intervention represents one tool for supporting development in at-risk toddlers, but gender-differences in effects of intervention are rarely described. The current studies assessed the effects of Early Head Start (EHS) on children’s productive vocabulary in the context of parenting stress and examined gender differences in program effects on vocbulary. Data were from the national EHS Research and Evaluation (EHSRE) study (Study 1, N = 3,001), and from a dataset associated with one EHSRE site (Study 2, N = 146) where additional data on productive vocabulary were collected. Study 1 found that at 24 months of age, the EHS program protected girls’ productive vocabulary from the negative effects of parenting stress, but had little impact on boys’ vocabulary. In Study 2, the local EHS site promoted girls’ vocabulary development over time from 14 to 36 months despite the negative effects of parenting stress, and protected boys’ vocabulary from the negative parenting stress effects. These results suggest differential ways in which at-risk toddlers are affected by early intervention. PMID:23166405

Regulatory/Scientific Supports for Micro-, Small-, and Medium-Sized Enterprises (SMEs) With Medicinal Products Provided by the PMDA and EMA.

PubMed

Kondo, Hideyuki; Shibatsuji, Masayoshi; Yasuda, Naoyuki

2018-01-01

Micro-, small-, and medium-sized enterprises (SMEs) have been considered as key players who can bring innovative medicinal products and/or technologies into the field. However, they may need much regulatory/scientific supports to provide their products, technologies, or services to the market in a timely way. Both the Pharmaceuticals and Medical Devices Agency (PMDA) and the European Medicines Agency (EMA), regulatory authorities for medicinal products in Japan and the EU, respectively, have prepared supportive measures for SMEs from the early phase of product/technology development to the postmarketing phase. With respect to supports for SMEs, both agencies have provided similar SME-specific supportive activities, including routine administrative assistance, consultations about product development strategy from an early phase, as well as specific regulatory/scientific issues and fee incentives. In addition, there is a system to register SME status in the EU, which can be a tool for regulators to know how much potential SME-driven activities have and with whom they should communicate to provide necessary supports. Furthermore, as new technologies and novel products from SMEs are not limited to the region where they are developed, close communication about these topics between the PMDA and the EMA will contribute to advancing patients' access to necessary medicinal products.

Early zebrafish development: It’s in the maternal genes

PubMed Central

Abrams, Elliott W.; Mullins, Mary C.

2009-01-01

Summary The earliest stages of embryonic development in all animals examined rely on maternal gene products that are generated during oogenesis and supplied to the egg. The period of maternal control of embryonic development varies among animals according to the onset of zygotic transcription and the persistence of maternal gene products. This maternal regulation has been little studied in vertebrates, due to the difficulty in manipulating maternal gene function and lack of basic molecular information. However, recent maternal-effect screens in the zebrafish have generated more than 40 unique mutants that are providing new molecular entry points to the maternal control of early vertebrate development. Here we discuss recent studies of 12 zebrafish mutant genes that illuminate the maternal molecular controls on embryonic development, including advances in the regulation of animal-vegetal polarity, egg activation, cleavage development, body plan formation, tissue morphogenesis, microRNA function and germ cell development. PMID:19608405

Early decision-analytic modeling - a case study on vascular closure devices.

PubMed

Brandes, Alina; Sinner, Moritz F; Kääb, Stefan; Rogowski, Wolf H

2015-10-27

As economic considerations become more important in healthcare reimbursement, decisions about the further development of medical innovations need to take into account not only medical need and potential clinical effectiveness, but also cost-effectiveness. Already early in the innovation process economic evaluations can support decisions on development in specific indications or patient groups by anticipating future reimbursement and implementation decisions. One potential concept for early assessment is value-based pricing. The objective is to assess the feasibility of value-based pricing and product design for a hypothetical vascular closure device in the pre-clinical stage which aims at decreasing bleeding events. A deterministic decision-analytic model was developed to estimate the cost-effectiveness of established vascular closure devices from the perspective of the Statutory Health Insurance system. To identify early benchmarks for pricing and product design, three strategies of determining the product's value are explored: 1) savings from complications avoided by the new device; 2) valuation of the avoided complications based on an assumed willingness-to-pay-threshold (the efficiency frontier approach); 3) value associated with modifying the care pathways within which the device would be applied. Use of established vascular closure devices is dominated by manual compression. The hypothetical vascular closure device reduces overall complication rates at higher costs than manual compression. Maximum cost savings of only about €4 per catheterization could be realized by applying the hypothetical device. Extrapolation of an efficiency frontier is only possible for one subgroup where vascular closure devices are not a dominated strategy. Modifying care in terms of same-day discharge of patients treated with vascular closure devices could result in cost savings of €400-600 per catheterization. It was partially feasible to calculate value-based prices for the novel closure device which can be used to inform product design. However, modifying the care pathway may generate much more value from the payers' perspective than modifying the device per se. Manufacturers should thus explore the feasibility of combining reimbursement of their product with arrangements that make same-day discharge attractive also for hospitals. Due to the early nature of the product, the results are afflicted with substantial uncertainty.

Spatiotemporal transcriptome provides insights into early fruit development of tomato (Solanum lycopersicum).

PubMed

Zhang, Shuaibin; Xu, Meng; Qiu, Zhengkun; Wang, Ketao; Du, Yongchen; Gu, Lianfeng; Cui, Xia

2016-03-18

Early fruit development is crucial for crop production in tomato. After fertilization, the ovary undergoes cell division and cell expansion before maturation. Although the roles of regulatory signals such as hormone and carbohydrate during early fruit development have been studied, the spatial distribution and the sequential initiation of these regulatory signals still need to be explored. Using the tomato cultivar 'Moneymaker', we analyzed the transcriptome of the ovule and the ovary wall/pericarp dissected from four different stages of the early developing fruits by stereoscope. These datasets give us the whole picture about the spatial and temporal signal distribution in early development of ovule and pericarp. Our results indicate that the hormone signal was initiated in both ovule and pericarp after fertilization. After that, different signals were activated in ovule and pericarp due to their distinct developmental processes. Our study provides spatiotemporal regulatory landscape of gene expression with sequential information which was not studied by previous work and further strengthens the comprehension of the regulatory and metabolic events controlling early fruit development.

Early rationality in action perception and production? A theoretical exposition.

PubMed

Paulus, Markus; Király, Ildikó

2013-10-01

Within recent years, the question of early rationality in action perception and production has become a topic of great interest in developmental psychology. On the one hand, studies have provided evidence for rational action perception and action imitation even in very young infants. On the other hand, scholars have recently questioned these interpretations and proposed that the ability to rationally evaluate actions is not yet in place in infancy. Others have examined the development of the ability to make rational action choices and have indicated limitations of young children's ability to act rationally. This editorial to the special issue on Early Rationality in Action Perception and Production? introduces the reader to the current debate. It elucidates the underlying theoretical assumptions that drive the debate on whether or not young children's action perception and production is rational. Finally, it summarizes the papers and their contributions to the theoretical debate. Copyright © 2013 Elsevier Inc. All rights reserved.

48 CFR 48.104-1 - Determining sharing period.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., based on planning and programming or production documentation at the time the VECP is accepted. The.... (c) For engineering-development contracts and contracts containing low-rate-initial-production or early production units, the end of the sharing period is based not on a calendar date, but on acceptance...

48 CFR 48.104-1 - Determining sharing period.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., based on planning and programming or production documentation at the time the VECP is accepted. The.... (c) For engineering-development contracts and contracts containing low-rate-initial-production or early production units, the end of the sharing period is based not on a calendar date, but on acceptance...

48 CFR 48.104-1 - Determining sharing period.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., based on planning and programming or production documentation at the time the VECP is accepted. The.... (c) For engineering-development contracts and contracts containing low-rate-initial-production or early production units, the end of the sharing period is based not on a calendar date, but on acceptance...

48 CFR 48.104-1 - Determining sharing period.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., based on planning and programming or production documentation at the time the VECP is accepted. The.... (c) For engineering-development contracts and contracts containing low-rate-initial-production or early production units, the end of the sharing period is based not on a calendar date, but on acceptance...

The French-Farsi Simultaneous Early Bilingualism in an Iranian Child--Study on the Regularity of the Presence of the Minority Language in the First Lexical Productions of a Bilingual Child

ERIC Educational Resources Information Center

Jalilian, Sahar; Rahmatian, Rouhollah; Safa, Parivash; Letafati, Roya

2017-01-01

In a simultaneous bilingual education, there are many factors that can affect its success, primarily the age of the child and socio-cognitive elements. This phenomenon can be initially studied in the first lexical productions of either language in a child. The present study focuses on the early lexical developments of a child, who lives in the…

Synthesizing Graphene Production with Polymeric Injection Molding for Enhancing EMI Shielding Effectiveness of Plastics

DTIC Science & Technology

2017-09-01

Ulrich, Karl T., and Steven D. Eppinger. 2012. Product Design and Development, 5th ed. New York: McGraw-Hill Irwin. Warner, Jamie H., Franziska Schaffel...of tasks that an organization or business generally follows to transform a thought or idea of a product to a manufactured good. In the early stages...established product design and development processes. Karl Ulrich and Steven Eppinger (2012) state that one of the initial steps in the opportunity

Deciphering early events involved in hyperosmotic stress-induced programmed cell death in tobacco BY-2 cells.

PubMed

Monetti, Emanuela; Kadono, Takashi; Tran, Daniel; Azzarello, Elisa; Arbelet-Bonnin, Delphine; Biligui, Bernadette; Briand, Joël; Kawano, Tomonori; Mancuso, Stefano; Bouteau, François

2014-03-01

Hyperosmotic stresses represent one of the major constraints that adversely affect plants growth, development, and productivity. In this study, the focus was on early responses to hyperosmotic stress- (NaCl and sorbitol) induced reactive oxygen species (ROS) generation, cytosolic Ca(2+) concentration ([Ca(2+)]cyt) increase, ion fluxes, and mitochondrial potential variations, and on their links in pathways leading to programmed cell death (PCD). By using BY-2 tobacco cells, it was shown that both NaCl- and sorbitol-induced PCD seemed to be dependent on superoxide anion (O2·(-)) generation by NADPH-oxidase. In the case of NaCl, an early influx of sodium through non-selective cation channels participates in the development of PCD through mitochondrial dysfunction and NADPH-oxidase-dependent O2·(-) generation. This supports the hypothesis of different pathways in NaCl- and sorbitol-induced cell death. Surprisingly, other shared early responses, such as [Ca(2+)]cyt increase and singlet oxygen production, do not seem to be involved in PCD.

The early phase of /see symbol/ production development in adult Japanese learners of English.

PubMed

Saito, Kazuya; Munro, Murray J

2014-12-01

Although previous research indicates that Japanese speakers' second language (L2) perception and production of English /see symbol/ may improve with increased L2 experience, relatively little is known about the fine phonetic details of their /see symbol/ productions, especially during the early phase of L2 speech learning. This cross-sectional study examined acoustic properties of word-initial /see symbol/ from 60 Japanese learners with a length of residence of between one month and one year in Canada. Their performance was compared to that of 15 native speakers of English and 15 low-proficiency Japanese learners of English. Formant frequencies (F2 and F3) and F1 transition durations were evaluated under three task conditions--word reading, sentence reading, and timed picture description. Learners with as little as two to three months of residence demonstrated target-like F2 frequencies. In addition, increased LOR was predictive of more target-like transition durations. Although the learners showed some improvement in F3 as a function of LOR, they did so mainly at a controlled level of speech production. The findings suggest that during the early phase of L2 segmental development, production accuracy is task-dependent and is influenced by the availability of L1 phonetic cues for redeployment in L2.

Early deictic but not other gestures predict later vocabulary in both typical development and autism.

PubMed

Özçalışkan, Şeyda; Adamson, Lauren B; Dimitrova, Nevena

2016-08-01

Research with typically developing children suggests a strong positive relation between early gesture use and subsequent vocabulary development. In this study, we ask whether gesture production plays a similar role for children with autism spectrum disorder. We observed 23 18-month-old typically developing children and 23 30-month-old children with autism spectrum disorder interact with their caregivers (Communication Play Protocol) and coded types of gestures children produced (deictic, give, conventional, and iconic) in two communicative contexts (commenting and requesting). One year later, we assessed children's expressive vocabulary, using Expressive Vocabulary Test. Children with autism spectrum disorder showed significant deficits in gesture production, particularly in deictic gestures (i.e. gestures that indicate objects by pointing at them or by holding them up). Importantly, deictic gestures-but not other gestures-predicted children's vocabulary 1 year later regardless of communicative context, a pattern also found in typical development. We conclude that the production of deictic gestures serves as a stepping-stone for vocabulary development. © The Author(s) 2015.

[Relevant factors of early puberty timing in urban primary schools in Chongqing].

PubMed

Luo, Yan; Liu, Qin; Wen, Yi; Liu, Shudan; Lei, Xun; Wang, Hong

2016-05-01

To investigate the status of puberty timing and relevant factors of early puberty timing in children from grade one to four in urban primary schools of Chongqing. According to the purposive sample method, four urban primary schools in Chongqing were selected and of which 1471 children from grade one to four who have obtained informed consent were recruited. Questionnaire survey on social-demographic characteristics and family environment (e.g., age, parents' relationship, diet and lifestyle, etc), and Pubertal Development Scale (PDS) survey and physical examination (measurements of height, weight, pubertal development status, etc) were conducted. P25, P50, P75 ages of each important pubertal event were calculated by probit regression. Univariate and multivariate analysis were used to analyze relevant factors. The detection rate of early puberty timing was 17.7%, and the median ages of the onset of breast and testicular development were 10.77 and 11.48 years old, respectively. Multivariate logistic regression showed that early puberty timing occurred more likely in girls than in boys (OR = 0.561, 95% CI 0.406-0.774), and bad relationship between parents (OR = 1.320, 95% CI 1.007-1.729) and hair-products-use (OR = 1.685, 95%, CI 1.028-2.762) were risk factors of early puberty timing. Early onset of puberty in urban Chongqing is still exist. Gender, parents' relationship, and hair-products-use have an essential impact on early puberty timing.

A Discrepancy in Comprehension and Production in Early Language Development in ASD: Is it Clinically Relevant?

PubMed

Davidson, Meghan M; Ellis Weismer, Susan

2017-07-01

This study examined the extent to which a discrepant comprehension-production profile (i.e., relatively more delayed comprehension than production) is characteristic of the early language phenotype in autism spectrum disorders (ASD) and tracked the developmental progression of the profile. Our findings indicated that a discrepant comprehension-production profile distinguished toddlers (30 months) with ASD from late talkers without ASD (91% sensitivity, 100% specificity) in groups that were comparable on expressive language, age, and socioeconomic status. Longitudinal data for children with ASD revealed that the discrepant profile steadily decreased from 30 to 44 months until there was no significant comprehension-production difference at 66 months. In conclusion, results suggest that lower comprehension than production may be an age-specific marker of toddlers with ASD.

Potential economic value of drought information to support early warning in Africa

NASA Astrophysics Data System (ADS)

Quiroga, S.; Iglesias, A.; Diz, A.; Garrote, L.

2012-04-01

We present a methodology to estimate the economic value of advanced climate information for food production in Africa under climate change scenarios. The results aim to facilitate better choices in water resources management. The methodology includes 4 sequential steps. First two contrasting management strategies (with and without early warning) are defined. Second, the associated impacts of the management actions are estimated by calculating the effect of drought in crop productivity under climate change scenarios. Third, the optimal management option is calculated as a function of the drought information and risk aversion of potential information users. Finally we use these optimal management simulations to compute the economic value of enhanced water allocation rules to support stable food production in Africa. Our results show how a timely response to climate variations can help reduce loses in food production. The proposed framework is developed within the Dewfora project (Early warning and forecasting systems to predict climate related drought vulnerability and risk in Africa) that aims to improve the knowledge on drought forecasting, warning and mitigation, and advance the understanding of climate related vulnerability to drought and to develop a prototype operational forecasting.

Toward a Survivability/Lethality Analysis Directorate (SLAD) Methodology for Conducting System of Systems Analysis (SoSA)

DTIC Science & Technology

2011-06-01

alternative technologies early in the product life cycle. Use case 3 reflects SLAD’s response to changes in the way the Army acquires technical...development on the one hand, and to systems evaluated for production and deployment on the other. Together, these three use cases provide the Army...Package E x a m p le P ro b le m Mission based SLVA of networked-enabled small units subject to one or more threats. Mission based early

The Framework for Life Cycle Cost Management,

DTIC Science & Technology

1982-01-01

in the early phases of system development before full- scale development and initial production, O&S cost projections are too un- certain to...Ensure that each increment of cost and schedule investment in R&M contributes significantly to the above objectives. DoDD 5000.40, Reliability and...Major systems are characterized by large investments of time and resources in the uncertain periods of development, production, and deployment and in

Low adiposity during early infancy is associated with a low risk for developing dengue hemorrhagic fever: a preliminary model.

PubMed

Libraty, Daniel H; Zhang, Lei; Woda, Marcia; Giaya, Kris; Kathivu, Chido Loveness; Acosta, Luz P; Tallo, Veronica; Segubre-Mercado, Edelwisa; Bautista, Analisa; Obcena, AnaMae; Brion, Job D; Capeding, Rosario Z

2014-01-01

Dengue virus (DENV) infections range from asymptomatic or mild illness to a severe and potentially life threatening disease, dengue hemorrhagic fever (DHF). DHF occurs in primary DENV infections during early infancy. A prospective clinical study of DENV infections during infancy was conducted in San Pablo, Philippines. We found that infants who developed DHF with a primary DENV infection had higher WHO weight-for-age z scores before and at the time of infection compared to infants with primary DENV infections who did not develop DHF. In addition, TLR 7/8-stimulated tumor necrosis factor-α (TNF-α) production from myeloid-derived cells was higher among well-nourished infants. Leptin augmented TLR 7/8-mediated TNF-α production in monocytes and decreased intracellular cAMP levels. Circulating leptin levels were elevated during early infancy and correlated with WHO weight-for-age z scores. Our data support a plausible hypothesis as to why well-nourished infants are at risk for developing DHF with their first DENV infection.

Low Adiposity during Early Infancy Is Associated with a Low Risk for Developing Dengue Hemorrhagic Fever: A Preliminary Model

PubMed Central

Libraty, Daniel H.; Zhang, Lei; Woda, Marcia; Giaya, Kris; Kathivu, Chido Loveness; Acosta, Luz P.; Tallo, Veronica; Segubre-Mercado, Edelwisa; Bautista, Analisa; Obcena, AnaMae; Brion, Job D.; Capeding, Rosario Z.

2014-01-01

Dengue virus (DENV) infections range from asymptomatic or mild illness to a severe and potentially life threatening disease, dengue hemorrhagic fever (DHF). DHF occurs in primary DENV infections during early infancy. A prospective clinical study of DENV infections during infancy was conducted in San Pablo, Philippines. We found that infants who developed DHF with a primary DENV infection had higher WHO weight-for-age z scores before and at the time of infection compared to infants with primary DENV infections who did not develop DHF. In addition, TLR 7/8-stimulated tumor necrosis factor-α (TNF-α) production from myeloid-derived cells was higher among well-nourished infants. Leptin augmented TLR 7/8-mediated TNF-α production in monocytes and decreased intracellular cAMP levels. Circulating leptin levels were elevated during early infancy and correlated with WHO weight-for-age z scores. Our data support a plausible hypothesis as to why well-nourished infants are at risk for developing DHF with their first DENV infection. PMID:24533162

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

Not Available

This paper reports on Amoco's Yombo offshore oil field development on Marine I permit which is well under way with installation of decks on two wellhead platforms. Initial production from the field has begun at about 6,000 bopd. With production estimated to be 40,000 bopd by early 1992, it will bring Congo's total production to more than 200,000 bopd.

Integrating health economics modeling in the product development cycle of medical devices: a Bayesian approach.

PubMed

Vallejo-Torres, Laura; Steuten, Lotte M G; Buxton, Martin J; Girling, Alan J; Lilford, Richard J; Young, Terry

2008-01-01

Medical device companies are under growing pressure to provide health-economic evaluations of their products. Cost-effectiveness analyses are commonly undertaken as a one-off exercise at the late stage of development of new technologies; however, the benefits of an iterative use of economic evaluation during the development process of new products have been acknowledged in the literature. Furthermore, the use of Bayesian methods within health technology assessment has been shown to be of particular value in the dynamic framework of technology appraisal when new information becomes available in the life cycle of technologies. In this study, we set out a methodology to adapt these methods for their application to directly support investment decisions in a commercial setting from early stages of the development of new medical devices. Starting with relatively simple analysis from the very early development phase and proceeding to greater depth of analysis at later stages, a Bayesian approach facilitates the incorporation of all available evidence and would help companies to make better informed choices at each decision point.

A Regional Study of Loblolly Pine (Pinus taeda) Plantation Development During the First 15 Years After Early Complete Woody and/or Herbaceous Plant Control

Treesearch

James H. Miller; Bruce R. Zutter; Shepard M. Zedaker; M. Boyd Edwards; Ray A. Newbold

2002-01-01

Conifer plantations in North America and elsewhere in the world are increasingly cultured using early control of herbaceous and woody plants. Development of sustainable cultural practices are hindered by the absence of long-term data on productivity gains relative to competition levels, crop- competition dynamics, and ecological changes. There are lmany reports of...

Origins of the Sexual Division of Labor.

ERIC Educational Resources Information Center

Leibowitz, Lila

An interactive, biosocial model of early hominids presents evidence that physical sex differences are not the basis for the sexual division of labor as is commonly believed. Production (the deliberate collection and distribution of food) developed among early hominids as a prerequisite for survival. Although the population appears to have had…

Shared Understanding and Idiosyncratic Expression in Early Vocabularies

ERIC Educational Resources Information Center

Mayor, Julien; Plunkett, Kim

2014-01-01

To what extent do toddlers have shared vocabularies? We examined CDI data collected from 14,607 infants and toddlers in five countries and measured the amount of variability between individual lexicons during development for both comprehension and production. Early lexicons are highly overlapping. However, beyond 100 words, toddlers share more…

Communication in the second and third year of life: Relationships between nonverbal social skills and language.

PubMed

Cochet, Hélène; Byrne, Richard W

2016-08-01

We aimed to investigate developmental continuities between a range of early social and communicative abilities (including gestural communication) and language acquisition in children aged between 11 and 41 months. Initiation of joint attention and imitation were strongly correlated to language comprehension and production. Moreover, the analysis of different communicative gestures revealed significant relationships between language development and the production of symbolic gestures, declarative pointing (declarative informative pointing in particular), and head nodding. Other gestures such as imperative pointing, showing, and head shaking were not found to correlate with language level. Our results also suggest that distinct processes are involved in the development of language comprehension and production, and highlight the importance of considering various characteristics of children's early communicative skills. Copyright © 2016 Elsevier Inc. All rights reserved.

Comprehensive Cell-specific Protein Analysis in Early and Late Pollen Development from Diploid Microsporocytes to Pollen Tube Growth*

PubMed Central

Ischebeck, Till; Valledor, Luis; Lyon, David; Gingl, Stephanie; Nagler, Matthias; Meijón, Mónica; Egelhofer, Volker; Weckwerth, Wolfram

2014-01-01

Pollen development in angiosperms is one of the most important processes controlling plant reproduction and thus productivity. At the same time, pollen development is highly sensitive to environmental fluctuations, including temperature, drought, and nutrition. Therefore, pollen biology is a major focus in applied studies and breeding approaches for improving plant productivity in a globally changing climate. The most accessible developmental stages of pollen are the mature pollen and the pollen tubes, and these are thus most frequently analyzed. To reveal a complete quantitative proteome map, we additionally addressed the very early stages, analyzing eight stages of tobacco pollen development: diploid microsporocytes, meiosis, tetrads, microspores, polarized microspores, bipolar pollen, desiccated pollen, and pollen tubes. A protocol for the isolation of the early stages was established. Proteins were extracted and analyzed by means of a new gel LC-MS fractionation protocol. In total, 3817 protein groups were identified. Quantitative analysis was performed based on peptide count. Exceedingly stage-specific differential protein regulation was observed during the conversion from the sporophytic to the gametophytic proteome. A map of highly specialized functionality for the different stages could be revealed from the metabolic activity and pronounced differentiation of proteasomal and ribosomal protein complex composition up to protective mechanisms such as high levels of heat shock proteins in the very early stages of development. PMID:24078888

Comprehensive cell-specific protein analysis in early and late pollen development from diploid microsporocytes to pollen tube growth.

PubMed

Ischebeck, Till; Valledor, Luis; Lyon, David; Gingl, Stephanie; Nagler, Matthias; Meijón, Mónica; Egelhofer, Volker; Weckwerth, Wolfram

2014-01-01

Pollen development in angiosperms is one of the most important processes controlling plant reproduction and thus productivity. At the same time, pollen development is highly sensitive to environmental fluctuations, including temperature, drought, and nutrition. Therefore, pollen biology is a major focus in applied studies and breeding approaches for improving plant productivity in a globally changing climate. The most accessible developmental stages of pollen are the mature pollen and the pollen tubes, and these are thus most frequently analyzed. To reveal a complete quantitative proteome map, we additionally addressed the very early stages, analyzing eight stages of tobacco pollen development: diploid microsporocytes, meiosis, tetrads, microspores, polarized microspores, bipolar pollen, desiccated pollen, and pollen tubes. A protocol for the isolation of the early stages was established. Proteins were extracted and analyzed by means of a new gel LC-MS fractionation protocol. In total, 3817 protein groups were identified. Quantitative analysis was performed based on peptide count. Exceedingly stage-specific differential protein regulation was observed during the conversion from the sporophytic to the gametophytic proteome. A map of highly specialized functionality for the different stages could be revealed from the metabolic activity and pronounced differentiation of proteasomal and ribosomal protein complex composition up to protective mechanisms such as high levels of heat shock proteins in the very early stages of development.

Differences in Early Cytokine Production Are Associated With Development of a Greater Number of Symptoms Following West Nile Virus Infection.

PubMed

Hoffman, Kevin W; Sachs, David; Bardina, Susana V; Michlmayr, Daniela; Rodriguez, Carlos A; Sum, Janet; Foster, Gregory A; Krysztof, David; Stramer, Susan L; Lim, Jean K

2016-08-15

West Nile virus (WNV) is an emerging cause of meningitis and encephalitis in the United States. Although severe neuroinvasive disease and death can occur in rare instances, the majority of infected individuals remain asymptomatic or present with a range of clinical manifestations associated with West Nile fever. To better understand the interindividual variability associated with the majority of WNV infections, we evaluated the association of cytokine/chemokine production and outcome of infection among 115 WNV-positive US blood donors identified in 2008-2011. All subjects self-reported symptoms as having occurred during the 2 weeks following blood donation, using a standardized questionnaire. We discovered that, prior to seroconversion, an early potent, largely type I interferon-mediated response correlated with development of a greater number of symptoms in WNV-infected individuals. Interestingly, individuals who developed fewer symptoms had not only a more modest type I interferon response initially, but also a protracted cytokine response after seroconversion, marked by the production of monocyte and T-cell-associated chemokines. Collectively, our data suggest that, although an early type I interferon response appears to be crucial to control WNV infection, successful immunity may require a modest early response that is maintained during the course of infection. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Challenges of Moving IPG into Production

NASA Technical Reports Server (NTRS)

Schulbach, Cathy

2004-01-01

Over the past 5-6 years, NASA has been developing the Information Power Grid and has a persistent testbed currently based on GT2.4.2. This presentation will begin with an overview of IPG status and services, discuss key milestones in IPG development, and present early as well as expected applications. The presentation will discuss some of the issues encountered in developing a grid including the tension between providing centralized and distributed computing. These issues also affect how the grid is moved into full production. Finally, the presentation will provide current plans for moving IPG into full production, including gaining broad user input, developing acceptance criteria from the production operations group, planning upgrades, and training users.

Earthquake Early Warning ShakeAlert System: Testing and certification platform

USGS Publications Warehouse

Cochran, Elizabeth S.; Kohler, Monica D.; Given, Douglas; Guiwits, Stephen; Andrews, Jennifer; Meier, Men-Andrin; Ahmad, Mohammad; Henson, Ivan; Hartog, Renate; Smith, Deborah

2017-01-01

Earthquake early warning systems provide warnings to end users of incoming moderate to strong ground shaking from earthquakes. An earthquake early warning system, ShakeAlert, is providing alerts to beta end users in the western United States, specifically California, Oregon, and Washington. An essential aspect of the earthquake early warning system is the development of a framework to test modifications to code to ensure functionality and assess performance. In 2016, a Testing and Certification Platform (TCP) was included in the development of the Production Prototype version of ShakeAlert. The purpose of the TCP is to evaluate the robustness of candidate code that is proposed for deployment on ShakeAlert Production Prototype servers. TCP consists of two main components: a real‐time in situ test that replicates the real‐time production system and an offline playback system to replay test suites. The real‐time tests of system performance assess code optimization and stability. The offline tests comprise a stress test of candidate code to assess if the code is production ready. The test suite includes over 120 events including local, regional, and teleseismic historic earthquakes, recentering and calibration events, and other anomalous and potentially problematic signals. Two assessments of alert performance are conducted. First, point‐source assessments are undertaken to compare magnitude, epicentral location, and origin time with the Advanced National Seismic System Comprehensive Catalog, as well as to evaluate alert latency. Second, we describe assessment of the quality of ground‐motion predictions at end‐user sites by comparing predicted shaking intensities to ShakeMaps for historic events and implement a threshold‐based approach that assesses how often end users initiate the appropriate action, based on their ground‐shaking threshold. TCP has been developed to be a convenient streamlined procedure for objectively testing algorithms, and it has been designed with flexibility to accommodate significant changes in development of new or modified system code. It is expected that the TCP will continue to evolve along with the ShakeAlert system, and the framework we describe here provides one example of how earthquake early warning systems can be evaluated.

Development and application of a biorelevant dissolution method using USP apparatus 4 in early phase formulation development.

PubMed

Fang, Jiang B; Robertson, Vivian K; Rawat, Archana; Flick, Tawnya; Tang, Zhe J; Cauchon, Nina S; McElvain, James S

2010-10-04

Dissolution testing is frequently used to determine the rate and extent at which a drug is released from a dosage form, and it plays many important roles throughout drug product development. However, the traditional dissolution approach often emphasizes its application in quality control testing and usually strives to obtain 100% drug release. As a result, dissolution methods are not necessarily biorelevant and meaningful application of traditional dissolution methods in the early phases of drug product development can be very limited. This article will describe the development of a biorelevant in vitro dissolution method using USP apparatus 4, biorelevant media, and real-time online UV analysis. Several case studies in the areas of formulation selection, lot-to-lot variability, and food effect will be presented to demonstrate the application of this method in early phase formulation development. This biorelevant dissolution method using USP apparatus 4 provides a valuable tool to predict certain aspects of the in vivo drug release. It can be used to facilitate the formulation development/selection for pharmacokinetic (PK) and clinical studies. It may also potentially be used to minimize the number of PK studies, and to aid in the design of more efficient PK and clinical studies.

Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development.

PubMed

Brown, Traci Ann; Holian, Andrij; Pinkerton, Kent E; Lee, Joong Won; Cho, Yoon Hee

2016-07-01

Asbestos in combination with tobacco smoke exposure reportedly leads to more severe physiological consequences than asbestos alone; limited data also show an increased disease risk due to environmental tobacco smoke (ETS) exposure. Environmental influences during gestation and early lung development can result in physiological changes that alter risk for disease development throughout an individual's lifetime. Therefore, maternal lifestyle may impact the ability of offspring to subsequently respond to environmental insults and alter overall disease susceptibility. In this study, we examined the effects of exposure to ETS in utero and during early postnatal development on asbestos-related inflammation and disease in adulthood. ETS exposure in utero appeared to shift inflammation towards a Th2 phenotype, via suppression of Th1 inflammatory cytokine production. This effect was further pronounced in mice exposed to ETS in utero and during early postnatal development. In utero ETS exposure led to increased collagen deposition, a marker of fibrotic disease, when the offspring was later exposed to asbestos, which was further increased with additional ETS exposure during early postnatal development. These data suggest that ETS exposure in utero alters the immune responses and leads to greater disease development after asbestos exposure, which is further exacerbated when exposure to ETS continues during early postnatal development.

Early dialogue with health technology assessment bodies: a European perspective.

PubMed

Cuche, Matthieu; Beckerman, Rachel; Chowdhury, Cyrus A; van Weelden, Marije A

2014-12-01

Evidence requirements may differ across HTA bodies, and so pharmaceutical companies must plan to synergize their evidence generation strategy, across global regulatory and HTA bodies. Until recently, companies had no official platform to discuss the clinical development of a drug with HTA bodies; however, this is changing. To achieve broad usage in the EU, products must achieve both regulatory and reimbursement approval, the latter of which is based on HTA appraisal in many markets. The objective of this study is to present and evaluate the different options available for early HTA consultation (during drug development/Phase III) in the major European markets from the industry perspective. An exploratory (nonsystematic) literature review was performed to identify the European markets offering early HTA consultations, and each process was analyzed using a set of predefined metrics that are relevant to industry (the ability to consult with the regulatory body in parallel, consultation fees, length of consultation meeting, language of consultation meeting, maximum number of pharmaceutical company employees attending, procedural timelines, nature of data for which consultative advice can be sought, the output of the process, and the ability to involve external experts). Four different types of early HTA consultation processes were identified across the major European HTA markets. The nature of these processes varied in terms of the types and number of questions that can be addressed, the length of the meeting, the reporting output, and the ability to involve external experts. The availability of various options for early HTA consultation may help to avoid a mismatch between the evidence generated by means of a product's clinical development program, and the evidence expected by HTA bodies and payers, which can facilitate the pricing and reimbursement process upon a product's market authorization.

Early adolescent childbearing in low- and middle-income countries: associations with income inequity, human development and gender equality.

PubMed

Decker, Michele R; Kalamar, Amanda; Tunçalp, Özge; Hindin, Michelle J

2017-03-01

Reducing unwanted adolescent childbearing is a global priority. Little is known about how national-level economic and human development indicators relate to early adolescent childbearing. This ecological study evaluates associations of Gross Domestic Product (GDP), GINI index, Human Development Index (HDI) and Gender-related Development Index (GDI; i.e. the HDI adjusted for gender disparities) with early adolescent childbearing in 27 low- and middle-income countries (LMICs) across three time periods. Among women ages 18–24, prevalence estimates for early birth (<16 years) were calculated by nation, and weighted linear regressions evaluated associations between national indicators and early childbearing. To examine temporal trends, analyses were stratified by year groupings. Early adolescent childbearing declined over time, with the greatest change observed in Bangladesh (31.49% in 1996/7 to 19.69% in 2011). In adjusted models, GDI was negatively associated with early childbearing, i.e. early childbearing prevalence decreased as GDI increased. In the most recent time period, relative to the lowest GDI group, the average prevalence of early childbearing was significantly lower in the middle (-12.40, P < 0.00) and upper (-10.96, P = 0.03) tertiles after adjustment for the other indicators. These other indicators showed no consistent association with early childbearing. As national-level GDI increased, early adolescent childbearing declined. The GDI, which reflects human development adjusted for gender disparities in educational and economic prospects, was more consistently related to early adolescent childbearing than the absolute development prospects as given by the HDI. While creating gender equality is an important goal in and of itself, the findings emphasize the potential for improved national-level gender equitable development as a means to improve adolescents’ sexual and reproductive health.

The Relationship of Morale and Productivity: An Historical Overview.

ERIC Educational Resources Information Center

Cooper, John F.

This brief survey of the conceptual development of the morale-productivity relationship examines some of the major representative studies of this subject from the 1930s through the 1970s. The author notes the trend away from thinking of productivity and morale as simply and directly related, the traditional view assumed in the early research. He…

The new role of HSE in chemical product development

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

Purinton, R.J. Jr.; Manning, T.S.; Dowell, S.

1996-11-01

Today, Health, Safety, and Environmental issues take a more prominent role than ever before in chemical product development for the global oilfield service industry. Prior to widespread regulatory guidelines, technical problems were solved and well treatment programs were developed using the chemicals which performed the best and were the least expensive for the application. HSE concerns were sometimes addressed from a remedial standpoint, rather than a preventive one throughout the process. With a clearer understanding of the potential impact of chemicals upon people and the environment, along with the ever-increasing array of government regulations, service companies are taking a newmore » approach to product development. HSE-related risks and costs are being assessed early and continued throughout chemical development, with both product and treatment process features then designed accordingly. One service company reflects this approach with its {open_quotes}cradle-to-grave{close_quotes} Product Development and Stewardship program. Integral to this program are planned HSE assessments at each step of development, including Feasibility, Lab Development, Field Testing, Manufacturing, and Commercial Field Introduction. These assessments provide the data necessary to {open_quotes}engineer-in{close_quotes} solutions to potential HSE-related problems, produce viable Risk Management Plans, and promote a smoother path to commercialization. This avoids arriving at the commercial launch point with a product which poses unacceptably high personal or environmental risks, may be restricted or banned in key markets, or requires lengthy and expensive government registrations. In order to optimize R&E resources and ensure continuous evaluation, decision points (to continue, modify, or abandon) are built into the process. Early HSE screenings must be accurate but also relatively quick and inexpensive to be meaningful and economical.« less

Early Combination of Material Characteristics and Toxicology Is Useful in the Design of Low Toxicity Carbon Nanofiber

PubMed Central

Jensen, Ellen K.; Larsen, Sten Y.; Nygaard, Unni C.; Marioara, Calin D.; Syversen, Tore

2012-01-01

This paper describes an approach for the early combination of material characterization and toxicology testing in order to design carbon nanofiber (CNF) with low toxicity. The aim was to investigate how the adjustment of production parameters and purification procedures can result in a CNF product with low toxicity. Different CNF batches from a pilot plant were characterized with respect to physical properties (chemical composition, specific surface area, morphology, surface chemistry) as well as toxicity by in vitro and in vivo tests. A description of a test battery for both material characterization and toxicity is given. The results illustrate how the adjustment of production parameters and purification, thermal treatment in particular, influence the material characterization as well as the outcome of the toxic tests. The combination of the tests early during product development is a useful and efficient approach when aiming at designing CNF with low toxicity. Early quality and safety characterization, preferably in an iterative process, is expected to be efficient and promising for this purpose. The toxicity tests applied are preliminary tests of low cost and rapid execution. For further studies, effects such as lung inflammation, fibrosis and respiratory cancer are recommended for the more in-depth studies of the mature CNF product.

Development of a loop-mediated isothermal amplification method for rapid campylobacter jejuni detection

USDA-ARS?s Scientific Manuscript database

Introduction: Campylobacter jejuni is the leading foodborne pathogen that causes human bacterial gastroenteritis worldwide. Poultry products are regarded as a major source for human infection. Early, rapid detection of this microorganism in poultry products is necessary for contamination control ...

Early Development of Graphical Literacy through Knowledge Building

ERIC Educational Resources Information Center

Gan, Yongcheng; Scardamalia, Marlene; Hong, Huang-Yao; Zhang, Jianwei

2010-01-01

This study examined growth in graphical literacy for students contributing to an online, multimedia, communal environment as they advanced their understanding of biology, history and optics. Their science and history studies started early in Grade 3 and continued to the end of Grade 4; students did not receive instruction in graphics production,…

Effect of Harvest Residue Management on Tree Productivity and Carbon Pools during Early Stand Development in a Loblolly Pine Plantation

Treesearch

Chris A. Maier; Kurt H. Johnsen; Phillip Dougherty; Daniel McInnis; Pete Anderson; Steve Patterson

2012-01-01

Soil incorporation of postharvest forest floor or logging residues during site preparation increased mineral soil carbon (C) and nitrogen (N) concentration and had a differential effect on early stand growth in a clonal loblolly pine (Pinus taeda L.) plantation. Incorporating 25 Mg ha

Developing Productive Lifeskills in Children: Priming Entrepreneurial Mindsets through Socialisation in Family Occupations

ERIC Educational Resources Information Center

Mbebeb, Fomba E.

2009-01-01

Building on the premise that societal sustainability depends on mental and behavioural sustainability, this paper provides a framework within which the complex challenges of sustainable early childhood education in the majority world is discussed. The work contends that entrepreneurial mindsets priming is a viable component of early childhood…

From Parent to Child to Parent...: Paths in and out of Problem Behavior

ERIC Educational Resources Information Center

Bradley, Robert H.; Corwyn, Robert

2013-01-01

This study used data from the NICHD Study of Early Child Care and Youth Development to examine relations between parenting, self-control and externalizing behavior from early childhood to mid-adolescence (N = 956; 49.9 % male). Results indicated that maternal sensitivity, parental harshness and productive activity are related to externalizing…

Is a Response to Intervention (RTI) Approach to Preschool Language and Early Literacy Instruction Needed?

ERIC Educational Resources Information Center

Greenwood, Charles R.; Carta, Judith J.; Atwater, Jane; Goldstein, Howard; Kaminski, Ruth; McConnell, Scott

2013-01-01

Preschool experience plays a role in children's development. However, for programs with language and early literacy goals, the question remains whether preschool instructional experiences are sufficiently effective to achieve these goals for all children. In a multisite study, the authors conducted a process-product description of preschool…

Deciphering early events involved in hyperosmotic stress-induced programmed cell death in tobacco BY-2 cells

PubMed Central

Monetti, Emanuela; Kadono, Takashi; Bouteau, François

2014-01-01

Hyperosmotic stresses represent one of the major constraints that adversely affect plants growth, development, and productivity. In this study, the focus was on early responses to hyperosmotic stress- (NaCl and sorbitol) induced reactive oxygen species (ROS) generation, cytosolic Ca2+ concentration ([Ca2+]cyt) increase, ion fluxes, and mitochondrial potential variations, and on their links in pathways leading to programmed cell death (PCD). By using BY-2 tobacco cells, it was shown that both NaCl- and sorbitol-induced PCD seemed to be dependent on superoxide anion (O2·–) generation by NADPH-oxidase. In the case of NaCl, an early influx of sodium through non-selective cation channels participates in the development of PCD through mitochondrial dysfunction and NADPH-oxidase-dependent O2·– generation. This supports the hypothesis of different pathways in NaCl- and sorbitol-induced cell death. Surprisingly, other shared early responses, such as [Ca2+]cyt increase and singlet oxygen production, do not seem to be involved in PCD. PMID:24420571

The Early Development of the Open University: Report of the Vice-Chancellor January 1969-December 1970.

ERIC Educational Resources Information Center

Open Univ., Walton, Bletchley, Bucks (England).

This report concerns the extablishment and development of the British Open University. Contents include the descriptions of: the development of the institution; staffing the open university; development of the Milton Keynes Campus; undergraduate course development; regional organization; demand for open university courses; development, production,…

Life cycle analysis within pharmaceutical process optimization and intensification: case study of active pharmaceutical ingredient production.

PubMed

Ott, Denise; Kralisch, Dana; Denčić, Ivana; Hessel, Volker; Laribi, Yosra; Perrichon, Philippe D; Berguerand, Charline; Kiwi-Minsker, Lioubov; Loeb, Patrick

2014-12-01

As the demand for new drugs is rising, the pharmaceutical industry faces the quest of shortening development time, and thus, reducing the time to market. Environmental aspects typically still play a minor role within the early phase of process development. Nevertheless, it is highly promising to rethink, redesign, and optimize process strategies as early as possible in active pharmaceutical ingredient (API) process development, rather than later at the stage of already established processes. The study presented herein deals with a holistic life-cycle-based process optimization and intensification of a pharmaceutical production process targeting a low-volume, high-value API. Striving for process intensification by transfer from batch to continuous processing, as well as an alternative catalytic system, different process options are evaluated with regard to their environmental impact to identify bottlenecks and improvement potentials for further process development activities. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Suprasegmental Features Are Not Acquired Early: Perception and Production of Monosyllabic Cantonese Lexical Tones in 4- to 6-Year-Old Preschool Children.

PubMed

Wong, Puisan; Tsz-Tin Leung, Carrie

2018-05-17

Previous studies reported that children acquire Cantonese tones before 3 years of age, supporting the assumption in models of phonological development that suprasegmental features are acquired rapidly and early in children. Yet, recent research found a large disparity in the age of Cantonese tone acquisition. This study investigated Cantonese tone development in 4- to 6-year-old children. Forty-eight 4- to 6-year-old Cantonese-speaking children and 28 mothers of the children labeled 30 pictures representing familiar words in the 6 tones in a picture-naming task and identified pictures representing words in different Cantonese tones in a picture-pointing task. To control for lexical biases in tone assessment, tone productions were low-pass filtered to eliminate lexical information. Five judges categorized the tones in filtered stimuli. Tone production accuracy, tone perception accuracy, and correlation between tone production and perception accuracy were examined. Children did not start to produce adultlike tones until 5 and 6 years of age. Four-year-olds produced none of the tones with adultlike accuracy. Five- and 6-year-olds attained adultlike productions in 2 (T5 and T6) to 3 (T4, T5, and T6) tones, respectively. Children made better progress in tone perception and achieved higher accuracy in perception than in production. However, children in all age groups perceived none of the tones as accurately as adults, except that T1 was perceived with adultlike accuracy by 6-year-olds. Only weak association was found between children's tone perception and production accuracy. Contradicting to the long-held assumption that children acquire lexical tone rapidly and early before the mastery of segmentals, this study found that 4- to 6-year-old children have not mastered the perception or production of the full set of Cantonese tones in familiar monosyllabic words. Larger development was found in children's tone perception than tone production. The higher tone perception accuracy but weak correlation between tone perception and production abilities in children suggested that tone perception accuracy is not sufficient for children's tone production accuracy. The findings have clinical and theoretical implications.

Carbonate fuel cells: Milliwatts to megawatts

NASA Astrophysics Data System (ADS)

Farooque, M.; Maru, H. C.

The carbonate fuel cell power plant is an emerging high efficiency, ultra-clean power generator utilizing a variety of gaseous, liquid, and solid carbonaceous fuels for commercial and industrial applications. The primary mover of this generator is a carbonate fuel cell. The fuel cell uses alkali metal carbonate mixtures as electrolyte and operates at ∼650 °C. Corrosion of the cell hardware and stability of the ceramic components have been important design considerations in the early stages of development. The material and electrolyte choices are founded on extensive fundamental research carried out around the world in the 60s and early 70s. The cell components were developed in the late 1970s and early 1980s. The present day carbonate fuel cell construction employs commonly available stainless steels. The electrodes are based on nickel and well-established manufacturing processes. Manufacturing process development, scale-up, stack tests, and pilot system tests dominated throughout the 1990s. Commercial product development efforts began in late 1990s leading to prototype field tests beginning in the current decade leading to commercial customer applications. Cost reduction has been an integral part of the product effort. Cost-competitive product designs have evolved as a result. Approximately half a dozen teams around the world are pursuing carbonate fuel cell product development. The power plant development efforts to date have mainly focused on several hundred kW (submegawatt) to megawatt-class plants. Almost 40 submegawatt units have been operating at customer sites in the US, Europe, and Asia. Several of these units are operating on renewable bio-fuels. A 1 MW unit is operating on the digester gas from a municipal wastewater treatment plant in Seattle, Washington (US). Presently, there are a total of approximately 10 MW capacity carbonate fuel cell power plants installed around the world. Carbonate fuel cell products are also being developed to operate on coal-derived gases, diesel, and other logistic fuels. Innovative carbonate fuel cell/turbine hybrid power plant designs promising record energy conversion efficiencies approaching 75% have also emerged. This paper will review the historical development of this unique technology from milliwatt-scale laboratory cells to present megawatt-scale commercial power plants.

Available Tools to Facilitate Early Patient Access to Medicines in the EU and the USA: Analysis of Conditional Approvals and the Implications for Personalized Medicine.

PubMed

Leyens, Lada; Richer, Étienne; Melien, Øyvind; Ballensiefen, Wolfgang; Brand, Angela

2015-01-01

Scientific knowledge and our understanding of the human body and diseases have limited any possible treatment tailoring to each patient. The technological advances enabling the integration of various data sets (e.g. '-omics', microbiome, epigenetics and environmental exposure) have facilitated a greater understanding of the human body, the molecular basis of disease and all the factors influencing disease onset, progression and response to treatment, thereby ushering in the era of personalized medicine. We evaluate the regulatory approaches available to facilitate early patient access to efficacious and safe compounds in the EU and the USA in order to make more informed recommendations in the future as to the gaps in regulations for early patient access. An in-depth analysis of conditional approvals (EU) and accelerated approvals (USA) is performed based on the publicly available information (European public assessment reports and a summary review of products approved under both programmes). The types of product, indications, time to approval and type of evidence submitted were analysed. Between 2007 and early 2015, 17 products were conditionally approved in the EU and 25 in the USA, most of them in the area of oncology and based on evidence from phase II clinical trial data. Early approval of promising products based on data from early phases of development is already possible in the EU and the USA. Some of the improvements could entail implementing a rolling assessment of evidence in Europe and extending the scope of early dialogues. © 2015 S. Karger AG, Basel.

Early-life enteric infections: relation between chronic systemic inflammation and poor cognition in children

PubMed Central

Murray-Kolb, Laura E.; Scharf, Rebecca J.; Pendergast, Laura L.; Lang, Dennis R.; Kolling, Glynis L.; Guerrant, Richard L.

2016-01-01

The intestinal microbiota undergoes active remodeling in the first 6 to 18 months of life, during which time the characteristics of the adult microbiota are developed. This process is strongly influenced by the early diet and enteric pathogens. Enteric infections and malnutrition early in life may favor microbiota dysbiosis and small intestinal bacterial overgrowth, resulting in intestinal barrier dysfunction and translocation of intestinal bacterial products, ultimately leading to low-grade, chronic, subclinical systemic inflammation. The leaky gut–derived low-grade systemic inflammation may have profound consequences on the gut–liver–brain axis, compromising normal growth, metabolism, and cognitive development. This review examines recent data suggesting that early-life enteric infections that lead to intestinal barrier disruption may shift the intestinal microbiota toward chronic systemic inflammation and subsequent impaired cognitive development. PMID:27142301

Developing consistent time series landsat data products

USDA-ARS?s Scientific Manuscript database

The Landsat series satellite has provided earth observation data record continuously since early 1970s. There are increasing demands on having a consistent time series of Landsat data products. In this presentation, I will summarize the work supported by the USGS Landsat Science Team project from 20...

Clinical Development of Cell Therapies: Setting the Stage for Academic Success.

PubMed

Abou-El-Enein, M; Volk, H-D; Reinke, P

2017-01-01

Cellular therapies have potential to treat a wide range of diseases with autologous immunotherapies showing unprecedented therapeutic promise in clinical trials. Such therapies are mainly developed by academic researchers applying small-scale production, targeting rare and unmet medical needs. Here, we highlight the clinical translation of immunotherapy product in an academic setting, which may serve as a success model for early academic development of cell-based therapeutics. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Co-creation and Co-innovation in a Collaborative Networked Environment

NASA Astrophysics Data System (ADS)

Klen, Edmilson Rampazzo

Leveraged by the advances in communication and information Technologies, producers and consumers are developing a new behavior. Together with the new emerging collaborative manifestations this behavior may directly impact the way products are developed. This powerful combination indicates that consumers will be involved in a very early stage in product development processes supporting even more the creation and innovation of products. This new way of collaboration gives rise to a new collaborative networked environment based on co-creation and co-innovation. This work will present some evolutionary steps that point to the development of this environment where prosumer communities and virtual organizations interact and collaborate.

Ontogenetic development in the morphology and behavior of loach ( Misgurnus anguillicaudatus) during early life stages

NASA Astrophysics Data System (ADS)

Gao, Lei; Duan, Ming; Cheng, Fei; Xie, Songguang

2014-09-01

Loach ( Misgurnus anguillicaudatus) are a commercially important fish in China and an ideal aquaculture species. However, culturists experience high larval and juvenile mortality during mass production. To provide insight into ways to improve larviculture techniques, we describe the morphological characteristics and behavior of loach during the larval and early juvenile stages. Yolksac larvae ranged from 2.8 to 4.0 mm body length (BL) between days 0 to 4; preflexion larvae ranged from 3.6 to 5.5 mm BL between days 4 to 6; flexion larvae ranged from 4.8 to 8.1 mm BL between days 5 and 14; and postflexion larvae ranged from 7.1 to 15.7 mm BL between days 11 to 27; the minimum length and age of juveniles was 14.1 mm BL and 23 d, respectively. Loach are demersal from hatch through to the early juvenile stages. A suite of morphological characteristics (e.g., external gill filament and ventral mouth opening) and behavioral traits have developed to adapt to demersal living. We observed positive allometric growth in eye diameter, head length, head height, and pectoral fin length during the early larval stages, reflecting the priorities in the development of the organs essential for survival. Our results provide a basis for developing techniques to improve the survival of larval and juvenile loach during mass production.

Prenatal concentrations of Perfluoroalkyl substances and early communication development in British girls.

PubMed

Jeddy, Zuha; Hartman, Terryl J; Taylor, Ethel V; Poteete, Cayla; Kordas, Katarzyna

2017-06-01

Perfluoroalkyl substances (PFAS), found in many household products and classed as endocrine disrupting chemicals, can be transferred through the placenta and are associated with multiple developmental deficits in offspring. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we investigated the association between intrauterine exposure to PFAS and early communication development in 432 mother-daughter dyads at 15 and 38months of age. Concentrations of perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) were measured in maternal serum collected during pregnancy. Early communication development was measured with the ALSPAC-adapted MacArthur Communicative Development Inventories for Infants and Toddlers. The infant questionnaire measured verbal comprehension, vocabulary comprehension and production, nonverbal communication, and social development. The toddler questionnaire measured language, intelligibility, and communicative sub-scores. Multivariable linear regression was used to examine associations between each PFAS exposure and each communication sub-scale score. The association between maternal PFAS concentrations and early communication development at 15 and 38months of age varied by maternal age at delivery. In daughters of younger mothers (<25years of age), every 1ng/mL of PFOS was associated with a 3.82 point (95% confidence interval (CI): -6.18, -1.47) lower vocabulary score at 15months and a 0.80 point (95% CI: -1.74, 0.14) lower language score at 38months. Prenatal exposure to select PFAS was positively and negatively associated with communication development among girls, with inconsistent pattern of association across all measured PFAS and endpoints. Copyright © 2017 Elsevier B.V. All rights reserved.

Prenatal concentrations of Perfluoroalkyl substances and early communication development in British girls

PubMed Central

Jeddy, Zuha; Hartman, Terryl J.; Taylor, Ethel V.; Poteete, Cayla; Kordas, Katarzyna

2017-01-01

Perfluoroalkyl substances (PFAS), found in many household products and classed as endocrine disrupting chemicals, can be transferred through the placenta and are associated with multiple developmental deficits in offspring. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we investigated the association between intrauterine exposure to PFAS and early communication development in 432 mother-daughter dyads at 15 and 38 months of age. Concentrations of perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) were measured in maternal serum collected during pregnancy. Early communication development was measured with the ALSPAC-adapted MacArthur Communicative Development Inventories for Infants and Toddlers. The infant questionnaire measured verbal comprehension, vocabulary comprehension and production, nonverbal communication, and social development. The toddler questionnaire measured language, intelligibility, and communicative subscores. Multivariable linear regression was used to examine associations between each PFAS exposure and each communication sub-scale score. The association between maternal PFAS concentrations and early communication development at 15 and 38 months of age varied by maternal age at delivery. In daughters of younger mothers (< 25 years of age), every 1 ng/mL of PFOS was associated with a 3.82 point (95% confidence interval (CI): −6.18, −1.47) lower vocabulary score at 15 months and a 0.80 point (95% CI: −1.74, 0.14) lower language score at 38 months. Prenatal exposure to select PFAS was positively and negatively associated with communication development among girls, with inconsistent pattern of association across all measured PFAS and endpoints. PMID:28411449

Education Journals and Newsletters, 1987-88. Revised.

ERIC Educational Resources Information Center

Anderson, Deborah J., Ed.; Moore, John L., Ed.

Compiled for educators, product developers, researchers, librarians, publishers, consultants, and others interested in the educational field, this directory lists 412 periodicals covering education and related topics such as special education, educational technologies, educational media and materials, early childhood development, rehabilitation…

Bioreactor and process design for biohydrogen production.

PubMed

Show, Kuan-Yeow; Lee, Duu-Jong; Chang, Jo-Shu

2011-09-01

Biohydrogen is regarded as an attractive future clean energy carrier due to its high energy content and environmental-friendly conversion. It has the potential for renewable biofuel to replace current hydrogen production which rely heavily on fossil fuels. While biohydrogen production is still in the early stage of development, there have been a variety of laboratory- and pilot-scale systems developed with promising potential. This work presents a review of advances in bioreactor and bioprocess design for biohydrogen production. The state-of-the art of biohydrogen production is discussed emphasizing on production pathways, factors affecting biohydrogen production, as well as bioreactor configuration and operation. Challenges and prospects of biohydrogen production are also outlined. Copyright © 2011 Elsevier Ltd. All rights reserved.

Ovation Pharmaceuticals, Inc.

PubMed

Deutsch, Barry

2002-11-01

Ovation Pharmaceuticals, Inc. is a privately held specialty pharmaceutical company that focuses on products in central nervous system (CNS) disorders, oncology and other therapeutic areas where a small number of specialized physicians treat patients. Ovation serves unmet medical needs by acquiring underpromoted branded pharmaceutical products and promising late-stage development products no longer being actively promoted or developed by larger companies. Ovation supports acquired products through active sales and marketing activities and a clinical development program focused on new formulations, new indications and other product improvements. In April 2002, Ovation received a US$150 million commitment in private equity financing, believed to be the largest private equity investment received to date by an early-stage specialty pharmaceutical firm. Ovation used a portion of those funds to purchase its first two products from a major pharmaceutical company in August 2002.

The Large Area Crop Inventory Experiment /LACIE/ - A summary of three years' experience

NASA Technical Reports Server (NTRS)

Erb, R. B.; Moore, B. H.

1979-01-01

Aims, history and schedule of the Large Area Crop Inventory Experiment (LACIE) conducted by NASA, USDA and NOAA from 1974-1977 are described. The LACIE experiment designed to research, develop, apply and evaluate a technology to monitor wheat production in important regions throughout the world (U.S., Canada, USSR, Brasil) utilized quantitative multispectral data collected by Landsat in concert with current weather data and historical information. The experiment successfully exploited computer data and mathematical models to extract timely corp information. A follow-on activities for the early 1980's is planned focusing especially on the early warning of changes affecting production and quality of renewable resources and commodity production forecast.

The guanosine nucleotide (p)ppGpp initiates development and A-factor production in myxococcus xanthus.

PubMed

Harris, B Z; Kaiser, D; Singer, M

1998-04-01

Guanosine 3'-di-5'-(tri)di-phosphate nucleotides [(p)ppGpp], synthesized in response to amino acid limitation, induce early gene expression leading to multicellular fruiting body formation in Myxococcus xanthus. A mutant (DK527) that fails to accumulate (p)ppGpp in response to starvation was found to be blocked in development prior to aggregation. By use of a series of developmentally regulated Tn5lac transcriptional fusion reporters, the time of developmental arrest in DK527 was narrowed to within the few hours of development, the period of starvation recognition. The mutant is also defective in the production of A-factor, an early extracellular cell-density signal. The relA gene from Escherichia coli, which encodes a ribosome-dependent (p)ppGpp synthetase, rescues this mutant. We also demonstrate that inactivation of the M. xanthus relA homolog blocks development and the accumulation of (p)ppGpp. Moreover, the wild-type allele of Myxococcus relA rescues DK527. These observations support a model in which accumulation of (p)ppGpp, in response to starvation, initiates the program of fruiting body development, including the production of A-factor.

ADP-ribosyl cyclases regulate early development of the sea urchin.

PubMed

Ramakrishnan, Latha; Uhlinger, Kevin; Dale, Leslie; Hamdoun, Amro; Patel, Sandip

2016-06-01

ADP-ribosyl cyclases are multifunctional enzymes involved in the metabolism of nucleotide derivatives necessary for Ca 2+ signalling such as cADPR and NAADP. Although Ca 2+ signalling is a critical regulator of early development, little is known of the role of ADP-ribosyl cyclases during embryogenesis. Here we analyze the expression, activity and function of ADP-ribosyl cyclases in the embryo of the sea urchin - a key organism for study of both Ca 2+ signalling and embryonic development. ADP-ribosyl cyclase isoforms (SpARC1-4) showed unique changes in expression during early development. These changes were associated with an increase in the ratio of cADPR:NAADP production. Over-expression of SpARC4 (a preferential cyclase) disrupted gastrulation. Our data highlight the importance of ADP-ribosyl cyclases during embryogenesis.

The Effects of Research & Development Funding on Scientific Productivity: Academic Chemistry, 1990-2009.

PubMed

Rosenbloom, Joshua L; Ginther, Donna K; Juhl, Ted; Heppert, Joseph A

2015-01-01

This article examines the relationship between Research & Development (R&D) funding and the production of knowledge by academic chemists. Using articles published, either raw counts or adjusted for quality, we find a strong, positive causal effect of funding on knowledge production. This effect is similar across subsets of universities, suggesting a relatively efficient allocation of R&D funds. Finally, we document a rapid acceleration in the rate at which chemical knowledge was produced in the late 1990s and early 2000s relative to the financial and human resources devoted to its production.

The Effects of Research & Development Funding on Scientific Productivity: Academic Chemistry, 1990-2009

PubMed Central

Rosenbloom, Joshua L.; Ginther, Donna K.; Juhl, Ted; Heppert, Joseph A.

2015-01-01

This article examines the relationship between Research & Development (R&D) funding and the production of knowledge by academic chemists. Using articles published, either raw counts or adjusted for quality, we find a strong, positive causal effect of funding on knowledge production. This effect is similar across subsets of universities, suggesting a relatively efficient allocation of R&D funds. Finally, we document a rapid acceleration in the rate at which chemical knowledge was produced in the late 1990s and early 2000s relative to the financial and human resources devoted to its production. PMID:26372555

Fifty years of successful MCT research and production in France

NASA Astrophysics Data System (ADS)

Bensussan, Philippe; Tribolet, Philippe; Destéfanis, Gérard; Sirieix, Michel

2009-05-01

France has a long and fruitful history regarding Mercury Cadmium Telluride (MCT) research and production and is still one of the leading countries for the production of MCT IR detectors. To give a historical account of its development and progress, SAGEM Défense Sécurité will describe the early days of MCT developments in France. CEA-Leti (the French Atomic Energy Commission and a leading applied research center in electronics) will then present the research carried out on second- and third-generation MCT technologies, followed by Sofradir who will discuss the production of these new detector types.

Importance of Speech Production for Phonological Awareness and Word Decoding: The Case of Children with Cerebral Palsy

ERIC Educational Resources Information Center

Peeters, Marieke; Verhoeven, Ludo; de Moor, Jan; van Balkom, Hans

2009-01-01

The goal of this longitudinal study was to investigate the precursors of early reading development in 52 children with cerebral palsy at kindergarten level in comparison to 65 children without disabilities. Word Decoding was measured to investigate early reading skills, while Phonological Awareness, Phonological Short-term Memory (STM), Speech…

Early Metalinguistic Awareness of Derivational Morphology: Observations from a Comparison of English and French

ERIC Educational Resources Information Center

Duncan, Lynne G.; Casalis, Severine; Cole, Pascale

2009-01-01

This cross-linguistic comparison of metalinguistic development in French and English examines early ability to manipulate derivational suffixes in oral language games as a function of chronological age, receptive vocabulary, and year of schooling. Data from judgment and production tasks are presented for children aged between 5 and 8 years in…

Phonological Constraints on Children's Production of English Third Person Singular -S

ERIC Educational Resources Information Center

Song, Jae Yung; Sundara, Megha; Demuth, Katherine

2009-01-01

Purpose: Children variably produce grammatical morphemes at early stages of development, often omitting inflectional morphemes in obligatory contexts. This has typically been attributed to immature syntactic or semantic representations. In this study, the authors investigated the hypothesis that children's variable production of the 3rd person…

Chapter 16: Soy Proteins as Wood Adhesives

Treesearch

Charles R. Frihart; Christopher G. Hunt; Michael J. Birkeland

2014-01-01

Protein adhesives allowed the development of bonded wood products such as plywood and glulam in the early 20th century. Petrochemical-based adhesives replaced proteins in most wood bonding applications because of lower cost, improved production efficiencies, and enhanced durability. However, several technological and environmental factors have led to a resurgence of...

Collaborative Practitioner Research: Opening a Third Space for Local Knowledge Production

ERIC Educational Resources Information Center

Skattebol, Jen; Arthur, Leonie Maree

2014-01-01

Early childhood education and care is currently experiencing unprecedented policy interest and expansion. This policy and practice landscape requires new forms of adaptive leadership, new spaces for production of the knowledge necessary for this changing context, and tools that can support the development of leadership qualities. This paper…

Developing Structural Specification: Productivity in Early Hebrew Verb Usage

ERIC Educational Resources Information Center

Lustigman, Lyle

2013-01-01

The study investigates acquisition of verb inflections by four monolingual Hebrew-acquiring children from middle-class backgrounds, audio-recorded in longitudinal, weekly samples at a mean age-range of between 18 and 26 months. Productive use of inflectional morphology is shown to manifest increasing structural specification, as a function of…

Parent Reports of Young Spanish-English Bilingual Children's Productive Vocabulary: A Development and Validation Study.

PubMed

Mancilla-Martinez, Jeannette; Gámez, Perla B; Vagh, Shaher Banu; Lesaux, Nonie K

2016-01-01

This 2-phase study aims to extend research on parent report measures of children's productive vocabulary by investigating the development (n = 38) of the Spanish Vocabulary Extension and validity (n = 194) of the 100-item Spanish and English MacArthur-Bates Communicative Development Inventories Toddler Short Forms and Upward Extension (Fenson et al., 2000, 2007; Jackson-Maldonado, Marchman, & Fernald, 2013) and the Spanish Vocabulary Extension for use with parents from low-income homes and their 24- to 48-month-old Spanish-English bilingual children. Study participants were drawn from Early Head Start and Head Start collaborative programs in the Northeastern United States in which English was the primary language used in the classroom. All families reported Spanish or Spanish-English as their home language(s). The MacArthur Communicative Development Inventories as well as the researcher-designed Spanish Vocabulary Extension were used as measures of children's English and Spanish productive vocabularies. Findings revealed the forms' concurrent and discriminant validity, on the basis of standardized measures of vocabulary, as measures of productive vocabulary for this growing bilingual population. These findings suggest that parent reports, including our researcher-designed form, represent a valid, cost-effective mechanism for vocabulary monitoring purposes in early childhood education settings.

Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development

PubMed Central

Brown, Traci A.; Holian, Andrij; Pinkerton, Kent E.; Lee, Joong Won; Cho, Yoon Hee

2016-01-01

Asbestos in combination with tobacco smoke exposure reportedly leads to more severe physiological consequences than asbestos alone; limited data also show an increased disease risk due to environmental tobacco smoke (ETS) exposure. Environmental influences during gestation and early lung development can result in physiological changes that alter risk for disease development throughout an individual’s lifetime. Therefore, maternal lifestyle may impact the ability of offspring to subsequently respond to environmental insults and alter overall disease susceptibility. In this study, we examined the effects of exposure to ETS in utero and during early postnatal development on asbestos-related inflammation and disease in adulthood. ETS exposure in utero appeared to shift inflammation towards a Th2 phenotype, via suppression of Th1 inflammatory cytokine production. This effect was further pronounced in mice exposed to ETS in utero and during early postnatal development. In utero ETS exposure led to increased collagen deposition, a marker of fibrotic disease, when the offspring was later exposed to asbestos, which was further increased with additional ETS exposure during early postnatal development. These data suggest that ETS exposure in utero alters the immune responses and leads to greater disease development after asbestos exposure, which is further exacerbated when exposure to ETS continues during early postnatal development. PMID:27138493

77 FR 9947 - Guidance for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-21

...] Guidance for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry, Manufacturing... ``Guidance for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry, Manufacturing... for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry, Manufacturing, and...

LANGUAGE DEVELOPMENT. The developmental dynamics of marmoset monkey vocal production.

PubMed

Takahashi, D Y; Fenley, A R; Teramoto, Y; Narayanan, D Z; Borjon, J I; Holmes, P; Ghazanfar, A A

2015-08-14

Human vocal development occurs through two parallel interactive processes that transform infant cries into more mature vocalizations, such as cooing sounds and babbling. First, natural categories of sounds change as the vocal apparatus matures. Second, parental vocal feedback sensitizes infants to certain features of those sounds, and the sounds are modified accordingly. Paradoxically, our closest living ancestors, nonhuman primates, are thought to undergo few or no production-related acoustic changes during development, and any such changes are thought to be impervious to social feedback. Using early and dense sampling, quantitative tracking of acoustic changes, and biomechanical modeling, we showed that vocalizations in infant marmoset monkeys undergo dramatic changes that cannot be solely attributed to simple consequences of growth. Using parental interaction experiments, we found that contingent parental feedback influences the rate of vocal development. These findings overturn decades-old ideas about primate vocalizations and show that marmoset monkeys are a compelling model system for early vocal development in humans. Copyright © 2015, American Association for the Advancement of Science.

The Maricopa Colleges.

ERIC Educational Resources Information Center

Bush, Ronald W.; Ames, W. Clark

1984-01-01

A college personnel policy developed to respond to changing conditions has 10 elements: establishment of a master planning process, policy and procedures review, early retirement, extended leave, recruitment and hiring of new faculty, flexible benefits, productivity and career development, internship opportunities, faculty renewal opportunities,…

The Lesson of Hiroshima and Nagasaki--Part I: The Past.

ERIC Educational Resources Information Center

Kauffman, George B.

1985-01-01

Examines scientific discoveries which underlie the atomic bomb and its technological development in the United States during World War II. Changing views, super-weapon development, early American efforts, production/dropping the bombs, and the Oppenheimer case are considered. (DH)

The Early Development of Programmable Machinery.

ERIC Educational Resources Information Center

Collins, Martin D.

1985-01-01

Programmable equipment innovations, precursors of today's technology, are examined, including the development of the binary code and feedback control systems, such as temperature sensing devices, interchangeable parts, punched cards carrying instructions, continuous flow oil refining process, assembly lines for mass production, and the…

Report of the NASA Mammalian Developmental Biology Working Group

NASA Technical Reports Server (NTRS)

Keefe, J. R.

1985-01-01

Development is considered to encompass all aspects of the mammalian life span from initial initial germ cell production through the complete life cycle to death of the organism. Thus, gamete production, fertilization, embryogenesis, implantation, fetogenesis, birth, peri- and postnatal maturation, and aging were all considered as stages of a development continuum relevant to problems of Space Biology. Deliberations thus far have been limited to stages of the development cycle from fertilization to early postnatal life. The deliberations are detailed.

Functional groups show distinct differences in nitrogen cycling during early stand development: implications for forest management.

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

Aubrey, Doug, P.; Coyle, David, R. Coleman, Mark, D.

2011-08-26

Nutrient acquisition of forest stands is controlled by soil resource availability and belowground production, but tree species are rarely compared in this regard. Here, we examine ecological and management implications of nitrogen (N) dynamics during early forest stand development in productive commercial tree species with narrow (Populus deltoides Bartr. and Platanus occidentalis L.) and broad (Liquidambar styraciflua L. and Pinus taeda L.) site requirements while grown with a range of nutrient and water resources. We constructed N budgets by measuring N concentration ([N]) and N content (N{sub C}) of above- and belowground perennial and ephemeral tissues, determined N uptake (N{submore » UP}), and calculated N use efficiency (NUE). Forest stands regulated [N] within species-specific operating ranges without clear temporal or treatment patterns, thus demonstrating equilibrium between tissue [N] and biomass accumulation. Forest stand N{sub C} and N{sub UP} increased with stand development and paralleled treatment patterns of biomass accumulation, suggesting productivity is tightly linked to N{sub UP}. Inclusion of above- and belowground ephemeral tissue turnover in N{sub UP} calculations demonstrated that maximum N demand for narrow-sites adapted species exceeded 200 kg N ha{sup -1} year{sup -1} while demand for broad-site adapted species was below this level. NUE was species dependent but not consistently influenced by N availability, suggesting relationships between NUE and resource availability were species dependent. Based on early stand development, species with broad site adaptability are favored for woody cropping systems because they maintain high above- and belowground productivity with minimal fertilization requirements due to higher NUE than narrow site adapted species.« less

Risk-based Process Development of Biosimilars as Part of the Quality by Design Paradigm.

PubMed

Zalai, Dénes; Dietzsch, Christian; Herwig, Christoph

2013-01-01

In the last few years, several quality by design (QbD) studies demonstrated the benefit of systematic approaches for biopharmaceutical development. However, only very few studies identified biosimilars as a special case of product development. The targeted quality profile of biosimilars is strictly defined by the originator's product characteristic. Moreover, the major source of prior knowledge is the experience with the originator product itself. Processing this information in biosimilar development has a major effect on risk management and process development strategies. The main objective of this contribution is to demonstrate how risk management can facilitate the implementation of QbD in early-stage product development with special emphasis on fitting the reported approaches to biosimilars. Risk assessments were highlighted as important tools to integrate prior knowledge in biosimilar development. The risk assessment process as suggested by the International Conference on Harmonization (ICH Q9) was reviewed and three elements were identified to play a key role in targeted risk assessment approaches: proper understanding of target linkage, risk assessment tool compliance, and criticality threshold value. Adjusting these steps to biosimilar applications helped to address some unique challenges of these products such as a strictly defined quality profile or a lack of process knowledge. This contribution demonstrates the need for tailored risk management approaches for the risk-based development of biosimilars and provides novel tools for the integration of additional knowledge available for these products. The pharmaceutical industry is facing challenges such as profit loss and price competition. Companies are forced to rationalize business models and to cut costs in development as well as manufacturing. These trends recently hinder the implementation of any concepts that do not offer certain financial benefit or promise a long return of investment. Quality by design (QbD) is a concept that is currently struggling for more acceptance from the side of the pharmaceutical industry. To achieve this, the major goals of QbD have to be revisited and QbD tools have to be subsequently developed. This contribution offers an example as to how implement risk management in early-stage biosimilar development as part of the QbD concept. The main goal was to go beyond the conventional QbD workflow and to adjust risk management to the challenges of biosimilar products. Accordingly, instead of using methods like failure mode and effects analysis, recommendations of the ICH Q9 guideline were reviewed and put into practice by creating tailored risk assessment tools. The novelty of this contribution is to report those tailored tools ready-to-use for early bioprocess development of biosimilars along QbD principles.

Aspherical Supernovae: Effects on Early Light Curves

NASA Astrophysics Data System (ADS)

Afsariardchi, Niloufar; Matzner, Christopher D.

2018-04-01

Early light from core-collapse supernovae, now detectable in high-cadence surveys, holds clues to a star and its environment just before it explodes. However, effects that alter the early light have not been fully explored. We highlight the possibility of nonradial flows at the time of shock breakout. These develop in sufficiently nonspherical explosions if the progenitor is not too diffuse. When they do develop, nonradial flows limit ejecta speeds and cause ejecta–ejecta collisions. We explore these phenomena and their observational implications using global, axisymmetric, nonrelativistic FLASH simulations of simplified polytropic progenitors, which we scale to representative stars. We develop a method to track photon production within the ejecta, enabling us to estimate band-dependent light curves from adiabatic simulations. Immediate breakout emission becomes hidden as an oblique flow develops. Nonspherical effects lead the shock-heated ejecta to release a more constant luminosity at a higher, evolving color temperature at early times, effectively mixing breakout light with the early light curve. Collisions between nonradial ejecta thermalize a small fraction of the explosion energy; we will address emission from these collisions in a subsequent paper.

Early communicative gestures and play as predictors of language development in children born with and without family risk for dyslexia.

PubMed

Unhjem, Astrid; Eklund, Kenneth; Nergård-Nilssen, Trude

2014-08-01

The present study investigated early communicative gestures, play, and language skills in children born with family risk for dyslexia (FR) and a control group of children without this inheritable risk at ages 12, 15, 18, and 24 months. Participants were drawn from the Tromsø Longitudinal study of Dyslexia (TLD) which follows children's cognitive and language development from age 12 months through Grade 2 in order to identify early markers of developmental dyslexia. Results showed that symbolic play and parent reported play at age 12 months and communicative gestures at age 15 months explained 61% of the variance in productive language at 24 months in the FR group. These early nonlinguistic measures seem to be potentially interesting markers of later language development in children born at risk for dyslexia. © 2014 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Software Product Lines: Report of the 2009 U.S. Army Software Product Line Workshop

DTIC Science & Technology

2009-04-01

record system was fielded in 2008. One early challenge for Overwatch was coming up with a funding model that would support core asset development (a...match the organizational model to the funding model . Product line architecture is essential. Address product line requirements up front. Put processes...when trying to move from a customer-driven, product-specific funding model to one in which at least some of the funds are allocated to the creation and

Medical devices early assessment methods: systematic literature review.

PubMed

Markiewicz, Katarzyna; van Til, Janine A; IJzerman, Maarten J

2014-04-01

The aim of this study was to get an overview of current theory and practice in early assessments of medical devices, and to identify aims and uses of early assessment methods used in practice. A systematic literature review was conducted in September 2013, using computerized databases (PubMed, Science Direct, and Scopus), and references list search. Selected articles were categorized based on their type, objective, and main target audience. The methods used in the application studies were extracted and mapped throughout the early stages of development and for their particular aims. Of 1,961 articles identified, eighty-three studies passed the inclusion criteria, and thirty were included by searching reference lists. There were thirty-one theoretical papers, and eighty-two application papers included. Most studies investigated potential applications/possible improvement of medical devices, developed early assessment framework or included stakeholder perspective in early development stages. Among multiple qualitative and quantitative methods identified, only few were used more than once. The methods aim to inform strategic considerations (e.g., literature review), economic evaluation (e.g., cost-effectiveness analysis), and clinical effectiveness (e.g., clinical trials). Medical devices were often in the prototype product development stage, and the results were usually aimed at informing manufacturers. This study showed converging aims yet widely diverging methods for early assessment during medical device development. For early assessment to become an integral part of activities in the development of medical devices, methods need to be clarified and standardized, and the aims and value of assessment itself must be demonstrated to the main stakeholders for assuring effective and efficient medical device development.

Metallographic examination of the structure of the metal of cold arms of the nineteenth-early twentieth centuries made at the Zlatoust arms factory

NASA Astrophysics Data System (ADS)

Schastlivtsev, V. M.; Rodionov, D. P.; Gerasimov, V. Yu.; Khlebnikova, Yu. V.

2010-11-01

Data are given concerning the structure and the chemical composition of carbon steel used for making cold arms, which was produced at the Zlatoust arms factory in the nineteenth and early twentieth centuries. The results of the analysis of the structure of metal demonstrates the general trend of the development of metallurgy both at the Ural plants and in the world: from the creation of the crucible methods of production of cast steel to the mass production of cast steel by the Bessemer and Martin methods.

History of ancient copper smelting pollution during Roman and Medieval times recorded in Greenland ice

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

Hong, Sungmin; Candelone, J.P.; Patterson, C.C.

1996-04-12

Determination of copper concentrations in Greenland ice dated from seven millennia ago to the present showed values exceeding natural levels, beginning about 2500 years ago. This early large-scale pollution of the atmosphere of the Northern Hemisphere is attributed to emissions from the crude, highly polluting smelting technologies used for copper production during Roman and medieval times, especially in Europe and China. This study opens the way to a quantitative assessment of the history of early metal production, which was instrumental in the development of human cultures during ancient eras. 27 refs., 1 fig., 2 tabs.

Immunotherapy in the management of sepsis.

PubMed Central

Fagan, E. A.; Singer, M.

1995-01-01

The pathophysiological effects of severe sepsis, septic shock and related syndromes result from tissues damaged by the uncontrolled production of the mediators of inflammation. Early deaths are related primarily to the acute effects of the systemic inflammatory response. Later deaths are related more closely to the consequences of multiple organ dysfunction. Monoclonal antibodies and other immunotherapies have been developed against bacterial products, cytokines and other mediators involved in this systemic inflammatory response. Immunotherapies may improve outcome in the critically ill with sepsis if used early and as part of the therapeutic regimen of antimicrobial agents and intensive care support. PMID:7724438

Development of 3D and 4D Bridge Models and Plans

DOT National Transportation Integrated Search

2018-05-28

Since 2012, MDOT has been leading national efforts to modernize design development with 3D modeling. Early focus on roadway projects yielded streamlined plan production and digital data for construction. As MDOT pivots to 3D model-centric design, nat...

Improvement of Early Strength of Cement Mortar Containing Granulated Blast Furnace Slag Using Industrial Byproducts.

PubMed

Kim, Jin-Hyoung; Lee, Han-Seung

2017-09-07

In the field of construction, securing the early strength of concrete (on the first and third days of aging) has been an important problem in deciding the mold release time (i.e., shortening the construction time period). Therefore, the problem of reduced compressive strength in the early aging stage caused by mixing granulated blast furnace slag (GBFS) with concrete must certainly be resolved. In this study, we conduct experiments to explore methods for generating a concrete that develops an early strength equivalent to that of 100% OPC. The objective of this study is the development of an early-strength accelerator (ESA) made from an industrial by-product, for a GBFS-mixed cement mortar. This study also analyzes the mechanism of the early-strength generation in the concrete to evaluate the influence of the burning temperature of ESA on the optimal compressive strength of the concrete. According to the results of the experiment, GBFS, whose ESA is burnt at 800 °C, shows an activation factor of 102.6-104.7% in comparison with 100% OPC on the first and third days during early aging, thereby meeting the target compressive strength. The results of the micro-analytic experiment are as follows: ESA showed a pH of strongly alkaline. In addition, it was found that the content of SO₃ was high in the chemical components, thus activating the hydration reaction of GBFS in the early age. This initial hydration reaction was thought to be due to the increase in the filling effect of the hydrate and the generation of C-S-H of the early age by the mass production of Ettringite.

Improvement of Early Strength of Cement Mortar Containing Granulated Blast Furnace Slag Using Industrial Byproducts

PubMed Central

Kim, Jin-Hyoung; Lee, Han-Seung

2017-01-01

In the field of construction, securing the early strength of concrete (on the first and third days of aging) has been an important problem in deciding the mold release time (i.e., shortening the construction time period). Therefore, the problem of reduced compressive strength in the early aging stage caused by mixing granulated blast furnace slag (GBFS) with concrete must certainly be resolved. In this study, we conduct experiments to explore methods for generating a concrete that develops an early strength equivalent to that of 100% OPC. The objective of this study is the development of an early-strength accelerator (ESA) made from an industrial by-product, for a GBFS-mixed cement mortar. This study also analyzes the mechanism of the early-strength generation in the concrete to evaluate the influence of the burning temperature of ESA on the optimal compressive strength of the concrete. According to the results of the experiment, GBFS, whose ESA is burnt at 800 °C, shows an activation factor of 102.6–104.7% in comparison with 100% OPC on the first and third days during early aging, thereby meeting the target compressive strength. The results of the micro-analytic experiment are as follows: ESA showed a pH of strongly alkaline. In addition, it was found that the content of SO3 was high in the chemical components, thus activating the hydration reaction of GBFS in the early age. This initial hydration reaction was thought to be due to the increase in the filling effect of the hydrate and the generation of C-S-H of the early age by the mass production of Ettringite. PMID:28880256

Process and product development in the manufacturing of molecular therapeutics.

PubMed

Atkinson, E M; Christensen, J R

1999-08-01

In the development of molecular therapies, a great deal of attention has focused on tissue targets, gene delivery vectors, and expression cassettes. In order to become an approved therapy, however, a molecular therapeutic has to pass down the same product registration pathway as any other biological product. Moving from research into industrial production requires careful attention to regulatory, manufacturing and quality concerns. Early work on developing and characterizing robust and scaleable manufacturing processes will ultimately be rewarded by ease of implementation as the product is successful in clinical trials. Regulatory agencies require solid process and product characterization studies to demonstrate control and understanding of the molecular therapeutic. As the gene therapy industry matures, standards will continue to rise, creating an industry that is capable of producing safe, high-quality and effective therapies for many of the world's most difficult disease targets.

Bioeconomic model and selection indices in Aberdeen Angus cattle.

PubMed

Campos, G S; Braccini Neto, J; Oaigen, R P; Cardoso, F F; Cobuci, J A; Kern, E L; Campos, L T; Bertoli, C D; McManus, C M

2014-08-01

A bioeconomic model was developed to calculate economic values for biological traits in full-cycle production systems and propose selection indices based on selection criteria used in the Brazilian Aberdeen Angus genetic breeding programme (PROMEBO). To assess the impact of changes in the performance of the traits on the profit of the production system, the initial values ​​of the traits were increased by 1%. The economic values for number of calves weaned (NCW) and slaughter weight (SW) were, respectively, R$ 6.65 and R$ 1.43/cow/year. The selection index at weaning showed a 44.77% emphasis on body weight, 14.24% for conformation, 30.36% for early maturing and 10.63% for muscle development. The eighteen-month index showed emphasis of 77.61% for body weight, 4.99% for conformation, 11.09% for early maturing, 6.10% for muscle development and 0.22% for scrotal circumference. NCW showed highest economic impact, and SW had important positive effect on the economics of the production system. The selection index proposed can be used by breeders and should contribute to greater profitability. © 2014 Blackwell Verlag GmbH.

Defining the Application Readiness of Products when Developing Earth Observing Remote Sensing Data Products

NASA Astrophysics Data System (ADS)

Escobar, V. M.

2017-12-01

Satellite remote sensing technology has contributed to the transformation of multiple earth science domains, putting space observations at the forefront of innovation in Earth Science. With new satellite missions being launched every year, new types of Earth Science data are being incorporated into science models and decision-making systems in a broad array of organizations. These applications help hazard mitigation and decision-making in government, private, and civic institutions working to reduce its impact on human wellbeing. Policy guidance and knowledge of product maturity can influence mission design as well as development of product applications in user organizations. Ensuring that satellite missions serve both the scientific and user communities without becoming unfocused and overly expensive is a critical outcome from engagement of user communities. Tracking the applications and product maturity help improve the use of data. NASA's Applications Readiness Levels reduce cost and increase the confidence in applications. ARLs help identify areas where NASA products are most useful while allowing the user to leverage products in early development as well as those ready for operational uses. By considering the needs of the user community early on in the mission-design process, agencies can use ARLs to ensure that satellites meet the needs of multiple constituencies and the development of products are integrated into user organizations organically. ARLs and user integration provide a perspective on the maturity and readiness of a products ability to influence policy and decision-making. This paper describes the mission application development process at NASA and within the Earth Science Directorate. We present the successes and challenges faced by NASA data users and explain how ARLs helps link NASA science to the appropriate policies and decision frameworks. The methods presented here can be adapted to other programs and institutions seeking to rapidly move scientific research to applications that have societal impact.

Soil health assessment and maintenance in Central and South Central Brazil

USDA-ARS?s Scientific Manuscript database

Brazil has evolved from a food insecure country in the early 1970´s into one of the most important food producers and exporters in the world. During the past 45 years, a science-based advanced tropical agriculture was developed throughout Brazil. Production has increased steadily and productivity ga...

Does Sequence Matter? Productive Failure and Designing Online Authentic Learning for Process Engineering

ERIC Educational Resources Information Center

Lai, Polly K.; Portolese, Alisha; Jacobson, Michael J.

2017-01-01

This paper presents a study that applied both "productive failure" (PF) and "authentic learning" instructional approaches in online learning activities for early-career process engineers' professional development. This study compares participants learning with either a PF (low-to-high [LH]) or a more traditional (high-to-low)…

The Emergence of Productive Speech and Language in Spanish-Learning Paediatric Cochlear Implant Users

ERIC Educational Resources Information Center

Moreno-Torres, Ignacio

2014-01-01

It has been proposed that cochlear implant users may develop robust categorical perception skills, but that they show limited precision in perception. This article explores if a parallel contrast is observable in production, and if, despite acquiring typical linguistic representations, their early words are inconsistent. The participants were…

Teacher Acceptance of Evaluation through Productivity Management.

ERIC Educational Resources Information Center

Garrett, A. Warren

This paper describes the purposes of educational evaluation with particular emphasis on school improvement. The evaluation process used was based upon the analytical tools developed and tested by the Educational Productivity Council (EPC) of the University of Texas. An early form of this model and reporting system was introduced to a group of 68…

PCMO L01-Setting Specifications for Biological Investigational Medicinal Products.

PubMed

Krause, Stephan O

2015-01-01

This paper provides overall guidance and best practices for the setting of specifications for clinical biological drug substances and drug products within the framework of ICH guidelines on pharmaceutical development [Q8(R2) and Q11], quality risk management (Q9), and quality systems (Q10). A review is provided of the current regulatory expectations for the specification setting process as part of a control strategy during product development, pointing to existing challenges for the investigational new drug/investigational medicinal product dossier (IND/IMPD) sponsor. A case study illustrates how the investigational medicinal product specification revision process can be managed within a flexible quality system, and how specifications can be set and justified for early and late development stages. This paper provides an overview for the setting of product specifications for investigational medicinal products used in clinical trials. A case study illustrates how product specifications of investigational medicinal products can be justified and managed within a modern product quality system. © PDA, Inc. 2015.

The ARS Culture Collection and Developments in Biotechnology

USDA-ARS?s Scientific Manuscript database

The ARS Culture Collection (NRRL) has played a prominent role in the development of biotechnology since its founding in 1940 when the Northern Regional Research Laboratory opened. Early discoveries included selection of production strains for penicillin, dextran blood extender, xanthan gum and the v...

Research and Development of High-performance Explosives

PubMed Central

Cornell, Rodger; Wrobel, Erik; Anderson, Paul E.

2016-01-01

Developmental testing of high explosives for military applications involves small-scale formulation, safety testing, and finally detonation performance tests to verify theoretical calculations. small-scale For newly developed formulations, the process begins with small-scale mixes, thermal testing, and impact and friction sensitivity. Only then do subsequent larger scale formulations proceed to detonation testing, which will be covered in this paper. Recent advances in characterization techniques have led to unparalleled precision in the characterization of early-time evolution of detonations. The new technique of photo-Doppler velocimetry (PDV) for the measurement of detonation pressure and velocity will be shared and compared with traditional fiber-optic detonation velocity and plate-dent calculation of detonation pressure. In particular, the role of aluminum in explosive formulations will be discussed. Recent developments led to the development of explosive formulations that result in reaction of aluminum very early in the detonation product expansion. This enhanced reaction leads to changes in the detonation velocity and pressure due to reaction of the aluminum with oxygen in the expanding gas products. PMID:26966969

Educating the Human Brain. Human Brain Development Series

ERIC Educational Resources Information Center

Posner, Michael I.; Rothbart, Mary K.

2006-01-01

"Educating the Human Brain" is the product of a quarter century of research. This book provides an empirical account of the early development of attention and self regulation in infants and young children. It examines the brain areas involved in regulatory networks, their connectivity, and how their development is influenced by genes and…

Hydrological and thermal effects of hydropeaking on early life stages of salmonids: A modelling approach for implementing mitigation strategies.

PubMed

Casas-Mulet, Roser; Saltveit, Svein Jakob; Alfredsen, Knut Tore

2016-12-15

Alterations in hydrological and thermal regimes can potentially affect salmonid early life stages development and survival. The dewatering of salmon spawning redds due to hydropeaking can lead to mortality in early life stages, with higher impact on the alevins as they have lower tolerance to dewatering than the eggs. Flow-related mitigation measures can reduce early life stage mortality. We present a set of modelling tools to assess impacts and mitigation options to minimise the risk of mortality in early life stages in hydropeaking rivers. We successfully modelled long-term hydrological and thermal alterations and consequences for development rates. We estimated the risk of early life stages mortality and assessed the cost-effectiveness of implementing three release-related mitigation options (A,B,C). The economic cost of mitigation was low and ranged between 0.7% and 2.6% of the annual hydropower production. Options reducing the flow during spawning (B and C) in addition to only release minimum flows during development (A) were considered more effective for egg and alevin survival. Options B and C were however constraint by water availability in the system for certain years, and therefore only option A was always feasible. The set of modelling tools used in this study were satisfactory and their applications can be useful especially in systems where little field data is available. Targeted measures built on well-informed modelling tools can be tested on their effectiveness to mitigate dewatering effects vs. the hydropower system capacity to release or conserve water for power production. Environmental flow releases targeting specific ecological objectives can provide better cost-effective options than conventional operational rules complying with general legislation. Copyright © 2016 Elsevier B.V. All rights reserved.

'Learn the signs. Act early': a campaign to help every child reach his or her full potential.

PubMed

Daniel, K L; Prue, C; Taylor, M K; Thomas, J; Scales, M

2009-09-01

To examine the application of a social marketing approach to increase the early identification and treatment of autism and other developmental disorders. The intervention used formative research, behaviour change theory and traditional social marketing techniques to develop a campaign targeting parents, healthcare professionals and early educators to increase awareness of autism and other developmental delays, and to prompt action if a developmental delay was suspected. Using social marketing principles, the Centers for Disease Control and Prevention applied baseline research with the target audiences to understand the barriers and motivators to behaviour change, which included a lack of knowledge and resources (barriers), along with a willingness to learn and do more (motivators). Focus group testing of potential campaign concepts led to one particular approach and accompanying images, which together increased perceived severity of the problem and encouraged taking action. The audience research also helped to shape the marketing mix (product, price, place and promotion). Three-year follow-up research in this case study indicates a significant change in parent target behaviours, particularly among parents aware of the campaign, and substantially more healthcare professionals believe that they have the resources to educate parents about monitoring their child's cognitive, social and physical development. Qualitative results from early educators and childcare professional associations have been positive about products developed for daycare settings. The application of social marketing principles, behavior change theory and audience research was an effective approach to changing behaviours in this case. Understanding what the target audiences want and need, looking beyond parents to engage healthcare professionals and early educators, and engaging many strategic partners to extend the reach of the message helped campaign planners to develop a campaign that resonated with the target audiences and, importantly, moved them towards action.

Consumer-directed health plans: mixed employer signals, complex market dynamics.

PubMed

Tynan, Ann; Christianson, Jon B

2008-03-01

Health plans have expanded consumer-directed health plan (CDHP) product offerings--typically high-deductible health plans coupled with a spending account--and more employers are offering these products to workers, according to findings from the Center for Studying Health System Change's (HSC) 2007 site visits to 12 nationally representative metropolitan communities. In developing CDHPs, health plans are responding to a broader employer strategy to confer more responsibility on workers for their health care costs, lifestyle choices and treatment decisions. CDHP adoption by employers and consumers depends on a range of factors, including product features and employer characteristics, and varies across the 12 communities. While more large employers are introducing CDHPs into health benefit programs, adoption of CDHPs remains modest. Health plans and employers expect CDHP enrollment to grow as employers and employees become more knowledgeable about CDHP features, health plans develop more sophisticated support tools for plan enrollees, and there are more opportunities to learn from early adopters' experiences.early

Space Mission Operations Concept

NASA Technical Reports Server (NTRS)

Squibb, Gael F.

1996-01-01

This paper will discuss the concept of developing a space mission operations concept; the benefits of starting this system engineering task early; the neccessary inputs to the process; and the products that are generated.

Mucosal IgA increase in rats by continuous CLA feeding during suckling and early infancy.

PubMed

Pérez-Cano, Francisco J; Ramírez-Santana, Carolina; Molero-Luís, Marta; Castell, Margarida; Rivero, Montserrat; Castellote, Cristina; Franch, Angels

2009-03-01

The aim of this work was to establish the effect of the cis9,trans11 conjugated linoleic acid (CLA) isomer on mucosal immunity during early life in rats, a period when mucosal immunoglobulin production is poorly developed, as is also the case in humans. CLA supplementation was performed during three life periods: gestation, suckling, and early infancy. The immune status of supplemented animals was evaluated at two time points: at the end of the suckling period (21-day-old rats) and 1 week after weaning (28-day-old rats). Secretory IgA was quantified in intestinal washes from 28-day-old rats by ELISA technique. IgA, TGFbeta, and PPARgamma mRNA expression was measured in small intestine and colon by real time PCR, using Taqman specific probes and primers. IgA mucosal production was enhanced in animals supplemented with CLA during suckling and early infancy: in 28-day-old rats, IgA mRNA expression was increased in small intestine and colon by approximately 6- and 4-fold, respectively, and intestinal IgA protein by approximately 2-fold. TGFbeta gene expression was independent of age and type of tissue considered, and was not modified by dietary CLA. Gene expression of PPARgamma, a possible mediator of CLA's effects was also upregulated in animals receiving CLA during early life. In conclusion, dietary supplementation with CLA during suckling and extended to early infancy enhances development of the intestinal immune response in rats.

On the Performance Potential of Bioelectrochemical Life Support Systems

NASA Technical Reports Server (NTRS)

Mansell, J. Matthew

2013-01-01

An area of growing multi-disciplinary research and revolutionary development for bio-processing on Earth is bioelectrochemical systems. These systems exploit the capability of many microorganisms to act as biocatalysts, enhancing the performance of electrochemical processes which convert low-value materials into valuable products. Many varieties of such processes hold potential value for space exploration as means to recycle metabolic waste and other undesirable materials or insitu resources into oxygen, water, and other valuable substances. However, the wide range of possible reactants, products, configurations, and operating parameters, along with the early stage of development and application on the ground necessitate thorough consideration of which, if any, possibilities could outperform existing technologies and should thus receive investment for space applications. In turn, the decision depends on the theoretical and practical limits of performance and the value of the reactant-product conversions within spaceflight scenarios, and should, to the greatest extent possible, be examined from the perspective of a fully designed, integrated system, rather than as an isolated unit lacking critical components like valves and pumps. Herein, we select a series of possible reactant-product conversions, develop concept process flow diagrams for each, and estimate theoretical and (where sufficient literature data allows) practical performance limitations of each. The objective was to estimate the costs, benefits, and risks of each concept in order to aid strategic decisions in the early-phase technology development effort.

Drug-device combination products in the twenty-first century: epinephrine auto-injector development using human factors engineering.

PubMed

Edwards, Eric S; Edwards, Evan T; Simons, F Estelle R; North, Robert

2015-05-01

The systematic application of human factors engineering (HFE) principles to the development of drug-device combination products, including epinephrine auto-injectors (EAIs), has the potential to improve the effectiveness and safety of drug administration. A PubMed search was performed to assess the role of HFE in the development of drug-device combination products. The following keywords were used in different combinations: 'human factors engineering,' 'human factors,' 'medical products,' 'epinephrine/adrenaline auto-injector,' 'healthcare' and 'patient safety.' This review provides a summary of HFE principles and their application to the development of drug-device combination products as advised by the US FDA. It also describes the HFE process that was applied to the development of Auvi-Q, a novel EAI, highlighting specific steps that occurred during the product-development program. For drug-device combination products, device labeling and usability are critical and have the potential to impact clinical outcomes. Application of HFE principles to the development of drug-delivery devices has the potential to improve product quality and reliability, reduce risk and improve patient safety when applied early in the development process. Additional clinical and real-world studies will confirm whether the application of HFE has helped to develop an EAI that better meets the needs of patients at risk of anaphylaxis.

The Role of Experience in the Acquisition and Production of Diminutives and Gender in Spanish: Evidence from L2 Learners and Heritage Speakers

ERIC Educational Resources Information Center

Montrul, Silvina; de la Fuente, Israel; Davidson, Justin; Foote, Rebecca

2013-01-01

This study examined whether type of early language experience provides advantages to heritage speakers over second language (L2) learners with morphology, and investigated knowledge of gender agreement and its interaction with diminutive formation. Diminutives are a hallmark of Child Directed Speech in early language development and a highly…

Early stage hot spot analysis through standard cell base random pattern generation

NASA Astrophysics Data System (ADS)

Jeon, Joong-Won; Song, Jaewan; Kim, Jeong-Lim; Park, Seongyul; Yang, Seung-Hune; Lee, Sooryong; Kang, Hokyu; Madkour, Kareem; ElManhawy, Wael; Lee, SeungJo; Kwan, Joe

2017-04-01

Due to limited availability of DRC clean patterns during the process and RET recipe development, OPC recipes are not tested with high pattern coverage. Various kinds of pattern can help OPC engineer to detect sensitive patterns to lithographic effects. Random pattern generation is needed to secure robust OPC recipe. However, simple random patterns without considering real product layout style can't cover patterning hotspot in production levels. It is not effective to use them for OPC optimization thus it is important to generate random patterns similar to real product patterns. This paper presents a strategy for generating random patterns based on design architecture information and preventing hotspot in early process development stage through a tool called Layout Schema Generator (LSG). Using LSG, we generate standard cell based on random patterns reflecting real design cell structure - fin pitch, gate pitch and cell height. The output standard cells from LSG are applied to an analysis methodology to assess their hotspot severity by assigning a score according to their optical image parameters - NILS, MEEF, %PV band and thus potential hotspots can be defined by determining their ranking. This flow is demonstrated on Samsung 7nm technology optimizing OPC recipe and early enough in the process avoiding using problematic patterns.

Cost-effectiveness analysis of early versus non-early intervention in acute migraine based on evidence from the 'Act when Mild' study.

PubMed

Slof, John

2012-05-01

In spite of the important progress made in the abortive treatment of acute migraine episodes since the introduction of triptans, reduction of pain and associated symptoms is in many cases still not as effective nor as fast as would be desirable. Recent research pays more attention to the timing of the treatment, and taking triptans early in the course of an attack when pain is still mild has been found more efficacious than the usual strategy of waiting for the attack to develop to a higher pain intensity level. To investigate the cost effectiveness of early versus non-early intervention with almotriptan in acute migraine. An economic evaluation was conducted from the perspectives of French society and the French public health system based on patient-level data collected in the AwM (Act when Mild) study, a placebo-controlled trial that compared the response to early and non-early treatment of acute migraine with almotriptan. Incremental cost-effectiveness ratios (ICERs) were determined in terms of QALYs, migraine hours and productive time lost. Costs were expressed in Euros (year 2010 values). Bootstrapping was used to derive cost-effectiveness acceptability curves. Early treatment has shown to lead to shorter attack duration, less productive time lost, better quality of life, and is, with 92% probability, overall cost saving from a societal point of view. In terms of drug costs only, however, non-early treatment is less expensive. From the public health system perspective, the (bootstrap) mean ICER of early treatment amounts to €0.38 per migraine hour avoided, €1.29 per hour of productive time lost avoided, and €14,296 per QALY gained. Considering willingness-to-pay values of approximately €1 to avoid an hour of migraine, €10 to avoid the loss of a productive hour, or €30,000 to gain one QALY, the approximate probability that early treatment is cost effective is 90%, 90% and 70%, respectively. These results remain robust in different scenarios for the major elements of the economic evaluation. Compared with non-early treatment, a strategy of early treatment of acute migraine with almotriptan when pain is still mild is, with high probability, cost saving from the French societal perspective and can be considered cost effective from the public health system point of view.

Machine Learning Methods for Production Cases Analysis

NASA Astrophysics Data System (ADS)

Mokrova, Nataliya V.; Mokrov, Alexander M.; Safonova, Alexandra V.; Vishnyakov, Igor V.

2018-03-01

Approach to analysis of events occurring during the production process were proposed. Described machine learning system is able to solve classification tasks related to production control and hazard identification at an early stage. Descriptors of the internal production network data were used for training and testing of applied models. k-Nearest Neighbors and Random forest methods were used to illustrate and analyze proposed solution. The quality of the developed classifiers was estimated using standard statistical metrics, such as precision, recall and accuracy.

Cost Effectiveness of Natural Regeneration for Sustaining Production Continuity in Commercial Pine Plantations

Treesearch

T.R. Clason

2002-01-01

Reforestation is a key to production continuity in commercial pine plantations. Although natural and artificial regeneration methods have been used successfully for pine seedling establishment, it is seedling growth during early stage of plantation development that affects the financial potential of a pine plantation. A study was initiated to determine the effect of...

Wood adhesives : vital for producing most wood products

Treesearch

Charles R. Frihart

2011-01-01

A main route for the efficient utilization of wood resources is to reduce wood to small pieces and then bond them together (Frihart and Hunt 2010). Although humankind has been bonding wood since early Egyptian civilizations, the quality and quantity of bonded wood products has increased dramatically over the past 100 years with the development of new adhesives and...

Harvest operations for density management: planning requirements, production, costs, stand damage, and recommendations

Treesearch

Loren D. Kellogg; Stephen J. Pilkerton

2013-01-01

Since the early 1990s, several studies have been undertaken to determine the planning requirements, productivity, costs, and residual stand damage of harvest operations in thinning treatments designed to promote development of complex forest structure in order to enhance ecological functioning and biological diversity. Th ese studies include the Oregon State...

Segmental Production in Mandarin-Learning Infants

ERIC Educational Resources Information Center

Chen, Li-Mei; Kent, Raymond D.

2010-01-01

The early development of vocalic and consonantal production in Mandarin-learning infants was studied at the transition from babbling to producing first words. Spontaneous vocalizations were recorded for 24 infants grouped by age: G1 (0 ; 7 to 1 ; 0) and G2 (1 ; 1 to 1 ; 6). Additionally, the infant-directed speech of 24 caregivers was recorded…

Different implications of paternal and maternal atopy for perinatal IgE production and asthma development.

PubMed

Wu, Chih-Chiang; Chen, Rong-Fu; Kuo, Ho-Chang

2012-01-01

Asthma is a hereditary disease associated with IgE-mediated reaction. Whether maternal atopy and paternal atopy have different impacts on perinatal IgE production and asthma development remains unclear. This paper reviews and summarizes the effects of maternal and paternal atopy on the developmental aspects of IgE production and asthma. Maternal atopy affects both pre- and postnatal IgE production, whereas paternal atopy mainly affects the latter. Maternally transmitted genes GSTP1 and FceRI-beta are associated with lung function and allergic sensitization, respectively. In IgE production and asthma development, the maternal influence on gene-environment interaction is greater than paternal influence. Maternal, paternal, and/or postnatal environmental modulation of allergic responses have been linked to epigenetic mechanisms, which may be good targets for early prevention of asthma.

Different Implications of Paternal and Maternal Atopy for Perinatal IgE Production and Asthma Development

PubMed Central

Wu, Chih-Chiang; Chen, Rong-Fu; Kuo, Ho-Chang

2012-01-01

Asthma is a hereditary disease associated with IgE-mediated reaction. Whether maternal atopy and paternal atopy have different impacts on perinatal IgE production and asthma development remains unclear. This paper reviews and summarizes the effects of maternal and paternal atopy on the developmental aspects of IgE production and asthma. Maternal atopy affects both pre- and postnatal IgE production, whereas paternal atopy mainly affects the latter. Maternally transmitted genes GSTP1 and FceRI-beta are associated with lung function and allergic sensitization, respectively. In IgE production and asthma development, the maternal influence on gene-environment interaction is greater than paternal influence. Maternal, paternal, and/or postnatal environmental modulation of allergic responses have been linked to epigenetic mechanisms, which may be good targets for early prevention of asthma. PMID:22272211

Use of Multi-Year MODIS Phenological Data Products to Detect and Monitor Forest Disturbances at Regional and National Scales

NASA Technical Reports Server (NTRS)

Spruce, Joseph; Hargrove, William W.; Gasser, Jerry; Smoot, James; Ross, Kenton

2010-01-01

This presentation discusses an effort to use select MODIS phenological products for forest disturbance monitoring at the regional and CONUS scales. Forests occur on 1/3 of the U.S. land base and include regionally prevalent forest disturbances that can threaten forest sustainability. Regional and CONUS forest disturbance monitoring is needed for a national forest threat early warning system being developed by the USDA Forest Service with help from NASA, ORNL, and USGS. MODIS NDVI phenology products are being used to develop forest disturbance monitoring capabilities of this EWS.

The calcium sensor GhCaM7 promotes cotton fiber elongation by modulating reactive oxygen species (ROS) production.

PubMed

Tang, Wenxin; Tu, Lili; Yang, Xiyan; Tan, Jiafu; Deng, Fenglin; Hao, Juan; Guo, Kai; Lindsey, Keith; Zhang, Xianlong

2014-04-01

Fiber elongation is the key determinant of fiber quality and output in cotton (Gossypium hirsutum). Although expression profiling and functional genomics provide some data, the mechanism of fiber development is still not well understood. Here, a gene encoding a calcium sensor, GhCaM7, was isolated based on its high expression level relative to other GhCaMs in fiber cells at the fast elongation stage. The level of expression of GhCaM7 in the wild-type and the fuzzless/lintless mutant correspond to the presence and absence, respectively, of fiber initials. Overexpressing GhCaM7 promotes early fiber elongation, whereas GhCaM7 suppression by RNAi delays fiber initiation and inhibits fiber elongation. Reactive oxygen species (ROS) play important roles in early fiber development. ROS induced by exogenous hydrogen peroxide (H2 O2 ) and Ca(2+) starvation promotes early fiber elongation. GhCaM7 overexpression fiber cells show increased ROS concentrations compared with the wild-type, while GhCaM7 RNAi fiber cells have reduced concentrations. Furthermore, we show that H2 O2 enhances Ca(2+) influx into the fiber and feedback-regulates the expression of GhCaM7. We conclude that GhCaM7, Ca(2+) and ROS are three important regulators involved in early fiber elongation. GhCaM7 might modulate ROS production and act as a molecular link between Ca(2+) and ROS signal pathways in early fiber development. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Suomi NPP VIIRS Ocean Color Data Product Early Mission Assessment

NASA Technical Reports Server (NTRS)

Turpie, Kevin R.; Robinson, Wayne D.; Franz, Bryan A.; Eplee, Robert E., Jr.; Meister, Gerhard; Fireman, Gwyn F.; Patt, Frederick S.; Barnes, Robert A.; McClain, Charles R.

2013-01-01

Following the launch of the Visible Infrared Imaging Radiometer Suite (VIIRS) aboard the Suomi National Polarorbiting Partnership (NPP) spacecraft, the NASA NPP VIIRS Ocean Science Team (VOST) began an evaluation of ocean color data products to determine whether they could continue the existing NASA ocean color climate data record (CDR). The VOST developed an independent evaluation product based on NASA algorithms with a reprocessing capability. Here we present a preliminary assessment of both the operational ocean color data products and the NASA evaluation data products regarding their applicability to NASA science objectives.

Assessment of global precipitation measurement satellite products over Saudi Arabia

NASA Astrophysics Data System (ADS)

Mahmoud, Mohammed T.; Al-Zahrani, Muhammad A.; Sharif, Hatim O.

2018-04-01

Most hydrological analysis and modeling studies require reliable and accurate precipitation data for successful simulations. However, precipitation measurements should be more representative of the true precipitation distribution. Many approaches and techniques are used to collect precipitation data. Recently, hydrometeorological and climatological applications of satellite precipitation products have experienced a significant improvement with the emergence of the latest satellite products, namely, the Integrated Multi-satellitE Retrievals for Global Precipitation Measurement (GPM) mission (IMERG) products, which can be utilized to estimate and analyze precipitation data. This study focuses on the validation of the IMERG early, late and final run rainfall products using ground-based rain gauge observations throughout Saudi Arabia for the period from October 2015 to April 2016. The accuracy of each IMERG product is assessed using six statistical performance measures to conduct three main evaluations, namely, regional, event-based and station-based evaluations. The results indicate that the early run product performed well in the middle and eastern parts as well as some of the western parts of the country; meanwhile, the satellite estimates for the other parts fluctuated between an overestimation and an underestimation. The late run product showed an improved accuracy over the southern and western parts; however, over the northern and middle parts, it showed relatively high errors. The final run product revealed significantly improved precipitation estimations and successfully obtained higher accuracies over most parts of the country. This study provides an early assessment of the performance of the GPM satellite products over the Middle East. The study findings can be used as a beneficial reference for the future development of the IMERG algorithms.

Contribution of Near Real Time MODIS-Based Forest Disturbance Detection Products to a National Forest Threat Early Warning System

NASA Technical Reports Server (NTRS)

Spruce, Joseph; Hargrove, William; Gasser, Gerald; Smoot, James; Kuper, Philip

2011-01-01

U.S. forests occupy approx. 751 million acres (approx. 1/3 of total land). These forests are exposed to multiple biotic and abiotic threats that collectively damage extensive acreages each year. Hazardous forest disturbances can threaten human life and property, bio-diversity and water supplies. Timely regional forest monitoring products are needed to aid forest management and decision making by the US Forest Service and its state and private partners. Daily MODIS data products provide a means to monitor regional forest disturbances on a weekly basis. In response, we began work in 2006 to develop a Near Real Time (NRT) forest monitoring capability, based on MODIS NDVI data, as part of a national forest threat early warning system (EWS)

Prize for Industrial Applications of Physics: Reflective Cholesteric Liquid Crystals - Innovations in Materials, Display Technology, and Commercialization

NASA Astrophysics Data System (ADS)

Khan, Asad

Reflective Cholesteric Liquid Crystals have been the subject of much research, development, and commercialization - in display technology as well as other embodiments, such as sensors, privacy films, etc. The liquid Crystal Institute (LCI) at Kent State University (KSU) served as a hot bed of much of the research and development in this field in the early 1990's. From here, the reflective technology was licensed to Kent Displays (KDI) to further develop and commercialize. The 90's saw some development in flexible technologies, drive scheme, display design, as well as materials. The early part of the century took a turn with a strong effort in encapsulation based flexible display development. In 2006, KDI engineers and technologists started firming up ambitious plans for the world's first roll-to-roll manufacturing line for bistable cholesteric displays. In 2009, this became a reality! In early 2010, the first eWriter product was launched into the consumer market under the brand Boogie Board®. Within months, this became a success forcing the rapid development of the manufacturing process for the flexible displays. Today, the company has two manufacturing lines, 24 hour roll-to-roll production of flexible displays, millions of Boogie Board products in the global market place, and a growing OEM business in the Boogie Board technology. KDI continues to do basic research, development, and exploration in the bistable display field. It also has had to become an expert in the supply chain management of the unique raw materials needed for flexible display manufacturing, while still managing global operations with sales offices in several continents and a growing and diversified group of individuals. In this presentation, we will present the story, research, development, technology, and latest trends in bistable cholesteric liquid crystal materials with a particular emphasis on the eWriter technology and market.

Disturbance ecology in the Northern Rockies: One perspective

Treesearch

Al Harvey; Penny Morgan

2001-01-01

Since early 1900s forestry, ecology and related professions have been aware that external disturbances had important effects on the development of vegetation. However, the integral part they play in ecosystem development and sustainability across time and space was largely underappreciated. Failure to provide appropriate disturbances can place stable and productive...

How Children Grow--Musically.

ERIC Educational Resources Information Center

Scott, Carol Rogel

1989-01-01

Reviews current research findings in the field of music in early childhood. Focuses on the musical development of the average child, citing evidence of music cognition and of music production. Reports some model programs established by music educators to work with parents and preschools to encourage musical development in the young child. (LS)

OZI: Australian English Communicative Development Inventory

ERIC Educational Resources Information Center

Kalashnikova, Marina; Schwarz, Iris-Corinna; Burnham, Denis

2016-01-01

For more than 20 years, the MacArthur-Bates Communicative Development Inventory (CDI) and its adaptations for languages other than English have been used as reliable measures of infants' and toddlers' early receptive and productive vocabulary size. This article introduces the OZI, the Australian English adaptation of the MacArthur-Bates CDI, now…

Species trials for biomass plantations in Hawaii: a first appraisal

Treesearch

Thomas H. Shubert; Craig D. Whitesell

1985-01-01

Species trials have been conducted in Hawaii since the 1870's. Many species have been successfully established and harvested, whereas native species have failed in numerous reforestation projects. Since the early 1960's silviculture research concentrated on developing methodology for establishing and developing forest stands for timber production.

Sociocultural Contexts for the Early Development of Semiotic Production

ERIC Educational Resources Information Center

Braswell, Gregory S.

2006-01-01

Children constantly encounter signs during cultural practices, although many theories do not fully acknowledge sociocultural aspects of semiotic development. The author examines research on cultural practices and contexts in which children learn to produce signs involving representational drawing and pretend play. This work is contrasted with more…

Symbols in motion: Flexible cultural boundaries and the fast spread of the Neolithic in the western Mediterranean

PubMed Central

Manen, Claire; García-Martínez de Lagrán, Iñigo

2018-01-01

The rapid diffusion of farming technologies in the western Mediterranean raises questions about the mechanisms that drove the development of intensive contact networks and circulation routes between incoming Neolithic communities. Using a statistical method to analyze a brand-new set of cultural and chronological data, we document the large-scale processes that led to variations between Mediterranean archaeological cultures, and micro-scale processes responsible for the transmission of cultural practices within farming communities. The analysis of two symbolic productions, pottery decorations and personal ornaments, shed light on the complex interactions developed by Early Neolithic farmers in the western Mediterranean area. Pottery decoration diversity correlates with local processes of circulation and exchange, resulting in the emergence and the persistence of stylistic and symbolic boundaries between groups, while personal ornaments reflect extensive networks and the high level of mobility of Early Neolithic farmers. The two symbolic productions express different degrees of cultural interaction that may have facilitated the successful and rapid expansion of early farming societies in the western Mediterranean. PMID:29715284

Impacts of Early Summer Eurasian Snow Cover Change on Atmospheric Circulation in Northern Mid-Latitudes

NASA Astrophysics Data System (ADS)

Nozawa, T.

2016-12-01

Recently, Japan Aerospace Exploration Agency (JAXA) has developed a new long-term snow cover extent (SCE) product using Advanced Very High Resolution Radiometer (AVHRR) and Moderate Resolution Imaging Spectroradiometer (MODIS) data spanning from 1980's to date. This new product (JAXA/SCE) has higher spatial resolution and smaller commission error compared with traditional SCE dataset of National Oceanic and Atmospheric Administration (NOAA/SCE). Continuity of the algorithm is another strong point in JAXA/SCE. According to the new JAXA/SCE dataset, the Eurasian SCE has been significantly retreating since 1980's, especially in late spring and early summer. Here, we investigate impacts of early summer Eurasian snow cover change on atmospheric circulation in Northern mid-latitudes, especially over the East Asia, using the new JAXA/SCE dataset and a few reanalysis data. We will present analyzed results on relationships between early summer SCE anomaly over the Eurasia and changes in atmospheric circulations such as upper level zonal jets (changes in strength, positions, etc.) over the East Asia.

Deriving fractional rate of degradation of logistic-exponential (LE) model to evaluate early in vitro fermentation.

PubMed

Wang, M; Sun, X Z; Tang, S X; Tan, Z L; Pacheco, D

2013-06-01

Water-soluble components of feedstuffs are mainly utilized during the early phase of microbial fermentation, which could be deemed an important determinant of gas production behavior in vitro. Many studies proposed that the fractional rate of degradation (FRD) estimated by fitting gas production curves to mathematical models might be used to characterize the early incubation for in vitro systems. In this study, the mathematical concept of FRD was developed on the basis of the Logistic-Exponential (LE) model, with initial gas volume being zero (LE0). The FRD of the LE0 model exhibits a continuous increase from initial (FRD 0) toward final asymptotic value (FRD F) with longer incubation time. The relationships between the FRD and gas production at incubation times 2, 4, 6, 8, 12 and 24 h were compared for four models, in addition to LE0, Generalization of the Mitscherlich (GM), c th order Michaelis-Menten (MM) and Exponential with a discrete LAG (EXPLAG). A total of 94 in vitro gas curves from four subsets with a wide range of feedstuffs from different laboratories and incubation periods were used for model testing. Results indicated that compared with the GM, MM and EXPLAG models, the FRD of LE0 model consistently had stronger correlations with gas production across the four subsets, especially at incubation times 2, 4, 6, 8 and 12 h. Thus, the LE0 model was deemed to provide a better representation of the early fermentation rates. Furthermore, the FRD 0 also exhibited strong correlations (P < 0.05) with gas production at early incubation times 2, 4, 6 and 8 h across all four subsets. In summary, the FRD of LE0 model provides an alternative to quantify the rate of early stage incubation, and its initial value could be an important starting parameter of rate.

Metabolic Response to Heat Stress in Late-Pregnant and Early Lactation Dairy Cows: Implications to Liver-Muscle Crosstalk.

PubMed

Koch, Franziska; Lamp, Ole; Eslamizad, Mehdi; Weitzel, Joachim; Kuhla, Björn

2016-01-01

Climate changes lead to rising temperatures during summer periods and dramatic economic losses in dairy production. Modern high-yielding dairy cows experience severe metabolic stress during the transition period between late gestation and early lactation to meet the high energy and nutrient requirements of the fetus or the mammary gland, and additional thermal stress during this time has adverse implications on metabolism and welfare. The mechanisms enabling metabolic adaptation to heat apart from the decline in feed intake and milk yield are not fully elucidated yet. To distinguish between feed intake and heat stress related effects, German Holstein dairy cows were first kept at thermoneutral conditions at 15°C followed by exposure to heat-stressed (HS) at 28°C or pair-feeding (PF) at 15°C for 6 days; in late-pregnancy and again in early lactation. Liver and muscle biopsies and plasma samples were taken to assess major metabolic pathway regulation using real-time PCR and Western Blot. The results indicate that during heat stress, late pregnant cows activate Cahill but reduce Cori cycling, prevent increase in skeletal muscle fatty acid oxidation, and utilize increased amounts of pyruvate for gluconeogenesis, without altering ureagenesis despite reduced plane of nutrition. These homeorhetic adaptations are employed to reduce endogenous heat production while diverting amino acids to the growing fetus. Metabolic adaptation to heat stress in early lactation involves increased long-chain fatty acid degradation in muscle peroxisomes, allowance for muscle glucose utilization but diminished hepatic use of amino acid-derived pyruvate for gluconeogenesis and reduced peroxisomal fatty acid oxidation and ATP production in liver of HS compared to PF cows in early lactation. Consequently, metabolic adaptation to heat stress and reduced feed intake differ between late pregnancy and early lactation of dairy cows to maintain energy supply for fetus development or milk production simultaneously reducing endogenous heat production.

Metabolic Response to Heat Stress in Late-Pregnant and Early Lactation Dairy Cows: Implications to Liver-Muscle Crosstalk

PubMed Central

Eslamizad, Mehdi; Weitzel, Joachim; Kuhla, Björn

2016-01-01

Climate changes lead to rising temperatures during summer periods and dramatic economic losses in dairy production. Modern high-yielding dairy cows experience severe metabolic stress during the transition period between late gestation and early lactation to meet the high energy and nutrient requirements of the fetus or the mammary gland, and additional thermal stress during this time has adverse implications on metabolism and welfare. The mechanisms enabling metabolic adaptation to heat apart from the decline in feed intake and milk yield are not fully elucidated yet. To distinguish between feed intake and heat stress related effects, German Holstein dairy cows were first kept at thermoneutral conditions at 15°C followed by exposure to heat-stressed (HS) at 28°C or pair-feeding (PF) at 15°C for 6 days; in late-pregnancy and again in early lactation. Liver and muscle biopsies and plasma samples were taken to assess major metabolic pathway regulation using real-time PCR and Western Blot. The results indicate that during heat stress, late pregnant cows activate Cahill but reduce Cori cycling, prevent increase in skeletal muscle fatty acid oxidation, and utilize increased amounts of pyruvate for gluconeogenesis, without altering ureagenesis despite reduced plane of nutrition. These homeorhetic adaptations are employed to reduce endogenous heat production while diverting amino acids to the growing fetus. Metabolic adaptation to heat stress in early lactation involves increased long-chain fatty acid degradation in muscle peroxisomes, allowance for muscle glucose utilization but diminished hepatic use of amino acid-derived pyruvate for gluconeogenesis and reduced peroxisomal fatty acid oxidation and ATP production in liver of HS compared to PF cows in early lactation. Consequently, metabolic adaptation to heat stress and reduced feed intake differ between late pregnancy and early lactation of dairy cows to maintain energy supply for fetus development or milk production simultaneously reducing endogenous heat production. PMID:27513961

Production Is Only Half the Story - First Words in Two East African Languages.

PubMed

Alcock, Katherine J

2017-01-01

Theories of early learning of nouns in children's vocabularies divide into those that emphasize input (language and non-linguistic aspects) and those that emphasize child conceptualisation. Most data though come from production alone, assuming that learning a word equals speaking it. Methodological issues can mean production and comprehension data within or across input languages are not comparable. Early vocabulary production and comprehension were examined in children hearing two Eastern Bantu languages whose grammatical features may encourage early verb knowledge. Parents of 208 infants aged 8-20 months were interviewed using Communicative Development Inventories that assess infants' first spoken and comprehended words. Raw totals, and proportions of chances to know a word, were compared to data from other languages. First spoken words were mainly nouns (75-95% were nouns versus less than 10% verbs) but first comprehended words included more verbs (15% were verbs) than spoken words did. The proportion of children's spoken words that were verbs increased with vocabulary size, but not the proportion of comprehended words. Significant differences were found between children's comprehension and production but not between languages. This may be for pragmatic reasons, rather than due to concepts with which children approach language learning, or directly due to the input language.

Production Is Only Half the Story — First Words in Two East African Languages

PubMed Central

Alcock, Katherine J.

2017-01-01

Theories of early learning of nouns in children’s vocabularies divide into those that emphasize input (language and non-linguistic aspects) and those that emphasize child conceptualisation. Most data though come from production alone, assuming that learning a word equals speaking it. Methodological issues can mean production and comprehension data within or across input languages are not comparable. Early vocabulary production and comprehension were examined in children hearing two Eastern Bantu languages whose grammatical features may encourage early verb knowledge. Parents of 208 infants aged 8–20 months were interviewed using Communicative Development Inventories that assess infants’ first spoken and comprehended words. Raw totals, and proportions of chances to know a word, were compared to data from other languages. First spoken words were mainly nouns (75–95% were nouns versus less than 10% verbs) but first comprehended words included more verbs (15% were verbs) than spoken words did. The proportion of children’s spoken words that were verbs increased with vocabulary size, but not the proportion of comprehended words. Significant differences were found between children’s comprehension and production but not between languages. This may be for pragmatic reasons, rather than due to concepts with which children approach language learning, or directly due to the input language. PMID:29163280

An investigation of low ergonomics risk awareness, among staffs at early product development phase in Malaysia automotive industries

NASA Astrophysics Data System (ADS)

Aziz, Fazilah Abdul; Razali, Noraini; Najmiyah Jaafar, Nur

2016-02-01

Currently there are many automotive companies still unable to effectively prevent consequences of poor ergonomics in their manufacturing processes. This study purpose is to determine the surrounding factors that influence low ergonomics risk awareness among staffs at early product development phase in Malaysia automotive industry. In this study there are four variables, low ergonomic risk awareness, inappropriate method and tools, tight development schedule and lack of management support. The survey data were gathered from 245 respondents of local automotive companies in Malaysia. The data was analysed through multiple regression and moderated regression using the IBM SPSS software. Study results revealed that low ergonomic risk awareness has influenced by inappropriate method and tool, and tight development schedule. There were positive linear relationships between low ergonomic risk awareness and inappropriate method and tools, and tight development schedule. The more inappropriate method and tools applied; the lower their ergonomic risk awareness. The more tight development schedule is the lower ergonomic risk awareness. The relationship between low ergonomic risk awareness and inappropriate method and tools depends on staff's age, and education level. Furthermore the relationship between low ergonomic risk awareness and tight development schedule depends on staff's working experience and number of project involvement. The main contribution of this paper was identified the number of factors of low ergonomics risk awareness and offers better understanding on ergonomics among researchers and automotive manufacturer's employees during product development process.

Radiation Status of Sub-65 nm Electronics

NASA Technical Reports Server (NTRS)

Pellish, Jonathan A.

2011-01-01

Ultra-scaled complementary metal oxide semiconductor (CMOS) includes commercial foundry capabilities at and below the 65 nm technology node Radiation evaluations take place using standard products and test characterization vehicles (memories, logic/latch chains, etc.) NEPP focus is two-fold: (1) Conduct early radiation evaluations to ascertain viability for future NASA missions (i.e. leverage commercial technology development). (2) Uncover gaps in current testing methodologies and mechanism comprehension -- early risk mitigation.

Omega-6 Fatty Acids

MedlinePlus

... not coordination or movement in children with DCD. Laser eye surgery. Early research suggests that taking a tablet that ... improve tear production and improve eye healing after laser eye surgery. Improving mental development or growth in infants.Adding ...

Strategies to advance vaccine technologies for resource-poor settings.

PubMed

Kristensen, Debra; Chen, Dexiang

2013-04-18

New vaccine platform and delivery technologies that can have significant positive impacts on the effectiveness, acceptability, and safety of immunizations in developing countries are increasingly available. Although donor support for vaccine technology development is strong, the uptake of proven technologies by the vaccine industry and demand for them by purchasers continues to lag. This article explains the challenges and opportunities associated with accelerating the availability of innovative and beneficial vaccine technologies to meet critical needs in resource-poor settings over the next decade. Progress will require increased dialog between the public and private sectors around vaccine product attributes; establishment of specifications for vaccines that mirror programmatic needs; stronger encouragement of vaccine developers to consider novel technologies early in the product development process; broader facilitation of research and access to technologies through the formation of centers of excellence; the basing of vaccine purchase decisions on immunization systems costs rather than price per dose alone; possible subsidization of early technology adoption costs for vaccine producers that take on the risks of new technologies of importance to the public sector; and the provision of data to purchasers, better enabling them to make informed decisions that take into account the value of specific product attributes. Copyright © 2012 Elsevier Ltd. All rights reserved.

Regulation of early human growth: impact on long-term health.

PubMed

Koletzko, Berthold; Chourdakis, Michael; Grote, Veit; Hellmuth, Christian; Prell, Christine; Rzehak, Peter; Uhl, Olaf; Weber, Martina

2014-01-01

Growth and development are central characteristics of childhood. Deviations from normal growth can indicate serious health challenges. The adverse impact of early growth faltering and malnutrition on later health has long been known. In contrast, the impact of rapid early weight and body fat gain on programming of later disease risk have only recently received increased attention. Numerous observational studies related diet in early childhood and rapid early growth to the risk of later obesity and associated disorders. Causality was confirmed in a large, double-blind randomised trial testing the 'Early Protein Hypothesis'. In this trial we found that attenuation of protein supply in infancy normalized early growth and markedly reduced obesity prevalence in early school age. These results indicate the need to describe and analyse growth patterns and their regulation through diet in more detail and to characterize the underlying metabolic and epigenetic mechanisms, given the potential major relevance for public health and policy. Better understanding of growth patterns and their regulation could have major benefits for the promotion of public health, consumer-orientated nutrition recommendations, and the development of improved food products for specific target populations. © 2014 S. Karger AG, Basel.

The Challenges of Developing Disciplinary Knowledge and Making Links across the Disciplines in Early Years and Primary Humanities

ERIC Educational Resources Information Center

Swift, Diane

2017-01-01

This article argues that an understanding of disciplinary knowledge production helps to underpin a conceptual structure for the humanities curriculum. This is important as a conceptual curriculum more overtly supports knowledge production for both pupils and teachers than one that is solely focused on propositional knowledge. It can mean the…

Consonant Cluster Production in Children with Cochlear Implants: A Comparison with Normally Hearing Peers

ERIC Educational Resources Information Center

Faes, Jolien; Gillis, Steven

2017-01-01

In early word productions, the same types of errors are manifest in children with cochlear implants (CI) as in their normally hearing (NH) peers with respect to consonant clusters. However, the incidence of those types and their longitudinal development have not been examined or quantified in the literature thus far. Furthermore, studies on the…

Production and early field performance of RPM® seedlings in Missouri floodplains

Treesearch

Daniel C. Dey; Wayne Lovelace; John M. Kabrick; Michael A. Gold

2004-01-01

A new nursery culture process has been developed to produce large container RPM? seedlings in an effort to improve the success in artificially regenerating hardwoods. Major features of the process include air root pruning of seedlings grown in a well aerated soil medium to encourage a dense, fibrous root system. Production has focused on native bottomland tree, shrub,...

Factors affecting acorn production and germination and early growth of seedlings and seedling sprouts

Treesearch

David F. Olson; Stephen G. Boyce

1971-01-01

Acorn production is extremely variable and unpredictable. Flowering is copious, but many climatic factors influence acorn development from initiation of flowers to acorn maturity. Acorns are consumed by birds, animals, insects, and microorganisms. The establishment of seedlings is more closely related to favorable site factors than to size of crops. A majority of oaks...

Alaska forest products: using resources well.

Treesearch

Valerie Rapp

2003-01-01

Despite abundant forest resources in the state, the Alaska forest products industry declined throughout the 1990s and early 21st century. In a state with lots of trees, mills are going out of business and most finished lumber used in the state is imported from the lower 48 United States and Canada. The Alaska Wood Utilization Research and Development Center (Wood...

Fluorescence from the maillard reaction and its potential applications in food science.

PubMed

Matiacevich, Silvia B; Santagapita, Patricio R; Buera, M Pilar

2005-01-01

The chemistry of the Maillard reaction involves a complex set of steps, and its interpretation represents a challenge in basic and applied aspects of Food Science. Fluorescent compounds have been recognized as important early markers of the reaction in food products since 1942. However, the recent advances in the characterization of fluorophores' development were observed in biological and biomedical areas. The in vivo non-enzymatic glycosylation of proteins produces biological effects, promoting health deterioration. The characteristic fluorescence of advanced glycosylation end products (AGEs) is similar to that of Maillard food products and represents an indicator of the level of AGE-modified proteins, but the structure of the fluorescent groups is, typically, unknown. Application of fluorescence measurement is considered a potential tool for addressing key problems of food deterioration as an early marker or index of the damage of biomolecules. Fluorophores may be precursors of the brown pigments and/or end products. A general scheme of the Maillard reaction is proposed in this article, incorporating the pool concept. A correct interpretation of the effect of environmental and compositional conditions and their influences on the reaction kinetics may help to define the meaning of fluorescence development for each particular system.

Application of Geographical Information Systems and Remote Sensing technologies for assessing and monitoring malaria risk.

PubMed

Ceccato, P; Connor, S J; Jeanne, I; Thomson, M C

2005-03-01

Despite over 30 years of scientific research, algorithm development and multitudes of publications relating Remote Sensing (RS) information with the spatial and temporal distribution of malaria, it is only in recent years that operational products have been adopted by malaria control decision-makers. The time is ripe for the wealth of research knowledge and products from developed countries be made available to the decision-makers in malarious regions of the globe where this information is urgently needed. This paper reviews the capability of RS to provide useful information for operational malaria early warning systems. It also reviews the requirements for monitoring the major components influencing emergence of malaria and provides examples of applications that have been made. Discussion of the issues that have impeded implementation on a global scale and how those barriers are disappearing with recent economic, technological and political developments are explored; and help pave the way for implementation of an integrated Malaria Early Warning System framework using RS technologies.

Clinical development of gene- and cell-based therapies: overview of the European landscape

PubMed Central

de Wilde, Sofieke; Guchelaar, Henk-Jan; Zandvliet, Maarten Laurens; Meij, Pauline

2016-01-01

In the last decade, many clinical trials with gene- and cell-based therapies were performed and increasing interest in the development was established by (national) authorities, academic developers, and commercial companies. However, until now only eight products have received marketing authorization (MA) approval. In this study, a comprehensive overview of the clinical development of gene- and cell-based therapies in Europe is presented, with a strong focus on product-technical aspects. Public data regarding clinical trials with gene- and cell-based therapies, obtained from the European Union (EU) clinical trial database (EudraCT) between 2004 and 2014 were analyzed, including product-technical variables as potential determinants affecting development. 198 unique gene and cell therapy products were identified, which were studied in 278 clinical trials, mostly in phase 1/2 trials and with cell therapies as major group. Furthermore, most products were manufactured from autologous starting material mostly manufactured from stem cells. The majority of the trials were sponsored by academia, whereas phase 3 trials mostly by large companies. Academia dominated early-stage development by mainly using bone marrow derived products and stem cells. Conversely, commercial sponsors were more actively pursuing in vivo gene therapy medicinal product development, and cell therapies derived from differentiated tissue in later-stage development. PMID:27990447

Hydrogen production from algal biomass - Advances, challenges and prospects.

PubMed

Show, Kuan-Yeow; Yan, Yuegen; Ling, Ming; Ye, Guoxiang; Li, Ting; Lee, Duu-Jong

2018-06-01

Extensive effort is being made to explore renewable energy in replacing fossil fuels. Biohydrogen is a promising future fuel because of its clean and high energy content. A challenging issue in establishing hydrogen economy is sustainability. Biohydrogen has the potential for renewable biofuel, and could replace current hydrogen production through fossil fuel thermo-chemical processes. A promising source of biohydrogen is conversion from algal biomass, which is abundant, clean and renewable. Unlike other well-developed biofuels such as bioethanol and biodiesel, production of hydrogen from algal biomass is still in the early stage of development. There are a variety of technologies for algal hydrogen production, and some laboratory- and pilot-scale systems have demonstrated a good potential for full-scale implementation. This work presents an elucidation on development in biohydrogen encompassing biological pathways, bioreactor designs and operation and techno-economic evaluation. Challenges and prospects of biohydrogen production are also outlined. Copyright © 2018 Elsevier Ltd. All rights reserved.

Working with the U.S. Food and Drug Administration to obtain approval of products under the Animal Rule.

PubMed

Park, Glen D; Mitchel, Jules T

2016-06-01

While the development of medical products and approval by the U.S. Food and Drug Administration (FDA) is well known, the development of countermeasures against exposure to toxic levels of radiation, chemicals, and infectious agents requires special consideration, and there has been, to date, little experience in working with the FDA to obtain approval of these products. The FDA has published a regulation entitled "Approval of Biological Products when Human Efficacy Studies are not Ethical or Feasible." This regulation, known simply as the "Animal Rule," was designed to permit approval or licensing of drugs and biologics when efficacy studies in humans are not ethical or feasible. To date, 12 products have been approved under the Animal Rule. It is highly recommended that sponsors of products that are to be developed under the Animal Rule meet with the FDA and other government entities early in the development process to ensure that the efficacy and safety studies that are planned will meet the FDA's requirements for approval of the product. © 2016 New York Academy of Sciences.

Career Benchmarks From the Burroughs Wellcome Fund's Early Faculty Career Development Awards.

PubMed

McGovern, Victoria; Kramarik, Jean; Wilkins, Gary

2013-11-01

Documenting the career characteristics of a highly selective group of researchers provides some insight into how a successful career begins. This knowledge is of value to early-career faculty and those who evaluate them, as well as trainees who aspire to the professoriate and those who educate them. In 2010, the authors extracted information by hand from the curricula vitae of 196 basic scientists who have been supported by the Burroughs Wellcome Fund's early faculty career development programs from 1982 to 2010. Data were collected on awardees' education, awards and honors, funding, promotion, publication, service, and training activities. The end point for data was December 2010. Analyses quantified participants' time to terminal degree, faculty appointment, and first R01; determined their publication productivity; and calculated their rates of training graduate students and postdoctoral fellows. This group moved into jobs and gained first R01s faster than average. Surprisingly, those who train the most students and fellows do not publish the most. Women and men trained different numbers of undergraduates, PhDs, and postdocs. Women awardees had fewer publications on average than men. Researchers who are highly competitive at the early faculty career stage have generally been both timely in their arrival at important benchmarks and productive in terms of their scientific output. Newly trained researchers and the people and institutions that train them share responsibility for attaining expeditious progress, developing a substantial track record, and staking out fertile intellectual ground from which to grow an independent faculty career.

Early Evaluation of the VIIRS Calibration, Cloud Mask and Surface Reflectance Earth Data Records

NASA Technical Reports Server (NTRS)

Vermote, Eric; Justice, Chris; Csiszar, Ivan

2014-01-01

Surface reflectance is one of the key products fromVIIRS and as withMODIS, is used in developing several higherorder land products. The VIIRS Surface Reflectance (SR) Intermediate Product (IP) is based on the heritageMODIS Collection 5 product (Vermote, El Saleous, & Justice, 2002). The quality and character of surface reflectance depend on the accuracy of the VIIRS Cloud Mask (VCM), the aerosol algorithms and the adequate calibration of the sensor. The focus of this paper is the early evaluation of the VIIRS SR product in the context of the maturity of the operational processing system, the Interface Data Processing System (IDPS). After a brief introduction, the paper presents the calibration performance and the role of the surface reflectance in calibration monitoring. The analysis of the performance of the cloud mask with a focus on vegetation monitoring (no snow conditions) shows typical problems over bright surfaces and high elevation sites. Also discussed is the performance of the aerosol input used in the atmospheric correction and in particular the artifacts generated by the use of the Navy Aerosol Analysis and Prediction System. Early quantitative results of the performance of the SR product over the AERONET sites showthatwith the fewadjustments recommended, the accuracy iswithin the threshold specifications. The analysis of the adequacy of the SR product (Land PEATE adjusted version) in applications of societal benefits is then presented. We conclude with a set of recommendations to ensure consistency and continuity of the JPSS mission with the MODIS Land Climate Data Record.

Teotihuacan, tepeapulco, and obsidian exploitation.

PubMed

Charlton, T H

1978-06-16

Current cultural ecological models of the development of civilization in central Mexico emphasize the role of subsistence production techniques and organization. The recent use of established and productive archeological surface survey techniques along natural corridors of communication between favorable niches for cultural development within the Central Mexican symbiotic region resulted in the location of sites that indicate an early development of a decentralized resource exploitation, manufacturing, and exchange network. The association of the development of this system with Teotihuacán indicates the importance such nonsubsistence production and exchange had in the evolution of this first central Mexican civilization. The later expansion of Teotihuacán into more distant areas of Mesoamerica was based on this resource exploitation model. Later civilizations centered at Tula and Tenochtitlán also used such a model in their expansion.

Developing an operational rangeland water requirement satisfaction index

USGS Publications Warehouse

Senay, Gabriel B.; Verdin, James P.; Rowland, James

2011-01-01

Developing an operational water requirement satisfaction index (WRSI) for rangeland monitoring is an important goal of the famine early warning systems network. An operational WRSI has been developed for crop monitoring, but until recently a comparable WRSI for rangeland was not successful because of the extremely poor performance of the index when based on published crop coefficients (K c) for rangelands. To improve the rangeland WRSI, we developed a simple calibration technique that adjusts the K c values for rangeland monitoring using long-term rainfall distribution and reference evapotranspiration data. The premise for adjusting the K c values is based on the assumption that a viable rangeland should exhibit above-average WRSI (values >80%) during a normal year. The normal year was represented by a median dekadal rainfall distribution (satellite rainfall estimate from 1996 to 2006). Similarly, a long-term average for potential evapotranspiration was used as input to the famine early warning systems network WRSI model in combination with soil-water-holding capacity data. A dekadal rangeland WRSI has been operational for east and west Africa since 2005. User feedback has been encouraging, especially with regard to the end-of-season WRSI anomaly products that compare the index's performance to ‘normal’ years. Currently, rangeland WRSI products are generated on a dekadal basis and posted for free distribution on the US Geological Survey early warning website at http://earlywarning.usgs.gov/adds/

Androgen imprinting of the brain in animal models and humans with intersex disorders: review and recommendations.

PubMed

Hrabovszky, Zoltan; Hutson, John M

2002-11-01

Psychosexual development, gender assignment and surgical treatment in patients with intersex are controversial issues in the medical literature. Some groups are of the opinion that gender identity and sexual orientation are determined prenatally secondary to the fetal hormonal environment causing irreversible development of the nervous system. We reviewed the evidence in animal and human studies to determine the possible role of early postnatal androgen production in gender development. An extensive literature review was performed of data from animal experiments and human studies. RESULTS Many animal studies show that adding or removing hormonal stimulus in early postnatal life can profoundly alter gender behavior of the adult animal. Human case studies show that late intervention is unable to reverse gender orientation from male to female. Most studies have not permitted testing of whether early gender assignment and treatment as female with suppression/ablation of postnatal androgen production leads to improved concordance of the gender identity and sex of rearing. Animal studies support a role for postnatal androgens in brain/behavior development with human studies neither completely supportive nor antagonistic. Therefore, gender assignment in infants with intersex should be made with the possibility in mind that postnatal testicular hormones at ages 1 to 6 months may affect gender identity. A case-control study is required to test the hypothesis that postnatal androgen exposure may convert ambisexual brain functions to committed male behavior patterns.

Early Identification of SE-Related Program Risks

DTIC Science & Technology

2009-09-30

development of feasibility evidence for a 100-KSLOC project . It is good to note that the “sweet spots” are... models , or experiments with planned technologies and increasingly detailed analysis of development approaches and project productivity rates. The ...incomplete without the FED, it becomes a first-class project deliverable. This implies that it needs a plan for its development , and that each task

Aerospace Engineering Systems

NASA Technical Reports Server (NTRS)

VanDalsem, William R.; Livingston, Mary E.; Melton, John E.; Torres, Francisco J.; Stremel, Paul M.

1999-01-01

Continuous improvement of aerospace product development processes is a driving requirement across much of the aerospace community. As up to 90% of the cost of an aerospace product is committed during the first 10% of the development cycle, there is a strong emphasis on capturing, creating, and communicating better information (both requirements and performance) early in the product development process. The community has responded by pursuing the development of computer-based systems designed to enhance the decision-making capabilities of product development individuals and teams. Recently, the historical foci on sharing the geometrical representation and on configuration management are being augmented: Physics-based analysis tools for filling the design space database; Distributed computational resources to reduce response time and cost; Web-based technologies to relieve machine-dependence; and Artificial intelligence technologies to accelerate processes and reduce process variability. Activities such as the Advanced Design Technologies Testbed (ADTT) project at NASA Ames Research Center study the strengths and weaknesses of the technologies supporting each of these trends, as well as the overall impact of the combination of these trends on a product development event. Lessons learned and recommendations for future activities will be reported.

Potency assay development for cellular therapy products: an ISCT review of the requirements and experiences in the industry.

PubMed

Bravery, Christopher A; Carmen, Jessica; Fong, Timothy; Oprea, Wanda; Hoogendoorn, Karin H; Woda, Juliana; Burger, Scott R; Rowley, Jon A; Bonyhadi, Mark L; Van't Hof, Wouter

2013-01-01

The evaluation of potency plays a key role in defining the quality of cellular therapy products (CTPs). Potency can be defined as a quantitative measure of relevant biologic function based on the attributes that are linked to relevant biologic properties. To achieve an adequate assessment of CTP potency, appropriate in vitro or in vivo laboratory assays and properly controlled clinical data need to be created. The primary objective of a potency assay is to provide a mechanism by which the manufacturing process and the final product for batch release are scrutinized for quality, consistency and stability. A potency assay also provides the basis for comparability assessment after process changes, such as scale-up, site transfer and new starting materials (e.g., a new donor). Potency assays should be in place for early clinical development, and validated assays are required for pivotal clinical trials. Potency is based on the individual characteristics of each individual CTP, and the adequacy of potency assays will be evaluated on a case-by-case basis by regulatory agencies. We provide an overview of the expectations and challenges in development of potency assays specific for CTPs; several real-life experiences from the cellular therapy industry are presented as illustrations. The key observation and message is that aggressive early investment in a solid potency evaluation strategy can greatly enhance eventual CTP deployment because it can mitigate the risk of costly product failure in late-stage development. Copyright © 2013. Published by Elsevier Inc.

Building a Framework in Improving Drought Monitoring and Early Warning Systems in Africa

NASA Astrophysics Data System (ADS)

Tadesse, T.; Wall, N.; Haigh, T.; Shiferaw, A. S.; Beyene, S.; Demisse, G. B.; Zaitchik, B.

2015-12-01

Decision makers need a basic understanding of the prediction models and products of hydro-climatic extremes and their suitability in time and space for strategic resource and development planning to develop mitigation and adaptation strategies. Advances in our ability to assess and predict climate extremes (e.g., droughts and floods) under evolving climate change suggest opportunity to improve management of climatic/hydrologic risk in agriculture and water resources. In the NASA funded project entitled, "Seasonal Prediction of Hydro-Climatic Extremes in the Greater Horn of Africa (GHA) under Evolving Climate Conditions to Support Adaptation Strategies," we are attempting to develop a framework that uses dialogue between managers and scientists on how to enhance the use of models' outputs and prediction products in the GHA as well as improve the delivery of this information in ways that can be easily utilized by managers. This process is expected to help our multidisciplinary research team obtain feedback on the models and forecast products. In addition, engaging decision makers is essential in evaluating the use of drought and flood prediction models and products for decision-making processes in drought and flood management. Through this study, we plan to assess information requirements to implement a robust Early Warning Systems (EWS) by engaging decision makers in the process. This participatory process could also help the existing EWSs in Africa and to develop new local and regional EWSs. In this presentation, we report the progress made in the past two years of the NASA project.

Investing in the foundation of sustainable development: pathways to scale up for early childhood development

PubMed Central

Richter, Linda M; Daelmans, Bernadette; Lombardi, Joan; Heymann, Jody; Boo, Florencia Lopez; Behrman, Jere R; Lu, Chunling; Lucas, Jane E; Perez-Escamilla, Rafael; Dua, Tarun; Bhutta, Zulfiqar A; Stenberg, Karin; Gertler, Paul; Darmstadt, Gary L

2018-01-01

Building on long-term benefits of early intervention (Paper 2 of this Series) and increasing commitment to early childhood development (Paper 1 of this Series), scaled up support for the youngest children is essential to improving health, human capital, and wellbeing across the life course. In this third paper, new analyses show that the burden of poor development is higher than estimated, taking into account additional risk factors. National programmes are needed. Greater political prioritisation is core to scale-up, as are policies that afford families time and financial resources to provide nurturing care for young children. Effective and feasible programmes to support early child development are now available. All sectors, particularly education, and social and child protection, must play a role to meet the holistic needs of young children. However, health provides a critical starting point for scaling up, given its reach to pregnant women, families, and young children. Starting at conception, interventions to promote nurturing care can feasibly build on existing health and nutrition services at limited additional cost. Failure to scale up has severe personal and social consequences. Children at elevated risk for compromised development due to stunting and poverty are likely to forgo about a quarter of average adult income per year, and the cost of inaction to gross domestic product can be double what some countries currently spend on health. Services and interventions to support early childhood development are essential to realising the vision of the Sustainable Development Goals. PMID:27717610

Rapid high-throughput characterisation, classification and selection of recombinant mammalian cell line phenotypes using intact cell MALDI-ToF mass spectrometry fingerprinting and PLS-DA modelling.

PubMed

Povey, Jane F; O'Malley, Christopher J; Root, Tracy; Martin, Elaine B; Montague, Gary A; Feary, Marc; Trim, Carol; Lang, Dietmar A; Alldread, Richard; Racher, Andrew J; Smales, C Mark

2014-08-20

Despite many advances in the generation of high producing recombinant mammalian cell lines over the last few decades, cell line selection and development is often slowed by the inability to predict a cell line's phenotypic characteristics (e.g. growth or recombinant protein productivity) at larger scale (large volume bioreactors) using data from early cell line construction at small culture scale. Here we describe the development of an intact cell MALDI-ToF mass spectrometry fingerprinting method for mammalian cells early in the cell line construction process whereby the resulting mass spectrometry data are used to predict the phenotype of mammalian cell lines at larger culture scale using a Partial Least Squares Discriminant Analysis (PLS-DA) model. Using MALDI-ToF mass spectrometry, a library of mass spectrometry fingerprints was generated for individual cell lines at the 96 deep well plate stage of cell line development. The growth and productivity of these cell lines were evaluated in a 10L bioreactor model of Lonza's large-scale (up to 20,000L) fed-batch cell culture processes. Using the mass spectrometry information at the 96 deep well plate stage and phenotype information at the 10L bioreactor scale a PLS-DA model was developed to predict the productivity of unknown cell lines at the 10L scale based upon their MALDI-ToF fingerprint at the 96 deep well plate scale. This approach provides the basis for the very early prediction of cell lines' performance in cGMP manufacturing-scale bioreactors and the foundation for methods and models for predicting other mammalian cell phenotypes from rapid, intact-cell mass spectrometry based measurements. Copyright © 2014 Elsevier B.V. All rights reserved.

Nondestructive phenotyping of lettuce plants in early stages of development with optical sensors

USDA-ARS?s Scientific Manuscript database

Rapid development of plants is important for the production of ‘baby-leaf’ lettuce that is harvested when plants reach the four- to eight-leaf stage of growth. However, environmental factors, such as high or low temperature, or elevated concentrations of salt, inhibit lettuce growth. Therefore, nond...

The Foundations of Lifelong Health Are Built in Early Childhood

ERIC Educational Resources Information Center

National Forum on Early Childhood Policy and Programs, 2010

2010-01-01

A vital and productive society with a prosperous and sustainable future is built on a foundation of healthy child development. Health in the earliest years--beginning with the future mother's well-being before she becomes pregnant--lays the groundwork for a lifetime of vitality. When developing biological systems are strengthened by positive early…

78 FR 14103 - Request for Information (RFI) Regarding the Planned Biotechnology Development Module (BDM) as...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-04

... the United States Department of Agriculture (USDA), Agricultural Research Service (ARS) and Animal and...-ARS, USDA-APHIS, and DHS) to implement early product development initiatives in partnership with... will support customers from all three NBAF user groups (DHS S&T, ARS, and APHIS) as well as potential...

Transverse vibration techniques : logs to structural systems

Treesearch

Robert J. Ross

2008-01-01

Transverse vibration as a nondestructive testing and evaluation technique was first examined in the early 1960s. Initial research and development efforts focused on clear wood, lumber, and laminated products. Out of those efforts, tools were developed that are used today to assess lumber properties. Recently, use of this technique has been investigated for evaluating a...

Baby Sign but Not Spontaneous Gesture Predicts Later Vocabulary in Children with Down Syndrome

ERIC Educational Resources Information Center

Özçaliskan, Seyda; Adamson, Lauren B.; Dimitrova, Nevena; Bailey, Jhonelle; Schmuck, Lauren

2016-01-01

Early spontaneous gesture, specifically deictic gesture, predicts subsequent vocabulary development in typically developing (TD) children. Here, we ask whether deictic gesture plays a similar role in predicting later vocabulary size in children with Down Syndrome (DS), who have been shown to have difficulties in speech production, but strengths in…

Commercialising genetically engineered animal biomedical products.

PubMed

Sullivan, Eddie J; Pommer, Jerry; Robl, James M

2008-01-01

Research over the past two decades has increased the quality and quantity of tools available to produce genetically engineered animals. The number of potentially viable biomedical products from genetically engineered animals is increasing. However, moving from cutting-edge research to development and commercialisation of a biomedical product that is useful and wanted by the public has significant challenges. Even early stage development of genetically engineered animal applications requires consideration of many steps, including quality assurance and quality control, risk management, gap analysis, founder animal establishment, cell banking, sourcing of animals and animal-derived material, animal facilities, product collection facilities and processing facilities. These steps are complicated and expensive. Biomedical applications of genetically engineered animals have had some recent successes and many applications are well into development. As researchers consider applications for their findings, having a realistic understanding of the steps involved in the development and commercialisation of a product, produced in genetically engineered animals, is useful in determining the risk of genetic modification to the animal nu. the potential public benefit of the application.

Case history of Yakin field: its development and sand control

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

Sawolo, N.; Krueger, R.F.; Maly, G.P.

1983-01-01

This paper deals with the development of the Yakin field in East Kalimantan, Indonesia, with emphasis on the sand control methods used. Implementation of an effective sand control program ensured the successful development of this field. Gravel-packed wells had substantially lower production decline rates than the initial completions without gravel packs. Control of sand production also has been demonstrated by the lack of sand problems during the 4 1/2 years since the sand control program was initiated. During this time there have been no submersible pump failures associated with sand production. The successful sand control program was achieved by amore » well-coordinated and cooperative effort of drilling, reservoir engineering, production research, and service company personnel. Establishment of communication among all people involved, starting early in the planning process and continuing through the rig operations to the final production phase, coupled with intensive training at all levels of responsibility, on-site supervision, and quality control were important factors in the success of the development program.« less

GEOGLAM Crop Assessment Tool: Adapting from global agricultural monitoring to food security monitoring

NASA Astrophysics Data System (ADS)

Humber, M. L.; Becker-Reshef, I.; Nordling, J.; Barker, B.; McGaughey, K.

2014-12-01

The GEOGLAM Crop Monitor's Crop Assessment Tool was released in August 2013 in support of the GEOGLAM Crop Monitor's objective to develop transparent, timely crop condition assessments in primary agricultural production areas, highlighting potential hotspots of stress/bumper crops. The Crop Assessment Tool allows users to view satellite derived products, best available crop masks, and crop calendars (created in collaboration with GEOGLAM Crop Monitor partners), then in turn submit crop assessment entries detailing the crop's condition, drivers, impacts, trends, and other information. Although the Crop Assessment Tool was originally intended to collect data on major crop production at the global scale, the types of data collected are also relevant to the food security and rangelands monitoring communities. In line with the GEOGLAM Countries at Risk philosophy of "foster[ing] the coordination of product delivery and capacity building efforts for national and regional organizations, and the development of harmonized methods and tools", a modified version of the Crop Assessment Tool is being developed for the USAID Famine Early Warning Systems Network (FEWS NET). As a member of the Countries at Risk component of GEOGLAM, FEWS NET provides agricultural monitoring, timely food security assessments, and early warnings of potential significant food shortages focusing specifically on countries at risk of food security emergencies. While the FEWS NET adaptation of the Crop Assessment Tool focuses on crop production in the context of food security rather than large scale production, the data collected is nearly identical to the data collected by the Crop Monitor. If combined, the countries monitored by FEWS NET and GEOGLAM Crop Monitor would encompass over 90 countries representing the most important regions for crop production and food security.

Early warning indicators for process failure due to organic overloading by rapeseed oil in one-stage continuously stirred tank reactor, sewage sludge and waste digesters.

PubMed

Kleyböcker, A; Liebrich, M; Verstraete, W; Kraume, M; Würdemann, H

2012-11-01

Early warning indicators for process failures were investigated to develop a reliable method to increase the production efficiency of biogas plants. Organic overloads by the excessive addition of rapeseed oil were used to provoke the decrease in the gas production rate. Besides typical monitoring parameters, as pH, methane and hydrogen contents, biogas production rate and concentrations of fatty acids; carbon dioxide content, concentrations of calcium and phosphate were monitored. The concentration ratio of volatile fatty acids to calcium acted as an early warning indicator (EWI-VFA/Ca). The EWI-VFA/Ca always clearly and reliably indicated a process imbalance by exhibiting a 2- to 3-fold increase 3-7days before the process failure occurred. At this time, it was still possible to take countermeasures successfully. Furthermore, increases in phosphate concentration and in the concentration ratio of phosphate to calcium also indicated a process failure, in some cases, even earlier than the EWI-VFA/Ca. Copyright © 2012 Elsevier Ltd. All rights reserved.

Integrating health economics into the product development cycle: a case study of absorbable pins for treating hallux valgus.

PubMed

Vallejo-Torres, Laura; Steuten, Lotte; Parkinson, Bonny; Girling, Alan J; Buxton, Martin J

2011-01-01

The probability of reimbursement is a key factor in determining whether to proceed with or abandon a product during its development. The purpose of this article is to illustrate how the methods of iterative Bayesian economic evaluation proposed in the literature can be incorporated into the development process of new medical devices, adapting them to face the relative scarcity of data and time that characterizes the process. A 3-stage economic evaluation was applied: an early phase in which simple methods allow for a quick prioritization of competing products; a mid-stage in which developers synthesize the data into a decision model, identify the parameters for which more information is most valuable, and explore uncertainty; and a late stage, in which all relevant information is synthesized. A retrospective analysis was conducted of the case study of absorbable pins, compared with metallic fixation, in osteotomy to treat hallux valgus. The results from the early analysis suggest absorbable pins to be cost-effective under the beliefs and assumptions applied. The outputs from the models at the mid-stage analyses show the device to be cost-effective with a high probability. Late-stage analysis synthesizes evidence from a randomized controlled trial and informative priors, which are based on previous evidence. It also suggests that absorbable pins are the most cost-effective strategy, although the uncertainty in the model output increased considerably. This example illustrates how the method proposed allows decisions in the product development cycle to be based on the best knowledge that is available at each stage.

Tobacco industry consumer research on smokeless tobacco users and product development.

PubMed

Mejia, Adrienne B; Ling, Pamela M

2010-01-01

Since 2006, RJ Reynolds (RJR) and Philip Morris have both introduced new smokeless "snus" tobacco products. We analyzed previously secret tobacco industry documents describing the history of RJR and Philip Morris's consumer research, smokeless product development, and marketing strategies. We found that RJR had invested in smokeless research, development, and marketing since 1968. RJR first targeted low-income males through sampling and sponsorship at fishing, rodeo, and baseball events, and through advertising portraying the user as "hard working." In the early 1990s, Philip Morris and RJR hoped to attract more urban, female smokeless users. The current "snus" campaigns appear to appeal to these targeted consumers and smokers in smoke-free environments. These efforts may expand the tobacco market and undermine smoking cessation.

Aspect-Oriented Model-Driven Software Product Line Engineering

NASA Astrophysics Data System (ADS)

Groher, Iris; Voelter, Markus

Software product line engineering aims to reduce development time, effort, cost, and complexity by taking advantage of the commonality within a portfolio of similar products. The effectiveness of a software product line approach directly depends on how well feature variability within the portfolio is implemented and managed throughout the development lifecycle, from early analysis through maintenance and evolution. This article presents an approach that facilitates variability implementation, management, and tracing by integrating model-driven and aspect-oriented software development. Features are separated in models and composed of aspect-oriented composition techniques on model level. Model transformations support the transition from problem to solution space models. Aspect-oriented techniques enable the explicit expression and modularization of variability on model, template, and code level. The presented concepts are illustrated with a case study of a home automation system.

Earthquake early Warning ShakeAlert system: West coast wide production prototype

USGS Publications Warehouse

Kohler, Monica D.; Cochran, Elizabeth S.; Given, Douglas; Guiwits, Stephen; Neuhauser, Doug; Hensen, Ivan; Hartog, Renate; Bodin, Paul; Kress, Victor; Thompson, Stephen; Felizardo, Claude; Brody, Jeff; Bhadha, Rayo; Schwarz, Stan

2017-01-01

Earthquake early warning (EEW) is an application of seismological science that can give people, as well as mechanical and electrical systems, up to tens of seconds to take protective actions before peak earthquake shaking arrives at a location. Since 2006, the U.S. Geological Survey has been working in collaboration with several partners to develop EEW for the United States. The goal is to create and operate an EEW system, called ShakeAlert, for the highest risk areas of the United States, starting with the West Coast states of California, Oregon, and Washington. In early 2016, the Production Prototype v.1.0 was established for California; then, in early 2017, v.1.2 was established for the West Coast, with earthquake notifications being distributed to a group of beta users in California, Oregon, and Washington. The new ShakeAlert Production Prototype was an outgrowth from an earlier demonstration EEW system that began sending test notifications to selected users in California in January 2012. ShakeAlert leverages the considerable physical, technical, and organizational earthquake monitoring infrastructure of the Advanced National Seismic System, a nationwide federation of cooperating seismic networks. When fully implemented, the ShakeAlert system may reduce damage and injury caused by large earthquakes, improve the nation’s resilience, and speed recovery.

[Formation of antioxidant defence system of geese in embryogenesis and early postnatal ontogenesis].

PubMed

Danchenko, O O; Kalytka, V V

2002-01-01

The features of antioxidant protection of tissues of a liver and blood of the gooses in embriogenesis and early postnatal ontogenesis are found out. Maximal contents TBA active products both in a liver, and in a blood are observed in 28 diurnal embriones. Is shown, that in a liver the activity of basic antioxidant enzymes (superoxide dismutases, catalase and glutathione peroxidase) in a liver is developed already at early stages embriogenesis and is considerably enlarged in the end embriogenesis. The becoming of enzymatic system of a blood descends much more slower.

Production and aerial application of wood shreds as a post-fire hillslope erosion mitigation treatment

Treesearch

Peter R. Robichaud; Louise E. Ashmun; Randy B. Foltz; Charles G. Showers; J. Scott Groenier; Jennifer Kesler; Claire DeLeo; Mary Moore

2013-01-01

Guidelines for the production and aerial application of wood shred mulch as a post-fire hillslope treatment were developed from laboratory and field studies, several field operations, and the evaluations of professionals involved in those operations. At two early trial sites, the wood shred mulch was produced off-site and transported to the area of use. At the 2010...

Using the scanning electron microscope on the production line to assure quality semiconductors

NASA Technical Reports Server (NTRS)

Adolphsen, J. W.; Anstead, R. J.

1972-01-01

The use of the scanning electron microscope to detect metallization defects introduced during batch processing of semiconductor devices is discussed. A method of determining metallization integrity was developed which culminates in a procurement specification using the scanning microscope on the production line as a quality control tool. Batch process control of the metallization operation is monitored early in the manufacturing cycle.

Sustained effects of atmospheric [CO2] and nitrogen availability on forest soil CO2 efflux

Treesearch

A. Christopher Oishi; Sari Palmroth; Kurt H. Johnsen; Heather R. McCarthy; Ram Oren

2014-01-01

Soil CO2 efflux (Fsoil) is the largest source of carbon from forests and reflects primary productivity as well as how carbon is allocated within forest ecosystems. Through early stages of stand development, both elevated [CO2] and availability of soil nitrogen (N; sum of mineralization, deposition, and fixation) have been shown to increase gross primary productivity,...

Optimization of insect cell based protein production processes - online monitoring, expression systems, scale up.

PubMed

Druzinec, Damir; Salzig, Denise; Brix, Alexander; Kraume, Matthias; Vilcinskas, Andreas; Kollewe, Christian; Czermak, Peter

2013-01-01

Due to the increasing use of insect cell based expression systems in research and industrial recombinant protein production, the development of efficient and reproducible production processes remains a challenging task. In this context, the application of online monitoring techniques is intended to ensure high and reproducible product qualities already during the early phases of process development. In the following chapter, the most common transient and stable insect cell based expression systems are briefly introduced. Novel applications of insect cell based expression systems for the production of insect derived antimicrobial peptides/proteins (AMPs) are discussed using the example of G. mellonella derived gloverin. Suitable in situ sensor techniques for insect cell culture monitoring in disposable and common bioreactor systems are outlined with respect to optical and capacitive sensor concepts. Since scale up of production processes is one of the most critical steps in process development, a conclusive overview is given about scale up aspects for industrial insect cell culture processes.

Maternal Gesture Use and Language Development in Infant Siblings of Children with Autism Spectrum Disorder

PubMed Central

Talbott, Meagan R.; Tager-Flusberg, Helen

2013-01-01

Impairments in language and communication are an early-appearing feature of autism spectrum disorders (ASD), with delays in language and gesture evident as early as the first year of life. Research with typically developing populations highlights the importance of both infant and maternal gesture use in infants’ early language development. The current study explores the gesture production of infants at risk for autism and their mothers at 12 months of age, and the association between these early maternal and infant gestures and between these early gestures and infants’ language at 18 months. Gestures were scored from both a caregiver-infant interaction (both infants and mothers) and from a semi-structured task (infants only). Mothers of non-diagnosed high risk infant siblings gestured more frequently than mothers of low risk infants. Infant and maternal gesture use at 12 months was associated with infants’ language scores at 18 months in both low risk and non-diagnosed high risk infants. These results demonstrate the impact of risk status on maternal behavior and the importance of considering the role of social and contextual factors on the language development of infants at risk for autism. Results from the subset of infants who meet preliminary criteria for ASD are also discussed. PMID:23585026

Enhancing international collaboration among early career researchers.

PubMed

Carroll, Jennifer K; Albada, Akke; Farahani, Mansoureh; Lithner, Maria; Neumann, Melanie; Sandhu, Harbinder; Shepherd, Heather L

2010-09-01

The European Association of Communication in Healthcare (EACH) Early Career Researchers Network (ECRN) aims are to (1) promote international collaboration among young investigators and (2) provide a support network for future innovative communication research projects. In October 2009, Miami, USA at a workshop facilitated by the ECRN at the International Conference on Communication in Healthcare (ICCH) hosted by the American Academy of Communication in Healthcare we explored common facilitators and challenges faced by early career researchers in health communication research. Attendees introduced themselves, their research area(s) of interest, and listed one facilitator and one barrier for their career development. EACH ECRN members then led a discussion of facilitators and challenges encountered in communication research projects and career development. We discussed potential collaboration opportunities, future goals, and activities. Having supportive collegial relationships, institutional support, job security, and funding are critical facilitators for early career investigators. Key challenges include difficulty with time management and prioritizing, limited resources, and contacts. International collaboration among early career researchers is a feasible and effective means to address important challenges, by increasing opportunities for professional support and networking, problem-solving, discussion of data, and ultimately publishing. Future AACH-EACH Early Career Researcher Networks should continue to build collaborations by developing shared research projects, papers, and other scholarly products. Copyright (c) 2010. Published by Elsevier Ireland Ltd.

The decline of venture capital investment in early-stage life sciences poses a challenge to continued innovation.

PubMed

Fleming, Jonathan J

2015-02-01

A key element required for translating new knowledge into effective therapies is early-stage venture capital that finances the work needed to identify a lead molecule or medical device prototype and to develop it to the proof-of-concept stage. This early investment is distinguished by great uncertainty over whether the molecule or prototype is safe and effective, the stability of the regulatory standards to which clinical trials are designed, and the likelihood that large follow-on investments for commercial development can be secured. Regulatory and reimbursement policies have a profound impact on the amount of capital and the types of life science projects that investors pursue. In this article I analyze several recent trends in early-stage venture capital funding, describe how these trends are influenced by regulatory and reimbursement policies, and discuss the role of policy makers in bringing new treatments to market. Policy makers can foster renewed private investment into critically needed early-stage products by increasing Small Business Innovation Research (SBIR) funding and public support for clinical trials in targeted areas of interest; creating regulatory pathways to enable early testing of experimental compounds in limited populations; and offering economic incentives for investors and developers in designated therapeutic areas. Project HOPE—The People-to-People Health Foundation, Inc.

Enhancing international collaboration among early-career researchers

PubMed Central

Carroll, Jennifer K; Albada, Akke; Farahani, Mansoureh; Lithner, Maria; Neumann, Melanie; Sandhu, Harbinder; Shepherd, Heather L

2010-01-01

Objective The European Association of Communication in Healthcare (EACH) Early Career Researchers Network (ECRN) aims are to (1) promote international collaboration among young investigators and (2) provide a support network for future innovative communication research projects. In October 2009, Miami, USA at a workshop facilitated by the ECRN at the International Conference on Communication in Healthcare (ICCH) hosted by the American Academy of Communication in Healthcare we explored common facilitators and challenges faced by early career researchers in health communication research. Methods Attendees introduced themselves, their research area(s) of interest, and listed one facilitator and one barrier for their career development. EACH ECRN members then led a discussion of facilitators and challenges encountered in communication research projects and career development. We discussed potential collaboration opportunities, future goals, and activities. Results Having supportive collegial relationships, institutional support, job security, and funding are critical facilitators for early career investigators. Key challenges include difficulty with time management and prioritizing, limited resources, and contacts. Conclusion International collaboration among early career researchers is a feasible and effective means to address important challenges, by increasing opportunities for professional support and networking, problem-solving, discussion of data, and ultimately publishing. Practice Implications Future AACH-EACH Early Career Researcher Networks should continue to build collaborations by developing shared research projects, papers, and other scholarly products. PMID:20663630

Genesis of a flexible turning center

NASA Astrophysics Data System (ADS)

Sanclemente, Paul; French, Robert D.

GE - Aircraft Engines has designed, built, and is operating a flexible turning center for jet engine hardware. Although the plant is in the forefront of manufacturing technology development, it was intended from the start to be a production facility. So while there was much to learn from being involved in all phases of the project, meeting production schedules was, and is, key to its success. This paper reviews the early history of the project and ends with a view of its recent production status.

Early season monitoring of corn and soybeans with TerraSAR-X and RADARSAT-2

NASA Astrophysics Data System (ADS)

McNairn, H.; Kross, A.; Lapen, D.; Caves, R.; Shang, J.

2014-05-01

Early and on-going crop production forecasts are important to facilitate food price stability for regions at risk, and for agriculture exporters, to set market value. Most regional and global efforts in forecasting rely on multiple sources of information from the field. With increased access to data from spaceborne Synthetic Aperture Radar (SAR), these sensors could contribute information on crop acreage. But these acreage estimates must be available early in the season to assist with production forecasts. This study acquired TerraSAR-X and RADARSAT-2 data over a region in eastern Canada dominated by economically important corn and soybean production. Using a supervised decision tree classifier, results determined that either sensor was capable of delivering highly accurate maps of corn and soybeans at the end of the growing season. Accuracies far exceeded 90%. Spatial and multi-temporal filtering approaches were compared and small improvements in accuracies were found by applying the multi-temporal filter to the RADARSAT-2 data. Of significant interest, this study determined that by using only three TerraSAR-X images corn could be accurately identified by the end of June, a mere six weeks after planting and at a vegetative growth stage (V6 - sixth leaf collar developed). However, soybeans required additional acquisitions given the variance in planting densities and planting dates in this region of Canada. In this case, accurate soybean classification required TerraSAR-X images until early August at the start of the reproductive stage (R5 - seed development is beginning). Also important, by applying a multi-temporal filter accurate mapping (close to 90%) of corn and soybeans from RADARSAT-2 could occur five weeks earlier (by August 19) than if a spatial filter was used. Thus application of this filtering approach could accelerate delivery of a crop inventory for this region of Canada. Corn and soybeans are important commodities both globally and within Canada. This study makes an important contribution as it demonstrates that TerraSAR-X can deliver acreage estimates of these two crops early enough to assist with in-season production forecasting.

LIF inhibits osteoblast differentiation at least in part by regulation of HAS2 and its product hyaluronan.

PubMed

Falconi, Dominic; Aubin, Jane E

2007-08-01

LIF arrests osteogenesis in fetal rat calvaria cells in a differentiation stage-specific manner. Differential display identified HAS2 as a LIF-induced gene and its product, HA, modulated osteoblast differentiation similarly to LIF. Our data suggest that LIF arrests osteoblast differentiation by altering HA content of the extracellular matrix. Leukemia inhibitory factor (LIF) elicits both anabolic and catabolic effects on bone. We previously showed in the fetal rat calvaria (RC) cell system that LIF inhibits osteoblast differentiation at the late osteoprogenitor/early osteoblast stage. To uncover potential molecular mediators of this inhibitory activity, we used a positive-negative genome-wide differential display screen to identify LIF-induced changes in the developing osteoblast transcriptome. Although LIF signaling is active throughout the RC cell proliferation-differentiation sequence, only a relatively small number of genes, in several different functional clusters, are modulated by LIF specifically during the LIF-sensitive inhibitory time window. Based on their known and predicted functions, most of the LIF-regulated genes identified are plausible candidates to be involved in the LIF-induced arrest of osteoprogenitor differentiation. To test this hypothesis, we further analyzed the function of one of the genes identified, hyaluronan synthase 2 (HAS2), in the LIF-induced inhibition. Synthesis of hyaluronan (HA), the product of HAS enzymatic activity, was stimulated by LIF and mimicked the HAS2 expression profile, with highest expression in early/proliferative and late/maturing cultures and lowest levels in intermediate/late osteoprogenitor-early osteoblast cultures. Exogenously added high molecular weight HA, the product of HAS2, dose-dependently inhibited osteoblast differentiation, with pulse-treatment effective in the same differentiation stage-specific inhibitory window as seen with LIF. In addition, however, pulse treatment with HA in early cultures slightly increased bone nodule formation. Treatment with hyaluronidase, on the other hand, stimulated bone nodule formation in early cultures but caused a small dose-dependent inhibition of osteoblast differentiation in the LIF- and HA-sensitive late time window. Together the data suggest that osteoblast differentiation is acutely sensitive to HA levels and that LIF inhibits osteoblast development at least in part by stimulating high molecular weight HA synthesis through HAS2.

Early experience shapes vocal neural coding and perception in songbirds

PubMed Central

Woolley, Sarah M. N.

2012-01-01

Songbirds, like humans, are highly accomplished vocal learners. The many parallels between speech and birdsong and conserved features of mammalian and avian auditory systems have led to the emergence of the songbird as a model system for studying the perceptual mechanisms of vocal communication. Laboratory research on songbirds allows the careful control of early life experience and high-resolution analysis of brain function during vocal learning, production and perception. Here, I review what songbird studies have revealed about the role of early experience in the development of vocal behavior, auditory perception and the processing of learned vocalizations by auditory neurons. The findings of these studies suggest general principles for how exposure to vocalizations during development and into adulthood influences the perception of learned vocal signals. PMID:22711657

Early-Stage Biotech Companies: Strategies for Survival and Growth

PubMed Central

Tsai, Wendy; Erickson, Stanford

2006-01-01

The promise of start-up biotechnology companies is enormous. So are the risks and the uncertainty of product development. The authors present a checklist for young biotech companies, covering environmental factors, alliances, and strategic planning. PMID:23424362

Earth Observations for Early Detection of Agricultural Drought: Contributions of the Famine Early Warning Systems Network (FEWS NET)

NASA Astrophysics Data System (ADS)

Budde, M. E.; Funk, C.; Husak, G. J.; Peterson, P.; Rowland, J.; Senay, G. B.; Verdin, J. P.

2016-12-01

The U.S. Geological Survey (USGS) has a long history of supporting the use of Earth observation data for food security monitoring through its role as an implementing partner of the Famine Early Warning Systems Network (FEWS NET) program. The use of remote sensing and crop modeling to address food security threats in the form of drought, floods, pests, and changing climatic regimes has been a core activity in monitoring FEWS NET countries. In recent years, it has become a requirement that FEWS NET apply monitoring and modeling frameworks at global scales to assess emerging crises in regions that FEWS NET does not traditionally monitor. USGS FEWS NET, in collaboration with the University of California, Santa Barbara, has developed a number of new global applications of satellite observations, derived products, and efficient tools for visualization and analyses to address these requirements. (1) A 35-year quasi-global (+/- 50 degrees latitude) time series of gridded rainfall estimates, the Climate Hazards Infrared Precipitation with Stations (CHIRPS) dataset, based on infrared satellite imagery and station observations. Data are available as 5-day (pentadal) accumulations at 0.05 degree spatial resolution. (2) Global actual evapotranspiration data based on application of the Simplified Surface Energy Balance (SSEB) model using 10-day MODIS Land Surface Temperature composites at 1-km resolution. (3) Production of global expedited MODIS (eMODIS) 10-day NDVI composites updated every 5 days. (4) Development of an updated Early Warning eXplorer (EWX) tool for data visualization, analysis, and sharing. (5) Creation of stand-alone tools for enhancement of gridded rainfall data and trend analyses. (6) Establishment of an agro-climatology analysis tool and knowledge base for more than 90 countries of interest to FEWS NET. In addition to these new products and tools, FEWS NET has partnered with the GEOGLAM community to develop a Crop Monitor for Early Warning (CM4EW) which brings together global expertise in agricultural monitoring to reach consensus on growing season status of "countries at risk". Such engagements will result in enhanced capabilities for extending our monitoring efforts globally.

HCPCS Coding: An Integral Part of Your Reimbursement Strategy.

PubMed

Nusgart, Marcia

2013-12-01

The first step to a successful reimbursement strategy is to ensure that your wound care product has the most appropriate Healthcare Common Procedure Coding System (HCPCS) code (or billing) for your product. The correct HCPCS code plays an essential role in patient access to new and existing technologies. When devising a strategy to obtain a HCPCS code for its product, companies must consider a number of factors as follows: (1) Has the product gone through the Food and Drug Administration (FDA) regulatory process or does it need to do so? Will the FDA code designation impact which HCPCS code will be assigned to your product? (2) In what "site of service" do you intend to market your product? Where will your customers use the product? Which coding system (CPT ® or HCPCS) applies to your product? (3) Does a HCPCS code for a similar product already exist? Does your product fit under the existing HCPCS code? (4) Does your product need a new HCPCS code? What is the linkage, if any, between coding, payment, and coverage for the product? Researchers and companies need to start early and place the same emphasis on a reimbursement strategy as it does on a regulatory strategy. Your reimbursement strategy staff should be involved early in the process, preferably during product research and development and clinical trial discussions.

Transcriptome Analysis of Honeybee (Apis Mellifera) Haploid and Diploid Embryos Reveals Early Zygotic Transcription during Cleavage

PubMed Central

Pires, Camilla Valente; Freitas, Flávia Cristina de Paula; Cristino, Alexandre S.; Dearden, Peter K.; Simões, Zilá Luz Paulino

2016-01-01

In honeybees, the haplodiploid sex determination system promotes a unique embryogenesis process wherein females develop from fertilized eggs and males develop from unfertilized eggs. However, the developmental strategies of honeybees during early embryogenesis are virtually unknown. Similar to most animals, the honeybee oocytes are supplied with proteins and regulatory elements that support early embryogenesis. As the embryo develops, the zygotic genome is activated and zygotic products gradually replace the preloaded maternal material. The analysis of small RNA and mRNA libraries of mature oocytes and embryos originated from fertilized and unfertilized eggs has allowed us to explore the gene expression dynamics in the first steps of development and during the maternal-to-zygotic transition (MZT). We localized a short sequence motif identified as TAGteam motif and hypothesized to play a similar role in honeybees as in fruit flies, which includes the timing of early zygotic expression (MZT), a function sustained by the presence of the zelda ortholog, which is the main regulator of genome activation. Predicted microRNA (miRNA)-target interactions indicated that there were specific regulators of haploid and diploid embryonic development and an overlap of maternal and zygotic gene expression during the early steps of embryogenesis. Although a number of functions are highly conserved during the early steps of honeybee embryogenesis, the results showed that zygotic genome activation occurs earlier in honeybees than in Drosophila based on the presence of three primary miRNAs (pri-miRNAs) (ame-mir-375, ame-mir-34 and ame-mir-263b) during the cleavage stage in haploid and diploid embryonic development. PMID:26751956

Early assessment of Integrated Multi-satellite Retrievals for Global Precipitation Measurement over China

NASA Astrophysics Data System (ADS)

Guo, Hao; Chen, Sheng; Bao, Anming; Behrangi, Ali; Hong, Yang; Ndayisaba, Felix; Hu, Junjun; Stepanian, Phillip M.

2016-07-01

Two post-real time precipitation products from the Integrated Multi-satellite Retrievals for Global Precipitation Measurement Mission (IMERG) are systematically evaluated over China with China daily Precipitation Analysis Product (CPAP) as reference. The IMERG products include the gauge-corrected IMERG product (IMERG_Cal) and the version of IMERG without direct gauge correction (IMERG_Uncal). The post-research TRMM Multisatellite Precipitation Analysis version 7 (TMPA-3B42V7) is also evaluated concurrently with IMERG for better perspective. In order to be consistent with CPAP, the evaluation and comparison of selected products are performed at 0.25° and daily resolutions from 12 March 2014 through 28 February 2015. The results show that: Both IMERG and 3B42V7 show similar performances. Compared to IMERG_Uncal, IMERG_Cal shows significant improvement in overall and conditional bias and in the correlation coefficient. Both IMERG_Cal and IMERG_Uncal perform relatively poor in winter and over-detect slight precipitation events in northwestern China. As an early validation of the GPM-era IMERG products that inherit the TRMM-era global satellite precipitation products, these findings will provide useful feedbacks and insights for algorithm developers and data users over China and beyond.

Developmental biotechnology for aquaculture, with special reference to surrogate production in teleost fishes

NASA Astrophysics Data System (ADS)

Yamaha, Etsuro; Saito, Taiju; Goto-Kazeto, Rie; Arai, Katsutoshi

2007-07-01

This review introduces surrogate production as a new technique for fish-seed production in aquaculture. Surrogate production in fish is a technique used to obtain the gametes of a certain genotype through the gonad of another genotype. It is achieved by inducing germ-line chimerism between different species during early development. Primordial germ cells (PGCs) are the key material of this technique to induce germ-line chimera. In several species, it has been reported that PGCs differentiated from the blastomeres inherited some maternally supplied mRNA located in the terminal regions of the early cleavage furrows. PGCs from donor species (or strains) are isolated and transplanted into host species to induce the germ-line chimera. Four methods for inducing germ-line chimera are described: blastomere transplantation, blastoderm-graft transplantation, transplantation of PGC from the genital ridge, and transplantation visualised PGC with GFP fluorescence. Several problems preventing the successful induction of germ-line chimera in various fish species are discussed. Surrogate production, however, opens the possibility of efficient fish-seed production and effective breeding and transfer of biodiversity to an aquaculture strain. Conservation and efficient utilisation of genetic resources will be achieved through surrogate production combined with the cryopreservation of PGCs.

Alterations in early cytokine-mediated immune responses to Plasmodium falciparum infection in Tanzanian children with mineral element deficiencies: a cross-sectional survey

PubMed Central

2010-01-01

Background Deficiencies in vitamins and mineral elements are important causes of morbidity in developing countries, possibly because they lead to defective immune responses to infection. The aim of the study was to assess the effects of mineral element deficiencies on early innate cytokine responses to Plasmodium falciparum malaria. Methods Peripheral blood mononuclear cells from 304 Tanzanian children aged 6-72 months were stimulated with P. falciparum-parasitized erythrocytes obtained from in vitro cultures. Results The results showed a significant increase by 74% in geometric mean of TNF production in malaria-infected individuals with zinc deficiency (11% to 240%; 95% CI). Iron deficiency anaemia was associated with increased TNF production in infected individuals and overall with increased IL-10 production, while magnesium deficiency induced increased production of IL-10 by 46% (13% to 144%) in uninfected donors. All donors showed a response towards IL-1β production, drawing special attention for its possible protective role in early innate immune responses to malaria. Conclusions In view of these results, the findings show plasticity in cytokine profiles of mononuclear cells reacting to malaria infection under conditions of different micronutrient deficiencies. These findings lay the foundations for future inclusion of a combination of precisely selected set of micronutrients rather than single nutrients as part of malaria vaccine intervention programmes in endemic countries. PMID:20470442

Overview of the SMAP Applications and the SMAP Early Adopters Program - NASA's First Mission-Directed Outreach Effort

NASA Technical Reports Server (NTRS)

Escobar, V. M.; Delgado Arias, S.; Nearing, G.; Entekhabi, D.; Njoku, E.; Yueh, S.; Doorn, B.; Reichle, R.

2016-01-01

Satellite data provide global observations of many of the earths system processes and features. These data are valuable for developing scientific products that increase our understanding of how the earths systems are integrated. The water, energy and carbon cycle exchanges between the land and atmosphere are linked by soil moisture. NASAs Soil Moisture Active Passive (SMAP) mission provides soil moisture and freeze thaw measurements from space and allows scientists to link the water energy and carbon cycles. In order for SMAP data to be best integrated into decision support systems, the mission has engaged with the stakeholder community since 2009 and has attempted to scale the utility of the data to the thematic societal impacts of the satellite product applications. The SMAP Mission, which launched on January 31, 2015, has actively grown an Early Adopter (EA) community as part of its applications effort and worked with these EAs to demonstrate a scaled thematic impact of SMAP data product in societally relevant decision support applications. The SMAP mission provides global observations of the Earths surface soil moisture, providing high accuracy, resolution and continuous global coverage. Through the Early Adopters Program, the SMAP Applications Team will spend the next 2 years after launch documenting and evaluating the use of SMAP science products in applications related to weather forecasting, drought, agriculture productivity, floods, human health and national security.

From Parent to Child to Parent…: Paths In and Out of Problem Behavior

PubMed Central

Bradley, Robert H.; Corwyn, Robert

2014-01-01

This study used data from the NICHD Study of Early Child Care and Youth Development to examine relations between parenting, self-control and externalizing behavior from early childhood to mid-adolescence (N=956; 49.9% male). Results indicated that maternal sensitivity, parental harshness and productive activity are related to externalizing problems but that patterns of relations change from early childhood to middle childhood to adolescence, with evidence suggesting that externalizing behavior influences parenting more than the reverse from middle childhood onward. Self-control measured during early adolescence partially mediated relations between maternal sensitivity and adolescent-reported externalizing behavior. Parental monitoring during adolescence was also related to externalizing behavior at age 15. Monitoring partially mediated the relation between externalizing behavior in early adolescence and externalizing at age 15. PMID:23135289

Proinsulin in development: New roles for an ancient prohormone.

PubMed

Hernández-Sánchez, C; Mansilla, A; de la Rosa, E J; de Pablo, F

2006-06-01

In postnatal organisms, insulin is well known as an essential anabolic hormone responsible for maintaining glucose homeostasis. Its biosynthesis by the pancreatic beta cell has been considered a model of tissue-specific gene expression. However, proinsulin mRNA and protein have been found in embryonic stages before the formation of the pancreatic primordium, and later, in extrapancreatic tissues including the nervous system. Phylogenetic studies have also confirmed that production of insulin-like peptides antecedes the morphogenesis of a pancreas, and that these peptides contribute to normal development. In recent years, other roles for insulin distinct from its metabolic function have emerged also in vertebrates. During embryonic development, insulin acts as a survival factor and is involved in early morphogenesis. These findings are consistent with the observation that, at these stages, the proinsulin gene product remains as the precursor form, proinsulin. Independent of its low metabolic activity, proinsulin stimulates proliferation in developing neuroretina, as well as cell survival and cardiogenesis in early embryos. Insulin/proinsulin levels are finely regulated during development, since an excess of the protein interferes with correct morphogenesis and is deleterious for the embryo. This fine-tuned regulation is achieved by the expression of alternative embryonic proinsulin transcripts that have diminished translational activity.

Relationship between the linguistic environments and early bilingual language development of hearing children in deaf-parented families.

PubMed

Kanto, Laura; Huttunen, Kerttu; Laakso, Marja-Leena

2013-04-01

We explored variation in the linguistic environments of hearing children of Deaf parents and how it was associated with their early bilingual language development. For that purpose we followed up the children's productive vocabulary (measured with the MCDI; MacArthur Communicative Development Inventory) and syntactic complexity (measured with the MLU10; mean length of the 10 longest utterances the child produced during videorecorded play sessions) in both Finnish Sign Language and spoken Finnish between the ages of 12 and 30 months. Additionally, we developed new methodology for describing the linguistic environments of the children (N = 10). Large variation was uncovered in both the amount and type of language input and language acquisition among the children. Language exposure and increases in productive vocabulary and syntactic complexity were interconnected. Language acquisition was found to be more dependent on the amount of exposure in sign language than in spoken language. This was judged to be related to the status of sign language as a minority language. The results are discussed in terms of parents' language choices, family dynamics in Deaf-parented families and optimal conditions for bilingual development.

Early sepsis does not stimulate reactive oxygen species production and does not reduce cardiac function despite an increased inflammation status.

PubMed

Léger, Thibault; Charrier, Alice; Moreau, Clarisse; Hininger-Favier, Isabelle; Mourmoura, Evangelia; Rigaudière, Jean-Paul; Pitois, Elodie; Bouvier, Damien; Sapin, Vincent; Pereira, Bruno; Azarnoush, Kasra; Demaison, Luc

2017-07-01

If it is sustained for several days, sepsis can trigger severe abnormalities of cardiac function which leads to death in 50% of cases. This probably occurs through activation of toll-like receptor-9 by bacterial lipopolysaccharides and overproduction of proinflammatory cytokines such as TNF- α and IL-1 β In contrast, early sepsis is characterized by the development of tachycardia. This study aimed at determining the early changes in the cardiac function during sepsis and at finding the mechanism responsible for the observed changes. Sixty male Wistar rats were randomly assigned to two groups, the first one being made septic by cecal ligation and puncture (sepsis group) and the second one being subjected to the same surgery without cecal ligation and puncture (sham-operated group). The cardiac function was assessed in vivo and ex vivo in standard conditions. Several parameters involved in the oxidative stress and inflammation were determined in the plasma and heart. As evidenced by the plasma level of TNF- α and gene expression of IL-1 β and TNF- α in the heart, inflammation was developed in the sepsis group. The cardiac function was also slightly stimulated by sepsis in the in vivo and ex vivo situations. This was associated with unchanged levels of oxidative stress, but several parameters indicated a lower cardiac production of reactive oxygen species in the septic group. In conclusion, despite the development of inflammation, early sepsis did not increase reactive oxygen species production and did not reduce myocardial function. The depressant effect of TNF- α and IL-1 β on the cardiac function is known to occur at very high concentrations. The influence of low- to moderate-grade inflammation on the myocardial mechanical behavior must thus be revisited. © 2017 French National Institute of Agronomical Research (INRA). Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Alterations in NO- and PGI2- dependent function in aorta in the orthotopic murine model of metastatic 4T1 breast cancer: relationship with pulmonary endothelial dysfunction and systemic inflammation.

PubMed

Buczek, E; Denslow, A; Mateuszuk, L; Proniewski, B; Wojcik, T; Sitek, B; Fedorowicz, A; Jasztal, A; Kus, E; Chmura-Skirlinska, A; Gurbiel, R; Wietrzyk, J; Chlopicki, S

2018-05-22

Patients with cancer develop endothelial dysfunction and subsequently display a higher risk of cardiovascular events. The aim of the present work was to examine changes in nitric oxide (NO)- and prostacyclin (PGI 2 )-dependent endothelial function in the systemic conduit artery (aorta), in relation to the formation of lung metastases and to local and systemic inflammation in a murine orthotopic model of metastatic breast cancer. BALB/c female mice were orthotopically inoculated with 4T1 breast cancer cells. Development of lung metastases, lung inflammation, changes in blood count, systemic inflammatory response (e.g. SAA, SAP and IL-6), as well as changes in NO- and PGI 2 -dependent endothelial function in the aorta, were examined 2, 4, 5 and 6 weeks following cancer cell transplantation. As early as 2 weeks following transplantation of breast cancer cells, in the early metastatic stage, lungs displayed histopathological signs of inflammation, NO production was impaired and nitrosylhemoglobin concentration in plasma was decreased. After 4 to 6 weeks, along with metastatic development, progressive leukocytosis and systemic inflammation (as seen through increased SAA, SAP, haptoglobin and IL-6 plasma concentrations) were observed. Six weeks following cancer cell inoculation, but not earlier, endothelial dysfunction in aorta was detected; this involved a decrease in basal NO production and a decrease in NO-dependent vasodilatation, that was associated with a compensatory increase in cyclooxygenase-2 (COX-2)- derived PGI 2 production. In 4 T1 metastatic breast cancer in mice early pulmonary metastasis was correlated with lung inflammation, with an early decrease in pulmonary as well as systemic NO availability. Late metastasis was associated with robust, cancer-related, systemic inflammation and impairment of NO-dependent endothelial function in the aorta that was associated with compensatory upregulation of the COX-2-derived PGI 2 pathway.

Green toxicology.

PubMed

Maertens, Alexandra; Anastas, Nicholas; Spencer, Pamela J; Stephens, Martin; Goldberg, Alan; Hartung, Thomas

2014-01-01

Historically, early identification and characterization of adverse effects of industrial chemicals was difficult because conventional toxicological test methods did not meet R&D needs for rapid, relatively inexpensive methods amenable to small amounts of test material. The pharmaceutical industry now front-loads toxicity testing, using in silico, in vitro, and less demanding animal tests at earlier stages of product development to identify and anticipate undesirable toxicological effects and optimize product development. The Green Chemistry movement embraces similar ideas for development of less toxic products, safer processes, and less waste and exposure. Further, the concept of benign design suggests ways to consider possible toxicities before the actual synthesis and to apply some structure/activity rules (SAR) and in silico methods. This requires not only scientific development but also a change in corporate culture in which synthetic chemists work with toxicologists. An emerging discipline called Green Toxicology (Anastas, 2012) provides a framework for integrating the principles of toxicology into the enterprise of designing safer chemicals, thereby minimizing potential toxicity as early in production as possible. Green Toxicology`s novel utility lies in driving innovation by moving safety considerations to the earliest stage in a chemical`s lifecycle, i.e., to molecular design. In principle, this field is no different than other subdisciplines of toxicology that endeavor to focus on a specific area - for example, clinical, environmental or forensic toxicology. We use the same principles and tools to evaluate an existing substance or to design a new one. The unique emphasis is in using 21st century toxicology tools as a preventative strategy to "design out" undesired human health and environmental effects, thereby increasing the likelihood of launching a successful, sustainable product. Starting with the formation of a steering group and a series of workshops, the Green Toxicology concept is currently spreading internationally and is being refined via an iterative process.

Different Preclimacteric Events in Apple Cultivars with Modified Ripening Physiology

PubMed Central

Singh, Vikram; Weksler, Asya; Friedman, Haya

2017-01-01

“Anna” is an early season apple cultivar exhibiting a fast softening and juiciness loss during storage, in comparison to two mid-late season cultivars “Galaxy” and “GD.” The poor storage capacity of “Anna” was correlated with high lipid oxidation-related autoluminescence, high respiration and ethylene production rates, associated with high expression of MdACO1, 2, 4, 7, and MdACS1. All cultivars at harvest responded to exogenous ethylene by enhancing ethylene production, typical of system-II. The contribution of pre-climacteric events to the poor storage capacity of “Anna” was examined by comparing respiration and ethylene production rates, response to exogenous ethylene, expression of genes responsible for ethylene biosynthesis and response, and developmental regulators in the three cultivars throughout fruit development. In contrast to the “Galaxy” and “GD,” “Anna” showed higher ethylene production and respiration rates during fruit development, and exhibited auto-stimulatory (system II-like) effect in response to exogenous ethylene. The higher ethylene production rate in “Anna” was correlated with higher expression of ethylene biosynthesis genes, MdACS3a MdACO2, 4, and 7 during early fruit development. The expression of negative regulators of ripening (AP2/ERF) and ethylene response pathway, (MdETR1,2 and MdCTR1) was lower in “Anna” in comparison to the other two cultivars throughout development and ripening. Similar pattern of gene expression was found for SQUAMOSA promoter binding protein (SBP)-box genes, including MdCNR and for MdFUL. Taken together, this study provides new understanding on pre-climacteric events in “Anna” that might affect its ripening behavior and physiology following storage. PMID:28928755

The Foundations of Lifelong Health Are Built in Early Childhood: Summary of Essential Findings

ERIC Educational Resources Information Center

National Forum on Early Childhood Policy and Programs, 2010

2010-01-01

A vital and productive society with a prosperous and sustainable future is built on a foundation of healthy child development. Health in the earliest years--beginning with the future mother's well-being before she becomes pregnant--lays the groundwork for a lifetime of vitality. When developing biological systems are strengthened by positive early…

Measuring Perceptions of Engagement in Teamwork in Youth Development Programs

ERIC Educational Resources Information Center

Cater, Melissa; Jones, Kimberly Y.

2014-01-01

The literature regarding teamwork has supported the idea that the key to improving team performance is to understand team processes. Early work within the realm of teamwork focused on quantifiable measures of team performance, like number of products developed. The measure of a successful team hinged on whether or not the team accomplished the end…

Screening Protocol for Early Identification of Brazilian Children at Risk for Dyslexia

PubMed Central

Germano, Giseli D.; César, Alexandra B. P. de C.; Capellini, Simone A.

2017-01-01

Early identification of students at risk of dyslexia has been an educational challenge in the past years. This research had two main goals. First, we aimed to develop a screening protocol for early identification of Brazilian children at risk for dyslexia; second, we aimed to identify the predictive variables of this protocol using Principal Component Analysis. The major step involved in developing this protocol was the selection of variables, which were chosen based on the literature review and linguistic criteria. The screening protocol was composed of seven cognitive-linguistic skills: Letter naming; Phonological Awareness (which comprises the following subtests: Rhyme production, Rhyme identification, Syllabic segmentation, Production of words from a given phoneme, Phonemic Synthesis, and Phonemic analysis); Phonological Working memory, Rapid naming Speed; Silent reading; Reading of words and non-words; and Auditory Comprehension of sentences from pictures. A total of 149 children, aged from 6 years to 6 and 11, of both genders who were enrolled in the 1st grade of elementary public schools were submitted to the screening protocol. Principal Component Analysis revealed four factors, accounting for 64.45% of the variance of the Protocol variables: first factor (“pre-reading”), second factor (“decoding”), third factor (“Reading”), and fourth factor “Auditory processing.” The factors found corroborate those reported in the National and International literature and have been described as early signs of dyslexia and reading problems. PMID:29163246

Oral treatment with enrofloxacin early in life promotes Th2-mediated immune response in mice.

PubMed

Strzępa, Anna; Majewska-Szczepanik, Monika; Kowalczyk, Paulina; Woźniak, Dorota; Motyl, Sylwia; Szczepanik, Marian

2016-02-01

Th2 lymphocytes play a crucial role in the development of allergy. These pathologies are caused by coordinated production of the cytokines IL-4, IL-5 and IL-13 that regulate the activity of eosinophils, basophils and B cells. According to the 'hygiene hypothesis', the reduced exposure to microorganisms favors allergy occurrence. The advances in medicine in the field of infection therapy promoted an increasing application of antibiotics which, apart from eliminating pathogens, also partially eliminate the microbiota. Epicutaneous (EC) immunization with ovalbumin (OVA) followed by OVA challenge was used to study the influence of partial gut flora depletion by oral treatment with enrofloxacin on type-2 immune response. Current work describes the influence of enrofloxacin application on anti-OVA antibody production and cytokine synthesis in young and adult mice. Immune response in adult mice is less sensitive to modification of natural gut flora. We observed that enrofloxacin treatment of adult mice leads to significant decrease of anti-OVA IgG2a production while synthesis of anti-OVA IgE was not changed. The production of type-1 (IFN-γ), type-2 (IL-4, IL-5, IL-10, IL-13) and Th17-associated (IL-17A) cytokines was inhibited. On the other hand, treatment of young mice with enrofloxacin significantly upregulates the production of anti-OVA IgE and inhibits the secretion of anti-OVA IgG2a antibodies. Additionally, treatment with enrofloxacin early in life prior to OVA immunization results in increased production of type-2 (IL-4, IL-10 and IL-13) cytokines. Our results clearly indicate that the immune system is more vulnerable to decreased bacterial exposure early in life that may promote development of allergy. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Developing the science product algorithm testbed for Chinese next-generation geostationary meteorological satellites: Fengyun-4 series

NASA Astrophysics Data System (ADS)

Min, Min; Wu, Chunqiang; Li, Chuan; Liu, Hui; Xu, Na; Wu, Xiao; Chen, Lin; Wang, Fu; Sun, Fenglin; Qin, Danyu; Wang, Xi; Li, Bo; Zheng, Zhaojun; Cao, Guangzhen; Dong, Lixin

2017-08-01

Fengyun-4A (FY-4A), the first of the Chinese next-generation geostationary meteorological satellites, launched in 2016, offers several advances over the FY-2: more spectral bands, faster imaging, and infrared hyperspectral measurements. To support the major objective of developing the prototypes of FY-4 science algorithms, two science product algorithm testbeds for imagers and sounders have been developed by the scientists in the FY-4 Algorithm Working Group (AWG). Both testbeds, written in FORTRAN and C programming languages for Linux or UNIX systems, have been tested successfully by using Intel/g compilers. Some important FY-4 science products, including cloud mask, cloud properties, and temperature profiles, have been retrieved successfully through using a proxy imager, Himawari-8/Advanced Himawari Imager (AHI), and sounder data, obtained from the Atmospheric InfraRed Sounder, thus demonstrating their robustness. In addition, in early 2016, the FY-4 AWG was developed based on the imager testbed—a near real-time processing system for Himawari-8/AHI data for use by Chinese weather forecasters. Consequently, robust and flexible science product algorithm testbeds have provided essential and productive tools for popularizing FY-4 data and developing substantial improvements in FY-4 products.

Mission Applications Support at NASA: The Proposal Surface Water and Ocean Topography Mission

NASA Astrophysics Data System (ADS)

Srinivasan, Margaret; Peterson, Craig; Callahan, Phil

2013-09-01

The NASA Applied Sciences Program is actively supporting an agency-wide effort to formalize a mission-level data applications approach. The program goal is to engage early-phase NASA Earth satellite mission project teams with applied science representation in the flight mission planning process. The end objective is to "to engage applications-oriented users and organizations early in the satellite mission lifecycle to enable them to envision possible applications and integrate end-user needs into satellite mission planning as a way to increase the benefits to the nation."Two mission applications representatives have been selected for each early phase Tier 2 mission, including the Surface Water and Ocean Topography (SWOT) mission concept. These representatives are tasked with identifying and organizing the applications communities and developing and promoting a process for the mission to optimize the reach of existing applications efforts in order to enhance the applications value of the missions. An early project-level awareness of mission planning decisions that may increase or decrease the utility of data products to diverse user and potential user communities (communities of practice and communities of potential, respectively) has high value and potential return to the mission and to the users.Successful strategies to enhance science and practical applications of projected SWOT data streams will require engaging with and facilitating between representatives in the science, societal applications, and mission planning communities.Some of the elements of this program include:• Identify early adopters of data products• Coordinate applications team, including;Project Scientist, Payload Scientist, ProjectManager, data processing lead• Describe mission and products sufficiently inearly stage of development to effectively incorporate all potential usersProducts and activities resulting from this effort will include (but are not limited to); workshops, workshop summaries, web pages, email lists of interested users/scientists, an Applications Plan, printed materials (posters, brochures) and participation in key meetings.

Inflorescence photosynthetic contribution to fitness releases Arabidopsis thaliana plants from trade-off constraints on early flowering.

PubMed

Gnan, Sebastian; Marsh, Tom; Kover, Paula X

2017-01-01

Leaves are thought to be the primary carbon source for reproduction in plants, so a positive relationship between vegetative size and reproductive output is expected, establishing a trade-off between time to reproduction and reproductive output. A common response to higher temperatures due to climate changes is the induction of earlier transition into reproduction. Thus, in annual plants, earlier transition into flowering can potentially constrain plant size and reduce seed production. However, trade-offs between early reproduction and fitness are not always observed, suggesting mechanisms to escape the constraints of early flowering do exist. Here, we test whether inflorescence photosynthesis contribution to the reproductive output of Arabidopsis thaliana can offset the cost of early reproduction. We followed the development, growth rate and fitness of 15 accessions, and removed all rosette leaves at flowering (prior to the completion of inflorescence development or any fruit production) in half of the plants to determine the ability of inflorescences to maintain fitness in the absence of leaves. Although leaf removal significantly reduced fruit number, seed weight and plant height, even the most severely impacted accessions maintained 35% of their fitness with the inflorescence as the sole photosynthetic organ; and some accessions experienced no reduction in fitness. Differences between accessions in their ability to maintain fitness after leaf removal is best explained by earlier flowering time and the ability to maintain as many or more branches after leaf removal as in the control treatment. Although earlier flowering does constrain plant vegetative size, we found that inflorescence photosynthesis can significantly contribute to seed production, explaining why early flowering plants can maintain high fitness despite a reduction in vegetative size. Thus, plants can be released from the usually assumed trade-offs associated with earlier reproduction, and selection on inflorescence traits can mediate the impact of climate change on phenology.

Security Requirements Management in Software Product Line Engineering

NASA Astrophysics Data System (ADS)

Mellado, Daniel; Fernández-Medina, Eduardo; Piattini, Mario

Security requirements engineering is both a central task and a critical success factor in product line development due to the complexity and extensive nature of product lines. However, most of the current product line practices in requirements engineering do not adequately address security requirements engineering. Therefore, in this chapter we will propose a security requirements engineering process (SREPPLine) driven by security standards and based on a security requirements decision model along with a security variability model to manage the variability of the artefacts related to security requirements. The aim of this approach is to deal with security requirements from the early stages of the product line development in a systematic way, in order to facilitate conformance with the most relevant security standards with regard to the management of security requirements, such as ISO/IEC 27001 and ISO/IEC 15408.

Frequent use of chemical household products is associated with persistent wheezing in pre-school age children.

PubMed

Sherriff, A; Farrow, A; Golding, J; Henderson, J

2005-01-01

In the UK and other developed countries the prevalence of asthma symptoms has increased in recent years. This is likely to be the result of increased exposure to environmental factors. A study was undertaken to investigate the association between maternal use of chemical based products in the prenatal period and patterns of wheeze in early childhood. In the population based Avon Longitudinal Study of Parents and Children (ALSPAC), the frequency of use of 11 chemical based domestic products was determined from questionnaires completed by women during pregnancy and a total chemical burden (TCB) score was derived. Four mutually exclusive wheezing patterns were defined for the period from birth to 42 months based on parental questionnaire responses (never wheezed, transient early wheeze, persistent wheeze, and late onset wheeze). Multinomial logistic regression models were used to assess the relationship between these wheezing outcomes and TCB exposure while accounting for numerous potential confounding variables. Complete data for analysis was available for 7019 of 13, 971 (50%) children. The mean (SD) TCB score was 9.4 (4.1), range 0-30. Increased use of domestic chemical based products was associated with persistent wheezing during early childhood (adjusted odds ratio (OR) per unit increase of TCB 1.06 (95% confidence interval (CI) 1.03 to 1.09)) but not with transient early wheeze or late onset wheeze. Children whose mothers had high TCB scores (>90th centile) were more than twice as likely to wheeze persistently throughout early childhood than children whose mothers had a low TCB score (<10th centile) (adjusted OR 2.3 (95% CI 1.2 to 4.4)). These findings suggest that frequent use of chemical based products in the prenatal period is associated with persistent wheezing in young children. Follow up of this cohort is underway to determine whether TCB is associated with wheezing, asthma, and atopy at later stages in childhood.

Frequent use of chemical household products is associated with persistent wheezing in pre-school age children

PubMed Central

Sherriff, A; Farrow, A; Golding, J; the, A; Henderson, J

2005-01-01

Background: In the UK and other developed countries the prevalence of asthma symptoms has increased in recent years. This is likely to be the result of increased exposure to environmental factors. A study was undertaken to investigate the association between maternal use of chemical based products in the prenatal period and patterns of wheeze in early childhood. Methods: In the population based Avon Longitudinal Study of Parents and Children (ALSPAC), the frequency of use of 11 chemical based domestic products was determined from questionnaires completed by women during pregnancy and a total chemical burden (TCB) score was derived. Four mutually exclusive wheezing patterns were defined for the period from birth to 42 months based on parental questionnaire responses (never wheezed, transient early wheeze, persistent wheeze, and late onset wheeze). Multinomial logistic regression models were used to assess the relationship between these wheezing outcomes and TCB exposure while accounting for numerous potential confounding variables. Complete data for analysis was available for 7019 of 13 971 (50%) children. Results: The mean (SD) TCB score was 9.4 (4.1), range 0–30. Increased use of domestic chemical based products was associated with persistent wheezing during early childhood (adjusted odds ratio (OR) per unit increase of TCB 1.06 (95% confidence interval (CI) 1.03 to 1.09)) but not with transient early wheeze or late onset wheeze. Children whose mothers had high TCB scores (>90th centile) were more than twice as likely to wheeze persistently throughout early childhood than children whose mothers had a low TCB score (<10th centile) (adjusted OR 2.3 (95% CI 1.2 to 4.4)). Conclusion: These findings suggest that frequent use of chemical based products in the prenatal period is associated with persistent wheezing in young children. Follow up of this cohort is underway to determine whether TCB is associated with wheezing, asthma, and atopy at later stages in childhood. PMID:15618582

Diffusion of subsidized ACTs in accredited drug shops in Tanzania: determinants of stocking and characteristics of early and late adopters

PubMed Central

2013-01-01

Background Many households in sub-Saharan Africa utilize the private sector as a primary source of treatment for malaria episodes. Expanding access to effective treatment in private drug shops may help reduce incidence of severe disease and mortality. This research leveraged a longitudinal survey of stocking of subsidized artemisinin combination therapies (ACTs), an effective anti-malarial, in Accredited Drug Dispensing Outlets (ADDOs) in two regions of Tanzania. This provided a unique opportunity to explore shop and market level determinants of product diffusion in a developing country retail market. Methods 356 ADDOs in the Rukwa and Mtwara regions of Tanzania were surveyed at seven points between Feb 2011 and May 2012. Shop level audits were used to measure the availability of subsidized ACTs at each shop. Data on market and shop level factors were collected during the survey and also extracted from GIS layers. Regression and network based methodologies were used. Shops classified as early and late adopters, following Rogers’ model of product diffusion, were compared. The Bass model of product diffusion was applied to determine whether shops stocked ACTs out of a need to imitate market competitors or a desire to satisfy customer needs. Results Following the introduction of a subsidy for ACTs, stocking increased from 12% to nearly 80% over the seven survey rounds. Stocking was influenced by higher numbers of proximal shops and clinics, larger customer traffic and the presence of a licensed pharmacist. Early adopters were characterized by a larger percentage of customers seeking care for malaria, a larger catchment and sourcing from specific wholesalers/suppliers. The Bass model of product diffusion indicated that shops were adopting products in response to competitor behavior, rather than customer demand. Conclusions Decisions to stock new pharmaceutical products in Tanzanian ADDOs are influenced by a combination of factors related to both market competition and customer demand, but are particularly influenced by the behavior of competing shops. Efforts to expand access to new pharmaceutical products in developing country markets could benefit from initial targeting of high profile shops in competitive markets and wholesale suppliers to encourage faster product diffusion across all drug retailers. PMID:24350611

Diffusion of subsidized ACTs in accredited drug shops in Tanzania: determinants of stocking and characteristics of early and late adopters.

PubMed

Larson, Peter S; Yadav, Prashant; Alphs, Sarah; Arkedis, Jean; Massaga, Julius; Sabot, Oliver; Cohen, Jessica L

2013-12-18

Many households in sub-Saharan Africa utilize the private sector as a primary source of treatment for malaria episodes. Expanding access to effective treatment in private drug shops may help reduce incidence of severe disease and mortality. This research leveraged a longitudinal survey of stocking of subsidized artemisinin combination therapies (ACTs), an effective anti-malarial, in Accredited Drug Dispensing Outlets (ADDOs) in two regions of Tanzania. This provided a unique opportunity to explore shop and market level determinants of product diffusion in a developing country retail market. 356 ADDOs in the Rukwa and Mtwara regions of Tanzania were surveyed at seven points between Feb 2011 and May 2012. Shop level audits were used to measure the availability of subsidized ACTs at each shop. Data on market and shop level factors were collected during the survey and also extracted from GIS layers. Regression and network based methodologies were used. Shops classified as early and late adopters, following Rogers' model of product diffusion, were compared. The Bass model of product diffusion was applied to determine whether shops stocked ACTs out of a need to imitate market competitors or a desire to satisfy customer needs. Following the introduction of a subsidy for ACTs, stocking increased from 12% to nearly 80% over the seven survey rounds. Stocking was influenced by higher numbers of proximal shops and clinics, larger customer traffic and the presence of a licensed pharmacist. Early adopters were characterized by a larger percentage of customers seeking care for malaria, a larger catchment and sourcing from specific wholesalers/suppliers. The Bass model of product diffusion indicated that shops were adopting products in response to competitor behavior, rather than customer demand. Decisions to stock new pharmaceutical products in Tanzanian ADDOs are influenced by a combination of factors related to both market competition and customer demand, but are particularly influenced by the behavior of competing shops. Efforts to expand access to new pharmaceutical products in developing country markets could benefit from initial targeting of high profile shops in competitive markets and wholesale suppliers to encourage faster product diffusion across all drug retailers.

Vowel normalization for accent: An investigation of perceptual plasticity in young adults

NASA Astrophysics Data System (ADS)

Evans, Bronwen G.; Iverson, Paul

2004-05-01

Previous work has emphasized the role of early experience in the ability to accurately perceive and produce foreign or foreign-accented speech. This study examines how listeners at a much later stage in language development-early adulthood-adapt to a non-native accent within the same language. A longitudinal study investigated whether listeners who had had no previous experience of living in multidialectal environments adapted their speech perception and production when attending university. Participants were tested before beginning university and then again 3 months later. An acoustic analysis of production was carried out and perceptual tests were used to investigate changes in word intelligibility and vowel categorization. Preliminary results suggest that listeners are able to adjust their phonetic representations and that these patterns of adjustment are linked to the changes in production that speakers typically make due to sociolinguistic factors when living in multidialectal environments.

An Update on Experimental Climate Prediction and Analysis Products Being Developed at NASA's Global Modeling and Assimilation Office

NASA Technical Reports Server (NTRS)

Schubert, Siegfried

2011-01-01

The Global Modeling and Assimilation Office at NASA's Goddard Space Flight Center is developing a number of experimental prediction and analysis products suitable for research and applications. The prediction products include a large suite of subseasonal and seasonal hindcasts and forecasts (as a contribution to the US National MME), a suite of decadal (10-year) hindcasts (as a contribution to the IPCC decadal prediction project), and a series of large ensemble and high resolution simulations of selected extreme events, including the 2010 Russian and 2011 US heat waves. The analysis products include an experimental atlas of climate (in particular drought) and weather extremes. This talk will provide an update on those activities, and discuss recent efforts by WCRP to leverage off these and similar efforts at other institutions throughout the world to develop an experimental global drought early warning system.

A neurocomputational account of taxonomic responding and fast mapping in early word learning.

PubMed

Mayor, Julien; Plunkett, Kim

2010-01-01

We present a neurocomputational model with self-organizing maps that accounts for the emergence of taxonomic responding and fast mapping in early word learning, as well as a rapid increase in the rate of acquisition of words observed in late infancy. The quality and efficiency of generalization of word-object associations is directly related to the quality of prelexical, categorical representations in the model. We show how synaptogenesis supports coherent generalization of word-object associations and show that later synaptic pruning minimizes metabolic costs without being detrimental to word learning. The role played by joint-attentional activities is identified in the model, both at the level of selecting efficient cross-modal synapses and at the behavioral level, by accelerating and refining overall vocabulary acquisition. The model can account for the qualitative shift in the way infants use words, from an associative to a referential-like use, for the pattern of overextension errors in production and comprehension observed during early childhood and typicality effects observed in lexical development. Interesting by-products of the model include a potential explanation of the shift from prototype to exemplar-based effects reported for adult category formation, an account of mispronunciation effects in early lexical development, and extendability to include accounts of individual differences in lexical development and specific disorders such as Williams syndrome. The model demonstrates how an established constraint on lexical learning, which has often been regarded as domain-specific, can emerge from domain-general learning principles that are simultaneously biologically, psychologically, and socially plausible.

Investing in the foundation of sustainable development: pathways to scale up for early childhood development.

PubMed

Richter, Linda M; Daelmans, Bernadette; Lombardi, Joan; Heymann, Jody; Boo, Florencia Lopez; Behrman, Jere R; Lu, Chunling; Lucas, Jane E; Perez-Escamilla, Rafael; Dua, Tarun; Bhutta, Zulfiqar A; Stenberg, Karin; Gertler, Paul; Darmstadt, Gary L

2017-01-07

Building on long-term benefits of early intervention (Paper 2 of this Series) and increasing commitment to early childhood development (Paper 1 of this Series), scaled up support for the youngest children is essential to improving health, human capital, and wellbeing across the life course. In this third paper, new analyses show that the burden of poor development is higher than estimated, taking into account additional risk factors. National programmes are needed. Greater political prioritisation is core to scale-up, as are policies that afford families time and financial resources to provide nurturing care for young children. Effective and feasible programmes to support early child development are now available. All sectors, particularly education, and social and child protection, must play a role to meet the holistic needs of young children. However, health provides a critical starting point for scaling up, given its reach to pregnant women, families, and young children. Starting at conception, interventions to promote nurturing care can feasibly build on existing health and nutrition services at limited additional cost. Failure to scale up has severe personal and social consequences. Children at elevated risk for compromised development due to stunting and poverty are likely to forgo about a quarter of average adult income per year, and the cost of inaction to gross domestic product can be double what some countries currently spend on health. Services and interventions to support early childhood development are essential to realising the vision of the Sustainable Development Goals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Recombinant Protein Production from TPO Gen Cloning and Expression for Early Detection of Autoimmune Thyroid Diseases

NASA Astrophysics Data System (ADS)

Aulanni'am, Aulanni'am; Kinasih Wuragil, Dyah; Wahono Soeatmadji, Djoko; Zulkarnain; Marhendra, Agung Pramana W.

2018-01-01

Autoimmune Thyroid Disease (AITD) is an autoimmune disease that has many clinical symptoms but is difficult to detect at the onset of disease progression. Most thyroid autoimmune disease patients are positive with high titre of thyroid autoantibodies, especially thyroid peroxidase (TPO). The detection AITD are still needed because these tests are extremely high cost and have not regularly been performed in most of clinical laboratories. In the past, we have explored the autoimmune disease marker and it has been developed as source of polyclonal antibodies from patient origin. In the current study, we develop recombinant protein which resulted from cloning and expression of TPO gene from normal person and AITD patients. This work flows involves: DNA isolation and PCR to obtain TPO gene from human blood, insertion of TPO gene to plasmid and transformation to E. coli BL21, Bacterial culture to obtain protein product, protein purification and product analysis. This products can use for application to immunochromatography based test. This work could achieved with the goal of producing autoimmune markers with a guaranteed quality, sensitive, specific and economically. So with the collaboration with industries these devices could be used for early detection. Keywords: recombinant protein, TPO gene, Autoimmune thyroid diseases (AITD)ction of the diseases in the community.

Corrosion detection in steel-reinforced concrete using a spectroscopic technique

NASA Astrophysics Data System (ADS)

Garboczi, E. J.; Stutzman, P. E.; Wang, S.; Martys, N. S.; Hassan, A. M.; Duthinh, D.; Provenzano, V.; Chou, S. G.; Plusquellic, D. F.; Surek, J. T.; Kim, S.; McMichael, R. D.; Stiles, M. D.

2014-02-01

Detecting the early corrosion of steel that is embedded in reinforced concrete (rebar) is a goal that would greatly facilitate the inspection and measurement of corrosion in the US physical infrastructure. Since 2010, the National Institute of Standards and Technology (NIST) has been working on a large project to develop an electromagnetic (EM) probe that detects the specific corrosion products via spectroscopic means. Several principal iron corrosion products, such as hematite and goethite, are antiferromagnetic at field temperatures. At a given applied EM frequency, which depends on temperature, these compounds undergo a unique absorption resonance that identifies the presence of these particular iron corrosion products. The frequency of the resonances tends to be on the order of 100 GHz or higher, so transmitting EM waves through the cover concrete and back out again at a detectable level has been challenging. NIST has successfully detected these two iron corrosion products, and is developing equipment and methodologies that will be capable of penetrating the typical 50 mm of cover concrete in the field. The novel part of this project is the detection of specific compounds, rather than only geometrical changes in rebar cross-section. This method has the potential of providing an early-corrosion probe for steel in reinforced concrete, and for other applications where steel is covered by various layers and coatings.

Searching for “Environmentally-Benign” Antifouling Biocides

PubMed Central

Cui, Yan Ting; Teo, Serena L. M.; Leong, Wai; Chai, Christina L. L.

2014-01-01

As the result of the ecological impacts from the use of tributyltins (TBT) in shipping, environmental legislation for the registration of chemicals for use in the environment has grown to a monumental challenge requiring product dossiers to include information on the environmental fate and behavior of any chemicals. Specifically, persistence, bioaccumulation and toxicity, collectively known as PBT, are properties of concern in the assessment of chemicals. However, existing measurements of PBT properties are a cumbersome and expensive process, and thus not applied in the early stages of the product discovery and development. Inexpensive methods for preliminary PBT screening would minimize risks arising with the subsequent registration of products. In this article, we evaluated the PBT properties of compounds reported to possess anti-fouling properties using QSAR (quantitative structure-activity relationship) prediction programs such as BIOWIN™ (a biodegradation probability program), KOWWIN™ (log octanol-water partition coefficient calculation program) and ECOSAR™ (Ecological Structure Activity Relationship Programme). The analyses identified some small (Mr < 400) synthetic and natural products as potential candidates for environmentally benign biocides. We aim to demonstrate that while these methods of estimation have limitations, when applied with discretion, they are powerful tools useful in the early stages of research for compound selection for further development as anti-foulants. PMID:24865489

Tobacco Industry Consumer Research on Smokeless Tobacco Users and Product Development

PubMed Central

Mejia, Adrienne B.

2010-01-01

Since 2006, RJ Reynolds (RJR) and Philip Morris have both introduced new smokeless “snus” tobacco products. We analyzed previously secret tobacco industry documents describing the history of RJR and Philip Morris's consumer research, smokeless product development, and marketing strategies. We found that RJR had invested in smokeless research, development, and marketing since 1968. RJR first targeted low-income males through sampling and sponsorship at fishing, rodeo, and baseball events, and through advertising portraying the user as “hard working.” In the early 1990s, Philip Morris and RJR hoped to attract more urban, female smokeless users. The current “snus” campaigns appear to appeal to these targeted consumers and smokers in smoke-free environments. These efforts may expand the tobacco market and undermine smoking cessation. PMID:19910355

The Development of a Rapid Prototyping Environment

DTIC Science & Technology

1989-12-01

constraints is a very complex, time- consuming and costly took. This situation can be iaproved by the use of adequate development methods and powerful support...was an essential factor in our decision . The previous development of CAPS tools utilized and assuumed the availa- bility of a Sun Workstation. There...the development of a production * 23 sys(tCm. An early decision was mIade to accept dependence upon the best locally avail- able resources. Portability

Risk factors for postpartum ovarian cysts and their spontaneous recovery or persistence in lactating dairy cows.

PubMed

López-Gatius, F; Santolaria, P; Yániz, J; Fenech, M; López-Béjar, M

2002-11-01

Cystic ovarian disease is a major cause of reproductive failure and economic loss for the dairy industry. Many cysts that develop during the early postpartum period regress spontaneously. However, it is difficult to decide at what point it would be more cost effective to treat ovarian cysts than to wait for spontaneous recovery. The objective of this study was to analyze risk factors for the development of the ovarian cystic condition during early and late postpartum, and for its persistence or recovery during the pre-service period in lactating dairy cows. Using multiple logistic regression, we analyzed data derived from 873 lactating dairy cows from a single herd. An ovarian cyst was diagnosed if it was possible to observe a single follicular structure with an antrum diameter > or = 25 mm in the absence of a corpus luteum in three sonograms performed at 7-day intervals. The cystic condition was denoted as early if the cyst was diagnosed 43-49 days postpartum, and late if detected 57-63-day postpartum. Spontaneous cyst regression before 60-day postpartum was regarded as early cystic recovery. For the early cystic group, there were no significant effects of lactation number, body condition score on prepartum Day 60, at parturition or on postpartum Day 30, or of body condition loss from parturition to 30-day postpartum. Cows calving in summer were 2.6 times more likely to develop ovarian cysts than those giving birth in winter. The risk of having a cyst was 1.9 times higher in cows with an abnormal puerperium. A 1-kg increase in milk yield raised the risk of cysts by a factor of 1.05. A 1-unit increase in body condition score (scale from 1 to 5) from prepartum Day 60 to parturition increased the risk of cyst development 8.4 times. Milk production and lactation number were negatively correlated with spontaneous early cyst recovery. A 1-kg decrease in milk production increased the probability of cyst recovery by a factor of 1.06, and a 1-unit drop in lactation number was associated with a 1.4-fold increased probability of cyst recovery. For the late cystic group, there were no significant effects of abnormal puerperium and body score data, except for a prepartum change in body score. Calving season (Odds ratio: 2.3), lactation number (Odds ratio: 1.36), increased milk production (Odds ratio: 1.05) and increased body condition score during the prepartum period (Odds ratio: 4.3) were all related to an increased risk of ovarian cysts. The probability of having a late cyst was 36.6 times greater in cows with early cysts. These findings suggest that it would be profitable to treat multiparous cows having cysts very early in the postpartum period, while treatment of primiparous cows should be delayed, at least until the end of the pre-service period, to provide the opportunity for spontaneous recovery.

Multicriteria analysis of product operational effectiveness at design stages

NASA Astrophysics Data System (ADS)

Irzaev, G. Kh

2018-03-01

The multicriteria rapid assessment method of techno-economic parameters of new products is developed. It avoids expensive engineering changes during the operational stages through the analysis of external and internal factors at an early stage in the design that affect the maintainability and manufacturability of the product. The expert selection of the initial multitude of indicators from the five enlarged criteria groups and their subsequent pairwise comparison allow one to distinguish the complex compliance criteria of product design with the average and optimum values of the operational effectiveness. The values comparison provides an opportunity to decide on the continuation of the process for designing and preparation of the product manufacture.

Use of Spray-Dried Dispersions in Early Pharmaceutical Development: Theoretical and Practical Challenges.

PubMed

Li, Jinjiang; Patel, Dhaval; Wang, George

2017-03-01

Spray-dried dispersions (SDDs) have become an important formulation technology for the pharmaceutical product development of poorly water-soluble (PWS) compounds. Although this technology is now widely used in the industry, especially in the early-phase development, the lack of mechanistic understanding still causes difficulty in selecting excipients and predicting stability of SDD-based drug products. In this review, the authors aim to discuss several principles of polymer science pertaining to the development of SDDs, in terms of selecting polymers and solvents, optimizing drug loading, as well as assessing physical stability on storage and supersaturation maintenance after dissolution, from both thermodynamic and kinetic considerations. In order to choose compatible solvents with both polymers and active pharmaceutical ingredients (APIs), a symmetric Flory-Huggins interaction (Δχ ∼0) approach was introduced. Regarding spray drying of polymer-API solutions, low critical solution temperature (LCST) was discussed for setting the inlet temperature for drying. In addition, after being exposed to moisture, SDDs are practically converted to ternary systems with asymmetric Flory-Huggins interactions, which are thermodynamically not favored. In this case, the kinetics of phase separation plays a significant role during the storage and dissolution of SDD-based drug products. The impact of polymers on the supersaturation maintenance of APIs in dissolution media was also discussed. Moreover, the nature of SDDs, with reference to solid solution and the notion of solid solubility, was examined in the context of pharmaceutical application. Finally, the importance of robust analytical techniques to characterize the SDD-based drug products was emphasized, considering their complexity.

Effects of heat stress on mammalian reproduction

PubMed Central

Hansen, Peter J.

2009-01-01

Heat stress can have large effects on most aspects of reproductive function in mammals. These include disruptions in spermatogenesis and oocyte development, oocyte maturation, early embryonic development, foetal and placental growth and lactation. These deleterious effects of heat stress are the result of either the hyperthermia associated with heat stress or the physiological adjustments made by the heat-stressed animal to regulate body temperature. Many effects of elevated temperature on gametes and the early embryo involve increased production of reactive oxygen species. Genetic adaptation to heat stress is possible both with respect to regulation of body temperature and cellular resistance to elevated temperature. PMID:19833646

Role of MODIS Vegetation Phenology Products in the U.S. for Warn Early Warning System for Forest Threats

NASA Technical Reports Server (NTRS)

Spruce, Joseph; Hargrove, William; Norman, Steve; Gasser, Gerald; Smoot, James; Kuper, Philip

2012-01-01

U.S. forests occupy approx 751 million acres (approx 1/3 of total land). Several abiotic and biotic damage agents disturb, damage, kill, and/or threaten these forests. Regionally extensive forest disturbances can also threaten human life and property, bio-diversity and water supplies. timely regional forest disturbance monitoring products are needed to aid forest health management work at finer scales. daily MODIS data provide a means to monitor regional forest disturbances on a weekly basis, leveraging vegetation phenology. In response, the USFS and NASA began collaborating in 2006 to develop a Near Real Time (NRT) forest monitoring capability, based on MODIS NDVI data, as part of a national forest threat Early Warning System (EWS).

Ceratopteris richardii: a productive model for revealing secrets of signaling and development

NASA Technical Reports Server (NTRS)

Chatterjee, A.; Roux, S. J.

2000-01-01

Ceratopteris richardii is an aquatic fern grown in tropical and subtropical regions of the world. It is proven to be a productive model system for studies in the genetics, biochemistry, and cell biology of basic biologic processes that occur in early gametophytic development. It provides several advantages to biologists, especially those interested in gravitational biology, polarity development, and in the genetics of sexual development. It is easy to culture, has a relatively short life cycle, and offers an array of attractive features that facilitate genetic studies. The germination and early development of large populations of genetically identical spores are easy to synchronize, and both the direction of polarity development and cell-level gravity responses can be measured and readily manipulated within the first 24 h of spore development. Although there is no reliable transformation system available yet in Ceratopteris, recent studies suggest that the technique of RNA interference can be used to block translation of specific genes in a related fern, Marsilea, and current studies will soon reveal the applicability of this approach, as well as of other transformation approaches, in Ceratopteris. A recently completed expressed sequence tag (EST) sequencing project makes available the partial sequence of more than 2000 cDNAs, representing a significant percentage of the genes being expressed during the first 24 h of spore germination, when many developmentally interesting processes are occurring. A microarray of these ESTs is being constructed, so especially for those scientists interested in basic cellular phenomena that occur early in spore germination, the availability of the ESTs and of the microarray will make Ceratopteris an even more attractive model system.

Ceratopteris richardii: a productive model for revealing secrets of signaling and development.

PubMed

Chatterjee, A; Roux, S J

2000-09-01

Ceratopteris richardii is an aquatic fern grown in tropical and subtropical regions of the world. It is proven to be a productive model system for studies in the genetics, biochemistry, and cell biology of basic biologic processes that occur in early gametophytic development. It provides several advantages to biologists, especially those interested in gravitational biology, polarity development, and in the genetics of sexual development. It is easy to culture, has a relatively short life cycle, and offers an array of attractive features that facilitate genetic studies. The germination and early development of large populations of genetically identical spores are easy to synchronize, and both the direction of polarity development and cell-level gravity responses can be measured and readily manipulated within the first 24 h of spore development. Although there is no reliable transformation system available yet in Ceratopteris, recent studies suggest that the technique of RNA interference can be used to block translation of specific genes in a related fern, Marsilea, and current studies will soon reveal the applicability of this approach, as well as of other transformation approaches, in Ceratopteris. A recently completed expressed sequence tag (EST) sequencing project makes available the partial sequence of more than 2000 cDNAs, representing a significant percentage of the genes being expressed during the first 24 h of spore germination, when many developmentally interesting processes are occurring. A microarray of these ESTs is being constructed, so especially for those scientists interested in basic cellular phenomena that occur early in spore germination, the availability of the ESTs and of the microarray will make Ceratopteris an even more attractive model system.

Increased gibberellin contents contribute to accelerated growth and development of transgenic tobacco overexpressing a wheat ubiquitin gene.

PubMed

Wang, Guo-Kun; Zhang, Meng; Gong, Jiang-Feng; Guo, Qi-Fang; Feng, Ya-Nan; Wang, Wei

2012-12-01

Overexpressing TaUb2 promoted stem growth and resulted in early flowering in transgenic tobacco plants. Ubiquitin are involved in the production, metabolism and proper function of gibberellin. The ubiquitin-26S proteasome system (UPS), in which ubiquitin (Ub) functions as a marker, is a post-translational regulatory system that plays a prominent role in various biological processes. To investigate the impact of different Ub levels on plant growth and development, transgenic tobacco (Nicotiana tabacum L.) plants were engineered to express an Ub gene (TaUb2) from wheat (Triticum aestivum L.) under the control of cauliflower mosaic virus 35S promoter. Transgenic tobacco plants overexpressing TaUb2 demonstrated an accelerated growth rate at early stage and an early flowering phenotype in development. The preceding expression of MADS-box genes also corresponded to the accelerated developmental phenotypes of the transgenic tobacco plants compared to that of wild-type (WT). Total gibberellin (GA) and active GA contents in transgenic tobacco plants were higher than those in WT at the corresponding developmental stages, and some GA metabolism genes were upregulated. Treatment with GA(3) conferred a similarly accelerated grown rate in WT plants to that of transgenic tobacco plants, while growth was inhibited when transgenic tobacco plants were treated with a GA biosynthesis inhibitor. Thus, the results suggest that Ub are involved in the production, metabolism and proper function of GA, which is important in the regulation of plant growth and development.

Early childhood poverty, immune-mediated disease processes, and adult productivity.

PubMed

Ziol-Guest, Kathleen M; Duncan, Greg J; Kalil, Ariel; Boyce, W Thomas

2012-10-16

This study seeks to understand whether poverty very early in life is associated with early-onset adult conditions related to immune-mediated chronic diseases. It also tests the role that these immune-mediated chronic diseases may play in accounting for the associations between early poverty and adult productivity. Data (n = 1,070) come from the US Panel Study of Income Dynamics and include economic conditions in utero and throughout childhood and adolescence coupled with adult (age 30-41 y) self-reports of health and economic productivity. Results show that low income, particularly in very early childhood (between the prenatal and second year of life), is associated with increases in early-adult hypertension, arthritis, and limitations on activities of daily living. Moreover, these relationships and particularly arthritis partially account for the associations between early childhood poverty and adult productivity as measured by adult work hours and earnings. The results suggest that the associations between early childhood poverty and these adult disease states may be immune-mediated.

Trade-offs mathematical modelling of 3DCE in new product development: real three dimensions and directions for development

NASA Astrophysics Data System (ADS)

Ilhami, M. A.; Subagyo; Masruroh, N. A.

2018-04-01

In the last two decades, coordinating product, process, and supply chain has become the main focus in recent years as a growing body of research, which mathematical modelling is leading technique used in the early phase design. In this paper, we aim to conduct a comprehensive literature review of published paper and propose directions for future research, especially in mathematical modelling. Our findings exhibit fact that evidently there are only a few papers coordinate “real three dimensions”. The other papers, in fact, show simply two dimensions. Finally, some suggestions are proposed such as paying more attention to “real three dimensions” research-based and more focus on minimizing time to market, product life cycle consideration, and product rollover.

A feasibility study of large-scale photobiological hydrogen production utilizing mariculture-raised cyanobacteria.

PubMed

Sakurai, Hidehiro; Masukawa, Hajime; Kitashima, Masaharu; Inoue, Kazuhito

2010-01-01

In order to decrease CO(2) emissions from the burning of fossil fuels, the development of new renewable energy sources sufficiently large in quantity is essential. To meet this need, we propose large-scale H(2) production on the sea surface utilizing cyanobacteria. Although many of the relevant technologies are in the early stage of development, this chapter briefly examines the feasibility of such H(2) production, in order to illustrate that under certain conditions large-scale photobiological H(2) production can be viable. Assuming that solar energy is converted to H(2) at 1.2% efficiency, the future cost of H(2) can be estimated to be about 11 (pipelines) and 26.4 (compression and marine transportation) cents kWh(-1), respectively.

A review of test results on parabolic dish solar thermal power modules with dish-mounted Rankine engines and for production of process steam

NASA Technical Reports Server (NTRS)

Jaffe, Leonard D.

1988-01-01

This paper presents results of development testing of various solar thermal parabolic dish modules and assemblies. Most of the tests were at modules and assemblies that used a dish-mounted, organic Rankine cycle turbine for production of electric power. Some tests were also run on equipment for production of process steam or for production of electricity using dish-mounted reciprocating steam engines. These tests indicate that early modules achieve efficiencies of about 18 percent in converting sunlight to electricity (excluding the inverter but including parasitics). A number of malfunctions occurred. The performance measurements, as well as the malfunctions and other operating experience, provided information that should be of value in developing systems with improved performance and reduced maintenance.

The Role of Capital Productivity in British Airways' Financial Recovery

NASA Technical Reports Server (NTRS)

Morrell, Peter

1999-01-01

British Airways (BA) was privatized in 1987, but its financial recovery occurred a number of years earlier, This recovery was sustained throughout the early 1990s economic recession, a period when few major airlines were operating profitably. This paper examines the role of productivity developments at British Airways from the early 1980s through 1996. The emphasis is on capital productivity and investment, but changes in capital intensity and labour productivity are also evaluated. Various measures are considered for both capital and labour productivity: outputs are measured in available tonne-kms (ATKs) and revenue tonne-kms (RTKs), with the former preferred over the latter two measures, after adjustment for work performed by BA for others. Capital inputs are measured in equivalent lease costs adjusted to constant prices with a different treatment of flight and ground equipment or assets. Labour inputs are derived from total payroll costs deflated by a UK wage price index. The airline made considerable capital investments over the period and at the same time went through two major processes of labour restructuring. This resulted in a gradual increase in capital intensity, relative high labour productivity growth, but poor capital productivity performance, However, capital investment played an important role in the airline's sustained labour and total factor productivity over the whole period.

The Role of Capital Productivity in British Airways' Financial Recovery

NASA Technical Reports Server (NTRS)

Morrell, Peter

1999-01-01

British Airways (BA) was privatised in 1987, but its financial recovery occurred a number of years earlier. This recovery was sustained throughout the early 1990s economic recession, a period when few major airlines were operating profitably. This paper examines the role of productivity developments at British Airways from the early 1980s through 1996. The emphasis is on capital productivity and investment, but changes in capital intensity and labour productivity are also evaluated. Various measures are considered for both capital and labour productivity: outputs are measured in available tonne-kms (ATKS) and revenue tonne-kms (RTKs), with the former preferred over the latter two measures, after adjustment for work performed by BA for others. Capital inputs are measured in equivalent lease costs adjusted to constant prices with a different treatment of flight and ground equipment or assets. Labour inputs are derived from total payroll costs deflated by a UK wage price index. The airline made considerable capital investments over the period and at the same time went through two major processes of labour restructuring. This resulted in a gradual increase in capital intensity, relative high labour productivity growth, but poor capital productivity performance. However, capital investment played an important role in the airline's sustained labour and total factor productivity over the whole period.

PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2.

PubMed

Zheng, Sika; Gray, Erin E; Chawla, Geetanjali; Porse, Bo Torben; O'Dell, Thomas J; Black, Douglas L

2012-01-15

Postsynaptic density protein 95 (PSD-95) is essential for synaptic maturation and plasticity. Although its synaptic regulation has been widely studied, the control of PSD-95 cellular expression is not understood. We found that Psd-95 was controlled post-transcriptionally during neural development. Psd-95 was transcribed early in mouse embryonic brain, but most of its product transcripts were degraded. The polypyrimidine tract binding proteins PTBP1 and PTBP2 repressed Psd-95 (also known as Dlg4) exon 18 splicing, leading to premature translation termination and nonsense-mediated mRNA decay. The loss of first PTBP1 and then of PTBP2 during embryonic development allowed splicing of exon 18 and expression of PSD-95 late in neuronal maturation. Re-expression of PTBP1 or PTBP2 in differentiated neurons inhibited PSD-95 expression and impaired the development of glutamatergic synapses. Thus, expression of PSD-95 during early neural development is controlled at the RNA level by two PTB proteins whose sequential downregulation is necessary for synapse maturation.

Aerospace Engineering Systems and the Advanced Design Technologies Testbed Experience

NASA Technical Reports Server (NTRS)

VanDalsem, William R.; Livingston, Mary E.; Melton, John E.; Torres, Francisco J.; Stremel, Paul M.

1999-01-01

Continuous improvement of aerospace product development processes is a driving requirement across much of the aerospace community. As up to 90% of the cost of an aerospace product is committed during the first 10% of the development cycle, there is a strong emphasis on capturing, creating, and communicating better information (both requirements and performance) early in the product development process. The community has responded by pursuing the development of computer-based systems designed to enhance the decision-making capabilities of product development individuals and teams. Recently, the historical foci on sharing the geometrical representation and on configuration management are being augmented: 1) Physics-based analysis tools for filling the design space database; 2) Distributed computational resources to reduce response time and cost; 3) Web-based technologies to relieve machine-dependence; and 4) Artificial intelligence technologies to accelerate processes and reduce process variability. The Advanced Design Technologies Testbed (ADTT) activity at NASA Ames Research Center was initiated to study the strengths and weaknesses of the technologies supporting each of these trends, as well as the overall impact of the combination of these trends on a product development event. Lessons learned and recommendations for future activities are reported.

Implications of intelligent, integrated microsystems for product design and development

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

MYERS,DAVID R.; MCWHORTER,PAUL J.

2000-04-19

Intelligent, integrated microsystems combine some or all of the functions of sensing, processing information, actuation, and communication within a single integrated package, and preferably upon a single silicon chip. As the elements of these highly integrated solutions interact strongly with each other, the microsystem can be neither designed nor fabricated piecemeal, in contrast to the more familiar assembled products. Driven by technological imperatives, microsystems will best be developed by multi-disciplinary teams, most likely within the flatter, less hierarchical organizations. Standardization of design and process tools around a single, dominant technology will expedite economically viable operation under a common production infrastructure.more » The production base for intelligent, integrated microsystems has elements in common with the mathematical theory of chaos. Similar to chaos theory, the development of microsystems technology will be strongly dependent on, and optimized to, the initial product requirements that will drive standardization--thereby further rewarding early entrants to integrated microsystem technology.« less

Uneven colonization of the lymphoid periphery by T cells that undergo early TCR{alpha} rearrangements.

PubMed

Hendricks, Deborah W; Fink, Pamela J

2009-04-01

A sparse population of thymocytes undergoes TCRalpha gene rearrangement early in development, before the double-positive stage. The potential of these cells to contribute to the peripheral T cell pool is unknown. To examine the peripheral T cell compartment expressing a repertoire biased to early TCR gene rearrangements, we developed a mouse model in which TCRalpha rearrangements are restricted to the double-negative stage of thymocyte development. These mice carry floxed RAG2 alleles and a Cre transgene driven by the CD4 promoter. As expected, conventional T cell development is compromised in such Cre(+) RAG2(fl/fl) mice, and the TCRalphabeta(+) T cells that develop are limited in their TCRalpha repertoire, preferentially using early rearranging Valpha genes. In the gut, the Thy-1(+)TCRalphabeta(+) intraepithelial lymphocyte (IEL) compartment is surprisingly intact, whereas the Thy-1(-)TCRalphabeta(+) subset is almost completely absent. Thus, T cells expressing a TCRalpha repertoire that is the product of early gene rearrangements can preferentially populate distinct IEL compartments. Despite this capacity, Cre(+) RAG2(fl/fl) T cell progenitors cannot compete with wild-type T cell progenitors in mixed bone marrow chimeras, suggesting that in normal mice, there is only a small contribution to the peripheral T cell pool by cells that have undergone early TCRalpha rearrangements. In the absence of wild-type competitors, aggressive homeostatic proliferation in the IEL compartment can promote a relatively normal Thy-1(+) TCRalphabeta(+) T cell pool from the limited population derived from Cre(+) RAG2(fl/fl) progenitors.

Uneven colonization of the lymphoid periphery by T cells that undergo early TCRα rearrangements1

PubMed Central

Hendricks, Deborah W.; Fink, Pamela J.

2009-01-01

A sparse population of thymocytes undergoes TCRα gene rearrangement early in development, before the double positive stage. The potential of these cells to contribute to the peripheral T cell pool is unknown. To examine the peripheral T cell compartment expressing a repertoire biased to early TCR gene rearrangements, we developed a mouse model in which TCRα rearrangements are restricted to the double negative stage of thymocyte development. These mice carry floxed RAG2 alleles and a Cre transgene driven by the CD4 promoter. As expected, conventional T cell development is compromised in such Cre(+) RAG2fl/fl mice, and the TCRαβ+ T cells that develop are limited in their TCRα repertoire, preferentially utilizing early-rearranging Vα genes. In the gut, the Thy-1+TCRαβ+ intraepithelial lymphocyte (IEL) compartment is surprisingly intact, while the Thy-1−TCRαβ+ subset is almost completely absent. Thus, T cells expressing a TCRα repertoire that is the product of early gene rearrangements can preferentially populate distinct IEL compartments. Despite this capacity, Cre(+) RAG2fl/fl T cell progenitors cannot compete with wild-type (WT) T cell progenitors in mixed bone marrow chimeras, suggesting that in normal mice, there is only a small contribution to the peripheral T cell pool by cells that have undergone early TCRα rearrangements. In the absence of WT competitors, aggressive homeostatic proliferation in the IEL compartment can promote a relatively normal Thy-1+ TCRαβ+ T cell pool from the limited population derived from Cre(+) RAG2fl/fl progenitors. PMID:19299725

Characteristics of Phonological Development as a Risk Factor for Language Development in Italian-Speaking Pre-Term Children: A Longitudinal Study

ERIC Educational Resources Information Center

D'Odorico, Laura; Majorano, Marinella; Fasolo, Mirco; Salerni, Nicoletta; Suttora, Chiara

2011-01-01

This study analysed the early linguistic development of Italian pre-term children. Samples of spontaneous pre-linguistic and verbal production were recorded at 12 and 18 months of age from two groups of children: 24 pre-term children and 15 full-term children. The Italian version of the MacArthur-Bates Questionnaire was administered at 24 months…

Metabolic Energy Demand Is Not Increased during Initial Shell Formation of Bivalves Exposed to Aragonite Undersaturation

NASA Astrophysics Data System (ADS)

Pan, F.; Frieder, C.; Applebaum, S.; Manahan, D. T.

2016-02-01

The Pacific oyster, Crassostrea gigas, is a major commercial species in global aquaculture. Ocean acidification is having a negative effect on larval production of this species, so the mechanisms of this impact are of considerable interest. Formation of new shell in C. gigas during the first 2-days post-fertilization results in a rapid six-fold increase in total mass. This period of early development has high sensitivity to changes in carbonate chemistry, in particular aragonite saturation state (Ω). An elevated energy cost for calcification at low Ω is often invoked as a mechanism. In this study, we characterized the developmental progression of first shell formation, total metabolic expenditure, and underlying biochemical processes of energy allocation during early development of C. gigas, under control (Ω >> 1) and undersaturated conditions (Ω < 1). While undersaturated conditions delayed the onset of calcification and resulted in decreased shell mass, there was no change in total metabolic energy demand. Furthermore, partitioning of total metabolic energy showed no major re-allocation of ATP to protein synthesis or ion pump activity (Na+, K+-ATPase) between the two treatments. We conclude that early development to the shelled-veliger larval stage does not require more energy at undersaturation. This finding helps constrain potential mechanisms of larval sensitivity to ocean acidification and narrows the focus for possible mitigation strategies for oyster aquaculture production.

Child Art and the Emergence of Learning Styles.

ERIC Educational Resources Information Center

Wieder, Charles G.

1998-01-01

Looks at individuality, in the sense of a personal expressive idiom or style, in children's art production. Shows that early stylistic differences manifest in children's art making correspond to basic cognitive/affective learning processes. Outlines implications for ideas about child development. (DSK)

Prevention of food allergy - Early dietary interventions.

PubMed

Du Toit, George; Foong, Ru-Xin M; Lack, Gideon

2016-10-01

The prevalence of food allergy has increased over the last 30 years and remains a disease, which significantly impacts on the quality of life of children and their families. Several hypotheses have been formulated to explain the increasing prevalence; this review will focus on the hypothesis that dietary factors may influence the development of food allergy. Historically, the prevention of food allergy has focused on allergen avoidance. However, recent findings from interventional studies have prompted a shift in the mind set from avoidance to early introduction of potentially allergenic foods. This review aims to facilitate a better understanding of contemporary research studies that make use of early introduction of common allergenic foods into infant diets as a preventative strategy against the development of food allergy. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Peer Contexts in Schools: Avenues Toward Behavioral Health in Early Adolescence.

PubMed

Cappella, Elise; Hwang, Sophia H J

2015-01-01

Peer contexts play an important role in the behavioral health of early adolescents in schools. Behavioral health involves the observable academic and social behaviors that relate to and influence youths' subsequent health and development. Setting-level research on peer networks and social norms indicates these aspects of peer contexts vary by peer group, classroom, and school and dynamically relate to individual students' academic and social behaviors. Yet, although peer contexts are both influential and potentially malleable, little research examines the effects of school and classroom interventions on the development and maintenance of positive and productive peer contexts in schools. The current article identifies school structures and classroom processes theorized to directly or indirectly shift peer networks and social norms-and thereby increase the behavioral health of early adolescents in schools. We discuss the need for more rigorous and relevant research to better understand the role of schools and classrooms in strengthening these peer contexts and promoting behavioral health in early adolescence.

Posibilidades y limites de un fomento cognitivo temprano (Possibilities and Limits of Early Cognitive Development).

ERIC Educational Resources Information Center

Schmalohr, Emil

This article discusses preschool education and the research conducted in that field on various relevant topics in an effort to establish recommendations and programs. Cognitive development is the main issue and is seen as a product of maturation as well as of a broad base of experience which results from interaction between the mind and the…

Handbook for Implementing Agile in Department of Defense Information Technology Acquisition

DTIC Science & Technology

2010-12-15

Wire-frame Mockup of iTunes Cover Flow Feature (source: http://www.balsamiq.com/products/mockups/examples#mytunez...programming. The JOPES customer was included early in the development process in order to understand requirements management (story cards ), observe...transition by teaching the new members Agile processes, such as story card development, refactoring, and pair programming. Additionally, the team worked to

Externalizing Problems in Fifth Grade: Relations with Productive Activity, Maternal Sensitivity, and Harsh Parenting from Infancy through Middle Childhood

ERIC Educational Resources Information Center

Bradley, Robert H.; Corwyn, Robert F.

2007-01-01

This study used data from the National Institute of Child Health and Human Development's Study of Early Child Care and Youth Development to examine relations between parenting, self-control, and externalizing behavior from infancy through 5th grade. Results indicate that self-control measured during middle childhood mediates relations between…

Child Care Effects in Context: Quality, Stability, and Multiplicity in Nonmaternal Child Care Arrangements during the First 15 Months of Life

ERIC Educational Resources Information Center

Tran, Henry; Weinraub, Marsha

2006-01-01

Main and interactive effects of child care quality, stability, and multiplicity on infants' attachment security, language comprehension, language production, and cognitive development at 15 months were examined using data from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care. Thirty-nine percent of the…

A Prominence Account of Syllable Reduction in Early Speech Development: The Child's Prosodic Phonology of "Tiger" and "Giraffe."

ERIC Educational Resources Information Center

Snow, David

1998-01-01

This paper tested a theory of syllable prominence with 11 children (ages 11 to 26 months). The theory proposes that syllable prominence is a product of two orthogonal suprasegmental systems: stress/accent peaks and phrase boundaries. Use of the developed prominence scale found it parsimoniously accounted for observed biases in syllable omissions…

AgRISTARS: Agriculture and resources inventory surveys through aerospace remote sensing

NASA Technical Reports Server (NTRS)

1982-01-01

The rationale, objectives, participants, and approach of the AgRISTARS program are described. Progress is reported in activities related to early warning and crop condition assessment; inventory technology development (formerly foreign commodity production forecasting); yield model development; supporting research; soil moisture; renewable resources inventory; domestic crops and land cover; and conservation and pollution. Emphasis is on technological highlights.

Evaluating the Use of Remote Sensing Data in the U.S. Agency for International Development Famine Early Warning Systems Network

NASA Technical Reports Server (NTRS)

Brown, Molly Elizabeth; Brickley, Elizabeth B

2012-01-01

The U.S. Agency for International Development (USAID)'s Famine Early Warning System Network (FEWS NET) provides monitoring and early warning support to decision makers responsible for responding to food insecurity emergencies on three continents. FEWS NET uses satellite remote sensing and ground observations of rainfall and vegetation in order to provide information on drought, floods, and other extreme weather events to decision makers. Previous research has presented results from a professional review questionnaire with FEWS NET expert end-users whose focus was to elicit Earth observation requirements. The review provided FEWS NET operational requirements and assessed the usefulness of additional remote sensing data. We analyzed 1342 food security update reports from FEWS NET. The reports consider the biophysical, socioeconomic, and contextual influences on the food security in 17 countries in Africa from 2000 to 2009. The objective was to evaluate the use of remote sensing information in comparison with other important factors in the evaluation of food security crises. The results show that all 17 countries use rainfall information, agricultural production statistics, food prices, and food access parameters in their analysis of food security problems. The reports display large-scale patterns that are strongly related to history of the FEWS NET program in each country. We found that rainfall data were used 84% of the time, remote sensing of vegetation 28% of the time, and gridded crop models 10% of the time, reflecting the length of use of each product in the regions. More investment is needed in training personnel on remote sensing products to improve use of data products throughout the FEWS NET system.

Holistic Design for Total Product Well Being

NASA Technical Reports Server (NTRS)

Adams, Chris W.; Hamilton, George S.

2004-01-01

Recent hardware development work at NASA's Marshall Space Flight Center creates and argument for the use of a holistic design approach as opposed to a piece part design approach. A piece part design approach being one where individual pieces are developed to their finished state having to meet certain interface and human engineering requirements without much consideration to the final product as a whole. A holistic design approach being one where the final product is evaluated early and frequently during the design process, and individual parts are developed with consideration to how they interact a whole,and how they interact with the user and environment. Examples from the development of the Materials Science Research Rack - 1 will illustrate: a design failure due to piece part design; a design save, due to a failure of piece part design, but saved by evaluating the design holistically; and a design success due to a holistic design approach.

Designing medical technology for resilience: integrating health economics and human factors approaches.

PubMed

Borsci, Simone; Uchegbu, Ijeoma; Buckle, Peter; Ni, Zhifang; Walne, Simon; Hanna, George B

2018-01-01

The slow adoption of innovation into healthcare calls into question the manner of evidence generation for medical technology. This paper identifies potential reasons for this including a lack of attention to human factors, poor evaluation of economic benefits, lack of understanding of the existing healthcare system and a failure to recognise the need to generate resilient products. Areas covered: Recognising a cross-disciplinary need to enhance evidence generation early in a technology's life cycle, the present paper proposes a new approach that integrates human factors and health economic evaluation as part of a wider systems approach to the design of technology. This approach (Human and Economic Resilience Design for Medical Technology or HERD MedTech) supports early stages of product development and is based on the recent experiences of the National Institute for Health Research London Diagnostic Evidence Co-operative in the UK. Expert commentary: HERD MedTech i) proposes a shift from design for usability to design for resilience, ii) aspires to reduce the need for service adaptation to technological constraints iii) ensures value of innovation at the time of product development, and iv) aims to stimulate discussion around the integration of pre- and post-market methods of assessment of medical technology.

Best practices in early phase medical device development: Engineering, prototyping, and the beginnings of a quality management system.

PubMed

Fearis, Kristy; Petrie, Aidan

2017-03-01

Kristy Fearis is the founder and president of KPConsulting. She has held various positions in the medical device and research industry. She has led programs for medical industry leaders Medtronic, Edward Lifesciences, and Kimberly-Clark Healthcare to develop and commercialize Class II and III devices. Although a true quality management systems specialist at heart, Kristy has a passion for effectively and efficiently applying quality systems principles to early stage development to maximize benefit while minimizing impact on resources and time to market. Kristy works with both precommercial and commercial companies to build and implement quality systems that are "right sized" and support both an effective business model and high product quality. Aidan Petrie is the cofounder and chief innovation officer of Ximedica. Aidan drives innovation in Ximedica's core markets of medical device development and consumer healthcare. With a focus on human-centered design, usability, technical innovation and industrial design, Aidan has helped bring hundreds of products to market. Ranging from simple drug compliance aids to wearable therapeutics, home monitoring products, and complex surgical systems, Aidan challenges his teams to rethink the role design plays in the success of each product. Covering topics around usability, sensor and wearable technology, and current trends in medical design and development, Aidan is a sought-after industry speaker and widely published author. In addition to his role at Ximedica, Aidan advises multiple startups in the healthcare space and has interests in a number of related companies. He sits on the Board of MassArt and teaches and lectures at the Rhode Island School of Design, Massachusetts Institute of Technology, the Harvard iLab, and others. Aidan holds an undergraduate degree from Central St Martins in product design/engineering and a Masters in industrial design from the Rhode Island School of Design. Copyright © 2016 Elsevier Inc. All rights reserved.

James Webb Space Telescope - Applying Lessons Learned to I&T

NASA Technical Reports Server (NTRS)

Johns, Alan; Seaton, Bonita; Gal-Edd, Jonathan; Jones, Ronald; Fatig, Curtis; Wasiak, Francis

2008-01-01

The James Webb Space Telescope (JWST) is part of a new generation of spacecraft acquiring large data volumes from remote regions in space. To support a mission such as the JWST, it is imperative that lessons learned from the development of previous missions such as the Hubble Space Telescope and the Earth Observing System mission set be applied throughout the development and operational lifecycles. One example of a key lesson that should be applied is that core components, such as the command and telemetry system and the project database, should be developed early, used throughout development and testing, and evolved into the operational system. The purpose of applying lessons learned is to reap benefits in programmatic or technical parameters such as risk reduction, end product quality, cost efficiency, and schedule optimization. In the cited example, the early development and use of the operational command and telemetry system as well as the establishment of the intended operational database will allow these components to be used by the developers of various spacecraft components such that development, testing, and operations will all use the same core components. This will reduce risk through the elimination of transitions between development and operational components and improve end product quality by extending the verification of those components through continual use. This paper will discuss key lessons learned that have been or are being applied to the JWST Ground Segment integration and test program.

Primesupplier Podcast

NASA Technical Reports Server (NTRS)

Galluzzi, Michael; Ferrari, Pasquale; Fair, Jennifer

2009-01-01

PrimeSupplier, s supplier cross program and element impact simulation model with supplier solvency indicator (SSI), has been developed so that the Shuttle Program can see an early indicator of supplier and product line stability while identifying the various elements and/or programs that have a particular supplier of product designed into the system. The model calculates two categories of benchmarks to determine the SSI with one category focusing on Agency programmatic and the other being a supplier financial liquidity.

Nanomaterials in preventive dentistry

NASA Astrophysics Data System (ADS)

Hannig, Matthias; Hannig, Christian

2010-08-01

The prevention of tooth decay and the treatment of lesions and cavities are ongoing challenges in dentistry. In recent years, biomimetic approaches have been used to develop nanomaterials for inclusion in a variety of oral health-care products. Examples include liquids and pastes that contain nano-apatites for biofilm management at the tooth surface, and products that contain nanomaterials for the remineralization of early submicrometre-sized enamel lesions. However, the treatment of larger visible cavities with nanomaterials is still at the research stage. Here, we review progress in the development of nanomaterials for different applications in preventive dentistry and research, including clinical trials.

Early childhood adversity, toxic stress, and the role of the pediatrician: translating developmental science into lifelong health.

PubMed

Garner, Andrew S; Shonkoff, Jack P

2012-01-01

Advances in a wide range of biological, behavioral, and social sciences are expanding our understanding of how early environmental influences (the ecology) and genetic predispositions (the biologic program) affect learning capacities, adaptive behaviors, lifelong physical and mental health, and adult productivity. A supporting technical report from the American Academy of Pediatrics (AAP) presents an integrated ecobiodevelopmental framework to assist in translating these dramatic advances in developmental science into improved health across the life span. Pediatricians are now armed with new information about the adverse effects of toxic stress on brain development, as well as a deeper understanding of the early life origins of many adult diseases. As trusted authorities in child health and development, pediatric providers must now complement the early identification of developmental concerns with a greater focus on those interventions and community investments that reduce external threats to healthy brain growth. To this end, AAP endorses a developing leadership role for the entire pediatric community-one that mobilizes the scientific expertise of both basic and clinical researchers, the family-centered care of the pediatric medical home, and the public influence of AAP and its state chapters-to catalyze fundamental change in early childhood policy and services. AAP is committed to leveraging science to inform the development of innovative strategies to reduce the precipitants of toxic stress in young children and to mitigate their negative effects on the course of development and health across the life span.

Veal marketing could return more than traditional weaning

USDA-ARS?s Scientific Manuscript database

How profitable is a system of marketing early-weaned calves for veal production versus a traditional system based on more traditional weaning and marketing feeder calves? In an attempt to answer this question, decision support software (Decision Evaluator for the Cattle Industry, DECI) developed at...

Plant vasculature-mediated signaling involved in early phosphate stress response

USDA-ARS?s Scientific Manuscript database

Depletion of finite global rock phosphate (Pi) reserves will impose major limitations on future agricultural productivity and food security. Hence, modern breeding programs seek to develop Pi-efficient crops with sustainable yields under reduced Pi fertilizer inputs. In this regard, although the lon...

Proteomic responses of switchgrass and prairie cordgrass to senescence

USDA-ARS?s Scientific Manuscript database

Senescence in biofuel grasses is a critical issue because early senescence decreases potential biomass production by limiting aerial growth and development. 2-Dimensional,differential in-gel electrophoresis (2D-DIGE) followed by mass spectrometry of selected protein spots was used to evaluate differ...

Are There Really Animals Like That? The Larvae That Never Develop.

ERIC Educational Resources Information Center

Blackwelder, R. E.; Garoian, George S.

1984-01-01

Discusses the life cycle of a fluke to illustrate a form of larval reproduction which occurs in many trematode flatworms. Polyembryony, production of many embryos by the breakup of the one early embryo that resulted from sexual reproduction, is considered. (JN)

Pheromone-Based Pest Management in China: Past, Present, and Future Prospects.

PubMed

Cui, Gen Zhong; Zhu, Junwei Jerry

2016-07-01

Semiochemical-based pest management technology has been widely used to monitor and control insect pests in agricultural, forestry, and public health sectors in the western world. It became a popular tool in the early 1970s with tremendous efforts in developing environment-friendly control technologies for the integrated pest management. However, in China, similar research lagged 15 to 20 years and was not initiated until the late 1980s. In this review, we present the early history of pheromone research that has led to the current practical applications in China, particularly in the development of pheromone-based pest management products. We also provide information regarding the current status of pheromone-based product manufacturing, marketing, and regulatory issues related to local semiochemical industries, which may be useful to other international companies interested in pursuing business in China. In addition, we share some research topics that represent new directions of the present pheromone research to explore novel tools for advancing semiochemical-based pest management in China.

Cross-fostering alters advertisement vocalizations of grasshopper mice (Onychomys): Evidence for the developmental stress hypothesis.

PubMed

Pasch, Bret; Abbasi, Mustafa Z; Wilson, Macey; Zhao, Daniel; Searle, Jeremy B; Webster, Michael S; Rice, Aaron N

2016-04-01

Nutritional stress can have lasting impacts on the development of traits involved in vocal production. Cross-fostering experiments are often used to examine the propensity for vocal learning in a variety of taxa, but few studies assess the influence of malnourishment that can occur as a byproduct of this technique. In this study, we reciprocally cross-fostered sister taxa of voluble grasshopper mice (genus Onychomys) to explore their propensity for vocal learning. Vocalizations of Onychomys leucogaster did not differ between control and cross-fostered animals, but cross-fostered Onychomys arenicola produced vocalizations that were higher in frequency in a direction away from tutors. These same animals exhibited a transient reduction in body mass early in development, indicative of malnutrition. Our findings simultaneously refute vocal learning and support the developmental stress hypothesis to highlight the importance of early ontogeny on the production of vocalizations later in life. Copyright © 2016 Elsevier Inc. All rights reserved.

FTR GO14246

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

Bentley, Martha

2008-06-30

The Maine Forest Bioproducts Research and Development project originally focused on the State’s interest in the development of an integrated forest products refinery (IFPR). The original intent was that Research and Development (R&D) funded by this award will allow Maine to refine its strategy and pursue development of an integrated biorefinery. Activities were to be divided into three major R&D projects: (a) Establish the potential for a forest products biorefinery in Maine, by determining the technical and economic feasibility and resource availability. (b) Investigate and develop conversion processes for forest bioproducts to utilize the sugars available from hemicellulose. Research projectsmore » will determine how to best utilize refinery waste streams to recover heat value and recycle remaining components. (c) Cost share very early stage R&D efforts to engage the private sector and stimulate innovative efforts that will build upon the research efforts in (b) above, utilize the information gleaned from (a), and lead to commercialization of new products or services and development of the forest bioproducts industrial sector in Maine.« less

Early development of abstract language knowledge: evidence from perception–production transfer of birth-language memory

PubMed Central

Cutler, Anne; Broersma, Mirjam

2017-01-01

Children adopted early in life into another linguistic community typically forget their birth language but retain, unaware, relevant linguistic knowledge that may facilitate (re)learning of birth-language patterns. Understanding the nature of this knowledge can shed light on how language is acquired. Here, international adoptees from Korea with Dutch as their current language, and matched Dutch-native controls, provided speech production data on a Korean consonantal distinction unlike any Dutch distinctions, at the outset and end of an intensive perceptual training. The productions, elicited in a repetition task, were identified and rated by Korean listeners. Adoptees' production scores improved significantly more across the training period than control participants' scores, and, for adoptees only, relative production success correlated significantly with the rate of learning in perception (which had, as predicted, also surpassed that of the controls). Of the adoptee group, half had been adopted at 17 months or older (when talking would have begun), while half had been prelinguistic (under six months). The former group, with production experience, showed no advantage over the group without. Thus the adoptees' retained knowledge of Korean transferred from perception to production and appears to be abstract in nature rather than dependent on the amount of experience. PMID:28280567

Pharma Success in Product Development—Does Biotechnology Change the Paradigm in Product Development and Attrition.

PubMed

Evens, Ronald P

2016-01-01

The biotechnology segment of the overall biopharma industry has existed for only about 40–45 years, as a driver of new product development. This driving force was initiated with the FDA approval of recombinant human insulin in 1982, originating from the Genentech company. The pharma industry in the early years of 1970s and 1980s engaged with biotechnology companies only to a small extent with their in-licensing of a few recombinant molecules, led by Roche, Eli Lilly, and Johnson and Johnson. However, subsequently and dramatically over the last 25 years, biotechnology has become a primary driver of product and technology innovation and has become a cornerstone in new product development by all biopharma companies. This review demonstrates these evolutionary changes regarding approved products, product pipelines, novelty of the products, FDA approval rates, product sales, financial R&D investments in biotechnology, partnerships, mergers and acquisitions, and patent issues. We now have about 300 biotechnology products approved in USA covering 16 medical disciplines and about 250 indications, with the engagement of 25 pharma companies, along with their biotechnology company innovators and partners. The biotechnology pipeline involves over 1000 molecules in clinical trials, including over 300 molecules associated with the top 10 pharma companies. Product approval rates by the FDA for biotechnology products are over double the rate for drugs. Yes, the R&D paradigm has changed with biotechnology now as one of the major focuses for new product development with novel molecules by the whole biopharma industry.

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

Thompson, D.

The coal seams uplifted by the Perija and Sierra Nevada de Santa marta Mountains along the border of Colombia and Venezuela are high quality reserves with low mining ratios that are in close proximity to the coast. Since the late 70`s and early 80`s, various mining developments have increased the production of these reserves to its current level of 37 million tons per year. Most of the production is shipped to European and to North and South American markets. Further exploitation of these reserves will require significant investments in mine development, inland transportation, and port facilities. This paper will summarizemore » the current status of the Colombian and Venezuelan coal industry, as well as the potential and challenges for increased production and exportation.« less

Early Results from the Global Precipitation Measurement (GPM) Mission in Japan

NASA Astrophysics Data System (ADS)

Kachi, Misako; Kubota, Takuji; Masaki, Takeshi; Kaneko, Yuki; Kanemaru, Kaya; Oki, Riko; Iguchi, Toshio; Nakamura, Kenji; Takayabu, Yukari N.

2015-04-01

The Global Precipitation Measurement (GPM) mission is an international collaboration to achieve highly accurate and highly frequent global precipitation observations. The GPM mission consists of the GPM Core Observatory jointly developed by U.S. and Japan and Constellation Satellites that carry microwave radiometers and provided by the GPM partner agencies. The Dual-frequency Precipitation Radar (DPR) was developed by the Japan Aerospace Exploration Agency (JAXA) and the National Institute of Information and Communications Technology (NICT), and installed on the GPM Core Observatory. The GPM Core Observatory chooses a non-sun-synchronous orbit to carry on diurnal cycle observations of rainfall from the Tropical Rainfall Measuring Mission (TRMM) satellite and was successfully launched at 3:37 a.m. on February 28, 2014 (JST), while the Constellation Satellites, including JAXA's Global Change Observation Mission (GCOM) - Water (GCOM-W1) or "SHIZUKU," are launched by each partner agency sometime around 2014 and contribute to expand observation coverage and increase observation frequency JAXA develops the DPR Level 1 algorithm, and the NASA-JAXA Joint Algorithm Team develops the DPR Level 2 and DPR-GMI combined Level2 algorithms. JAXA also develops the Global Rainfall Map (GPM-GSMaP) algorithm, which is a latest version of the Global Satellite Mapping of Precipitation (GSMaP), as national product to distribute hourly and 0.1-degree horizontal resolution rainfall map. Major improvements in the GPM-GSMaP algorithm is; 1) improvements in microwave imager algorithm based on AMSR2 precipitation standard algorithm, including new land algorithm, new coast detection scheme; 2) Development of orographic rainfall correction method for warm rainfall in coastal area (Taniguchi et al., 2012); 3) Update of database, including rainfall detection over land and land surface emission database; 4) Development of microwave sounder algorithm over land (Kida et al., 2012); and 5) Development of gauge-calibrated GSMaP algorithm (Ushio et al., 2013). In addition to those improvements in the algorithms number of passive microwave imagers and/or sounders used in the GPM-GSMaP was increased compared to the previous version. After the early calibration and validation of the products and evaluation that all products achieved the release criteria, all GPM standard products and the GPM-GSMaP product has been released to the public since September 2014. The GPM products can be downloaded via the internet through the JAXA G-Portal (https://www.gportal.jaxa.jp).

Development of high-performance blended cements

NASA Astrophysics Data System (ADS)

Wu, Zichao

2000-10-01

This thesis presents the development of high-performance blended cements from industrial by-products. To overcome the low-early strength of blended cements, several chemicals were studied as the activators for cement hydration. Sodium sulfate was discovered as the best activator. The blending proportions were optimized by Taguchi experimental design. The optimized blended cements containing up to 80% fly ash performed better than Type I cement in strength development and durability. Maintaining a constant cement content, concrete produced from the optimized blended cements had equal or higher strength and higher durability than that produced from Type I cement alone. The key for the activation mechanism was the reaction between added SO4 2- and Ca2+ dissolved from cement hydration products.

Microbicide dosage forms.

PubMed

Rohan, L C; Devlin, B; Yang, H

2014-01-01

Microbicides are topically applied, user controlled dosage forms that are being developed to prevent the transmission of HIV during coitus. Early candidates focused on coitally dependent dosage forms such as gels and creams. More recent development has focused on broadening the coitally dependent options through the introduction of films and fast dissolving tablets. Additionally, it has become important to have longer acting products to minimize the burden of user compliance and thus vaginal rings have been developed providing sustained delivery of antiretroviral drugs. This chapter discusses the history of microbicides along with a detailed description of coitally dependent products, gels, films, tablets diaphragms, as well as coitally independent dosage forms such as vaginal rings and the introduction of a new technology, electrospun fibers.

Are the economics of pharmaceutical research and development changing?: productivity, patents and political pressures.

PubMed

Grabowski, Henry

2004-01-01

Pharmaceutical research and development (R&D) competition in the 1980s and 1990 s was characterised by rising R&D expenditures, favourable returns to innovators and the introduction of many new classes of drugs with high social benefits. However, in the past 3 years, the number of new drug introductions has been well below the historical trend, while the cost per new drug continues to increase. In addition to lagging R&D productivity, the industry has been characterised by other economic and policy uncertainties. These include a wave of early patent challenges and growing political pressure to contain pharmaceutical expenditures. This paper examines the consequences of these developments.

Swimming upstream: developing and commercializing diabetes products in a patent protected world.

PubMed

Hopkins, Brian P; Miller, Katherine J

2013-03-01

Many, if not most, commercially available diabetes treatment products are protected by some form of intellectual property. This article discusses the development and commercialization of products in view of the state of intellectual property for the diabetes treatment market, with respect to possible discouragement, for some, from seeking patent protection or commercializing a new product under the belief that patent protection is either unavailable or difficult to come by, or for fear of infringing existing patents. Upon closer investigation, the evolution of technology almost always creates opportunities for new improvements, which likely can be patent protected. Furthermore, while avoiding the claims of existing patents is sometimes challenging and opinion based, and thus not a guarantee of avoiding a patent litigation, patent litigation may be delayed and is often settled early on. © 2013 Diabetes Technology Society.

Swimming Upstream: Developing and Commercializing Diabetes Products in a Patent Protected World

PubMed Central

Hopkins, Brian P.; Miller, Katherine J.

2013-01-01

Many, if not most, commercially available diabetes treatment products are protected by some form of intellectual property. This article discusses the development and commercialization of products in view of the state of intellectual property for the diabetes treatment market, with respect to possible discouragement, for some, from seeking patent protection or commercializing a new product under the belief that patent protection is either unavailable or difficult to come by, or for fear of infringing existing patents. Upon closer investigation, the evolution of technology almost always creates opportunities for new improvements, which likely can be patent protected. Furthermore, while avoiding the claims of existing patents is sometimes challenging and opinion based, and thus not a guarantee of avoiding a patent litigation, patent litigation may be delayed and is often settled early on. PMID:23566985

The biopharmaceutics risk assessment roadmap for optimizing clinical drug product performance.

PubMed

Selen, Arzu; Dickinson, Paul A; Müllertz, Anette; Crison, John R; Mistry, Hitesh B; Cruañes, Maria T; Martinez, Marilyn N; Lennernäs, Hans; Wigal, Tim L; Swinney, David C; Polli, James E; Serajuddin, Abu T M; Cook, Jack A; Dressman, Jennifer B

2014-11-01

The biopharmaceutics risk assessment roadmap (BioRAM) optimizes drug product development and performance by using therapy-driven target drug delivery profiles as a framework to achieve the desired therapeutic outcome. Hence, clinical relevance is directly built into early formulation development. Biopharmaceutics tools are used to identify and address potential challenges to optimize the drug product for patient benefit. For illustration, BioRAM is applied to four relatively common therapy-driven drug delivery scenarios: rapid therapeutic onset, multiphasic delivery, delayed therapeutic onset, and maintenance of target exposure. BioRAM considers the therapeutic target with the drug substance characteristics and enables collection of critical knowledge for development of a dosage form that can perform consistently for meeting the patient's needs. Accordingly, the key factors are identified and in vitro, in vivo, and in silico modeling and simulation techniques are used to elucidate the optimal drug delivery rate and pattern. BioRAM enables (1) feasibility assessment for the dosage form, (2) development and conduct of appropriate "learning and confirming" studies, (3) transparency in decision-making, (4) assurance of drug product quality during lifecycle management, and (5) development of robust linkages between the desired clinical outcome and the necessary product quality attributes for inclusion in the quality target product profile. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

NASA CYGNSS Mission Overview

NASA Astrophysics Data System (ADS)

Ruf, C. S.; Balasubramaniam, R.; Gleason, S.; McKague, D. S.; O'Brien, A.

2017-12-01

The CYGNSS constellation of eight satellites was successfully launched on 15 December 2016 into a low inclination (tropical) Earth orbit. Each satellite carries a four-channel bi-static radar receiver that measures GPS signals scattered by the ocean, from which ocean surface roughness, near surface wind speed, and air-sea latent heat flux are estimated. The measurements are unique in several respects, most notably in their ability to penetrate through all levels of precipitation, made possible by the low frequency at which GPS operates, and in the frequent sampling of tropical cyclone intensification and of the diurnal cycle of winds, made possible by the large number of satellites. Engineering commissioning of the constellation was successfully completed in March 2017 and the mission is currently in the early phase of science operations. Level 2 science data products have been developed for near surface (10 m referenced) ocean wind speed, ocean surface roughness (mean square slope) and latent heat flux. Level 3 gridded versions of the L2 products have also been developed. A set of Level 4 products have also been developed specifically for direct tropical cyclone overpasses. These include the storm intensity (peak sustained winds) and size (radius of maximum winds), its extent (34, 50 and 64 knot wind radii), and its integrated kinetic energy. Assimilation of CYGNSS L2 wind speed data into the HWRF hurricane weather prediction model has also been developed. An overview and the current status of the mission will be presented, together with highlights of early on-orbit performance and scientific results.

Predicting Production Costs for Advanced Aerospace Vehicles

NASA Technical Reports Server (NTRS)

Bao, Han P.; Samareh, J. A.; Weston, R. P.

2002-01-01

For early design concepts, the conventional approach to cost is normally some kind of parametric weight-based cost model. There is now ample evidence that this approach can be misleading and inaccurate. By the nature of its development, a parametric cost model requires historical data and is valid only if the new design is analogous to those for which the model was derived. Advanced aerospace vehicles have no historical production data and are nowhere near the vehicles of the past. Using an existing weight-based cost model would only lead to errors and distortions of the true production cost. This paper outlines the development of a process-based cost model in which the physical elements of the vehicle are soared according to a first-order dynamics model. This theoretical cost model, first advocated by early work at MIT, has been expanded to cover the basic structures of an advanced aerospace vehicle. Elemental costs based on the geometry of the design can be summed up to provide an overall estimation of the total production cost for a design configuration. This capability to directly link any design configuration to realistic cost estimation is a key requirement for high payoff MDO problems. Another important consideration in this paper is the handling of part or product complexity. Here the concept of cost modulus is introduced to take into account variability due to different materials, sizes, shapes, precision of fabrication, and equipment requirements. The most important implication of the development of the proposed process-based cost model is that different design configurations can now be quickly related to their cost estimates in a seamless calculation process easily implemented on any spreadsheet tool.

Characterization, expression profiles, intracellular distribution and association analysis of porcine PNAS-4 gene with production traits.

PubMed

Mo, Delin; Zhu, Zhengmao; te Pas, Marinus F W; Li, Xinyun; Yang, Shulin; Wang, Heng; Wang, Huanling; Li, Kui

2008-06-30

In a previous screen to identify differentially expressed genes associated with embryonic development, the porcine PNAS-4 gene had been found. Considering differentially expressed genes in early stages of muscle development are potential candidate genes to improve meat quality and production efficiency, we determined how porcine PNAS-4 gene regulates meat production. Therefore, this gene has been sequenced, expression analyzed and associated with meat production traits. We cloned the full-length cDNA of porcine PNAS-4 gene encoding a protein of 194 amino acids which was expressed in the Golgi complex. This gene was mapped to chromosome 10, q11-16, in a region of conserved synteny with human chromosome 1 where the human homologous gene was localized. Real-time PCR revealed that PNAS-4 mRNA was widely expressed with highest expression levels in skeletal muscle followed by lymph, liver and other tissues, and showed a down-regulated expression pattern during prenatal development while a up-regulated expression pattern after weaning. Association analysis revealed that allele C of SNP A1813C was prevalent in Chinese indigenous breeds whereas A was dominant allele in Landrace and Large White, and the pigs with homozygous CC had a higher fat content than those of the pigs with other genotypes (P < 0.05). Porcine PNAS-4 protein tagged with green fluorescent protein accumulated in the Golgi complex, and its mRNA showed a widespread expression across many tissues and organs in pigs. It may be an important factor affecting the meat production efficiency, because its down-regulated expression pattern during early embryogenesis suggests involvement in increase of muscle fiber number. In addition, the SNP A1813C associated with fat traits might be a genetic marker for molecular-assisted selection in animal breeding.

Characterization of TAP Ambr 250 disposable bioreactors, as a reliable scale-down model for biologics process development.

PubMed

Xu, Ping; Clark, Colleen; Ryder, Todd; Sparks, Colleen; Zhou, Jiping; Wang, Michelle; Russell, Reb; Scott, Charo

2017-03-01

Demands for development of biological therapies is rapidly increasing, as is the drive to reduce time to patient. In order to speed up development, the disposable Automated Microscale Bioreactor (Ambr 250) system is increasingly gaining interest due to its advantages, including highly automated control, high throughput capacity, and short turnaround time. Traditional early stage upstream process development conducted in 2 - 5 L bench-top bioreactors requires high foot-print, and running cost. The establishment of the Ambr 250 as a scale-down model leads to many benefits in process development. In this study, a comprehensive characterization of mass transfer coefficient (k L a) in the Ambr 250 was conducted to define optimal operational conditions. Scale-down approaches, including dimensionless volumetric flow rate (vvm), power per unit volume (P/V) and k L a have been evaluated using different cell lines. This study demonstrates that the Ambr 250 generated comparable profiles of cell growth and protein production, as seen at 5-L and 1000-L bioreactor scales, when using k L a as a scale-down parameter. In addition to mimicking processes at large scales, the suitability of the Ambr 250 as a tool for clone selection, which is traditionally conducted in bench-top bioreactors, was investigated. Data show that cell growth, productivity, metabolite profiles, and product qualities of material generated using the Ambr 250 were comparable to those from 5-L bioreactors. Therefore, Ambr 250 can be used for clone selection and process development as a replacement for traditional bench-top bioreactors minimizing resource utilization during the early stages of development in the biopharmaceutical industry. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:478-489, 2017. © 2017 American Institute of Chemical Engineers.

Current, Short Term, Future and Star Wars Research Projects for Ornamental Crops

USDA-ARS?s Scientific Manuscript database

The USDA-ARS Greenhouse Production Research Group is involved in fundamental and developmental plant research aimed at developing tools for early stress detection and efficient agrochemical utilization for protected horticulture crops. The group conducts basic plant biology research with the goal o...

Reading across Workplace Learning Research to Build Dialogue

ERIC Educational Resources Information Center

Sawchuk, Peter H.

2010-01-01

The field of workplace learning scholarship in Western countries is reviewed. First, the emergence of workplace learning scholarship is discussed historically for its relation to the emergence and ongoing development of capitalism beginning from early thought on markets and productivity, 20th century scientific management, industrialism and…

Child Mental Health.

ERIC Educational Resources Information Center

Fredericks, Jeff, Ed.

2002-01-01

Children's school experience is more positive and productive when they have a sense of personal well being and when they are grounded in stable caring relationships in their early lives. Developed for Head Start staff, administrators and program supervisors, this issue includes features, resources and articles. Some of the most current…

Extraterrestrial resource utilization for economy in space missions

NASA Technical Reports Server (NTRS)

Lewis, J. S.; Ramohalli, K.; Triffet, T.

1990-01-01

The NASA/University of Arizona Space Engineering Research Center is dedicated to research on the discovery, characterization, mapping, beneficiation, extraction, processing, and fabrication of useful products from extraterrestrial material. Schemes for the automated production of low-technology products that are likely to be desired in large quantities in the early stages of any large-scale space activity are identified and developed. This paper summarizes the research program, concentrating upon the production of (1) propellants, both cryogenic and storable, (2) volatiles such as water, nitrogen, and carbon dioxide for use in life-support systems (3) structural metals, and (4) refractories for use in aerobrakes and furnace linings.

QWIP status and future trends at Thales

NASA Astrophysics Data System (ADS)

Bois, P.; Guériaux, V.; Briere de l'Isle, N.; Manissadjian, A.; Facoetti, H.; Marcadet, X.; Costard, E.; Nedelcu, A.

2012-01-01

Since 2005, Thales is successfully manufacturing QWIPs in high rate production through III-V Lab. All the early claimed advantages of QWIPs are now demonstrated. The versatility of the band-gap engineering allows the custom design of detectors to fulfill specific application requirements in MWIR, LWIR or VLWIR ranges. The maturity of the III-V microelectronics based on GaAs substrates gives uniformity, stability and high production rate. In this presentation we will discuss the specific advantages of this type of detector. An overview of the available performances and production status will be presented including under-development products such as dual band and polarimetric sensors.

Data Management System

NASA Technical Reports Server (NTRS)

1997-01-01

CENTRA 2000 Inc., a wholly owned subsidiary of Auto-trol technology, obtained permission to use software originally developed at Johnson Space Center for the Space Shuttle and early Space Station projects. To support their enormous information-handling needs, a product data management, electronic document management and work-flow system was designed. Initially, just 33 database tables comprised the original software, which was later expanded to about 100 tables. This system, now called CENTRA 2000, is designed for quick implementation and supports the engineering process from preliminary design through release-to-production. CENTRA 2000 can also handle audit histories and provides a means to ensure new information is distributed. The product has 30 production sites worldwide.

Calvarial defect reconstruction.

PubMed

Jimenez, D F; Barone, C M

1994-04-01

The history of skull trepanation is almost as old as that of humanity. For thousands of years it has been performed for the treatment of numerous medical maladies. The Andean Incas, early Asians and South Seas Islanders, are amongst the many people to perform calvarial trepanation. Hippocrates described techniques for the use of the trepan in early Greek times. With the production of a skull opening comes the challenge of developing methods for closing the defect. It is in reality, more challenging to repair the defect than to create it. Man, with his never ending ingenuity, has tried to develop many techniques. We will discuss some of them and present our method of choice for closure of skull defects.

Manufacturing Affordability

DTIC Science & Technology

2011-10-01

Effective planning early in and throughout program develop - ment is critical to enabling manufacturing affordability. There is no silver bullet and no...unexpected lessons. “Gee, this stove is hot” may be an unexpected lesson for the toddler but should not be so for the adult. All production programs...in program design efforts from day 1 of Engineer- ing and Manufacturing Development , you should be seriously worried. A program that includes the

[Historical and Hygienic Aspects on Roles of Quality Requirements for Antibiotic Products in Japan: Part 1--Development of Antibiotic Products].

PubMed

Yagisawa, Morimasa; Foster, Patrick J; Kurokawa, Tatsuo

2015-01-01

Antibiotic products have contributed greatly to keep Japanese people healthy by controlling lethal infections. In the early days, antibiotics such as penicillin and streptomycin were produced using microbial fermentation processes. Therefore, the component ratio of the active element and related substances varied lot by lot. For the purpose of efficacy and assuring safety, minimum requirements for penicillin and streptomycin products were enacted. Both variations and the number of clinically available antibiotic products have increased due to the pharmaceutical development of novel natural antibiotics. In addition, semi-synthetic derivatives of various antibiotics have been developed for the purpose of enhancing antimicrobial activity or improving pharmacological properties. As a result, 202 entities of antibiotic products have been approved and used clinically as of 2012. We conducted a detailed investigation of the progress made in the field of antibiotic products, and analyzed the characteristics of those belonging to each class of antibiotics by means of setting up a system of classification that reflects clinical applications. This report is intended to serve as an introduction to our series of investigations into the role and influence of quality requirements on development of antibacterial antibiotic products in Japan. As described here, the general view of antibacterial antibiotic products spanning a time frame of 67 years in Japan might serve as an ideal reference for future reports.

Longitudinal Effects on Early Adolescent Language: A Twin Study

PubMed Central

DeThorne, Laura Segebart; Smith, Jamie Mahurin; Betancourt, Mariana Aparicio; Petrill, Stephen A.

2016-01-01

Purpose We evaluated genetic and environmental contributions to individual differences in language skills during early adolescence, measured by both language sampling and standardized tests, and examined the extent to which these genetic and environmental effects are stable across time. Method We used structural equation modeling on latent factors to estimate additive genetic, shared environmental, and nonshared environmental effects on variance in standardized language skills (i.e., Formal Language) and productive language-sample measures (i.e., Productive Language) in a sample of 527 twins across 3 time points (mean ages 10–12 years). Results Individual differences in the Formal Language factor were influenced primarily by genetic factors at each age, whereas individual differences in the Productive Language factor were primarily due to nonshared environmental influences. For the Formal Language factor, the stability of genetic effects was high across all 3 time points. For the Productive Language factor, nonshared environmental effects showed low but statistically significant stability across adjacent time points. Conclusions The etiology of language outcomes may differ substantially depending on assessment context. In addition, the potential mechanisms for nonshared environmental influences on language development warrant further investigation. PMID:27732720

Microstructural Developments Leading to New Advanced High Strength Sheet Steels: A Historical Assessment of Critical Metallographic Observations

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

Matlock, David K; Thomas, Larrin S; Taylor, Mark D

In the past 30+ years significant advancements have been made in the development of higher strength sheet steels with improved combinations of strength and ductility that have enabled important product improvements leading to safer, lighter weight, and more fuel efficient automobiles and in other applications. Properties of the primarily low carbon, low alloy steels are derived through careful control of time-temperature processing histories designed to produce multiphase ferritic based microstructures that include martensite and other constituents including retained austenite. The basis for these developments stems from the early work on dual-phase steels which was the subject of much interest. Inmore » response to industry needs, dual-phase steels have evolved as a unique class of advanced high strength sheet steels (AHSS) in which the thermal and mechanical processing histories have been specifically designed to produce constituent combinations for the purpose of simultaneously controlling strength and deformation behavior, i.e. stress-strain curve shapes. Improvements continue as enhanced dual-phase steels have recently been produced with finer microstructures, higher strengths, and better overall formability. Today, dual phase steels are the primary AHSS products used in vehicle manufacture, and several companies have indicated that the steels will remain as important design materials well into the future. In this presentation, fundamental results from the early work on dual-phase steels will be reviewed and assessed in light of recent steel developments. Specific contributions from industry/university cooperative research leading to product improvements will be highlighted. The historical perspective provided in the evolution of dual-phase steels represents a case-study that provides important framework and lessons to be incorporated in next generation AHSS products.« less

Developing an Automated Method for Detection of Operationally Relevant Ocean Fronts and Eddies

NASA Astrophysics Data System (ADS)

Rogers-Cotrone, J. D.; Cadden, D. D. H.; Rivera, P.; Wynn, L. L.

2016-02-01

Since the early 90's, the U.S. Navy has utilized an observation-based process for identification of frontal systems and eddies. These Ocean Feature Assessments (OFA) rely on trained analysts to identify and position ocean features using satellite-observed sea surface temperatures. Meanwhile, as enhancements and expansion of the navy's Hybrid Coastal Ocean Model (HYCOM) and Regional Navy Coastal Ocean Model (RNCOM) domains have proceeded, the Naval Oceanographic Office (NAVO) has provided Tactical Oceanographic Feature Assessments (TOFA) that are based on data-validated model output but also rely on analyst identification of significant features. A recently completed project has migrated OFA production to the ArcGIS-based Acoustic Reach-back Cell Ocean Analysis Suite (ARCOAS), enabling use of additional observational datasets and significantly decreasing production time; however, it has highlighted inconsistencies inherent to this analyst-based identification process. Current efforts are focused on development of an automated method for detecting operationally significant fronts and eddies that integrates model output and observational data on a global scale. Previous attempts to employ techniques from the scientific community have been unable to meet the production tempo at NAVO. Thus, a system that incorporates existing techniques (Marr-Hildreth, Okubo-Weiss, etc.) with internally-developed feature identification methods (from model-derived physical and acoustic properties) is required. Ongoing expansions to the ARCOAS toolset have shown promising early results.

High temperature combined with drought affect rainfed spring wheat and barley in South-Eastern Russia: I. Phenology and growth

PubMed Central

Hossain, Akbar; Teixeira da Silva, Jaime A.; Lozovskaya, Marina Viacheslavovna; Zvolinsky, Vacheslav Petrovich

2012-01-01

Heat stress, when combined with drought, is one of the major limitations to food production worldwide, especially in areas that use rainfed agriculture. As the world population continues to grow, and water resources for the crop production decline and temperature increases, so the development of heat- and drought-tolerant cultivars is an issue of global concern. In this context, four barley and two wheat genotypes were evaluated in south-eastern Russia to identify heat- and drought-tolerant genotypes for future breeding programmes by identifying suitable sowing times for specific genotypes. High temperature stress, when combined with drought during late sowing, decreased the days to visible awns, days to heading and days to ripe harvest, finally negatively affecting the growth and development of plants and resulting in a lower plant population m−2, tillers plant−1, plant height and dry matter production m−2. On the other hand, low temperature in combination with early sowing increased the number of days to germination, reduced seedling stand establishment and tillering capacity, finally affecting the growth and development of the crops. Compared to overall performance and optimum sowing date, barley genotypes ‘Zernograd.770’ and ‘Nutans’, and wheat genotype ‘Line4’ performed best in both late (high temperature with drought) and early (low temperature) stress conditions. PMID:23961209

Effect of Omega-3 and -6 Supplementation on Language in Preterm Toddlers Exhibiting Autism Spectrum Disorder Symptoms.

PubMed

Sheppard, Kelly W; Boone, Kelly M; Gracious, Barbara; Klebanoff, Mark A; Rogers, Lynette K; Rausch, Joseph; Bartlett, Christopher; Coury, Daniel L; Keim, Sarah A

2017-11-01

Delayed language development may be an early indicator of autism spectrum disorder (ASD). Early intervention is critical for children with ASD, and the present study presents pilot data on a clinical trial of omega-3 and -6 fatty acid supplementation and language development, a secondary trial outcome, in children at risk for ASD. We randomized 31 children to receive an omega-3 and -6 supplement or a placebo for 3 months, and measured their language abilities at baseline and after supplementation. Gesture use, but not word production, increased for children in the treatment group more than children in the placebo group. These results suggest possible effectiveness of omega-3 and -6 supplementation for language development in children at risk for ASD.

Water Use and Requirements of PtFT1 Plums for Long Duration Space Missions

NASA Technical Reports Server (NTRS)

Wheeler, Raymond

2017-01-01

Early applications of bioregenerative life support technologies for space exploration will likely start with supplemental food production for the crew. This could include fresh, perishable foods that cannot be stored for long and but have a high impact on the diet acceptability bioavailable nutrients. Because of the limited working volume in spacecraft, these plants must be small in size. A combination of CIF (Center Innovation Fund) and NASA Post Doctoral funding was used in FY15 to develop horticultural approaches for propagation, production and fruiting of several dwarf plum lines and evaluate their suitability as candidates for long duration space missions. Collaborators at the USDA Agricultural Research Service transformed Prunus domestica with the FT1 (Flowering Locus T1) flowering gene from Populus trichocarpa (PtFTl), which resulted in early flowering, driving the plant out of its juvenile growth phase and into reproductive development years earlier than would normally occur. The result is a plum line that has potential as a component of food production system on long-duration space missions since it completes complete generation (seed-to-seed) within less than a year and maintains a dwarf-bush or vine-like growth habit. Further, there appears to be no obligatory requirement for a dormancy period, resulting in continuous fruit production on a given plant. This potential is described in Graham et al (2015, in press).

The cleanroom case study in the Software Engineering Laboratory: Project description and early analysis

NASA Technical Reports Server (NTRS)

Green, Scott; Kouchakdjian, Ara; Basili, Victor; Weidow, David

1990-01-01

This case study analyzes the application of the cleanroom software development methodology to the development of production software at the NASA/Goddard Space Flight Center. The cleanroom methodology emphasizes human discipline in program verification to produce reliable software products that are right the first time. Preliminary analysis of the cleanroom case study shows that the method can be applied successfully in the FDD environment and may increase staff productivity and product quality. Compared to typical Software Engineering Laboratory (SEL) activities, there is evidence of lower failure rates, a more complete and consistent set of inline code documentation, a different distribution of phase effort activity, and a different growth profile in terms of lines of code developed. The major goals of the study were to: (1) assess the process used in the SEL cleanroom model with respect to team structure, team activities, and effort distribution; (2) analyze the products of the SEL cleanroom model and determine the impact on measures of interest, including reliability, productivity, overall life-cycle cost, and software quality; and (3) analyze the residual products in the application of the SEL cleanroom model, such as fault distribution, error characteristics, system growth, and computer usage.

Speech motor planning and execution deficits in early childhood stuttering.

PubMed

Walsh, Bridget; Mettel, Kathleen Marie; Smith, Anne

2015-01-01

Five to eight percent of preschool children develop stuttering, a speech disorder with clearly observable, hallmark symptoms: sound repetitions, prolongations, and blocks. While the speech motor processes underlying stuttering have been widely documented in adults, few studies to date have assessed the speech motor dynamics of stuttering near its onset. We assessed fundamental characteristics of speech movements in preschool children who stutter and their fluent peers to determine if atypical speech motor characteristics described for adults are early features of the disorder or arise later in the development of chronic stuttering. Orofacial movement data were recorded from 58 children who stutter and 43 children who do not stutter aged 4;0 to 5;11 (years; months) in a sentence production task. For single speech movements and multiple speech movement sequences, we computed displacement amplitude, velocity, and duration. For the phrase level movement sequence, we computed an index of articulation coordination consistency for repeated productions of the sentence. Boys who stutter, but not girls, produced speech with reduced amplitudes and velocities of articulatory movement. All children produced speech with similar durations. Boys, particularly the boys who stuttered, had more variable patterns of articulatory coordination compared to girls. This study is the first to demonstrate sex-specific differences in speech motor control processes between preschool boys and girls who are stuttering. The sex-specific lag in speech motor development in many boys who stutter likely has significant implications for the dramatically different recovery rates between male and female preschoolers who stutter. Further, our findings document that atypical speech motor development is an early feature of stuttering.

Final Report: Computer Games to Teach Geography: El Nino: Mysteries of the Pacific and Mysteries of the Antarctic, August 15, 1994 - June 20, 1998

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

Gautier-Downes, Catherine

During the period covered by this project we have accomplished all the objectives described in our original proposal. The main achievement, however, has been to bring to the commercial market an excellent quality education software product. This highest level of quality has been recognized by the Software Publisher Association, which has awarded its most prestigious appreciation, the Codie Award, for our first product Ocean Expeditions: El Nino. With regards to commercialization, we have developed, as a Phase III project, a comprehensive business plan which we have used to find a publisher/distributor of our products (Tom Snyder Productions) and are presentlymore » updating to raise private funding. Also, we have been awarded a 5-year Cooperative Agreement by NASA to continue the development of our products and bring five new products to the education market by the early part of the millennium.« less

Leveraging object-oriented development at Ames

NASA Technical Reports Server (NTRS)

Wenneson, Greg; Connell, John

1994-01-01

This paper presents lessons learned by the Software Engineering Process Group (SEPG) from results of supporting two projects at NASA Ames using an Object Oriented Rapid Prototyping (OORP) approach supported by a full featured visual development environment. Supplemental lessons learned from a large project in progress and a requirements definition are also incorporated. The paper demonstrates how productivity gains can be made by leveraging the developer with a rich development environment, correct and early requirements definition using rapid prototyping, and earlier and better effort estimation and software sizing through object-oriented methods and metrics. Although the individual elements of OO methods, RP approach and OO metrics had been used on other separate projects, the reported projects were the first integrated usage supported by a rich development environment. Overall the approach used was twice as productive (measured by hours per OO Unit) as a C++ development.

Integration of active pharmaceutical ingredient solid form selection and particle engineering into drug product design.

PubMed

Ticehurst, Martyn David; Marziano, Ivan

2015-06-01

This review seeks to offer a broad perspective that encompasses an understanding of the drug product attributes affected by active pharmaceutical ingredient (API) physical properties, their link to solid form selection and the role of particle engineering. While the crucial role of active pharmaceutical ingredient (API) solid form selection is universally acknowledged in the pharmaceutical industry, the value of increasing effort to understanding the link between solid form, API physical properties and drug product formulation and manufacture is now also being recognised. A truly holistic strategy for drug product development should focus on connecting solid form selection, particle engineering and formulation design to both exploit opportunities to access simpler manufacturing operations and prevent failures. Modelling and predictive tools that assist in establishing these links early in product development are discussed. In addition, the potential for differences between the ingoing API physical properties and those in the final product caused by drug product processing is considered. The focus of this review is on oral solid dosage forms and dry powder inhaler products for lung delivery. © 2015 Royal Pharmaceutical Society.

Unpacking Neoliberal Policies: Interrupting the Global and Local Production of the Norms

ERIC Educational Resources Information Center

Lee, I-Fang

2012-01-01

Early Childhood Education and Care (ECEC) has been constructed as a new site for educational, sociocultural, political, and economic investment. Coupled with such a growing and popular recognition of ECEC as a significant period of children's learning and development are critical issues concerning accountability, affordability, and accessibility…

Making Child Care Better: State Initiatives.

ERIC Educational Resources Information Center

Groginsky, Scott; Robison, Susan; Smith, Shelley

In light of increasing evidence that good early childhood programs lead to school success, reduced delinquency and crime, and better job opportunities and productivity, state legislators are developing policies to improve these services. This report is designed to provide state lawmakers and their staff with research and state examples of policy…

ASSESSING UST CORRECTIVE ACTION TECHNOLOGIES: EARLY SCREENING OF CLEANUP TECHNOLOGIES FOR THE SATURATED ZONE

EPA Science Inventory

This manual assists the user in making a preliminary evaluation of the likely effectiveness of various remediation technologies in the event of a release of petroleum products into the saturated zone. he manual: 1) helps the user develop a conceptual understanding of site conditi...

Reduced energy expenditure and increased inflammation are early events in the development of ovariectomy-induced obesity

USDA-ARS?s Scientific Manuscript database

Menopause, an age-related loss of ovarian hormone production, promotes increased adiposity and associated metabolic pathologies. However, the diet-independent mechanism(s) by which loss of ovarian function promotes increased adipose tissue mass and insulin resistance remain unclear. We investigate...

Early Vocabulary and Gestures in Estonian Children

ERIC Educational Resources Information Center

Schults, Astra; Tulviste, Tiia; Konstabel, Kenn

2012-01-01

Parents of 592 children between the age of 0 ; 8 and 1 ; 4 completed the Estonian adaptation of the MacArthur-Bates Communicative Development Inventory (ECDI Infant Form). The relationships between comprehension and production of different categories of words and gestures were examined. According to the results of regression modelling the…

Condition of Education in the Commonwealth: 2016 Data Report

ERIC Educational Resources Information Center

Rennie Center for Education Research & Policy, 2016

2016-01-01

The "2016 Data Report" identifies and measures state-level indicators linked to outcomes to inform decision-making among Massachusetts education leaders. These indicators focus on critical stages in learning and development from school readiness and early learning to the emergence of a strong and productive workforce. Important…

Infestation ratings database for soybean aphid on early-maturity wild soybean lines

USDA-ARS?s Scientific Manuscript database

Soybean aphid (Aphis glycines Matsumura; SA) is a major invasive pest of soybean [Glycine max (L.) Merr.] in northern production regions of North America. Although insecticides are currently the main method for controlling this pest, SA-resistant cultivars are being developed to sustainably manage ...

Performativity, Propriety and Productivity: The Unintended Consequences of Investing in the Early Years

ERIC Educational Resources Information Center

Macfarlane, Kym; Lakhani, Ali

2015-01-01

This paper examines notions of childhood development in a significant Australian policy document. Using Fairclough's approaches to discourse analysis as guides, Foucault's understanding of regimes of truth and discourses as systems of power relations and Nikolas Rose's concept of "responsibilisation," the paper argues that discourses of…

Mathemagenic Activities Program: [Reports on Cognitive/Language Development].

ERIC Educational Resources Information Center

Smock, Charles D., Ed.

This set of 13 research reports, bulletins and papers is a product of the Mathemagenic Activities Program (MAP) for early childhood education of the University of Georgia Follow Through Program. Based on Piagetian theory, the MAP provides sequentially structured sets of curriculum materials and processes that are designed to continually challenge…

The Nutcracker--Theater Activity Packet.

ERIC Educational Resources Information Center

New York City Board of Education, Brooklyn, NY. Div. of Curriculum and Instruction.

A part of the New York City Board of Education Early Stages educational program, this activity packet was developed to assist teachers in preparing students for viewing the American Ballet Theatre's production of "The Nutcracker." The guide begins with a section on preparing for the performance, and includes information on the Early…

The Small- and Medium-sized Enterprises Office (SME Office) at the European Medicines Agency.

PubMed

Carr, M

2010-01-01

On 15 December 2005, the European Medicines Agency (EMEA) launched an "SME Office" to provide financial and administrative assistance to micro-, small- and medium-sized enterprises (SMEs), with the aim of promoting innovation and the development of new human and veterinary medicinal products by SMEs. According to current EU definition of an SME, companies with fewer than 250 employees, and an annual turnover of not more than 50 million euro or an annual balance sheet total of not more than 43 million euro, are eligible for assistance from the SME Office. Incentives available from the EMEA for SMEs, include: Administrative and procedural assistance from SME Office within the Agency; Fee reductions (90%) for scientific advice and inspections; Fee exemptions for certain administrative services (excluding parallel distribution); Deferral of the fee payable for an application for marketing authorisation or related inspection until after the grant of the marketing authorisation; Conditional fee exemption where scientific advice followed and marketing application is unsuccessful; Assistance with translations of the product information documents. At the end of May 2009, more than 380 companies from 21 countries across the European Economic Area (EEA) had SME status assigned by the EMEA. The large majority of companies are developing medicinal products for human use, 16 are veterinary companies, 15 companies are developing products for both human and veterinary use and 38 are regulatory consultants. Since the SME initiative started the Agency has processed more than 130 requests for scientific advice with fee reductions totalling of 6.9 million euro. Regulatory assistance has been provided to more than 170 companies and 12 companies have benefited from the SME translation service. Stakeholders have acknowledged the significant role the SME Office now plays as a service provider. In the period between January 2006 and June 2009, 34 applications for marketing authorization from SME applicants were filed for medicinal products for human use. Current analysis shows SMEs to have a lower success rate compared to non-SME companies. Major objections for SMEs are particularly high in the area of quality. Although the SME initiative is still at an early stage, it is apparent from the experience gained with applications for marketing authorisation to date that it is important for companies to open up an early dialogue with the EMEA. Scientific advice should be sought early, proactively and comprehensively on key issues in development (quality, non-clinical, clinical) and follow-up advice should be sought as development proceeds. For advanced therapy medicinal products, the assistance available to SMEs will be reinforced in 2009, with the introduction of the certification process.

Forests and Phenology: Designing the Early Warning System to Understand Forest Change

NASA Astrophysics Data System (ADS)

Pierce, T.; Phillips, M. B.; Hargrove, W. W.; Dobson, G.; Hicks, J.; Hutchins, M.; Lichtenstein, K.

2010-12-01

Vegetative phenology is the study of plant development and changes with the seasons, such as the greening-up and browning-down of forests, and how these events are influenced by variations in climate. A National Phenology Data Set, based on Moderate Resolution Imaging Spectroradiometer satellite images covering 2002 through 2009, is now available from work by NASA, the US Forest Service, and Oak Ridge National Laboratory. This new data set provides an easily interpretable product useful for detecting changes to the landscape due to long-term factors such as climate change, as well as finding areas affected by short-term forest threats such as insects or disease. The Early Warning System (EWS) is a toolset being developed by the US Forest Service and the University of North Carolina-Asheville to support distribution and use of the National Phenology Data Set. The Early Warning System will help research scientists, US Forest Service personnel, forest and natural resources managers, decision makers, and the public in the use of phenology data to better understand unexpected change within our nation’s forests. These changes could have multiple natural sources such as insects, disease, or storm damage, or may be due to human-induced events, like thinning, harvest, forest conversion to agriculture, or residential and commercial use. The primary goal of the Early Warning System is to provide a seamless integration between monitoring, detection, early warning and prediction of these forest disturbances as observed through phenological data. The system consists of PC and web-based components that are structured to support four user stages of increasing knowledge and data sophistication. Building Literacy: This stage of the Early Warning System educates potential users about the system, why the system should be used, and the fundamentals about the data the system uses. The channels for this education include a website, interactive tutorials, pamphlets, and other technology transfer methodologies. Achieving Context and Meaning: To provide deeper meaning and knowledge about the Early Warning System to users, this stage of the Early Warning System provides more information about specific examples of disturbances seen in the phenological data, as well the spatial and temporal context to these disturbances. The main components of this stage are specific case studies of forest disturbances. Accessing Data: This component of the Early Warning System includes products for research scientists, the aerial detection survey sketch mapper community, and others who will access and analyze the Early Warning System and phenological data. Products and data will be available through online GIS mashups and WMS and KML downloads. Utilizing Services: The final stage of the Early Warning System supports the analysis of phenological data and serves the results to those end users, including forest managers, the forest industry, and the public, who need to locate past, present, and potential forest disturbances. The main components of this stage include data-driven web tools, automated analysis processes, and end user training programs.

Improvement of the zygote utilization and reduction of the seedling loss in the early stage of seedling production of Sargassum thunbergii (Fucales, Phaeophyta)

NASA Astrophysics Data System (ADS)

Liu, Wei; Wu, Haiyi; Liu, Mengxia; Duan, Delin

2016-05-01

Artificial seedling production of Sargassum thunbergii is an effective way to relieve pressure on natural resources. In order to improve the utilization of zygotes and reduce the loss of seedlings, studies on the characteristic of the zygotes release, the development of rhizoids, the attachment of germlings, and the influence of jet washing were conducted. Results show that the percent of zygotes released was increased with time in the first 60 h. The capacity of germlings attached to the substratum was significantly increased, especially coincident with the time of the new rhizoids emerged and elongated. The detachment rate of germlings significantly decreased with the delay of starting time of jet washing or the reduction of jet washing velocity. However, the jet washing at any level applied in the experiment could cause considerable loss of germlings within the 20 days after the attachment. Our study provided some parameters to optimize the operation in the early stage of seedling production.

2005 AG20/20 Annual Review

NASA Technical Reports Server (NTRS)

Ross, Kenton W.; McKellip, Rodney D.

2005-01-01

Topics covered include: Implementation and Validation of Sensor-Based Site-Specific Crop Management; Enhanced Management of Agricultural Perennial Systems (EMAPS) Using GIS and Remote Sensing; Validation and Application of Geospatial Information for Early Identification of Stress in Wheat; Adapting and Validating Precision Technologies for Cotton Production in the Mid-Southern United States - 2004 Progress Report; Development of a System to Automatically Geo-Rectify Images; Economics of Precision Agriculture Technologies in Cotton Production-AG 2020 Prescription Farming Automation Algorithms; Field Testing a Sensor-Based Applicator for Nitrogen and Phosphorus Application; Early Detection of Citrus Diseases Using Machine Vision and DGPS; Remote Sensing of Citrus Tree Stress Levels and Factors; Spectral-based Nitrogen Sensing for Citrus; Characterization of Tree Canopies; In-field Sensing of Shallow Water Tables and Hydromorphic Soils with an Electromagnetic Induction Profiler; Maintaining the Competitiveness of Tree Fruit Production Through Precision Agriculture; Modeling and Visualizing Terrain and Remote Sensing Data for Research and Education in Precision Agriculture; Thematic Soil Mapping and Crop-Based Strategies for Site-Specific Management; and Crop-Based Strategies for Site-Specific Management.

Oocyte-granulosa-theca cell interactions during preantral follicular development

PubMed Central

Orisaka, Makoto; Tajima, Kimihisa; Tsang, Benjamin K; Kotsuji, Fumikazu

2009-01-01

The preantral-early antral follicle transition is the penultimate stage of follicular development in terms of gonadotropin dependence and follicle destiny (growth versus atresia). Follicular growth during this period is tightly regulated by oocyte-granulosa-theca cell interactions. Formation of the theca cell layer is a key event that occurs during this transitional stage. Granulosal factor(s) stimulates the recruitment of theca cells from cortical stromal cells, while oocyte-derived growth differentiation factor-9 (GDF-9) is involved in the differentiation of theca cells during this early stage of follicular development. The preantral to early antral transition is most susceptible to follicular atresia. GDF-9 promotes follicular survival and growth during transition from preantral stage to early antral stage by suppressing granulosa cell apoptosis and follicular atresia. GDF-9 also enhances preantral follicle growth by up-regulating theca cell androgen production. Thecal factor(s) promotes granulosa cell proliferation and suppress granulosa cell apoptosis. Understanding the intraovarian mechanisms in the regulation of follicular growth and atresia during this stage may be of clinical significance in the selection of the best quality germ cells for assisted reproduction. In addition, since certain ovarian dysfunctions, such as polycystic ovarian syndrome and gonadotropin poor-responsiveness, are consequences of dysregulated follicle growth at this transitional stage, understanding the molecular and cellular mechanisms in the control of follicular development during the preantral-early antral transition may provide important insight into the pathophysiology and rational treatment of these conditions. PMID:19589134

UN TRISO Compaction in SiC for FCM Fuel Irradiations

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

Terrani, Kurt A.; Trammell, Michael P.; Kiggans, James O.

2016-11-01

The U.S. Department of Energy Office of Nuclear Energy (DOE-NE) Advanced Fuels Campaign (AFC) is conducting research and development to elevate the technology readiness level of Fully Ceramic Microencapsulated (FCM) fuels, a candidate nuclear fuel with potentially enhanced accident tolerance due to very high fission product retention. One of the early activities in FY17 was to demonstrate production of FCM pellets with uranium nitride TRISO particles. This was carried out in preparation of the larger pellet production campaign in support of the upcoming irradiation testing of this fuel form at INL’s Advanced Test Reactor.

Reply to Comment on ``Emergence of Complex Societies After Sea Level Stabilized''

NASA Astrophysics Data System (ADS)

Day, John W.; Gunn, Joel D.; Folan, William J.; Yáñez-Arancibia, Alejandro; Horton, Benjamin P.

2007-10-01

Washington [this issue] raised a number of interesting points that serve to clarify the origins of civilizations on continental margins. We linked the initial development of civilizations to coastal margin productivity [Day et al., 2007]. Washington argues that a number of early civilizations were not related to marine productivity, but rather were centered around the exploitation and cultivation of riparian grains. However, we defined coastal margins to include upwellings, estuaries, and lower floodplains affected by coastal water levels. Thus, the Nile, Mesopotamia, Indus, Mississippi, and Yellow societies were influenced by coastal margin productivity.

Non-Specific Microbicide Product Development: Then and Now

PubMed Central

Romano, Joseph W.; Robbiani, Melissa; Doncel, Gustavo F.; Moench, Thomas

2015-01-01

Despite the identification of HIV-1 as the etiological agent responsible for AIDS nearly 30 years ago, a sterilizing vaccine capable of preventing transmission of the virus remains elusive. In response to struggles on the vaccine development front, significant effort has been devoted to preventing the transmission of HIV with alternative products, technologies, and strategies. One of the early alternative HIV prevention strategies was microbicides, which are topical products that can be used to prevent sexual transmission of HIV either vaginally or rectally. First generation microbicide products were designed to be simple gel formulations comprised of readily available active agents that were inexpensive and broadly active (i.e., non-specific). Unfortunately, despite the clinical investigation of multiple product concepts satisfying these requirements, none were shown to be efficacious in pivotal trials. More recently, microbicide and oral prevention strategies involving highly specific and potent anti-retroviral (ARV) drugs have shown to be efficacious in trials. Although building on these successes continues, these products have a number of issues including potential toxicity with long term use, selection of HIV resistance, and cost. Further, all of the original justifications for non-specific microbicide products remain valid. This review provides a brief history of non-specific microbicide development, outlines the evolution to, and limitations of, ARV based microbicides, and summarizes the current activity on non-specific microbicide product development. PMID:22264041

Development and Validation of a High Throughput System for Discovery of Antigens for Autoantibody Detection

PubMed Central

Macdonald, Isabel K.; Allen, Jared; Murray, Andrea; Parsy-Kowalska, Celine B.; Healey, Graham F.; Chapman, Caroline J.; Sewell, Herbert F.; Robertson, John F. R.

2012-01-01

An assay employing a panel of tumor-associated antigens has been validated and is available commercially (EarlyCDT®-Lung) to aid the early detection of lung cancer by measurement of serum autoantibodies. The high throughput (HTP) strategy described herein was pursued to identify new antigens to add to the EarlyCDT-Lung panel and to assist in the development of new panels for other cancers. Two ligation-independent cloning vectors were designed and synthesized, producing fusion proteins suitable for the autoantibody ELISA. We developed an abridged HTP version of the validated autoantibody ELISA, determining that results reflected the performance of the EarlyCDT assay, by comparing results on both formats. Once validated this HTP ELISA was utilized to screen multiple fusion proteins prepared on small-scale, by a HTP expression screen. We determined whether the assay performance for these HTP protein batches was an accurate reflection of the performance of R&D or commercial batches. A HTP discovery platform for the identification and optimal production of tumor- associated antigens which detects autoantibodies has been developed and validated. The most favorable conditions for the exposure of immunogenic epitopes were assessed to produce discriminatory proteins for use in a commercial ELISA. This process is rapid and cost-effective compared to standard cloning and screening technologies and enables rapid advancement in the field of autoantibody assay discovery. This approach will significantly reduce timescale and costs for developing similar panels of autoantibody assays for the detection of other cancer types with the ultimate aim of improved overall survival due to early diagnosis and treatment. PMID:22815807

Synthetic biology: Emerging bioengineering in Indonesia

NASA Astrophysics Data System (ADS)

Suhandono, Sony

2017-05-01

The development of synthetic biology will shape the new era of science and technology. It is an emerging bioengineering technique involving genetic engineering which can alter the phenotype and behavior of the cell or the new product. Synthetic biology may produce biomaterials, drugs, vaccines, biosensors, and even a recombinant secondary metabolite used in herbal and complementary medicine, such as artemisinin, a malaria drug which is usually extracted from the plant Artemisia annua. The power of synthetic biology has encouraged scientists in Indonesia, and is still in early development. This paper also covers some research from an Indonesian research institute in synthetic biology such as observing the production of bio surfactants and the enhanced production of artemisinin using a transient expression system. Synthetic biology development in Indonesia may also be related to the iGEM competition, a large synthetic biology research competition which was attended by several universities in Indonesia. The application of synthetic biology for drug discovery will be discussed.

Discoveries, developments boost interest in Bangladesh

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

NONE

1996-11-11

The government of Bangladesh is expected to open a new exploration licensing round by yearend, following approval of a new model production sharing contract this fall. Initial interest in new licenses from international companies is high, and a number of new contracts are expected to be signed in 1997. State firm Petrobangla is expected to give companies 90 days to submit bids once the exploration round is announced. It is now known whether the round will include rights to undeveloped or partially developed fields. Discovery of multipay Sangu gas field by Cairn Energy plc, Edinburgh, early this year created greatmore » interest among international companies. The analyst estimated Sangu reserves at 1 tcf of gas. Sangu, on Block 16 in the Bay of Bengal, is being considered for development with a small production platform and a pipeline to shore. The paper discusses the existing licenses and production prospects.« less

The roles of a process development group in biopharmaceutical process startup.

PubMed

Goochee, Charles F

2002-01-01

The transfer of processes for biotherapeutic products into finalmanufacturing facilities was frequently problematic during the 1980's and early 1990's, resulting in costly delays to licensure(Pisano 1997). While plant startups for this class of products can become chaotic affairs, this is not an inherent or intrinsic feature. Major classes of process startup problems have been identified andmechanisms have been developed to reduce their likelihood of occurrence. These classes of process startup problems and resolution mechanisms are the major topic of this article. With proper planning and sufficient staffing, the probably of a smooth process startup for a biopharmaceutical product can be very high - i.e., successful process performance will often beachieved within the first two full-scale process lots in the plant. The primary focus of this article is the role of the Process Development Group in helping to assure this high probability of success.

Molecular basis of high viscosity in concentrated antibody solutions: Strategies for high concentration drug product development.

PubMed

Tomar, Dheeraj S; Kumar, Sandeep; Singh, Satish K; Goswami, Sumit; Li, Li

2016-01-01

Effective translation of breakthrough discoveries into innovative products in the clinic requires proactive mitigation or elimination of several drug development challenges. These challenges can vary depending upon the type of drug molecule. In the case of therapeutic antibody candidates, a commonly encountered challenge is high viscosity of the concentrated antibody solutions. Concentration-dependent viscosity behaviors of mAbs and other biologic entities may depend on pairwise and higher-order intermolecular interactions, non-native aggregation, and concentration-dependent fluctuations of various antibody regions. This article reviews our current understanding of molecular origins of viscosity behaviors of antibody solutions. We discuss general strategies and guidelines to select low viscosity candidates or optimize lead candidates for lower viscosity at early drug discovery stages. Moreover, strategies for formulation optimization and excipient design are also presented for candidates already in advanced product development stages. Potential future directions for research in this field are also explored.

Mechanical stress regulation of plant growth and development

NASA Technical Reports Server (NTRS)

Mitchell, C. A.; Myers, P. N.

1995-01-01

The authors introduce the chapter with a discussion of lessons from nature, agriculture, and landscapes; terms and definitions; and an historical perspective of mechanical stress regulation of plant growth and development. Topics include developmental responses to mechanical stress; mechanical stress-environment interactions; metabolic, productivity, and compositional changes; hormonal involvement; mechanoperception and early transduction mechanisms; applications in agriculture; and research implications. The discussion of hormonal involvement in mechanical stress physiology includes ethylene, auxin, gibberellins, and other phytohormones. The discussion of applications in agriculture examines windbreaks, nursery practices, height control and conditioning, and enhancement of growth and productivity. Implications for research are related to handling plant materials, space biology, and future research needs.

A mechanism of adaptation to hypergravity in the statocyst of Aplysia californica

NASA Technical Reports Server (NTRS)

Pedrozo, H. A.; Schwartz, Z.; Luther, M.; Dean, D. D.; Boyan, B. D.; Wiederhold, M. L.

1996-01-01

The gravity-sensing organ of Aplysia californica consists of bilaterally paired statocysts containing statoconia, which are granules composed of calcium carbonate crystals in an organic matrix. In early embryonic development, Aplysia contain a single granule called a statolith, and as the animal matures, statoconia production takes place. The objective of this study was to determine the effect of hypergravity on statoconia production and homeostasis and explore a possible physiologic mechanism for regulating this process. Embryonic Aplysia were exposed to normogravity or 3 x g or 5.7 x g and each day samples were analyzed for changes in statocyst, statolith, and body dimensions until they hatched. In addition, early metamorphosed Aplysia (developmental stages 7-10) were exposed to hypergravity (2 x g) for 3 weeks, and statoconia number and statocyst and statoconia volumes were determined. We also determined the effects of hypergravity on statoconia production and homeostasis in statocysts isolated from developmental stage 10 Aplysia. Since prior studies demonstrated that urease was important in the regulation of statocyst pH and statoconia formation, we also evaluated the effect of hypergravity on urease activity. The results show that hypergravity decreased statolith and body diameter in embryonic Aplysia in a magnitude-dependent fashion. In early metamorphosed Aplysia, hypergravity decreased statoconia number and volume. Similarly, there was an inhibition of statoconia production and a decrease in statoconia volume in isolated statocysts exposed to hypergravity in culture. Urease activity in statocysts decreased after exposure to hypergravity and was correlated with the decrease in statoconia production observed. In short, there was a decrease in statoconia production with exposure to hypergravity both in vivo and in vitro and a decrease in urease activity. It is concluded that exposure to hypergravity downregulates urease activity, resulting in a significant decrease in the formation of statoconia.

A Market-Basket Approach to Predict the Acute Aquatic Toxicity of Munitions and Energetic Materials.

PubMed

Burgoon, Lyle D

2016-06-01

An ongoing challenge in chemical production, including the production of insensitive munitions and energetics, is the ability to make predictions about potential environmental hazards early in the process. To address this challenge, a quantitative structure activity relationship model was developed to predict acute fathead minnow toxicity of insensitive munitions and energetic materials. Computational predictive toxicology models like this one may be used to identify and prioritize environmentally safer materials early in their development. The developed model is based on the Apriori market-basket/frequent itemset mining approach to identify probabilistic prediction rules using chemical atom-pairs and the lethality data for 57 compounds from a fathead minnow acute toxicity assay. Lethality data were discretized into four categories based on the Globally Harmonized System of Classification and Labelling of Chemicals. Apriori identified toxicophores for categories two and three. The model classified 32 of the 57 compounds correctly, with a fivefold cross-validation classification rate of 74 %. A structure-based surrogate approach classified the remaining 25 chemicals correctly at 48 %. This result is unsurprising as these 25 chemicals were fairly unique within the larger set.

Rise and demise of the Bahama-Grand Banks gigaplatform, northern margin of the Jurassic proto-Atlantic seaway

USGS Publications Warehouse

Poag, C. Wylie

1991-01-01

An extinct, > 5000-km-long Jurassic carbonate platform and barrier reef system lies buried beneath the Atlantic continental shelf and slope of the United States. A revised stratigraphic framework, a series of regional isopach maps, and paleogeographic reconstructions are used to illustrate the 42-m.y. history of this Bahama-Grand Banks gigaplatform from its inception in Aalenian(?) (early Middle Jurassic) time to its demise and burial in Berriasian-Valanginian time (early Early Cretaceous). Aggradation-progradation rates for the gigaplatform are comparable to those of the familiar Capitan shelf margin (Permian) and are closely correlated with volumetric rates of siliciclastic sediment accumulation and depocenter migration. Siliciclastic encroachment behind the carbonate tracts appears to have been an important impetus for shelf-edge progradation. During the Early Cretaceous, sea-level changes combined with eutrophication (due to landward soil development and seaward upwelling) and the presence of cooler upwelled waters along the outer shelf appear to have decimated the carbonate producers from the Carolina Trough to the Grand Banks. This allowed advancing siliciclastic deltas to overrun the shelf edge despite a notable reduction in siliciclastic accumulation rates. However, upwelling did not extend southward to the Blake-Bahama megabank, so platform carbonate production proceeded there well into the Cretaceous. Subsequent stepwise carbonate abatement characterized the Blake Plateau Basin, whereas the Bahamas have maintained production to the present. The demise of carbonate production on the northern segments of the gigaplatform helped to escalate deep-water carbonate deposition in the Early Cretaceous, but the sudden augmentation of deep-water carbonate reservoirs in the Late Jurassic was triggered by other agents, such as global expansion of nannoplankton communities. ?? 1991.

WATER FORMATION IN THE UPPER ATMOSPHERE OF THE EARLY EARTH

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

Fleury, Benjamin; Carrasco, Nathalie; Marcq, Emmanuel

2015-07-10

The water concentration and distribution in the early Earth's atmosphere are important parameters that contribute to the chemistry and the radiative budget of the atmosphere. If the atmosphere above the troposphere is generally considered as dry, photochemistry is known to be responsible for the production of numerous minor species. Here we used an experimental setup to study the production of water in conditions simulating the chemistry above the troposphere of the early Earth with an atmospheric composition based on three major molecules: N{sub 2}, CO{sub 2}, and H{sub 2}. The formation of gaseous products was monitored using infrared spectroscopy. Watermore » was found as the major product, with approximately 10% of the gas products detected. This important water formation is discussed in the context of the early Earth.« less

A European regulatory perspective on cystic fibrosis: current treatments, trends in drug development and translational challenges for CFTR modulators.

PubMed

Ponzano, Stefano; Nigrelli, Giulia; Fregonese, Laura; Eichler, Irmgard; Bertozzi, Fabio; Bandiera, Tiziano; Galietta, Luis J V; Papaluca, Marisa

2018-06-30

In this article we analyse the current authorised treatments and trends in early drug development for cystic fibrosis (CF) in the European Union for the time period 2000-2016. The analysis indicates a significant improvement in the innovation and development of new potential medicines for CF, shifting from products that act on the symptoms of the disease towards new therapies targeting the cause of CF. However, within these new innovative medicines, results for CF transmembrane conductance regulator (CFTR) modulators indicate that one major challenge for turning a CF concept product into an actual medicine for the benefit of patients resides in the fact that, although pre-clinical models have shown good predictability for certain mutations, a good correlation to clinical end-points or biomarkers ( e.g. forced expiratory volume in 1 s and sweat chloride) for all mutations has not yet been achieved. In this respect, the use of alternative end-points and innovative nonclinical models could be helpful for the understanding of those translational discrepancies. Collaborative endeavours to promote further research and development in these areas as well as early dialogue with the regulatory bodies available at the European competent authorities are recommended. Copyright ©ERS 2018.

The development of perceptual attention and articulatory skill in one or two languages

NASA Astrophysics Data System (ADS)

Fowler, Carol; Best, Catherine

2002-05-01

Infants acquire properties of their native language especially during the second half of the first year of life. Models, such as Jusczyk's WRAPSA, Best's PAM, Kuhl's NLM, and Werker's account describe changes in perceptual or attentional space that may underlie the perceptual changes that infants exhibit. Unknown is the relation of these changes to changes in speechlike vocalizations that occur at the same time. Future research should address whether the perceptual models predict production learning. Other issues concern how the perceptual and articulatory systems develop for infants exposed to more than one language. Do multiple perceptual spaces develop, or does one space accommodate both languages? For infants exposed to just one language, but living in an environment where the ambient and pedagogical language is different (say, infants in a monolingual Spanish home in the U.S.), early language learning fosters learning the native language, but it may impede learning the ambient language. How much or how little does early exposure to the ambient language allow development of perceptual and articulatory systems for the ambient language? A final issue addresses whether the emergence of lexical, morphological and/or syntactic abilities in the second year is related to further changes in speech perception and production. [Work supported by NICHD.

[European Union regulatory and quality requirements for botanical drugs and their implications for Chinese herbal medicinal products development].

PubMed

Zhu, You-Ping

2017-06-01

This paper introduces regulatory pathways and characteristic quality requirements for marketing authorization of herbal medicinal products in the European Union（EU）, and the legal status and applications of "European Union list of herbal substances, preparations and combinations" and "European Union herbal monographs". Also introduced are Chinese herbs that have been granted the EU list entry, those with EU herbal monographs, and registered EU traditional herbal medicinal products with Chinese herbs as active ingredients. Special attention is paid to the technical details of three authorized EU herbal medicinal products (Veregen, Sativex and Episalvan) in comparison with Andrographis paniculata extract HMPL-004 that failed the phase Ⅲ clinical trial for ulcerative colitis. The paper further emphasizes the importance of enriching active fractions of herbal extracts and taking regulatory and quality considerations into account in early stage of botanical drug development. Copyright© by the Chinese Pharmaceutical Association.

Syllabic Patterns in the Early Vocalizations of Quichua Children

ERIC Educational Resources Information Center

Gildersleeve-Neumann, Christina E.; Davis, Barbara L.; Macneilage, Peter F.

2013-01-01

To understand the interactions between production patterns common to children regardless of language environment and the early appearance of production effects based on perceptual learning from the ambient language requires the study of languages with diverse phonological properties. Few studies have evaluated early phonological acquisition…

Patient centric drug product design in modern drug delivery as an opportunity to increase safety and effectiveness.

PubMed

Stegemann, Sven

2018-06-01

The advances in drug delivery technologies have enabled pharmaceutical scientists to deliver a drug through various administration routes and optimize the drug release and absorption. The wide range of drug delivery systems and dosage forms represent a toolbox of technology for the development of pharmaceutical drug products but might also be a source of medication errors and nonadherence. Patient centric drug product development is being suggested as an important factor to increase therapeutic outcomes. Areas covered: Patients have impaired health and potentially disabilities and they are not medical or pharmaceutical experts but are requested to manage complex therapeutic regimens. As such the application of technology should also serve to reduce complexity, build on patients' intuition and ease of use. Patients form distinct populations based on the targeted disease, disease cluster or age group with specific characteristics or therapeutic contexts. Expert opinion: Establishing a target product and patient profile is essential to guide drug product design development. Including the targeted patient populations in the process is a prerequisite to achieve patient-centric pharmaceutical drug product design. Addressing the needs early on in the product design process, will create more universal design, avoiding the necessity for multiple product presentations to cover the different patient populations.

Maillard reaction products and their relation to complications in insulin-dependent diabetes mellitus.

PubMed Central

McCance, D R; Dyer, D G; Dunn, J A; Bailie, K E; Thorpe, S R; Baynes, J W; Lyons, T J

1993-01-01

Glycation, oxidation, and browning of proteins have all been implicated in the development of diabetic complications. We measured the initial Amadori adduct, fructoselysine (FL); two Maillard products, N epsilon-(carboxymethyl) lysine (CML) and pentosidine; and fluorescence (excitation = 328 nm, emission = 378 nm) in skin collagen from 39 type 1 diabetic patients (aged 41.5 +/- 15.3 [17-73] yr; duration of diabetes 17.9 +/- 11.5 [0-46] yr, [mean +/- SD, range]). The measurements were related to the presence of background (n = 9) or proliferative (n = 16) retinopathy; early nephropathy (24-h albumin excretion rate [AER24] > or = 20 micrograms/min; n = 9); and limited joint mobility (LJM; n = 20). FL, CML, pentosidine, and fluorescence increased progressively across diabetic retinopathy (P < 0.05, P < 0.001, P < 0.05, P < 0.01, respectively). FL, CML, pentosidine, and fluorescence were also elevated in patients with early nephropathy (P < 0.05, P < 0.001, P < 0.01, P < 0.01, respectively). There was no association with LJM. Controlling for age, sex, and duration of diabetes using logistic regression, FL and CML were independently associated with retinopathy (FL odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.01-1.12, P < 0.05; CML OR = 6.77, 95% CI = 1.33-34.56, P < 0.05) and with early nephropathy (FL OR = 1.05, 95% CI = 1.01-1.10, P < 0.05; CML OR = 13.44, 95% CI = 2.00-93.30, P < 0.01). The associations between fluorescence and retinopathy and between pentosidine and nephropathy approached significance (P = 0.05). These data show that FL and Maillard products in skin correlate with functional abnormalities in other tissues and suggest that protein glycation and oxidation (glycoxidation) may be implicated in the development of diabetic retinopathy and early nephropathy. PMID:8514859

Silicon in broiler drinking water promotes bone development in broiler chickens.

PubMed

Sgavioli, S; de Faria Domingues, C H; Castiblanco, D M C; Praes, M F F M; Andrade-Garcia, Giuliana M; Santos, E T; Baraldi-Artoni, S M; Garcia, R G; Junqueira, O M

2016-10-01

Skeletal abnormalities, bone deformities and fractures cause significant losses in broiler production during both rearing and processing. Silicon is an essential mineral for bone and connective tissue synthesis and for calcium absorption during the early stages of bone formation. Performance was not affected by the addition of silicon. However, broilers receiving silicon showed a significant increase of phosphorus, zinc, copper, manganese and ash in the tibia. In conclusion, broiler performance was not impaired by adding the tested silicon product to the drinking water. In addition, bone development improved, as demonstrated by higher mineral and ash content. Further studies are required to determine the optimal concentration of silicon, including heat stress simulations, to better understand the effects of silicon on bone development.

Subgingival Microbiome Colonization and Cytokine Production during Early Dental Implant Healing.

PubMed

Payne, Jeffrey B; Johnson, Paul G; Kok, Car Reen; Gomes-Neto, João C; Ramer-Tait, Amanda E; Schmid, Marian J; Hutkins, Robert W

2017-01-01

Little is known about longitudinal development of the peri-implant subgingival microbiome and cytokine production as a new sulcus forms after dental implant placement. Therefore, the purpose of this observational study was to evaluate simultaneous longitudinal changes in the oral microbiome and cytokine production in the developing peri-implant sulcus compared to control natural teeth. Four and 12 weeks after implant placement and abutment connection, a dental implant and a natural tooth were sampled in 25 patients for subgingival plaque and gingival crevicular fluid (GCF [around teeth] and peri-implant crevicular fluid [PICF] around implants). DNA from plaque samples was extracted and sequenced using Illumina-based 16S rRNA sequencing. GCF and PICF samples were analyzed using a customized Milliplex human cytokine and chemokine magnetic bead panel. Beta diversity analysis revealed that natural teeth and implants had similar subgingival microbiomes, while teeth had greater alpha diversity than implants. At the genus level, however, few differences were noted between teeth and dental implants over 12 weeks. Specifically, Actinomyces and Selenomonas were significantly elevated around teeth versus dental implants at both 4 weeks and 12 weeks, while Corynebacterium and Campylobacter were significantly elevated only at 4 weeks around teeth. The only difference between PICF and GCF biomarkers was significantly elevated granulocyte-macrophage colony-stimulating factor levels around teeth versus dental implants at the 4-week visit. The subgingival microbiome and cytokine production were similar between teeth and implants during early healing, suggesting that these profiles are driven by the patient following dental implant placement and are not determined by anatomical niche. IMPORTANCE Dental implants are a common treatment option offered to patients for tooth replacement. However, little is known regarding initial colonization of the subgingival microbiome and simultaneous longitudinal cytokine production in humans during the early healing phase following implant placement. We report findings from an in vivo study that assessed initial colonization of the subgingival microbiome and concomitant early cytokine production in a newly formed anatomical space, namely, an implant sulcus. This approach may be useful in future interventional studies to influence dental implant success. Our data showed that the subgingival microbiome and cytokine profile were similar for control natural teeth and dental implants at both 4 and 12 weeks after implant placement. These data suggest that these profiles are driven by the patient and not by anatomical location (i.e., tooth versus dental implant).

Temporal variation in phenotypic gender and expected functional gender within and among individuals in an annual plant.

PubMed

Austen, Emily J; Weis, Arthur E

2014-07-01

Adaptive explanations for variation in sex allocation centre on variation in resource status and variation in the mating environment. The latter can occur when dichogamy causes siring opportunity to vary across the flowering season. In this study, it is hypothesized that the widespread tendency towards declining fruit-set from first to last flowers on plants can similarly lead to a varying mating environment by causing a temporal shift in the quality (not quantity) of siring opportunities. A numerical model was developed to examine the effects of declining fruit-set on the expected male versus female reproductive success (functional gender) of first and last flowers on plants, and of early- and late-flowering plants. Within- and among-plant temporal variation in pollen production, ovule production and fruit-set in 70 Brassica rapa plants was then characterized to determine if trends in male and female investment mirror expected trends in functional gender. Under a wide range of model conditions, functional femaleness decreased sharply in the last flowers on plants, and increased from early- to late-flowering plants in the population. In B. rapa, pollen production decreased more rapidly than ovule production from first to last flowers, leading to a within-plant increase in phenotypic femaleness. Among plants, ovule production decreased from early- to late-flowering plants, causing a temporal decrease in phenotypic femaleness. The numerical model confirmed that declining fruit-set can drive temporal variation in functional gender, especially among plants. The discrepancy between observed trends in phenotypic gender in B. rapa and expected functional gender predicted by the numerical model does not rule out the possibility that male reproductive success decreases with later flowering onset. If so, plants may experience selection for early flowering through male fitness. © The Author 2014. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Berries and other natural products in the pancreatic cancer chemoprevention in human clinical trials.

PubMed

Pan, Pan; Skaer, Chad; Yu, Jianhua; Zhao, Hui; Ren, He; Oshima, Kiyoko; Wang, Li-Shu

2017-01-01

Pancreatic ductal adenocarcinoma (PDAC) was the 12 th and 11 th most common cancer in men and women worldwide in 2012, with the highest incidence in North America and Europe and the lowest in Africa and Asia. Due to the lack of efficient early diagnosis and rapid disease progression, PDAC patients have a 5-year survival rate of just 5%. Epidemiological studies suggest that smoking, obesity, type II diabetes, and pancreatitis are common risk factors for PDAC development. By contrast, high intake of fresh fruit, vegetables, and nuts rich in phytochemicals could reduce PDAC risk. This review summarizes the human clinical studies that have used berries or other natural products for chemoprevention of PDAC. Developing chemopreventive agents against PDAC would be tremendously valuable for the high-risk population and patients with premalignant lesions. Although some clinical trials of these agents have been completed, most are in early phases, and the results are not promising, which may be due to administration of the natural products at advanced stages of PDAC. Thus, further mechanistic studies using genetic animal models that recapitulate the tumor microenvironment and immunology of human PDAC would be informative for selecting an effective window for intervention with berries or other natural compounds.

Berries and other natural products in the pancreatic cancer chemoprevention in human clinical trials

PubMed Central

Pan, Pan; Skaer, Chad; Yu, Jianhua; Zhao, Hui; Ren, He; Oshima, Kiyoko; Wang, Li-Shu

2017-01-01

Pancreatic ductal adenocarcinoma (PDAC) was the 12th and 11th most common cancer in men and women worldwide in 2012, with the highest incidence in North America and Europe and the lowest in Africa and Asia. Due to the lack of efficient early diagnosis and rapid disease progression, PDAC patients have a 5-year survival rate of just 5%. Epidemiological studies suggest that smoking, obesity, type II diabetes, and pancreatitis are common risk factors for PDAC development. By contrast, high intake of fresh fruit, vegetables, and nuts rich in phytochemicals could reduce PDAC risk. This review summarizes the human clinical studies that have used berries or other natural products for chemoprevention of PDAC. Developing chemopreventive agents against PDAC would be tremendously valuable for the high-risk population and patients with premalignant lesions. Although some clinical trials of these agents have been completed, most are in early phases, and the results are not promising, which may be due to administration of the natural products at advanced stages of PDAC. Thus, further mechanistic studies using genetic animal models that recapitulate the tumor microenvironment and immunology of human PDAC would be informative for selecting an effective window for intervention with berries or other natural compounds. PMID:29367867

75 FR 63188 - Draft Guidance for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-14

...] Draft Guidance for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry...: Chemistry, Manufacturing, and Control Information'' dated September 2010. The draft guidance provides... Products: Chemistry, Manufacturing, and Control Information'' dated September 2010. The draft guidance...

Evaluation of the influence of dominance rules for the assembly line design problem under consideration of product design alternatives

NASA Astrophysics Data System (ADS)

Oesterle, Jonathan; Lionel, Amodeo

2018-06-01

The current competitive situation increases the importance of realistically estimating product costs during the early phases of product and assembly line planning projects. In this article, several multi-objective algorithms using difference dominance rules are proposed to solve the problem associated with the selection of the most effective combination of product and assembly lines. The list of developed algorithms includes variants of ant colony algorithms, evolutionary algorithms and imperialist competitive algorithms. The performance of each algorithm and dominance rule is analysed by five multi-objective quality indicators and fifty problem instances. The algorithms and dominance rules are ranked using a non-parametric statistical test.

Concise Review: Guidance in Developing Commercializable Autologous/Patient-Specific Cell Therapy Manufacturing

PubMed Central

Armant, Myriam; Brandwein, Harvey; Burger, Scott; Campbell, Andrew; Carpenito, Carmine; Clarke, Dominic; Fong, Timothy; Karnieli, Ohad; Niss, Knut; Van't Hof, Wouter; Wagey, Ravenska

2013-01-01

Cell therapy is poised to play an enormous role in regenerative medicine. However, little guidance is being made available to academic and industrial entities in the start-up phase. In this technical review, members of the International Society for Cell Therapy provide guidance in developing commercializable autologous and patient-specific manufacturing strategies from the perspective of process development. Special emphasis is placed on providing guidance to small academic or biotech researchers as to what simple questions can be addressed or answered at the bench in order to make their cell therapy products more feasible for commercial-scale production. We discuss the processes that are required for scale-out at the manufacturing level, and how many questions can be addressed at the bench level. The goal of this review is to provide guidance in the form of topics that can be addressed early in the process of development to better the chances of the product being successful for future commercialization. PMID:24101671

Engineering Changes in Product Design - A Review

NASA Astrophysics Data System (ADS)

Karthik, K.; Janardhan Reddy, K., Dr

2016-09-01

Changes are fundamental to product development. Engineering changes are unavoidable and can arise at any phase of the product life cycle. The consideration of market requirements, customer/user feedbacks, manufacturing constraints, design innovations etc., turning them into viable products can be accomplished when product change is managed properly. In the early design cycle, informal changes are accepted. However, changes become formal when its complexity and cost increases, and as product matures. To maximize the market shares, manufacturers have to effectively and efficiently manage engineering changes by means of Configuration Control. The paper gives a broad overview about ‘Engineering Change Management’ (ECM) through configuration management and its implications in product design. The aim is to give an idea and understanding about the engineering changes in product design scenario to the new researchers. This paper elaborates the significant aspect of managing the engineering changes and the importance of ECM in a product life cycle.

Reimbursement challenges with cancer immunotherapeutics

PubMed Central

Kudrin, Alex

2012-01-01

Today the task of cancer vaccine developers is not only to excel in cancer immunology and art of conducting immunotherapy trials but also in the analysis and forecasting the cost-effectiveness of the final product. This article reviews methodology used by EU health-technology bodies in the appraisal of new therapies based on economic and clinical values and different budgetary uncertainties. Increasingly, new oncology treatments were able to access EU market only under provision of risk-sharing agreements with payers and examples of such agreements are given here. Cancer vaccine developers should consider early collection of patient reported outcomes in order to project additional clinical and economic value with immunotherapy. Furthermore, early interaction with different stakeholders including patient organizations, physicians and payer bodies can facilitate market access. PMID:22894969

Formulation of US international energy policies

NASA Astrophysics Data System (ADS)

1980-09-01

To find out how the United States develops international energy policy, GAO reviewed five major energy issues covering the period from early 1977 through 1979. The issues are: vulnerabilities to petroleum supply interruptions; long term national security strategy on imported oil prices; export of U.S. oil and gas production equipment and technology to the Soviety Union; World Bank initiatives to assist in financing oil and gas exploration and development in oil-importing developing countries; and the role of gas imports relative to the nation's future sources of gas.

Large project experiences with object-oriented methods and reuse

NASA Technical Reports Server (NTRS)

Wessale, William; Reifer, Donald J.; Weller, David

1992-01-01

The SSVTF (Space Station Verification and Training Facility) project is completing the Preliminary Design Review of a large software development using object-oriented methods and systematic reuse. An incremental developmental lifecycle was tailored to provide early feedback and guidance on methods and products, with repeated attention to reuse. Object oriented methods were formally taught and supported by realistic examples. Reuse was readily accepted and planned by the developers. Schedule and budget issues were handled by agreements and work sharing arranged by the developers.

Detection of early changes in lung cell cytology by flow-systems analysis techniques, July 1--December 31, 1975

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

Steinkamp, J.A.; Ingram, M.; Hansen, K.M.

1976-03-01

This report summarizes results of preliminary experiments to demonstrate the feasibility of using automated flow-systems analysis in detecting early changes of respiratory epithelium exposed to physical and chemical agents associated with the by-products of nonnuclear energy production. The Syrian hamster was selected as the experimental test animal to begin investigation of the effects of toxic agents to cells of the respiratory tract. Since initiation of the program approximately six months ago, the goals have been acquisition of adequate numbers of exfoliated cells from the lung; adaptation of cytological techniques developed on human exfoliated gynecological samples to hamster lung epithelium formore » obtaining single-cell suspensions; utilization of existing cell staining methods to measure DNA content in lung cells; and analysis of DNA content and cell size. As the flow-system cell analysis technology is adapted to the measurement of exfoliated lung cells, rapid and quantitative determination of early changes in the physical and biochemical cellular properties will be attempted as a function of exposure to the toxic agents. (auth)« less

Recent patents for detecting the species of origin in animal feedstuff, and raw and processed meat products.

PubMed

Rogberg-Muñoz, Andrés; Posik, Diego M; Rípoli, María V; Falomir Lockhart, Agustín H; Peral-García, Pilar; Giovambattista, Guillermo

2013-04-01

The value of the traceability and labeling of food is attributable to two main aspects: health safety and/or product or process certification. The identification of the species related to meat production is still a major concern for economic, religious and health reasons. Many approaches and technologies have been used for species identification in animal feedstuff and food. The early methods for meat products identification include physical, anatomical, histological and chemical. Since 1970, a variety of methods were developed, these include electrophoresis (i.e. isoelectrofocusing), chromatography (i.e. HPLC), immunological techniques (i.e. ELISA), Nuclear Magnetic Resonance, Mass Spectrometry and PCR (DNA and RNA based methods). The recent patents on species detection in animal feedstuffs, raw meat and meat processed products, listed in this work, are mainly based on monoclonal antibodies and PCR, especially RT-PCR. The new developments under research are looking for more sensible, specific, less time consuming and quantitatively detection methods, which can be used in highly processed or heated treated meat food.

New Tobacco and Tobacco-Related Products: Early Detection of Product Development, Marketing Strategies, and Consumer Interest

PubMed Central

Staal, Yvonne CM; van de Nobelen, Suzanne; Havermans, Anne

2018-01-01

Background A wide variety of new tobacco and tobacco-related products have emerged on the market in recent years. Objective To understand their potential implications for public health and to guide tobacco control efforts, we have used an infoveillance approach to identify new tobacco and tobacco-related products. Methods Our search for tobacco(-related) products consists of several tailored search profiles using combinations of keywords such as “e-cigarette” and “new” to extract information from almost 9000 preselected sources such as websites of online shops, tobacco manufacturers, and news sites. Results Developments in e-cigarette design characteristics show a trend toward customization by possibilities to adjust temperature and airflow, and by the large variety of flavors of e-liquids. Additionally, more e-cigarettes are equipped with personalized accessories, such as mobile phones, applications, and Bluetooth. Waterpipe products follow the trend toward electronic vaping. Various heat-not-burn products were reintroduced to the market. Conclusions Our search for tobacco(-related) products was specific and timely, though advances in product development require ongoing optimization of the search strategy. Our results show a trend toward products resembling tobacco cigarettes vaporizers that can be adapted to the consumers’ needs. Our search for tobacco(-related) products could aid in the assessment of the likelihood of new products to gain market share, as a possible health risk or as an indicator for the need on independent and reliable information of the product to the general public. PMID:29807884

Age-dependent trade-offs between immunity and male, but not female, reproduction.

PubMed

McNamara, Kathryn B; van Lieshout, Emile; Jones, Therésa M; Simmons, Leigh W

2013-01-01

Immune function is costly and must be traded off against other life-history traits, such as gamete production. Studies of immune trade-offs typically focus on adult individuals, yet the juvenile stage can be a highly protracted period when reproductive resources are acquired and immune challenges are ubiquitous. Trade-offs during development are likely to be important, yet no studies have considered changes in adult responses to immune challenges imposed at different stages of juvenile development. By manipulating the timing of a bacterial immune challenge to the larvae of the cotton bollworm moth, we examined potential trade-offs between investment into immunity at different stages of juvenile development (early or late) and subsequent adult reproductive investment into sperm or egg production. Our data reveal an age-dependent trade-off between juvenile immune function and adult male reproductive investment. Activation of the immune response during late development resulted in a reduced allocation of resources to eupyrene (fertilizing) sperm production. Immune activation from the injection procedure itself (irrespective of whether individuals were injected with an immune elicitor or a control solution) also caused reproductive trade-offs; males injected early in development produced fewer apyrene (nonfertilizing) sperm. Contrary to many other studies, our study demonstrates these immune trade-offs under ad libitum nutritional conditions. No trade-offs were observed between female immune activation and adult reproductive investment. We suggest the differences in trade-offs observed between male sperm types and the absence of reproductive trade-offs in females may be the result of ontogenetic differences in gamete production in this species. Our data reveal developmental windows when trade-offs between immune function and gametic investment are made, and highlight the importance of considering multiple developmental periods when making inferences regarding the fundamental trade-offs expected between immune function and reproduction. © 2012 The Authors. Journal of Animal Ecology © 2012 British Ecological Society.

A Case Study Assessing the Auditory and Speech Development of Four Children Implanted with Cochlear Implants by the Chronological Age of 12 Months

PubMed Central

2013-01-01

Children with severe hearing loss most likely receive the greatest benefit from a cochlear implant (CI) when implanted at less than 2 years of age. Children with a hearing loss may also benefit greater from binaural sensory stimulation. Four children who received their first CI under 12 months of age were included in this study. Effects on auditory development were determined using the German LittlEARS Auditory Questionnaire, closed- and open-set monosyllabic word tests, aided free-field, the Mainzer and Göttinger speech discrimination tests, Monosyllabic-Trochee-Polysyllabic (MTP), and Listening Progress Profile (LiP). Speech production and grammar development were evaluated using a German language speech development test (SETK), reception of grammar test (TROG-D) and active vocabulary test (AWST-R). The data showed that children implanted under 12 months of age reached open-set monosyllabic word discrimination at an age of 24 months. LiP results improved over time, and children recognized 100% of words in the MTP test after 12 months. All children performed as well as or better than their hearing peers in speech production and grammar development. SETK showed that the speech development of these children was in general age appropriate. The data suggests that early hearing loss intervention benefits speech and language development and supports the trend towards early cochlear implantation. Furthermore, the data emphasizes the potential benefits associated with bilateral implantation. PMID:23509653

A case study assessing the auditory and speech development of four children implanted with cochlear implants by the chronological age of 12 months.

PubMed

May-Mederake, Birgit; Shehata-Dieler, Wafaa

2013-01-01

Children with severe hearing loss most likely receive the greatest benefit from a cochlear implant (CI) when implanted at less than 2 years of age. Children with a hearing loss may also benefit greater from binaural sensory stimulation. Four children who received their first CI under 12 months of age were included in this study. Effects on auditory development were determined using the German LittlEARS Auditory Questionnaire, closed- and open-set monosyllabic word tests, aided free-field, the Mainzer and Göttinger speech discrimination tests, Monosyllabic-Trochee-Polysyllabic (MTP), and Listening Progress Profile (LiP). Speech production and grammar development were evaluated using a German language speech development test (SETK), reception of grammar test (TROG-D) and active vocabulary test (AWST-R). The data showed that children implanted under 12 months of age reached open-set monosyllabic word discrimination at an age of 24 months. LiP results improved over time, and children recognized 100% of words in the MTP test after 12 months. All children performed as well as or better than their hearing peers in speech production and grammar development. SETK showed that the speech development of these children was in general age appropriate. The data suggests that early hearing loss intervention benefits speech and language development and supports the trend towards early cochlear implantation. Furthermore, the data emphasizes the potential benefits associated with bilateral implantation.

Geologic Tests for Snowmelt Runoff on Early Mars

NASA Astrophysics Data System (ADS)

Kite, E. S.; Sneed, J.; Mayer, D. P.

2017-12-01

Data from the Curiosity rover have sharpened the question: was Early Mars climate warm enough for rainfall, or was the climate cold? The hypothesis of a cold (snow-and-ice melt) climate on Early Mars can be tested using runoff production. Runoff production cannot exceed snowmelt rate in a cold climate. Therefore, high runoff production would rule out cold conditions, and would suggest rain (or catastrophic melting of snow). How can runoff production be reliably measured? To constrain runoff production, the lead author is measuring paleochannel widths and meander wavelengths for Early Mars watersheds with well-defined drainage area. The measurement method is the same as in Kite et al., EPSL, 2015. >250 channel-width measurements and 89 meander wavelength measurements are included, representing 158 drainage areas. The catalog emphasizes better-preserved (post-Noachian) paleochannels, but includes a re-survey of previously-reported paleochannel width and wavelength measurement sites. Channel widths and wavelengths are a proxy for paleodischarge. Discharge (m3/s) can be divided by drainage area (m2) to obtain a lower bound on runoff-production (mm/hr). If runoff production >(1-3) mm/hr, then a seasonal melting snow-and-ice climate is strongly disfavored. However, high runoff production would be consistent with rainfall. Initial results will be reported at the conference. The figure shows the locations of measurement sites for Early Mars channel width (black) and meander wavelength (red).

[Sea urchin embryo, DNA-damaged cell cycle checkpoint and the mechanisms initiating cancer development].

PubMed

Bellé, Robert; Le Bouffant, Ronan; Morales, Julia; Cosson, Bertrand; Cormier, Patrick; Mulner-Lorillon, Odile

2007-01-01

Cell division is an essential process for heredity, maintenance and evolution of the whole living kingdom. Sea urchin early development represents an excellent experimental model for the analysis of cell cycle checkpoint mechanisms since embryonic cells contain a functional DNA-damage checkpoint and since the whole sea urchin genome is sequenced. The DNA-damaged checkpoint is responsible for an arrest in the cell cycle when DNA is damaged or incorrectly replicated, for activation of the DNA repair mechanism, and for commitment to cell death by apoptosis in the case of failure to repair. New insights in cancer biology lead to two fundamental concepts about the very first origin of cancerogenesis. Cancers result from dysfunction of DNA-damaged checkpoints and cancers appear as a result of normal stem cell (NCS) transformation into a cancer stem cell (CSC). The second aspect suggests a new definition of "cancer", since CSC can be detected well before any clinical evidence. Since early development starts from the zygote, which is a primary stem cell, sea urchin early development allows analysis of the early steps of the cancerization process. Although sea urchins do not develop cancers, the model is alternative and complementary to stem cells which are not easy to isolate, do not divide in a short time and do not divide synchronously. In the field of toxicology and incidence on human health, the sea urchin experimental model allows assessment of cancer risk from single or combined molecules long before any epidemiologic evidence is available. Sea urchin embryos were used to test the worldwide used pesticide Roundup that contains glyphosate as the active herbicide agent; it was shown to activate the DNA-damage checkpoint of the first cell cycle of development. The model therefore allows considerable increase in risk evaluation of new products in the field of cancer and offers a tool for the discovery of molecular markers for early diagnostic in cancer biology. Prevention and early diagnosis are two decisive elements of human cancer therapy.

21 CFR 101.79 - Health claims: Folate and neural tube defects.

Code of Federal Regulations, 2013 CFR

2013-04-01

... result in infant mortality or serious disability. The birth defects anencephaly and spina bifida are the... development. Because the neural tube forms and closes during early pregnancy, the defect may occur before a... pregnancy had a reduced risk of having a child with a neural tube defect. (Products containing this level of...

21 CFR 101.79 - Health claims: Folate and neural tube defects.

Code of Federal Regulations, 2014 CFR

2014-04-01

... result in infant mortality or serious disability. The birth defects anencephaly and spina bifida are the... development. Because the neural tube forms and closes during early pregnancy, the defect may occur before a... pregnancy had a reduced risk of having a child with a neural tube defect. (Products containing this level of...

21 CFR 101.79 - Health claims: Folate and neural tube defects.

Code of Federal Regulations, 2012 CFR

2012-04-01

... result in infant mortality or serious disability. The birth defects anencephaly and spina bifida are the... development. Because the neural tube forms and closes during early pregnancy, the defect may occur before a... pregnancy had a reduced risk of having a child with a neural tube defect. (Products containing this level of...

The Acquisition of Gender Labels in Infancy: Implications for Gender-Typed Play

ERIC Educational Resources Information Center

Zosuls, Kristina M.; Ruble, Diane N.; Tamis-LeMonda, Catherine S.; Shrout, Patrick E.; Bornstein, Marc H.; Greulich, Faith K.

2009-01-01

Two aspects of children's early gender development--the spontaneous production of gender labels and gender-typed play--were examined longitudinally in a sample of 82 children. Survival analysis, a statistical technique well suited to questions involving developmental transitions, was used to investigate the timing of the onset of children's gender…

Conflicts and Contradictions: Conceptions of Empathy and the Work of Good-Intentioned Early Career White Female Teachers

ERIC Educational Resources Information Center

Warren, Chezare A.

2015-01-01

Empathy is theorized to help teachers build strategic student--teacher relationships, develop productive parent partnerships, and acquire professionally informed social and cultural perspectives of students and families. However, this literature offers little empirical evidence regarding how practicing teachers conceive of and enact empathy in…

ORNL Lightweighting Research Featured on MotorWeek

ScienceCinema

None

2018-06-06

PBS MotorWeek, television's longest running automotive series, featured ORNL lightweighting research for vehicle applications in an episode that aired in early April 2014. The crew captured footage of research including development of new metal alloys, additive manufacturing, carbon fiber production, advanced batteries, power electronics components, and neutron imaging applications for materials evaluation.

The Teening of Childhood.

ERIC Educational Resources Information Center

Hymowitz, Kay S.

2000-01-01

The market and advertising media aimed at children has skyrocketed in recent years. Many new products targeting 8-12-year-olds appeal to their sense of teen fashion, image consciousness, and independence from adults. Describes the development of this market aimed at early adolescents and how it is changing childhood as Americans have known it. (SM)

Establishment and early development of 'Kanza', 'Peruque', and other pecan cultivars in northern U.S. growing regions

USDA-ARS?s Scientific Manuscript database

Most pecan (Carya illinoensis) nut production in the northern range of the species (Missouri, Kansas, Northern Arkansas) is from managed wild trees. Orchards of trees grafted to improved cultivars are slowly being established in the region as economic opportunities improve. Pecan cultivars that are ...

First 5 Kern Annual Report, Fiscal Year 2011-2012

ERIC Educational Resources Information Center

Wang, Jianjun

2013-01-01

Scientific discoveries repeatedly confirmed the importance of brain growth during the first 5 years of child life. To support early childhood development, California voters passed Proposition 10 in 1998 to collect a 50 cent per pack tax on cigarettes and other tobacco products. Kern County Children and Families Commission (First 5 Kern) was…

First 5 Kern Annual Report: Fiscal Year 2012-2013

ERIC Educational Resources Information Center

Wang, Jianjun

2014-01-01

Scientific discoveries indicated the importance of brain growth during the first 5 years of child life. To support early childhood development, California voter passed Proposition 10 in 1998 to collect a 50 cent per pack tax on cigarettes and other tobacco products. Kern County Children and Families Commission (First 5 Kern) receives funding from…

Difficult Behavior in Early Childhood: Positive Discipline for PreK-3 Classrooms and Beyond

ERIC Educational Resources Information Center

Mah, Ronald

2006-01-01

Creating a classroom of attentive learners takes more than swift discipline. "Difficult Behavior" can help inspire positive behavioral change and healthy, productive development. Following Acknowledgments, About the Author and Introduction, the book is divided into five sections. Part I, The Role of Discipline, includes: (1) Discipline in…

Grazing effects on aboveground primary production and root biomass of early-seral, mid-seral, and undisturbed semiarid grassland

USGS Publications Warehouse

Milchunas, D.G.; Vandever, M.W.

2013-01-01

Annual/perennial and tall/short plant species differentially dominate early to late successional shortgrass steppe communities. Plant species can have different ratios of above-/below-ground biomass distributions and this can be modified by precipitation and grazing. We compared grazing effects on aboveground production and root biomass in early- and mid-seral fields and undisturbed shortgrass steppe. Production averaged across four years and grazed and ungrazed treatments were 246, 134, and 102 g m−2 yr−1 for the early-, mid-seral, and native sites, respectively, while root biomass averaged 358, 560, and 981 g m−2, respectively. Early- and mid-seral communities provided complimentary forage supplies but at the cost of root biomass. Grazing increased, decreased, or had no effect on aboveground production in early-, mid-seral, and native communities, and had no effect on roots in any. Grazing had some negative effects on early spring forage species, but not in the annual dominated early-seral community. Dominant species increased with grazing in native communities with a long evolutionary history of grazing by large herbivores, but had no effects on the same species in mid-seral communities. Effects of grazing in native communities in a region cannot necessarily be used to predict effects at other seral stages.

A study of material composition disclosure practices in green footwear products.

PubMed

Jacques, Jocelise J; Guimarães, Lia B M

2012-01-01

This work is based on the study of pioneering sustainable product development initiatives, and the analysis was guided by the cradle-to-cradle concept, which sees the waste of a given process as raw material for another, just like it happens in nature. Several studies on human factors have focused on factory conditions and workers dealing with product assembly. This research, however, relates more to consumer behavior, product use and end-of-life. The purchase of more environmentally- friendly products, in particular, is heavily influenced by the information made available by the companies. In this scenario, this article discusses three early but notable efforts on green product development, focusing on the disclosure practices adopted by the companies regarding the composition of their products. Research and data collection has focused on the footwear industry, whose products satisfy a basic human need and are ubiquitous worldwide. The use of hazardous materials and chemicals in shoe manufacturing, particularly the use of chromium - a highly toxic element - in addition to toxic solvents and adhesives and non-recyclable synthetic materials can pose serious risks to human health and the environment, even though the consumer usually is not aware of all the relevant characteristics of this kind of product.

Marijuana, Spice ‘herbal high’, and early neural development: implications for rescheduling and legalization

PubMed Central

Psychoyos, Delphine; Vinod, K. Yaragudri

2014-01-01

Marijuana is the most widely used illicit drug by pregnant women in the world. In utero exposure to Δ9-tetrahydrocannabinol (Δ9-THC), a major psychoactive component of marijuana, is associated with an increased risk for anencephaly and neurobehavioural deficiencies in the offspring, including attention deficit hyperactivity disorder (ADHD), learning disabilities, and memory impairment. Recent studies demonstrate that the developing central nervous system (CNS) is susceptible to the effects of Δ9-THC and other cannabimimetics, including the psychoactive ingredients of the branded product ‘Spice’ branded products. These exocannabinoids interfere with the function of an endocannabinoid (eCB) system, present in the developing CNS from E12.5 (week 5 of gestation in humans), and required for proliferation, migration, and differentiation of neurons. Until recently, it was not known whether the eCB system is also present in the developing CNS during the initial stages of its ontogeny, i.e. from E7.0 onwards (week 2 of gestation in humans), and if so, whether this system is also susceptible to the action of exocannabinoids. Here, we review current data, in which the presence of an eCB system during the initial stage of development of the CNS is demonstrated. Furthermore, we focus on recent advances on the effect of canabimimetics on early gestation. The relevance of these findings and potential adverse developmental consequences of in utero exposure to ‘high potency’ marijuana, Spice branded products and/or cannabinoid research chemicals during this period is discussed. Finally, we address the implication of these findings in terms of the potential dangers of synthetic cannabinoid use during pregnancy, and the ongoing debate over legalization of marijuana. PMID:22887867

Differential involvement of ipsilateral and contralateral spinal cord astrocyte D-serine in carrageenan-induced mirror-image pain: role of σ1 receptors and astrocyte gap junctions.

PubMed

Choi, Hoon-Seong; Roh, Dae-Hyun; Yoon, Seo-Yeon; Choi, Sheu-Ran; Kwon, Soon-Gu; Kang, Suk-Yun; Moon, Ji-Young; Han, Ho-Jae; Beitz, Alvin J; Lee, Jang-Hern

2018-02-01

Although we have recently demonstrated that spinal astrocyte gap junctions mediate the development of mirror-image pain (MIP), it is still unclear which astrocyte-derived factor is responsible for the development of MIP and how its production is controlled. In the present study, we focused on the role of ipsilateral versus contralateral D-serine in the development of MIP and investigated the possible involvement of σ1 receptors and gap junctions in astrocyte D-serine production. Following carrageenan injection, mechanical allodynia was tested at various time points to examine the effect of individual drugs. Immunohistochemistry and Western blot analyses were performed to clarify the expression levels of spinal D-serine, serine racemase, σ1 receptors and connexin 43. The expression of ipsilateral D-serine was up-regulated during the early phase of inflammation, while contralateral D-serine increased during the later phase of inflammation. The pharmacological inhibition of D-serine during the early phase blocked the development of both ipsilateral and contralateral mechanical allodynia. However, the inhibition of D-serine during the later phase of inflammation blocked contralateral, but not ipsilateral mechanical allodynia. Furthermore, the inhibition of σ1 receptors during the earlier phase of inflammation inhibited the increase in ipsilateral D-serine. Conversely, the blockade of astrocyte gap junctions suppressed the up-regulation of contralateral D-serine during the later phase of inflammation. Spinal astrocyte D-serine plays an important role in the development of mirror-image pain. Furthermore, σ1 receptors and astrocyte gap junction signalling mediate ipsilateral and contralateral D-serine production respectively. © 2017 The British Pharmacological Society.

Early career mentoring for translational researchers: mentee perspectives on challenges and issues.

PubMed

Keller, Thomas E; Collier, Peter J; Blakeslee, Jennifer E; Logan, Kay; McCracken, Karen; Morris, Cynthia

2014-01-01

The education and training of early career biomedical translational researchers often involves formal mentoring by more experienced colleagues. This study investigated the nature of these mentoring relationships from the perspective of mentees. The objective was to understand the challenges and issues encountered by mentees in forming and maintaining productive mentoring relationships. Three focus groups (n=14) were conducted with early career researchers who had mentored career development awards. Thematic analysis identified, categorized, and illustrated the challenges and issues reported by mentees. The range of mentee challenges was reflected in five major categories: (a) network--finding appropriate mentors to meet various needs; (b) access--structuring schedules and opportunities to receive mentoring; (c) expectations--negotiating the mechanics of the mentoring relationship and its purpose; (d) alignment--managing mentor-mentee mismatches regarding interests, priorities, and goals; and (e) skills and supports--developing the institutional supports to be successful. Mentoring relationships created for academic training and career development contend with tasks common to many other relationships, namely, recognizing compatibility, finding time, establishing patterns, agreeing to goals, and achieving aims. Identifying challenges faced by mentees can facilitate the development of appropriate trainings and supports to foster mentoring relationships in academic and career settings.

Mitochondrial Reactive Oxygen Species and Kidney Hypoxia in the Development of Diabetic Nephropathy

PubMed Central

Schiffer, Tomas A.; Friederich-Persson, Malou

2017-01-01

The underlying mechanisms in the development of diabetic nephropathy are currently unclear and likely consist of a series of dynamic events from the early to late stages of the disease. Diabetic nephropathy is currently without curative treatments and it is acknowledged that even the earliest clinical manifestation of nephropathy is preceded by an established morphological renal injury that is in turn preceded by functional and metabolic alterations. An early manifestation of the diabetic kidney is the development of kidney hypoxia that has been acknowledged as a common pathway to nephropathy. There have been reports of altered mitochondrial function in the diabetic kidney such as altered mitophagy, mitochondrial dynamics, uncoupling, and cellular signaling through hypoxia inducible factors and AMP-kinase. These factors are also likely to be intertwined in a complex manner. In this review, we discuss how these pathways are connected to mitochondrial production of reactive oxygen species (ROS) and how they may relate to the development of kidney hypoxia in diabetic nephropathy. From available literature, it is evident that early correction and/or prevention of mitochondrial dysfunction may be pivotal in the prevention and treatment of diabetic nephropathy. PMID:28443030

Mitochondrial Reactive Oxygen Species and Kidney Hypoxia in the Development of Diabetic Nephropathy.

PubMed

Schiffer, Tomas A; Friederich-Persson, Malou

2017-01-01

The underlying mechanisms in the development of diabetic nephropathy are currently unclear and likely consist of a series of dynamic events from the early to late stages of the disease. Diabetic nephropathy is currently without curative treatments and it is acknowledged that even the earliest clinical manifestation of nephropathy is preceded by an established morphological renal injury that is in turn preceded by functional and metabolic alterations. An early manifestation of the diabetic kidney is the development of kidney hypoxia that has been acknowledged as a common pathway to nephropathy. There have been reports of altered mitochondrial function in the diabetic kidney such as altered mitophagy, mitochondrial dynamics, uncoupling, and cellular signaling through hypoxia inducible factors and AMP-kinase. These factors are also likely to be intertwined in a complex manner. In this review, we discuss how these pathways are connected to mitochondrial production of reactive oxygen species (ROS) and how they may relate to the development of kidney hypoxia in diabetic nephropathy. From available literature, it is evident that early correction and/or prevention of mitochondrial dysfunction may be pivotal in the prevention and treatment of diabetic nephropathy.

[The role of oxidative stress in placental-related diseases of pregnancy].

PubMed

Jauniaux, E; Burton, G J

2016-10-01

In normal pregnancies, the earliest stages of development take place in a low oxygen (O 2 ) environment. This physiological hypoxia of the early gestational sac protects the developing fetus against the deleterious and teratogenic effects of O 2 free radicals. Oxidative stress is manifested at the maternal-fetal interface from early pregnancy onwards. In early pregnancy, a well-controlled oxidative stress plays a role in modulating placental development, functions and remodelling. Focal trophoblastic oxidative damage and progressive villous degeneration trigger the formation of the fetal membranes, which is an essential developmental step enabling vaginal delivery. Our data have demonstrated that the first trimester placenta in humans is histiotrophic and not haemochorial. The development and maintenance of a physiological O 2 gradient between the uterine and fetal circulations is also essential for placental functions, such as transport and hormonal synthesis. Pathological oxidative stress arises when the production of reactive O 2 species overwhelms the intrinsic anti-oxidant defences causing indiscriminate damage to biological molecules, leading to loss of function and cell death. We here review the role of oxidative stress in the pathophysiology of miscarriage, pre-eclampsia and fetal growth restriction. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Driving CT developments the last mile: case examples of successful and somewhat less successful translations into clinical practice

NASA Astrophysics Data System (ADS)

Sodickson, Aaron D.

2017-03-01

CT technology has advanced rapidly in recent years, yet not all innovations translate readily into clinical practice. Technology advances must meet certain key requirements to make it into routine use: They must provide a well-defined clinical benefit. They must be easy to use and integrate readily into existing workflows, or better still, further streamline these workflows. These requirements heavily favor fully integrated or automated solutions that remove the human factor and provide a reproducible output independent of operator skill level. Further, to achieve these aims, collaboration with the ultimate end users is needed as early as possible in the development cycle, not just at the point of product testing. Technology innovators are encouraged to engage such collaborators even at early stages of feature or product definition. This manuscript highlights these concepts through exploration of challenging areas in CT imaging in an Emergency Department setting. Technique optimization for pulmonary embolus CT is described as an example of successful integration of multiple advances in radiation dose reduction and imaging speed. The typical workflow of a trauma "pan-scan" (incorporating scans from head through pelvis) is described to highlight workflow challenges and opportunities for improvement. Finally, Dual Energy CT is discussed to highlight the undeniable clinical value of the material characterization it provides, yet also its surprisingly slow integration into routine use beyond early adopters.

Detecting early signs of the 2007–2008 crisis in the world trade

PubMed Central

Saracco, Fabio; Di Clemente, Riccardo; Gabrielli, Andrea; Squartini, Tiziano

2016-01-01

Since 2007, several contributions have tried to identify early-warning signals of the financial crisis. However, the vast majority of analyses has focused on financial systems and little theoretical work has been done on the economic counterpart. In the present paper we fill this gap and employ the theoretical tools of network theory to shed light on the response of world trade to the financial crisis of 2007 and the economic recession of 2008–2009. We have explored the evolution of the bipartite World Trade Web (WTW) across the years 1995–2010, monitoring the behavior of the system both before and after 2007. Our analysis shows early structural changes in the WTW topology: since 2003, the WTW becomes increasingly compatible with the picture of a network where correlations between countries and products are progressively lost. Moreover, the WTW structural modification can be considered as concluded in 2010, after a seemingly stationary phase of three years. We have also refined our analysis by considering specific subsets of countries and products: the most statistically significant early-warning signals are provided by the most volatile macrosectors, especially when measured on developing countries, suggesting the emerging economies as being the most sensitive ones to the global economic cycles. PMID:27461469

Detecting early signs of the 2007-2008 crisis in the world trade.

PubMed

Saracco, Fabio; Di Clemente, Riccardo; Gabrielli, Andrea; Squartini, Tiziano

2016-07-27

Since 2007, several contributions have tried to identify early-warning signals of the financial crisis. However, the vast majority of analyses has focused on financial systems and little theoretical work has been done on the economic counterpart. In the present paper we fill this gap and employ the theoretical tools of network theory to shed light on the response of world trade to the financial crisis of 2007 and the economic recession of 2008-2009. We have explored the evolution of the bipartite World Trade Web (WTW) across the years 1995-2010, monitoring the behavior of the system both before and after 2007. Our analysis shows early structural changes in the WTW topology: since 2003, the WTW becomes increasingly compatible with the picture of a network where correlations between countries and products are progressively lost. Moreover, the WTW structural modification can be considered as concluded in 2010, after a seemingly stationary phase of three years. We have also refined our analysis by considering specific subsets of countries and products: the most statistically significant early-warning signals are provided by the most volatile macrosectors, especially when measured on developing countries, suggesting the emerging economies as being the most sensitive ones to the global economic cycles.

Detecting early signs of the 2007-2008 crisis in the world trade

NASA Astrophysics Data System (ADS)

Saracco, Fabio; di Clemente, Riccardo; Gabrielli, Andrea; Squartini, Tiziano

2016-07-01

Since 2007, several contributions have tried to identify early-warning signals of the financial crisis. However, the vast majority of analyses has focused on financial systems and little theoretical work has been done on the economic counterpart. In the present paper we fill this gap and employ the theoretical tools of network theory to shed light on the response of world trade to the financial crisis of 2007 and the economic recession of 2008-2009. We have explored the evolution of the bipartite World Trade Web (WTW) across the years 1995-2010, monitoring the behavior of the system both before and after 2007. Our analysis shows early structural changes in the WTW topology: since 2003, the WTW becomes increasingly compatible with the picture of a network where correlations between countries and products are progressively lost. Moreover, the WTW structural modification can be considered as concluded in 2010, after a seemingly stationary phase of three years. We have also refined our analysis by considering specific subsets of countries and products: the most statistically significant early-warning signals are provided by the most volatile macrosectors, especially when measured on developing countries, suggesting the emerging economies as being the most sensitive ones to the global economic cycles.

Human dimensions of early successional landscapes in the eastern United States

Treesearch

Paul H. Gobster

2001-01-01

People interactions wit early successional landscapes are varied and diverse. I review 3 key ways thta people perceive, use, and value forest landscapes, emphasizing selected types of early successional landscapes in the eastern United States(U.S.): production and comsumption of timber and nontimber forest products, visual and aesthetic perceptions , and recreational...

IL-17 Production of Neutrophils Enhances Antibacteria Ability but Promotes Arthritis Development During Mycobacterium tuberculosis Infection.

PubMed

Hu, Shengfeng; He, Wenting; Du, Xialin; Yang, Jiahui; Wen, Qian; Zhong, Xiao-Ping; Ma, Li

2017-09-01

To our knowledge, no studies have examined the role of IL-17 production by neutrophils in immune defense against Mycobacterium tuberculosis (MTB) infection and the pathogenesis of rheumatoid arthritis (RA) caused by MTB infection. Here, we determined that neutrophils express IL-17 in an autocrine IL-6- and IL-23-dependent manner during MTB infection. MTB H37Rv-induced IL-6 production was dependent on the NF-κB, p38, and JNK signaling pathways; however, IL-23 production was dependent on NF-κB and EKR in neutrophils. Furthermore, we found that Toll-like receptor 2 (TLR2) and TLR4 mediated the activation of the kinases NF-κB, p38, ERK, and JNK and the production of IL-6, IL-23, and IL-17 in neutrophils infected with MTB H37Rv. Autocrine IL-17 produced by neutrophils played a vital role in inhibiting MTB H37Rv growth by mediating reactive oxygen species production and the migration of neutrophils in the early stages of infection. However, IL-17 production by neutrophils contributed to collagen-induced arthritis development during MTB infection. Our findings identify a protective mechanism against mycobacteria and the pathogenic role of MTB in arthritis development. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

IPAD: Integrated Programs for Aerospace-vehicle Design

NASA Technical Reports Server (NTRS)

Miller, R. E., Jr.

1985-01-01

Early work was performed to apply data base technology in support of the management of engineering data in the design and manufacturing environments. The principal objective of the IPAD project is to develop a computer software system for use in the design of aerospace vehicles. Two prototype systems are created for this purpose. Relational Information Manager (RIM) is a successful commercial product. The IPAD Information Processor (IPIP), a much more sophisticated system, is still under development.

Situation Awareness: Papers and Annotated Bibliography

DTIC Science & Technology

1994-06-01

identification 133. McKinley, R.L., Erikson , M.A., and D’Angelo, W.R. (1994). 3-Dimensional auditory displays: Development , applications, and...constructed. The second paper, by Dr. Michael Vidulich, was originally written during the early stages of the SAINT team’s response to SA concerns raised...refers to how SA is developed and maintained during flight, while the product is the resultant, elusive thing we call SA itself (Tenney, Adams, Pew

MOD-2 wind turbine system concept and preliminary design report. Volume 2: Detailed report

NASA Technical Reports Server (NTRS)

1979-01-01

The configuration development of the MOD-2 wind turbine system (WTS) is documented. The MOD-2 WTS project is a continuation of DOE programs to develop and achieve early commercialization of wind energy. The MOD-2 is design optimized for commercial production rates which, in multiunit installations, will be integrated into a utility power grid and achieve a cost of electricity at less than four cents per kilowatt hour.

Concept of Operations Visualization for Ares I Production

NASA Technical Reports Server (NTRS)

Chilton, Jim; Smith, David Alan

2008-01-01

Establishing Computer Aided Design models of the Ares I production facility, tooling and vehicle components and integrating them into manufacturing visualizations/simulations allows Boeing and NASA to collaborate real time early in the design/development cycle. This collaboration identifies cost effective and lean solutions that can be easily shared with Ares stakeholders (e.g., other NASA Centers and potential science users). These Ares I production visualizations and analyses by their nature serve as early manufacturing improvement precursors for other Constellation elements to be built at the Michoud Assembly Facility such as Ares V and the Altair Lander. Key to this Boeing and Marshall Space Flight Center collaboration has been the use of advanced virtual manufacturing tools to understand the existing Shuttle era infrastructure and trade potential modifications to support Ares I production. These approaches are then used to determine an optimal manufacturing configuration in terms of labor efficiency, safety and facility enhancements. These same models and tools can be used in an interactive simulation of Ares I and V flight to the Space Station or moon to educate the human space constituency (e.g., government, academia, media and the public) in order to increase national and international understanding of Constellation goals and benefits.

User Experience Evaluation Methods in Product Development (UXEM'09)

NASA Astrophysics Data System (ADS)

Roto, Virpi; Väänänen-Vainio-Mattila, Kaisa; Law, Effie; Vermeeren, Arnold

High quality user experience (UX) has become a central competitive factor of product development in mature consumer markets [1]. Although the term UX originated from industry and is a widely used term also in academia, the tools for managing UX in product development are still inadequate. A prerequisite for designing delightful UX in an industrial setting is to understand both the requirements tied to the pragmatic level of functionality and interaction and the requirements pertaining to the hedonic level of personal human needs, which motivate product use [2]. Understanding these requirements helps managers set UX targets for product development. The next phase in a good user-centered design process is to iteratively design and evaluate prototypes [3]. Evaluation is critical for systematically improving UX. In many approaches to UX, evaluation basically needs to be postponed until the product is fully or at least almost fully functional. However, in an industrial setting, it is very expensive to find the UX failures only at this phase of product development. Thus, product development managers and developers have a strong need to conduct UX evaluation as early as possible, well before all the parts affecting the holistic experience are available. Different types of products require evaluation on different granularity and maturity levels of a prototype. For example, due to its multi-user characteristic, a community service or an enterprise resource planning system requires a broader scope of UX evaluation than a microwave oven or a word processor that is meant for a single user at a time. Before systematic UX evaluation can be taken into practice, practical, lightweight UX evaluation methods suitable for different types of products and different phases of product readiness are needed. A considerable amount of UX research is still about the conceptual frameworks and models for user experience [4]. Besides, applying existing usability evaluation methods (UEMs) without adaptation to evaluate UX may lead to some scoping issues. Consequently, there is a strong need to put UX evaluation from research into practice.

Early Morphological Productivity in Hungarian: Evidence from Sentence Repetition and Elicited Production

ERIC Educational Resources Information Center

Gabor, Balint; Lukacs, Agnes

2012-01-01

This paper investigates early productivity of morpheme use in Hungarian children aged between 2 ; 1 and 5 ; 3. Hungarian has a rich morphology which is the core marker of grammatical functions. A new method is introduced using the novel word paradigm in a sentence repetition task with masked inflections (i.e. a disguised elicited production task).…

Time-dependent mediators of HPA axis activation following live Escherichia coli

PubMed Central

Zimomra, Z. R.; Porterfield, V. M.; Camp, R. M.

2011-01-01

The hypothalamus-pituitary-adrenal (HPA) axis is activated during an immune challenge to liberate energy and modulate immune responses via feedback and regulatory mechanisms. Inflammatory cytokines and prostaglandins are known contributors to HPA activation; however, most previous studies only looked at specific time points following LPS administration. Since whole bacteria have different immune stimulatory properties compared with LPS, the aim of the present studies was to determine whether different immune products contribute to HPA activation at different times following live Escherichia coli challenge. Sprague-Dawley rats were injected intraperitoneally with E. coli (2.5 × 107 CFU) and a time course of circulating corticosterone, ACTH, inflammatory cytokines, and PGE2 was developed. Plasma corticosterone peaked 0.5 h after E. coli and steadily returned to baseline by 4 h. Plasma PGE2 correlated with the early rise in plasma corticosterone, whereas inflammatory cytokines were not detected until 2 h. Pretreatment with indomethacin, a nonselective cyclooxygenase inhibitor, completely blocked the early rise in plasma corticosterone, but not at 2 h, whereas pretreatment with IL-6 antibodies had no effect on the early rise in corticosterone but attenuated corticosterone at 2 h. Interestingly, indomethacin pretreatment did not completely block the early rise in corticosterone following a higher concentration of E. coli (2.5 × 108 CFU). Further studies revealed that only animals receiving indomethacin prior to E. coli displayed elevated plasma and liver cytokines at early time points (0.5 and 1 h), suggesting prostaglandins suppress early inflammatory cytokine production. Overall, these data indicate prostaglandins largely mediate the early rise in plasma corticosterone, while inflammatory cytokines contribute to maintaining levels of corticosterone at later time points. PMID:21917906

CAT--the new committee for advanced therapies at the European Medicines Agency.

PubMed

Celis, P

2010-01-01

The Regulation on Advanced Therapies (Regulation (EC) 1394/2007) establishes a new scientific committee, the Committee for Advanced Therapies (CAT), at the European Medicines Agency. The CAT is composed of experts in the field of Advanced Therapy Medicinal Products (ATMPs)--gene and cell therapy and tissue engineered products--and is responsible for the evaluation of the marketing authorisation applications for this novel class of products. The CAT is also involved in all scientific advice on ATMPs and in two new regulatory procedures for ATMPs, the classification and the certification procedures. The CAT will also play a key role in early contacts with developers of ATMPs.

The bradykinin B2 receptor in the early immune response against Listeria infection.

PubMed

Kaman, Wendy E; Wolterink, Arthur F W M; Bader, Michael; Boele, Linda C L; van der Kleij, Desiree

2009-02-01

The endogenous danger signal bradykinin was recently found implicated in the development of immunity against parasites via dendritic cells. We here report an essential role of the B(2) (B(2)R) bradykinin receptor in the early immune response against Listeria infection. Mice deficient in B(2)R (B(2)R(-/-) mice) were shown to suffer from increased hepatic bacterial burden and concomitant dramatic weight loss during infection with Listeria monocytogenes. Levels of cytokines known to play a pivotal role in the early phase immune response against L. monocytogenes, IL-12p70 and IFN-gamma, were reduced in B(2)R(-/-) mice. To extend these findings to the human system, we show that bradykinin potentiates the production of IL-12p70 in human monocyte-derived dendritic cells. Thus, we show that bradykinin and the B(2)R play a role in early innate immune functions during bacterial infection.

Comparing different models of the development of verb inflection in early child Spanish.

PubMed

Aguado-Orea, Javier; Pine, Julian M

2015-01-01

How children acquire knowledge of verb inflection is a long-standing question in language acquisition research. In the present study, we test the predictions of some current constructivist and generativist accounts of the development of verb inflection by focusing on data from two Spanish-speaking children between the ages of 2;0 and 2;6. The constructivist claim that children's early knowledge of verb inflection is only partially productive is tested by comparing the average number of different inflections per verb in matched samples of child and adult speech. The generativist claim that children's early use of verb inflection is essentially error-free is tested by investigating the rate at which the children made subject-verb agreement errors in different parts of the present tense paradigm. Our results show: 1) that, although even adults' use of verb inflection in Spanish tends to look somewhat lexically restricted, both children's use of verb inflection was significantly less flexible than that of their caregivers, and 2) that, although the rate at which the two children produced subject-verb agreement errors in their speech was very low, this overall error rate hid a consistent pattern of error in which error rates were substantially higher in low frequency than in high frequency contexts, and substantially higher for low frequency than for high frequency verbs. These results undermine the claim that children's use of verb inflection is fully productive from the earliest observable stages, and are consistent with the constructivist claim that knowledge of verb inflection develops only gradually.

MODIS Land Data Products: Generation, Quality Assurance and Validation

NASA Technical Reports Server (NTRS)

Masuoka, Edward; Wolfe, Robert; Morisette, Jeffery; Sinno, Scott; Teague, Michael; Saleous, Nazmi; Devadiga, Sadashiva; Justice, Christopher; Nickeson, Jaime

2008-01-01

The Moderate Resolution Imaging Spectrometer (MODIS) on-board NASA's Earth Observing System (EOS) Terra and Aqua Satellites are key instruments for providing data on global land, atmosphere, and ocean dynamics. Derived MODIS land, atmosphere and ocean products are central to NASA's mission to monitor and understand the Earth system. NASA has developed and generated on a systematic basis a suite of MODIS products starting with the first Terra MODIS data sensed February 22, 2000 and continuing with the first MODIS-Aqua data sensed July 2, 2002. The MODIS Land products are divided into three product suites: radiation budget products, ecosystem products, and land cover characterization products. The production and distribution of the MODIS Land products are described, from initial software delivery by the MODIS Land Science Team, to operational product generation and quality assurance, delivery to EOS archival and distribution centers, and product accuracy assessment and validation. Progress and lessons learned since the first MODIS data were in early 2000 are described.

A Measurement Framework for Team Level Assessment of Innovation Capability in Early Requirements Engineering

NASA Astrophysics Data System (ADS)

Regnell, Björn; Höst, Martin; Nilsson, Fredrik; Bengtsson, Henrik

When developing software-intensive products for a market-place it is important for a development organisation to create innovative features for coming releases in order to achieve advantage over competitors. This paper focuses on assessment of innovation capability at team level in relation to the requirements engineering that is taking place before the actual product development projects are decided, when new business models, technology opportunities and intellectual property rights are created and investigated through e.g. prototyping and concept development. The result is a measurement framework focusing on four areas: innovation elicitation, selection, impact and ways-of-working. For each area, candidate measurements were derived from interviews to be used as inspiration in the development of a tailored measurement program. The framework is based on interviews with participants of a software team with specific innovation responsibilities and validated through cross-case analysis and feedback from practitioners.

Water requirements for livestock production: a global perspective.

PubMed

Schlink, A C; Nguyen, M L; Viljoen, G J

2010-12-01

Water is a vital but poorly studied component of livestock production. It is estimated that livestock industries consume 8% of the global water supply, with most of that water being used for intensive, feed-based production. This study takes a broad perspective of livestock production as a component of the human food chain, and considers the efficiency of its water use. Global models are in the early stages of development and do not distinguish between developing and developed countries, or the production systems within them. However, preliminary indications are that, when protein production is adjusted for biological value in the human diet, no plant protein is significantly more efficient at using water than protein produced from eggs, and only soybean is more water efficient than milk and goat and chicken meat. In some regions, especially developing countries, animals are not used solely for food production but also provide draught power, fibre and fertiliser for crops. In addition, animals make use of crop by-products that would otherwise go to waste. The livestock sector is the fastest-growing agricultural sector, which has led to increasing industrialisation and, in some cases, reduced environmental constraints. In emerging economies, increasing involvement in livestock is related to improving rural wealth and increasing consumption of animal protein. Water usage for livestock production should be considered an integral part of agricultural water resource management, taking into account the type of production system (e.g. grain-fed or mixed crop-livestock) and scale (intensive or extensive), the species and breeds of livestock, and the social and cultural aspects of livestock farming in various countries.

Abundance of adverse environmental conditions during critical stages of crop production in Northern Germany.

PubMed

Strer, Maximilian; Svoboda, Nikolai; Herrmann, Antje

2018-01-01

Understanding the abundance of adverse environmental conditions e.g. frost, drought, and heat during critical crop growth stages, which are assumed to be altered by climate change, is crucial for an accurate risk assessment for cropping systems. While a lengthening of the vegetation period may be beneficial, higher frequencies of heat or frost events and drought spells are generally regarded as harmful. The objective of the present study was to quantify shifts in maize and wheat phenology and the occurrence of adverse environmental conditions during critical growth stages for four regions located in the North German Plain. First, a statistical analysis of phenological development was conducted based on recent data (1981-2010). Next, these data were used to calibrate the DSSAT-CERES wheat and maize models, which were then used to run three climate projections representing the maximum, intermediate and minimum courses of climate development within the RCP 8.5 continuum during the years 2021-2050. By means of model simulation runs and statistical analysis, the climate data were evaluated for the abundance of adverse environmental conditions during critical development stages, i.e. the stages of early crop development, anthesis, sowing and harvest. Proxies for adverse environmental conditions included thresholds of low and high temperatures as well as soil moisture. The comparison of the baseline climate and future climate projections showed a significant increase in the abundance of adverse environmental conditions during critical growth stages in the future. The lengthening of the vegetation period in spring did not compensate for the increased abundance of high temperatures, e.g. during anthesis. The results of this study indicate the need to develop adaptation strategies, such as implementing changes in cropping calendars. An increase in frost risk during early development, however, reveals the limited feasibility of early sowing as a mitigation strategy. In addition, the abundance of low soil water contents that hamper important production processes such as sowing and harvest were found to increase locally.

Out of the Ashes: The Life, Death, and Rebirth of the “Safer” Cigarette in the United States

PubMed Central

Fairchild, Amy; Colgrove, James

2004-01-01

From 1964 through the early 1980s, both federal and voluntary agencies endorsed the concept of “safer” cigarettes. Beginning in the mid-1980s, several factors, including revelations of tobacco industry malfeasance, the development of nicotine replacement therapy, and the reconceptualization of smoking as a chronic disease, led to “safer” cigarettes being discredited. In the past few years, some public health professionals have begun to reconsider the viability of developing such products. The issue before us is stark: will a commitment to limiting the toll exacted by smoking preclude the tolerance of a product that while not safe may possibly be safer? PMID:14759927

A turbocharger for the 1990s

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

Johnson, E.R.

1991-07-01

This paper reports that the large-bore engines of the 1970s and 1980s have seen tremendous amounts of technological improvements. The key buzzwords were: Lower the emissions, and improve the fuel consumption. As the 1990s approach dramatic improvements in specific outputs along with continued research to further improve emissions and fuel consumption. One of the keys to success will have to be the degree to which the industry responds with improvements in turbocharger performance. In 1985, Cooper Bessemer Rotating Products Division began a program to develop the turbocharger of the 1990s. This paper will describe the development of the CB turbochargermore » series from concept to early production.« less

PrimeSupplier Cross-Program Impact Analysis and Supplier Stability Indicator Simulation Model

NASA Technical Reports Server (NTRS)

Calluzzi, Michael

2009-01-01

PrimeSupplier, a supplier cross-program and element-impact simulation model, with supplier solvency indicator (SSI), has been developed so that the shuttle program can see early indicators of supplier and product line stability, while identifying the various elements and/or programs that have a particular supplier or product designed into the system. The model calculates two categories of benchmarks to determine the SSI, with one category focusing on agency programmatic data and the other focusing on a supplier's financial liquidity. PrimeSupplier was developed to help NASA smoothly transition design, manufacturing, and repair operations from the Shuttle program to the Constellation program, without disruption in the industrial supply base.

Design study of RL10 derivatives. Volume 3, part 2: Operational and flight support plan. [analysis of transportation requirements for rocket engine in support of space tug program

NASA Technical Reports Server (NTRS)

Shubert, W. C.

1973-01-01

Transportation requirements are considered during the engine design layout reviews and maintenance engineering analyses. Where designs cannot be influenced to avoid transportation problems, the transportation representative is advised of the problems permitting remedies early in the program. The transportation representative will monitor and be involved in the shipment of development engine and GSE hardware between FRDC and vehicle manufacturing plant and thereby will be provided an early evaluation of the transportation plans, methods and procedures to be used in the space tug support program. Unanticipated problems discovered in the shipment of development hardware will be known early enough to permit changes in packaging designs and transportation plans before the start of production hardware and engine shipments. All conventional transport media can be used for the movement of space tug engines. However, truck transport is recommended for ready availability, variety of routes, short transit time, and low cost.

Dietary aspirin decreases the stage of ovarian cancer in the hen.

PubMed

Urick, M E; Giles, J R; Johnson, P A

2009-01-01

We aimed to determine the effects of dietary aspirin treatment on ovarian cancer incidence and progression in the hen as a model for the human disease. Hens were fed a standard layer diet (control) or the same diet containing 0.1% aspirin for 1 year. Liver prostaglandin E(2) (PGE(2)) was measured using an enzyme immunoassay. Incidence and stage of ovarian cancer were determined through necropsy and immunohistochemical analysis of ovarian sections for each hen. Aspirin treatment decreased liver PGE(2) in treated hens as compared to control hens. Treatment with aspirin did not decrease ovarian cancer incidence. Significantly more control hens developed late stage ovarian cancer than early stage, while the same was not true for aspirin-treated hens. Hens that developed ovarian cancer, even early ovarian cancer, produced significantly fewer eggs in the year prior to diagnosis than hens without ovarian cancer. Aspirin treatment may inhibit the progression of ovarian cancer in the hen and egg production may be used to identify hens with early stages of the disease.

Early life mortality and height in Indian states

PubMed Central

Coffey, Diane

2014-01-01

Height is a marker for health, cognitive ability and economic productivity. Recent research on the determinants of height suggests that postneonatal mortality predicts height because it is a measure of the early life disease environment to which a cohort is exposed. This article advances the literature on the determinants of height by examining the role of early life mortality, including neonatal mortality, in India, a large developing country with a very short population. It uses state level variation in neonatal mortality, postneonatal mortality, and pre-adult mortality to predict the heights of adults born between 1970 and 1983, and neonatal and postneonatal mortality to predict the heights of children born between 1995 and 2005. In contrast to what is found in the literature on developed countries, I find that state level variation in neonatal mortality is a strong predictor of adult and child heights. This may be due to state level variation in, and overall poor levels of, pre-natal nutrition in India. PMID:25499239

Discrimination of dynamical system models for biological and chemical processes.

PubMed

Lorenz, Sönke; Diederichs, Elmar; Telgmann, Regina; Schütte, Christof

2007-06-01

In technical chemistry, systems biology and biotechnology, the construction of predictive models has become an essential step in process design and product optimization. Accurate modelling of the reactions requires detailed knowledge about the processes involved. However, when concerned with the development of new products and production techniques for example, this knowledge often is not available due to the lack of experimental data. Thus, when one has to work with a selection of proposed models, the main tasks of early development is to discriminate these models. In this article, a new statistical approach to model discrimination is described that ranks models wrt. the probability with which they reproduce the given data. The article introduces the new approach, discusses its statistical background, presents numerical techniques for its implementation and illustrates the application to examples from biokinetics.

Recovery Act: Waste Energy Project at AK Steel Corporation Middletown

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

Joyce, Jeffrey

2012-06-30

In 2008, Air Products and Chemicals, Inc. (“Air Products”) began development of a project to beneficially utilize waste blast furnace “topgas” generated in the course of the iron-making process at AK Steel Corporation’s Middletown, Ohio works. In early 2010, Air Products was awarded DOE Assistance Agreement DE-EE002736 to further develop and build the combined-cycle power generation facility. In June 2012, Air Products and AK Steel Corporation terminated work when it was determined that the project would not be economically viable at that time nor in the foreseeable future. The project would have achieved the FOA-0000044 Statement of Project Objectives bymore » demonstrating, at a commercial scale, the technology to capture, treat, and convert blast furnace topgas into electric power and thermal energy.« less

Concise Review: Process Development Considerations for Cell Therapy

PubMed Central

Brieva, Thomas; Raviv, Lior; Rowley, Jon; Niss, Knut; Brandwein, Harvey; Oh, Steve; Karnieli, Ohad

2015-01-01

The development of robust and well-characterized methods of production of cell therapies has become increasingly important as therapies advance through clinical trials toward approval. A successful cell therapy will be a consistent, safe, and effective cell product, regardless of the cell type or application. Process development strategies can be developed to gain efficiency while maintaining or improving safety and quality profiles. This review presents an introduction to the process development challenges of cell therapies and describes some of the tools available to address production issues. This article will provide a summary of what should be considered to efficiently advance a cellular therapy from the research stage through clinical trials and finally toward commercialization. The identification of the basic questions that affect process development is summarized in the target product profile, and considerations for process optimization are discussed. The goal is to identify potential manufacturing concerns early in the process so they may be addressed effectively and thus increase the probability that a therapy will be successful. Significance The present study contributes to the field of cell therapy by providing a resource for those transitioning a potential therapy from the research stage to clinical and commercial applications. It provides the necessary steps that, when followed, can result in successful therapies from both a clinical and commercial perspective. PMID:26315572

Mentoring Early-Career Faculty Researchers Is Important-But First "Train the Trainer".

PubMed

Sood, Akshay; Tigges, Beth; Helitzer, Deborah

2016-12-01

It has long been known that mentoring is critical to the success of junior faculty researchers. The controlled intervention study by Libby et al published in this issue of Academic Medicine demonstrates that institutional investment in a mentored research career development program for early-career faculty investigators provided significant long-term gains in grant productivity. Academic institutions hoping to replicate this program's success by launching similar mentoring programs for their junior faculty investigators will, however, find that the Achilles' heel lies in the scarcity of skilled research mentors and the relative lack of attention to and recognition of the importance of a supportive institutional climate for mentoring. It is essential, therefore, to begin by developing programs to "train the trainer" as well as programs and policies to support mentors. As a recent trial at 16 Clinical and Translational Science Award institutions demonstrated, competency-based, structured research mentor training can improve mentors' skills.In this Commentary, the authors offer a comprehensive two-pronged framework for mentor development with elements that address both individual mentoring competencies and the institutional climate for mentoring. The framework depicts the gaps, activities, and outcomes that a mentor development program can address. Activities directed at changing the institutional climate related to mentor development should complement training activities for individual mentors. The authors propose that employing this framework's approach to mentor development will lead to the desired impact: to increase the competence, productivity, and retention of a diverse clinical and translational research workforce.

New Capabilities With Dry Silver Recording Materials

NASA Astrophysics Data System (ADS)

Morgan, David A.

1987-04-01

Dry Silver technology was discovered at 3M and introduced into various imaging applications in the mid-sixties. In the early 1980's, quality films and papers with extended spectral responses, greater dynamic ranges, and improved sensitivity and edge acuity were introduced into sophisticated imaging systems. These products also have improved shelf life at elevated storage temperatures, and improved print stability. At the present time, 3M is developing a full-color dry silver product. This product has the same rapid-access, easy-to-use characteristics as the black and white dry silver recording materials. It has high resolution, long gray scale, and adequate sensitivity for CRT's and other electronically addressable exposure devices. The product can be processed in the same processors used for the black and white dry silver products.

Economic evaluation of medical tests at the early phases of development: a systematic review of empirical studies.

PubMed

Frempong, Samuel N; Sutton, Andrew J; Davenport, Clare; Barton, Pelham

2018-02-01

There is little specific guidance on the implementation of cost-effectiveness modelling at the early stage of test development. The aim of this study was to review the literature in this field to examine the methodologies and tools that have been employed to date. Areas Covered: A systematic review to identify relevant studies in established literature databases. Five studies were identified and included for narrative synthesis. These studies revealed that there is no consistent approach in this growing field. The perspective of patients and the potential for value of information (VOI) to provide information on the value of future research is often overlooked. Test accuracy is an essential consideration, with most studies having described and included all possible test results in their analysis, and conducted extensive sensitivity analyses on important parameters. Headroom analysis was considered in some instances but at the early development stage (not the concept stage). Expert commentary: The techniques available to modellers that can demonstrate the value of conducting further research and product development (i.e. VOI analysis, headroom analysis) should be better utilized. There is the need for concerted efforts to develop rigorous methodology in this growing field to maximize the value and quality of such analysis.

Guidelines for Successful Use and Communication of Instrument Heritage in Early Mission Development with a Focus on Spectrometers

NASA Technical Reports Server (NTRS)

Baker, Elizabeth E.

2012-01-01

Heritage is important for both cost and risk related issues and as such, it is heavily discussed in NASA proposal evaluations. If used and communicated efficiently, heritage can lower both the perception of risk and the associated costs. Definitions of heritage vary between engineering, cost, and scientific communities, but when applied appropriately, heritage provides a benefit to the proposed mission. By making an instrument at least once before, the cost of producing it again can be reduced. The time and effort needed to develop the instrument concept and test the product represent an expense that can be lowered through the use of a previously built and developed instrument. This same thought can be applied when using a flight spare or build-to-print model of the heritage instrument. The lowered perception of risk is a result of the confidence gained in the instrument through successful use in the target environment. This is extremely important in early mission development to the evaluation board. This analysis will use JPL-managed proposals from 2003 to 2011, including Discovery, New Frontiers, and Mars Scout missions. Through the examination of these proposals and their associated debriefs, a set of guidelines have been created for successful use and communication of instrument heritage in early mission development

Normal Development of the Perineuronal Net in Humans; In Patients with and without Epilepsy.

PubMed

Rogers, Stephanie L; Rankin-Gee, Elyse; Risbud, Rashmi M; Porter, Brenda E; Marsh, Eric D

2018-06-07

The perineuronal net (PN), a highly organized extracellular matrix structure, is believed to play an important role in synaptic function, including maturation and stabilization. In addition to its role in restricting plasticity, alterations in the PN are implicated in disorders such as epilepsy and schizophrenia. However, the time course of PN development is not known in humans. Therefore we set out to document the developmental timeline of the PN formation in humans in 14 frontal and hippocampal specimens from donors aged 27 days to 31 years old. Using immunohistochemistry and western blotting, we demonstrate that the PN begins to form as early as the second month of life but does not reach its robust, mature appearance until around 8 years of age, though aggrecan cleavage products are observed prior to this. A similar developmental time course was observed in specimens from epilepsy patients. Our data suggest that aggrecan is present early in development but the structured PN develops throughout early childhood, similar to what has been observed in rodents. This timeline provides information for future pathological studies on the role of the PN in disease and an additional parallel between human and rodent development. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Early sound patterns in the speech of two Brazilian Portuguese speakers.

PubMed

Teixeira, Elizabeth Reis; Davis, Barbara L

2002-06-01

Sound patterns in the speech of two Brazilian-Portuguese speaking children are compared with early production patterns in English-learning children as well as English and Brazilian-Portuguese (BP) characteristics. The relationship between production system effects and ambient language influences in the acquisition of early sound patterns is of primary interest, as English and BP are characterized by differing phonological systems. Results emphasize the primacy of production system effects in early acquisition, although even the earliest word forms show evidence of perceptual effects from the ambient language in both BP children. Use of labials and coronals and low and midfront vowels in simple syllable shapes is consistent with acquisition data for this period across languages. However, potential ambient language influences include higher frequencies of dorsals, use of multisyllabic words, and different phone types in syllable-offset position. These results suggest that to fully understand early acquisition of sound systems one must account for both production system effects and perceptual effects from the ambient language.

Basin Wide Erosion and Soil Production Rates of a High Altitude Plateau in the Korean Peninsula Considered as an Uplifted Paleo Erosional Surface: Implications for Its Development Process and the Tectonics

NASA Astrophysics Data System (ADS)

Byun, J.; Seong, Y.

2012-12-01

The development process of High Altitude Plateaus (HAPs) has been a controversial issue in geomorphology. HAPs have been interpreted as uplifted erosional surfaces mainly controlled by fluvial processes. Recent studies, however, argued that the definition of the Paleo Erosional Surfaces (PESs) is ambiguous and HAPs, considered as the uplifted PESs, could be formed under various local lithologic, tectonic and climatic conditions. But these suggestions were severely limited by the lack of quantitative data in the field. Here, we investigate this issue of the development process of HAPs through estimating both basin wide erosion rates and soil production rates of the Daegwanryeong area in the Korean Peninsula (KP), where a HAP with low-relief hilly landscape is found. Study area has been known as a typical one of PESs in the KP, which have been uplifted since the early Miocene. Particularly deeply weathered saprolites, easily found in the study area, have also been believed to be resulted from the Tertiary deep weathering under higher temperature at the paleo sea level. First, analysis of 10Be in saprolite from the base of the soil column, except one under no soil mantle, shows that soil production rates decline linearly with increasing soil depth. These data provide a soil production function with a maximum soil production rate of 70.6m/m.y. under 24cm of soil and a minimum of 22m/m.y. under 75cm of soil. Accordingly it means that the interface between soil and saprolite have gone down maximum 141.2 m since the Quaternary. Thus it suggests that the saprolites are the results under current local climatic and geomorphic conditions rather than the relict of the Tertiary deep weathering. Second, measurements of 10Be in alluvial sediments show that the average erosion rate (70.7m/m.y.) of the study area is close to the maximum soil production rate, thus basin wide erosion rates of the study area are controlled by the current soil production rates. It means that about 1,400m has been eroded off since the early Miocene, when uplift of the KP seems to begin. Consequently it is difficult to think the HAP of the study area as the PES as well as one, which has been eroded keeping the original form of the PES. Furthermore, the erosion rates are lower than the uplift rates during the late Quaternary (about 300m/m.y.), but similar to the uplift rates before the early Miocene (about 100m/m.y.). Therefore, it suggests that the HAP of the study area has been uplifted since the early Miocene, but has not approached the steady state with the neotectonics of the KP. In summary, we suggest that the HAP of the study area is the result of the geomorphic process under current climatic and geomorphic condition rather than the relict of the PES.

Research on early warning of food security using a system dynamics model: evidence from Jiangsu province in China.

PubMed

Xu, Jianling; Ding, Yi

2015-01-01

Analyzing the early warning of food security, this paper sets the self-sufficiency rate as the principal indicator in a standpoint of supplement. It is common to use the quantitative methods to forecast and warning the insecurity. However, this paper considers more about the probable outcome when the government intervenes. By constructing the causal feedbacks among grain supplement, demand, productive input, and the policy factors to simulate the future food security in Jiangsu province, conclusions can be drawn as the following: (1) The situation of food security is insecure if the self-sufficiency rate is under 68.3% according to the development of system inertia. (2) it is difficult to guarantee the food security in Jiangsu just depending on the increase of grain sown area. (3) The valid solution to ensure the food security in Jiangsu is to improve the productivity. © 2015 Institute of Food Technologists®

Hydrogen peroxide and the evolution of oxygenic photosynthesis

NASA Technical Reports Server (NTRS)

Mckay, C. P.; Hartman, H.

1991-01-01

Possible pathways for the evolution of oxygenic photosynthesis in the early reducing atmosphere of the earth are discussed. It is suggested that the abiotic production of atmospheric oxidants could have provided a mechanism by which locally oxidizing conditions were sustained within spatially confined habitats thus removing the available reductants and forcing photosynthetic organisms to utilize water (rather than ferrous or sulfide ions) as the electron donor. It is argued that atmospheric H2O2 played the key role in inducing oxygenic photosynthesis, because, as peroxide concentrations local environments increased, primitive organisms would not only be faced with a loss of a reductant, but would be also forced to develop a biochemical apparatus (such as catalase) that would protect them against the products of oxygenic photosynthesis. This scenario allows for the early evolution of oxygenic photosynthesis at the time when global conditions were still anaerobic.

Drugs, consumption, and supply in Asia: the case of cocaine in colonial India, c. 1900 - c. 1930.

PubMed

Mills, James H

2007-05-01

This article examines the market for cocaine in India during the early twentieth century and the efforts of the colonial state to control it. The British authorities issued regulations to prohibit the drug's use as early as 1900, and yet by the start of World War I, cocaine's appeal had become socially diverse and geographically wide. This account of a significant market for a powerful new drug suggests that Indian society was able to rapidly develop a demand for such products even when the colonial state had no part in their introduction. Indians used these new products in complex ways- as medicines, as tonics, and as intoxicants, albeit through the localized medium of the everyday paan leaf. The study points to a reconsideration of a number of debates about the history of drugs and modern medicines in Asia.

Frequency Effects or Context Effects in Second Language Word Learning: What Predicts Early Lexical Production?

ERIC Educational Resources Information Center

Crossley, Scott A.; Subtirelu, Nicholas; Salsbury, Tom

2013-01-01

This study examines frequency, contextual diversity, and contextual distinctiveness effects in predicting produced versus not-produced frequent nouns and verbs by early second language (L2) learners of English. The study analyzes whether word frequency is the strongest predictor of early L2 word production independent of contextual diversity and…

Identification, cloning, and expression analysis of three putative Lymantria dispar nuclear polyhedrosis virus immediate early genes

Treesearch

James M. Slavicek; Nancy Hayes-Plazolles

1991-01-01

Viral immediate early gene products are usually regulatory proteins that control expression of other viral genes at the transcriptional level or are proteins that are part of the viral DNA replication complex. The identification and functional characterization of the immediate early gene products of Lymantria dispar nuclear polyhedrosis virus (LdNPV...

Lessons from reproductive health to inform multipurpose prevention technologies: don't reinvent the wheel.

PubMed

Brady, Martha; Manning, Judy

2013-12-01

This paper presents the public health rationale for multipurpose prevention technologies (MPTs) for sexual and reproductive health (SRH) based on regional trends in demographic and SRH indicators. It then distils important lessons gleaned from the introduction of contraceptive and reproductive health products over the past several decades in order to inform the development and future introduction of MPTs for SRH. A comparison of current demographic and public health regional data clearly revealed that the greatest confluence of women's SRH concerns occurs in sub-Saharan Africa and South/West Asia. These regional overlaps of SRH risks and outcomes present a strong rationale for developing MPTs designed to simultaneously protect against unintended pregnancy, HIV and other STIs. Information from acceptability, marketing, and operations research on the female condom, emergency contraception, pills and intravaginal rings identified key product characteristics and socio-behavioral issues to be considered in the development and introduction of MPTs. Product characteristics such as formulation, duration of action, presence and magnitude of side effects, prescription status (over-the-counter vs. prescribed), provider type and training and user perspectives, all contributed in varying degrees to both provider and user bias, and subsequent uptake of these family planning methods. Underlying socio-behavioral issues, including risk perception, ambivalence, and social costs also contributed to demand and use. Early identification of target populations will be critical to market shaping, demand creation and defining appropriate service delivery channels for MPTs. Ultimately, knowledge, attitudes, perceptions and practices of users (and their partners) will drive the success- or failure- of product introduction. MPTs provide a compelling response to the multiple and reinforcing SRH risks faced by women in key regions of the world, but specific product characteristics and their socio-behavioral correlates must be taken into account early in the development process. Successful introduction of new MPTs will require solid understanding of socio-behavioral correlates, effective demand generation, appropriate integration into health service delivery systems, quality counseling for proper use and active engagement of both public and private sectors. This article is based on a presentation at the "Product Development Workshop 2013: HIV and Multipurpose Prevention Technologies," held in Arlington, Virginia on February 21-22, 2013. It forms part of a special supplement to Antiviral Research. Copyright © 2013 Elsevier B.V. All rights reserved.

Stage- and tissue-expression of genes involved in the biosynthesis and signalling of ethylene in reproductive organs of damson plum (Prunus domestica L. subsp. insititia).

PubMed

Fernández-Otero, C I; de la Torre, F; Iglesias, R; Rodríguez-Gacio, M C; Matilla, A J

2007-01-01

In this work, four cDNA clones (Pd-ACS1,AJ890088; Pd-ETR1 and Pd-ERS1, AJ890092, AJ890091; and Pd-CTR1, AJ890089) encoding an ACC-synthase, two putative ethylene (ET) receptors, and a putative MAPKKK, respectively, were isolated and phylogenetically characterized in Prunus domestica L. subsp. insititia. Their expression was studied by real-time PCR during flower (closed, open and senescent) and fruit (early green, late green, maturation and ripening) development of damson plum, which is climateric. While two peaks of ET production were quantified at early green and ripening stages in whole fruits, the seed was not able to produce it during maturation and ripening stages. All studied genes were differentially expressed during flower and fruit development. In general, the level of transcripts of Pd-ACS1 was higher in fruits than in flowers. However, it was noteworthy that: (1) Pd-ACS1 expression was hardly detected in closed flowers and at low levels during early green stage; and fruit development provoked a notable differential expression in seeds, and pericarp; (2) the results of Pd-ACS1 expression during fruit development suggest a preponderant role of this gene from late green stage onward. The stamen was the only floral organ in which expression of both Pd-ETR1 and Pd-ERS1 receptor genes was not significantly altered during development; however, their expression decreased concomitantly with development of pistil (only floral organ to register a net ET production when fertilized) and during first days of ovary development (the highest ET production during all fruit development). Contrary to Pd-ERS1, the level of Pd-ETR1 mRNA was temporally quite similar in the seed. With regard Pd-ETR1, even its expression was very scarce during maturation of mesocarp, was stimulated during ripening. In the epicarp, Pd-ERS1 and Pd-ETR1 were low expressed during pit hardening increasing onward and decreasing during ripening. Pd-CTR1 expression was in the seed>mesocarp>epicarp. Spatial and temporal levels of Pd-ACS1, Pd-ETR1, Pd-ERS1 and Pd-CTR1 mRNAs described in this work demonstrate that the expression of these genes is not always constitutive and that control of its transcription may play an important role in regulating the development of reproductive organs of damson plum.

Dutch national rainfallradar project: a unique corporation

NASA Astrophysics Data System (ADS)

Schuurmans, Hanneke; Maarten Verbree, Jan; Leijnse, Hidde; van Heeringen, Klaas-Jan; Uijlenhoet, Remko; Bierkens, Mark; van de Giesen, Nick; Gooijer, Jan; van den Houten, Gert

2013-04-01

Since January 2013 Dutch watermanagers have access to innovative high-quality rainfall data. This product is innovative because of the following reasons. (i) The product is developed in a 'golden triangle' construction - corporation between government, business and research institutes. (ii) Second the rainfall products are developed according to the open-source GPL license. The initiative comes from a group of water boards in the Netherlands that joined their forces to fund the development of a new rainfall product. Not only data from Dutch radar stations (as is currently done by the Dutch meteorological organization KNMI) is used but also data from radars in Germany and Belgium. After a radarcomposite is made, it is adjusted according to data from raingauges (ground truth). This results in 9 different rainfall products that give for each moment the best rainfall data. This data will be used, depending on the end-user for several applications: (i) forecasts: input for flood early warning systems, (ii) water system analysis: hydrological model input, (iii) optimization: real time control and (iv) investigation of incidents: in case of flooding, who's responsible. The latter is mainly insight in the return period of heavy rainfall events. More info (in Dutch): www.nationaleregenradar.nl

Developing new products in cystic fibrosis: needs and obstacles for activities of small and middle-sized companies.

PubMed

Schlangen, Miriam; Reimann, Andreas L G

2011-06-01

Small and middle-sized enterprises (SMEs) can make important contributions to medical progress through the development of new safe and effective drugs that address the greatest unmet needs of patients. Regulatory inconsistencies across agencies in various countries, however, remain major challenges in cystic fibrosis (CF) drug development. Clear and consistent treatment guidelines, well educated clinical trial sites, a patient registry and grant funding for early development programs are important success-factors for an efficient development process. SMEs developing products for CF need partners in the CF community to assist with disease education and awareness for ongoing clinical trials. SMEs should collaborate and communicate with the CF community in a legally compliant way to take a patient-centric approach to drug design, development and administration. Furthermore, they can help to develop educational tools and fund medical education activities to increase the understanding of the underlying defects and mechanisms of CF disease. Copyright © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Simulation/Emulation Techniques: Compressing Schedules With Parallel (HW/SW) Development

NASA Technical Reports Server (NTRS)

Mangieri, Mark L.; Hoang, June

2014-01-01

NASA has always been in the business of balancing new technologies and techniques to achieve human space travel objectives. NASA's Kedalion engineering analysis lab has been validating and using many contemporary avionics HW/SW development and integration techniques, which represent new paradigms to NASA's heritage culture. Kedalion has validated many of the Orion HW/SW engineering techniques borrowed from the adjacent commercial aircraft avionics solution space, inserting new techniques and skills into the Multi - Purpose Crew Vehicle (MPCV) Orion program. Using contemporary agile techniques, Commercial-off-the-shelf (COTS) products, early rapid prototyping, in-house expertise and tools, and extensive use of simulators and emulators, NASA has achieved cost effective paradigms that are currently serving the Orion program effectively. Elements of long lead custom hardware on the Orion program have necessitated early use of simulators and emulators in advance of deliverable hardware to achieve parallel design and development on a compressed schedule.

Best Practices in Stability Indicating Method Development and Validation for Non-clinical Dose Formulations.

PubMed

Henry, Teresa R; Penn, Lara D; Conerty, Jason R; Wright, Francesca E; Gorman, Gregory; Pack, Brian W

2016-11-01

Non-clinical dose formulations (also known as pre-clinical or GLP formulations) play a key role in early drug development. These formulations are used to introduce active pharmaceutical ingredients (APIs) into test organisms for both pharmacokinetic and toxicological studies. Since these studies are ultimately used to support dose and safety ranges in human studies, it is important to understand not only the concentration and PK/PD of the active ingredient but also to generate safety data for likely process impurities and degradation products of the active ingredient. As such, many in the industry have chosen to develop and validate methods which can accurately detect and quantify the active ingredient along with impurities and degradation products. Such methods often provide trendable results which are predictive of stability, thus leading to the name; stability indicating methods. This document provides an overview of best practices for those choosing to include development and validation of such methods as part of their non-clinical drug development program. This document is intended to support teams who are either new to stability indicating method development and validation or who are less familiar with the requirements of validation due to their position within the product development life cycle.

Robo signaling regulates the production of cranial neural crest cells.

PubMed

Li, Yan; Zhang, Xiao-Tan; Wang, Xiao-Yu; Wang, Guang; Chuai, Manli; Münsterberg, Andrea; Yang, Xuesong

2017-12-01

Slit/Robo signaling plays an important role in the guidance of developing neurons in developing embryos. However, it remains obscure whether and how Slit/Robo signaling is involved in the production of cranial neural crest cells. In this study, we examined Robo1 deficient mice to reveal developmental defects of mouse cranial frontal and parietal bones, which are derivatives of cranial neural crest cells. Therefore, we determined the production of HNK1 + cranial neural crest cells in early chick embryo development after knock-down (KD) of Robo1 expression. Detection of markers for pre-migratory and migratory neural crest cells, PAX7 and AP-2α, showed that production of both was affected by Robo1 KD. In addition, we found that the transcription factor slug is responsible for the aberrant delamination/EMT of cranial neural crest cells induced by Robo1 KD, which also led to elevated expression of E- and N-Cadherin. N-Cadherin expression was enhanced when blocking FGF signaling with dominant-negative FGFR1 in half of the neural tube. Taken together, we show that Slit/Robo signaling influences the delamination/EMT of cranial neural crest cells, which is required for cranial bone development. Copyright © 2017. Published by Elsevier Inc.

Developing reforestation technology for southern pines: a historical perspective

Treesearch

James Barnett

2013-01-01

Early in the 20th century, the forests of the South were decimated by aggressive harvesting, resulting in millions of acres of forest land in need of reforestation. Foresighted individuals committed efforts to restore this harvested land to a productive condition. The effort required dedication, cooperation, and leadership. The efforts of this small cadre of...

Ecological Technologies for Small-Diameter Tree Harvesting

Treesearch

Bryce J. Stokes; John F. Klepac

1997-01-01

Production, costs, and merchantable chip recovery values were developed for a tree-length, flail/chip, and cut-to-length system. The systems were evaluated for three representative stands: early thinning, late thinning, and a clearcut. A sensitivity analysis was completed for the three systems over a range of tree diameters. Recovery was affected by stand type and...

Technology: Presentations in the Cloud with a Twist

ERIC Educational Resources Information Center

Siegle, Del

2011-01-01

Technology tools have come a long way from early word processing applications and opportunities for students to engage in simple programming. Many tools now exist for students to develop and share products in a variety of formats and for a wide range of audiences. PowerPoint is probably the most ubiquitously used tool for student projects. In…

From Tappan to Lange: Evolution of the Public Junior College Idea.

ERIC Educational Resources Information Center

Gallagher, Edward Arthur

This study is a historical analysis of the public junior college idea and its emergence. The thoughts and actions of Henry P. Tappan, William W. Folwell, William R. Harper, David S. Jordan, and Alexis Lange contributed most to its origin and development. These men, products of the late nineteenth and early twentieth centuries, were strongly…

Early Detection of Emotional Disorders in South Australia: The First Two Years.

ERIC Educational Resources Information Center

Martin, G.; Roeger, L.; Dadds, V.; Allison, S.

Each year about 30 young South Australians die from suicide. Schools have a responsibility to help address the mental health concerns of students to ensure the development of mature and productive citizens for the future. The program outlined in this booklet is designed to help reduce the suicidal behaviors in young people. The report summarizes…

Impact of drought on morphological, physiological and nutrient use efficiency of elite cacao genotypes from Bahia-Brazil, Tarapoto-Peru and Puerto Rico-USA

USDA-ARS?s Scientific Manuscript database

Worldwide, drought is considered one of the most limiting abiotic stress factors for cacao growth, development and production. A series of greenhouse and growth chamber experiments were undertaken to assess drought effects on early cacao morphological and physiological traits and nutrient use effici...

Active Trilingualism in Early Childhood: The Motivating Role of Caregivers in Interaction

ERIC Educational Resources Information Center

Chevalier, Sarah

2012-01-01

The present paper is concerned with the language development of two young children from two different families growing up exposed to three languages. The children live in Switzerland and have been exposed to English, French and Swiss German from infancy. The focus is on the children's production of these languages, and the contextual and affective…