Transcriptional Landscape of the Prenatal Human Brain

PubMed Central

Miller, Jeremy A.; Ding, Song-Lin; Sunkin, Susan M.; Smith, Kimberly A; Ng, Lydia; Szafer, Aaron; Ebbert, Amanda; Riley, Zackery L.; Aiona, Kaylynn; Arnold, James M.; Bennet, Crissa; Bertagnolli, Darren; Brouner, Krissy; Butler, Stephanie; Caldejon, Shiella; Carey, Anita; Cuhaciyan, Christine; Dalley, Rachel A.; Dee, Nick; Dolbeare, Tim A.; Facer, Benjamin A. C.; Feng, David; Fliss, Tim P.; Gee, Garrett; Goldy, Jeff; Gourley, Lindsey; Gregor, Benjamin W.; Gu, Guangyu; Howard, Robert E.; Jochim, Jayson M.; Kuan, Chihchau L.; Lau, Christopher; Lee, Chang-Kyu; Lee, Felix; Lemon, Tracy A.; Lesnar, Phil; McMurray, Bergen; Mastan, Naveed; Mosqueda, Nerick F.; Naluai-Cecchini, Theresa; Ngo, Nhan-Kiet; Nyhus, Julie; Oldre, Aaron; Olson, Eric; Parente, Jody; Parker, Patrick D.; Parry, Sheana E.; Player, Allison Stevens; Pletikos, Mihovil; Reding, Melissa; Royall, Joshua J.; Roll, Kate; Sandman, David; Sarreal, Melaine; Shapouri, Sheila; Shapovalova, Nadiya V.; Shen, Elaine H.; Sjoquist, Nathan; Slaughterbeck, Clifford R.; Smith, Michael; Sodt, Andy J.; Williams, Derric; Zöllei, Lilla; Fischl, Bruce; Gerstein, Mark B.; Geschwind, Daniel H.; Glass, Ian A.; Hawrylycz, Michael J.; Hevner, Robert F.; Huang, Hao; Jones, Allan R.; Knowles, James A.; Levitt, Pat; Phillips, John W.; Sestan, Nenad; Wohnoutka, Paul; Dang, Chinh; Bernard, Amy; Hohmann, John G.; Lein, Ed S.

2014-01-01

Summary The anatomical and functional architecture of the human brain is largely determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and postmitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and human-expanded outer subventricular zones. Both germinal and postmitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in frontal lobe. Finally, many neurodevelopmental disorder and human evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development. PMID:24695229

Defending Against Smallpox: a Focus on Vaccines

PubMed Central

Voigt, Emily A.; Kennedy, Richard B.; Poland, Gregory A.

2016-01-01

Smallpox has shaped human history, from the earliest human civilizations well into the 20th century. With high mortality rates, rapid transmission, and serious long-term effects on survivors, smallpox was a much-feared disease. The eradication of smallpox represents an unprecedented medical victory for the lasting benefit of human health and prosperity. Concerns remain, however, about the development and use of the smallpox virus as a biological weapon, which necessitates the need for continued vaccine development. Smallpox vaccine development is thus a much-reviewed topic of high interest. This review focuses on the current state of smallpox vaccines and their context in biodefense efforts. PMID:27049653

Defending against smallpox: a focus on vaccines.

PubMed

Voigt, Emily A; Kennedy, Richard B; Poland, Gregory A

2016-09-01

Smallpox has shaped human history, from the earliest human civilizations well into the 20th century. With high mortality rates, rapid transmission, and serious long-term effects on survivors, smallpox was a much-feared disease. The eradication of smallpox represents an unprecedented medical victory for the lasting benefit of human health and prosperity. Concerns remain, however, about the development and use of the smallpox virus as a biological weapon, which necessitates the need for continued vaccine development. Smallpox vaccine development is thus a much-reviewed topic of high interest. This review focuses on the current state of smallpox vaccines and their context in biodefense efforts.

High-Power Hall Propulsion Development at NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Kamhawi, Hani; Manzella, David H.; Smith, Timothy D.; Schmidt, George R.

2014-01-01

The NASA Office of the Chief Technologist Game Changing Division is sponsoring the development and testing of enabling technologies to achieve efficient and reliable human space exploration. High-power solar electric propulsion has been proposed by NASA's Human Exploration Framework Team as an option to achieve these ambitious missions to near Earth objects. NASA Glenn Research Center (NASA Glenn) is leading the development of mission concepts for a solar electric propulsion Technical Demonstration Mission. The mission concepts are highlighted in this paper but are detailed in a companion paper. There are also multiple projects that are developing technologies to support a demonstration mission and are also extensible to NASA's goals of human space exploration. Specifically, the In-Space Propulsion technology development project at NASA Glenn has a number of tasks related to high-power Hall thrusters including performance evaluation of existing Hall thrusters; performing detailed internal discharge chamber, near-field, and far-field plasma measurements; performing detailed physics-based modeling with the NASA Jet Propulsion Laboratory's Hall2De code; performing thermal and structural modeling; and developing high-power efficient discharge modules for power processing. This paper summarizes the various technology development tasks and progress made to date

High-Power Hall Propulsion Development at NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Kamhawi, Hani; Manzella, David H.; Smith, Timothy D.; Schmidt, George R.

2012-01-01

The NASA Office of the Chief Technologist Game Changing Division is sponsoring the development and testing of enabling technologies to achieve efficient and reliable human space exploration. High-power solar electric propulsion has been proposed by NASA's Human Exploration Framework Team as an option to achieve these ambitious missions to near Earth objects. NASA Glenn Research Center is leading the development of mission concepts for a solar electric propulsion Technical Demonstration Mission. The mission concepts are highlighted in this paper but are detailed in a companion paper. There are also multiple projects that are developing technologies to support a demonstration mission and are also extensible to NASA's goals of human space exploration. Specifically, the In-Space Propulsion technology development project at the NASA Glenn has a number of tasks related to high-power Hall thrusters including performance evaluation of existing Hall thrusters; performing detailed internal discharge chamber, near-field, and far-field plasma measurements; performing detailed physics-based modeling with the NASA Jet Propulsion Laboratory's Hall2De code; performing thermal and structural modeling; and developing high-power efficient discharge modules for power processing. This paper summarizes the various technology development tasks and progress made to date.

Development of a highly sensitive immunochromatographic detection kit for H5 influenza virus hemagglutinin using silver amplification.

PubMed

Wada, Atsuhiko; Sakoda, Yoshihiro; Oyamada, Takayoshi; Kida, Hiroshi

2011-12-01

H5N1, a highly pathogenic avian influenza virus (HPAIV), has become a serious epizootic threat to the poultry population in Asia. In addition, significant numbers of human cases of HPAIV infection have been reported to date. To prevent the spread of HPAIV among humans and to allow for timely medical intervention, a rapid and high sensitive method is needed to detect and subtype the causative HPAIVs. In the present study, a silver amplification technique used in photographic development was combined with immunochromatography technologies and a highly sensitive and rapid diagnostic test to detect the hemagglutinin of H5 influenza viruses was developed. The sensitivity of the test kit was increased 500 times by silver amplification. The sensitivity of the method was more than 10 times higher than those of conventional rapid influenza diagnostic tests, which detect viral nucleoproteins. The diagnostic system developed in the present study can therefore provide rapid and highly sensitive results and will be useful for diagnosis of H5 HPAIV infection in humans and animals. Copyright © 2011 Elsevier B.V. All rights reserved.

The use of high-fidelity human patient simulation as an evaluative tool in the development of clinical research protocols and procedures.

PubMed

Wright, Melanie C; Taekman, Jeffrey M; Barber, Linda; Hobbs, Gene; Newman, Mark F; Stafford-Smith, Mark

2005-12-01

Errors in clinical research can be costly, in terms of patient safety, data integrity, and data collection. Data inaccuracy in early subjects of a clinical study may be associated with problems in the design of the protocol, procedures, and data collection tools. High-fidelity patient simulation centers provide an ideal environment to apply human-centered design to clinical trial development. A draft of a complex clinical protocol was designed, evaluated and modified using a high-fidelity human patient simulator in the Duke University Human Simulation and Patient Safety Center. The process included walk-throughs, detailed modifications of the protocol and development of procedural aids. Training of monitors and coordinators provided an opportunity for observation of performance that was used to identify further improvements to the protocol. Evaluative steps were used to design the research protocol and procedures. Iterative modifications were made to the protocol and data collection tools. The success in use of human simulation in the preparation of a complex clinical drug trial suggests the benefits of human patient simulation extend beyond training and medical equipment evaluation. Human patient simulation can provide a context for informal expert evaluation of clinical protocol design and for formal "rehearsal" to evaluate the efficacy of procedures and support tools.

New Funding Opportunity from the Human Biomolecular Atlas Program (HuBMAP)! | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

The NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) aims to develop a framework for functional mapping the human body with cellular resolution to enhance our understanding of cellular organization-function. HuBMAP will accelerate the development of the next generation of tools and techniques to generate 3D tissue maps using validated high-content, high-throughput imaging and omics assays, and establish an open data platform for integrating, visualizing data to build multi-dimensional maps.

Conservation hotspots for marine turtle nesting in the United States based on coastal development.

PubMed

Fuentes, Mariana M P B; Gredzens, Christian; Bateman, Brooke L; Boettcher, Ruth; Ceriani, Simona A; Godfrey, Matthew H; Helmers, David; Ingram, Dianne K; Kamrowski, Ruth L; Pate, Michelle; Pressey, Robert L; Radeloff, Volker C

2016-12-01

Coastal areas provide nesting habitat for marine turtles that is critical for the persistence of their populations. However, many coastal areas are highly affected by coastal development, which affects the reproductive success of marine turtles. Knowing the extent to which nesting areas are exposed to these threats is essential to guide management initiatives. This information is particularly important for coastal areas with both high nesting density and dense human development, a combination that is common in the United States. We assessed the extent to which nesting areas of the loggerhead (Caretta caretta), the green (Chelonia mydas), the Kemp's ridley (Lepidochelys kempii), and leatherback turtles (Dermochelys coriacea) in the continental United States are exposed to coastal development and identified conservation hotspots that currently have high reproductive importance and either face high exposure to coastal development (needing intervention), or have low exposure to coastal development, and are good candidates for continued and future protection. Night-time light, housing, and population density were used as proxies for coastal development and human disturbance. About 81.6% of nesting areas were exposed to housing and human population, and 97.8% were exposed to light pollution. Further, most (>65%) of the very high- and high-density nesting areas for each species/subpopulation, except for the Kemp's ridley, were exposed to coastal development. Forty-nine nesting sites were selected as conservation hotspots; of those high-density nesting sites, 49% were sites with no/low exposure to coastal development and the other 51% were exposed to high-density coastal development. Conservation strategies need to account for ~66.8% of all marine turtle nesting areas being on private land and for nesting sites being exposed to large numbers of seasonal residents. © 2016 by the Ecological Society of America.

Integrated Human-in-the-Loop Ground Testing - Value, History, and the Future

NASA Technical Reports Server (NTRS)

Henninger, Donald L.

2016-01-01

Systems for very long-duration human missions to Mars will be designed to operate reliably for many years and many of these systems will never be returned to Earth. The need for high reliability is driven by the requirement for safe functioning of remote, long-duration crewed systems and also by unsympathetic abort scenarios. Abort from a Mars mission could be as long as 450 days to return to Earth. The key to developing a human-in-the-loop architecture is a development process that allows for a logical sequence of validating successful development in a stepwise manner, with assessment of key performance parameters (KPPs) at each step; especially important are KPPs for technologies evaluated in a full systems context with human crews on Earth and on space platforms such as the ISS. This presentation will explore the implications of such an approach to technology development and validation including the roles of ground and space-based testing necessary to develop a highly reliable system for long duration human exploration missions. Historical development and systems testing from Mercury to the International Space Station (ISS) to ground testing will be reviewed. Current work as well as recommendations for future work will be described.

Human pluripotent stem cells: an emerging model in developmental biology.

PubMed

Zhu, Zengrong; Huangfu, Danwei

2013-02-01

Developmental biology has long benefited from studies of classic model organisms. Recently, human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, have emerged as a new model system that offers unique advantages for developmental studies. Here, we discuss how studies of hPSCs can complement classic approaches using model organisms, and how hPSCs can be used to recapitulate aspects of human embryonic development 'in a dish'. We also summarize some of the recently developed genetic tools that greatly facilitate the interrogation of gene function during hPSC differentiation. With the development of high-throughput screening technologies, hPSCs have the potential to revolutionize gene discovery in mammalian development.

The use of BLT humanized mice to investigate the immune reconstitution of the gastrointestinal tract.

PubMed

Wahl, Angela; Victor Garcia, J

2014-08-01

The gastrointestinal (GI) track represents an important battlefield where pathogens first try to gain entry into a host. It is also a universe where highly diverse and ever changing inhabitants co-exist in an exceptional equilibrium without parallel in any other organ system of the body. The gut as an organ has its own well-developed and fully functional immune organization that is similar and yet different in many important ways to the rest of the immune system. Both a compromised and an overactive immune system in the gut can have dire and severe consequences to human health. It has therefore been of great interest to develop animal models that recapitulate key aspects of the human condition to better understand the interplay of the host immune system with its friends and its foes. However, reconstitution of the GI tract in humanized mice has been difficult and highly variable in different systems. A better molecular understanding of the development of the gut immune system in mice has provided critical cues that have been recently used to develop novel humanized mouse models that fully recapitulate the genesis and key functions of the gut immune system of humans. Of particular interest is the presence of human gut-associated lymphoid tissue (GALT) aggregates in the gut of NOD/SCID BLT humanized mice that demonstrate the faithful development of bona fide human plasma cells capable of migrating to the lamina propria and producing human IgA1 and IgA2. Copyright © 2014 Elsevier B.V. All rights reserved.

Wearable Wide-Range Strain Sensors Based on Ionic Liquids and Monitoring of Human Activities

PubMed Central

Zhang, Shao-Hui; Wang, Feng-Xia; Li, Jia-Jia; Peng, Hong-Dan; Yan, Jing-Hui; Pan, Ge-Bo

2017-01-01

Wearable sensors for detection of human activities have encouraged the development of highly elastic sensors. In particular, to capture subtle and large-scale body motion, stretchable and wide-range strain sensors are highly desired, but still a challenge. Herein, a highly stretchable and transparent stain sensor based on ionic liquids and elastic polymer has been developed. The as-obtained sensor exhibits impressive stretchability with wide-range strain (from 0.1% to 400%), good bending properties and high sensitivity, whose gauge factor can reach 7.9. Importantly, the sensors show excellent biological compatibility and succeed in monitoring the diverse human activities ranging from the complex large-scale multidimensional motions to subtle signals, including wrist, finger and elbow joint bending, finger touch, breath, speech, swallow behavior and pulse wave. PMID:29135928

High-speed adaptive optics line scan confocal retinal imaging for human eye

PubMed Central

Wang, Xiaolin; Zhang, Yuhua

2017-01-01

Purpose Continuous and rapid eye movement causes significant intraframe distortion in adaptive optics high resolution retinal imaging. To minimize this artifact, we developed a high speed adaptive optics line scan confocal retinal imaging system. Methods A high speed line camera was employed to acquire retinal image and custom adaptive optics was developed to compensate the wave aberration of the human eye’s optics. The spatial resolution and signal to noise ratio were assessed in model eye and in living human eye. The improvement of imaging fidelity was estimated by reduction of intra-frame distortion of retinal images acquired in the living human eyes with frame rates at 30 frames/second (FPS), 100 FPS, and 200 FPS. Results The device produced retinal image with cellular level resolution at 200 FPS with a digitization of 512×512 pixels/frame in the living human eye. Cone photoreceptors in the central fovea and rod photoreceptors near the fovea were resolved in three human subjects in normal chorioretinal health. Compared with retinal images acquired at 30 FPS, the intra-frame distortion in images taken at 200 FPS was reduced by 50.9% to 79.7%. Conclusions We demonstrated the feasibility of acquiring high resolution retinal images in the living human eye at a speed that minimizes retinal motion artifact. This device may facilitate research involving subjects with nystagmus or unsteady fixation due to central vision loss. PMID:28257458

High-speed adaptive optics line scan confocal retinal imaging for human eye.

PubMed

Lu, Jing; Gu, Boyu; Wang, Xiaolin; Zhang, Yuhua

2017-01-01

Continuous and rapid eye movement causes significant intraframe distortion in adaptive optics high resolution retinal imaging. To minimize this artifact, we developed a high speed adaptive optics line scan confocal retinal imaging system. A high speed line camera was employed to acquire retinal image and custom adaptive optics was developed to compensate the wave aberration of the human eye's optics. The spatial resolution and signal to noise ratio were assessed in model eye and in living human eye. The improvement of imaging fidelity was estimated by reduction of intra-frame distortion of retinal images acquired in the living human eyes with frame rates at 30 frames/second (FPS), 100 FPS, and 200 FPS. The device produced retinal image with cellular level resolution at 200 FPS with a digitization of 512×512 pixels/frame in the living human eye. Cone photoreceptors in the central fovea and rod photoreceptors near the fovea were resolved in three human subjects in normal chorioretinal health. Compared with retinal images acquired at 30 FPS, the intra-frame distortion in images taken at 200 FPS was reduced by 50.9% to 79.7%. We demonstrated the feasibility of acquiring high resolution retinal images in the living human eye at a speed that minimizes retinal motion artifact. This device may facilitate research involving subjects with nystagmus or unsteady fixation due to central vision loss.

Student Centered Homogeneous Ability Grouping: Using Bronfenbrenner's Theory of Human Development to Investigate the Ecological Factors Contributing to the Academic Achievement of High School Students in Mathematics

ERIC Educational Resources Information Center

Webb, Karla Denise

2011-01-01

The purpose of this qualitative study was to explore the interconnectedness of the environment, human development, and the factors that influence students' academic performance in a homogeneous ability grouped mathematics classroom. The study consisted of four African American urban high school juniors, 2 male and 2 female. During the 12 week…

Development, upscaling and validation of the purification process for human-cl rhFVIII (Nuwiq®), a new generation recombinant factor VIII produced in a human cell-line.

PubMed

Winge, Stefan; Yderland, Louise; Kannicht, Christoph; Hermans, Pim; Adema, Simon; Schmidt, Torben; Gilljam, Gustav; Linhult, Martin; Tiemeyer, Maya; Belyanskaya, Larisa; Walter, Olaf

2015-11-01

Human-cl rhFVIII (Nuwiq®), a new generation recombinant factor VIII (rFVIII), is the first rFVIII produced in a human cell-line approved by the European Medicines Agency. To describe the development, upscaling and process validation for industrial-scale human-cl rhFVIII purification. The purification process involves one centrifugation, two filtration, five chromatography columns and two dedicated pathogen clearance steps (solvent/detergent treatment and 20 nm nanofiltration). The key purification step uses an affinity resin (VIIISelect) with high specificity for FVIII, removing essentially all host-cell proteins with >80% product recovery. The production-scale multi-step purification process efficiently removes process- and product-related impurities and results in a high-purity rhFVIII product, with an overall yield of ∼50%. Specific activity of the final product was >9000 IU/mg, and the ratio between active FVIII and total FVIII protein present was >0.9. The entire production process is free of animal-derived products. Leaching of potential harmful compounds from chromatography resins and all pathogens tested were below the limit of quantification in the final product. Human-cl rhFVIII can be produced at 500 L bioreactor scale, maintaining high purity and recoveries. The innovative purification process ensures a high-purity and high-quality human-cl rhFVIII product with a high pathogen safety margin. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Transcriptional landscape of the prenatal human brain.

PubMed

Miller, Jeremy A; Ding, Song-Lin; Sunkin, Susan M; Smith, Kimberly A; Ng, Lydia; Szafer, Aaron; Ebbert, Amanda; Riley, Zackery L; Royall, Joshua J; Aiona, Kaylynn; Arnold, James M; Bennet, Crissa; Bertagnolli, Darren; Brouner, Krissy; Butler, Stephanie; Caldejon, Shiella; Carey, Anita; Cuhaciyan, Christine; Dalley, Rachel A; Dee, Nick; Dolbeare, Tim A; Facer, Benjamin A C; Feng, David; Fliss, Tim P; Gee, Garrett; Goldy, Jeff; Gourley, Lindsey; Gregor, Benjamin W; Gu, Guangyu; Howard, Robert E; Jochim, Jayson M; Kuan, Chihchau L; Lau, Christopher; Lee, Chang-Kyu; Lee, Felix; Lemon, Tracy A; Lesnar, Phil; McMurray, Bergen; Mastan, Naveed; Mosqueda, Nerick; Naluai-Cecchini, Theresa; Ngo, Nhan-Kiet; Nyhus, Julie; Oldre, Aaron; Olson, Eric; Parente, Jody; Parker, Patrick D; Parry, Sheana E; Stevens, Allison; Pletikos, Mihovil; Reding, Melissa; Roll, Kate; Sandman, David; Sarreal, Melaine; Shapouri, Sheila; Shapovalova, Nadiya V; Shen, Elaine H; Sjoquist, Nathan; Slaughterbeck, Clifford R; Smith, Michael; Sodt, Andy J; Williams, Derric; Zöllei, Lilla; Fischl, Bruce; Gerstein, Mark B; Geschwind, Daniel H; Glass, Ian A; Hawrylycz, Michael J; Hevner, Robert F; Huang, Hao; Jones, Allan R; Knowles, James A; Levitt, Pat; Phillips, John W; Sestan, Nenad; Wohnoutka, Paul; Dang, Chinh; Bernard, Amy; Hohmann, John G; Lein, Ed S

2014-04-10

The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development.

Genome-wide analysis of alternative splicing during human heart development

NASA Astrophysics Data System (ADS)

Wang, He; Chen, Yanmei; Li, Xinzhong; Chen, Guojun; Zhong, Lintao; Chen, Gangbing; Liao, Yulin; Liao, Wangjun; Bin, Jianping

2016-10-01

Alternative splicing (AS) drives determinative changes during mouse heart development. Recent high-throughput technological advancements have facilitated genome-wide AS, while its analysis in human foetal heart transition to the adult stage has not been reported. Here, we present a high-resolution global analysis of AS transitions between human foetal and adult hearts. RNA-sequencing data showed extensive AS transitions occurred between human foetal and adult hearts, and AS events occurred more frequently in protein-coding genes than in long non-coding RNA (lncRNA). A significant difference of AS patterns was found between foetal and adult hearts. The predicted difference in AS events was further confirmed using quantitative reverse transcription-polymerase chain reaction analysis of human heart samples. Functional foetal-specific AS event analysis showed enrichment associated with cell proliferation-related pathways including cell cycle, whereas adult-specific AS events were associated with protein synthesis. Furthermore, 42.6% of foetal-specific AS events showed significant changes in gene expression levels between foetal and adult hearts. Genes exhibiting both foetal-specific AS and differential expression were highly enriched in cell cycle-associated functions. In conclusion, we provided a genome-wide profiling of AS transitions between foetal and adult hearts and proposed that AS transitions and deferential gene expression may play determinative roles in human heart development.

Physical environment virtualization for human activities recognition

NASA Astrophysics Data System (ADS)

Poshtkar, Azin; Elangovan, Vinayak; Shirkhodaie, Amir; Chan, Alex; Hu, Shuowen

2015-05-01

Human activity recognition research relies heavily on extensive datasets to verify and validate performance of activity recognition algorithms. However, obtaining real datasets are expensive and highly time consuming. A physics-based virtual simulation can accelerate the development of context based human activity recognition algorithms and techniques by generating relevant training and testing videos simulating diverse operational scenarios. In this paper, we discuss in detail the requisite capabilities of a virtual environment to aid as a test bed for evaluating and enhancing activity recognition algorithms. To demonstrate the numerous advantages of virtual environment development, a newly developed virtual environment simulation modeling (VESM) environment is presented here to generate calibrated multisource imagery datasets suitable for development and testing of recognition algorithms for context-based human activities. The VESM environment serves as a versatile test bed to generate a vast amount of realistic data for training and testing of sensor processing algorithms. To demonstrate the effectiveness of VESM environment, we present various simulated scenarios and processed results to infer proper semantic annotations from the high fidelity imagery data for human-vehicle activity recognition under different operational contexts.

[Development of antibody medicines by bio-venture: lesson from license negotiations with mega pharmacies].

PubMed

Takada, Kenzo

2013-01-01

The current method of antibody production is mainly the hybridoma method, in which mice are immunized with an excess amount of antigen for a short period to promote activation and proliferation of B-lymphocytes producing the antibodies of interest. Because of the excess antigen, those producing low-affinity antibodies are activated. In contrast, human blood B-lymphocytes are activated through natural immune reactions, such as the reaction to infection. B-lymphocytes are stimulated repeatedly with a small amount of antigen, and thus only those producing high-affinity antibodies are activated. Consequently, the lymphocytes producing the high-affinity antibodies are accumulated in human blood. Therefore, human lymphocytes are an excellent source of high-affinity antibodies. Evec, Inc. has established a unique method to produce high-affinity antibodies from human lymphocytes using Epstein-Barr virus (EBV), which induces the proliferation of B-lymphocytes. The method first induces the proliferation of B-lymphocytes from human blood using EBV, and then isolates those producing the antibodies of interest. The key features of the Evec technique are: 1) development of a lymphocyte library consisting of 150 donors' lymphocytes from which donors suited to develop the antibodies of interest can be selected in 4 days; and 2) development of a sorting method and cell microarray method for selecting lymphocyte clones producing the target antibodies. Licensing agreements have been concluded with European and Japanese pharmaceutical companies for two types of antibody. This paper describes Evec's antibody technology and experience in license negotiations with Mega Pharmacies.

Developmental Plasticity and Language: A Comparative Perspective.

PubMed

Griebel, Ulrike; Pepperberg, Irene M; Oller, D Kimbrough

2016-04-01

The growing field of evo-devo is increasingly demonstrating the complexity of steps involved in genetic, intracellular regulatory, and extracellular environmental control of the development of phenotypes. A key result of such work is an account for the remarkable plasticity of organismal form in many species based on relatively minor changes in regulation of highly conserved genes and genetic processes. Accounting for behavioral plasticity is of similar potential interest but has received far less attention. Of particular interest is plasticity in communication systems, where human language represents an ultimate target for research. The present paper considers plasticity of language capabilities in a comparative framework, focusing attention on examples of a remarkable fact: Whereas there exist design features of mature human language that have never been observed to occur in non-humans in the wild, many of these features can be developed to notable extents when non-humans are enculturated through human training (especially with intensive social interaction). These examples of enculturated developmental plasticity across extremely diverse taxa suggest, consistent with the evo-devo theme of highly conserved processes in evolution, that human language is founded in part on cognitive capabilities that are indeed ancient and that even modern humans show self-organized emergence of many language capabilities in the context of rich enculturation, built on the special social/ecological history of the hominin line. Human culture can thus be seen as a regulatory system encouraging language development in the context of a cognitive background with many highly conserved features. Copyright © 2016 Cognitive Science Society, Inc.

Development of human epithelial cell systems for radiation risk assessment

NASA Astrophysics Data System (ADS)

Yang, C. H.; Craise, L. M.

1994-10-01

The most important health effect of space radiation for astronauts is cancer induction. For radiation risk assessment, an understanding of carcinogenic effect of heavy ions in human cells is most essential. In our laboratory, we have successfully developed a human mammary epithelial cell system for studying the neoplastic transformation in vitro. Growth variants were obtained from heavy ion irradiated immortal mammary cell line. These cloned growth variants can grow in regular tissue culture media and maintain anchorage dependent growth and density inhibition property. Upon further irradiation with high-LET radiation, transformed foci were found. Experimental results from these studies suggest that multiexposure of radiation is required to induce neoplastic transformation of human epithelial cells. This multihits requirement may be due to high genomic stability of human cells. These growth variants can be useful model systems for space flight experiments to determine the carcinogenic effect of space radiation in human epithelial cells.

Development of human epithelial cell systems for radiation risk assessment

NASA Technical Reports Server (NTRS)

Yang, C. H.; Craise, L. M.

1994-01-01

The most important health effect of space radiation for astronauts is cancer induction. For radiation risk assessment, an understanding of carcinogenic effect of heavy ions in human cells is most essential. In our laboratory, we have successfully developed a human mammary epithelial cell system for studying the neoplastic transformation in vitro. Growth variants were obtained from heavy ion irradiated immortal mammary cell line. These cloned growth variants can grow in regular tissue culture media and maintain anchorage dependent growth and density inhibition property. Upon further irradiation with high-Linear Energy Transfer (LET) radiation, transformed foci were found. Experimental results from these studies suggest that multiexposure of radiation is required to induce neoplastic tranformation of human epithelial cells. This multihits requirement may be due to high genomic stability of human cells. These growth variants can be useful model systems for space flight experiments to determine the carcinogenic effect of space radiation in human epithelial cells.

Human pluripotent stem cells: an emerging model in developmental biology

PubMed Central

Zhu, Zengrong; Huangfu, Danwei

2013-01-01

Developmental biology has long benefited from studies of classic model organisms. Recently, human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, have emerged as a new model system that offers unique advantages for developmental studies. Here, we discuss how studies of hPSCs can complement classic approaches using model organisms, and how hPSCs can be used to recapitulate aspects of human embryonic development ‘in a dish’. We also summarize some of the recently developed genetic tools that greatly facilitate the interrogation of gene function during hPSC differentiation. With the development of high-throughput screening technologies, hPSCs have the potential to revolutionize gene discovery in mammalian development. PMID:23362344

Characterizing synaptic protein development in human visual cortex enables alignment of synaptic age with rat visual cortex

PubMed Central

Pinto, Joshua G. A.; Jones, David G.; Williams, C. Kate; Murphy, Kathryn M.

2015-01-01

Although many potential neuroplasticity based therapies have been developed in the lab, few have translated into established clinical treatments for human neurologic or neuropsychiatric diseases. Animal models, especially of the visual system, have shaped our understanding of neuroplasticity by characterizing the mechanisms that promote neural changes and defining timing of the sensitive period. The lack of knowledge about development of synaptic plasticity mechanisms in human cortex, and about alignment of synaptic age between animals and humans, has limited translation of neuroplasticity therapies. In this study, we quantified expression of a set of highly conserved pre- and post-synaptic proteins (Synapsin, Synaptophysin, PSD-95, Gephyrin) and found that synaptic development in human primary visual cortex (V1) continues into late childhood. Indeed, this is many years longer than suggested by neuroanatomical studies and points to a prolonged sensitive period for plasticity in human sensory cortex. In addition, during childhood we found waves of inter-individual variability that are different for the four proteins and include a stage during early development (<1 year) when only Gephyrin has high inter-individual variability. We also found that pre- and post-synaptic protein balances develop quickly, suggesting that maturation of certain synaptic functions happens within the 1 year or 2 of life. A multidimensional analysis (principle component analysis) showed that most of the variance was captured by the sum of the four synaptic proteins. We used that sum to compare development of human and rat visual cortex and identified a simple linear equation that provides robust alignment of synaptic age between humans and rats. Alignment of synaptic ages is important for age-appropriate targeting and effective translation of neuroplasticity therapies from the lab to the clinic. PMID:25729353

Develop Recovery Systems for Separations of Salts from Process Streams for use in Advanced Life Support System

NASA Technical Reports Server (NTRS)

Colon, Guillermo

1998-01-01

The main objectives of this project were the development of a four-compartment electrolytic cell using high selective membranes to remove nitrate from crop residue leachate and convert it to nitric acid, and the development of an six compartment electrodialysis cell to remove selectively sodium from urine wastes. The recovery of both plant inedible biomass and human wastes nutrients to sustain a biomass production system are important aspects in the development of a controlled ecological life support system (CELSS) to provide the basic human needs required for life support during long term space missions. A four-compartment electrolytic cell has been proposed to remove selectively nitrate from crop residue and to convert it to nitric acid, which is actually used in the NASA-KSC Controlled Ecological Life Support System to control the pH of the aerobic bioreactors and biomass production chamber. Human activities in a closed system require large amount of air, water and minerals to sustain life and also generate wastes. Before using human wastes as nutrients, these must be treated to reduce organic content and to remove some minerals which have adverse effects on plant growth. Of all the minerals present in human urine, sodium chloride (NACl) is the only one that can not be used as nutrient for most plants. Human activities also requires sodium chloride as part of the diet. Therefore, technology to remove and recover sodium chloride from wastes is highly desirable. A six-compartment electrodialysis cell using high selective membranes has been proposed to remove and recover NaCl from human urine.

Genetically engineered mouse models and human osteosarcoma

PubMed Central

2012-01-01

Osteosarcoma is the most common form of bone cancer. Pivotal insight into the genes involved in human osteosarcoma has been provided by the study of rare familial cancer predisposition syndromes. Three kindreds stand out as predisposing to the development of osteosarcoma: Li-Fraumeni syndrome, familial retinoblastoma and RecQ helicase disorders, which include Rothmund-Thomson Syndrome in particular. These disorders have highlighted the important roles of P53 and RB respectively, in the development of osteosarcoma. The association of OS with RECQL4 mutations is apparent but the relevance of this to OS is uncertain as mutations in RECQL4 are not found in sporadic OS. Application of the knowledge or mutations of P53 and RB in familial and sporadic OS has enabled the development of tractable, highly penetrant murine models of OS. These models share many of the cardinal features associated with human osteosarcoma including, importantly, a high incidence of spontaneous metastasis. The recent development of these models has been a significant advance for efforts to improve our understanding of the genetics of human OS and, more critically, to provide a high-throughput genetically modifiable platform for preclinical evaluation of new therapeutics. PMID:23036272

Strategies for Opportunity: Creating a High Performance Workforce for Ohio. A Comprehensive Workforce Development Strategy Developed by the Governor's Human Resources Advisory Council.

ERIC Educational Resources Information Center

Ohio State Bureau of Employment Services, Columbus.

The growing gap between the skill requirements of jobs and workers' capabilities, the slow growth of the U.S. work force, and the demands of a global economy will reshape the work force in Ohio. To meet these challenges, the Governor's Human Resources Advisory Council proposes as its mission the achievement and maintenance of a high performance…

High School Students' Written Argumentation Qualities with Problem-Based Computer-Aided Material (PBCAM) Designed about Human Endocrine System

ERIC Educational Resources Information Center

Vekli, Gülsah Sezen; Çimer, Atilla

2017-01-01

This study investigated development of students' scientific argumentation levels in the applications made with Problem-Based Computer-Aided Material (PBCAM) designed about Human Endocrine System. The case study method was used: The study group was formed of 43 students in the 11th grade of the science high school in Rize. Human Endocrine System…

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

Roger Lew; Ronald L. Boring; Thomas A. Ulrich

Operators of critical processes, such as nuclear power production, must contend with highly complex systems, procedures, and regulations. Developing human-machine interfaces (HMIs) that better support operators is a high priority for ensuring the safe and reliable operation of critical processes. Human factors engineering (HFE) provides a rich and mature set of tools for evaluating the performance of HMIs, but the set of tools for developing and designing HMIs is still in its infancy. Here we propose that Microsoft Windows Presentation Foundation (WPF) is well suited for many roles in the research and development of HMIs for process control.

Development of a High Angular Resolution Diffusion Imaging Human Brain Template

PubMed Central

Varentsova, Anna; Zhang, Shengwei; Arfanakis, Konstantinos

2014-01-01

Brain diffusion templates contain rich information about the microstructure of the brain, and are used as references in spatial normalization or in the development of brain atlases. The accuracy of diffusion templates constructed based on the diffusion tensor (DT) model is limited in regions with complex neuronal micro-architecture. High angular resolution diffusion imaging (HARDI) overcomes limitations of the DT model and is capable of resolving intravoxel heterogeneity. However, when HARDI is combined with multiple-shot sequences to minimize image artifacts, the scan time becomes inappropriate for human brain imaging. In this work, an artifact-free HARDI template of the human brain was developed from low angular resolution multiple-shot diffusion data. The resulting HARDI template was produced in ICBM-152 space based on Turboprop diffusion data, was shown to resolve complex neuronal micro-architecture in regions with intravoxel heterogeneity, and contained fiber orientation information consistent with known human brain anatomy. PMID:24440528

Fully integrated biochip platforms for advanced healthcare.

PubMed

Carrara, Sandro; Ghoreishizadeh, Sara; Olivo, Jacopo; Taurino, Irene; Baj-Rossi, Camilla; Cavallini, Andrea; de Beeck, Maaike Op; Dehollain, Catherine; Burleson, Wayne; Moussy, Francis Gabriel; Guiseppi-Elie, Anthony; De Micheli, Giovanni

2012-01-01

Recent advances in microelectronics and biosensors are enabling developments of innovative biochips for advanced healthcare by providing fully integrated platforms for continuous monitoring of a large set of human disease biomarkers. Continuous monitoring of several human metabolites can be addressed by using fully integrated and minimally invasive devices located in the sub-cutis, typically in the peritoneal region. This extends the techniques of continuous monitoring of glucose currently being pursued with diabetic patients. However, several issues have to be considered in order to succeed in developing fully integrated and minimally invasive implantable devices. These innovative devices require a high-degree of integration, minimal invasive surgery, long-term biocompatibility, security and privacy in data transmission, high reliability, high reproducibility, high specificity, low detection limit and high sensitivity. Recent advances in the field have already proposed possible solutions for several of these issues. The aim of the present paper is to present a broad spectrum of recent results and to propose future directions of development in order to obtain fully implantable systems for the continuous monitoring of the human metabolism in advanced healthcare applications.

Fully Integrated Biochip Platforms for Advanced Healthcare

PubMed Central

Carrara, Sandro; Ghoreishizadeh, Sara; Olivo, Jacopo; Taurino, Irene; Baj-Rossi, Camilla; Cavallini, Andrea; de Beeck, Maaike Op; Dehollain, Catherine; Burleson, Wayne; Moussy, Francis Gabriel; Guiseppi-Elie, Anthony; De Micheli, Giovanni

2012-01-01

Recent advances in microelectronics and biosensors are enabling developments of innovative biochips for advanced healthcare by providing fully integrated platforms for continuous monitoring of a large set of human disease biomarkers. Continuous monitoring of several human metabolites can be addressed by using fully integrated and minimally invasive devices located in the sub-cutis, typically in the peritoneal region. This extends the techniques of continuous monitoring of glucose currently being pursued with diabetic patients. However, several issues have to be considered in order to succeed in developing fully integrated and minimally invasive implantable devices. These innovative devices require a high-degree of integration, minimal invasive surgery, long-term biocompatibility, security and privacy in data transmission, high reliability, high reproducibility, high specificity, low detection limit and high sensitivity. Recent advances in the field have already proposed possible solutions for several of these issues. The aim of the present paper is to present a broad spectrum of recent results and to propose future directions of development in order to obtain fully implantable systems for the continuous monitoring of the human metabolism in advanced healthcare applications. PMID:23112644

Human genetics and genomics a decade after the release of the draft sequence of the human genome.

PubMed

Naidoo, Nasheen; Pawitan, Yudi; Soong, Richie; Cooper, David N; Ku, Chee-Seng

2011-10-01

Substantial progress has been made in human genetics and genomics research over the past ten years since the publication of the draft sequence of the human genome in 2001. Findings emanating directly from the Human Genome Project, together with those from follow-on studies, have had an enormous impact on our understanding of the architecture and function of the human genome. Major developments have been made in cataloguing genetic variation, the International HapMap Project, and with respect to advances in genotyping technologies. These developments are vital for the emergence of genome-wide association studies in the investigation of complex diseases and traits. In parallel, the advent of high-throughput sequencing technologies has ushered in the 'personal genome sequencing' era for both normal and cancer genomes, and made possible large-scale genome sequencing studies such as the 1000 Genomes Project and the International Cancer Genome Consortium. The high-throughput sequencing and sequence-capture technologies are also providing new opportunities to study Mendelian disorders through exome sequencing and whole-genome sequencing. This paper reviews these major developments in human genetics and genomics over the past decade.

Human genetics and genomics a decade after the release of the draft sequence of the human genome

PubMed Central

2011-01-01

Substantial progress has been made in human genetics and genomics research over the past ten years since the publication of the draft sequence of the human genome in 2001. Findings emanating directly from the Human Genome Project, together with those from follow-on studies, have had an enormous impact on our understanding of the architecture and function of the human genome. Major developments have been made in cataloguing genetic variation, the International HapMap Project, and with respect to advances in genotyping technologies. These developments are vital for the emergence of genome-wide association studies in the investigation of complex diseases and traits. In parallel, the advent of high-throughput sequencing technologies has ushered in the 'personal genome sequencing' era for both normal and cancer genomes, and made possible large-scale genome sequencing studies such as the 1000 Genomes Project and the International Cancer Genome Consortium. The high-throughput sequencing and sequence-capture technologies are also providing new opportunities to study Mendelian disorders through exome sequencing and whole-genome sequencing. This paper reviews these major developments in human genetics and genomics over the past decade. PMID:22155605

Health indicators and human development in the Arab region

PubMed Central

Boutayeb, Abdesslam; Serghini, Mansour

2006-01-01

Background The present paper deals with the relationship between health indicators and human development in the Arab region. Beyond descriptive analysis showing geographic similarities and disparities inter countries, the main purpose is to point out health deficiencies and to propose pragmatic strategies susceptible to improve health conditions and consequently enhance human development in the Arab world. Methods Data analysis using Principal Components Analysis is used to compare the achievements of the Arab countries in terms of direct and indirect health indicators. The variables (indicators) are seen to be well represented on the circle of correlation, allowing for interesting interpretation and analysis. The 19 countries are projected on the first and second plane respectively. Results The results given by the present analysis give a good panorama of the Arab countries with their geographic similarities and disparities. The high correlation between health indicators and human development is well illustrated and consequently, countries are classified by groups having similar human development. The analysis shows clearly how health deficits are impeding human development in the majority of Arab countries and allows us to formulate suggestions to improve health conditions and enhance human development in the Arab World. Discussion The discussion is based on the link between different direct and indirect health indicators and the relationship between these indicators and human development index. Without including the GDP indicator, our analysis has shown that the 19 Arab countries may be classified, independently of their geographic proximity, in three different groups according to their global human development level (Low, Medium and High). Consequently, while identifying health deficiencies in each group, the focus was made on the countries presenting a high potential of improvement in health indicators. In particular, maternal mortality and infant mortality which are really challenging health authorities of the first and third group were critically discussed. Conclusion The Arab countries have made substantial economic and social progress during the last decades by improving life expectancy and reducing maternal and infant mortality. However, considering its natural wealth and human resources, the Arab region has accomplished less than expected in terms of human development. Huge social inequalities and health inequities exist inter and intra Arab countries. In most Arab countries, a large percentage of populations, especially in rural areas, are deprived of access to health facilities. Consequently, many women still die during pregnancy and labour, yielding unacceptable levels of maternal and infant mortality. However, the problem is seen to be more complex, going beyond geography and technical accessibility to health care, it compasses, among others, levels of literacy, low social and economic status of women, qualification of health staff, general behaviour and interactions between patients and medical personnel (including corruption). PMID:17194309

Development of DNA markers for newly identified high-oleate peanut mutants

USDA-ARS?s Scientific Manuscript database

Development of high-oleate cultivars is one of the important objectives of peanut breeding because consuming products containing high oleate can benefit human health in many aspects. By screening the entire USDA cultivated peanut collection, we have identified two new high-oleate mutants (PI 342664...

Provincial Human Development Index, a Guide for Efficiency Level Analysis: The Case of Iran

PubMed Central

SABERMAHANI, Asma; BAROUNI, Mohsen; SEYEDIN, Hesam; ARYANKHESAL, Aidin

2013-01-01

Background Human Development Index (HDI) is a composite indicator that can show the impact of economic strategies on human life standards. The index is calculated by three main factors of income, education and health. This research studies the status of HDI across the Iranian provinces, its changes over time and the efficiency of provinces in using resources. Methods: The data for 2001 and 2009 was obtained from the Iranian Center of Statistics. Data envelopment analysis technique was used to analyze the data. To calculate the efficiency, Banker, Charnes and Cooper’s model was used. Results: The national mean for the HDI in 2001 was 0.717 while it grew to 0.747 in 2009. Except for one province, all others had an improved human development index. Low ranked provinces such as Sistan & Baluchistan and Kurdistan stayed at the bottom in 2009 as well. Some provinces such as Bushehr with developing oil industries, or those purposively benefited from national oil income showed good growth. In some provinces, such as Hormozgan, out-migration of manpower to its neighboring province, Bushehr, was associated with decrease of the provincial income level. The number of efficient provinces increased from 5 to 13 in 2009. Conclusion: Iran falls among countries with high human development index based on the 2009 data. However, the distribution of HDI status across provinces was highly varied and the difference between high- and low-developed provinces increased in 2009. The government needs to revise policies concerning distribution of resources among the provinces. PMID:23515434

Expression of HLA Class II Molecules in Humanized NOD.Rag1KO.IL2RgcKO Mice Is Critical for Development and Function of Human T and B Cells

PubMed Central

Danner, Rebecca; Chaudhari, Snehal N.; Rosenberger, John; Surls, Jacqueline; Richie, Thomas L.; Brumeanu, Teodor-Doru; Casares, Sofia

2011-01-01

Background Humanized mice able to reconstitute a surrogate human immune system (HIS) can be used for studies on human immunology and may provide a predictive preclinical model for human vaccines prior to clinical trials. However, current humanized mouse models show sub-optimal human T cell reconstitution and limited ability to support immunoglobulin class switching by human B cells. This limitation has been attributed to the lack of expression of Human Leukocyte Antigens (HLA) molecules in mouse lymphoid organs. Recently, humanized mice expressing HLA class I molecules have been generated but showed little improvement in human T cell reconstitution and function of T and B cells. Methods We have generated NOD.Rag1KO.IL2RγcKO mice expressing HLA class II (HLA-DR4) molecules under the I-Ed promoter that were infused as adults with HLA-DR-matched human hematopoietic stem cells (HSC). Littermates lacking expression of HLA-DR4 molecules were used as control. Results HSC-infused HLA-DR4.NOD.Rag1KO.IL-2RγcKO mice developed a very high reconstitution rate (>90%) with long-lived and functional human T and B cells. Unlike previous humanized mouse models reported in the literature and our control mice, the HLA-DR4 expressing mice reconstituted serum levels (natural antibodies) of human IgM, IgG (all four subclasses), IgA, and IgE comparable to humans, and elicited high titers of specific human IgG antibodies upon tetanus toxoid vaccination. Conclusions Our study demonstrates the critical role of HLA class II molecules for development of functional human T cells able to support immunoglobulin class switching and efficiently respond to vaccination. PMID:21611197

Managing and Mobilising Talent in Malaysia: Issues, Challenges and Policy Implications for Malaysian Universities

ERIC Educational Resources Information Center

Azman, Norzaini; Sirat, Morshidi; Pang, Vincent

2016-01-01

The future of Malaysia as a high-income and competitive nation largely depends on its pool of highly skilled human capital. Hence, the issue of human capital development has taken centre stage in numerous reform agendas of Malaysia. This paper seeks to provide examples of policy initiatives aimed at facilitating the management of highly educated…

Teaching, Learning, Literacy in Our High-Risk High-Tech World: A Framework for Becoming Human

ERIC Educational Resources Information Center

Gee, James Paul

2017-01-01

This is a profound look at learning, language, and literacy. It is also about brains and bodies. And it is about talk, texts, media, and society. These topics, though usually studied in different narrow academic silos, are all part of one highly interactive process--human development. Gee argues that children will need to be resilient,…

RODENT AND HUMAN NEUROPROGENITOR CELLS FOR HIGH-CONTENT SCREENS OF CHEMICAL EFFECTS ON PROLIFERATION AND APOPTOSIS

EPA Science Inventory

The objective of these experiments is to develop high-throughput screens for proliferation and apoptosis in order to compare rodent and human neuroprogenitor cell responses to potential developmental neurotoxicants. Effects of 4 chemicals on proliferation and apoptosis in mouse c...

Transgenic nude mouse with green fluorescent protein expression-based human glioblastoma multiforme animal model with EGFR expression and invasiveness.

PubMed

Tan, Guo-Wei; Lan, Fo-Lin; Gao, Jian-Guo; Jiang, Cai-Mou; Zhang, Yi; Huang, Xiao-Hong; Ma, Yue-Hong; Shao, He-Dui; He, Xue-Yang; Chen, Jin-Long; Long, Jian-Wu; Xiao, Hui-Sheng; Guo, Zhi-Tong; Diao, Yi

2012-08-01

Previously, we developed an orthotopic xenograft model of human glioblastoma multiforme (GBM) with high EGFR expression and invasiveness in Balb/c nu/nu nude mice. Now we also developed the same orthotopic xenograft model in transgenic nude mice with green fluorescent protein (GFP) expression. The present orthotopic xenografts labeled by phycoerythrin fluorescing red showed high EGFR expression profile, and invasive behavior under a bright green-red dual-color fluorescence background. A striking advantage in the present human GBM model is that the change of tumor growth can be observed visually instead of sacrificing animals in our further antitumor therapy studies.

Encapsulating Non-Human Primate Multipotent Stromal Cells in Alginate via High Voltage for Cell-Based Therapies and Cryopreservation

PubMed Central

Gryshkov, Oleksandr; Pogozhykh, Denys; Hofmann, Nicola; Pogozhykh, Olena; Mueller, Thomas; Glasmacher, Birgit

2014-01-01

Alginate cell-based therapy requires further development focused on clinical application. To assess engraftment, risk of mutations and therapeutic benefit studies should be performed in an appropriate non-human primate model, such as the common marmoset (Callithrix jacchus). In this work we encapsulated amnion derived multipotent stromal cells (MSCs) from Callithrix jacchus in defined size alginate beads using a high voltage technique. Our results indicate that i) alginate-cell mixing procedure and cell concentration do not affect the diameter of alginate beads, ii) encapsulation of high cell numbers (up to 10×106 cells/ml) can be performed in alginate beads utilizing high voltage and iii) high voltage (15–30 kV) does not alter the viability, proliferation and differentiation capacity of MSCs post-encapsulation compared with alginate encapsulated cells produced by the traditional air-flow method. The consistent results were obtained over the period of 7 days of encapsulated MSCs culture and after cryopreservation utilizing a slow cooling procedure (1 K/min). The results of this work show that high voltage encapsulation can further be maximized to develop cell-based therapies with alginate beads in a non-human primate model towards human application. PMID:25259731

Human Sexuality: Responsible Life Choices.

ERIC Educational Resources Information Center

Ryder, Verdene; Smith, Peggy B.

This book provides a complete course in human sexuality. It can also be used to supplement a family living course. Text content provides current information for teaching high school students about sexuality issues. The text offers basic information on growth and development, sexual development, pregnancy, and birth. It explains the sexual decision…

Modeling congenital disease and inborn errors of development in Drosophila melanogaster

PubMed Central

Moulton, Matthew J.; Letsou, Anthea

2016-01-01

ABSTRACT Fly models that faithfully recapitulate various aspects of human disease and human health-related biology are being used for research into disease diagnosis and prevention. Established and new genetic strategies in Drosophila have yielded numerous substantial successes in modeling congenital disorders or inborn errors of human development, as well as neurodegenerative disease and cancer. Moreover, although our ability to generate sequence datasets continues to outpace our ability to analyze these datasets, the development of high-throughput analysis platforms in Drosophila has provided access through the bottleneck in the identification of disease gene candidates. In this Review, we describe both the traditional and newer methods that are facilitating the incorporation of Drosophila into the human disease discovery process, with a focus on the models that have enhanced our understanding of human developmental disorders and congenital disease. Enviable features of the Drosophila experimental system, which make it particularly useful in facilitating the much anticipated move from genotype to phenotype (understanding and predicting phenotypes directly from the primary DNA sequence), include its genetic tractability, the low cost for high-throughput discovery, and a genome and underlying biology that are highly evolutionarily conserved. In embracing the fly in the human disease-gene discovery process, we can expect to speed up and reduce the cost of this process, allowing experimental scales that are not feasible and/or would be too costly in higher eukaryotes. PMID:26935104

The Unrealised Value of Human Motion--"Moving Back to Movement!"

ERIC Educational Resources Information Center

Dodd, Graham D.

2015-01-01

The unrealised and under-estimated value of human motion in human development, functioning and learning is the central cause for its devaluation in Australian society. This paper provides a greater insight into why human motion has high value and should be utilised more in advocacy and implementation in health and education, particularly school…

Mobile element biology – new possibilities with high-throughput sequencing

PubMed Central

Xing, Jinchuan; Witherspoon, David J.; Jorde, Lynn B.

2014-01-01

Mobile elements compose more than half of the human genome, but until recently their large-scale detection was time-consuming and challenging. With the development of new high-throughput sequencing technologies, the complete spectrum of mobile element variation in humans can now be identified and analyzed. Thousands of new mobile element insertions have been discovered, yielding new insights into mobile element biology, evolution, and genomic variation. We review several high-throughput methods, with an emphasis on techniques that specifically target mobile element insertions in humans, and we highlight recent applications of these methods in evolutionary studies and in the analysis of somatic alterations in human cancers. PMID:23312846

Balancing Life & Work: The Humanities as an Essential Part of Career Exploration.

ERIC Educational Resources Information Center

Haynes, Leslie; Blake, Amy

This guide explains why the humanities are important in school-to-work systems and how high schools can develop one of two types of programs integrating humanities coursework and career exploration: the study of humanities as a way to enrich individuals' work lives and the study of humanities as career fields in their own right. The first half of…

BLT-humanized C57BL/6 Rag2-/-γc-/-CD47-/- mice are resistant to GVHD and develop B- and T-cell immunity to HIV infection.

PubMed

Lavender, Kerry J; Pang, Wendy W; Messer, Ronald J; Duley, Amanda K; Race, Brent; Phillips, Katie; Scott, Dana; Peterson, Karin E; Chan, Charles K; Dittmer, Ulf; Dudek, Timothy; Allen, Todd M; Weissman, Irving L; Hasenkrug, Kim J

2013-12-12

The use of C57BL/6 Rag2(-/-)γc(-/-) mice as recipients for xenotransplantation with human immune systems (humanization) has been problematic because C57BL/6 SIRPα does not recognize human CD47, and such recognition is required to suppress macrophage-mediated phagocytosis of transplanted human hematopoietic stem cells (HSCs). We show that genetic inactivation of CD47 on the C57BL/6 Rag2(-/-)γc(-/-) background negates the requirement for CD47-signal recognition protein α (SIRPα) signaling and induces tolerance to transplanted human HSCs. These triple-knockout, bone marrow, liver, thymus (TKO-BLT) humanized mice develop organized lymphoid tissues including mesenteric lymph nodes, splenic follicles and gut-associated lymphoid tissue that demonstrate high levels of multilineage hematopoiesis. Importantly, these mice have an intact complement system and showed no signs of graft-versus-host disease (GVHD) out to 29 weeks after transplantation. Sustained, high-level HIV-1 infection was observed via either intrarectal or intraperitoneal inoculation. TKO-BLT mice exhibited hallmarks of human HIV infection including CD4(+) T-cell depletion, immune activation, and development of HIV-specific B- and T-cell responses. The lack of GVHD makes the TKO-BLT mouse a significantly improved model for long-term studies of pathogenesis, immune responses, therapeutics, and vaccines to human pathogens.

The tragedy of Tauccamarca: a human rights perspective on the pesticide poisoning deaths of 4 children in the Peruvian Andes.

PubMed

Rosenthal, Erika

2003-01-01

The pesticide poisoning deaths of 24 children in an isolated Peruvian village make a compelling case that corporate accountability for pesticide poisonings in the developing south should be examined from a human rights perspective. Highly toxic pesticides cannot be used safely under prevailing socioeconomic conditions. The industry asserts that the deaths of these children were accidental, blaming misuse. Tragedies such as these poisonings are not accidents, but foreseeable, and therefore preventable. Sales of highly toxic pesticides that cause repeated and predictable poisonings violate the fundamental human rights to life, health, and security of person. The Tauccamarca tragedy is a clear example of the urgency of applying a precautionary, human rights approach to pesticide issues in the developing south.

Yellowstone grizzly bear mortality, human habituation, and whitebark pine seed crops

USGS Publications Warehouse

Mattson, David J.; Blanchard, Bonnie M.; Knight, Richard R.

1992-01-01

The Yellowstone grizzly bear (Ursus arctos horribilis) population may be extirpated during the next 100-200 years unless mortality rates stabilize and remain at acceptable low levels. Consequently, we analyzed relationships between Yellowstone grizzly bear mortality and frequency of human habituation among bears and size of the whitebark pine (Pinus albicaulis) seed crop. During years of large seed crops, bears used areas within 5 km of roads and 8 km of developments half as intensively as during years of small seed crops because whitebark pine's high elevation distribution is typically remote from human facilities. On average, management trappings of bears were 6.2 times higher, mortality of adult females 2.3 times higher, and mortality of subadult males 3.3 times higher during years of small seed crops. We hypothesize that high mortality of adult females and subadult males during small seed crop years was a consequence of their tendency to range closest (of all sex-age cohorts) to human facilities; they also had a higher frequency of human habituation compared with adult males. We also hypothesize that low morality among subadult females during small seed crop years was a result of fewer energetic stressors compared with adult females and greater familiarity with their range compared with subadult males; mortality was low even though they ranged close to humans and exhibited a high frequency of human habituation. Human-habituated and food-conditioned bears were 2.9 times as likely to range within 4 km of developments and 3.1 times as often killed by humans compared with nonhabituated bears. We argue that destruction of habituated bears that use native foods near humans results in a decline in the overall ability of bears to use available habitat; and that the number and extent of human facilities in occupied grizzly bear habitat needs to be minimized unless habituated bears are preserved and successful ways to manage the associated risks to humans are developed.

Developing human capital: what is the impact on nurse turnover?

PubMed

Rondeau, Kent V; Williams, Eric S; Wagar, Terry H

2009-09-01

To investigate the impact that increasing human capital through staff training makes on the voluntary turnover of registered nurses. Healthcare organizations in Canada, the United Kingdom, the United States, and Australia are experiencing turbulent nursing labour markets characterized by extreme staff shortages and high levels of turnover. Organizations that invest in the development of their nursing human resources may be able to mitigate high turnover through the creation of conditions that more effectively develop and utilize their existing human capital. A questionnaire was sent to the chief nursing officers of 2208 hospitals and long-term care facilities in every province and territory of Canada yielding a response rate of 32.3%. The analysis featured a three-step hierarchical regression with two sets of control variables. After controlling for establishment demographics and local labour market conditions, perceptions of nursing human capital and the level of staff training provided were modestly associated with lower levels of establishment turnover. and implications for Nursing Management The results suggest that healthcare organizations that have made greater investments in their nursing human capital are more likely to demonstrate lower levels of turnover of their registered nursing personnel.

A high density of human communication-associated genes in chromosome 7q31-q36: differential expression in human and non-human primate cortices.

PubMed

Schneider, E; Jensen, L R; Farcas, R; Kondova, I; Bontrop, R E; Navarro, B; Fuchs, E; Kuss, A W; Haaf, T

2012-01-01

The human brain is distinguished by its remarkable size, high energy consumption, and cognitive abilities compared to all other mammals and non-human primates. However, little is known about what has accelerated brain evolution in the human lineage. One possible explanation is that the appearance of advanced communication skills and language has been a driving force of human brain development. The phenotypic adaptations in brain structure and function which occurred on the way to modern humans may be associated with specific molecular signatures in today's human genome and/or transcriptome. Genes that have been linked to language, reading, and/or autism spectrum disorders are prime candidates when searching for genes for human-specific communication abilities. The database and genome-wide expression analyses we present here revealed a clustering of such communication-associated genes (COAG) on human chromosomes X and 7, in particular chromosome 7q31-q36. Compared to the rest of the genome, we found a high number of COAG to be differentially expressed in the cortices of humans and non-human primates (chimpanzee, baboon, and/or marmoset). The role of X-linked genes for the development of human-specific cognitive abilities is well known. We now propose that chromosome 7q31-q36 also represents a hot spot for the evolution of human-specific communication abilities. Selective pressure on the T cell receptor beta locus on chromosome 7q34, which plays a pivotal role in the immune system, could have led to rapid dissemination of positive gene variants in hitchhiking COAG. Copyright © 2012 S. Karger AG, Basel.

Environmental Education. Nevada Competency-Based Adult High School Diploma Project.

ERIC Educational Resources Information Center

Nevada Univ., Las Vegas. Coll. of Education.

This document is one of ten curriculum guides developed by the Nevada Competency-Based Adult High School Diploma (CBAHSD) Project. This curriculum guide on environmental education is divided into seven topics. The topics included are Human Carrying Capacity (The Ability to Foresee and Forestall), Human Population Growth, The Atmosphere, The…

Utility of Hantzsch reaction for development of highly sensitive spectrofluorimetric method for determination of alfuzosin and terazosin in bulk, dosage forms and human plasma.

PubMed

Hammad, Mohamed A; Omar, Mahmoud A; Salman, Baher I

2017-09-01

A highly sensitive, cheap, simple and accurate spectrofluorimetric method has been developed and validated for the determination of alfuzosin hydrochloride and terazosin hydrochloride in their pharmaceutical dosage forms and in human plasma. The developed method is based on the reaction of the primary amine moiety in the studied drugs with acetylacetone and formaldehyde according to the Hantzsch reaction, producing yellow fluorescent products that can be measured spectrofluorimetrically at 480 nm after excitation at 415 nm. Different experimental parameters affecting the development and stability of the reaction products were carefully studied and optimized. The fluorescence-concentration plots of alfuzosin and terazosin were rectilinear over a concentration range of 70-900 ng ml -1 , with quantitation limits 27.1 and 32.2 ng ml -1 for alfuzosin and terazosin, respectively. The proposed method was validated according to ICH guidelines and successfully applied to the analysis of the investigated drugs in dosage forms, content uniformity test and spiked human plasma with high accuracy. Copyright © 2017 John Wiley & Sons, Ltd.

Strategies for Developing a High-Skilled Workforce

ERIC Educational Resources Information Center

Sleezer, Catherine M.; Denny, Dan

2004-01-01

This article focuses on the human performance improvement and human resource development task of providing an organization with a skilled workforce. We begin by describing the U.S. demographic trends and the changing job skill requirements that will lead to a shortage of skilled workers and that highlight the importance of considering the various…

HIGH INFORMATION CONTENT TOXICITY SCREENING USING MOUSE AND HUMAN STEM CELL MODELS OF ENDOCRINE DEVELOPMENT AND FUNCTION

EPA Science Inventory

The project will result in the rapid assessment of chemicals for adverse effects on the development of gametes, adipocytes, and islet B-cells; and on the adipocyte and B-cell endocrine signaling function in human and murine embryonic stem cells. Based on the data, hierarchical...

Democracy, Human Development, and Happiness Indices as Precursors of International Student Success

ERIC Educational Resources Information Center

Demirbolat, Ayse Ottekin

2018-01-01

This paper aims to explore the relationships between educational attainment as expressed in PISA scores and several socio-economic and political variables some of which are sub-indices of Human Development Index. The correlation analysis reveals that there are highly significant associations between educational attainment and civil liberties,…

Sensitive genotyping of foodborne-associated human noroviruses and hepatitis A virus using an array-based platform

USDA-ARS?s Scientific Manuscript database

The viral pathogens, human norovirus (NoV) and hepatitis A virus (HAV), are significant contributors of foodborne associated outbreaks. To develop a typing tool for foodborne viruses, a focused, low-density DNA microarray was developed in conjunction with a rapid and high-throughput fluorescent meth...

Demonstrating the Financial Benefit of Human Resource Development: Status and Update on the Theory and Practice.

ERIC Educational Resources Information Center

Swanson, Richard A.

1998-01-01

A research review identified findings about the financial analysis method, forecasting of the financial benefits of human resource development (HRD), and recent financial analysis research: (1) HRD embedded in a performance improvement framework yielded high return on investment; and (2) HRD interventions focused on performance variables forecast…

Strategic Planning for Economic Development.

ERIC Educational Resources Information Center

Groff, Warren H.

The Ohio Task Force on High Technology (TFHT) was formed in 1982 to make recommendations in four areas: (1) the development of future scenarios for Ohio; (2) human resource development of providers and consumers of postsecondary educational services; (3) equipment and capital plan expenditures; and (4) implications of high technology for academic…

A translatable predictor of human radiation exposure.

PubMed

Lucas, Joseph; Dressman, Holly K; Suchindran, Sunil; Nakamura, Mai; Chao, Nelson J; Himburg, Heather; Minor, Kerry; Phillips, Gary; Ross, Joel; Abedi, Majid; Terbrueggen, Robert; Chute, John P

2014-01-01

Terrorism using radiological dirty bombs or improvised nuclear devices is recognized as a major threat to both public health and national security. In the event of a radiological or nuclear disaster, rapid and accurate biodosimetry of thousands of potentially affected individuals will be essential for effective medical management to occur. Currently, health care providers lack an accurate, high-throughput biodosimetric assay which is suitable for the triage of large numbers of radiation injury victims. Here, we describe the development of a biodosimetric assay based on the analysis of irradiated mice, ex vivo-irradiated human peripheral blood (PB) and humans treated with total body irradiation (TBI). Interestingly, a gene expression profile developed via analysis of murine PB radiation response alone was inaccurate in predicting human radiation injury. In contrast, generation of a gene expression profile which incorporated data from ex vivo irradiated human PB and human TBI patients yielded an 18-gene radiation classifier which was highly accurate at predicting human radiation status and discriminating medically relevant radiation dose levels in human samples. Although the patient population was relatively small, the accuracy of this classifier in discriminating radiation dose levels in human TBI patients was not substantially confounded by gender, diagnosis or prior exposure to chemotherapy. We have further incorporated genes from this human radiation signature into a rapid and high-throughput chemical ligation-dependent probe amplification assay (CLPA) which was able to discriminate radiation dose levels in a pilot study of ex vivo irradiated human blood and samples from human TBI patients. Our results illustrate the potential for translation of a human genetic signature for the diagnosis of human radiation exposure and suggest the basis for further testing of CLPA as a candidate biodosimetric assay.

Human Relations Class. A Syllabus.

ERIC Educational Resources Information Center

Guillen, Mary A.

A junior high level human relations class develops human interaction and oral communication skills. A week-by-week syllabus contains the following components: introduction of the students to each other and to the principles of body language, transactional analysis, and group interaction; behavior contracts; group dynamics topics and exercises;…

Tendencies of International Career of Romanian Researchers: Brain Drain?

ERIC Educational Resources Information Center

Popescu, Dan; Patrasca, Mihaela; Chivu, Iulia

2006-01-01

Recent economic and technological developments have led to a growing international demand for highly skilled human resources. The increased competition for human capital has determined numerous OECD countries to take special measures for attracting and retaining human capital in such fields as: information technology, biotechnology,…

Development of a high angular resolution diffusion imaging human brain template.

PubMed

Varentsova, Anna; Zhang, Shengwei; Arfanakis, Konstantinos

2014-05-01

Brain diffusion templates contain rich information about the microstructure of the brain, and are used as references in spatial normalization or in the development of brain atlases. The accuracy of diffusion templates constructed based on the diffusion tensor (DT) model is limited in regions with complex neuronal micro-architecture. High angular resolution diffusion imaging (HARDI) overcomes limitations of the DT model and is capable of resolving intravoxel heterogeneity. However, when HARDI is combined with multiple-shot sequences to minimize image artifacts, the scan time becomes inappropriate for human brain imaging. In this work, an artifact-free HARDI template of the human brain was developed from low angular resolution multiple-shot diffusion data. The resulting HARDI template was produced in ICBM-152 space based on Turboprop diffusion data, was shown to resolve complex neuronal micro-architecture in regions with intravoxel heterogeneity, and contained fiber orientation information consistent with known human brain anatomy. Copyright © 2014 Elsevier Inc. All rights reserved.

Human-animal chimeras for vaccine development: an endangered species or opportunity for the developing world?

PubMed Central

2010-01-01

Background In recent years, the field of vaccines for diseases such as Human Immunodeficiency Virus (HIV) which take a heavy toll in developing countries has faced major failures. This has led to a call for more basic science research, and development as well as evaluation of new vaccine candidates. Human-animal chimeras, developed with a 'humanized' immune system could be useful to study infectious diseases, including many neglected diseases. These would also serve as an important tool for the efficient testing of new vaccine candidates to streamline promising candidates for further trials in humans. However, developing human-animal chimeras has proved to be controversial. Discussion Development of human-animal chimeras for vaccine development has been slowed down because of opposition by some philosophers, ethicists and policy makers in the west-they question the moral status of such animals, and also express discomfort about transgression of species barriers. Such opposition often uses a contemporary western world view as a reference point. Human-animal chimeras are often being created for diseases which cause significantly higher morbidity and mortality in the developing world as compared to the developed world. We argue in our commentary that given this high disease burden, we should look at socio-cultural perspectives on human-animal chimera like beings in the developing world. On examination, it's clear that such beings have been part of mythology and cultural descriptions in many countries in the developing world. Summary To ensure that important research on diseases afflicting millions like malaria, HIV, Hepatitis-C and dengue continues to progress, we recommend supporting human-animal chimera research for vaccine development in developing countries (especially China and India which have growing technical expertise in the area). The negative perceptions in some parts of the west about human-animal chimeras can be used as an opportunity for nurturing important vaccine development research in the developing world. PMID:20482820

Training of cosmonauts and astronauts

NASA Technical Reports Server (NTRS)

Gurovskiy, N. N.; Link, M. M.

1975-01-01

The biomedical and preflight training of spacecraft crews is discussed based on a survey of scientific and technical literature in the U.S. and U.S.S.R. Experience gained from high velocity and high altitude aircraft flights, predictions of human reactions and theoretical models of human adaptation to the new environment of space, and actual spaceflight experience provided scientists and specialists with data from which the state of human health in space could be predicted and life support measures developed.

Enhancement of Immune Memory Responses to Respiratory Infection

DTIC Science & Technology

2017-08-01

induction of highly specific B and T cell responses against viral infections. Despite recent progress in vaccine development, the molecular mechanisms...highly expressed in memory B cells in mice, and Atg7 is required for maintenance of long-term memory B cells needed to protect against influenza...infection. Human influenza-specific memory B cells also have high levels of autophagy, but whether autophagy protects memory B cell survival in humans

Phosphodiesterase inhibitors as a new generation of antiprotozoan drugs: exploiting the benefit of enzymes that are highly conserved between host and parasite

PubMed Central

Seebeck, Thomas; Sterk, Geert Jan; Ke, Hengming

2011-01-01

Protozoan infections remain a major unsolved medical problem in many parts of our world. A major obstacle to their treatment is the blatant lack of medication that is affordable, effective, safe and easy to administer. For some of these diseases, including human sleeping sickness, very few compounds are available, many of them old and all of them fraught with toxic side effects. We explore a new concept for developing new-generation antiprotozoan drugs that are based on phosphodiesterase (PDE) inhibitors. Such inhibitors are already used extensively in human pharmacology. Given the high degree of structural similarity between the human and the protozoan PDEs, the vast expertise available in the human field can now be applied to developing disease-specific PDE inhibitors as new antiprotozoan drugs. PMID:21859303

Development and evaluation of a study design typology for human research.

PubMed

Carini, Simona; Pollock, Brad H; Lehmann, Harold P; Bakken, Suzanne; Barbour, Edward M; Gabriel, Davera; Hagler, Herbert K; Harper, Caryn R; Mollah, Shamim A; Nahm, Meredith; Nguyen, Hien H; Scheuermann, Richard H; Sim, Ida

2009-11-14

A systematic classification of study designs would be useful for researchers, systematic reviewers, readers, and research administrators, among others. As part of the Human Studies Database Project, we developed the Study Design Typology to standardize the classification of study designs in human research. We then performed a multiple observer masked evaluation of active research protocols in four institutions according to a standardized protocol. Thirty-five protocols were classified by three reviewers each into one of nine high-level study designs for interventional and observational research (e.g., N-of-1, Parallel Group, Case Crossover). Rater classification agreement was moderately high for the 35 protocols (Fleiss' kappa = 0.442) and higher still for the 23 quantitative studies (Fleiss' kappa = 0.463). We conclude that our typology shows initial promise for reliably distinguishing study design types for quantitative human research.

Developmental plasticity and language: A comparative perspective

PubMed Central

Griebel, Ulrike; Pepperberg, Irene; Oller, D. Kimbrough

2016-01-01

The growing field of evo-devo is increasingly demonstrating the complexity of steps involved in genetic, intracellular regulatory, and extracellular environmental control of the development of phenotypes. A key result of such work is an account for the remarkable plasticity of organismal form in many species based on relatively minor changes in regulation of highly conserved genes and genetic processes. Accounting for behavioral plasticity is of similar potential interest but has received far less attention. Of particular interest is plasticity in communication systems, where human language represents an ultimate target for research. The present paper considers plasticity of language capabilities in a comparative framework, focusing attention on examples of a remarkable fact: Whereas there exist design features of mature human language that have never been observed to occur in nonhumans in the wild, many of these features can be developed to notable extents when nonhumans are enculturated through human training (especially with intensive social interaction). These examples of enculturated developmental plasticity across extremely diverse taxa suggest, consistent with the evo-devo theme of highly conserved processes in evolution, that human language is founded in part on cognitive capabilities that are indeed ancient and that even modern humans show self-organized emergence of many language capabilities in the context of rich enculturation, built on the special social/ecological history of the hominin line. Human culture can thus be seen as a regulatory system encouraging language development in the context of a cognitive background with many highly conserved features. PMID:27003391

Next Generation Life Support (NGLS): High Performance EVA Glove (HPEG) Technology Development Element

NASA Technical Reports Server (NTRS)

Walsh, Sarah; Barta, Daniel; Stephan, Ryan; Gaddis, Stephen

2015-01-01

The overall objective is to develop advanced gloves for extra vehicular activity (EVA) for future human space exploration missions and generate corresponding standards by which progress may be quantitatively assessed. The glove prototypes that result from the successful completion of this technology development activity will be delivered to NASA's Human Exploration Operations Mission Directorate (HEOMD) and ultimately to be included in an integrated test with the next generation spacesuit currently under development.

Pathways of human development and carbon emissions embodied in trade

NASA Astrophysics Data System (ADS)

Steinberger, Julia K.; Timmons Roberts, J.; Peters, Glen P.; Baiocchi, Giovanni

2012-02-01

It has long been assumed that human development depends on economic growth, that national economic expansion in turn requires greater energy use and, therefore, increased greenhouse-gas emissions. These interdependences are the topic of current research. Scarcely explored, however, is the impact of international trade: although some nations develop socio-economically and import high-embodied-carbon products, it is likely that carbon-exporting countries gain significantly fewer benefits. Here, we use new consumption-based measures of national carbon emissions to explore how the relationship between human development and carbon changes when we adjust national emission rates for trade. Without such adjustment of emissions, some nations seem to be getting far better development `bang' for the carbon `buck' than others, who are showing scant gains for disproportionate shares of global emissions. Adjusting for the transfer of emissions through trade explains many of these outliers, but shows that further socio-economic benefits are accruing to carbon-importing rather than carbon-exporting countries. We also find that high life expectancies are compatible with low carbon emissions but high incomes are not. Finally, we see that, despite strong international trends, there is no deterministic industrial development trajectory: there is great diversity in pathways, and national histories do not necessarily follow the global trends.

A High School Program in Human Ecology: Helping Everyone Live Productively. Student Handbook.

ERIC Educational Resources Information Center

Brandywine School District, Claymont, DE.

The program's goal is to provide high school students an opportunity to become an active force in the advancement of the human condition and to develop positive attitudes to improve their effectiveness in dealing with their environment. The student handbook consists of eight chapters, including an introduction to the program in chapter I. Chapter…

Designer Babies? Teacher Views on Gene Technology and Human Medicine.

ERIC Educational Resources Information Center

Schibeci, Renato

1999-01-01

Summarizes the views of a sample of primary and high school teachers on the application of gene technology to human medicine. In general, high school teachers are more positive about these developments than primary teachers, and both groups of teachers are more positive than interested lay publics. Highlights ways in which this topic can be…

A High School English Chairman Looks at the Humanities Approach for All Students.

ERIC Educational Resources Information Center

Mersand, Joseph

As the humanities approach to education expands, the high school English chairman can aid his teachers in developing this approach by suggesting useful teaching methods, praising successful teaching techniques, and permitting teachers to pursue independent methods of instruction. One method is an in-depth study of an historical period (such as the…

Human iPSC-derived neurons and lymphoblastoid cells for personalized medicine research in neuropsychiatric disorders.

PubMed

Gurwitz, David

2016-09-01

The development and clinical implementation of personalized medicine crucially depends on the availability of high-quality human biosamples; animal models, although capable of modeling complex human diseases, cannot reflect the large variation in the human genome, epigenome, transcriptome, proteome, and metabolome. Although the biosamples available from public biobanks that store human tissues and cells may represent the large human diversity for most diseases, these samples are not always sufficient for developing biomarkers for patient-tailored therapies for neuropsychiatric disorders. Postmortem human tissues are available from many biobanks; nevertheless, collections of neuronal human cells from large patient cohorts representing the human diversity remain scarce. Two tools are gaining popularity for personalized medicine research on neuropsychiatric disorders: human induced pluripotent stem cell-derived neurons and human lymphoblastoid cell lines. This review examines and contrasts the advantages and limitations of each tool for personalized medicine research.

LungMAP: The Molecular Atlas of Lung Development Program

PubMed Central

Ardini-Poleske, Maryanne E.; Ansong, Charles; Carson, James P.; Corley, Richard A.; Deutsch, Gail H.; Hagood, James S.; Kaminski, Naftali; Mariani, Thomas J.; Potter, Steven S.; Pryhuber, Gloria S.; Warburton, David; Whitsett, Jeffrey A.; Palmer, Scott M.; Ambalavanan, Namasivayam

2017-01-01

The National Heart, Lung, and Blood Institute is funding an effort to create a molecular atlas of the developing lung (LungMAP) to serve as a research resource and public education tool. The lung is a complex organ with lengthy development time driven by interactive gene networks and dynamic cross talk among multiple cell types to control and coordinate lineage specification, cell proliferation, differentiation, migration, morphogenesis, and injury repair. A better understanding of the processes that regulate lung development, particularly alveologenesis, will have a significant impact on survival rates for premature infants born with incomplete lung development and will facilitate lung injury repair and regeneration in adults. A consortium of four research centers, a data coordinating center, and a human tissue repository provides high-quality molecular data of developing human and mouse lungs. LungMAP includes mouse and human data for cross correlation of developmental processes across species. LungMAP is generating foundational data and analysis, creating a web portal for presentation of results and public sharing of data sets, establishing a repository of young human lung tissues obtained through organ donor organizations, and developing a comprehensive lung ontology that incorporates the latest findings of the consortium. The LungMAP website (www.lungmap.net) currently contains more than 6,000 high-resolution lung images and transcriptomic, proteomic, and lipidomic human and mouse data and provides scientific information to stimulate interest in research careers for young audiences. This paper presents a brief description of research conducted by the consortium, database, and portal development and upcoming features that will enhance the LungMAP experience for a community of users. PMID:28798251

The Learning Alliance: Systems Thinking in Human Resource Development. First Edition. The Jossey-Bass Management Series.

ERIC Educational Resources Information Center

Brinkerhoff, Robert O.; Gill, Stephen J.

This book presents an approach that organizes the principles and processes of an emerging human resource development (HRD) paradigm requiring training to be everyone's business. Chapter 1 describes the paradigm and presents a practical approach for applying it. Chapter 2 draws a picture of highly effective training (HET), focusing particularly on…

Characteristics of Highly Talented International Business Professionals Defined: Qualitative Study among International Business Professionals

ERIC Educational Resources Information Center

van Heugten, Petra; Heijne-Penninga, Marjolein; Paans, Wolter; Wolfensberger, Marca

2016-01-01

Purpose: The purpose of this paper is to explore the characteristics of talent in relation to international business to facilitate selection and development of talent in human resources (HR) and human resource development (HRD). Design/methodology/approach: A mixed method design was used: focus groups with business professionals to identify the…

Planning, Plumbing, or Posturing? Explaining the Weakness of Human Resource Development Structures and Policies in South Africa

ERIC Educational Resources Information Center

Allais, Stephanie; Marock, Carmel; Ngcwangu, Siphelo

2017-01-01

In South Africa, a national peak structure, the Human Resource Development Council, led by the Deputy President and consisting of key Cabinet Ministers, senior leaders from organised labour and business, community representatives, professional bodies and experts from research and higher education, was established to enable high-level coordination…

75 FR 41873 - Prospective Grant of Exclusive License: The Development of Human Therapeutics for the Treatment...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-19

... preferentially expressed on several types of hematological cancer cells, the anti-CD22 antibody binding fragment... Exclusive License: The Development of Human Therapeutics for the Treatment of Cancer AGENCY: National... Immunotoxin in Which All B-Cell Epitopes Have Been Removed and Which Has High Cytotoxic Activity'' [HHS Ref. E...

Utilizing Immersive Visualization Systems: How to Dynamically Revolutionize Site-based Professional Development Experiences within Human Resources Management?

ERIC Educational Resources Information Center

Craft, Kirby A.

2009-01-01

How can we train today's workforce with innovative technologies when families are surrounded by state-of-the-art video games and high-definition televisions? Human resource managers and administrators are faced with difficult challenges to prepare beneficial and relevant professional development exercises that engage the minds of their employees.…

Impact of human development on safety consciousness in construction.

PubMed

Baradan, Selim; Dikmen, Seyyit Umit; Akboga Kale, Ozge

2018-05-03

The International Labour Organization (ILO) reports that the risk of fatal occupational injuries in developing countries is almost twice as high as in developed countries, indicating a potential relationship between the fatality rates and the development level. The human development index (HDI), based on life expectancy, knowledge level and purchasing power parity, endorsed by the United Nations Development Programme, is a widely accepted measure of the development level. This study investigates the relationship between the HDI and the fatality rates reported by the ILO. A 23-country data set is used to demonstrate the general trend of the relationship followed by country-specific analyses for Australia, Spain, Hungary and Turkey. The study conducted is limited to fatal occupational injuries in construction, where the accidents are notoriously high. The results demonstrate a statistically significant inverse relationship between the fatality rates and the HDI.

Comprehensive transcriptional map of primate brain development

PubMed Central

Bakken, Trygve E.; Miller, Jeremy A.; Ding, Song-Lin; Sunkin, Susan M.; Smith, Kimberly A.; Ng, Lydia; Szafer, Aaron; Dalley, Rachel A.; Royall, Joshua J.; Lemon, Tracy; Shapouri, Sheila; Aiona, Kaylynn; Arnold, James; Bennett, Jeffrey L.; Bertagnolli, Darren; Bickley, Kristopher; Boe, Andrew; Brouner, Krissy; Butler, Stephanie; Byrnes, Emi; Caldejon, Shiella; Carey, Anita; Cate, Shelby; Chapin, Mike; Chen, Jefferey; Dee, Nick; Desta, Tsega; Dolbeare, Tim A.; Dotson, Nadia; Ebbert, Amanda; Fulfs, Erich; Gee, Garrett; Gilbert, Terri L.; Goldy, Jeff; Gourley, Lindsey; Gregor, Ben; Gu, Guangyu; Hall, Jon; Haradon, Zeb; Haynor, David R.; Hejazinia, Nika; Hoerder-Suabedissen, Anna; Howard, Robert; Jochim, Jay; Kinnunen, Marty; Kriedberg, Ali; Kuan, Chihchau L.; Lau, Christopher; Lee, Chang-Kyu; Lee, Felix; Luong, Lon; Mastan, Naveed; May, Ryan; Melchor, Jose; Mosqueda, Nerick; Mott, Erika; Ngo, Kiet; Nyhus, Julie; Oldre, Aaron; Olson, Eric; Parente, Jody; Parker, Patrick D.; Parry, Sheana; Pendergraft, Julie; Potekhina, Lydia; Reding, Melissa; Riley, Zackery L.; Roberts, Tyson; Rogers, Brandon; Roll, Kate; Rosen, David; Sandman, David; Sarreal, Melaine; Shapovalova, Nadiya; Shi, Shu; Sjoquist, Nathan; Sodt, Andy J.; Townsend, Robbie; Velasquez, Lissette; Wagley, Udi; Wakeman, Wayne B.; White, Cassandra; Bennett, Crissa; Wu, Jennifer; Young, Rob; Youngstrom, Brian L.; Wohnoutka, Paul; Gibbs, Richard A.; Rogers, Jeffrey; Hohmann, John G.; Hawrylycz, Michael J.; Hevner, Robert F.; Molnár, Zoltán; Phillips, John W.; Dang, Chinh; Jones, Allan R.; Amaral, David G.; Bernard, Amy; Lein, Ed S.

2017-01-01

The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high resolution transcriptional atlas of rhesus monkey brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical parcellation of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons, and cortical layers and areas acquire adult-like molecular profiles surprisingly late postnatally. Disparate cell populations exhibit distinct developmental timing but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, autism spectrum disorder, intellectual disability, and schizophrenia show disease-specific spatiotemporal enrichment within developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, and approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny. PMID:27409810

Training medical students in human rights: a fifteen-year experience in Geneva

PubMed Central

Chastonay, Philippe; Zesiger, Véronique; Ferreira, Jackeline; Mpinga, Emmanuel Kabengele

2012-01-01

Background Training health professionals in the field of human rights has long been advocated by the United Nations. Over the past decade some medical schools have introduced health and human rights courses, yet by far not all. This paper describes the objectives and the content of the Health and Human Rights program developed at the Faculty of Medicine, University of Geneva. Methods The health and human rights program was developed through the identification of the course objectives, contents, and educational modalities using consensus techniques, and through a step by step implementation procedure integrating multiple evaluation processes. Results Defined objectives included the familiarization with the concepts, instruments and mechanisms of human rights, the links between health and human rights, and the role of health professionals in promoting human rights. The content ultimately adopted focused on the typology of human rights, their mechanisms of protection, their instruments, as well as social inequalities and vulnerable groups of the population. The implementation proceeded through a step by step approach. Evaluation showed high satisfaction of students, good achievement of learning objectives, and some academic and community impact. Conclusions High interest of students for a human rights course is encouraging. Furthermore, the community projects initiated and implemented by students may contribute to the social responsibility of the academic institution. PMID:26451186

Humanized Mouse Model of Ebola Virus Disease Mimics the Immune Responses in Human Disease.

PubMed

Bird, Brian H; Spengler, Jessica R; Chakrabarti, Ayan K; Khristova, Marina L; Sealy, Tara K; Coleman-McCray, JoAnn D; Martin, Brock E; Dodd, Kimberly A; Goldsmith, Cynthia S; Sanders, Jeanine; Zaki, Sherif R; Nichol, Stuart T; Spiropoulou, Christina F

2016-03-01

Animal models recapitulating human Ebola virus disease (EVD) are critical for insights into virus pathogenesis. Ebola virus (EBOV) isolates derived directly from human specimens do not, without adaptation, cause disease in immunocompetent adult rodents. Here, we describe EVD in mice engrafted with human immune cells (hu-BLT). hu-BLT mice developed EVD following wild-type EBOV infection. Infection with high-dose EBOV resulted in rapid, lethal EVD with high viral loads, alterations in key human antiviral immune cytokines and chemokines, and severe histopathologic findings similar to those shown in the limited human postmortem data available. A dose- and donor-dependent clinical course was observed in hu-BLT mice infected with lower doses of either Mayinga (1976) or Makona (2014) isolates derived from human EBOV cases. Engraftment of the human cellular immune system appeared to be essential for the observed virulence, as nonengrafted mice did not support productive EBOV replication or develop lethal disease. hu-BLT mice offer a unique model for investigating the human immune response in EVD and an alternative animal model for EVD pathogenesis studies and therapeutic screening. Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Why Pop? A Conversation about Language with John Cawelti. The National Humanities Faculty Why Series.

ERIC Educational Resources Information Center

Cawelti, John; Rogerson, Don F.

This is a conversation concerning pop culture between Don F. Rogerson, Head of the Humanities Department of Baltimore City College and chairman of a faculty committee for the development of an experimental, humanities-oriented three-year high school, and John Cawelti, Professor of English and Humanities at the University of Chicago and chairman of…

Considerations for human exposure standards for fast-rise-time high-peak-power electromagnetic pulses.

PubMed

Merritt, J H; Kiel, J L; Hurt, W D

1995-06-01

Development of new emitter systems capable of producing high-peak-power electromagnetic pulses with very fast rise times and narrow pulse widths is continuing. Such directed energy weapons systems will be used in the future to defeat electronically vulnerable targets. Human exposures to these pulses can be expected during testing and operations. Development of these technologies for radar and communications purposes has the potential for wider environmental exposure, as well. Current IEEE C95.1-1991 human exposure guidelines do not specifically address these types of pulses, though limits are stated for pulsed emissions. The process for developing standards includes an evaluation of the relevant bioeffects data base. A recommendation has been made that human exposure to ultrashort electromagnetic pulses that engender electromagnetic transients, called precursor waves, should be avoided. Studies that purport to show the potential for tissue damage induced by such pulses were described. The studies cited in support of the recommendation were not relevant to the issues of tissue damage by propagated pulses. A number of investigations are cited in this review that directly address the biological effects of electromagnetic pulses. These studies have not shown evidence of tissue damage as a result of exposure to high-peak-power pulsed microwaves. It is our opinion that the current guidelines are sufficiently protective for human exposure to these pulses.

Identification and functional analysis of long non-coding RNAs in human and mouse early embryos based on single-cell transcriptome data

PubMed Central

Qiu, Jia-jun; Ren, Zhao-rui; Yan, Jing-bin

2016-01-01

Epigenetics regulations have an important role in fertilization and proper embryonic development, and several human diseases are associated with epigenetic modification disorders, such as Rett syndrome, Beckwith-Wiedemann syndrome and Angelman syndrome. However, the dynamics and functions of long non-coding RNAs (lncRNAs), one type of epigenetic regulators, in human pre-implantation development have not yet been demonstrated. In this study, a comprehensive analysis of human and mouse early-stage embryonic lncRNAs was performed based on public single-cell RNA sequencing data. Expression profile analysis revealed that lncRNAs are expressed in a developmental stage–specific manner during human early-stage embryonic development, whereas a more temporal-specific expression pattern was identified in mouse embryos. Weighted gene co-expression network analysis suggested that lncRNAs involved in human early-stage embryonic development are associated with several important functions and processes, such as oocyte maturation, zygotic genome activation and mitochondrial functions. We also found that the network of lncRNAs involved in zygotic genome activation was highly preservative between human and mouse embryos, whereas in other stages no strong correlation between human and mouse embryo was observed. This study provides insight into the molecular mechanism underlying lncRNA involvement in human pre-implantation embryonic development. PMID:27542205

Diabetes-associated dry eye syndrome in a new humanized transgenic model of type 1 diabetes.

PubMed

Imam, Shahnawaz; Elagin, Raya B; Jaume, Juan Carlos

2013-01-01

Patients with Type 1 Diabetes (T1D) are at high risk of developing lacrimal gland dysfunction. We have developed a new model of human T1D using double-transgenic mice carrying HLA-DQ8 diabetes-susceptibility haplotype instead of mouse MHC-class II and expressing the human beta cell autoantigen Glutamic Acid Decarboxylase in pancreatic beta cells. We report here the development of dry eye syndrome (DES) after diabetes induction in our humanized transgenic model. Double-transgenic mice were immunized with DNA encoding human GAD65, either naked or in adenoviral vectors, to induce T1D. Mice monitored for development of diabetes developed lacrimal gland dysfunction. Animals developed lacrimal gland disease (classically associated with diabetes in Non Obese Diabetic [NOD] mice and with T1D in humans) as they developed glucose intolerance and diabetes. Animals manifested obvious clinical signs of dry eye syndrome (DES), from corneal erosions to severe keratitis. Histological studies of peri-bulbar areas revealed lymphocytic infiltration of glandular structures. Indeed, infiltrative lesions were observed in lacrimal/Harderian glands within weeks following development of glucose intolerance. Lesions ranged from focal lymphocytic infiltration to complete acinar destruction. We observed a correlation between the severity of the pancreatic infiltration and the severity of the ocular disease. Our results demonstrate development of DES in association with antigen-specific insulitis and diabetes following immunization with clinically relevant human autoantigen concomitantly expressed in pancreatic beta cells of diabetes-susceptible mice. As in the NOD mouse model and as in human T1D, our animals developed diabetes-associated DES. This specific finding stresses the relevance of our model for studying these human diseases. We believe our model will facilitate studies to prevent/treat diabetes-associated DES as well as human diabetes.

Mutually Augmented Cognition

NASA Astrophysics Data System (ADS)

Friesdorf, Florian; Pangercic, Dejan; Bubb, Heiner; Beetz, Michael

In mac, an ergonomic dialog-system and algorithms will be developed that enable human experts and companions to be integrated into knowledge gathering and decision making processes of highly complex cognitive systems (e.g. Assistive Household as manifested further in the paper). In this event we propose to join algorithms and methodologies coming from Ergonomics and Artificial Intelligence that: a) make cognitive systems more congenial for non-expert humans, b) facilitate their comprehension by utilizing a high-level expandable control code for human experts and c) augment representation of such cognitive system into “deep representation” obtained through an interaction with human companions.

Origins and early development of human body knowledge.

PubMed

Slaughter, Virginia; Heron, Michelle

2004-01-01

As a knowable object, the human body is highly complex. Evidence from several converging lines of research, including psychological studies, neuroimaging and clinical neuropsychology, indicates that human body knowledge is widely distributed in the adult brain, and is instantiated in at least three partially independent levels of representation. Sensorimotor body knowledge is responsible for on-line control and movement of one's own body and may also contribute to the perception of others' moving bodies; visuo-spatial body knowledge specifies detailed structural descriptions of the spatial attributes of the human body; and lexical-semantic body knowledge contains language-based knowledge about the human body. In the first chapter of this Monograph, we outline the evidence for these three hypothesized levels of human body knowledge, then review relevant literature on infants' and young children's human body knowledge in terms of the three-level framework. In Chapters II and III, we report two complimentary series of studies that specifically investigate the emergence of visuo-spatial body knowledge in infancy. Our technique is to compare infants'responses to typical and scrambled human bodies, in order to evaluate when and how infants acquire knowledge about the canonical spatial layout of the human body. Data from a series of visual habituation studies indicate that infants first discriminate scrambled from typical human body picture sat 15 to 18 months of age. Data from object examination studies similarly indicate that infants are sensitive to violations of three-dimensional human body stimuli starting at 15-18 months of age. The overall pattern of data supports several conclusions about the early development of human body knowledge: (a) detailed visuo-spatial knowledge about the human body is first evident in the second year of life, (b) visuo-spatial knowledge of human faces and human bodies are at least partially independent in infancy and (c) infants' initial visuo-spatial human body representations appear to be highly schematic, becoming more detailed and specific with development. In the final chapter, we explore these conclusions and discuss how levels of body knowledge may interact in early development.

Conserved and Divergent Features of Human and Mouse Kidney Organogenesis.

PubMed

Lindström, Nils O; McMahon, Jill A; Guo, Jinjin; Tran, Tracy; Guo, Qiuyu; Rutledge, Elisabeth; Parvez, Riana K; Saribekyan, Gohar; Schuler, Robert E; Liao, Christopher; Kim, Albert D; Abdelhalim, Ahmed; Ruffins, Seth W; Thornton, Matthew E; Basking, Laurence; Grubbs, Brendan; Kesselman, Carl; McMahon, Andrew P

2018-03-01

Human kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron number is linked to disease. Human kidney development initiates around 4 weeks of gestation and ends around 34-37 weeks of gestation. Over this period, a reiterative inductive process establishes the nephron complement. Studies have provided insightful anatomic descriptions of human kidney development, but the limited histologic views are not readily accessible to a broad audience. In this first paper in a series providing comprehensive insight into human kidney formation, we examined human kidney development in 135 anonymously donated human kidney specimens. We documented kidney development at a macroscopic and cellular level through histologic analysis, RNA in situ hybridization, immunofluorescence studies, and transcriptional profiling, contrasting human development (4-23 weeks) with mouse development at selected stages (embryonic day 15.5 and postnatal day 2). The high-resolution histologic interactive atlas of human kidney organogenesis generated can be viewed at the GUDMAP database (www.gudmap.org) together with three-dimensional reconstructions of key components of the data herein. At the anatomic level, human and mouse kidney development differ in timing, scale, and global features such as lobe formation and progenitor niche organization. The data also highlight differences in molecular and cellular features, including the expression and cellular distribution of anchor gene markers used to identify key cell types in mouse kidney studies. These data will facilitate and inform in vitro efforts to generate human kidney structures and comparative functional analyses across mammalian species. Copyright © 2018 by the American Society of Nephrology.

Organizing Principles of Human Cortical Development--Thickness and Area from 4 to 30 Years: Insights from Comparative Primate Neuroanatomy.

PubMed

Amlien, Inge K; Fjell, Anders M; Tamnes, Christian K; Grydeland, Håkon; Krogsrud, Stine K; Chaplin, Tristan A; Rosa, Marcello G P; Walhovd, Kristine B

2016-01-01

The human cerebral cortex undergoes a protracted, regionally heterogeneous development well into young adulthood. Cortical areas that expand the most during human development correspond to those that differ most markedly when the brains of macaque monkeys and humans are compared. However, it remains unclear to what extent this relationship derives from allometric scaling laws that apply to primate brains in general, or represents unique evolutionary adaptations. Furthermore, it is unknown whether the relationship only applies to surface area (SA), or also holds for cortical thickness (CT). In 331 participants aged 4 to 30, we calculated age functions of SA and CT, and examined the correspondence of human cortical development with macaque to human expansion, and with expansion across nonhuman primates. CT followed a linear negative age function from 4 to 30 years, while SA showed positive age functions until 12 years with little further development. Differential cortical expansion across primates was related to regional maturation of SA and CT, with age trajectories differing between high- and low-expanding cortical regions. This relationship adhered to allometric scaling laws rather than representing uniquely macaque-human differences: regional correspondence with human development was as large for expansion across nonhuman primates as between humans and macaque. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

ATHENA, the Desktop Human "Body"

ScienceCinema

Iyer, Rashi; Harris, Jennifer

2018-05-18

Creating surrogate human organs, coupled with insights from highly sensitive mass spectrometry technologies, a new project is on the brink of revolutionizing the way we screen new drugs and toxic agents. ATHENA, the Advanced Tissue-engineered Human Ectypal Network Analyzer project team, is developing four human organ constructs - liver, heart, lung and kidney - that are based on a significantly miniaturized platform. Each organ component will be about the size of a smartphone screen, and the whole ATHENA "body" of interconnected organs would fit neatly on a desk. "By developing this 'homo minutus,' we are stepping beyond the need for animal or Petri dish testing: There are huge benefits in developing drug and toxicity analysis systems that can mimic the response of actual human organs," said Rashi Iyer, a senior scientist at Los Alamos National Laboratory, the lead laboratory on the five-year, $19 million multi-institutional effort. The project is supported by the Defense Threat Reduction Agency (DTRA). Some 40 percent of pharmaceuticals fail their clinical trials, Iyer noted, and there are thousands of chemicals whose effects on humans are simply unknown. Providing a realistic, cost-effective and rapid screening system such as ATHENA with high-throughput capabilities could provide major benefits to the medical field, screening more accurately and offering a greater chance of clinical trial success.

ATHENA, the Desktop Human "Body"

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

Iyer, Rashi; Harris, Jennifer

2014-09-29

Creating surrogate human organs, coupled with insights from highly sensitive mass spectrometry technologies, a new project is on the brink of revolutionizing the way we screen new drugs and toxic agents. ATHENA, the Advanced Tissue-engineered Human Ectypal Network Analyzer project team, is developing four human organ constructs - liver, heart, lung and kidney - that are based on a significantly miniaturized platform. Each organ component will be about the size of a smartphone screen, and the whole ATHENA "body" of interconnected organs would fit neatly on a desk. "By developing this 'homo minutus,' we are stepping beyond the need formore » animal or Petri dish testing: There are huge benefits in developing drug and toxicity analysis systems that can mimic the response of actual human organs," said Rashi Iyer, a senior scientist at Los Alamos National Laboratory, the lead laboratory on the five-year, $19 million multi-institutional effort. The project is supported by the Defense Threat Reduction Agency (DTRA). Some 40 percent of pharmaceuticals fail their clinical trials, Iyer noted, and there are thousands of chemicals whose effects on humans are simply unknown. Providing a realistic, cost-effective and rapid screening system such as ATHENA with high-throughput capabilities could provide major benefits to the medical field, screening more accurately and offering a greater chance of clinical trial success.« less

Transgenic mouse strains as platforms for the successful discovery and development of human therapeutic monoclonal antibodies.

PubMed

Green, Larry L

2014-03-01

Transgenic mice have yielded seven of the ten currently-approved human antibody drugs, making them the most successful platform for the discovery of fully human antibody therapeutics. The use of the in vivo immune system helps drive this success by taking advantage of the natural selection process that produces antibodies with desirable characteristics. Appropriately genetically-engineered mice act as robust engines for the generation of diverse repertoires of affinity- matured fully human variable regions with intrinsic properties necessary for successful antibody drug development including high potency, specificity, manufacturability, solubility and low risk of immunogenicity. A broad range of mAb drug targets are addressable in these mice, comprising both secreted and transmembrane targets, including membrane multi-spanning targets, as well as human target antigens that share high sequence identity with their mouse orthologue. Transgenic mice can routinely yield antibodies with sub-nanomolar binding affinity for their antigen, with lead candidate mAbs frequently possessing affinities for binding to their target of less than 100 picomolar, without requiring any ex vivo affinity optimization. While the originator transgenic mice platforms are no longer broadly available, a new generation of transgenic platforms is in development for discovery of the next wave of human therapeutic antibodies.

A high-resolution probabilistic in vivo atlas of human subcortical brain nuclei

PubMed Central

Pauli, Wolfgang M.; Nili, Amanda N.; Tyszka, J. Michael

2018-01-01

Recent advances in magnetic resonance imaging methods, including data acquisition, pre-processing and analysis, have benefited research on the contributions of subcortical brain nuclei to human cognition and behavior. At the same time, these developments have led to an increasing need for a high-resolution probabilistic in vivo anatomical atlas of subcortical nuclei. In order to address this need, we constructed high spatial resolution, three-dimensional templates, using high-accuracy diffeomorphic registration of T1- and T2- weighted structural images from 168 typical adults between 22 and 35 years old. In these templates, many tissue boundaries are clearly visible, which would otherwise be impossible to delineate in data from individual studies. The resulting delineations of subcortical nuclei complement current histology-based atlases. We further created a companion library of software tools for atlas development, to offer an open and evolving resource for the creation of a crowd-sourced in vivo probabilistic anatomical atlas of the human brain. PMID:29664465

Development of a quantitative morphological assessment of toxicant-treated zebrafish larvae using brightfield imaging and high-content analysis.

PubMed

Deal, Samantha; Wambaugh, John; Judson, Richard; Mosher, Shad; Radio, Nick; Houck, Keith; Padilla, Stephanie

2016-09-01

One of the rate-limiting procedures in a developmental zebrafish screen is the morphological assessment of each larva. Most researchers opt for a time-consuming, structured visual assessment by trained human observer(s). The present studies were designed to develop a more objective, accurate and rapid method for screening zebrafish for dysmorphology. Instead of the very detailed human assessment, we have developed the computational malformation index, which combines the use of high-content imaging with a very brief human visual assessment. Each larva was quickly assessed by a human observer (basic visual assessment), killed, fixed and assessed for dysmorphology with the Zebratox V4 BioApplication using the Cellomics® ArrayScan® V(TI) high-content image analysis platform. The basic visual assessment adds in-life parameters, and the high-content analysis assesses each individual larva for various features (total area, width, spine length, head-tail length, length-width ratio, perimeter-area ratio). In developing the computational malformation index, a training set of hundreds of embryos treated with hundreds of chemicals were visually assessed using the basic or detailed method. In the second phase, we assessed both the stability of these high-content measurements and its performance using a test set of zebrafish treated with a dose range of two reference chemicals (trans-retinoic acid or cadmium). We found the measures were stable for at least 1 week and comparison of these automated measures to detailed visual inspection of the larvae showed excellent congruence. Our computational malformation index provides an objective manner for rapid phenotypic brightfield assessment of individual larva in a developmental zebrafish assay. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The human footprint in the west: a large-scale analysis of anthropogenic impacts.

USGS Publications Warehouse

Leu, M.; Hanser, S.E.; Knick, S.T.

2008-01-01

Anthropogenic features such as urbanization, roads, and power lines, are increasing in western United States landscapes in response to rapidly growing human populations. However, their spatial effects have not been evaluated. Our goal was to model the human footprint across the western United States. We first delineated the actual area occupied by anthropogenic features, the physical effect area. Next, we developed the human footprint model based on the ecological effect area, the zone influenced by features beyond their physical presence, by combining seven input models: three models quantified top-down anthropogenic influences of synanthropic predators (avian predators, domestic dog and cat presence risk), and four models quantified bottom-up anthropogenic influences on habitat (invasion of exotic plants, human-caused fires, energy extraction, and anthropogenic wildland fragmentation). Using independent bird population data, we found bird abundance of four synanthropic species to correlate positively with human footprint intensity and negatively for three of the six species influenced by habitat fragmentation. We then evaluated the extent of the human footprint in relation to terrestrial (ecoregions) and aquatic systems (major rivers and lakes), regional management and conservation status, physical environment, and temporal changes in human actions. The physical effect area of anthropogenic features covered 13% of the western United States with agricultural land (9.8%) being most dominant. High-intensity human footprint areas (class 8–10) overlapped highly productive low-elevation private landholdings and covered 7% of the western United States compared to 48% for low-intensity areas (class 1–3), which were confined to low-productivity high-elevation federal landholdings. Areas within 1 km of rivers were more affected by the human footprint compared to lakes. Percentage human population growth was higher in low-intensity human footprint areas. The disproportional regional effects of the human footprint on landscapes in the western United States create a challenge to management of ecosystems and wildlife populations. Using footprint models, managers can plan land use actions, develop restoration scenarios, and identify areas of high conservation value at local landscapes within a regional context. Moreover, human footprint models serve as a tool to stratify landscapes for studies investigating floral and faunal response to human disturbance intensity gradients.

From brain passage to cell adaptation: the road of human rabies vaccine development.

PubMed

Wu, Xianfu; Smith, Todd G; Rupprecht, Charles E

2011-11-01

A major challenge for global rabies prevention and control is the lack of sufficient and affordable high quality vaccines. Such candidates should be pure, potent, safe, effective and economical to produce, with broad cross-reactivity against viral variants of public health and veterinary importance. The history of licensed human vaccines reviewed herein demonstrates clearly how the field has evolved to the current state of more passive development and postexposure management. Modern cell culture techniques provide adequate viral substrates for production of representative verified virus seeds. In contrast to outdated nervous tissue-based rabies vaccines, once a suitable substrate is identified, production of high titer virus results in a major qualitative and quantitative difference. Given the current scenario of only inactivated vaccines for humans, highly cell-adapted and stable, attenuated rabies viruses are ideal candidates for consideration to meet the need for seed viruses in the future.

Radiopharmaceutical development based on human blood albumin microspheres and 90Y

NASA Astrophysics Data System (ADS)

Petriev, V. M.; Vlasova, O. P.; Postnov, A. A.; Epstein, N. B.

2017-01-01

New radiopharmaceutial (RP) based on human serum albumin microspheres (MSA) and 90Y was developed for treatment of liver cancer. The optimized synthesis using chelation resulted in approximately 80% yield with high specific activity. The RP developed was tested in mice with inoculated sarcoma-37. In two weeks the tumor size reduced by 43% after the treatment with the dose of 500 μCi injected into the tumor site.

Greenhouse Gas Inventory of a Typical High-End Industrial Park in China

PubMed Central

Chen, Bin; He, Guoxuan; Qi, Jing; Zhou, Shiyi; Jiang, Meiming

2013-01-01

Global climate change caused by greenhouse gas (GHG) emissions, which severely limits the development of human society and threatens the survival of humanity, has drawn the international community's long-term attention. Gathering the most important production factors in the region, an industrial park usually represents the development level of specific industries in the region. Therefore, the industrial park should be regarded as the base unit for developing a low-carbon economy and reducing GHG emissions. Focusing on a typical high-end industrial park in Beijing, we analyze the carbon sources within the system boundary and probe into the emission structure in view of life-cycle analysis. A GHG inventory is thereby set up to calculate all GHG emissions from the concerned park. Based on the results, suggestions are presented to guide the low-carbon development of the high-end industrial park. PMID:23431258

Greenhouse gas inventory of a typical high-end industrial park in China.

PubMed

Chen, Bin; He, Guoxuan; Qi, Jing; Su, Meirong; Zhou, Shiyi; Jiang, Meiming

2013-01-01

Global climate change caused by greenhouse gas (GHG) emissions, which severely limits the development of human society and threatens the survival of humanity, has drawn the international community's long-term attention. Gathering the most important production factors in the region, an industrial park usually represents the development level of specific industries in the region. Therefore, the industrial park should be regarded as the base unit for developing a low-carbon economy and reducing GHG emissions. Focusing on a typical high-end industrial park in Beijing, we analyze the carbon sources within the system boundary and probe into the emission structure in view of life-cycle analysis. A GHG inventory is thereby set up to calculate all GHG emissions from the concerned park. Based on the results, suggestions are presented to guide the low-carbon development of the high-end industrial park.

Traditional neighborhood development (TND) guidelines

DOT National Transportation Integrated Search

2000-08-01

A Traditional Neighborhood Development (TND) is a human scale, walkable community with moderate to high residential densities and a mixed use core. Compared with conventional suburban developments, TNDs have a higher potential to increase modal split...

X chromosome inactivation in human pluripotent stem cells as a model for human development: back to the drawing board?

PubMed

Geens, Mieke; Chuva De Sousa Lopes, Susana M

2017-09-01

Human pluripotent stem cells (hPSC), both embryonic and induced (hESC and hiPSC), are regarded as a valuable in vitro model for early human development. In order to fulfil this promise, it is important that these cells mimic as closely as possible the in vivo molecular events, both at the genetic and epigenetic level. One of the most important epigenetic events during early human development is X chromosome inactivation (XCI), the transcriptional silencing of one of the two X chromosomes in female cells. XCI is important for proper development and aberrant XCI has been linked to several pathologies. Recently, novel data obtained using high throughput single-cell technology during human preimplantation development have suggested that the XCI mechanism is substantially different from XCI in mouse. It has also been suggested that hPSC show higher complexity in XCI than the mouse. Here we compare the available recent data to understand whether XCI during human preimplantation can be properly recapitulated using hPSC. We will summarize what is known on the timing and mechanisms of XCI during human preimplantation development. We will compare this to the XCI patterns that are observed during hPSC derivation, culture and differentiation, and comment on the cause of the aberrant XCI patterns observed in hPSC. Finally, we will discuss the implications of the aberrant XCI patterns on the applicability of hPSC as an in vitro model for human development and as cell source for regenerative medicine. Combinations of the following keywords were applied as search criteria in the PubMed database: X chromosome inactivation, preimplantation development, embryonic stem cells, induced pluripotent stem cells, primordial germ cells, differentiation. Recent single-cell RNASeq data have shed new light on the XCI process during human preimplantation development. These indicate a gradual inactivation on both XX chromosomes, starting from Day 4 of development and followed by a random choice to inactivate one of them, instead of the mechanism in mice where imprinted XCI is followed by random XCI. We have put these new findings in perspective using previous data obtained in human (and mouse) embryos. In addition, there is an ongoing discussion whether or not hPSC lines show X chromosome reactivation upon derivation, mimicking the earliest embryonic cells, and the XCI states observed during culture of hPSC are highly variable. Recent studies have shown that hPSC rapidly progress to highly aberrant XCI patterns and that this process is probably driven by suboptimal culture conditions. Importantly, these aberrant XCI states seem to be inherited by the differentiated hPSC-progeny. The aberrant XCI states (and epigenetic instability) observed in hPSC throw a shadow on their applicability as an in vitro model for development and disease modelling. Moreover, as the aberrant XCI states observed in hPSC seem to shift to a more malignant phenotype, this may also have important consequences for the safety aspect of using hPSC in the clinic. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Expressive Writing: Enhancing the Emotional Intelligence of Human Services Majors

ERIC Educational Resources Information Center

Castillo, Yuleinys; Fischer, Jerome M.

2017-01-01

The skills and tasks in the human services field are highly connected to emotional intelligence abilities. The purpose of the study was to investigate the effect of an expressive writing program involving human service students in an undergraduate rehabilitation services course. The program was developed to enhance their emotional intelligence.…

DEVELOPING A HUMAN RIGHTS-BASED PROGRAM FOR TUBERCULOSIS CONTROL IN GEORGIAN PRISONS

PubMed Central

Gegia, Medea; Kalandadze, Iagor; Madzgharashvili, Mikheil; Furin, Jennifer

2013-01-01

Tuberculosis (TB) is one of the leading infectious killers of adults globally. Incarcerated individuals represent a vulnerable population when it comes to TB exposure, development of disease, and poor treatment outcomes. The TB pandemic in prisons is a serious human rights issue, and multiple global organizations have called for human rights-based strategies to address it. There are, however, few countries implementing such programs on the ground. Georgia, a former Soviet republic located in the Caucasus Mountains, has high rates of TB and a large prison population. This paper describes a needs assessment carried out in one prison in Georgia and the human rights-based strategy being implemented by the Georgian National TB Program to address TB control in the prison setting. It is hoped that the proposed program can serve as a model for other countries with high rates of TB among incarcerated individuals. PMID:22773034

Development of an Effective School-Based Financial Management Profile in Malaysia: The Delphi Method Application

ERIC Educational Resources Information Center

Radzi, Norfariza Mohd; Ghani, Muhammad Faizal A.; Siraj, Saedah

2015-01-01

The agenda for national development requires a persistent improvement in education as a tool for creating knowledgeable human capital, highly skilled labour, a high technology society and ultimately a highly civilized nation for the future challenging world. It requires considerable financial and technical investment as well as effective and…

Advanced Collaborative Environments Supporting Systems Integration and Design

DTIC Science & Technology

2003-03-01

concurrently view a virtual system or product model while maintaining natural, human communication . These virtual systems operate within a computer-generated...These environments allow multiple individuals to concurrently view a virtual system or product model while simultaneously maintaining natural, human ... communication . As a result, TARDEC researchers and system developers are using this advanced high-end visualization technology to develop future

Affordable Development and Qualification Strategy for Nuclear Thermal Propulsion

NASA Technical Reports Server (NTRS)

Gerrish, Harold P., Jr.; Doughty, Glen E.; Bhattacharyya, Samit K.

2013-01-01

A number of recent assessments have confirmed the results of several earlier studies that Nuclear Thermal Propulsion (NTP) is a leading technology for human exploration of Mars. It is generally acknowledged that NTP provides the best prospects for the transportation of humans to Mars in the 2030's. Its high Isp coupled with the high thrusts achievable, allow reasonable trip times, thereby alleviating concerns about space radiation and "claustrophobia" effects. NASA has embarked on the latest phase of the development of NTP systems, and is adopting an affordable approach in response to the pressure of the times. The affordable strategy is built on maximizing the use of the large NTP technology base developed in the 1950's and 60's. The fact that the NTP engines were actually demonstrated to work as planned, is a great risk reduction feature in its development. The strategy utilizes non-nuclear testing to the fullest extent possible, and uses focused nuclear tests for the essential qualification and certification tests. The perceived cost risk of conducting the ground tests is being addressed by considering novel testing approaches. This includes the use of boreholes to contain radioactive effluents, and use of fuel with very high retention capability for fission products. The use of prototype flight tests is being considered as final steps in the development prior to undertaking human flight missions. In addition to the technical issues, plans are being prepared to address the institutional and political issues that need to be considered in this major venture. While the development and deployment of NTP system is not expected to be cheap, the value of the system will be very high, and amortized over the many missions that it enables and enhances, the imputed costs will be very reasonable. Using the approach outlined, NASA and its partners, currently the DOE, and subsequently industry, have a good chance of creating a sustained development program leading to human missions to Mars within the next few decades.

The mad cow problem in the UK: risk perceptions, risk management, and health policy development.

PubMed

Lanska, D J

1998-01-01

Mad cow disease or bovine spongiform encephalopathy (BSE) is a fatal neurological disease of cattle first recognized in the United Kingdom (UK) in 1986. Until recently, the UK government considered the chance of a human becoming infected with the BSE agent to be extremely remote. As a result of new developments, alarmist media attention, bureaucratic mishandling of the issues, scientific uncertainty, bickering among technical experts, and a dearth of easily assimilated and balanced information on the problem, widespread fears that affected cattle could enter the human food supply and transmit the disease to humans have periodically erupted, causing social, economic, and political consequences of tremendous magnitude. Better management of the mad cow problem could have minimized the magnitude of the epidemic among cattle, the risk to humans, and the public outrage. Trust in the British government was seriously eroded, an entire industry crippled, and international relations severely tried. Although the scientific data concerning BSE and its transmissibility to humans are still not conclusive, a growing body of (still largely circumstantial) evidence suggests that BSE may be transmissible to humans. Unfortunately, policy decisions cannot wait for a final scientific answer. Therefore, high-stakes decisions must be made in the face of this uncertainty. Such decisions should be made with the primary purpose of protecting the public, and not preferentially the economics of an industry, political alliances, or other considerations. Given that the risk to humans from BSE was (and still is) unknown and may be high, and that the perceived risk among the British public was (and still is) extraordinarily high, policies should support more aggressive interventions. Of necessity, such interventions will be preventive, as there is presently no available treatment. Such policies should be modified as necessary as the developing scientific data warrants.

Repetitive Elements May Comprise Over Two-Thirds of the Human Genome

PubMed Central

de Koning, A. P. Jason; Gu, Wanjun; Castoe, Todd A.; Batzer, Mark A.; Pollock, David D.

2011-01-01

Transposable elements (TEs) are conventionally identified in eukaryotic genomes by alignment to consensus element sequences. Using this approach, about half of the human genome has been previously identified as TEs and low-complexity repeats. We recently developed a highly sensitive alternative de novo strategy, P-clouds, that instead searches for clusters of high-abundance oligonucleotides that are related in sequence space (oligo “clouds”). We show here that P-clouds predicts >840 Mbp of additional repetitive sequences in the human genome, thus suggesting that 66%–69% of the human genome is repetitive or repeat-derived. To investigate this remarkable difference, we conducted detailed analyses of the ability of both P-clouds and a commonly used conventional approach, RepeatMasker (RM), to detect different sized fragments of the highly abundant human Alu and MIR SINEs. RM can have surprisingly low sensitivity for even moderately long fragments, in contrast to P-clouds, which has good sensitivity down to small fragment sizes (∼25 bp). Although short fragments have a high intrinsic probability of being false positives, we performed a probabilistic annotation that reflects this fact. We further developed “element-specific” P-clouds (ESPs) to identify novel Alu and MIR SINE elements, and using it we identified ∼100 Mb of previously unannotated human elements. ESP estimates of new MIR sequences are in good agreement with RM-based predictions of the amount that RM missed. These results highlight the need for combined, probabilistic genome annotation approaches and suggest that the human genome consists of substantially more repetitive sequence than previously believed. PMID:22144907

Energetic and nutritional constraints on infant brain development: implications for brain expansion during human evolution.

PubMed

Cunnane, Stephen C; Crawford, Michael A

2014-12-01

The human brain confronts two major challenges during its development: (i) meeting a very high energy requirement, and (ii) reliably accessing an adequate dietary source of specific brain selective nutrients needed for its structure and function. Implicitly, these energetic and nutritional constraints to normal brain development today would also have been constraints on human brain evolution. The energetic constraint was solved in large measure by the evolution in hominins of a unique and significant layer of body fat on the fetus starting during the third trimester of gestation. By providing fatty acids for ketone production that are needed as brain fuel, this fat layer supports the brain's high energy needs well into childhood. This fat layer also contains an important reserve of the brain selective omega-3 fatty acid, docosahexaenoic acid (DHA), not available in other primates. Foremost amongst the brain selective minerals are iodine and iron, with zinc, copper and selenium also being important. A shore-based diet, i.e., fish, molluscs, crustaceans, frogs, bird's eggs and aquatic plants, provides the richest known dietary sources of brain selective nutrients. Regular access to these foods by the early hominin lineage that evolved into humans would therefore have helped free the nutritional constraint on primate brain development and function. Inadequate dietary supply of brain selective nutrients still has a deleterious impact on human brain development on a global scale today, demonstrating the brain's ongoing vulnerability. The core of the shore-based paradigm of human brain evolution proposes that sustained access by certain groups of early Homo to freshwater and marine food resources would have helped surmount both the nutritional as well as the energetic constraints on mammalian brain development. Copyright © 2014 Elsevier Ltd. All rights reserved.

Development of human locomotion.

PubMed

Lacquaniti, Francesco; Ivanenko, Yuri P; Zago, Myrka

2012-10-01

Neural control of locomotion in human adults involves the generation of a small set of basic patterned commands directed to the leg muscles. The commands are generated sequentially in time during each step by neural networks located in the spinal cord, called Central Pattern Generators. This review outlines recent advances in understanding how motor commands are expressed at different stages of human development. Similar commands are found in several other vertebrates, indicating that locomotion development follows common principles of organization of the control networks. Movements show a high degree of flexibility at all stages of development, which is instrumental for learning and exploration of variable interactions with the environment. Copyright © 2012 Elsevier Ltd. All rights reserved.

Metabolic costs and evolutionary implications of human brain development

PubMed Central

Kuzawa, Christopher W.; Chugani, Harry T.; Grossman, Lawrence I.; Lipovich, Leonard; Muzik, Otto; Hof, Patrick R.; Wildman, Derek E.; Sherwood, Chet C.; Leonard, William R.; Lange, Nicholas

2014-01-01

The high energetic costs of human brain development have been hypothesized to explain distinctive human traits, including exceptionally slow and protracted preadult growth. Although widely assumed to constrain life-history evolution, the metabolic requirements of the growing human brain are unknown. We combined previously collected PET and MRI data to calculate the human brain’s glucose use from birth to adulthood, which we compare with body growth rate. We evaluate the strength of brain–body metabolic trade-offs using the ratios of brain glucose uptake to the body’s resting metabolic rate (RMR) and daily energy requirements (DER) expressed in glucose-gram equivalents (glucosermr% and glucoseder%). We find that glucosermr% and glucoseder% do not peak at birth (52.5% and 59.8% of RMR, or 35.4% and 38.7% of DER, for males and females, respectively), when relative brain size is largest, but rather in childhood (66.3% and 65.0% of RMR and 43.3% and 43.8% of DER). Body-weight growth (dw/dt) and both glucosermr% and glucoseder% are strongly, inversely related: soon after birth, increases in brain glucose demand are accompanied by proportionate decreases in dw/dt. Ages of peak brain glucose demand and lowest dw/dt co-occur and subsequent developmental declines in brain metabolism are matched by proportionate increases in dw/dt until puberty. The finding that human brain glucose demands peak during childhood, and evidence that brain metabolism and body growth rate covary inversely across development, support the hypothesis that the high costs of human brain development require compensatory slowing of body growth rate. PMID:25157149

Metabolic costs and evolutionary implications of human brain development.

PubMed

Kuzawa, Christopher W; Chugani, Harry T; Grossman, Lawrence I; Lipovich, Leonard; Muzik, Otto; Hof, Patrick R; Wildman, Derek E; Sherwood, Chet C; Leonard, William R; Lange, Nicholas

2014-09-09

The high energetic costs of human brain development have been hypothesized to explain distinctive human traits, including exceptionally slow and protracted preadult growth. Although widely assumed to constrain life-history evolution, the metabolic requirements of the growing human brain are unknown. We combined previously collected PET and MRI data to calculate the human brain's glucose use from birth to adulthood, which we compare with body growth rate. We evaluate the strength of brain-body metabolic trade-offs using the ratios of brain glucose uptake to the body's resting metabolic rate (RMR) and daily energy requirements (DER) expressed in glucose-gram equivalents (glucosermr% and glucoseder%). We find that glucosermr% and glucoseder% do not peak at birth (52.5% and 59.8% of RMR, or 35.4% and 38.7% of DER, for males and females, respectively), when relative brain size is largest, but rather in childhood (66.3% and 65.0% of RMR and 43.3% and 43.8% of DER). Body-weight growth (dw/dt) and both glucosermr% and glucoseder% are strongly, inversely related: soon after birth, increases in brain glucose demand are accompanied by proportionate decreases in dw/dt. Ages of peak brain glucose demand and lowest dw/dt co-occur and subsequent developmental declines in brain metabolism are matched by proportionate increases in dw/dt until puberty. The finding that human brain glucose demands peak during childhood, and evidence that brain metabolism and body growth rate covary inversely across development, support the hypothesis that the high costs of human brain development require compensatory slowing of body growth rate.

An integrated approach to develop, validate and operate thermo-physiological human simulator for the development of protective clothing.

PubMed

Psikuta, Agnes; Koelblen, Barbara; Mert, Emel; Fontana, Piero; Annaheim, Simon

2017-12-07

Following the growing interest in the further development of manikins to simulate human thermal behaviour more adequately, thermo-physiological human simulators have been developed by coupling a thermal sweating manikin with a thermo-physiology model. Despite their availability and obvious advantages, the number of studies involving these devices is only marginal, which plausibly results from the high complexity of the development and evaluation process and need of multi-disciplinary expertise. The aim of this paper is to present an integrated approach to develop, validate and operate such devices including technical challenges and limitations of thermo-physiological human simulators, their application and measurement protocol, strategy for setting test scenarios, and the comparison to standard methods and human studies including details which have not been published so far. A physical manikin controlled by a human thermoregulation model overcame the limitations of mathematical clothing models and provided a complementary method to investigate thermal interactions between the human body, protective clothing, and its environment. The opportunities of these devices include not only realistic assessment of protective clothing assemblies and equipment but also potential application in many research fields ranging from biometeorology, automotive industry, environmental engineering, and urban climate to clinical and safety applications.

An integrated approach to develop, validate and operate thermo-physiological human simulator for the development of protective clothing

PubMed Central

PSIKUTA, Agnes; KOELBLEN, Barbara; MERT, Emel; FONTANA, Piero; ANNAHEIM, Simon

2017-01-01

Following the growing interest in the further development of manikins to simulate human thermal behaviour more adequately, thermo-physiological human simulators have been developed by coupling a thermal sweating manikin with a thermo-physiology model. Despite their availability and obvious advantages, the number of studies involving these devices is only marginal, which plausibly results from the high complexity of the development and evaluation process and need of multi-disciplinary expertise. The aim of this paper is to present an integrated approach to develop, validate and operate such devices including technical challenges and limitations of thermo-physiological human simulators, their application and measurement protocol, strategy for setting test scenarios, and the comparison to standard methods and human studies including details which have not been published so far. A physical manikin controlled by a human thermoregulation model overcame the limitations of mathematical clothing models and provided a complementary method to investigate thermal interactions between the human body, protective clothing, and its environment. The opportunities of these devices include not only realistic assessment of protective clothing assemblies and equipment but also potential application in many research fields ranging from biometeorology, automotive industry, environmental engineering, and urban climate to clinical and safety applications. PMID:28966294

Investigation of in-body path loss in different human subjects for localization of capsule endoscope.

PubMed

Ara, Perzila; Cheng, Shaokoon; Heimlich, Michael; Dutkiewicz, Eryk

2015-01-01

Recent developments in capsule endoscopy have highlighted the need for accurate techniques to estimate the location of a capsule endoscope. A highly accurate location estimation of a capsule endoscope in the gastrointestinal (GI) tract in the range of several millimeters is a challenging task. This is mainly because the radio-frequency signals encounter high loss and a highly dynamic channel propagation environment. Therefore, an accurate path-loss model is required for the development of accurate localization algorithms. This paper presents an in-body path-loss model for the human abdomen region at 2.4 GHz frequency. To develop the path-loss model, electromagnetic simulations using the Finite-Difference Time-Domain (FDTD) method were carried out on two different anatomical human models. A mathematical expression for the path-loss model was proposed based on analysis of the measured loss at different capsule locations inside the small intestine. The proposed path-loss model is a good approximation to model in-body RF propagation, since the real measurements are quite infeasible for the capsule endoscopy subject.

Analysis of serotonin concentrations in human milk by high-performance liquid chromatography with fluorescence detection.

PubMed

Chiba, Takeshi; Maeda, Tomoji; Tairabune, Tomohiko; Tomita, Takashi; Sanbe, Atsushi; Takeda, Rika; Kikuchi, Akihiko; Kudo, Kenzo

2017-03-25

Serotonin (5-hydroxytryptamine, 5-HT) plays an important role in milk volume homeostasis in the mammary gland during lactation; 5-HT in milk may also affect infant development. However, there are few reports on 5-HT concentrations in human breast milk. To address this issue, we developed a simple method based on high-performance liquid chromatography with fluorescence detection (HPLC-FD) for measuring 5-HT concentrations in human breast milk. Breast milk samples were provided by four healthy Japanese women. Calibration curves for 5-HT in each sample were prepared with the standard addition method between 5 and 1000 ng/ml, and all had correlation coefficients >0.999. The recovery of 5-HT was 96.1%-101.0%, with a coefficient of variation of 3.39%-8.62%. The range of 5-HT concentrations estimated from the calibration curves was 11.1-51.1 ng/ml. Thus, the HPLC-FD method described here can effectively extract 5-HT from human breast milk with high reproducibility. Copyright © 2017 Elsevier Inc. All rights reserved.

LungMAP: The Molecular Atlas of Lung Development Program.

PubMed

Ardini-Poleske, Maryanne E; Clark, Robert F; Ansong, Charles; Carson, James P; Corley, Richard A; Deutsch, Gail H; Hagood, James S; Kaminski, Naftali; Mariani, Thomas J; Potter, Steven S; Pryhuber, Gloria S; Warburton, David; Whitsett, Jeffrey A; Palmer, Scott M; Ambalavanan, Namasivayam

2017-11-01

The National Heart, Lung, and Blood Institute is funding an effort to create a molecular atlas of the developing lung (LungMAP) to serve as a research resource and public education tool. The lung is a complex organ with lengthy development time driven by interactive gene networks and dynamic cross talk among multiple cell types to control and coordinate lineage specification, cell proliferation, differentiation, migration, morphogenesis, and injury repair. A better understanding of the processes that regulate lung development, particularly alveologenesis, will have a significant impact on survival rates for premature infants born with incomplete lung development and will facilitate lung injury repair and regeneration in adults. A consortium of four research centers, a data coordinating center, and a human tissue repository provides high-quality molecular data of developing human and mouse lungs. LungMAP includes mouse and human data for cross correlation of developmental processes across species. LungMAP is generating foundational data and analysis, creating a web portal for presentation of results and public sharing of data sets, establishing a repository of young human lung tissues obtained through organ donor organizations, and developing a comprehensive lung ontology that incorporates the latest findings of the consortium. The LungMAP website (www.lungmap.net) currently contains more than 6,000 high-resolution lung images and transcriptomic, proteomic, and lipidomic human and mouse data and provides scientific information to stimulate interest in research careers for young audiences. This paper presents a brief description of research conducted by the consortium, database, and portal development and upcoming features that will enhance the LungMAP experience for a community of users. Copyright © 2017 the American Physiological Society.

High-Rate Laser Communications for Human Exploration and Science

NASA Astrophysics Data System (ADS)

Robinson, B. S.; Shih, T.; Khatri, F. I.; King, T.; Seas, A.

2018-02-01

Laser communication links has been successfully demonstrated on recent near-Earth and lunar missions. We present a status of this development work and its relevance to a future Deep Space Gateway supporting human exploration and science activities.

Performance Characterization of the Air Force Transformational Satellite 12 kW Hall Thruster

NASA Technical Reports Server (NTRS)

Kamhawi, Hani; Haag, Thomas W.; Smith, Timothy; Herman, Daniel; Huang, Wensheng; Shastry, Rohit; Peterson, Peter; Mathers, Alex

2013-01-01

The STMD GCD ISP project is tasked with developing, maturing, and testing enabling human exploration propulsion requirements and potential designs for advanced high-energy, in-space propulsion systems to support deep-space human exploration and reduce travel time between Earth's orbit and future destinations for human activity. High-power Hall propulsion systems have been identified as enabling technologies and have been the focus of the activities at NASA Glenn-In-house effort to evaluate performance and interrogate operation of NASA designed and manufactured Hall thrusters. Evaluate existing high TRL EP devices that may be suitable for implementation in SEP TDM.

Innate Immunity to H5N1 Influenza Viruses in Humans

PubMed Central

Ramos, Irene; Fernandez-Sesma, Ana

2012-01-01

Avian influenza virus infections in the human population are rare due to their inefficient direct human-to-human transmission. However, when humans are infected, a strong inflammatory response is usually induced, characterized by elevated levels of cytokines and chemokines in serum, believed to be important in the severe pathogenesis that develops in a high proportion of these patients. Extensive research has been performed to understand the molecular viral mechanisms involved in the H5N1 pathogenesis in humans, providing interesting insights about the virus-host interaction and the regulation of the innate immune response by these highly pathogenic viruses. In this review we summarize and discuss the most important findings in this field, focusing mainly on H5N1 virulence factors and their impact on the modulation of the innate immunity in humans. PMID:23342363

High-speed adaptive optics for imaging of the living human eye

PubMed Central

Yu, Yongxin; Zhang, Tianjiao; Meadway, Alexander; Wang, Xiaolin; Zhang, Yuhua

2015-01-01

The discovery of high frequency temporal fluctuation of human ocular wave aberration dictates the necessity of high speed adaptive optics (AO) correction for high resolution retinal imaging. We present a high speed AO system for an experimental adaptive optics scanning laser ophthalmoscope (AOSLO). We developed a custom high speed Shack-Hartmann wavefront sensor and maximized the wavefront detection speed based upon a trade-off among the wavefront spatial sampling density, the dynamic range, and the measurement sensitivity. We examined the temporal dynamic property of the ocular wavefront under the AOSLO imaging condition and improved the dual-thread AO control strategy. The high speed AO can be operated with a closed-loop frequency up to 110 Hz. Experiment results demonstrated that the high speed AO system can provide improved compensation for the wave aberration up to 30 Hz in the living human eye. PMID:26368408

Humanizing the High School: The Power of Peers.

ERIC Educational Resources Information Center

Stader, David L.; Gagnepain, F. J.

2000-01-01

Discusses what high schools can do to improve student relationships, highlighting a St. Louis area school's efforts to develop peer-mentoring and peer-mediation programs. Offers guidelines to help other schools develop a school culture that promotes caring, teaches constructive conflict resolution, and reduces potential for violence. (MLH)

Inverse colloidal crystal membranes for hydrophobic interaction membrane chromatography.

PubMed

Vu, Anh T; Wang, Xinying; Wickramasinghe, S Ranil; Yu, Bing; Yuan, Hua; Cong, Hailin; Luo, Yongli; Tang, Jianguo

2015-08-01

Hydrophobic interaction membrane chromatography has gained interest due to its excellent performance in the purification of humanized monoclonal antibodies. The membrane material used in hydrophobic interaction membrane chromatography has typically been commercially available polyvinylidene fluoride. In this contribution, newly developed inverse colloidal crystal membranes that have uniform pores, high porosity and, therefore, high surface area for protein binding are used as hydrophobic interaction membrane chromatography membranes for humanized monoclonal antibody immunoglobulin G purification. The capacity of the inverse colloidal crystal membranes developed here is up to ten times greater than commercially available polyvinylidene fluoride membranes with a similar pore size. This work highlights the importance of developing uniform pore size high porosity membranes in order to maximize the capacity of hydrophobic interaction membrane chromatography. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A model of type 2 diabetes in the guinea pig using sequential diet-induced glucose intolerance and streptozotocin treatment

PubMed Central

Ackart, David F.; Richardson, Michael A.; DiLisio, James E.; Pulford, Bruce; Basaraba, Randall J.

2017-01-01

ABSTRACT Type 2 diabetes is a leading cause of morbidity and mortality among noncommunicable diseases, and additional animal models that more closely replicate the pathogenesis of human type 2 diabetes are needed. The goal of this study was to develop a model of type 2 diabetes in guinea pigs, in which diet-induced glucose intolerance precedes β-cell cytotoxicity, two processes that are crucial to the development of human type 2 diabetes. Guinea pigs developed impaired glucose tolerance after 8 weeks of feeding on a high-fat, high-carbohydrate diet, as determined by oral glucose challenge. Diet-induced glucose intolerance was accompanied by β-cell hyperplasia, compensatory hyperinsulinemia, and dyslipidemia with hepatocellular steatosis. Streptozotocin (STZ) treatment alone was ineffective at inducing diabetic hyperglycemia in guinea pigs, which failed to develop sustained glucose intolerance or fasting hyperglycemia and returned to euglycemia within 21 days after treatment. However, when high-fat, high-carbohydrate diet-fed guinea pigs were treated with STZ, glucose intolerance and fasting hyperglycemia persisted beyond 21 days post-STZ treatment. Guinea pigs with diet-induced glucose intolerance subsequently treated with STZ demonstrated an insulin-secretory capacity consistent with insulin-independent diabetes. This insulin-independent state was confirmed by response to oral antihyperglycemic drugs, metformin and glipizide, which resolved glucose intolerance and extended survival compared with guinea pigs with uncontrolled diabetes. In this study, we have developed a model of sequential glucose intolerance and β-cell loss, through high-fat, high-carbohydrate diet and extensive optimization of STZ treatment in the guinea pig, which closely resembles human type 2 diabetes. This model will prove useful in the study of insulin-independent diabetes pathogenesis with or without comorbidities, where the guinea pig serves as a relevant model species. PMID:28093504

Inhibition of the Human ABC Efflux Transporters P-gp and BCRP by the BDE-47 Hydroxylated Metabolite 6-OH-BDE-47: Considerations for Human Exposure

EPA Science Inventory

High body burdens of polybrominated diphenyl ethers (PBDEs) in infants and young children have led to increased concern over their potential impact on human development. PBDE exposure can alter the expression of genes involved in thyroid homeostasis, including those of ATP-bindin...

Defining Advancement Career Paths and Succession Plans: Critical Human Capital Retention Strategies for High-Performing Advancement Divisions

ERIC Educational Resources Information Center

Croteau, Jon Derek; Wolk, Holly Gordon

2010-01-01

There are many factors that can influence whether a highly talented staff member will build a career within an institution or use it as a stepping stone. This article defines and explores the notions of developing career paths and succession planning and why they are critical human capital investment strategies in retaining the highest performers…

Human papilloma virus in the tonsillar microbiota of an Afghan population group.

PubMed

Ruggiero, F; Carbone, D; Mugavero, R; Cura, F; Baggi, L; Arcuri, C; Nardone, M; Gaudio, R M; Gatto, R; Scapoli, L; Carinci, F

2018-01-01

Cancer of the oral cavity is known to have a diverse aetiology that includes infectious agents. Human papilloma virus has been found to be associated with several types of human cancer, inclusive of cervical, vulvar, vaginal, penile, anal, and cancer of tonsil. The aim of this manuscript is to investigate the presence of human papilloma virus in tonsillar microbiota of an Afghan population group. A sample of the tonsillar microbiota was collected by oral swab paper stick from 80 healthy donors. The sample was investigated for the presence of high-risk human papillomavirus types 16, 18, 31 and 45 by real time PCR. Eight samples produced some positive endpoint signals for human papillomaviruses. The human papillomavirus 31 was the unique papillomavirus detected; its calculated prevalence rate was 0.10 (C.I. 0.05-0.19). However, the viral load was always very low, in the order of 10-3 viral genomes per cell. The high prevalence of high-risk human papillomavirus in healthy population suggest a need for further investigation on virus spreading and supports the development of vaccination strategies.

Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines

PubMed Central

Kim, Shin-Hee; Samal, Siba K.

2016-01-01

Viral vaccine vectors have shown to be effective in inducing a robust immune response against the vaccine antigen. Newcastle disease virus (NDV), an avian paramyxovirus, is a promising vaccine vector against human and veterinary pathogens. Avirulent NDV strains LaSota and B1 have long track records of safety and efficacy. Therefore, use of these strains as vaccine vectors is highly safe in avian and non-avian species. NDV replicates efficiently in the respiratory track of the host and induces strong local and systemic immune responses against the foreign antigen. As a vaccine vector, NDV can accommodate foreign sequences with a good degree of stability and as a RNA virus, there is limited possibility for recombination with host cell DNA. Using NDV as a vaccine vector in humans offers several advantages over other viral vaccine vectors. NDV is safe in humans due to host range restriction and there is no pre-existing antibody to NDV in the human population. NDV is antigenically distinct from common human pathogens. NDV replicates to high titer in a cell line acceptable for human vaccine development. Therefore, NDV is an attractive vaccine vector for human pathogens for which vaccines are currently not available. NDV is also an attractive vaccine vector for animal pathogens. PMID:27384578

Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines.

PubMed

Kim, Shin-Hee; Samal, Siba K

2016-07-04

Viral vaccine vectors have shown to be effective in inducing a robust immune response against the vaccine antigen. Newcastle disease virus (NDV), an avian paramyxovirus, is a promising vaccine vector against human and veterinary pathogens. Avirulent NDV strains LaSota and B1 have long track records of safety and efficacy. Therefore, use of these strains as vaccine vectors is highly safe in avian and non-avian species. NDV replicates efficiently in the respiratory track of the host and induces strong local and systemic immune responses against the foreign antigen. As a vaccine vector, NDV can accommodate foreign sequences with a good degree of stability and as a RNA virus, there is limited possibility for recombination with host cell DNA. Using NDV as a vaccine vector in humans offers several advantages over other viral vaccine vectors. NDV is safe in humans due to host range restriction and there is no pre-existing antibody to NDV in the human population. NDV is antigenically distinct from common human pathogens. NDV replicates to high titer in a cell line acceptable for human vaccine development. Therefore, NDV is an attractive vaccine vector for human pathogens for which vaccines are currently not available. NDV is also an attractive vaccine vector for animal pathogens.

At the Very Root of the Development of Interest: Using Human Body Contexts to Improve Women's Emotional Engagement in Introductory Physics

ERIC Educational Resources Information Center

Allaire-Duquette, Geneviève; Charland, Patrick; Riopel, Martin

2014-01-01

In physics, women find contexts concerning human biology, medical applications, or natural phenomena highly relevant (Hoffmann, 2002), and the rareness or absence of these in physics curricula may make it more difficult for women to develop and maintain their interest in physics. To date, research in physics education addressing student's…

Quest for Quality. Proceedings of National Research Conference on Human Resource Development (College Station, Texas, April 22-24, 1993).

ERIC Educational Resources Information Center

Mathis, Laura, Ed.; Mizer, Kaye, Ed.

Papers on the theme of quality in human resource development include the following: "Missing Link to Quality: An Examination of the Use of Steven Covey's '7 Habits of Highly Effective People' in State Agencies" (Adair et al.); "Executive Women in Business in the United States" (Bierema); "Extent and Nature of Employee Initiated Learning in the…

Feasibility of Large High-Powered Solar Electric Propulsion Vehicles: Issues and Solutions

NASA Technical Reports Server (NTRS)

Capadona, Lynn A.; Woytach, Jeffrey M.; Kerslake, Thomas W.; Manzella, David H.; Christie, Robert J.; Hickman, Tyler A.; Schneidegger, Robert J.; Hoffman, David J.; Klem, Mark D.

2012-01-01

Human exploration beyond low Earth orbit will require the use of enabling technologies that are efficient, affordable, and reliable. Solar electric propulsion (SEP) has been proposed by NASA s Human Exploration Framework Team as an option to achieve human exploration missions to near Earth objects (NEOs) because of its favorable mass efficiency as compared to traditional chemical systems. This paper describes the unique challenges and technology hurdles associated with developing a large high-power SEP vehicle. A subsystem level breakdown of factors contributing to the feasibility of SEP as a platform for future exploration missions to NEOs is presented including overall mission feasibility, trip time variables, propellant management issues, solar array power generation, array structure issues, and other areas that warrant investment in additional technology or engineering development.

Spatially explicit assessment of heat health risk by using multi-sensor remote sensing images and socioeconomic data in Yangtze River Delta, China.

PubMed

Chen, Qian; Ding, Mingjun; Yang, Xuchao; Hu, Kejia; Qi, Jiaguo

2018-05-25

The increase in the frequency and intensity of extreme heat events, which are potentially associated with climate change in the near future, highlights the importance of heat health risk assessment, a significant reference for heat-related death reduction and intervention. However, a spatiotemporal mismatch exists between gridded heat hazard and human exposure in risk assessment, which hinders the identification of high-risk areas at finer scales. A human settlement index integrated by nighttime light images, enhanced vegetation index, and digital elevation model data was utilized to assess the human exposure at high spatial resolution. Heat hazard and vulnerability index were generated by land surface temperature and demographic and socioeconomic census data, respectively. Spatially explicit assessment of heat health risk and its driving factors was conducted in the Yangtze River Delta (YRD), east China at 250 m pixel level. High-risk areas were mainly distributed in the urbanized areas of YRD, which were mostly driven by high human exposure and heat hazard index. In some less-urbanized cities and suburban and rural areas of mega-cities, the heat health risks are in second priority. The risks in some less-developed areas were high despite the low human exposure index because of high heat hazard and vulnerability index. This study illustrated a methodology for identifying high-risk areas by combining freely available multi-source data. Highly urbanized areas were considered hotspots of high heat health risks, which were largely driven by the increasing urban heat island effects and population density in urban areas. Repercussions of overheating were weakened due to the low social vulnerability in some central areas benefitting from the low proportion of sensitive population or the high level of socioeconomic development. By contrast, high social vulnerability intensifies heat health risks in some less-urbanized cities and suburban areas of mega-cities.

Potent cocktails: Effects of phthalate mixtures on reproductive development

EPA Science Inventory

Phthalate diesters are high-production volume chemicals used for many applications in consumer, health, medical and industrial products. Multiple phthalate metabolites have been detected in humans of all ages, including in pregnant mothers' urine and human amniotic fluid. Certain...

WiFi-Based Real-Time Calibration-Free Passive Human Motion Detection.

PubMed

Gong, Liangyi; Yang, Wu; Man, Dapeng; Dong, Guozhong; Yu, Miao; Lv, Jiguang

2015-12-21

With the rapid development of WLAN technology, wireless device-free passive human detection becomes a newly-developing technique and holds more potential to worldwide and ubiquitous smart applications. Recently, indoor fine-grained device-free passive human motion detection based on the PHY layer information is rapidly developed. Previous wireless device-free passive human detection systems either rely on deploying specialized systems with dense transmitter-receiver links or elaborate off-line training process, which blocks rapid deployment and weakens system robustness. In the paper, we explore to research a novel fine-grained real-time calibration-free device-free passive human motion via physical layer information, which is independent of indoor scenarios and needs no prior-calibration and normal profile. We investigate sensitivities of amplitude and phase to human motion, and discover that phase feature is more sensitive to human motion, especially to slow human motion. Aiming at lightweight and robust device-free passive human motion detection, we develop two novel and practical schemes: short-term averaged variance ratio (SVR) and long-term averaged variance ratio (LVR). We realize system design with commercial WiFi devices and evaluate it in typical multipath-rich indoor scenarios. As demonstrated in the experiments, our approach can achieve a high detection rate and low false positive rate.

WiFi-Based Real-Time Calibration-Free Passive Human Motion Detection †

PubMed Central

Gong, Liangyi; Yang, Wu; Man, Dapeng; Dong, Guozhong; Yu, Miao; Lv, Jiguang

2015-01-01

With the rapid development of WLAN technology, wireless device-free passive human detection becomes a newly-developing technique and holds more potential to worldwide and ubiquitous smart applications. Recently, indoor fine-grained device-free passive human motion detection based on the PHY layer information is rapidly developed. Previous wireless device-free passive human detection systems either rely on deploying specialized systems with dense transmitter-receiver links or elaborate off-line training process, which blocks rapid deployment and weakens system robustness. In the paper, we explore to research a novel fine-grained real-time calibration-free device-free passive human motion via physical layer information, which is independent of indoor scenarios and needs no prior-calibration and normal profile. We investigate sensitivities of amplitude and phase to human motion, and discover that phase feature is more sensitive to human motion, especially to slow human motion. Aiming at lightweight and robust device-free passive human motion detection, we develop two novel and practical schemes: short-term averaged variance ratio (SVR) and long-term averaged variance ratio (LVR). We realize system design with commercial WiFi devices and evaluate it in typical multipath-rich indoor scenarios. As demonstrated in the experiments, our approach can achieve a high detection rate and low false positive rate. PMID:26703612

High early life mortality in free-ranging dogs is largely influenced by humans

PubMed Central

Paul, Manabi; Sen Majumder, Sreejani; Sau, Shubhra; Nandi, Anjan K.; Bhadra, Anindita

2016-01-01

Free-ranging dogs are a ubiquitous part of human habitations in many developing countries, leading a life of scavengers dependent on human wastes for survival. The effective management of free-ranging dogs calls for understanding of their population dynamics. Life expectancy at birth and early life mortality are important factors that shape life-histories of mammals. We carried out a five year-long census based study in seven locations of West Bengal, India, to understand the pattern of population growth and factors affecting early life mortality in free-ranging dogs. We observed high rates of mortality, with only ~19% of the 364 pups from 95 observed litters surviving till the reproductive age; 63% of total mortality being human influenced. While living near people increases resource availability for dogs, it also has deep adverse impacts on their population growth, making the dog-human relationship on streets highly complex. PMID:26804633

Gene promoter methylation and protein expression of BRMS1 in uterine cervix in relation to high-risk human papilloma virus infection and cancer.

PubMed

Panagopoulou, Maria; Lambropoulou, Maria; Balgkouranidou, Ioanna; Nena, Evangelia; Karaglani, Makrina; Nicolaidou, Christina; Asimaki, Anthi; Konstantinidis, Theocharis; Constantinidis, Theodoros C; Kolios, George; Kakolyris, Stylianos; Agorastos, Theodoros; Chatzaki, Ekaterini

2017-04-01

Cervical cancer is strongly related to certain high-risk types of human papilloma virus infection. Breast cancer metastasis suppressor 1 (BRMS1) is a tumor suppressor gene, its expression being regulated by DNA promoter methylation in several types of cancers. This study aims to evaluate the methylation status of BRMS1 promoter in relation to high-risk types of human papilloma virus infection and the development of pre-cancerous lesions and describe the pattern of BRMS1 protein expression in normal, high-risk types of human papilloma virus-infected pre-cancerous and malignant cervical epithelium. We compared the methylation status of BRMS1 in cervical smears of 64 women with no infection by high-risk types of human papilloma virus to 70 women with proven high-risk types of human papilloma virus infection, using real-time methylation-specific polymerase chain reaction. The expression of BRMS1 protein was described by immunohistochemistry in biopsies from cervical cancer, pre-cancerous lesions, and normal cervices. Methylation of BRMS1 promoter was detected in 37.5% of women with no high-risk types of human papilloma virus infection and was less frequent in smears with high-risk types of human papilloma virus (11.4%) and in women with pathological histology (cervical intraepithelial neoplasia) (11.9%). Methylation was detected also in HeLa cervical cancer cells. Immunohistochemistry revealed nuclear BRMS1 protein staining in normal high-risk types of human papilloma virus-free cervix, in cervical intraepithelial neoplasias, and in malignant tissues, where staining was occasionally also cytoplasmic. In cancer, expression was stronger in the more differentiated cancer blasts. In conclusion, BRMS1 promoter methylation and aberrant protein expression seem to be related to high-risk types of human papilloma virus-induced carcinogenesis in uterine cervix and is worthy of further investigation.

Dissecting the human immunologic memory for pathogens.

PubMed

Zielinski, Christina E; Corti, Davide; Mele, Federico; Pinto, Dora; Lanzavecchia, Antonio; Sallusto, Federica

2011-03-01

Studies on immunologic memory in animal models and especially in the human system are instrumental to identify mechanisms and correlates of protection necessary for vaccine development. In this article, we provide an overview of the cellular basis of immunologic memory. We also describe experimental approaches based on high throughput cell cultures, which we have developed to interrogate human memory T cells, B cells, and plasma cells. We discuss how these approaches can provide new tools and information for vaccine design, in a process that we define as 'analytic vaccinology'. © 2011 John Wiley & Sons A/S.

Inequality in Human Development: An Empirical Assessment of 32 Countries

PubMed Central

Harttgen, Kenneth; Klasen, Stephan; Misselhorn, Mark; Munzi, Teresa; Smeeding, Timothy

2009-01-01

One of the most frequent critiques of the HDI is that is does not take into account inequality within countries in its three dimensions. In this paper, we apply a simply approach to compute the three components and the overall HDI for quintiles of the income distribution. This allows a comparison of the level in human development of the poor with the level of the non-poor within countries, but also across countries. This is an application of the method presented in Grimm et al. (World Development 36(12):2527–2546, 2008) to a sample of 21 low and middle income countries and 11 industrialized countries. In particular the inclusion of the industrialized countries, which were not included in the previous work, implies to deal with a number of additional challenges, which we outline in this paper. Our results show that inequality in human development within countries is high, both in developed and industrialized countries. In fact, the HDI of the lowest quintiles in industrialized countries is often below the HDI of the richest quintile in many middle income countries. We also find, however, a strong overall negative correlation between the level of human development and inequality in human development. PMID:20461123

An intelligent multi-media human-computer dialogue system

NASA Technical Reports Server (NTRS)

Neal, J. G.; Bettinger, K. E.; Byoun, J. S.; Dobes, Z.; Thielman, C. Y.

1988-01-01

Sophisticated computer systems are being developed to assist in the human decision-making process for very complex tasks performed under stressful conditions. The human-computer interface is a critical factor in these systems. The human-computer interface should be simple and natural to use, require a minimal learning period, assist the user in accomplishing his task(s) with a minimum of distraction, present output in a form that best conveys information to the user, and reduce cognitive load for the user. In pursuit of this ideal, the Intelligent Multi-Media Interfaces project is devoted to the development of interface technology that integrates speech, natural language text, graphics, and pointing gestures for human-computer dialogues. The objective of the project is to develop interface technology that uses the media/modalities intelligently in a flexible, context-sensitive, and highly integrated manner modelled after the manner in which humans converse in simultaneous coordinated multiple modalities. As part of the project, a knowledge-based interface system, called CUBRICON (CUBRC Intelligent CONversationalist) is being developed as a research prototype. The application domain being used to drive the research is that of military tactical air control.

Application of chimeric mice with humanized liver for study of human-specific drug metabolism.

PubMed

Bateman, Thomas J; Reddy, Vijay G B; Kakuni, Masakazu; Morikawa, Yoshio; Kumar, Sanjeev

2014-06-01

Human-specific or disproportionately abundant human metabolites of drug candidates that are not adequately formed and qualified in preclinical safety assessment species pose an important drug development challenge. Furthermore, the overall metabolic profile of drug candidates in humans is an important determinant of their drug-drug interaction susceptibility. These risks can be effectively assessed and/or mitigated if human metabolic profile of the drug candidate could reliably be determined in early development. However, currently available in vitro human models (e.g., liver microsomes, hepatocytes) are often inadequate in this regard. Furthermore, the conduct of definitive radiolabeled human ADME studies is an expensive and time-consuming endeavor that is more suited for later in development when the risk of failure has been reduced. We evaluated a recently developed chimeric mouse model with humanized liver on uPA/SCID background for its ability to predict human disposition of four model drugs (lamotrigine, diclofenac, MRK-A, and propafenone) that are known to exhibit human-specific metabolism. The results from these studies demonstrate that chimeric mice were able to reproduce the human-specific metabolite profile for lamotrigine, diclofenac, and MRK-A. In the case of propafenone, however, the human-specific metabolism was not detected as a predominant pathway, and the metabolite profiles in native and humanized mice were similar; this was attributed to the presence of residual highly active propafenone-metabolizing mouse enzymes in chimeric mice. Overall, the data indicate that the chimeric mice with humanized liver have the potential to be a useful tool for the prediction of human-specific metabolism of xenobiotics and warrant further investigation.

Suicide rate in relation to the Human Development Index and other health related factors: A global ecological study from 91 countries.

PubMed

Khazaei, Salman; Armanmehr, Vajihe; Nematollahi, Shahrzad; Rezaeian, Shahab; Khazaei, Somayeh

2017-06-01

There has been no worldwide ecological study on suicide as a global major public health problem. This study aimed to identify the variations in suicide specific rates using the Human Development Index (HDI) and some health related variables among countries around the world. In this ecological study, we obtained the data from the World Bank Report 2013. The analysis was restricted to 91 countries for which both the epidemiologic data from the suicide rates and HDI were available. Overall, the global prevalence of suicide rate was 10.5 (95% confidence intervals: 8.8, 12.2) per 100,000 individuals, which significantly varied according to gender (16.3 in males vs. 4.6 in females, p<0.001) and different levels of human development (11.64/100,000 individuals in very high development countries, 7.93/100,000 individuals in medium development countries, and 13.94/100,000 individuals in high development countries, p=0.004). In conclusion, the suicide rate varies greatly between countries with different development levels. Our findings also suggest that male gender and HDI components are associated with an increased risk of suicide behaviors. Hence, detecting population subgroups with a high suicide risk and reducing the inequality of socioeconomic determinants are necessary to prevent this disorder around the world. Copyright © 2017 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

Development of high definition OCT system for clinical therapy of skin diseases

NASA Astrophysics Data System (ADS)

Baek, Daeyul; Seo, Young-Seok; Kim, Jung-Hyun

2018-02-01

OCT is a non-invasive imaging technique that can be applied to diagnose various skin disease. Since its introduction in 1997, dermatology has used OCT technology to obtain high quality images of human skin. Recently, in order to accurately diagnose skin diseases, it is essential to develop OCT equipment that can obtain high quality images. Therefore, we developed the system that can obtain a high quality image by using a 1300 nm light source with a wide bandwidth and deep penetration depth, high-resolution image, and a camera capable of high sensitivity and high speed processing. We introduce the performance of the developed system and the clinical application data.

Overview of Radiation Environments and Human Exposures

NASA Technical Reports Server (NTRS)

Wilson, John W.

2004-01-01

Human exposures to ionizing radiation have been vastly altered by developing technology in the last century. This has been most obvious in the development of radiation generating devices and the utilization of nuclear energy. But even air travel has had its impact on human exposure. Human exposure increases with advancing aircraft technology as a result of the higher operating altitudes reducing the protective cover provided by the Earth s atmosphere from extraterrestrial radiations. This increase in operating altitudes is taken to a limit by human operations in space. Less obvious is the changing character of the radiations at higher altitudes. The associated health risks are less understood with increasing altitude due to the increasing complexity and new field components found in high altitude and space operations.

Economic Adjustment, Education and Human Resource Development in Africa: The Case of Nigeria

NASA Astrophysics Data System (ADS)

Geo-Jaja, Macleans A.; Mangum, Garth

2003-07-01

On the basis of the Nigerian experience, this article argues that the structural adjustment programs of the World Bank and the International Monetary Fund, when misapplied, can have a devastating effect on the educational systems that are essential to human resource development. The paper considers how the objectives of structural adjustment might have been accomplished without harming education, and recommends an outcomes-based educational policy for Nigeria which could serve equally well in other developing nations. The key message of the paper is that the ongoing austerity programs have been secured at excessively high human cost, and that it is time for a policy redirection that reaffirms education as the essential tool of all development.

Low-Latency Telerobotics from Mars Orbit: The Case for Synergy Between Science and Human Exploration

NASA Technical Reports Server (NTRS)

Valinia, A.; Garvin, J. B.; Vondrak, R.; Thronson, H.; Lester, D.; Schmidt, G.; Fong, T.; Wilcox, B.; Sellers, P.; White, N.

2012-01-01

Initial, science-directed human exploration of Mars will benefit from capabilities in which human explorers remain in orbit to control telerobotic systems on the surface (Figure 1). Low-latency, high-bandwidth telerobotics (LLT) from Mars orbit offers opportunities for what the terrestrial robotics community considers to be high-quality telepresence. Such telepresence would provide high quality sensory perception and situation awareness, and even capabilities for dexterous manipulation as required for adaptive, informed selection of scientific samples [1]. Astronauts on orbit in close communication proximity to a surface exploration site (in order to minimize communication latency) represent a capability that would extend human cognition to Mars (and potentially for other bodies such as asteroids, Venus, the Moon, etc.) without the challenges, expense, and risk of putting those humans on hazardous surfaces or within deep gravity wells. Such a strategy may be consistent with goals for a human space flight program that, are currently being developed within NASA.

Robotics for Human Exploration

NASA Technical Reports Server (NTRS)

Fong, Terrence; Deans, Mathew; Bualat, Maria

2013-01-01

Robots can do a variety of work to increase the productivity of human explorers. Robots can perform tasks that are tedious, highly repetitive or long-duration. Robots can perform precursor tasks, such as reconnaissance, which help prepare for future human activity. Robots can work in support of astronauts, assisting or performing tasks in parallel. Robots can also perform "follow-up" work, completing tasks designated or started by humans. In this paper, we summarize the development and testing of robots designed to improve future human exploration of space.

Differences and similarities between human and chimpanzee neural progenitors during cerebral cortex development

PubMed Central

Mora-Bermúdez, Felipe; Badsha, Farhath; Kanton, Sabina; Camp, J Gray; Vernot, Benjamin; Köhler, Kathrin; Voigt, Birger; Okita, Keisuke; Maricic, Tomislav; He, Zhisong; Lachmann, Robert; Pääbo, Svante; Treutlein, Barbara; Huttner, Wieland B

2016-01-01

Human neocortex expansion likely contributed to the remarkable cognitive abilities of humans. This expansion is thought to primarily reflect differences in proliferation versus differentiation of neural progenitors during cortical development. Here, we have searched for such differences by analysing cerebral organoids from human and chimpanzees using immunohistofluorescence, live imaging, and single-cell transcriptomics. We find that the cytoarchitecture, cell type composition, and neurogenic gene expression programs of humans and chimpanzees are remarkably similar. Notably, however, live imaging of apical progenitor mitosis uncovered a lengthening of prometaphase-metaphase in humans compared to chimpanzees that is specific to proliferating progenitors and not observed in non-neural cells. Consistent with this, the small set of genes more highly expressed in human apical progenitors points to increased proliferative capacity, and the proportion of neurogenic basal progenitors is lower in humans. These subtle differences in cortical progenitors between humans and chimpanzees may have consequences for human neocortex evolution. DOI: http://dx.doi.org/10.7554/eLife.18683.001 PMID:27669147

Sex steroids and human behavior: prenatal androgen exposure and sex-typical play behavior in children.

PubMed

Hines, Melissa

2003-12-01

Gonadal hormones, particularly androgens, direct certain aspects of brain development and exert permanent influences on sex-typical behavior in nonhuman mammals. Androgens also influence human behavioral development, with the most convincing evidence coming from studies of sex-typical play. Girls exposed to unusually high levels of androgens prenatally, because they have the genetic disorder, congenital adrenal hyperplasia (CAH), show increased preferences for toys and activities usually preferred by boys, and for male playmates, and decreased preferences for toys and activities usually preferred by girls. Normal variability in androgen prenatally also has been related to subsequent sex-typed play behavior in girls, and nonhuman primates have been observed to show sex-typed preferences for human toys. These findings suggest that androgen during early development influences childhood play behavior in humans at least in part by altering brain development.

A multiplexed chip-based assay system for investigating the functional development of human skeletal myotubes in vitro.

PubMed

Smith, A S T; Long, C J; Pirozzi, K; Najjar, S; McAleer, C; Vandenburgh, H H; Hickman, J J

2014-09-20

This report details the development of a non-invasive in vitro assay system for investigating the functional maturation and performance of human skeletal myotubes. Data is presented demonstrating the survival and differentiation of human myotubes on microscale silicon cantilevers in a defined, serum-free system. These cultures can be stimulated electrically and the resulting contraction quantified using modified atomic force microscopy technology. This system provides a higher degree of sensitivity for investigating contractile waveforms than video-based analysis, and represents the first system capable of measuring the contractile activity of individual human muscle myotubes in a reliable, high-throughput and non-invasive manner. The development of such a technique is critical for the advancement of body-on-a-chip platforms toward application in pre-clinical drug development screens. Copyright © 2014 Elsevier B.V. All rights reserved.

H3ABioNet, a sustainable pan-African bioinformatics network for human heredity and health in Africa

PubMed Central

Mulder, Nicola J.; Adebiyi, Ezekiel; Alami, Raouf; Benkahla, Alia; Brandful, James; Doumbia, Seydou; Everett, Dean; Fadlelmola, Faisal M.; Gaboun, Fatima; Gaseitsiwe, Simani; Ghazal, Hassan; Hazelhurst, Scott; Hide, Winston; Ibrahimi, Azeddine; Jaufeerally Fakim, Yasmina; Jongeneel, C. Victor; Joubert, Fourie; Kassim, Samar; Kayondo, Jonathan; Kumuthini, Judit; Lyantagaye, Sylvester; Makani, Julie; Mansour Alzohairy, Ahmed; Masiga, Daniel; Moussa, Ahmed; Nash, Oyekanmi; Ouwe Missi Oukem-Boyer, Odile; Owusu-Dabo, Ellis; Panji, Sumir; Patterton, Hugh; Radouani, Fouzia; Sadki, Khalid; Seghrouchni, Fouad; Tastan Bishop, Özlem; Tiffin, Nicki; Ulenga, Nzovu

2016-01-01

The application of genomics technologies to medicine and biomedical research is increasing in popularity, made possible by new high-throughput genotyping and sequencing technologies and improved data analysis capabilities. Some of the greatest genetic diversity among humans, animals, plants, and microbiota occurs in Africa, yet genomic research outputs from the continent are limited. The Human Heredity and Health in Africa (H3Africa) initiative was established to drive the development of genomic research for human health in Africa, and through recognition of the critical role of bioinformatics in this process, spurred the establishment of H3ABioNet, a pan-African bioinformatics network for H3Africa. The limitations in bioinformatics capacity on the continent have been a major contributory factor to the lack of notable outputs in high-throughput biology research. Although pockets of high-quality bioinformatics teams have existed previously, the majority of research institutions lack experienced faculty who can train and supervise bioinformatics students. H3ABioNet aims to address this dire need, specifically in the area of human genetics and genomics, but knock-on effects are ensuring this extends to other areas of bioinformatics. Here, we describe the emergence of genomics research and the development of bioinformatics in Africa through H3ABioNet. PMID:26627985

The Food Production Environment and the Development of Antimicrobial Resistance in Human Pathogens of Animal Origin.

PubMed

Lekshmi, Manjusha; Ammini, Parvathi; Kumar, Sanath; Varela, Manuel F

2017-03-14

Food-borne pathogens are a serious human health concern worldwide, and the emergence of antibiotic-resistant food pathogens has further confounded this problem. Once-highly-efficacious antibiotics are gradually becoming ineffective against many important pathogens, resulting in severe treatment crises. Among several reasons for the development and spread of antimicrobial resistance, their overuse in animal food production systems for purposes other than treatment of infections is prominent. Many pathogens of animals are zoonotic, and therefore any development of resistance in pathogens associated with food animals can spread to humans through the food chain. Human infections by antibiotic-resistant pathogens such as Campylobacter spp., Salmonella spp., Escherichia coli and Staphylococcus aureus are increasing. Considering the human health risk due to emerging antibiotic resistance in food animal-associated bacteria, many countries have banned the use of antibiotic growth promoters and the application in animals of antibiotics critically important in human medicine. Concerted global efforts are necessary to minimize the use of antimicrobials in food animals in order to control the development of antibiotic resistance in these systems and their spread to humans via food and water.

Spatial analysis on human brucellosis incidence in mainland China: 2004–2010

PubMed Central

Zhang, Junhui; Yin, Fei; Zhang, Tao; Yang, Chao; Zhang, Xingyu; Feng, Zijian; Li, Xiaosong

2014-01-01

Objectives China has experienced a sharply increasing rate of human brucellosis in recent years. Effective spatial monitoring of human brucellosis incidence is very important for successful implementation of control and prevention programmes. The purpose of this paper is to apply exploratory spatial data analysis (ESDA) methods and the empirical Bayes (EB) smoothing technique to monitor county-level incidence rates for human brucellosis in mainland China from 2004 to 2010 by examining spatial patterns. Methods ESDA methods were used to characterise spatial patterns of EB smoothed incidence rates for human brucellosis based on county-level data obtained from the China Information System for Disease Control and Prevention (CISDCP) in mainland China from 2004 to 2010. Results EB smoothed incidence rates for human brucellosis were spatially dependent during 2004–2010. The local Moran test identified significantly high-risk clusters of human brucellosis (all p values <0.01), which persisted during the 7-year study period. High-risk counties were centred in the Inner Mongolia Autonomous Region and other Northern provinces (ie, Hebei, Shanxi, Jilin and Heilongjiang provinces) around the border with the Inner Mongolia Autonomous Region where animal husbandry was highly developed. The number of high-risk counties increased from 25 in 2004 to 54 in 2010. Conclusions ESDA methods and the EB smoothing technique can assist public health officials in identifying high-risk areas. Allocating more resources to high-risk areas is an effective way to reduce human brucellosis incidence. PMID:24713215

04-ERD-052-Final Report

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

Loots, G G; Ovcharenko, I; Collette, N

2007-02-26

Generating the sequence of the human genome represents a colossal achievement for science and mankind. The technical use for the human genome project information holds great promise to cure disease, prevent bioterror threats, as well as to learn about human origins. Yet converting the sequence data into biological meaningful information has not been immediately obvious, and we are still in the preliminary stages of understanding how the genome is organized, what are the functional building blocks and how do these sequences mediate complex biological processes. The overarching goal of this program was to develop novel methods and high throughput strategiesmore » for determining the functions of ''anonymous'' human genes that are evolutionarily deeply conserved in other vertebrates. We coupled analytical tool development and computational predictions regarding gene function with novel high throughput experimental strategies and tested biological predictions in the laboratory. The tools required for comparative genomic data-mining are fundamentally the same whether they are applied to scientific studies of related microbes or the search for functions of novel human genes. For this reason the tools, conceptual framework and the coupled informatics-experimental biology paradigm we developed in this LDRD has many potential scientific applications relevant to LLNL multidisciplinary research in bio-defense, bioengineering, bionanosciences and microbial and environmental genomics.« less

The MIT Summit Speech Recognition System: A Progress Report

DTIC Science & Technology

1989-01-01

understanding of the human communication process. Despite recent development of some speech recognition systems with high accuracy, the performance of such...over the past four decades on human communication , in the hope that such systems will one day have a performance approaching that of humans. We are...optimize its use. Third, the system must have a stochastic component to deal with the present state of ignorance in our understanding of the human

NASA's Advanced Life Support Systems Human-Rated Test Facility

NASA Technical Reports Server (NTRS)

Henninger, D. L.; Tri, T. O.; Packham, N. J.

1996-01-01

Future NASA missions to explore the solar system will be long-duration missions, requiring human life support systems which must operate with very high reliability over long periods of time. Such systems must be highly regenerative, requiring minimum resupply, to enable the crews to be largely self-sufficient. These regenerative life support systems will use a combination of higher plants, microorganisms, and physicochemical processes to recycle air and water, produce food, and process wastes. A key step in the development of these systems is establishment of a human-rated test facility specifically tailored to evaluation of closed, regenerative life supports systems--one in which long-duration, large-scale testing involving human test crews can be performed. Construction of such a facility, the Advanced Life Support Program's (ALS) Human-Rated Test Facility (HRTF), has begun at NASA's Johnson Space Center, and definition of systems and development of initial outfitting concepts for the facility are underway. This paper will provide an overview of the HRTF project plan, an explanation of baseline configurations, and descriptive illustrations of facility outfitting concepts.

The Nile Rat (Arvicanthis niloticus) as a Superior Carbohydrate-Sensitive Model for Type 2 Diabetes Mellitus (T2DM)

PubMed Central

Landstrom, Michelle; Luu, Alice; Hayes, K. C.

2018-01-01

Type II diabetes mellitus (T2DM) is a multifactorial disease involving complex genetic and environmental interactions. No single animal model has so far mirrored all the characteristics or complications of diabetes in humans. Since this disease represents a chronic nutritional insult based on a diet bearing a high glycemic load, the ideal model should recapitulate the underlying dietary issues. Most rodent models have three shortcomings: (1) they are genetically or chemically modified to produce diabetes; (2) unlike humans, most require high-fat feeding; (3) and they take too long to develop diabetes. By contrast, Nile rats develop diabetes rapidly (8–10 weeks) with high-carbohydrate (hiCHO) diets, similar to humans, and are protected by high fat (with low glycemic load) intake. This review describes diabetes progression in the Nile rat, including various aspects of breeding, feeding, and handling for best experimental outcomes. The diabetes is characterized by a striking genetic permissiveness influencing hyperphagia and hyperinsulinemia; random blood glucose is the best index of disease progression; and kidney failure with chronic morbidity and death are outcomes, all of which mimic uncontrolled T2DM in humans. Non-alcoholic fatty liver disease (NAFLD), also described in diabetic humans, results from hepatic triglyceride and cholesterol accumulation associated with rising blood glucose. Protection is afforded by low glycemic load diets rich in certain fibers or polyphenols. Accordingly, the Nile rat provides a unique opportunity to identify the nutritional factors and underlying genetic and molecular mechanisms that characterize human T2DM. PMID:29463026

Validation of a mapping and prediction model for human fasciolosis transmission in Andean very high altitude endemic areas using remote sensing data.

PubMed

Fuentes, M V; Malone, J B; Mas-Coma, S

2001-04-27

The present paper aims to validate the usefulness of the Normalized Difference Vegetation Index (NDVI) obtained by satellite remote sensing for the development of local maps of risk and for prediction of human fasciolosis in the Northern Bolivian Altiplano. The endemic area, which is located at very high altitudes (3800-4100 m) between Lake Titicaca and the valley of the city of La Paz, presents the highest prevalences and intensities of fasciolosis known in humans. NDVI images of 1.1 km resolution from the Advanced Very High Resolution Radiometer (AVHRR) sensor on board the National Oceanic and Atmospheric Administration (NOAA) series of environmental satellites appear to provide adequate information for a study area such as that of the Northern Bolivian Altiplano. The predictive value of the remotely sensed map based on NDVI data appears to be better than that from forecast indices based only on climatic data. A close correspondence was observed between real ranges of human fasciolosis prevalence at 13 localities of known prevalence rates and the predicted ranges of fasciolosis prevalence using NDVI maps. However, results based on NDVI map data predicted zones as risk areas where, in fact, field studies have demonstrated the absence of lymnaeid populations during snail surveys, corroborated by the absence of the parasite in humans and livestock. NDVI data maps represent a useful data component in long-term efforts to develop a comprehensive geographical information system control program model that accurately fits real epidemiological and transmission situations of human fasciolosis in high altitude endemic areas in Andean countries.

Affinity chromatography on monolithic supports for simultaneous and high-throughput isolation of immunoglobulins from human serum.

PubMed

Martinović, Tamara; Andjelković, Uroš; Klobučar, Marko; Černigoj, Urh; Vidič, Jana; Lučić, Marina; Pavelić, Krešimir; Josić, Djuro

2017-11-01

Posttranslational modifications of immunoglobulins have been a topic of great interest and have been repeatedly reported as a major factor in disease pathology. Cost-effective, reproducible, and high-throughput (HTP) isolation of immunoglobulins from human serum is vital for studying the changes in protein structure and the following understanding of disease development. Although there are many methods for the isolation of specific immunoglobulin classes, only a few of them are applicable for isolation of all subtypes and variants. Here, we present the development of a scheme for fast and simultaneous affinity purification of α (A), γ (G), and μ (M) immunoglobulins from human serum through affinity monolith chromatography. Affinity-based monolithic columns with immobilized protein A, G, or L were used for antibody isolation. Monolithic stationary phases have a high surface accessibility of binding sites, large flow-through channels, and can be operated at high flow rates, making them the ideal supports for HTP isolation of biopolymers. The presented method can be used for HTP screening of human serum in order to simultaneously isolate all three above-mentioned immunoglobulins and determine their concentration and changes in their glycosylation pattern as potential prognostic and diagnostic disease biomarkers. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Remote monitoring of the progression of primary pneumonic plague in Brown Norway rats in high-capacity, high-containment housing

PubMed Central

Coate, Eric A.; Kocsis, Andrew G.; Peters, Kristen N.; Anderson, Paul E.; Ellersieck, Mark R.; Fine, Deborah M.; Anderson, Deborah M.

2014-01-01

Development of new vaccines, diagnostics and therapeutics for biodefense or other relatively rare infectious diseases is hindered by the lack of naturally occurring human disease on which to conduct clinical trials of efficacy. To overcome this experimental gap, the U.S. Food and Drug Administration established the Animal Rule, in which efficacy testing in two well-characterized animal models that closely resemble human disease may be accepted in lieu of large scale clinical trials for diseases with limited natural human incidence. In this report, we evaluated the Brown Norway rat as a model for pneumonic plague and describe the natural history of clinical disease following inhalation exposure to Yersinia pestis. In high-capacity, high-containment housing, we monitored temperature, activity, heart rate and rhythm by capturing electronic impulses transmitted from abdominal telemeter implants. Using this system, we show that reduced activity and development of fever are sensitive indications of disease progression. Furthermore, we identified heart arrhythmias as contributing factors to the rapid progression to lethality following the fever response. Together these data validate the Brown Norway rat as an experimental model for human pneumonic plague and provide new insight that may ultimately lead to novel approaches in post-exposure treatment of this devastating infection. PMID:24719212

Use of Validation by Enterprises for Human Resource and Career Development Purposes. Cedefop Reference Series No 96

ERIC Educational Resources Information Center

Cedefop - European Centre for the Development of Vocational Training, 2014

2014-01-01

European enterprises give high priority to assessing skills and competences, seeing this as crucial for recruitment and human resource management. Based on a survey of 400 enterprises, 20 in-depth case studies and interviews with human resource experts in 10 countries, this report analyses the main purposes of competence assessment, the standards…

The human footprint in Mexico: physical geography and historical legacies.

PubMed

González-Abraham, Charlotte; Ezcurra, Exequiel; Garcillán, Pedro P; Ortega-Rubio, Alfredo; Kolb, Melanie; Bezaury Creel, Juan E

2015-01-01

Using publicly available data on land use and transportation corridors we calculated the human footprint index for the whole of Mexico to identify large-scale spatial patterns in the anthropogenic transformation of the land surface. We developed a map of the human footprint for the whole country and identified the ecological regions that have most transformed by human action. Additionally, we analyzed the extent to which (a) physical geography, expressed spatially in the form of biomes and ecoregions, compared to (b) historical geography, expressed as the spatial distribution of past human settlements, have driven the patterns of human modification of the land. Overall Mexico still has 56% of its land surface with low impact from human activities, but these areas are not evenly distributed. The lowest values are on the arid north and northwest, and the tropical southeast, while the highest values run along the coast of the Gulf of Mexico and from there inland along an east-to-west corridor that follows the Mexican transversal volcanic ranges and the associated upland plateau. The distribution of low- and high footprint areas within ecoregions forms a complex mosaic: the generally well-conserved Mexican deserts have some highly transformed agro-industrial areas, while many well-conserved, low footprint areas still persist in the highly-transformed ecoregions of central Mexico. We conclude that the spatial spread of the human footprint in Mexico is both the result of the limitations imposed by physical geography to human development at the biome level, and, within different biomes, of a complex history of past civilizations and technologies, including the 20th Century demographic explosion but also the spatial pattern of ancient settlements that were occupied by the Spanish Colony.

The Human Footprint in Mexico: Physical Geography and Historical Legacies

PubMed Central

Ortega-Rubio, Alfredo; Kolb, Melanie; Bezaury Creel, Juan E.

2015-01-01

Using publicly available data on land use and transportation corridors we calculated the human footprint index for the whole of Mexico to identify large-scale spatial patterns in the anthropogenic transformation of the land surface. We developed a map of the human footprint for the whole country and identified the ecological regions that have most transformed by human action. Additionally, we analyzed the extent to which (a) physical geography, expressed spatially in the form of biomes and ecoregions, compared to (b) historical geography, expressed as the spatial distribution of past human settlements, have driven the patterns of human modification of the land. Overall Mexico still has 56% of its land surface with low impact from human activities, but these areas are not evenly distributed. The lowest values are on the arid north and northwest, and the tropical southeast, while the highest values run along the coast of the Gulf of Mexico and from there inland along an east-to-west corridor that follows the Mexican transversal volcanic ranges and the associated upland plateau. The distribution of low- and high footprint areas within ecoregions forms a complex mosaic: the generally well-conserved Mexican deserts have some highly transformed agro-industrial areas, while many well-conserved, low footprint areas still persist in the highly-transformed ecoregions of central Mexico. We conclude that the spatial spread of the human footprint in Mexico is both the result of the limitations imposed by physical geography to human development at the biome level, and, within different biomes, of a complex history of past civilizations and technologies, including the 20th Century demographic explosion but also the spatial pattern of ancient settlements that were occupied by the Spanish Colony. PMID:25803839

Redefining Professional Development. Newsletter

ERIC Educational Resources Information Center

Center for Comprehensive School Reform and Improvement, 2006

2006-01-01

The research on effective professional development is consistent across many studies. Researchers Willis Hawley and Linda Valli (Westchester Institute for Human Services Research, n.d.), in their synthesis of the professional development literature, find that high-quality teacher development is as follows: (1) Informed by research on teaching and…

Progenitor cell dose determines the pace and completeness of engraftment in a xenograft model for cord blood transplantation

PubMed Central

Liu, Congxiao; Chen, Benny J.; DeOliveira, Divinomar; Sempowski, Gregory D.; Chao, Nelson J.

2010-01-01

Two critical concerns in clinical cord blood transplantation are the initial time to engraftment and the subsequent restoration of immune function. These studies measured the impact of progenitor cell dose on both the pace and strength of hematopoietic reconstitution by transplanting nonobese diabetic/severe combined immunodeficiency/interleukin-2 receptor-gamma–null (NSγ) mice with lineage-depleted aldehyde dehydrogenase-bright CD34+ human cord blood progenitors. The progress of each transplant was monitored over an extended time course by repeatedly analyzing the peripheral blood for human hematopoietic cells. In vivo human hematopoietic development was complete. After long-term transplantation assays (≥ 19 weeks), human T-cell development was documented within multiple tissues in 16 of 32 NSγ mice. Human T-cell differentiation was active within NSγ thymuses, as documented by the presence of CD4+ CD8+ T-cell progenitors as well as T-cell receptor excision circles. It is important to note that although myeloid and B-cell engraftment was detected as early as 4 weeks after transplantation, human T-cell development was exclusively late onset. High progenitor cell doses were associated with a robust human hematopoietic chimerism that accelerated both initial time to engraftment and subsequent T-cell development. At lower progenitor cell doses, the chimerism was weak and the human hematopoietic lineage development was frequently incomplete. PMID:20833978

Natural Selection of Human Embryos: Decidualizing Endometrial Stromal Cells Serve as Sensors of Embryo Quality upon Implantation

PubMed Central

Teklenburg, Gijs; Salker, Madhuri; Molokhia, Mariam; Lavery, Stuart; Trew, Geoffrey; Aojanepong, Tepchongchit; Mardon, Helen J.; Lokugamage, Amali U.; Rai, Raj; Landles, Christian; Roelen, Bernard A. J.; Quenby, Siobhan; Kuijk, Ewart W.; Kavelaars, Annemieke; Heijnen, Cobi J.; Regan, Lesley; Brosens, Jan J.; Macklon, Nick S.

2010-01-01

Background Pregnancy is widely viewed as dependent upon an intimate dialogue, mediated by locally secreted factors between a developmentally competent embryo and a receptive endometrium. Reproductive success in humans is however limited, largely because of the high prevalence of chromosomally abnormal preimplantation embryos. Moreover, the transient period of endometrial receptivity in humans uniquely coincides with differentiation of endometrial stromal cells (ESCs) into highly specialized decidual cells, which in the absence of pregnancy invariably triggers menstruation. The role of cyclic decidualization of the endometrium in the implantation process and the nature of the decidual cytokines and growth factors that mediate the crosstalk with the embryo are unknown. Methodology/Principal Findings We employed a human co-culture model, consisting of decidualizing ESCs and single hatched blastocysts, to identify the soluble factors involved in implantation. Over the 3-day co-culture period, approximately 75% of embryos arrested whereas the remainder showed normal development. The levels of 14 implantation factors secreted by the stromal cells were determined by multiplex immunoassay. Surprisingly, the presence of a developing embryo had no significant effect on decidual secretions, apart from a modest reduction in IL-5 levels. In contrast, arresting embryos triggered a strong response, characterized by selective inhibition of IL-1β, -6, -10, -17, -18, eotaxin, and HB-EGF secretion. Co-cultures were repeated with undifferentiated ESCs but none of the secreted cytokines were affected by the presence of a developing or arresting embryo. Conclusions Human ESCs become biosensors of embryo quality upon differentiation into decidual cells. In view of the high incidence of gross chromosomal errors in human preimplantation embryos, cyclic decidualization followed by menstrual shedding may represent a mechanism of natural embryo selection that limits maternal investment in developmentally impaired pregnancies. PMID:20422011

Fast liquid chromatography combined with mass spectrometry for the analysis of metabolites and proteins in human body fluids.

PubMed

Kortz, Linda; Helmschrodt, Christin; Ceglarek, Uta

2011-03-01

In the last decade various analytical strategies have been established to enhance separation speed and efficiency in high performance liquid chromatography applications. Chromatographic supports based on monolithic material, small porous particles, and porous layer beads have been developed and commercialized to improve throughput and separation efficiency. This paper provides an overview of current developments in fast chromatography combined with mass spectrometry for the analysis of metabolites and proteins in clinical applications. Advances and limitations of fast chromatography for the combination with mass spectrometry are discussed. Practical aspects of, recent developments in, and the present status of high-throughput analysis of human body fluids for therapeutic drug monitoring, toxicology, clinical metabolomics, and proteomics are presented.

The Emerging External Labor Market and the Impact on Enterprise's Human Resource Development in China.

ERIC Educational Resources Information Center

Benson, John; Zhu, Ying

2002-01-01

Labor strategies of eight enterprises in Shanghai and Beijing were profiled. Changes in national policy had created a highly competitive market. High skill requirements of jobs and shortages of skilled labor meant companies emphasized internal employee development over recruitment. However, they lacked strategies for retaining trained employees.…

The impact of leptin on perinatal development and psychopathology.

PubMed

Valleau, Jeanette C; Sullivan, Elinor L

2014-11-01

Leptin has long been associated with metabolism as it is a critical regulator of both food intake and energy expenditure, but recently, leptin dysregulation has been proposed as a mechanism of psychopathology. This review discusses the evidence supporting a role for leptin in mental health disorders and describes potential mechanisms that may underlie this association. Leptin plays a critical role in pregnancy and in fetal growth and development. Leptin's role and profile during development is examined in available human studies, and the validity of applying studies conducted in animal models to the human population are discussed. Rodents experience a postnatal leptin surge, which does not occur in humans or larger animal models. This suggests that further research using large mammal models, which have a leptin profile across pregnancy and development similar to humans, are of high importance. Maternal obesity and hyperleptinemia correlate with increased leptin levels in the umbilical cord, placenta, and fetus. Leptin levels are thought to impact fetal brain development; likely by activating proinflammatory cytokines that are known to impact many of the neurotransmitter systems that regulate behavior. Leptin is likely involved in behavioral regulation as leptin receptors are widely distributed in the brain, and leptin influences cortisol release, the mesoaccumbens dopamine pathway, serotonin synthesis, and hippocampal synaptic plasticity. In humans, both high and low levels of leptin are reported to be associated with psychopathology. This inconsistency is likely due to differences in the metabolic state of the study populations. Leptin resistance, which occurs in the obese state, may explain how both high and low levels of leptin are associated with psychopathology, as well as the comorbidity of obesity with numerous mental illnesses. Leptin resistance is likely to influence disorders such as depression and anxiety where high leptin levels have been correlated with symptomatology. Schizophrenia is also associated with both low and high leptin levels. However, as anti-psychotics pharmacotherapy induces weight gain, which elevates leptin levels, drug-naïve populations are needed for further studies. Elevated circulating leptin is consistently found in childhood neurodevelopmental disorders including autism spectrum disorders and Rhett disorder. Further, studies on the impact of leptin and leptin resistance on psychopathology and neurodevelopmental disorders are important directions for future research. Studies examining the mechanisms by which exposure to maternal obesity and hyperleptinemia during fetal development impact brain development and behavior are critical for the health of future generations. Copyright © 2014 Elsevier B.V. All rights reserved.

The Impact of Leptin on Perinatal Development and Psychopathology

PubMed Central

Valleau, Jeanette C.; Sullivan, Elinor L.

2014-01-01

Leptin has long been associated with metabolism as it is a critical regulator of both food intake and energy expenditure, but recently, leptin dysregulation has been proposed as a mechanism of psychopathology. This review discusses the evidence supporting a role for leptin in mental health disorders and describes potential mechanisms that may underlie this association. Leptin plays a critical role in pregnancy and in fetal growth and development. Leptin’s role and profile during development is examined in available human studies and the validity of applying studies conducted in animal models to the human population are discussed. Rodents experience a postnatal leptin surge, which does not occur in humans or larger animal models. This suggests that further research using large mammal models, which have a leptin profile across pregnancy and development similar to humans, are of high importance. Maternal obesity and hyperleptinemia correlate with increased leptin levels in the umbilical cord, placenta, and fetus. Leptin levels are thought to impact fetal brain development; likely by activating proinflammatory cytokines that are known to impact many of the neurotransmitter systems that regulate behavior. Leptin is likely involved in behavioral regulation as leptin receptors are widely distributed in the brain, and leptin influences cortisol release, the mesoaccumbens dopamine pathway, serotonin synthesis, and hippocampal synaptic plasticity. In humans, both high and low levels of leptin are reported to be associated with psychopathology. This inconsistency is likely due to differences in the metabolic state of the study populations. Leptin resistance, which occurs in the obese state, may explain how both high and low levels of leptin are associated with psychopathology, as well as the comorbidity of obesity with numerous mental illnesses. Leptin resistance is likely to influence disorders such as depression and anxiety where both high and low leptin levels have been correlated with symptomatology. Schizophrenia is also associated with both low and high leptin levels. However, as antipsychotics pharmacotherapy induces weight gain, which elevates leptin levels, drug-naïve populations are needed for further studies. Elevated circulating leptin is consistently found in childhood neurodevelopmental disorders including Autism Spectrum Disorders and Rhett disorder. Further studies on the impact of leptin and leptin resistance on psychopathology and neurodevelopmental disorders are important directions for future research. Studies examining the mechanisms by which exposure to maternal obesity and hyperleptinemia during fetal development impact brain development and behavior are critical for the health of future generations. PMID:24862904

Sleeping Beauty transposon mutagenesis identifies genes that cooperate with mutant Smad4 in gastric cancer development

PubMed Central

Takeda, Haruna; Rust, Alistair G.; Ward, Jerrold M.; Yew, Christopher Chin Kuan; Jenkins, Nancy A.; Copeland, Neal G.

2016-01-01

Mutations in SMAD4 predispose to the development of gastrointestinal cancer, which is the third leading cause of cancer-related deaths. To identify genes driving gastric cancer (GC) development, we performed a Sleeping Beauty (SB) transposon mutagenesis screen in the stomach of Smad4+/− mutant mice. This screen identified 59 candidate GC trunk drivers and a much larger number of candidate GC progression genes. Strikingly, 22 SB-identified trunk drivers are known or candidate cancer genes, whereas four SB-identified trunk drivers, including PTEN, SMAD4, RNF43, and NF1, are known human GC trunk drivers. Similar to human GC, pathway analyses identified WNT, TGF-β, and PI3K-PTEN signaling, ubiquitin-mediated proteolysis, adherens junctions, and RNA degradation in addition to genes involved in chromatin modification and organization as highly deregulated pathways in GC. Comparative oncogenomic filtering of the complete list of SB-identified genes showed that they are highly enriched for genes mutated in human GC and identified many candidate human GC genes. Finally, by comparing our complete list of SB-identified genes against the list of mutated genes identified in five large-scale human GC sequencing studies, we identified LDL receptor-related protein 1B (LRP1B) as a previously unidentified human candidate GC tumor suppressor gene. In LRP1B, 129 mutations were found in 462 human GC samples sequenced, and LRP1B is one of the top 10 most deleted genes identified in a panel of 3,312 human cancers. SB mutagenesis has, thus, helped to catalog the cooperative molecular mechanisms driving SMAD4-induced GC growth and discover genes with potential clinical importance in human GC. PMID:27006499

Sleeping Beauty transposon mutagenesis identifies genes that cooperate with mutant Smad4 in gastric cancer development.

PubMed

Takeda, Haruna; Rust, Alistair G; Ward, Jerrold M; Yew, Christopher Chin Kuan; Jenkins, Nancy A; Copeland, Neal G

2016-04-05

Mutations in SMAD4 predispose to the development of gastrointestinal cancer, which is the third leading cause of cancer-related deaths. To identify genes driving gastric cancer (GC) development, we performed a Sleeping Beauty (SB) transposon mutagenesis screen in the stomach of Smad4(+/-) mutant mice. This screen identified 59 candidate GC trunk drivers and a much larger number of candidate GC progression genes. Strikingly, 22 SB-identified trunk drivers are known or candidate cancer genes, whereas four SB-identified trunk drivers, including PTEN, SMAD4, RNF43, and NF1, are known human GC trunk drivers. Similar to human GC, pathway analyses identified WNT, TGF-β, and PI3K-PTEN signaling, ubiquitin-mediated proteolysis, adherens junctions, and RNA degradation in addition to genes involved in chromatin modification and organization as highly deregulated pathways in GC. Comparative oncogenomic filtering of the complete list of SB-identified genes showed that they are highly enriched for genes mutated in human GC and identified many candidate human GC genes. Finally, by comparing our complete list of SB-identified genes against the list of mutated genes identified in five large-scale human GC sequencing studies, we identified LDL receptor-related protein 1B (LRP1B) as a previously unidentified human candidate GC tumor suppressor gene. In LRP1B, 129 mutations were found in 462 human GC samples sequenced, and LRP1B is one of the top 10 most deleted genes identified in a panel of 3,312 human cancers. SB mutagenesis has, thus, helped to catalog the cooperative molecular mechanisms driving SMAD4-induced GC growth and discover genes with potential clinical importance in human GC.

Development, fabrication, and modeling of highly sensitive conjugated polymer based piezoresistive sensors in electronic skin applications

NASA Astrophysics Data System (ADS)

Khalili, Nazanin; Naguib, Hani E.; Kwon, Roy H.

2016-04-01

Human intervention can be replaced through development of tools resulted from utilizing sensing devices possessing a wide range of applications including humanoid robots or remote and minimally invasive surgeries. Similar to the five human senses, sensors interface with their surroundings to stimulate a suitable response or action. The sense of touch which arises in human skin is among the most challenging senses to emulate due to its ultra high sensitivity. This has brought forth novel challenging issues to consider in the field of biomimetic robotics. In this work, using a multiphase reaction, a polypyrrole (PPy) based hydrogel is developed as a resistive type pressure sensor with an intrinsically elastic microstructure stemming from three dimensional hollow spheres. Furthermore, a semi-analytical constriction resistance model accounting for the real contact area between the PPy hydrogel sensors and the electrode along with the dependency of the contact resistance change on the applied load is developed. The model is then solved using a Monte Carlo technique and the sensitivity of the sensor is obtained. The experimental results showed the good tracking ability of the proposed model.

Assessment of the Risk to Public Health due to Use of Antimicrobials in Pigs—An Example of Pleuromutilins in Denmark

PubMed Central

Alban, Lis; Ellis-Iversen, Johanne; Andreasen, Margit; Dahl, Jan; Sönksen, Ute W.

2017-01-01

Antibiotic consumption in pigs can be optimized by developing treatment guidelines, which encourage veterinarians to use effective drugs with low probability of developing resistance of importance for human health. In Denmark, treatment guidelines for use in swine production are currently under review at the Danish Veterinary and Food Administration. Use of pleuromutilins in swine has previously been associated with a very low risk for human health. However, recent international data and sporadic findings of novel resistance genes suggest a change of risk. Consequently, a reassessment was undertaken inspired by a risk assessment framework developed by the European Medicines Agency. Livestock-associated methicillin-resistant Staphylococcus aureus of clonal complex 398 (MRSA CC398) and enterococci were identified as relevant hazards. The release assessment showed that the probability of development of pleuromutilin resistance was high in MRSA CC398 (medium uncertainty) and low in enterococci (high uncertainty). A relatively small proportion of Danes has an occupational exposure to pigs, and foodborne transmission was only considered of relevance for enterococci, resulting in an altogether low exposure risk. The human consequences of infection with pleuromutilin-resistant MRSA CC398 or enterococci were assessed as low for the public in general but high for vulnerable groups such as hospitalized and immunocompromised persons. For MRSA CC398, the total risk was estimated as low (low uncertainty), among other due to the current guidelines on prevention of MRSA in place at Danish hospitals, which include screening of patients with daily contact to pigs on admittance. Moreover, MRSA CC398 has a medium human–human transmission potential. For enterococci, the total risk was estimated as low due to low prevalence of resistance, low probability of spread to humans, low virulence, but no screening of hospitalized patients, high ability of acquiring resistance genes, and a limited number of alternative antimicrobials (high uncertainty). This assessment reflects the current situation and should be repeated if pleuromutilin consumption increases substantially, resulting in increased prevalence of mobile, easily transmissible resistance mechanisms. Continuous monitoring of pleuromutilin resistance in selected human pathogens should therefore be considered. This also includes monitoring of linezolid resistance, since resistance mechanisms for pleuromutilins and oxazolidones are often coupled. PMID:28603717

Generation and characterization of high affinity humanized fab against hepatitis B surface antigen.

PubMed

Tiwari, Ashutosh; Dutta, Durgashree; Khanna, Navin; Acharya, Subrat K; Sinha, Subrata

2009-09-01

5S is a mouse monoclonal IgG1 that binds to the 'a' epitope of the Hepatitis B surface antigen (HBsAg) and tested positive in an in vitro test for virus neutralization. We have earlier reported the generation of humanized single chain variable fragment (scFv) from the same. In this article we report the generation of a recombinant Fab molecule by fusing humanized variable domains of 5S with the constant domains of human IgG1. The humanized Fab expressed in E. coli and subsequently purified, retained a high binding affinity (K(D) = 3.63 nmol/L) to HBsAg and bound to the same epitope of HBsAg as the parent molecule. The humanized Fab also maintained antigen binding in the presence of various destabilizing agents like 3 M NaCl, 30% DMSO, 8 M urea, and extreme pH. This high affinity humanized Fab provides a basis for the development of therapeutic molecules that can be safely utilized for the prophylaxis and treatment for Hepatitis B infection.

Development of a generic GMCC simulator.

DOT National Transportation Integrated Search

2001-11-01

This document describes the development and current status of a high fidelity, human-in-the-loop simulator for Airway Facilities : Maintenance Control Centers and Operations Control Centers. Applications include Event Manager, Maintenance Automation ...

Progressive Recruitment of Mesenchymal Progenitors Reveals a Time-Dependent Process of Cell Fate Acquisition in Mouse and Human Nephrogenesis.

PubMed

Lindström, Nils O; De Sena Brandine, Guilherme; Tran, Tracy; Ransick, Andrew; Suh, Gio; Guo, Jinjin; Kim, Albert D; Parvez, Riana K; Ruffins, Seth W; Rutledge, Elisabeth A; Thornton, Matthew E; Grubbs, Brendan; McMahon, Jill A; Smith, Andrew D; McMahon, Andrew P

2018-06-04

Mammalian nephrons arise from a limited nephron progenitor pool through a reiterative inductive process extending over days (mouse) or weeks (human) of kidney development. Here, we present evidence that human nephron patterning reflects a time-dependent process of recruitment of mesenchymal progenitors into an epithelial nephron precursor. Progressive recruitment predicted from high-resolution image analysis and three-dimensional reconstruction of human nephrogenesis was confirmed through direct visualization and cell fate analysis of mouse kidney organ cultures. Single-cell RNA sequencing of the human nephrogenic niche provided molecular insights into these early patterning processes and predicted developmental trajectories adopted by nephron progenitor cells in forming segment-specific domains of the human nephron. The temporal-recruitment model for nephron polarity and patterning suggested by direct analysis of human kidney development provides a framework for integrating signaling pathways driving mammalian nephrogenesis. Copyright © 2018 Elsevier Inc. All rights reserved.

Translating Vision into Design: A Method for Conceptual Design Development

NASA Technical Reports Server (NTRS)

Carpenter, Joyce E.

2003-01-01

One of the most challenging tasks for engineers is the definition of design solutions that will satisfy high-level strategic visions and objectives. Even more challenging is the need to demonstrate how a particular design solution supports the high-level vision. This paper describes a process and set of system engineering tools that have been used at the Johnson Space Center to analyze and decompose high-level objectives for future human missions into design requirements that can be used to develop alternative concepts for vehicles, habitats, and other systems. Analysis and design studies of alternative concepts and approaches are used to develop recommendations for strategic investments in research and technology that support the NASA Integrated Space Plan. In addition to a description of system engineering tools, this paper includes a discussion of collaborative design practices for human exploration mission architecture studies used at the Johnson Space Center.

Development of a bespoke human factors taxonomy for gliding accident analysis and its revelations about highly inexperienced UK glider pilots.

PubMed

Jarvis, Steve; Harris, Don

2009-08-01

Low-hours solo glider pilots have a high risk of accidents compared to more experienced pilots. Numerous taxonomies for causal accident analysis have been produced for powered aviation but none of these is suitable for gliding, so a new taxonomy was required. A human factors taxonomy specifically for glider operations was developed and used to analyse all UK gliding accidents from 2002 to 2006 for their overall causes as well as factors specific to low hours pilots. Fifty-nine categories of pilot-related accident causation emerged, which were formed into progressively larger categories until four overall human factors groups were arrived at: 'judgement'; 'handling'; 'strategy'; 'attention'. 'Handling' accounted for a significantly higher proportion of injuries than other categories. Inexperienced pilots had considerably more accidents in all categories except 'strategy'. Approach control (path judgement, airbrake and speed handling) as well as landing flare misjudgement were chiefly responsible for the high accident rate in early solo glider pilots.

Human papillomavirus in the HIV-infected host: epidemiology and pathogenesis in the antiretroviral era.

PubMed

Brickman, Cristina; Palefsky, Joel M

2015-03-01

Human papillomavirus (HPV) infection is associated with essentially all cervical cancers, 80-90 % of anal cancers, and a high proportion of oropharyngeal, vaginal, penile, and vulvar cancers. Malignancy is preceded by the development of precancerous lesions termed high-grade squamous intraepithelial lesions (HSIL). Men and women with human immunodeficiency virus (HIV) infection are at high risk of HPV-related malignancies. The incidence of anal cancer in particular has markedly risen during the antiretroviral era due to the increased longevity of patients with HIV and the absence of anal malignancy screening programs. HIV infection may facilitate initial HPV infection by disrupting epithelial cell tight junctions. Once infection is established, HIV may promote HSIL development via the up-regulation of HPV oncogene expression and impairment of the immune response needed to clear the lesion. HIV-infected women should be screened for cervical HSIL and cancer, and HIV-infected men and women should be considered for anal screening programs.

First Attempt To Validate Human IgG Antibody Response to Nterm-34kDa Salivary Peptide as Biomarker for Evaluating Exposure to Aedes aegypti Bites

PubMed Central

Elanga Ndille, Emmanuel; Doucoure, Souleymane; Damien, Georgia; Mouchet, François; Drame, Papa Makhtar; Cornelie, Sylvie; Noukpo, Herbert; Yamadjako, Sandra; Djenontin, Armel; Moiroux, Nicolas; Misse, Dorothee; Akogbeto, Martin; Corbel, Vincent; Henry, Marie-Claire; Chandre, Fabrice; Baldet, Thierry; Remoue, Franck

2012-01-01

Background Much effort is being devoted for developing new indicators to evaluate the human exposure to Aedes mosquito bites and the risk of arbovirus transmission. Human antibody (Ab) responses to mosquito salivary components could represent a promising tool for evaluating the human-vector contact. Methodology/Principal findings To develop a specific biomarker of human exposure to Aedes aegypti bites, we measured IgG Ab response to Ae. aegypti Nterm-34 kDa salivary peptide in exposed children in 7 villages of Southern Benin (West Africa). Results showed that specific IgG response presented high inter-individual heterogeneity between villages. IgG response was associated with rainfall and IgG level increased from dry (low exposure) to rainy (high exposure) seasons. These findings indicate that IgG Ab to Nterm-34 kDa salivary peptide may represent a reliable biomarker to detect variation in human exposure to Ae. aegypti bites. Conclusion/Significance This preliminary study highlights the potential use of Ab response to this salivary peptide for evaluating human exposure to Ae. aegypti. This biomarker could represent a new promising tool for assessing the risk of arbovirus transmission and for evaluating the efficacy of vector control interventions. PMID:23166852

Directional and sectional ride comfort estimation using an integrated human biomechanical-seat foam model

NASA Astrophysics Data System (ADS)

Mohajer, Navid; Abdi, Hamid; Nahavandi, Saeid; Nelson, Kyle

2017-09-01

In the methodology of objective measurement of ride comfort, application of a Human Biomechanical Model (HBM) is valuable for Whole Body Vibration (WBV) analysis. In this study, using a computational Multibody System (MBS) approach, development of a 3D passive HBM for a seated human is considered. For this purpose, the existing MBS-based HBMs of seated human are briefly reviewed first. The Equations of Motion (EoM) for the proposed model are then obtained and the simulation results are shown and compared with idealised ranges of experimental results suggested in the literature. The human-seat interaction is established using a nonlinear vibration model of foam with respect to the sectional behaviour of the seat foam. The developed system is then used for ride comfort estimation offered by a ride dynamic model. The effects of human weight, road class, and vehicle speed on the vibration of the human body segments in different directions are studied. It is shown that the there is a high correlation (more than 99.2%) between the vibration indices of the proposed HBM-foam model and the corresponding ISO 2631 WBV indices. In addition, relevant ISO 2631 indices that show a high correlation with the directional vibration of the head are identified.

Development of a high-throughput assay for human proprotein convertase 5/6 for detecting uterine receptivity.

PubMed

Heng, Sophea; Dynon, Kemperly; Li, Ying; Edgell, Tracey; Walton, Kelly; Rombauts, Luk J; Vollenhoven, Beverley; Nie, Guiying

2015-04-15

Embryo implantation requires a healthy embryo and a receptive uterus. In women, the inner lining of the uterus, the endometrium, remains in a hostile state and becomes receptive for embryo implantation for only a short period during each menstrual cycle. Determining endometrial receptivity is vital in in vitro fertilization (IVF) treatment because the timing of embryo transfer needs to be synchronized with endometrial receptivity. We have previously demonstrated that proprotein convertase 5/6A (PC6) is highly expressed in the receptive endometrium and that PC6 is critical for receptivity establishment in women. Furthermore, endometrial PC6 is secreted into the uterine fluid, and levels correlate with receptivity status. Detection of PC6 in uterine fluids, therefore, would provide a nonsurgical assessment of endometrial receptivity. However, to date no assays are available for human PC6. In this study, we produced three PC6 monoclonal antibodies (mAbs) and developed a sandwich enzyme-linked immunosorbent assay (ELISA) for PC6 detection in human uterine fluids. The PC6 mAbs were confirmed to be highly specific to PC6, and the ELISA detected PC6 in human uterine fluids with a significantly higher level during the receptive phase. This newly established PC6 ELISA provides an important tool in the development of noninvasive strategies to detect endometrial receptivity in women. Copyright © 2015. Published by Elsevier Inc.

Direct Hydrogel Encapsulation of Pluripotent Stem Cells Enables Ontomimetic Differentiation and Growth of Engineered Human Heart Tissues

PubMed Central

Kerscher, Petra; Turnbull, Irene C; Hodge, Alexander J; Kim, Joonyul; Seliktar, Dror; Easley, Christopher J; Costa, Kevin D; Lipke, Elizabeth A

2016-01-01

Human engineered heart tissues have potential to revolutionize cardiac development research, drug-testing, and treatment of heart disease; however, implementation is limited by the need to use pre-differentiated cardiomyocytes (CMs). Here we show that by providing a 3D poly(ethylene glycol)-fibrinogen hydrogel microenvironment, we can directly differentiate human pluripotent stem cells (hPSCs) into contracting heart tissues. Our straight-forward, ontomimetic approach, imitating the process of development, requires only a single cell-handling step, provides reproducible results for a range of tested geometries and size scales, and overcomes inherent limitations in cell maintenance and maturation, while achieving high yields of CMs with developmentally appropriate temporal changes in gene expression. Here we demonstrate that hPSCs encapsulated within this biomimetic 3D hydrogel microenvironment develop into functional cardiac tissues composed of self-aligned CMs with evidence of ultrastructural maturation, mimicking heart development, and enabling investigation of disease mechanisms and screening of compounds on developing human heart tissue. PMID:26826618

Small-molecule-directed, efficient generation of retinal pigment epithelium from human pluripotent stem cells.

PubMed

Maruotti, Julien; Sripathi, Srinivas R; Bharti, Kapil; Fuller, John; Wahlin, Karl J; Ranganathan, Vinod; Sluch, Valentin M; Berlinicke, Cynthia A; Davis, Janine; Kim, Catherine; Zhao, Lijun; Wan, Jun; Qian, Jiang; Corneo, Barbara; Temple, Sally; Dubey, Ramin; Olenyuk, Bogdan Z; Bhutto, Imran; Lutty, Gerard A; Zack, Donald J

2015-09-01

Age-related macular degeneration (AMD) is associated with dysfunction and death of retinal pigment epithelial (RPE) cells. Cell-based approaches using RPE-like cells derived from human pluripotent stem cells (hPSCs) are being developed for AMD treatment. However, most efficient RPE differentiation protocols rely on complex, stepwise treatments and addition of growth factors, whereas small-molecule-only approaches developed to date display reduced yields. To identify new compounds that promote RPE differentiation, we developed and performed a high-throughput quantitative PCR screen complemented by a novel orthogonal human induced pluripotent stem cell (hiPSC)-based RPE reporter assay. Chetomin, an inhibitor of hypoxia-inducible factors, was found to strongly increase RPE differentiation; combination with nicotinamide resulted in conversion of over one-half of the differentiating cells into RPE. Single passage of the whole culture yielded a highly pure hPSC-RPE cell population that displayed many of the morphological, molecular, and functional characteristics of native RPE.

Small-molecule–directed, efficient generation of retinal pigment epithelium from human pluripotent stem cells

PubMed Central

Maruotti, Julien; Sripathi, Srinivas R.; Bharti, Kapil; Fuller, John; Wahlin, Karl J.; Ranganathan, Vinod; Sluch, Valentin M.; Berlinicke, Cynthia A.; Davis, Janine; Kim, Catherine; Zhao, Lijun; Wan, Jun; Qian, Jiang; Corneo, Barbara; Temple, Sally; Dubey, Ramin; Olenyuk, Bogdan Z.; Bhutto, Imran; Lutty, Gerard A.; Zack, Donald J.

2015-01-01

Age-related macular degeneration (AMD) is associated with dysfunction and death of retinal pigment epithelial (RPE) cells. Cell-based approaches using RPE-like cells derived from human pluripotent stem cells (hPSCs) are being developed for AMD treatment. However, most efficient RPE differentiation protocols rely on complex, stepwise treatments and addition of growth factors, whereas small-molecule–only approaches developed to date display reduced yields. To identify new compounds that promote RPE differentiation, we developed and performed a high-throughput quantitative PCR screen complemented by a novel orthogonal human induced pluripotent stem cell (hiPSC)-based RPE reporter assay. Chetomin, an inhibitor of hypoxia-inducible factors, was found to strongly increase RPE differentiation; combination with nicotinamide resulted in conversion of over one-half of the differentiating cells into RPE. Single passage of the whole culture yielded a highly pure hPSC-RPE cell population that displayed many of the morphological, molecular, and functional characteristics of native RPE. PMID:26269569

Creating virtual humans for simulation-based training and planning

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

Stansfield, S.; Sobel, A.

1998-05-12

Sandia National Laboratories has developed a distributed, high fidelity simulation system for training and planning small team Operations. The system provides an immersive environment populated by virtual objects and humans capable of displaying complex behaviors. The work has focused on developing the behaviors required to carry out complex tasks and decision making under stress. Central to this work are techniques for creating behaviors for virtual humans and for dynamically assigning behaviors to CGF to allow scenarios without fixed outcomes. Two prototype systems have been developed that illustrate these capabilities: MediSim, a trainer for battlefield medics and VRaptor, a system formore » planning, rehearsing and training assault operations.« less

Mining Human Biomonitoring Data to Identify Prevalent Chemical Mixtures (SOT abstract)

EPA Science Inventory

Through food, water, air, and consumer products, humans are exposed to tens of thousands of environmental chemicals, and most of these have not been evaluated to determine their potential toxicities. In recent years, high-throughput screening (HTS) methods have been developed tha...

Development of a prediction model for crash occurrence by analyzing traffic crash and citation data : final report.

DOT National Transportation Integrated Search

2017-04-30

It is commonly acknowledged that factors such as human factors, vehicle characteristics, road design and environmental factors highly contribute to the occurrence of traffic crashes (WHO, 2004). Since human factors usually have the most significant i...

DETERMINING THE ECONOMIC VALUE OF IMPROVED HUMAN EXPOSURE DATA

EPA Science Inventory

The U.S. EPA develops and revises environmental regulations and policies to protect the environment and human health. One of the key components of the regulatory process is establishing the proposed action level, which requires high quality exposure data. In many cases, expos...

In Praise of Robots

ERIC Educational Resources Information Center

Sagan, Carl

1975-01-01

The author of this article believes that human survival depends upon the ability to develop and work with machines of high artificial intelligence. He lists uses of such machines, including terrestrial mining, outer space exploration, and other tasks too dangerous, too expensive, or too boring for human beings. (MA)

Student performance in and perceptions of a high structure undergraduate human anatomy course.

PubMed

Shaffer, Justin F

2016-11-01

Human anatomy has usually been taught in a didactic fashion in colleges and universities. However, recent calls from United States governmental agencies have called for the transformation of undergraduate life sciences education to include active learning in the classroom. In addition, high structure courses have been shown to increase student engagement both in and out of the classroom and to improve student performance. Due to these reform efforts and the evidence on the benefits of these student-centered pedagogies, the goal of this study was to develop and assess a high structure college undergraduate human anatomy course with a lecture and laboratory component. The course was taught using a systems anatomy approach that required students to read the textbook and complete assignments before class, actively participate in class, and complete review quizzes after class. Results showed that teaching with high structure methods did not negatively affect any student groups (based on gender, ethnicity, or major) as measured by performance on lecture examinations and laboratory practical examinations. Students reported that reading the textbook and working with anatomical models were the most important towards helping them learn the course material and students' confidence in achieving the course goals significantly increased at the end of the course. The successful development and implementation of this course suggests that it is possible to teach human anatomy using active learning and high structure. Future studies can now be conducted to determine the contributions of specific course components to student success in high structure human anatomy courses. Anat Sci Educ 9: 516-528. © 2016 American Association of Anatomists. © 2016 American Association of Anatomists.

Ground-based research with heavy ions for space radiation protection

NASA Astrophysics Data System (ADS)

Durante, M.; Kronenberg, A.

Human exposure to ionizing radiation is one of the acknowledged potential showstoppers for long duration manned interplanetary missions. Human exploratory missions cannot be safely performed without a substantial reduction of the uncertainties associated with different space radiation health risks, and the development of effective countermeasures. Most of our knowledge of the biological effects of heavy charged particles comes from accelerator-based experiments. During the 35th COSPAR meeting, recent ground-based experiments with high-energy iron ions were discussed, and these results are briefly summarised in this paper. High-quality accelerator-based research with heavy ions will continue to be the main source of knowledge of space radiation health effects and will lead to reductions of the uncertainties in predictions of human health risks. Efforts in materials science, nutrition and pharmaceutical sciences and their rigorous evaluation with biological model systems in ground-based accelerator experiments will lead to the development of safe and effective countermeasures to permit human exploration of the Solar System.

An episomal vector-based CRISPR/Cas9 system for highly efficient gene knockout in human pluripotent stem cells.

PubMed

Xie, Yifang; Wang, Daqi; Lan, Feng; Wei, Gang; Ni, Ting; Chai, Renjie; Liu, Dong; Hu, Shijun; Li, Mingqing; Li, Dajin; Wang, Hongyan; Wang, Yongming

2017-05-24

Human pluripotent stem cells (hPSCs) represent a unique opportunity for understanding the molecular mechanisms underlying complex traits and diseases. CRISPR/Cas9 is a powerful tool to introduce genetic mutations into the hPSCs for loss-of-function studies. Here, we developed an episomal vector-based CRISPR/Cas9 system, which we called epiCRISPR, for highly efficient gene knockout in hPSCs. The epiCRISPR system enables generation of up to 100% Insertion/Deletion (indel) rates. In addition, the epiCRISPR system enables efficient double-gene knockout and genomic deletion. To minimize off-target cleavage, we combined the episomal vector technology with double-nicking strategy and recent developed high fidelity Cas9. Thus the epiCRISPR system offers a highly efficient platform for genetic analysis in hPSCs.

Density-dependent blood stage Plasmodium falciparum suppresses malaria super-infection in a malaria holoendemic population.

PubMed

Pinkevych, Mykola; Petravic, Janka; Chelimo, Kiprotich; Vulule, John; Kazura, James W; Moormann, Ann M; Davenport, Miles P

2013-11-01

Recent studies of Plasmodium berghei malaria in mice show that high blood-stage parasitemia levels inhibit the development of subsequent liver-stage infections. Whether a similar inhibitory effect on liver-stage Plasmodium falciparum by blood-stage infection occurs in humans is unknown. We have analyzed data from a treatment-time-to-infection cohort of children < 10 years of age residing in a malaria holoendemic area of Kenya where people experience a new blood-stage infection approximately every 2 weeks. We hypothesized that if high parasitemia blocked the liver stage, then high levels of parasitemia should be followed by a "skipped" peak of parasitemia. Statistical analysis of "natural infection" field data and stochastic simulation of infection dynamics show that the data are consistent with high P. falciparum parasitemia inhibiting liver-stage parasite development in humans.

Glanders: an overview of infection in humans.

PubMed

Van Zandt, Kristopher E; Greer, Marek T; Gelhaus, H Carl

2013-09-03

Glanders is a highly contagious and often fatal zoonotic disease, primarily of solipds. In the developed world, glanders has been eradicated. However, prior use of B. mallei as a biological weapon and its high mortality in inhalation animal studies has affirmed B. mallei as a biodefense concern. This threat requires the development of new glanders medical countermeasures (MCMs), as there is a lack of an effective vaccine and lengthy courses of multiple antibiotics needed to eradicate B. mallei. Here, we present a literature review of human glanders in which we discuss the clinical epidemiology and risk factors, potential routes of exposure, symptoms, the incubation period, and specific diagnostics. This review focuses on pulmonary glanders, as this is the most likely outcome of a biological weapons attack. Additionally, we outline current treatment regimens and propose a clinical definition of human pulmonary glanders infection.

Glanders: an overview of infection in humans

PubMed Central

2013-01-01

Glanders is a highly contagious and often fatal zoonotic disease, primarily of solipds. In the developed world, glanders has been eradicated. However, prior use of B. mallei as a biological weapon and its high mortality in inhalation animal studies has affirmed B. mallei as a biodefense concern. This threat requires the development of new glanders medical countermeasures (MCMs), as there is a lack of an effective vaccine and lengthy courses of multiple antibiotics needed to eradicate B. mallei. Here, we present a literature review of human glanders in which we discuss the clinical epidemiology and risk factors, potential routes of exposure, symptoms, the incubation period, and specific diagnostics. This review focuses on pulmonary glanders, as this is the most likely outcome of a biological weapons attack. Additionally, we outline current treatment regimens and propose a clinical definition of human pulmonary glanders infection. PMID:24004906

Development of a Mars Environmental Control and Life Support System (ECLSS).

NASA Technical Reports Server (NTRS)

Henninger, Donald L.

2016-01-01

ECLS systems for very long-duration human missions to Mars will be designed to operate reliably for many years and will never be returned to Earth. The need for high reliability is driven by unsympathetic abort scenarios. Abort from a Mars mission could be as long as 450 days to return to Earth. Simply put, the goal of an ECLSS is to duplicate the functions the Earth provides in terms of human living and working on our home planet but without the benefit of the Earth's large buffers - the atmospheres, the oceans and land masses. With small buffers a space-based ECLSS must operate as a true dynamic system rather than independent processors taking things from tanks, processing them, and then returning them to product tanks. Key is a development process that allows for a logical sequence of validating successful development (maturation) in a stepwise manner with key performance parameters (KPPs) at each step; especially KPPs for technologies evaluated in a full systems context with human crews on Earth and on space platforms such as the ISS. This paper will explore the implications of such an approach to ECLSS development and the roles of ground and space-based testing necessary to develop a highly reliable life support system for long duration human exploration missions. Historical development and testing of ECLS systems from Mercury to the International Space Station (ISS) will be reviewed. Current work as well as recommendations for future work will be described.

A human factors approach to range scheduling for satellite control

NASA Technical Reports Server (NTRS)

Wright, Cameron H. G.; Aitken, Donald J.

1991-01-01

Range scheduling for satellite control presents a classical problem: supervisory control of a large-scale dynamic system, with unwieldy amounts of interrelated data used as inputs to the decision process. Increased automation of the task, with the appropriate human-computer interface, is highly desirable. The development and user evaluation of a semi-automated network range scheduling system is described. The system incorporates a synergistic human-computer interface consisting of a large screen color display, voice input/output, a 'sonic pen' pointing device, a touchscreen color CRT, and a standard keyboard. From a human factors standpoint, this development represents the first major improvement in almost 30 years to the satellite control network scheduling task.

Recent Mitochondrial DNA Mutations Increase the Risk of Developing Common Late-Onset Human Diseases

PubMed Central

Hudson, Gavin; Gomez-Duran, Aurora; Wilson, Ian J.; Chinnery, Patrick F.

2014-01-01

Mitochondrial DNA (mtDNA) is highly polymorphic at the population level, and specific mtDNA variants affect mitochondrial function. With emerging evidence that mitochondrial mechanisms are central to common human diseases, it is plausible that mtDNA variants contribute to the “missing heritability” of several complex traits. Given the central role of mtDNA genes in oxidative phosphorylation, the same genetic variants would be expected to alter the risk of developing several different disorders, but this has not been shown to date. Here we studied 38,638 individuals with 11 major diseases, and 17,483 healthy controls. Imputing missing variants from 7,729 complete mitochondrial genomes, we captured 40.41% of European mtDNA variation. We show that mtDNA variants modifying the risk of developing one disease also modify the risk of developing other diseases, thus providing independent replication of a disease association in different case and control cohorts. High-risk alleles were more common than protective alleles, indicating that mtDNA is not at equilibrium in the human population, and that recent mutations interact with nuclear loci to modify the risk of developing multiple common diseases. PMID:24852434

NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Di-n-Butyl Phthalate (DBP).

PubMed

2003-04-01

TThe National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for di-n-butyl phthalate (DBP) to cause adverse effects on reproduction and development in humans. DBP is one of 7 phthalate chemicals evaluated by the NTP CERHR Phthalates Expert Panel. These phthalates were selected for evaluation because of high production volume, extent of human exposures, use in children's products, and/or published evidence of reproductive or developmental toxicity. Unlike many phthalates, DBP is not currently used as a plasticizer in polyvinyl chloride plastics. DBP is a component of latex adhesives and is used in cosmetics and other personal care products, as a plasticizer in cellulose plastics, and as a solvent for dyes. The results of this evaluation on DBP are published in a NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Di-n-Butyl Phthalate, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to DBP on human development and reproduction. First, although DBP could possibly affect human reproduction and development if exposures are sufficiently high, the NTP concludes that there is negligible concern for reproductive toxicity in exposed adults. Second, the NTP concludes that there is minimal concern for developmental effects when pregnant women are exposed to DBP levels estimated by the panel (2-10 mug/kg body weight/day). There is no direct evidence that exposure of people to DBP adversely affects reproduction or development, but studies reviewed by the expert panel show that oral exposure to high doses of DBP (>/=100 mg/kg body weight/day) may adversely affect the prenatal and early postnatal development in rodents. Finally, based on exposure estimates in women of reproductive age, the NTP concludes that there is some concern for DBP causing adverse effects to human development, particularly development of the male reproductive system. NTP-CERHR monographs are transmitted to federal and state agencies, interested parties, and the public and are available electronically in PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32, Research Triangle Park, NC; fax: 919-316-4511).

Experimental comparisons between McKibben type artificial muscles and straight fibers type artificial muscles

NASA Astrophysics Data System (ADS)

Nakamura, Taro

2007-01-01

This paper describes experimental comparison between a conventional McKibben type artificial muscle and a straight fibers type artificial muscle developed by the authors. A wearable device and a rehabilitation robot which assists a human muscle should have characteristics similar to those of human muscle. In addition, because the wearable device and the rehabilitation robot should be light, an actuator with a high power/weight ratio is needed. At present, the McKibben type is widely used as an artificial muscle, but in fact its physical model is highly nonlinear. Further, the heat and mechanical loss of this actuator are large because of the friction caused by the expansion and contraction of the sleeve. Therefore, the authors have developed an artificial muscle tube in which high strength glass fibers have been built into the tube made from natural latex rubber. As results, experimental results demonstrated that the developed artificial muscle is more effective regarding its fundamental characteristics than that of the McKibben type; the straight fibers types of artificial muscle have more contraction ratio and power, longer lifetime than the McKibben types. And it has almost same characteristics of human muscle for isotonic and isometric that evaluate it dynamically.

Environment, diet and CpG island methylation: epigenetic signals in gastrointestinal neoplasia.

PubMed

Johnson, Ian T; Belshaw, Nigel J

2008-04-01

The epithelial surfaces of the mammalian alimentary tract are characterised by very high rates of cell proliferation and DNA synthesis, and in humans they are highly susceptible to cancer. The role of somatic mutations as drivers of carcinogenesis in the alimentary tract is well established, but the importance of gene silencing by epigenetic mechanisms is increasingly recognised. Methylation of CpG islands is an important component of the epigenetic code that regulates gene expression during development and normal cellular differentiation, and a number of genes are well known to become abnormally methylated during the development of tumours of the oesophagus, stomach and colorectum. Aberrant patterns of DNA methylation develop as a result of pathological processes such as chronic inflammation, and in response to various dietary factors, including imbalances in the supply of methyl donors, particularly folates, and exposure to DNA methyltransferase inhibitors, which include polyphenols and possibly isothiocyanates from plant foods. However the importance of these environmental interactions in human health and disease remains to be established. Recent moves to modify the exposure of human populations to folate, by mandatory supplementation of cereal foods, emphasise the importance of understanding the susceptibility of the human epigenome to dietary and other environmental effects.

Detection of Human Epididymis Protein 4 (HE4) in Human Serum Samples Using a Specific Monoclonal Antibody-Based Sandwich Enzyme-Linked Immunosorbent Assay (ELISA).

PubMed

Zhou, Lijun; Lv, Zhiqiang; Shao, Jing; Xu, Ying; Luo, Xiaohong; Zhang, Yuming; Hu, Yang; Zhang, Wenji; Luo, Shuhong; Fang, Jianmin; Wang, Ying; Duan, Chaohui; Huang, Ruopan

2016-09-01

The human epididymis protein 4 (HE4) may have high specificity in the detection of malignant diseases, making the development of an immunoassay for HE4 essential. In our study, a fusion gene was constructed encoded with the HE4 protein. This protein was then produced in the bacterial cells (Escherichia coli) and used to immunize mice in order to eventually generate hybridomas specific to HE4. The hybridoma supernatants were then screened, and four positive anti-HE4 cell lines were selected. These cell lines produce monoclonal antibodies against HE4 epitopes, as demonstrated in the Western blot as well as by direct enzyme-linked immunosorbent assay (ELISA). Using the developed antibodies, we successfully identified several good antibody pairs from the hybridomas, which allowed for the development of a sandwich ELISA to measure HE4 levels. By using the HE4 ELISA, we measured HE4 levels of 60 clinical human serum samples. Compared with the Food and Drug Administration (FDA) approved kit (Roche), our results showed a strong positive correlation to those of the FDA-approved kit. In summary, highly sensitive antibody pairs were screened against HE4, and a sandwich ELISA was developed as an accurate analytical tool for the detection of HE4 in human serum, which could be especially valuable for diagnosing ovarian carcinomas. © 2015 Wiley Periodicals, Inc.

Global Dental Research Productivity and Its Association With Human Development, Gross National Income, and Political Stability.

PubMed

Allareddy, Veerasathpurush; Allareddy, Veeratrishul; Rampa, Sankeerth; Nalliah, Romesh P; Elangovan, Satheesh

2015-09-01

The objective of this study is to examine the associations between country level factors (such as human development, economic productivity, and political stability) and their dental research productivity. This study is a cross-sectional analysis of bibliometric data from Scopus search engine. Human Development Index (HDI), Gross National Income per capita (GNI), and Failed State Index measures were the independent variables. Outcomes were "Total number of publications (articles or articles in press) in the field of dentistry" and "Total number of publications in the field of dentistry per million population." Non-parametric tests were used to examine the association between the independent and outcome variables. During the year 2013, a total of 11,952 dental research articles were published across the world. The top 5 publishing countries were United States, Brazil, India, Japan, and United Kingdom. "Very High" HDI countries had significantly higher number of total dental research articles and dental research articles per million population when compared to the "High HDI," "Medium HDI," and "Low HDI" countries (p < 0.0001). There was a significant linear relationship between the GNI quartile income levels and outcome metrics (p ≤ 0.007). Countries which were highly politically stable were associated with significantly higher dental research productivity (p < 0.0001). There appears to be a regional concentration of articles with just five countries contributing to over 50% of all articles. The human development and economic development of a country are linearly correlated with dental research productivity. Dental research productivity also increases with increasing political stability of a country. Copyright © 2015 Elsevier Inc. All rights reserved.

Assessment of chimeric mice with humanized livers in new drug development: generation of pharmacokinetics, metabolism and toxicity data for selecting the final candidate compound.

PubMed

Kamimura, Hidetaka; Ito, Satoshi

2016-01-01

1. Chimeric mice with humanized livers are expected to be a novel tool for new drug development. This review discusses four applications where these animals can be used efficiently to collect supportive data for selecting the best compound in the final stage of drug discovery. 2. The first application is selection of the final compound based on estimated pharmacokinetic parameters in humans. Since chimeric mouse livers are highly repopulated with human hepatocytes, hepatic clearance values in vivo could be used preferentially to estimate pharmacokinetic profiles for humans. 3. The second is prediction of human-specific or disproportionate metabolites. Chimeric mice reproduce human-specific metabolites of drugs under development to conform to ICH guidance M3(R2), except for compounds that were extensively eliminated by co-existing mouse hepatocytes. 4. The third is identifying metabolites with distinct pharmacokinetic profiles in humans. Slow metabolite elimination specifically in humans increases its exposure level, but if its elimination is faster in laboratory animals, the animal exposure level might not satisfy ICH guidance M3(R2). 5. Finally, two examples of reproducing acute liver toxicity in chimeric mice are introduced. Integrated pharmacokinetics, metabolism and toxicity information are expected to assist pharmaceutical scientists in selecting the best candidate compound in new drug development.

Activation of Wnt signalling promotes development of dysplasia in Barrett's oesophagus.

PubMed

Moyes, Lisa H; McEwan, Hamish; Radulescu, Sorina; Pawlikowski, Jeff; Lamm, Catherine G; Nixon, Colin; Sansom, Owen J; Going, James J; Fullarton, Grant M; Adams, Peter D

2012-09-01

Barrett's oesophagus is a precursor of oesophageal adenocarcinoma, via intestinal metaplasia and dysplasia. Risk of cancer increases substantially with dysplasia, particularly high-grade dysplasia. Thus, there is a clinical need to identify and treat patients with early-stage disease (metaplasia and low-grade dysplasia) that are at high risk of cancer. Activated Wnt signalling is critical for normal intestinal development and homeostasis, but less so for oesophageal development. Therefore, we asked whether abnormally increased Wnt signalling contributes to the development of Barrett's oesophagus (intestinal metaplasia) and/or dysplasia. Forty patients with Barrett's metaplasia, dysplasia or adenocarcinoma underwent endoscopy and biopsy. Mice with tamoxifen- and β-naphthoflavone-induced expression of activated β-catenin were used to up-regulate Wnt signalling in mouse oesophagus. Immunohistochemistry of β-catenin, Ki67, a panel of Wnt target genes, and markers of intestinal metaplasia was performed on human and mouse tissues. In human tissues, expression of nuclear activated β-catenin was found in dysplasia, particularly high grade. Barrett's metaplasia did not show high levels of activated β-catenin. Up-regulation of Ki67 and Wnt target genes was also mostly associated with high-grade dysplasia. Aberrant activation of Wnt signalling in mouse oesophagus caused marked tissue disorganization with features of dysplasia, but only selected molecular indicators of metaplasia. Based on these results in human tissues and a mouse model, we conclude that abnormal activation of Wnt signalling likely plays only a minor role in initiation of Barrett's metaplasia but a more critical role in progression to dysplasia. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

HtrA3 as an Early Marker for Preeclampsia: Specific Monoclonal Antibodies and Sensitive High-Throughput Assays for Serum Screening

PubMed Central

Dynon, Kemperly; Heng, Sophea; Puryer, Michelle; Li, Ying; Walton, Kelly; Endo, Yaeta; Nie, Guiying

2012-01-01

Mammalian HtrA3 (high temperature requirement A3) is a serine protease of the HtrA family. It has two isoforms [long (HtrA3-L) and short (HtrA3-S)] and is important for placental development and cancer progression. Recently, HtrA3 was identified as a potential diagnostic marker for early detection of preeclampsia, a life-threatening pregnancy-specific disorder. Currently there are no high-throughput assays available to detect HtrA3 in human serum. In this study we generated and fully tested a panel of five HtrA3 mouse monoclonal antibodies (mAbs). Three mAbs recognised both HtrA3-L and HtrA3-S and the other two detected HtrA3-L only. All five mAbs were highly specific to HtrA3 and applicable in western blotting and immunohistochemical analysis of endogenous HtrA3 proteins in the mouse and human tissues. Amplified luminescent proximity homogeneous assays-linked immunosorbent assays (AlphaLISAs), were developed to detect HtrA3 isoforms in picomolar levels in serum. The HtrA3 AlphaLISA detected significantly higher serum levels of HtrA3 in women at 13–14 weeks of gestation who subsequently developed preeclampsia compared to gestational-age matched controls. These HtrA3 mAbs are valuable for the development of immunoassays and characterisation of HtrA3 isoform-specific biology. The newly developed HtrA3 AlphaLISA assays are suitable for large scale screening of human serum. PMID:23049902

[Study of pathogenicity of Nipah virus and its vaccine development].

PubMed

Yoneda, Misako

2014-01-01

Nipah virus (NiV), a paramyxovirus, was first discovered in Malaysia in 1998 in an outbreak of infection in pigs and humans, and incurred a high fatality rate in humans. We established a system that enabled the rescue of replicating NiVs from a cloned DNA. Using the system, we analyzed the functions of accessory proteins in infected cells and the implications in in vivo pathogenicity. Further, we have developed a recombinant measles virus (rMV) vaccine expressing NiV envelope glycoproteins, which appeared to be an appropriate to NiV vaccine candidate for use in humans.

High-Content Electrophysiological Analysis of Human Pluripotent Stem Cell-Derived Cardiomyocytes (hPSC-CMs).

PubMed

Kong, Chi-Wing; Geng, Lin; Li, Ronald A

2018-01-01

Considerable interest has been raised to develop human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) as a model for drug discovery and cardiotoxicity screening. High-content electrophysiological analysis of currents generated by transmembrane cell surface ion channels has been pursued to complement such emerging applications. Here we describe practical procedures and considerations for accomplishing successful assays of hPSC-CMs using an automated planar patch-clamp system.

The development and psychometric analysis of the Chinese HIV-Related Fatigue Scale.

PubMed

Li, Su-Yin; Wu, Hua-Shan; Barroso, Julie

2016-04-01

To develop a Chinese version of the human immunodeficiency virus-related Fatigue Scale and examine its reliability and validity. Fatigue is found in more than 70% of people infected with human immunodeficiency virus. However, a scale to assess fatigue in human immunodeficiency virus-positive people has not yet been developed for use in Chinese-speaking countries. A methodologic study involving instrument development and psychometric evaluation was used. The human immunodeficiency virus-related Fatigue Scale was examined through a two-step procedure: (1) translation and back translation and (2) psychometric analysis. A sample of 142 human immunodeficiency virus-positive patients was recruited from the Infectious Disease Outpatient Clinic in central Taiwan. Their fatigue data were analysed with Cronbach's α for internal consistency. Two weeks later, the data of a random sample of 28 patients from the original 142 were analysed for test-retest reliability. The correlation between the World Health Organization Quality of Life Assessment-Human Immunodeficiency Virus and the Chinese version of the human immunodeficiency virus-related Fatigue Scale was analysed for concurrent validity. The Chinese version of the human immunodeficiency virus-related Fatigue Scale scores of human immunodeficiency virus-positive patients with highly active antiretroviral therapy and those without were compared to demonstrate construct validity. The internal consistency and test-retest reliability of the Chinese version of the human immunodeficiency virus-related Fatigue Scale were 0·97 and 0·686, respectively. In regard to concurrent validity, a negative correlation was found between the scores of the Chinese version of the human immunodeficiency virus-related Fatigue Scale and the World Health Organization Quality of Life Assessment-Human Immunodeficiency Virus. Additionally, the Chinese version of the human immunodeficiency virus-related Fatigue Scale could be used to effectively distinguish fatigue differences between the human immunodeficiency virus-positive patients with highly active antiretroviral therapy and those without. The Chinese version of the human immunodeficiency virus-related Fatigue Scale presents good reliability and validity through a robust psychometric analysis. This scale can be appropriately applied to human immunodeficiency virus-positive patients by clinical staff and case managers in Chinese-speaking countries. The Chinese version of the human immunodeficiency virus-related Fatigue Scale is an effective and comprehensive tool that can help clinical professionals measure the frequency, strength and impact on the quality of life of fatigue in Chinese human immunodeficiency virus-positive patients. © 2016 John Wiley & Sons Ltd.

Development and validation of the Hospitality Axiological Scale for Humanization of Nursing Care

PubMed Central

Galán González-Serna, José María; Ferreras-Mencia, Soledad; Arribas-Marín, Juan Manuel

2017-01-01

ABSTRACT Objective: to develop and validate a scale to evaluate nursing attitudes in relation to hospitality for the humanization of nursing care. Participants: the sample consisted of 499 nursing professionals and undergraduate students of the final two years of the Bachelor of Science in Nursing program. Method: the instrument has been developed and validated to evaluate the ethical values related to hospitality using a methodological approach. Subsequently, a model was developed to measure the dimensions forming the construct hospitality. Results: the Axiological Hospitality Scale showed a high internal consistency, with Cronbach’s Alpha=0.901. The validation of the measuring instrument was performed using factorial, exploratory and confirmatory analysis techniques with high goodness of fit measures. Conclusions: the developed instrument showed an adequate validity and a high internal consistency. Based on the consistency of its psychometric properties, it is possible to affirm that the scale provides a reliable measurement of the hospitality. It was also possible to determine the dimensions or sources that embrace it: respect, responsibility, quality and transpersonal care. PMID:28793127

75 FR 21636 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-26

... antibody phage display library against Ephrin-B2 and EphB4. These human monoclonal antibodies have high... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Government-Owned Inventions... commercialization of results of federally-funded research and development. Foreign patent applications are filed on...

Effects of in utero exposure to phthalate plasticizers on reproductive development in rats and possible human health concerns

EPA Science Inventory

Phthalate diesters (PEs) are high-production chemicals used to impart flexibiliyt to pllyvinylchloride products. Humans are ubiquitously exposed to these chemicals. Certain PEs are reporductive toxicants in laboratory rats. This presentation will review the effects and mechanisms...

Developing a Salivary Antibody Multiplex Immunoassay to Measure Human Exposure to Environmental Pathogens

EPA Science Inventory

The etiology and impacts of human exposure to environmental pathogens are of major concern worldwide and, thus, the ability to assess exposure and infections using cost effective, high-throughput approaches would be indispensable. The principal objective of this work is to devel...

A Co-Receptor Independent Transgenic Human TCR Mediates Anti-Tumor and Anti-Self Immunity in Mice

PubMed Central

Mehrotra, Shikhar; Al-Khami, Amir A.; Klarquist, Jared; Husain, Shahid; Naga, Osama; Eby, Jonathan M.; Murali, Anuradha K.; Lyons, Gretchen E.; Li, Mingli; Spivey, Natali D.; Norell, Håkan; Martins da Palma, Telma; Onicescu, Georgiana; Diaz-Montero, C. Marcela; Garrett-Mayer, Elizabeth; Cole, David J.; Le Poole, I. Caroline; Nishimura, Michael I.

2013-01-01

Recent advancements in T cell immunotherapy suggest that T cells engineered with high affinity T cell receptors (TCR) can offer better tumor regression. However, whether a high affinity TCR alone is sufficient to control tumor growth, or the T cell subset bearing the TCR is also important remains unclear. Using the human tyrosinase epitope reactive, CD8 independent, high affinity TCR isolated from MHC class-I restricted CD4+ T cells obtained from tumor infiltrating lymphocytes of a metastatic melanoma patient, we developed a novel TCR transgenic mouse with a C57BL/6 background. This HLA-A2 restricted TCR was positively selected on both CD4+ and CD8+ single-positive (SP) cells. However, when the TCR transgenic mouse was developed with an HLA-A2 background, the transgenic TCR was primarily expressed by CD3+CD4-CD8- double-negative (DN) T cells. TIL 1383I TCR transgenic CD4+, CD8+ and CD4-CD8- T cells were functional and retained the ability to control tumor growth without the need for vaccination or cytokine support in vivo. Furthermore, the HLA-A2+/human tyrosinase TCR double transgenic mice developed spontaneous hair depigmentation and had visual defects that progressed with age. Our data show that the expression of the high affinity TIL 1383I TCR alone in CD3+ T cells is sufficient to control the growth of murine and human melanoma and the presence or absence of CD4 and CD8 co-receptors had little effect on its functional capacity. PMID:22798675

Pathway Based Toxicology and Fit-for-Purpose Assays.

PubMed

Clewell, Rebecca A; McMullen, Patrick D; Adeleye, Yeyejide; Carmichael, Paul L; Andersen, Melvin E

The field of toxicity testing for non-pharmaceutical chemicals is in flux with multiple initiatives in North America and the EU to move away from animal testing to mode-of-action based in vitro assays. In this arena, there are still obstacles to overcome, such as developing appropriate cellular assays, creating pathway-based dose-response models and refining in vitro-in vivo extrapolation (IVIVE) tools. Overall, it is necessary to provide assurances that these new approaches are adequately protective of human and ecological health. Another major challenge for individual scientists and regulatory agencies is developing a cultural willingness to shed old biases developed around animal tests and become more comfortable with mode-of-action based assays in human cells. At present, most initiatives focus on developing in vitro alternatives and assessing how well these alternative methods reproduce past results related to predicting organism level toxicity in intact animals. The path forward requires looking beyond benchmarking against high dose animal studies. We need to develop targeted cellular assays, new cell biology-based extrapolation models for assessing regions of safety for chemical exposures in human populations, and mode-of-action-based approaches which are constructed on an understanding of human biology. Furthermore, it is essential that assay developers have the flexibility to 'validate' against the most appropriate mode-of-action data rather than against apical endpoints in high dose animal studies. This chapter demonstrates the principles of fit-for-purpose assay development using pathway-targeted case studies. The projects include p53-mdm2-mediated DNA-repair, estrogen receptor-mediated cell proliferation and PPARα receptor-mediated liver responses.

Junior High School Science: A Manual for Teachers. A Search for Structure. Grade 7.

ERIC Educational Resources Information Center

Baltimore County Public Schools, Towson, MD.

GRADES OR AGES: Grade 7. SUBJECT MATTER: Science. ORGANIZATION AND PHYSICAL APPEARANCE: The introduction describes the development of the junior high school science program. The main text is divided into three phases: Processes and Skills, Developing a Model of Matter, and Human Structure and Function. Phase I contains two subcategories: Rocks and…

High-level manpower movement and Japan's foreign aid.

PubMed

Furuya, K

1992-01-01

"Japan's technical assistance programs to Asian countries are summarized. Movements of high-level manpower accompanying direct foreign investments by private enterprise are also reviewed. Proposals for increased human resources development include education and training of foreigners in Japan as well as the training of Japanese aid experts and the development of networks for information exchange." excerpt

Timing of High-Quality Child Care and Cognitive, Language, and Preacademic Development

ERIC Educational Resources Information Center

Li, Weilin; Farkas, George; Duncan, Greg J.; Burchinal, Margaret R.; Vandell, Deborah Lowe

2013-01-01

The effects of high- versus low-quality child care during 2 developmental periods (infant-toddlerhood and preschool) were examined using data from the National Institute of Child Health and Human Development Study of Early Child Care. Propensity score matching was used to account for differences in families who used different combinations of child…

Trajectories of Maternal Depressive Symptoms, Maternal Sensitivity, and Children's Functioning at School Entry

ERIC Educational Resources Information Center

Campbell, Susan B.; Matestic, Patricia; von Stauffenberg, Camilla; Mohan, Roli; Kirchner, Thomas

2007-01-01

Using data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development, the authors modeled trajectories of maternal depressive symptoms from infant age 1 month to 7 years. The authors identified 6 trajectories of maternal depressive symptoms: high-chronic, moderate-increasing, high-decreasing,…

Human factors in waste management - potential and reality

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

Thompson, J.S.

There is enormous potential for human factors contributions in the realm of waste management. The reality, however, is very different from the potential. This is particularly true for low-level and low-level mixed-waste management. The hazards are less severe; therefore, health and safety requirements (including human factors) are not as rigorous as for high-level waste. High-level waste management presents its own unique challenges and opportunities. Waste management is strongly driven by regulatory compliance. When regulations are flexible and open to interpretation and the environment is driven so strongly by regulatory compliance, standard practice is to drop {open_quotes}nice to have{close_quotes} features, likemore » a human factors program, to save money for complying with other requirements. The challenge is to convince decision makers that human factors can help make operations efficient and cost-effective, as well as improving safety and complying with regulations. A human factors program should not be viewed as competing with compliance efforts; in fact, it should complement them and provide additional cost-effective means of achieving compliance with other regulations. Achieving this synergy of human factors with ongoing waste management operations requires educating program and facility managers and other technical specialists about human factors and demonstrating its value {open_quotes}through the back door{close_quotes} on existing efforts. This paper describes ongoing projects at Los Alamos National Laboratory (LANL) in support of their waste management groups. It includes lessons learned from hazard and risk analyses, safety analysis reports, job and task analyses, operating procedure development, personnel qualification/certification program development, and facility- and job-specific training program and course development.« less

NASA Human Health and Performance Center (NHHPC)

NASA Technical Reports Server (NTRS)

Davis, J. R.; Richard, E. E.

2010-01-01

The NASA Human Health and Performance Center (NHHPC) will provide a collaborative and virtual forum to integrate all disciplines of the human system to address spaceflight, aviation, and terrestrial human health and performance topics and issues. The NHHPC will serve a vital role as integrator, convening members to share information and capture a diverse knowledge base, while allowing the parties to collaborate to address the most important human health and performance topics of interest to members. The Center and its member organizations will address high-priority risk reduction strategies, including research and technology development, improved medical and environmental health diagnostics and therapeutics, and state-of-the art design approaches for human factors and habitability. Once full established in 2011, the NHHPC will focus on a number of collaborative projects focused on human health and performance, including workshops, education and outreach, information sharing and knowledge management, and research and technology development projects, to advance the study of the human system for spaceflight and other national and international priorities.

Defining the Genomic Signature of Totipotency and Pluripotency during Early Human Development

PubMed Central

Galan, Amparo; Diaz-Gimeno, Patricia; Poo, Maria Eugenia; Valbuena, Diana; Sanchez, Eva; Ruiz, Veronica; Dopazo, Joaquin; Montaner, David; Conesa, Ana; Simon, Carlos

2013-01-01

The genetic mechanisms governing human pre-implantation embryo development and the in vitro counterparts, human embryonic stem cells (hESCs), still remain incomplete. Previous global genome studies demonstrated that totipotent blastomeres from day-3 human embryos and pluripotent inner cell masses (ICMs) from blastocysts, display unique and differing transcriptomes. Nevertheless, comparative gene expression analysis has revealed that no significant differences exist between hESCs derived from blastomeres versus those obtained from ICMs, suggesting that pluripotent hESCs involve a new developmental progression. To understand early human stages evolution, we developed an undifferentiation network signature (UNS) and applied it to a differential gene expression profile between single blastomeres from day-3 embryos, ICMs and hESCs. This allowed us to establish a unique signature composed of highly interconnected genes characteristic of totipotency (61 genes), in vivo pluripotency (20 genes), and in vitro pluripotency (107 genes), and which are also proprietary according to functional analysis. This systems biology approach has led to an improved understanding of the molecular and signaling processes governing human pre-implantation embryo development, as well as enabling us to comprehend how hESCs might adapt to in vitro culture conditions. PMID:23614026

Accurate Prediction of Drug-Induced Liver Injury Using Stem Cell-Derived Populations

PubMed Central

Szkolnicka, Dagmara; Farnworth, Sarah L.; Lucendo-Villarin, Baltasar; Storck, Christopher; Zhou, Wenli; Iredale, John P.; Flint, Oliver

2014-01-01

Despite major progress in the knowledge and management of human liver injury, there are millions of people suffering from chronic liver disease. Currently, the only cure for end-stage liver disease is orthotopic liver transplantation; however, this approach is severely limited by organ donation. Alternative approaches to restoring liver function have therefore been pursued, including the use of somatic and stem cell populations. Although such approaches are essential in developing scalable treatments, there is also an imperative to develop predictive human systems that more effectively study and/or prevent the onset of liver disease and decompensated organ function. We used a renewable human stem cell resource, from defined genetic backgrounds, and drove them through developmental intermediates to yield highly active, drug-inducible, and predictive human hepatocyte populations. Most importantly, stem cell-derived hepatocytes displayed equivalence to primary adult hepatocytes, following incubation with known hepatotoxins. In summary, we have developed a serum-free, scalable, and shippable cell-based model that faithfully predicts the potential for human liver injury. Such a resource has direct application in human modeling and, in the future, could play an important role in developing renewable cell-based therapies. PMID:24375539

Understanding social collaboration between actors and technology in an automated and digitised deep mining environment.

PubMed

Sanda, M-A; Johansson, J; Johansson, B; Abrahamsson, L

2011-10-01

The purpose of this article is to develop knowledge and learning on the best way to automate organisational activities in deep mines that could lead to the creation of harmony between the human, technical and the social system, towards increased productivity. The findings showed that though the introduction of high-level technological tools in the work environment disrupted the social relations developed over time amongst the employees in most situations, the technological tools themselves became substitute social collaborative partners to the employees. It is concluded that, in developing a digitised mining production system, knowledge of the social collaboration between the humans (miners) and the technology they use for their work must be developed. By implication, knowledge of the human's subject-oriented and object-oriented activities should be considered as an important integral resource for developing a better technological, organisational and human interactive subsystem when designing the intelligent automation and digitisation systems for deep mines. STATEMENT OF RELEVANCE: This study focused on understanding the social collaboration between humans and the technologies they use to work in underground mines. The learning provides an added knowledge in designing technologies and work organisations that could better enhance the human-technology interactive and collaborative system in the automation and digitisation of underground mines.

Anti-Cocaine Vaccine Based on Coupling a Cocaine Analog to a Disrupted Adenovirus

PubMed Central

Koob, George; Hicks, Martin J.; Wee, Sunmee; Rosenberg, Jonathan B.; De, Bishnu P.; Kaminksy, Stephen M.; Moreno, Amira; Janda, Kim D.; Crystal, Ronald G.

2012-01-01

The challenge in developing an anti-cocaine vaccine is that cocaine is a small molecule, invisible to the immune system. Leveraging the knowledge that adenovirus (Ad) capsid proteins are highly immunogenic in humans, we hypothesized that linking a cocaine hapten to Ad capsid proteins would elicit high-affinity, high-titer antibodies against cocaine, sufficient to sequester systemically administered cocaine and prevent access to the brain, thus suppressing cocaine-induced behaviors. Based on these concepts, we developed dAd5GNE, a disrupted E1−E3− serotype 5 Ad with GNE, a stable cocaine analog, covalently linked to the Ad capsid proteins. In pre-clinical studies, dAd5GNE evoked persistent, high titer, high affinity IgG anti-cocaine antibodies, and was highly effective in blocking cocaine-induced hyperactivity and cocaine self-administration behavior in rats. Future studies will be designed to expand the efficacy studies, carry out relevant toxicology studies, and test dAd5GNE in human cocaine addicts. PMID:22229312

Optimization of methods for the genetic modification of human T cells.

PubMed

Bilal, Mahmood Y; Vacaflores, Aldo; Houtman, Jon Cd

2015-11-01

CD4(+) T cells are not only critical in the fight against parasitic, bacterial and viral infections, but are also involved in many autoimmune and pathological disorders. Studies of protein function in human T cells are confined to techniques such as RNA interference (RNAi) owing to ethical reasons and relative simplicity of these methods. However, introduction of RNAi or genes into primary human T cells is often hampered by toxic effects from transfection or transduction methods that yield cell numbers inadequate for downstream assays. Additionally, the efficiency of recombinant DNA expression is frequently low because of multiple factors including efficacy of the method and strength of the targeting RNAs. Here, we describe detailed protocols that will aid in the study of primary human CD4(+) T cells. First, we describe a method for development of effective microRNA/shRNAs using available online algorithms. Second, we illustrate an optimized protocol for high efficacy retroviral or lentiviral transduction of human T-cell lines. Importantly, we demonstrate that activated primary human CD4(+) T cells can be transduced efficiently with lentiviruses, with a highly activated population of T cells receiving the largest number of copies of integrated DNA. We also illustrate a method for efficient lentiviral transduction of hard-to-transduce un-activated primary human CD4(+) T cells. These protocols will significantly assist in understanding the activation and function of human T cells and will ultimately aid in the development or improvement of current drugs that target human CD4(+) T cells.

Improvements and Limitations of Humanized Mouse Models for HIV Research: NIH/NIAID "Meet the Experts" 2015 Workshop Summary.

PubMed

Akkina, Ramesh; Allam, Atef; Balazs, Alejandro B; Blankson, Joel N; Burnett, John C; Casares, Sofia; Garcia, J Victor; Hasenkrug, Kim J; Kashanchi, Fatah; Kitchen, Scott G; Klein, Florian; Kumar, Priti; Luster, Andrew D; Poluektova, Larisa Y; Rao, Mangala; Sanders-Beer, Brigitte E; Shultz, Leonard D; Zack, Jerome A

2016-02-01

The number of humanized mouse models for the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and other infectious diseases has expanded rapidly over the past 8 years. Highly immunodeficient mouse strains, such as NOD/SCID/gamma chain(null) (NSG, NOG), support better human hematopoietic cell engraftment. Another improvement is the derivation of highly immunodeficient mice, transgenic with human leukocyte antigens (HLAs) and cytokines that supported development of HLA-restricted human T cells and heightened human myeloid cell engraftment. Humanized mice are also used to study the HIV reservoir using new imaging techniques. Despite these advances, there are still limitations in HIV immune responses and deficits in lymphoid structures in these models in addition to xenogeneic graft-versus-host responses. To understand and disseminate the improvements and limitations of humanized mouse models to the scientific community, the NIH sponsored and convened a meeting on April 15, 2015 to discuss the state of knowledge concerning these questions and best practices for selecting a humanized mouse model for a particular scientific investigation. This report summarizes the findings of the NIH meeting.

Neuromuscular Junction Formation between Human Stem cell-derived Motoneurons and Human Skeletal Muscle in a Defined System

PubMed Central

Guo, Xiufang; Gonzalez, Mercedes; Stancescu, Maria; Vandenburgh, Herman; Hickman, James

2011-01-01

Functional in vitro models composed of human cells will constitute an important platform in the next generation of system biology and drug discovery. This study reports a novel human-based in vitro Neuromuscular Junction (NMJ) system developed in a defined serum-free medium and on a patternable non-biological surface. The motoneurons and skeletal muscles were derived from fetal spinal stem cells and skeletal muscle stem cells. The motoneurons and skeletal myotubes were completely differentiated in the co-culture based on morphological analysis and electrophysiology. NMJ formation was demonstrated by phase contrast microscopy, immunocytochemistry and the observation of motoneuron-induced muscle contractions utilizing time lapse recordings and their subsequent quenching by D-Tubocurarine. Generally, functional human based systems would eliminate the issue of species variability during the drug development process and its derivation from stem cells bypasses the restrictions inherent with utilization of primary human tissue. This defined human-based NMJ system is one of the first steps in creating functional in vitro systems and will play an important role in understanding NMJ development, in developing high information content drug screens and as test beds in preclinical studies for spinal or muscular diseases/injuries such as muscular dystrophy, Amyotrophic lateral sclerosis and spinal cord repair. PMID:21944471

Neuromuscular junction formation between human stem cell-derived motoneurons and human skeletal muscle in a defined system.

PubMed

Guo, Xiufang; Gonzalez, Mercedes; Stancescu, Maria; Vandenburgh, Herman H; Hickman, James J

2011-12-01

Functional in vitro models composed of human cells will constitute an important platform in the next generation of system biology and drug discovery. This study reports a novel human-based in vitro Neuromuscular Junction (NMJ) system developed in a defined serum-free medium and on a patternable non-biological surface. The motoneurons and skeletal muscles were derived from fetal spinal stem cells and skeletal muscle stem cells. The motoneurons and skeletal myotubes were completely differentiated in the co-culture based on morphological analysis and electrophysiology. NMJ formation was demonstrated by phase contrast microscopy, immunocytochemistry and the observation of motoneuron-induced muscle contractions utilizing time-lapse recordings and their subsequent quenching by d-Tubocurarine. Generally, functional human based systems would eliminate the issue of species variability during the drug development process and its derivation from stem cells bypasses the restrictions inherent with utilization of primary human tissue. This defined human-based NMJ system is one of the first steps in creating functional in vitro systems and will play an important role in understanding NMJ development, in developing high information content drug screens and as test beds in preclinical studies for spinal or muscular diseases/injuries such as muscular dystrophy, Amyotrophic lateral sclerosis and spinal cord repair. Copyright © 2011 Elsevier Ltd. All rights reserved.

The old and new face of craniofacial research: How animal models inform human craniofacial genetic and clinical data.

PubMed

Van Otterloo, Eric; Williams, Trevor; Artinger, Kristin Bruk

2016-07-15

The craniofacial skeletal structures that comprise the human head develop from multiple tissues that converge to form the bones and cartilage of the face. Because of their complex development and morphogenesis, many human birth defects arise due to disruptions in these cellular populations. Thus, determining how these structures normally develop is vital if we are to gain a deeper understanding of craniofacial birth defects and devise treatment and prevention options. In this review, we will focus on how animal model systems have been used historically and in an ongoing context to enhance our understanding of human craniofacial development. We do this by first highlighting "animal to man" approaches; that is, how animal models are being utilized to understand fundamental mechanisms of craniofacial development. We discuss emerging technologies, including high throughput sequencing and genome editing, and new animal repository resources, and how their application can revolutionize the future of animal models in craniofacial research. Secondly, we highlight "man to animal" approaches, including the current use of animal models to test the function of candidate human disease variants. Specifically, we outline a common workflow deployed after discovery of a potentially disease causing variant based on a select set of recent examples in which human mutations are investigated in vivo using animal models. Collectively, these topics will provide a pipeline for the use of animal models in understanding human craniofacial development and disease for clinical geneticist and basic researchers alike. Copyright © 2016 Elsevier Inc. All rights reserved.

Issues and consequences of using nutrition to modulate the avian immune response

USDA-ARS?s Scientific Manuscript database

Combatting antimicrobial resistant bacteria is a high priority for both public health and agriculture in the United States and globally. Antibiotic use in animals and humans is considered a major risk factor in the development of antibiotic resistant bacteria in animals, humans, and the environment...

Computational Modeling and Simulation of Developmental Toxicity. What can we learn from a virtual embryo? (FDA-CFSAN workshop)

EPA Science Inventory

SYNOPSIS: The question of how tissues and organs are shaped during development is crucial for understanding human birth defects. Data from high-throughput screening assays on human stem cells may be utilized predict developmental toxicity with reasonable accuracy. Other types of ...

TESTING DUPLICATE DIET SAMPLE COLLECTION METHODS FOR MEASURING PERSONAL DIETARY EXPOSURES TO CHEMICAL CONTAMINANTS

EPA Science Inventory

Dietary ingestion may be a significant pathway of human exposure to many potentially toxic chemicals. The U.S.Environmental Protection Agency-National Human Exposure Laboratory has made the development of methods for measuring persoanl dietary exposures a high priority for its di...

Dynamics of an Anthropogenic Fire Regime

Treesearch

R. P. Guyette; R. M. Muzika; D. C. Dey

2002-01-01

Human interaction with fire and vegetation occurs at many levels of human population density and cultural development, from subsistence cultures to highly technological societies. The dynamics of these interactions with respect to wildland fire are often difficult to understand and identify at short temporal scales. Dendrochronological fire histories from the Missouri...

Dynamics of an anthropogenic fire regime

Treesearch

Richard P. Guyette; R. M. Muzika; Daniel C. Dey

2002-01-01

Human interaction with fire and vegetation occurs at many levels of human population density and cultural development, from subsistence cultures to highly technological societies. The dynamics of these interactions with respect to wildland fire are often difficult to understand and identify at short temporal scales. Dendrochronological fire histories from the Missouri...

Identification of hotspots and trends of fecal surface water pollution in developing countries

NASA Astrophysics Data System (ADS)

Reder, Klara; Flörke, Martina; Alcamo, Joseph

2015-04-01

Water is the essential resource ensuring human life on earth, which can only prosper when water is available and accessible. But of importance is not only the quantity of accessible water but also its quality, which in case of pollution may pose a risk to human health. The pollutants which pose a risk to human health are manifold, covering several groups such as pathogens, nutrients, human pharmaceuticals, heavy metals, and others. With regards to human health, pathogen contamination is of major interest as 4% of all death and 5.7% of disability or ill health in the world can be attributed to poor water supply, sanitation and personal and domestic hygiene. In developing countries, 2.6 billion people lacked access to improved sanitation in 2011. The lack of sanitation poses a risk to surface water pollution which is a threat to human health. A typical indicator for pathogen pollution is fecal coliform bacteria. The objective our study is to assess fecal pollution in the developing regions Africa, Asia and Latin America using the large-scale water quality model WorldQual. Model runs were carried-out to calculate in-stream concentrations and the respective loadings reaching rivers for the time period 1990 to 2010. We identified hotspots of fecal coliform loadings and in-stream concentrations which were further analyzed and ranked in terms of fecal surface water pollution. Main findings are that loadings mainly originate from the domestic sector, thus loadings are high in highly populated areas. In general, domestic loadings can be attributed to the two subsectors domestic sewered and domestic non sewered. The spatial distribution of both sectors varies across catchments. Hotspot pattern of in-stream concentrations are similar to the loadings pattern although they are different in seasonality. As the dilution varies with climate its dilution capacity is high during seasons with high precipitation, which in turn decreases the in-stream concentrations. The fecal pollution is increasing from 1990 to 2010 with increased loadings and larger number of river kilometers with high fecal pollution. Fecal pollution is mainly caused by the domestic sector, and hence, the sanitation type, collection and treatment (level) of collected wastewater are highly important to ensure good quality of water bodies.

Human endogenous retrovirus rec interferes with germ cell development in mice and may cause carcinoma in situ, the predecessor lesion of germ cell tumors.

PubMed

Galli, Uwe M; Sauter, Marlies; Lecher, Bernd; Maurer, Simone; Herbst, Hermann; Roemer, Klaus; Mueller-Lantzsch, Nikolaus

2005-04-28

Germ cell tumors (GCTs) are among the most common malignancies in young men. We have previously documented that patients with GCT frequently produce serum antibodies directed against proteins encoded by human endogenous retrovirus (HERV) type K sequences. Transcripts originating from the env gene of HERV-K, including the rec-relative of human immunodeficiency virus rev, are highly expressed in GCTs. We report here that mice that inducibly express HERV-K rec show a disturbed germ cell development and may exhibit, by 19 months of age, changes reminiscent of carcinoma in situ, the predecessor lesion of classic seminoma in humans. This provides the first direct evidence that the expression of a human endogenous retroviral gene previously established as a marker in human germ cell tumors may contribute to organ-specific tumorigenesis in a transgenic mouse model.

Plasmodium falciparum full life cycle and Plasmodium ovale liver stages in humanized mice.

PubMed

Soulard, Valérie; Bosson-Vanga, Henriette; Lorthiois, Audrey; Roucher, Clémentine; Franetich, Jean-François; Zanghi, Gigliola; Bordessoulles, Mallaury; Tefit, Maurel; Thellier, Marc; Morosan, Serban; Le Naour, Gilles; Capron, Frédérique; Suemizu, Hiroshi; Snounou, Georges; Moreno-Sabater, Alicia; Mazier, Dominique

2015-07-24

Experimental studies of Plasmodium parasites that infect humans are restricted by their host specificity. Humanized mice offer a means to overcome this and further provide the opportunity to observe the parasites in vivo. Here we improve on previous protocols to achieve efficient double engraftment of TK-NOG mice by human primary hepatocytes and red blood cells. Thus, we obtain the complete hepatic development of P. falciparum, the transition to the erythrocytic stages, their subsequent multiplication, and the appearance of mature gametocytes over an extended period of observation. Furthermore, using sporozoites derived from two P. ovale-infected patients, we show that human hepatocytes engrafted in TK-NOG mice sustain maturation of the liver stages, and the presence of late-developing schizonts indicate the eventual activation of quiescent parasites. Thus, TK-NOG mice are highly suited for in vivo observations on the Plasmodium species of humans.

Beta-palmitate - a natural component of human milk in supplemental milk formulas.

PubMed

Havlicekova, Zuzana; Jesenak, Milos; Banovcin, Peter; Kuchta, Milan

2016-03-17

The composition and function of human milk is unique and gives a basis for the development of modern artificial milk formulas that can provide an appropriate substitute for non-breastfed infants. Although human milk is not fully substitutable, modern milk formulas are attempting to mimic human milk and partially substitute its complex biological positive effects on infants. Besides the immunomodulatory factors from human milk, research has been focused on the composition and structure of human milk fat with a high content of β-palmitic acid (sn-2 palmitic acid, β-palmitate). According to the available studies, increasing the content of β-palmitate added to milk formulas promotes several beneficial physiological functions. β-palmitate positively influences fatty acid metabolism, increases calcium absorption, improves bone matrix quality and the stool consistency, and has a positive effect on the development of the intestinal microbiome.

Reasserting the primacy of human needs to reclaim the 'lost half' of sustainable development.

PubMed

Everard, Mark; Longhurst, James W S

2018-04-15

The concept of sustainable development evolved from growing awareness of the interdependence of social and economic progress with the limits of the supporting natural environment, becoming progressively integrated into global agreements and transposition into local regulatory and implementation frameworks. We argue that transposition of the concept into regulation and supporting tools reduced the focus to minimal environmental and social standards, perceived as imposing constraints rather than opportunities for innovation to meet human needs. The aspirational 'half' of the concept of sustainable development specifically addressing human needs was thus lost in transposing high ideals into regulatory instruments. The Sustainable Development Goals (SDGs) restore focus on interlinked human needs, stimulating innovation of products and processes to satisfy them. Through three case studies - PVC water pipes, river quality management in England, and UK local air quality management - we explore the current operationalisation of the concept in diverse settings, using the SDG framework to highlight the broader societal purposes central to sustainable development. Partnerships involving civil society support evolution of regulatory instruments and their implementation, optimising social and ecological benefits thereby serving more human needs. Restoring the visionary 'lost half' of sustainable development - meeting human needs in sustainable ways - creates incentives for innovation and partnership; an innovation framework rather than a perceived constraint. Copyright © 2017 Elsevier B.V. All rights reserved.

An improved high-throughput lipid extraction method for the analysis of human brain lipids.

PubMed

Abbott, Sarah K; Jenner, Andrew M; Mitchell, Todd W; Brown, Simon H J; Halliday, Glenda M; Garner, Brett

2013-03-01

We have developed a protocol suitable for high-throughput lipidomic analysis of human brain samples. The traditional Folch extraction (using chloroform and glass-glass homogenization) was compared to a high-throughput method combining methyl-tert-butyl ether (MTBE) extraction with mechanical homogenization utilizing ceramic beads. This high-throughput method significantly reduced sample handling time and increased efficiency compared to glass-glass homogenizing. Furthermore, replacing chloroform with MTBE is safer (less carcinogenic/toxic), with lipids dissolving in the upper phase, allowing for easier pipetting and the potential for automation (i.e., robotics). Both methods were applied to the analysis of human occipital cortex. Lipid species (including ceramides, sphingomyelins, choline glycerophospholipids, ethanolamine glycerophospholipids and phosphatidylserines) were analyzed via electrospray ionization mass spectrometry and sterol species were analyzed using gas chromatography mass spectrometry. No differences in lipid species composition were evident when the lipid extraction protocols were compared, indicating that MTBE extraction with mechanical bead homogenization provides an improved method for the lipidomic profiling of human brain tissue.

Generation and characterization of a unique reagent that recognizes a panel of recombinant human monoclonal antibody therapeutics in the presence of endogenous human IgG.

PubMed

Wang, Xiangdan; Quarmby, Valerie; Ng, Carl; Chuntharapai, Anan; Shek, Theresa; Eigenbrot, Charles; Kelley, Robert F; Shia, Steven; McCutcheon, Krista; Lowe, John; Leddy, Cecilia; Coachman, Kyle; Cain, Gary; Chu, Felix; Hotzel, Isidro; Maia, Mauricio; Wakshull, Eric; Yang, Jihong

2013-01-01

Pharmacokinetic (PK) and immunohistochemistry (IHC) assays are essential to the evaluation of the safety and efficacy of therapeutic monoclonal antibodies (mAb) during drug development. These methods require reagents with a high degree of specificity because low concentrations of therapeutic antibody need to be detected in samples containing high concentrations of endogenous human immunoglobulins. Current assay reagent generation practices are labor-intensive and time-consuming. Moreover, these practices are molecule-specific and so only support one assay for one program at a time. Here, we describe a strategy to generate a unique assay reagent, 10C4, that preferentially recognizes a panel of recombinant human mAbs over endogenous human immunoglobulins. This "panel-specific" feature enables the reagent to be used in PK and IHC assays for multiple structurally-related therapeutic mAbs. Characterization revealed that the 10C4 epitope is conformational, extensive and mainly composed of non-CDR residues. Most key contact residues were conserved among structurally-related therapeutic mAbs, but the combination of these residues exists at low prevalence in endogenous human immunoglobulins. Interestingly, an indirect contact residue on the heavy chain of the therapeutic appears to play a critical role in determining whether or not it can bind to 10C4, but has no affect on target binding. This may allow us to improve the binding of therapeutic mAbs to 10C4 for assay development in the future. Here, for the first time, we present a strategy to develop a panel-specific reagent that can expedite the development of multiple clinical assays for structurally-related therapeutic mAbs.

Development of a Novel Human scFv Against EGFR L2 Domain by Phage Display Technology.

PubMed

Rahbarnia, Leila; Farajnia, Safar; Babaei, Hossein; Majidi, Jafar; Veisi, Kamal; Khosroshahi, Shiva Ahdi; Tanomand, Asghar

2017-01-01

Epidermal growth factor receptor (EGFR) as a transmembrane tyrosine kinase receptor frequently overexpresses in tumors with epithelial origin. The L2 domain from extracellular part of EGFR is involved in ligand binding and the blockage of this domain prevents activation of related signaling pathways. This study was aimed to develop a novel human scFv against EGFR L2 domain as a promising target for cancer therapy. The L2 recombinant protein was purified and used for panning a human scFv phage library (Tomlinson I). In this study, a novel screening strategy was applied to select clones with high binding and enrichment of rare specific phage clones of the L2 protein. After five biopanning rounds several specific clones were isolated which among them one phage clone with high binding was purified for further analysis. The specific interaction of selected clone against target antigen was confirmed by ELISA and western blotting. Immunofluorescence staining showed that purified scFv binds to A431 cells surface, displaying EGFR surface receptor. In the present study, we isolated for the first time a novel human scFv against EGFR L2 domain. This study can be the groundwork for developing more effective diagnostic and therapeutic agents against EGFR overexpressing cancers using this novel human anti-L2 ScFv. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

High-Throughput Phenotypic Screening of Human Astrocytes to Identify Compounds That Protect Against Oxidative Stress.

PubMed

Thorne, Natasha; Malik, Nasir; Shah, Sonia; Zhao, Jean; Class, Bradley; Aguisanda, Francis; Southall, Noel; Xia, Menghang; McKew, John C; Rao, Mahendra; Zheng, Wei

2016-05-01

Astrocytes are the predominant cell type in the nervous system and play a significant role in maintaining neuronal health and homeostasis. Recently, astrocyte dysfunction has been implicated in the pathogenesis of many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Astrocytes are thus an attractive new target for drug discovery for neurological disorders. Using astrocytes differentiated from human embryonic stem cells, we have developed an assay to identify compounds that protect against oxidative stress, a condition associated with many neurodegenerative diseases. This phenotypic oxidative stress assay has been optimized for high-throughput screening in a 1,536-well plate format. From a screen of approximately 4,100 bioactive tool compounds and approved drugs, we identified a set of 22 that acutely protect human astrocytes from the consequences of hydrogen peroxide-induced oxidative stress. Nine of these compounds were also found to be protective of induced pluripotent stem cell-differentiated astrocytes in a related assay. These compounds are thought to confer protection through hormesis, activating stress-response pathways and preconditioning astrocytes to handle subsequent exposure to hydrogen peroxide. In fact, four of these compounds were found to activate the antioxidant response element/nuclear factor-E2-related factor 2 pathway, a protective pathway induced by toxic insults. Our results demonstrate the relevancy and utility of using astrocytes differentiated from human stem cells as a disease model for drug discovery and development. Astrocytes play a key role in neurological diseases. Drug discovery efforts that target astrocytes can identify novel therapeutics. Human astrocytes are difficult to obtain and thus are challenging to use for high-throughput screening, which requires large numbers of cells. Using human embryonic stem cell-derived astrocytes and an optimized astrocyte differentiation protocol, it was possible to screen approximately 4,100 compounds in titration to identify 22 that are cytoprotective of astrocytes. This study is the largest-scale high-throughput screen conducted using human astrocytes, with a total of 17,536 data points collected in the primary screen. The results demonstrate the relevancy and utility of using astrocytes differentiated from human stem cells as a disease model for drug discovery and development. ©AlphaMed Press.

Generation and expansion of highly pure motor neuron progenitors from human pluripotent stem cells.

PubMed

Du, Zhong-Wei; Chen, Hong; Liu, Huisheng; Lu, Jianfeng; Qian, Kun; Huang, CindyTzu-Ling; Zhong, Xiaofen; Fan, Frank; Zhang, Su-Chun

2015-03-25

Human pluripotent stem cells (hPSCs) have opened new opportunities for understanding human development, modelling disease processes and developing new therapeutics. However, these applications are hindered by the low efficiency and heterogeneity of cell types, such as motorneurons (MNs), differentiated from hPSCs as well as our inability to maintain the potency of lineage-committed progenitors. Here by using a combination of small molecules that regulate multiple signalling pathways, we develop a method to guide human embryonic stem cells to a near-pure population (>95%) of motor neuron progenitors (MNPs) in 12 days, and an enriched population (>90%) of functionally mature MNs in an additional 16 days. More importantly, the MNPs can be expanded for at least five passages so that a single MNP can be amplified to 1 × 10(4). This method is reproducible in human-induced pluripotent stem cells and is applied to model MN-degenerative diseases and in proof-of-principle drug-screening assays.

Single-Cell RNA-Seq Analysis Maps Development of Human Germline Cells and Gonadal Niche Interactions.

PubMed

Li, Li; Dong, Ji; Yan, Liying; Yong, Jun; Liu, Xixi; Hu, Yuqiong; Fan, Xiaoying; Wu, Xinglong; Guo, Hongshan; Wang, Xiaoye; Zhu, Xiaohui; Li, Rong; Yan, Jie; Wei, Yuan; Zhao, Yangyu; Wang, Wei; Ren, Yixin; Yuan, Peng; Yan, Zhiqiang; Hu, Boqiang; Guo, Fan; Wen, Lu; Tang, Fuchou; Qiao, Jie

2017-06-01

Human fetal germ cells (FGCs) are precursors to sperm and eggs and are crucial for maintenance of the species. However, the developmental trajectories and heterogeneity of human FGCs remain largely unknown. Here we performed single-cell RNA-seq analysis of over 2,000 FGCs and their gonadal niche cells in female and male human embryos spanning several developmental stages. We found that female FGCs undergo four distinct sequential phases characterized by mitosis, retinoic acid signaling, meiotic prophase, and oogenesis. Male FGCs develop through stages of migration, mitosis, and cell-cycle arrest. Individual embryos of both sexes simultaneously contain several subpopulations, highlighting the asynchronous and heterogeneous nature of FGC development. Moreover, we observed reciprocal signaling interactions between FGCs and their gonadal niche cells, including activation of the bone morphogenic protein (BMP) and Notch signaling pathways. Our work provides key insights into the crucial features of human FGCs during their highly ordered mitotic, meiotic, and gametogenetic processes in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

Highly sensitive strain sensors based on fragmentized carbon nanotube/polydimethylsiloxane composites.

PubMed

Gao, Yang; Fang, Xiaoliang; Tan, Jianping; Lu, Ting; Pan, Likun; Xuan, Fuzhen

2018-06-08

Wearable strain sensors based on nanomaterial/elastomer composites have potential applications in flexible electronic skin, human motion detection, human-machine interfaces, etc. In this research, a type of high performance strain sensors has been developed using fragmentized carbon nanotube/polydimethylsiloxane (CNT/PDMS) composites. The CNT/PDMS composites were ground into fragments, and a liquid-induced densification method was used to fabricate the strain sensors. The strain sensors showed high sensitivity with gauge factors (GFs) larger than 200 and a broad strain detection range up to 80%, much higher than those strain sensors based on unfragmentized CNT/PDMS composites (GF < 1). The enhanced sensitivity of the strain sensors is ascribed to the sliding of individual fragmentized-CNT/PDMS-composite particles during mechanical deformation, which causes significant resistance change in the strain sensors. The strain sensors can differentiate mechanical stimuli and monitor various human body motions, such as bending of the fingers, human breathing, and blood pulsing.

Simple high-performance liquid chromatography method for formaldehyde determination in human tissue through derivatization with 2,4-dinitrophenylhydrazine.

PubMed

Yilmaz, Bilal; Asci, Ali; Kucukoglu, Kaan; Albayrak, Mevlut

2016-08-01

A simple high-performance liquid chromatography method has been developed for the determination of formaldehyde in human tissue. FA Formaldehyde was derivatized with 2,4-dinitrophenylhydrazine. It was extracted from human tissue with ethyl acetate by liquid-liquid extraction and analyzed by high-performance liquid chromatography. The calibration curve was linear in the concentration range of 5.0-200 μg/mL. Intra- and interday precision values for formaldehyde in tissue were <6.9%, and accuracy (relative error) was better than 6.5%. The extraction recoveries of formaldehyde from human tissue were between 88 and 98%. The limits of detection and quantification of formaldehyde were 1.5 and 5.0 μg/mL, respectively. Also, this assay was applied to liver samples taken from a biopsy material. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Avian influenza A (H5N1).

PubMed

de Jong, Menno D; Hien, Tran Tinh

2006-01-01

Since their reemergence in 2003, highly pathogenic avian influenza A (H5N1) viruses have reached endemic levels among poultry in several southeast Asian countries and have caused a still increasing number of more than 100 reported human infections with high mortality. These developments have ignited global fears of an imminent influenza pandemic. The current knowledge of the virology, clinical spectrum, diagnosis and treatment of human influenza H5N1 virus infections is reviewed herein.

Chemotherapy induced toxicity is highly heritable in Drosophila melanogaster

PubMed Central

Kislukhin, Galina; Murphy, Maura L.; Jafari, Mahtab; Long, Anthony D.

2012-01-01

Objectives Identifying the genes responsible for chemotherapy toxicity in Drosophila melanogaster may allow for the identification of human orthologs that similarly mediate toxicity in humans. In order to develop Drosophila melanogaster as a model of dissecting chemotoxicity, we first need to develop standardized high throughput toxicity assays and prove that inter-individual variation in toxicity as measured by such assays is highly heritable. Methods We developed a method for the oral delivery of commonly used chemotherapy drugs to Drosophila. Post-treatment female fecundity displayed a dose dependent response to varying levels of the chemotherapy drug delivered. We fixed the dose for each drug at a level that resulted in a 50% reduction in fecundity and used a paternal half-sibling heritability design to calculate the heritability attributable to chemotherapy toxicity assayed via a decrease in female fecundity. Chemotherapy agents tested were carboplatin, floxuridine, gemcitabine hydrochloride, methotrexate, mitomycin C, and topotecan hydrochloride. Results We found that six currently widely prescribed chemotherapeutic agents lowered fecundity in D. melanogaster in both a dose dependent and highly heritable manner. The following heritability estimates were found: carboplatin – 0.72, floxuridine – 0.52, gemcitabine hydrochloride – 0.72, methotrexate – 0.99, mitomycin C – 0.64, and topotecan hydrochloride – 0.63. Conclusions The high heritability estimates observed in this study, irrespective of the particular class of drug examined, suggest that human toxicity may also have a sizable genetic component. PMID:22336958

Comparative proteomic analysis reveals the suppressive effects of dietary high glucose on the midgut growth of silkworm.

PubMed

Feng, Fan; Chen, Liang; Lian, Chaoqun; Xia, Hengchuan; Zhou, Yang; Yao, Qin; Chen, Keping

2014-08-28

The silkworm, Bombyx mori, is an important model of lepidoptera insect, and it has been used for several models of human diseases. In human being, long-term high-sugar diet can induce the occurrence of diabetes and other related diseases. Interestingly, our experiments revealed the high glucose diet also has a suppressive effect on the development of silkworms. To investigate the molecular mechanism by which high-glucose diet inhibited the midgut growth in silkworms, we employed comparative proteomic analysis to globally identify proteins differentially expressed in normal and high-glucose diet group silkworms. In all, 28 differently proteins were suppressed and 5 proteins induced in high-glucose diet group. Gene ontology analysis showed that most of these differently proteins are mainly involved in metabolic process, catalytic and cellular process. A development related protein, imaginal disk growth factor (IDGF), was further confirmed by western blot exclusively expressing in the normal diet group silkworms. Taken together, our data suggests that IDGF plays a critical role in impairing the development of silkworms by a high-glucose diet. Glucose has been thought to play essential roles in growth and development of silkworm. In this paper, we certified firstly that high-glucose diet can suppress the growth of silkworm, and comparative proteomic was employed to reveal the inhibition mechanism. Moreover, an important regulation related protein (IDGF) was found to involve in this inhibition process. These results will help us get a deeper understanding of the relationship between diet and healthy. Furthermore, IDGF may be the critical protein for reducing the blood sugar in silkworm, and it may be used for screening human hypoglycemic drug. The work has not been submitted elsewhere for publication, in whole or in part, and all the authors have approved the manuscript. Copyright © 2014 Elsevier B.V. All rights reserved.

Complex torso reconstruction with human acellular dermal matrix: long-term clinical follow-up.

PubMed

Nemeth, Nicole L; Butler, Charles E

2009-01-01

Although reports have demonstrated good early outcomes with human acellular dermal matrix even when used for complex, contaminated defects, no long-term outcomes have been reported. The authors reviewed the long-term outcomes of 13 patients who had complex torso reconstructions that included human acellular dermal matrix. All patients were at increased risk for mesh-related complications. Eight patients died as a result of progression of their oncologic disease at a mean of 258 days postoperatively. The mean follow-up for the remaining five patients was 43.7 months. Six patients had early complications (none were human acellular dermal matrix-related) and were reported on previously. Two patients had developed complications since the initial report. One patient developed a flap donor-site seroma remote from the reconstruction site, and another developed a recurrent ventral hernia. No patients have required additional surgery for human acellular dermal matrix-related complications. This follow-up report indicates that human acellular dermal matrix repair of large, complex torso defects can result in good long-term outcomes even when patients are at high risk for mesh-related complications.

Recapitulation of Human Retinal Development from Human Pluripotent Stem Cells Generates Transplantable Populations of Cone Photoreceptors.

PubMed

Gonzalez-Cordero, Anai; Kruczek, Kamil; Naeem, Arifa; Fernando, Milan; Kloc, Magdalena; Ribeiro, Joana; Goh, Debbie; Duran, Yanai; Blackford, Samuel J I; Abelleira-Hervas, Laura; Sampson, Robert D; Shum, Ian O; Branch, Matthew J; Gardner, Peter J; Sowden, Jane C; Bainbridge, James W B; Smith, Alexander J; West, Emma L; Pearson, Rachael A; Ali, Robin R

2017-09-12

Transplantation of rod photoreceptors, derived either from neonatal retinae or pluripotent stem cells (PSCs), can restore rod-mediated visual function in murine models of inherited blindness. However, humans depend more upon cone photoreceptors that are required for daylight, color, and high-acuity vision. Indeed, macular retinopathies involving loss of cones are leading causes of blindness. An essential step for developing stem cell-based therapies for maculopathies is the ability to generate transplantable human cones from renewable sources. Here, we report a modified 2D/3D protocol for generating hPSC-derived neural retinal vesicles with well-formed ONL-like structures containing cones and rods bearing inner segments and connecting cilia, nascent outer segments, and presynaptic structures. This differentiation system recapitulates human photoreceptor development, allowing the isolation and transplantation of a pure population of stage-matched cones. Purified human long/medium cones survive and become incorporated within the adult mouse retina, supporting the potential of photoreceptor transplantation for treating retinal degeneration. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Non-animal methodologies within biomedical research and toxicity testing.

PubMed

Knight, Andrew

2008-01-01

Laboratory animal models are limited by scientific constraints on human applicability, and increasing regulatory restrictions, driven by social concerns. Reliance on laboratory animals also incurs marked - and in some cases, prohibitive - logistical challenges, within high-throughput chemical testing programmes, such as those currently underway within Europe and the US. However, a range of non-animal methodologies is available within biomedical research and toxicity testing. These include: mechanisms to enhance the sharing and assessment of existing data prior to conducting further studies, and physicochemical evaluation and computerised modelling, including the use of structure-activity relationships and expert systems. Minimally-sentient animals from lower phylogenetic orders or early developmental vertebral stages may be used, as well as microorganisms and higher plants. A variety of tissue cultures, including immortalised cell lines, embryonic and adult stem cells, and organotypic cultures, are also available. In vitro assays utilising bacterial, yeast, protozoal, mammalian or human cell cultures exist for a wide range of toxic and other endpoints. These may be static or perfused, and may be used individually, or combined within test batteries. Human hepatocyte cultures and metabolic activation systems offer potential assessment of metabolite activity and organ-organ interaction. Microarray technology may allow genetic expression profiling, increasing the speed of toxin detection, well prior to more invasive endpoints. Enhanced human clinical trials utilising micro- dosing, staggered dosing, and more representative study populations and durations, as well as surrogate human tissues, advanced imaging modalities and human epidemiological, sociological and psycho- logical studies, may increase our understanding of illness aetiology and pathogenesis, and facilitate the development of safe and effective pharmacologic interventions. Particularly when human tissues are used, non-animal models may generate faster, cheaper results, more reliably predictive for humans, whilst yielding greater insights into human biochemical processes. Greater commitment to their development and implementation is necessary, however, to efficiently meet the needs of high-throughput chemical testing programmes, important emerging testing needs, and the ongoing development of human clinical interventions.

Are Liberal Studies Teachers Ready to Prepare Human Rights Respecting Students? A Portrait of Teachers' Attitudes towards Human Rights

ERIC Educational Resources Information Center

Leung, Yan Wing; Lo, Yan Lam

2012-01-01

As in most countries, human rights education (HRE) in Hong Kong has never been high on the educational agenda. In 2009, a compulsory subject, Liberal Studies (LS), which could be used as a platform for HRE, was introduced. The Hong Kong Institute of Education launched a research and development project which, as one of its objectives, studied LS…

Effects of Caffeine and Warrior Stress on Behavioral : An Animal Model

DTIC Science & Technology

2016-03-14

contributes invaluably to ethical and humane research. A special thank you to Erin Barry for providing statistical expertise and methodological support...of behavioral health in rats. Several ethical and logistical issues prevent the use of humans in true controlled experiments that manipulate stress...play in the development or maintenance of behavioral problems. There are ethical issues associated with exposing humans to high caffeine doses and

Employers' Perspectives on the Roles of Human Capital Development and Management in Creating Value. OECD Education Working Papers, No. 18

ERIC Educational Resources Information Center

Bassi, Laurie J.; McMurrer, Daniel P.

2006-01-01

Human capital--the productive capacity that is embedded in people--is one of the most important contributors to the growth in nations' output and standard of living. Globalisation and technological change have increased the importance of human capital in recent years, to the point that there are now only two options to sustain high profits and…

Ferrets develop fatal influenza after inhaling small particle aerosols of highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1)

USDA-ARS?s Scientific Manuscript database

There is limited knowledge about the potential routes for H5N1 influenza virus transmission to and between humans, and it is not clear whether humans can be infected through inhalation of aerosolized H5N1 virus particles. Ferrets are often used as a surrogate for humans in influenza pathogenicity a...

Human Gut Microbiome: Function Matters.

PubMed

Heintz-Buschart, Anna; Wilmes, Paul

2017-11-22

The human gut microbiome represents a complex ecosystem contributing essential functions to its host. Recent large-scale metagenomic studies have provided insights into its structure and functional potential. However, the functional repertoire which is actually contributed to human physiology remains largely unexplored. Here, by leveraging recent omics datasets, we challenge current assumptions regarding key attributes of the functional gut microbiome, in particular with respect to its variability. We further argue that the closing of existing gaps in functional knowledge should be addressed by a most-wanted gene list, the development and application of molecular and cellular high-throughput measurements, the development and sensible use of experimental models, as well as the direct study of observable molecular effects in the human host. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Development of the certified reference material of mercury in lyophilized human urine].

PubMed

Zhao, Wei; Zhang, Fu-gang; DU, Hui-fang; Pan, Ya-juan; Yan, Hui-fang

2011-02-01

To develop the certified reference material of mercury in lyophilized human urine. Human urine samples from normal level mercury districts were filtered, homogenized, dispensed, lyophilized and radio-sterilized. Homogeneity test, stability inspection and certification were conducted using a atom fluorescence spectrophotometric method. The physical and chemical stability of the certified reference material were assessed for 18 months. The certified values are based on analysis made by three independent laboratories. The certified values are as follows: low level was (35.6 ± 2.1) µg/L, high level was (50.5 ± 3.0) µg/L. The certified reference material of mercury in lyophilized human urine in this research reached the national certified reference material requirements and could be used for the quality control.

Unhealthy Behaviours: An International Comparison

PubMed Central

Ferretti, Fabrizio

2015-01-01

In the current global economy, chronic non-communicable diseases (NCDs) have become the leading cause of death and a major health concern for both developed and developing countries. Among other factors, the worldwide spread of NCDs is driven by the globalisation of unhealthy habits. The purpose of this paper is to develop a simple statistic to measure, at the national level, the average population’s exposure to the main NCDs modifiable risk factors. The approach and methodology followed by the United Nations Development Programme to compute the Human Development Index (HDI) is applied to four basic indicators of NCD-related preventable risk factors (alcohol consumption, excess caloric intake, non-balanced diet and tobacco use) in 112 countries worldwide in 2012–14. We obtain a summary composite index, which we call the Unhealthy Behaviour Index (UBI), which ranks countries by the average level of the unhealthy habits (drinking, eating and smoking) of their populations. We find that Belarus and Russian federation are the two countries with the unhealthiest NCD-related lifestyle. With the exception of Canada, the first twenty populations more exposed to the main NCDs preventable risk factors all live in European countries, and mainly in countries of Eastern Europe. Overall, the UBI tends to increase along with the level of human development. In medium, high and very high HDI countries, however, the same level of human development may be associated with very different kinds of NCD-related lifestyles. Finally, economic growth may push populations toward either more unhealthy or healthy habits, depending on the countries’ level of development; the elasticity of unhealthy habits with respect to income per capita is positive (but less than one: on average 0.6) until $30,000, decreases as income rises, and becomes negative (around -0.3) in very high income countries. PMID:26512717

Unhealthy Behaviours: An International Comparison.

PubMed

Ferretti, Fabrizio

2015-01-01

In the current global economy, chronic non-communicable diseases (NCDs) have become the leading cause of death and a major health concern for both developed and developing countries. Among other factors, the worldwide spread of NCDs is driven by the globalisation of unhealthy habits. The purpose of this paper is to develop a simple statistic to measure, at the national level, the average population's exposure to the main NCDs modifiable risk factors. The approach and methodology followed by the United Nations Development Programme to compute the Human Development Index (HDI) is applied to four basic indicators of NCD-related preventable risk factors (alcohol consumption, excess caloric intake, non-balanced diet and tobacco use) in 112 countries worldwide in 2012-14. We obtain a summary composite index, which we call the Unhealthy Behaviour Index (UBI), which ranks countries by the average level of the unhealthy habits (drinking, eating and smoking) of their populations. We find that Belarus and Russian federation are the two countries with the unhealthiest NCD-related lifestyle. With the exception of Canada, the first twenty populations more exposed to the main NCDs preventable risk factors all live in European countries, and mainly in countries of Eastern Europe. Overall, the UBI tends to increase along with the level of human development. In medium, high and very high HDI countries, however, the same level of human development may be associated with very different kinds of NCD-related lifestyles. Finally, economic growth may push populations toward either more unhealthy or healthy habits, depending on the countries' level of development; the elasticity of unhealthy habits with respect to income per capita is positive (but less than one: on average 0.6) until $30,000, decreases as income rises, and becomes negative (around -0.3) in very high income countries.

Antibodies to VP1 of swine pasivirus in humans without evidence of transmission from a pig source.

PubMed

Arnold, Francoise; Hober, Didier; Chaussade, Hélène; Dumarest, Marine; Sané, Famara; Nowakowsjki, Mireille; Rigaud, Emma; Bellalou, Jacques; Desailloud, Rachel; Coursaget, Pierre; Eloit, Marc

2015-08-01

Swine pasivirus (SPaV1) is a recently described enteric virus close to human parechoviruses and highly prevalent in pigs. Antibodies to Escherichia coli-expressed VP1 of SpaV1 have been found in a majority of humans in China. The objectives were to estimate the antibody prevalence in a European country, to test if exposure to the virus was linked to pig products and if this exposure was a risk factor for the development of diabetes type 1. An ELISA test was developed and used to screen 842 healthy subjects with known exposure to pig products, 39 patients with diabetes type 1 and 20 controls. We identified a high seroprevalence (15.6%) reacting to VP1 of SPaV1 among healthy human subjects. Analysis of risk factors argues against cross-species transmission from pigs as the source of infection. Data also indicate that the presence of SPaV1 VP1-binding antibodies is not associated with diabetes type 1 in humans. Our results suggest that the seroreactivity frequently found in humans against SpaV1 is due to cross-reactivity with related antigen, perhaps a picornavirus, and that SpaV1 is not a zoonotic virus. Copyright © 2015 Elsevier B.V. All rights reserved.

Rich-club organization of the newborn human brain

PubMed Central

Ball, Gareth; Aljabar, Paul; Zebari, Sally; Tusor, Nora; Arichi, Tomoki; Merchant, Nazakat; Robinson, Emma C.; Ogundipe, Enitan; Rueckert, Daniel; Edwards, A. David; Counsell, Serena J.

2014-01-01

Combining diffusion magnetic resonance imaging and network analysis in the adult human brain has identified a set of highly connected cortical hubs that form a “rich club”—a high-cost, high-capacity backbone thought to enable efficient network communication. Rich-club architecture appears to be a persistent feature of the mature mammalian brain, but it is not known when this structure emerges during human development. In this longitudinal study we chart the emergence of structural organization in mid to late gestation. We demonstrate that a rich club of interconnected cortical hubs is already present by 30 wk gestation. Subsequently, until the time of normal birth, the principal development is a proliferation of connections between core hubs and the rest of the brain. We also consider the impact of environmental factors on early network development, and compare term-born neonates to preterm infants at term-equivalent age. Though rich-club organization remains intact following premature birth, we reveal significant disruptions in both in cortical–subcortical connectivity and short-distance corticocortical connections. Rich club organization is present well before the normal time of birth and may provide the fundamental structural architecture for the subsequent emergence of complex neurological functions. Premature exposure to the extrauterine environment is associated with altered network architecture and reduced network capacity, which may in part account for the high prevalence of cognitive problems in preterm infants. PMID:24799693

77 FR 49412 - Takes of Marine Mammals Incidental to Specified Activities; Navy Research, Development, Test and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-16

...; high-pitched sounds contain high frequencies and low-pitched sounds contain low frequencies. Natural... estimated to occur between approximately 150 Hz and 160 kHz. High-frequency cetaceans (eight species of true... masking by high frequency sound. Human data indicate low-frequency sound can mask high-frequency sounds (i...

A model of type 2 diabetes in the guinea pig using sequential diet-induced glucose intolerance and streptozotocin treatment.

PubMed

Podell, Brendan K; Ackart, David F; Richardson, Michael A; DiLisio, James E; Pulford, Bruce; Basaraba, Randall J

2017-02-01

Type 2 diabetes is a leading cause of morbidity and mortality among noncommunicable diseases, and additional animal models that more closely replicate the pathogenesis of human type 2 diabetes are needed. The goal of this study was to develop a model of type 2 diabetes in guinea pigs, in which diet-induced glucose intolerance precedes β-cell cytotoxicity, two processes that are crucial to the development of human type 2 diabetes. Guinea pigs developed impaired glucose tolerance after 8 weeks of feeding on a high-fat, high-carbohydrate diet, as determined by oral glucose challenge. Diet-induced glucose intolerance was accompanied by β-cell hyperplasia, compensatory hyperinsulinemia, and dyslipidemia with hepatocellular steatosis. Streptozotocin (STZ) treatment alone was ineffective at inducing diabetic hyperglycemia in guinea pigs, which failed to develop sustained glucose intolerance or fasting hyperglycemia and returned to euglycemia within 21 days after treatment. However, when high-fat, high-carbohydrate diet-fed guinea pigs were treated with STZ, glucose intolerance and fasting hyperglycemia persisted beyond 21 days post-STZ treatment. Guinea pigs with diet-induced glucose intolerance subsequently treated with STZ demonstrated an insulin-secretory capacity consistent with insulin-independent diabetes. This insulin-independent state was confirmed by response to oral antihyperglycemic drugs, metformin and glipizide, which resolved glucose intolerance and extended survival compared with guinea pigs with uncontrolled diabetes. In this study, we have developed a model of sequential glucose intolerance and β-cell loss, through high-fat, high-carbohydrate diet and extensive optimization of STZ treatment in the guinea pig, which closely resembles human type 2 diabetes. This model will prove useful in the study of insulin-independent diabetes pathogenesis with or without comorbidities, where the guinea pig serves as a relevant model species. © 2017. Published by The Company of Biologists Ltd.

Prioritizing human pharmaceuticals for ecological risks in the freshwater environment of Korea.

PubMed

Ji, Kyunghee; Han, Eun Jeong; Back, Sunhyoung; Park, Jeongim; Ryu, Jisung; Choi, Kyungho

2016-04-01

Pharmaceutical residues are potential threats to aquatic ecosystems. Because more than 3000 active pharmaceutical ingredients (APIs) are in use, identifying high-priority pharmaceuticals is important for developing appropriate management options. Priority pharmaceuticals may vary by geographical region, because their occurrence levels can be influenced by demographic, societal, and regional characteristics. In the present study, the authors prioritized human pharmaceuticals of potential ecological risk in the Korean water environment, based on amount of use, biological activity, and regional hydrologic characteristics. For this purpose, the authors estimated the amounts of annual production of 695 human APIs in Korea. Then derived predicted environmental concentrations, using 2 approaches, to develop an initial candidate list of target pharmaceuticals. Major antineoplastic drugs and hormones were added in the initial candidate list regardless of their production amount because of their high biological activity potential. The predicted no effect concentrations were derived for those pharmaceuticals based on ecotoxicity information available in the literature or by model prediction. Priority lists of human pharmaceuticals were developed based on ecological risks and availability of relevant information. Those priority APIs identified include acetaminophen, clarithromycin, ciprofloxacin, ofloxacin, metformin, and norethisterone. Many of these pharmaceuticals have been neither adequately monitored nor assessed for risks in Korea. Further efforts are needed to improve these lists and to develop management decisions for these compounds in Korean water. © 2015 SETAC.

Influence of a Non-formal Environmental Education Programme on Junior High-School Students' Environmental Literacy

NASA Astrophysics Data System (ADS)

Goldman, Daphne; Ben Zvi Assaraf, Orit; Shaharabani, Dina

2013-02-01

One of the solutions implemented by schools for conducting value-based environmental education (EE) is outsourcing: allocating external environmental organizations that develop and conduct EE programmes. This study addressed such a programme-the Green Council Programme (GCP)-developed and implemented in schools by the Israeli Society for Protection of Nature. A pre-test/post-test design was used to investigate the influence of participation in the GCP on components of junior high-school students' environmental literacy. Conceptualizations of 'environment', environmental attitudes and sense of ability to act on environmental issues were studied employing quantitative and qualitative tools. Contribution of the programme to the cognitive domain, in developing a systemic understanding of the environment, was limited. On the other hand, participating in this programme heightened students' sensitivity to human-environment interrelationships and developed a more ecological worldview. After the programme, students demonstrated greater perception of humans as part of the environment, an increased sensitivity to human impact on the environment and their value for non-human nature moved from an anthropocentric to a more ecocentric orientation. While students' internal locus-of-control increased, when environmental protection entailed personal economic trade-offs, their support was limited and remained unchanged. The article concludes with recommendations, based on the findings, regarding supplementing the school (science) curriculum with external EE enrichment programmes.

THE IMPORTANCE OF DIETARY CARBOHYDRATE IN HUMAN EVOLUTION.

PubMed

Hardy, Karen; Brand-Miller, Jennie; Brown, Katherine D; Thomas, Mark G; Copeland, Les

2015-09-01

ABSTRACT We propose that plant foods containing high quantities of starch were essential for the evolution of the human phenotype during the Pleistocene. Although previous studies have highlighted a stone tool-mediated shift from primarily plant-based to primarily meat-based diets as critical in the development of the brain and other human traits, we argue that digestible carbohydrates were also necessary to accommodate the increased metabolic demands of a growing brain. Furthermore, we acknowledge the adaptive role cooking played in improving the digestibility and palatability of key carbohydrates. We provide evidence that cooked starch, a source of preformed glucose, greatly increased energy availability to human tissues with high glucose demands, such as the brain, red blood cells, and the developing fetus. We also highlight the auxiliary role copy number variation in the salivary amylase genes may have played in increasing the importance of starch in human evolution following the origins of cooking. Salivary amylases are largely ineffective on raw crystalline starch, but cooking substantially increases both their energy-yielding potential and glycemia. Although uncertainties remain regarding the antiquity of cooking and the origins of salivary amylase gene copy number variation, the hypothesis we present makes a testable prediction that these events are correlated.

Cell fiber-based three-dimensional culture system for highly efficient expansion of human induced pluripotent stem cells.

PubMed

Ikeda, Kazuhiro; Nagata, Shogo; Okitsu, Teru; Takeuchi, Shoji

2017-06-06

Human pluripotent stem cells are a potentially powerful cellular resource for application in regenerative medicine. Because such applications require large numbers of human pluripotent stem cell-derived cells, a scalable culture system of human pluripotent stem cell needs to be developed. Several suspension culture systems for human pluripotent stem cell expansion exist; however, it is difficult to control the thickness of cell aggregations in these systems, leading to increased cell death likely caused by limited diffusion of gases and nutrients into the aggregations. Here, we describe a scalable culture system using the cell fiber technology for the expansion of human induced pluripotent stem (iPS) cells. The cells were encapsulated and cultured within the core region of core-shell hydrogel microfibers, resulting in the formation of rod-shaped or fiber-shaped cell aggregations with sustained thickness and high viability. By encapsulating the cells with type I collagen, we demonstrated a long-term culture of the cells by serial passaging at a high expansion rate (14-fold in four days) while retaining its pluripotency. Therefore, our culture system could be used for large-scale expansion of human pluripotent stem cells for use in regenerative medicine.

Can Inhibitors of Snake Venom Phospholipases A₂ Lead to New Insights into Anti-Inflammatory Therapy in Humans? A Theoretical Study.

PubMed

Sales, Thaís A; Marcussi, Silvana; da Cunha, Elaine F F; Kuca, Kamil; Ramalho, Teodorico C

2017-10-25

Human phospholipase A₂ ( h PLA₂) of the IIA group (HGIIA) catalyzes the hydrolysis of membrane phospholipids, producing arachidonic acid and originating potent inflammatory mediators. Therefore, molecules that can inhibit this enzyme are a source of potential anti-inflammatory drugs, with different action mechanisms of known anti-inflammatory agents. For the study and development of new anti-inflammatory drugs with this action mechanism, snake venom PLA₂ ( sv PLA₂) can be employed, since the sv PLA₂ has high similarity with the human PLA₂ HGIIA. Despite the high similarity between these secretory PLA₂s , it is still not clear if these toxins can really be employed as an experimental model to predict the interactions that occur with the human PLA₂ HGIIA and its inhibitors. Thus, the present study aims to compare and evaluate, by means of theoretical calculations, docking and molecular dynamics simulations, as well as experimental studies, the interactions of human PLA₂ HGIIA and two sv PLA₂s , Bothrops toxin II and Crotoxin B (BthTX-II and CB, respectively). Our theoretical findings corroborate experimental data and point out that the human PLA₂ HGIIA and sv PLA₂ BthTX-II lead to similar interactions with the studied compounds. From our results, the sv PLA₂ BthTX-II can be used as an experimental model for the development of anti-inflammatory drugs for therapy in humans.

Building human resources capability in health care: a global analysis of best practice--Part III.

PubMed

Zairi, M

1998-01-01

This is the last part of a series of three papers which discussed very comprehensively best practice applications in human resource management by drawing special inferences to the healthcare context. It emerged from parts I and II that high performing organisations plan and intend to build sustainable capability through a systematic consideration of the human element as the key asset and through a continuous process of training, developing, empowering and engaging people in all aspects of organisational excellence. Part III brings this debate to a close by demonstrating what brings about organisational excellence and proposes a road map for effective human resource development and management, based on world class standards. Healthcare human resource professionals can now rise to the challenge and plan ahead for building organisational capability and sustainable performance.

critcial human health issues in connection with future human missions to mMars: the HUMEX study of ESA

NASA Astrophysics Data System (ADS)

Horneck, G.; Humex Team

ESA has recently initiated a study of the human responses, limits and needs with regard to the stress environments of interplanetary and planetary missions. Emphasis was laid on human health and performance care as well as Advanced Life Support Developments including Bioregenerative Life Support Systems and environmental monitoring. The overall study goals were as follows: (i) to define reference scenarios for a European participation in human exploration and to estimate their influence on the Life Sciences and Life Support requirements; (ii) for selected mission scenarios, to critically assess the limiting factors for human health, wellbeing, and performance and to recommend relevant countermeasures; (iii) for selected mission scenarios, to critically assess the potential of Advanced Life Support Developments and to pro-pose a European strategy including terrestrial applications; (iv) to critically assess the feasibility of existing facilities and technologies on ground and in space as test-beds in preparation for human exploratory missions and to develop a test plan for ground and ISS campaigns; (v) to develop a roadmap for a future European strategy towards human exploratory missions, including preparatory activities and terrestrial applications and benefits. Two scenarios for a Mars mission were selected: (i) with a 30 days stay on Mars, and (ii) with about 500 days stay on Mars. The impact on human health, perform-ance and well being has been investigated from the view point of (i) the effects of microgravity (during space travel), reduced gravity (on Mars) and abrupt gravity changes (during launch and landing), (ii) the effects of cosmic radiation including solar particle events, (iii) psychological issues as well as general health care. Coun-termeasures as well as necessary research using ground-based testbeds and/or the ISS have been defined. The need for highly intelligent autonomous diagnostic and therapy systems was emphasized. Advanced life support systems with a high degree of autonomy and regenerative capacity and synergy effects were considered where bioregenerative life support systems and biodiagnostic systems become essential especially for the long-term Mars scenario. The considerations have been incorpo-rated into a roadmap for a future European strategy in human health issues for a potential European participation in a cooperative international exploration of our solar system by humans. Ref. Horneck et al, 2003, HUMEX, study on the Survivability and Adaptation of Humans to Long-Duration Exploratory Missions, ESA SP 1264

High-throughput determination of vancomycin in human plasma by a cost-effective system of two-dimensional liquid chromatography.

PubMed

Sheng, Yanghao; Zhou, Boting

2017-05-26

Therapeutic drug monitoring (TDM) is one of the most important services of clinical laboratories. Two main techniques are commonly used: the immunoassay and chromatography method. We have developed a cost-effective system of two-dimensional liquid chromatography with ultraviolet detection (2D-LC-UV) for high-throughput determination of vancomycin in human plasma that combines the automation and low start-up costs of the immunoassay with the high selectivity and sensitivity of the liquid chromatography coupled with mass spectrometric detection without incurring their disadvantages, achieving high cost-effectiveness. This 2D-LC system offers a large volume injection to provide sufficient sensitivity and uses simulated gradient peak compression technology to control peak broadening and to improve peak shape. A middle column was added to reduce the analysis cycle time and make it suitable for high-throughput routine clinical assays. The analysis cycle time was 4min and the peak width was 0.8min. Compared with other chromatographic methods that have been developed, the analysis cycle time and peak width for vancomycin was reduced significantly. The lower limit of quantification was 0.20μg/mL for vancomycin, which is the same as certain LC-MS/MS methods that have been recently developed and validated. The method is rapid, automated, and low-cost and has high selectivity and sensitivity for the quantification of vancomycin in human plasma, thus making it well-suited for use in hospital clinical laboratories. Copyright © 2017 Elsevier B.V. All rights reserved.

Research and Development Annual Report, 1992

NASA Technical Reports Server (NTRS)

1993-01-01

Issued as a companion to Johnson Space Center's Research and Technology Annual Report, which reports JSC accomplishments under NASA Research and Technology Operating Plan (RTOP) funding, this report describes 42 additional JSC projects that are funded through sources other than the RTOP. Emerging technologies in four major disciplines are summarized: space systems technology, medical and life sciences, mission operations, and computer systems. Although these projects focus on support of human spacecraft design, development, and safety, most have wide civil and commercial applications in areas such as advanced materials, superconductors, advanced semiconductors, digital imaging, high density data storage, high performance computers, optoelectronics, artificial intelligence, robotics and automation, sensors, biotechnology, medical devices and diagnosis, and human factors engineering.

The JSC Research and Development Annual Report 1993

NASA Technical Reports Server (NTRS)

1994-01-01

Issued as a companion to Johnson Space Center's Research and Technology Annual Report, which reports JSC accomplishments under NASA Research and Technology Operating Plan (RTOP) funding, this report describes 47 additional projects that are funded through sources other than the RTOP. Emerging technologies in four major disciplines are summarized: space systems technology, medical and life sciences, mission operations, and computer systems. Although these projects focus on support of human spacecraft design, development, and safety, most have wide civil and commercial applications in areas such as advanced materials, superconductors, advanced semiconductors, digital imaging, high density data storage, high performance computers, optoelectronics, artificial intelligence, robotics and automation, sensors, biotechnology, medical devices and diagnosis, and human factors engineering.

Highly Developed Information-oriented Society and Humanity ; Medical Information Services and Library

NASA Astrophysics Data System (ADS)

Wakimoto, Atsuko

Change in social circumstances caused by arrival of highly developed information-oriented society has altered what information services in medical libraries should be dramatically. Keeping with complication and diversification of needs by users such as medical doctors, researchers, medical technicians and so on medical librarians have been playing important role in the information activities, and are required to master more specialized knowledge. This paper outlines changes in circumstances surrounding medical libraries, discusses role of medical librarians in online information retrieval services, and introduces various curriculum for library education. The author proposes that humanity of librarian him or herself is still a key factor for library services regardless of advancement of computerization.

Carbohydrate-based vaccine adjuvants - discovery and development.

PubMed

Hu, Jing; Qiu, Liying; Wang, Xiaoli; Zou, Xiaopeng; Lu, Mengji; Yin, Jian

2015-10-01

The addition of a suitable adjuvant to a vaccine can generate significant effective adaptive immune responses. There is an urgent need for the development of novel po7tent and safe adjuvants for human vaccines. Carbohydrate molecules are promising adjuvants for human vaccines due to their high biocompatibility and good tolerability in vivo. The present review covers a few promising carbohydrate-based adjuvants, lipopolysaccharide, trehalose-6,6'-dibehenate, QS-21 and inulin as examples, which have been extensively studied in human vaccines in a number of preclinical and clinical studies. The authors discuss the current status, applications and strategies of development of each adjuvant and different adjuvant formulation systems. This information gives insight regarding the exciting prospect in the field of carbohydrate-based adjuvant research. Carbohydrate-based adjuvants are promising candidates as an alternative to the Alum salts for human vaccines development. Furthermore, combining two or more adjuvants in one formulation is one of the effective strategies in adjuvant development. However, further research efforts are needed to study and develop novel adjuvants systems, which can be more stable, potent and safe. The development of synthetic carbohydrate chemistry can improve the study of carbohydrate-based adjuvants.

National HIV/AIDS mortality, prevalence, and incidence rates are associated with the Human Development Index.

PubMed

Lou, Li-Xia; Chen, Yi; Yu, Chao-Hui; Li, You-Ming; Ye, Juan

2014-10-01

HIV/AIDS is a worldwide threat to human health with mortality, prevalence, and incidence rates varying widely. We evaluated the association between the global HIV/AIDS epidemic and national socioeconomic development. We obtained global age-standardized HIV/AIDS mortality, prevalence, and incidence rates from World Health Statistics Report of the World Health Organization. The human development indexes (HDIs) of 141 countries were obtained from a Human Development Report. Countries were divided into 4 groups according to the HDI distribution. We explored the association between HIV/AIDS epidemic and HDI information using Spearman correlation analysis, regression analysis, and the Kruskal-Wallis test. HIV/AIDS mortality, prevalence, and incidence rates were inversely correlated with national HDI (r = -0.675, -0.519, and -0.398, respectively; P < .001), as well as the 4 indicators of HDI (ie, life expectancy at birth, mean years of schooling, expected years of schooling, and gross national income per capita). Low HDI countries had higher HIV/AIDS mortality, prevalence, and incidence rates than that of medium, high, and very high HDI countries. Quantile regression results indicated that HDI had a greater negative effect on the HIV/AIDS epidemic in countries with more severe HIV/AIDS epidemic. Less-developed countries are likely to have more severe HIV/AIDS epidemic. There is a need to pay more attention to HIV/AIDS control in less-developed countries, where lower socioeconomic status might have accelerated the HIV/AIDS epidemic more rapidly. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Construction of human antibody gene libraries and selection of antibodies by phage display.

PubMed

Frenzel, André; Kügler, Jonas; Wilke, Sonja; Schirrmann, Thomas; Hust, Michael

2014-01-01

Antibody phage display is the most commonly used in vitro selection technology and has yielded thousands of useful antibodies for research, diagnostics, and therapy.The prerequisite for successful generation and development of human recombinant antibodies using phage display is the construction of a high-quality antibody gene library. Here, we describe the methods for the construction of human immune and naive scFv gene libraries.The success also depends on the panning strategy for the selection of binders from these libraries. In this article, we describe a panning strategy that is high-throughput compatible and allows parallel selection in microtiter plates.

Observation of human embryonic behavior in vitro by high-resolution time-lapse cinematography.

PubMed

Iwata, Kyoko; Mio, Yasuyuki

2016-07-01

Assisted reproductive technology (ART) has yielded vast amounts of information and knowledge on human embryonic development in vitro; however, still images provide limited data on dynamic changes in the developing embryos. Using our high-resolution time-lapse cinematography (hR-TLC) system, we were able to describe normal human embryonic development continuously from the fertilization process to the hatched blastocyst stage in detail. Our hR-TLC observation also showed the embryonic abnormality of a third polar body (PB)-like substance likely containing a small pronucleus being extruded and resulting in single-pronucleus (1PN) formation, while our molecular biological investigations suggested the possibility that some 1PN embryos could be diploid, carrying both maternal and paternal genomes. Furthermore, in some embryos the extruded third PB-like substance was eventually re-absorbed into the ooplasm resulting in the formation of an uneven-sized, two-PN zygote. In addition, other hR-TLC observations showed that cytokinetic failure was correlated with equal-sized, multi-nucleated blastomeres that were also observed in the embryo showing early initiation of compaction. Assessment combining our hR-TLC with molecular biological techniques enables a better understanding of embryonic development and potential improvements in ART outcomes.

Microbial metaproteomics for characterizing the range of metabolic functions and activities of human gut microbiota.

PubMed

Xiong, Weili; Abraham, Paul E; Li, Zhou; Pan, Chongle; Hettich, Robert L

2015-10-01

The human gastrointestinal tract is a complex, dynamic ecosystem that consists of a carefully tuned balance of human host and microbiota membership. The microbiome is not merely a collection of opportunistic parasites, but rather provides important functions to the host that are absolutely critical to many aspects of health, including nutrient transformation and absorption, drug metabolism, pathogen defense, and immune system development. Microbial metaproteomics provides the ability to characterize the human gut microbiota functions and metabolic activities at a remarkably deep level, revealing information about microbiome development and stability as well as their interactions with their human host. Generally, microbial and human proteins can be extracted and then measured by high performance MS-based proteomics technology. Here, we review the field of human gut microbiome metaproteomics, with a focus on the experimental and informatics considerations involved in characterizing systems ranging from low-complexity model gut microbiota in gnotobiotic mice, to the emerging gut microbiome in the GI tract of newborn human infants, and finally to an established gut microbiota in human adults. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Silicon as Versatile Player in Plant and Human Biology: Overlooked and Poorly Understood

PubMed Central

Farooq, Muhammad Ansar; Dietz, Karl-Josef

2015-01-01

Silicon (Si) serves as bioactive beneficial element. Si is highly abundant in soil, and occurs ubiquitously in all organisms including plants and humans. During the last three decades, nutritional significance of Si for plant and human health has received increasing attention. Plant Si plays a pivotal role in growth and development, and this beneficial effect depends usually on accumulation in plant tissues, which are then protected from various forms of biotic and abiotic stresses. Likewise, human exposure to Si imparts health benefits and essentially occurs through plant-derived food products. Si bioavailability in human diet, e.g., strengthens bones and improves immune response, as well as neuronal and connective tissue health. Despite this empiric knowledge, the essentiality of Si still remains enigmatic. Thus the link between Si availability for plant development and its profound implication for human welfare should receive attention. This review aims to provide a broad perspective on Si as important element for plant and human nutrition and to define research fields for interdisciplinary research. PMID:26617630

The role of human papillomavirus vaccines in cervical neoplasia.

PubMed

Stern, P L; Faulkner, R; Veranes, E C; Davidson, E J

2001-10-01

Cervical cancer is the second most common cause of cancer-related death in women, in some developing countries accounting for the highest cancer mortality. The evidence for the association of high-risk human papillomavirus types with the aetiology of cervical neoplasia is firmly established, human papillomavirus being detected in virtually all cervical cancers. The risk of progression of precursor cervical intra-epithelial neoplasia lesions is associated with persistence of human papillomavirus infection. One strategy for the management of cervical neoplasia worldwide could be the development of prophylactic and/or therapeutic human papillomavirus vaccines. This chapter will discuss the natural history of human papillomavirus infection, viral immunity and the clinical course of resultant disease as the background to the effective design and use of human papillomavirus vaccines for protection or therapy. The progress of ongoing phase I and II clinical trials for several different vaccine preparations and the challenges for establishing their future use will be discussed. Copyright 2001 Harcourt Publishers Ltd.

Methods for Determining the Level of Autonomy to Design into a Human Spaceflight Vehicle: A Function Specific Approach

NASA Technical Reports Server (NTRS)

Proud, Ryan W.; Hart, Jeremy J.; Mrozinski, Richard B.

2003-01-01

The next-generation human spaceflight vehicle is in a unique position to realize the benefits of more than thirty years of technological advancements since the Space Shuttle was designed. Computer enhancements, the emergence of highly reliable decision-making algorithms, and an emphasis on efficiency make an increased use of autonomous systems highly likely. NASA is in a position to take advantage of these advances and apply them to the human spaceflight environment. One of the key paradigm shifts will be the shift, where appropriate, of monitoring, option development, decision-making, and execution responsibility from humans to an Autonomous Flight Management (AFM) system. As an effort to reduce risk for development of an AFM system, NASA engineers are developing a prototype to prove the utility of previously untested autonomy concepts. This prototype, called SMART (Spacecraft Mission Assessment and Replanning Tool), is a functionally decomposed flight management system with an appropriate level of autonomy for each of its functions. As the development of SMART began, the most important and most often asked question was, How autonomous should an AFM system be? A thorough study of the literature through 2002 surrounding autonomous systems has not yielded a standard method for designing a level of autonomy into either a crewed vehicle or an uncrewed vehicle. The current focus in the literature on defining autonomy is centered on developing IQ tests for built systems. The literature that was analyzed assumes that the goal of all systems is to strive for complete autonomy from human intervention, rather than identifying how autonomous each function within the system should have been. In contrast, the SMART team developed a method for determining the appropriate level of autonomy to be designed into each function within a system. This paper summarizes the development of the Level of Autonomy Assessment Tool and its application to the SMART project.

United States trade and possible restrictions in high-technology products

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

Kreinin, M.E.

This paper assesses the changing US competitive position in high-technology products, and examines reasons for changes. It then inquires into the potential value of restrictive trade policies for promoting the US interest in this sector, including mutual restrictions between the US, the EC, and Japan. The paper shows that the US market share in most high-technology products, while still high, is declining. While industrial policy in other countries may have been a facilitating factor in this adverse development, the main explanation appears to lie in changing factor endowments, particularly the marked increase in the human capital/labor endowment ratios of Japanmore » and Germany relative to that of the US. When considering all the criteria relevant to trade policy, the differences between the high-technology industries bring into question the validity of lumping them into one sector for the purpose of strategic trade policy. Each industry needs to be treated separately. Their main common characteristic is intensity in human capital input. When they are viewed as one sector, a move to redress the declining US lead calls for a domestic rather than a trade policy: massive US investment in human capital and in research and development of the post-sputnik variety.« less

Hitting bacteria at the heart of the central dogma: sequence-specific inhibition.

PubMed

Rasmussen, Louise Carøe Vohlander; Sperling-Petersen, Hans Uffe; Mortensen, Kim Kusk

2007-08-10

An important objective in developing new drugs is the achievement of high specificity to maximize curing effect and minimize side-effects, and high specificity is an integral part of the antisense approach. The antisense techniques have been extensively developed from the application of simple long, regular antisense RNA (asRNA) molecules to highly modified versions conferring resistance to nucleases, stability of hybrid formation and other beneficial characteristics, though still preserving the specificity of the original nucleic acids. These new and improved second- and third-generation antisense molecules have shown promising results. The first antisense drug has been approved and more are in clinical trials. However, these antisense drugs are mainly designed for the treatment of different human cancers and other human diseases. Applying antisense gene silencing and exploiting RNA interference (RNAi) are highly developed approaches in many eukaryotic systems. But in bacteria RNAi is absent, and gene silencing by antisense compounds is not nearly as well developed, despite its great potential and the intriguing possibility of applying antisense molecules in the fight against multiresistant bacteria. Recent breakthrough and current status on the development of antisense gene silencing in bacteria including especially phosphorothioate oligonucleotides (PS-ODNs), peptide nucleic acids (PNAs) and phosphorodiamidate morpholino oligomers (PMOs) will be presented in this review.

A variety of human monoclonal antibodies against epidermal growth factor receptor isolated from a phage antibody library.

PubMed

Kurosawa, Gene; Kondo, Mariko; Kurosawa, Yoshikazu

2016-11-04

When the technology for constructing human antibody (Ab) libraries using a phage-display system was developed, many researchers in Ab-related fields anticipated that it would be widely applied to the development of pharmaceutical drugs against various diseases, including cancers. However, successful examples of such applications are very limited. Moreover, researchers who utilize phage-display technology now show divergent ways of thinking about phage Ab libraries. For example, there is debate about what should be the source of V H and V L genes for the construction of libraries to cover the whole repertoire of Abs present in the human body. In the immune system, the introduction of mutations into V genes followed by selection based on binding activity, termed Ab maturation, is required for the production of Abs exhibiting high affinity to the antigen (Ag). Therefore, introduction of mutations and selection are required for isolation of Abs with high affinity after isolation of clones from phage Ab libraries. We constructed a large human Ab library termed AIMS, developed a screening method termed ICOS, and succeeded in isolating many human monoclonal Abs (mAbs) that specifically and strongly bind to various tumor-associated Ags. Eight anti-EGFR mAbs were included, which we characterized. These mAbs showed various different activities against EGFR-expressing cancer cells. In this paper, we describe these data and discuss the possibility and necessity that the mAbs isolated from the AIMS library might be developed as therapeutic drugs against cancers without introduction of mutations. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Development of a SARS Coronavirus Vaccine from Recombinant Spike Protein Plus Delta Inulin Adjuvant.

PubMed

McPherson, Clifton; Chubet, Richard; Holtz, Kathy; Honda-Okubo, Yoshikazu; Barnard, Dale; Cox, Manon; Petrovsky, Nikolai

2016-01-01

Given periodic outbreaks of fatal human infections caused by coronaviruses, development of an optimal coronavirus vaccine platform capable of rapid production is an ongoing priority. This chapter describes the use of an insect cell expression system for rapid production of a recombinant vaccine against severe acute respiratory syndrome coronavirus (SARS). Detailed methods are presented for expression, purification, and release testing of SARS recombinant spike protein antigen, followed by adjuvant formulation and animal testing. The methods herein described for rapid development of a highly protective SARS vaccine are equally suited to rapid development of vaccines against other fatal human coronavirus infections, e.g., the MERS coronavirus.

Transformational Technologies to Expedite Space Access and Development

NASA Astrophysics Data System (ADS)

Rather, John D. G.

2010-01-01

Throughout history the emergence of new technologies has enabled unforeseen breakthrough capabilities that rapidly transformed the world. Some global examples from the twentieth century include AC electric power, nuclear energy, and turbojet engines. At the systems level, success of both Apollo and the Space Shuttle programs depended upon taming hydrogen propulsion and developing high-temperature atmospheric reentry materials. Human space development now is stymied because of a great need for breakthrough technologies and strategies. It is believed that new capabilities exist within the present states-of-the-art of superconducting technology that can be implemented to transform the future of human space development. This paper is an overview of three other papers presented within this forum, which summarizes the principles and consequences of StarTram, showing how the resulting breakthrough advantages can lead directly to safe space tourism and massive development of the moon, Mars and the outer solar system. StarTram can implement cost-effective solar power from space, simple utilization of asteroid material to protect humans from ionizing radiation, and effective defense of the Earth from devastating cosmic impacts. Synergistically, StarTram technologies will revolutionize ground transportation on the Earth, leading to enormous reduction in energy consumption and creation of millions of jobs. High energy lasers will also be discussed because of their importance to power beaming applications.

Challenges of Biobanking in South Africa to Facilitate Indigenous Research in an Environment Burdened with Human Immunodeficiency Virus, Tuberculosis, and Emerging Noncommunicable Diseases

PubMed Central

Christoffels, Alan; Grewal, Ravnit; Karam, Locunda A.; Rossouw, Catherine; Staunton, Ciara; Swanepoel, Carmen; van Rooyen, Beverley

2013-01-01

The high burden of infectious diseases and the growing problem of noncommunicable and metabolic disease syndromes in South Africa (SA) forces a more focused research approach to facilitate cutting-edge scientific growth and public health development. Increased SA research on these diseases and syndromes and the collection of associated biospecimens has ensured a plethora of biobanks created by individuals, albeit without the foresight of prospective and collective use by other local and international researchers. As the need for access to high-quality specimens in statistically relevant numbers has increased, so has the necessity for the development of national human biobanks in SA and across the Continent. The prospects of achieving sustainable centralized biobanks are still an emerging and evolving concept, primarily and recently driven by the launch of the H3Africa consortium, which includes the development of harmonized and standardized biobanking operating procedures. This process is hindered by a myriad of complex societal considerations and ethico-legal challenges. Efforts to consolidate and standardize biological sample collections are further compromised by the lack of full appreciation by national stakeholders of the biological value inherent in these collections, and the availability of high quality human samples with well-annotated data for future scientific research and development. Inadequate or nonexistent legislative structures that specifically regulate the storage, use, dispersal, and disposal of human biological samples are common phenomena and pose further challenges. Furthermore, concerns relating to consent for unspecified future uses, as well as access to information and data protection, are all new paradigms that require further consideration and public engagement. This article reviews important fundamental issues such as governance, ethics, infrastructure, and bioinformatics that are important foundational prerequisites for the establishment and evolution of successful human biobanking in South Africa. PMID:24835364

Exploration planning in the context of human exploration and development of the Moon

NASA Technical Reports Server (NTRS)

Duke, Michael B.; Morrison, Donald A.

1993-01-01

It is widely believed that the next step beyond low Earth orbit in attaining the United States' stated goal of 'Expanding human presence beyond the Earth' should be to reestablish a lunar capability, building on the Apollo program, and preparing the way for eventual human missions to Mars. The Moon offers important questions in planetary and Earth science, can provide a unique platform for making astronomical observations of high resolution and sensitivity, and can be in the development path for unlocking resources of the inner solar system to support space activities and return benefits to Earth. NASA's Office of Exploration has undertaken the planning of future lunar exploration missions with the assistance of the Solar System Exploration Division in matters dealing with the quality of scientific data and the manner in which it will be made available to the scientific community. The initial elements of the proposed program include the Lunar Scout missions, which consist of two small identical spacecraft in polar orbit around the Moon, which can accomplish most of the objectives associated with previous proposals for Lunar Polar Orbiters. These missions would be followed by 'Artemis' landers, capable of emplacing up to 200 kg payloads anywhere on the Moon. In addition, the exploration program must incorporate data obtained from other missions, including the Galileo lunar flybys, the Clementine high orbital observations, and Japanese penetrator missions. In the past year, a rather detailed plan for a 'First Lunar Outpost (FLO)' which would place 4 astronauts on the lunar surface for 45 days has been developed as a possible initial step of a renewed human exploration program. In the coming year, the FLO concept will be reviewed and evolved to become more highly integrated with planning for the initial human exploration of Mars, which could come perhaps 5 years after the reestablishment of lunar capability. Both programs could benefit from the common development of systems and subsystems, where that is sensible from a performance perspective.

Principles of establishing material cycling with a high degree of closure in the experimental model of a BTLSS intended for a rated "fraction of a human"

NASA Astrophysics Data System (ADS)

Tikhomirov, Alexander A.; Ushakova, Sofya; Velichko, Vladimir; Tikhomirova, Natalia; Shikhov, Valentin; Trifonov, Sergey V.

2016-07-01

A promising way to develop future biotechnical life support systems (BTLSS) is to construct experimental models and establish the cycling intended for a fraction of a human. Being of relatively low cost, such models provide an opportunity to test effectively closed process that could be further transferred to the real BTLSS with humans. Researchers of the IBP SB RAS are developing an adequate BTLSS model with the loops closed to a high degree. To attain high closure of mass exchange processes, plants in the phototrophic compartment are cultivated under intensive lighting conditions, created by using modern LED irradiators of enhanced power, equipped with lens optics. The higher plant compartment has been renewed and broadened by including soybean plants, which improve the vegetable part of the human diet and make it more diverse. It is very important that the operation of the physicochemical installation for waste mineralization fully matches the composition of the atmosphere of plant growth chambers: the purified gaseous components of this installation enter the common atmosphere of the system, without causing any deviations from the norm in the gaseous composition. This proves the eco-friendliness of the developed physicochemical method of waste mineralization and shows that the gaseous components resulting from waste mineralization can be included in the system mass exchange. A system for including human respiration into the gas exchange of the BTLSS has been developed and tested; the associated gas exchange and water exchange dynamics have been analyzed. Results of the functioning of the experimental model of the BTLSS for several months are proposed for discussion in order to get insight into the formation of dynamic characteristics of cycling processes and factors determining them. The study was supported by the grant of the Russian Science Foundation (Project 14-14-00599) and carried out at the IBP SB RAS.

Trends in the application of high-resolution mass spectrometry for human biomonitoring: An analytical primer to studying the environmental chemical space of the human exposome.

PubMed

Andra, Syam S; Austin, Christine; Patel, Dhavalkumar; Dolios, Georgia; Awawda, Mahmoud; Arora, Manish

2017-03-01

Global profiling of xenobiotics in human matrices in an untargeted mode is gaining attention for studying the environmental chemical space of the human exposome. Defined as the study of a comprehensive inclusion of environmental influences and associated biological responses, human exposome science is currently evolving out of the metabolomics science. In analogy to the latter, the development and applications of high resolution mass spectrometry (HRMS) has shown potential and promise to greatly expand our ability to capture the broad spectrum of environmental chemicals in exposome studies. HRMS can perform both untargeted and targeted analysis because of its capability of full- and/or tandem-mass spectrum acquisition at high mass accuracy with good sensitivity. The collected data from target, suspect and non-target screening can be used not only for the identification of environmental chemical contaminants in human matrices prospectively but also retrospectively. This review covers recent trends and advances in this field. We focus on advances and applications of HRMS in human biomonitoring studies, and data acquisition and mining. The acquired insights provide stepping stones to improve understanding of the human exposome by applying HRMS, and the challenges and prospects for future research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Agonistic Human Antibodies Binding to Lecithin-Cholesterol Acyltransferase Modulate High Density Lipoprotein Metabolism*

PubMed Central

Gunawardane, Ruwanthi N.; Fordstrom, Preston; Piper, Derek E.; Masterman, Stephanie; Siu, Sophia; Liu, Dongming; Brown, Mike; Lu, Mei; Tang, Jie; Zhang, Richard; Cheng, Janet; Gates, Andrew; Meininger, David; Chan, Joyce; Carlson, Tim; Walker, Nigel; Schwarz, Margrit; Delaney, John; Zhou, Mingyue

2016-01-01

Drug discovery opportunities where loss-of-function alleles of a target gene link to a disease-relevant phenotype often require an agonism approach to up-regulate or re-establish the activity of the target gene. Antibody therapy is increasingly recognized as a favored drug modality due to multiple desirable pharmacological properties. However, agonistic antibodies that enhance the activities of the target enzymes are rarely developed because the discovery of agonistic antibodies remains elusive. Here we report an innovative scheme of discovery and characterization of human antibodies capable of binding to and agonizing a circulating enzyme lecithin cholesterol acyltransferase (LCAT). Utilizing a modified human LCAT protein with enhanced enzymatic activity as an immunogen, we generated fully human monoclonal antibodies using the XenoMouseTM platform. One of the resultant agonistic antibodies, 27C3, binds to and substantially enhances the activity of LCAT from humans and cynomolgus macaques. X-ray crystallographic analysis of the 2.45 Å LCAT-27C3 complex shows that 27C3 binding does not induce notable structural changes in LCAT. A single administration of 27C3 to cynomolgus monkeys led to a rapid increase of plasma LCAT enzymatic activity and a 35% increase of the high density lipoprotein cholesterol that was observed up to 32 days after 27C3 administration. Thus, this novel scheme of immunization in conjunction with high throughput screening may represent an effective strategy for discovering agonistic antibodies against other enzyme targets. 27C3 and other agonistic human anti-human LCAT monoclonal antibodies described herein hold potential for therapeutic development for the treatment of dyslipidemia and cardiovascular disease. PMID:26644477

Molecular Epidemiology and Strain Comparison between Hepatitis E Viruses in Human Sera and Pig Livers during 2014 to 2016 in Hong Kong.

PubMed

Chan, Martin C W; Kwok, Kirsty; Hung, Tin-Nok; Chan, Paul K S

2017-05-01

Hepatitis E virus (HEV) causes substantial morbidity and mortality in developing countries and is considered an emerging foodborne pathogen in developed countries in which it was previously not endemic. To investigate genetic association between human HEV infection and HEV-contaminated high-risk food in Hong Kong, we compared local virus strains obtained from hepatitis E patient sera with those surveyed from high-risk food items during 2014 to 2016. Twenty-four cases of laboratory-confirmed human HEV infections were identified from January 2014 to March 2016 in our hospitals. Five types of food items at risk of HEV contamination were purchased on a biweekly basis from April 2014 to March 2016 in two local market settings: supermarkets (lamb, oyster, and pig liver) and wet markets (oyster, pig blood curd, pig large intestine, and pig liver). HEV RNA detection was performed by a real-time reverse transcription-PCR assay. HEV RNA was detected in pig liver, pig intestine, and oyster samples with prevalences of 1.5%, 0.4%, and 0.2%, respectively. Neighbor-joining phylogenetic inference showed that all human and swine HEV strains belonged to genotype 4. HEV subtype distributions in humans and swine were highly comparable: subtype 4b predominated, while subtype 4d was the minority. Local human and swine HEV genotype 4 strains shared over 95% nucleotide identity and were genetically very similar, implicating swine as an important foodborne source of autochthonous human HEV infections in Hong Kong. Action should be taken to raise the awareness among public and health care professionals of hepatitis E as an emerging foodborne disease. Copyright © 2017 American Society for Microbiology.

The German VR Simulation Realism Scale--psychometric construction for virtual reality applications with virtual humans.

PubMed

Poeschl, Sandra; Doering, Nicola

2013-01-01

Virtual training applications with high levels of immersion or fidelity (for example for social phobia treatment) produce high levels of presence and therefore belong to the most successful Virtual Reality developments. Whereas display and interaction fidelity (as sub-dimensions of immersion) and their influence on presence are well researched, realism of the displayed simulation depends on the specific application and is therefore difficult to measure. We propose to measure simulation realism by using a self-report questionnaire. The German VR Simulation Realism Scale for VR training applications was developed based on a translation of scene realism items from the Witmer-Singer-Presence Questionnaire. Items for realism of virtual humans (for example for social phobia training applications) were supplemented. A sample of N = 151 students rated simulation realism of a Fear of Public Speaking application. Four factors were derived by item- and principle component analysis (Varimax rotation), representing Scene Realism, Audience Behavior, Audience Appearance and Sound Realism. The scale developed can be used as a starting point for future research and measurement of simulation realism for applications including virtual humans.

Development of a bespoke human factors taxonomy for gliding accident analysis and its revelations about highly inexperienced UK glider pilots.

PubMed

Jarvis, Steve; Harris, Don

2010-02-01

Low-hours solo glider pilots have a high risk of accidents compared to more experienced pilots. Numerous taxonomies for causal accident analysis have been produced for powered aviation but none of these is suitable for gliding, so a new taxonomy was required. A human factors taxonomy specifically for glider operations was developed and used to analyse all UK gliding accidents from 2002 to 2006 for their overall causes as well as factors specific to low hours pilots. Fifty-nine categories of pilot-related accident causation emerged, which were formed into progressively larger categories until four overall human factors groups were arrived at: 'judgement'; 'handling'; 'strategy'; 'attention'. 'Handling' accounted for a significantly higher proportion of injuries than other categories. Inexperienced pilots had considerably more accidents in all categories except 'strategy'. Approach control (path judgement, airbrake and speed handling) as well as landing flare misjudgement were chiefly responsible for the high accident rate in early solo glider pilots. Statement of Relevance: This paper uses extant accident data to produce a taxonomy of underlying human factors causes to analyse gliding accidents and identify the specific causes associated with low hours pilots. From this specific, well-targeted remedial measures can be identified.

Development of high-yield influenza B virus vaccine viruses

PubMed Central

Ping, Jihui; Lopes, Tiago J. S.; Neumann, Gabriele; Kawaoka, Yoshihiro

2016-01-01

The burden of human infections with influenza A and B viruses is substantial, and the impact of influenza B virus infections can exceed that of influenza A virus infections in some seasons. Over the past few decades, viruses of two influenza B virus lineages (Victoria and Yamagata) have circulated in humans, and both lineages are now represented in influenza vaccines, as recommended by the World Health Organization. Influenza B virus vaccines for humans have been available for more than half a century, yet no systematic efforts have been undertaken to develop high-yield candidates. Therefore, we screened virus libraries possessing random mutations in the six “internal” influenza B viral RNA segments [i.e., those not encoding the major viral antigens, hemagglutinin (HA) and neuraminidase NA)] for mutants that confer efficient replication. Candidate viruses that supported high yield in cell culture were tested with the HA and NA genes of eight different viruses of the Victoria and Yamagata lineages. We identified combinations of mutations that increased the titers of candidate vaccine viruses in mammalian cells used for human influenza vaccine virus propagation and in embryonated chicken eggs, the most common propagation system for influenza viruses. These influenza B virus vaccine backbones can be used for improved vaccine virus production. PMID:27930325

Magnetic dispersive solid-phase extraction based on modified magnetic nanoparticles for the detection of cocaine and cocaine metabolites in human urine by high-performance liquid chromatography-mass spectrometry.

PubMed

Yang, Feiyu; Zou, Yun; Ni, Chunfang; Wang, Rong; Wu, Min; Liang, Chen; Zhang, Jiabin; Yuan, Xiaoliang; Liu, Wenbin

2017-11-01

An easy-to-handle magnetic dispersive solid-phase extraction procedure was developed for preconcentration and extraction of cocaine and cocaine metabolites in human urine. Divinyl benzene and vinyl pyrrolidone functionalized silanized Fe 3 O 4 nanoparticles were synthesized and used as adsorbents in this procedure. Scanning electron microscopy, vibrating sample magnetometry, and infrared spectroscopy were employed to characterize the modified adsorbents. A high-performance liquid chromatography with mass spectrometry method for determination of cocaine and its metabolites in human urine sample has been developed with pretreatment of the samples by magnetic dispersive solid-phase extraction. The obtained results demonstrated the higher extraction capacity of the prepared nanoparticles with recoveries between 75.1 to 105.7% and correlation coefficients higher than 0.9971. The limits of detection for the cocaine and cocaine metabolites were 0.09-1.10 ng/mL. The proposed magnetic dispersive solid-phase extraction method provided a rapid, environmentally friendly and magnetic stuff recyclable approach and it was confirmed that the prepared adsorbents material was a kind of highly effective extraction materials for the trace cocaine and cocaine metabolites analyses in human urine. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development of high-yield influenza B virus vaccine viruses.

PubMed

Ping, Jihui; Lopes, Tiago J S; Neumann, Gabriele; Kawaoka, Yoshihiro

2016-12-20

The burden of human infections with influenza A and B viruses is substantial, and the impact of influenza B virus infections can exceed that of influenza A virus infections in some seasons. Over the past few decades, viruses of two influenza B virus lineages (Victoria and Yamagata) have circulated in humans, and both lineages are now represented in influenza vaccines, as recommended by the World Health Organization. Influenza B virus vaccines for humans have been available for more than half a century, yet no systematic efforts have been undertaken to develop high-yield candidates. Therefore, we screened virus libraries possessing random mutations in the six "internal" influenza B viral RNA segments [i.e., those not encoding the major viral antigens, hemagglutinin (HA) and neuraminidase NA)] for mutants that confer efficient replication. Candidate viruses that supported high yield in cell culture were tested with the HA and NA genes of eight different viruses of the Victoria and Yamagata lineages. We identified combinations of mutations that increased the titers of candidate vaccine viruses in mammalian cells used for human influenza vaccine virus propagation and in embryonated chicken eggs, the most common propagation system for influenza viruses. These influenza B virus vaccine backbones can be used for improved vaccine virus production.

Human Factors Tools for Improving Simulation Activities in Continuing Medical Education

ERIC Educational Resources Information Center

Seagull, F. Jacob

2012-01-01

Human factors (HF) is a discipline often drawn upon when there is a need to train people to perform complex, high-stakes tasks and effectively assess their performance. Complex tasks often present unique challenges for training and assessment. HF has developed specialized techniques that have been effective in overcoming several of these…

Meta-QTL analysis of seed iron and zinc concentration in common bean (Phaseolus vulgaris L.)

USDA-ARS?s Scientific Manuscript database

Common bean (Phaseolus vulgaris L.) is the most important legume for human consumption worldwide and it is an important source of microelements, especially iron and zinc. Bean biofortification programs develop new varieties with high levels of Fe and Zn targeted for countries with human micronutrien...

Statistical methods for analysing responses of wildlife to human disturbance

Treesearch

Haiganoush K. Preisler; Alan A. Ager; Michael J. Wisdom

2006-01-01

Off-road recreation is increasing rapidly in many areas of the world, and effects on wildlife can be highly detrimental. Consequently, we have developed methods for studying wildlife responses to off-road recreation with the use of new technologies that allow frequent and accurate monitoring of human-wildlife interactions. To...

Human Resources Administration: A School-Based Perspective. Fourth Edition

ERIC Educational Resources Information Center

Smith, Richard

2009-01-01

Enhanced and updated, this Fourth Edition of Richard E. Smith's highly successful text examines the growing role of the principal in planning, hiring, staff development, supervision, and other human resource functions. The Fourth Edition includes new sections on ethics, induction, and the role of the mentor teacher. This edition also introduces…

Using four capitals to assess watershed sustainability.

PubMed

Pérez-Maqueo, Octavio; Martinez, M Luisa; Vázquez, Gabriela; Equihua, Miguel

2013-03-01

The La Antigua watershed drains into the Gulf of Mexico and can be considered as one of the most important areas in Mexico because of its high productivity, history, and biodiversity, although poverty remains high in the area in spite of these positive attributes. In this study, we performed an integrated assessment of the watershed to recommend a better direction toward a sustainable management in which the four capitals (natural, human, social, and built) are balanced. We contrasted these four capitals in the municipalities of the upper, middle and lower watershed and found that natural capital (natural ecosystems and ecosystem services) was higher in the upper and middle watershed, while human and social capitals (literacy, health, education and income) were generally higher downstream. Overall, Human Development Index was negatively correlated with the percentage of natural ecosystems in the watershed, especially in the upper and lower watershed regions. Our results indicate that natural capital must be fully considered in projections for increasing human development, so that natural resources can be preserved and managed adequately while sustaining intergenerational well-being.

Using Four Capitals to Assess Watershed Sustainability

NASA Astrophysics Data System (ADS)

Pérez-Maqueo, Octavio; Martinez, M. Luisa; Vázquez, Gabriela; Equihua, Miguel

2013-03-01

The La Antigua watershed drains into the Gulf of Mexico and can be considered as one of the most important areas in Mexico because of its high productivity, history, and biodiversity, although poverty remains high in the area in spite of these positive attributes. In this study, we performed an integrated assessment of the watershed to recommend a better direction toward a sustainable management in which the four capitals (natural, human, social, and built) are balanced. We contrasted these four capitals in the municipalities of the upper, middle and lower watershed and found that natural capital (natural ecosystems and ecosystem services) was higher in the upper and middle watershed, while human and social capitals (literacy, health, education and income) were generally higher downstream. Overall, Human Development Index was negatively correlated with the percentage of natural ecosystems in the watershed, especially in the upper and lower watershed regions. Our results indicate that natural capital must be fully considered in projections for increasing human development, so that natural resources can be preserved and managed adequately while sustaining intergenerational well-being.

Ultrasensitive and Highly Stable Resistive Pressure Sensors with Biomaterial-Incorporated Interfacial Layers for Wearable Health-Monitoring and Human-Machine Interfaces.

PubMed

Chang, Hochan; Kim, Sungwoong; Jin, Sumin; Lee, Seung-Woo; Yang, Gil-Tae; Lee, Ki-Young; Yi, Hyunjung

2018-01-10

Flexible piezoresistive sensors have huge potential for health monitoring, human-machine interfaces, prosthetic limbs, and intelligent robotics. A variety of nanomaterials and structural schemes have been proposed for realizing ultrasensitive flexible piezoresistive sensors. However, despite the success of recent efforts, high sensitivity within narrower pressure ranges and/or the challenging adhesion and stability issues still potentially limit their broad applications. Herein, we introduce a biomaterial-based scheme for the development of flexible pressure sensors that are ultrasensitive (resistance change by 5 orders) over a broad pressure range of 0.1-100 kPa, promptly responsive (20 ms), and yet highly stable. We show that employing biomaterial-incorporated conductive networks of single-walled carbon nanotubes as interfacial layers of contact-based resistive pressure sensors significantly enhances piezoresistive response via effective modulation of the interlayer resistance and provides stable interfaces for the pressure sensors. The developed flexible sensor is capable of real-time monitoring of wrist pulse waves under external medium pressure levels and providing pressure profiles applied by a thumb and a forefinger during object manipulation at a low voltage (1 V) and power consumption (<12 μW). This work provides a new insight into the material candidates and approaches for the development of wearable health-monitoring and human-machine interfaces.

The European AntibotABE Framework Program and Its Update: Development of Innovative Botulinum Antibodies

PubMed Central

Avril, Arnaud; Miethe, Sebastian; Derman, Yagmur; Selby, Katja; Thullier, Philippe; Pelat, Thibaut; Urbain, Remi; Korkeala, Hannu; Sesardic, Dorothea; Popoff, Michel R.

2017-01-01

The goal of the AntiBotABE Program was the development of recombinant antibodies that neutralize botulinum neurotoxins (BoNT) A, B and E. These serotypes are lethal and responsible for most human botulinum cases. To improve therapeutic efficacy, the heavy and light chains (HC and LC) of the three BoNT serotypes were targeted to achieve a synergistic effect (oligoclonal antibodies). For antibody isolation, macaques were immunized with the recombinant and non-toxic BoNT/A, B or E, HC or LC, followed by the generation of immune phage-display libraries. Antibodies were selected from these libraries against the holotoxin and further analyzed in in vitro and ex vivo assays. For each library, the best ex vivo neutralizing antibody fragments were germline-humanized and expressed as immunoglobulin G (IgGs). The IgGs were tested in vivo, in a standardized model of protection, and challenged with toxins obtained from collections of Clostridium strains. Protective antibody combinations against BoNT/A and BoNT/B were evidenced and for BoNT/E, the anti-LC antibody alone was found highly protective. The combination of these five antibodies as an oligoclonal antibody cocktail can be clinically and regulatorily developed while their high “humanness” predicts a high tolerance in humans. PMID:28974033

Laboratory Directed Research and Development Program

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

Ogeka, G.J.; Romano, A.J.

This report briefly discusses the following research: Advances in Geoexploration; Transvenous Coronary Angiography with Synchrotron X-Rays; Borehole Measurements of Global Warming; Molecular Ecology: Development of Field Methods for Microbial Growth Rate and Activity Measurements; A New Malaria Enzyme - A Potential Source for a New Diagnostic Test for Malaria and a Target for a New Antimalarial Drug; Basic Studies on Thoron and Thoron Precursors; Cloning of the cDNA for a Human Serine/Threonine Protein Kinase that is Activated Specifically by Double-Stranded DNA; Development of an Ultra-Fast Laser System for Accelerator Applications; Cluster Impact Fusion; Effect of a Bacterial Spore Protein onmore » Mutagenesis; Structure and Function of Adenovirus Penton Base Protein; High Resolution Fast X-Ray Detector; Coherent Synchrotron Radiation Longitudinal Bunch Shape Monitor; High Grain Harmonic Generation Experiment; BNL Maglev Studies; Structural Investigations of Pt-Based Catalysts; Studies on the Cellular Toxicity of Cocaine and Cocaethylene; Human Melanocyte Transformation; Exploratory Applications of X-Ray Microscopy; Determination of the Higher Ordered Structure of Eukaryotic Chromosomes; Uranium Neutron Capture Therapy; Tunneling Microscopy Studies of Nanoscale Structures; Nuclear Techiques for Study of Biological Channels; RF Sources for Accelerator Physics; Induction and Repair of Double-Strand Breaks in the DNA of Human Lymphocytes; and An EBIS Source of High Charge State Ions up to Uranium.« less

Laboratory Directed Research and Development Program. Annual report

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

Ogeka, G.J.; Romano, A.J.

This report briefly discusses the following research: Advances in Geoexploration; Transvenous Coronary Angiography with Synchrotron X-Rays; Borehole Measurements of Global Warming; Molecular Ecology: Development of Field Methods for Microbial Growth Rate and Activity Measurements; A New Malaria Enzyme - A Potential Source for a New Diagnostic Test for Malaria and a Target for a New Antimalarial Drug; Basic Studies on Thoron and Thoron Precursors; Cloning of the cDNA for a Human Serine/Threonine Protein Kinase that is Activated Specifically by Double-Stranded DNA; Development of an Ultra-Fast Laser System for Accelerator Applications; Cluster Impact Fusion; Effect of a Bacterial Spore Protein onmore » Mutagenesis; Structure and Function of Adenovirus Penton Base Protein; High Resolution Fast X-Ray Detector; Coherent Synchrotron Radiation Longitudinal Bunch Shape Monitor; High Grain Harmonic Generation Experiment; BNL Maglev Studies; Structural Investigations of Pt-Based Catalysts; Studies on the Cellular Toxicity of Cocaine and Cocaethylene; Human Melanocyte Transformation; Exploratory Applications of X-Ray Microscopy; Determination of the Higher Ordered Structure of Eukaryotic Chromosomes; Uranium Neutron Capture Therapy; Tunneling Microscopy Studies of Nanoscale Structures; Nuclear Techiques for Study of Biological Channels; RF Sources for Accelerator Physics; Induction and Repair of Double-Strand Breaks in the DNA of Human Lymphocytes; and An EBIS Source of High Charge State Ions up to Uranium.« less

Morphometric Characterization of Rat and Human Alveolar Macrophage Cell Models and their Response to Amiodarone using High Content Image Analysis.

PubMed

Hoffman, Ewelina; Patel, Aateka; Ball, Doug; Klapwijk, Jan; Millar, Val; Kumar, Abhinav; Martin, Abigail; Mahendran, Rhamiya; Dailey, Lea Ann; Forbes, Ben; Hutter, Victoria

2017-12-01

Progress to the clinic may be delayed or prevented when vacuolated or "foamy" alveolar macrophages are observed during non-clinical inhalation toxicology assessment. The first step in developing methods to study this response in vitro is to characterize macrophage cell lines and their response to drug exposures. Human (U937) and rat (NR8383) cell lines and primary rat alveolar macrophages obtained by bronchoalveolar lavage were characterized using high content fluorescence imaging analysis quantification of cell viability, morphometry, and phospholipid and neutral lipid accumulation. Cell health, morphology and lipid content were comparable (p < 0.05) for both cell lines and the primary macrophages in terms of vacuole number, size and lipid content. Responses to amiodarone, a known inducer of phospholipidosis, required analysis of shifts in cell population profiles (the proportion of cells with elevated vacuolation or lipid content) rather than average population data which was insensitive to the changes observed. A high content image analysis assay was developed and used to provide detailed morphological characterization of rat and human alveolar-like macrophages and their response to a phospholipidosis-inducing agent. This provides a basis for development of assays to predict or understand macrophage vacuolation following inhaled drug exposure.

Physiological level production of antigen-specific human immunoglobulin in cloned transchromosomic cattle.

PubMed

Sano, Akiko; Matsushita, Hiroaki; Wu, Hua; Jiao, Jin-An; Kasinathan, Poothappillai; Sullivan, Eddie J; Wang, Zhongde; Kuroiwa, Yoshimi

2013-01-01

Therapeutic human polyclonal antibodies (hpAbs) derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc) cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH) and kappa-chain (hIGK) germline loci (named as κHAC) are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO). However, B lymphocyte development in these Tc cattle is compromised, and the overall production of hpAbs is low. Here, we report the construction of an improved HAC, designated as cKSL-HACΔ, by incorporating all of the human immunoglobulin germline loci into the HAC. Furthermore, for avoiding the possible human-bovine interspecies incompatibility between the human immunoglobulin mu chain protein (hIgM) and bovine transmembrane α and β immunoglobulins (bIgα and bIgβ) in the pre-B cell receptor (pre-BCR) complex, we partially replaced (bovinized) the hIgM constant domain with the counterpart of bovine IgM (bIgM) that is involved in the interaction between bIgM and bIgα/Igβ; human IgM bovinization would also improve the functionality of hIgM in supporting B cell activation and proliferation. We also report the successful production of DKO Tc cattle carrying the cKSL-HACΔ (cKSL-HACΔ/DKO), the dramatic improvement of B cell development in these cattle and the high level production of hpAbs (as measured for the human IgG isotype) in the plasma. We further demonstrate that, upon immunization by tumor immunogens, high titer tumor immunogen-specific human IgG (hIgG) can be produced from such Tc cattle.

EGFR gene overexpression retained in an invasive xenograft model by solid orthotopic transplantation of human glioblastoma multiforme into nude mice.

PubMed

Yi, Diao; Hua, Tian Xin; Lin, Huang Yan

2011-03-01

Orthotopic xenograft animal model from human glioblastoma multiforme (GBM) cell lines often do not recapitulate an extremely important aspect of invasive growth and epidermal growth factor receptor (EGFR) gene overexpression of human GBM. We developed an orthotopic xenograft model by solid transplantation of human GBM into the brain of nude mouse. The orthotopic xenografts sharing the same histopathological features with their original human GBMs were highly invasive and retained the overexpression of EGFR gene. The murine orthotopic GBM models constitute a valuable in vivo system for preclinical studies to test novel therapies for human GBM.

Genes uniquely expressed in human growth plate chondrocytes uncover a distinct regulatory network.

PubMed

Li, Bing; Balasubramanian, Karthika; Krakow, Deborah; Cohn, Daniel H

2017-12-20

Chondrogenesis is the earliest stage of skeletal development and is a highly dynamic process, integrating the activities and functions of transcription factors, cell signaling molecules and extracellular matrix proteins. The molecular mechanisms underlying chondrogenesis have been extensively studied and multiple key regulators of this process have been identified. However, a genome-wide overview of the gene regulatory network in chondrogenesis has not been achieved. In this study, employing RNA sequencing, we identified 332 protein coding genes and 34 long non-coding RNA (lncRNA) genes that are highly selectively expressed in human fetal growth plate chondrocytes. Among the protein coding genes, 32 genes were associated with 62 distinct human skeletal disorders and 153 genes were associated with skeletal defects in knockout mice, confirming their essential roles in skeletal formation. These gene products formed a comprehensive physical interaction network and participated in multiple cellular processes regulating skeletal development. The data also revealed 34 transcription factors and 11,334 distal enhancers that were uniquely active in chondrocytes, functioning as transcriptional regulators for the cartilage-selective genes. Our findings revealed a complex gene regulatory network controlling skeletal development whereby transcription factors, enhancers and lncRNAs participate in chondrogenesis by transcriptional regulation of key genes. Additionally, the cartilage-selective genes represent candidate genes for unsolved human skeletal disorders.

Quantitative Developments of Biomolecular Databases, Measurement Methodology, and Comprehensive Transport Models for Bioanalytical Microfluidics

DTIC Science & Technology

2006-10-01

Gibbs, E. M., Fletterick, R. J., Day, Y. S. N., Myszka, D. G., and Rath, V. L. (2002) “Structure-activity analysis of the purine-binding site of human ...Rich, R. L., Day, Y. S. N., Morton, T. A., and Myszka, D. G., (2001) “High- resolution and high-throughput protocols for measuring drug/ human serum...entire text) 1. Attard, P., Images of nanobubbles on hydrophobic surfaces and their interactions. Phys. Rev. Lett., 2001. 87. 2. Ottino, J.M

Human guidance of mobile robots in complex 3D environments using smart glasses

NASA Astrophysics Data System (ADS)

Kopinsky, Ryan; Sharma, Aneesh; Gupta, Nikhil; Ordonez, Camilo; Collins, Emmanuel; Barber, Daniel

2016-05-01

In order for humans to safely work alongside robots in the field, the human-robot (HR) interface, which enables bi-directional communication between human and robot, should be able to quickly and concisely express the robot's intentions and needs. While the robot operates mostly in autonomous mode, the human should be able to intervene to effectively guide the robot in complex, risky and/or highly uncertain scenarios. Using smart glasses such as Google Glass∗, we seek to develop an HR interface that aids in reducing interaction time and distractions during interaction with the robot.

Multifunctional devices based on SnO2@rGO-coated fibers for human motion monitoring, ethanol detection, and photo response

NASA Astrophysics Data System (ADS)

Mi, Qing; Wang, Qi; Zang, Siyao; Chai, Zhaoer; Zhang, Jinnan; Ren, Xiaomin

2018-05-01

In this study, we developed a multifunctional device based on SnO2@rGO-coated fibers utilizing plasma treatment, dip coating, and microwave irradiation in sequence, and finally realized highly sensitive human motion monitoring, relatively good ethanol detection, and an obvious photo response. Moreover, the high level of comfort and compactness derived from highly elastic and comfortable fabrics contributes to the long-term availability and test accuracy. As an attempt at multifunctional integration of smart clothing, this work provides an attractive and relatively practical research direction.

Multifunctional devices based on SnO2@rGO-coated fibers for human motion monitoring, ethanol detection, and photo response.

PubMed

Mi, Qing; Wang, Qi; Zang, Siyao; Chai, Zhaoer; Zhang, Jinnan; Ren, Xiaomin

2018-05-11

In this study, we developed a multifunctional device based on SnO 2 @rGO-coated fibers utilizing plasma treatment, dip coating, and microwave irradiation in sequence, and finally realized highly sensitive human motion monitoring, relatively good ethanol detection, and an obvious photo response. Moreover, the high level of comfort and compactness derived from highly elastic and comfortable fabrics contributes to the long-term availability and test accuracy. As an attempt at multifunctional integration of smart clothing, this work provides an attractive and relatively practical research direction.

Clean water, clean hands or new vaccines?

PubMed

Luby, Stephen P

2017-06-01

Throughout human history, pathogens transmitted through feces from person to person have caused substantial mortality. Over a century ago civil engineers in high income countries developed approaches to collect and remove feces from the environment that in communities with high incomes and strong governments markedly reduced the burden of enteric disease. These approaches, however, have not been successfully extended to impoverished communities in low income countries. Water/sanitation/hygiene professionals have attempted, with only limited success, to reduce fecal exposure and human disease in the absence of definitive civil engineering approaches. Medical professionals have worked to develop vaccines against some of the most important fecal oral pathogens. Each of these approaches needs further development and adaptation to optimally address the burden of fecally transmitted diseases in impoverished communities. © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

U.S. Army Medical Department Journal (January-March 2004)

DTIC Science & Technology

2004-03-01

posted is relevant to both audiences. Posted information includes: (1) a warning against human use of flea and tick collars meant for animals; (2...Radiologic Chemistry team of the Center’s Directorate of Laboratory Sciences has developed a highly sensitive method for detecting depleted uranium in human ...Disease,” and the human form of the disease variant Creutzfeld-Jacob Disease (vCJD).1 At the time, European health officials were growing increasingly

Hypercholesterolemia induces T cell expansion in humanized immune mice.

PubMed

Proto, Jonathan D; Doran, Amanda C; Subramanian, Manikandan; Wang, Hui; Zhang, Mingyou; Sozen, Erdi; Rymond, Christina C; Kuriakose, George; D'Agati, Vivette; Winchester, Robert; Sykes, Megan; Yang, Yong-Guang; Tabas, Ira

2018-06-01

Emerging data suggest that hypercholesterolemia has stimulatory effects on adaptive immunity and that these effects can promote atherosclerosis and perhaps other inflammatory diseases. However, research in this area has relied primarily on inbred strains of mice whose adaptive immune system can differ substantially from that of humans. Moreover, the genetically induced hypercholesterolemia in these models typically results in plasma cholesterol levels that are much higher than those in most humans. To overcome these obstacles, we studied human immune system-reconstituted mice (hu-mice) rendered hypercholesterolemic by treatment with adeno-associated virus 8-proprotein convertase subtilisin/kexin type 9 (AAV8-PCSK9) and a high-fat/high-cholesterol Western-type diet (WD). These mice had a high percentage of human T cells and moderate hypercholesterolemia. Compared with hu-mice that had lower plasma cholesterol, the PCSK9-WD mice developed a T cell-mediated inflammatory response in the lung and liver. Human CD4+ and CD8+ T cells bearing an effector memory phenotype were significantly elevated in the blood, spleen, and lungs of PCSK9-WD hu-mice, whereas splenic and circulating regulatory T cells were reduced. These data show that moderately high plasma cholesterol can disrupt human T cell homeostasis in vivo. This process may not only exacerbate atherosclerosis, but also contribute to T cell-mediated inflammatory diseases in the hypercholesterolemia setting.

Reconstructing life history of hominids and humans.

PubMed

Crews, Douglas E; Gerber, Linda M

2003-06-01

Aspects of life history, such as processes and timing of development, age at maturation, and life span are consistently associated with one another across the animal kingdom. Species that develop rapidly tend to mature and reproduce early, have many offspring, and exhibit shorter life spans (r-selection) than those that develop slowly, have extended periods of premature growth, mature later in life, reproduce later and less frequently, have few offspring and/or single births, and exhibit extended life spans (K-selection). In general, primates are among the most K-selected of species. A suite of highly derived life history traits characterizes humans. Among these are physically immature neonates, slowed somatic development both in utero and post-natally, late attainment of reproductive maturity and first birth, and extended post-mature survival. Exactly when, why, and through what types of evolutionary interactions this suite arose is currently the subject of much conjecture and debate. Humankind's biocultural adaptations have helped to structure human life history evolution in unique ways not seen in other animal species. Among all species, life history traits may respond rapidly to alterations in selective pressures through hormonal processes. Selective pressures on life history likely varied widely among hominids and humans over their evolutionary history. This suggests that current patterns of human growth, development, maturation, reproduction, and post-mature survival may be of recent genesis, rather then long-standing adaptations. Thus, life history patterns observed among contemporary human and chimpanzee populations may provide little insight to those that existed earlier in hominid/human evolution.

Development and Evaluation of Novel Real-Time Reverse Transcription-PCR Assays with Locked Nucleic Acid Probes Targeting Leader Sequences of Human-Pathogenic Coronaviruses

PubMed Central

Chan, Jasper Fuk-Woo; Choi, Garnet Kwan-Yue; Tsang, Alan Ka-Lun; Tee, Kah-Meng; Lam, Ho-Yin; Yip, Cyril Chik-Yan; To, Kelvin Kai-Wang; Cheng, Vincent Chi-Chung; Yeung, Man-Lung; Lau, Susanna Kar-Pui; Woo, Patrick Chiu-Yat; Chan, Kwok-Hung; Tang, Bone Siu-Fai

2015-01-01

Based on findings in small RNA-sequencing (Seq) data analysis, we developed highly sensitive and specific real-time reverse transcription (RT)-PCR assays with locked nucleic acid probes targeting the abundantly expressed leader sequences of Middle East respiratory syndrome coronavirus (MERS-CoV) and other human coronaviruses. Analytical and clinical evaluations showed their noninferiority to a commercial multiplex PCR test for the detection of these coronaviruses. PMID:26019210

Certified reference materials (GBW09170 and 09171) of creatinine in human serum.

PubMed

Dai, Xinhua; Fang, Xiang; Shao, Mingwu; Li, Ming; Huang, Zejian; Li, Hongmei; Jiang, You; Song, Dewei; He, Yajuan

2011-02-15

Creatinine is the most widely used clinical marker for assessing renal function. Concentrations of creatinine in human serum need to be carefully checked in order to ensure accurate diagnosis of renal function. Therefore, development of certified reference materials (CRMs) of creatinine in serum is of increasing importance. In this study, two new CRMs (Nos. GBW09170 and 09171) for creatinine in human serum have been developed. They were prepared with mixtures of several dozens of healthy people's and kidney disease patient's serum, respectively. The certified values of 8.10, 34.1 mg/kg for these two CRMs have been assigned by liquid chromatography-isotope dilution mass spectrometry (LC-IDMS) method which was validated by using standard reference material (SRM) of SRM909b (a reference material obtained from National Institute of Standards and Technology, NIST). The expanded uncertainties of certified values for low and high concentrations were estimated to be 1.2 and 1.1%, respectively. The certified values were further confirmed by an international intercomparison for the determination of creatinine in human serum (Consultative Committee for Amount of Substance, CCQM) of K80 (CCQM-K80). These new CRMs of creatinine in human serum pool are totally native without additional creatinine spiked for enrichment. These new CRMs are capable of validating routine clinical methods for ensuring accuracy, reliability and comparability of analytical results from different clinical laboratories. They can also be used for instrument validation, development of secondary reference materials, and evaluating the accuracy of high order clinical methods for the determination of creatinine in human serum. Copyright © 2011 Elsevier B.V. All rights reserved.

Project ATHENA Creates Surrogate Human Organ Systems

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

MacQueen, Luke; Knospel, Fanny; Sherrod, Stacy

2015-06-15

The development of miniature surrogate human organs, coupled with highly sensitive mass spectrometry technologies, could one day revolutionize the way new drugs and toxic agents are studied. “By developing this ‘homo minutus,’ we are stepping beyond the need for animal or Petri dish testing: There are huge benefits in developing drug and toxicity analysis systems that can mimic the response of actual human organs,” said Rashi Iyer, a senior scientist at Los Alamos National Laboratory. ATHENA, the Advanced Tissue-engineered Human Ectypal Network Analyzer project team, is nearing the full integration of four human organ constructs — liver, heart, lung andmore » kidney — each organ component is about the size of a smartphone screen, and the whole ATHENA “body” of interconnected organs will fit neatly on a desk. A new video available on the Los Alamos National Laboratory YouTube channel updates the ATHENA project as it begins to integrate the various organ systems into a single system. Some 40 percent of pharmaceuticals fail their clinical trials and there are thousands of chemicals whose effects on humans are simply unknown. Providing a realistic, cost-effective and rapid screening system such as ATHENA with high-throughput capabilities could provide major benefits to the medical field, screening more accurately and offering a greater chance of clinical trial success. ATHENA is funded by the Defense Threat Reduction Agency (DTRA) and is a collaboration of Los Alamos National Laboratory, Harvard University, Vanderbilt University, Charité Universitätsmedizin, Berlin, Germany, CFD Research Corporation, and the University of California San Francisco.« less

Summary of Martian Dust Filtering Challenges and Current Filter Development

NASA Technical Reports Server (NTRS)

O'Hara, William J., IV

2017-01-01

Traditional air particulate filtering in manned spaceflight (Apollo, Shuttle, ISS, etc.) has used cleanable or replaceable catch filters such as screens and High-Efficiency Particulate Arrestance (HEPA) filters. However, the human mission to Mars architecture will require a new approach. It is Martian dust that is the particulate of concern but the need also applies to particulates generated by crew. The Mars Exploration Program Analysis Group (MEPAG) high-lighted this concern in its Mars Science, Goals, Objectives, Investigations and Priorities document [7], by saying specifically that one high priority investigation will be to "Test ISRU atmospheric processing systems to measure resilience with respect to dust and other environmental challenge performance parameters that are critical to the design of a full-scale system." By stating this as high priority the MEPAG is acknowledging that developing and adequately verifying this capability is critical to success of a human mission to Mars. This architecture will require filtering capabilities that are highly reliable, will not restrict the flow path with clogging, and require little to no maintenance. This paper will summarize why this is the case, the general requirements for developing the technology, and the status of the progress made in this area.

Beyond Population Distribution: Enhancing Sociocultural Resolution from Remote Sensing

NASA Astrophysics Data System (ADS)

Bhaduri, B. L.; Rose, A.

2017-12-01

At Oak Ridge National Laboratory, since late 1990s, we have focused on developing high resolution population distribution and dynamics data from local to global scales. Increasing resolutions of geographic data has been mirrored by population data sets developed across the community. However, attempts to increase temporal and sociocultural resolutions have been limited given the lack of high resolution data on human settlements and activities. While recent advancements in moderate to high resolution earth observation have led to better physiographic data, the approach of exploiting very high resolution (sub-meter resolution) imagery has also proven useful for generating accurate human settlement maps. It allows potential (social and vulnerability) characterization of population from settlement structures by exploiting image texture and spectral features. Our recent research utilizing machine learning and geocomputation has not only validated "poverty mapping from imagery" hypothesis, but has delineated a new paradigm of rapid analysis of high resolution imagery to enhance such "neighborhood" mapping techniques. Such progress in GIScience is allowing us to move towards the goal of creating a global foundation level database for impervious surfaces and "neighborhoods," and holds tremendous promise for key applications focusing on sustainable development including many social science applications.

High-throughput identification of small molecules that affect human embryonic vascular development

PubMed Central

Vazão, Helena; Rosa, Susana; Barata, Tânia; Costa, Ricardo; Pitrez, Patrícia R.; Honório, Inês; de Vries, Margreet R.; Papatsenko, Dimitri; Benedito, Rui; Saris, Daniel; Khademhosseini, Ali; Quax, Paul H. A.; Pereira, Carlos F.; Mercader, Nadia; Ferreira, Lino

2017-01-01

Birth defects, which are in part caused by exposure to environmental chemicals and pharmaceutical drugs, affect 1 in every 33 babies born in the United States each year. The current standard to screen drugs that affect embryonic development is based on prenatal animal testing; however, this approach yields low-throughput and limited mechanistic information regarding the biological pathways and potential adverse consequences in humans. To develop a screening platform for molecules that affect human embryonic development based on endothelial cells (ECs) derived from human pluripotent stem cells, we differentiated human pluripotent stem cells into embryonic ECs and induced their maturation under arterial flow conditions. These cells were then used to screen compounds that specifically affect embryonic vasculature. Using this platform, we have identified two compounds that have higher inhibitory effect in embryonic than postnatal ECs. One of them was fluphenazine (an antipsychotic), which inhibits calmodulin kinase II. The other compound was pyrrolopyrimidine (an antiinflammatory agent), which inhibits vascular endothelial growth factor receptor 2 (VEGFR2), decreases EC viability, induces an inflammatory response, and disrupts preformed vascular networks. The vascular effect of the pyrrolopyrimidine was further validated in prenatal vs. adult mouse ECs and in embryonic and adult zebrafish. We developed a platform based on human pluripotent stem cell-derived ECs for drug screening, which may open new avenues of research for the study and modulation of embryonic vasculature. PMID:28348206

High-throughput identification of small molecules that affect human embryonic vascular development.

PubMed

Vazão, Helena; Rosa, Susana; Barata, Tânia; Costa, Ricardo; Pitrez, Patrícia R; Honório, Inês; de Vries, Margreet R; Papatsenko, Dimitri; Benedito, Rui; Saris, Daniel; Khademhosseini, Ali; Quax, Paul H A; Pereira, Carlos F; Mercader, Nadia; Fernandes, Hugo; Ferreira, Lino

2017-04-11

Birth defects, which are in part caused by exposure to environmental chemicals and pharmaceutical drugs, affect 1 in every 33 babies born in the United States each year. The current standard to screen drugs that affect embryonic development is based on prenatal animal testing; however, this approach yields low-throughput and limited mechanistic information regarding the biological pathways and potential adverse consequences in humans. To develop a screening platform for molecules that affect human embryonic development based on endothelial cells (ECs) derived from human pluripotent stem cells, we differentiated human pluripotent stem cells into embryonic ECs and induced their maturation under arterial flow conditions. These cells were then used to screen compounds that specifically affect embryonic vasculature. Using this platform, we have identified two compounds that have higher inhibitory effect in embryonic than postnatal ECs. One of them was fluphenazine (an antipsychotic), which inhibits calmodulin kinase II. The other compound was pyrrolopyrimidine (an antiinflammatory agent), which inhibits vascular endothelial growth factor receptor 2 (VEGFR2), decreases EC viability, induces an inflammatory response, and disrupts preformed vascular networks. The vascular effect of the pyrrolopyrimidine was further validated in prenatal vs. adult mouse ECs and in embryonic and adult zebrafish. We developed a platform based on human pluripotent stem cell-derived ECs for drug screening, which may open new avenues of research for the study and modulation of embryonic vasculature.

Mothers' knowledge of and attitudes toward human milk banking in South Australia: a qualitative study.

PubMed

Mackenzie, Catherine; Javanparast, Sara; Newman, Lareen

2013-05-01

The beneficial effects of breastfeeding for mothers and babies are well recognized. When maternal breast milk is not available in sufficient quantity, donor breast milk is recommended as an alternate source of nutrition, particularly in preterm and other high-risk infants. Australia lags behind the rest of the developed world in establishing and promoting human milk banks; there is no human milk bank in South Australia and little is known concerning mothers' perceptions of using human milk banks in that state. This study explored mothers' knowledge of and attitudes toward human milk banks, to inform the development of human milk banking policies and guidelines in South Australia should a milk bank be established. In-depth semistructured interviews were conducted with 12 mothers who were breastfeeding and/or had preterm or sick babies. In addition, 2 focus groups were conducted-1 with breastfeeding mothers as potential donors (n = 5) and the other with mothers of preterm or high-risk infants (n = 4)-to answer questions raised by early analysis of the individual interview data. Breastfeeding mothers, as potential donors, unanimously supported donating their breast milk to a human milk bank, provided it would be easy (especially if required to drop off milk) and not overly time consuming. Mothers of preterm or sick infants would use a human milk bank if they were assured the milk was safe and appropriate for their babies. Study participants would welcome having access to a human milk bank for both donating and receiving milk in South Australia.

Development of an Intracellular Screen for New Compounds Able To Inhibit Mycobacterium tuberculosis Growth in Human Macrophages.

PubMed

Sorrentino, Flavia; Gonzalez del Rio, Ruben; Zheng, Xingji; Presa Matilla, Jesus; Torres Gomez, Pedro; Martinez Hoyos, Maria; Perez Herran, Maria Esther; Mendoza Losana, Alfonso; Av-Gay, Yossef

2016-01-01

Here we describe the development and validation of an intracellular high-throughput screening assay for finding new antituberculosis compounds active in human macrophages. The assay consists of a luciferase-based primary identification assay, followed by a green fluorescent protein-based secondary profiling assay. Standard tuberculosis drugs and 158 previously recognized active antimycobacterial compounds were used to evaluate assay robustness. Data show that the assay developed is a short and valuable tool for the discovery of new antimycobacterial compounds. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Virtual reality applications to automated rendezvous and capture

NASA Technical Reports Server (NTRS)

Hale, Joseph; Oneil, Daniel

1991-01-01

Virtual Reality (VR) is a rapidly developing Human/Computer Interface (HCI) technology. The evolution of high-speed graphics processors and development of specialized anthropomorphic user interface devices, that more fully involve the human senses, have enabled VR technology. Recently, the maturity of this technology has reached a level where it can be used as a tool in a variety of applications. This paper provides an overview of: VR technology, VR activities at Marshall Space Flight Center (MSFC), applications of VR to Automated Rendezvous and Capture (AR&C), and identifies areas of VR technology that requires further development.

Developmental neurotoxicity testing: Past, present and future.

EPA Science Inventory

Adverse effects on the nervous system following exposure to environmental contaminants during development have been well documented. Indeed, in a number of cases (e.g., lead, methyl mercury) the developing human nervous system appears to be a highly susceptible target. There ar...

"High Stage" Organizing.

ERIC Educational Resources Information Center

Torbert, William R.

Although a psychological theory of stages of transformation in human development currently exists, organizational researchers have yet to elaborate and test any theory of organizational transformation of comparable elegance. According to the organizational stage theory being developed since 1974 by William Torbert, bureaucratic organization, which…

HTLV-1, the Other Pathogenic Yet Neglected Human Retrovirus: From Transmission to Therapeutic Treatment

PubMed Central

Futsch, Nicolas; Mahieux, Renaud; Dutartre, Hélène

2017-01-01

Going back to their discovery in the early 1980s, both the Human T-cell Leukemia virus type-1 (HTLV-1) and the Human Immunodeficiency Virus type-1 (HIV-1) greatly fascinated the virology scene, not only because they were the first human retroviruses discovered, but also because they were associated with fatal diseases in the human population. In almost four decades of scientific research, both viruses have had different fates, HTLV-1 being often upstaged by HIV-1. However, although being very close in terms of genome organization, cellular tropism, and viral replication, HIV-1 and HTLV-1 are not completely commutable in terms of treatment, especially because of the opposite fate of the cells they infect: death versus immortalization, respectively. Nowadays, the antiretroviral therapies developed to treat HIV-1 infected individuals and to limit HIV-1 spread among the human population have a poor or no effect on HTLV-1 infected individuals, and thus, do not prevent the development of HTLV-1-associated diseases, which still lack highly efficient treatments. The present review mainly focuses on the course of HTLV-1 infection, from the initial infection of the host to diseases development and associated treatments, but also investigates HIV-1/HTLV-1 co-infection events and their impact on diseases development. PMID:29267225

Diversity of human copy number variation and multicopy genes.

PubMed

Sudmant, Peter H; Kitzman, Jacob O; Antonacci, Francesca; Alkan, Can; Malig, Maika; Tsalenko, Anya; Sampas, Nick; Bruhn, Laurakay; Shendure, Jay; Eichler, Evan E

2010-10-29

Copy number variants affect both disease and normal phenotypic variation, but those lying within heavily duplicated, highly identical sequence have been difficult to assay. By analyzing short-read mapping depth for 159 human genomes, we demonstrated accurate estimation of absolute copy number for duplications as small as 1.9 kilobase pairs, ranging from 0 to 48 copies. We identified 4.1 million "singly unique nucleotide" positions informative in distinguishing specific copies and used them to genotype the copy and content of specific paralogs within highly duplicated gene families. These data identify human-specific expansions in genes associated with brain development, reveal extensive population genetic diversity, and detect signatures consistent with gene conversion in the human species. Our approach makes ~1000 genes accessible to genetic studies of disease association.

HT-COMET: a novel automated approach for high throughput assessment of human sperm chromatin quality.

PubMed

Albert, Océane; Reintsch, Wolfgang E; Chan, Peter; Robaire, Bernard

2016-05-01

Can we make the comet assay (single-cell gel electrophoresis) for human sperm a more accurate and informative high throughput assay? We developed a standardized automated high throughput comet (HT-COMET) assay for human sperm that improves its accuracy and efficiency, and could be of prognostic value to patients in the fertility clinic. The comet assay involves the collection of data on sperm DNA damage at the level of the single cell, allowing the use of samples from severe oligozoospermic patients. However, this makes comet scoring a low throughput procedure that renders large cohort analyses tedious. Furthermore, the comet assay comes with an inherent vulnerability to variability. Our objective is to develop an automated high throughput comet assay for human sperm that will increase both its accuracy and efficiency. The study comprised two distinct components: a HT-COMET technical optimization section based on control versus DNAse treatment analyses ( ITALIC! n = 3-5), and a cross-sectional study on 123 men presenting to a reproductive center with sperm concentrations categorized as severe oligozoospermia, oligozoospermia or normozoospermia. Sperm chromatin quality was measured using the comet assay: on classic 2-well slides for software comparison; on 96-well slides for HT-COMET optimization; after exposure to various concentrations of a damage-inducing agent, DNAse, using HT-COMET; on 123 subjects with different sperm concentrations using HT-COMET. Data from the 123 subjects were correlated to classic semen quality parameters and plotted as single-cell data in individual DNA damage profiles. We have developed a standard automated HT-COMET procedure for human sperm. It includes automated scoring of comets by a fully integrated high content screening setup that compares well with the most commonly used semi-manual analysis software. Using this method, a cross-sectional study on 123 men showed no significant correlation between sperm concentration and sperm DNA damage, confirming the existence of hidden chromatin damage in men with apparently normal semen characteristics, and a significant correlation between percentage DNA in the tail and percentage of progressively motile spermatozoa. Finally, the use of DNA damage profiles helped to distinguish subjects between and within sperm concentration categories, and allowed a determination of the proportion of highly damaged cells. The main limitations of the HT-COMET are the high, yet indispensable, investment in an automated liquid handling system and heating block to ensure accuracy, and the availability of an automated plate reading microscope and analysis software. This standardized HT-COMET assay offers many advantages, including higher accuracy and evenness due to automation of sensitive steps, a 14.4-fold increase in sample analysis capacity, and an imaging and scoring time of 1 min/well. Overall, HT-COMET offers a decrease in total experimental time of more than 90%. Hence, this assay constitutes a more efficient option to assess sperm chromatin quality, paves the way to using this assay to screen large cohorts, and holds prognostic value for infertile patients. Funded by the CIHR Institute of Human Development, Child and Youth Health (IHDCYH; RHF 100625). O.A. is a fellow supported by the Fonds de la Recherche du Québec - Santé (FRQS) and the CIHR Training Program in Reproduction, Early Development, and the Impact on Health (REDIH). B.R. is a James McGill Professor. The authors declare no conflicts of interest. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cyber warfare and electronic warfare integration in the operational environment of the future: cyber electronic warfare

NASA Astrophysics Data System (ADS)

Askin, Osman; Irmak, Riza; Avsever, Mustafa

2015-05-01

For the states with advanced technology, effective use of electronic warfare and cyber warfare will be the main determining factor of winning a war in the future's operational environment. The developed states will be able to finalize the struggles they have entered with a minimum of human casualties and minimum cost thanks to high-tech. Considering the increasing number of world economic problems, the development of human rights and humanitarian law it is easy to understand the importance of minimum cost and minimum loss of human. In this paper, cyber warfare and electronic warfare concepts are examined in conjunction with the historical development and the relationship between them is explained. Finally, assessments were carried out about the use of cyber electronic warfare in the coming years.

[Retention management by means of applied human resource development: lessons from cardiovascular anaesthesiology].

PubMed

Padosch, Stephan A; Schmidt, Christian E; Spöhr, Fabian A M

2011-05-01

At present, besides well-known financial problems, German hospitals are facing a serious lack of qualified medical staff. Given these facts, it is of great importance, especially in work load burdened disciplines, such as cardiovascular anaesthesiology, to retain highly qualified medical staff. Here, human resource development measures offer valuable tools for efficient retention management. Moreover, most of these are applicable to almost any clinical specialty. Surprisingly, financial aspects play a minor role in such concepts, in contrast to human resource development tools, such as mentoring, interviews, training and motivational activities. Especially, with regard to "Generation Y", an efficient retention management will play a key role to keep these physicians as hospital employees of long duration in the future. © Georg Thieme Verlag Stuttgart · New York.

Human System Drivers for Exploration Missions

NASA Technical Reports Server (NTRS)

Kundrot, Craig E.; Steinberg, Susan; Charles, John B.

2010-01-01

Evaluation of DRM4 in terms of the human system includes the ability to meet NASA standards, the inclusion of the human system in the design trade space, preparation for future missions and consideration of a robotic precursor mission. Ensuring both the safety and the performance capability of the human system depends upon satisfying NASA Space Flight Human System Standards.1 These standards in turn drive the development of program-specific requirements for Near-earth Object (NEO) missions. In evaluating DRM4 in terms of these human system standards, the currently existing risk models, technologies and biological countermeasures were used. A summary of this evaluation is provided below in a structure that supports a mission architecture planning activities. 1. Unacceptable Level of Risk The duration of the DRM4 mission leads to an unacceptable level of risk for two aspects of human system health: A. The permissible exposure limit for space flight radiation exposure (a human system standard) would be exceeded by DRM4. B. The risk of visual alterations and abnormally high intracranial pressure would be too high. 1

Recent advances in recombinant protein-based malaria vaccines

PubMed Central

Draper, Simon J.; Angov, Evelina; Horii, Toshihiro; Miller, Louis H.; Srinivasan, Prakash; Theisen, Michael; Biswas, Sumi

2015-01-01

Plasmodium parasites are the causative agent of human malaria, and the development of a highly effective vaccine against infection, disease and transmission remains a key priority. It is widely established that multiple stages of the parasite's complex lifecycle within the human host and mosquito vector are susceptible to vaccine-induced antibodies. The mainstay approach to antibody induction by subunit vaccination has been the delivery of protein antigen formulated in adjuvant. Extensive efforts have been made in this endeavor with respect to malaria vaccine development, especially with regard to target antigen discovery, protein expression platforms, adjuvant testing, and development of soluble and virus-like particle (VLP) delivery platforms. The breadth of approaches to protein-based vaccines is continuing to expand as innovative new concepts in next-generation subunit design are explored, with the prospects for the development of a highly effective multi-component/multi-stage/multi-antigen formulation seeming ever more likely. This review will focus on recent progress in protein vaccine design, development and/or clinical testing for a number of leading malaria antigens from the sporozoite-, merozoite- and sexual-stages of the parasite's lifecycle–including PfCelTOS, PfMSP1, PfAMA1, PfRH5, PfSERA5, PfGLURP, PfMSP3, Pfs48/45 and Pfs25. Future prospects and challenges for the development, production, human delivery and assessment of protein-based malaria vaccines are discussed. PMID:26458807

Monitoring of aflatoxins and ochratoxin A in Czechoslovak human sera by immunoassay

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

Fukal, L.; Reisnerova, H.

1990-03-01

Since a level of food contamination with aflatoxins and ochratoxin A has been found low in Czechoslovakia, human exposure to these mycotoxins may not be negligible. However, analysis of food samples provides only indirect evidence of mycotoxin ingestion and no evidence about mycotoxin absorption. Direct evidence can only be obtained by analysis of human body fluids. Therefore, the authors decided to carry out a monitoring of aflatoxin and ochratoxin A level in human sera. In general, TLC and HPLC are most commonly used to analyze mycotoxins and its metabolites. The recent development of immunochemical techniques opens the possibility of determiningmore » individual exposure in a relatively large human population. These assays have the advantage of high specificity and sensitivity. Sample through-put is high, and the methods are technically simple and can be performed at low cost.« less

Development of the "Highly Sensitive Dog" questionnaire to evaluate the personality dimension "Sensory Processing Sensitivity" in dogs.

PubMed

Braem, Maya; Asher, Lucy; Furrer, Sibylle; Lechner, Isabel; Würbel, Hanno; Melotti, Luca

2017-01-01

In humans, the personality dimension 'sensory processing sensitivity (SPS)', also referred to as "high sensitivity", involves deeper processing of sensory information, which can be associated with physiological and behavioral overarousal. However, it has not been studied up to now whether this dimension also exists in other species. SPS can influence how people perceive the environment and how this affects them, thus a similar dimension in animals would be highly relevant with respect to animal welfare. We therefore explored whether SPS translates to dogs, one of the primary model species in personality research. A 32-item questionnaire to assess the "highly sensitive dog score" (HSD-s) was developed based on the "highly sensitive person" (HSP) questionnaire. A large-scale, international online survey was conducted, including the HSD questionnaire, as well as questions on fearfulness, neuroticism, "demographic" (e.g. dog sex, age, weight; age at adoption, etc.) and "human" factors (e.g. owner age, sex, profession, communication style, etc.), and the HSP questionnaire. Data were analyzed using linear mixed effect models with forward stepwise selection to test prediction of HSD-s by the above-mentioned factors, with country of residence and dog breed treated as random effects. A total of 3647 questionnaires were fully completed. HSD-, fearfulness, neuroticism and HSP-scores showed good internal consistencies, and HSD-s only moderately correlated with fearfulness and neuroticism scores, paralleling previous findings in humans. Intra- (N = 447) and inter-rater (N = 120) reliabilities were good. Demographic and human factors, including HSP score, explained only a small amount of the variance of HSD-s. A PCA analysis identified three subtraits of SPS, comparable to human findings. Overall, the measured personality dimension in dogs showed good internal consistency, partial independence from fearfulness and neuroticism, and good intra- and inter-rater reliability, indicating good construct validity of the HSD questionnaire. Human and demographic factors only marginally affected the HSD-s suggesting that, as hypothesized for human SPS, a genetic basis may underlie this dimension within the dog species.

Development of real-time motion capture system for 3D on-line games linked with virtual character

NASA Astrophysics Data System (ADS)

Kim, Jong Hyeong; Ryu, Young Kee; Cho, Hyung Suck

2004-10-01

Motion tracking method is being issued as essential part of the entertainment, medical, sports, education and industry with the development of 3-D virtual reality. Virtual human character in the digital animation and game application has been controlled by interfacing devices; mouse, joysticks, midi-slider, and so on. Those devices could not enable virtual human character to move smoothly and naturally. Furthermore, high-end human motion capture systems in commercial market are expensive and complicated. In this paper, we proposed a practical and fast motion capturing system consisting of optic sensors, and linked the data with 3-D game character with real time. The prototype experiment setup is successfully applied to a boxing game which requires very fast movement of human character.

Improvements and Limitations of Humanized Mouse Models for HIV Research: NIH/NIAID “Meet the Experts” 2015 Workshop Summary

PubMed Central

Akkina, Ramesh; Allam, Atef; Balazs, Alejandro B.; Blankson, Joel N.; Burnett, John C.; Casares, Sofia; Garcia, J. Victor; Hasenkrug, Kim J.; Kitchen, Scott G.; Klein, Florian; Kumar, Priti; Luster, Andrew D.; Poluektova, Larisa Y.; Rao, Mangala; Shultz, Leonard D.; Zack, Jerome A.

2016-01-01

Abstract The number of humanized mouse models for the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and other infectious diseases has expanded rapidly over the past 8 years. Highly immunodeficient mouse strains, such as NOD/SCID/gamma chainnull (NSG, NOG), support better human hematopoietic cell engraftment. Another improvement is the derivation of highly immunodeficient mice, transgenic with human leukocyte antigens (HLAs) and cytokines that supported development of HLA-restricted human T cells and heightened human myeloid cell engraftment. Humanized mice are also used to study the HIV reservoir using new imaging techniques. Despite these advances, there are still limitations in HIV immune responses and deficits in lymphoid structures in these models in addition to xenogeneic graft-versus-host responses. To understand and disseminate the improvements and limitations of humanized mouse models to the scientific community, the NIH sponsored and convened a meeting on April 15, 2015 to discuss the state of knowledge concerning these questions and best practices for selecting a humanized mouse model for a particular scientific investigation. This report summarizes the findings of the NIH meeting. PMID:26670361

The United States and the universality of human rights.

PubMed

Chomsky, N

1999-01-01

The United States takes a highly relativistic stance toward the Universal Declaration of Human Rights. It regards the socio-economic rights and the right to development as without status; exempts itself from all provisions of the Declaration by failing to sign the conventions designed to implement these provisions; and unilaterally qualifies its support of civil and political rights. Leading recipients of U.S. aid have traditionally included regimes with atrocious human rights records. Those struggling for human rights should have no illusions about the systems of power and their servants.

The Social Development Summit and the developing countries.

PubMed

Barnabas, A P; Kulkarni, P D; Nanavatty, M C; Singh, R R

1996-01-01

This article discusses some concerns of the 1996 UN Summit on Social Development. Conference organizers identified the three key conference issues as poverty alleviation, social integration of the marginalized and disadvantaged, and expansion of productive employment. The goal of a "society for all" means dealing with the increasing differences between rich and poor countries, the survival of weaker economies in a competitive market system, wide variations in consumption patterns between countries, attainment of political stability while respecting ethnic identity, the rise in social problems among countries with a high human development index, and increasing joblessness. The Human Development Report for 1994 emphasizes human security. Social development is not the equivalent of human resource development nor a side issue of economic growth. The integration of ethnic groups poses social and political problems. There remains a question about what political system and culture would be best for social integration. Developed countries define poverty as the inability of people and government to provide resources and necessary services for people's productive activity. Poverty in developing countries is blamed on colonialism. Globally, developed countries control 71% of world trade. Sharing resources to meet basic needs throughout the world is not an operational ideal. The highest 20% of income earners receive 83% of the world income. The culture of poverty is the strategy used by the poor to survive. Welfare is not an end in itself but does enable the poor to improve their conditions. Development that focuses on productive employment is uncertain. Developed and developing countries do not share similar perceptions of human rights. There is a question as to who should set the priorities for social development. Sustainable social development is related to preservation of natural resources, control of population growth, and promotion of social security.

Cloning of non-human primates: the road “less traveled by”

PubMed Central

SPARMAN, MICHELLE L.; TACHIBANA, MASAHITO; MITALIPOV, SHOUKHRAT M.

2011-01-01

Early studies on cloning of non-human primates by nuclear transfer utilized embryonic blastomeres from preimplantation embryos which resulted in the reproducible birth of live offspring. Soon after, the focus shifted to employing somatic cells as a source of donor nuclei (somatic cell nuclear transfer, SCNT). However, initial efforts were plagued with inefficient nuclear reprogramming and poor embryonic development when standard SCNT methods were utilized. Implementation of several key SCNT modifications was critical to overcome these problems. In particular, a non-invasive method of visualizing the metaphase chromosomes during enucleation was developed to preserve the reprogramming capacity of monkey oocytes. These modifications dramatically improved the efficiency of SCNT, yielding high blastocyst development in vitro. To date, SCNT has been successfully used to derive pluripotent embryonic stem cells (ESCs) from adult monkey skin fibroblasts. These remarkable advances have the potential for development of human autologous ESCs and cures for many human diseases. Reproductive cloning of nonhuman primates by SCNT has not been achieved yet. We have been able to establish several pregnancies with SCNT embryos which, so far, did not progress to term. In this review, we summarize the approaches, obstacles and accomplishments of SCNT in a non-human primate model. PMID:21404187

Cloning of non-human primates: the road "less traveled by".

PubMed

Sparman, Michelle L; Tachibana, Masahito; Mitalipov, Shoukhrat M

2010-01-01

Early studies on cloning of non-human primates by nuclear transfer utilized embryonic blastomeres from preimplantation embryos which resulted in the reproducible birth of live offspring. Soon after, the focus shifted to employing somatic cells as a source of donor nuclei (somatic cell nuclear transfer, SCNT). However, initial efforts were plagued with inefficient nuclear reprogramming and poor embryonic development when standard SCNT methods were utilized. Implementation of several key SCNT modifications was critical to overcome these problems. In particular, a non-invasive method of visualizing the metaphase chromosomes during enucleation was developed to preserve the reprogramming capacity of monkey oocytes. These modifications dramatically improved the efficiency of SCNT, yielding high blastocyst development in vitro. To date, SCNT has been successfully used to derive pluripotent embryonic stem cells (ESCs) from adult monkey skin fibroblasts. These remarkable advances have the potential for development of human autologous ESCs and cures for many human diseases. Reproductive cloning of nonhuman primates by SCNT has not been achieved yet. We have been able to establish several pregnancies with SCNT embryos which, so far, did not progress to term. In this review, we summarize the approaches, obstacles and accomplishments of SCNT in a non-human primate model.

Inadequately Treated Wastewater as a Source of Human Enteric Viruses in the Environment

PubMed Central

Okoh, Anthony I.; Sibanda, Thulani; Gusha, Siyabulela S.

2010-01-01

Human enteric viruses are causative agents in both developed and developing countries of many non-bacterial gastrointestinal tract infections, respiratory tract infections, conjunctivitis, hepatitis and other more serious infections with high morbidity and mortality in immunocompromised individuals such as meningitis, encephalitis and paralysis. Human enteric viruses infect and replicate in the gastrointestinal tract of their hosts and are released in large quantities in the stools of infected individuals. The discharge of inadequately treated sewage effluents is the most common source of enteric viral pathogens in aquatic environments. Due to the lack of correlation between the inactivation rates of bacterial indicators and viral pathogens, human adenoviruses have been proposed as a suitable index for the effective indication of viral contaminants in aquatic environments. This paper reviews the major genera of pathogenic human enteric viruses, their pathogenicity and epidemiology, as well as the role of wastewater effluents in their transmission. PMID:20644692

Human excreta for plant production.

PubMed

Heinonen-Tanski, Helvi; van Wijk-Sijbesma, Christine

2005-03-01

Human excreta are a natural resource which is always available in all societies. Unfortunately, their value is highly underestimated in present agriculture and horticulture including in many tropical developing countries. Especially human urine is rich in nitrogen. This "free" fertiliser should be used as much as possible and needed. In many cases, human urine and composted human faeces could be fortified with wood ash and kitchen and garden waste to meet the potassium and phosphorus needs of plants and to improve soil structure. Avoiding health risks and dosage requirements are also discussed. The ideas presented here can be used even with the cheap pit latrines that are common in the rural and peri-urban areas of developing countries. They do not require electricity and/or tap water. They may also fit conditions in areas of Eastern Europe where piped water and sewerage are absent and/or people lack money for fertilisers and maintenance of wastewater treatment plants.

Animal versus human oral drug bioavailability: Do they correlate?

PubMed Central

Musther, Helen; Olivares-Morales, Andrés; Hatley, Oliver J.D.; Liu, Bo; Rostami Hodjegan, Amin

2014-01-01

Oral bioavailability is a key consideration in development of drug products, and the use of preclinical species in predicting bioavailability in human has long been debated. In order to clarify whether any correlation between human and animal bioavailability exist, an extensive analysis of the published literature data was conducted. Due to the complex nature of bioavailability calculations inclusion criteria were applied to ensure integrity of the data. A database of 184 compounds was assembled. Linear regression for the reported compounds indicated no strong or predictive correlations to human data for all species, individually and combined. The lack of correlation in this extended dataset highlights that animal bioavailability is not quantitatively predictive of bioavailability in human. Although qualitative (high/low bioavailability) indications might be possible, models taking into account species-specific factors that may affect bioavailability are recommended for developing quantitative prediction. PMID:23988844

Cyanobacteria and Cyanotoxins: From Impacts on Aquatic Ecosystems and Human Health to Anticarcinogenic Effects

PubMed Central

Zanchett, Giliane; Oliveira-Filho, Eduardo C.

2013-01-01

Cyanobacteria or blue-green algae are among the pioneer organisms of planet Earth. They developed an efficient photosynthetic capacity and played a significant role in the evolution of the early atmosphere. Essential for the development and evolution of species, they proliferate easily in aquatic environments, primarily due to human activities. Eutrophic environments are conducive to the appearance of cyanobacterial blooms that not only affect water quality, but also produce highly toxic metabolites. Poisoning and serious chronic effects in humans, such as cancer, have been described. On the other hand, many cyanobacterial genera have been studied for their toxins with anticancer potential in human cell lines, generating promising results for future research toward controlling human adenocarcinomas. This review presents the knowledge that has evolved on the topic of toxins produced by cyanobacteria, ranging from their negative impacts to their benefits. PMID:24152991

Quantitative bioanalysis of strontium in human serum by inductively coupled plasma-mass spectrometry

PubMed Central

Somarouthu, Srikanth; Ohh, Jayoung; Shaked, Jonathan; Cunico, Robert L; Yakatan, Gerald; Corritori, Suzana; Tami, Joe; Foehr, Erik D

2015-01-01

Aim: A bioanalytical method using inductively-coupled plasma-mass spectrometry to measure endogenous levels of strontium in human serum was developed and validated. Results & methodology: This article details the experimental procedures used for the method development and validation thus demonstrating the application of the inductively-coupled plasma-mass spectrometry method for quantification of strontium in human serum samples. The assay was validated for specificity, linearity, accuracy, precision, recovery and stability. Significant endogenous levels of strontium are present in human serum samples ranging from 19 to 96 ng/ml with a mean of 34.6 ± 15.2 ng/ml (SD). Discussion & conclusion: Calibration procedures and sample pretreatment were simplified for high throughput analysis. The validation demonstrates that the method was sensitive, selective for quantification of strontium (88Sr) and is suitable for routine clinical testing of strontium in human serum samples. PMID:28031925

Cyanobacteria and cyanotoxins: from impacts on aquatic ecosystems and human health to anticarcinogenic effects.

PubMed

Zanchett, Giliane; Oliveira-Filho, Eduardo C

2013-10-23

Cyanobacteria or blue-green algae are among the pioneer organisms of planet Earth. They developed an efficient photosynthetic capacity and played a significant role in the evolution of the early atmosphere. Essential for the development and evolution of species, they proliferate easily in aquatic environments, primarily due to human activities. Eutrophic environments are conducive to the appearance of cyanobacterial blooms that not only affect water quality, but also produce highly toxic metabolites. Poisoning and serious chronic effects in humans, such as cancer, have been described. On the other hand, many cyanobacterial genera have been studied for their toxins with anticancer potential in human cell lines, generating promising results for future research toward controlling human adenocarcinomas. This review presents the knowledge that has evolved on the topic of toxins produced by cyanobacteria, ranging from their negative impacts to their benefits.

Dressing for Altitude: U.S. Aviation Pressure Suits--Wiley Post to Space Shuttle

NASA Technical Reports Server (NTRS)

Jenkins, Dennis R.

2012-01-01

Since its earliest days, flight has been about pushing the limits of technology and, in many cases, pushing the limits of human endurance. The human body can be the limiting factor in the design of aircraft and spacecraft. Humans cannot survive unaided at high altitudes. There have been a number of books written on the subject of spacesuits, but the literature on the high-altitude pressure suits is lacking. This volume provides a high-level summary of the technological development and operational use of partial- and full-pressure suits, from the earliest models to the current high altitude, full-pressure suits used for modern aviation, as well as those that were used for launch and entry on the Space Shuttle. The goal of this work is to provide a resource on the technology for suits designed to keep humans alive at the edge of space. Hopefully, future generations will learn from the hard-fought lessons of the past. NASA is committed to the future of aerospace, and a key component of that future is the workforce. Without these men and women, technological advancements would not be possible. Dressing for Altitude is designed to provide the history of the technology and to explore the lessons learned through years of research in creating, testing, and utilizing today s high-altitude suits. It is our hope that this information will prove helpful in the development of future suits. Even with the closeout of the Space Shuttle and the planned ending of the U-2 program, pressure suits will be needed for protection as long as humans seek to explore high frontiers. The NASA Aeronautics Research Mission Directorate is committed to the training of the current and future aerospace workforce. This book and the other books published by the NASA Aeronautics Research Mission Directorate are in support of this commitment. Hopefully, you will find this book a valuable resource for many years to come.

Method development for the determination of 24S-hydroxycholesterol in human plasma without derivatization by high-performance liquid chromatography with tandem mass spectrometry in atmospheric pressure chemical ionization mode.

PubMed

Sugimoto, Hiroshi; Kakehi, Masaaki; Satomi, Yoshinori; Kamiguchi, Hidenori; Jinno, Fumihiro

2015-10-01

We developed a highly sensitive and specific high-performance liquid chromatography with tandem mass spectrometry method with an atmospheric pressure chemical ionization interface to determine 24S-hydroxycholesterol, a major metabolite of cholesterol formed by cytochrome P450 family 46A1, in human plasma without any derivatization step. Phosphate buffered saline including 1% Tween 80 was used as the surrogate matrix for preparation of calibration curves and quality control samples. The saponification process to convert esterified 24S-hydroxycholesterol to free sterols was optimized, followed by liquid-liquid extraction using hexane. Chromatographic separation of 24S-hydroxycholesterol from other isobaric endogenous oxysterols was successfully achieved with gradient mobile phase comprised of 0.1% propionic acid and acetonitrile using L-column2 ODS (2 μm, 2.1 mm id × 150 mm). This assay was capable of determining 24S-hydroxycholesterol in human plasma (200 μL) ranging from 1 to 100 ng/mL with acceptable intra- and inter-day precision and accuracy. The potential risk of in vitro formation of 24S-hydroxycholesterol by oxidation from endogenous cholesterol in human plasma was found to be negligible. The stability of 24S-hydroxycholesterol in relevant solvents and human plasma was confirmed. This method was successfully applied to quantify the plasma concentrations of 24S-hydroxycholesterol in male and female volunteers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bladder carcinoma in a transplant recipient: evidence to implicate the BK human polyomavirus as a causal transforming agent.

PubMed

Geetha, Duvuru; Tong, Betty C; Racusen, Lorraine; Markowitz, Jay S; Westra, William H

2002-06-27

The BK polyomavirus (BKV) infects most of the human population, but clinically relevant infections are mostly limited to individuals who are immunosuppressed. In transplant recipients, BKV has been associated with ureteral stenosis, interstitial nephritis, and hemorrhagic cystitis. The role of BKV in the development of human tumors is intriguing but uncertain. BKV has been identified in various tumor types including urothelial carcinoma, but the ubiquitous presence of BKV as a latent infection has confounded efforts to validate any causal role in cancer development. We report the case of a simultaneous pancreas and kidney transplant recipient who developed BKV interstitial nephritis and carcinoma of the bladder with widespread metastases. High level expression of BKV large T antigen in the primary and metastatic carcinoma, but not in the nonneoplastic urothelium, implicates BKV as an etiologic agent in the development of this tumor.

Future Challenges in Managing Human Health and Performance Risks for Space Flight

NASA Technical Reports Server (NTRS)

Corbin, Barbara J.; Barratt, Michael

2013-01-01

The global economy forces many nations to consider their national investments and make difficult decisions regarding their investment in future exploration. To enable safe, reliable, and productive human space exploration, we must pool global resources to understand and mitigate human health & performance risks prior to embarking on human exploration of deep space destinations. Consensus on the largest risks to humans during exploration is required to develop an integrated approach to mitigating risks. International collaboration in human space flight research will focus research on characterizing the effects of spaceflight on humans and the development of countermeasures or systems. Sharing existing data internationally will facilitate high quality research and sufficient power to make sound recommendations. Efficient utilization of ISS and unique ground-based analog facilities allows greater progress. Finally, a means to share results of human research in time to influence decisions for follow-on research, system design, new countermeasures and medical practices should be developed. Although formidable barriers to overcome, International working groups are working to define the risks, establish international research opportunities, share data among partners, share flight hardware and unique analog facilities, and establish forums for timely exchange of results. Representatives from the ISS partnership research and medical communities developed a list of the top ten human health & performance risks and their impact on exploration missions. They also drafted a multilateral data sharing plan to establish guidelines and principles for sharing human spaceflight data. Other working groups are also developing methods to promote international research solicitations. Collaborative use of analog facilities and shared development of space flight research and medical hardware continues. Establishing a forum for exchange of results between researchers, aerospace physicians and program managers takes careful consideration of researcher concerns and decision maker needs. Active participation by researchers in the development of this forum is essential, and the benefit can be tremendous. The ability to rapidly respond to research results without compromising publication rights and intellectual property will facilitate timely reduction in human health and performance risks in support of international exploration missions.

Human development index, children's health-related quality of life and movement behaviors: a compositional data analysis.

PubMed

Dumuid, Dorothea; Maher, Carol; Lewis, Lucy K; Stanford, Tyman E; Martín Fernández, Josep Antoni; Ratcliffe, Julie; Katzmarzyk, Peter T; Barreira, Tiago V; Chaput, Jean-Philippe; Fogelholm, Mikael; Hu, Gang; Maia, José; Sarmiento, Olga L; Standage, Martyn; Tremblay, Mark S; Tudor-Locke, Catrine; Olds, Timothy

2018-06-01

Health-related quality of life has been related to physical activity, sedentary behavior, and sleep among children from developed nations. These relationships have rarely been assessed in developing nations, nor have behaviors been considered in their true context, as mutually exclusive and exhaustive parts of the movement behavior composition. This study aimed to explore whether children's health-related quality of life is related to their movement behavior composition and if the relationship differs according to human development index. Children aged 9-11 years (n = 5855), from the 12-nation cross-sectional observational International Study of Childhood Obesity, Lifestyle and the Environment 2011-2013, self-reported their health-related quality of life (KIDSCREEN-10). Daily movement behaviors were from 24-h, 7-day accelerometry. Isometric log-ratio mixed-effect linear models were used to calculate estimates for difference in health-related quality of life for the reallocation of time between daily movement behaviors. Children from countries of higher human development index reported stronger positive relationships between health-related quality of life and moderate-to-vigorous physical activity, relative to the remaining behaviors (r = 0.75, p = 0.005) than those from lower human development index countries. In the very high human development index strata alone, health-related quality of life was significantly related to the movement behavior composition (p = 0.005), with moderate-to-vigorous physical activity (relative to remaining behaviors) being positively associated with health-related quality of life. The relationship between children's health-related quality of life and their movement behaviors is moderated by their country's human development index. This should be considered when 24-h movement behavior guidelines are developed for children around the world.

Development of a highly sensitive lateral immunochromatographic assay for rapid detection of Vibrio parahaemolyticus.

PubMed

Liu, Xinfeng; Guan, Yuyao; Cheng, Shiliang; Huang, Yidan; Yan, Qin; Zhang, Jun; Huang, Guanjun; Zheng, Jian; Liu, Tianqiang

2016-12-01

Vibrio parahaemolyticus is widely present in brackish water all over the world, causing infections in certain aquatic animals. It is also a foodborne pathogen that causes diarrhea in humans. The aim of this study is to develop an immunochromatographic lateral flow assay (LFA) for rapid detection of V. parahaemolyticus in both aquatic products and human feces of diarrheal patients. Two monoclonal antibody (MAb) pairs, GA1a-IC9 and IC9-KB4c, were developed and proven to be highly specific and sensitive to V. parahaemolyticus. Based on the two MAb pairs, two types of LFA strips were prepared. Their testing limits for V. parahaemolyticus culture were both 1.2×10 3 CFU/ml. The diagnostic sensitivities and specificities were both 100% for the 32 tested microbial species, including 6 Vibrio species. Subsequently, the LFA strips were used to test Whiteleg shrimps and human feces. The type II strip showed a higher diagnostic sensitivity. Its sensitivity and specificity for hepatopancreas and fecal samples from 13 Whiteleg shrimps and fecal samples from 146 human diarrheal patients were all 100%. In conclusion, our homemade type II LFA is a very promising testing device for rapid and convenient detection of V. parahaemolyticus infection not only in aquatic animals, but also in human diarrheal patients. This sensitive immunochromtographic LFA allows rapid detection of V. parahaemolyticus without requirement of culture enrichment. Copyright © 2016. Published by Elsevier B.V.

Human genomic DNA quantitation system, H-Quant: development and validation for use in forensic casework.

PubMed

Shewale, Jaiprakash G; Schneida, Elaine; Wilson, Jonathan; Walker, Jerilyn A; Batzer, Mark A; Sinha, Sudhir K

2007-03-01

The human DNA quantification (H-Quant) system, developed for use in human identification, enables quantitation of human genomic DNA in biological samples. The assay is based on real-time amplification of AluYb8 insertions in hominoid primates. The relatively high copy number of subfamily-specific Alu repeats in the human genome enables quantification of very small amounts of human DNA. The oligonucleotide primers present in H-Quant are specific for human DNA and closely related great apes. During the real-time PCR, the SYBR Green I dye binds to the DNA that is synthesized by the human-specific AluYb8 oligonucleotide primers. The fluorescence of the bound SYBR Green I dye is measured at the end of each PCR cycle. The cycle at which the fluorescence crosses the chosen threshold correlates to the quantity of amplifiable DNA in that sample. The minimal sensitivity of the H-Quant system is 7.6 pg/microL of human DNA. The amplicon generated in the H-Quant assay is 216 bp, which is within the same range of the common amplifiable short tandem repeat (STR) amplicons. This size amplicon enables quantitation of amplifiable DNA as opposed to a quantitation of degraded or nonamplifiable DNA of smaller sizes. Development and validation studies were performed on the 7500 real-time PCR system following the Quality Assurance Standards for Forensic DNA Testing Laboratories.

Reductions in global biodiversity loss predicted from conservation spending.

PubMed

Waldron, Anthony; Miller, Daniel C; Redding, Dave; Mooers, Arne; Kuhn, Tyler S; Nibbelink, Nate; Roberts, J Timmons; Tobias, Joseph A; Gittleman, John L

2017-11-16

Halting global biodiversity loss is central to the Convention on Biological Diversity and United Nations Sustainable Development Goals, but success to date has been very limited. A critical determinant of success in achieving these goals is the financing that is committed to maintaining biodiversity; however, financing decisions are hindered by considerable uncertainty over the likely impact of any conservation investment. For greater effectiveness, we need an evidence-based model that shows how conservation spending quantitatively reduces the rate of biodiversity loss. Here we demonstrate such a model, and empirically quantify how conservation investment reduced biodiversity loss in 109 countries (signatories to the Convention on Biological Diversity and Sustainable Development Goals), by a median average of 29% per country between 1996 and 2008. We also show that biodiversity changes in signatory countries can be predicted with high accuracy, using a dual model that balances the effects of conservation investment against those of economic, agricultural and population growth (human development pressures). Decision-makers can use this model to forecast the improvement that any proposed biodiversity budget would achieve under various scenarios of human development pressure, and then compare these forecasts to any chosen policy target. We find that the impact of spending decreases as human development pressures grow, which implies that funding may need to increase over time. The model offers a flexible tool for balancing the Sustainable Development Goals of human development and maintaining biodiversity, by predicting the dynamic changes in conservation finance that will be needed as human development proceeds.

Reductions in global biodiversity loss predicted from conservation spending

NASA Astrophysics Data System (ADS)

Waldron, Anthony; Miller, Daniel C.; Redding, Dave; Mooers, Arne; Kuhn, Tyler S.; Nibbelink, Nate; Roberts, J. Timmons; Tobias, Joseph A.; Gittleman, John L.

2017-11-01

Halting global biodiversity loss is central to the Convention on Biological Diversity and United Nations Sustainable Development Goals, but success to date has been very limited. A critical determinant of success in achieving these goals is the financing that is committed to maintaining biodiversity; however, financing decisions are hindered by considerable uncertainty over the likely impact of any conservation investment. For greater effectiveness, we need an evidence-based model that shows how conservation spending quantitatively reduces the rate of biodiversity loss. Here we demonstrate such a model, and empirically quantify how conservation investment between 1996 and 2008 reduced biodiversity loss in 109 countries (signatories to the Convention on Biological Diversity and Sustainable Development Goals), by a median average of 29% per country. We also show that biodiversity changes in signatory countries can be predicted with high accuracy, using a dual model that balances the effects of conservation investment against those of economic, agricultural and population growth (human development pressures). Decision-makers can use this model to forecast the improvement that any proposed biodiversity budget would achieve under various scenarios of human development pressure, and then compare these forecasts to any chosen policy target. We find that the impact of spending decreases as human development pressures grow, which implies that funding may need to increase over time. The model offers a flexible tool for balancing the Sustainable Development Goals of human development and maintaining biodiversity, by predicting the dynamic changes in conservation finance that will be needed as human development proceeds.

A base-modified PNA-graphene oxide platform as a turn-on fluorescence sensor for the detection of human telomeric repeats

NASA Astrophysics Data System (ADS)

Sabale, Pramod M.; George, Jerrin Thomas; Srivatsan, Seergazhi G.

2014-08-01

Given the biological and therapeutic significance of telomeres and other G-quadruplex forming sequences in human genome, it is highly desirable to develop simple methods to study these structures, which can also be implemented in screening formats for the discovery of G-quadruplex binders. The majority of telomere detection methods developed so far are laborious and use elaborate assay and instrumental setups, and hence, are not amenable to discovery platforms. Here, we describe the development of a simple homogeneous fluorescence turn-on method, which uses a unique combination of an environment-sensitive fluorescent nucleobase analogue, the superior base pairing property of PNA, and DNA-binding and fluorescence quenching properties of graphene oxide, to detect human telomeric DNA repeats of varying lengths. Our results demonstrate that this method, which does not involve a rigorous assay setup, would provide new opportunities to study G-quadruplex structures.Given the biological and therapeutic significance of telomeres and other G-quadruplex forming sequences in human genome, it is highly desirable to develop simple methods to study these structures, which can also be implemented in screening formats for the discovery of G-quadruplex binders. The majority of telomere detection methods developed so far are laborious and use elaborate assay and instrumental setups, and hence, are not amenable to discovery platforms. Here, we describe the development of a simple homogeneous fluorescence turn-on method, which uses a unique combination of an environment-sensitive fluorescent nucleobase analogue, the superior base pairing property of PNA, and DNA-binding and fluorescence quenching properties of graphene oxide, to detect human telomeric DNA repeats of varying lengths. Our results demonstrate that this method, which does not involve a rigorous assay setup, would provide new opportunities to study G-quadruplex structures. Electronic supplementary information (ESI) available. Figures, tables, experimental procedures and NMR spectra. See DOI: 10.1039/c4nr00878b

Medaka: a promising model animal for comparative population genomics

PubMed Central

Matsumoto, Yoshifumi; Oota, Hiroki; Asaoka, Yoichi; Nishina, Hiroshi; Watanabe, Koji; Bujnicki, Janusz M; Oda, Shoji; Kawamura, Shoji; Mitani, Hiroshi

2009-01-01

Background Within-species genome diversity has been best studied in humans. The international HapMap project has revealed a tremendous amount of single-nucleotide polymorphisms (SNPs) among humans, many of which show signals of positive selection during human evolution. In most of the cases, however, functional differences between the alleles remain experimentally unverified due to the inherent difficulty of human genetic studies. It would therefore be highly useful to have a vertebrate model with the following characteristics: (1) high within-species genetic diversity, (2) a variety of gene-manipulation protocols already developed, and (3) a completely sequenced genome. Medaka (Oryzias latipes) and its congeneric species, tiny fresh-water teleosts distributed broadly in East and Southeast Asia, meet these criteria. Findings Using Oryzias species from 27 local populations, we conducted a simple screening of nonsynonymous SNPs for 11 genes with apparent orthology between medaka and humans. We found medaka SNPs for which the same sites in human orthologs are known to be highly differentiated among the HapMap populations. Importantly, some of these SNPs show signals of positive selection. Conclusion These results indicate that medaka is a promising model system for comparative population genomics exploring the functional and adaptive significance of allelic differentiations. PMID:19426554

Just Working with the Cellular Machine: A High School Game for Teaching Molecular Biology

ERIC Educational Resources Information Center

Cardoso, Fernanda Serpa; Dumpel, Renata; Gomes da Silva, Luisa B.; Rodrigues, Carlos R.; Santos, Dilvani O.; Cabral, Lucio Mendes; Castro, Helena C.

2008-01-01

Molecular biology is a difficult comprehension subject due to its high complexity, thus requiring new teaching approaches. Herein, we developed an interdisciplinary board game involving the human immune system response against a bacterial infection for teaching molecular biology at high school. Initially, we created a database with several…

Gait Analysis by High School Students

ERIC Educational Resources Information Center

Heck, Andre; van Dongen, Caroline

2008-01-01

Human walking is a complicated motion. Movement scientists have developed various research methods to study gait. This article describes how a high school student collected and analysed high quality gait data in much the same way that movement scientists do, via the recording and measurement of motions with a video analysis tool and via…

Evaluation of High-Throughput Chemical Exposure Models via Analysis of Matched Environmental and Biological Media Measurements

EPA Science Inventory

The U.S. EPA, under its ExpoCast program, is developing high-throughput near-field modeling methods to estimate human chemical exposure and to provide real-world context to high-throughput screening (HTS) hazard data. These novel modeling methods include reverse methods to infer ...

A Serological Point-of-Care Test for the Detection of IgG Antibodies against Ebola Virus in Human Survivors.

PubMed

Brangel, Polina; Sobarzo, Ariel; Parolo, Claudio; Miller, Benjamin S; Howes, Philip D; Gelkop, Sigal; Lutwama, Julius J; Dye, John M; McKendry, Rachel A; Lobel, Leslie; Stevens, Molly M

2018-01-23

Ebola virus disease causes widespread and highly fatal epidemics in human populations. Today, there is still great need for point-of-care tests for diagnosis, patient management and surveillance, both during and post outbreaks. We present a point-of-care test comprising an immunochromatographic strip and a smartphone reader, which detects and semiquantifies Ebola-specific antibodies in human survivors. We developed a Sudan virus glycoprotein monoplex platform and validated it using sera from 90 human survivors and 31 local noninfected controls. The performance of the glycoprotein monoplex was 100% sensitivity and 98% specificity compared to standard whole antigen enzyme-linked immunosorbent assay (ELISA), and it was validated with freshly collected patient samples in Uganda. Moreover, we constructed a multiplex test for simultaneous detection of antibodies against three recombinant Sudan virus proteins. A pilot study comprising 15 survivors and 5 noninfected controls demonstrated sensitivity and specificity of 100% compared to standard ELISA. Finally, we developed a second multiplex subtype assay for the identification of exposure to three related EVD species: Sudan virus, Bundibugyo virus and Ebola virus (formerly Zaire) using recombinant viral glycoprotein. This multiplex test could distinguish between the host's immunity to specific viral species and identify cross-reactive immunity. These developed serological platforms consisted of capture ligands with high specificity and sensitivity, in-house developed strips and a compatible smartphone application. These platforms enabled rapid and portable testing, data storage and sharing as well as geographical tagging of the tested individuals in Uganda. This platform holds great potential as a field tool for diagnosis, vaccine development, and therapeutic evaluation.

Developing a Personnel Capacity Indicator for a high turnover Cartographic Production Sector

NASA Astrophysics Data System (ADS)

Mandarino, Flávia; Pessôa, Leonardo A. M.

2018-05-01

This paper describes a framework for development of an indicator for human re-sources capacity management in a military organization responsible for nautical chart production. Graphic chart for the results of the model COPPE-COSENZA (Cosenza et al. 2015) is used to properly present the personnel capacity within a high people turnover environment. The specific skills for the nautical charts production allied to the turnover rate require continuous and adequate personnel in-corporation and a capacity building through education and on-the-job training. The adopted approach for the study establishes quantitative values to fulfill quality requirements, and also presents graphically a profile for the human resources on a specific job to facilitate diagnosis and corrective actions.

[Development of alternative to animal experiment in evaluation of skin irritation caused by alcohol-based hand rubs].

PubMed

Yamamoto, Nobuyuki; Miyamoto, Koji; Katoh, Masakazu

2010-08-01

Alcohol-based hand rubs are widely used for infection control in clinical practice. However, it is known that frequent use of the alcohol-based hand rubs may cause skin irritation. To predict the skin irritation in human, animal experiments are quite useful. Especially, the Draize Test using rabbits is suitable for this purpose because their skin is highly sensitive. On the other hand, the development of alternative to animal experiments is important not only from the viewpoint of ethical aspects but also from the efficient research and development. Reconstructed human epidermis (RhE) was developed as a human skin equivalent model in vitro, and has been applied to the evaluation of skin irritation. But the RhE has not been utilized for the evaluation of alcohol-based hand rubs because of the high skin permeability and cytotoxicity of alcohols. The aim of this study was to develop a new method using the RhE in evaluation of skin irritation caused by alcohol-based hand rubs. The authors propose an experimental technique named "Skin model blowing method (SMBM)" consisting of the sequential procedure as follows; applying small amount of testing sample on RhE, blow-dry, post incubation, and cell viability measurement. According to the SMBM, the skin irritation caused by alcohol-based hand rubs could be evaluated under the similar condition of their actual use. It was found that a high correlation existed between the cell viability obtained from SMBM and the skin irritation index in rabbit which had been reported previously.

Welfare and Jobs: Rebuilding the Labor Market from the Bottom Down.

ERIC Educational Resources Information Center

Baldwin, Marc

1998-01-01

Discusses the new welfare law's elements that affect low-wage labor: work requirements, time limits, relaxed protections, and expanded state authority. Outlines high-road versus low-road policies in terms of economic development, human resource development, and administration. (SK)

Development of a low cost portable fluorometry technology and quantification of cannabinoids in body fluids

DOT National Transportation Integrated Search

1977-05-04

Technology was developed for determining delta sup 9-tetrahydrocannabinol (I) and its major metabolite 11-nor-delta sup 9-tetrahydrocannabinol-9-carboxylic acid (II) in human blood plasma utilizing high pressure liquid chromatography (hplc)-ultraviol...

Developing a High Level Data Base to Teach Reproductive Endocrinology Using the HyperCard Program.

ERIC Educational Resources Information Center

Friedler, Yael; Shabo, Amnon

1990-01-01

Describes a database courseware using the HyperCard program on the subject of human reproductive endocrinology and feedback mechanisms. Discusses some issues concerning database courseware development. Presents several examples of the courseware display. (Author/YP)

Solar Electric Propulsion Technology Development for Electric Propulsion

NASA Technical Reports Server (NTRS)

Mercer, Carolyn R.; Kerslake, Thomas W.; Scheidegger, Robert J.; Woodworth, Andrew A.; Lauenstein, Jean-Marie

2015-01-01

NASA is developing technologies to prepare for human exploration missions to Mars. Solar electric propulsion (SEP) systems are expected to enable a new cost effective means to deliver cargo to the Mars surface. Nearer term missions to Mars moons or near-Earth asteroids can be used to both develop and demonstrate the needed technology for these future Mars missions while demonstrating new capabilities in their own right. This presentation discusses recent technology development accomplishments for high power, high voltage solar arrays and power management that enable a new class of SEP missions.

Review of the Human Resources, Finance, and Information Technology Operations of the Seattle Public Schools

ERIC Educational Resources Information Center

Council of the Great City Schools, 2008

2008-01-01

In late 2007, the Council of the Great City Schools conducted a high-level management review of the school district's human resources, financial, and technology operations to: (1) Review and evaluate the leadership, management, organization, and operations of the respective departments; and (2) Develop recommendations and proposals that would…

The bee microbiome: impact on bee health and model for evolution and ecology of host-microbe interactions

USDA-ARS?s Scientific Manuscript database

Fanconi anemia (FA) is a rare genetic disorder caused by defects in DNA damage repair. FA patients often develop squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) are known to cause cancer, including the cervix. However, SCCs found in human FA patients are often HP...

Returns to Education: An International Comparison. Studies on Education; Vol. 2.

ERIC Educational Resources Information Center

Psacharopoulos, George; Hinchliffe, Keith

Since the education boom of the sixties enough time has passed for estimates to be made of the profitability of such a highly speculative investment of human capital. Only from these sources of information can we determine future education and manpower, and develop human resources. Returns to education are clearly visible, whether they differ…

Statistical methods for analysing responses of wildlife to human disturbance.

Treesearch

Haiganoush K. Preisler; Alan A. Ager; Michael J. Wisdom

2006-01-01

1. Off-road recreation is increasing rapidly in many areas of the world, and effects on wildlife can be highly detrimental. Consequently, we have developed methods for studying wildlife responses to off-road recreation with the use of new technologies that allow frequent and accurate monitoring of human-wildlife interactions. To illustrate these methods, we studied the...

Contrasting State-of-the-Art in the Machine Scoring of Short-Form Constructed Responses

ERIC Educational Resources Information Center

Shermis, Mark D.

2015-01-01

This study compared short-form constructed responses evaluated by both human raters and machine scoring algorithms. The context was a public competition on which both public competitors and commercial vendors vied to develop machine scoring algorithms that would match or exceed the performance of operational human raters in a summative high-stakes…

Perspectives on the Development and Future of Advanced Placement® Human Geography

ERIC Educational Resources Information Center

Hildebrant, Barbara

2016-01-01

Advanced Placement (AP) Human Geography faced a number of hurdles that nearly derailed the course before it launched in 2000-2001. A dedicated cadre of geography professionals and high school teachers rose to the challenge and the course remains one of the fastest growing AP courses currently offered by College Board. Seventeen readers and leaders…

Surveying an Ecosystem: An Exercise for High School Biology Students.

ERIC Educational Resources Information Center

Lewis, James K.

This activity is used to introduce students to biology in general and the significance of environmental studies. The focus of the ecosystem survey is to examine the effects humans have on the environment. After completing a series of investigations, students develop their own hypothesis about human impact on the environment, and then test this on…

Workshop on Numerical Analysis of Human and Surrogate Response to Accelerative Loading

DTIC Science & Technology

2014-05-01

calcaneal fractures with high rates of amputation and poor outcome [1].The first body part in contact with the loading boundary is the heel fat pad...Laboratory • “Material Properties of the Human Heel Fat Pad Across Loading Rates” by Grigoris Grigoriadis, Nic Newell, Spyros Masouros, and Anthony Bull...and Micro/Sub-structural Details on the Fracture Response of Human Cortical Bones” by Tusit Weerasooriya, ARL • “Recent Developments in a

A Modified Protocol for the Isolation of Primary Human Hepatocytes with Improved Viability and Function from Normal and Diseased Human Liver.

PubMed

Bartlett, David C; Newsome, Philip N

2017-01-01

Successful hepatocyte isolation is critical for continued development of cellular transplantation. However, most tissue available for research is from diseased liver and the results of hepatocyte isolation from such tissue are inferior compared to normal tissue. Here we describe a modified method, combining the use of Liberase and N-acetylcysteine (NAC), for the isolation of primary human hepatocytes with high viability from normal and diseased liver.

Reducing the Risk of Human Space Missions with INTEGRITY

NASA Technical Reports Server (NTRS)

Jones, Harry W.; Dillon-Merill, Robin L.; Tri, Terry O.; Henninger, Donald L.

2003-01-01

The INTEGRITY Program will design and operate a test bed facility to help prepare for future beyond-LEO missions. The purpose of INTEGRITY is to enable future missions by developing, testing, and demonstrating advanced human space systems. INTEGRITY will also implement and validate advanced management techniques including risk analysis and mitigation. One important way INTEGRITY will help enable future missions is by reducing their risk. A risk analysis of human space missions is important in defining the steps that INTEGRITY should take to mitigate risk. This paper describes how a Probabilistic Risk Assessment (PRA) of human space missions will help support the planning and development of INTEGRITY to maximize its benefits to future missions. PRA is a systematic methodology to decompose the system into subsystems and components, to quantify the failure risk as a function of the design elements and their corresponding probability of failure. PRA provides a quantitative estimate of the probability of failure of the system, including an assessment and display of the degree of uncertainty surrounding the probability. PRA provides a basis for understanding the impacts of decisions that affect safety, reliability, performance, and cost. Risks with both high probability and high impact are identified as top priority. The PRA of human missions beyond Earth orbit will help indicate how the risk of future human space missions can be reduced by integrating and testing systems in INTEGRITY.

Photorealistic virtual anatomy based on Chinese Visible Human data.

PubMed

Heng, P A; Zhang, S X; Xie, Y M; Wong, T T; Chui, Y P; Cheng, C Y

2006-04-01

Virtual reality based learning of human anatomy is feasible when a database of 3D organ models is available for the learner to explore, visualize, and dissect in virtual space interactively. In this article, we present our latest work on photorealistic virtual anatomy applications based on the Chinese Visible Human (CVH) data. We have focused on the development of state-of-the-art virtual environments that feature interactive photo-realistic visualization and dissection of virtual anatomical models constructed from ultra-high resolution CVH datasets. We also outline our latest progress in applying these highly accurate virtual and functional organ models to generate realistic look and feel to advanced surgical simulators. (c) 2006 Wiley-Liss, Inc.

Mapping and Sequencing the Human Genome

DOE R&D Accomplishments Database

1988-01-01

Numerous meetings have been held and a debate has developed in the biological community over the merits of mapping and sequencing the human genome. In response a committee to examine the desirability and feasibility of mapping and sequencing the human genome was formed to suggest options for implementing the project. The committee asked many questions. Should the analysis of the human genome be left entirely to the traditionally uncoordinated, but highly successful, support systems that fund the vast majority of biomedical research. Or should a more focused and coordinated additional support system be developed that is limited to encouraging and facilitating the mapping and eventual sequencing of the human genome. If so, how can this be done without distorting the broader goals of biological research that are crucial for any understanding of the data generated in such a human genome project. As the committee became better informed on the many relevant issues, the opinions of its members coalesced, producing a shared consensus of what should be done. This report reflects that consensus.

Rapid Molecular Identification of Human Taeniid Cestodes by Pyrosequencing Approach

PubMed Central

Thanchomnang, Tongjit; Tantrawatpan, Chairat; Intapan, Pewpan M.; Sanpool, Oranuch; Janwan, Penchom; Lulitanond, Viraphong; Tourtip, Somjintana; Yamasaki, Hiroshi; Maleewong, Wanchai

2014-01-01

Taenia saginata, T. solium, and T. asiatica are causative agents of taeniasis in humans. The difficulty of morphological identification of human taeniids can lead to misdiagnosis or confusion. To overcome this problem, several molecular methods have been developed, but use of these tends to be time-consuming. Here, a rapid and high-throughput pyrosequencing approach was developed for the identification of three human taeniids originating from various countries. Primers targeting the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of the three Taenia species were designed. Variations in a 26-nucleotide target region were used for identification. The reproducibility and accuracy of the pyrosequencing technology was confirmed by Sanger sequencing. This technique will be a valuable tool to distinguish between sympatric human taeniids that occur in Thailand, Asia and Pacific countries. This method could potentially be used for the molecular identification of the taeniid species that might be associated with suspicious cysts and lesions, or cyst residues in humans or livestock at the slaughterhouse. PMID:24945530

Progress in Brucella vaccine development

PubMed Central

YANG, Xinghong; SKYBERG, Jerod A.; CAO, Ling; CLAPP, Beata; THORNBURG, Theresa; PASCUAL, David W.

2012-01-01

Brucella spp. are zoonotic, facultative intracellular pathogens, which cause animal and human disease. Animal disease results in abortion of fetuses; in humans, it manifests flu-like symptoms with an undulant fever, with osteoarthritis as a common complication of infection. Antibiotic regimens for human brucellosis patients may last several months and are not always completely effective. While there are no vaccines for humans, several licensed live Brucella vaccines are available for use in livestock. The performance of these animal vaccines is dependent upon the host species, dose, and route of immunization. Newly engineered live vaccines, lacking well-defined virulence factors, retain low residual virulence, are highly protective, and may someday replace currently used animal vaccines. These also have possible human applications. Moreover, due to their enhanced safety and efficacy in animal models, subunit vaccines for brucellosis show great promise for their application in livestock and humans. This review summarizes the progress of brucellosis vaccine development and presents an overview of candidate vaccines. PMID:23730309

An assessment system for rating scientific journals in the field of ergonomics and human factors.

PubMed

Dul, Jan; Karwowski, Waldemar

2004-05-01

A method for selecting and rating scientific and professional journals representing the discipline of ergonomics and human factors is proposed. The method is based upon the journal list, impact factors and citations provided by the Institute of Scientific Information (ISI), and the journal list published in the Ergonomics Abstracts. Three groups of journals were distinguished. The 'ergonomics journals' focus exclusively on ergonomics and human factors. The 'related journals' focus on other disciplines than ergonomics and human factors, but regularly publish ergonomics/human factors papers. The 'basic journals' focus on other technical, medical or social sciences than ergonomics, but are important for the development of ergonomics/human factors. Journal quality was rated using a maximum of four categories: top quality (A-level), high quality (B-level), good quality (C-level)) and professional (P-level). The above methods were applied to develop the Ergonomics Journal List 2004. A total of 25 'ergonomics journals', 58 'related journals' and 142 'basic journals' were classified.

Practical use of high-speed cameras for research and development within the automotive industry: yesterday and today

NASA Astrophysics Data System (ADS)

Steinmetz, Klaus

1995-05-01

Within the automotive industry, especially for the development and improvement of safety systems, we find a lot of high accelerated motions, that can not be followed and consequently not be analyzed by human eye. For the vehicle safety tests at AUDI, which are performed as 'Crash Tests', 'Sled Tests' and 'Static Component Tests', 'Stalex', 'Hycam', and 'Locam' cameras are in use. Nowadays the automobile production is inconceivable without the use of high speed cameras.

Developing people: a strategy for competitive advantage.

PubMed

King, S

1995-05-01

This article will provide vital insights, acquired in a recent study with eight manufacturing companies, to guide the development of a human resource development strategy. This study was a pilot for a larger study, planned for the fall of 1995 with 50 manufacturing companies randomly chosen from the Directory of Massachusetts High Technology Companies.

Chimpanzee Adenovirus Vaccine Provides Multispecies Protection against Rift Valley Fever.

PubMed

Warimwe, George M; Gesharisha, Joseph; Carr, B Veronica; Otieno, Simeon; Otingah, Kennedy; Wright, Danny; Charleston, Bryan; Okoth, Edward; Elena, Lopez-Gil; Lorenzo, Gema; Ayman, El-Behiry; Alharbi, Naif K; Al-dubaib, Musaad A; Brun, Alejandro; Gilbert, Sarah C; Nene, Vishvanath; Hill, Adrian V S

2016-02-05

Rift Valley Fever virus (RVFV) causes recurrent outbreaks of acute life-threatening human and livestock illness in Africa and the Arabian Peninsula. No licensed vaccines are currently available for humans and those widely used in livestock have major safety concerns. A 'One Health' vaccine development approach, in which the same vaccine is co-developed for multiple susceptible species, is an attractive strategy for RVFV. Here, we utilized a replication-deficient chimpanzee adenovirus vaccine platform with an established human and livestock safety profile, ChAdOx1, to develop a vaccine for use against RVFV in both livestock and humans. We show that single-dose immunization with ChAdOx1-GnGc vaccine, encoding RVFV envelope glycoproteins, elicits high-titre RVFV-neutralizing antibody and provides solid protection against RVFV challenge in the most susceptible natural target species of the virus-sheep, goats and cattle. In addition we demonstrate induction of RVFV-neutralizing antibody by ChAdOx1-GnGc vaccination in dromedary camels, further illustrating the potency of replication-deficient chimpanzee adenovirus vaccine platforms. Thus, ChAdOx1-GnGc warrants evaluation in human clinical trials and could potentially address the unmet human and livestock vaccine needs.

Anaerobic Probiotics: The Key Microbes for Human Health.

PubMed

El Enshasy, Hesham; Malik, Khairuddin; Malek, Roslinda Abd; Othman, Nor Zalina; Elsayed, Elsayed Ahmed; Wadaan, Mohammad

Human gastrointestinal microbiota (HGIM) incorporate a large number of microbes from different species. Anaerobic bacteria are the dominant organisms in this microbial consortium and play a crucial role in human health. In addition to their functional role as the main source of many essential metabolites for human health, they are considered as biotherapeutic agents in the regulation of different human metabolites. They are also important in the prevention and in the treatment of different physical and mental diseases. Bifidobacteria are the dominant anaerobic bacteria in HGIM and are widely used in the development of probiotic products for infants, children and adults. To develop bifidobacteria-based bioproducts, therefore, it is necessary to develop a large-scale biomass production platform based on a good understanding of the ideal medium and bioprocessing parameters for their growth and viability. In addition, high cell viability should be maintained during downstream processing and storage of probiotic cell powder or the final formulated product. In this work we review the latest information about the biology, therapeutic activities, cultivation and industrial production of bifidobacteria.

Cyber situation awareness as distributed socio-cognitive work

NASA Astrophysics Data System (ADS)

Tyworth, Michael; Giacobe, Nicklaus A.; Mancuso, Vincent

2012-06-01

A key challenge for human cybersecurity operators is to develop an understanding of what is happening within, and to, their network. This understanding, or situation awareness, provides the cognitive basis for human operators to take action within their environments. Yet developing situation awareness of cyberspace (cyber-SA) is understood to be extremely difficult given the scope of the operating environment, the highly dynamic nature of the environment and the absence of physical constraints that serve to bound the cognitive task23. As a result, human cybersecurity operators are often "flying blind" regarding understanding the source, nature, and likely impact of malicious activity on their networked assets. In recent years, many scholars have dedicated their attention to finding ways to improve cyber-SA in human operators. In this paper we present our findings from our ongoing research of how cybersecurity analysts develop and maintain cyber-SA. Drawing from over twenty interviews of analysts working in the military, government, industrial, and educational domains, we find that cyber-SA to be distributed across human operators and technological artifacts operating in different functional areas.

Research of Face Recognition with Fisher Linear Discriminant

NASA Astrophysics Data System (ADS)

Rahim, R.; Afriliansyah, T.; Winata, H.; Nofriansyah, D.; Ratnadewi; Aryza, S.

2018-01-01

Face identification systems are developing rapidly, and these developments drive the advancement of biometric-based identification systems that have high accuracy. However, to develop a good face recognition system and to have high accuracy is something that’s hard to find. Human faces have diverse expressions and attribute changes such as eyeglasses, mustache, beard and others. Fisher Linear Discriminant (FLD) is a class-specific method that distinguishes facial image images into classes and also creates distance between classes and intra classes so as to produce better classification.

Biosphere as a complex life-support system (LSS) for human civilization

NASA Astrophysics Data System (ADS)

Pechurkin, Nickolay

As a continuously growing link of the Biosphere, we should keep in mind that biotic cycles induced by flows of a solar energy are the source of Biosphere and ecosystems functioning. Our pressure on the Biosphere which is connected with biotic cycle’s alterations and damages is menacingly growing. There are innumerable examples of atmosphere, water and soil pollution. We have contaminated even Earth-Space orbits with different uncontrolled debris. Ecological Footprint (EF) is a proper quantitative measure of anthropogenic impact on the Biosphere and ecosystems functioning. The comparative dynamics of the United Nations’ Human Development Index (HDI) and Ecological Footprint (EF) is discussed in the paper. The main call of sustainable development of mankind: all humans can have opportunity to fulfill their lives without degrading the Biosphere. To support sustainability, we should make an effort to develop each nation and the mankind as a whole with a high HDI and with a low ecological footprint. It means: to have high level of HDI at low level of EF. But current tendency of economical and social development shows: the higher HDI, the bigger EF. EF of mankind is rising threateningly. Now actual pressure of the human civilization of our planet (2014) upon 60 % exceeds its potential possibilities (biological capacity, measured as the area of "global" green hectares). It means that now we require more than 1.5 planets of the Earth’s type for sustainable development. It leads to ecological incident in the scale of Biosphere. Our Biosphere is the large, multilevel, hierarchically organized system, and our civilization is only a part of it. This part is not central; it can disappear for ever, if we do not cope to be included in the Biosphere as a great complex system. An example of Krasnoyarsk region as a representative region with high level of industry and technological energy production is considered in the paper. This work was supported by the Russian Foundation for Basic Research, project number 13-06-00060.

Development of a new methodology for the creation of water temperature scenarios using frequency analysis tool.

PubMed

Val, Jonatan; Pino, María Rosa; Chinarro, David

2018-03-15

Thermal quality in river ecosystems is a fundamental property for the development of biological processes and many of the human activities linked to the aquatic environment. In the future, this property is going to be threatened due to global change impacts, and basin managers will need useful tools to evaluate these impacts. Currently, future projections in temperature modelling are based on the historical data for air and water temperatures, and the relationship with past temperature scenarios; however, this represents a problem when evaluating future scenarios with new thermal impacts. Here, we analysed the thermal impacts produced by several human activities, and linked them with the decoupling degree of the thermal transfer mechanism from natural systems measured with frequency analysis tools (wavelet coherence). Once this relationship has been established we develop a new methodology for simulating different thermal impacts scenarios in order to project them into future. Finally, we validate this methodology using a site that changed its thermal quality during the studied period due to human impacts. Results showed a high correlation (r 2 =0.84) between the decoupling degree of the thermal transfer mechanisms and the quantified human impacts, obtaining 3 thermal impact scenarios. Furthermore, the graphic representation of these thermal scenarios with its wavelet coherence spectrums showed the impacts of an extreme drought period and the agricultural management. The inter-conversion between the scenarios gave high morphological similarities in the obtained wavelet coherence spectrums, and the validation process clearly showed high efficiency of the developed model against old methodologies when comparing with Nash-Stucliffe criterion. Although there is need for further investigation with different climatic and anthropic management conditions, the developed frequency models could be useful in decision-making processes by managers when faced with future global change impacts. Copyright © 2017 Elsevier B.V. All rights reserved.

High-Speed and Scalable Whole-Brain Imaging in Rodents and Primates.

PubMed

Seiriki, Kaoru; Kasai, Atsushi; Hashimoto, Takeshi; Schulze, Wiebke; Niu, Misaki; Yamaguchi, Shun; Nakazawa, Takanobu; Inoue, Ken-Ichi; Uezono, Shiori; Takada, Masahiko; Naka, Yuichiro; Igarashi, Hisato; Tanuma, Masato; Waschek, James A; Ago, Yukio; Tanaka, Kenji F; Hayata-Takano, Atsuko; Nagayasu, Kazuki; Shintani, Norihito; Hashimoto, Ryota; Kunii, Yasuto; Hino, Mizuki; Matsumoto, Junya; Yabe, Hirooki; Nagai, Takeharu; Fujita, Katsumasa; Matsuda, Toshio; Takuma, Kazuhiro; Baba, Akemichi; Hashimoto, Hitoshi

2017-06-21

Subcellular resolution imaging of the whole brain and subsequent image analysis are prerequisites for understanding anatomical and functional brain networks. Here, we have developed a very high-speed serial-sectioning imaging system named FAST (block-face serial microscopy tomography), which acquires high-resolution images of a whole mouse brain in a speed range comparable to that of light-sheet fluorescence microscopy. FAST enables complete visualization of the brain at a resolution sufficient to resolve all cells and their subcellular structures. FAST renders unbiased quantitative group comparisons of normal and disease model brain cells for the whole brain at a high spatial resolution. Furthermore, FAST is highly scalable to non-human primate brains and human postmortem brain tissues, and can visualize neuronal projections in a whole adult marmoset brain. Thus, FAST provides new opportunities for global approaches that will allow for a better understanding of brain systems in multiple animal models and in human diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

HUMEX, a study on the survivability and adaptation of humans to long- duration exploratory missions

NASA Astrophysics Data System (ADS)

Horneck, G.

ESA has recently initiated a study of the human responses, limits and needs with regard to the stress environments of interplanetary and planetary missions. Emphasis was laid on human health and performance care as well as Advanced Life Support Developments including Bioregenerative Life Support Systems and environmental monitoring. The overall study goals were as follows: (i) to define reference scenarios for a European participation in human exploration and to estimate their influence on the Life Sciences and Life Support requirements; (ii) for selected mission scenarios, to critically assess the limiting factors for human health, wellbeing, and performance and to recommend relevant countermeasures; (iii) for selected mission scenarios, to critically assess the potential of Advanced Life Support Developments and to propose a European strategy including terrestrial applications; (iv) to critically assess the feasibility of existing facilities and technologies on ground and in space as testbeds in preparation for human exploratory missions and to develop a test plan for ground and ISS campaigns; (v) to develop a roadmap for a future European strategy towards human exploratory missions, including preparatory activities and terrestrial applications and benefits. A lunar base at the south pole where constant sunlight and potential water ice deposits could be assumed was selected as the moon scenario. the impact on human health, performance and well being has been investigated from the view point of the effects of microgravity (during space travel), reduced gravity (on the Moon) and abrupt gravity changes (during launch and landing), of the effects of cosmic radiation including solar particle events, of psychological issues as well as general health care. Countermeasures as well as necessary research using ground- based testbeds and/or the ISS have been defined. The need for highly intelligent autonomous diagnostic and therapy systems was considered as a driver also for terrestrial applications. Likewise advanced life support systems with a high degree of autonomy and regenerative capacity and synergy effects were considered where bioregenerative life support systems and biodiagnistic systems become essential especially for the long-term Mars scenario. A roadmap for a future European strategy leading to a potential European participation in a cooperative human exploratory mission, either to the Moon or to Mars, was produced. Ref. Horneck et al. HUMEX, study on the Survivability and Adaptation of Humans to Long-Duration Exploratory Missions, ESA SP (in press)

Towards large-scale, human-based, mesoscopic neurotechnologies.

PubMed

Chang, Edward F

2015-04-08

Direct human brain recordings have transformed the scope of neuroscience in the past decade. Progress has relied upon currently available neurophysiological approaches in the context of patients undergoing neurosurgical procedures for medical treatment. While this setting has provided precious opportunities for scientific research, it also has presented significant constraints on the development of new neurotechnologies. A major challenge now is how to achieve high-resolution spatiotemporal neural recordings at a large scale. By narrowing the gap between current approaches, new directions tailored to the mesoscopic (intermediate) scale of resolution may overcome the barriers towards safe and reliable human-based neurotechnology development, with major implications for advancing both basic research and clinical translation. Copyright © 2015 Elsevier Inc. All rights reserved.

The Acinar Cage: Basement Membranes Determine Molecule Exchange and Mechanical Stability of Human Breast Cell Acini.

PubMed

Gaiko-Shcherbak, Aljona; Fabris, Gloria; Dreissen, Georg; Merkel, Rudolf; Hoffmann, Bernd; Noetzel, Erik

2015-01-01

The biophysical properties of the basement membrane that surrounds human breast glands are poorly understood, but are thought to be decisive for normal organ function and malignancy. Here, we characterize the breast gland basement membrane with a focus on molecule permeation and mechanical stability, both crucial for organ function. We used well-established and nature-mimicking MCF10A acini as 3D cell model for human breast glands, with ether low- or highly-developed basement membrane scaffolds. Semi-quantitative dextran tracer (3 to 40 kDa) experiments allowed us to investigate the basement membrane scaffold as a molecule diffusion barrier in human breast acini in vitro. We demonstrated that molecule permeation correlated positively with macromolecule size and intriguingly also with basement membrane development state, revealing a pore size of at least 9 nm. Notably, an intact collagen IV mesh proved to be essential for this permeation function. Furthermore, we performed ultra-sensitive atomic force microscopy to quantify the response of native breast acini and of decellularized basement membrane shells against mechanical indentation. We found a clear correlation between increasing acinar force resistance and basement membrane formation stage. Most important native acini with highly-developed basement membranes as well as cell-free basement membrane shells could both withstand physiologically relevant loads (≤ 20 nN) without loss of structural integrity. In contrast, low-developed basement membranes were significantly softer and more fragile. In conclusion, our study emphasizes the key role of the basement membrane as conductor of acinar molecule influx and mechanical stability of human breast glands, which are fundamental for normal organ function.

Human factors in the Naval Air Systems Command: Computer based training

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

Seamster, T.L.; Snyder, C.E.; Terranova, M.

1988-01-01

Military standards applied to the private sector contracts have a substantial effect on the quality of Computer Based Training (CBT) systems procured for the Naval Air Systems Command. This study evaluated standards regulating the following areas in CBT development and procurement: interactive training systems, cognitive task analysis, and CBT hardware. The objective was to develop some high-level recommendations for evolving standards that will govern the next generation of CBT systems. One of the key recommendations is that there be an integration of the instructional systems development, the human factors engineering, and the software development standards. Recommendations were also made formore » task analysis and CBT hardware standards. (9 refs., 3 figs.)« less

The HIV-1 Epidemic: Low- to Middle-Income Countries

PubMed Central

Shao, Yiming; Williamson, Carolyn

2012-01-01

Low- to middle-income countries bear the overwhelming burden of the human immunodeficiency virus type 1 (HIV-1) epidemic in terms of the numbers of their citizens living with HIV/AIDS (acquired immunodeficiency syndrome), the high degrees of viral diversity often involving multiple HIV-1 clades circulating within their populations, and the social and economic factors that compromise current control measures. Distinct epidemics have emerged in different geographical areas. These epidemics differ in their severity, the population groups they affect, their associated risk behaviors, and the viral strains that drive them. In addition to inflicting great human cost, the high burden of HIV infection has a major impact on the social and economic development of many low- to middle-income countries. Furthermore, the high degrees of viral diversity associated with multiclade HIV epidemics impacts viral diagnosis and pathogenicity and treatment and poses daunting challenges for effective vaccine development. PMID:22393534

Finite element analysis of human joints

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

Bossart, P.L.; Hollerbach, K.

1996-09-01

Our work focuses on the development of finite element models (FEMs) that describe the biomechanics of human joints. Finite element modeling is becoming a standard tool in industrial applications. In highly complex problems such as those found in biomechanics research, however, the full potential of FEMs is just beginning to be explored, due to the absence of precise, high resolution medical data and the difficulties encountered in converting these enormous datasets into a form that is usable in FEMs. With increasing computing speed and memory available, it is now feasible to address these challenges. We address the first by acquiringmore » data with a high resolution C-ray CT scanner and the latter by developing semi-automated method for generating the volumetric meshes used in the FEM. Issues related to tomographic reconstruction, volume segmentation, the use of extracted surfaces to generate volumetric hexahedral meshes, and applications of the FEM are described.« less

Reconnecting to the biosphere.

PubMed

Folke, Carl; Jansson, Asa; Rockström, Johan; Olsson, Per; Carpenter, Stephen R; Chapin, F Stuart; Crépin, Anne-Sophie; Daily, Gretchen; Danell, Kjell; Ebbesson, Jonas; Elmqvist, Thomas; Galaz, Victor; Moberg, Fredrik; Nilsson, Måns; Osterblom, Henrik; Ostrom, Elinor; Persson, Asa; Peterson, Garry; Polasky, Stephen; Steffen, Will; Walker, Brian; Westley, Frances

2011-11-01

Humanity has emerged as a major force in the operation of the biosphere, with a significant imprint on the Earth System, challenging social-ecological resilience. This new situation calls for a fundamental shift in perspectives, world views, and institutions. Human development and progress must be reconnected to the capacity of the biosphere and essential ecosystem services to be sustained. Governance challenges include a highly interconnected and faster world, cascading social-ecological interactions and planetary boundaries that create vulnerabilities but also opportunities for social-ecological change and transformation. Tipping points and thresholds highlight the importance of understanding and managing resilience. New modes of flexible governance are emerging. A central challenge is to reconnect these efforts to the changing preconditions for societal development as active stewards of the Earth System. We suggest that the Millennium Development Goals need to be reframed in such a planetary stewardship context combined with a call for a new social contract on global sustainability. The ongoing mind shift in human relations with Earth and its boundaries provides exciting opportunities for societal development in collaboration with the biosphere--a global sustainability agenda for humanity.

Developing an Index to Measure Health System Performance: Measurement for Districts of Nepal.

PubMed

Kandel, N; Fric, A; Lamichhane, J

2014-01-01

Various frameworks for measuring health system performance have been proposed and discussed. The scope of using performance indicators are broad, ranging from examining national health system to individual patients at various levels of health system. Development of innovative and easy index is essential to measure multidimensionality of health systems. We used indicators, which also serve as proxy to the set of activities, whose primary goal is to maintain and improve health. We used eleven indicators of MDGs, which represent all dimensions of health to develop index. These indicators are computed with similar methodology that of human development index. We used published data of Nepal for computation of the index for districts of Nepal as an illustration. To validate our finding, we compared the indices of these districts with other development indices of Nepal. An index for each district has been computed from eleven indicators. Then indices are compared with that of human development index, socio-economic and infrastructure development indices and findings has shown the similarity on distribution of districts. Categories of low and high performing districts on health system performance are also having low and high human development, socio-economic, and infrastructure indices respectively. This methodology of computing index from various indicators could assist policy makers and program managers to prioritize activities based on their performance. Validation of the findings with that of other development indicators show that this can be one of the tools, which can assist on assessing health system performance for policy makers, program managers and others.

Epididymal genomics and the search for a male contraceptive.

PubMed

Turner, T T; Johnston, D S; Jelinsky, S A

2006-05-16

This report represents the joint efforts of three laboratories, one with a primary interest in understanding regulatory processes in the epididymal epithelium (TTT) and two with a primary interest in identifying and characterizing new contraceptive targets (DSJ and SAJ). We have developed a highly refined mouse epididymal transcriptome and have used it as a starting point for determining genes in the human epididymis, which may serve as targets for male contraceptives. Our database represents gene expression information for approximately 39,000 transcripts, of which over 17,000 are significantly expressed in at least one segment of the mouse epididymis. Over 2000 of these transcripts are up- or down-regulated by at least four-fold between at least two segments. In addition, human databases have been queried to determine expression of orthologs in the human epididymis and the specificity of their expression in the epididymis. Genes highly regulated in the human epididymis and showing high tissue specificity are potential targets for male contraceptives.

Ebselen Reversibly Inhibits Human Glutamate Dehydrogenase at the Catalytic Site.

PubMed

Jin, Yanhong; Li, Di; Lu, Shiying; Zhao, Han; Chen, Zhao; Hou, Wei; Ruan, Benfang Helen

Human glutamate dehydrogenase (GDH) plays an important role in neurological diseases, tumor metabolism, and hyperinsulinism-hyperammonemia syndrome (HHS). However, there are very few inhibitors known for human GDH. Recently, Ebselen was reported to crosslink with Escherichia coli GDH at the active site cysteine residue (Cys321), but the sequence alignment showed that the corresponding residue is Ala329 in human GDH. To investigate whether Ebselen could be an inhibitor for human GDH, we cloned and expressed an N-terminal His-tagged human GDH in E. coli. The recombinant human GDH enzyme showed expected properties such as adenosine diphosphate activation and nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate dual recognition. Further, we developed a 2-(3-(2-methoxy-4-nitrophenyl)-2-(4-nitrophenyl)-2H-tetrazol-3-ium-5-yl) benzenesulfonate sodium salt (EZMTT)-based assay for human GDH, which was highly sensitive and is suitable for high-throughput screening for potent GDH inhibitors. In addition, ForteBio binding assays demonstrated that Ebselen is a reversible active site inhibitor for human GDH. Since Ebselen is a multifunctional organoselenium compound in Phase III clinical trials for inflammation, an Ebselen-based GDH inhibitor might be valuable for future drug discovery for HHS patients.

Functional impact of the human mobilome.

PubMed

Babatz, Timothy D; Burns, Kathleen H

2013-06-01

The human genome is replete with interspersed repetitive sequences derived from the propagation of mobile DNA elements. Three families of human retrotransposons remain active today: LINE1, Alu, and SVA elements. Since 1988, de novo insertions at previously recognized disease loci have been shown to generate highly penetrant alleles in Mendelian disorders. Only recently has the extent of germline-transmitted retrotransposon insertion polymorphism (RIP) in human populations been fully realized. Also exciting are recent studies of somatic retrotransposition in human tissues and reports of tumor-specific insertions, suggesting roles in tissue heterogeneity and tumorigenesis. Here we discuss mobile elements in human disease with an emphasis on exciting developments from the last several years. Copyright © 2013 Elsevier Ltd. All rights reserved.

Characterization of the Epigenetic Changes During Human Gonadal Primordial Germ Cells Reprogramming.

PubMed

Eguizabal, C; Herrera, L; De Oñate, L; Montserrat, N; Hajkova, P; Izpisua Belmonte, J C

2016-09-01

Epigenetic reprogramming is a central process during mammalian germline development. Genome-wide DNA demethylation in primordial germ cells (PGCs) is a prerequisite for the erasure of epigenetic memory, preventing the transmission of epimutations to the next generation. Apart from DNA demethylation, germline reprogramming has been shown to entail reprogramming of histone marks and chromatin remodelling. Contrary to other animal models, there is limited information about the epigenetic dynamics during early germ cell development in humans. Here, we provide further characterization of the epigenetic configuration of the early human gonadal PGCs. We show that early gonadal human PGCs are DNA hypomethylated and their chromatin is characterized by low H3K9me2 and high H3K27me3 marks. Similarly to previous observations in mice, human gonadal PGCs undergo dynamic chromatin changes concomitant with the erasure of genomic imprints. Interestingly, and contrary to mouse early germ cells, expression of BLIMP1/PRDM1 persists in through all gestational stages in human gonadal PGCs and is associated with nuclear lysine-specific demethylase-1. Our work provides important additional information regarding the chromatin changes associated with human PGCs development between 6 and 13 weeks of gestation in male and female gonads. Stem Cells 2016;34:2418-2428. © 2016 AlphaMed Press.

Screening of Compounds Toxicity against Human Monocytic cell line-THP-1 by Flow Cytometry

PubMed Central

Pick, Neora; Cameron, Scott; Arad, Dorit

2004-01-01

The worldwide rapid increase in bacterial resistance to numerous antibiotics requires on-going development of new drugs to enter the market. As the development of new antibiotics is lengthy and costly, early monitoring of compound's toxicity is essential in the development of novel agents. Our interest is in a rapid, simple, high throughput screening method to assess cytotoxicity induced by potential agents. Some intracellular pathogens, such as Mycobacterium tuberculosis primary site of infection is human alveolar macrophages. Thus, evaluation of candidate drugs for macrophage toxicity is crucial. Protocols for high throughput drug toxicity screening of macrophages using flow cytometry are lacking in the literature. For this application we modified a preexisting technique, propidium iodide (PI) exclusion staining and utilized it for rapid toxicity tests. Samples were prepared in 96 well plates and analyzed by flow cytometry, which allowed for rapid, inexpensive and precise assessment of compound's toxicity associated with cell death. PMID:15472722

The Ion Propulsion System for the Asteroid Redirect Robotic Mission

NASA Technical Reports Server (NTRS)

Herman, Daniel A.; Santiago, Walter; Kamhawi, Hani; Polk, James E.; Snyder, John Steven; Hofer, Richard R.; Sekerak, Michael J.

2016-01-01

The Asteroid Redirect Robotic Mission is a Solar Electric Propulsion Technology Demonstration Mission (ARRM) whose main objectives are to develop and demonstrate a high-power solar electric propulsion capability for the Agency and return an asteroidal mass for rendezvous and characterization in a companion human-crewed mission. This high-power solar electric propulsion capability, or an extensible derivative of it, has been identified as a critical part of NASA'a future beyond-low-Earth-orbit, human-crewed exploration plans. Under the NASA Space Technology Mission Directorate the critical electric propulsion and solar array technologies are being developed. This paper presents the conceptual design of the ARRM ion propulsion system, the status of the NASA in-house thruster and power processing development activities, the status of the planned technology maturation for the mission through flight hardware delivery, and the status of the mission formulation and spacecraft acquisition.

Midkine and Pleiotrophin Concentrations in Amniotic Fluid in Healthy and Complicated Pregnancies.

PubMed

Jee, Youn Hee; Lebenthal, Yael; Chaemsaithong, Piya; Yan, Gai; Peran, Ivana; Wellstein, Anton; Romero, Roberto; Baron, Jeffrey

2016-01-01

Midkine (MDK) and pleiotrophin (PTN) are heparin-binding growth factors that, in rodents, are highly expressed in early life and decrease to undetectable levels by adulthood. The potential roles of MDK and PTN in human growth and development are not completely elucidated. To delineate the role of MDK and PTN in human development, we developed high sensitivity assays to measure their concentrations in amniotic fluid (AF) at various gestational ages in both healthy and complicated pregnancies. We found that both of these growth factors could be readily measured in AF and that the concentrations were higher than most cytokines previously reported in AF. The concentration of MDK but not that of PTN declined with gestational age. Both MDK and PTN concentrations were found to be lower in pregnancies that were complicated by chorioamnionitis at term, raising the possibility that these growth factors might be useful as markers for infection.

Developing and sustaining human resources in the health supply chain in Ethiopia: barriers and enablers.

PubMed

Kälvemark Sporrong, Sofia; Traulsen, Janine M; Damene Kabtimer, Woynabeba; Mekasha Habtegiorgis, Bitsatab; Teshome Gebregeorgise, Dawit; Essah, Nana Am; Khan, Sara A; Brown, Andrew N

2016-01-01

The health supply chain is often the weakest link in achieving the health-related Millennium Development Goals and universal health coverage, requiring trained professionals who are often unavailable. In Ethiopia there have been recent developments in the area of health supply chain management. The aim of this study was to explore the current status of the development of human resources in health supply chain management in Ethiopia and to identify important factors affecting this development. A series of face-to-face interviews with key stakeholders was carried out in 2014. The interviews were conducted using a semi-structured interview guide. The interview guide comprised 51 questions. A qualitative analysis of transcripts was made. A total of 25 interviews were conducted. Three themes were identified: General changes: recognition, commitment and resources, Education and training, and Barriers and enablers. Results confirm the development of human resources in health supply chain management in many areas. However, several problems were identified including lack of coordination, partly due to the large number of stakeholders; reported high staff mobility; and a lack of overall strategy regarding the job/career structures necessary for maintaining human resources. Rural areas have a particular set of problems, including in transportation of goods and personnel, attracting and keeping personnel, and in communication and access to information. Ethiopia is on the way to developing a nationwide viable system for health supply chain management. However, there are still challenges. Short-term challenges include the importance of highlighting strategies and programs for human resources in health supply chain management. In the long term, commitments to financial support must be obtained. A strategy is needed for the further development and sustainability of human resources in the health supply chain in Ethiopia.

High-Throughput Dietary Exposure Predictions for Chemical Migrants from Food Packaging Materials

EPA Science Inventory

United States Environmental Protection Agency researchers have developed a Stochastic Human Exposure and Dose Simulation High -Throughput (SHEDS-HT) model for use in prioritization of chemicals under the ExpoCast program. In this research, new methods were implemented in SHEDS-HT...

Approaching Leadership Education in the New Millennium

ERIC Educational Resources Information Center

Huber, Nancy S.

2002-01-01

Leadership is cast in many roles and, thus, leadership educators may be found in a variety of venues, including youth club organizers, junior high and high school teachers, college professors, student program directors in higher education, community development professionals, military trainers, religious groups, human resource development…

Cross-Border Higher Education for Labor Market Needs: Mobility of Public-Funded Malaysian Students to Japan over Years. JICA-RI Working Paper. No. 29

ERIC Educational Resources Information Center

Koda, Yoshiko; Yuki, Takako; Hong, Yeeyoung

2011-01-01

As globalization and the knowledge economy spreads, the demand for highly skilled workers has increased and developing countries are engaged in cross-border higher education to develop high level human resources for their nations. Using data on a cross-border higher education program between Malaysia and Japan, namely the Higher Education Loan…

Generation of a high-fidelity antibody against nerve growth factor using library scanning mutagenesis and validation with structures of the initial and optimized Fab-antigen complexes

PubMed Central

La Porte, Sherry L; Eigenbrot, Charles; Ultsch, Mark; Ho, Wei-Hsien; Foletti, Davide; Forgie, Alison; Lindquist, Kevin C; Shelton, David L; Pons, Jaume

2014-01-01

Nerve growth factor (NGF) is indispensable during normal embryonic development and critical for the amplification of pain signals in adults. Intervention in NGF signaling holds promise for the alleviation of pain resulting from human diseases such as osteoarthritis, cancer and chronic lower back disorders. We developed a fast, high-fidelity method to convert a hybridoma-derived NGF-targeted mouse antibody into a clinical candidate. This method, termed Library Scanning Mutagenesis (LSM), resulted in the ultra-high affinity antibody tanezumab, a first-in-class anti-hyperalgesic specific for an NGF epitope. Functional and structural comparisons between tanezumab and the mouse 911 precursor antibody using neurotrophin-specific cell survival assays and X-ray crystal structures of both Fab-antigen complexes illustrated high fidelity retention of the NGF epitope. These results suggest the potential for wide applicability of the LSM method for optimization of well-characterized antibodies during humanization. PMID:24830649

Spatial and gender scenario of literate life expectancy at birth in India.

PubMed

Chattopadhyay, Aparajita; Sinha, Kumar Chiman

2010-10-01

Measuring human quality of life is academically challenging. The human development index (HDI) substantially captures the overall country level status on human welfare. However, this index has some drawbacks. Therefore, Lutz composed a simple index in 1995 combining life expectancy and literacy, called literate life expectancy (LLE). LLE can be calculated for subpopulations depending on availability of data. This article captures the LLE in major states in India and the gender differences in LLE at rural and urban levels. The authors have tried to highlight the social development scenario in India and its major states by using this pure social indicator that intentionally does not use any economic measurement. The state scenario comprehensively depicts gender differentials in social development, and it calls for implementing development measures more seriously in states like Haryana, Bihar, Rajasthan, Madhya Pradesh, and Uttar Pradesh to reduce the gender gap. Being highly correlated with the HDI, the LLE index proves to be a very clear and simple comprehensive measure of social development for different subpopulations.

Challenges and future in vaccines, drug development, and immunomodulatory therapy.

PubMed

Kling, Heather M; Nau, Gerard J; Ross, Ted M; Evans, Thomas G; Chakraborty, Krishnendu; Empey, Kerry M; Flynn, JoAnne L

2014-08-01

Pulmonary diseases and infections are among the top contributors to human morbidity and mortality worldwide, and despite the successful history of vaccines and antimicrobial therapeutics, infectious disease still presents a significant threat to human health. Effective vaccines are frequently unavailable in developing countries, and successful vaccines have yet to be developed for major global maladies, such as tuberculosis. Furthermore, antibiotic resistance poses a growing threat to human health. The "Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy" session of the 2013 Pittsburgh International Lung Conference highlighted several recent and current studies related to treatment and prevention of antibiotic-resistant bacterial infections, highly pathogenic influenza, respiratory syncytial virus, and tuberculosis. Research presented here focused on novel antimicrobial therapies, new vaccines that are either in development or currently in clinical trials, and the potential for immunomodulatory therapies. These studies are making important contributions to the areas of microbiology, virology, and immunology related to pulmonary diseases and infections and are paving the way for improvements in the efficacy of vaccines and antimicrobials.

Autoreactive T Cells and Chronic Fungal Infection Drive Esophageal Carcinogenesis

PubMed Central

Zhu, Feng; Willette-Brown, Jami; Song, Na-Young; Lomada, Dakshayani; Song, Yongmei; Xue, Liyan; Gray, Zane; Zhao, Zitong; Davis, Sean R.; Sun, Zhonghe; Zhang, Peilin; Wu, Xiaolin; Zhan, Qimin; Richie, Ellen R.; Hu, Yinling

2018-01-01

SUMMARY Humans with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a T cell–driven autoimmune disease caused by impaired central tolerance, are susceptible to developing chronic fungal infection and esophageal squamous cell carcinoma (ESCC). However, the relationship between autoreactive T cells and chronic fungal infection in ESCC development remains unclear. We find that kinase-dead Ikkα knockin mice develop phenotypes reminiscent of APECED, including impaired central tolerance, autoreactive T cells, chronic fungal infection, and ESCCs expressing specific human ESCC markers. Using this model, we investigated the potential link between ESCC and fungal infection. Autoreactive CD4 T cells permit fungal infection and incite tissue injury and inflammation. Antifungal treatment or depletion of autoreactive CD4 T cells rescues, whereas oral fungal administration promotes, ESCC development. Inhibition of inflammation or EGFR activity decreases fungal burden. Importantly, fungal infection is highly associated with ESCCs in non-autoimmune human patients. Therefore, autoreactive T cells and chronic fungal infection, fostered by inflammation and epithelial injury, promote ESCC development. PMID:28407484

The importance of human resources management in health care: a global context.

PubMed

Kabene, Stefane M; Orchard, Carole; Howard, John M; Soriano, Mark A; Leduc, Raymond

2006-07-27

This paper addresses the health care system from a global perspective and the importance of human resources management (HRM) in improving overall patient health outcomes and delivery of health care services. We explored the published literature and collected data through secondary sources. Various key success factors emerge that clearly affect health care practices and human resources management. This paper will reveal how human resources management is essential to any health care system and how it can improve health care models. Challenges in the health care systems in Canada, the United States of America and various developing countries are examined, with suggestions for ways to overcome these problems through the proper implementation of human resources management practices. Comparing and contrasting selected countries allowed a deeper understanding of the practical and crucial role of human resources management in health care. Proper management of human resources is critical in providing a high quality of health care. A refocus on human resources management in health care and more research are needed to develop new policies. Effective human resources management strategies are greatly needed to achieve better outcomes from and access to health care around the world.

The importance of human resources management in health care: a global context

PubMed Central

Kabene, Stefane M; Orchard, Carole; Howard, John M; Soriano, Mark A; Leduc, Raymond

2006-01-01

Background This paper addresses the health care system from a global perspective and the importance of human resources management (HRM) in improving overall patient health outcomes and delivery of health care services. Methods We explored the published literature and collected data through secondary sources. Results Various key success factors emerge that clearly affect health care practices and human resources management. This paper will reveal how human resources management is essential to any health care system and how it can improve health care models. Challenges in the health care systems in Canada, the United States of America and various developing countries are examined, with suggestions for ways to overcome these problems through the proper implementation of human resources management practices. Comparing and contrasting selected countries allowed a deeper understanding of the practical and crucial role of human resources management in health care. Conclusion Proper management of human resources is critical in providing a high quality of health care. A refocus on human resources management in health care and more research are needed to develop new policies. Effective human resources management strategies are greatly needed to achieve better outcomes from and access to health care around the world. PMID:16872531

Isolated Ficus trees deliver dual conservation and development benefits in a rural landscape.

PubMed

Cottee-Jones, H Eden W; Bajpai, Omesh; Chaudhary, Lal B; Whittaker, Robert J

2015-11-01

Many of the world's rural populations are dependent on the local provision of economically and medicinally important plant resources. However, increasing land-use intensity is depleting these resources, reducing human welfare, and thereby constraining development. Here we investigate a low cost strategy to manage the availability of valuable plant resources, facilitated by the use of isolated Ficus trees as restoration nuclei. We surveyed the plants growing under 207 isolated trees in Assam, India, and categorized them according to their local human-uses. We found that Ficus trees were associated with double the density of important high-grade timber, firewood, human food, livestock fodder, and medicinal plants compared to non-Ficus trees. Management practices were also important in determining the density of valuable plants, with grazing pressure and land-use intensity significantly affecting densities in most categories. Community management practices that conserve isolated Ficus trees, and restrict livestock grazing and high-intensity land-use in their vicinity, can promote plant growth and the provision of important local resources.

A Human Serum-Based Enzyme-Free Continuous Glucose Monitoring Technique Using a Needle-Type Bio-Layer Interference Sensor.

PubMed

Seo, Dongmin; Paek, Sung-Ho; Oh, Sangwoo; Seo, Sungkyu; Paek, Se-Hwan

2016-09-24

The incidence of diabetes is continually increasing, and by 2030, it is expected to have increased by 69% and 20% in underdeveloped and developed countries, respectively. Therefore, glucose sensors are likely to remain in high demand in medical device markets. For the current study, we developed a needle-type bio-layer interference (BLI) sensor that can continuously monitor glucose levels. Using dialysis procedures, we were able to obtain hypoglycemic samples from commercial human serum. These dialysis-derived samples, alongside samples of normal human serum were used to evaluate the utility of the sensor for the detection of the clinical interest range of glucose concentrations (70-200 mg/dL), revealing high system performance for a wide glycemic state range (45-500 mg/dL). Reversibility and reproducibility were also tested over a range of time spans. Combined with existing BLI system technology, this sensor holds great promise for use as a wearable online continuous glucose monitoring system for patients in a hospital setting.

Mind and body: concepts of human cognition, physiology and false belief in children with autism or typical development.

PubMed

Peterson, Candida C

2005-08-01

This study examined theory of mind (ToM) and concepts of human biology (eyes, heart, brain, lungs and mind) in a sample of 67 children, including 25 high functioning children with autism (age 6-13), plus age-matched and preschool comparison groups. Contrary to Baron-Cohen [1989, Journal of Autism and Developmental Disorders, 19(4), 579-600], most children with autism correctly understood the functions of the brain (84%) and the mind (64%). Their explanations were predominantly mentalistic. They outperformed typically developing preschoolers in understanding inner physiological (heart, lungs) and cognitive (brain, mind) systems, and scored as high as age-matched typical children. Yet, in line with much previous ToM research, most children with autism (60%) failed false belief, and their ToM performance was unrelated to their understanding of. human biology. Results were discussed in relation to neurobiological and social-experiential accounts of the ToM deficit in autism.

High-throughput identification of antigen-specific TCRs by TCR gene capture.

PubMed

Linnemann, Carsten; Heemskerk, Bianca; Kvistborg, Pia; Kluin, Roelof J C; Bolotin, Dmitriy A; Chen, Xiaojing; Bresser, Kaspar; Nieuwland, Marja; Schotte, Remko; Michels, Samira; Gomez-Eerland, Raquel; Jahn, Lorenz; Hombrink, Pleun; Legrand, Nicolas; Shu, Chengyi Jenny; Mamedov, Ilgar Z; Velds, Arno; Blank, Christian U; Haanen, John B A G; Turchaninova, Maria A; Kerkhoven, Ron M; Spits, Hergen; Hadrup, Sine Reker; Heemskerk, Mirjam H M; Blankenstein, Thomas; Chudakov, Dmitriy M; Bendle, Gavin M; Schumacher, Ton N M

2013-11-01

The transfer of T cell receptor (TCR) genes into patient T cells is a promising approach for the treatment of both viral infections and cancer. Although efficient methods exist to identify antibodies for the treatment of these diseases, comparable strategies to identify TCRs have been lacking. We have developed a high-throughput DNA-based strategy to identify TCR sequences by the capture and sequencing of genomic DNA fragments encoding the TCR genes. We establish the value of this approach by assembling a large library of cancer germline tumor antigen-reactive TCRs. Furthermore, by exploiting the quantitative nature of TCR gene capture, we show the feasibility of identifying antigen-specific TCRs in oligoclonal T cell populations from either human material or TCR-humanized mice. Finally, we demonstrate the ability to identify tumor-reactive TCRs within intratumoral T cell subsets without knowledge of antigen specificities, which may be the first step toward the development of autologous TCR gene therapy to target patient-specific neoantigens in human cancer.

Is domestication driven by reduced fear of humans? Boldness, metabolism and serotonin levels in divergently selected red junglefowl (Gallus gallus).

PubMed

Agnvall, Beatrix; Katajamaa, Rebecca; Altimiras, Jordi; Jensen, Per

2015-09-01

Domesticated animals tend to develop a coherent set of phenotypic traits. Tameness could be a central underlying factor driving this, and we therefore selected red junglefowl, ancestors of all domestic chickens, for high or low fear of humans during six generations. We measured basal metabolic rate (BMR), feed efficiency, boldness in a novel object (NO) test, corticosterone reactivity and basal serotonin levels (related to fearfulness) in birds from the fifth and sixth generation of the high- and low-fear lines, respectively (44-48 individuals). Corticosterone response to physical restraint did not differ between selection lines. However, BMR was higher in low-fear birds, as was feed efficiency. Low-fear males had higher plasma levels of serotonin and both low-fear males and females were bolder in an NO test. The results show that many aspects of the domesticated phenotype may have developed as correlated responses to reduced fear of humans, an essential trait for successful domestication. © 2015 The Author(s).

Biological data sciences in genome research

PubMed Central

Schatz, Michael C.

2015-01-01

The last 20 years have been a remarkable era for biology and medicine. One of the most significant achievements has been the sequencing of the first human genomes, which has laid the foundation for profound insights into human genetics, the intricacies of regulation and development, and the forces of evolution. Incredibly, as we look into the future over the next 20 years, we see the very real potential for sequencing more than 1 billion genomes, bringing even deeper insight into human genetics as well as the genetics of millions of other species on the planet. Realizing this great potential for medicine and biology, though, will only be achieved through the integration and development of highly scalable computational and quantitative approaches that can keep pace with the rapid improvements to biotechnology. In this perspective, I aim to chart out these future technologies, anticipate the major themes of research, and call out the challenges ahead. One of the largest shifts will be in the training used to prepare the class of 2035 for their highly interdisciplinary world. PMID:26430150

Human rights and the requirement for international medical aid.

PubMed

Tolchin, Benjamin

2008-08-01

Every year approximately 18 million people die prematurely from treatable medical conditions including infectious diseases and nutritional deficiencies. The deaths occur primarily amongst the poorest citizens of poor developing nations. Various groups and individuals have advanced plans for major international medical aid to avert many of these unnecessary deaths. For example, the World Health Organization's Commission on Macroeconomics and Health estimated that eight million premature deaths could be prevented annually by interventions costing roughly US$57 bn per year. This essay advances an argument that human rights require high-income nations to provide such aid. The essay briefly examines John Rawls' obligations of justice and the reasons that their applicability to cases of international medical aid remains controversial. Regardless, the essay argues that purely humanitarian obligations bind the governments and citizens of high-income liberal democracies at a minimum to provide major medical aid to avert premature deaths in poor nations. In refusing to undertake such medical relief efforts, developed nations fail to adequately protect a fundamental human right to life.

Development of nurses with specialties: the nurse administrators' perspective.

PubMed

Onishi, Mami; Sasaki, Minako; Nagata, Ayako; Kanda, Katsuya

2008-10-01

This study clarified how Japanese nurse administrators consider the current status and future prospects of development and utilization of nurses with specialties. The demand for specialized nurses is not satisfied throughout the country. Nine nurse administrators participated in three focus-group discussions. Data were analyzed using qualitative content analysis technique. On development of specialized nurses, four categories were abstracted: offering opportunities for career development; establishing an environment of life-term continuous learning; providing well-balanced support for the needs of organizations and individual nurses; and support for career development as a specialist. To develop specialized nurses effectively it is important to focus more attention on qualitative aspects of nurses' professional experience in in-service education and to support appropriate personnel for strategic human resource development. Facilitating frequent contacts between specialized and general nurses should be highly valued as making an environment where nurses can face career goals daily leads to steady preservation of human resources. It is necessary for nurse administrators to keep human resources quantitatively and to clarify the developmental process after nurses obtain special roles to plan for continuous education.

JUNIOR AND SENIOR HIGH SCHOOL GRADUATION REQUIREMENTS AND CURRICULA.

ERIC Educational Resources Information Center

GOLDBLUM, JANICE; AND OTHERS

GRADUATION REQUIREMENTS AND CURRICULUMS IN THE LOS ANGELES CITY SCHOOL SYSTEM INSURE INTELLECTUAL DEVELOPMENT, CIVIC RESPONSIBILITY, ECONOMIC COMPETENCY, CREATIVITY, DEVELOPMENT OF MORAL VALUES, GOOD HUMAN RELATIONS, AND HEALTH. GRADING, TRANSFERS, HOMEWORK, CREDIT, AND SPECIAL POLICIES ARE DISCUSSED. THE CURRICULUM IN JUNIOR AND SENIOR HIGH…

Ready or Not: Preparation through Simulation

ERIC Educational Resources Information Center

Spellman, Joy

2008-01-01

Immediately after 9/11, Burlington County College (BCC) realized that the focus of emergency preparedness must change. BCC responded by identifying community needs, developing customized simulation training using high-fidelity human patient simulators and laptop/desktop technology; developing partnerships, and securing outside funding. Over 8,500…

[Human resources for local health systems].

PubMed

Linger, C

1989-01-01

The economic and social crises affecting Latin America have had a profound social and political effect on its structures. This paper analyzes this impact from 2 perspectives: 1) the impact on the apparatus of the state, in particular on its health infra-structures; and 2) the direction of the democratic process in the continent and the participatory processes of civil societies. The institutionalization of the Local Health Systems (SILOS) is an effort to analyze the problem from within the health sector and propose solutions. This paper discusses the issues of human resource development in health systems; training in human resource development and human resource development in local health care systems. There are 3 strategies used to change health systems: 1) The judicial-political system: The state's apparatus 2) The political-administrative system: the national health care system; and 3) the political-operative system: local health care systems. To assure implementation of SILOS there are 4 steps to be followed: 1) create political conditions that allow the transformation and development of local health systems; 2) development of high-level institutional and political initiatives to develop health care networks; 3) offer key players institutional space and social action to develop the SILOS process; 4) rapidly develop SILOS in regions to assure its integration with other development efforts. The labor force in the health sector and organized communities play critical roles in proposing and institutionalizing health programs.

Human preferences for sexually dimorphic faces may be evolutionarily novel

PubMed Central

Scott, Isabel M.; Clark, Andrew P.; Josephson, Steven C.; Boyette, Adam H.; Cuthill, Innes C.; Fried, Ruby L.; Gibson, Mhairi A.; Hewlett, Barry S.; Jamieson, Mark; Jankowiak, William; Honey, P. Lynne; Huang, Zejun; Liebert, Melissa A.; Purzycki, Benjamin G.; Shaver, John H.; Snodgrass, J. Josh; Sosis, Richard; Sugiyama, Lawrence S.; Swami, Viren; Yu, Douglas W.; Zhao, Yangke; Penton-Voak, Ian S.

2014-01-01

A large literature proposes that preferences for exaggerated sex typicality in human faces (masculinity/femininity) reflect a long evolutionary history of sexual and social selection. This proposal implies that dimorphism was important to judgments of attractiveness and personality in ancestral environments. It is difficult to evaluate, however, because most available data come from large-scale, industrialized, urban populations. Here, we report the results for 12 populations with very diverse levels of economic development. Surprisingly, preferences for exaggerated sex-specific traits are only found in the novel, highly developed environments. Similarly, perceptions that masculine males look aggressive increase strongly with development and, specifically, urbanization. These data challenge the hypothesis that facial dimorphism was an important ancestral signal of heritable mate value. One possibility is that highly developed environments provide novel opportunities to discern relationships between facial traits and behavior by exposing individuals to large numbers of unfamiliar faces, revealing patterns too subtle to detect with smaller samples. PMID:25246593

HIV-associated malignancies in children.

PubMed

Singh, Elvira; Naidu, Gita; Davies, Mary-Ann; Bohlius, Julia

2017-01-01

HIV-infected children are at an increased risk of developing cancer. Many of the cancers in HIV-infected children are linked to immunosuppression and oncogenic coinfections. Worldwide most HIV-infected children live in sub-Saharan Africa, but cancer data for this population are scarce. In this article, we review the current literature on the epidemiology and prevention of cancer in HIV-infected children. Combined antiretroviral therapy (cART) reduces the risk of developing cancer in HIV-infected children. Cancer risk remains increased in children who start cART at older ages or more advanced immunosuppression as compared with children who start cART at younger age and with mild immunosuppression. Starting cART before severe immunosuppression develops is key to prevent cancer in HIV-infected children but most children in low-income countries start cART at severe immunosuppression levels. Vaccination against high-risk variants of human papillomavirus may protect again human papillomavirus-associated cancer later in life. However, tailoring of human papillomavirus vaccination guidelines for HIV-infected children and young women awaits answers to determine the best vaccination strategies. Better data on the short-term and long-term risks of developing cancer and the effects of preventive measures in HIV-infected children from regions with high burden of HIV/AIDS are urgently needed.

[New social and economical issues in the assessment of Romanian population's health status].

PubMed

Duma, Odetta

2008-01-01

Health status is determined by a combination of biological, environmental (physical and socio-economic), behavioural/lifestyle and medical care factors. The social and economic factors include many influences over which an individual may have limited control, such as economic status or educational level. The most important measures of these factors are represented by: gross domestic product per capita, employment rate, unemployment rate, literacy rate, poverty line, and human development index. From this point of view, the following positive issues have been recorded in Romania: a low unemployment rate (6.1%) compared to European Union countries; a high literacy rate (97.3%), very close to the maximum of 100% reported by all developed countries; and a human development index of 0.805 (rank 60 in the international hierarchy), specific to a country with a high human development. Negative issues have been reported in case of the following indicators: the reported gross domestic product per capita expressed in PPP US$ was 8480, among the lowest in Europe, specific to a country with a medium income; population living with less than 2 US$ per day of 13% and living with less than 1 US$ per day 2.1%; the employment rate was 57.4%, but in female population only 51.3%, whereas in male population it was 63.9%.

Micro-patterned graphene-based sensing skins for human physiological monitoring

NASA Astrophysics Data System (ADS)

Wang, Long; Loh, Kenneth J.; Chiang, Wei-Hung; Manna, Kausik

2018-03-01

Ultrathin, flexible, conformal, and skin-like electronic transducers are emerging as promising candidates for noninvasive and nonintrusive human health monitoring. In this work, a wearable sensing membrane is developed by patterning a graphene-based solution onto ultrathin medical tape, which can then be attached to the skin for monitoring human physiological parameters and physical activity. Here, the sensor is validated for monitoring finger bending/movements and for recognizing hand motion patterns, thereby demonstrating its future potential for evaluating athletic performance, physical therapy, and designing next-generation human-machine interfaces. Furthermore, this study also quantifies the sensor’s ability to monitor eye blinking and radial pulse in real-time, which can find broader applications for the healthcare sector. Overall, the printed graphene-based sensing skin is highly conformable, flexible, lightweight, nonintrusive, mechanically robust, and is characterized by high strain sensitivity.

Cumulative cultural learning: Development and diversity

PubMed Central

2017-01-01

The complexity and variability of human culture is unmatched by any other species. Humans live in culturally constructed niches filled with artifacts, skills, beliefs, and practices that have been inherited, accumulated, and modified over generations. A causal account of the complexity of human culture must explain its distinguishing characteristics: It is cumulative and highly variable within and across populations. I propose that the psychological adaptations supporting cumulative cultural transmission are universal but are sufficiently flexible to support the acquisition of highly variable behavioral repertoires. This paper describes variation in the transmission practices (teaching) and acquisition strategies (imitation) that support cumulative cultural learning in childhood. Examining flexibility and variation in caregiver socialization and children’s learning extends our understanding of evolution in living systems by providing insight into the psychological foundations of cumulative cultural transmission—the cornerstone of human cultural diversity. PMID:28739945

Cumulative cultural learning: Development and diversity.

PubMed

Legare, Cristine H

2017-07-24

The complexity and variability of human culture is unmatched by any other species. Humans live in culturally constructed niches filled with artifacts, skills, beliefs, and practices that have been inherited, accumulated, and modified over generations. A causal account of the complexity of human culture must explain its distinguishing characteristics: It is cumulative and highly variable within and across populations. I propose that the psychological adaptations supporting cumulative cultural transmission are universal but are sufficiently flexible to support the acquisition of highly variable behavioral repertoires. This paper describes variation in the transmission practices (teaching) and acquisition strategies (imitation) that support cumulative cultural learning in childhood. Examining flexibility and variation in caregiver socialization and children's learning extends our understanding of evolution in living systems by providing insight into the psychological foundations of cumulative cultural transmission-the cornerstone of human cultural diversity.

Electromagnetic Modeling of Human Body Using High Performance Computing

NASA Astrophysics Data System (ADS)

Ng, Cho-Kuen; Beall, Mark; Ge, Lixin; Kim, Sanghoek; Klaas, Ottmar; Poon, Ada

Realistic simulation of electromagnetic wave propagation in the actual human body can expedite the investigation of the phenomenon of harvesting implanted devices using wireless powering coupled from external sources. The parallel electromagnetics code suite ACE3P developed at SLAC National Accelerator Laboratory is based on the finite element method for high fidelity accelerator simulation, which can be enhanced to model electromagnetic wave propagation in the human body. Starting with a CAD model of a human phantom that is characterized by a number of tissues, a finite element mesh representing the complex geometries of the individual tissues is built for simulation. Employing an optimal power source with a specific pattern of field distribution, the propagation and focusing of electromagnetic waves in the phantom has been demonstrated. Substantial speedup of the simulation is achieved by using multiple compute cores on supercomputers.

Early variability in the conceptualisation of "sustainable development and human factors".

PubMed

Thatcher, Andrew

2012-01-01

The sub-discipline of "sustainable development and human factors" is relatively new, first being used in 2006 with a Technical Committee of the IEA being established only in 2009 and a similar special interest group on "green ergonomics" at the Institute of Ergonomics and Human Factors being established in 2010. In general though, the definitions and practice of "sustainable development" is highly contentious and ambiguous across a range of disciplines. This paper examines the diversity of definitions and approaches to sustainable development and human factors in the early papers in this sub-discipline. An examination of 45 chapters and papers (from 2008 to 2011) reveals a surprising consistency in the definitions used for sustainable development but also a large proportion of the papers where no definitions are given at all. The majority of papers were, however, biased towards an economic capital and social capital emphasis, which is to be expected of work traditionally in the ergonomics paradigm. Further, most papers were theoretical in nature demonstrating a great opportunity for empirical work. The variability in definitions is discussed in relation to the future challenges facing the growth of this emergent sub-discipline and opportunities for further theoretical and empirical work.

From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.

PubMed

Hilgenfeld, Rolf; Peiris, Malik

2013-10-01

This article introduces a series of invited papers in Antiviral Research marking the 10th anniversary of the outbreak of severe acute respiratory syndrome (SARS), caused by a novel coronavirus that emerged in southern China in late 2002. Until that time, coronaviruses had not been recognized as agents causing severe disease in humans, hence, the emergence of the SARS-CoV came as a complete surprise. Research during the past ten years has revealed the existence of a diverse pool of coronaviruses circulating among various bat species and other animals, suggesting that further introductions of highly pathogenic coronaviruses into the human population are not merely probable, but inevitable. The recent emergence of another coronavirus causing severe disease, Middle East respiratory syndrome (MERS), in humans, has made it clear that coronaviruses pose a major threat to human health, and that more research is urgently needed to elucidate their replication mechanisms, identify potential drug targets, and develop effective countermeasures. In this series, experts in many different aspects of coronavirus replication and disease will provide authoritative, up-to-date reviews of the following topics: - clinical management and infection control of SARS; - reservoir hosts of coronaviruses; - receptor recognition and cross-species transmission of SARS-CoV; - SARS-CoV evasion of innate immune responses; - structures and functions of individual coronaviral proteins; - anti-coronavirus drug discovery and development; and - the public health legacy of the SARS outbreak. Each article will be identified in the last line of its abstract as belonging to the series "From SARS to MERS: 10years of research on highly pathogenic human coronaviruses." Copyright © 2013 Elsevier B.V. All rights reserved.

Sinanthropus in Britain: human origins and international science, 1920-1939.

PubMed

Manias, Chris

2015-06-01

The Peking Man fossils discovered at Zhoukoudian in north-east China in the 1920s and 1930s were some of the most extensive palaeoanthropological finds of the twentieth century. This article examines their publicization and discussion in Britain, where they were engaged with by some of the world's leading authorities in human evolution, and a media and public highly interested in human-origins research. This international link - simultaneously promoted by scientists in China and in Britain itself - reflected wider debates on international networks; the role of science in the modern world; and changing definitions of race, progress and human nature. This article illustrates how human-origins research was an important means of binding these areas together and presenting scientific work as simultaneously authoritative and credible, but also evoking mystery and adventurousness. Examining this illustrates important features of contemporary views of both science and human development, showing not only the complexities of contemporary regard for the international and public dynamics of scientific research, but wider concerns over human nature, which oscillated between optimistic notions of unity and progress and pessimistic ones of essential differences and misdirected development.

Transformational Technologies to Expedite Space Access and Development

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

Rather, John D. G.

Throughout history the emergence of new technologies has enabled unforeseen breakthrough capabilities that rapidly transformed the world. Some global examples from the twentieth century include AC electric power, nuclear energy, and turbojet engines. At the systems level, success of both Apollo and the Space Shuttle programs depended upon taming hydrogen propulsion and developing high-temperature atmospheric reentry materials. Human space development now is stymied because of a great need for breakthrough technologies and strategies. It is believed that new capabilities exist within the present states-of-the-art of superconducting technology that can be implemented to transform the future of human space development. Thismore » paper is an overview of three other papers presented within this forum, which summarizes the principles and consequences of StarTram, showing how the resulting breakthrough advantages can lead directly to safe space tourism and massive development of the moon, Mars and the outer solar system. StarTram can implement cost-effective solar power from space, simple utilization of asteroid material to protect humans from ionizing radiation, and effective defense of the Earth from devastating cosmic impacts. Synergistically, StarTram technologies will revolutionize ground transportation on the Earth, leading to enormous reduction in energy consumption and creation of millions of jobs. High energy lasers will also be discussed because of their importance to power beaming applications.« less

Optical effects of exposing intact human lenses to ultraviolet radiation and visible light.

PubMed

Kessel, Line; Eskildsen, Lars; Lundeman, Jesper Holm; Jensen, Ole Bjarlin; Larsen, Michael

2011-12-30

The human lens is continuously exposed to high levels of light. Ultraviolet radiation is believed to play a causative role in the development of cataract. In vivo, however, the lens is mainly exposed to visible light and the ageing lens absorbs a great part of the short wavelength region of incoming visible light. The aim of the present study was to examine the optical effects on human lenses of short wavelength visible light and ultraviolet radiation. Naturally aged human donor lenses were irradiated with UVA (355 nm), violet (400 and 405 nm) and green (532 nm) lasers. The effect of irradiation was evaluated qualitatively by photography and quantitatively by measuring the direct transmission before and after irradiation. Furthermore, the effect of pulsed and continuous laser systems was compared as was the effect of short, intermediate and prolonged exposures. Irradiation with high intensity lasers caused scattering lesions in the human lenses. These effects were more likely to be seen when using pulsed lasers because of the high pulse intensity. Prolonged irradiation with UVA led to photodarkening whereas no detrimental effects were observed after irradiation with visible light. Irradiation with visible light does not seem to be harmful to the human lens except if the lens is exposed to laser irradiances that are high enough to warrant thermal protein denaturation that is more readily seen using pulsed laser systems.

Estimation of hepatitis E virus (HEV) pig seroprevalence using ELISA and Western blot and comparison between human and pig HEV sequences in Belgium.

PubMed

Thiry, Damien; Mauroy, Axel; Saegerman, Claude; Thomas, Isabelle; Wautier, Magali; Miry, Cora; Czaplicki, Guy; Berkvens, Dirk; Praet, Nicolas; van der Poel, Wim; Cariolet, Roland; Brochier, Bernard; Thiry, Etienne

2014-08-27

Zoonotic transmission of hepatitis E virus (HEV) is of special concern, particularly in high income countries were waterborne infections are less frequent than in developing countries. High HEV seroprevalences can be found in European pig populations. The aims of this study were to obtain prevalence data on HEV infection in swine in Belgium and to phylogenetically compare Belgian human HEV sequences with those obtained from swine. An ELISA screening prevalence of 73% (95% CI 68.8-77.5) was determined in Belgian pigs and a part of the results were re-evaluated by Western blot (WB). A receiver operating characteristic curve analysis was performed and scenarios varying the ELISA specificity relative to WB were analysed. The seroprevalences estimated by the different scenarios ranged between 69 and 81% and are in agreement with the high exposure of the European pig population to HEV. Pig HEV sequences were genetically compared to those detected in humans in Belgium and a predominance of genotype 3 subtype f was shown in both swine and humans. The high HEV seroprevalence in swine and the close phylogenetic relationships between pig and human HEV sequences further support the risk for zoonotic transmission of HEV between humans and pigs. Copyright © 2014 Elsevier B.V. All rights reserved.

Project ATHENA Creates Surrogate Human Organ Systems

ScienceCinema

MacQueen, Luke; Knospel, Fanny; Sherrod, Stacy; Iy

2018-06-06

The development of miniature surrogate human organs, coupled with highly sensitive mass spectrometry technologies, could one day revolutionize the way new drugs and toxic agents are studied. “By developing this ‘homo minutus,’ we are stepping beyond the need for animal or Petri dish testing: There are huge benefits in developing drug and toxicity analysis systems that can mimic the response of actual human organs,” said Rashi Iyer, a senior scientist at Los Alamos National Laboratory. ATHENA, the Advanced Tissue-engineered Human Ectypal Network Analyzer project team, is nearing the full integration of four human organ constructs — liver, heart, lung and kidney — each organ component is about the size of a smartphone screen, and the whole ATHENA “body” of interconnected organs will fit neatly on a desk. A new video available on the Los Alamos National Laboratory YouTube channel updates the ATHENA project as it begins to integrate the various organ systems into a single system. Some 40 percent of pharmaceuticals fail their clinical trials and there are thousands of chemicals whose effects on humans are simply unknown. Providing a realistic, cost-effective and rapid screening system such as ATHENA with high-throughput capabilities could provide major benefits to the medical field, screening more accurately and offering a greater chance of clinical trial success. ATHENA is funded by the Defense Threat Reduction Agency (DTRA) and is a collaboration of Los Alamos National Laboratory, Harvard University, Vanderbilt University, Charité Universitätsmedizin, Berlin, Germany, CFD Research Corporation, and the University of California San Francisco.

Seroepidemiology and molecular characterization of hepatitis E virus infection in swine and occupationally exposed workers in Punjab, India.

PubMed

Bansal, M; Kaur, S; Deka, D; Singh, R; Gill, J P S

2017-12-01

Hepatitis E virus (HEV) has two discrete epidemiological patterns: waterborne epidemics in developing countries only, caused by HEV genotype I, and sporadic zoonotic outbreaks in developing and developed countries caused by genotypes III and IV. This study was designed to investigate seroprevalence, molecular detection and the characterization of HEV by nested RT-PCR in swine as well as the occupational risk to exposed human population in Punjab state of north-western India. The occupational risk-exposed group comprised of swine farmers (organized - mixed feed feeders and unorganized - swill feeders), slaughterhouse workers, sewage workers and veterinary internes. During the study period, blood and faecal samples were collected from 320 swine and 360 humans with both high and low occupational exposure risks. The overall seroprevalence of swine HEV was 65.00%, with a significantly higher seropositivity in growing pigs (2-8 months of age). The prevalence of HEV RNA in swine faecal samples by nRT-PCR was 8.75% with a significantly higher detection in swill-fed pigs. With humans in the high occupational exposure risk population, significantly higher anti-HEV IgG seropositivity was observed (60.48%) as compared to control population (10.71%). Strong evidence of association between human anti-HEV IgG seropositivity and certain occupational exposure risk groups was observed (p < 0.05). This indicates that unorganized swine farmers, slaughterhouse workers and sewage workers have higher odds of HEV infection in this study region. Percentage of nucleotide similarity between swine and human HEV isolates was less than that found in countries with zoonotic HEV outbreaks. Molecular characterization revealed the circulation of G IV and G I genotypes among swine and human population in Punjab state, respectively. © 2017 Blackwell Verlag GmbH.

Development of Cross-Assembly Phage PCR-Based Methods ...

EPA Pesticide Factsheets

Technologies that can characterize human fecal pollution in environmental waters offer many advantages over traditional general indicator approaches. However, many human-associated methods cross-react with non-human animal sources and lack suitable sensitivity for fecal source identification applications. The genome of a newly discovered bacteriophage (~97 kbp), the Cross-Assembly phage or “crAssphage”, assembled from a human gut metagenome DNA sequence library is predicted to be both highly abundant and predominately occur in human feces suggesting that this double stranded DNA virus may be an ideal human fecal pollution indicator. We report the development of two human-associated crAssphage endpoint PCR methods (crAss056 and crAss064). A shotgun strategy was employed where 384 candidate primers were designed to cover ~41 kbp of the crAssphage genome deemed favorable for method development based on a series of bioinformatics analyses. Candidate primers were subjected to three rounds of testing to evaluate assay optimization, specificity, limit of detection (LOD95), geographic variability, and performance in environmental water samples. The top two performing candidate primer sets exhibited 100% specificity (n = 70 individual samples from 8 different animal species), >90% sensitivity (n = 10 raw sewage samples from different geographic locations), LOD95 of 0.01 ng/µL of total DNA per reaction, and successfully detected human fecal pollution in impaired envi

[Functional state of various physiological systems of the human body during respiration of neon-oxygen mixture at depth up to 400 meters].

PubMed

Poleshuk, I P; Genin, A M; Unku, R D; Mikhnenko, A E; Sementsov, V N; Suvorov, A V

1991-01-01

Hyperbaric neon-oxygen mixture has been studied for the effect of its high density under pressure of 41 ata on basic physiological functions of human organism. Typical changes of the cardiorespiratory system and tissue respiration parameters are revealed. Changes in physical working capacity are shown. Exposure to gaseous medium of high pressure and density is accompanied by the development of some compensatory-adaptive reactions. The possibility to perform mid-hard physical work is attained with overstrain of respiration and circulation function.

Materials Challenges in Space Exploration

NASA Technical Reports Server (NTRS)

Vickers, John; Shah, Sandeep

2005-01-01

The new vision of space exploration encompasses a broad range of human and robotic missions to the Moon, Mars and beyond. Extended human space travel requires high reliability and high performance systems for propulsion, vehicle structures, thermal and radiation protection, crew habitats and health monitoring. Advanced materials and processing technologies are necessary to meet the exploration mission requirements. Materials and processing technologies must be sufficiently mature before they can be inserted into a development program leading to an exploration mission. Exploration will be more affordable by in-situ utilization of materials on the Moon and Mars.

Hemophilia and von Willebrand's disease: 2. Management. Association of Hemophilia Clinic Directors of Canada.

PubMed Central

1995-01-01

OBJECTIVE: To present current strategies for the treatment of hemophilia and von Willebrand's disease. OPTIONS: Prophylactic and corrective therapy with hemostatic and adjunctive agents: DDAVP (1-desamino-8-D-arginine vasopressin [desmopressin acetate]), recombinant coagulation products (human Factor VIII and human Factor VIIa) or virally inactivated plasma-derived products (high- or ultra-high-purity human Factor VIII or human Factor VIII concentrate containing von Willebrand factor activity, porcine Factor VIII, high-purity human Factor IX, human prothrombin-complex concentrate, human activated prothrombin-complex concentrate), adjunctive antifibrinolytic agents, topical thrombin and fibrin sealant. The induction of immune tolerance in patients in whom inhibitors develop should also be considered. OUTCOMES: Morbidity and quality of life associated with bleeding and treatment. EVIDENCE: Relevant clinical studies and reports published from 1974 to 1994 were examined. A search was conducted of our reprint files, MEDLINE, citations in the articles reviewed and references provided by colleagues. In the MEDLINE search the following terms were used singly or in combination: "hemophilia," "von Willebrand's disease," "Factor VIII," "Factor IX," "von Willebrand factor," "diagnosis," "management," "home care," "comprehensive care," "inhibitor," "AIDS," "hepatitis," "life expectancy," "complications," "practice guidelines," "consensus statement" and "controlled trial." The in-depth review included only articles written in English from North America and Europe that were relevant to human disease and pertinent to a predetermined outline. The availability of treatment products in Canada was also considered. VALUES: Minimizing morbidity and maximizing functional status and quality of life were given a high value. BENEFITS, HARMS AND COSTS: Proper prophylactic or early treatment with appropriate hemostatic agents minimizes morbidity and functional disability and improves quality of life. Economic gains are realized through the reduction of mortality and morbidity and their associated costs. The patient has a better opportunity to contribute to society through gainful employment and the fulfillment of social roles. Potential harms include HIV infection, hepatitis B, hepatitis C and the development of inhibitor antibodies to clotting-factor concentrates. The risk of viral transmission has been minimized through the development of procedures for the viral inactivation of plasma-derived clotting-factor concentrates and through the use of recombinant coagulation-factor concentrates and other non-plasma-derived hemostatic agents. RECOMMENDATIONS: DDAVP is the drug of choice for patients with mild hemophilia or type 1 or 2 (except 2B) von Willebrand's disease whose response to DDAVP in previous testing has been found to be adequate. Therapeutic blood components of choice include recombinant products and virally inactivated plasma-derived products. In Canada the recommended products are recombinant Factor VIII for hemophilia A, high-purity plasma-derived Factor IX for hemophilia B and plasma-derived Factor VIII concentrates containing adequate von Willebrand factor (e.g., Haemate P) for von Willebrand's disease. Dosages vary according to specific indications. Adjunctive antifibrinolytic agents, topical thrombin and fibrin sealant are useful for the treatment of oral or dental bleeds and localized bleeds in accessible sites. In patients with inhibitor antibodies, high-dose human or porcine Factor VIII is usually effective when the inhibitor titre is less than 5 Bethesda units/mL. In nonresponsive patients, or in those whose inhibitor titre is higher, "bypassing" agents (e.g., activated prothrombin-complex concentrate and recombinant Factor VIIa) are useful. Long-term management may include immune-tolerance induction.VALIDATION: These recommendations were reviewed and approved by the Association of Hemophilia Clinic Directors of Canada (AHCDC) and the Medical and Scientific Advisory Committee of the Canadian Hemophilia Society. No similar consensus statements or practice guidelines are available for comparison. SPONSORS: These recommendations were developed at the request of the Canadian Blood Agency, which funds the provision of all coagulation-factor concentrates for people with congenital bleeding disorders, and were developed and endorsed by the AHCDC and the Medical and Scientific Advisory Committee of the Canadian Hemophilia Society. PMID:7600466

Health, Human Capital, and Development*

PubMed Central

Bleakley, Hoyt

2013-01-01

How much does disease depress development in human capital and income around the world? I discuss a range of micro evidence, which finds that health is both human capital itself and an input to producing other forms of human capital. I use a standard model to integrate these results, and suggest a re-interpretation of much of the micro literature. I then discuss the aggregate implications of micro estimates, but note the complications in extrapolating to general equilibrium, especially because of health’s effect on population size. I also review the macro evidence on this topic, which consists of either cross-country comparisons or measuring responses to health shocks. Micro estimates are 1–2 orders of magnitude smaller than the cross-country relationship, but nevertheless imply high benefit-to-cost ratios from improving certain forms of health. PMID:24147187

Self-organizing human cardiac microchambers mediated by geometric confinement

NASA Astrophysics Data System (ADS)

Ma, Zhen; Wang, Jason; Loskill, Peter; Huebsch, Nathaniel; Koo, Sangmo; Svedlund, Felicia L.; Marks, Natalie C.; Hua, Ethan W.; Grigoropoulos, Costas P.; Conklin, Bruce R.; Healy, Kevin E.

2015-07-01

Tissue morphogenesis and organ formation are the consequences of biochemical and biophysical cues that lead to cellular spatial patterning in development. To model such events in vitro, we use PEG-patterned substrates to geometrically confine human pluripotent stem cell colonies and spatially present mechanical stress. Modulation of the WNT/β-catenin pathway promotes spatial patterning via geometric confinement of the cell condensation process during epithelial-mesenchymal transition, forcing cells at the perimeter to express an OCT4+ annulus, which is coincident with a region of higher cell density and E-cadherin expression. The biochemical and biophysical cues synergistically induce self-organizing lineage specification and creation of a beating human cardiac microchamber confined by the pattern geometry. These highly defined human cardiac microchambers can be used to study aspects of embryonic spatial patterning, early cardiac development and drug-induced developmental toxicity.

Establishment of a novel human medulloblastoma cell line characterized by highly aggressive stem-like cells.

PubMed

Silva, Patrícia Benites Gonçalves da; Rodini, Carolina Oliveira; Kaid, Carolini; Nakahata, Adriana Miti; Pereira, Márcia Cristina Leite; Matushita, Hamilton; Costa, Silvia Souza da; Okamoto, Oswaldo Keith

2016-08-01

Medulloblastoma is a highly aggressive brain tumor and one of the leading causes of morbidity and mortality related to childhood cancer. These tumors display differential ability to metastasize and respond to treatment, which reflects their high degree of heterogeneity at the genetic and molecular levels. Such heterogeneity of medulloblastoma brings an additional challenge to the understanding of its physiopathology and impacts the development of new therapeutic strategies. This translational effort has been the focus of most pre-clinical studies which invariably employ experimental models using human tumor cell lines. Nonetheless, compared to other cancers, relatively few cell lines of human medulloblastoma are available in central repositories, partly due to the rarity of these tumors and to the intrinsic difficulties in establishing continuous cell lines from pediatric brain tumors. Here, we report the establishment of a new human medulloblastoma cell line which, in comparison with the commonly used and well-established cell line Daoy, is characterized by enhanced proliferation and invasion capabilities, stem cell properties, increased chemoresistance, tumorigenicity in an orthotopic metastatic model, replication of original medulloblastoma behavior in vivo, strong chromosome structural instability and deregulation of genes involved in neural development. These features are advantageous for designing biologically relevant experimental models in clinically oriented studies, making this novel cell line, named USP-13-Med, instrumental for the study of medulloblastoma biology and treatment.

Development of enhanced piezoelectric energy harvester induced by human motion.

PubMed

Minami, Y; Nakamachi, E

2012-01-01

In this study, a high frequency piezoelectric energy harvester converted from the human low vibrated motion energy was newly developed. This hybrid energy harvester consists of the unimorph piezoelectric cantilever and a couple of permanent magnets. One magnet was attached at the end of cantilever, and the counterpart magnet was set at the end of the pendulum. The mechanical energy provided through the human walking motion, which is a typical ubiquitous presence of vibration, is converted to the electric energy via the piezoelectric cantilever vibration system. At first, we studied the energy convert mechanism and the performance of our energy harvester, where the resonance free vibration of unimorph cantilever with one permanent magnet under a rather high frequency was induced by the artificial low frequency vibration. The counterpart magnet attached on the pendulum. Next, we equipped the counterpart permanent magnet pendulum, which was fluctuated under a very low frequency by the human walking, and the piezoelectric cantilever, which had the permanent magnet at the end. The low-to-high frequency convert "hybrid system" can be characterized as an enhanced energy harvest one. We examined and obtained maximum values of voltage and power in this system, as 1.2V and 1.2 µW. Those results show the possibility to apply for the energy harvester in the portable and implantable Bio-MEMS devices.

Global issues and opportunities for optimized retinoblastoma care.

PubMed

Gallie, Brenda L; Zhao, Junyang; Vandezande, Kirk; White, Abigail; Chan, Helen S L

2007-12-01

The RB1 gene is important in all human cancers. Studies of human retinoblastoma point to a rare retinal cell with extreme dependency on RB1 for initiation but not progression to full malignancy. In developed countries, genetic testing within affected families can predict children at high risk of retinoblastoma before birth; chemotherapy with local therapy often saves eyes and vision; and mortality is 4%. In less developed countries where 92% of children with retinoblastoma are born, mortality reaches 90%. Global collaboration is building for the dramatic change in mortality that awareness, simple expertise and therapies could achieve in less developed countries. Copyright 2007 Wiley-Liss, Inc.

Proceedings of the 1993 Complex Systems Engineering Synthesis and Assessment Technology Workshop (CSESAW 󈨡)

DTIC Science & Technology

1993-10-17

34, "in criteria, and scoring each applicable high resolution mode’, "within 10 minutes of element as I (satisfactory) or 0 power -on...everone ese, humanity. We humans are kowledg limited and we The specificatio concept development design, and ye the problem caused by that limitation...human task that is component, we would have 53=125 integration spaces. within the power of a normal, single, specialized As you can imagine this could

Latest animal models for anti-HIV drug discovery.

PubMed

Sliva, Katja

2015-02-01

HIV research is limited by the fact that lentiviruses are highly species specific. The need for appropriate models to promote research has led to the development of many elaborate surrogate animal models. This review looks at the history of animal models for HIV research. Although natural animal lentivirus infections and chimeric viruses such as chimera between HIV and simian immunodeficiency virus and simian-tropic HIV are briefly discussed, the main focus is on small animal models, including the complex design of the 'humanized' mouse. The review also traces the historic evolution and milestones as well as depicting current models and future prospects for HIV research. HIV research is a complex and challenging task that is highly manpower-, money- and time-consuming. Besides factors such as hypervariability and latency, the lack of appropriate animal models that exhibit and recapitulate the entire infectious process of HIV, is one of the reasons behind the failure to eliminate the lentivirus from the human population. This obstacle has led to the exploitation and further development of many sophisticated surrogate animal models for HIV research. While there is no animal model that perfectly mirrors and mimics HIV infections in humans, there are a variety of host species and viruses that complement each other. Combining the insights from each model, and critically comparing the results obtained with data from human clinical trials should help expand our understanding of HIV pathogenesis and drive future drug development.

Application of machine learning methods in bioinformatics

NASA Astrophysics Data System (ADS)

Yang, Haoyu; An, Zheng; Zhou, Haotian; Hou, Yawen

2018-05-01

Faced with the development of bioinformatics, high-throughput genomic technology have enabled biology to enter the era of big data. [1] Bioinformatics is an interdisciplinary, including the acquisition, management, analysis, interpretation and application of biological information, etc. It derives from the Human Genome Project. The field of machine learning, which aims to develop computer algorithms that improve with experience, holds promise to enable computers to assist humans in the analysis of large, complex data sets.[2]. This paper analyzes and compares various algorithms of machine learning and their applications in bioinformatics.

Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors

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

Pecic, Stevan; Pakhomova, Svetlana; Newcomer, Marcia E.

2013-09-27

A series of potent amide non-urea inhibitors of soluble epoxide hydrolase (sEH) is disclosed. The inhibition of soluble epoxide hydrolase leads to elevated levels of epoxyeicosatrienoic acids (EETs), and thus inhibitors of sEH represent one of a novel approach to the development of vasodilatory and anti-inflammatory drugs. Structure–activities studies guided optimization of a lead compound, identified through high-throughput screening, gave rise to sub-nanomolar inhibitors of human sEH with stability in human liver microsomal assay suitable for preclinical development.

Identifying and Prioritizing Greater Sage-Grouse Nesting and Brood-Rearing Habitat for Conservation in Human-Modified Landscapes

PubMed Central

Dzialak, Matthew R.; Olson, Chad V.; Harju, Seth M.; Webb, Stephen L.; Mudd, James P.; Winstead, Jeffrey B.; Hayden-Wing, L.D.

2011-01-01

Background Balancing animal conservation and human use of the landscape is an ongoing scientific and practical challenge throughout the world. We investigated reproductive success in female greater sage-grouse (Centrocercus urophasianus) relative to seasonal patterns of resource selection, with the larger goal of developing a spatially-explicit framework for managing human activity and sage-grouse conservation at the landscape level. Methodology/Principal Findings We integrated field-observation, Global Positioning Systems telemetry, and statistical modeling to quantify the spatial pattern of occurrence and risk during nesting and brood-rearing. We linked occurrence and risk models to provide spatially-explicit indices of habitat-performance relationships. As part of the analysis, we offer novel biological information on resource selection during egg-laying, incubation, and night. The spatial pattern of occurrence during all reproductive phases was driven largely by selection or avoidance of terrain features and vegetation, with little variation explained by anthropogenic features. Specifically, sage-grouse consistently avoided rough terrain, selected for moderate shrub cover at the patch level (within 90 m2), and selected for mesic habitat in mid and late brood-rearing phases. In contrast, risk of nest and brood failure was structured by proximity to anthropogenic features including natural gas wells and human-created mesic areas, as well as vegetation features such as shrub cover. Conclusions/Significance Risk in this and perhaps other human-modified landscapes is a top-down (i.e., human-mediated) process that would most effectively be minimized by developing a better understanding of specific mechanisms (e.g., predator subsidization) driving observed patterns, and using habitat-performance indices such as those developed herein for spatially-explicit guidance of conservation intervention. Working under the hypothesis that industrial activity structures risk by enhancing predator abundance or effectiveness, we offer specific recommendations for maintaining high-performance habitat and reducing low-performance habitat, particularly relative to the nesting phase, by managing key high-risk anthropogenic features such as industrial infrastructure and water developments. PMID:22022587

High Schools on a Human Scale: How Small Schools Can Transform American Education.

ERIC Educational Resources Information Center

Toch, Thomas

This book argues that large American high schools have become obsolete and uses case studies of four new or restructured schools to show why smallness and distinctiveness are prerequisites for school reform. The large comprehensive high school developed as an economical means of providing a range of "tracks," from practical subjects for future…

The Impact of Career Academy Programs on Student Achievement in a New Jersey Urban High School

ERIC Educational Resources Information Center

Ahmad, Abdul-Azeem

2009-01-01

The Talent Development High School (TDHS) reform model, with career academy programs, was introduced at Randolph High School. Three academies were implemented, one called the Arts and Humanities Academy (A&H) focused on careers in creative arts, law, and public service; another titled the Business and Industrial Technology Academy (BAIT) was…

Novelty and Fear Conditioning Induced Gene Expression in High and Low States of Anxiety

ERIC Educational Resources Information Center

Donley, Melanie P.; Rosen, Jeffrey B.

2017-01-01

Emotional states influence how stimuli are interpreted. High anxiety states in humans lead to more negative, threatening interpretations of novel information, typically accompanied by activation of the amygdala. We developed a handling protocol that induces long-lasting high and low anxiety-like states in rats to explore the role of state anxiety…