Sample records for human development due

  1. Theoretical Bridge-Building: The Career Development Project for the 21st Century Meets the New Era of Human Resource Development

    ERIC Educational Resources Information Center

    Cameron, Roslyn

    2009-01-01

    There are theoretical and disciplinary field links between career development and human resource development, however interdisciplinary dialogue between the two fields has been essentially limited to one-way dialogue. This one-way dialogue occurs from within the human resource development field, due to the explicit inclusion of career development…

  2. Narcolepsy: Autoimmunity, Effector T Cell Activation Due to Infection, or T Cell Independent, Major Histocompatibility Complex Class II Induced Neuronal Loss?

    ERIC Educational Resources Information Center

    Fontana, Adriano; Gast, Heidemarie; Reith, Walter; Recher, Mike; Birchler, Thomas; Bassetti, Claudio L.

    2010-01-01

    Human narcolepsy with cataplexy is a neurological disorder, which develops due to a deficiency in hypocretin producing neurons in the hypothalamus. There is a strong association with human leucocyte antigens HLA-DR2 and HLA-DQB1*0602. The disease typically starts in adolescence. Recent developments in narcolepsy research support the hypothesis of…

  3. Human Resource Development, Ethics, and the Social Good

    ERIC Educational Resources Information Center

    Quinn, Floyd F.

    2018-01-01

    Businesses can achieve competitive advantage and better productivity and performance by attracting and developing exceptional employees, by caring for and listening to stakeholders, and by avoiding financial and reputational damage due to unethical and illegal behaviors. As a profession, human resource development (HRD) engages in practices that…

  4. Development and Application of a Human PBPK Model for Bromodichloromethane (BDCM) to Investigate Impacts of Multi-Route Exposure

    EPA Science Inventory

    Due to its presence in water as a volatile disinfection byproduct, BDCM, which is mutagenic and a rodent carcinogen, poses a risk for exposure via multiple routes. We developed a refined human PBPK model for BDCM (including new chemical-specific human parameters) to evaluate the...

  5. 77 FR 33751 - Eunice Kennedy Shriver National Institute of Child Health and Human Development; Notice of Closed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-07

    ... Institute of Child Health and Human Development Special Emphasis Panel, Asthma Control During Pregnancy: Predictors of Variability in Maternal Impairment Due to Asthma and Associated Maternal and Pregnancy Outcomes...

  6. 75 FR 18217 - Eunice Kennedy Shriver National Institute of Child Health & Human Development; Notice of Closed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-09

    ... Institute of Child Health and Human Development Special Emphasis Panel; Gene Therapy for Urea Disorders... prior to the meeting due to the timing limitations imposed by the review and funding cycle. (Catalogue...

  7. Aligning Learning and Talent Development Performance Outcomes with Organizational Objectives: A Proposed Model

    ERIC Educational Resources Information Center

    Ware, Iris

    2017-01-01

    The value proposition for learning and talent development (LTD) is often challenged due to human resources' inability to demonstrate meaningful outcomes in relation to organizational needs and return-on-investment. The primary role of human resources (HR) and the learning and talent development (LTD) function is to produce meaningful outcomes to…

  8. Investigation of brain science and neurological/psychiatric disorders using genetically modified non-human primates.

    PubMed

    Okano, Hideyuki; Kishi, Noriyuki

    2018-06-01

    Although mice have been the most frequently used experimental animals in many research fields due to well-established gene manipulation techniques, recent evidence has revealed that rodent models do not always recapitulate pathophysiology of human neurological and psychiatric diseases due to the differences between humans and rodents. The recent developments in gene manipulation of non-human primate have been attracting much attention in the biomedical research field, because non-human primates have more applicable brain structure and function than rodents. In this review, we summarize recent progress on genetically-modified non-human primates including transgenic and knockout animals using genome editing technology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Citation Analysis for Collection Development: A Comparative Study of Eight Humanities Fields

    ERIC Educational Resources Information Center

    Knievel, Jennifer E.; Kellsey, Charlene

    2005-01-01

    This study analyzes 9,131 citations from the 2002 volumes of journals in eight humanities fields: art, classics, history, linguistics, literature, music, philosophy, and religion. This study found that citation patterns varied widely among humanities disciplines. Due to these differences, it is important for librarians with humanities collection…

  10. Development of a Human Physiologically Based Pharmacokinetics (PBPK) Model For Dermal Permeability for Lindane

    EPA Science Inventory

    Lindane is a neurotoxicant used for the treatment of lice and scabies present on human skin. Due to its pharmaceutical application, an extensive pharmacokinetic database exists in humans. Mathematical diffusion models allow for calculation of lindane skin permeability coefficient...

  11. Girls' and Boys' Reasoning on Cultural and Religious Practices: A Human Rights Education Perspective

    ERIC Educational Resources Information Center

    de Wet, Annamagriet; Roux, Cornelia; Simmonds, Shan; ter Avest, Ina

    2012-01-01

    Human rights play a vital role in citizens' political, religious and cultural life (Wang 2002, 171). Due to the prominence of human rights in the everyday life of citizens, including those of South Africa, human rights education has been included in many school curricula. Human rights education aims to develop responsible citizens who "inter…

  12. Planning A Town To Save the Environment

    EPA Science Inventory

    Much of the environment is compromised due to land-use change and development to meet human needs. Because the environment also sustains human life, the amount of the environment that can be compromised is limited by how much must remain to meet human needs. Although people can...

  13. Human-ignited wildfire patterns and responses to policy shifts

    Treesearch

    M. L. Chas-Amil; J. P. Prestemon; C. J. McClean; J. Touza

    2015-01-01

    Development of efficient forest wildfire policies requires an understanding of the underlying reasons behind forest fire occurrences. Globally, there is a close relationship between forest wildfires and human activities; most wildfires are human events due to negligence (e.g., agricultural burning escapes) and deliberate actions (e.g., vandalism, pyromania, revenge,...

  14. 40 CFR Appendix C to Part 132 - Great Lakes Water Quality Initiative Methodologies for Development of Human Health Criteria and...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... organisms where higher doses or concentrations resulted in an adverse effect. Quantitative structure... probable or possible human carcinogen, when, because of major qualitative or quantitative limitations, the... quantitative risk assessment, but for which data are inadequate for Tier I criterion development due to a tumor...

  15. 40 CFR Appendix C to Part 132 - Great Lakes Water Quality Initiative Methodologies for Development of Human Health Criteria and...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... organisms where higher doses or concentrations resulted in an adverse effect. Quantitative structure... probable or possible human carcinogen, when, because of major qualitative or quantitative limitations, the... quantitative risk assessment, but for which data are inadequate for Tier I criterion development due to a tumor...

  16. 40 CFR Appendix C to Part 132 - Great Lakes Water Quality Initiative Methodologies for Development of Human Health Criteria and...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... organisms where higher doses or concentrations resulted in an adverse effect. Quantitative structure... probable or possible human carcinogen, when, because of major qualitative or quantitative limitations, the... quantitative risk assessment, but for which data are inadequate for Tier I criterion development due to a tumor...

  17. New insights into human primordial germ cells and early embryonic development from single-cell analysis.

    PubMed

    Otte, Jörg; Wruck, Wasco; Adjaye, James

    2017-08-01

    Human preimplantation developmental studies are difficult to accomplish due to associated ethical and moral issues. Preimplantation cells are rare and exist only in transient cell states. From a single cell, it is very challenging to analyse the origination of the heterogeneity and complexity inherent to the human body. However, recent advances in single-cell technology and data analysis have provided new insights into the process of early human development and germ cell specification. In this Review, we examine the latest single-cell datasets of human preimplantation embryos and germ cell development, compare them to bulk cell analyses, and interpret their biological implications. © 2017 Federation of European Biochemical Societies.

  18. Human Factors Lessons Learned from Flight Testing Wingless Lifting Body Vehicles

    NASA Technical Reports Server (NTRS)

    Merlin, Peter William

    2014-01-01

    Since the 1960s, NASA, the Air Force, and now private industry have attempted to develop an operational human crewed reusable spacecraft with a wingless, lifting body configuration. This type of vehicle offers increased mission flexibility and greater reentry cross range than capsule type craft, and is particularly attractive due to the capability to land on a runway. That capability, however, adds complexity to the human factors engineering requirements of developing such aircraft.

  19. COUNTERACTING ECOSYSTEM LOSSES DUE TO DEVELOPMENT

    EPA Science Inventory

    Sustainability in any ecosystem is conditioned by properties established by nature. Intervention into ecosystems for the purposes of developing the built/socio-physical environment involves value judgments regarding human well-being. Therefore, if development is sustainable, it m...

  20. 75 FR 19980 - Eunice Kennedy Shriver National Institute of Child Health & Human Development; Notice of Closed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-16

    ... Institute of Child Health and Human Development Special Emphasis Panel; Gene Therapy for Urea Cycle Disorders. Date: April 30, 2010. Time: 1:30 p.m. to 3 p.m. Agenda: To review and evaluate grant applications... prior to the meeting due to the timing limitations imposed by the review and funding cycle. (Catalogue...

  1. Coastal sedimentary research examines critical issues of national and global priority

    USGS Publications Warehouse

    Fletcher, Chip; Anderson, John; Crook, Keith A.W.; Kaminsky, George; Larcombe, Piers; Murray-Wallace, Colin V.; Sansone, Frank; Scott, David B.; Riggs, Stan; Sallenger, Asbury; Shennan, Ian; Thieler, E. Robert; Wehmiller, John F.

    2000-01-01

    An international conference was held recently in Honolulu, Hawaii, to examine and plan for coastal sedimentary research in the United States and globally. Participants agreed that sedimentary coastal environments constitute a critical national and global resource that suffers widespread degradation due to human impacts. Moreover, human population growth and inappropriate development in the coastal zone are escalating public asset losses due to coastal hazards and placing large numbers of communities at growing risk (Figure 1).

  2. Generation of transgenic monkeys with human inherited genetic disease.

    PubMed

    Chan, Anthony W S; Yang, Shang-Hsun

    2009-09-01

    Modeling human diseases using nonhuman primates including chimpanzee, rhesus, cynomolgus, marmoset and squirrel monkeys has been reported in the past decades. Due to the high similarity between nonhuman primates and humans, including genome constitution, cognitive behavioral functions, anatomical structure, metabolic, reproductive, and brain functions; nonhuman primates have played an important role in understanding physiological functions of the human body, clarifying the underlying mechanism of human diseases, and the development of novel treatments for human diseases. However, nonhuman primate research has been restricted to cognitive, behavioral, biochemical and pharmacological approaches of human diseases due to the limitation of gene transfer technology in nonhuman primates. The recent advancement in transgenic technology that has led to the generation of the first transgenic monkey in 2001 and a transgenic monkey model of Huntington's disease (HD) in 2008 has changed that focus. The creation of transgenic HD monkeys that replicate key pathological features of human HD patients further suggests the crucial role of nonhuman primates in the future development of biomedicine. These successes have opened the door to genetic manipulation in nonhuman primates and a new era in modeling human inherited genetic disorders. We focused on the procedures in creating transgenic Huntington's disease monkeys, but our work can be applied to transgenesis in other nonhuman primate species.

  3. Different level of population differentiation among human genes.

    PubMed

    Wu, Dong-Dong; Zhang, Ya-Ping

    2011-01-14

    During the colonization of the world, after dispersal out of African, modern humans encountered changeable environments and substantial phenotypic variations that involve diverse behaviors, lifestyles and cultures, were generated among the different modern human populations. Here, we study the level of population differentiation among different populations of human genes. Intriguingly, genes involved in osteoblast development were identified as being enriched with higher FST SNPs, a result consistent with the proposed role of the skeletal system in accounting for variation among human populations. Genes involved in the development of hair follicles, where hair is produced, were also found to have higher levels of population differentiation, consistent with hair morphology being a distinctive trait among human populations. Other genes that showed higher levels of population differentiation include those involved in pigmentation, spermatid, nervous system and organ development, and some metabolic pathways, but few involved with the immune system. Disease-related genes demonstrate excessive SNPs with lower levels of population differentiation, probably due to purifying selection. Surprisingly, we find that Mendelian-disease genes appear to have a significant excessive of SNPs with high levels of population differentiation, possibly because the incidence and susceptibility of these diseases show differences among populations. As expected, microRNA regulated genes show lower levels of population differentiation due to purifying selection. Our analysis demonstrates different level of population differentiation among human populations for different gene groups.

  4. Aquinas's account of human embryogenesis and recent interpretations.

    PubMed

    Eberl, Jason T

    2005-08-01

    In addressing bioethical issues at the beginning of human life, such as abortion, in vitro fertilization, and embryonic stem cell research, one primary concern regards establishing when a developing human embryo or fetus can be considered a person. Thomas Aquinas argues that an embryo or fetus is not a human person until its body is informed by a rational soul. Aquinas's explicit account of human embryogenesis has been generally rejected by contemporary scholars due to its dependence upon medieval biological data, which has been far surpassed by current scientific research. A number of scholars, however, have attempted to combine Aquinas's basic metaphysical account of human nature with current embryological data to develop a contemporary Thomistic account of a human person's beginning. In this article, I discuss two recent interpretations in which it is argued that a human person does not begin to exist until a fetus has developed a functioning cerebral cortex.

  5. Quantifying the risk of human Toxoplasma gondii infection due to consumption of domestically-produced lamb in the United States

    USDA-ARS?s Scientific Manuscript database

    Toxoplasma gondii is a widely prevalent protozoan parasite worldwide. Human toxoplasmosis is responsible for considerable morbidity and mortality in the United States. Meat products have been identified as an important source of T. gondii infections in humans. The goal of this study was to develop a...

  6. Self-organized amniogenesis by human pluripotent stem cells in a biomimetic implantation-like niche

    NASA Astrophysics Data System (ADS)

    Shao, Yue; Taniguchi, Kenichiro; Gurdziel, Katherine; Townshend, Ryan F.; Xue, Xufeng; Yong, Koh Meng Aw; Sang, Jianming; Spence, Jason R.; Gumucio, Deborah L.; Fu, Jianping

    2017-04-01

    Amniogenesis--the development of amnion--is a critical developmental milestone for early human embryogenesis and successful pregnancy. However, human amniogenesis is poorly understood due to limited accessibility to peri-implantation embryos and a lack of in vitro models. Here we report an efficient biomaterial system to generate human amnion-like tissue in vitro through self-organized development of human pluripotent stem cells (hPSCs) in a bioengineered niche mimicking the in vivo implantation environment. We show that biophysical niche factors act as a switch to toggle hPSC self-renewal versus amniogenesis under self-renewal-permissive biochemical conditions. We identify a unique molecular signature of hPSC-derived amnion-like cells and show that endogenously activated BMP-SMAD signalling is required for the amnion-like tissue development by hPSCs. This study unveils the self-organizing and mechanosensitive nature of human amniogenesis and establishes the first hPSC-based model for investigating peri-implantation human amnion development, thereby helping advance human embryology and reproductive medicine.

  7. Declaring the Existence of Human Germ-Cell Mutagens

    EPA Science Inventory

    After more than 80 years of searching for human germ-cell mutagens, I think that sufficient evidence already exists for a number of agents to be so considered, and definitive confirmation seems imminent due to the application ofrecently developed genomic techniques. In preparatio...

  8. COUNTERACTING ECOSYSTEM LOSSES DUE TO DEVELOPMENT

    EPA Science Inventory

    Interventions into ecosystems to develop the built/socio-physical environment involve normative decisions regarding human well-being that inevitably compromise ecosystem capacities, but ecosystem sustainability is conditioned by properties established by ecosystems and unrelated ...

  9. Losing Sight of the Child? Human Capital Theory and Its Role for Early Childhood Education and Care Policies in Finland and England since the Mid-1990s

    ERIC Educational Resources Information Center

    Campbell-Barr, Verity; Nygård, Mikael

    2014-01-01

    The international interest in early childhood education and care (ECEC) by supranational organisations, including the European Union, has grown considerably due to its dual function of sustaining parental employment and fostering child development. Focussing primarily on child development debates around ECEC, this article argues that human capital…

  10. Development of a Physiologically Based Model to Describe the Pharmacokinetics of Methylphenidate in Juvenile and Adult Humans and Nonhuman Primates

    PubMed Central

    Yang, Xiaoxia; Morris, Suzanne M.; Gearhart, Jeffery M.; Ruark, Christopher D.; Paule, Merle G.; Slikker, William; Mattison, Donald R.; Vitiello, Benedetto; Twaddle, Nathan C.; Doerge, Daniel R.; Young, John F.; Fisher, Jeffrey W.

    2014-01-01

    The widespread usage of methylphenidate (MPH) in the pediatric population has received considerable attention due to its potential effect on child development. For the first time a physiologically based pharmacokinetic (PBPK) model has been developed in juvenile and adult humans and nonhuman primates to quantitatively evaluate species- and age-dependent enantiomer specific pharmacokinetics of MPH and its primary metabolite ritalinic acid. The PBPK model was first calibrated in adult humans using in vitro enzyme kinetic data of MPH enantiomers, together with plasma and urine pharmacokinetic data with MPH in adult humans. Metabolism of MPH in the small intestine was assumed to account for the low oral bioavailability of MPH. Due to lack of information, model development for children and juvenile and adult nonhuman primates primarily relied on intra- and interspecies extrapolation using allometric scaling. The juvenile monkeys appear to metabolize MPH more rapidly than adult monkeys and humans, both adults and children. Model prediction performance is comparable between juvenile monkeys and children, with average root mean squared error values of 4.1 and 2.1, providing scientific basis for interspecies extrapolation of toxicity findings. Model estimated human equivalent doses in children that achieve similar internal dose metrics to those associated with pubertal delays in juvenile monkeys were found to be close to the therapeutic doses of MPH used in pediatric patients. This computational analysis suggests that continued pharmacovigilance assessment is prudent for the safe use of MPH. PMID:25184666

  11. Challenges of Global Change for Lakes

    NASA Astrophysics Data System (ADS)

    Seekell, D.

    2016-12-01

    Lakes comprise a tiny fraction of Earth's surface, but contribute significantly to human life and wellbeing. Many lakes are disappearing due to climate change and water diversions, and there are widespread disruptions to ecosystem processes due to human influences. For example, pollution by nutrients and toxic chemicals causes toxicity to humans, livestock, fish, and wildlife. Lake desiccation reduces economic opportunity and food security, displacing entire communities. Understanding these changes at the global scale, and their implications for human societies, are a key challenges for aquatic scientists. In this talk, I will use results from my research to highlight some of the key uncertainties related to global change and lakes, as well as recent developments by aquatic scientists aimed at predicting, mitigating, and coping with these changes.

  12. Co-evolutionary dynamics of the human-environment system in the Heihe River basin in the past 2000years.

    PubMed

    Lu, Zhixiang; Wei, Yongping; Feng, Qi; Xie, Jiali; Xiao, Honglang; Cheng, Guodong

    2018-09-01

    There is limited quantitative understanding of interactions between human and environmental systems over the millennial scale. We aim to reveal the co-evolutionary dynamics of the human-environment system in a river basin by simulating the water use and net primary production (NPP) allocation for human and environmental systems over the last 2000years in Heihe River basin (HRB) in northwest China. We partition the catchment total evapotranspiration (ET) into ET for human and environmental systems with a social-hydrological framework and estimate the NPP for human and environmental systems using the Box-Lieth model, then classify the co-evolutionary processes of the human-environment system into distinct phases using the rate of changes of NPP over time, and discover the trade-offs or synergies relationships between them based on the elasticity of change of the NPP for humans to the change of NPP for environment. The co-evolutionary dynamics of human-environment system in the HRB can be divided into four periods, including: Phase I (Han Dynasty-Yuan Dynasty): predevelopment characterized by nearly no trade-offs between human and environment; Phase II (Yuan Dynasty-RC): slow agricultural development: characterized by a small human win due to small trade-offs between human and environment; Phase III (RC-2000): rapid agricultural development: characterized by a large human win due to large trade-offs between human and environment, and Phase IV (2000-2010): a rebalance characterized by large human wins with a small-environment win due to synergies, although these occurred very occasionally. This study provides a quantitative approach to describe the co-evolution of the human-environment system from the perspective of trade-offs and synergies in the millennial scale for the first time. The relationships between humans and environment changed from trade-off to synergy with the implementation of the water reallocation scheme in 2000. These findings improve the understanding of how humans influence environmental systems and responses to environmental stresses. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Copy Number Variation in Patients with Disorders of Sex Development Due to 46,XY Gonadal Dysgenesis

    PubMed Central

    White, Stefan; Ohnesorg, Thomas; Notini, Amanda; Roeszler, Kelly; Hewitt, Jacqueline; Daggag, Hinda; Smith, Craig; Turbitt, Erin; Gustin, Sonja; van den Bergen, Jocelyn; Miles, Denise; Western, Patrick; Arboleda, Valerie; Schumacher, Valerie; Gordon, Lavinia; Bell, Katrina; Bengtsson, Henrik; Speed, Terry; Hutson, John; Warne, Garry; Harley, Vincent; Koopman, Peter; Vilain, Eric; Sinclair, Andrew

    2011-01-01

    Disorders of sex development (DSD), ranging in severity from mild genital abnormalities to complete sex reversal, represent a major concern for patients and their families. DSD are often due to disruption of the genetic programs that regulate gonad development. Although some genes have been identified in these developmental pathways, the causative mutations have not been identified in more than 50% 46,XY DSD cases. We used the Affymetrix Genome-Wide Human SNP Array 6.0 to analyse copy number variation in 23 individuals with unexplained 46,XY DSD due to gonadal dysgenesis (GD). Here we describe three discrete changes in copy number that are the likely cause of the GD. Firstly, we identified a large duplication on the X chromosome that included DAX1 (NR0B1). Secondly, we identified a rearrangement that appears to affect a novel gonad-specific regulatory region in a known testis gene, SOX9. Surprisingly this patient lacked any signs of campomelic dysplasia, suggesting that the deletion affected expression of SOX9 only in the gonad. Functional analysis of potential SRY binding sites within this deleted region identified five putative enhancers, suggesting that sequences additional to the known SRY-binding TES enhancer influence human testis-specific SOX9 expression. Thirdly, we identified a small deletion immediately downstream of GATA4, supporting a role for GATA4 in gonad development in humans. These CNV analyses give new insights into the pathways involved in human gonad development and dysfunction, and suggest that rearrangements of non-coding sequences disturbing gene regulation may account for significant proportion of DSD cases. PMID:21408189

  14. Advanced manufacturing: Technology and international competitiveness

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

    Tesar, A.

    1995-02-01

    Dramatic changes in the competitiveness of German and Japanese manufacturing have been most evident since 1988. All three countries are now facing similar challenges, and these challenges are clearly observed in human capital issues. Our comparison of human capital issues in German, Japanese, and US manufacturing leads us to the following key judgments: Manufacturing workforces are undergoing significant changes due to advanced manufacturing technologies. As companies are forced to develop and apply these technologies, the constituency of the manufacturing workforce (especially educational requirements, contingent labor, job content, and continuing knowledge development) is being dramatically and irreversibly altered. The new workforcemore » requirements which result due to advanced manufacturing require a higher level of worker sophistication and responsibility.« less

  15. The monetary value of human lives lost due to neglected tropical diseases in Africa.

    PubMed

    Kirigia, Joses Muthuri; Mburugu, Gitonga N

    2017-12-18

    Neglected tropical diseases (NTDs) are an important cause of death and disability in Africa. This study estimates the monetary value of human lives lost due to NTDs in the continent in 2015. The lost output or human capital approach was used to evaluate the years of life lost due to premature deaths from NTDs among 10 high/upper-middle-income (Group 1), 17 middle-income (Group 2) and 27 low-income (Group 3) countries in Africa. The future losses were discounted to their present values at a 3% discount rate. The model was re-analysed using 5% and 10% discount rates to assess the impact on the estimated total value of human lives lost. The estimated value of 67 860 human lives lost in 2015 due to NTDs was Int$ 5 112 472 607. Out of that, 14.6% was borne by Group 1, 57.7% by Group 2 and 27.7% by Group 3 countries. The mean value of human life lost per NTD death was Int$ 231 278, Int$ 109 771 and Int$ 37 489 for Group 1, Group 2 and Group 3 countries, respectively. The estimated value of human lives lost in 2015 due to NTDs was equivalent to 0.1% of the cumulative gross domestic product of the 53 continental African countries. Even though NTDs are not a major cause of death, they impact negatively on the productivity of those affected throughout their life-course. Thus, the case for investing in NTDs control should also be influenced by the value of NTD morbidity, availability of effective donated medicines, human rights arguments, and need to achieve the NTD-related target 3.3 of the United Nations Sustainable Development Goal 3 (on health) by 2030.

  16. Development of a Multiroute Human PBPK Model for Bromodichloromethane (BDCM)

    EPA Science Inventory

    BDCM is an animal carcinogen and developmental toxicant. Due to its presence as a disinfection byproduct in finished drinking water, BDCM may pose a risk for exposure via ingestion, inhalation or dermal exposure. Utilizing a unique data set in which human subjects were exposed ...

  17. Origin of Somatic Mutations in β-Catenin versus Adenomatous Polyposis Coli in Colon Cancer: Random Mutagenesis in Animal Models versus Nonrandom Mutagenesis in Humans.

    PubMed

    Yang, Da; Zhang, Min; Gold, Barry

    2017-07-17

    Wnt signaling is compromised early in the development of human colorectal cancer (CRC) due to truncating nonsense mutations in adenomatous polyposis coli (APC). CRC induced by chemical carcinogens, such as heterocyclic aromatic amines and azoxymethane, in mice also involves dysregulation of Wnt signaling but via activating missense mutations in the β-catenin oncogene despite the fact that genetically modified mice harboring an inactive APC allele efficiently develop CRC. In contrast, activating mutations in β-catenin are rarely observed in human CRC. Dysregulation of the Wnt signaling pathway by the two distinct mechanisms reveals insights into the etiology of human CRC. On the basis of calculations related to DNA adduct levels produced in mouse CRC models using mutagens, and the number of stem cells in the mouse colon, we show that two nonsense mutations required for biallelic disruption of APC are statistically unlikely to produce CRC in experiments using small numbers of mice. We calculate that an activating mutation in one allele near the critical GSK3β phosphorylation site on β-catenin is >10 5 -times more likely to produce CRC by random mutagenesis due to chemicals than inactivating two alleles in APC, yet it does not occur in humans. Therefore, the mutagenesis mechanism in human CRC cannot be random. We explain that nonsense APC mutations predominate in human CRC because of deamination at 5-methylcytosine at CGA and CAG codons, coupled with the number of human colonic stem cells and lifespan. Our analyses, including a comparison of mutation type and age at CRC diagnosis in U.S. and Chinese patients, also indicate that APC mutations in CRC are not due to environmental mutagens that randomly damage DNA.

  18. The importance of touch in the development of attachment.

    PubMed

    Duhn, Lenora

    2010-12-01

    Until recently the role of human touch in the social world of the developing infant has not been given special attention. Instead the focus, in part due to John Bowlby's Attachment Theory, has centered on the critical need for a child to develop a secure attachment to his caregiver. To be sure, this has provided a valuable contribution to understanding and promoting a child's well-being in his early years and beyond. Yet Bowlby's theory is limited in its discussion of the meaning of human touch and its role in development of attachment. As such, it now becomes more critical to delve into the factors that significantly foster development of attachment, specifically the concept of human touch. With recognition of the importance for a child to develop secure attachment to his caregiver, the essential function that human nurturing touch provides in facilitating that connection is explored.

  19. Necrotizing fasciitis due to Streptococcus mitis caused by accidental human bite.

    PubMed

    Bastug, Aliye; Kislak, Sumeyye; Mutlu, Nevzat Mehmet; Akcaboy, Zeynep Nur; Koksal, Asude; Sertcelik, Ahmet; Ünlü, Ramazan Erkin; Akinci, Esragul; Bodur, Hurrem

    2016-01-31

    Human bite wounds are more prone to infection than animal bites, which may cause necrotizing soft tissue infections such as myositis, fasciitis. Both aerobic and anaerobic microorganisms may be responsible, including Streptococcus spp., Staphylococcus aureus, Peptostreptococcus spp. Necrotizing fasciitis is characterized by serious tissue destruction and systemic toxicity with high morbidity and mortality. We report a patient with Streptococcus mitis associated necrotizing fasciitis on the upper extremity resulting from an accidental human bite, which caused nearly fatal infection. Prophylactic antibiotic treatment should be given after a human bite to prevent infection. If the infection signs and symptoms develop, rapid diagnosis, appropriate antibiotic and surgical therapy should be administered immediately. Streptococcus mitis is a viridans streptococcus, usually known as a relatively benign oral streptococcus. To our knowledge, this is the first necrotizing fasciitis case due to Streptococcus mitis after human bite.

  20. Social and environmental sustainability in large-scale coastal zones: Taking an issue-based approach to the implementation of the Prince William Sound sustainable human use framework

    Treesearch

    Dale J. Blahna; Aaron Poe; Courtney Brown; Clare M. Ryan; H. Randy Gimblett

    2017-01-01

    Following the grounding of the Exxon Valdez in 1989, a sustainable human use framework (human use framework) for Prince William Sound (PWS), AK was developed by the Chugach National Forest after concerns emerged about the social and environmental impacts of expanding human use due to cleanup activities and increased recreation visitation. A practical, issue-based...

  1. Time for paradigmatic substitution in psychology. What are the alternatives?

    PubMed

    Kolstad, Arnulf

    2010-03-01

    This article focuses on the "machine paradigm" in psychology and its consequences for (mis)understanding of human beings. It discusses causes of the mainstream epistemology in Western societies, referring to philosophical traditions, the prestige of some natural sciences and mathematical statistics. It emphasizes how the higher psychological functions develop dialectically from a biological basis and how the brain due to its plasticity changes with mental and physical activity. This makes a causal machine paradigm unfit to describe and explain human psychology and human development. Some concepts for an alternative paradigm are suggested.

  2. Figure of Merit Characteristics Compared to Engineering Parameters

    NASA Technical Reports Server (NTRS)

    Rickman, Doug L.; Schrader, Christian M.

    2008-01-01

    Current NASA lunar architecture calls for permanent human habitation of the moon by the year 2020. Due to the expense of delivering materials into orbit, technologies are being developed to use lunar regolith for building and as a material resource for fabrication, oxygen production, and other needs. Additionally, constant exposure to the finest size fraction of lunar regolith may present hazards to human health. Towards developing these technologies and mitigating hazards, lunar regolith simulants are becoming an increasingly important part of the development paradigm.

  3. Science, ethics, and the historical roots of our ecological crisis - was White right?

    USDA-ARS?s Scientific Manuscript database

    In 1967 historian Lynn White Jr. suggested that values developed and perpetuated by Christian theology permeate Western science and technology and are responsible for human's seemingly continuous abuse of the environment. Our failure to solve environmental problems is due to a belief that humans are...

  4. Economic Barriers To Improvement Of Human Health Associated With Wastewater Irrigation In The Mezquital Valley, Mexico

    NASA Astrophysics Data System (ADS)

    Yamagata, H.; Sedlak, D. L.

    2008-12-01

    To improve public health, the United Nations' Johannesburg Summit on Sustainable Development in 2002 set Millennium Development Goals (MDGs) of reducing by half the proportion of people without sustainable access to safe drinking water and sanitation by 2015. The Mezquital Valley of Mexico is one of the places suffering serious human health problems such as ascariasis due to agricultural irrigation with untreated wastewater discharged by Mexico City. Despite the existence of serious health problems, wastewater treatment has not been installed due to economic barriers: the agricultural benefit of nutrients in the wastewater and cost of building and operating wastewater treatment plants. To develop solutions to this problem, the human health damage and the benefits of nutrient input were evaluated. The health impact caused by untreated wastewater reuse in the Mezquital Valley was estimated to be about 14 DALYs (disability-adjusted life year) per 100,000, which was 2.8 times higher than the DALYs lost by ascariasis in Mexico in 2002 estimated by WHO. The economic damage of the health impact was evaluated at 77,000 /year using willingness-to-pay (WTP) for reducing DALYs. The value of nutrient inputs (nitrogen and phosphorus) due to reuse of untreated wastewater was evaluated at 33 million /year using fertilizer prices. Therefore, attempts to decrease public health problems associated with reuse in the Mezquital Valley need to address losses of economic benefits associated with nutrients in sewage. In 2007, the Mexican Government announced plans to install wastewater treatment plants in this area. Although nutrient inputs in irrigated water is expected to decrease by 33% due to the wastewater treatment, farmers in the Mezquital Valley would still benefit from improved public health in the community and increases of crop values due to the ability to grow raw-eaten vegetables.

  5. Hardness map of human meta tarsals and phalanges of toes.

    PubMed

    Manarvi, Irfan

    2016-08-01

    Predicting location of fracture in human bones has been a keen area of research for the past few decades. A variety of tests for hardness, deformation and strain field measurement have been conducted in the past; but considered insufficient due to various limitations. Researchers therefore have proposed further studies due to inaccuracies in measurement methods, testing machines and experimental errors. Advancement and availability of hardware, measuring instrumentation and testing machines can now provide remedies to these limitations. Human foot is a critical part of body exposed to various forces throughout its life. A number of products are developed for using over it for protection and care. Which many times do not provide sufficient protection and may itself become a source of stress due to non-consideration of the delicacy of bones in the feet. A continuous strain or overloading on feet may occur resulting to discomfort and even fracture. Not knowing how the hardness is spread all over the Meta tarsals and phalanges is one of major contributory factor for unsatisfactory design of foot protection products. This paper provides a complete hardness distribution map developed by experimental testing of all the Meta tarsals and Phalanges of toes for a typical human foot. The bones were taken from two left feet of a 40 and 42 year old male cadaver. These were dehydrated prior to measurements of hardness using Leeb hardness testing method. Hardness was measured around the circumference of a bone as well as along its length. Hardness values can be related to tensile strength of the bones to predict possible values of stress that could be borne by these bones. Results may also be used for design and developing various accessories for human feet health care and comfort.

  6. [Strategic approaches to risk management to reduce human vulnerability due to water factor changes].

    PubMed

    Rakhmanin, Iu A; Doronina, O D

    2010-01-01

    The current globalization tendencies give rise to serious human health risks associated with the problems in providing the safety of water resources, with their intense microbiological contamination due to sewage disposal, with the loss of capacity of water ecosystems for self-repair. To guarantee access to safe drinking water and basic sanitary services is considered to be one of the most priority tasks of the international community, which are embodied in the Plan of Implementation of the World Summit on Sustainable Development approved by the United Nations Organization.

  7. Challenges facing the development of the Arabic chatbot

    NASA Astrophysics Data System (ADS)

    AlHagbani, Eman Saad; Khan, Muhammad Badruddin

    2016-07-01

    The future information systems are expected to be more intelligent and will take human queries in natural language as input and answer them promptly. To develop a chatbot or a computer program that can chat with humans in realistic manner to extent that human get impressions that he/she is talking with other human is a challenging task. To make such chatbots, different technologies will work together ranging from artificial intelligence to development of semantic resources. Sophisticated chatbots are developed to perform conversation in number of languages. Arabic chatbots can be helpful in automating many operations and serve people who only know Arabic language. However, the technology for Arabic language is still in its infancy stage due to some challenges surrounding the Arabic language. This paper offers an overview of the chatbot application and the several obstacles and challenges that need to be resolved to develop an effective Arabic chatbot.

  8. Cognition in Space Workshop. 1; Metrics and Models

    NASA Technical Reports Server (NTRS)

    Woolford, Barbara; Fielder, Edna

    2005-01-01

    "Cognition in Space Workshop I: Metrics and Models" was the first in a series of workshops sponsored by NASA to develop an integrated research and development plan supporting human cognition in space exploration. The workshop was held in Chandler, Arizona, October 25-27, 2004. The participants represented academia, government agencies, and medical centers. This workshop addressed the following goal of the NASA Human System Integration Program for Exploration: to develop a program to manage risks due to human performance and human error, specifically ones tied to cognition. Risks range from catastrophic error to degradation of efficiency and failure to accomplish mission goals. Cognition itself includes memory, decision making, initiation of motor responses, sensation, and perception. Four subgoals were also defined at the workshop as follows: (1) NASA needs to develop a human-centered design process that incorporates standards for human cognition, human performance, and assessment of human interfaces; (2) NASA needs to identify and assess factors that increase risks associated with cognition; (3) NASA needs to predict risks associated with cognition; and (4) NASA needs to mitigate risk, both prior to actual missions and in real time. This report develops the material relating to these four subgoals.

  9. The zebrafish eye—a paradigm for investigating human ocular genetics

    PubMed Central

    Richardson, R; Tracey-White, D; Webster, A; Moosajee, M

    2017-01-01

    Although human epidemiological and genetic studies are essential to elucidate the aetiology of normal and aberrant ocular development, animal models have provided us with an understanding of the pathogenesis of multiple developmental ocular malformations. Zebrafish eye development displays in depth molecular complexity and stringent spatiotemporal regulation that incorporates developmental contributions of the surface ectoderm, neuroectoderm and head mesenchyme, similar to that seen in humans. For this reason, and due to its genetic tractability, external fertilisation, and early optical clarity, the zebrafish has become an invaluable vertebrate system to investigate human ocular development and disease. Recently, zebrafish have been at the leading edge of preclinical therapy development, with their amenability to genetic manipulation facilitating the generation of robust ocular disease models required for large-scale genetic and drug screening programmes. This review presents an overview of human and zebrafish ocular development, genetic methodologies employed for zebrafish mutagenesis, relevant models of ocular disease, and finally therapeutic approaches, which may have translational leads in the future. PMID:27612182

  10. A case report and literature overview: Abiotrophia defectiva aortic valve endocarditis in developing countries.

    PubMed

    Ramos, J N; dos Santos, L S; Vidal, L M R; Pereira, P M A; Salgado, A A; Fortes, C Q; Vieira, V V; Mattos-Guaraldi, A L; Júnior, R H; Damasco, P V

    2014-06-01

    A fatal case of aortic valve endocarditis due to Abiotrophia defectiva was reported in Brazil. An overview of cases of endocarditis and other human infections related to A. defectiva in developing countries was also accomplished.

  11. Plague vaccines and the molecular basis of immunity against Yersinia pestis.

    PubMed

    Quenee, Lauriane E; Schneewind, Olaf

    2009-12-01

    Yersinia pestis is the causative agent of bubonic and pneumonic plague, human diseases with high mortality. Due to the microbe's ability to spread rapidly, plague epidemics present a serious public health threat. A search for prophylactic measures was initially based on historical reports of bubonic plague survivors and their apparent immunity. Due to safety and efficacy concerns, killed whole-cell preparations or live-attenuated plague vaccines are no longer considered in the United States. Vaccine developers have focused on specific subunits of plague bacteria. LcrV, a protein at the tip of type III secretion needles, and F1, the capsular pilus antigen, are both recognized as plague protective antigens. Antibodies against LcrV and F1 interfere with Y. pestis type III injection of host cells. While LcrV is absolutely essential for Y. pestis virulence, expression of F1 is dispensable for plague pathogenesis in small animals, non-human primates and presumably also in humans. Several subunit vaccines, for example rF1+rV (rYP002), rF1V or rV10, are being developed to generate plague protection in humans. Efficacy testing and licensure for human use requires the establishment of correlates for plague immunity.

  12. 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.

  13. Effects of aqueous humor hydrodynamics on human eye heat transfer under external heat sources.

    PubMed

    Tiang, Kor L; Ooi, Ean H

    2016-08-01

    The majority of the eye models developed in the late 90s and early 00s considers only heat conduction inside the eye. This assumption is not entirely correct, since the anterior and posterior chambers are filled aqueous humor (AH) that is constantly in motion due to thermally-induced buoyancy. In this paper, a three-dimensional model of the human eye is developed to investigate the effects AH hydrodynamics have on the human eye temperature under exposure to external heat sources. If the effects of AH flow are negligible, then future models can be developed without taking them into account, thus simplifying the modeling process. Two types of external thermal loads are considered; volumetric and surface irradiation. Results showed that heat convection due to AH flow contributes to nearly 95% of the total heat flow inside the anterior chamber. Moreover, the circulation inside the anterior chamber can cause an upward shift of the location of hotspot. This can have significant consequences to our understanding of heat-induced cataractogenesis. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

  14. Cognitive Awareness Prototype Development on User Interface Design

    ERIC Educational Resources Information Center

    Rosli, D'oria Islamiah

    2015-01-01

    Human error is a crucial problem in manufacturing industries. Due to the misinterpretation of information on interface system design, accidents or death may occur at workplace. Lack of human cognition criteria in interface system design is also one of the contributions to the failure in using the system effectively. Therefore, this paper describes…

  15. Improving Faculty Perceptions of and Intent to Use Simulation: An Intervention Project

    ERIC Educational Resources Information Center

    Tucker, Charles

    2013-01-01

    Human patient simulation is an innovative teaching strategy that can facilitate practice development and preparation for entry into today's healthcare environment for nursing students. Unfortunately, the use of human patient simulation has been limited due to the perceptions of nursing faculty members. This project sought to explore those…

  16. Epistasis-list.org: A Curated Database of Gene-Gene and Gene-Environment Interactions in Human Epidemiology

    EPA Science Inventory

    The field of human genetics has experienced a paradigm shift in that common diseases are now thought to be due to the complex interactions among numerous genetic and environmental factors. This paradigm shift has prompted the development of myriad novel methods to detect such int...

  17. Adaptive collab orative restoration: a key concept in invasive plant management

    Treesearch

    James H. Miller; John. Schelhas

    2009-01-01

    Nonnative invasive species (NNIS) present a severe human dilemma due to their collective threat of replacing and damaging human sustaining ecosystems (U.S. Congress Office of Technology Assessment 1993; Mack et al. 2000; Pimentel 2002). Rapid developments in global trade have caught governments and their regulatory agencies unaware and...

  18. The immune response to bovine tuberculosis: Correlates of protection and relevance to human tuberculosis

    USDA-ARS?s Scientific Manuscript database

    Tuberculosis (TB), primarily due to Mycobacterium tuberculosis in humans and Mycobacterium bovis in cattle, is a classic model for demonstration of the One Health Concept. Early studies with cattle were instrumental in the development of the use of Koch’s tuberculin as an in vivo measure of cell-med...

  19. Human DAZL, DAZ and BOULE genes modulate primordial germ cell and haploid gamete formation

    PubMed Central

    Kee, Kehkooi; Angeles, Vanessa T; Flores, Martha; Nguyen, Ha Nam; Pera, Renee A Reijo

    2009-01-01

    The leading cause of infertility in men and women is quantitative and qualitative defects in human germ cell (oocyte and sperm) development. Yet, it has not been possible to examine the unique developmental genetics of human germ cell formation and differentiation due to inaccessibility of germ cells during fetal development. Although several studies have shown that germ cells can be differentiated from mouse and human embryonic stem cells, human germ cells differentiated in these studies generally did not develop beyond the earliest stages1-8. Here we used a germ cell reporter to quantitate and isolate primordial germ cells derived from both male and female hESCs. Then, by silencing and overexpressing genes that encode germ cell-specific cytoplasmic RNA-binding proteins (not transcription factors), we modulated human germ cell formation and developmental progression. We observed that human DAZL (Deleted in AZoospermia-Like) functions in primordial germ cell formation, whereas closely-related genes, DAZ and BOULE, promote later stages of meiosis and development of haploid gametes. These results are significant to the generation of gametes for future basic science and potential clinical applications. PMID:19865085

  20. Human Factors Engineering Guidelines for Overhead Cranes

    NASA Technical Reports Server (NTRS)

    Chandler, Faith; Delgado, H. (Technical Monitor)

    2001-01-01

    This guideline provides standards for overhead crane cabs that can be applied to the design and modification of crane cabs to reduce the potential for human error due to design. This guideline serves as an aid during the development of a specification for purchases of cranes or for an engineering support request for crane design modification. It aids human factors engineers in evaluating existing cranes during accident investigations or safety reviews.

  1. Human induced coastal changes and their impact on the coastal urban landscape. The case of Heraklion, Crete

    NASA Astrophysics Data System (ADS)

    Rempis, Nikolaos; Alexandrakis, George; Kampanis, Nikolaos

    2017-04-01

    Coastal zone is a vital part of human society due to sea activities. Α variety of activities and uses are present and are further developing in the coastal and marine are. Coastal ecosystems and landscape are under severe pressure due to population growth and continuous expansion of human activities and supplemented from the effects of climate change (e.g. coastal flooding, erosion). Heraklion is the largest urban center in Crete. Its suburban and coastal area receives intensive urban sprawl pressures, changing the urban landscape and resulting negative impacts on the human and natural environment. The saturation of coastal area of Heraklion creates the need for new development interventions (e.g. new marina, coastal protection, urban regeneration). This study examine the impacts of the new programmed coastal development intervention in the coastal landscape of Heraklion. A decision analytic approach was implemented, based on the need of stakeholders for the protection and further development of coastal area of Heraklion. In this direction, local authorities have proposed the realization of several development interventions which include a new marina, expansion of bathing beaches and coastal regeneration project in a large beach. The results indicate that the realization of any coastal development projects, also increases the negative effects that are related to land-sea interaction. The negative effects are a result of the interaction between different human activities but also between human activities and the environment. The development of the marina in the selected location, increases the pressure on the sea area as the navigation will increase, but also increases the pressure on land space, as traffic flows will change, creating new pressures in urban areas. The extension of bathing beaches implies larger number of bathers, thus creating greater needs for infrastructures in land area for their service. Coastal protection projects, as planned, will upgrade the inland section of the city coastal walls and upgrade them as tourist attraction.

  2. Engineering Education Development to Enhance Human Skill in DENSO

    NASA Astrophysics Data System (ADS)

    Isogai, Emiko; Nuka, Takeji

    Importance of human skills such as communication or instruction capability to their staff members has recently been highlighted in a workplace, due to decreasing opportunity of face-to-face communication between supervisors and their staff, or Instruction capability through OJT (On the Job Training) . Currently, communication skills are being reinforced mainly through OJT at DENSO. Therefore, as part of supplemental support tools, DENSO has established comprehensive engineers training program on off-JT basis for developing human skills, covering from newly employeed enginners up to managerial class since 2003. This paper describes education activities and reports the results.

  3. Current Translational Research and Murine Models For Duchenne Muscular Dystrophy

    PubMed Central

    Rodrigues, Merryl; Echigoya, Yusuke; Fukada, So-ichiro; Yokota, Toshifumi

    2016-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder characterized by progressive muscle degeneration. Mutations in the DMD gene result in the absence of dystrophin, a protein required for muscle strength and stability. Currently, there is no cure for DMD. Since murine models are relatively easy to genetically manipulate, cost effective, and easily reproducible due to their short generation time, they have helped to elucidate the pathobiology of dystrophin deficiency and to assess therapies for treating DMD. Recently, several murine models have been developed by our group and others to be more representative of the human DMD mutation types and phenotypes. For instance, mdx mice on a DBA/2 genetic background, developed by Fukada et al., have lower regenerative capacity and exhibit very severe phenotype. Cmah-deficient mdx mice display an accelerated disease onset and severe cardiac phenotype due to differences in glycosylation between humans and mice. Other novel murine models include mdx52, which harbors a deletion mutation in exon 52, a hot spot region in humans, and dystrophin/utrophin double-deficient (dko), which displays a severe dystrophic phenotype due the absence of utrophin, a dystrophin homolog. This paper reviews the pathological manifestations and recent therapeutic developments in murine models of DMD such as standard mdx (C57BL/10), mdx on C57BL/6 background (C57BL/6-mdx), mdx52, dystrophin/utrophin double-deficient (dko), mdxβgeo, Dmd-null, humanized DMD (hDMD), mdx on DBA/2 background (DBA/2-mdx), Cmah-mdx, and mdx/mTRKO murine models. PMID:27854202

  4. Emerging Technologies to Create Inducible and Genetically Defined Porcine Cancer Models.

    PubMed

    Schook, Lawrence B; Rund, Laurie; Begnini, Karine R; Remião, Mariana H; Seixas, Fabiana K; Collares, Tiago

    2016-01-01

    There is an emerging need for new animal models that address unmet translational cancer research requirements. Transgenic porcine models provide an exceptional opportunity due to their genetic, anatomic, and physiological similarities with humans. Due to recent advances in the sequencing of domestic animal genomes and the development of new organism cloning technologies, it is now very feasible to utilize pigs as a malleable species, with similar anatomic and physiological features with humans, in which to develop cancer models. In this review, we discuss genetic modification technologies successfully used to produce porcine biomedical models, in particular the Cre-loxP System as well as major advances and perspectives the CRISPR/Cas9 System. Recent advancements in porcine tumor modeling and genome editing will bring porcine models to the forefront of translational cancer research.

  5. [The population's insurance protection as a mechanism responsible for provision of sanitary and epidemiological well-being].

    PubMed

    Iarushin, S V

    2007-01-01

    The paper describes a principal scheme of insurance protection organization due to the negative human influences of environmental factors and industrial risks as one of the most effective mechanisms responsible for controlling sanitary-and-epidemiological well-being and human health. It also considers how a voluntary medical collective insurance program and a civil responsibility insurance one are being implemented due to unforeseen damages done to the population's health and how the quality and safety of goods (work, services) are controlled. Organizational, methodic, and normative legal approaches are proposed to developing the population's insurance protection system.

  6. Natural and social factors influencing forest fire occurrence at a local spatial scale

    Treesearch

    Maria Luisa Chas-Amil; Julia M. Touza; Jeffrey P. Prestemon; Colin J. McClean

    2012-01-01

    Development of efficient forest fire policies requires an understanding of the underlying reasons behind forest fire ignitions. Globally, there is a close relationship between forest fires and human activities, i.e., fires understood as human events due to negligence (e.g., agricultural burning escapes), and deliberate actions (e.g., pyromania, revenge, land use change...

  7. Genetic characterization and plasmid replicon typing of ß-lactam resistant Escherichia coli from humans and companion animals in Egypt

    USDA-ARS?s Scientific Manuscript database

    Limited therapeutic options due to antimicrobial resistance (AR) is a major threat to human and animal health worldwide. There is a paucity of information on ß-lactam resistant Esherichia coli isolated from companion animals in developing countries; therefore their zoonotic impact is unknown. This s...

  8. Agricultural Students and Their Academic Performance: A Study of Students in Punjab, Pakistan

    ERIC Educational Resources Information Center

    Arshad, Muhammad; Ullah, Muhammad I.; Mehmood, Muhammad U.; Arshad, Muhammad R.; Khan, Muhammad F.

    2016-01-01

    Reading is considered as essential to develop the personality of human being. However, reading habits of human being especially young generation is at decline due to initiation of modern digital technologies like mobile phones, social networking on internet along with other ways of different entertainment. The study was conducted to assess the…

  9. Trial and error: how the unclonable human mitochondrial genome was cloned in yeast.

    PubMed

    Bigger, Brian W; Liao, Ai-Yin; Sergijenko, Ana; Coutelle, Charles

    2011-11-01

    Development of a human mitochondrial gene delivery vector is a critical step in the ability to treat diseases arising from mutations in mitochondrial DNA. Although we have previously cloned the mouse mitochondrial genome in its entirety and developed it as a mitochondrial gene therapy vector, the human mitochondrial genome has been dubbed unclonable in E. coli, due to regions of instability in the D-loop and tRNA(Thr) gene. We tested multi- and single-copy vector systems for cloning human mitochondrial DNA in E. coli and Saccharomyces cerevisiae, including transformation-associated recombination. Human mitochondrial DNA is unclonable in E. coli and cannot be retained in multi- or single-copy vectors under any conditions. It was, however, possible to clone and stably maintain the entire human mitochondrial genome in yeast as long as a single-copy centromeric plasmid was used. D-loop and tRNA(Thr) were both stable and unmutated. This is the first report of cloning the entire human mitochondrial genome and the first step in developing a gene delivery vehicle for human mitochondrial gene therapy.

  10. Effects of modifying water environments on water supply and human health

    NASA Astrophysics Data System (ADS)

    Takizawa, S.; Nguyen, H. T.; Takeda, T.; Tran, N. T.

    2008-12-01

    Due to increasing population and per-capita water demand, demands for water are increasing in many parts of the world. Consequently, overuse of limited water resources leaves only small amounts of water in rivers and is bringing about rapid drawdown of groundwater tables. Water resources are affected by human activities such as excessive inputs of nutrients and other contaminants, agriculture and aquaculture expansions, and many development activities. The combined effects of modifying the water environments, both in terms of quantity and quality, on water supply and human health are presented in the paper with some examples from the Asian countries. In rural and sub-urban areas in Bangladesh and Vietnam, for example, the traditional way of obtaining surface water from ponds had been replaced by taking groundwaters to avert the microbial health risks that had arisen from contamination by human wastes. Such a change of water sources, however, has brought about human health impact caused by arsenic on a massive scale. In Thailand, the industrial development has driven the residents to get groundwater leaden with very high fluoride. Monitoring the urine fluoride levels reveal the risk of drinking fluoride-laden groundwaters. Rivers are also affected by extensive exploitation such as sand mining. As a result, turbidity changes abruptly after a heavy rainfall. In cities, due to shrinking water resources they have to take poor quality waters from contaminated sources. Algal blooms are seen in many reservoirs and lakes due to increasing levels of nutrients. Hence, it is likely that algal toxins may enter the water supply systems. Because most of the water treatment plants are not designed to remove those known and unknown contaminants, it is estimated that quite a large number of people are now under the threat of the public health "gtime bomb,"h which may one day bring about mass-scale health problems. In order to mitigate the negative impacts of modifying the water environments on human health, we have to develop tools to assess and predict such impacts. This paper presents methodologies to assess the current status of water resources degradation and resultant effects on human health are discussed based on some case studies.

  11. Alternatives to In Vivo Draize Rabbit Eye and Skin Irritation Tests with a Focus on 3D Reconstructed Human Cornea-Like Epithelium and Epidermis Models

    PubMed Central

    Lee, Miri; Hwang, Jee-Hyun; Lim, Kyung-Min

    2017-01-01

    Human eyes and skin are frequently exposed to chemicals accidentally or on purpose due to their external location. Therefore, chemicals are required to undergo the evaluation of the ocular and dermal irritancy for their safe handling and use before release into the market. Draize rabbit eye and skin irritation test developed in 1944, has been a gold standard test which was enlisted as OECD TG 404 and OECD TG 405 but it has been criticized with respect to animal welfare due to invasive and cruel procedure. To replace it, diverse alternatives have been developed: (i) For Draize eye irritation test, organotypic assay, in vitro cytotoxicity-based method, in chemico tests, in silico prediction model, and 3D reconstructed human cornea-like epithelium (RhCE); (ii) For Draize skin irritation test, in vitro cytotoxicity-based cell model, and 3D reconstructed human epidermis models (RhE). Of these, RhCE and RhE models are getting spotlight as a promising alternative with a wide applicability domain covering cosmetics and personal care products. In this review, we overviewed the current alternatives to Draize test with a focus on 3D human epithelium models to provide an insight into advancing and widening their utility. PMID:28744350

  12. Assessing the Risk of Crew Injury Due to Dynamic Loads During Spaceflight

    NASA Technical Reports Server (NTRS)

    Somers, J. T.; Gernhardt, M.; Newby, N.

    2014-01-01

    Spaceflight requires tremendous amounts of energy to achieve Earth orbit and to attain escape velocity for interplanetary missions. Although the majority of the energy is managed in such a way as to limit the accelerations on the crew, several mission phases may result in crew exposure to dynamic loads. In the automotive industry, risk of serious injury can be tolerated because the probability of a crash is remote each time a person enters a vehicle, resulting in a low total risk of injury. For spaceflight, the level of acceptable injury risk must be lower to achieve a low total risk of injury because the dynamic loads are expected on each flight. To mitigate the risk of injury due to dynamic loads, the NASA Human Research Program has developed a research plan to inform the knowledge gaps and develop relevant tools for assessing injury risk. The risk of injury due to dynamic loads can be further subdivided into extrinsic and intrinsic risk factors. Extrinsic risk factors include the vehicle dynamic profile, seat and restraint design, and spacesuit design. Human tolerance to loads varies considerably depending on the direction, amplitude, and rise-time of acceleration therefore the orientation of the body to the dynamic vector is critical to determining crew risk of injury. Although a particular vehicle dynamic profile may be safe for a particular design, the seat, restraint, and suit designs can affect the risk of injury due to localized effects. In addition, characteristics intrinsic to the crewmember may also contribute to the risk of injury, such as crewmember sex, age, anthropometry, and deconditioning due to spaceflight, and each astronaut may have a different risk profile because of these factors. The purpose of the research plan is to address any knowledge gaps in the risk factors to mitigate injury risk. Methods for assessing injury risk have been well documented in other analogous industries and include human volunteer testing, human exposure to dynamic environments, post-mortem human subject (PMHS) testing, animal testing, anthropomorphic test devices (ATD), dynamic models of the human, numerical models of ATDs, and numerical models of the human. Each has inherent strengths and limitations. For example, human volunteer testing is advantageous because a population can be selected that is similar to the astronaut corps; however, because of the inherent ethical limitations, only sub-injurious conditions can be tested. PMHSs can be tested in a variety of conditions including injurious levels, but the responses are not completely analogous to living human subjects. In addition, it is exceedingly difficult to select a PMHS population that is similar to the astronaut corps. ATDs are currently widely used in the automotive industry and military because they are highly repeatable and durable. Unfortunately, because they are mechanical models of the human body, the biofidelity of the responses are limited to dynamic conditions used to validate the ATD. Numerical models of the ATD, in addition to the strengths and limitations for ATDs, are easy to use for a variety of designs before a design is fabricated, but also have additional limitations for ATDs, are easy to use for a variety of designs before a design is fabricated, but also have additional uncertainty. Dynamic models are simple and easy to use, but do not account for localized effects of the seat and suit. Finally, numerical models of the human have the potential to have the most advantages; however, the current models are not validated for the conditions expected during spaceflight. To properly assess spaceflight conditions with numerical human models, human data would be needed to optimize the model responses for those conditions. Using the appropriate assessment method with the knowledge gained for each risk factor, an appropriate approach for mitigating the risk of injury due to dynamic loads can be developed ensuring crew safety in future NASA vehicles.

  13. 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.

  14. On quantum models of the human mind.

    PubMed

    Wang, Hongbin; Sun, Yanlong

    2014-01-01

    Recent years have witnessed rapidly increasing interests in developing quantum theoretical models of human cognition. Quantum mechanisms have been taken seriously to describe how the mind reasons and decides. Papers in this special issue report the newest results in the field. Here we discuss why the two levels of commitment, treating the human brain as a quantum computer and merely adopting abstract quantum probability principles to model human cognition, should be integrated. We speculate that quantum cognition models gain greater modeling power due to a richer representation scheme. Copyright © 2013 Cognitive Science Society, Inc.

  15. Ebolavirus Vaccines for Humans and Apes

    PubMed Central

    Fausther-Bovendo, Hugues; Mulangu, Sabue

    2012-01-01

    Due to high case fatality proportions, person-to-person transmission, and potential use in bioterrorism, the development of a vaccine against ebolavirus remains a top priority. Although no licensed vaccine or treatment against ebolavirus is currently available, progress in preclinical testing of countermeasures has been made. Here, we will review ebolavirus vaccine candidates and considerations for their use in humans and wild apes. PMID:22560007

  16. Human Brain Modeling with Its Anatomical Structure and Realistic Material Properties for Brain Injury Prediction.

    PubMed

    Atsumi, Noritoshi; Nakahira, Yuko; Tanaka, Eiichi; Iwamoto, Masami

    2018-05-01

    Impairments of executive brain function after traumatic brain injury (TBI) due to head impacts in traffic accidents need to be obviated. Finite element (FE) analyses with a human brain model facilitate understanding of the TBI mechanisms. However, conventional brain FE models do not suitably describe the anatomical structure in the deep brain, which is a critical region for executive brain function, and the material properties of brain parenchyma. In this study, for better TBI prediction, a novel brain FE model with anatomical structure in the deep brain was developed. The developed model comprises a constitutive model of brain parenchyma considering anisotropy and strain rate dependency. Validation was performed against postmortem human subject test data associated with brain deformation during head impact. Brain injury analyses were performed using head acceleration curves obtained from reconstruction analysis of rear-end collision with a human whole-body FE model. The difference in structure was found to affect the regions of strain concentration, while the difference in material model contributed to the peak strain value. The injury prediction result by the proposed model was consistent with the characteristics in the neuroimaging data of TBI patients due to traffic accidents.

  17. Semantic Likelihood Models for Bayesian Inference in Human-Robot Interaction

    NASA Astrophysics Data System (ADS)

    Sweet, Nicholas

    Autonomous systems, particularly unmanned aerial systems (UAS), remain limited in au- tonomous capabilities largely due to a poor understanding of their environment. Current sensors simply do not match human perceptive capabilities, impeding progress towards full autonomy. Recent work has shown the value of humans as sources of information within a human-robot team; in target applications, communicating human-generated 'soft data' to autonomous systems enables higher levels of autonomy through large, efficient information gains. This requires development of a 'human sensor model' that allows soft data fusion through Bayesian inference to update the probabilistic belief representations maintained by autonomous systems. Current human sensor models that capture linguistic inputs as semantic information are limited in their ability to generalize likelihood functions for semantic statements: they may be learned from dense data; they do not exploit the contextual information embedded within groundings; and they often limit human input to restrictive and simplistic interfaces. This work provides mechanisms to synthesize human sensor models from constraints based on easily attainable a priori knowledge, develops compression techniques to capture information-dense semantics, and investigates the problem of capturing and fusing semantic information contained within unstructured natural language. A robotic experimental testbed is also developed to validate the above contributions.

  18. Adding the Human Element to Ship Manoeuvring Simulations

    NASA Astrophysics Data System (ADS)

    Aarsæther, Karl Gunnar; Moan, Torgeir

    Time-domain simulation of ship manoeuvring has been utilized in risk analysis to assess the effect of changes to the ship-lane, development in traffic volume and the associated risk. The process of ship manoeuvring in a wider socio-technical context consists of the technical systems, operational procedures, the human operators and support functions. Automated manoeuvring simulations without human operators in the simulation loop have often been preferred in simulation studies due to the low time required for simulations. Automatic control has represented the human element with little effort devoted to explain the relationship between the guidance and control algorithms and the human operator which they replace. This paper describes the development and application of a model for the human element for autonomous time-domain manoeuvring simulations. The method is applicable in the time-domain, modular and found to be capable of reproducing observed manoeuvre patterns, but limited to represent the intended behaviour.

  19. 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.

  20. 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.

  1. Using the Optical Fractionator to Estimate Total Cell Numbers in the Normal and Abnormal Developing Human Forebrain.

    PubMed

    Larsen, Karen B

    2017-01-01

    Human fetal brain development is a complex process which is vulnerable to disruption at many stages. Although histogenesis is well-documented, only a few studies have quantified cell numbers across normal human fetal brain growth. Due to the present lack of normative data it is difficult to gauge abnormal development. Furthermore, many studies of brain cell numbers have employed biased counting methods, whereas innovations in stereology during the past 20-30 years enable reliable and efficient estimates of cell numbers. However, estimates of cell volumes and densities in fetal brain samples are unreliable due to unpredictable shrinking artifacts, and the fragility of the fetal brain requires particular care in handling and processing. The optical fractionator design offers a direct and robust estimate of total cell numbers in the fetal brain with a minimum of handling of the tissue. Bearing this in mind, we have used the optical fractionator to quantify the growth of total cell numbers as a function of fetal age. We discovered a two-phased development in total cell numbers in the human fetal forebrain consisting of an initial steep rise in total cell numbers between 13 and 20 weeks of gestation, followed by a slower linear phase extending from mid-gestation to 40 weeks of gestation. Furthermore, we have demonstrated a reduced total cell number in the forebrain in fetuses with Down syndome at midgestation and in intrauterine growth-restricted fetuses during the third trimester.

  2. Emerging Technologies to Create Inducible and Genetically Defined Porcine Cancer Models

    PubMed Central

    Schook, Lawrence B.; Rund, Laurie; Begnini, Karine R.; Remião, Mariana H.; Seixas, Fabiana K.; Collares, Tiago

    2016-01-01

    There is an emerging need for new animal models that address unmet translational cancer research requirements. Transgenic porcine models provide an exceptional opportunity due to their genetic, anatomic, and physiological similarities with humans. Due to recent advances in the sequencing of domestic animal genomes and the development of new organism cloning technologies, it is now very feasible to utilize pigs as a malleable species, with similar anatomic and physiological features with humans, in which to develop cancer models. In this review, we discuss genetic modification technologies successfully used to produce porcine biomedical models, in particular the Cre-loxP System as well as major advances and perspectives the CRISPR/Cas9 System. Recent advancements in porcine tumor modeling and genome editing will bring porcine models to the forefront of translational cancer research. PMID:26973698

  3. Current applications and future prospects of nanomaterials in tumor therapy.

    PubMed

    Huang, Yu; Fan, Chao-Qiang; Dong, Hui; Wang, Su-Min; Yang, Xiao-Chao; Yang, Shi-Ming

    2017-01-01

    Tumors are one of the most serious human diseases and cause numerous global deaths per year. In spite of many strategies applied in tumor therapy, such as radiation therapy, chemotherapy, surgery, and a combination of these treatments, tumors are still the foremost killer worldwide among human diseases, due to their specific limitations, such as multidrug resistance and side effects. Therefore, it is urgent and necessary to develop new strategies for tumor therapy. Recently, the fast development of nanoscience has paved the way for designing new strategies to treat tumors. Nanomaterials have shown great potential in tumor therapy, due to their unique properties, including passive targeting, hyperthermia effects, and tumor-specific inhibition. This review summarizes the recent progress using the innate antitumor properties of metallic and nonmetallic nanomaterials to treat tumors, and related challenges and prospects are discussed.

  4. Human milk 90K (Mac-2 BP): possible protective effects against acute respiratory infections.

    PubMed

    Fornarini, B; Iacobelli, S; Tinari, N; Natoli, C; De Martino, M; Sabatino, G

    1999-01-01

    Eighty-six children fed human milk were followed prospectively from birth to 12 months of age to assess the effect of milk 90K, a secreted glycoprotein with immune-stimulatory properties, on development of acute respiratory infections (ARI). The level of human milk 90K was inversely related to episodes of ARI (r = - 0.34; P = 0.001). The average 90K level in human milk fed to children who did not develop ARI was significantly higher than in milk fed to children in whom infection occurred on multiple occasions (156.6 +/- 144.8 microg/ml versus 70.9 +/- 92.3 microg/ml; P = 0.001). These data suggest that the protective effects of human milk against ARI may be due in part to immune maturation effects by secreted 90K.

  5. Insights from zebrafish on human pigment cell disease and treatment.

    PubMed

    Cooper, Cynthia D

    2017-11-01

    Black pigment cells, melanocytes, arise early during development from multipotent neural crest cells. Melanocytes protect human skin from DNA damaging sunrays and provide color for hair, eyes, and skin. Several disorders and diseases originate from these cells, including the deadliest skin cell cancer, melanoma. Thus, melanocytes are critical for a healthy life and for protecting humans from disease. Due to the ease of visualizing pigment cells through transparent larvae skin and conserved roles for zebrafish melanophore genes to mammalian melanocyte genes, zebrafish larvae offer a biologically relevant model for understanding pigment cell development and disease in humans. This review discusses our current knowledge of melanophore biology and how zebrafish are contributing to improving how diseases of melanocytes are understood and treated in humans. Developmental Dynamics 246:889-896, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  6. Label-free detection of protein biomolecules secreted from a heart-on-a-chip model for drug cardiotoxicity evaluation

    NASA Astrophysics Data System (ADS)

    DeLuna, Frank; Zhang, Yu Shrike; Bustamante, Gilbert; Li, Le; Lauderdale, Matthew; Dokmeci, Mehmet R.; Khademhosseini, Ali; Ye, Jing Yong

    2018-02-01

    Efficient methods for the accurate analysis of drug toxicities are in urgent demand as failures of newly discovered drug candidates due to toxic side effects have resulted in about 30% of clinical attrition. The high failure rate is partly due to current inadequate models to study drug side effects, i.e., common animal models may fail due to its misrepresentation of human physiology. Therefore, much effort has been allocated in the development of organ-on-a-chip models which offer a variety of human organ models mimicking a multitude of human physiological conditions. However, it is extremely challenging to analyze the transient and long-term response of the organ models to drug treatments during drug toxicity tests, as the proteins secreted from the organ-on-a-chip model are minute due to its volumetric size, and current methods for detecting said biomolecules are not suitable for real-time monitoring. As protein biomolecules are being continuously secreted from the human organ model, fluorescence techniques are practically impossible to achieve real-time fluorescence labeling in the dynamically changing environment, thus making a label-free approach highly desirable for the organ-on-achip applications. In this paper, we report the use of a photonic-crystal biosensor integrated with a microfluidic system for sensitive label-free bioassays of secreted protein biomolecules from a heart-on-the-chip model created with cardiomyocytes derived from human induced pluripotent stem cells.

  7. Quantitative Risk Assessment of Antimicrobial-Resistant Foodborne Infections in Humans Due to Recombinant Bovine Somatotropin Usage in Dairy Cows.

    PubMed

    Singer, Randall S; Ruegg, Pamela L; Bauman, Dale E

    2017-07-01

    Recombinant bovine somatotropin (rbST) is a production-enhancing technology that allows the dairy industry to produce milk more efficiently. Concern has been raised that cows supplemented with rbST are at an increased risk of developing clinical mastitis, which would potentially increase the use of antimicrobial agents and increase human illnesses associated with antimicrobial-resistant bacterial pathogens delivered through the dairy beef supply. The purpose of this study was to conduct a quantitative risk assessment to estimate the potential increased risk of human infection with antimicrobial-resistant bacteria and subsequent adverse health outcomes as a result of rbST usage in dairy cattle. The quantitative risk assessment included the following steps: (i) release of antimicrobial-resistant organisms from the farm, (ii) exposure of humans via consumption of contaminated beef products, and (iii) consequence of the antimicrobial-resistant infection. The model focused on ceftiofur (parenteral and intramammary) and oxytetracycline (parenteral) treatment of clinical mastitis in dairy cattle and tracked the bacteria Campylobacter spp., Salmonella enterica subsp. enterica, and Escherichia coli in the gastrointestinal tract of the cow. Parameter estimates were developed to be maximum risk to overestimate the risk to humans. The excess number of cows in the U.S. dairy herd that were predicted to carry resistant bacteria at slaughter due to rbST administration was negligible. The total number of excess human illnesses caused by resistant bacteria due to rbST administration was also predicted to be negligible with all risks considerably less than one event per 1 billion people at risk per year for all bacteria. The results indicate a high probability that the use of rbST according to label instructions presents a negligible risk for increasing the number of human illnesses and subsequent adverse outcomes associated with antimicrobial-resistant Campylobacter, Salmonella, or E. coli .

  8. Analysis of an epigenetic argument against human reproductive cloning.

    PubMed

    Nordgren, Anders

    2006-08-01

    Human reproductive cloning is a much disputed ethical issue. This technology is often condemned as being contrary to human dignity. However, there are also risk arguments. An ethical argument that is often put forward by scientists but seldom developed in more detail focuses on health risks in animal cloning. There is a high risk that animal clones exhibit abnormalities and these are increasingly believed to be due to errors in epigenetic reprogramming. The argument is that human reproductive cloning should not be carried out because human clones are also likely to exhibit abnormalities due to inappropriate epigenetic reprogramming. Different versions of this epigenetic argument are analysed, a categorical version and a non-categorical. The non-categorical version is suggested to be more well-considered. With regard to policy making on human reproductive cloning, the categorical version can be used to prescribe a permanent ban, while the non-categorical version can be used to prescribe a temporary ban. The implications of the precautionary principle--as interpreted in the European Union--are investigated. The conclusion is that it seems possible to support a temporary ban by reference to this principle.

  9. The gender gap in mobility: a global cross-sectional study.

    PubMed

    Mechakra-Tahiri, Samia Djemâa; Freeman, Ellen E; Haddad, Slim; Samson, Elodie; Zunzunegui, Maria Victoria

    2012-08-02

    Several studies have demonstrated that women have greater mobility disability than men. The goals of this research were: 1) to assess the gender gap in mobility difficulty in 70 countries; 2) to determine whether the gender gap is explained by sociodemographic and health factors; 3) to determine whether the gender gap differs across 6 regions of the world with different degrees of gender equality according to United Nations data. Population-based data were used from the World Health Survey (WHS) conducted in 70 countries throughout the world. 276,647 adults aged 18 years and over were recruited from 6 world regions. Mobility was measured by asking the level of difficulty people had moving around in the last 30 days and then creating a dichotomous measure (no difficulty, difficulty). The human development index and the gender-related development index for each country were obtained from the United Nations Development Program website. Poisson regression with Taylor series linearized variance estimation was used. Women were more likely than men to report mobility difficulty (38% versus 27%, P < 0.0001). The age-adjusted prevalence rate ratio for female gender was 1.35 (95% CI 1.31-1.38). The addition of education, marital status, and urban versus rural setting reduced the prevalence rate ratio to 1.30 (95% CI 1.26-1.33). The addition of the presence of back pain, arthritis, angina, depressive symptoms, and cognitive difficulties further reduced the prevalence rate ratio to 1.12 (95% CI 1.09-1.15). There was statistical interaction on the multiplicative scale between female gender and region (P < 0.01). The Eastern Mediterranean region, which had the greatest loss of human development due to gender inequality, showed the largest gender gap in mobility difficulty, while the Western Pacific region, with the smallest loss of human development due to gender inequality, had the smallest gender gap in mobility difficulty. These are the first world-wide data to examine the gender gap in mobility. Differences in chronic diseases are the main reasons for this gender gap. The gender gap seems to be greater in regions with the largest loss of human development due to gender inequality.

  10. In Genes We Trust: Germline Engineering, Eugenics, and the Future of the Human Genome.

    PubMed

    Powell, Russell

    2015-12-01

    Liberal proponents of genetic engineering maintain that developing human germline modification technologies is morally desirable because it will result in a net improvement in human health and well-being. Skeptics of germline modification, in contrast, fear evolutionary harms that could flow from intervening in the human germline, and worry that such programs, even if well intentioned, could lead to a recapitulation of the scientifically and morally discredited projects of the old eugenics. Some bioconservatives have appealed as well to the value of retaining our "given" human biological nature as a reason for restraining the development and use of human genetic modification technologies even where they would tend to increase well-being. In this article, I argue that germline intervention will be necessary merely to sustain the levels of genetic health that we presently enjoy for future generations-a goal that should appeal to bioliberals and bioconservatives alike. This is due to the population-genetic consequences of relaxed selection pressures in human populations caused by the increasing efficacy and availability of conventional medicine. This heterodox conclusion, which I present as a problem of intergenerational justice, has been overlooked in medicine and bioethics due to certain misconceptions about human evolution, which I attempt to rectify, as well as the sordid history of Darwinian approaches to medicine and social policy, which I distinguish from the present argument. © The Author 2015. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Corneal cell culture models: a tool to study corneal drug absorption.

    PubMed

    Dey, Surajit

    2011-05-01

    In recent times, there has been an ever increasing demand for ocular drugs to treat sight threatening diseases such as glaucoma, age-related macular degeneration and diabetic retinopathy. As more drugs are developed, there is a great need to test in vitro permeability of these drugs to predict their efficacy and bioavailability in vivo. Corneal cell culture models are the only tool that can predict drug absorption across ocular layers accurately and rapidly. Cell culture studies are also valuable in reducing the number of animals needed for in vivo studies which can increase the cost of the drug developmental process. Currently, rabbit corneal cell culture models are used to predict human corneal absorption due to the difficulty in human corneal studies. More recently, a three dimensional human corneal equivalent has been developed using three different cell types to mimic the human cornea. In the future, human corneal cell culture systems need to be developed to be used as a standardized model for drug permeation.

  12. Genetic thinking in the study of social relationships: Five points of entry

    PubMed Central

    Reiss, David

    2014-01-01

    For nearly a generation, researchers studying human behavioral development have combined genetically informed research designs with careful measures of social relationships: parenting, sibling relationships, peer relationships, marital processes, social class stratifications and patterns of social engagement in the elderly. In what way have these genetically informed studies altered the construction and testing of social theories of human development? We consider five points where genetic thinking is taking hold. First, genetic findings suggest an alternative scenario for explaining social data. Associations between measures of the social environment and human development may be due to genes that influence both. Second, genetic studies add to other prompts to study the early developmental origins of current social phenomena in mid-life and beyond. Third, genetic analyses promise to bring to the surface understudied social systems, such as sibling relationships, that have an impact on human development independent of genotype. Fourth, genetic analyses anchor in neurobiology individual differences in resilience and sensitivity to both adverse and favorable social environments. Finally, genetic analyses increase the utility of laboratory simulations of human social processes and of animal models. PMID:25419225

  13. Effects of male sex hormones on gender identity, sexual behavior, and cognitive function.

    PubMed

    Zhu, Yuan-shan; Cai, Li-qun

    2006-04-01

    Androgens, the male sex hormones, play an essential role in male sexual differentiation and development. However, the influence of these sex hormones extends beyond their roles in sexual differentiation and development. In many animal species, sex hormones have been shown to be essential for sexual differentiation of the brain during development and for maintaining sexually dimorphic behavior throughout life. The principals of sex determination in humans have been demonstrated to be similar to other mammals. However, the hormonal influence on sexual dimorphic differences in the nervous system in humans, sex differences in behaviors, and its correlations with those of other mammals is still an emerging field. In this review, the roles of androgens in gender and cognitive function are discussed with the emphasis on subjects with androgen action defects including complete androgen insensitivity due to androgen receptor mutations and 5alpha-reductase-2 deficiency syndromes due to 5alpha-reductase-2 gene mutations. The issue of the complex interaction of nature versus nurture is addressed.

  14. Linguistics, Cognitive Science and Liberal Education. Linguistics in the Undergraduate Curriculum, Appendix 4-H.

    ERIC Educational Resources Information Center

    Heny, Frank

    The goals of liberal education are to deepen the understanding of the nature of humankind and of the human condition. In the last half century, fundamental changes have occurred in perceptions of how the human species relates to the rest of the universe, due to developments in science and the creation of the cognitive sciences. There is now the…

  15. Dynamic response due to behind helmet blunt trauma measured with a human head surrogate.

    PubMed

    Freitas, Christopher J; Mathis, James T; Scott, Nikki; Bigger, Rory P; Mackiewicz, James

    2014-01-01

    A Human Head Surrogate has been developed for use in behind helmet blunt trauma experiments. This human head surrogate fills the void between Post-Mortem Human Subject testing (with biofidelity but handling restrictions) and commercial ballistic head forms (with no biofidelity but ease of use). This unique human head surrogate is based on refreshed human craniums and surrogate materials representing human head soft tissues such as the skin, dura, and brain. A methodology for refreshing the craniums is developed and verified through material testing. A test methodology utilizing these unique human head surrogates is also developed and then demonstrated in a series of experiments in which non-perforating ballistic impact of combat helmets is performed with and without supplemental ceramic appliques for protecting against larger caliber threats. Sensors embedded in the human head surrogates allow for direct measurement of intracranial pressure, cranial strain, and head and helmet acceleration. Over seventy (70) fully instrumented experiments have been executed using this unique surrogate. Examples of the data collected are presented. Based on these series of tests, the Southwest Research Institute (SwRI) Human Head Surrogate has demonstrated great potential for providing insights in to injury mechanics resulting from non-perforating ballistic impact on combat helmets, and directly supports behind helmet blunt trauma studies.

  16. Dynamic Response Due to Behind Helmet Blunt Trauma Measured with a Human Head Surrogate

    PubMed Central

    Freitas, Christopher J.; Mathis, James T.; Scott, Nikki; Bigger, Rory P.; MacKiewicz, James

    2014-01-01

    A Human Head Surrogate has been developed for use in behind helmet blunt trauma experiments. This human head surrogate fills the void between Post-Mortem Human Subject testing (with biofidelity but handling restrictions) and commercial ballistic head forms (with no biofidelity but ease of use). This unique human head surrogate is based on refreshed human craniums and surrogate materials representing human head soft tissues such as the skin, dura, and brain. A methodology for refreshing the craniums is developed and verified through material testing. A test methodology utilizing these unique human head surrogates is also developed and then demonstrated in a series of experiments in which non-perforating ballistic impact of combat helmets is performed with and without supplemental ceramic appliques for protecting against larger caliber threats. Sensors embedded in the human head surrogates allow for direct measurement of intracranial pressure, cranial strain, and head and helmet acceleration. Over seventy (70) fully instrumented experiments have been executed using this unique surrogate. Examples of the data collected are presented. Based on these series of tests, the Southwest Research Institute (SwRI) Human Head Surrogate has demonstrated great potential for providing insights in to injury mechanics resulting from non-perforating ballistic impact on combat helmets, and directly supports behind helmet blunt trauma studies. PMID:24688303

  17. AACP Special Taskforce White Paper on Diversifying Our Investment in Human Capital.

    PubMed

    White, Carla; Conway, Jeannine M; Davis, Paula K; Johnson-Fannin, Arcelia M; Jurkas, Jeffrey G; Murphy, Nanci L; Smith, W Thomas; Echeverri, Margarita; Youmans, Sharon L; Owings, Katie C; Adams, Jennifer L

    2017-10-01

    The 2015-2017 American Association of Colleges of Pharmacy (AACP) Special Taskforce on Diversifying our Investment in Human Capital was appointed for a two-year term, due to the rigors and complexities of its charges. This report serves as a white paper for academic pharmacy on diversifying our investment in human capital. The Taskforce developed and recommended a representation statement that was adapted and adopted by the AACP House of Delegates at the 2016 AACP Annual Meeting. In addition, the Taskforce developed a diversity statement for the Association that was adopted by the AACP Board of Directors in 2017. The Taskforce also provides recommendations to AACP and to academic pharmacy in this white paper.

  18. 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

  19. Shifting human salty taste preference: Potential opportunities and challenges in reducing dietary salt intake of Americans

    PubMed Central

    Bobowski, Nuala

    2015-01-01

    Dietary salt reduction of Americans has been a focus of public health initiatives for more than 40 years primarily due to the association between high salt intake and development of hypertension. Despite past efforts, salt intake of Americans has remained at levels well above dietary recommendations, likely due in part to the hedonic appeal of salty taste. As such, in 2010 the Institute of Medicine suggested a strategy of gradual salt reduction of processed foods, the primary source of Americans’ dietary salt intake, via an approach intended to minimize impact on consumer acceptability of lower-sodium foods. This brief review discusses the ontogeny and development of human salt taste preference, the role of experience in shifting salt preference, and sources of dietary salt. Our current understanding of shifting human salt taste preference is discussed within the context of potential opportunities for success in reducing dietary salt, and gaps in the research that both limit our ability to predict effectiveness of gradual salt reduction and that need be addressed before a strategy to shift salt preference can realistically be implemented. PMID:26451233

  20. Robonaut 2 and You: Specifying and Executing Complex Operations

    NASA Technical Reports Server (NTRS)

    Baker, William; Kingston, Zachary; Moll, Mark; Badger, Julia; Kavraki, Lydia

    2017-01-01

    Crew time is a precious resource due to the expense of trained human operators in space. Efficient caretaker robots could lessen the manual labor load required by frequent vehicular and life support maintenance tasks, freeing astronaut time for scientific mission objectives. Humanoid robots can fluidly exist alongside human counterparts due to their form, but they are complex and high-dimensional platforms. This paper describes a system that human operators can use to maneuver Robonaut 2 (R2), a dexterous humanoid robot developed by NASA to research co-robotic applications. The system includes a specification of constraints used to describe operations, and the supporting planning framework that solves constrained problems on R2 at interactive speeds. The paper is developed in reference to an illustrative, typical example of an operation R2 performs to highlight the challenges inherent to the problems R2 must face. Finally, the interface and planner is validated through a case-study using the guiding example on the physical robot in a simulated microgravity environment. This work reveals the complexity of employing humanoid caretaker robots and suggest solutions that are broadly applicable.

  1. Cultural capital as a measurand

    NASA Astrophysics Data System (ADS)

    Taymanov, R.; Sapozhnikova, K.

    2016-11-01

    The necessity for developing metrology due to extension of its application sphere is noted. The efficiency of the metrological approach to measurement of multidimensional quantities in the field of humanities is shown using the development of cultural capital interpreted by L. Harrison. The cultural capital is defined as a measure of the society structure complexity and adaptive capacity.

  2. Human impacts on 20th century fire dynamics and implications for global carbon and water trajectories

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

    Li, Fang; Lawrence, David M.; Bond-Lamberty, Ben

    Fire is a fundamental Earth system process and the primary ecosystem disturbance on the global scale. It affects carbon and water cycles through changing terrestrial ecosystems, and at the same time, is regulated by weather and climate, vegetation characteristics, and, importantly, human ignitions and suppression (i.e., the direct human effect on fire). Here, we utilize the Community Land Model version 4.5 (CLM4.5) to quantify the impacts of changes in human ignition and suppression on fire dynamics and associated carbon and water cycles. We find that the impact is to significantly reduce the 20th century global burned area by a centurymore » average of 38 Mha/yr and by 103 Mha/yr at the end of the century. Land carbon gain is weakened by 17% over the 20th century, mainly due to increased human deforestation fires and associated escape fires (i.e., degradation fires) in the tropical humid forests, even though the decrease in burned area in many other regions due to human fire suppression acts to increase land carbon gain. The direct human effect on fire weakens the upward trend in global runoff throughout the century by 6% and enhances the upward trend in global evapotranspiration since ~ 1945 by 7%. In addition, the above impacts in densely populated, highly developed (if population density > 0.1 person/km2), or moderately populated and developed regions are of opposite sign to those in other regions. Our study suggests that particular attention should be paid to human deforestation and degradation fires in the tropical humid forests when reconstructing and projecting fire carbon emissions and net atmosphere-land carbon exchange and estimating resultant impacts of direct human effect on fire.« less

  3. Human impacts on 20th century fire dynamics and implications for global carbon and water trajectories

    NASA Astrophysics Data System (ADS)

    Li, Fang; Lawrence, David M.; Bond-Lamberty, Ben

    2018-03-01

    Fire is a fundamental Earth system process and the primary ecosystem disturbance on the global scale. It affects carbon and water cycles through changing terrestrial ecosystems, and at the same time, is regulated by weather and climate, vegetation characteristics, and, importantly, human ignitions and suppression (i.e., the direct human effect on fire). Here, we utilize the Community Land Model version 4.5 (CLM4.5) to quantify the impacts of changes in human ignition and suppression on fire dynamics and associated carbon and water cycles. We find that the impact is to significantly reduce the 20th century global burned area by a century average of 38 Mha/yr and by 103 Mha/yr at the end of the century. Land carbon gain is weakened by 17% over the 20th century, mainly due to increased human deforestation fires and associated escape fires (i.e., degradation fires) in the tropical humid forests, even though the decrease in burned area in many other regions due to human fire suppression acts to increase land carbon gain. The direct human effect on fire weakens the upward trend in global runoff throughout the century by 6% and enhances the upward trend in global evapotranspiration since 1945 by 7%. In addition, the above impacts in densely populated, highly developed (if population density > 0.1 person/km2), or moderately populated and developed regions are of opposite sign to those in other regions. Our study suggests that particular attention should be paid to human deforestation and degradation fires in the tropical humid forests when reconstructing and projecting fire carbon emissions and net atmosphere-land carbon exchange and estimating resultant impacts of direct human effect on fire.

  4. Therapeutic options for diseases due to potential viral agents of bioterrorism.

    PubMed

    Bronze, Michael S; Greenfield, Ronald A

    2003-02-01

    The etiologic agents of smallpox and viral hemorrhagic fever have emerged as potential agents of bioterrorism due to their virulence, potential for human to human dissemination and limited strategies for treatment and prevention. Cidofovir has shown significant promise in animal models, and limited case reports in humans are encouraging. Ribavirin is the treatment of choice for certain hemorrhagic fever viral infections, but has no current application to Ebola and Marburg infections. Current vaccine strategies for smallpox are effective, but carry significant risk for complications. Licensed vaccines for hemorrhagic fever viruses are limited to yellow fever, but animal studies are promising. Genomic analysis of the viral pathogen and the animal model response to infection may provide valuable information enabling the development of novel treatment and prevention strategies. Current knowledge of these strategies is reviewed.

  5. Progression of Mortality due to Diseases of the Circulatory System and Human Development Index in Rio de Janeiro Municipalities

    PubMed Central

    Soares, Gabriel Porto; Klein, Carlos Henrique; Silva, Nelson Albuquerque de Souza e; de Oliveira, Glaucia Maria Moraes

    2016-01-01

    Background Diseases of the circulatory system (DCS) are the major cause of death in Brazil and worldwide. Objective To correlate the compensated and adjusted mortality rates due to DCS in the Rio de Janeiro State municipalities between 1979 and 2010 with the Human Development Index (HDI) from 1970 onwards. Methods Population and death data were obtained in DATASUS/MS database. Mortality rates due to ischemic heart diseases (IHD), cerebrovascular diseases (CBVD) and DCS adjusted by using the direct method and compensated for ill-defined causes. The HDI data were obtained at the Brazilian Institute of Applied Research in Economics. The mortality rates and HDI values were correlated by estimating Pearson linear coefficients. The correlation coefficients between the mortality rates of census years 1991, 2000 and 2010 and HDI data of census years 1970, 1980 and 1991 were calculated with discrepancy of two demographic censuses. The linear regression coefficients were estimated with disease as the dependent variable and HDI as the independent variable. Results In recent decades, there was a reduction in mortality due to DCS in all Rio de Janeiro State municipalities, mainly because of the decline in mortality due to CBVD, which was preceded by an elevation in HDI. There was a strong correlation between the socioeconomic indicator and mortality rates. Conclusion The HDI progression showed a strong correlation with the decline in mortality due to DCS, signaling to the relevance of improvements in life conditions. PMID:27849263

  6. Progression of Mortality due to Diseases of the Circulatory System and Human Development Index in Rio de Janeiro Municipalities.

    PubMed

    Soares, Gabriel Porto; Klein, Carlos Henrique; Silva, Nelson Albuquerque de Souza E; Oliveira, Glaucia Maria Moraes de

    2016-10-01

    Diseases of the circulatory system (DCS) are the major cause of death in Brazil and worldwide. To correlate the compensated and adjusted mortality rates due to DCS in the Rio de Janeiro State municipalities between 1979 and 2010 with the Human Development Index (HDI) from 1970 onwards. Population and death data were obtained in DATASUS/MS database. Mortality rates due to ischemic heart diseases (IHD), cerebrovascular diseases (CBVD) and DCS adjusted by using the direct method and compensated for ill-defined causes. The HDI data were obtained at the Brazilian Institute of Applied Research in Economics. The mortality rates and HDI values were correlated by estimating Pearson linear coefficients. The correlation coefficients between the mortality rates of census years 1991, 2000 and 2010 and HDI data of census years 1970, 1980 and 1991 were calculated with discrepancy of two demographic censuses. The linear regression coefficients were estimated with disease as the dependent variable and HDI as the independent variable. In recent decades, there was a reduction in mortality due to DCS in all Rio de Janeiro State municipalities, mainly because of the decline in mortality due to CBVD, which was preceded by an elevation in HDI. There was a strong correlation between the socioeconomic indicator and mortality rates. The HDI progression showed a strong correlation with the decline in mortality due to DCS, signaling to the relevance of improvements in life conditions.

  7. Global alert to avian influenza virus infection: From H5N1 to H7N9

    PubMed Central

    Poovorawan, Yong; Pyungporn, Sunchai; Prachayangprecha, Slinporn; Makkoch, Jarika

    2013-01-01

    Outbreak of a novel influenza virus is usually triggered by mutational change due to the process known as ‘antigenic shift’ or re-assortment process that allows animal-to-human or avian-to-human transmission. Birds are a natural reservoir for the influenza virus, and subtypes H5, H7, and H9 have all caused outbreaks of avian influenza in human populations. An especially notorious strain is the HPAI influenza virus H5N1, which has a mortality rate of approximately 60% and which has resulted in numerous hospitalizations, deaths, and significant economic loss. In March 2013, in Eastern China, there was an outbreak of the novel H7N9 influenza virus, which although less pathogenic in avian species, resulted in 131 confirmed cases and 36 deaths in humans over a two-month span. The rapid outbreak of this virus caused global concern but resulted in international cooperation to control the outbreak. Furthermore, cooperation led to valuable research-sharing including genome sequencing of the virus, the development of rapid and specific diagnosis, specimen sharing for future studies, and vaccine development. Although a H7N9 pandemic in the human population is possible due to its rapid transmissibility and extensive surveillance, the closure of the live-bird market will help mitigate the possibility of another H7N9 outbreak. In addition, further research into the source of the outbreak, pathogenicity of the virus, and the development of specific and sensitive detection assays will be essential for controlling and preparing for future H7N9 outbreaks. PMID:23916331

  8. 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

  9. 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

  10. 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

  11. 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.

  12. Holistic Design for Total Product Well Being

    NASA Technical Reports Server (NTRS)

    Adams, Chris W.; Hamilton, George S.

    2004-01-01

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

  13. Noninvasive oxygen partial pressure measurement of human body fluids in vivo using magnetic resonance imaging.

    PubMed

    Zaharchuk, Greg; Busse, Reed F; Rosenthal, Guy; Manley, Geoffery T; Glenn, Orit A; Dillon, William P

    2006-08-01

    The oxygen partial pressure (pO2) of human body fluids reflects the oxygenation status of surrounding tissues. All existing fluid pO2 measurements are invasive, requiring either microelectrode/optode placement or fluid removal. The purpose of this study is to develop a noninvasive magnetic resonance imaging method to measure the pO2 of human body fluids. We developed an imaging paradigm that exploits the paramagnetism of molecular oxygen to create quantitative images of fluid oxygenation. A single-shot fast spin echo pulse sequence was modified to minimize artifacts from motion, fluid flow, and partial volume. Longitudinal relaxation rate (R1 = 1/T1) was measured with a time-efficient nonequilibrium saturation recovery method and correlated with pO2 measured in phantoms. pO2 images of human and fetal cerebrospinal fluid, bladder urine, and vitreous humor are presented and quantitative oxygenation levels are compared with prior literature estimates, where available. Significant pO2 increases are shown in cerebrospinal fluid and vitreous following 100% oxygen inhalation. Potential errors due to temperature, fluid flow, and partial volume are discussed. Noninvasive measurements of human body fluid pO2 in vivo are presented, which yield reasonable values based on prior literature estimates. This rapid imaging-based measurement of fluid oxygenation may provide insight into normal physiology as well as changes due to disease or during treatment.

  14. Pervasive polymorphic imprinted methylation in the human placenta

    PubMed Central

    Hanna, Courtney W.; Peñaherrera, Maria S.; Saadeh, Heba; Andrews, Simon; McFadden, Deborah E.; Kelsey, Gavin; Robinson, Wendy P.

    2016-01-01

    The maternal and paternal copies of the genome are both required for mammalian development, and this is primarily due to imprinted genes, those that are monoallelically expressed based on parent-of-origin. Typically, this pattern of expression is regulated by differentially methylated regions (DMRs) that are established in the germline and maintained after fertilization. There are a large number of germline DMRs that have not yet been associated with imprinting, and their function in development is unknown. In this study, we developed a genome-wide approach to identify novel imprinted DMRs in the human placenta and investigated the dynamics of these imprinted DMRs during development in somatic and extraembryonic tissues. DNA methylation was evaluated using the Illumina HumanMethylation450 array in 134 human tissue samples, publicly available reduced representation bisulfite sequencing in the human embryo and germ cells, and targeted bisulfite sequencing in term placentas. Forty-three known and 101 novel imprinted DMRs were identified in the human placenta by comparing methylation between diandric and digynic triploid conceptions in addition to female and male gametes. Seventy-two novel DMRs showed a pattern consistent with placental-specific imprinting, and this monoallelic methylation was entirely maternal in origin. Strikingly, these DMRs exhibited polymorphic imprinted methylation between placental samples. These data suggest that imprinting in human development is far more extensive and dynamic than previously reported and that the placenta preferentially maintains maternal germline-derived DNA methylation. PMID:26769960

  15. 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.

  16. Development of Osseointegrated Implants for Soldier Amputees Following Orthopaedic Extremity Trauma

    DTIC Science & Technology

    2008-08-01

    specimens, histology and mechanical testing of implants. The second focus of Year 2 was human morphometric studies on variations due to ethnicity, gender...custom implants in above-knee patients with amputations would require expensive custom type implants, a morphometric study was conducted on human...male and female cadaveric femurs. Morphometric variations of the periosteal surface of long bones have been identified with changing age, gender and

  17. Modeling human-machine interactions for operations room layouts

    NASA Astrophysics Data System (ADS)

    Hendy, Keith C.; Edwards, Jack L.; Beevis, David

    2000-11-01

    The LOCATE layout analysis tool was used to analyze three preliminary configurations for the Integrated Command Environment (ICE) of a future USN platform. LOCATE develops a cost function reflecting the quality of all human-human and human-machine communications within a workspace. This proof- of-concept study showed little difference between the efficacy of the preliminary designs selected for comparison. This was thought to be due to the limitations of the study, which included the assumption of similar size for each layout and a lack of accurate measurement data for various objects in the designs, due largely to their notional nature. Based on these results, the USN offered an opportunity to conduct a LOCATE analysis using more appropriate assumptions. A standard crew was assumed, and subject matter experts agreed on the communications patterns for the analysis. Eight layouts were evaluated with the concepts of coordination and command factored into the analysis. Clear differences between the layouts emerged. The most promising design was refined further by the USN, and a working mock-up built for human-in-the-loop evaluation. LOCATE was applied to this configuration for comparison with the earlier analyses.

  18. Human activity and damaging landslides and floods on Madeira Island

    NASA Astrophysics Data System (ADS)

    Baioni, D.

    2011-11-01

    Over the last few decades, the island of Madeira has become an important offshore tourism and business center, with rapid economic and demographic development that has caused changes to the landscape due to human activity. In Madeira's recent history, there has been an increase over time in the frequency of occurrence of damaging landslide and flood events. As a result, the costs of restoration work due to damage caused by landslide and flood events have become a larger and larger component of Madeira's annual budget. Landslides and floods in Madeira deserve particular attention because they represent the most serious hazard to human life, to property, and to the natural environment and its important heritage value. The work reported on in this paper involved the analysis of historical data regarding damaging landslide and flood events on Madeira (in particular from 1941 to 1991) together with data on geological characteristics, topographic features, and climate, and from field observations. This analysis showed that the main factor triggering the occurrence of damaging landslide and flood events is rainfall, but that the increase in the number of damaging events recorded on Madeira Island, especially in recent times, seems to be related mostly to human activity, specifically to economic development and population growth, rather than to natural factors.

  19. Magnetic factor in solar-terrestrial relations and its impact on the human body: physical problems and prospects for research

    NASA Astrophysics Data System (ADS)

    Breus, T. K.; Binhi, V. N.; Petrukovich, A. A.

    2016-05-01

    The body of current heliobiological evidence suggests that very weak variable magnetic fields due to solar- and geomagnetic-activities do have a biological effect. Geomagnetic disturbances can cause a nonspecific reaction in the human body - a kind of general adaptation syndrome which occurs due to any external stress factor. Also, specific reactions can develop. One of the reasons discussed for the similarity between biological and heliogeophysical rhythms is that geomagnetic variations have a direct influence on organisms, although exact magnetoreception mechanisms are not yet clear. The paper briefly reviews the current state of empirical and theoretical work on this fundamental multidisciplinary problem.

  20. 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.

  1. Function of FEZF1 during early neural differentiation of human embryonic stem cells.

    PubMed

    Liu, Xin; Su, Pei; Lu, Lisha; Feng, Zicen; Wang, Hongtao; Zhou, Jiaxi

    2018-01-01

    The understanding of the mechanism underlying human neural development has been hampered due to lack of a cellular system and complicated ethical issues. Human embryonic stem cells (hESCs) provide an invaluable model for dissecting human development because of unlimited self-renewal and the capacity to differentiate into nearly all cell types in the human body. In this study, using a chemical defined neural induction protocol and molecular profiling, we identified Fez family zinc finger 1 (FEZF1) as a potential regulator of early human neural development. FEZF1 is rapidly up-regulated during neural differentiation in hESCs and expressed before PAX6, a well-established marker of early human neural induction. We generated FEZF1-knockout H1 hESC lines using CRISPR-CAS9 technology and found that depletion of FEZF1 abrogates neural differentiation of hESCs. Moreover, loss of FEZF1 impairs the pluripotency exit of hESCs during neural specification, which partially explains the neural induction defect caused by FEZF1 deletion. However, enforced expression of FEZF1 itself fails to drive neural differentiation in hESCs, suggesting that FEZF1 is necessary but not sufficient for neural differentiation from hESCs. Taken together, our findings identify one of the earliest regulators expressed upon neural induction and provide insight into early neural development in human.

  2. A decision framework to enhance sustainable groundwater management

    USDA-ARS?s Scientific Manuscript database

    Groundwater aquifers, which supply water for billions of the world’s inhabitants, are under stress due to increasing human population, water demand for economic development, and environmental constraints. Projected climate change increases uncertainty regarding sustainability of groundwater systems...

  3. Multi-component biocide protects wood from fungi and insects in UC2 applications

    Treesearch

    Carol A. Clausen; Vina W. Yang

    2007-01-01

    Development of synergistic biocides to protect wood in interior applications has been of particular interest since the recent increase of indoor mold infestations. Many products have been developed to address the recent influx of indoor mold infestations. Researchers must emphasize the use of environmentally benign chemicals due to the need for safety of human...

  4. 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

  5. Total body nitrogen analysis. [neutron activation analysis

    NASA Technical Reports Server (NTRS)

    Palmer, H. E.

    1975-01-01

    Studies of two potential in vivo neutron activation methods for determining total and partial body nitrogen in animals and humans are described. A method using the CO-11 in the expired air as a measure of nitrogen content was found to be adequate for small animals such as rats, but inadequate for human measurements due to a slow excretion rate. Studies on the method of measuring the induced N-13 in the body show that with further development, this method should be adequate for measuring muscle mass changes occurring in animals or humans during space flight.

  6. Radiation Analysis for the Human Lunar Return Mission

    NASA Technical Reports Server (NTRS)

    Wilson, J. W.; Simonsen, L. C.; Shinn, J. L.; Kim, M.; Dubey, R. R.; Jordan, W.

    1997-01-01

    An analysis of the radiation hazards that are anticipated on an early Human Lunar Return (HLR) mission in support of NASA deep space exploration activities is presented. The HLR mission study emphasized a low cost lunar return to expand human capabilities in exploration, to answer fundamental science questions, and to seek opportunities for commercial development. As such, the radiation issues are cost related because the parasitic shield mass is expensive due to high launch costs. The present analysis examines the shield requirements and their impact on shield design.

  7. AACP Special Taskforce White Paper on Diversifying Our Investment in Human Capital

    PubMed Central

    White, Carla; Conway, Jeannine M.; Davis, Paula K.; Johnson-Fannin, Arcelia M.; Jurkas, Jeffrey G.; Murphy, Nanci L.; Smith, W. Thomas; Echeverri, Margarita; Youmans, Sharon L.; Owings, Katie C.; Adams, Jennifer L.

    2017-01-01

    EXECUTIVE SUMMARY The 2015-2017 American Association of Colleges of Pharmacy (AACP) Special Taskforce on Diversifying our Investment in Human Capital was appointed for a two-year term, due to the rigors and complexities of its charges. This report serves as a white paper for academic pharmacy on diversifying our investment in human capital. The Taskforce developed and recommended a representation statement that was adapted and adopted by the AACP House of Delegates at the 2016 AACP Annual Meeting. In addition, the Taskforce developed a diversity statement for the Association that was adopted by the AACP Board of Directors in 2017. The Taskforce also provides recommendations to AACP and to academic pharmacy in this white paper. PMID:29200461

  8. Nuclear Fragmentation Processes Relevant for Human Space Radiation Protection

    NASA Technical Reports Server (NTRS)

    Lin, Zi-Wei

    2007-01-01

    Space radiation from cosmic ray particles is one of the main challenges for human space explorations such-as a moon base or a trip to Mars. Models have been developed in order to predict the radiation exposure to astronauts and to evaluate the effectiveness of different shielding materials, and a key ingredient in these models is the physics of nuclear fragmentations. We have developed a semi-analytical method to determine which partial cross sections of nuclear fragmentations most affect the radiation dose behind shielding materials due to exposure to galactic cosmic rays. The cross sections thus determined will require more theoretical and/or experimental studies in order for us to better predict, reduce and mitigate the radiation exposure in human space explorations.

  9. Genetic Thinking in the Study of Social Relationships: Five Points of Entry.

    PubMed

    Reiss, David

    2010-09-01

    For nearly a generation, researchers studying human behavioral development have combined genetically informed research designs with careful measures of social relationships such as parenting, sibling relationships, peer relationships, marital processes, social class stratifications, and patterns of social engagement in the elderly. In what way have these genetically informed studies altered the construction and testing of social theories of human development? We consider five points of entry where genetic thinking is taking hold. First, genetic findings suggest an alternative scenario for explaining social data. Associations between measures of the social environment and human development may be due to genes that influence both. Second, genetic studies add to other prompts to study the early developmental origins of current social phenomena in midlife and beyond. Third, genetic analyses promise to shed light on understudied social systems, such as sibling relationships, that have an impact on human development independent of genotype. Fourth, genetic analyses anchor in neurobiology individual differences in resilience and sensitivity to both adverse and favorable social environments. Finally, genetic analyses increase the utility of laboratory simulations of human social processes and of animal models. © The Author(s) 2010.

  10. Simple deterministic models and applications. Comment on "Coupled disease-behavior dynamics on complex networks: A review" by Z. Wang et al.

    NASA Astrophysics Data System (ADS)

    Yang, Hyun Mo

    2015-12-01

    Currently, discrete modellings are largely accepted due to the access to computers with huge storage capacity and high performance processors and easy implementation of algorithms, allowing to develop and simulate increasingly sophisticated models. Wang et al. [7] present a review of dynamics in complex networks, focusing on the interaction between disease dynamics and human behavioral and social dynamics. By doing an extensive review regarding to the human behavior responding to disease dynamics, the authors briefly describe the complex dynamics found in the literature: well-mixed populations networks, where spatial structure can be neglected, and other networks considering heterogeneity on spatially distributed populations. As controlling mechanisms are implemented, such as social distancing due 'social contagion', quarantine, non-pharmaceutical interventions and vaccination, adaptive behavior can occur in human population, which can be easily taken into account in the dynamics formulated by networked populations.

  11. Organoid Models of Human and Mouse Ductal Pancreatic Cancer

    PubMed Central

    Boj, Sylvia F.; Hwang, Chang-Il; Baker, Lindsey A.; Chio, Iok In Christine; Engle, Dannielle D.; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Hervé; Spector, Mona S.; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H.; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D.; Wilson, John P.; Feigin, Michael E.; Öhlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M.; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N.; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H.M.; Molenaar, I. Quintus; Borel Rinkes, Inne H.; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J.; Iacobuzio-Donahue, Christine; Leach, Steven D.; Pappin, Darryl J.; Hammell, Molly; Klimstra, David S.; Basturk, Olca; Hruban, Ralph H.; Offerhaus, George Johan; Vries, Robert G.J.; Clevers, Hans; Tuveson, David A.

    2015-01-01

    SUMMARY Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation and exhibit ductal- and disease stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy. PMID:25557080

  12. Environment Challenges for Exploration of the Moon

    NASA Technical Reports Server (NTRS)

    Minow, Joseph I.; Blackwell, William C., Jr.; Coffey, Victoria N.; Cooke, William B.; Howard, James W.; Parker, Linda N.; Sharp, John; Schunck, Greg; Suggs. Robert W.; Wang, Joseph W.

    2008-01-01

    NASA's Constellation Program is designing a new generation of human rated launch and space transportation vehicles to first replace the Space Shuttle fleet, then support develop of a permanent human habitat on the Moon, and ultimately prepare for human exploration of Mars. The ambitious first step beyond low Earth orbit is to develop the infrastructure required for conducting missions to a variety of locations on the lunar surface for periods of a week and establishment of a permanent settlement at one of the lunar poles where crews will serve for periods on the order of approx.200 days. We present an overview of the most challenging aspects of the lunar environment that will need to be addressed when developing transport and habitat infrastructure for long term human presence on the Moon including low temperatures and dusty regolith surfaces, radiation environments due to galactic cosmic rays and solar energetic particles, charging of lunar infrastructure when exposed to lunar plasma environments, and secondary meteor environments generated by primary impacts on the lunar surface.

  13. Modeling Human Steering Behavior During Path Following in Teleoperation of Unmanned Ground Vehicles.

    PubMed

    Mirinejad, Hossein; Jayakumar, Paramsothy; Ersal, Tulga

    2018-04-01

    This paper presents a behavioral model representing the human steering performance in teleoperated unmanned ground vehicles (UGVs). Human steering performance in teleoperation is considerably different from the performance in regular onboard driving situations due to significant communication delays in teleoperation systems and limited information human teleoperators receive from the vehicle sensory system. Mathematical models capturing the teleoperation performance are a key to making the development and evaluation of teleoperated UGV technologies fully simulation based and thus more rapid and cost-effective. However, driver models developed for the typical onboard driving case do not readily address this need. To fill the gap, this paper adopts a cognitive model that was originally developed for a typical highway driving scenario and develops a tuning strategy that adjusts the model parameters in the absence of human data to reflect the effect of various latencies and UGV speeds on driver performance in a teleoperated path-following task. Based on data collected from a human subject test study, it is shown that the tuned model can predict both the trend of changes in driver performance for different driving conditions and the best steering performance of human subjects in all driving conditions considered. The proposed model with the tuning strategy has a satisfactory performance in predicting human steering behavior in the task of teleoperated path following of UGVs. The established model is a suited candidate to be used in place of human drivers for simulation-based studies of UGV mobility in teleoperation systems.

  14. DEVELOPMENT OF PROTOCOLS TO IDENTIFY CRITICAL ECOSYSTEMS

    EPA Science Inventory

    Healthy, functioning ecosystems are critical to the sustainability of human and natural communities, but the identification of areas of healthy ecosystems in an area as large as Region 5 is difficult due to time and information constraints. Geographic Information Systems (GIS) a...

  15. Environmental management as a pillar for sustainable development.

    PubMed

    Mikulčić, Hrvoje; Duić, Neven; Dewil, Raf

    2017-12-01

    There is a growing concern about how to minimize the impact of human activities on the environment. Already nowadays, in some places adaptation efforts are needed in order to avoid the irreversibility of negative human activities. Due to climate changes, and corresponding environmental and social changes, there is a great need for a more sustainable development of mankind. Over the years, research studies that analyzed the sustainable development of different communities with a multi-disciplinary approach, stressed the necessity of preserving the environment for next generations. Therefore, responsible and conscientious management of the environment is a pillar of the sustainable development concept. This review introduction article provides an overview of the recent top scientific publications related to sustainable development that mostly originated from previous SDEWES conferences. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Human health risk assessment due to global warming--a case study of the Gulf countries.

    PubMed

    Husain, Tahir; Chaudhary, Junaid Rafi

    2008-12-01

    Accelerated global warming is predicted by the Intergovernmental Panel on Climatic Change (IPCC) due to increasing anthropogenic greenhouse gas emissions. The climate changes are anticipated to have a long-term impact on human health, marine and terrestrial ecosystems, water resources and vegetation. Due to rising sea levels, low lying coastal regions will be flooded, farmlands will be threatened and scarcity of fresh water resources will be aggravated. This will in turn cause increased human suffering in different parts of the world. Spread of disease vectors will contribute towards high mortality, along with the heat related deaths. Arid and hot climatic regions will face devastating effects risking survival of the fragile plant species, wild animals, and other desert ecosystems. The paper presents future changes in temperature, precipitation and humidity and their direct and indirect potential impacts on human health in the coastal regions of the Gulf countries including Yemen, Oman, United Arab Emirates, Qatar, and Bahrain. The analysis is based on the long-term changes in the values of temperature, precipitation and humidity as predicted by the global climatic simulation models under different scenarios of GHG emission levels. Monthly data on temperature, precipitation, and humidity were retrieved from IPCC databases for longitude 41.25 degrees E to 61.875 degrees E and latitude 9.278 degrees N to 27.833 degrees N. Using an average of 1970 to 2000 values as baseline, the changes in the humidity, temperature and precipitation were predicted for the period 2020 to 2050 and 2070 to 2099. Based on epidemiological studies on various diseases associated with the change in temperature, humidity and precipitation in arid and hot regions, empirical models were developed to assess human health risk in the Gulf region to predict elevated levels of diseases and mortality rates under different emission scenarios as developed by the IPCC.The preliminary assessment indicates increased mortality rates due to cardiovascular and respiratory illnesses, thermal stress, and increased frequency of infectious vector borne diseases in the region between 2070 and 2099.

  17. Hormone Replacement Therapy, Iron, and Breast Cancer

    DTIC Science & Technology

    2004-11-01

    accumulates due to the mutation of the HFE gene (hemochromatosis EeJ, iron elevated in the mouse body mimics the post-menopausal condition. In the present...model. Since iron slowly accumulates due to the mutation of the HFE gene (hemochromatosis Fe), iron elevated in the mouse body mimics the post...menopausal condition. Development of iron overloaded transgenic mice: The murine HFE gene is structurally similar to the human gene . Four different HFE gene

  18. Spatial sexual dimorphism of X and Y homolog gene expression in the human central nervous system during early male development.

    PubMed

    Johansson, Martin M; Lundin, Elin; Qian, Xiaoyan; Mirzazadeh, Mohammadreza; Halvardson, Jonatan; Darj, Elisabeth; Feuk, Lars; Nilsson, Mats; Jazin, Elena

    2016-01-01

    Renewed attention has been directed to the functions of the Y chromosome in the central nervous system during early human male development, due to the recent proposed involvement in neurodevelopmental diseases. PCDH11Y and NLGN4Y are of special interest because they belong to gene families involved in cell fate determination and formation of dendrites and axon. We used RNA sequencing, immunocytochemistry and a padlock probing and rolling circle amplification strategy, to distinguish the expression of X and Y homologs in situ in the human brain for the first time. To minimize influence of androgens on the sex differences in the brain, we focused our investigation to human embryos at 8-11 weeks post-gestation. We found that the X- and Y-encoded genes are expressed in specific and heterogeneous cellular sub-populations of both glial and neuronal origins. More importantly, we found differential distribution patterns of X and Y homologs in the male developing central nervous system. This study has visualized the spatial distribution of PCDH11X/Y and NLGN4X/Y in human developing nervous tissue. The observed spatial distribution patterns suggest the existence of an additional layer of complexity in the development of the male CNS.

  19. Insights into female germ cell biology: from in vivo development to in vitro derivations.

    PubMed

    Jung, Dajung; Kee, Kehkooi

    2015-01-01

    Understanding the mechanisms of human germ cell biology is important for developing infertility treatments. However, little is known about the mechanisms that regulate human gametogenesis due to the difficulties in collecting samples, especially germ cells during fetal development. In contrast to the mitotic arrest of spermatogonia stem cells in the fetal testis, female germ cells proceed into meiosis and began folliculogenesis in fetal ovaries. Regulations of these developmental events, including the initiation of meiosis and the endowment of primordial follicles, remain an enigma. Studying the molecular mechanisms of female germ cell biology in the human ovary has been mostly limited to spatiotemporal characterizations of genes or proteins. Recent efforts in utilizing in vitro differentiation system of stem cells to derive germ cells have allowed researchers to begin studying molecular mechanisms during human germ cell development. Meanwhile, the possibility of isolating female germline stem cells in adult ovaries also excites researchers and generates many debates. This review will mainly focus on presenting and discussing recent in vivo and in vitro studies on female germ cell biology in human. The topics will highlight the progress made in understanding the three main stages of germ cell developments: namely, primordial germ cell formation, meiotic initiation, and folliculogenesis.

  20. A review of the design and development processes of simulation for training in healthcare - A technology-centered versus a human-centered perspective.

    PubMed

    Persson, Johanna

    2017-01-01

    This article reviews literature about simulation systems for training in healthcare regarding the prevalence of human-centered approaches in the design and development of these systems, motivated by a tradition in this field of working technology-centered. The results show that the focus on human needs and context of use is limited. It is argued that a reduction of the focus on technical advancements in favor of the needs of the users and the healthcare community, underpinned by human factors and ergonomics theory, is favorable. Due to the low number of identified articles describing or discussing human-centered approaches it is furthermore concluded that the publication culture promotes technical descriptions and summative evaluations rather than descriptions and reflections regarding the design and development processes. Shifting the focus from a technology-centered approach to a human-centered one can aid in the process of creating simulation systems for training in healthcare that are: 1) relevant to the learning objectives, 2) adapted to the needs of users, context and task, and 3) not selected based on technical or fidelity criteria. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Changes in river water temperature between 1980 and 2012 in Yongan watershed, eastern China: Magnitude, drivers and models

    NASA Astrophysics Data System (ADS)

    Chen, Dingjiang; Hu, Minpeng; Guo, Yi; Dahlgren, Randy A.

    2016-02-01

    Climate warming is expected to have major impacts on river water quality, water column/hyporheic zone biogeochemistry and aquatic ecosystems. A quantitative understanding of spatio-temporal air (Ta) and water (Tw) temperature dynamics is required to guide river management and to facilitate adaptations to climate change. This study determined the magnitude, drivers and models for increasing Tw in three river segments of the Yongan watershed in eastern China. Over the 1980-2012 period, Tw in the watershed increased by 0.029-0.046 °C yr-1 due to a ∼0.050 °C yr-1 increase of Ta and changes in local human activities (e.g., increasing developed land and population density and decreasing forest area). A standardized multiple regression model was developed for predicting annual Tw (R2 = 0.88-0.91) and identifying/partitioning the impact of the principal drivers on increasing Tw:Ta (76 ± 1%), local human activities (14 ± 2%), and water discharge (10 ± 1%). After normalizing water discharge, climate warming and local human activities were estimated to contribute 81-95% and 5-19% of the observed rising Tw, respectively. Models forecast a 0.32-1.76 °C increase in Tw by 2050 compared with the 2000-2012 baseline condition based on four future scenarios. Heterogeneity of warming rates existed across seasons and river segments, with the lower flow river and dry season demonstrating a more pronounced response to climate warming and human activities. Rising Tw due to changes in climate, local human activities and hydrology has a considerable potential to aggravate river water quality degradation and coastal water eutrophication in summer. Thus it should be carefully considered in developing watershed management strategies in response to climate change.

  2. Population growth and consumption.

    PubMed

    Chalkley, K

    1997-04-01

    The relationship between population growth, resource consumption, and environmental degradation is complex. The rise in "greenhouse gases" that will cause climatic change is clearly due to human activity, and pollutants are often concentrated in densely populated areas. However, even an area with a negative population growth, such as Russia, can experience severe environmental degradation due to poor management. Consumption patterns have the most effect on ozone depletion, while population growth threatens biodiversity of and within species through the destruction of ecosystems. Migration joins population growth and social factors, such as land inequality, as major causes of deforestation, and global demand for water is expected to increase faster than the rate of population growth. Coastal development and over-fishing threaten to deplete the oceans, while soil quality is threatened by inappropriate land use. Estimates of the earth's carrying capacity range from less than 3 billion to more than 44 billion people, indicating how difficult it is to assess this figure. Development efforts throughout the world may lead to human gains that will ultimately be negated by environmental losses. These factors have led to growing support for environmentally sustainable development.

  3. Human impacts on 20th century fire dynamics and implications for global carbon and water trajectories

    NASA Astrophysics Data System (ADS)

    Li, F.; Lawrence, D. M.; Bond-Lamberty, B. P.

    2017-12-01

    Fire is a fundamental Earth system process and the primary ecosystem disturbance on the global scale. It affects carbon and water cycles through its impact on terrestrial ecosystems, and at the same time, is regulated by weather and climate, vegetation characteristics, and, importantly, human ignition and efforts to suppress fires (i.e., the direct human effect on fire). Here, we utilize the Community Land Model version 4.5 (CLM4.5) to generate a quantitative understanding of the impacts on fire dynamics and associated carbon and water cycling that can be attributed to changes in human ignition and suppression over the 20th century. We find that the net impact of increases in human ignition and suppression significantly reduce the 20th century averaged global burned area by 38 Mha/yr. The reduction increases since 1920, rising to 103 Mha/yr less burned area at the end of the century. Land carbon gain is weakened by 17% over the 20th century, mainly due to increased human deforestation fires and associated escape fires (i.e., degradation fires) in the tropical humid forests, even though the decrease in burned area in many other regions due to human fire suppression acts to increase land carbon gain. The direct human effect on fire also weakens the 20th century upward trend of global runoff by 6%, and enhances the upward trend in global evaportranspiration since 1945 by 7%. In addition, the above impacts in densely populated, highly developed (if population density > 0.1 person/km2), or moderately populated and developed regions are of opposite sign to those in other regions. Our study suggests that particular attention should be paid to human deforestation and degradation fires in the tropical humid forests when reconstructing and projecting fire carbon emissions and net atmosphere-land carbon exchange and estimating resultant impacts of direct human effect on fire.

  4. Vaccines for Canine Leishmaniasis

    PubMed Central

    Palatnik-de-Sousa, Clarisa B.

    2012-01-01

    Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL) is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global warming, coinfection with immunosuppressive diseases, and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL) in the Americas, the Middle East, Central Asia, China, and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases, and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost–effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine VL. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans and dogs against VL. PMID:22566950

  5. The current status and future directions of myxoma virus, a master in immune evasion.

    PubMed

    Spiesschaert, Bart; McFadden, Grant; Hermans, Katleen; Nauwynck, Hans; Van de Walle, Gerlinde R

    2011-06-09

    Myxoma virus (MYXV) gained importance throughout the twentieth century because of the use of the highly virulent Standard Laboratory Strain (SLS) by the Australian government in the attempt to control the feral Australian population of Oryctolagus cuniculus (European rabbit) and the subsequent illegal release of MYXV in Europe. In the European rabbit, MYXV causes a disease with an exceedingly high mortality rate, named myxomatosis, which is passively transmitted by biting arthropod vectors. MYXV still has a great impact on European rabbit populations around the world. In contrast, only a single cutaneous lesion, restricted to the point of inoculation, is seen in its natural long-term host, the South-American Sylvilagus brasiliensis and the North-American S. Bachmani. Apart from being detrimental for European rabbits, however, MYXV has also become of interest in human medicine in the last two decades for two reasons. Firstly, due to the strong immune suppressing effects of certain MYXV proteins, several secreted virus-encoded immunomodulators (e.g. Serp-1) are being developed to treat systemic inflammatory syndromes such as cardiovascular disease in humans. Secondly, due to the inherent ability of MYXV to infect a broad spectrum of human cancer cells, the live virus is also being developed as an oncolytic virotherapeutic to treat human cancer. In this review, an update will be given on the current status of MYXV in rabbits as well as its potential in human medicine in the twenty-first century.

  6. Investment in Education as a Rural Development Strategy: Do Increased Inputs Have an Impact?

    ERIC Educational Resources Information Center

    McNamara, Kevin T.; Deaton, Brady J.

    Support for public education wavers in a number of states due to a lack of evidence indicating that increased funding is associated with increases in output. Maintaining and increasing this support, however, is critical for rural communities as they seek to strengthen their human capital base as a strategy for economic growth and development. The…

  7. Parents' Views of the Relevance of a Violence Prevention Program in High, Medium, and Low Human Development Contexts

    ERIC Educational Resources Information Center

    Durrant, Joan; Plateau, Dominique Pierre; Ateah, Christine A.; Holden, George W.; Barker, Leslie A.; Stewart-Tufescu, Ashley; Jones, Alysha D.; Ly, Gia; Ahmed, Rashid

    2017-01-01

    Every day, almost one billion children around the world experience violent punishment. Eliminating all violence against children is a key target of the United Nations' 2030 Agenda for Sustainable Development. This is a monumental challenge due to the diversity of cultural, economic and social contexts in which children live. Violence-prevention…

  8. Mapping impervious surface expansion using medium resolution satellite image time series: A case study in Yangtze river delta, China

    USDA-ARS?s Scientific Manuscript database

    Due to the rapid growth of population and economic development in the developing countries, more people are now living in the cities than in the rural areas in the world for the first time in human history. As a result, cities are sprawling rapidly into their surroundings. A characteristic change as...

  9. DEVELOPMENT OF PROTOCOLS TO STUDY TO IDENTIFY CRITICAL ECOSYSTEMS

    EPA Science Inventory

    Healthy, functioning ecosystems are critical to the sustainability of human and natural communities, but the identification of areas of healthy ecosystems in an area as large as Region 5 is difficult due to time and information constraints. Geographic Information Systems (GIS) a...

  10. Label-free detection of protein molecules secreted from an organ-on-a-chip model for drug toxicity assays

    NASA Astrophysics Data System (ADS)

    Morales, Andres W.; Zhang, Yu S.; Aleman, Julio; Alerasool, Parissa; Dokmeci, Mehmet R.; Khademhosseini, Ali; Ye, Jing Yong

    2016-03-01

    Clinical attrition is about 30% from failure of drug candidates due to toxic side effects, increasing the drug development costs significantly and slowing down the drug discovery process. This partly originates from the fact that the animal models do not accurately represent human physiology. Hence there is a clear unmet need for developing drug toxicity assays using human-based models that are complementary to traditional animal models before starting expensive clinical trials. Organ-on-a-chip techniques developed in recent years have generated a variety of human organ models mimicking different human physiological conditions. However, it is extremely challenging to monitor the transient and long-term response of the organ models to drug treatments during drug toxicity tests. First, when an organ-on-a-chip model interacts with drugs, a certain amount of protein molecules may be released into the medium due to certain drug effects, but the amount of the protein molecules is limited, since the organ tissue grown inside microfluidic bioreactors have minimum volume. Second, traditional fluorescence techniques cannot be utilized for real-time monitoring of the concentration of the protein molecules, because the protein molecules are continuously secreted from the tissue and it is practically impossible to achieve fluorescence labeling in the dynamically changing environment. Therefore, direct measurements of the secreted protein molecules with a label-free approach is strongly desired for organs-on-a-chip applications. In this paper, we report the development of a photonic crystal-based biosensor for label-free assays of secreted protein molecules from a liver-on-a-chip model. Ultrahigh detection sensitivity and specificity have been demonstrated.

  11. Oral vaccination of fish: Lessons from humans and veterinary species.

    PubMed

    Embregts, Carmen W E; Forlenza, Maria

    2016-11-01

    The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen breakdown in the harsh gastric environment, but also to the high tolerogenic gut environment and to inadequate vaccine design. In this review we discuss current approaches used to develop oral vaccines for mass vaccination of farmed fish species. Furthermore, using various examples from the human and veterinary vaccine development, we propose additional approaches to fish vaccine design also considering recent advances in fish mucosal immunology and novel molecular tools. Finally, we discuss the pros and cons of using the zebrafish as a pre-screening animal model to potentially speed up vaccine design and testing for aquaculture fish species. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Poverty-led higher population growth in Bangladesh.

    PubMed

    Nakibullah, A; Rahman, A

    1996-01-01

    This article discusses the issue whether population growth is exogenous or endogenous in the economic development of Bangladesh. Overpopulation adversely affects food supplies, foreign exchange, and human resources. Moreover, it depresses savings per capita and retards growth of physical capital per labor. Underdeveloped countries, like Bangladesh, are faced with the problem of allocating resources between infrastructure, education, and health service that are essential for human capital development and population control measures. With this, determination whether fertility is exogenous or endogenous is important for policy purposes in the context of Bangladesh. Results showed that there is a correlation between population growth and real gross domestic products per capita. Based on Granger causality test, population growth is endogenous in the development process of Bangladesh and its overpopulation is due to poverty. Thus, there is a need for appropriate policy to take measures to improve human capital and decrease fertility rates.

  13. ART culture conditions change the probability of mouse embryo gestation through defined cellular and molecular responses.

    PubMed

    Schwarzer, Caroline; Esteves, Telma Cristina; Araúzo-Bravo, Marcos J; Le Gac, Séverine; Nordhoff, Verena; Schlatt, Stefan; Boiani, Michele

    2012-09-01

    Do different human ART culture protocols prepare embryos differently for post-implantation development? The type of ART culture protocol results in distinct cellular and molecular phenotypes in vitro at the blastocyst stage as well as subsequently during in vivo development. It has been reported that ART culture medium affects human development as measured by gestation rates and birthweights. However, due to individual variation across ART patients, it is not possible as yet to pinpoint a cause-effect relationship between choice of culture medium and developmental outcome. In a prospective study, 13 human ART culture protocols were compared two at a time against in vivo and in vitro controls. Superovulated mouse oocytes were fertilized in vivo using outbred and inbred mating schemes. Zygotes were cultured in medium or in the oviduct and scored for developmental parameters 96 h later. Blastocysts were either analyzed or transferred into fosters to measure implantation rates and fetal development. In total, 5735 fertilized mouse oocytes, 1732 blastocysts, 605 fetuses and 178 newborns were examined during the course of the study (December 2010-December 2011). Mice of the B6C3F1, C57Bl/6 and CD1 strains were used as oocyte donors, sperm donors and recipients for embryo transfer, respectively. In vivo fertilized B6C3F1 oocytes were allowed to cleave in 13 human ART culture protocols compared with mouse oviduct and optimized mouse medium (KSOM(aa)). Cell lineage composition of resultant blastocysts was analyzed by immunostaining and confocal microscopy (trophectoderm, Cdx2; primitive ectoderm, Nanog; primitive endoderm, Sox17), global gene expression by microarray analysis, and rates of development to midgestation and to term. Mouse zygotes show profound variation in blastocyst (49.9-91.9%) and fetal (15.7-62.0%) development rates across the 13 ART culture protocols tested (R(2)= 0.337). Two opposite protocols, human tubal fluid/multiblast (high fetal rate) and ISM1/ISM2 (low fetal rate), were analyzed in depth using outbred and inbred fertilization schemes. Resultant blastocysts show imbalances of cell lineage composition; culture medium-specific deviation of gene expression (38 genes, ≥ 4-fold) compared with the in vivo pattern; and produce different litter sizes (P ≤ 0.0076) after transfer into fosters. Confounding effects of subfertility, life style and genetic heterogeneity are reduced to a minimum in the mouse model compared with ART patients. This is an animal model study. Mouse embryo responses to human ART media are not transferable 1-to-1 to human development due to structural and physiologic differences between oocytes of the two species. Our data promote awareness that human ART culture media affect embryo development. Effects reported here in the mouse may apply also in human, because no ART medium presently available on the market has been optimized for human embryo development. The mouse embryo assay (MEA), which requires ART media to support at least 80% blastocyst formation, is in need of reform and should be extended to include post-implantation development.

  14. Employment of the Triple Helix concept for development of regenerative medicine applications based on human pluripotent stem cells

    PubMed Central

    2014-01-01

    Using human pluripotent stem cells as a source to generate differentiated progenies for regenerative medicine applications has attracted substantial interest during recent years. Having the capability to produce large quantities of human cells that can replace damaged tissue due to disease or injury opens novel avenues for relieving symptoms and also potentially offers cures for many severe human diseases. Although tremendous advancements have been made, there is still much research and development left before human pluripotent stem cell derived products can be made available for cell therapy applications. In order to speed up the development processes, we argue strongly in favor of cross-disciplinary collaborative efforts which have many advantages, especially in a relatively new field such as regenerative medicine based on human pluripotent stem cells. In this review, we aim to illustrate how some of the hurdles for bringing human pluripotent stem cell derivatives from bench-to-bed can be effectively addressed through the establishment of collaborative programs involving academic institutions, biotech industries, and pharmaceutical companies. By taking advantage of the strengths from each organization, innovation and productivity can be maximized from a resource perspective and thus, the chances of successfully bringing novel regenerative medicine treatment options to patients increase. PMID:24872863

  15. OCT-based label-free in vivo lymphangiography within human skin and areola

    NASA Astrophysics Data System (ADS)

    Baran, Utku; Qin, Wan; Qi, Xiaoli; Kalkan, Goknur; Wang, Ruikang K.

    2016-02-01

    Due to the limitations of current imaging techniques, visualization of lymphatic capillaries within tissue in vivo has been challenging. Here, we present a label-free high resolution optical coherence tomography (OCT) based lymphangiography (OLAG) within human skin in vivo. OLAG enables rapid (~seconds) mapping of lymphatic networks, along with blood vessel networks, over 8 mm x 8 mm of human skin and 5 mm x 5 mm of human areola. Moreover, lymphatic system’s response to inflammation within human skin is monitored throughout an acne lesion development over 7 days. The demonstrated results promise OLAG as a revolutionary tool in the clinical research and treatment of patients with pathologic conditions such as cancer, diabetes, and autoimmune diseases.

  16. A Culture-Behavior-Brain Loop Model of Human Development.

    PubMed

    Han, Shihui; Ma, Yina

    2015-11-01

    Increasing evidence suggests that cultural influences on brain activity are associated with multiple cognitive and affective processes. These findings prompt an integrative framework to account for dynamic interactions between culture, behavior, and the brain. We put forward a culture-behavior-brain (CBB) loop model of human development that proposes that culture shapes the brain by contextualizing behavior, and the brain fits and modifies culture via behavioral influences. Genes provide a fundamental basis for, and interact with, the CBB loop at both individual and population levels. The CBB loop model advances our understanding of the dynamic relationships between culture, behavior, and the brain, which are crucial for human phylogeny and ontogeny. Future brain changes due to cultural influences are discussed based on the CBB loop model. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. The cytogenetics of preimplantation human development: insights provided by traditional and novel techniques.

    PubMed

    Tempest, Helen G; Griffin, Darren K

    2005-09-01

    Our understanding of the incidence and origin of chromosome abnormalities in human preimplantation embryos is very limited due to the necessary ethical constraints involved in studying such material and the limited data ultimately produced. Several studies have addressed this issue, however, using techniques such as interphase fluorescence in situ hybridisation, modified G-banding preparation and the use of single-cell comparative genomic hybridisation (CGH). This review discusses the use of these techniques in assessing chromosome abnormalities in this, the earliest of human developmental stages. In addition, the prospects for the clinical use of CGH are discussed.

  18. Development and Evaluation of the Habitat Demonstration Unit Medical Operations Workstation and Opportunities for Future Research

    NASA Technical Reports Server (NTRS)

    Howard, Robert L., Jr.

    2012-01-01

    As NASA develops missions to leave Earth orbit and explore distant destinations (Mars, Moon, Asteroids) it is necessary to rethink human spaceflight paradigms in the life sciences. Standards developed for low earth orbit human spaceflight may not be fully applicable and in-space research may be required to develop new standards. Preventative and emergency medical care may require new capabilities never before used in space. Due to spacecraft volume limitations, this work area may also be shared with various animal and plant life science research. This paper explores the prototype Medical Operations Workstation within the NASA Habitat Demonstration Unit and discusses some of the lessons learned from field analogue missions involving the workstation. Keywords: Exploration, medical, health, crew, injury emergency, biology, animal, plant, science, preventative, emergency.

  19. 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

  20. Development of microcomputer-based mental acuity tests.

    PubMed

    Turnage, J J; Kennedy, R S; Smith, M G; Baltzley, D R; Lane, N E

    1992-10-01

    Recent disasters have focused attention on performance problems due to the use of alcohol and controlled substances in the workplace. Environmental stressors such as thermal extremes, mixed gases, noise, motion, and vibration also have adverse effects on human performance and operator efficiency. However, the lack of a standardized, sensitive, human performance assessment battery has probably delayed the systematic study of the deleterious effects of various toxic chemicals and drugs at home and in the workplace. The collective goal of the research reported here is the development of a menu of tests embedded in a coherent package of hardware and software that may be useful in repeated-measures studies of a broad range of agents that can degrade human performance. A menu of 40 tests from the Automated Performance Test System (APTS) is described, and the series of interlocking studies supporting its development is reviewed. The APTS tests, which run on several versions of laptop portables and desktop personal computers, have been shown to be stable, reliable, and factorially rich, and to have predictive validities with holistic measures of intelligence and simulator performances. In addition, sensitivity studies have been conducted in which performance changes due to stressors, agents, and treatments were demonstrated. We believe that tests like those described here have prospective use as an adjunct to urine testing for the screening for performance loss of individuals who are granted access to workplaces and stations that impact public safety.

  1. Development of microcomputer-based mental acuity tests

    NASA Technical Reports Server (NTRS)

    Turnage, J. J.; Kennedy, R. S.; Smith, M. G.; Baltzley, D. R.; Lane, N. E.

    1992-01-01

    Recent disasters have focused attention on performance problems due to the use of alcohol and controlled substances in the workplace. Environmental stressors such as thermal extremes, mixed gases, noise, motion, and vibration also have adverse effects on human performance and operator efficiency. However, the lack of a standardized, sensitive, human performance assessment battery has probably delayed the systematic study of the deleterious effects of various toxic chemicals and drugs at home and in the workplace. The collective goal of the research reported here is the development of a menu of tests embedded in a coherent package of hardware and software that may be useful in repeated-measures studies of a broad range of agents that can degrade human performance. A menu of 40 tests from the Automated Performance Test System (APTS) is described, and the series of interlocking studies supporting its development is reviewed. The APTS tests, which run on several versions of laptop portables and desktop personal computers, have been shown to be stable, reliable, and factorially rich, and to have predictive validities with holistic measures of intelligence and simulator performances. In addition, sensitivity studies have been conducted in which performance changes due to stressors, agents, and treatments were demonstrated. We believe that tests like those described here have prospective use as an adjunct to urine testing for the screening for performance loss of individuals who are granted access to workplaces and stations that impact public safety.

  2. 75 FR 5601 - Eunice Kennedy Shriver National Institute of Child Health & Human Development; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-03

    ... Mouse Models for Cytogenetic Disorders. Date: February 16, 2010. Time: 2 p.m. to 3 p.m. Agenda: To... to the meeting due to the timing limitations imposed by the review and funding cycle. (Catalogue of...

  3. High-fat diet and maternal obesity-associated epigenetic regulation of bone development

    USDA-ARS?s Scientific Manuscript database

    Due to the worldwide epidemic in obesity, maternal obesity has recently seen an explosion in investigations in both animal models and humans on its effects on offspring phenotype and pathologies including diabetes, hyperlipidemia, cardiovascular disease, and cancer. Epigenetic mechanisms presumably ...

  4. Mouse models to study the interaction of risk factors for human liver cancer.

    PubMed

    Sell, Stewart

    2003-11-15

    Each of the risk factors for human liver cancer (aflatoxin exposure, hepatitis B virus-associated liver injury, p53 loss, p53ser249 mutation, and male sex) also increases the incidence of hepatocellular carcinoma (HCC) in mouse models of hepatocarcinogenesis. Neonatal mice, partially hepatectomized adult mice, and p53-deficient mice each have a higher hepatocyte proliferation rate, are less able to detoxify AFB1, and form more DNA adducts than do normal wild-type controls. However, transgenic hepatitis B surface antigen mice, expressing hepatitis B surface antigen under control of the albumin promoter (alb/psx), are able to detoxify AFB1 at the same level as do wild-type mice. Thus, AFB1-induced HCC development in neonatal mice and p53+/- mice may be due to "immature" carcinogen metabolism, whereas increased HCC in transgenic hepatitis B virus mice may be due to promotion effects of increased proliferation. Future studies will explore the effects of modifying factors on the development of HCC.

  5. Human heart rate variability relation is unchanged during motion sickness

    NASA Technical Reports Server (NTRS)

    Mullen, T. J.; Berger, R. D.; Oman, C. M.; Cohen, R. J.

    1998-01-01

    In a study of 18 human subjects, we applied a new technique, estimation of the transfer function between instantaneous lung volume (ILV) and instantaneous heart rate (HR), to assess autonomic activity during motion sickness. Two control recordings of ILV and electrocardiogram (ECG) were made prior to the development of motion sickness. During the first, subjects were seated motionless, and during the second they were seated rotating sinusoidally about an earth vertical axis. Subjects then wore prism goggles that reverse the left-right visual field and performed manual tasks until they developed moderate motion sickness. Finally, ILV and ECG were recorded while subjects maintained a relatively constant level of sickness by intermittent eye closure during rotation with the goggles. Based on analyses of ILV to HR transfer functions from the three conditions, we were unable to demonstrate a change in autonomic control of heart rate due to rotation alone or due to motion sickness. These findings do not support the notion that moderate motion sickness is manifested as a generalized autonomic response.

  6. Running With an Elastic Lower Limb Exoskeleton.

    PubMed

    Cherry, Michael S; Kota, Sridhar; Young, Aaron; Ferris, Daniel P

    2016-06-01

    Although there have been many lower limb robotic exoskeletons that have been tested for human walking, few devices have been tested for assisting running. It is possible that a pseudo-passive elastic exoskeleton could benefit human running without the addition of electrical motors due to the spring-like behavior of the human leg. We developed an elastic lower limb exoskeleton that added stiffness in parallel with the entire lower limb. Six healthy, young subjects ran on a treadmill at 2.3 m/s with and without the exoskeleton. Although the exoskeleton was designed to provide ~50% of normal leg stiffness during running, it only provided 24% of leg stiffness during testing. The difference in added leg stiffness was primarily due to soft tissue compression and harness compliance decreasing exoskeleton displacement during stance. As a result, the exoskeleton only supported about 7% of the peak vertical ground reaction force. There was a significant increase in metabolic cost when running with the exoskeleton compared with running without the exoskeleton (ANOVA, P < .01). We conclude that 2 major roadblocks to designing successful lower limb robotic exoskeletons for human running are human-machine interface compliance and the extra lower limb inertia from the exoskeleton.

  7. Computational Simulation on Facial Expressions and Experimental Tensile Strength for Silicone Rubber as Artificial Skin

    NASA Astrophysics Data System (ADS)

    Amijoyo Mochtar, Andi

    2018-02-01

    Applications of robotics have become important for human life in recent years. There are many specification of robots that have been improved and encriched with the technology advances. One of them are humanoid robot with facial expression which closer with the human facial expression naturally. The purpose of this research is to make computation on facial expressions and conduct the tensile strength for silicone rubber as artificial skin. Facial expressions were calculated by determining dimension, material properties, number of node elements, boundary condition, force condition, and analysis type. A Facial expression robot is determined by the direction and the magnitude external force on the driven point. The expression face of robot is identical with the human facial expression where the muscle structure in face according to the human face anatomy. For developing facial expression robots, facial action coding system (FACS) in approached due to follow expression human. The tensile strength is conducting due to check the proportional force of artificial skin that can be applied on the future of robot facial expression. Combining of calculated and experimental results can generate reliable and sustainable robot facial expression that using silicone rubber as artificial skin.

  8. Development of Human System Integration at NASA

    NASA Technical Reports Server (NTRS)

    Whitmore, Mihriban; McGuire, Kerry; Thompson, Shelby; Vos, Gordon

    2012-01-01

    Human Systems Integration seeks to design systems around the capabilities and limitations of the humans which use and interact with the system, ensuring greater efficiency of use, reduced error rates, and less rework in the design, manufacturing and operational deployment of hardware and software. One of the primary goals of HSI is to get the human factors practitioner involved early in the design process. In doing so, the aim is to reduce future budget costs and resources in redesign and training. By the preliminary design phase of a project nearly 80% of the total cost of the project is locked in. Potential design changes recommended by evaluations past this point will have little effect due to lack of funding or a huge cost in terms of resources to make changes. Three key concepts define an effective HSI program. First, systems are comprised of hardware, software, and the human, all of which operate within an environment. Too often, engineers and developers fail to consider the human capacity or requirements as part of the system. This leads to poor task allocation within the system. To promote ideal task allocation, it is critical that the human element be considered early in system development. Poor design, or designs that do not adequately consider the human component, could negatively affect physical or mental performance, as well as, social behavior. Second, successful HSI depends upon integration and collaboration of all the domains that represent acquisition efforts. Too often, these domains exist as independent disciplines due to the location of expertise within the service structure. Proper implementation of HSI through participation would help to integrate these domains and disciplines to leverage and apply their interdependencies to attain an optimal design. Via this process domain interests can be integrated to perform effective HSI through trade-offs and collaboration. This provides a common basis upon which to make knowledgeable decisions. Finally, HSI must be considered early in the requirements development phase of system design and acquisition. This will provide the best opportunity to maximize return on investment (ROI) and system performance. HSI requirements must be developed in conjunction with capability ]based requirements generation through functional. HSI requirements will drive HSI metrics and embed HSI issues within the system design. After a system is designed, implementation of HSI oversights can be very expensive. An HSI program should be included as an integral part of a total system approach to vehicle and habitat development. This would include, but not limited to, workstation design, D&C development, volumetric analysis, training, operations, and human -robotic interaction. HSI is a necessary process for Human Space Flight programs to meet the Agency Human ]System standards and thus mitigate human risks to acceptable levels. NASA has been involved in HSI planning, procedures development, process, and implementation for many years, and has been building several internal and publicly accessible products to facilitate HSI fs inclusion in the NASA Systems Engineering Lifecycle. Some of these products include: NASA STD 3001 Volumes 1 and 2, Human Integration Design Handbook, NASA HSI Implementation Plan, NASA HSI Implementation Plan Templates, NASA HSI Implementation Handbook, and a 2 ]hour short course on HSI delivered as part of the NASA Space and Life Sciences Directorate Academy. These products have been created leveraging industry best practices and lessons learned from other Federal Government agencies.

  9. Laboratory Diagnosis of Human Rabies: Recent Advances

    PubMed Central

    Mani, Reeta Subramaniam; Madhusudana, Shampur Narayan

    2013-01-01

    Rabies, an acute progressive, fatal encephalomyelitis, transmitted most commonly through the bite of a rabid animal, is responsible for an estimated 61,000 human deaths worldwide. The true disease burden and public health impact due to rabies remain underestimated due to lack of sensitive laboratory diagnostic methods. Rapid diagnosis of rabies can help initiate prompt infection control and public health measures, obviate the need for unnecessary treatment/medical tests, and assist in timely administration of pre- or postexposure prophylactic vaccination to family members and medical staff. Antemortem diagnosis of human rabies provides an impetus for clinicians to attempt experimental therapeutic approaches in some patients, especially after the reported survival of a few cases of human rabies. Traditional methods for antemortem and postmortem rabies diagnosis have several limitations. Recent advances in technology have led to the improvement or development of several diagnostic assays which include methods for rabies viral antigen and antibody detection and assays for viral nucleic acid detection and identification of specific biomarkers. These assays which complement traditional methods have the potential to revolutionize rabies diagnosis in future. PMID:24348170

  10. Genomic Perspectives of Transcriptional Regulation in Forebrain Development

    DOE PAGES

    Nord, Alex S.; Pattabiraman, Kartik; Visel, Axel; ...

    2015-01-07

    The forebrain is the seat of higher-order brain functions, and many human neuropsychiatric disorders are due to genetic defects affecting forebrain development, making it imperative to understand the underlying genetic circuitry. We report that recent progress now makes it possible to begin fully elucidating the genomic regulatory mechanisms that control forebrain gene expression. Here, we discuss the current knowledge of how transcription factors drive gene expression programs through their interactions with cis-acting genomic elements, such as enhancers; how analyses of chromatin and DNA modifications provide insights into gene expression states; and how these approaches yield insights into the evolution ofmore » the human brain.« less

  11. Construction vs. development: polarizing models of human gestation.

    PubMed

    Stith, Richard

    2014-12-01

    This essay argues that the polarization of our public debate over embryo-destructive research may be due, to a large extent, not to different valuations of individual human life but to different conceptions of the process of gestation, with one group treating the process as a making or construction and the other treating it as a development. These two incompatible models of reproduction are shown to explain the various positions commonly encountered in this debate over the treatment of embryos, and to a significant degree those encountered in the debate over abortion as well. Finally, the historical, theoretical, and intuitive strengths of each model are examined.

  12. Breath Activity Monitoring With Wearable UWB Radars: Measurement and Analysis of the Pulses Reflected by the Human Body.

    PubMed

    Pittella, Erika; Pisa, Stefano; Cavagnaro, Marta

    2016-07-01

    Measurements of ultrawideband (UWB) pulses reflected by the human body are conducted to evidence the differences in the received signal time behaviors due to respiration phases, and to experimentally verify previously obtained numerical results on the body's organs responsible for pulse reflection. Two experimental setups are used. The first one is based on a commercially available impulse radar system integrated on a single chip, while the second one implements an indirect time-domain reflectometry technique using a vector network analyzer controlled by a LabVIEW virtual instrument running on a laptop. When the UWB source is placed close to the human body, a small reflection due to the lung boundaries is present in the received pulse well distanced in time from the reflection due to the air-skin interface; this reflection proved to be linked to the different respiration phases. The changes in the reflected pulse could be used to detect, through wearable radar systems, lung movements associated with the breath activity. The development of a wearable radar system is of great importance because it allows the breath activity sensing without interfering with the subject daily activities.

  13. Expression and immunoaffinity purification of recombinant soluble human GPR56 protein for the analysis of GPR56 receptor shedding by ELISA.

    PubMed

    Yang, Tai-Yun; Chiang, Nien-Yi; Tseng, Wen-Yi; Pan, Hsiao-Lin; Peng, Yen-Ming; Shen, Jiann-Jong; Wu, Kuo-An; Kuo, Ming-Ling; Chang, Gin-Wen; Lin, Hsi-Hsien

    2015-05-01

    GPR56 is a multi-functional adhesion-class G protein-coupled receptor involved in biological systems as diverse as brain development, male gonad development, myoblast fusion, hematopoietic stem cell maintenance, tumor growth and metastasis, and immune-regulation. Ectodomain shedding of human GPR56 receptor has been demonstrated previously, however the quantitative detection of GPR56 receptor shedding has not been investigated fully due to the lack of appropriate assays. Herein, an efficient system of expression and immune-affinity purification of the recombinant soluble extracellular domain of human GPR56 (sGPR56) protein from a stably transduced human melanoma cell line was established. The identity and functionality of the recombinant human sGPR56 protein were verified by Western blotting and mass spectrometry, and ligand-binding assays, respectively. Combined with the use of two recently generated anti-GPR56 monoclonal antibodies, a sensitive sandwich ELISA assay was successfully developed for the quantitative detection of human sGPR56 molecule. We found that GPR56 receptor shedding occurred constitutively and was further increased in activated human melanoma cells expressing endogenous GPR56. In conclusion, we report herein an efficient system for the production and purification of human sGPR56 protein for the establishment of a quantitative ELISA analysis of GPR56 receptor shedding. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Bacterial expression of human kynurenine 3-monooxygenase: Solubility, activity, purification☆

    PubMed Central

    Wilson, K.; Mole, D.J.; Binnie, M.; Homer, N.Z.M.; Zheng, X.; Yard, B.A.; Iredale, J.P.; Auer, M.; Webster, S.P.

    2014-01-01

    Kynurenine 3-monooxygenase (KMO) is an enzyme central to the kynurenine pathway of tryptophan metabolism. KMO has been implicated as a therapeutic target in several disease states, including Huntington’s disease. Recombinant human KMO protein production is challenging due to the presence of transmembrane domains, which localise KMO to the outer mitochondrial membrane and render KMO insoluble in many in vitro expression systems. Efficient bacterial expression of human KMO would accelerate drug development of KMO inhibitors but until now this has not been achieved. Here we report the first successful bacterial (Escherichia coli) expression of active FLAG™-tagged human KMO enzyme expressed in the soluble fraction and progress towards its purification. PMID:24316190

  15. Shrinking wild lands: Assessing human intrusion in the Highlands of Scotland, 1870 to 2004, using Geographical Information Systems

    Treesearch

    Steve Carver; Mark Wrightham

    2007-01-01

    Wild land in Scotland has been subject to steady attrition due to various types of development. This paper explores approaches that might be used to describe this attrition in Scotland, in order to promote more informed debate and assist policy development. Current digital map databases showing roads, bulldozed trails, plantation forest and hydropower schemes were...

  16. Human response to aviation noise : development of dose-response relationships for backcountry visitors - volume II : results and analysis

    DOT National Transportation Integrated Search

    2014-03-01

    The Federal Aviation Administration and National Park Service conducted joint research to better understand the effects of noise due to commercial air tour operations over units of the National Park System. To evaluate the relationship between aircra...

  17. Human response to aviation noise : development of dose-response relationships for backcountry visitors - volume I: study methods

    DOT National Transportation Integrated Search

    2014-03-01

    The Federal Aviation Administration and National Park Service conducted joint research to better understand the effects of noise due to commercial air tour operations over units of the National Park System. To evaluate the relationship between aircra...

  18. Chemical characterization and sources of PM2.5 at 12-h resolution in Guiyang, China

    EPA Science Inventory

    The increasing emission of primary and gaseous precursors of secondarily formed atmospheric particulate matter due to continuing industrial development and urbanization are leading to an increased public awareness of environmental issues and human health risks in China. As part o...

  19. METHODS DEVELOPMENT FOR THE DETERMINATION OF SELECTED ORGANOTINS IN DRINKING WATER

    EPA Science Inventory

    Organotin compounds, due to their versatility, have been exploited for use in a plethora of diverse applications with the intent to benefit human society. And, as a consequence, they have exerted a profound effect on the environment and the economy. For example, organotin compo...

  20. Separation and measurement of silver nanoparticles and silver ions using magnetic particles

    EPA Science Inventory

    The recent surge in consumer products and applications using metallic nanoparticles has increased the possibility of human or ecosystem exposure due to unintentional release into the environment. To protect consumer health and the environment, there is an urgent need to develop t...

  1. Human Rabies in the WHO Southeast Asia Region: Forward Steps for Elimination

    PubMed Central

    Gongal, Gyanendra; Wright, Alice E.

    2011-01-01

    There are eleven Member States in the WHO southeast Asia region (Bangladesh, Bhutan, Democratic People's Republic of Korea, India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand, Timor-Leste) of which eight are endemic for rabies. More than 1.4 billion people in the Region are at risk of rabies infection, and approximately 45% of worldwide rabies deaths occur in Asia. Dog bites account for 96% of human rabies cases. Progress in preventing human rabies through control of the disease in dogs has been slow due to various factors. Innovative control tools and techniques have been developed and standardized in recent years. The introduction of cost-effective intradermal rabies vaccination regimens in Asian countries has increased the availability and affordability of postexposure prophylaxis. Elimination of rabies is not possible without regional and intersectoral cooperation. Considering the importance of consolidating achievements in rabies control in Member countries, the WHO Regional Office for southeast Asia has developed a regional strategy for elimination of human rabies transmitted by dogs in the Region. They have committed to provide technical leadership, to advocate national health authorities to develop major stakeholder consensus for a comprehensive rabies elimination programme, and to implement national strategies for elimination of human rabies. PMID:21991437

  2. 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.

  3. Delivery of aerosolized drugs encapsulated in liposomes

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

    Cheng, Yung-Sung; Lyons, C.R.; Schmid, M.H.

    1995-12-01

    Mycobacterium tuberculosis (Mtb) is an infectious disease that resides in the human lung. Due to the difficulty in completely killing off the disease in infected individuals, Mtb has developed drug-resistant forms and is on the rise in the human population. Therefore, ITRI and the University of New Mexico are collaborating to explore the treatment of Mtb by an aerosolized drug delivered directly to the lungs. In conclusion, it is feasible to obtain an appropriate size and concentration of the liposomes before and after aerosolization.

  4. Marine cosmeceuticals.

    PubMed

    Kim, Se-Kwon

    2014-03-01

    Recently, a great deal of interest has been expressed in the cosmetic industry regarding marine-derived cosmetic active ingredients due to their numerous beneficial effects on human skin health. Bioactive substances derived from marine resources have diverse functional roles as natural skin care agents, and these properties can be applied to the development of novel cosmetics as well as nutricosmetics (from edible seaweeds and edible marine animals). This contribution focuses on marine-derived cosmeceutical active ingredients and presents an overview of their health beneficial effects on human skin. © 2014 Wiley Periodicals, Inc.

  5. The Possible Effects of Potential Key Technological Developments on the Force Structure of the Australian Army in 2040

    DTIC Science & Technology

    2014-12-01

    time as detection abilities improve. • There is a danger of a loss of human skills in collection that becomes evident when the network connection...perceptions.”[3]. The WS elements in this area are weighted to human populations due to the nature of the operations conducted in this area and the...structures. Before too much weight is placed on the tentative conclusions that are presented in this section it would be necessary to talk with

  6. 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.

  7. Hemispheric dominance underlying the neural substrate for learned vocalizations develops with experience.

    PubMed

    Chirathivat, Napim; Raja, Sahitya C; Gobes, Sharon M H

    2015-06-22

    Many aspects of song learning in songbirds resemble characteristics of speech acquisition in humans. Genetic, anatomical and behavioural parallels have most recently been extended with demonstrated similarities in hemispheric dominance between humans and songbirds: the avian higher order auditory cortex is left-lateralized for processing song memories in juvenile zebra finches that already have formed a memory of their fathers' song, just like Wernicke's area in the left hemisphere of the human brain is dominant for speech perception. However, it is unclear if hemispheric specialization is due to pre-existing functional asymmetry or the result of learning itself. Here we show that in juvenile male and female zebra finches that had never heard an adult song before, neuronal activation after initial exposure to a conspecific song is bilateral. Thus, like in humans, hemispheric dominance develops with vocal proficiency. A left-lateralized functional system that develops through auditory-vocal learning may be an evolutionary adaptation that could increase the efficiency of transferring information within one hemisphere, benefiting the production and perception of learned communication signals.

  8. Hemispheric dominance underlying the neural substrate for learned vocalizations develops with experience

    PubMed Central

    Chirathivat, Napim; Raja, Sahitya C.; Gobes, Sharon M. H.

    2015-01-01

    Many aspects of song learning in songbirds resemble characteristics of speech acquisition in humans. Genetic, anatomical and behavioural parallels have most recently been extended with demonstrated similarities in hemispheric dominance between humans and songbirds: the avian higher order auditory cortex is left-lateralized for processing song memories in juvenile zebra finches that already have formed a memory of their fathers’ song, just like Wernicke’s area in the left hemisphere of the human brain is dominant for speech perception. However, it is unclear if hemispheric specialization is due to pre-existing functional asymmetry or the result of learning itself. Here we show that in juvenile male and female zebra finches that had never heard an adult song before, neuronal activation after initial exposure to a conspecific song is bilateral. Thus, like in humans, hemispheric dominance develops with vocal proficiency. A left-lateralized functional system that develops through auditory-vocal learning may be an evolutionary adaptation that could increase the efficiency of transferring information within one hemisphere, benefiting the production and perception of learned communication signals. PMID:26098840

  9. Heavy metals in drinking water: Occurrences, implications, and future needs in developing countries.

    PubMed

    Chowdhury, Shakhawat; Mazumder, M A Jafar; Al-Attas, Omar; Husain, Tahir

    2016-11-01

    Heavy metals in drinking water pose a threat to human health. Populations are exposed to heavy metals primarily through water consumption, but few heavy metals can bioaccumulate in the human body (e.g., in lipids and the gastrointestinal system) and may induce cancer and other risks. To date, few thousand publications have reported various aspects of heavy metals in drinking water, including the types and quantities of metals in drinking water, their sources, factors affecting their concentrations at exposure points, human exposure, potential risks, and their removal from drinking water. Many developing countries are faced with the challenge of reducing human exposure to heavy metals, mainly due to their limited economic capacities to use advanced technologies for heavy metal removal. This paper aims to review the state of research on heavy metals in drinking water in developing countries; understand their types and variability, sources, exposure, possible health effects, and removal; and analyze the factors contributing to heavy metals in drinking water. This study identifies the current challenges in developing countries, and future research needs to reduce the levels of heavy metals in drinking water. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Human resource development for nuclear generation - from the perspective of a utility company

    NASA Astrophysics Data System (ADS)

    Kahar, Wan Shakirah Wan Abdul; Mostafa, Nor Azlan; Salim, Mohd Faiz

    2017-01-01

    Malaysia is currently in the planning phase of its nuclear power program, with the first unit targeted to be operational in 2030. Training of nuclear power plant (NPP) staffs are usually long and rigorous due to the complexity and safety aspects of nuclear power. As the sole electricity utility in the country, it is therefore essential that Tenaga Nasional Berhad (TNB) prepares early in developing its human resource and nuclear expertise as a potential NPP owner-operator. A utility also has to be prudent in managing its work force efficiently and effectively, while ensuring that adequate preparations are being made to acquire the necessary nuclear knowledge with sufficient training lead time. There are several approaches to training that can be taken by a utility company with no experience in nuclear power. These include conducting feasibility studies and benchmarking exercises, preparing long term human resource development, increasing the exposure on nuclear power technology to both the top management and general staff, and employing the assistance of relevant agencies locally and abroad. This paper discusses the activities done and steps taken by TNB in its human resource development for Malaysia's nuclear power program.

  11. The human obesity epidemic, the mismatch paradigm, and our modern "captive" environment.

    PubMed

    Power, Michael L

    2012-01-01

    In the distant past obesity in humans was rare and likely caused by metabolic dysregulation due to genetic or disease-related pathology. External factors precluded the ability of most people to overeat or under exert. Socio-cultural obesity came about due to the rareness of obesity and its difficulty to achieve. What is rare becomes valuable and what is difficult to achieve becomes a badge of prestige. The modern human obesity epidemic would appear to represent a third class of obesity: environmental obesity. Much like the captive environments which humans construct for the captive/companion animals in our care, the modern human environment has greatly decreased the challenges of life that would restrict food intake and enforce exertion. And like us, our captive/companion animal populations are also experiencing obesity epidemics. A further concern is that maternal obesity alters maternal signaling to offspring, in utero through the placenta and after birth through breast milk, in ways that perpetuate an enhanced vulnerability to obesity. Molecules such as leptin, produced by adipose tissue and placenta, have significant developmental effects on brain areas associated with feeding behavior. Leptin and other cytokines and growth factors are found in breast milk. These molecules have positive effects on gut maturation; their effects on metabolism and brain development are unclear. Placenta and brain also are hotspots for epigenetic regulation, and epigenetic changes may play significant roles in the later vulnerability to obesity and to the development of a diverse array of diseases, including heart disease, hypertension, and noninsulin-dependent diabetes. Copyright © 2012 Wiley Periodicals, Inc.

  12. Global assessment of human losses due to earthquakes

    USGS Publications Warehouse

    Silva, Vitor; Jaiswal, Kishor; Weatherill, Graeme; Crowley, Helen

    2014-01-01

    Current studies have demonstrated a sharp increase in human losses due to earthquakes. These alarming levels of casualties suggest the need for large-scale investment in seismic risk mitigation, which, in turn, requires an adequate understanding of the extent of the losses, and location of the most affected regions. Recent developments in global and uniform datasets such as instrumental and historical earthquake catalogues, population spatial distribution and country-based vulnerability functions, have opened an unprecedented possibility for a reliable assessment of earthquake consequences at a global scale. In this study, a uniform probabilistic seismic hazard assessment (PSHA) model was employed to derive a set of global seismic hazard curves, using the open-source software OpenQuake for seismic hazard and risk analysis. These results were combined with a collection of empirical fatality vulnerability functions and a population dataset to calculate average annual human losses at the country level. The results from this study highlight the regions/countries in the world with a higher seismic risk, and thus where risk reduction measures should be prioritized.

  13. The excess salt appetite of humans is not due to sodium loss in adulthood.

    PubMed

    Leshem, Micah

    2009-09-07

    In seeking the determinants of high salt intake, studies in rat have shown that sodium depletion in utero, neonatally, or in maturity, permanently enhances salt appetite. In humans too, salt appetite is permanently enhanced after perinatal sodium loss, but it is not known if sodium loss in adults also enhances salt intake. If it does, it might contribute to high sodium intake and its associated pathologies. Therefore, using methods that revealed the perinatal determinants of sodium appetite, here we evaluated whether salt appetite is enhanced in adults with a varied history of sodium loss. We find that putative sodium loss due to hyperhidrosis, hemorrhage, dehydration, or breastfeeding, does not increase salt appetite significantly. The findings contrast with the many studies showing enduring enhancement of salt appetite by perinatal sodium loss in humans, and suggest that lifelong salt appetite is established very early in development. In turn this counsels very early intervention to prevent lifelong excess sodium intake.

  14. A mouse model for the human pathogen Salmonella Typhi

    PubMed Central

    Song, Jeongmin; Willinger, Tim; Rongvaux, Anthony; Eynon, Elizabeth E.; Stevens, Sean; Manz, Markus G.; Flavell, Richard A.; Galán, Jorge E.

    2010-01-01

    SUMMARY Salmonella enterica serovar Typhi (S. Typhi) is the cause of typhoid fever, a life-threatening disease of humans. The lack of an animal model due to S. typhi's strict human host specificity has been a significant obstacle in the understanding of its pathogenesis and the development of a safe and effective vaccine against typhoid fever. We report here the development of a mouse model for S. Typhi infection. We showed that immunodeficient Rag2 -/- γc -/- mice engrafted with human fetal liver hematopoietic stem and progenitor cells were able to support S. Typhi replication and persistent infection. A S. Typhi strain carrying a mutation in a gene required for its virulence in humans was not able to replicate in these humanized mice. In contrast, another mutant strain unable to produce the recently identified typhoid toxin, exhibited increased replication suggesting a potential role for this toxin in the establishment of persistent infection. Furthermore, infected animals mounted a human innate and adaptive immune response to S. Typhi resulting in the production of cytokines and pathogen-specific antibodies. These results therefore indicate that this animal model can be used to study S. Typhi pathogenesis and to evaluate potential vaccine candidates against typhoid fever. PMID:20951970

  15. Diagnosis of human fascioliasis by stool and blood techniques: update for the present global scenario.

    PubMed

    Mas-Coma, S; Bargues, M D; Valero, M A

    2014-12-01

    Before the 1990s, human fascioliasis diagnosis focused on individual patients in hospitals or health centres. Case reports were mainly from developed countries and usually concerned isolated human infection in animal endemic areas. From the mid-1990s onwards, due to the progressive description of human endemic areas and human infection reports in developing countries, but also new knowledge on clinical manifestations and pathology, new situations, hitherto neglected, entered in the global scenario. Human fascioliasis has proved to be pronouncedly more heterogeneous than previously thought, including different transmission patterns and epidemiological situations. Stool and blood techniques, the main tools for diagnosis in humans, have been improved for both patient and survey diagnosis. Present availabilities for human diagnosis are reviewed focusing on advantages and weaknesses, sample management, egg differentiation, qualitative and quantitative diagnosis, antibody and antigen detection, post-treatment monitoring and post-control surveillance. Main conclusions refer to the pronounced difficulties of diagnosing fascioliasis in humans given the different infection phases and parasite migration capacities, clinical heterogeneity, immunological complexity, different epidemiological situations and transmission patterns, the lack of a diagnostic technique covering all needs and situations, and the advisability for a combined use of different techniques, at least including a stool technique and a blood technique.

  16. Human rights in the world of the genetic revolution.

    PubMed

    Castro-Rios, A

    1999-01-01

    The Biotechnological Revolution provides enormous possibilities to human development (nutrition, medicine, industry), while at the same time, creates social-ethical apprehensions due to the dangers to Human Rights that an improper use could generate. In this respect, Human Rights are presented as the "religion" of our time: accepted by all, although not equally practised. These rights, classified in the Universal Declaration of the United Nations, are the terms which society uses to ponder the ethical peformance of individuals and organizations. Harmonisation between Biotechnology and Human Rights should be based on a continuous social debate in which the principles that contribute to the respect of the human's essential nature should arise. As a starting point, considerations concerning the repercussions which the different genetic techniques have on each of the individually considered Human Rights, i.e. on dignity, equality, freedom, the right to health, to intimacy or to a worthy environment should be developed. Moreover, an international vision of the problem should be imposed since it should be remembered that initiatives that avoid attacks on Human Rights are either taken internationally or are condemned to failure. The following work was not written to give practical solutions to ethical conflicts but simply to consider some of the aspects which can create controversy in the search for a coherent future for human nature.

  17. Bacterial colonization stimulates a complex physiological response in the immature human intestinal epithelium

    PubMed Central

    Hill, David R; Huang, Sha; Nagy, Melinda S; Yadagiri, Veda K; Fields, Courtney; Mukherjee, Dishari; Bons, Brooke; Dedhia, Priya H; Chin, Alana M; Tsai, Yu-Hwai; Thodla, Shrikar; Schmidt, Thomas M; Walk, Seth

    2017-01-01

    The human gastrointestinal tract is immature at birth, yet must adapt to dramatic changes such as oral nutrition and microbial colonization. The confluence of these factors can lead to severe inflammatory disease in premature infants; however, investigating complex environment-host interactions is difficult due to limited access to immature human tissue. Here, we demonstrate that the epithelium of human pluripotent stem-cell-derived human intestinal organoids is globally similar to the immature human epithelium and we utilize HIOs to investigate complex host-microbe interactions in this naive epithelium. Our findings demonstrate that the immature epithelium is intrinsically capable of establishing a stable host-microbe symbiosis. Microbial colonization leads to complex contact and hypoxia driven responses resulting in increased antimicrobial peptide production, maturation of the mucus layer, and improved barrier function. These studies lay the groundwork for an improved mechanistic understanding of how colonization influences development of the immature human intestine. PMID:29110754

  18. Human natural killer cells prevent infectious mononucleosis features by targeting lytic Epstein-Barr virus infection

    PubMed Central

    Chijioke, Obinna; Müller, Anne; Feederle, Regina; Barros, Mario Henrique M.; Krieg, Carsten; Emmel, Vanessa; Marcenaro, Emanuela; Leung, Carol S.; Antsiferova, Olga; Landtwing, Vanessa; Bossart, Walter; Moretta, Alessandro; Hassan, Rocio; Boyman, Onur; Niedobitek, Gerald; Delecluse, Henri-Jacques; Capaul, Riccarda; Münz, Christian

    2014-01-01

    SUMMARY Primary infection with the human oncogenic Epstein Barr virus (EBV) can result in infectious mononucleosis (IM), a self-limiting disease caused by massive lymphocyte expansion, which predisposes for the development of distinct EBV-associated lymphomas. It remains unclear why some individuals experience this symptomatic primary EBV infection, while the majority acquires the virus asymptomatically. Using a mouse model with reconstituted human immune system components, we show here that depletion of human natural killer (NK) cells enhances IM symptoms and promotes EBV-associated tumorigenesis, mainly due to loss of immune control over lytic EBV infection. These data suggest that failure of innate immune control by human NK cells augments symptomatic lytic EBV infection, which drives lymphocyte expansion and predisposes for EBV-associated malignancies. PMID:24360958

  19. Investigation of the presence of human or bovine respiratory syncytial virus in the lungs of mink (Neovison vison) with hemorrhagic pneumonia due to Pseudomonas aeruginosa.

    PubMed

    Salomonsen, Charlotte M; Breum, Solvej Ø; Larsen, Lars E; Jakobsen, Jeanette; Høiby, Niels; Hammer, Anne S

    2012-11-26

    Hemorrhagic pneumonia is a disease of farmed mink (Neovison vison) caused by Pseudomonas aeruginosa. The disease is highly seasonal in Danish mink with outbreaks occurring almost exclusively in the autumn. Human respiratory syncytial virus (RSV) has been shown to augment infection with P. aeruginosa in mice and to promote adhesion of P. aeruginosa to human respiratory cells. We tested 50 lung specimens from mink with hemorrhagic pneumonia for bovine RSV by reverse transcriptase polymerase chain reaction (PCR) and for human RSV by a commercial real-time PCR. RSV was not found. This study indicates that human and bovine RSV is not a major co-factor for development of hemorrhagic pneumonia in Danish mink.

  20. A visco-hyperelastic constitutive model for human spine ligaments.

    PubMed

    Jiang, Yugang; Wang, Yu; Peng, Xiongqi

    2015-03-01

    Human spine ligaments show a highly non-linear, strain rate dependent biomechanical behavior under tensile tests. A visco-hyperelastic fiber-reinforced constitutive model was accordingly developed for human ligaments, in which the energy density function is decomposed into two parts. The first part represents the elastic strain energy stored in the soft tissue, and the second part denotes the energy dissipated due to its inherent viscous characteristics. The model is applied to various human spinal ligaments including the anterior and posterior longitudinal ligaments, ligamentum flavum, capsular ligament, and interspinous ligament. Material parameters for each type of ligament were obtained by curve-fitting with corresponding experimental data available in the literature. The results indicate that the model presented here can properly characterize the visco-hyperelastic biomechanical behavior of human spine ligaments.

  1. Developing a Strategic Plan for NASA JSC's Technology Investments

    NASA Technical Reports Server (NTRS)

    Stecklein, Jonette M.

    2012-01-01

    Human space exploration has always been heavily influenced by goals to achieve a specific mission on a specific schedule. This approach drove rapid technology development, the rapidity of which adds risks as well as provides a major driver for costs. The National Aeronautics and Space Administration (NASA) is now approaching the extension of human presence throughout the solar system by balancing a proactive yet less schedule-driven development of technology with opportunistic scheduling of missions as the needed technologies are realized. This approach should provide cost effective, low risk technology development that will enable efficient and effective manned spaceflight missions. As a first step, the NASA Human Spaceflight Architecture Team (HAT) has identified a suite of critical technologies needed to support future manned missions across a range of destinations, including in cislunar space, near earth asteroid visits, lunar exploration, Mars space, and Mars exploration. The challenge now is to develop a strategy and plan for technology development that efficiently enables these missions over a reasonable time period, without increasing technology development costs unnecessarily due to schedule pressure, and subsequently mitigating development and mission risks. NASA fs Johnson Space Center (JSC), as the nation's primary center for human exploration, is addressing this challenge through an innovative approach allocating Internal Research and Development funding to projects that have been prioritized using four focus criteria, with appropriate importance weighting. These four focus criteria are the Human Space Flight Technology Needs, JSC Core Technology Competencies, Commercialization Potential, and Partnership Potential. The inherent coupling in these focus criteria have been captured in a database and have provided an initial prioritization for allocation of technology development research funding. This paper will describe this process and this database, and the preliminary technology development prioritization results.

  2. IN SITU LEAD IMMOBILIZATION BY APATITE

    EPA Science Inventory

    Lead contamination is of environmental concern due to its effect on human health. The purpose of this study was to develop a technology to immobilize Pb in situ in contaminated soils and wastes using apatite. Hydroxyapatite [Ca10(PO4)6(O...

  3. Investigating Microadaptation in One-to-One Human Tutoring

    ERIC Educational Resources Information Center

    Siler, Stephanie Ann; VanLehn, Kurt

    2015-01-01

    The authors investigated whether some advantages of tutoring over other instructional methods are due to microadaptation, or, tutors basing their actions on assessments of tutees they develop during tutoring. In a 2 × 2 between-subjects experiment, independent variables were shared experience (tutors either worked with the same or a different…

  4. The Store Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2014-01-01

    Biomedical and robotic technologies are merging to present a wonderful opportunity to develop artificial limbs and prosthetic devices for humans injured on the job, in the military, or due to disease. In this challenge, students will have the opportunity to design a store or online service that specifically dedicates itself to amputees. Described…

  5. Effects of Sulfur Mustard on Intracellular Calcium and Synthesis of Basement Membrane Zone Proteins in Human Skin

    DTIC Science & Technology

    1993-08-04

    development of blisters. They postulated that DNA single strand breaks (SSB) due to spontaneous or enzymatically induced depurination of alkylated DNA ... bases activate the chromosomal enzyme poly(ADP-ribose)transferase (PADPRT). The latter would deplete cellular NAD÷ pools. In literature, this

  6. 45 CFR 1355.36 - Withholding Federal funds due to failure to achieve substantial conformity or failure to...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON CHILDREN, YOUTH AND FAMILIES, FOSTER CARE MAINTENANCE PAYMENTS, ADOPTION ASSISTANCE, AND CHILD AND FAMILY SERVICES GENERAL... the immediately preceding child and family services review; (ii) The increased withholding of funds...

  7. Mentoring--Is It Failing Women?

    ERIC Educational Resources Information Center

    Ghosh, Rajashi

    2015-01-01

    Mentoring programs are gaining traction as human resource development initiatives that can support women to advance in their careers in organizations. However, some of these programs are falling short of delivering on this promise due to particular inherent flaws. This case study considers the following three potential flaws of formal mentoring…

  8. Budgetary Challenges of Higher Education: Evidence from Bangladesh

    ERIC Educational Resources Information Center

    Sarkar, Shakhawat Hossain; Hossain, Syed Zabid

    2016-01-01

    This study strives to ascertain the financial and nonfinancial challenges of higher education budget for human resources development (HRD) based on both primary and secondary sources of data. Inadequate budgetary support from the government and inappropriate implementation of the same due to nonexistence of good governance and inefficient…

  9. Microchemical urinalysis. IX - Determination of hydroxyproline in urine.

    NASA Technical Reports Server (NTRS)

    Grunbaum, B. W.; Pace, N.

    1973-01-01

    A simplified procedure is described for the determination of hydroxyproline in human or monkey urine. In this procedure 1 ml of urine is subjected in succession to hydrolysis, oxidation, extraction, and color development. During these steps impurities and interfering substances are eliminated, thus resulting in a chromophore due to hydroxyproline alone.

  10. 76 FR 69743 - The Development and Evaluation of Human Cytomegalovirus Vaccines; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-09

    ... immune systems. Congenital HCMV infection causes mental retardation, learning disabilities, hearing loss, vision loss, and other disabilities. Patients undergoing stem cell or solid-organ transplants are at... available basis beginning at 8 a.m. If you need special accommodations due to a disability, please contact...

  11. Nitrogen Saturation in Temperate Forest Ecosystems

    Treesearch

    John Aber; William McDowell; Knute Nadelhoffer; Alison Magill; Glenn Berntson; Mark Kamakea; Steven McNulty; William Currie; Lindsey Rustad; Ivan Fernandez

    1998-01-01

    Nitrogen emissions to the atmosphere due to human activity remain elevated in industrialized regions of the world and are accelerating in many developing regions (Galloway 1995). Although the deposition of sulfur has been reduced over much of the United States and Europe by aggressive environmental protection policies, current nitrogen deposition reduction targets in...

  12. Effects of soil moisture on the diurnal pattern of pesticide emission: Numerical simulation and sensitivity analysis

    USDA-ARS?s Scientific Manuscript database

    Accurate prediction of pesticide volatilization is important for the protection of human and environmental health. Due to the complexity of the volatilization process, sophisticated predictive models are needed, especially for dry soil conditions. A mathematical model was developed to allow simulati...

  13. Assessment of particulate matter and ammonia emissions and respective plume profiles from a commercial poultry house

    USDA-ARS?s Scientific Manuscript database

    Poultry-emitted air pollutants, including particulate matter (PM) and ammonia, have raised concerns due to negative effects on human health and the environment. However, developing and optimizing remediation technologies requires a better understanding of air pollutant concentrations, the emission p...

  14. Information Competency and Creative Initiative of Personality and Their Manifestation in Activity

    ERIC Educational Resources Information Center

    Tabachuk, Natalia P.; Ledovskikh, Irina A.; Shulika, Nadezhda A.; Karpova, Irina V.; Kazinets, Victor A.; Polichka, Anatolii E.

    2018-01-01

    The relevance of the research is due to the global trends of development of the information society that are associated with the rapid advancement of civilization (IT penetration, increased computer availability, variability) and innovation processes in the sphere of education (competency-based approach, humanization and humanitarization). These…

  15. Genetic regulation of pituitary gland development in human and mouse.

    PubMed

    Kelberman, Daniel; Rizzoti, Karine; Lovell-Badge, Robin; Robinson, Iain C A F; Dattani, Mehul T

    2009-12-01

    Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke's pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans.

  16. Genetic Regulation of Pituitary Gland Development in Human and Mouse

    PubMed Central

    Kelberman, Daniel; Rizzoti, Karine; Lovell-Badge, Robin; Robinson, Iain C. A. F.; Dattani, Mehul T.

    2009-01-01

    Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke’s pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans. PMID:19837867

  17. When gender matters: new insights into the relationships between social systems and the genetic structure of human populations.

    PubMed

    Destro Bisol, Giovanni; Capocasa, Marco; Anagnostou, Paolo

    2012-10-01

    Due to its important effects on the ecological dynamics and the genetic structure of species, biologists have long been interested in gender-biased dispersal, a condition where one gender is more prone to move from the natal site. More recently, this topic has attracted a great attention from human evolutionary geneticists. Considering the close relations between residential rules and social structure, gender-biased dispersal is, in fact, regarded as an important case study concerning the effects of socio-cultural factors on human genetic variation. It all started with the seminal paper by Mark Seielstad, Erich Minch and Luigi Luca Cavalli Sforza from Stanford University (Seielstad et al. 1998). They observed a larger differentiation for Y-chromosome than mitochondrial DNA between extant human populations, purportedly a consequence of the prevalence of long-term patrilocality in human societies. Subsequent studies, however, have highlighted the need to consider geographically close and culturally homogeneous groups, disentangle signals due to different peopling events and obtain unbiased estimates of genetic diversity. In this issue of Molecular Ecology, not only do Marks et al. (2012) adopt an experimental design which addresses these concerns, but they also take a further and important step forward by integrating the genetic analysis of two distant populations, the Basotho and Spanish, with data regarding migration rates and matrimonial distances. Using both empirical evidence and simulations, the authors show that female-biased migration due to patrilocality might shape the genetic structure of human populations only at short ranges and under substantial differences in migration rates between genders. Providing a quantitative framework for future studies of the effects of residential rules on the human genome, this study paves the way for further developments in the field. On a wider perspective, Marks et al.'s work demonstrates the power of approaches which integrate biological, cultural and demographic lines of evidence in the study of relations between social and genetic structures of human populations.

  18. Recent Developments in Folate Nutrition.

    PubMed

    Naderi, Nassim; House, James D

    The term folate (vitamin B9) refers to a group of water-soluble compounds that are nutritionally essential for the support of optimal human health and development. Folates participate in numerous one-carbon transfer reactions, including the methylation of important biomolecules (lipids, amino acids, DNA). A deficiency of folate leads to pathological outcomes including anemia and impairments in reproductive health and fetal development. Due to the linkage of impaired folate status with an increased prevalence of neural tube defects (NTDs) in babies, several jurisdictions required the fortification of the food supply with folic acid, a synthetic and stable form of folate. Data from the postfortification era have provided strong evidence for the reduction of NTDs due to folic acid fortification. However, concern is now growing with respect to the amount of synthetic folic acid within the human food supply. Excess folic acid intake has been linked to a masking of vitamin B12 deficiency, and concerns regarding the promotion of folate-sensitive cancers, including colorectal cancer. New strategies to ensure the supply of optimal folate to at-risk populations may be needed, including the use of biofortification approaches, in order to address recent concerns. © 2018 Elsevier Inc. All rights reserved.

  19. Disorders of sex development expose transcriptional autonomy of genetic sex and androgen-programmed hormonal sex in human blood leukocytes

    PubMed Central

    Holterhus, Paul-Martin; Bebermeier, Jan-Hendrik; Werner, Ralf; Demeter, Janos; Richter-Unruh, Annette; Cario, Gunnar; Appari, Mahesh; Siebert, Reiner; Riepe, Felix; Brooks, James D; Hiort, Olaf

    2009-01-01

    Background Gender appears to be determined by independent programs controlled by the sex-chromosomes and by androgen-dependent programming during embryonic development. To enable experimental dissection of these components in the human, we performed genome-wide profiling of the transcriptomes of peripheral blood mononuclear cells (PBMC) in patients with rare defined "disorders of sex development" (DSD, e.g., 46, XY-females due to defective androgen biosynthesis) compared to normal 46, XY-males and 46, XX-females. Results A discrete set of transcripts was directly correlated with XY or XX genotypes in all individuals independent of male or female phenotype of the external genitalia. However, a significantly larger gene set in the PBMC only reflected the degree of external genital masculinization independent of the sex chromosomes and independent of concurrent post-natal sex steroid hormone levels. Consequently, the architecture of the transcriptional PBMC-"sexes" was either male, female or even "intersex" with a discordant alignment of the DSD individuals' genetic and hormonal sex signatures. Conclusion A significant fraction of gene expression differences between males and females in the human appears to have its roots in early embryogenesis and is not only caused by sex chromosomes but also by long-term sex-specific hormonal programming due to presence or absence of androgen during the time of external genital masculinization. Genetic sex and the androgen milieu during embryonic development might therefore independently modulate functional traits, phenotype and diseases associated with male or female gender as well as with DSD conditions. PMID:19570224

  20. [Psychiatry at the turn of the 20th and 21st centuries].

    PubMed

    Bilikiewicz, A

    1998-01-01

    The author makes an attempt at considering the most important achievements in psychiatry which have taken place in the global scale during the passing century, and the direction taken up by the development of global psychiatry in the coming century. The 20th century was characterised not only by the impressive development of science, thanks to which completely new possibilities opened up for global psychiatry, but also by the presence of extreme events that took place as a result of false ideologies such as fascism and communism. In the 20th century concepts like homicide, holocaust, the extermination of the mentally ill, experiments on people that are prohibited by the ethics of medicine and the elementary rules of humanity, etc. The paper includes the achievements of diagnosis and therapy of psychiatric disorders and the latest organisational solutions as well as the perspectives for further development of psychiatry. The author also implies the aims that psychiatry has to take up due to the numerous threats from our civilization: the technical-technological development, pollution of the natural environment, the negative changes in human values, the rising brutality in interhuman relations due to racial, national and religious conflicts and terrorism, the disappearing feeling of being safe in society, vision of hunger and poverty in many countries on a few continents, the danger of an epidemic outbreak of new unknown diseases caused by viral mutations, or genetics--the possible negative effects of genetic engineering (cloning of humans), etc. The author tries to define the role of psychiatry in preventing the threats of civilization.

  1. Epidemiology, incidence and mortality of lung cancer and their relationship with the development index in the world

    PubMed Central

    Rafiemanesh, Hosein; Mehtarpour, Mojtaba; Khani, Farah; Hesami, Sayed Mohammadali; Shamlou, Reza; Towhidi, Farhad; Makhsosi, Behnam Reza; Moini, Ali

    2016-01-01

    Background The highest incidence of lung cancer is seen in North America and the lowest incidence in central Africa. Socioeconomic factors of inequality reflect regional disparities in human development. Due to the importance of awareness about incidence and mortality of lung cancer in health programming and the possible role of the human development index (HDI), this study was done with the aim to investigate the epidemiology of lung cancer in the world and its relationship with HDI. Methods The study was conducted based on data from the world data of cancer and the World Bank (including the HDI and its components). Data about the age-specific incidence and mortality rate (ASR) for every country in 2012 were getting from the global cancer project. To analyze data, correlation tests between incidence and death rates, and HDI and its components were employed with a significance level of 0.05 using SPSS software. Results Lung cancer with standardized incidence rate (ASIR) and standardized mortality rate (ASMR), equal to 23.1 and 19.7 (in 100,000 people), respectively. The highest and lowest values of mortality incidence ratio (MIR) for lung cancer due to continents division were 0.93 and 0.71 for Eastern Africa and Australia/New Zealand, respectively. Univariate analysis showed significant relationship (P<0.0001) between ASIR and ASMR with life expectancy at birth and mean years of schooling. Conclusions The highest MIR for lung cancer was for medium human development countries. Linear regression analysis showed a reverse significant relationship between MIR and HDI. PMID:27293825

  2. Epidemiology, incidence and mortality of lung cancer and their relationship with the development index in the world.

    PubMed

    Rafiemanesh, Hosein; Mehtarpour, Mojtaba; Khani, Farah; Hesami, Sayed Mohammadali; Shamlou, Reza; Towhidi, Farhad; Salehiniya, Hamid; Makhsosi, Behnam Reza; Moini, Ali

    2016-06-01

    The highest incidence of lung cancer is seen in North America and the lowest incidence in central Africa. Socioeconomic factors of inequality reflect regional disparities in human development. Due to the importance of awareness about incidence and mortality of lung cancer in health programming and the possible role of the human development index (HDI), this study was done with the aim to investigate the epidemiology of lung cancer in the world and its relationship with HDI. The study was conducted based on data from the world data of cancer and the World Bank (including the HDI and its components). Data about the age-specific incidence and mortality rate (ASR) for every country in 2012 were getting from the global cancer project. To analyze data, correlation tests between incidence and death rates, and HDI and its components were employed with a significance level of 0.05 using SPSS software. Lung cancer with standardized incidence rate (ASIR) and standardized mortality rate (ASMR), equal to 23.1 and 19.7 (in 100,000 people), respectively. The highest and lowest values of mortality incidence ratio (MIR) for lung cancer due to continents division were 0.93 and 0.71 for Eastern Africa and Australia/New Zealand, respectively. Univariate analysis showed significant relationship (P<0.0001) between ASIR and ASMR with life expectancy at birth and mean years of schooling. The highest MIR for lung cancer was for medium human development countries. Linear regression analysis showed a reverse significant relationship between MIR and HDI.

  3. Apoptotic impact on Brugia malayi by sulphonamido-quinoxaline: search for a novel therapeutic rationale.

    PubMed

    Bhoj, Priyanka S; Ingle, Rahul G; Goswami, Kalyan; Jena, Lingaraj; Wadher, Shailesh

    2018-05-01

    Human lymphatic filariasis although not fatal but poses serious socioeconomic burden due to associated disability. This is reflected by the huge magnitude of the estimated disability-adjusted life years of about 5.09 million. Therefore, following WHO mandate, our earlier studies on antifilarial drug development revealed the significance of apoptosis. Apoptotic impact has been implicated in anticancer rationale of several drugs. In this study, we explored the antifilarial potential of sulphonamido-quinoxaline compounds, shown to be specific inhibitor for c-Met kinase in human cancer cells. Out of studied compounds, Q4, showing favorable drug-likeness and medicinal chemistry properties on bioinformatics platform along with subsequently recorded lowest IC 100 value, was considered as a suitable antifilarial candidate. Significant apoptosis due to mitochondrial involvement was recorded in drug-treated parasite unlike untreated control. In spite of homology between human c-Met kinase and Brugia malayi counterpart, comparative docking result of this compound showed more favorable binding parameters with the parasitic target. The wide gap between IC 100 and LD 50 values further confirmed the therapeutic safety. We propose sulphonamido-quinoxaline derivative as a lead candidate for antifilarial drug development. Further study is warranted to authenticate parasitic c-Met kinase as a novel therapeutic target reminiscent of anticancer rationale implicating inhibition of proliferation.

  4. Berries and other natural products in the pancreatic cancer chemoprevention in human clinical trials.

    PubMed

    Pan, Pan; Skaer, Chad; Yu, Jianhua; Zhao, Hui; Ren, He; Oshima, Kiyoko; Wang, Li-Shu

    2017-01-01

    Pancreatic ductal adenocarcinoma (PDAC) was the 12 th and 11 th most common cancer in men and women worldwide in 2012, with the highest incidence in North America and Europe and the lowest in Africa and Asia. Due to the lack of efficient early diagnosis and rapid disease progression, PDAC patients have a 5-year survival rate of just 5%. Epidemiological studies suggest that smoking, obesity, type II diabetes, and pancreatitis are common risk factors for PDAC development. By contrast, high intake of fresh fruit, vegetables, and nuts rich in phytochemicals could reduce PDAC risk. This review summarizes the human clinical studies that have used berries or other natural products for chemoprevention of PDAC. Developing chemopreventive agents against PDAC would be tremendously valuable for the high-risk population and patients with premalignant lesions. Although some clinical trials of these agents have been completed, most are in early phases, and the results are not promising, which may be due to administration of the natural products at advanced stages of PDAC. Thus, further mechanistic studies using genetic animal models that recapitulate the tumor microenvironment and immunology of human PDAC would be informative for selecting an effective window for intervention with berries or other natural compounds.

  5. Berries and other natural products in the pancreatic cancer chemoprevention in human clinical trials

    PubMed Central

    Pan, Pan; Skaer, Chad; Yu, Jianhua; Zhao, Hui; Ren, He; Oshima, Kiyoko; Wang, Li-Shu

    2017-01-01

    Pancreatic ductal adenocarcinoma (PDAC) was the 12th and 11th most common cancer in men and women worldwide in 2012, with the highest incidence in North America and Europe and the lowest in Africa and Asia. Due to the lack of efficient early diagnosis and rapid disease progression, PDAC patients have a 5-year survival rate of just 5%. Epidemiological studies suggest that smoking, obesity, type II diabetes, and pancreatitis are common risk factors for PDAC development. By contrast, high intake of fresh fruit, vegetables, and nuts rich in phytochemicals could reduce PDAC risk. This review summarizes the human clinical studies that have used berries or other natural products for chemoprevention of PDAC. Developing chemopreventive agents against PDAC would be tremendously valuable for the high-risk population and patients with premalignant lesions. Although some clinical trials of these agents have been completed, most are in early phases, and the results are not promising, which may be due to administration of the natural products at advanced stages of PDAC. Thus, further mechanistic studies using genetic animal models that recapitulate the tumor microenvironment and immunology of human PDAC would be informative for selecting an effective window for intervention with berries or other natural compounds. PMID:29367867

  6. Identifying Potential Areas of Human Zika Infection in the City of Los Angeles, California by Use of Remote Sensing Imagery

    NASA Astrophysics Data System (ADS)

    Lee, J.

    2017-12-01

    As of April 2017, California is the third most prevalent state on the United States for Zika Infection and Southern California has an ever growing population of Aedes mosquitos. Zika is a disease which poses a significant risk to humans and other mammals due to its effects on pregnancy. This emerging disease is highly contagious due to its spread of infection primarily by Aedes aegypti mosquitos. Aedes mosquitos are able to breed in small rain collecting containers which allow the species to persevere in urban and semi urban environments. We hope to identify potential areas with risk of human infection within Los Angeles and its surrounding areas. This study integrates remote sensing, GIS, statistical, and environmental techniques to study favorable habitats for this particular species of mosquitos and their larvae. The study of the geographic and landscape factors which promote the larvae development allow for the disease spread to be analyzed and modeled. There are several goals in the development of this study. These include the coordination of statistical data with local epidemiology departments, identify workflows to improve efficiency, create models which can be utilized for disease prevention, and identify geographic risk factors for the spread of Zika.

  7. Quantitative assessment of human and pet exposure to Salmonella associated with dry pet foods.

    PubMed

    Lambertini, Elisabetta; Buchanan, Robert L; Narrod, Clare; Ford, Randall M; Baker, Robert C; Pradhan, Abani K

    2016-01-04

    Recent Salmonella outbreaks associated with dry pet foods and treats highlight the importance of these foods as previously overlooked exposure vehicles for both pets and humans. In the last decade efforts have been made to raise the safety of this class of products, for instance by upgrading production equipment, cleaning protocols, and finished product testing. However, no comprehensive or quantitative risk profile is available for pet foods, thus limiting the ability to establish safety standards and assess the effectiveness of current and proposed Salmonella control measures. This study sought to develop an ingredients-to-consumer quantitative microbial exposure assessment model to: 1) estimate pet and human exposure to Salmonella via dry pet food, and 2) assess the impact of industry and household-level mitigation strategies on exposure. Data on prevalence and concentration of Salmonella in pet food ingredients, production process parameters, bacterial ecology, and contact transfer in the household were obtained through literature review, industry data, and targeted research. A probabilistic Monte Carlo modeling framework was developed to simulate the production process and basic household exposure routes. Under the range of assumptions adopted in this model, human exposure due to handling pet food is null to minimal if contamination occurs exclusively before extrusion. Exposure increases considerably if recontamination occurs post-extrusion during coating with fat, although mean ingested doses remain modest even at high fat contamination levels, due to the low percent of fat in the finished product. Exposure is highly variable, with the distribution of doses ingested by adult pet owners spanning 3Log CFU per exposure event. Child exposure due to ingestion of 1g of pet food leads to significantly higher doses than adult doses associated with handling the food. Recontamination after extrusion and coating, e.g., via dust or equipment surfaces, may also lead to exposure due to the absence of pathogen reduction steps after extrusion or at consumer households. Exposure is potentially highest when Salmonella is transferred to human food that is left at growth-promoting conditions. This model can be applied to evaluate the impact of alternative Salmonella control measures during production, risk communication to consumers, and regulatory standards. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Safety Psychology Applicating on Coal Mine Safety Management Based on Information System

    NASA Astrophysics Data System (ADS)

    Hou, Baoyue; Chen, Fei

    In recent years, with the increase of intensity of coal mining, a great number of major accidents happen frequently, the reason mostly due to human factors, but human's unsafely behavior are affected by insecurity mental control. In order to reduce accidents, and to improve safety management, with the help of application security psychology, we analyse the cause of insecurity psychological factors from human perception, from personality development, from motivation incentive, from reward and punishment mechanism, and from security aspects of mental training , and put forward countermeasures to promote coal mine safety production,and to provide information for coal mining to improve the level of safety management.

  9. Human exposure to endocrine disrupting chemicals: effects on the male and female reproductive systems.

    PubMed

    Sifakis, Stavros; Androutsopoulos, Vasilis P; Tsatsakis, Aristeidis M; Spandidos, Demetrios A

    2017-04-01

    Endocrine disrupting chemicals (EDCs) comprise a group of chemical compounds that have been examined extensively due to the potential harmful effects in the health of human populations. During the past decades, particular focus has been given to the harmful effects of EDCs to the reproductive system. The estimation of human exposure to EDCs can be broadly categorized into occupational and environmental exposure, and has been a major challenge due to the structural diversity of the chemicals that are derived by many different sources at doses below the limit of detection used by conventional methodologies. Animal and in vitro studies have supported the conclusion that endocrine disrupting chemicals affect the hormone dependent pathways responsible for male and female gonadal development, either through direct interaction with hormone receptors or via epigenetic and cell-cycle regulatory modes of action. In human populations, the majority of the studies point towards an association between exposure to EDCs and male and/or female reproduction system disorders, such as infertility, endometriosis, breast cancer, testicular cancer, poor sperm quality and/or function. Despite promising discoveries, a causal relationship between the reproductive disorders and exposure to specific toxicants is yet to be established, due to the complexity of the clinical protocols used, the degree of occupational or environmental exposure, the determination of the variables measured and the sample size of the subjects examined. Future studies should focus on a uniform system of examining human populations with regard to the exposure to specific EDCs and the direct effect on the reproductive system. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. 3D Proximal Tubule Tissues Recapitulate Key Aspects of Renal Physiology to Enable Nephrotoxicity Testing

    PubMed Central

    King, Shelby M.; Higgins, J. William; Nino, Celina R.; Smith, Timothy R.; Paffenroth, Elizabeth H.; Fairbairn, Casey E.; Docuyanan, Abigail; Shah, Vishal D.; Chen, Alice E.; Presnell, Sharon C.; Nguyen, Deborah G.

    2017-01-01

    Due to its exposure to high concentrations of xenobiotics, the kidney proximal tubule is a primary site of nephrotoxicity and resulting attrition in the drug development pipeline. Current pre-clinical methods using 2D cell cultures and animal models are unable to fully recapitulate clinical drug responses due to limited in vitro functional lifespan, or species-specific differences. Using Organovo's proprietary 3D bioprinting platform, we have developed a fully cellular human in vitro model of the proximal tubule interstitial interface comprising renal fibroblasts, endothelial cells, and primary human renal proximal tubule epithelial cells to enable more accurate prediction of tissue-level clinical outcomes. Histological characterization demonstrated formation of extensive microvascular networks supported by endogenous extracellular matrix deposition. The epithelial cells of the 3D proximal tubule tissues demonstrated tight junction formation and expression of renal uptake and efflux transporters; the polarized localization and function of P-gp and SGLT2 were confirmed. Treatment of 3D proximal tubule tissues with the nephrotoxin cisplatin induced loss of tissue viability and epithelial cells in a dose-dependent fashion, and cimetidine rescued these effects, confirming the role of the OCT2 transporter in cisplatin-induced nephrotoxicity. The tissues also demonstrated a fibrotic response to TGFβ as assessed by an increase in gene expression associated with human fibrosis and histological verification of excess extracellular matrix deposition. Together, these results suggest that the bioprinted 3D proximal tubule model can serve as a test bed for the mechanistic assessment of human nephrotoxicity and the development of pathogenic states involving epithelial-interstitial interactions, making them an important adjunct to animal studies. PMID:28337147

  11. Development of a methodology to assess man-made risks in Germany

    NASA Astrophysics Data System (ADS)

    Borst, D.; Jung, D.; Murshed, S. M.; Werner, U.

    2006-09-01

    Risk is a concept used to describe future potential outcomes of certain actions or events. Within the project "CEDIM - Risk Map Germany - Man-made Hazards" it is intended to develop methods for assessing and mapping the risk due to different human-induced hazards. This is a task that has not been successfully performed for Germany so far. Concepts of catastrophe modelling are employed including the spatial modelling of hazard, the compilation of different kinds of exposed elements, the estimation of their vulnerability and the direct loss potential in terms of human life and health. The paper is divided in two sections: First, an analytic framework for assessing the broad spectrum of human-induced risks is introduced. This approach is then applied for three important types of human-induced hazards that are representative for a whole class of hazards: Accidents due to nuclear power plants (NPP) or air traffic, and terrorism. For the analysis of accidents, risk is measured with respect to getting injured or dying when living in certain buffer zones around hazard locations. NPP hazard expert knowledge is used and supplemented with observations on aging effects leading to a proprietary index value for the risk. Air traffic risk is modelled as an area related phenomenon based on available accident statistics leading to an expected value of risk. Terrorism risk is assessed by the attraction certain elements (like embassies in the case of conventional threats) display in the eye of potential aggressors. For non-conventional targets like football games, a detailed approach measuring their susceptibility to different kinds of attacks within predefined scenarios was developed; this also allows a ranking of attack modes.

  12. Bacterial expression of human kynurenine 3-monooxygenase: solubility, activity, purification.

    PubMed

    Wilson, K; Mole, D J; Binnie, M; Homer, N Z M; Zheng, X; Yard, B A; Iredale, J P; Auer, M; Webster, S P

    2014-03-01

    Kynurenine 3-monooxygenase (KMO) is an enzyme central to the kynurenine pathway of tryptophan metabolism. KMO has been implicated as a therapeutic target in several disease states, including Huntington's disease. Recombinant human KMO protein production is challenging due to the presence of transmembrane domains, which localise KMO to the outer mitochondrial membrane and render KMO insoluble in many in vitro expression systems. Efficient bacterial expression of human KMO would accelerate drug development of KMO inhibitors but until now this has not been achieved. Here we report the first successful bacterial (Escherichia coli) expression of active FLAG™-tagged human KMO enzyme expressed in the soluble fraction and progress towards its purification. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  13. A perspective on space exploration technology catalysis: A rationale for initiating 21st Century expansion of human civilization into outer space

    NASA Technical Reports Server (NTRS)

    Horsham, Gary A. P.

    1988-01-01

    The rationale for human exploration of space is examined. Observations of the technocatalytic potential are presented. Transferability to the terrestrial environment of 21st Century Earth is discussed. The many threats to future survival of this planet's sensitive ecosystem are also discussed in relation to the technoecological harmony that might be achievable due to the extreme demands that are naturally imposed on the development of (civilian/human) space technology. The human attempt to inhabit the inner solar system (the Moon, Mars, etc.) is proposed as the ultimate and most appropriate technology driver for the myriad of socioeconomic, ecological, and technological needs that will accompany 21st Century Earth societies.

  14. Interventions to prevent adverse fetal programming due to maternal obesity during pregnancy.

    PubMed

    Nathanielsz, Peter W; Ford, Stephen P; Long, Nathan M; Vega, Claudia C; Reyes-Castro, Luis A; Zambrano, Elena

    2013-10-01

    Maternal obesity is a global epidemic affecting both developed and developing countries. Human and animal studies indicate that maternal obesity adversely programs the development of offspring, predisposing them to chronic diseases later in life. Several mechanisms act together to produce these adverse health effects. There is a consequent need for effective interventions that can be used in the management of human pregnancy to prevent these outcomes. The present review analyzes the dietary and exercise intervention studies performed to date in both altricial and precocial animals, rats and sheep, with the aim of preventing adverse offspring outcomes. The results of these interventions present exciting opportunities to prevent, at least in part, adverse metabolic and other outcomes in obese mothers and their offspring. © 2013 International Life Sciences Institute.

  15. Simultaneous assay of multiple antibiotics in human plasma by LC-MS/MS: importance of optimizing formic acid concentration.

    PubMed

    Chen, Feng; Hu, Zhe-Yi; Laizure, S Casey; Hudson, Joanna Q

    2017-03-01

    Optimal dosing of antibiotics in critically ill patients is complicated by the development of resistant organisms requiring treatment with multiple antibiotics and alterations in systemic exposure due to diseases and extracorporeal drug removal. Developing guidelines for optimal antibiotic dosing is an important therapeutic goal requiring robust analytical methods to simultaneously measure multiple antibiotics. An LC-MS/MS assay using protein precipitation for cleanup followed by a 6-min gradient separation was developed to simultaneously determine five antibiotics in human plasma. The precision and accuracy were within the 15% acceptance range. The formic acid concentration was an important determinant of signal intensity, peak shape and matrix effects. The method was designed to be simple and successfully applied to a clinical pharmacokinetic study.

  16. Neurotensin is an autocrine trophic factor stimulated by androgen withdrawal in human prostate cancer.

    PubMed Central

    Sehgal, I; Powers, S; Huntley, B; Powis, G; Pittelkow, M; Maihle, N J

    1994-01-01

    After therapeutic hormone deprivation, prostate cancer cells often develop androgen-insensitive growth through mechanisms thus far undefined. Neuropeptides have been previously implicated as growth factors in some prostate cancers. Here, we demonstrate that androgen-sensitive LNCaP human prostate cancer cells produce and secrete neurotensin following androgen withdrawal. We show that while LNCaP cells express the neurotensin receptor, only androgen-deprived cells exhibit a growth response to exogenous neurotensin. We further demonstrate that androgen-stimulated cells may be refractory to exogenous neurotensin due to androgen induction of a metalloprotease active toward neurotensin. Thus, prostate cancer cells deprived of androgen develop an alternative autocrine growth mechanism involving neurotensin. Images PMID:8197117

  17. Benefits of biodiverse marine resources to child nutrition in differing developmental contexts in Hispaniola.

    PubMed

    Temsah, Gheda; Johnson, Kiersten; Evans, Thea; Adams, Diane K

    2018-01-01

    There is an urgent need for an improved empirical understanding of the relationship among biodiverse marine resources, human health and development outcomes. Coral reefs are often at this intersection for developing nations in the tropics-an ecosystem targeted for biodiversity conservation and one that provides sustenance and livelihoods for many coastal communities. To explore these relationships, we use the comparative development contexts of Haiti and the Dominican Republic on the island of Hispaniola. We combine child nutrition data from the Demographic Health Survey with coastal proximity and coral reef habitat diversity, and condition to empirically test human benefits of marine natural resources in differing development contexts. Our results indicate that coastal children have a reduced likelihood of severe stunting in Haiti but have increased likelihoods of stunting and reduced dietary diversity in the Dominican Republic. These contrasting results are likely due to the differential in developed infrastructure and market access. Our analyses did not demonstrate an association between more diverse and less degraded coral reefs and better childhood nutrition. The results highlight the complexities of modelling interactions between the health of humans and natural systems, and indicate the next steps needed to support integrated development programming.

  18. Benefits of biodiverse marine resources to child nutrition in differing developmental contexts in Hispaniola

    PubMed Central

    Temsah, Gheda; Johnson, Kiersten; Evans, Thea

    2018-01-01

    There is an urgent need for an improved empirical understanding of the relationship among biodiverse marine resources, human health and development outcomes. Coral reefs are often at this intersection for developing nations in the tropics—an ecosystem targeted for biodiversity conservation and one that provides sustenance and livelihoods for many coastal communities. To explore these relationships, we use the comparative development contexts of Haiti and the Dominican Republic on the island of Hispaniola. We combine child nutrition data from the Demographic Health Survey with coastal proximity and coral reef habitat diversity, and condition to empirically test human benefits of marine natural resources in differing development contexts. Our results indicate that coastal children have a reduced likelihood of severe stunting in Haiti but have increased likelihoods of stunting and reduced dietary diversity in the Dominican Republic. These contrasting results are likely due to the differential in developed infrastructure and market access. Our analyses did not demonstrate an association between more diverse and less degraded coral reefs and better childhood nutrition. The results highlight the complexities of modelling interactions between the health of humans and natural systems, and indicate the next steps needed to support integrated development programming. PMID:29795591

  19. An integrated mathematical model of the human cardiopulmonary system: model development.

    PubMed

    Albanese, Antonio; Cheng, Limei; Ursino, Mauro; Chbat, Nicolas W

    2016-04-01

    Several cardiovascular and pulmonary models have been proposed in the last few decades. However, very few have addressed the interactions between these two systems. Our group has developed an integrated cardiopulmonary model (CP Model) that mathematically describes the interactions between the cardiovascular and respiratory systems, along with their main short-term control mechanisms. The model has been compared with human and animal data taken from published literature. Due to the volume of the work, the paper is divided in two parts. The present paper is on model development and normophysiology, whereas the second is on the model's validation on hypoxic and hypercapnic conditions. The CP Model incorporates cardiovascular circulation, respiratory mechanics, tissue and alveolar gas exchange, as well as short-term neural control mechanisms acting on both the cardiovascular and the respiratory functions. The model is able to simulate physiological variables typically observed in adult humans under normal and pathological conditions and to explain the underlying mechanisms and dynamics. Copyright © 2016 the American Physiological Society.

  20. Development of an errorable car-following driver model

    NASA Astrophysics Data System (ADS)

    Yang, H.-H.; Peng, H.

    2010-06-01

    An errorable car-following driver model is presented in this paper. An errorable driver model is one that emulates human driver's functions and can generate both nominal (error-free), as well as devious (with error) behaviours. This model was developed for evaluation and design of active safety systems. The car-following data used for developing and validating the model were obtained from a large-scale naturalistic driving database. The stochastic car-following behaviour was first analysed and modelled as a random process. Three error-inducing behaviours were then introduced. First, human perceptual limitation was studied and implemented. Distraction due to non-driving tasks was then identified based on the statistical analysis of the driving data. Finally, time delay of human drivers was estimated through a recursive least-square identification process. By including these three error-inducing behaviours, rear-end collisions with the lead vehicle could occur. The simulated crash rate was found to be similar but somewhat higher than that reported in traffic statistics.

  1. Docosahexaenoic acid (DHA), a fundamental fatty acid for the brain: New dietary sources.

    PubMed

    Echeverría, Francisca; Valenzuela, Rodrigo; Catalina Hernandez-Rodas, María; Valenzuela, Alfonso

    2017-09-01

    Docosahexaenoic acid (C22: 6n-3, DHA) is a long-chain polyunsaturated fatty acid of marine origin fundamental for the formation and function of the nervous system, particularly the brain and the retina of humans. It has been proposed a remarkable role of DHA during human evolution, mainly on the growth and development of the brain. Currently, DHA is considered a critical nutrient during pregnancy and breastfeeding due their active participation in the development of the nervous system in early life. DHA and specifically one of its derivatives known as neuroprotectin D-1 (NPD-1), has neuroprotective properties against brain aging, neurodegenerative diseases and injury caused after brain ischemia-reperfusion episodes. This paper discusses the importance of DHA in the human brain given its relevance in the development of the tissue and as neuroprotective agent. It is also included a critical view about the ways to supply this noble fatty acid to the population. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. The quantitative modelling of human spatial habitability

    NASA Technical Reports Server (NTRS)

    Wise, James A.

    1988-01-01

    A theoretical model for evaluating human spatial habitability (HuSH) in the proposed U.S. Space Station is developed. Optimizing the fitness of the space station environment for human occupancy will help reduce environmental stress due to long-term isolation and confinement in its small habitable volume. The development of tools that operationalize the behavioral bases of spatial volume for visual kinesthetic, and social logic considerations is suggested. This report further calls for systematic scientific investigations of how much real and how much perceived volume people need in order to function normally and with minimal stress in space-based settings. The theoretical model presented in this report can be applied to any size or shape interior, at any scale of consideration, for the Space Station as a whole to an individual enclosure or work station. Using as a point of departure the Isovist model developed by Dr. Michael Benedikt of the U. of Texas, the report suggests that spatial habitability can become as amenable to careful assessment as engineering and life support concerns.

  3. Analyzing urban ecosystem variation in the City of Dongguan: A stepwise cluster modeling approach.

    PubMed

    Sun, J; Li, Y P; Gao, P P; Suo, C; Xia, B C

    2018-06-13

    In this study, a stepwise cluster modeling approach (SCMA) is developed for analyzing urban ecosystem variation via Normalized Difference Vegetation Index (NDVI). NDVI is an indicator of vegetation growth and coverage and useful in reflecting urban ecosystem. SCMA is established on a cluster tree that can characterize the complex relationship between independent and dependent variables. SCMA is applied to the City of Dongguan for simulating the urban NDVI and identifying associated drivers of human activity, topography and meteorology without specific functions. Results show that SCMA performances better than conventional statistical methods, illustrating the ability of SCMA in capturing the complex and nonlinear features of urban ecosystem. Results disclose that human activities play negative effects on NDVI due to the destruction of green space for pursuing more space for buildings. NDVI reduces gradually from the south part to the north part of Dongguan due to increased gross domestic product and population density, indicating that the ecosystem in Dongguan is better in the south part. NDVI in the northeast part (dominated by agriculture) is sensitive to the growth of economy and population. More attention should be paid to this part for sustainable development, such as increasing afforestation, planting grass and constructing parks. Precipitation has a positive effect on NDVI due to the promotion of soil moisture that is beneficial to plants' growth. Awareness of these complexities is helpful for sustainable development of urban ecosystem. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Electrorheological Fluid Based Force Feedback Device

    NASA Technical Reports Server (NTRS)

    Pfeiffer, Charles; Bar-Cohen, Yoseph; Mavroidis, Constantinos; Dolgin, Benjamin

    1999-01-01

    Parallel to the efforts to develop fully autonomous robots, it is increasingly being realized that there are applications where it is essential to have a fully controlled robot and "feel" its operating conditions, i.e. telepresence. This trend is a result of the increasing efforts to address tasks where humans can perform significantly better but, due to associated hazards, distance, physical limitations and other causes, only robots can be employed to perform these tasks. Such robots need to be assisted by a human that remotely controls the operation. To address the goal of operating robots as human surrogates, the authors launched a study of mechanisms that provide mechanical feedback. For this purpose, electrorheological fluids (ERF) are being investigated for the potential application as miniature haptic devices. This family of electroactive fluids has the property of changing the viscosity during electrical stimulation. Consequently, ERF can be used to produce force feedback haptic devices for tele-operated control of medical and space robotic systems. Forces applied at the robot end-effector due to a compliant environment are reflected to the user using an ERF device where a change in the system viscosity will occur proportionally to the transmitted force. Analytical model and control algorithms are being developed taking into account the non-linearities of these type of devices. This paper will describe the concept and the developed mechanism of ERF based force feedback. The test process and the physical properties of this device will be described and the results of preliminary tests will be presented.

  5. Cell-SELEX-Based Identification of a Human and Mouse Cross-Reactive Endothelial Cell-Internalizing Aptamer.

    PubMed

    Dua, Pooja; Kang, Sinae; Shin, Hye-Soo; Kim, Soyoun; Lee, Dong-Ki

    2018-04-02

    Increased interest and insights gained by researchers on the roles of endothelial cells in the pathophysiology of cancer, inflammatory, and cardiovascular diseases have led to the design of pharmacological interventions aimed at the endothelium lining in the diseased sites. Toward this end, we used established brain microvascular endothelial cell lines mouse (bEND3), human (hCMEC/D3), and Toggle Cell-SELEX to identify a species cross-reactive, endothelial cell-internalizing aptamer R11-3. This 2'F-modified RNA aptamer is specific for endothelial cells as no internalization was seen with cells of nonendothelial origin. R11-3 was truncated in size, and its potential in endothelial targeted therapeutics was established using VEGFR2 targeting long interfering RNA (liRNA) aptamer chimera. Due to its specificity for both mouse and human endothelial cells, we believe that this aptamer not only fits for development of endothelial targeted drug development for human diseases but is also suitable for preclinical evaluation in mice.

  6. Myotonia congenita-associated mutations in chloride channel-1 affect zebrafish body wave swimming kinematics.

    PubMed

    Cheng, Wei; Tian, Jing; Burgunder, Jean-Marc; Hunziker, Walter; Eng, How-Lung

    2014-01-01

    Myotonia congenita is a human muscle disorder caused by mutations in CLCN1, which encodes human chloride channel 1 (CLCN1). Zebrafish is becoming an increasingly useful model for human diseases, including muscle disorders. In this study, we generated transgenic zebrafish expressing, under the control of a muscle specific promoter, human CLCN1 carrying mutations that have been identified in human patients suffering from myotonia congenita. We developed video analytic tools that are able to provide precise quantitative measurements of movement abnormalities in order to analyse the effect of these CLCN1 mutations on adult transgenic zebrafish swimming. Two new parameters for body-wave kinematics of swimming reveal changes in body curvature and tail offset in transgenic zebrafish expressing the disease-associated CLCN1 mutants, presumably due to their effect on muscle function. The capability of the developed video analytic tool to distinguish wild-type from transgenic zebrafish could provide a useful asset to screen for compounds that reverse the disease phenotype, and may be applicable to other movement disorders besides myotonia congenita.

  7. Myotonia Congenita-Associated Mutations in Chloride Channel-1 Affect Zebrafish Body Wave Swimming Kinematics

    PubMed Central

    Cheng, Wei; Tian, Jing; Burgunder, Jean-Marc; Hunziker, Walter; Eng, How-Lung

    2014-01-01

    Myotonia congenita is a human muscle disorder caused by mutations in CLCN1, which encodes human chloride channel 1 (CLCN1). Zebrafish is becoming an increasingly useful model for human diseases, including muscle disorders. In this study, we generated transgenic zebrafish expressing, under the control of a muscle specific promoter, human CLCN1 carrying mutations that have been identified in human patients suffering from myotonia congenita. We developed video analytic tools that are able to provide precise quantitative measurements of movement abnormalities in order to analyse the effect of these CLCN1 mutations on adult transgenic zebrafish swimming. Two new parameters for body-wave kinematics of swimming reveal changes in body curvature and tail offset in transgenic zebrafish expressing the disease-associated CLCN1 mutants, presumably due to their effect on muscle function. The capability of the developed video analytic tool to distinguish wild-type from transgenic zebrafish could provide a useful asset to screen for compounds that reverse the disease phenotype, and may be applicable to other movement disorders besides myotonia congenita. PMID:25083883

  8. 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

  9. 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.

  10. Understanding the Apothecaries Within: The Necessity of a Systematic Approach for Defining the Chemical Output of the Human Microbiome

    PubMed Central

    Sampey, Brante; Watkins, Steven M.; Milburn, Michael; Eckhart, Andrea D.

    2014-01-01

    Abstract The human microbiome harbors a massive diversity of microbes that effectively form an “organ” that strongly influences metabolism and immune function and hence, human health. Although the growing interest in the microbiome has chiefly arisen due to its impact on human physiology, the probable rules of operation are embedded in the roots of microbiology where chemical communication (i.e., with metabolites) is a dominant feature of coexistence. Indeed, recent examples in microbiome research offer the impression that the collective microbiome operates as an “apothecary,” creating chemical concoctions that influence health and alter drug response. Although these principles are not unappreciated, the majority of emphasis is on metagenomics and research efforts often omit systematic efforts to interrogate the chemical component of the complex equation between microbial community and host phenotype. One of the reasons for this omission may be due to the inaccessibility to high‐breadth, high‐throughput, and scalable technologies. Since these technologies are now available, we propose that a more systematic effort to survey the host–microbiota chemical output be embedded into microbiome research as there is strong likelihood, and growing precedence, that this component may often be integral to developing our understanding of these ultimate apothecaries and how they impact human health. PMID:24422665

  11. Roles of CDX2 and EOMES in human induced trophoblast progenitor cells

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

    Chen, Ying, E-mail: ying.chen@hc.msu.edu; Wang, Kai; Gong, Yun Guo

    Highlights: ► CDX2 and EOMES play critical roles in human induced trophoblast progenitors (iTP). ► iTP cells directly transformed from fibroblasts. ► Differentiation of iTP cells into extravillous trophoblasts and syncytiotrophoblasts. -- Abstract: Abnormal trophoblast lineage proliferation and differentiation in early pregnancy have been associated with the pathogenesis of placenta diseases of pregnancy. However, there is still a gap in understanding the molecular mechanisms of early placental development due to the limited primary trophoblast cultures and fidelity of immortalized trophoblast lines. Trophoblasts stem (TS) cells, an in vitro model of trophectoderm that can differentiate into syncytiotrophoblasts and extravillous trophoblasts, canmore » be an attractive tool for early pregnancy research. TS cells are well established in mouse but not in humans due to insufficient knowledge of which trophoblast lineage-specific transcription factors are involved in human trophectoderm (TE) proliferation and differentiation. Here, we applied induced pluripotent stem cell technique to investigate the human trophoblast lineage-specific transcription factors. We established human induced trophoblast progenitor (iTP) cells by direct reprogramming the fibroblasts with a pool of mouse trophoblast lineage-specific transcription factors consisting of CDX2, EOMES, and ELF5. The human iTP cells exhibit epithelial morphology and can be maintained in vitro for more than 2 months. Gene expression profile of these cells was tightly clustered with human trophectoderm but not with human neuron progenitor cells, mesenchymal stem cells, or endoderm cells. These cells are capable of differentiating into cells with an invasive capacity, suggesting extravillous trophoblasts. They also form multi-nucleated cells which secrete human chorionic gonadotropin and estradiol, consistent with a syncytiotrophoblast phenotype. Our results provide the evidence that transcription factors CDX2 and EOMES may play critical roles in human iTP cell generation.« less

  12. Lifespan development of attentiveness in domestic dogs: drawing parallels with humans

    PubMed Central

    Wallis, Lisa J.; Range, Friederike; Müller, Corsin A.; Serisier, Samuel; Huber, Ludwig; Zsó, Virányi

    2014-01-01

    Attention is pivotal to consciousness, perception, cognition, and working memory in all mammals, and therefore changes in attention over the lifespan are likely to influence development and aging of all of these functions. Due to their evolutionary and developmental history, the dog is being recognized as an important species for modeling human healthspan, aging and associated diseases. In this study, we investigated the normal lifespan development of attentiveness of pet dogs in naturalistic situations, and compared the resulting cross-sectional developmental trajectories with data from previous studies in humans. We tested a sample of 145 Border collies (6 months to 14 years) with humans and objects or food as attention attractors, in order to assess their attentional capture, sustained and selective attention, and sensorimotor abilities. Our results reveal differences in task relevance in sustained attentional performance when watching a human or a moving object, which may be explained by life-long learning processes involving such stimuli. During task switching we found that dogs’ selective attention and sensorimotor abilities showed differences between age groups, with performance peaking at middle age. Dogs’ sensorimotor abilities showed a quadratic distribution with age and were correlated with selective attention performance. Our results support the hypothesis that the development and senescence of sensorimotor and attentional control may be fundamentally interrelated. Additionally, attentional capture, sustained attention, and sensorimotor control developmental trajectories paralleled those found in humans. Given that the development of attention is similar across humans and dogs, we propose that the same regulatory mechanisms are likely to be present in both species. Finally, this cross-sectional study provides the first description of age group changes in attention over the lifespan of pet dogs. PMID:24570668

  13. Simulation of light transport in arthritic- and non-arthritic human fingers

    NASA Astrophysics Data System (ADS)

    Milanic, Matija; Paluchowski, Lukasz A.; Randeberg, Lise L.

    2014-03-01

    Rheumatoid arthritis is a disease that frequently leads to joint destruction. It has high incidence rates worldwide, and the disease significantly reduces patient's quality of life due to pain, swelling and stiffness of the affected joints. Early diagnosis is necessary to improve course of the disease, therefore sensitive and accurate diagnostic tools are required. Optical imaging techniques have capability for early diagnosis and monitoring of arthritis. As compared to conventional diagnostic techniques optical technique is a noninvasive, noncontact and fast way of collecting diagnostic information. However, a realistic model of light transport in human joints is needed for understanding and developing of such optical diagnostic tools. The aim of this study is to develop a 3D numerical model of light transport in a human finger. The model will guide development of a hyperspectral imaging (HSI) diagnostic modality for arthritis in human fingers. The implemented human finger geometry is based on anatomical data. Optical data of finger tissues are adjusted to represent either an arthritic or an unaffected finger. The geometry and optical data serve as input into a 3D Monte Carlo method, which calculate diffuse reflectance, transmittance and absorbed energy distributions. The parameters of the model are optimized based on HIS-measurements of human fingers. The presented model serves as an important tool for understanding and development of HSI as an arthritis diagnostic modality. Yet, it can be applied to other optical techniques and finger diseases.

  14. A review on endocrine disruptors and their possible impacts on human health.

    PubMed

    Kabir, Eva Rahman; Rahman, Monica Sharfin; Rahman, Imon

    2015-07-01

    Endocrine disruption is a named field of research which has been very active for over 10 years, although the effects of endocrine disruptors in wildlife have been studied mainly in vast since the 1940s. A large number of chemicals have been identified as endocrine disruptors and humans can be exposed to them either due to their occupations or through dietary and environmental exposure (water, soil and air). Endocrine disrupting chemicals are compounds that alter the normal functioning of the endocrine system of both humans and wildlife. In order to understand the vulnerability and risk factors of people due to endocrine disruptors as well as the remedies for these, methods need to be developed in order to predict effects on populations and communities from the knowledge of effects on individuals. For several years there have been a growing interest on the mechanism and effect of endocrine disruptors and their relation with environment and human health effect. This paper, based on extensive literature survey, briefly studies the progress mainly in human to provide information concerning causative substances, mechanism of action, ubiquity of effects and important issues related to endocrine disruptors. It also reviews the current knowledge of the potential impacts of endocrine disruptors on human health so that the effects can be known and remedies applied for the problem as soon as possible. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. The expanding scope of air pollution monitoring can facilitate sustainable development.

    PubMed

    Knox, Andrew; Mykhaylova, Natalia; Evans, Greg J; Lee, Colin J; Karney, Bryan; Brook, Jeffrey R

    2013-03-15

    This paper explores technologies currently expanding the physical scope of air pollution monitoring and their potential contributions to the assessment of sustainable development. This potential lies largely in the ability of these technologies to address issues typically on the fringe of the air pollution agenda. Air pollution monitoring tends to be primarily focused on human health, and largely neglects other aspects of sustainable development. Sensor networks, with their relatively inexpensive monitoring nodes, allow for monitoring with finer spatiotemporal resolution. This resolution can support more conclusive studies of air pollution's effect on socio-ecological justice and human quality of life. Satellite observation of air pollution allows for wider geographical scope, and in doing so can facilitate studies of air pollution's effects on natural capital and ecosystem resilience. Many air pollution-related aspects of the sustainability of development in human systems are not being given their due attention. Opportunities exist for air pollution monitoring to attend more to these issues. Improvements to the resolution and scale of monitoring make these opportunities realizable. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. GeneStoryTeller: a mobile app for quick and comprehensive information retrieval of human genes.

    PubMed

    Eleftheriou, Stergiani V; Bourdakou, Marilena M; Athanasiadis, Emmanouil I; Spyrou, George M

    2015-01-01

    In the last few years, mobile devices such as smartphones and tablets have become an integral part of everyday life, due to their software/hardware rapid development, as well as the increased portability they offer. Nevertheless, up to now, only few Apps have been developed in the field of bioinformatics, capable to perform fast and robust access to services. We have developed the GeneStoryTeller, a mobile application for Android platforms, where users are able to instantly retrieve information regarding any recorded human gene, derived from eight publicly available databases, as a summary story. Complementary information regarding gene-drugs interactions, functional annotation and disease associations for each selected gene is also provided in the gene story. The most challenging part during the development of the GeneStoryTeller was to keep balance between storing data locally within the app and obtaining the updated content dynamically via a network connection. This was accomplished with the implementation of an administrative site where data are curated and synchronized with the application requiring a minimum human intervention. © The Author(s) 2015. Published by Oxford University Press.

  17. 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.

  18. Human nature: a foundation for palliative care.

    PubMed

    Whelton, Beverly J B

    2008-04-01

    The Aristotelian-Thomist philosopher holds that human intellectual knowledge is possible because of the order in the world and natural human capacities. It is the position of this paper that there is a shared human form or nature that unites all humanity as members of the same kind. Moral treatment is due to every human being because they are human, and is not based upon expression of abilities. Humans have substantial dynamic existence in the world, an existence which overflows in expressive relationships. As both patient and health professional are human, human nature forms the natural foundation of health care. This paper looks towards human nature for moral guidance. The therapeutic relationship is seen as a part of the interpersonal moral space formed by human relationality, which tends towards community - in this case, the healthcare system. The therapeutic relationship is also a source of moral responsibility, as illness makes the patient vulnerable, while knowledge and nursing capacities generate in the nurse a duty to care. Nursing theory serves to connect philosophical reflection and nursing practice. Imogene King's conceptual system and theory of Goal Attainment is the theory that follows from the perspective of human person being presented. This synthesis of philosophy and theory is developed with the goal of shedding light on healthcare decisions in palliative care. The article concludes with the acknowledgement that the complexity of contextualized individual decisions requires the insight and discipline of the moral practitioner, and provides some thoughts on how education, development, and refinement transform an individual into a nurse.

  19. Longitudinal analysis of the lung microbiota of cynomolgous macaques during long-term SHIV infection.

    PubMed

    Morris, Alison; Paulson, Joseph N; Talukder, Hisham; Tipton, Laura; Kling, Heather; Cui, Lijia; Fitch, Adam; Pop, Mihai; Norris, Karen A; Ghedin, Elodie

    2016-07-08

    Longitudinal studies of the lung microbiome are challenging due to the invasive nature of sample collection. In addition, studies of the lung microbiome in human disease are usually performed after disease onset, limiting the ability to determine early events in the lung. We used a non-human primate model to assess lung microbiome alterations over time in response to an HIV-like immunosuppression and determined impact of the lung microbiome on development of obstructive lung disease. Cynomolgous macaques were infected with the SIV-HIV chimeric virus SHIV89.6P. Bronchoalveolar lavage fluid samples were collected pre-infection and every 4 weeks for 53 weeks post-infection. The microbiota was characterized at each time point by 16S ribosomal RNA (rRNA) sequencing. We observed individual variation in the composition of the lung microbiota with a proportion of the macaques having Tropheryma whipplei as the dominant organism in their lungs. Bacterial communities varied over time both within and between animals, but there did not appear to be a systematic alteration due to SHIV infection. Development of obstructive lung disease in the SHIV-infected animals was characterized by a relative increase in abundance of oral anaerobes. Network analysis further identified a difference in community composition that accompanied the development of obstructive disease with negative correlations between members of the obstructed and non-obstructed groups. This emphasizes how species shifts can impact multiple other species, potentially resulting in disease. This study is the first to investigate the dynamics of the lung microbiota over time and in response to immunosuppression in a non-human primate model. The persistence of oral bacteria in the lung and their association with obstruction suggest a potential role in pathogenesis. The lung microbiome in the non-human primate is a valuable tool for examining the impact of the lung microbiome in human health and disease.

  20. Non-invasive Investigation of Human Hippocampal Rhythms Using Magnetoencephalography: A Review.

    PubMed

    Pu, Yi; Cheyne, Douglas O; Cornwell, Brian R; Johnson, Blake W

    2018-01-01

    Hippocampal rhythms are believed to support crucial cognitive processes including memory, navigation, and language. Due to the location of the hippocampus deep in the brain, studying hippocampal rhythms using non-invasive magnetoencephalography (MEG) recordings has generally been assumed to be methodologically challenging. However, with the advent of whole-head MEG systems in the 1990s and development of advanced source localization techniques, simulation and empirical studies have provided evidence that human hippocampal signals can be sensed by MEG and reliably reconstructed by source localization algorithms. This paper systematically reviews simulation studies and empirical evidence of the current capacities and limitations of MEG "deep source imaging" of the human hippocampus. Overall, these studies confirm that MEG provides a unique avenue to investigate human hippocampal rhythms in cognition, and can bridge the gap between animal studies and human hippocampal research, as well as elucidate the functional role and the behavioral correlates of human hippocampal oscillations.

  1. Non-invasive Investigation of Human Hippocampal Rhythms Using Magnetoencephalography: A Review

    PubMed Central

    Pu, Yi; Cheyne, Douglas O.; Cornwell, Brian R.; Johnson, Blake W.

    2018-01-01

    Hippocampal rhythms are believed to support crucial cognitive processes including memory, navigation, and language. Due to the location of the hippocampus deep in the brain, studying hippocampal rhythms using non-invasive magnetoencephalography (MEG) recordings has generally been assumed to be methodologically challenging. However, with the advent of whole-head MEG systems in the 1990s and development of advanced source localization techniques, simulation and empirical studies have provided evidence that human hippocampal signals can be sensed by MEG and reliably reconstructed by source localization algorithms. This paper systematically reviews simulation studies and empirical evidence of the current capacities and limitations of MEG “deep source imaging” of the human hippocampus. Overall, these studies confirm that MEG provides a unique avenue to investigate human hippocampal rhythms in cognition, and can bridge the gap between animal studies and human hippocampal research, as well as elucidate the functional role and the behavioral correlates of human hippocampal oscillations. PMID:29755314

  2. Effect of fiber distribution and realignment on the nonlinear and inhomogeneous mechanical properties of human supraspinatus tendon under longitudinal tensile loading.

    PubMed

    Lake, Spencer P; Miller, Kristin S; Elliott, Dawn M; Soslowsky, Louis J

    2009-12-01

    Tendon exhibits nonlinear stress-strain behavior that may be partly due to movement of collagen fibers through the extracellular matrix. While a few techniques have been developed to evaluate the fiber architecture of other soft tissues, the organizational behavior of tendon under load has not been determined. The supraspinatus tendon (SST) of the rotator cuff is of particular interest for investigation due to its complex mechanical environment and corresponding inhomogeneity. In addition, SST injury occurs frequently with limited success in treatment strategies, illustrating the need for a better understanding of SST properties. Therefore, the objective of this study was to quantitatively evaluate the inhomogeneous tensile mechanical properties, fiber organization, and fiber realignment under load of human SST utilizing a novel polarized light technique. Fiber distributions were found to become more aligned under load, particularly during the low stiffness toe-region, suggesting that fiber realignment may be partly responsible for observed nonlinear behavior. Fiber alignment was found to correlate significantly with mechanical parameters, providing evidence for strong structure-function relationships in tendon. Human SST exhibits complex, inhomogeneous mechanical properties and fiber distributions, perhaps due to its complex loading environment. Surprisingly, histological grade of degeneration did not correlate with mechanical properties.

  3. Modeling and Design of an Electro-Rheological Fluid Based Haptic System for Tele-Operation of Space Robots

    NASA Technical Reports Server (NTRS)

    Mavroidis, Constantinos; Pfeiffer, Charles; Paljic, Alex; Celestino, James; Lennon, Jamie; Bar-Cohen, Yoseph

    2000-01-01

    For many years, the robotic community sought to develop robots that can eventually operate autonomously and eliminate the need for human operators. However, there is an increasing realization that there are some tasks that human can perform significantly better but, due to associated hazards, distance, physical limitations and other causes, only robot can be employed to perform these tasks. Remotely performing these types of tasks requires operating robots as human surrogates. While current "hand master" haptic systems are able to reproduce the feeling of rigid objects, they present great difficulties in emulating the feeling of remote/virtual stiffness. In addition, they tend to be heavy, cumbersome and usually they only allow limited operator workspace. In this paper a novel haptic interface is presented to enable human-operators to "feel" and intuitively mirror the stiffness/forces at remote/virtual sites enabling control of robots as human-surrogates. This haptic interface is intended to provide human operators intuitive feeling of the stiffness and forces at remote or virtual sites in support of space robots performing dexterous manipulation tasks (such as operating a wrench or a drill). Remote applications are referred to the control of actual robots whereas virtual applications are referred to simulated operations. The developed haptic interface will be applicable to IVA operated robotic EVA tasks to enhance human performance, extend crew capability and assure crew safety. The electrically controlled stiffness is obtained using constrained ElectroRheological Fluids (ERF), which changes its viscosity under electrical stimulation. Forces applied at the robot end-effector due to a compliant environment will be reflected to the user using this ERF device where a change in the system viscosity will occur proportionally to the force to be transmitted. In this paper, we will present the results of our modeling, simulation, and initial testing of such an electrorheological fluid (ERF) based haptic device.

  4. Testicular growth and development in puberty.

    PubMed

    Koskenniemi, Jaakko J; Virtanen, Helena E; Toppari, Jorma

    2017-06-01

    To describe pubertal testicular growth in humans, changes in testicular cell populations that result in testicular growth, and the role of testosterone and gonadotrophins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in testicular growth. When human data were not available, studies in nonhuman primates and/or rodents were used as surrogates. Testicular growth in puberty follows a sigmoidal growth curve, with a large variation in timing of testicular growth and adult testicular volume. Testicular growth early in puberty is due to increase in Sertoli cell number and length of seminiferous tubules, whereas the largest and fastest growth results from the increase in the diameter of the seminiferous tubules first due to spermatogonial proliferation and then due to the expansion of meiotic and haploid germ cells. FSH stimulates Sertoli cell and spermatogonial proliferation, whereas LH/testosterone is mandatory to complete spermatogenesis. However, FSH and LH/testosterone work in synergy and are both needed for normal spermatogenesis. Testicular growth during puberty is rapid, and mostly due to germ cell expansion and growth in seminiferous tubule diameter triggered by androgens. Pre-treatment with FSH before the induction of puberty may improve the treatment of hypogonadotropic hypogonadism, but remains to be proven.

  5. Review of the physiology of human thermal comfort while exercising in urban landscapes and implications for bioclimatic design.

    PubMed

    Vanos, Jennifer K; Warland, Jon S; Gillespie, Terry J; Kenny, Natasha A

    2010-07-01

    This review comprehensively examines scientific literature pertaining to human physiology during exercise, including mechanisms of heat formation and dissipation, heat stress on the body, the importance of skin temperature monitoring, the effects of clothing, and microclimatic measurements. This provides a critical foundation for microclimatologists and biometeorologists in the understanding of experiments involving human physiology. The importance of the psychological aspects of how an individual perceives an outdoor environment are also reviewed, emphasizing many factors that can indirectly affect thermal comfort (TC). Past and current efforts to develop accurate human comfort models are described, as well as how these models can be used to develop resilient and comfortable outdoor spaces for physical activity. Lack of suitable spaces plays a large role in the deterioration of human health due to physical inactivity, leading to higher rates of illness, heart disease, obesity and heat-related casualties. This trend will continue if urban designers do not make use of current knowledge of bioclimatic urban design, which must be synthesized with physiology, psychology and microclimatology. Increased research is required for furthering our knowledge on the outdoor human energy balance concept and bioclimatic design for health and well-being in urban areas.

  6. Review of the physiology of human thermal comfort while exercising in urban landscapes and implications for bioclimatic design

    NASA Astrophysics Data System (ADS)

    Vanos, Jennifer K.; Warland, Jon S.; Gillespie, Terry J.; Kenny, Natasha A.

    2010-07-01

    This review comprehensively examines scientific literature pertaining to human physiology during exercise, including mechanisms of heat formation and dissipation, heat stress on the body, the importance of skin temperature monitoring, the effects of clothing, and microclimatic measurements. This provides a critical foundation for microclimatologists and biometeorologists in the understanding of experiments involving human physiology. The importance of the psychological aspects of how an individual perceives an outdoor environment are also reviewed, emphasizing many factors that can indirectly affect thermal comfort (TC). Past and current efforts to develop accurate human comfort models are described, as well as how these models can be used to develop resilient and comfortable outdoor spaces for physical activity. Lack of suitable spaces plays a large role in the deterioration of human health due to physical inactivity, leading to higher rates of illness, heart disease, obesity and heat-related casualties. This trend will continue if urban designers do not make use of current knowledge of bioclimatic urban design, which must be synthesized with physiology, psychology and microclimatology. Increased research is required for furthering our knowledge on the outdoor human energy balance concept and bioclimatic design for health and well-being in urban areas.

  7. FRamework Assessing Notorious Contributing Influences for Error (FRANCIE): Perspective on Taxonomy Development to Support Error Reporting and Analysis

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

    Lon N. Haney; David I. Gertman

    2003-04-01

    Beginning in the 1980s a primary focus of human reliability analysis was estimation of human error probabilities. However, detailed qualitative modeling with comprehensive representation of contextual variables often was lacking. This was likely due to the lack of comprehensive error and performance shaping factor taxonomies, and the limited data available on observed error rates and their relationship to specific contextual variables. In the mid 90s Boeing, America West Airlines, NASA Ames Research Center and INEEL partnered in a NASA sponsored Advanced Concepts grant to: assess the state of the art in human error analysis, identify future needs for human errormore » analysis, and develop an approach addressing these needs. Identified needs included the need for a method to identify and prioritize task and contextual characteristics affecting human reliability. Other needs identified included developing comprehensive taxonomies to support detailed qualitative modeling and to structure meaningful data collection efforts across domains. A result was the development of the FRamework Assessing Notorious Contributing Influences for Error (FRANCIE) with a taxonomy for airline maintenance tasks. The assignment of performance shaping factors to generic errors by experts proved to be valuable to qualitative modeling. Performance shaping factors and error types from such detailed approaches can be used to structure error reporting schemes. In a recent NASA Advanced Human Support Technology grant FRANCIE was refined, and two new taxonomies for use on space missions were developed. The development, sharing, and use of error taxonomies, and the refinement of approaches for increased fidelity of qualitative modeling is offered as a means to help direct useful data collection strategies.« less

  8. Military Androids: A Vision for Human Replacement in 2035

    DTIC Science & Technology

    2010-01-01

    but has the potential to accelerate exponentially over the next twenty-five years due to reasons such as advancements in technology and aversion to...because of the enabling technologies associated with it. Asimo is capable of semi-autonomous operations and continued development will expand those...such as Moore’s Law or the Law of Accelerating Returns that attempt to account for the pace of technological improvements. Moore’s Law, developed by

  9. Inverness College: Innovations in Aquaculture Training.

    ERIC Educational Resources Information Center

    Regional Technology Strategies, Inc., Carrboro, NC.

    This paper describes the aquaculture program developed at Inverness College in Scotland. Inverness is located in the Scottish Highlands and serves an area roughly the size of Belgium, but with a population of only 300,000. The regional infrastructure and human capital resources in the Highlands are relatively weak due to inadequate transportation,…

  10. Improving restoration to control plant invasions under climate change

    Treesearch

    Qinfeng Guo; Steve Norman

    2012-01-01

    Native forests and grasslands worldwide have been converted to developed lands or invaded by exotic species due to human activities. These pressures are predicted to increase with population growth and climatic stress in coming decades, escalating concerns for the viability of native species and communities that are affected. Ecological restoration is frequently...

  11. Climate Change Impacts on Human Health Due to Changes in Ambient Ozone Concentrations (External Review Draft)

    EPA Science Inventory

    This report uses results from a previous report titled Assessment of the Impacts of Global Change on Regional U.S. Air Quality: A Synthesis of Climate Change Impacts on Ground-Level Ozone, a number of high-resolution, spatially explicit population projections developed ...

  12. The Impact of Interstate Migration on Human Capital Development in Washington

    ERIC Educational Resources Information Center

    Spaulding, Randy

    2010-01-01

    Washington State is a leader in the innovation economy largely due to the combination of aerospace, software, and biomedical industries centered in the greater Seattle area; and, the state's high level of international trade. Despite Washington's national ranking, the state is overly reliant on importing educated workers from other states and…

  13. Evaluation of Training in Organisations: A Proposal for an Integrated Model

    ERIC Educational Resources Information Center

    Pineda, Pilar

    2010-01-01

    Purpose: Training is a key strategy for human resources development and in achieving organisational objectives. Organisations and public authorities invest large amounts of resources in training, but rarely have the data to show the results of that investment. Only a few organisations evaluate training in depth due to the difficulty involved and…

  14. 45 CFR 1355.36 - Withholding Federal funds due to failure to achieve substantial conformity or failure to...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON CHILDREN, YOUTH AND FAMILIES, FOSTER CARE MAINTENANCE PAYMENTS, ADOPTION ASSISTANCE, AND CHILD AND FAMILY SERVICES GENERAL... foster care program under title IV-E. (b) Determination of the amount of Federal funds to be withheld...

  15. Re-Engineering Academic Library Services: The Case of the Technical Knowledge Center & Library of Denmark.

    ERIC Educational Resources Information Center

    Bjoernshauge, Lars

    The traditional mode of operation of academic libraries is in crisis due to a combination of zero growth funding, rapidly escalating pricing on information resources (especially scientific journals), necessary investments in technology and human resource development, and increasing customer expectations. These issues are addressed as they relate…

  16. 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…

  17. SUBCHRONIC TOXICITY OF INHALED TOLUENE IN RATS: IMMUNOLOGY, CARDIAC GENE EXPRESSION AND MARKERS OF OXIDATIVE STRESS.

    EPA Science Inventory

    The health effects of long-term exposure to volatile organic compounds (VOCs) are poorly understood, due primarily to insufficient human exposure data and inconsistent animal models. To develop a rodent model of long-term exposure to VOCs, a sub-chronic inhalation study with mult...

  18. Novel Informatic Approaches to Analyze Gene Expression Data with the ToxCast 320 Chemical Library in Cultures of Primary Human Hepatocytes

    EPA Science Inventory

    Prevailing methodologies in the analysis of gene expression data often neglect to incorporate full concentration and time response due to limitations in throughput and sensitivity with traditional microarray approaches. We have developed a high throughput assay suite using primar...

  19. A research review on clinical needs, technical requirements, and normativity in the design of surgical robots.

    PubMed

    Díaz, Carlos Eduardo; Fernández, Roemi; Armada, Manuel; García, Felipe

    2017-12-01

    Nowadays robots play an important role in society, mainly due to the significant benefits they provide when utilized for assisting human beings in the execution of dangerous or repetitive tasks. Medicine is one of the fields in which robots are gaining greater use and development, especially those employed in minimally invasive surgery (MIS). However, due to the particular conditions of the human body where robots have to act, the design of these systems is complex, not only from a technical point of view, but also because the clinical needs and the normativity aspects are important considerations that have to be taken into account in order to achieve better performances and more secure systems for patients and surgeons. Thus, this paper explores the clinical needs and the technical requirements that will trace the roadmap for the next scientific and technological advances in the field of robotic surgery, the metrics that should be defined for safe technology development and the standards that are being elaborated for boosting the industry and facilitating systems integration. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Elbow functional compensation using a lightweight magnetorheological clutch.

    PubMed

    Clemente, Alejandro Martín; Caballero, Antonio Flores; Rojas, Dolores Blanco; Copaci, Dorin-Sabin; Lorente, Luis Moreno

    2011-01-01

    There are many applications for which a patient needs functional compensation due to motor disorders in daily activities. Classic research has focused on robotics solutions in terms of actuators or motors, but the point of this paper is to analyze new solutions combining both biological and artificial structures, in order to improve standard developments. Nowadays wearable Robots are taking an important role in rehabilitation purposes, due to this issue lots of new designs are emerging, but most of them are not still prepared to be used in terms of autonomy, weight, etc. Under the Hybrid Neuroprosthetic and Neurorobotic devices for Functional Compensation and Rehabilitation (HYPER) project, new actuator technologies have been developed in order to improve the adaptability and portability of rehabilitation devices. The designed device is based on a lightweight magnetorheological (MR) clutch which is able to transmit torque from a motor to the injured joint. Though it is intended to work in human upper limb (elbow mainly), other future designs will also be studied for other human joints. Simulation results using Simulink®, MSC Adams®and MSMS®are reported to illustrate the viability of the proposed device.

  1. Metabolic enzyme microarray coupled with miniaturized cell-culture array technology for high-throughput toxicity screening.

    PubMed

    Lee, Moo-Yeal; Dordick, Jonathan S; Clark, Douglas S

    2010-01-01

    Due to poor drug candidate safety profiles that are often identified late in the drug development process, the clinical progression of new chemical entities to pharmaceuticals remains hindered, thus resulting in the high cost of drug discovery. To accelerate the identification of safer drug candidates and improve the clinical progression of drug candidates to pharmaceuticals, it is important to develop high-throughput tools that can provide early-stage predictive toxicology data. In particular, in vitro cell-based systems that can accurately mimic the human in vivo response and predict the impact of drug candidates on human toxicology are needed to accelerate the assessment of drug candidate toxicity and human metabolism earlier in the drug development process. The in vitro techniques that provide a high degree of human toxicity prediction will be perhaps more important in cosmetic and chemical industries in Europe, as animal toxicity testing is being phased out entirely in the immediate future.We have developed a metabolic enzyme microarray (the Metabolizing Enzyme Toxicology Assay Chip, or MetaChip) and a miniaturized three-dimensional (3D) cell-culture array (the Data Analysis Toxicology Assay Chip, or DataChip) for high-throughput toxicity screening of target compounds and their metabolic enzyme-generated products. The human or rat MetaChip contains an array of encapsulated metabolic enzymes that is designed to emulate the metabolic reactions in the human or rat liver. The human or rat DataChip contains an array of 3D human or rat cells encapsulated in alginate gels for cell-based toxicity screening. By combining the DataChip with the complementary MetaChip, in vitro toxicity results are obtained that correlate well with in vivo rat data.

  2. A Bioinspired Mineral Hydrogel as a Self-Healable, Mechanically Adaptable Ionic Skin for Highly Sensitive Pressure Sensing.

    PubMed

    Lei, Zhouyue; Wang, Quankang; Sun, Shengtong; Zhu, Wencheng; Wu, Peiyi

    2017-06-01

    In the past two decades, artificial skin-like materials have received increasing research interests for their broad applications in artificial intelligence, wearable devices, and soft robotics. However, profound challenges remain in terms of imitating human skin because of its unique combination of mechanical and sensory properties. In this work, a bioinspired mineral hydrogel is developed to fabricate a novel type of mechanically adaptable ionic skin sensor. Due to its unique viscoelastic properties, the hydrogel-based capacitive sensor is compliant, self-healable, and can sense subtle pressure changes, such as a gentle finger touch, human motion, or even small water droplets. It might not only show great potential in applications such as artificial intelligence, human/machine interactions, personal healthcare, and wearable devices, but also promote the development of next-generation mechanically adaptable intelligent skin-like devices. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Linking salmon aquaculture synergies and trade-offs on ecosystem services to human wellbeing constituents.

    PubMed

    Outeiro, Luis; Villasante, Sebastian

    2013-12-01

    Salmon aquaculture has emerged as a successful economic industry generating high economic revenues to invest in the development of Chiloe region, Southern Chile. However, salmon aquaculture also consumes a substantial amount of ecosystem services, and the direct and indirect impacts on human wellbeing are still unknown and unexplored. This paper identifies the synergies and trade-offs caused by the salmon industry on a range of ecosystem services. The results show that large economic benefits due to the increase of provisioning ecosystem services are also causing a reduction on regulating and cultural services. Despite the improvement on average income and poverty levels experienced in communities closely associated with the sector, this progress is not large enough and social welfare did not improve substantially over the last decade. The rest of human wellbeing constituents in Chiloe region have not changed significantly compared to the development in the rest of the country.

  4. Space medicine research: Needs for the 21st century

    NASA Technical Reports Server (NTRS)

    Pepper, L. J.

    1992-01-01

    Space medicine research in the 21st century will continue to focus on the four major areas including: (1) expansion of the current incomplete knowledge base of clinical and subclinical physiological changes due to microgravity; (2) development of countermeasures to extend the capabilities of the human performance envelope in extended duration flights; (3) development of novel methods for delivering all aspects of a comprehensive health care system in extreme remote conditions: and (4) further research and application of systems for biological materials processing. New space transportation vehicles will place unique physiologic and human factors demands on the human system, while providing better access to platforms for materials processing. Success in meeting the demands in each of the noted research areas will require an extensive, interactive team approach. Personnel from the medical research,operational, developmental, and basic science communities will be essential to success.

  5. Cloning and transgenesis in mammals: implications for xenotransplantation.

    PubMed

    Piedrahita, Jorge A; Mir, Bashir

    2004-01-01

    Availability of suitable organs for transplantation remains of major concern and projections indicate that the problem will continue to increase. Therefore, alternatives to the use of human organs for transplantation, continue to be explored including use of stem cells, artificial organs, and organs from other species (xenotransplantation). In xenotransplantation, the species of choice remains the pig due to its physiological similarities to humans, reduced costs, ease of manipulation, and reduced ethical concerns to its use. However, in order to develop pig organs that are suitable for xenotransplantation, complex genetic modification need to be undertaken. These modifications require the introduction of precise genetic changes into the pig that can only be accomplished at this time using somatic cell nuclear transfer. We cover in this review advances in transgenic manipulation and cloning in swine and how the development of these two technologies is critical to the eventual utilization of the pig as a human organ donor.

  6. Could viruses contribute to the worldwide epidemic of obesity?

    PubMed

    Atkinson, Richard L

    2008-01-01

    The prevalence of obesity in children increased rapidly starting about 1980 in both developed and developing countries. Studies of changes in diet and physical activity, television watching, and food advertisements on television suggest that these are not sufficient to explain the epidemic. The pattern of rapid spread is suggestive of an infectious origin. The concept of virus-induced obesity is not new. Eight viruses have been shown to cause obesity in animals and there is evidence for virus-induced obesity in humans. Recent evidence on animal and human adenoviruses suggests that these adenoviruses may infect adipocytes to alter enzymes and transcription factors resulting in accumulation of triglycerides and differentiation of preadipocytes into mature adipocytes. The E4orf1 gene of Ad-36 has been shown to be responsible for the adipogenic effect. It appears that a portion of the worldwide epidemic of obesity since 1980 could be due to infections with human adenoviruses.

  7. Large Mammalian Animal Models of Heart Disease

    PubMed Central

    Camacho, Paula; Fan, Huimin; Liu, Zhongmin; He, Jia-Qiang

    2016-01-01

    Due to the biological complexity of the cardiovascular system, the animal model is an urgent pre-clinical need to advance our knowledge of cardiovascular disease and to explore new drugs to repair the damaged heart. Ideally, a model system should be inexpensive, easily manipulated, reproducible, a biological representative of human disease, and ethically sound. Although a larger animal model is more expensive and difficult to manipulate, its genetic, structural, functional, and even disease similarities to humans make it an ideal model to first consider. This review presents the commonly-used large animals—dog, sheep, pig, and non-human primates—while the less-used other large animals—cows, horses—are excluded. The review attempts to introduce unique points for each species regarding its biological property, degrees of susceptibility to develop certain types of heart diseases, and methodology of induced conditions. For example, dogs barely develop myocardial infarction, while dilated cardiomyopathy is developed quite often. Based on the similarities of each species to the human, the model selection may first consider non-human primates—pig, sheep, then dog—but it also depends on other factors, for example, purposes, funding, ethics, and policy. We hope this review can serve as a basic outline of large animal models for cardiovascular researchers and clinicians. PMID:29367573

  8. Exurban Development and its Environmental Impact on Land Use in Kurgan City, Russia

    NASA Astrophysics Data System (ADS)

    Andrievskikh, Daria

    Exurban communities as one of the forms of urban sprawl can cause significant changes in natural land cover. Exurban development refers to an expansion of communities located outside a city and its suburbs. One of the main reasons these settlements develop is a desire to live closer to nature with better ecological conditions. Exurbs often represent prosperous regions inhabited by people with high income. However, exurban development involves the human consumption of natural environments. Specifically, it directly affects community patterns, species patterns, and demographic patterns of surrounding ecosystems, as well as land use. Therefore, it is important to study the impact of exurban settlements on the natural environment. This study uses remote sensing imagery, Census data and primary data to analyze land cover change due to the emergence of exurban communities around Kurgan City, Russia, with an emphasis on the change of natural vegetation such as, forests in addition to human behavior.

  9. Impacts of sanitation improvement on reduction of nitrogen discharges entering the environment from human excreta in China.

    PubMed

    Tong, Yindong; Bu, Xiaoge; Chen, Cen; Yang, Xi; Lu, Yiren; Liang, Huijiao; Liu, Maodian; Lin, Huiming; Zhang, Haoran; Lin, Yan; Zhou, Feng; Zhao, Shen; Wu, Tianyu; Mao, Guozhu; Zhang, Wei; Wang, Xuejun

    2017-09-01

    Identifying the sanitation efficacy in reducing contaminations entering the environment is an important step for water pollution controls and developing management strategies to further improve sanitation conditions. With continuous efforts in sanitation improvement during the past decade, reductions in discharges of aquatic nutrients are expected in China. In this study, we estimated the aquatic nitrogen discharges from human excreta in 31 provinces in China during 2006-2014. The results indicated that the nitrogen discharges entering the environment from human excreta are largely determined by both local population and sanitation conditions. In 2014, the nitrogen discharges from human excreta in the rural areas (2118(1219-3140) Gg per year) (median and 95% confidence interval) are higher than those in the urban areas (1485(626-2495) Gg per year). The significant relationship (R 2 =0.38, n=29) between the total nitrogen concentrations in lakes and corresponding local nitrogen discharges indicated that, the lakes might be potentially affected by the contaminant inputs from human excreta. The further calculations under two policy scenarios showed that through sanitation improvement, further reduction of nitrogen discharges from human excreta in the developed regions might be limited. The sanitation improvement in the less-developed regions, such as Tibet, Qinghai, and Ningxia, should be considered a priority due to the larger reduction potentials. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Analysis of human induced changes in a karst landscape - the filling of dolines in the Kras plateau, Slovenia.

    PubMed

    Kovačič, Gregor; Ravbar, Nataša

    2013-03-01

    A comprehensive analysis of the increased pressure on karst landscapes due to expansive economic and urban development is presented with the aim of evaluating changes in land use and their deleterious effects on karst relief forms. The study focuses on two areas surrounding the relatively quickly growing settlements of Hrpelje-Kozina and Divača on the Kras plateau (Slovenia) that have been subjected to intensive urban and business development and traffic since the motorway was brought to their vicinity fifteen years ago. National legislation loopholes and technological improvement were the cause of the commonly unsupervised human encroachment which caused the widespread degradation of the landscape. By comparing different topographical and ortophotographical materials from the past four decades and by detailed field inspection of land use and environmental changes, as well as the morphometrical characterization of dolines, the following results have been found: due to the population growth in the past four decades (39% and 50%, respectively), an increase of settlement area by 18 and 11 percentage points took place. Consequently, between 25 and 27% of dolines have disappeared or have been extensively modified (filled up and leveled). According to the local spatial plans, an additional 18% to 28% dolines are endangered. Broad human induced changes in the karst landscape have resulted in a noticeable increase in landscape deterioration, which is consistent with similar phenomena observed in other regions. Due to the extreme susceptibility of the karst to human activities that may lead to the degradation of its exceptional esthetic and environmental value, the alteration of karst processes such as corrosion, endangering of unique habitats and the quality of non-renewable natural resources, it is necessary to promptly define measures for its protection at the national level. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. [Human pharynx microflora as the indicator of resistance of human organisms].

    PubMed

    Lankina, M V

    2002-01-01

    The analysis of the results of 220 microbiological investigations of the aerobic microflora of the pharynx mucosa in males made it possible to divide the pharynx microbiocenosis of adults into normocenosis of the I, II, III orders and dysbacteriosis of the I, II, III degrees. The use of this division for the determination of the reaction of nonspecific resistance was proposed. The possibility of using it for the diagnostics of health disturbances of sportsmen-servicemen developing due to strains characteristic for modern sport and military service, was shown.

  12. Genetic enhancement of cognition in a kindred with cone–rod dystrophy due to RIMS1 mutation

    PubMed Central

    Sisodiya, Sanjay M; Thompson, Pamela J; Need, Anna; Harris, Sarah E; Weale, Michael E; Wilkie, Susan E; Michaelides, Michel; Free, Samantha L; Walley, Nicole; Gumbs, Curtis; Gerrelli, Dianne; Ruddle, Piers; Whalley, Lawrence J; Starr, John M; Hunt, David M; Goldstein, David B; Deary, Ian J; Moore, Anthony T

    2007-01-01

    Background The genetic basis of variation in human cognitive abilities is poorly understood. RIMS1 encodes a synapse active‐zone protein with important roles in the maintenance of normal synaptic function: mice lacking this protein have greatly reduced learning ability and memory function. Objective An established paradigm examining the structural and functional effects of mutations in genes expressed in the eye and the brain was used to study a kindred with an inherited retinal dystrophy due to RIMS1 mutation. Materials and methods Neuropsychological tests and high‐resolution MRI brain scanning were undertaken in the kindred. In a population cohort, neuropsychological scores were associated with common variation in RIMS1. Additionally, RIMS1 was sequenced in top‐scoring individuals. Evolution of RIMS1 was assessed, and its expression in developing human brain was studied. Results Affected individuals showed significantly enhanced cognitive abilities across a range of domains. Analysis suggests that factors other than RIMS1 mutation were unlikely to explain enhanced cognition. No association with common variation and verbal IQ was found in the population cohort, and no other mutations in RIMS1 were detected in the highest scoring individuals from this cohort. RIMS1 protein is expressed in developing human brain, but RIMS1 does not seem to have been subjected to accelerated evolution in man. Conclusions A possible role for RIMS1 in the enhancement of cognitive function at least in this kindred is suggested. Although further work is clearly required to explore these findings before a role for RIMS1 in human cognition can be formally accepted, the findings suggest that genetic mutation may enhance human cognition in some cases. PMID:17237123

  13. Residential development alters behavior, movement, and energetics in an apex predator, the puma

    PubMed Central

    Wang, Yiwei; Wilmers, Christopher C.

    2017-01-01

    Human development strongly influences large carnivore survival and persistence globally. Behavior changes are often the first measureable responses to human disturbances, and can have ramifications on animal populations and ecological communities. We investigated how a large carnivore responds to anthropogenic disturbances by measuring activity, movement behavior, and energetics in pumas along a housing density gradient. We used log-linear analyses to examine how habitat, time of day, and proximity to housing influenced the activity patterns of both male and female pumas in the Santa Cruz Mountains. We used spatial GPS location data in combination with Overall Dynamic Body Acceleration measurements recorded by onboard accelerometers to quantify how development density affected the average distances traveled and energy expended by pumas. Pumas responded to development differently depending on the time of day; at night, they were generally more active and moved further when they were in developed areas, but these relationships were not consistent during the day. Higher nighttime activity in developed areas increased daily caloric expenditure by 10.1% for females and 11.6% for males, resulting in increases of 3.4 and 4.0 deer prey required annually by females and males respectively. Our results support that pumas have higher energetic costs and resource requirements in human-dominated habitats due to human-induced behavioral change. Increased energetic costs for pumas are likely to have ramifications on prey species and exacerbate human-wildlife conflict, especially as exurban growth continues. Future conservation work should consider the consequences of behavioral shifts on animal energetics, individual fitness, and population viability. PMID:29020087

  14. Development and Function of the Human Fetal Adrenal Cortex: A Key Component in the Feto-Placental Unit

    PubMed Central

    Ishimoto, Hitoshi

    2011-01-01

    Continuous efforts have been devoted to unraveling the biophysiology and development of the human fetal adrenal cortex, which is structurally and functionally unique from other species. It plays a pivotal role, mainly through steroidogenesis, in the regulation of intrauterine homeostasis and in fetal development and maturation. The steroidogenic activity is characterized by early transient cortisol biosynthesis, followed by its suppressed synthesis until late gestation, and extensive production of dehydroepiandrosterone and its sulfate, precursors of placental estrogen, during most of gestation. The gland rapidly grows through processes including cell proliferation and angiogenesis at the gland periphery, cellular migration, hypertrophy, and apoptosis. Recent studies employing modern technologies such as gene expression profiling and laser capture microdissection have revealed that development and/or function of the fetal adrenal cortex may be regulated by a panoply of molecules, including transcription factors, extracellular matrix components, locally produced growth factors, and placenta-derived CRH, in addition to the primary regulator, fetal pituitary ACTH. The role of the fetal adrenal cortex in human pregnancy and parturition appears highly complex, probably due to redundant and compensatory mechanisms regulating these events. Mounting evidence indicates that actions of hormones operating in the human feto-placental unit are likely mediated by mechanisms including target tissue responsiveness, local metabolism, and bioavailability, rather than changes only in circulating levels. Comprehensive study of such molecular mechanisms and the newly identified factors implicated in adrenal development should help crystallize our understanding of the development and physiology of the human fetal adrenal cortex. PMID:21051591

  15. Chemically induced skin carcinogenesis: Updates in experimental models (Review)

    PubMed Central

    NEAGU, MONICA; CARUNTU, CONSTANTIN; CONSTANTIN, CAROLINA; BODA, DANIEL; ZURAC, SABINA; SPANDIDOS, DEMETRIOS A.; TSATSAKIS, ARISTIDIS M.

    2016-01-01

    Skin cancer is one of the most common malignancies affecting humans worldwide, and its incidence is rapidly increasing. The study of skin carcinogenesis is of major interest for both scientific research and clinical practice and the use of in vivo systems may facilitate the investigation of early alterations in the skin and of the mechanisms involved, and may also lead to the development of novel therapeutic strategies for skin cancer. This review outlines several aspects regarding the skin toxicity testing domain in mouse models of chemically induced skin carcinogenesis. There are important strain differences in view of the histological type, development and clinical evolution of the skin tumor, differences reported decades ago and confirmed by our hands-on experience. Using mouse models in preclinical testing is important due to the fact that, at the molecular level, common mechanisms with human cutaneous tumorigenesis are depicted. These animal models resemble human skin cancer development, in that genetic changes caused by carcinogens and pro-inflammatory cytokines, and simultaneous inflammation sustained by pro-inflammatory cytokines and chemokines favor tumor progression. Drugs and environmental conditions can be tested using these animal models. keeping in mind the differences between human and rodent skin physiology. PMID:26986013

  16. Human papilloma virus and lupus: the virus, the vaccine and the disease.

    PubMed

    Segal, Yahel; Calabrò, Michele; Kanduc, Darja; Shoenfeld, Yehuda

    2017-07-01

    Systemic lupus erythematosus (SLE) is a well known, widespread autoimmune disease, involving multiple organ systems, with a multifaceted, widely unmapped etiopathogenesis. Recently, a new aspect of morbidity has been described among SLE patients: infection with human papilloma virus (HPV). We set out to review data regarding the intricate relationship between the two and attempt to determine whether HPV may pose as a contributing factor to the development of SLE. We relate to epidemiological, molecular and clinical data. We have found evidence in all these fields suggesting HPV to be involved in the pathogenesis of SLE: increased prevalence of HPV infection among SLE patients; vast molecular homology between viral peptides and human proteins associated with SLE; several reports of SLE development post-HPV vaccination. Our findings suggest a possible involvement of HPV infection in the induction of SLE, via a mechanism of immune cross-reaction due to molecular homology. We review clinical, epidemiological and molecular data suggesting involvement of HPV infection in the pathogenesis of SLE. We suggest that these findings may justify the development of new HPV vaccines containing viral peptides that bear no homology to the human proteome, in order to avoid possible adverse immune cross-reactivity.

  17. Influence of probe pressure on diffuse reflectance spectra of human skin measured in vivo

    NASA Astrophysics Data System (ADS)

    Popov, Alexey P.; Bykov, Alexander V.; Meglinski, Igor V.

    2017-11-01

    Mechanical pressure superficially applied on the human skin surface by a fiber-optic probe influences the spatial distribution of blood within the cutaneous tissues. Upon gradual load of weight on the probe, a stepwise increase in the skin reflectance spectra is observed. The decrease in the load follows the similar inverse staircase-like tendency. The observed stepwise reflectance spectra changes are due to, respectively, sequential extrusion of blood from the topical cutaneous vascular beds and their filling afterward. The obtained results are confirmed by Monte Carlo modeling. This implies that pressure-induced influence during the human skin diffuse reflectance spectra measurements in vivo should be taken into consideration, in particular, in the rapidly developing area of wearable gadgets for real-time monitoring of various human body parameters.

  18. Finite-element modeling of the human neurocranium under functional anatomical aspects.

    PubMed

    Mall, G; Hubig, M; Koebke, J; Steinbuch, R

    1997-08-01

    Due to its functional significance the human skull plays an important role in biomechanical research. The present work describes a new Finite-Element model of the human neurocranium. The dry skull of a middle-aged woman served as a pattern. The model was developed using only the preprocessor (Mentat) of a commercial FE-system (Marc). Unlike that of other FE models of the human skull mentioned in the literature, the geometry in this model was designed according to functional anatomical findings. Functionally important morphological structures representing loci minoris resistentiae, especially the foramina and fissures of the skull base, were included in the model. The results of two linear static loadcase analyses in the region of the skull base underline the importance of modeling from the functional anatomical point of view.

  19. Developing Hydrogeological Site Characterization Strategies based on Human Health Risk

    NASA Astrophysics Data System (ADS)

    de Barros, F.; Rubin, Y.; Maxwell, R. M.

    2013-12-01

    In order to provide better sustainable groundwater quality management and minimize the impact of contamination in humans, improved understanding and quantification of the interaction between hydrogeological models, geological site information and human health are needed. Considering the joint influence of these components in the overall human health risk assessment and the corresponding sources of uncertainty aid decision makers to better allocate resources in data acquisition campaigns. This is important to (1) achieve remediation goals in a cost-effective manner, (2) protect human health and (3) keep water supplies clean in order to keep with quality standards. Such task is challenging since a full characterization of the subsurface is unfeasible due to financial and technological constraints. In addition, human exposure and physiological response to contamination are subject to uncertainty and variability. Normally, sampling strategies are developed with the goal of reducing uncertainty, but less often they are developed in the context of their impacts on the overall system uncertainty. Therefore, quantifying the impact from each of these components (hydrogeological, behavioral and physiological) in final human health risk prediction can provide guidance for decision makers to best allocate resources towards minimal prediction uncertainty. In this presentation, a multi-component human health risk-based framework is presented which allows decision makers to set priorities through an information entropy-based visualization tool. Results highlight the role of characteristic length-scales characterizing flow and transport in determining data needs within an integrated hydrogeological-health framework. Conditions where uncertainty reduction in human health risk predictions may benefit from better understanding of the health component, as opposed to a more detailed hydrogeological characterization, are also discussed. Finally, results illustrate how different dose-response models can impact the probability of human health risk exceeding a regulatory threshold.

  20. Assessing impacts of oil-shale development on the Piceance Basin mule deer herd

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

    White, G.C.; Garrott, R.A.

    Development of energy resources on big game ranges generally negatively impacts these important wildlife resources. Although habitat disturbance is generally important, this impact is overshadowed by the negative impacts due to an increasing human population in the area. Increased human activities particularly stress animals during winter periods when inadequate nutrition levels may have already severely impacted the population. Increased road traffic and poaching causes additional deaths, which a decline in survival rates expected, or at least changes in the cause of mortality. This paper describes the experimental design to monitor and mitigate the impact of oil shale development in northwesternmore » Colorado on the Piceance Basin mule deer herd. Biotelemetry techniques are used to measure changes through time in movements, habitat utilization, and survival rates between control and treatment areas. 2 figures.« less

  1. 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.

  2. Organ-on-a-chip: development and clinical prospects toward toxicity assessment with an emphasis on bone marrow.

    PubMed

    Kim, Jeehye; Lee, Hanna; Selimović, Šeila; Gauvin, Robert; Bae, Hojae

    2015-05-01

    Conventional approaches for toxicity evaluation of drugs and chemicals, such as animal tests, can be impractical due to the large experimental scale and the immunological differences between species. Organ-on-a-chip models have recently been recognized as a prominent alternative to conventional toxicity tests aiming to simulate the human in vivo physiology. This review focuses on the organ-on-a-chip applications for high-throughput screening of candidate drugs against toxicity, with a particular emphasis on bone-marrow-on-a-chip. Studies in which organ-on-a-chip models have been developed and utilized to maximize the efficiency and predictability in toxicity assessment are introduced. The potential of these devices to replace tests of acute systemic toxicity in animals, and the challenges that are inherent in simulating the human immune system are also discussed. As a promising approach to overcome the limitations, we further focus on an in-depth analysis of the development of bone-marrow-on-a-chip that is capable of simulating human immune responses against external stimuli due to the key roles of marrow in immune systems with hematopoietic activities. Owing to the complex interactions between hematopoietic stem cells and marrow microenvironments, precise control of both biochemical and physical niches that are critical in maintenance of hematopoiesis remains a key challenge. Thus, recently developed bone-marrow-on-a-chip models support immunogenicity and immunotoxicity testing in long-term cultivation with repeated antigen stimulation. In this review, we provide an overview of clinical studies that have been carried out on bone marrow transplants in patients with immune-related diseases and future aspects of clinical and pharmaceutical application of bone-marrow-on-a-chip.

  3. A seamless phase IIB/III adaptive outcome trial: design rationale and implementation challenges.

    PubMed

    Chen, Y H Joshua; Gesser, Richard; Luxembourg, Alain

    2015-02-01

    The licensed four-valent prophylactic human papillomavirus vaccine is highly efficacious in preventing cervical, vulvar, vaginal, and anal cancers and related precancers caused by human papillomavirus types 6, 11, 16, and 18. These four types account for approximately 70% of cervical cancers. A nine-valent human papillomavirus vaccine, including the four original types (6, 11, 16, and 18) plus the next five most prevalent types in cervical cancer (31, 33, 45, 52, and 58) could provide approximately 90% overall cervical cancer coverage. To expedite the nine-valent human papillomavirus vaccine clinical development, an adaptive, seamless Phase IIB/III outcome trial with ∼ 15,000 subjects was conducted to facilitate dose formulation selection and provide pivotal evidence of safety and efficacy for regulatory registrations. We discuss the design rationale and implementation challenges of the outcome trial, focusing on the adaptive feature of the seamless Phase IIB/III design. Subjects were enrolled in two parts (Part A and Part B). Approximately 1240 women, 16-26 years of age, were enrolled in Part A for Phase IIB evaluation and equally randomized to one of three dose formulations of the nine-valent human papillomavirus vaccine or the four-valent human papillomavirus vaccine (active control). Based on an interim analysis of immunogenicity and safety, one dose formulation of the nine-valent human papillomavirus vaccine was selected for evaluation in the Phase III part of the study. Subjects enrolled in Part A who received the selected dose formulation of the nine-valent human papillomavirus vaccine or four-valent human papillomavirus vaccine continued to be followed up and contributed to the final efficacy and safety analyses. In addition, ∼ 13,400 women 16-26 years of age were enrolled in Part B, randomized to nine-valent human papillomavirus vaccine at the selected dose formulation or four-valent human papillomavirus vaccine, and followed for immunogenicity, efficacy, and safety. A seamless Phase IIB/III design was justified by the extensive pre-existing knowledge of the licensed four-valent human papillomavirus vaccine and the development objectives for the nine-valent human papillomavirus vaccine. Subjects enrolled in Part A who received either the selected nine-valent human papillomavirus formulation or four-valent human papillomavirus vaccine contributed ∼ 10% of person-years of follow-up due to its earlier start-thereby maximizing the overall efficiency of the trial. Some of the challenges encountered in the implementation of the adaptive design included practical considerations during Phase IIB formulation selection by internal and external committees, End-of-Phase II discussion with health authorities and managing changes in the assay for immunological endpoints. Application of the experience and lesson learned from this seamless adaptive design to other clinical programs may depend on case-by-case consideration. A seamless Phase IIB/III adaptive design was successfully implemented in this large outcome study. The development time of the second-generation nine-valent human papillomavirus vaccine was shortened due to improved statistical efficiency. © The Author(s) 2014.

  4. Maternal hyperthyroidism after intrauterine insemination due to hypertrophic action of human chorionic gonadotropin: a case report.

    PubMed

    Bakas, P; Tzouma, C; Creatsa, M; Boutas, I; Hassiakos, D

    2016-01-01

    To report a rare case of maternal hyperthyroidism after intrauterine insemination due to hypertrophic action of hCG. A 36-year-old woman after successful intrauterine insemination and triplet pregnancy, developed hyperthyroidism with resistance to medical treatment. All signs of hyperthyroidism resolved and the results of thyroid function tests returned to normal without any medication after embryo meiosis. De novo maternal hyperthyroidism may develop during pregnancy as a result of pathological stimulation of the thyroid gland from the high levels of hCG hormone that can be seen in multiple pregnancies. The risk of hyperthyroidism is related to the number of fetuses. Reversibility of symptomatology can be seen after fetal reduction of multiple pregnancies.

  5. Improving human activity recognition and its application in early stroke diagnosis.

    PubMed

    Villar, José R; González, Silvia; Sedano, Javier; Chira, Camelia; Trejo-Gabriel-Galan, Jose M

    2015-06-01

    The development of efficient stroke-detection methods is of significant importance in today's society due to the effects and impact of stroke on health and economy worldwide. This study focuses on Human Activity Recognition (HAR), which is a key component in developing an early stroke-diagnosis tool. An overview of the proposed global approach able to discriminate normal resting from stroke-related paralysis is detailed. The main contributions include an extension of the Genetic Fuzzy Finite State Machine (GFFSM) method and a new hybrid feature selection (FS) algorithm involving Principal Component Analysis (PCA) and a voting scheme putting the cross-validation results together. Experimental results show that the proposed approach is a well-performing HAR tool that can be successfully embedded in devices.

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

    Amson, R.; Przedborski, S.; Telerman, A.

    The authors measured the human pim-1 protooncogene (PIM) expression during fetal development and in hematopoietic malignancies. The data indicate that during human fetal hematopoiesis the 33-kDa pim product, p33pim, is highly expressed in the liver and the spleen. In contrast, a the adult stage it is only slightly expressed in circulating granulocytes. Out of 70 hematopoietic malignancies analyzed, 51 patients and 19 cell lines, p33pim was overexpressed in {approx} 30% of the samples, particularly in myeloid and lymphoid acute leukemias. This overexpression was unrelated to any stage of cellular differentiation and was not due to gene rearrangement or amplification. Thesemore » results imply a physiological role of the pim-1 protooncogene during hematopoietic development and a deregulation in various leukemias.« less

  7. Control of a human-powered helicopter in hover

    NASA Technical Reports Server (NTRS)

    Totah, Joseph J.; Patterson, William

    1988-01-01

    The study of a control system for the Da Vinci 2 human-powered helicopter in hovering flight is documented. This helicopter has two very large, slowly rotating rotor blades and is considered to be unstable in hover. The control system is designed to introduce stability in hover by maintaining level rotors through the use of rotor tip mounted control surfaces. A five degree of freedom kinematic model was developed to study this control system and is documented. Results of this study show that the unaugmented configuration is unstable due to the large Lock Number, and the augmented configuration is stable. The role of NASA in this study included the development and analysis of the kinematic model and control laws. Both analytical and numerical techniques were used.

  8. Gynaecomastia in two men on stable antiretroviral therapy who commenced treatment for tuberculosis.

    PubMed

    Kratz, Jeremy D; El-Shazly, Ahmad Y; Mambuque, Santos G; Demetria, Elpidio; Veldkamp, Peter; Anderson, Timothy S

    2016-12-01

    Gynaecomastia is a common clinical presentation that varies from benign presentations in stages of human development to hormonal pathology, mainly due to hepatic dysfunction, malignancy, and adverse pharmacologic effects. We describe the development of significant bilateral gynaecomastia after starting treatment for pulmonary tuberculosis (TB) in two males with WHO stage III Human Immunodeficiency Virus (HIV) infection on stable antiretroviral regimens. Emerging reports suggest that distinct hepatic impairment in efavirenz metabolism modulates oestrogenic activity, which may be potentiated by anti-tuberculosis therapy. Clinical application includes early recognition of efavirenz-induced gynaecomastia, especially after commencing tuberculosis treatment. To avoid decreased adherence resulting from the distressing side effect of gynecomastia, transition to an alternative ART regimen over the course of tuberculosis treatment should be considered.

  9. [Lay emphasis on the treatment of massive burn casualties in conflagration].

    PubMed

    Tang, Hong-tai; Ma, Bing; Xia, Zhao-fan

    2012-06-01

    Burn surgery belongs to disaster medicine. Burn is a common trauma that occurs in social activities of human beings in all ages, either in the time of peace or war. During the development of human medicine in modern times, the summary of experience in treating massive burn casualties due to severe fire accidents has effectively promoted the renovation of treating technology and theory of burns and the development of burn surgery. The results of treatment of burn injury in casualties occurred in the fire of Cocoanut Grove night club in Boston in 1942, and the high-rise apartment house fire in Shanghai in 2010 were summarized and analyzed in this article, emphasizing the correlating issues of inhalation injury.

  10. Toxicological effects of nanoparticles from photocopiers

    NASA Astrophysics Data System (ADS)

    Khatri, Madhu

    Nanotechnology is expanding rapidly and its fast-track to commercialization offering highly promising products and materials. Various physical, chemical and biological processes also results in unintentional generation of nanoparticles (NPs) leading to much higher concentrations at certain workplaces. Thus, human exposures to NPs from anthropogenic sources have increased dramatically in the past few decades. Recently, concerns have been expressed about the potential risks to human health occurring due to NP exposures in various workplaces. Although, a few recent studies have shown that the workplace exposure to NPs has the potential to cause serious human health problems such as pulmonary and related cardiovascular diseases, yet the evidence to establish their association is still lacking. This is partly due to lack of easily accessible settings with continuous NP exposures and the unavailability of sufficiently large cohorts of exposed workers. High volume photocopy (PC) centers are common and are generally operated by a permanent staff. It is now well known that laser printers and photocopiers emit NPs. We have observed that photocopiers emit significantly more NPs than laser printers and that the copy center environments had more than 20 times elevated NP levels over the background. It is evident that a significant fraction of airborne NPs get deposited in the alveolar and nasal cavity regions. Therefore, photocopy centers not only offer an opportunity to study response pattern in workers who are chronically exposed to NPs, but also to test and develop necessary methodologies to link exposures to engineered NPs and early health effects. In this study, early human health effects associated with acute NP exposure were studied. This was done by exposing a few health subjects to PC center environment for a short duration and measuring inflammatory and oxidative stress biomarkers in their nasal lavage and urine samples in response to such exposure. Additionally, potential in-vitro cytotoxicity and induction of cytokines of the collected NP generated during photocopying was studied. Furthermore, airborne fine PM collected from copy center was evaluated for their capability to induce in-vitro cytotoxicity and induction of cytokines. The research addresses one major knowledge gap between possible adverse effects on human health caused due to NP exposure. Additionally, this would help develop useful biomarkers for such exposures. These biomarkers could then assists in early detection of such effects and can potentially be used to assess human health risk from exposures to such NPs and device effective interventions if needed.

  11. A UV-Independent Topical Small-Molecule Approach for Melanin Production in Human Skin.

    PubMed

    Mujahid, Nisma; Liang, Yanke; Murakami, Ryo; Choi, Hwan Geun; Dobry, Allison S; Wang, Jinhua; Suita, Yusuke; Weng, Qing Yu; Allouche, Jennifer; Kemeny, Lajos V; Hermann, Andrea L; Roider, Elisabeth M; Gray, Nathanael S; Fisher, David E

    2017-06-13

    The presence of dark melanin (eumelanin) within human epidermis represents one of the strongest predictors of low skin cancer risk. Topical rescue of eumelanin synthesis, previously achieved in "redhaired" Mc1r-deficient mice, demonstrated significant protection against UV damage. However, application of a topical strategy for human skin pigmentation has not been achieved, largely due to the greater barrier function of human epidermis. Salt-inducible kinase (SIK) has been demonstrated to regulate MITF, the master regulator of pigment gene expression, through its effects on CRTC and CREB activity. Here, we describe the development of small-molecule SIK inhibitors that were optimized for human skin penetration, resulting in MITF upregulation and induction of melanogenesis. When topically applied, pigment production was induced in Mc1r-deficient mice and normal human skin. These findings demonstrate a realistic pathway toward UV-independent topical modulation of human skin pigmentation, potentially impacting UV protection and skin cancer risk. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Photodynamic effects on human and chicken erythrocytes

    NASA Astrophysics Data System (ADS)

    Kimel, Sol; Koenig, Karsten; Berns, Michael W.

    1995-02-01

    The intracellular accumulation of a variety of photosensitizers in human (non-nucleated) and chicken (nucleated) erythrocytes, as well as the photodynamically induced hemolysis were studied using 488 nm laser microirradiation (15 (mu) W, 100X) and confocal laser scanning fluorescence microscopy. Cells incubated with the negatively charged hydrophilic compounds TPPS4 and Pd-TPPS4 exhibited no significant fluorescence before irradiation, but developed strong fluorescence in the cellular and nuclear membranes following photoinduced membrane damage. In contrast, microirradiation of Photofrin-incubated erythrocytes showed instantaneous fluorescence which decreased due to photodegradation. For the cationic, hydrophilic dye Methylene Blue, significant fluorescence was detected in the nucleus only. Following ALA incubation, large intercellular differences were observed in fluorescence in the red spectral region. These differences are probably due to the differential ability of individual erythrocytes to biosynthesize protoporphyrin IX. Photofrin was the most efficient photosensitizer to induce hemolysis. Higher radiant exposures were required for lysis of nucleated than of human red blood cells, except in the case of Methylene Blue. Irradiation was more efficient for unwashed cell suspensions than for washed suspensions, indicating the non-negligible role of extracellular photosensitizing molecules.

  13. The Mauve Stinger Pelagia noctiluca (Forsskål, 1775). Distribution, Ecology, Toxicity and Epidemiology of Stings. A Review

    PubMed Central

    Mariottini, Gian Luigi; Giacco, Elisabetta; Pane, Luigi

    2008-01-01

    The toxicity of Cnidaria is a subject of concern due to its influence on humans. In particular, jellyfish blooms can highly affect human economical activities, such as bathing, fishery, tourism, etc., as well as the public health. Stinging structures of Cnidaria (nematocysts) produce remarkable effects on human skin, such as erythema, swelling, burning and vesicles, and at times further severe dermonecrotic, cardio- and neurotoxic effects, which are particularly dangerous in sensitive subjects. In several zones the toxicity of jellyfish is a very important health problem, thus it has stimulated the research on these organisms; to date toxicological research on Cnidarian venoms in the Mediterranean region is not well developed due to the weak poisonousness of venoms of jellyfish and anemones living in this area. In spite of this, during last decades several problems were also caused in the Mediterranean by stinging consequent to Cnidarian blooms mainly caused by Pelagia noctiluca (Forsskål, 1775) which is known to be the most venomous Mediterranean jellyfish. This paper reviews the knowledge on this jellyfish species, particularly considering its occurrence and toxicity. PMID:19005582

  14. Non-invasive MRI detection of individual pellets in the human stomach.

    PubMed

    Knörgen, Manfred; Spielmann, Rolf Peter; Abdalla, Ahmed; Metz, Hendrik; Mäder, Karsten

    2010-01-01

    MRI is a powerful and non-invasive method to follow the fate of oral drug delivery systems in humans. Until now, most MRI studies focused on monolithic dosage forms (tablets and capsules). Small-sized multi-particulate drug delivery systems are very difficult to detect due to the poor differentiation between the delivery system and the food. A new approach was developed to overcome the described difficulties and permit the selective imaging of small multi-particulate dosage forms within the stomach. We took advantage of the different sensitivities to susceptibility artefacts of T(2)-weighted spin-echo sequences and T(2)-weighted gradient echo pulse sequences. Using a combination of both methods within a breath hold followed by a specific mathematical image analysis involving co-registration, motion correction, voxel-by-voxel comparison of the maps from different pulse sequences and graphic 2D-/3D-presentation, we were able to obtain pictures with a high sensitivity due to susceptibility effects caused by a 1% magnetite load. By means of the new imaging sequence, single pellets as small as 1mm can be detected with high selectivity within surrounding heterogeneous food in the human stomach. The developed method greatly expands the use of MRI to study the fate of oral multi-particulate drug delivery systems and their food dependency in men. Copyright 2009 Elsevier B.V. All rights reserved.

  15. Upgrading HepG2 cells with adenoviral vectors that encode drug-metabolizing enzymes: application for drug hepatotoxicity testing.

    PubMed

    Gómez-Lechón, M José; Tolosa, Laia; Donato, M Teresa

    2017-02-01

    Drug attrition rates due to hepatotoxicity are an important safety issue considered in drug development. The HepG2 hepatoma cell line is currently being used for drug-induced hepatotoxicity evaluations, but its expression of drug-metabolizing enzymes is poor compared with hepatocytes. Different approaches have been proposed to upgrade HepG2 cells for more reliable drug-induced liver injury predictions. Areas covered: We describe the advantages and limitations of HepG2 cells transduced with adenoviral vectors that encode drug-metabolizing enzymes for safety risk assessments of bioactivable compounds. Adenoviral transduction facilitates efficient and controlled delivery of multiple drug-metabolizing activities to HepG2 cells at comparable levels to primary human hepatocytes by generating an 'artificial hepatocyte'. Furthermore, adenoviral transduction enables the design of tailored cells expressing particular metabolic capacities. Expert opinion: Upgraded HepG2 cells that recreate known inter-individual variations in hepatic CYP and conjugating activities due to both genetic (e.g., polymorphisms) or environmental (e.g., induction, inhibition) factors seems a suitable model to identify bioactivable drug and conduct hepatotoxicity risk assessments. This strategy should enable the generation of customized cells by reproducing human pheno- and genotypic CYP variability to represent a valuable human hepatic cell model to develop new safer drugs and to improve existing predictive toxicity assays.

  16. Climate Change Science, Impacts, Solutions - A Senior Science Course for Post-Secondary Students

    NASA Astrophysics Data System (ADS)

    Byrne, J. M.; Little, L. J.; Barnes, C. C.; Mirmasoudi, S.; Mansouri Kouhestani, F.; Reiger, C.; Rodriguez Bueno, R. A.

    2015-12-01

    The role of humanity in warming the global climate is well defined. The research community has predicted and documented many of the early impacts of climate change. The research literature has extensive assessments of future impacts on environment, cities, agriculture, human health, infrastructure, social and political changes, and the risks of military conflict. Society is facing massive infrastructure redevelopment, protection and possible abandonment due to increasing weather extremes. We have reached the point where science consensus is obvious and the population over much of the developed and developing world understands the urgency - humanity is changing the climate. The challenge is helping people help themselves. People understand there are consequences - they want to know how to minimize those consequences, and how to adapt to minimize the impacts. There is a dire need for a senior level course that addresses the key issues across disciplines. This course should cover a range of topics across many disciplinary boundaries, including: an introduction to the science, politics, health and well-being challenges of climate change; likely changes to personal and community lifestyles; consumption of energy and other resources. Population migration due to climate change impacts is a critical topic. Most important, the course must address the solutions to climate change. The population is demanding the power to address this massive challenge. This course will provide a multimedia curriculum on the impacts and solutions to our climate change dilemma.

  17. Soft and Flexible Bilayer Thermoplastic Polyurethane Foam for Development of Bioinspired Artificial Skin.

    PubMed

    Li, Huan; Sinha, Tridib K; Oh, Jeong Seok; Kim, Jin Kuk

    2018-04-25

    Inspired by the epidermis-dermis composition of human skin, here we have simply developed a lightweight, robust, flexible, and biocompatible single-electrode triboelectric nanogenerator (S-TENG)-based prototype of bilayer artificial skin, by attaching one induction electrode with unfoamed skin layer of microcellular thermoplastic polyurethane (TPU) foam, which shows high-performance object manipulation [by responding differently toward different objects, viz., aluminum foil, balloon, cotton glove, human finger, glass, rubber glove, artificial leather, polyimide, poly(tetrafluoroethylene) (PTFE), paper, and wood], due to electrification and electrostatic induction during contact with the objects having different chemical functionalities. Comparative foaming behavior of ecofriendly supercritical fluids, viz., CO 2 over N 2 under variable temperatures (e.g., 130 and 150 °C) and constant pressure (15 MPa), have been examined here to pursue the soft and flexible triboelectric TPU foam. The foam derived by CO 2 foaming at 150 °C has been prioritized for development of S-TENG. Foam derived by CO 2 foaming at 130 °C did not respond as well due to the smaller cell size, higher hardness, and thicker skin. Inflexible N 2 -derived foam was not considered for S-TENG fabrication. Object manipulation performance has been visualized by principal component analysis (PCA), which shows good discrimination among responses to different objects.

  18. High-resolution temporal and regional mapping of MAPT expression and splicing in human brain development.

    PubMed

    Hefti, Marco M; Farrell, Kurt; Kim, SoongHo; Bowles, Kathryn R; Fowkes, Mary E; Raj, Towfique; Crary, John F

    2018-01-01

    The microtubule associated protein tau plays a critical role in the pathogenesis of neurodegenerative disease. Recent studies suggest that tau also plays a role in disorders of neuronal connectivity, including epilepsy and post-traumatic stress disorder. Animal studies have shown that the MAPT gene, which codes for the tau protein, undergoes complex pre-mRNA alternative splicing to produce multiple isoforms during brain development. Human data, particularly on temporal and regional variation in tau splicing during development are however lacking. In this study, we present the first detailed examination of the temporal and regional sequence of MAPT alternative splicing in the developing human brain. We used a novel computational analysis of large transcriptomic datasets (total n = 502 patients), quantitative polymerase chain reaction (qPCR) and western blotting to examine tau expression and splicing in post-mortem human fetal, pediatric and adult brains. We found that MAPT exons 2 and 10 undergo abrupt shifts in expression during the perinatal period that are unique in the canonical human microtubule-associated protein family, while exon 3 showed small but significant temporal variation. Tau isoform expression may be a marker of neuronal maturation, temporally correlated with the onset of axonal growth. Immature brain regions such as the ganglionic eminence and rhombic lip had very low tau expression, but within more mature regions, there was little variation in tau expression or splicing. We thus demonstrate an abrupt, evolutionarily conserved shift in tau isoform expression during the human perinatal period that may be due to tau expression in maturing neurons. Alternative splicing of the MAPT pre-mRNA may play a vital role in normal brain development across multiple species and provides a basis for future investigations into the developmental and pathological functions of the tau protein.

  19. Foundational Methane Propulsion Related Technology Efforts, and Challenges for Applications to Human Exploration Beyond Earth Orbit

    NASA Technical Reports Server (NTRS)

    Brown, Thomas; Klem, Mark; McRight, Patrick

    2016-01-01

    Current interest in human exploration beyond earth orbit is driving requirements for high performance, long duration space transportation capabilities. Continued advancement in photovoltaic power systems and investments in high performance electric propulsion promise to enable solar electric options for cargo delivery and pre-deployment of operational architecture elements. However, higher thrust options are required for human in-space transportation as well as planetary descent and ascent functions. While high thrust requirements for interplanetary transportation may be provided by chemical or nuclear thermal propulsion systems, planetary descent and ascent systems are limited to chemical solutions due to their higher thrust to weight and potential planetary protection concerns. Liquid hydrogen fueled systems provide high specific impulse, but pose challenges due to low propellant density and the thermal issues of long term propellant storage. Liquid methane fueled propulsion is a promising compromise with lower specific impulse, higher bulk propellant density and compatibility with proposed in-situ propellant production concepts. Additionally, some architecture studies have identified the potential for commonality between interplanetary and descent/ascent propulsion solutions using liquid methane (LCH4) and liquid oxygen (LOX) propellants. These commonalities may lead to reduced overall development costs and more affordable exploration architectures. With this increased interest, it is critical to understand the current state of LOX/LCH4 propulsion technology and the remaining challenges to its application to beyond earth orbit human exploration. This paper provides a survey of NASA's past and current methane propulsion related technology efforts, assesses the accomplishments to date, and examines the remaining risks associated with full scale development.

  20. Evolutionary and Cognitive Motivations for Fractal Art in Art and Design Education

    ERIC Educational Resources Information Center

    Joye, Yannick

    2005-01-01

    Humans are endowed with cognitive modules specialised in processing information about the class of natural things. Due to their naturalness, fractal art and design can contribute to developing these modules, and trigger affective responses that are associated with certain natural objects. It is argued that exposure to fractals in an art and design…

  1. Mercury cycling in peatland watersheds. Chapter 11.

    Treesearch

    Randall K. Kolka; Carl P.J. Mitchell; Jeffrey D. Jeremiason; Neal A. Hines; David F. Grigal; Daniel R. Engstrom; Jill K. Coleman-Wasik; Edward A. Nater; Edward B. Swain; Bruce A. Monson; Jacob A. Fleck; Brian Johnson; James E. Almendinger; Brian A. Branfireun; Patrick L. Brezonik; James B. Cotner

    2011-01-01

    Mercury (Hg) is of great environmental concern due to its transformation into the toxic methylmercury (MeHg) form that bioaccumulates within the food chain and causes health concerns for both humans and wildlife (U.S. Environmental Protection Agency 2002). Mercury can affect neurological development in fetuses and young children. In adults, exposure to Hg can lead to...

  2. Job and Task Analysis in the Evaluation of Vocational Education Programs. Special Interest Paper No. 19.

    ERIC Educational Resources Information Center

    Abramson, Theodore

    Vocational education is a major component of our educational systems at the secondary and postsecondary school level. The passage of the Vocational Education Act of 1963 broadened the definition of vocational education from training people for specific occupations to developing human potential and long-term employability. However, due to the…

  3. Creating Regional Futures: A Scenario-Based Inter- and Transdisciplinary Case Study as a Model for Applied Student-Centred Learning in Geography

    ERIC Educational Resources Information Center

    Fromhold-Eisebith, Martina; Freyer, Bernhard; Mose, Ingo; Muhar, Andreas; Vilsmaier, Ulli

    2009-01-01

    Human geography students face changing qualification requirements due to a shift towards new topics, educational tasks and professional options regarding issues of spatial development. This "practical turn" raises the importance of inter- and transdisciplinary work, management and capability building skills, with case study projects and…

  4. Sage-Grouse and Coal-Bed Methane: Can They Coexist within the Powder River Basin?

    ERIC Educational Resources Information Center

    Duncan, Michael B.

    2010-01-01

    Concerns are growing regarding the availability of sustainable energy sources due to a rapidly growing human population and a better understanding of climate change. In recent years, the United States has focused much attention on developing domestic energy sources, which include coal-bed methane (CBM). There are vast deposits of the natural gas…

  5. Homogenization of northern U.S. Great Lakes forests due to land use

    Treesearch

    Lisa A. Schulte; David J. Mladenoff; Thomas R. Crow; Laura C. Merrick; David T. Cleland

    2007-01-01

    Human land use of forested regions has intensified worldwide in recent decades, threatening long-term sustainability. Primary effects include conversion of land cover or reversion to an earlier stage of successional development. Both types of change can have cascading effects through ecosystems; however, the longterm effects where forests are allowed to regrow are...

  6. Invasive species and disturbances: Current and future roles of Forest Service Research and Development

    Treesearch

    Jim Slavicek; Allen M. Solomon

    2010-01-01

    The success of an invasive species is in large part due to favorable conditions resulting from the complex interactions among natural and anthropogenic factors such as native and nonnative pests, fires, droughts, hurricanes, wind storms, ice storms, climate warming, management practices, human travel, and trade. Reducing the negative effects of invasive species and...

  7. A Comprehensive Investigation of Visibility Problems on Highways: Developing Real Time Monitoring and Prediction System for Reduced Visibility and Understanding Traffic and Human Factors Implications

    DOT National Transportation Integrated Search

    2015-10-01

    Visibility is one of the most important impacts weather can have on road systems; weather-related visibility reduction is most often due to fog. Florida is among the top-rated states in the United States with regards to traffic safety problems result...

  8. Deep Learning in Medical Imaging: General Overview

    PubMed Central

    Lee, June-Goo; Jun, Sanghoon; Cho, Young-Won; Lee, Hyunna; Kim, Guk Bae

    2017-01-01

    The artificial neural network (ANN)–a machine learning technique inspired by the human neuronal synapse system–was introduced in the 1950s. However, the ANN was previously limited in its ability to solve actual problems, due to the vanishing gradient and overfitting problems with training of deep architecture, lack of computing power, and primarily the absence of sufficient data to train the computer system. Interest in this concept has lately resurfaced, due to the availability of big data, enhanced computing power with the current graphics processing units, and novel algorithms to train the deep neural network. Recent studies on this technology suggest its potentially to perform better than humans in some visual and auditory recognition tasks, which may portend its applications in medicine and healthcare, especially in medical imaging, in the foreseeable future. This review article offers perspectives on the history, development, and applications of deep learning technology, particularly regarding its applications in medical imaging. PMID:28670152

  9. Deep Learning in Medical Imaging: General Overview.

    PubMed

    Lee, June-Goo; Jun, Sanghoon; Cho, Young-Won; Lee, Hyunna; Kim, Guk Bae; Seo, Joon Beom; Kim, Namkug

    2017-01-01

    The artificial neural network (ANN)-a machine learning technique inspired by the human neuronal synapse system-was introduced in the 1950s. However, the ANN was previously limited in its ability to solve actual problems, due to the vanishing gradient and overfitting problems with training of deep architecture, lack of computing power, and primarily the absence of sufficient data to train the computer system. Interest in this concept has lately resurfaced, due to the availability of big data, enhanced computing power with the current graphics processing units, and novel algorithms to train the deep neural network. Recent studies on this technology suggest its potentially to perform better than humans in some visual and auditory recognition tasks, which may portend its applications in medicine and healthcare, especially in medical imaging, in the foreseeable future. This review article offers perspectives on the history, development, and applications of deep learning technology, particularly regarding its applications in medical imaging.

  10. Mechanics of airway and alveolar collapse in human breath-hold diving.

    PubMed

    Fitz-Clarke, John R

    2007-11-15

    A computational model of the human respiratory tract was developed to study airway and alveolar compression and re-expansion during deep breath-hold dives. The model incorporates the chest wall, supraglottic airway, trachea, branched airway tree, and elastic alveoli assigned time-dependent surfactant properties. Total lung collapse with degassing of all alveoli is predicted to occur around 235 m, much deeper than estimates for aquatic mammals. Hysteresis of the pressure-volume loop increases with maximum diving depth due to progressive alveolar collapse. Reopening of alveoli occurs stochastically as airway pressure overcomes adhesive and compressive forces on ascent. Surface area for gas exchange vanishes at collapse depth, implying that the risk of decompression sickness should reach a plateau beyond this depth. Pulmonary capillary transmural stresses cannot increase after local alveolar collapse. Consolidation of lung parenchyma might provide protection from capillary injury or leakage caused by vascular engorgement due to outward chest wall recoil at extreme depths.

  11. Vibration Therapy to Prevent Bone Loss and Falls: Mechanisms and Efficacy.

    PubMed

    Beck, Belinda R

    2015-12-01

    A considerable volume of evidence has accumulated to suggest that whole-body vibration (WBV) may have a therapeutic role to play in the prevention of osteoporotic fracture, particularly for individuals who are unable to tolerate vigorous exercise interventions. There is moderate to strong evidence that WBV will prevent falls (likely due to enhanced neuromuscular function), but also some indication that the effects of WBV do not outstrip those of targeted exercise. Animal data indicates that WBV will also improve bone mass, including preventing loss due to hormone withdrawal, disuse and glucocorticoid exposure. Human trials, however, have produced equivocal outcomes for bone. Positive trends are apparent at the hip and spine, but shortcomings in study designs have limited statistical power. The mechanism of the vibration effect on bone tissue is likely to be mechanical coupling between an oscillating cell nucleus and the cytoskeleton. More robust dose-response human data are required before therapeutic guidelines can be developed.

  12. Engineering education in Bangladesh - an indicator of economic development

    NASA Astrophysics Data System (ADS)

    Chowdhury, Harun; Alam, Firoz

    2012-05-01

    Developing nations including Bangladesh are significantly lagging behind the millennium development target due to the lack of science, technology and engineering education. Bangladesh as a least developing country has only 44 engineers per million people. Its technological education and gross domestic product growth are not collinear. Although limited progress was made in humanities, basic sciences, agriculture and medical sciences, a vast gap is left in technical and engineering education. This paper describes the present condition of engineering education in the country and explores ways to improve engineering education in order to meet the national as well as global skills demand.

  13. Genomics-enabled sensor platform for rapid detection of viruses related to disease outbreak.

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

    Brozik, Susan M; Manginell, Ronald P; Moorman, Matthew W

    2013-09-01

    Bioweapons and emerging infectious diseases pose growing threats to our national security. Both natural disease outbreak and outbreaks due to a bioterrorist attack are a challenge to detect, taking days after the outbreak to identify since most outbreaks are only recognized through reportable diseases by health departments and reports of unusual diseases by clinicians. In recent decades, arthropod-borne viruses (arboviruses) have emerged as some of the most significant threats to human health. They emerge, often unexpectedly, from cryptic transmission foci causing localized outbreaks that can rapidly spread to multiple continents due to increased human travel and trade. Currently, diagnosis ofmore » acute infections requires amplification of viral nucleic acids, which can be costly, highly specific, technically challenging and time consuming. No diagnostic devices suitable for use at the bedside or in an outbreak setting currently exist. The original goals of this project were to 1) develop two highly sensitive and specific diagnostic assays for detecting RNA from a wide range of arboviruses; one based on an electrochemical approach and the other a fluorescent based assay and 2) develop prototype microfluidic diagnostic platforms for preclinical and field testing that utilize the assays developed in goal 1. We generated and characterized suitable primers for West Nile Virus RNA detection. Both optical and electrochemical transduction technologies were developed for DNA-RNA hybridization detection and were implemented in microfluidic diagnostic sensing platforms that were developed in this project.« less

  14. Updates in the Development of ImmunoRNases for the Selective Killing of Tumor Cells

    PubMed Central

    Jordaan, Sandra; Akinrinmade, Olusiji A.; Nachreiner, Thomas; Cremer, Christian; Naran, Krupa; Chetty, Shivan; Barth, Stefan

    2018-01-01

    Targeted cancer therapy includes, amongst others, antibody-based delivery of toxic payloads to selectively eliminate tumor cells. This payload can be either a synthetic small molecule drug composing an antibody-drug conjugate (ADC) or a cytotoxic protein composing an immunotoxin (IT). Non-human cytotoxic proteins, while potent, have limited clinical efficacy due to their immunogenicity and potential off-target toxicity. Humanization of the cytotoxic payload is essential and requires harnessing of potent apoptosis-inducing human proteins with conditional activity, which rely on targeted delivery to contact their substrate. Ribonucleases are attractive candidates, due to their ability to induce apoptosis by abrogating protein biosynthesis via tRNA degradation. In fact, several RNases of the pancreatic RNase A superfamily have shown potential as anti-cancer agents. Coupling of a human RNase to a humanized antibody or antibody derivative putatively eliminates the immunogenicity of an IT (now known as a human cytolytic fusion protein, hCFP). However, RNases are tightly regulated in vivo by endogenous inhibitors, controlling the ribonucleolytic balance subject to the cell’s metabolic requirements. Endogenous inhibition limits the efficacy with which RNase-based hCFPs induce apoptosis. However, abrogating the natural interaction with the natural inhibitors by mutation has been shown to significantly enhance RNase activity, paving the way toward achieving cytolytic potency comparable to that of bacterial immunotoxins. Here, we review the immunoRNases that have undergone preclinical studies as anti-cancer therapeutic agents. PMID:29510557

  15. Updates in the Development of ImmunoRNases for the Selective Killing of Tumor Cells.

    PubMed

    Jordaan, Sandra; Akinrinmade, Olusiji A; Nachreiner, Thomas; Cremer, Christian; Naran, Krupa; Chetty, Shivan; Barth, Stefan

    2018-03-05

    Targeted cancer therapy includes, amongst others, antibody-based delivery of toxic payloads to selectively eliminate tumor cells. This payload can be either a synthetic small molecule drug composing an antibody-drug conjugate (ADC) or a cytotoxic protein composing an immunotoxin (IT). Non-human cytotoxic proteins, while potent, have limited clinical efficacy due to their immunogenicity and potential off-target toxicity. Humanization of the cytotoxic payload is essential and requires harnessing of potent apoptosis-inducing human proteins with conditional activity, which rely on targeted delivery to contact their substrate. Ribonucleases are attractive candidates, due to their ability to induce apoptosis by abrogating protein biosynthesis via tRNA degradation. In fact, several RNases of the pancreatic RNase A superfamily have shown potential as anti-cancer agents. Coupling of a human RNase to a humanized antibody or antibody derivative putatively eliminates the immunogenicity of an IT (now known as a human cytolytic fusion protein, hCFP). However, RNases are tightly regulated in vivo by endogenous inhibitors, controlling the ribonucleolytic balance subject to the cell's metabolic requirements. Endogenous inhibition limits the efficacy with which RNase-based hCFPs induce apoptosis. However, abrogating the natural interaction with the natural inhibitors by mutation has been shown to significantly enhance RNase activity, paving the way toward achieving cytolytic potency comparable to that of bacterial immunotoxins. Here, we review the immunoRNases that have undergone preclinical studies as anti-cancer therapeutic agents.

  16. Human CD22 cannot fully substitute murine CD22 functions in vivo, as shown in a new knockin mouse model.

    PubMed

    Wöhner, Miriam; Born, Stefanie; Nitschke, Lars

    2012-11-01

    CD22, an inhibitory co-receptor of the B-cell receptor, shows a B-cell-specific expression pattern and is expressed on most B-cell lymphomas. The anti-CD22 antibody Epratuzumab is in clinical trials for B-cell non-Hodgkin lymphoma and systemic lupus erythematosus, but shows a mostly unknown mode of action. We generated a new mouse model that expresses human CD22 instead of murine CD22 (Huki CD22 mice), in which human CD22 can be targeted. Expression of human CD22 on the B cells of Huki CD22 mice does not generally interfere with B-cell development. However, Huki CD22 mice show a reduction of the population of mature recirculating B cells in the bone marrow and reduced transitional and marginal zone B cells in the spleen, phenotypes resembling that of CD22-deficient mice. Similarly, enhanced BCR-induced Ca(2+) signalling is observed in Huki CD22 mice, which also mount normal immune responses toward different classes of antigens. Huki CD22 B cells show a normal anti-hCD22 antibody-mediated endocytosis. In conclusion, human CD22 cannot fully substitute for murine CD22 functions, possibly due to the changed intracellular tail of the protein or due to lower expression levels. Huki CD22 mice are a valuable new model for both antibody- and immunotoxin-mediated targeting of human CD22. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Assessment of the mode of action underlying development of forestomach tumors in rodents following oral exposure to ethyl acrylate and relevance to humans.

    PubMed

    Thompson, Chad M; Suh, Mina; Chappell, Grace; Borghoff, Susan; Ellis-Hutchings, Robert; Wiench, Karin; Finch, Lavorgie; Proctor, Deborah M

    2018-05-05

    Chronic repeated gavage dosing of high concentrations of ethyl acrylate (EA) causes forestomach tumors in rats and mice. For two decades, there has been general consensus that these tumors are unique to rodents because of: i) lack of carcinogenicity in other organs, ii) specificity to the forestomach (an organ unique to rodents which humans do not possess), iii) lack of carcinogenicity by other routes of exposure, and iv) obvious site of contact toxicity at carcinogenic doses. In 1986, EA was classified as possibly carcinogenic to humans by the International Agency for Research on Cancer (IARC). However, by applying a MOA analyses and human relevance framework assessment, the weight-of-evidence supports a cytotoxic MOA with the following key events: i) bolus delivery of EA to forestomach lumen and subsequent absorption, ii) cytotoxicity likely due to saturation of enzymatic detoxification, iii) chronic regenerative hyperplasia, and iv) spontaneous mutation due to increased cell replication and cell population. Clonal expansion of initiated cells thus results in late onset tumorigenesis. The key events in this 'wound and healing' MOA provide high confidence in the MOA as assessed by evolved Bradford-Hill Criteria. The weight-of-evidence supported by the proposed MOA, combined with a unique tissue that does not exist in humans, indicates that EA is highly unlikely to pose a human cancer hazard. Copyright © 2018. Published by Elsevier Inc.

  18. Comparison between surrogate indexes of insulin sensitivity/resistance and hyperinsulinemic euglycemic clamp estimates in rats

    PubMed Central

    Muniyappa, Ranganath; Chen, Hui; Muzumdar, Radhika H.; Einstein, Francine H.; Yan, Xu; Yue, Lilly Q.; Barzilai, Nir

    2009-01-01

    Assessing insulin resistance in rodent models gives insight into mechanisms that cause type 2 diabetes and the metabolic syndrome. The hyperinsulinemic euglycemic glucose clamp, the reference standard for measuring insulin sensitivity in humans and animals, is labor intensive and technically demanding. A number of simple surrogate indexes of insulin sensitivity/resistance have been developed and validated primarily for use in large human studies. These same surrogates are also frequently used in rodent studies. However, in general, these indexes have not been rigorously evaluated in animals. In a recent validation study in mice, we demonstrated that surrogates have a weaker correlation with glucose clamp estimates of insulin sensitivity/resistance than in humans. This may be due to increased technical difficulties in mice and/or intrinsic differences between human and rodent physiology. To help distinguish among these possibilities, in the present study, using data from rats substantially larger than mice, we compared the clamp glucose infusion rate (GIR) with surrogate indexes, including QUICKI, HOMA, 1/HOMA, log (HOMA), and 1/fasting insulin. All surrogates were modestly correlated with GIR (r = 0.34–0.40). Calibration analyses of surrogates adjusted for body weight demonstrated similar predictive accuracy for GIR among all surrogates. We conclude that linear correlations of surrogate indexes with clamp estimates and predictive accuracy of surrogate indexes in rats are similar to those in mice (but not as substantial as in humans). This additional rat study (taken with the previous mouse study) suggests that application of surrogate insulin sensitivity indexes developed for humans may not be appropriate for determining primary outcomes in rodent studies due to intrinsic differences in metabolic physiology. However, use of surrogates may be appropriate in rodents, where feasibility of clamps is an obstacle and measurement of insulin sensitivity is a secondary outcome. PMID:19706785

  19. A tissue-engineered humanized xenograft model of human breast cancer metastasis to bone

    PubMed Central

    Thibaudeau, Laure; Taubenberger, Anna V.; Holzapfel, Boris M.; Quent, Verena M.; Fuehrmann, Tobias; Hesami, Parisa; Brown, Toby D.; Dalton, Paul D.; Power, Carl A.; Hollier, Brett G.; Hutmacher, Dietmar W.

    2014-01-01

    ABSTRACT The skeleton is a preferred homing site for breast cancer metastasis. To date, treatment options for patients with bone metastases are mostly palliative and the disease is still incurable. Indeed, key mechanisms involved in breast cancer osteotropism are still only partially understood due to the lack of suitable animal models to mimic metastasis of human tumor cells to a human bone microenvironment. In the presented study, we investigate the use of a human tissue-engineered bone construct to develop a humanized xenograft model of breast cancer-induced bone metastasis in a murine host. Primary human osteoblastic cell-seeded melt electrospun scaffolds in combination with recombinant human bone morphogenetic protein 7 were implanted subcutaneously in non-obese diabetic/severe combined immunodeficient mice. The tissue-engineered constructs led to the formation of a morphologically intact ‘organ’ bone incorporating a high amount of mineralized tissue, live osteocytes and bone marrow spaces. The newly formed bone was largely humanized, as indicated by the incorporation of human bone cells and human-derived matrix proteins. After intracardiac injection, the dissemination of luciferase-expressing human breast cancer cell lines to the humanized bone ossicles was detected by bioluminescent imaging. Histological analysis revealed the presence of metastases with clear osteolysis in the newly formed bone. Thus, human tissue-engineered bone constructs can be applied efficiently as a target tissue for human breast cancer cells injected into the blood circulation and replicate the osteolytic phenotype associated with breast cancer-induced bone lesions. In conclusion, we have developed an appropriate model for investigation of species-specific mechanisms of human breast cancer-related bone metastasis in vivo. PMID:24713276

  20. New techniques for positron emission tomography in the study of human neurological disorders: Progress report, 15 June 1992--31 October 1992

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

    Not Available

    1992-01-01

    During the past six months, we have continued work on the fronts of kinetic modeling of radioligands for studying neurotransmitter/receptor systems, iterative reconstruction techniques, and methodology for PET cerebral blood flow activation studies. Initial human PET studies have been performed and analyzed with many different kinetic model formulations to determine the quantitative potential of the neuronwsmitter/receptor ligand, ({sup 11}C)N-methyl piperidyl benzilate (NMPB), a muscarinic cholinergic antagonist. In addition, initial human studies using ({sup 11}C)tetrabenazine (TBZ), a marker for monoantine nerve terminal density. Results of the NWB studies have indicated that this new agent yields better estimates of receptor density thanmore » previous muscarinic ligands developed at our facility, ({sup 11}C)-TRB and ({sup 11}C)scopolamine. TRB and scopolamine have previously been shown to be only partially successful ligands due to sub-optimal values of the individual rate constants, causing varying degrees of flow limitation. This is found to be much less of a problem for NMPB due to the 2.0--2.5 fold increase in ligand transport observed in the human studies ({approximately}60% first pass extraction). A 2-parameter 2-compartment simplification had previously been implemented for the benzodiazepine ligand, (C-11)FMZ, and a similar model appears to be suitable for TBZ based on the preliminary human data.« less

  1. New techniques for positron emission tomography in the study of human neurological disorders: Progress report, 15 June 1992--31 October 1992

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

    Not Available

    1992-10-01

    During the past six months, we have continued work on the fronts of kinetic modeling of radioligands for studying neurotransmitter/receptor systems, iterative reconstruction techniques, and methodology for PET cerebral blood flow activation studies. Initial human PET studies have been performed and analyzed with many different kinetic model formulations to determine the quantitative potential of the neuronwsmitter/receptor ligand, [{sup 11}C]N-methyl piperidyl benzilate (NMPB), a muscarinic cholinergic antagonist. In addition, initial human studies using [{sup 11}C]tetrabenazine (TBZ), a marker for monoantine nerve terminal density. Results of the NWB studies have indicated that this new agent yields better estimates of receptor density thanmore » previous muscarinic ligands developed at our facility, [{sup 11}C]-TRB and [{sup 11}C]scopolamine. TRB and scopolamine have previously been shown to be only partially successful ligands due to sub-optimal values of the individual rate constants, causing varying degrees of flow limitation. This is found to be much less of a problem for NMPB due to the 2.0--2.5 fold increase in ligand transport observed in the human studies ({approximately}60% first pass extraction). A 2-parameter 2-compartment simplification had previously been implemented for the benzodiazepine ligand, [C-11]FMZ, and a similar model appears to be suitable for TBZ based on the preliminary human data.« less

  2. Model-based safety analysis of human-robot interactions: the MIRAS walking assistance robot.

    PubMed

    Guiochet, Jérémie; Hoang, Quynh Anh Do; Kaaniche, Mohamed; Powell, David

    2013-06-01

    Robotic systems have to cope with various execution environments while guaranteeing safety, and in particular when they interact with humans during rehabilitation tasks. These systems are often critical since their failure can lead to human injury or even death. However, such systems are difficult to validate due to their high complexity and the fact that they operate within complex, variable and uncertain environments (including users), in which it is difficult to foresee all possible system behaviors. Because of the complexity of human-robot interactions, rigorous and systematic approaches are needed to assist the developers in the identification of significant threats and the implementation of efficient protection mechanisms, and in the elaboration of a sound argumentation to justify the level of safety that can be achieved by the system. For threat identification, we propose a method called HAZOP-UML based on a risk analysis technique adapted to system description models, focusing on human-robot interaction models. The output of this step is then injected in a structured safety argumentation using the GSN graphical notation. Those approaches have been successfully applied to the development of a walking assistant robot which is now in clinical validation.

  3. Genomic deletion of a long-range bone enhancer misregulatessclerostin in Van Buchem disease

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

    Loots, Gabriela G.; Kneissel, Michaela; Keller, Hansjoerg

    2005-04-15

    Mutations in distant regulatory elements can negatively impact human development and health, yet due to the difficulty of detecting these critical sequences we predominantly focus on coding sequences for diagnostic purposes. We have undertaken a comparative sequence-based approach to characterize a large noncoding region deleted in patients affected by Van Buchem disease (VB), a severe sclerosing bone dysplasia. Using BAC recombination and transgenesis we characterized the expression of human sclerostin (sost) from normal (hSOSTwt) or Van Buchem(hSOSTvb D) alleles. Only the hSOSTwt allele faithfully expressed high levels of human sost in the adult bone and impacted bone metabolism, consistent withmore » the model that the VB noncoding deletion removes a sost specific regulatory element. By exploiting cross-species sequence comparisons with in vitro and in vivo enhancer assays we were able to identify a candidate enhancer element that drives human sost expression in osteoblast-like cell lines in vitro and in the skeletal anlage of the E14.5 mouse embryo, and discovered a novel function for sclerostin during limb development. Our approach represents a framework for characterizing distant regulatory elements associated with abnormal human phenotypes.« less

  4. A magnetic bead-based ligand binding assay to facilitate human kynurenine 3-monooxygenase drug discovery.

    PubMed

    Wilson, Kris; Mole, Damian J; Homer, Natalie Z M; Iredale, John P; Auer, Manfred; Webster, Scott P

    2015-02-01

    Human kynurenine 3-monooxygenase (KMO) is emerging as an important drug target enzyme in a number of inflammatory and neurodegenerative disease states. Recombinant protein production of KMO, and therefore discovery of KMO ligands, is challenging due to a large membrane targeting domain at the C-terminus of the enzyme that causes stability, solubility, and purification difficulties. The purpose of our investigation was to develop a suitable screening method for targeting human KMO and other similarly challenging drug targets. Here, we report the development of a magnetic bead-based binding assay using mass spectrometry detection for human KMO protein. The assay incorporates isolation of FLAG-tagged KMO enzyme on protein A magnetic beads. The protein-bound beads are incubated with potential binding compounds before specific cleavage of the protein-compound complexes from the beads. Mass spectrometry analysis is used to identify the compounds that demonstrate specific binding affinity for the target protein. The technique was validated using known inhibitors of KMO. This assay is a robust alternative to traditional ligand-binding assays for challenging protein targets, and it overcomes specific difficulties associated with isolating human KMO. © 2014 Society for Laboratory Automation and Screening.

  5. Zoonotic helminths affecting the human eye

    PubMed Central

    2011-01-01

    Nowaday, zoonoses are an important cause of human parasitic diseases worldwide and a major threat to the socio-economic development, mainly in developing countries. Importantly, zoonotic helminths that affect human eyes (HIE) may cause blindness with severe socio-economic consequences to human communities. These infections include nematodes, cestodes and trematodes, which may be transmitted by vectors (dirofilariasis, onchocerciasis, thelaziasis), food consumption (sparganosis, trichinellosis) and those acquired indirectly from the environment (ascariasis, echinococcosis, fascioliasis). Adult and/or larval stages of HIE may localize into human ocular tissues externally (i.e., lachrymal glands, eyelids, conjunctival sacs) or into the ocular globe (i.e., intravitreous retina, anterior and or posterior chamber) causing symptoms due to the parasitic localization in the eyes or to the immune reaction they elicit in the host. Unfortunately, data on HIE are scant and mostly limited to case reports from different countries. The biology and epidemiology of the most frequently reported HIE are discussed as well as clinical description of the diseases, diagnostic considerations and video clips on their presentation and surgical treatment. Homines amplius oculis, quam auribus credunt Seneca Ep 6,5 Men believe their eyes more than their ears PMID:21429191

  6. [Development of the next generation humanized mouse for drug discovery].

    PubMed

    Ito, Ryoji

    A humanized mouse, which is efficiently engrafted human cells and tissues, is an important tool to mimic human physiology for biomedical researches. Since 2000s, severe combined immunodeficient mouse strains such as NOG, BRG, and NSG mice have been generated. They are great recipients to create humanized mouse models compared to previous other immunodeficient strains due to their multiple dysfunctions of innate and acquired immunity. Especially, the transfer of human hematopoietic stem cells into these immunodeficient mice has been enabled to reconstitute human immune systems, because the mice show high engraftment level of human leukocyte in peripheral blood (~50%), spleen and bone marrow (60~90%) and generate well-differentiated multilineage human immune cells including lymphoid and myeloid lineage cells. Using these mice, several human disease models such as cancer, allergy, graft-versus-host disease (GVHD), and etc. have been established to understand the pathogenic mechanisms of the diseases and to evaluate the efficacy and safety of novel drugs. In this review, I provide an overview of recent advances in the humanized mouse technology, including generation of novel platforms of genetically modified NOG (next generation NOG) mice and some applications of them to create human disease models for drug discovery in preclinical researches.

  7. A Reverse-Translational Approach to Bipolar Disorder: Rodent and human studies in the Behavioral Pattern Monitor

    PubMed Central

    Young, Jared W.; Minassian, Arpi; Paulus, Martin P.; Geyer, Mark A.; Perry, William

    2007-01-01

    Mania is the defining feature of Bipolar Disorder (BD). There has been limited progress in understanding the neurobiological underpinnings of BD mania and developing novel therapeutics, in part due to a paucity of relevant animal models with translational potential. Hyperactivity is a cardinal symptom of mania, traditionally measured in humans using observer-rated scales. Multivariate assessment of unconditioned locomotor behavior using the rat Behavioral Pattern Monitor (BPM) developed in our laboratory has shown that hyperactivity includes complex multifaceted behaviors. The BPM has been used to demonstrate differential effects of drugs on locomotor activity and exploratory behavior in rats. Studies of genetically engineered mice in a mouse BPM have confirmed its utility as a cross-species tool. In a “reverse-translational” approach to this work, we developed the human BPM to characterize motor activity in BD patients. Increased activity, object interactions, and altered locomotor patterns provide multidimensional phenotypes to model in the rodent BPM. This unique approach to modeling BD provides an opportunity to identify the neurobiology underlying BD mania and test novel antimanic agents. PMID:17706782

  8. Using cross-species comparisons and a neurobiological framework to understand early social deprivation effects on behavioral development.

    PubMed

    Brett, Zoë H; Humphreys, Kathryn L; Fleming, Alison S; Kraemer, Gary W; Drury, Stacy S

    2015-05-01

    Building upon the transactional model of brain development, we explore the impact of early maternal deprivation on neural development and plasticity in three neural systems: hyperactivity/impulsivity, executive function, and hypothalamic-pituitary-adrenal axis functioning across rodent, nonhuman primate, and human studies. Recognizing the complexity of early maternal-infant interactions, we limit our cross-species comparisons to data from rodent models of artificial rearing, nonhuman primate studies of peer rearing, and the relations between these two experimental approaches and human studies of children exposed to the early severe psychosocial deprivation associated with institutional care. In addition to discussing the strengths and limitations of these paradigms, we present the current state of research on the neurobiological impact of early maternal deprivation and the evidence of sensitive periods, noting methodological challenges. Integrating data across preclinical animal models and human studies, we speculate about the underlying biological mechanisms; the differential impact of deprivation due to temporal factors including onset, offset, and duration of the exposure; and the possibility and consequences of reopening of sensitive periods during adolescence.

  9. Kidney-on-a-Chip: a New Technology for Predicting Drug Efficacy, Interactions, and Drug-induced Nephrotoxicity.

    PubMed

    Lee, Jeonghwan; Kim, Sejoong

    2018-03-08

    The kidneys play a pivotal role in most drug-removal processes and are important when evaluating drug safety. Kidney dysfunction resulting from various drugs is an important issue in clinical practice and during the drug development process. Traditional in vivo animal experiments are limited with respect to evaluating drug efficacy and nephrotoxicity due to discrepancies in drug pharmacokinetics and pharmacodynamics between humans and animals, and static cell culture experiments cannot fully reflect the actual microphysiological environment in humans. A kidney-on-a-chip is a microfluidic device that allows the culture of living renal cells in 3-dimensional channels and mimics the human microphysiological environment, thus simulating the actual drug filtering, absorption, and secretion process.. In this review, we discuss recent developments in microfluidic culturing technique and describe current and future kidney-on-a-chip applications. We focus on pharmacological interactions and drug-induced nephrotoxicity, and additionally discuss the development of multi-organ chips and their possible applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Using cross-species comparisons and a neurobiological framework to understand early social deprivation effects on behavioral development

    PubMed Central

    BRETT, ZOË H.; HUMPHREYS, KATHRYN L.; FLEMING, ALISON S.; KRAEMER, GARY W.; DRURY, STACY S.

    2017-01-01

    Building upon the transactional model of brain development, we explore the impact of early maternal deprivation on neural development and plasticity in three neural systems: hyperactivity/impulsivity, executive function, and hypothalamic–pituitary–adrenal axis functioning across rodent, nonhuman primate, and human studies. Recognizing the complexity of early maternal–infant interactions, we limit our cross-species comparisons to data from rodent models of artificial rearing, nonhuman primate studies of peer rearing, and the relations between these two experimental approaches and human studies of children exposed to the early severe psychosocial deprivation associated with institutional care. In addition to discussing the strengths and limitations of these paradigms, we present the current state of research on the neurobiological impact of early maternal deprivation and the evidence of sensitive periods, noting methodological challenges. Integrating data across preclinical animal models and human studies, we speculate about the underlying biological mechanisms; the differential impact of deprivation due to temporal factors including onset, offset, and duration of the exposure; and the possibility and consequences of reopening of sensitive periods during adolescence. PMID:25997759

  11. Antimicrobial Compounds from Eukaryotic Microalgae against Human Pathogens and Diseases in Aquaculture

    PubMed Central

    Falaise, Charlotte; François, Cyrille; Travers, Marie-Agnès; Morga, Benjamin; Haure, Joël; Tremblay, Réjean; Turcotte, François; Pasetto, Pamela; Gastineau, Romain; Hardivillier, Yann; Leignel, Vincent; Mouget, Jean-Luc

    2016-01-01

    The search for novel compounds of marine origin has increased in the last decades for their application in various areas such as pharmaceutical, human or animal nutrition, cosmetics or bioenergy. In this context of blue technology development, microalgae are of particular interest due to their immense biodiversity and their relatively simple growth needs. In this review, we discuss about the promising use of microalgae and microalgal compounds as sources of natural antibiotics against human pathogens but also about their potential to limit microbial infections in aquaculture. An alternative to conventional antibiotics is needed as the microbial resistance to these drugs is increasing in humans and animals. Furthermore, using natural antibiotics for livestock could meet the consumer demand to avoid chemicals in food, would support a sustainable aquaculture and present the advantage of being environmentally friendly. Using natural and renewable microalgal compounds is still in its early days, but considering the important research development and rapid improvement in culture, extraction and purification processes, the valorization of microalgae will surely extend in the future. PMID:27598176

  12. The human sex ratio from conception to birth

    PubMed Central

    Orzack, Steven Hecht; Stubblefield, J. William; Akmaev, Viatcheslav R.; Colls, Pere; Munné, Santiago; Scholl, Thomas; Steinsaltz, David; Zuckerman, James E.

    2015-01-01

    We describe the trajectory of the human sex ratio from conception to birth by analyzing data from (i) 3- to 6-d-old embryos, (ii) induced abortions, (iii) chorionic villus sampling, (iv) amniocentesis, and (v) fetal deaths and live births. Our dataset is the most comprehensive and largest ever assembled to estimate the sex ratio at conception and the sex ratio trajectory and is the first, to our knowledge, to include all of these types of data. Our estimate of the sex ratio at conception is 0.5 (proportion male), which contradicts the common claim that the sex ratio at conception is male-biased. The sex ratio among abnormal embryos is male-biased, and the sex ratio among normal embryos is female-biased. These biases are associated with the abnormal/normal state of the sex chromosomes and of chromosomes 15 and 17. The sex ratio may decrease in the first week or so after conception (due to excess male mortality); it then increases for at least 10–15 wk (due to excess female mortality), levels off after ∼20 wk, and declines slowly from 28 to 35 wk (due to excess male mortality). Total female mortality during pregnancy exceeds total male mortality. The unbiased sex ratio at conception, the increase in the sex ratio during the first trimester, and total mortality during pregnancy being greater for females are fundamental insights into early human development. PMID:25825766

  13. Human biomonitoring data interpretation and ethics; obstacles or surmountable challenges?

    PubMed Central

    Sepai, Ovnair; Collier, Clare; Van Tongelen, Birgit; Casteleyn, Ludwine

    2008-01-01

    The use of human samples to assess environmental exposure and uptake of chemicals is more than an analytical exercise and requires consideration of the utility and interpretation of data as well as due consideration of ethical issues. These aspects are inextricably linked. In 2004 the EC expressed its commitment to the development of a harmonised approach to human biomonitoring (HBM) by including an action in the EU Environment and Health Strategy to develop a Human Biomonitoring Pilot Study. This further underlined the need for interpretation strategies as well as guidance on ethical issues. A workshop held in December 2006 brought together stakeholders from academia, policy makers as well as non-governmental organisations and chemical industry associations to a two day workshop built a mutual understanding of the issues in an open and frank discussion forum. This paper describes the discussion and recommendations from the workshop. The workshop developed key recommendations for a Pan-European HBM Study: 1. A strategy for the interpretation of human biomonitoring data should be developed. 2. The pilot study should include the development of a strategy to integrate health data and environmental monitoring with human biomonitoring data at national and international levels. 3. Communication strategies should be developed when designing the study and evolve as the study continues. 4. Early communication with stakeholders is essential to achieve maximum efficacy of policy developments and facilitate subsequent monitoring. 5. Member states will have to apply individually for project approval from their National Research Ethics Committees. 6. The study population needs to have sufficient information on the way data will be gathered, interpreted and disseminated and how samples will be stored and used in the future (if biobanking) before they can give informed consent. 7. The participants must be given the option of anonymity. This has an impact on follow-up. 8. The pilot study should develop guidelines and best practice for Ethics for pan European studies. In conclusion all participants felt there that there has to be stakeholder involvement in any planned pan-European Human Biomonitoring Study and the format of the workshop was appropriate for such dialogue. PMID:18541067

  14. An Earthling to an Astronaut: Medical Challenges

    NASA Technical Reports Server (NTRS)

    Davis, Jeffrey R.

    2011-01-01

    Humans can travel safely into space in low Earth orbit (LEO) or to near-Earth objects if several medical, physiological, environmental, and human factors issues risks are mitigated. Research must be performed in order to set standards in these four areas, and current NASA standards are contained in the Space Flight Human System Standards volumes 1 and 2, and crew medical certification standards. These three sets of standards drive all of the clinical, biomedical research and environmental technology development for the NASA human space flight program. These standards also drive the identification of specific risks to crew health and safety, and we currently manage 65 human system risks within the human space flight program. Each risk has a specific program of research, technology development, and development of operational procedures to mitigate the risks. Some of the more important risks tat will be discussed in this talk include exposure to radiation, behavioral health due to confinement in a closed cabin, physiological changes such as loss of bone, muscle and exercise capability, reduction in immune system capability, environmental threats of maintaining an adequate atmosphere and water for drinking, avoidance of toxic or infectious material, protection of hearing, and human factors issues of equipment and task design. A nutritious and varied food supply must also be provided. All of these risks will be discussed and current strategies for mitigating these risks for long-duration human space flight. In mitigating these 65 human system risks, novel approaches to problem solving must be employed to find the most appropriate research and technology based applications. Some risk mitigations are developed internally to NASA while others are found through research grants, technology procurements, and more recently open innovation techniques to seek solutions from the global technical community. Examples and results will be presented from all of these approaches including the more recent use of prizes to stimulate innovation.

  15. GeneStoryTeller: a mobile app for quick and comprehensive information retrieval of human genes

    PubMed Central

    Eleftheriou, Stergiani V.; Bourdakou, Marilena M.; Athanasiadis, Emmanouil I.; Spyrou, George M.

    2015-01-01

    In the last few years, mobile devices such as smartphones and tablets have become an integral part of everyday life, due to their software/hardware rapid development, as well as the increased portability they offer. Nevertheless, up to now, only few Apps have been developed in the field of bioinformatics, capable to perform fast and robust access to services. We have developed the GeneStoryTeller, a mobile application for Android platforms, where users are able to instantly retrieve information regarding any recorded human gene, derived from eight publicly available databases, as a summary story. Complementary information regarding gene–drugs interactions, functional annotation and disease associations for each selected gene is also provided in the gene story. The most challenging part during the development of the GeneStoryTeller was to keep balance between storing data locally within the app and obtaining the updated content dynamically via a network connection. This was accomplished with the implementation of an administrative site where data are curated and synchronized with the application requiring a minimum human intervention. Database URL: http://bioserver-3.bioacademy.gr/Bioserver/GeneStoryTeller/. PMID:26055097

  16. Energy Harvesting from Upper-Limb Pulling Motions for Miniaturized Human-Powered Generators

    PubMed Central

    Yeo, Jeongjin; Ryu, Mun-ho; Yang, Yoonseok

    2015-01-01

    The human-powered self-generator provides the best solution for individuals who need an instantaneous power supply for travel, outdoor, and emergency use, since it is less dependent on weather conditions and occupies less space than other renewable power supplies. However, many commercial portable self-generators that employ hand-cranking are not used as much as expected in daily lives although they have enough output capacity due to their intensive workload. This study proposes a portable human-powered generator which is designed to obtain mechanical energy from an upper limb pulling motion for improved human motion economy as well as efficient human-mechanical power transfer. A coreless axial-flux permanent magnet machine (APMM) and a flywheel magnet rotor were used in conjunction with a one-way clutched power transmission system in order to obtain effective power from the pulling motion. The developed prototype showed an average energy conversion efficiency of 30.98% and an average output power of 0.32 W with a maximum of 1.89 W. Its small form factor (50 mm × 32 mm × 43.5 mm, 0.05 kg) and the substantial electricity produced verify the effectiveness of the proposed method in the utilization of human power. It is expected that the developed generator could provide a mobile power supply. PMID:26151204

  17. Energy Harvesting from Upper-Limb Pulling Motions for Miniaturized Human-Powered Generators.

    PubMed

    Yeo, Jeongjin; Ryu, Mun-ho; Yang, Yoonseok

    2015-07-03

    The human-powered self-generator provides the best solution for individuals who need an instantaneous power supply for travel, outdoor, and emergency use, since it is less dependent on weather conditions and occupies less space than other renewable power supplies. However, many commercial portable self-generators that employ hand-cranking are not used as much as expected in daily lives although they have enough output capacity due to their intensive workload. This study proposes a portable human-powered generator which is designed to obtain mechanical energy from an upper limb pulling motion for improved human motion economy as well as efficient human-mechanical power transfer. A coreless axial-flux permanent magnet machine (APMM) and a flywheel magnet rotor were used in conjunction with a one-way clutched power transmission system in order to obtain effective power from the pulling motion. The developed prototype showed an average energy conversion efficiency of 30.98% and an average output power of 0.32 W with a maximum of 1.89 W. Its small form factor (50 mm × 32 mm × 43.5 mm, 0.05 kg) and the substantial electricity produced verify the effectiveness of the proposed method in the utilization of human power. It is expected that the developed generator could provide a mobile power supply.

  18. Phospholipids in Human Milk and Infant Formulas: Benefits and Needs for Correct Infant Nutrition.

    PubMed

    Cilla, Antonio; Diego Quintaes, Késia; Barberá, Reyes; Alegría, Amparo

    2016-08-17

    The composition of human milk has served as a basis for the development of infant formulas, which are used when breastfeeding is not possible. Among the human milk nutrients, 50% of the total energetic value corresponds to fat, with a high level of fatty acids and 0.2-2.0% present in the form of phospholipids (PLs). The PL contents and fatty acid distribution in PL species have been investigated as bioactive elements for the production of infant formulas, since they offer potential benefits for the optimum growth and health of the newborn infant. The differences in the amount of PLs and in fatty acid distribution in PL species between human milk and infant formulas can imply biologically significant differences for newborn infants fed with infant formulas versus human milk-mainly due to the greater proportion of sphingomyelin with respect to phosphatidylcholine in infant formulas. The limited information referred to the characterization of fatty acid distribution in PL species in infant formulas or in ingredients used to enrich them merits further research in order to obtain products with benefits similar to those of human milk in terms of infant growth, visual acuity, and neurological development. The present review establishes the scientific basis for helping to adjust formulations to the requirements of infant nutrition.

  19. 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.

  20. Human norovirus infection in Latin America.

    PubMed

    da Silva Poló, Tatiane; Peiró, Juliana R; Mendes, Luiz Cláudio Nogueira; Ludwig, Louisa F; de Oliveira-Filho, Edmilson F; Bucardo, Filemon; Huynen, Pascale; Melin, Pierrette; Thiry, Etienne; Mauroy, Axel

    2016-05-01

    Noroviruses are important enteric pathogens involved in non-bacterial gastroenteritis outbreaks worldwide. Noroviruses mainly occur from person to person via the fecal-oral route but also through contaminated food or water; indirect contamination is also possible due to the resistance of the virus in the environment. Latin American countries as a whole cover a vast North-to-South range, which is highly heterogeneous in terms of climate, ecosystem, human population distribution (urban areas with high human densities versus closed communities), economic development and genetic backgrounds resulting from each particular historical context. This review aims to present epidemiological and clinical patterns of human norovirus infections in Latin American countries. Divergent prevalences were observed depending on the country and the surveyed population. In particular, a shift in rotavirus/norovirus ratio in the etiologies of gastroenteritis was detected in some countries and could be attributed partly to rotavirus vaccine coverage in their infant population. While GII.4 noroviruses were seen to constitute the most common genotype, differences in genotype distribution were observed both in the environment (via sewage sampling proxy) and between genotypes circulating in healthy and diarrheic patients. Due to high climatic discrepancies, different patterns of seasonality were observed. Accordingly, this continent may condense the different particular epidemiological features encountered for HuNoV infections worldwide. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Testicular tissue cryopreservation and spermatogonial stem cell transplantation to restore fertility: from bench to bedside

    PubMed Central

    2014-01-01

    Male infertility management has made significant progress during the past three decades, especially after the introduction of intracytoplasmic sperm injection in 1992. However, many boys and men still suffer from primary testicular failure due to acquired or genetic causes. New and novel treatments are needed to address these issues. Spermatogenesis originates from spermatogonial stem cells (SSCs) that reside in the testis. Many of these men lack SSCs or have lost SSCs over time as a result of specific medical conditions or toxic exposures. Loss of SSCs is critical in prepubertal boys who suffer from cancer and are going through gonadotoxic cancer treatments, as there is no option of sperm cryopresrvation due to sexual immaturity. The development of SSC transplantation in a mouse model to repopulate spermatozoa in depleted testes has opened new avenues of research in other animal models, including non-human primates. Recent advances in cryopreservation and in vitro propagation of human SSCs offer promise for human SSC autotransplantation in the near future. Ongoing research is focusing on safety and technical issues of human SSC autotransplantation. This is the time to counsel parents and boys at risk of infertility on the possibility of cryopreserving and banking a small amount of testis tissue for potential future use in SSC transplantation. PMID:25157677

  2. Avian influenza A H5N1 virus: a continuous threat to humans

    PubMed Central

    To, Kelvin KW; Ng, Kenneth HL; Que, Tak-Lun; Chan, Jacky MC; Tsang, Kay-Yan; Tsang, Alan KL; Chen, Honglin; Yuen, Kwok-Yung

    2012-01-01

    We report the first case of severe pneumonia due to co-infection with the emerging avian influenza A (H5N1) virus subclade 2.3.2.1 and Mycoplasma pneumoniae. The patient was a returning traveller who had visited a poultry market in South China. We then review the epidemiology, virology, interspecies barrier limiting poultry-to-human transmission, clinical manifestation, laboratory diagnosis, treatment and control measures of H5N1 clades that can be transmitted to humans. The recent controversy regarding the experiments involving aerosol transmission of recombinant H5N1 virus between ferrets is discussed. We also review the relative contribution of the poor response to antiviral treatment and the virus-induced hyperinflammatory damage to the pathogenesis and the high mortality of this infection. The factors related to the host, virus or medical intervention leading to the difference in disease mortality of different countries remain unknown. Because most developing countries have difficulty in instituting effective biosecurity measures, poultry vaccination becomes an important control measure. The rapid evolution of the virus would adversely affect the efficacy of poultry vaccination unless a correctly matched vaccine was chosen, manufactured and administered in a timely manner. Vigilant surveillance must continue to allow better preparedness for another poultry or human pandemic due to new viral mutants. PMID:26038430

  3. Development of a Device for Objective Assessment of Tinnitus in Humans

    DTIC Science & Technology

    2017-10-01

    develop and refine the Gap Device and testing methodology . In the third year of the grant, we began to conduct a multisite research study to...in the last quarter of 2016. Secured IRB approvals for all study sites (SIU, Portland VA, Madigan Army Medical Center). HRPO approvals obtained for all... study sites. IRB Continuing Review (CR) and HRPO CR approvals also obtained for SIU and PVA. MAMC IRB CR and HRPO CR approvals are not due until

  4. Noise Protection

    NASA Technical Reports Server (NTRS)

    1980-01-01

    Environmental Health Systems puts forth an increasing effort in the U.S. to develop ways of controlling noise, particularly in industrial environments due to Federal and State laws, labor union insistence and new findings relative to noise pollution impact on human health. NASA's Apollo guidance control system aided in the development of a noise protection product, SMART. The basis of all SMART products is SMART compound a liquid plastic mixture with exceptional energy/sound absorbing qualities. The basic compound was later refined for noise protection use.

  5. Carbohydrates and the human gut microbiota.

    PubMed

    Chassard, Christophe; Lacroix, Christophe

    2013-07-01

    Due to its scale and its important role in maintaining health, the gut microbiota can be considered as a 'new organ' inside the human body. Many complex carbohydrates are degraded and fermented by the human gut microbiota in the large intestine to both yield basic energy salvage and impact gut health through produced metabolites. This review will focus on the gut microbes and microbial mechanisms responsible for polysaccharides degradation and fermentation in the large intestine. Gut microbes and bacterial metabolites impact the host at many levels, including modulation of inflammation, and glucose and lipid metabolisms. A complex relationship occurs in the intestine between the human gut microbiota, diet and the host. Research on carbohydrates and gut microbiota composition and functionality is fast developing and will open opportunities for prevention and treatment of obesity, diabetes and other related metabolic disorders through manipulation of the gut ecosystem.

  6. The Importance of Primary Martian Surface and Airfall Dust Sample Return for Toxicological Hazard Evaluations for Human Exploration

    NASA Technical Reports Server (NTRS)

    Harrington, A. D.; McCubbin, F. M.

    2018-01-01

    Manned missions to the Moon highlight a major hazard for future human exploration of the Moon and beyond: surface dust. Not only did the dust cause mechanical and structural integrity issues with the suits, the dust 'storm' generated upon reentrance into the crew cabin caused "lunar hay fever" and "almost blindness" . It was further reported that the allergic response to the dust worsened with each exposure. Due to the prevalence of these high exposures, the Human Research Roadmap developed by NASA identifies the Risk of Adverse Health and Performance Effects of Celestial Dust Exposure as an area of concern. Extended human exploration will further increase the probability of inadvertent and repeated exposures to celestial dusts. Going forward, hazard assessments of celestial dusts will be determined through sample return efforts prior to astronaut deployment.

  7. NASA's Human Research Program at The Glenn Research Center: Progress and Opportunities

    NASA Technical Reports Server (NTRS)

    Nall, Marsha; Griffin, DeVon; Myers, Jerry; Perusek, Gail

    2008-01-01

    The NASA Human Research Program is aimed at correcting problems in critical areas that place NASA human spaceflight missions at risk due to shortfalls in astronaut health, safety and performance. The Glenn Research Center (GRC) and partners from Ohio are significant contributors to this effort. This presentation describes several areas of GRC emphasis, the first being NASA s path to creating exercise hardware requirements and protocols that mitigate the effects of long duration spaceflight. Computational simulations will be a second area that is discussed. This includes deterministic models that simulate the effects of spaceflight on the human body, as well as probabilistic models that bound and quantify the probability that adverse medical incidents will happen during an exploration mission. Medical technology development for exploration will be the final area to be discussed.

  8. Revisit of Machine Learning Supported Biological and Biomedical Studies.

    PubMed

    Yu, Xiang-Tian; Wang, Lu; Zeng, Tao

    2018-01-01

    Generally, machine learning includes many in silico methods to transform the principles underlying natural phenomenon to human understanding information, which aim to save human labor, to assist human judge, and to create human knowledge. It should have wide application potential in biological and biomedical studies, especially in the era of big biological data. To look through the application of machine learning along with biological development, this review provides wide cases to introduce the selection of machine learning methods in different practice scenarios involved in the whole biological and biomedical study cycle and further discusses the machine learning strategies for analyzing omics data in some cutting-edge biological studies. Finally, the notes on new challenges for machine learning due to small-sample high-dimension are summarized from the key points of sample unbalance, white box, and causality.

  9. Design and Development of Card-Sized Virtual Keyboard Using Permanent Magnets and Hall Sensors

    NASA Astrophysics Data System (ADS)

    Demachi, Kazuyuki; Ohyama, Makoto; Kanemoto, Yoshiki; Masaie, Issei

    This paper proposes a method to distinguish the key-type of human fingers attached with the small permanent magnets. The Hall sensors arrayed in the credit card size area feel the distribution of the magnetic field due to the key-typing movement of the human fingers as if the keyboard exists, and the signal is analyzed using the generic algorithm or the neural network algorism to distinguish the typed keys. By this method, the keyboard can be miniaturized to the credit card size (54mm×85mm). We called this system `The virtual keyboard system'.

  10. Developmental and morphological studies in Japanese medaka with ultra-high resolution optical coherence tomography.

    PubMed

    Gladys, Fanny Moses; Matsuda, Masaru; Lim, Yiheng; Jackin, Boaz Jessie; Imai, Takuto; Otani, Yukitoshi; Yatagai, Toyohiko; Cense, Barry

    2015-02-01

    We propose ultra-high resolution optical coherence tomography to study the morphological development of internal organs in medaka fish in the post-embryonic stages at micrometer resolution. Different stages of Japanese medaka were imaged after hatching in vivo with an axial resolution of 2.8 µm in tissue. Various morphological structures and organs identified in the OCT images were then compared with the histology. Due to the medaka's close resemblance to vertebrates, including humans, these morphological features play an important role in morphogenesis and can be used to study diseases that also occur in humans.

  11. Not the Usual Viral Suspects: Parvovirus B19, West Nile Virus, and Human T-Cell Lymphotrophic Virus Infections After Kidney Transplantation.

    PubMed

    Razonable, Raymund R

    2016-09-01

    Kidney transplant recipients are at increased risk of developing clinical disease due to uncommon opportunistic viral pathogens. Refractory anemia is classically associated with parvovirus B19 infection. West Nile virus has the propensity to cause fever and neurologic symptoms, while spastic paresis and lymphoma can be triggered by human T cell lymphotrophic virus. In this review article, the epidemiology, clinical manifestations, diagnosis and treatment of less common viruses are discussed in the setting of kidney transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Nord, Alex S.; Pattabiraman, Kartik; Visel, Axel

    The forebrain is the seat of higher-order brain functions, and many human neuropsychiatric disorders are due to genetic defects affecting forebrain development, making it imperative to understand the underlying genetic circuitry. We report that recent progress now makes it possible to begin fully elucidating the genomic regulatory mechanisms that control forebrain gene expression. Here, we discuss the current knowledge of how transcription factors drive gene expression programs through their interactions with cis-acting genomic elements, such as enhancers; how analyses of chromatin and DNA modifications provide insights into gene expression states; and how these approaches yield insights into the evolution ofmore » the human brain.« less

  13. Maternal Obesity: Lifelong Metabolic Outcomes for Offspring from Poor Developmental Trajectories During the Perinatal Period.

    PubMed

    Zambrano, Elena; Ibáñez, Carlos; Martínez-Samayoa, Paola M; Lomas-Soria, Consuelo; Durand-Carbajal, Marta; Rodríguez-González, Guadalupe L

    2016-01-01

    The prevalence of obesity in women of reproductive age is increasing in developed and developing countries around the world. Human and animal studies indicate that maternal obesity adversely impacts both maternal health and offspring phenotype, predisposing them to chronic diseases later in life including obesity, dyslipidemia, type 2 diabetes mellitus, and hypertension. Several mechanisms act together to produce these adverse health effects including programming of hypothalamic appetite-regulating centers, increasing maternal, fetal and offspring glucocorticoid production, changes in maternal metabolism and increasing maternal oxidative stress. Effective interventions during human pregnancy are needed to prevent both maternal and offspring metabolic dysfunction due to maternal obesity. This review addresses the relationship between maternal obesity and its negative impact on offspring development and presents some maternal intervention studies that propose strategies to prevent adverse offspring metabolic outcomes. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

  14. Computational intelligence in bioinformatics: SNP/haplotype data in genetic association study for common diseases.

    PubMed

    Kelemen, Arpad; Vasilakos, Athanasios V; Liang, Yulan

    2009-09-01

    Comprehensive evaluation of common genetic variations through association of single-nucleotide polymorphism (SNP) structure with common complex disease in the genome-wide scale is currently a hot area in human genome research due to the recent development of the Human Genome Project and HapMap Project. Computational science, which includes computational intelligence (CI), has recently become the third method of scientific enquiry besides theory and experimentation. There have been fast growing interests in developing and applying CI in disease mapping using SNP and haplotype data. Some of the recent studies have demonstrated the promise and importance of CI for common complex diseases in genomic association study using SNP/haplotype data, especially for tackling challenges, such as gene-gene and gene-environment interactions, and the notorious "curse of dimensionality" problem. This review provides coverage of recent developments of CI approaches for complex diseases in genetic association study with SNP/haplotype data.

  15. Botulinum neurotoxin vaccines: Past history and recent developments.

    PubMed

    Rusnak, Janice M; Smith, Leonard A

    2009-12-01

    Botulinum toxin may cause a neuroparalytic illness that may result in respiratory failure and require prolonged mechanical ventilation. As medical resources needed for supportive care of botulism in a bioterrorist event may quickly overwhelm the local healthcare systems, biodefense research efforts have been directed towards the development of a vaccine to prevent botulism. While human botulism has been caused only by toxin serotypes A, B, and E (rarely serotype F), all seven known immunologically distinct toxin serotypes (A - G) may potentially cause intoxication in humans from a bioterrorist event. A pentavalent (ABCDE) botulinum toxoid (PBT) has been administered as an investigation new drug (IND) to at-risk individuals for nearly 50 years. Due to declining immunogenicity of the PBT, research efforts have been directed at development of both improved (less local reactogenicity) botulinum toxoids and recombinant vaccines as potential vaccine candidates to replace the PBT.

  16. Historical aspects of human presence in Space

    NASA Astrophysics Data System (ADS)

    Harsch, V.

    2007-02-01

    Purpose: This paper presents the development of human presence in Space from its beginnings. Study hypotheses were based on historical findings on scientific, medical, cultural, and political aspects of manned Space flight due to the different attitudes of Space minded nations and organizations. Impacts of aerospace medicine on the advances of biomedical sciences will be touched upon, as well as the historical development of aviation and Space medical achievements which are described briefly and visions for future developments are given. Methods: An overview was gained by literature-study, archives research and oral history taking. Results: Aviation Medicine evolved parallel to Man's ability to fly. War-triggered advancements in aviation brought mankind to the edge of space-equivalent conditions within a few decades of the first motor-flight, which took place in the USA in 1903 [V. Harsch, Aerospace medicine in Germany: from the very beginnings, Aviation and Space Environment Medicine 71 (2000) 447-450 [1

  17. [Neurophysiological Foundations and Practical Realizations of the Brain-Machine Interfaces the Technology in Neurological Rehabilitation].

    PubMed

    Kaplan, A Ya

    2016-01-01

    Technology brain-computer interface (BCI) based on the registration and interpretation of EEG has recently become one of the most popular developments in neuroscience and psychophysiology. This is due not only to the intended future use of these technologies in many areas of practical human activity, but also to the fact that IMC--is a completely new paradigm in psychophysiology, allowing test hypotheses about the possibilities of the human brain to the development of skills of interaction with the outside world without the mediation of the motor system, i.e. only with the help of voluntary modulation of EEG generators. This paper examines the theoretical and experimental basis, the current state and prospects of development of training, communicational and assisting complexes based on BCI to control them without muscular effort on the basis of mental commands detected in the EEG of patients with severely impaired speech and motor system.

  18. Toward a Social Psychophysics of Face Communication.

    PubMed

    Jack, Rachael E; Schyns, Philippe G

    2017-01-03

    As a highly social species, humans are equipped with a powerful tool for social communication-the face. Although seemingly simple, the human face can elicit multiple social perceptions due to the rich variations of its movements, morphology, and complexion. Consequently, identifying precisely what face information elicits different social perceptions is a complex empirical challenge that has largely remained beyond the reach of traditional methods. In the past decade, the emerging field of social psychophysics has developed new methods to address this challenge, with the potential to transfer psychophysical laws of social perception to the digital economy via avatars and social robots. At this exciting juncture, it is timely to review these new methodological developments. In this article, we introduce and review the foundational methodological developments of social psychophysics, present work done in the past decade that has advanced understanding of the face as a tool for social communication, and discuss the major challenges that lie ahead.

  19. Emergence of scaling in human-interest dynamics.

    PubMed

    Zhao, Zhi-Dan; Yang, Zimo; Zhang, Zike; Zhou, Tao; Huang, Zi-Gang; Lai, Ying-Cheng

    2013-12-11

    Human behaviors are often driven by human interests. Despite intense recent efforts in exploring the dynamics of human behaviors, little is known about human-interest dynamics, partly due to the extreme difficulty in accessing the human mind from observations. However, the availability of large-scale data, such as those from e-commerce and smart-phone communications, makes it possible to probe into and quantify the dynamics of human interest. Using three prototypical "Big Data" sets, we investigate the scaling behaviors associated with human-interest dynamics. In particular, from the data sets we uncover fat-tailed (possibly power-law) distributions associated with the three basic quantities: (1) the length of continuous interest, (2) the return time of visiting certain interest, and (3) interest ranking and transition. We argue that there are three basic ingredients underlying human-interest dynamics: preferential return to previously visited interests, inertial effect, and exploration of new interests. We develop a biased random-walk model, incorporating the three ingredients, to account for the observed fat-tailed distributions. Our study represents the first attempt to understand the dynamical processes underlying human interest, which has significant applications in science and engineering, commerce, as well as defense, in terms of specific tasks such as recommendation and human-behavior prediction.

  20. Emergence of scaling in human-interest dynamics

    NASA Astrophysics Data System (ADS)

    Zhao, Zhi-Dan; Yang, Zimo; Zhang, Zike; Zhou, Tao; Huang, Zi-Gang; Lai, Ying-Cheng

    2013-12-01

    Human behaviors are often driven by human interests. Despite intense recent efforts in exploring the dynamics of human behaviors, little is known about human-interest dynamics, partly due to the extreme difficulty in accessing the human mind from observations. However, the availability of large-scale data, such as those from e-commerce and smart-phone communications, makes it possible to probe into and quantify the dynamics of human interest. Using three prototypical ``Big Data'' sets, we investigate the scaling behaviors associated with human-interest dynamics. In particular, from the data sets we uncover fat-tailed (possibly power-law) distributions associated with the three basic quantities: (1) the length of continuous interest, (2) the return time of visiting certain interest, and (3) interest ranking and transition. We argue that there are three basic ingredients underlying human-interest dynamics: preferential return to previously visited interests, inertial effect, and exploration of new interests. We develop a biased random-walk model, incorporating the three ingredients, to account for the observed fat-tailed distributions. Our study represents the first attempt to understand the dynamical processes underlying human interest, which has significant applications in science and engineering, commerce, as well as defense, in terms of specific tasks such as recommendation and human-behavior prediction.

  1. Experimental study on trace chemical contaminant generation rates of human metabolism in spacecraft crew module

    NASA Astrophysics Data System (ADS)

    Lihua, Guo; Xinxing, He; Guoxin, Xu; Xin, Qi

    2012-12-01

    Trace chemical contaminants generated by human metabolism is a major source of contamination in spacecraft crew module. In this research, types and generation rates of pollutants from human metabolism were determined in the Chinese diets. Expired air, skin gas, and sweat of 20 subjects were analyzed at different exercise states in a simulated module. The exercise states were designed according to the basic activities in the orbit of astronauts. Qualitative and quantitative analyses of contaminants generated by human metabolic were performed with gas chromatography/mass spectrometry, gas chromatography and UV spectrophotometer. Sixteen chemical compounds from metabolic sources were found. With the increase in physical load, the concentrations of chemical compounds from human skin and expired air correspondingly increased. The species and the offgassing rates of pollutants from human metabolism are different among the Chinese, Americans and the Russians due to differences in ethnicity and dietary customs. This research provides data to aid in the design, development and operation of China's long duration space mission.

  2. Modeling the Western Diet for Preclinical Investigations.

    PubMed

    Hintze, Korry J; Benninghoff, Abby D; Cho, Clara E; Ward, Robert E

    2018-05-01

    Rodent models have been invaluable for biomedical research. Preclinical investigations with rodents allow researchers to investigate diseases by using study designs that are not suitable for human subjects. The primary criticism of preclinical animal models is that results are not always translatable to humans. Some of this lack of translation is due to inherent differences between species. However, rodent models have been refined over time, and translatability to humans has improved. Transgenic animals have greatly aided our understanding of interactions between genes and disease and have narrowed the translation gap between humans and model animals. Despite the technological innovations of animal models through advances in genetics, relatively little attention has been given to animal diets. Namely, developing diets that replicate what humans eat will help make animal models more relevant to human populations. This review focuses on commonly used rodent diets that are used to emulate the Western dietary pattern in preclinical studies of obesity and type 2 diabetes, nonalcoholic liver disease, maternal nutrition, and colorectal cancer.

  3. [The interface of public healthcare with the health of the oceans: proliferation of disease, socio-economic impacts and beneficial relationships].

    PubMed

    de Moura, Jailson Fulgencio; Cardozo, Marcelo; Belo, Mariana Soares da Silva Peixoto; Hacon, Sandra; Siciliano, Salvatore

    2011-08-01

    Over the past decades, human activities have had a heavy impact on the marine environment, causing alterations in ecological processes. The relationship between the health of the oceans, human activities and public healthcare is already generally accepted, though the mechanisms involved are still under scientific scrutiny. These relationships include a focus on climate change, toxic algal blooms, microbial and chemical contamination in marine waters and bioinvasion by exotic species. Moreover, there is the beneficial effect of the oceans on human health and wellbeing, such as natural products for the human diet, the development of biomedicine, or simply the satisfaction derived from human recreation, sports and other interactions of humans with oceans. The importance of appreciating the link between public healthcare and the health of the oceans is especially important due to the growing number of people living in coastal areas, mainly in tropical and subtropical regions. The backcloth to this is risk-related human activities that pose a danger to marine environmental health and the increase in the vulnerability of humans and biodiversity and socio-environmental iniquity.

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

    T.R. McJunkin; R.L. Boring; M.A. McQueen

    Situational awareness in the operations and supervision of a industrial system means that decision making entity, whether machine or human, have the important data presented in a timely manner. An optimal presentation of information such that the operator has the best opportunity accurately interpret and react to anomalies due to system degradation, failures or adversaries. Anticipated problems are a matter for system design; however, the paper will focus on concepts for situational awareness enhancement for a human operator when the unanticipated or unaddressed event types occur. Methodology for human machine interface development and refinement strategy is described for a syntheticmore » fuels plant model. A novel concept for adaptively highlighting the most interesting information in the system and a plan for testing the methodology is described.« less

  5. Development of a Space-Rated Proton Exchange Membrane Fuel Cell

    NASA Technical Reports Server (NTRS)

    Hoffman, William C., III; Vasquez, Arturo; Lazaroff, Scott M.; Downey, Michael G.

    1999-01-01

    Power systems for human spacecraft have historically included fuel cells due to the superior energy density they offer over battery systems depending on mission length and power consumption. As space exploration focuses on the evolution of reusable spacecraft and also considers planetary exploration power system requirements, fuel cells continue to be a factor in the potential system solutions.

  6. Improvement of CSCW Software Implementation in NPD: The CAM Mechanism for a Better Adoption by Users

    ERIC Educational Resources Information Center

    Restrepo, Tomas; Arbelaez, Natalia; Millet, Dominique; Gidel, Thierry

    2010-01-01

    Cooperation between disseminated actors is a key factor in improving new product development (NPD) performance. In the last years, numerous CSCW software applications have been introduced in the industry to support NPD with a low success rate. This is partly due to the limited insight of the organisational and human factors influencing user…

  7. Strategic Analysis of Sustainable Socioeconomic Situation of Rural Areas in the Samara Region of the Russian Federation

    ERIC Educational Resources Information Center

    Belyaeva, Galina I.; Ermoshkina, Ekaterina N.; Kosyakova, Inessa V.; Pankratova, Larisa E.; Zotova, Anna S.

    2016-01-01

    On the one hand, the relevance of this problem is primarily determined by a growing gap of rural territorial entities in socioeconomic development, and on the other hand, due to their significance in such prominent aspects for the country as food security, maintaining the existing land, industrial, ecological, demographic and human potential. The…

  8. The Efficacy of a Green Chemistry Laboratory-Based Pedagogy: Changes in Environmental Values of Malaysia Pre-Service Teachers

    ERIC Educational Resources Information Center

    Karpudewan, Mageswary; Ismail, Zurida; Roth, Wolff-Michael

    2012-01-01

    Every day, climate change due to greenhouse emissions, pollution and other environmental degradation appears to make the news. Rather than doing something about the environment, namely in the developing countries where populations frequently are less educated about the long-term impact of human actions, they tend to disregard these problems. There…

  9. The Breast Health Intervention Evaluation Study

    DTIC Science & Technology

    2001-08-01

    content due to its subtle almost subliminal impact even though this issue did not surface in the various pre-tests during video development. A third...A. (1990). Involuntary attention and physiological arousal evoked by structural features and emotional content in TV commercials. Communication...Human communication research, 13, 399-420. Pezdek, K., and Stevens, E. (1984). Children=s memory for auditory and visual information on television

  10. NELA: A Community Response to HIV/AIDS in Nigeria

    ERIC Educational Resources Information Center

    Soyinka, Femi; Ogundare, Dipo; Olowookere, Kemi; Akinsola, Yemisi; Alade, Adeyemi; Moronkola, O. A.

    2004-01-01

    The greatest current threat to humanity, most especially in the developing countries of the world, is HIV/AIDS. The first case of HIV/AIDS in Nigeria was in 1986 in Lagos. Due to inaction and denial by the people, there was a rapid but subtle transmission of the virus within Nigeria's various populations and communities. Presently, the disease has…

  11. Utilization of Cloud Computing in Education and Research to the Attainment of Millennium Development Goals and Vision 2030 in Kenya

    ERIC Educational Resources Information Center

    Waga, Duncan; Makori, Esther; Rabah, Kefa

    2014-01-01

    Kenya Educational and Research fraternity has highly qualified human resource capacity with globally gained experiences. However each research entity works in disparity due to the absence of a common digital platform while educational units don't even have the basic infrastructure. For sustainability of Education and research progression,…

  12. A Comparison of Japanese and Turkish Mothers' Views about Self Care Skill Acquisition Age and Their Expectations from Preschools

    ERIC Educational Resources Information Center

    Ramazan, M. Oya; Sakai, Aya

    2017-01-01

    Spanning the vital temporal interval between birth and the elementary school education, the preschool period is one of the most critical times of human life due to its importance in the formation and nourishment of personality. Specifically the preschool education enables children to acquire and develop basic knowledge, skills and habits, thus…

  13. Survival of Campylobacter jejuni and Campylobacter coli in retail broiler meat stored at -20, 4 and 12C, and development of predictive models of survival based on temperature and time

    USDA-ARS?s Scientific Manuscript database

    Retail broiler meat undergoes variable freezing and refrigeration temperatures during storage, transportation, display in retail outlets and in consumers’ refrigerators. Due to the relatively high prevalence of Campylobacter found in retail broilers and the low infective dose required to cause human...

  14. Wildland fire deficit and surplus in the western United States, 1984-2012

    Treesearch

    Sean A. Parks; Carol Miller; Marc-Andre Parisien; Lisa M. Holsinger; Solomon Z. Dobrowski; John Abatzoglou

    2015-01-01

    Wildland fire is an important disturbance agent in the western US and globally. However, the natural role of fire has been disrupted in many regions due to the influence of human activities, which have the potential to either exclude or promote fire, resulting in a "fire deficit" or "fire surplus", respectively. In this study, we developed...

  15. Decision Making: The Chesapeake Bay. An Interdisciplinary Environmental Education Curriculum Unit. Second Edition.

    ERIC Educational Resources Information Center

    Maryland Univ., College Park. Sea Grant Program.

    As the oceans rose due to melting glaciers, the Chesapeake Bay became a crowned valley. The Bay is a biologically rich system in which the success of each species depends on the quality of water in the parts of the Bay used during its life history. With the increase in human population, technological developments associated with industrial…

  16. Forest restoration in landscapes: beyond planting trees

    Treesearch

    Don C. Bragg

    2007-01-01

    Global-scale climate change, a burgeoning human population, and the rapid expansion of the world’s economy have all placed incredible pressures on environmental systems to sustain their production of goods and services. Furthermore, our developable frontiers have virtually run out—we must learn to make due with the landscapes we have already exploited. To aid in this...

  17. Cytokines, chemokines, and colony-stimulating factors in human milk: the 1997 update.

    PubMed

    Garofalo, R P; Goldman, A S

    1998-01-01

    Epidemiologic studies conducted over the past 30 years to investigate the protective functions of human milk strongly support the notion that breast-feeding prevents infantile infections, particularly those affecting the gastrointestinal and respiratory tracts. However, more recent clinical and experimental observations also suggest that human milk not only provides passive protection, but also can directly modulate the immunological development of the recipient infant. The study of this remarkable defense system in human milk has been difficult due to its biochemical complexity, the small concentration of certain bioactive components, the compartmentalization of some of these agents, the dynamic quantitative and qualitative changes of milk during lactation, and the lack of specific reagents to quantify these agents. Nevertheless, a host of bioactive substances including hormones, growth factors, and immunological factors such as cytokines have been identified in human milk. Cytokines are pluripotent polypeptides that act in autocrine/paracrine fashions by binding to specific cellular receptors. They operate in networks and orchestrate the development and functions of the immune system. Several different cytokines and chemokines have been discovered in human milk over the past years, and the list is growing very rapidly. This article will review the current knowledge about the increasingly complex network of chemoattractants, activators, and anti-inflammatory cytokines present in human milk and their potential role in compensating for the developmental delay of the neonate immune system.

  18. A Pathway to Personalizing Therapy for Metastases Using Liver-on-a-Chip Platforms.

    PubMed

    Khazali, A S; Clark, A M; Wells, A

    2017-06-01

    Metastasis accounts for most cancer-related deaths. The majority of solid cancers, including those of the breast, colorectum, prostate and skin, metastasize at significant levels to the liver due to its hemodynamic as well as tumor permissive microenvironmental properties. As this occurs prior to detection and treatment of the primary tumor, we need to target liver metastases to improve patients' outcomes. Animal models, while proven to be useful in mechanistic studies, do not represent the heterogeneity of human population especially in drug metabolism lack proper human cell-cell interactions, and this gap between animals and humans results in costly and inefficient drug discovery. This underscores the need to accurately model the human liver for disease studies and drug development. Further, the occurrence of liver metastases is influenced by the primary tumor type, sex and race; thus, modeling these specific settings will facilitate the development of personalized/targeted medicine for each specific group. We have adapted such all-human 3D ex vivo hepatic microphysiological system (MPS) (a.k.a. liver-on-a-chip) to investigate human micrometastases. This review focuses on the sources of liver resident cells, especially the iPS cell-derived hepatocytes, and examines some of the advantages and disadvantages of these sources. In addition, this review also examines other potential challenges and limitations in modeling human liver.

  19. 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

  20. 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.

  1. Human gastrointestinal nematode infections: are new control methods required?

    PubMed Central

    Stepek, Gillian; Buttle, David J; Duce, Ian R; Behnke, Jerzy M

    2006-01-01

    Gastrointestinal (GI) nematode infections affect 50% of the human population worldwide, and cause great morbidity as well as hundreds of thousands of deaths. Despite modern medical practices, the proportion of the population infected with GI nematodes is not falling. This is due to a number of factors, the most important being the lack of good healthcare, sanitation and health education in many developing countries. A relatively new problem is the development of resistance to the small number of drugs available to treat GI nematode infections. Here we review the most important parasitic GI nematodes and the methods available to control them. In addition, we discuss the current status of new anthelmintic treatments, particularly the plant cysteine proteinases from various sources of latex-bearing plants and fruits. PMID:16965561

  2. Enteric Protozoa in the Developed World: a Public Health Perspective

    PubMed Central

    Fletcher, Stephanie M.; Stark, Damien; Harkness, John

    2012-01-01

    Summary: Several enteric protozoa cause severe morbidity and mortality in both humans and animals worldwide. In developed settings, enteric protozoa are often ignored as a cause of diarrheal illness due to better hygiene conditions, and as such, very little effort is used toward laboratory diagnosis. Although these protozoa contribute to the high burden of infectious diseases, estimates of their true prevalence are sometimes affected by the lack of sensitive diagnostic techniques to detect them in clinical and environmental specimens. Despite recent advances in the epidemiology, molecular biology, and treatment of protozoan illnesses, gaps in knowledge still exist, requiring further research. There is evidence that climate-related changes will contribute to their burden due to displacement of ecosystems and human and animal populations, increases in atmospheric temperature, flooding and other environmental conditions suitable for transmission, and the need for the reuse of alternative water sources to meet growing population needs. This review discusses the common enteric protozoa from a public health perspective, highlighting their epidemiology, modes of transmission, prevention, and control. It also discusses the potential impact of climate changes on their epidemiology and the issues surrounding waterborne transmission and suggests a multidisciplinary approach to their prevention and control. PMID:22763633

  3. Anti-Heparanase Aptamers as Potential Diagnostic and Therapeutic Agents for Oral Cancer

    PubMed Central

    Silva, Dilson; Cortez, Celia M.; McKenzie, Edward A.; Bitu, Carolina C.; Salo, Sirpa; Nurmenniemi, Sini; Nyberg, Pia; Risteli, Juha; deAlmeida, Carlos E. B.; Brenchley, Paul E. C.; Salo, Tuula; Missailidis, Sotiris

    2014-01-01

    Heparanase is an endoglycosidase enzyme present in activated leucocytes, mast cells, placental tissue, neutrophils and macrophages, and is involved in tumour metastasis and tissue invasion. It presents a potential target for cancer therapies and various molecules have been developed in an attempt to inhibit the enzymatic action of heparanase. In an attempt to develop a novel therapeutic with an associated diagnostic assay, we have previously described high affinity aptamers selected against heparanase. In this work, we demonstrated that these anti-heparanase aptamers are capable of inhibiting tissue invasion of tumour cells associated with oral cancer and verified that such inhibition is due to inhibition of the enzyme and not due to other potentially cytotoxic effects of the aptamers. Furthermore, we have identified a short 30 bases aptamer as a potential candidate for further studies, as this showed a higher ability to inhibit tissue invasion than its longer counterpart, as well as a reduced potential for complex formation with other non-specific serum proteins. Finally, the aptamer was found to be stable and therefore suitable for use in human models, as it showed no degradation in the presence of human serum, making it a potential candidate for both diagnostic and therapeutic use. PMID:25295847

  4. Malformation syndromes caused by disorders of cholesterol synthesis

    PubMed Central

    Porter, Forbes D.; Herman, Gail E.

    2011-01-01

    Cholesterol homeostasis is critical for normal growth and development. In addition to being a major membrane lipid, cholesterol has multiple biological functions. These roles include being a precursor molecule for the synthesis of steroid hormones, neuroactive steroids, oxysterols, and bile acids. Cholesterol is also essential for the proper maturation and signaling of hedgehog proteins, and thus cholesterol is critical for embryonic development. After birth, most tissues can obtain cholesterol from either endogenous synthesis or exogenous dietary sources, but prior to birth, the human fetal tissues are dependent on endogenous synthesis. Due to the blood-brain barrier, brain tissue cannot utilize dietary or peripherally produced cholesterol. Generally, inborn errors of cholesterol synthesis lead to both a deficiency of cholesterol and increased levels of potentially bioactive or toxic precursor sterols. Over the past couple of decades, a number of human malformation syndromes have been shown to be due to inborn errors of cholesterol synthesis. Herein, we will review clinical and basic science aspects of Smith-Lemli-Opitz syndrome, desmosterolosis, lathosterolosis, HEM dysplasia, X-linked dominant chondrodysplasia punctata, Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects Syndrome, sterol-C-4 methyloxidase-like deficiency, and Antley-Bixler syndrome. PMID:20929975

  5. Engineered three-dimensional multicellular culture model to ...

    EPA Pesticide Factsheets

    Tissue fusion during early mammalian development requires crosstalk between multiple cell types. For example, paracrine signaling between palatal epithelial cells and palatal mesenchyme mediates the fusion of opposing palatal shelves during embryonic development. Fusion events in developmental processes including heart development, neural tube closure, and palatal fusion are dependent on epithelial-mesenchymal interactions (EMIs) and specific signaling pathways that have been elucidated largely using gene knockout mouse models. A broad analysis of literature using ToxRefDB identified 63 ToxCast chemicals associated with cleft palate in animal models. However, the influence of these and other putative teratogens on human palatal fusion has not been examined in depth due to the lack of in vitro models incorporating EMIs between human cell types. We sought to engineer the stratified mesenchymal and epithelial structure of the developing palate in vitro using spheroid culture of human Wharton’s Jelly mesenchymal stem cells (hMSC). hMSC spheroids exhibited uniform size over time (175 ± 21 µm mean diameter) that was proportional to starting cell density. Further, hMSCs in spheroid culture exhibited increased alkaline phosphatase activity and increased expression of bglap and runx2 after 7 days of culture in osteo-induction medium, which suggests that spheroid culture together with osteo-induction medium supports osteogenic differentiation. We developed a novel pro

  6. The Importance of Southern Hemisphere CZOs for Evaluating Spatial Patterns of Chemical Structure in the Critical Zone and Assisting Human Development

    NASA Astrophysics Data System (ADS)

    Chadwick, O.

    2014-12-01

    The US Critical Zone Exploration Network (CZEN) is a network of sites designed to provide a better understanding of the integrated Earth surface system. The capacity of the critical zone to withstand perturbations, whether driven by climate, land use change, or spread of invasive species, depends on its chemical composition and physical state, which in turn depends on the time evolution of the critical zone. Many temperate and/or tectonically active critical zones contain a relatively short history due to rapid erosion but tectonically quiescent, tropical regions of the planet contain much longer records that need to be understood to cover the full suite of critical zone processes. Southern Hemisphere Critical Zone Observatories such as those proposed for Kruger National Park (KNP) in South Africa and for portions of the Yilgarn Craton in Western Australa will allow us to extend our temporal understanding of development of spatial heterogeneity in the chemical and physical structure of the critical zone. In addition to considering Earth and climate boundary conditions, these sites incorporate the roles that humans play in driving critical zone processes. For instance along the edges of KNP there is strong evidence of soil erosions due to periurbanization and small-scale agriculture. The existence of KNP provides an important contrast between a "natural" and "human-dominated" landscape that can be exploited to evaluate human impacts on critical zone resources and to develop targeted mitigation strategies. Western Australia has an exploitive economy that relies on large-scale agriculture and mineral extraction, both are intensive users of water which is scarce. The proposed CZO there will be partly focused on managing water under intense economic pressures. It is evident that if funding can be found for these sites they will enhance both critical zone science and practical applied science.

  7. Genetics of human susceptibility to active and latent tuberculosis: present knowledge and future perspectives.

    PubMed

    Abel, Laurent; Fellay, Jacques; Haas, David W; Schurr, Erwin; Srikrishna, Geetha; Urbanowski, Michael; Chaturvedi, Nimisha; Srinivasan, Sudha; Johnson, Daniel H; Bishai, William R

    2018-03-01

    Tuberculosis is an ancient human disease, estimated to have originated and evolved over thousands of years alongside modern human populations. Despite considerable advances in disease control, tuberculosis remains one of the world's deadliest communicable diseases with 10 million incident cases and 1·8 million deaths in 2015 alone based on the annual WHO report, due to inadequate health service resources in less-developed regions of the world, and exacerbated by the HIV/AIDS pandemic and emergence of multidrug-resistant strains of Mycobacterium tuberculosis. Recent findings from studies of tuberculosis infection and of patients with Mendelian predisposition to severe tuberculosis have started to reveal human loci influencing tuberculosis outcomes. In this Review, we assess the current understanding of the contribution of host genetics to disease susceptibility and to drug treatment. Despite remarkable progress in technology, only a few associated genetic variants have so far been identified, strongly indicating the need for larger global studies that investigate both common and under-represented rare variants to develop new approaches to combat the disease. Pharmacogenomic discoveries are also likely to lead to more efficient drug design and development, and ultimately safer and more effective therapies for tuberculosis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. The application of a piezo-resistive cardiorespiratory sensor system in an automobile safety belt.

    PubMed

    Hamdani, Syed Talha Ali; Fernando, Anura

    2015-03-30

    Respiratory and heart failure are conditions that can occur with little warning and may also be difficult to predict. Therefore continuous monitoring of these bio-signals is advantageous for ensuring human health. The car safety belt is mainly designed to secure the occupants of the vehicle in the event of an accident. In the current research a prototype safety belt is developed, which is used to acquire respiratory and heart signals, under laboratory conditions. The current safety belt is constructed using a copper ink based nonwoven material, which works based on the piezo-resistive effect due to the pressure exerted on the sensor as a result of expansion of the thorax/abdomen area of the body for respiration and due to the principle of ballistocardiography (BCG) in heart signal sensing. In this research, the development of a theoretical model to qualitatively describe the piezo-resistive material is also presented in order to predict the relative change in the resistance of the piezo-resistive material due to the pressure applied.

  9. Close coupling of pre- and post-processing vision stations using inexact algorithms

    NASA Astrophysics Data System (ADS)

    Shih, Chi-Hsien V.; Sherkat, Nasser; Thomas, Peter D.

    1996-02-01

    Work has been reported using lasers to cut deformable materials. Although the use of laser reduces material deformation, distortion due to mechanical feed misalignment persists. Changes in the lace patten are also caused by the release of tension in the lace structure as it is cut. To tackle the problem of distortion due to material flexibility, the 2VMethod together with the Piecewise Error Compensation Algorithm incorporating the inexact algorithms, i.e., fuzzy logic, neural networks and neural fuzzy technique, are developed. A spring mounted pen is used to emulate the distortion of the lace pattern caused by tactile cutting and feed misalignment. Using pre- and post-processing vision systems, it is possible to monitor the scalloping process and generate on-line information for the artificial intelligence engines. This overcomes the problems of lace distortion due to the trimming process. Applying the algorithms developed, the system can produce excellent results, much better than a human operator.

  10. Human IgG subclass cross-species reactivity to mouse and cynomolgus monkey Fcγ receptors.

    PubMed

    Derebe, Mehabaw G; Nanjunda, Rupesh K; Gilliland, Gary L; Lacy, Eilyn R; Chiu, Mark L

    2018-05-01

    In therapeutic antibody discovery and early development, mice and cynomolgus monkey are used as animal models to assess toxicity, efficacy and other properties of candidate molecules. As more candidate antibodies are based on human immunoglobulin (IgG) subclasses, many strategies are pursued to simulate the human system in the test animal. However, translation rate from a successful preclinical trial to an approved drug is extremely low. This may partly be due to differences in interaction of human IgG based candidate molecules to endogenous Fcγ receptors of model animals in comparison to those of human Fcγ receptors. In this study, we compare binding characteristics of human IgG subclasses commonly used in drug development (IgG1, IgG2, IgG4) and their respective Fc silent versions (IgG1σ, IgG2σ, IgG4 PAA) to human, mouse, and cynomolgus monkey Fcγ receptors. To control interactions between Fab and Fc domains, the test IgGs all have the same variable region sequences. We found distinct variations of interaction of human IgG subclasses to model animal Fcγ receptors in comparison to their human counterparts. Particularly, cynomolgus monkey Fcγ receptors showed consistently tighter binding to human IgGs than human Fcγ receptors. Moreover, the presumably Fc silent human IgG4 PAA framework bound to cynomolgus monkey FcγRI with nanomolar affinity while only very weak binding was observed for the human FcγRI. Our results highlighted the need for a thorough in vitro affinity characterization of candidate IgGs against model animal Fcγ receptors and careful design of preclinical studies. Copyright © 2018. Published by Elsevier B.V.

  11. Microbiota in Allergy and Asthma and the Emerging Relationship with the Gut Microbiome

    PubMed Central

    Fujimura, Kei E.; Lynch, Susan V.

    2015-01-01

    Asthma and atopy, classically associated with hyper-activation of the T helper 2 (Th2) arm of adaptive immunity, are amongst the most common chronic illnesses worldwide. Emerging evidence relates atopy and asthma to the composition and function of the human microbiome, the collection of microbes that reside in and on and interact with the human body. The ability to interrogate microbial ecology of the human host is due in large part to recent technological developments that permit identification of microbes and their products using culture-independent molecular detection techniques. In this review we explore the roles of respiratory, gut and environmental microbiomes in asthma and allergic disease development, manifestation and attenuation. Though still a relatively nascent field of research, evidence to date suggests that the airway and/or gut microbiome may represent fertile targets for prevention or management of allergic asthma and other diseases in which adaptive immune dysfunction is a prominent feature. PMID:25974301

  12. Wetlands or aquatic ape? Availability of food resources.

    PubMed

    Ellis, D V

    1993-01-01

    A human evolutionary scenario including an ape inhabiting marine wetlands is rational in a number of contexts. The concept is viable ecologically due to the availability of abundant animal foods in a variety of habitats ranging from mangrove forests to coral reefs. The food resources include mollusks, crustacea and fish abundant in wet zones and pools between high and low tide levels. There is seasonal abundance of swarming marsh insects, turtles, eggs and chicks of colonial birds, and occasional beached and dying marine mammals. Some of these foods would provide an enriched source of polyunsaturated essential fatty acids needed for brain development, and thus allow a spiral of increasing brain development, tool utilisation for better food gathering, and vocal communication for group action. The concept is viable also in terms of availability of the ape-human stock in the African Rift Valley, isolated from montane forests during the late Pliocene, and as an adaptive explanation for many of the species-specific human characters not found in other ground living primates.

  13. Environmental and human health assessment of life cycle of nanoTiO2 functionalized porcelain stoneware tile.

    PubMed

    Pini, Martina; Bondioli, Federica; Montecchi, Rita; Neri, Paolo; Ferrari, Anna Maria

    2017-01-15

    Recently, there has been a rise in the interest in nanotechnology due to its enormous potential for the development of new products and applications with higher performance and new functionalities. However, while nanotechnology might revolutionize a number of industrial and consumer sectors, there are uncertainties and knowledge gaps regarding toxicological effects of this emerging science. The goal of this research concerns the implementation into Life Cycle Assessment (LCA) of preliminary frameworks developed to evaluate human toxicity and exposure factors related to the potential nanoparticle releases that could occur during the life cycle steps of a functionalized building material. The present LCA case study examines the ecodesign of nanoTiO 2 functionalized porcelain stoneware tile production. The aim of this investigation is to manufacture new eco-friendly products in order to protect human health and ecosystem quality and to offer the market, materials with higher technological properties obtained by the addition of specific nanomaterials. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. The Location of Lake Titicaca's Coastal Area During the Tiwanaku and Inca Periods: Methodology and Strategies of Underwater Archaeology

    NASA Astrophysics Data System (ADS)

    Delaere, Christophe

    2017-12-01

    For more than 30 years, numerous research projects have revealed the dense and complex human settlement of the lacustrine basin of Lake Titicaca in Bolivia and Peru. Physical evidence of such establishments has been discovered in plains, valleys, and highlands connected to the lake. These remains confirm human occupation and development in this environment, particularly during the Tiwanaku (AD 500-1150) and Inca (AD 1400-1532) Periods. The research project discussed in this paper includes consideration of submerged areas through underwater archaeology. This investigation involves analysis of two areas that have evidence of ancient human occupation but are poorly documented: the coastal and lacustrine regions. Due to its dominance in the landscape, Lake Titicaca has always been a major feature in the life and identity of populations of this vicinity. These inhabitants have developed socio-economic and ritual behaviours directly associated with the lake that have left cultural and material prints that are the foci of the present study.

  15. 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.

  16. Assessing Human Health Risk to Endocrine Disrupting Chemicals: a Focus on Prenatal Exposures and Oxidative Stress

    PubMed Central

    Neier, Kari; Marchlewicz, Elizabeth H.; Dolinoy, Dana C.; Padmanabhan, Vasantha

    2016-01-01

    Understanding the health risk posed by endocrine disrupting chemicals (EDCs) is a challenge that is receiving intense attention. The following study criteria should be considered to facilitate risk assessment for exposure to EDCs: 1) characterization of target health outcomes and their mediators, 2) study of exposures in the context of critical periods of development, 3) accurate estimates of human exposures and use of human-relevant exposures in animal studies, and 4) cross-species comparisons. In this commentary, we discuss the importance and relevance of each of these criteria in studying the effects of prenatal exposure to EDCs. Our discussion focuses on oxidative stress as a mediator of EDC-related health effects due to its association with both EDC exposure and health outcomes. Our recent study (Veiga-Lopez et al. 2015)1 addressed each of the four outlined criteria and demonstrated that prenatal bisphenol-A exposure is associated with oxidative stress, a risk factor for developing diabetes and cardiovascular diseases in adulthood. PMID:27231701

  17. Knockdown of zebrafish Fancd2 causes developmental abnormalities via p53-dependent apoptosis.

    PubMed

    Liu, Ting Xi; Howlett, Niall G; Deng, Min; Langenau, David M; Hsu, Karl; Rhodes, Jennifer; Kanki, John P; D'Andrea, Alan D; Look, A Thomas

    2003-12-01

    Mechanisms underlying the multiple developmental defects observed in Fanconi anemia (FA) patients are not well defined. We have identified the zebrafish homolog of human FANCD2, which encodes a nuclear effector protein that is monoubiquitinated in response to DNA damage, targeting it to nuclear foci where it preserves chromosomal integrity. Fancd2-deficient zebrafish embryos develop defects similar to those found in children with FA, including shortened body length, microcephaly, and microophthalmia, which are due to extensive cellular apoptosis. Developmental defects and increased apoptosis in Fancd2-deficient zebrafish were corrected by injection of human FANCD2 or zebrafish bcl2 mRNA, or by knockdown of p53, indicating that in the absence of Fancd2, developing tissues spontaneously undergo p53-dependent apoptosis. Thus, Fancd2 is essential during embryogenesis to prevent inappropriate apoptosis in neural cells and other tissues undergoing high levels of proliferative expansion, implicating this mechanism in the congenital abnormalities observed in human infants with FA.

  18. Microbiota in allergy and asthma and the emerging relationship with the gut microbiome.

    PubMed

    Fujimura, Kei E; Lynch, Susan V

    2015-05-13

    Asthma and atopy, classically associated with hyper-activation of the T helper 2 (Th2) arm of adaptive immunity, are among the most common chronic illnesses worldwide. Emerging evidence relates atopy and asthma to the composition and function of the human microbiome, the collection of microbes that reside in and on and interact with the human body. The ability to interrogate microbial ecology of the human host is due in large part to recent technological developments that permit identification of microbes and their products using culture-independent molecular detection techniques. In this review we explore the roles of respiratory, gut, and environmental microbiomes in asthma and allergic disease development, manifestation, and attenuation. Though still a relatively nascent field of research, evidence to date suggests that the airway and/or gut microbiome may represent fertile targets for prevention or management of allergic asthma and other diseases in which adaptive immune dysfunction is a prominent feature. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Incomplete development of human spermatozoa is associated with increased creatine phosphokinase concentration and abnormal head morphology.

    PubMed

    Huszar, G; Vigue, L

    1993-03-01

    Our previous creatine phosphokinase (CK) activity studies in human sperm revealed differences among men and among sperm populations within the same specimen. Samples with low sperm concentrations, high incidence of abnormal sperm morphology, and diminished fertility had higher per sperm CK activity. In the present work, we demonstrated, with 14C-FDNB covalent CK active site modification and with direct CK immunocytochemistry, that the higher CK activity is related to an increased content of CK and of other proteins in sperm. Also, sperm heads with higher CK content were significantly larger and rounder and showed a higher incidence of amorph configuration. We suggest that these biochemical and morphological irregularities are related and are due to a failure of spermatogenesis, more specifically, to a higher retention of cytoplasm, which in normal sperm development is lost to the Sertoli cells as residual bodies. Thus higher CK activity and larger or irregular head size in human sperm signify cellular immaturity and a failure to complete spermatogenesis.

  20. Antimicrobial activity of an aspartic protease from Salpichroa origanifolia fruits.

    PubMed

    Díaz, M E; Rocha, G F; Kise, F; Rosso, A M; Guevara, M G; Parisi, M G

    2018-05-08

    Plant proteases play a fundamental role in several processes like growth, development and in response to biotic and abiotic stress. In particular, aspartic proteases (AP) are expressed in different plant organs and have antimicrobial activity. Previously, we purified an AP from Salpichroa origanifolia fruits called salpichroin. The aim of this work was to determine the cytotoxic activity of this enzyme on selected plant and human pathogens. For this purpose, the growth of the selected pathogens was analysed after exposure to different concentrations of salpichroin. The results showed that the enzyme was capable of inhibiting Fusarium solani and Staphylococcus aureus in a dose-dependent manner. It was determined that 1·2 μmol l -1 of salpichroin was necessary to inhibit 50% of conidial germination, and the minimal bactericidal concentration was between 1·9 and 2·5 μmol l -1 . Using SYTOX Green dye we were able to demonstrate that salpichroin cause membrane permeabilization. Moreover, the enzyme treated with its specific inhibitor pepstatin A did not lose its antibacterial activity. This finding demonstrates that the cytotoxic activity of salpichroin is due to the alteration of the cell plasma membrane barrier but not due to its proteolytic activity. Antimicrobial activity of the AP could represent a potential alternative for the control of pathogens that affect humans or crops of economic interest. This study provides insights into the antimicrobial activity of an aspartic protease isolated from Salpichroa origanifolia fruits on plant and human pathogens. The proteinase inhibited Fusarium solani and Staphylococcus aureus in a dose-dependent manner due to the alteration of the cell plasma membrane barrier but not due to its proteolytic activity. Antimicrobial activity of salpichroin suggests its potential applications as an important tool for the control of pathogenic micro-organisms affecting humans and crops of economic interest. Therefore, it would represent a new alternative to avoid the problems of environmental pollution and antimicrobial resistance. © 2018 The Society for Applied Microbiology.

  1. The association between human papillomavirus and oropharyngeal squamous cell Carcinoma: Reviewed according to the Bradford Hill criteria for causality.

    PubMed

    Walvik, Lena; Svensson, Amanda Björk; Friborg, Jeppe; Lajer, Christel Bræmer

    2016-12-01

    There is emerging evidence of the association between human papillomavirus and a subset of head and neck cancers. However, the role of human papillomavirus as a causal factor is still debated. This review addresses the association between human papillomavirus and oropharyngeal squamous cell carcinoma using the Bradford Hill criteria. The strength of the association is supported by, detection of human papillomavirus infection and antibodies prior to oropharyngeal squamous cell carcinoma. This is furthermore reinforced by the absence of human papillomavirus DNA in healthy tonsils. The association is geographically consistent throughout the economically developed world. The presence and integration of high-risk human papillomavirus genome in tonsillar tumours, and expression of viral oncogenes, are specific and plausible. Analogous to human papillomavirus in cervical cancer, the rising incidence in human papillomavirus positive oropharyngeal squamous cell carcinoma is associated with sexual behaviour. These associations have been repeatedly observed and are in accordance with our current knowledge. The time relation between cause and effect remains the main challenge, due to the lack of well-defined premalignant lesions. However, a causal relationship between human papillomavirus infection and oropharyngeal squamous cell carcinoma seems evident. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Simplified human model and pedestrian simulation in the millimeter-wave region

    NASA Astrophysics Data System (ADS)

    Han, Junghwan; Kim, Seok; Lee, Tae-Yun; Ka, Min-Ho

    2016-02-01

    The 24 GHz and 77 GHz radar sensors have been studied as a strong candidate for advanced driver assistance systems(ADAS) because of their all-weather capability and accurate range and radial velocity measuring scheme. However, developing a reliable pedestrian recognition system hasmany obstacles due to the inaccurate and non-trivial radar responses at these high frequencies and the many combinations of clothes and accessories. To overcome these obstacles, many researchers used electromagnetic (EM) simulation to characterize the radar scattering response of a human. However, human simulation takes so long time because of the electrically huge size of a human in the millimeter-wave region. To reduce simulation time, some researchers assumed the skin of a human is the perfect electric conductor (PEC) and have simulated the PEC human model using physical optics (PO) algorithm without a specific explanation about how the human body could be modeled with PEC. In this study, the validity of the assumption that the surface of the human body is considered PEC in the EM simulation is verified, and the simulation result of the dry skin human model is compared with that of the PEC human model.

  3. Prioritizing and modelling of putative drug target proteins of Candida albicans by systems biology approach.

    PubMed

    Ismail, Tariq; Fatima, Nighat; Muhammad, Syed Aun; Zaidi, Syed Saoud; Rehman, Nisar; Hussain, Izhar; Tariq, Najam Us Sahr; Amirzada, Imran; Mannan, Abdul

    2018-01-01

    Candida albicans (Candida albicans) is one of the major sources of nosocomial infections in humans which may prove fatal in 30% of cases. The hospital acquired infection is very difficult to treat affectively due to the presence of drug resistant pathogenic strains, therefore there is a need to find alternative drug targets to cure this infection. In silico and computational level frame work was used to prioritize and establish antifungal drug targets of Candida albicans. The identification of putative drug targets was based on acquiring 5090 completely annotated genes of Candida albicans from available databases which were categorized into essential and non-essential genes. The result indicated that 9% of proteins were essential and could become potential candidates for intervention which might result in pathogen eradication. We studied cluster of orthologs and the subtractive genomic analysis of these essential proteins against human genome was made as a reference to minimize the side effects. It was seen that 14% of Candida albicans proteins were evolutionary related to the human proteins while 86% are non-human homologs. In the next step of compatible drug target selections, the non-human homologs were sequentially compared to the human microbiome data to minimize the potential effects against gut flora which accumulated to 38% of the essential genome. The sub-cellular localization of these candidate proteins in fungal cellular systems indicated that 80% of them are cytoplasmic, 10% are mitochondrial and the remaining 10% are associated with the cell wall. The role of these non-human and non-gut flora putative target proteins in Candida albicans biological pathways was studied. Due to their integrated and critical role in Candida albicans replication cycle, four proteins were selected for molecular modeling. For drug designing and development, four high quality and reliable protein models with more than 70% sequence identity were constructed. These proteins are used for the docking studies of the known and new ligands (unpublished data). Our study will be an effective framework for drug target identifications of pathogenic microbial strains and development of new therapies against the infections they cause.

  4. Monitoring of human populations for early markers of cadmium toxicity: A review

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

    Fowler, Bruce A.

    2009-08-01

    Exposure of human populations to cadmium (Cd) from air, food and water may produce effects in organs such as the kidneys, liver, lungs, cardiovascular, immune and reproductive systems. Since Cd has been identified as a human carcinogen, biomarkers for early detection of susceptibility to cancer are of an importance to public health. The ability to document Cd exposure and uptake of this element through biological monitoring is a first step towards understanding its health effects. Interpretation and application of biological monitoring data for predicting human health outcomes require correlation with biological measures of organ system responses to the documented exposure.more » Essential to this understanding is the detection and linkage of early biological responses toxic effects in target cell populations. Fortunately, advances in cell biology have resulted in the development of pre-clinical biological markers (biomarkers) that demonstrate measurable and characteristic molecular changes in organ systems following chemical exposures that occur prior to the onset of overt clinical disease or development of cancer. Technical advances have rendered a number of these biomarkers practical for monitoring Cd-exposed human populations. Biomarkers will be increasingly important in relation to monitoring effects from the exposure to new Cd-based high technology materials. For example, cadmium-selenium (CdSe), nano-materials made from combinations of these elements have greatly altered cellular uptake characteristics due to particle size. These differences may greatly alter effects at the target cell level and hence risks for organ toxicities from such exposures. The value of validated biomarkers for early detection of systemic Cd-induced effects in humans cannot be underestimated due to the rapid expansion of nano-material technologies. This review will attempt to briefly summarize the applications, to date, of biomarker endpoints for assessing target organ system effects in humans and experimental systems from Cd exposure. Further, it will attempt to provide a prospective look at the possible future of biomarkers. The emphasis will be on the detection of early toxic effects from exposure to Cd in new products such as nano-materials and identification of populations at special risk for Cd toxicity.« less

  5. Monitoring of human populations for early markers of cadmium toxicity: a review.

    PubMed

    Fowler, Bruce A

    2009-08-01

    Exposure of human populations to cadmium (Cd) from air, food and water may produce effects in organs such as the kidneys, liver, lungs, cardiovascular, immune and reproductive systems. Since Cd has been identified as a human carcinogen, biomarkers for early detection of susceptibility to cancer are of an importance to public health. The ability to document Cd exposure and uptake of this element through biological monitoring is a first step towards understanding its health effects. Interpretation and application of biological monitoring data for predicting human health outcomes require correlation with biological measures of organ system responses to the documented exposure. Essential to this understanding is the detection and linkage of early biological responses toxic effects in target cell populations. Fortunately, advances in cell biology have resulted in the development of pre-clinical biological markers (biomarkers) that demonstrate measurable and characteristic molecular changes in organ systems following chemical exposures that occur prior to the onset of overt clinical disease or development of cancer. Technical advances have rendered a number of these biomarkers practical for monitoring Cd-exposed human populations. Biomarkers will be increasingly important in relation to monitoring effects from the exposure to new Cd-based high technology materials. For example, cadmium-selenium (CdSe), nano-materials made from combinations of these elements have greatly altered cellular uptake characteristics due to particle size. These differences may greatly alter effects at the target cell level and hence risks for organ toxicities from such exposures. The value of validated biomarkers for early detection of systemic Cd-induced effects in humans cannot be underestimated due to the rapid expansion of nano-material technologies. This review will attempt to briefly summarize the applications, to date, of biomarker endpoints for assessing target organ system effects in humans and experimental systems from Cd exposure. Further, it will attempt to provide a prospective look at the possible future of biomarkers. The emphasis will be on the detection of early toxic effects from exposure to Cd in new products such as nano-materials and identification of populations at special risk for Cd toxicity.

  6. Bacterial uptake of antibiotics in model unsaturated systems

    NASA Astrophysics Data System (ADS)

    Zhang, W.; Chen, Z.; Zhang, Y.; Zhao, Z.; Wang, G.; Gao, Y.; Boyd, S. A.; Zhu, D.; Li, H.

    2016-12-01

    Anthropogenic antibiotics are ubiquitously present in the environment due to large uses in human medicine and animal agriculture, and are causing unintended consequence to human and ecosystem health. Bacterial uptake of antibiotics could exert selection pressure on antibiotic resistance development among bacteria population. Therefore, understanding environmental factors controlling bioavailability of antibiotics to bacteria is critical to better assessing exposure risks and developing mitigation strategies. Nonetheless, conventional bioavailability assays are often performed in water-saturated systems that do not represent unsaturated soils where most bacteria live, therefore neglecting soil water as a controlling factor in determining the extent of antibiotic bacterial uptake. Therefore, we propose to study bacterial uptake of antibiotics in model unsaturated systems using GFP-tagged Escherichia coli bioreporter for tetracyclines. Our preliminary studies demonstrated the important role of water content (or water matric potential) in determining the bioavailability of antibiotics, and complex interactions of water potential, tetracycline diffusion, and E. coli growth. Therefore, unsaturated processes are important for understanding antibiotic resistance development and developing mitigation strategies.

  7. Genetic identification of missing persons: DNA analysis of human remains and compromised samples.

    PubMed

    Alvarez-Cubero, M J; Saiz, M; Martinez-Gonzalez, L J; Alvarez, J C; Eisenberg, A J; Budowle, B; Lorente, J A

    2012-01-01

    Human identification has made great strides over the past 2 decades due to the advent of DNA typing. Forensic DNA typing provides genetic data from a variety of materials and individuals, and is applied to many important issues that confront society. Part of the success of DNA typing is the generation of DNA databases to help identify missing persons and to develop investigative leads to assist law enforcement. DNA databases house DNA profiles from convicted felons (and in some jurisdictions arrestees), forensic evidence, human remains, and direct and family reference samples of missing persons. These databases are essential tools, which are becoming quite large (for example the US Database contains 10 million profiles). The scientific, governmental and private communities continue to work together to standardize genetic markers for more effective worldwide data sharing, to develop and validate robust DNA typing kits that contain the reagents necessary to type core identity genetic markers, to develop technologies that facilitate a number of analytical processes and to develop policies to make human identity testing more effective. Indeed, DNA typing is integral to resolving a number of serious criminal and civil concerns, such as solving missing person cases and identifying victims of mass disasters and children who may have been victims of human trafficking, and provides information for historical studies. As more refined capabilities are still required, novel approaches are being sought, such as genetic testing by next-generation sequencing, mass spectrometry, chip arrays and pyrosequencing. Single nucleotide polymorphisms offer the potential to analyze severely compromised biological samples, to determine the facial phenotype of decomposed human remains and to predict the bioancestry of individuals, a new focus in analyzing this type of markers. Copyright © 2012 S. Karger AG, Basel.

  8. Cross-species comparison of aCGH data from mouse and human BRCA1- and BRCA2-mutated breast cancers

    PubMed Central

    2010-01-01

    Background Genomic gains and losses are a result of genomic instability in many types of cancers. BRCA1- and BRCA2-mutated breast cancers are associated with increased amounts of chromosomal aberrations, presumably due their functions in genome repair. Some of these genomic aberrations may harbor genes whose absence or overexpression may give rise to cellular growth advantage. So far, it has not been easy to identify the driver genes underlying gains and losses. A powerful approach to identify these driver genes could be a cross-species comparison of array comparative genomic hybridization (aCGH) data from cognate mouse and human tumors. Orthologous regions of mouse and human tumors that are commonly gained or lost might represent essential genomic regions selected for gain or loss during tumor development. Methods To identify genomic regions that are associated with BRCA1- and BRCA2-mutated breast cancers we compared aCGH data from 130 mouse Brca1Δ/Δ;p53Δ/Δ, Brca2Δ/Δ;p53Δ/Δ and p53Δ/Δ mammary tumor groups with 103 human BRCA1-mutated, BRCA2-mutated and non-hereditary breast cancers. Results Our genome-wide cross-species analysis yielded a complete collection of loci and genes that are commonly gained or lost in mouse and human breast cancer. Principal common CNAs were the well known MYC-associated gain and RB1/INTS6-associated loss that occurred in all mouse and human tumor groups, and the AURKA-associated gain occurred in BRCA2-related tumors from both species. However, there were also important differences between tumor profiles of both species, such as the prominent gain on chromosome 10 in mouse Brca2Δ/Δ;p53Δ/Δ tumors and the PIK3CA associated 3q gain in human BRCA1-mutated tumors, which occurred in tumors from one species but not in tumors from the other species. This disparity in recurrent aberrations in mouse and human tumors might be due to differences in tumor cell type or genomic organization between both species. Conclusions The selection of the oncogenome during mouse and human breast tumor development is markedly different, apart from the MYC gain and RB1-associated loss. These differences should be kept in mind when using mouse models for preclinical studies. PMID:20735817

  9. Humanization of pediatric care in the world: focus and review of existing models and measurement tools.

    PubMed

    Tripodi, Marina; Siano, Maria Anna; Mandato, Claudia; De Anseris, Anna Giulia Elena; Quitadamo, Paolo; Guercio Nuzio, Salvatore; Viggiano, Claudia; Fasolino, Francesco; Bellopede, Annalisa; Annunziata, Maria; Massa, Grazia; Pepe, Francesco Maria; De Chiara, Maria; Siani, Paolo; Vajro, Pietro

    2017-08-30

    The term "humanization" indicates the process by which people try to make something more human and civilized, more in line with what is believed to be the human nature. The humanization of care is an important and not yet a well-defined issue which includes a wide range of aspects related to the approach to the patient and care modalities. In pediatrics, the humanization concept is even vaguer due to the dual involvement of both the child and his/her family and by the existence of multiple proposed models. The present study aims to analyze the main existing humanization models regarding pediatric care, and the tools for assessing its grade. The main Humanization care programs have been elaborated and developed both in America (Brazil, USA) and Europe. The North American and European models specifically concern pediatric care, while the model developed in Brazil is part of a broader program aimed at all age groups. The first emphasis is on the importance of the family in child care, the second emphasis is on the child's right to be a leader, to be heard and to be able to express its opinion on the program's own care. Several tools have been created and used to evaluate humanization of care programs and related aspects. None, however, had been mutually compared. The major models of humanization care and the related assessment tools here reviewed highlight the urgent need for a more unifying approach, which may help in realizing health care programs closer to the young patient's and his/her family needs.

  10. Human neuron-astrocyte 3D co-culture-based assay for evaluation of neuroprotective compounds.

    PubMed

    Terrasso, Ana Paula; Silva, Ana Carina; Filipe, Augusto; Pedroso, Pedro; Ferreira, Ana Lúcia; Alves, Paula Marques; Brito, Catarina

    Central nervous system drug development has registered high attrition rates, mainly due to the lack of efficacy of drug candidates, highlighting the low reliability of the models used in early-stage drug development and the need for new in vitro human cell-based models and assays to accurately identify and validate drug candidates. 3D human cell models can include different tissue cell types and represent the spatiotemporal context of the original tissue (co-cultures), allowing the establishment of biologically-relevant cell-cell and cell-extracellular matrix interactions. Nevertheless, exploitation of these 3D models for neuroprotection assessment has been limited due to the lack of data to validate such 3D co-culture approaches. In this work we combined a 3D human neuron-astrocyte co-culture with a cell viability endpoint for the implementation of a novel in vitro neuroprotection assay, over an oxidative insult. Neuroprotection assay robustness and specificity, and the applicability of Presto Blue, MTT and CytoTox-Glo viability assays to the 3D co-culture were evaluated. Presto Blue was the adequate endpoint as it is non-destructive and is a simpler and reliable assay. Semi-automation of the cell viability endpoint was performed, indicating that the assay setup is amenable to be transferred to automated screening platforms. Finally, the neuroprotection assay setup was applied to a series of 36 test compounds and several candidates with higher neuroprotective effect than the positive control, Idebenone, were identified. The robustness and simplicity of the implemented neuroprotection assay with the cell viability endpoint enables the use of more complex and reliable 3D in vitro cell models to identify and validate drug candidates. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Dynamic landscapes in human evolution and dispersal

    NASA Astrophysics Data System (ADS)

    Devès, Maud; King, Geoffrey; Bailey, Geoffrey; Inglis, Robyn; Williams, Matthew; Winder, Isabelle

    2013-04-01

    Archaeological studies of human settlement in its wider landscape setting usually focus on climate change as the principal environmental driver of change in the physical features of the landscape, even on the long time scales of early human evolution. We emphasize that landscapes evolve dynamically due to an interplay of processes occurring over different timescales. Tectonic deformation, volcanism, sea level changes, by acting on the topography, the lithology and on the patterns of erosion-deposition in a given area, can moderate or amplify the influence of climate at the regional and local scale. These processes impose or alleviate physical barriers to movement, and modify the distribution and accessibility of plant and animal resources in ways critical to human ecological and evolutionary success (King and Bailey, JHE 2006; Bailey and King, Antiquity 2011, Winder et al. Antiquity in press). The DISPERSE project, an ERC-funded collaboration between the University of York and the Institut de Physique du Globe de Paris, aims to develop systematic methods for reconstructing landscapes associated with active tectonics, volcanism and sea level change at a variety of scales in order to study their potential impact on patterns of human evolution and dispersal. Examples are shown to illustrate the ways in which changes of significance to human settlement can occur at a range of geographical scales and on time scales that range from lifetimes to tens of millennia, creating and sustaining attractive conditions for human settlement and exercising powerful selective pressures on human development.

  12. Low-cholesterol and high-fat diets reduce atherosclerotic lesion development in ApoE-knockout mice.

    PubMed

    Calleja, L; París, M A; Paul, A; Vilella, E; Joven, J; Jiménez, A; Beltrán, G; Uceda, M; Maeda, N; Osada, J

    1999-10-01

    We have investigated the effect of most common oils used in human nutrition on the development of atherosclerosis in apoE-knockout mice. Seven groups of animals, separated according to sex, were fed for 10 weeks either chow diet or the chow diet 10% (wt/wt) enriched with different oils (palm, coconut, 2 types of olive oil, and 2 types of sunflower oil) without addition of cholesterol. At the end of this period, plasma lipid parameters were measured and vascular lesions scored. None of the diets induced changes in plasma cholesterol concentrations, whereas plasma triglycerides were uniformly reduced in all diet groups. Some diets caused significant reductions in the size of atherosclerotic lesions in males and others in females; males responded most to sunflower oils and females to palm oil and one olive oil (II). The lesion reduction in males consuming sunflower oils was associated with the decrease of triglycerides in triglyceride-rich lipoproteins, whereas the decrease in females consuming olive oil II or palm oil was accompanied by an increase in plasma apoA-I. The increase in plasma apoA-I in the latter condition, is mainly due to overexpression of hepatic message elicited by a mechanism independent of apoE ligand. The data suggest that the different diets modulate lesion development in a gender specific manner and by different mechanisms and that the development of atherosclerosis, due to genetic deficiencies, may be modulated by nutritional maneuvers that may be implemented in human nutrition.

  13. An Impossible Journey? The Development of Plasmodium falciparum NF54 in Culex quinquefasciatus

    PubMed Central

    Knöckel, Julia; Molina-Cruz, Alvaro; Fischer, Elizabeth; Muratova, Olga; Haile, Ashley; Barillas-Mury, Carolina; Miller, Louis H.

    2013-01-01

    Although Anopheles mosquitoes are the vectors for human Plasmodium spp., there are also other mosquito species–among them culicines (Culex spp., Aedes spp.)–present in malaria-endemic areas. Culicine mosquitoes transmit arboviruses and filarial worms to humans and are vectors for avian Plasmodium spp., but have never been observed to transmit human Plasmodium spp. When ingested by a culicine mosquito, parasites could either face an environment that does not allow development due to biologic incompatibility or be actively killed by the mosquito’s immune system. In the latter case, the molecular mechanism of killing must be sufficiently powerful that Plasmodium is not able to overcome it. To investigate how human malaria parasites develop in culicine mosquitoes, we infected Culex quinquefasciatus with Plasmodium falciparum NF54 and monitored development of parasites in the blood bolus and midgut epithelium at different time points. Our results reveal that ookinetes develop in the midgut lumen of C. quinquefasciatus in slightly lower numbers than in Anopheles gambiae G3. After 30 hours, parasites have invaded the midgut and can be observed on the basal side of the midgut epithelium by confocal and transmission electron microscopy. Very few of the parasites in C. quinquefasciatus are alive, most of them are lysed. Eight days after the mosquito’s blood meal, no oocysts can be found in C. quinquefasciatus. Our results suggest that the mosquito immune system could be involved in parasite killing early in development after ookinetes have crossed the midgut epithelium and come in contact with the mosquito hemolymph. PMID:23658824

  14. The perspectives for porcine-to-human xenografts.

    PubMed

    Petersen, Bjoern; Carnwath, Joseph W; Niemann, Heiner

    2009-03-01

    The shortage of donated human organs for transplantation continues to be a life threatening problem for patients suffering from complete organ failure. Although this gap is increasing due to the demographic changes in aging Western populations, it is generally accepted that international trading in human organ is not an ethical solution. Alternatives to the use of human organs for transplantation must be developed and these alternatives include stem cell therapy, artificial organs and organs from other species, i.e. xenografts. For practical reasons but most importantly because of its physiological similarity with humans, the pig is generally accepted as the species of choice for xenotransplantation. Nevertheless, before porcine organs can be used in human xenotransplantation, it is necessary to make a series of precise genetic modifications to the porcine genome, including the addition of genes for factors which suppress the rejection of transplanted porcine tissues and the inactivation or removal of undesirable genes which can only be accomplished at this time by targeted recombination and somatic nuclear transfer. This review will give an insight into the advances in transgenic manipulation and cloning in pigs--in the context of porcine-to-human xenotransplantation.

  15. Human-arm-and-hand-dynamic model with variability analyses for a stylus-based haptic interface.

    PubMed

    Fu, Michael J; Cavuşoğlu, M Cenk

    2012-12-01

    Haptic interface research benefits from accurate human arm models for control and system design. The literature contains many human arm dynamic models but lacks detailed variability analyses. Without accurate measurements, variability is modeled in a very conservative manner, leading to less than optimal controller and system designs. This paper not only presents models for human arm dynamics but also develops inter- and intrasubject variability models for a stylus-based haptic device. Data from 15 human subjects (nine male, six female, ages 20-32) were collected using a Phantom Premium 1.5a haptic device for system identification. In this paper, grip-force-dependent models were identified for 1-3-N grip forces in the three spatial axes. Also, variability due to human subjects and grip-force variation were modeled as both structured and unstructured uncertainties. For both forms of variability, the maximum variation, 95 %, and 67 % confidence interval limits were examined. All models were in the frequency domain with force as input and position as output. The identified models enable precise controllers targeted to a subset of possible human operator dynamics.

  16. Mi-DISCOVERER: A bioinformatics tool for the detection of mi-RNA in human genome.

    PubMed

    Arshad, Saadia; Mumtaz, Asia; Ahmad, Freed; Liaquat, Sadia; Nadeem, Shahid; Mehboob, Shahid; Afzal, Muhammad

    2010-11-27

    MicroRNAs (miRNAs) are 22 nucleotides non-coding RNAs that play pivotal regulatory roles in diverse organisms including the humans and are difficult to be identified due to lack of either sequence features or robust algorithms to efficiently identify. Therefore, we made a tool that is Mi-Discoverer for the detection of miRNAs in human genome. The tools used for the development of software are Microsoft Office Access 2003, the JDK version 1.6.0, BioJava version 1.0, and the NetBeans IDE version 6.0. All already made miRNAs softwares were web based; so the advantage of our project was to make a desktop facility to the user for sequence alignment search with already identified miRNAs of human genome present in the database. The user can also insert and update the newly discovered human miRNA in the database. Mi-Discoverer, a bioinformatics tool successfully identifies human miRNAs based on multiple sequence alignment searches. It's a non redundant database containing a large collection of publicly available human miRNAs.

  17. Mi-DISCOVERER: A bioinformatics tool for the detection of mi-RNA in human genome

    PubMed Central

    Arshad, Saadia; Mumtaz, Asia; Ahmad, Freed; Liaquat, Sadia; Nadeem, Shahid; Mehboob, Shahid; Afzal, Muhammad

    2010-01-01

    MicroRNAs (miRNAs) are 22 nucleotides non-coding RNAs that play pivotal regulatory roles in diverse organisms including the humans and are difficult to be identified due to lack of either sequence features or robust algorithms to efficiently identify. Therefore, we made a tool that is Mi-Discoverer for the detection of miRNAs in human genome. The tools used for the development of software are Microsoft Office Access 2003, the JDK version 1.6.0, BioJava version 1.0, and the NetBeans IDE version 6.0. All already made miRNAs softwares were web based; so the advantage of our project was to make a desktop facility to the user for sequence alignment search with already identified miRNAs of human genome present in the database. The user can also insert and update the newly discovered human miRNA in the database. Mi-Discoverer, a bioinformatics tool successfully identifies human miRNAs based on multiple sequence alignment searches. It's a non redundant database containing a large collection of publicly available human miRNAs. PMID:21364831

  18. Mapping Water Resources, Allocation and Consumption in the Mills River Basin

    NASA Astrophysics Data System (ADS)

    Hodes, J.; Jeuland, M. A.; Barros, A. P.

    2014-12-01

    Mountain basins and the headwaters of river basins along the foothills of major mountain ranges are undergoing rapid environmental change due to urban development, land acquisition by investors, population increase, and climate change. Classical water infrastructure in these regions is primarily designed to meet human water demand associated with agriculture, tourism, and economic development. Often overlooked and ignored is the fundamental interdependence of human water demand, ecosystem water demand, water rights and allocation, and water supply. A truly sustainable system for water resources takes into account ecosystem demand along with human infrastructure and economic demand, as well as the feedbacks that exist between them. Allocation policies need to take into account basin resilience that is the amount of stress the system can handle under varying future scenarios. Changes in stress on the system can be anthropogenic in the form of population increase, land use change, economic development, or may be natural in the form of climate change and decrease in water supply due to changes in precipitation. Mapping the water rights, supply, and demands within the basin can help determine the resiliency and sustainability of the basin. Here, we present a coupled natural human system project based in the French Broad River Basin, in the Southern Appalachians. In the first phase of the project, we are developing and implementing a coupled hydro-economics modeling framework in the Mills River Basin (MRB), a tributary of the French Broad. The Mills River Basin was selected as the core basin for implementing a sustainable system of water allocation that is adaptive and reflects the interdependence of water dependent sectors. The headwaters of the Mills River are in the foothills of the Appalachians, and are currently under substantial land use land cover (LULC) change pressure for agricultural purposes. In this regard, the MRB is representative of similar headwater basins in regions of complex terrain undergoing similar pressures such as the Andes and Himalayas. First results of the project including a quantitative organigram mapping water availability, water consumption, and the relationships among water stakeholders within the basin will be presented.

  19. Health worker motivation in Africa: the role of non-financial incentives and human resource management tools.

    PubMed

    Mathauer, Inke; Imhoff, Ingo

    2006-08-29

    There is a serious human resource crisis in the health sector in developing countries, particularly in Africa. One of the challenges is the low motivation of health workers. Experience and the evidence suggest that any comprehensive strategy to maximize health worker motivation in a developing country context has to involve a mix of financial and non-financial incentives. This study assesses the role of non-financial incentives for motivation in two cases, in Benin and Kenya. The study design entailed semi-structured qualitative interviews with doctors and nurses from public, private and NGO facilities in rural areas. The selection of health professionals was the result of a layered sampling process. In Benin 62 interviews with health professionals were carried out; in Kenya 37 were obtained. Results from individual interviews were backed up with information from focus group discussions. For further contextual information, interviews with civil servants in the Ministry of Health and at the district level were carried out. The interview material was coded and quantitative data was analysed with SPSS software. The study shows that health workers overall are strongly guided by their professional conscience and similar aspects related to professional ethos. In fact, many health workers are demotivated and frustrated precisely because they are unable to satisfy their professional conscience and impeded in pursuing their vocation due to lack of means and supplies and due to inadequate or inappropriately applied human resources management (HRM) tools. The paper also indicates that even some HRM tools that are applied may adversely affect the motivation of health workers. The findings confirm the starting hypothesis that non-financial incentives and HRM tools play an important role with respect to increasing motivation of health professionals. Adequate HRM tools can uphold and strengthen the professional ethos of doctors and nurses. This entails acknowledging their professionalism and addressing professional goals such as recognition, career development and further qualification. It must be the aim of human resources management/quality management (HRM/QM) to develop the work environment so that health workers are enabled to meet their personal and the organizational goals.

  20. Health worker motivation in Africa: the role of non-financial incentives and human resource management tools

    PubMed Central

    Mathauer, Inke; Imhoff, Ingo

    2006-01-01

    Background There is a serious human resource crisis in the health sector in developing countries, particularly in Africa. One of the challenges is the low motivation of health workers. Experience and the evidence suggest that any comprehensive strategy to maximize health worker motivation in a developing country context has to involve a mix of financial and non-financial incentives. This study assesses the role of non-financial incentives for motivation in two cases, in Benin and Kenya. Methods The study design entailed semi-structured qualitative interviews with doctors and nurses from public, private and NGO facilities in rural areas. The selection of health professionals was the result of a layered sampling process. In Benin 62 interviews with health professionals were carried out; in Kenya 37 were obtained. Results from individual interviews were backed up with information from focus group discussions. For further contextual information, interviews with civil servants in the Ministry of Health and at the district level were carried out. The interview material was coded and quantitative data was analysed with SPSS software. Results and discussion The study shows that health workers overall are strongly guided by their professional conscience and similar aspects related to professional ethos. In fact, many health workers are demotivated and frustrated precisely because they are unable to satisfy their professional conscience and impeded in pursuing their vocation due to lack of means and supplies and due to inadequate or inappropriately applied human resources management (HRM) tools. The paper also indicates that even some HRM tools that are applied may adversely affect the motivation of health workers. Conclusion The findings confirm the starting hypothesis that non-financial incentives and HRM tools play an important role with respect to increasing motivation of health professionals. Adequate HRM tools can uphold and strengthen the professional ethos of doctors and nurses. This entails acknowledging their professionalism and addressing professional goals such as recognition, career development and further qualification. It must be the aim of human resources management/quality management (HRM/QM) to develop the work environment so that health workers are enabled to meet their personal and the organizational goals. PMID:16939644

  1. Computational fluid dynamics modeling of Bacillus anthracis spore deposition in rabbit and human respiratory airways

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

    Kabilan, S.; Suffield, S. R.; Recknagle, K. P.

    Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived respectively from computed tomography (CT) and µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation–exhalation breathingmore » conditions using average species-specific minute volumes. Two different exposure scenarios were modeled in the rabbit based upon experimental inhalation studies. For comparison, human simulations were conducted at the highest exposure concentration used during the rabbit experimental exposures. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the nasal sinus compared to the human at the same air concentration of anthrax spores. In contrast, higher spore deposition was predicted in the lower conducting airways of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology for deposition.« less

  2. Computational Fluid Dynamics Modeling of Bacillus anthracis Spore Deposition in Rabbit and Human Respiratory Airways

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

    Kabilan, Senthil; Suffield, Sarah R.; Recknagle, Kurtis P.

    Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived from computed tomography (CT) or µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation-exhalation breathing conditionsmore » using average species-specific minute volumes. The highest exposure concentration was modeled in the rabbit based upon prior acute inhalation studies. For comparison, human simulation was also conducted at the same concentration. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the upper conducting airways compared to the human at the same air concentration of anthrax spores. As a result, higher particle deposition was predicted in the conducting airways and deep lung of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology.« less

  3. Novel Means for Photoprotection.

    PubMed

    Sondenheimer, Kevin; Krutmann, Jean

    2018-01-01

    Due to changes in human lifestyle (expanded sunbathing, the use of solaria, etc.) and, most importantly, increasing lifetime and thus higher cumulative exposure to solar radiation, skin aging and skin cancer have become major health issues. As a consequence effective photoprotection is of outmost importance to humans. In this regard a lot has been learned in the past about the cellular and molecular basis underlying ultraviolet (UV) radiation-induced skin damage and, based on this knowledge, numerous skin protective approaches including organic and inorganic UV-filters, but also topically applicable antioxidants, DNA repair enzymes and compatible solutes as well as oral photoprotective strategies based on nutritional supplements have been developed. A new aspect is here that sun protection of human skin might even be possible after solar radiation-induced skin damage has occurred. A second, very important development was prompted by the discovery that also wavelengths beyond the UV spectrum can damage human skin. These include the blue light region of visible light (VIS) as well as the near infrared range (IRA) and corresponding sunprotection strategies have thus recently been or are still being developed. In this article we will provide a state of the art summary of these two novel developments and, at the end, we will also critically discuss strengths and weaknesses of the current attempts, which mainly focus on the prevention of skin damage by selected wavelengths but greatly ignore the possibility that wavelengths might interfere with each other. Such combined effects, however, need to be taken into account if photoprotection of human skin is intended to be global in nature.

  4. Development of a rhesus monkey lung geometry model and application to particle deposition in comparison to humans

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

    Asgharian, Bahman; Price, Owen; McClellan, Gene

    2012-11-01

    The exposure-dose-response characterization of an inhalation hazard established in an animal species needs to be translated to an equivalent characterization in humans relative to comparable doses or exposure scenarios. Here, the first geometry model of the conducting airways for rhesus monkeys is developed based upon CT images of the conducting airways of a 6-month-old male, rhesus monkey. An algorithm was developed for adding the alveolar region airways using published rhesus morphometric data. The resultant lung geometry model can be used in mechanistic particle or gaseous dosimetry models. Such dosimetry models require estimates of the upper respiratory tract volume of themore » animal and the functional residual capacity, as well as of the tidal volume and breathing frequency of the animal. The relationship of these variables to rhesus monkeys of differing body weights was established by synthesizing and modeling published data as well as modeling pulmonary function measurements on 121 rhesus control animals. Deposition patterns of particles up to 10 µm in size were examined for endotracheal and and up to 5 µm for spontaneous breathing in infant and young adult monkeys and compared to those for humans. Deposition fraction of respirable size particles was found to be higher in the conducting airways of infant and young adult rhesus monkeys compared to humans. Due to the filtering effect of the conducting airways, pulmonary deposition in rhesus monkeys was lower than that in humans. Finally, future research areas are identified that would either allow replacing assumptions or improving the newly developed lung model.« less

  5. Development of a rhesus monkey lung geometry model and application to particle deposition in comparison to humans

    PubMed Central

    Asgharian, Bahman; Price, Owen; McClellan, Gene; Corley, Rick; Einstein, Daniel R.; Jacob, Richard E.; Harkema, Jack; Carey, Stephan A.; Schelegle, Edward; Hyde, Dallas; Kimbell, Julia S.; Miller, Frederick J.

    2016-01-01

    The exposure-dose-response characterization of an inhalation hazard established in an animal species needs to be translated to an equivalent characterization in humans relative to comparable doses or exposure scenarios. Here, the first geometry model of the conducting airways for rhesus monkeys is developed based upon CT images of the conducting airways of a 6-month-old male, rhesus monkey. An algorithm was developed for adding the alveolar region airways using published rhesus morphometric data. The resultant lung geometry model can be used in mechanistic particle or gaseous dosimetry models. Such dosimetry models require estimates of the upper respiratory tract volume of the animal and the functional residual capacity, as well as of the tidal volume and breathing frequency of the animal. The relationship of these variables to rhesus monkeys of differing body weights was established by synthesizing and modeling published data as well as modeling pulmonary function measurements on 121 rhesus control animals. Deposition patterns of particles up to 10 μm in size were examined for endotracheal and and up to 5 μm for spontaneous breathing in infant and young adult monkeys and compared to those for humans. Deposition fraction of respirable size particles was found to be higher in the conducting airways of infant and young adult rhesus monkeys compared to humans. Due to the filtering effect of the conducting airways, pulmonary deposition in rhesus monkeys was lower than that in humans. Future research areas are identified that would either allow replacing assumptions or improving the newly developed lung model. PMID:23121298

  6. Predicting the role of veterinary medicine in future health and food safety challenges

    NASA Astrophysics Data System (ADS)

    Fejzić, N.; Šerić-Haračić, S.

    2017-09-01

    Animals have always been a source of food, materials, protection and wellbeing for humans; however, animal diseases, including zoonoses, have both direct and indirect negative effects on human health, economy and the society. Since its establishment, the veterinary profession has provided crucial input in eradicating disease, increasing animal production and reducing losses due to diseases. Currently, foodborne diseases and zoonoses have raised awareness in developed countries, which have excellent systems for disease surveillance and reporting both in humans and animal populations. Due to lack of modern, integrated surveillance and reporting, the burden of zoonoses and foodborne diseases in developing European countries is much harder to assess. Differences in countries’ animal health status (demonstrated through disease surveillance) have been a main pivot point for international trade of animals and animal products. However, rapid and dramatic evolvement of the health trends in the world changed the principles of animal disease surveillance. Approaches requiring lower cost (i.e. risk-based surveillance) are now proposed, not only due to less available public funding, but also because the costs are harder to justify to policy makers if a disease is exotic and/or rare. Therefore, the veterinary profession has faced insufficient interest of governments and funds for further research into many persistent endemic animal diseases and zoonoses. On the other hand, eradication of selected diseases in some areas while elsewhere they still persist, and the continuous emergence of new diseases, cannot guarantee permanent epidemiological stability. As food safety and security become more important, global trends and events have highlighted the biological, health and economic inseparability of the relationships between humans, animals as pets and/or food sources and wildlife within the social and ecological framework of living space that these species share. Veterinarians are called on and expected to offer strategic and operational solutions for better integration of public health systems (i.e. One Health), animal health, food safety and environmental protection. At the same time, the profession faces challenges in the organisation and implementation of surveillance and disease mitigation measures.

  7. Near-infrared imaging of enamel hypomineralization due to developmental defects

    NASA Astrophysics Data System (ADS)

    Lee, Robert C.; Jang, Andrew; Fried, Daniel

    2017-02-01

    The increasing prevalence of mild hypomineralization due to developmental defects on tooth surfaces poses a challenge for caries detection and caries risk assessment and reliable methods need to be developed to discriminate such lesions from active caries lesions that need intervention. Previous studies have demonstrated that areas of hypomineralization are typically covered with a relatively thick surface layer of highly mineralized and transparent enamel similar to arrested lesions. Seventy-six extracted human teeth with mild to moderate degrees of suspicious fluorosis were imaged using near-infrared reflectance and transillumination. Enamel hypomineralization was clearly visible in both modalities. However, it was difficult to distinguish hypomineralization due to developmental defects from caries lesions with contrast measurements alone. The location of the lesion on tooth coronal surface (i.e. generalized vs. localized) seems to be the most important indicator for the presence of enamel hypomineralization due to developmental defects.

  8. Near-infrared imaging of enamel hypomineralization due to developmental defects.

    PubMed

    Lee, Robert C; Jang, Andrew; Fried, Daniel

    2017-01-28

    The increasing prevalence of mild hypomineralization due to developmental defects on tooth surfaces poses a challenge for caries detection and caries risk assessment and reliable methods need to be developed to discriminate such lesions from active caries lesions that need intervention. Previous studies have demonstrated that areas of hypomineralization are typically covered with a relatively thick surface layer of highly mineralized and transparent enamel similar to arrested lesions. Seventy-six extracted human teeth with mild to moderate degrees of suspicious fluorosis were imaged using near-infrared reflectance and transillumination. Enamel hypomineralization was clearly visible in both modalities. However, it was difficult to distinguish hypomineralization due to developmental defects from caries lesions with contrast measurements alone. The location of the lesion on tooth coronal surface (i.e. generalized vs. localized) seems to be the most important indicator for the presence of enamel hypomineralization due to developmental defects.

  9. [Viruses and bats: rabies and Lyssavirus].

    PubMed

    Tordo, N; Marianneau, M Ph

    2009-01-01

    Recent emerging zoonoses (hemorrhagic fevers due to Ebola or Marburg virus, encephalitis due to Nipah virus, severe acute respiratory syndrome due to SRAS virus...) outline the potential of bats as vectors for transmission of infectious disease to humans. Such a potential is already known for rabies encephalitis since seven out of the eight genotypes of Lyssavirus are transmitted by bats. In addition, phylogenetic reconstructions indicate that Lyssavirus have evolved in chiropters before their emergence in carnivores. Nevertheless, carnivores remain the most critical vectors for public health, in particular dogs that are originating 55.000 rabies deaths per year, essentially in developing countries. Rabies control in carnivores by parenteral (dog) or oral (wild carnivores) vaccination is efficacious and campaigns start to be more widely applied. On the other hand, rabies control in bat still remains non realistic, particularly as the pathogenicity of bat Lyssavirus for bats is still under debate, suggesting that a "diplomatic relationship" between partners would have arisen from a long term cohabitation. While comparing the interactions that humans and bats establish with Lyssavirus, scientists try to understand the molecular basis ofpathogenicity in man, a indispensable prerequisite to identify antiviral targets in a perspective of therapy.

  10. [Flame retardants--use and hazards for human].

    PubMed

    Góralczyk, Katarzyna; Struciński, Paweł; Czaja, Katarzyna; Hernik, Agnieszka; Ludwicki, Jan K

    2002-01-01

    Flame retardants (FRs) are chemicals which added to materials during or after manufacture, inhibit or even suppress the combustion process due to their thermal stability. Large quantities of FRs are added to the plastic material (resins) in variety of electrical and electronic appliances including television and computer casing. The other uses of these compounds include production of building materials, upholstered furniture, textiles, wall covering, carpets, hydraulic fluids as well as vehicles and aircraft. Taking into account the chemical structure, there are five main groups of FRs: brominated, chlorinated, phosphorous-containing, nitrogen-containing (i.e. melamines) and inorganic compounds. Halogenated compounds, especially polybrominated diphenyl ethers (PBDEs), a class of brominated flame retardants, due to their lipophilic characteristics and persistence have become ubiquitous environmental contaminants. There are indications that PBDEs may affect hormone function acting as endocrine disruption and may be toxic for developing brain. These compounds have been associated with non-Hodgkin's lymphoma in humans, a variety of cancers in rodents and disruption of thyroid hormones balance. Similarly to other persistent halogenated compounds they are also able to affect the xenobiotic metabolizing enzymes activity. PBDEs are now found as residues in sediments, wildlife and human (milk, serum adipose tissue) samples. The predominant congeners in environmental samples, including human specimens are two congeners: 47 and 99. Currently, the estimated daily intake of PBDEs by adult humans is equal 51 ng x day-1 while by breast-fed infants equals 110 ng x day-1.

  11. Recombinant follicle-stimulating hormone: new biotechnology for infertility.

    PubMed

    Prevost, R R

    1998-01-01

    The frequency of infertility in developed countries is approximately 8-10%. New drugs are available for assisted reproduction techniques. Two recombinant follicle-stimulating hormone (FSH) products, follitropin-beta (Follistim in the United States, Puregon in Europe) and follitropin-alpha (Gonal-F), join compounds derived through transfecting nonhuman cell lines with genetic material capable of replicating identical amino acid sequences to human compounds. The cell line used for recombinant (r)-FSH production is the Chinese hamster ovary (CHO). Previously, the only agents that showed benefit in controlled ovulatory stimulation were derived from the urine of menopausal women. Those compounds contain additional substances, such as urinary proteins and various amounts of luteininzing hormone. The amino acid sequence of r-FSH is identical to that of human FSH, but the two recombinant products exist in many different isoforms and differ from each other and from human FSH due to varied carbohydrate side chains. Due to variation in the carbohydrate side chains, follitropin-beta in solution has a higher pH than urine-derived FSH, which enhances receptor affinity and therefore is a greater inducer of folliculogenesis. Follitropin-beta does not cause endogenous production of anti-CHO or anti-FSH antibodies, and is well tolerated.

  12. An UGS radar with micro-Doppler capabilities for wide area persistent surveillance

    NASA Astrophysics Data System (ADS)

    Tahmoush, Dave; Silvious, Jerry; Clark, John

    2010-04-01

    Detecting humans and distinguishing them from natural fauna is an important issue in security applications to reduce false alarm rates. In particular, it is important to detect and classify people who are walking in remote locations and transmit back detections over extended periods at a low cost and with minimal maintenance. The ability to discriminate men versus animals and vehicles at long range would give a distinct sensor advantage. The reduction in false positive detections due to animals would increase the usefulness of detections, while dismount identification could reduce friendly-fire. We developed and demonstrate a compact radar technology that is scalable to a variety of ultra-lightweight and low-power platforms for wide area persistent surveillance as an unattended, unmanned, and man-portable ground sensor. The radar uses micro-Doppler processing to characterize the tracks of moving targets and to then eliminate unimportant detections due to animals or civilian activity. This paper presents the system and data on humans, vehicles, and animals at multiple angles and directions of motion, demonstrates the signal processing approach that makes the targets visually recognizable, and verifies that the UGS radar has enough micro-Doppler capability to distinguish between humans, vehicles, and animals.

  13. Acetyl CoA Carboxylase Inhibition Reduces Hepatic Steatosis but Elevates Plasma Triglycerides in Mice and Humans: A Bedside to Bench Investigation.

    PubMed

    Kim, Chai-Wan; Addy, Carol; Kusunoki, Jun; Anderson, Norma N; Deja, Stanislaw; Fu, Xiaorong; Burgess, Shawn C; Li, Cai; Ruddy, Marcie; Chakravarthy, Manu; Previs, Steve; Milstein, Stuart; Fitzgerald, Kevin; Kelley, David E; Horton, Jay D

    2017-08-01

    Inhibiting lipogenesis prevents hepatic steatosis in rodents with insulin resistance. To determine if reducing lipogenesis functions similarly in humans, we developed MK-4074, a liver-specific inhibitor of acetyl-CoA carboxylase (ACC1) and (ACC2), enzymes that produce malonyl-CoA for fatty acid synthesis. MK-4074 administered to subjects with hepatic steatosis for 1 month lowered lipogenesis, increased ketones, and reduced liver triglycerides by 36%. Unexpectedly, MK-4074 increased plasma triglycerides by 200%. To further investigate, mice that lack ACC1 and ACC2 in hepatocytes (ACC dLKO) were generated. Deletion of ACCs decreased polyunsaturated fatty acid (PUFA) concentrations in liver due to reduced malonyl-CoA, which is required for elongation of essential fatty acids. PUFA deficiency induced SREBP-1c, which increased GPAT1 expression and VLDL secretion. PUFA supplementation or siRNA-mediated knockdown of GPAT1 normalized plasma triglycerides. Thus, inhibiting lipogenesis in humans reduced hepatic steatosis, but inhibiting ACC resulted in hypertriglyceridemia due to activation of SREBP-1c and increased VLDL secretion. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Human health risks due to consumption of chemically contaminated fishery products.

    PubMed Central

    Ahmed, F E; Hattis, D; Wolke, R E; Steinman, D

    1993-01-01

    A small proportion of fishery products contaminated with appreciable amounts of potentially hazardous inorganic and organic contaminants from natural and environmental sources seem to pose the greatest potential for toxicity to consumers of fishery products in the United States. Health risks due to chemicals (e.g., modest changes in the overall risk of cancer, subtle deficits of neurological development in fetuses and children) are difficult to measure directly in people exposed to low levels. Immunocompetence may increase cancer risk. Inferences about the potential magnitude of these problems must be based on the levels of specific chemical present, observations of human populations and experimental animals exposed to relatively high doses, and theories about the likely mechanisms of action of specific intoxicants and the population distribution of sensitivity of human exposure. Lognormal distributions were found to provide good descriptions of the pattern of variation of contaminant concentrations among different species and geographic areas; this variability offers a solution for reduction of exposure through restricting harvest of aquatic animals from certain sites and by excluding certain species. Available information suggest that risks are not generally of high magnitude; nevertheless, their control will significantly improve public health.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8143635

  15. Steroids induce acetylcholine receptors on cultured human muscle: Implications for myasthenia gravis

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

    Kaplan, I.; Blakely, B.T.; Pavlath, G.K.

    1990-10-01

    Antibodies to the acetylcholine receptor (AChR), which are diagnostic of the human autoimmune disease myasthenia gravis, block AChR function and increase the rate of AChR degradation leading to impaired neuromuscular transmission. Steroids are frequently used to alleviate symptoms of muscle fatigue and weakness in patients with myasthenia gravis because of their well-documented immunosuppressive effects. The authors show here that the steroid dexamethasone significantly increases total surface AChRs on cultured human muscle exposed to myasthenia gravis sera. The results suggest that the clinical improvement observed in myasthenic patients treated with steroids is due not only to an effect on the immunemore » system but also a direct effect on muscle. They propose that the identification and development of pharmacologic agents that augment receptors and other proteins that are reduced by human genetic or autoimmune disease will have broad therapeutic applications.« less

  16. Highlights of human toxocariasis

    PubMed Central

    Glickman, Lawrence T.; Dorchies, Philippe; Morassin, Bruno

    2001-01-01

    Human toxocariasis is a helminthozoonosis due to the migration of Toxocara species larvae through human organism. Humans become infected by ingesting either embryonated eggs from soil (geophagia, pica), dirty hands or raw vegetables, or larvae from undercooked giblets. The diagnosis relies upon sensitive immunological methods (ELISA or western-blot) which use Toxocara excretory-secretory antigens. Seroprevalence is high in developed countries, especially in rural areas, and also in some tropical islands. The clinical spectrum of the disease comprises four syndromes, namely visceral larva migrans, ocular larva migrans, and the more recently recognized "common" (in adults) and "covert" (in children) pictures. Therapy of ocular toxocariasis is primarily based upon corticosteroids use, when visceral larva migrans and few cases of common or covert toxocariasis can be treated by anthelmintics whose the most efficient appeared to be diethylcarbamazine. When diagnosed, all of these syndromes require thorough prevention of recontamination (especially by deworming pets) and sanitary education. PMID:11301585

  17. Fuzzy Modelling for Human Dynamics Based on Online Social Networks

    PubMed Central

    Cuenca-Jara, Jesus; Valdes-Vela, Mercedes; Skarmeta, Antonio F.

    2017-01-01

    Human mobility mining has attracted a lot of attention in the research community due to its multiple implications in the provisioning of innovative services for large metropolises. In this scope, Online Social Networks (OSN) have arisen as a promising source of location data to come up with new mobility models. However, the human nature of this data makes it rather noisy and inaccurate. In order to deal with such limitations, the present work introduces a framework for human mobility mining based on fuzzy logic. Firstly, a fuzzy clustering algorithm extracts the most active OSN areas at different time periods. Next, such clusters are the building blocks to compose mobility patterns. Furthermore, a location prediction service based on a fuzzy rule classifier has been developed on top of the framework. Finally, both the framework and the predictor has been tested with a Twitter and Flickr dataset in two large cities. PMID:28837120

  18. High-mobility group B1 (HMGB1) and receptor for advanced glycation end-products (RAGE) expression in canine lymphoma.

    PubMed

    Sterenczak, Katharina A; Joetzke, Alexa E; Willenbrock, Saskia; Eberle, Nina; Lange, Sandra; Junghanss, Christian; Nolte, Ingo; Bullerdiek, Jörn; Simon, Daniela; Murua Escobar, Hugo

    2010-12-01

    Canine lymphoma is a commonly occurring, spontaneously developing neoplasia similar to human non-Hodgkin's lymphoma and, thus, is used as a valuable model for human malignancy. HMGB1 and RAGE are strongly associated with tumour progression and vascularisation. Consequently, deregulated RAGE and HMGB1 may play an important role in the mechanisms involved in lymphoma progression. Expression patterns of HMGB1 and RAGE were analysed in 22 canine lymphoma and three canine non-neoplastic control samples via real time PCR and canine beta-glucuronidase gene (GUSB) as endogenous control. HMGB1 was up-regulated in the neoplastic samples, while RAGE expression remained inconspicuous. This study demonstrated similar mechanisms in lymphoma progression in humans and dogs due to overexpression of HMGB1, which was described in human lymphomas. RAGE remained stable in terms of expression indicating that the extracellular HMGB1-induced effects are regulated by HMGB1 itself.

  19. Fuzzy Modelling for Human Dynamics Based on Online Social Networks.

    PubMed

    Cuenca-Jara, Jesus; Terroso-Saenz, Fernando; Valdes-Vela, Mercedes; Skarmeta, Antonio F

    2017-08-24

    Human mobility mining has attracted a lot of attention in the research community due to its multiple implications in the provisioning of innovative services for large metropolises. In this scope, Online Social Networks (OSN) have arisen as a promising source of location data to come up with new mobility models. However, the human nature of this data makes it rather noisy and inaccurate. In order to deal with such limitations, the present work introduces a framework for human mobility mining based on fuzzy logic. Firstly, a fuzzy clustering algorithm extracts the most active OSN areas at different time periods. Next, such clusters are the building blocks to compose mobility patterns. Furthermore, a location prediction service based on a fuzzy rule classifier has been developed on top of the framework. Finally, both the framework and the predictor has been tested with a Twitter and Flickr dataset in two large cities.

  20. Exploitation of Ubiquitous Wi-Fi Devices as Building Blocks for Improvised Motion Detection Systems.

    PubMed

    Soldovieri, Francesco; Gennarelli, Gianluca

    2016-02-27

    This article deals with a feasibility study on the detection of human movements in indoor scenarios based on radio signal strength variations. The sensing principle exploits the fact that the human body interacts with wireless signals, introducing variations of the radiowave fields due to shadowing and multipath phenomena. As a result, human motion can be inferred from fluctuations of radiowave power collected by a receiving terminal. In this paper, we investigate the potentialities of widely available wireless communication devices in order to develop an improvised motion detection system (IMDS). Experimental tests are performed in an indoor environment by using a smartphone as a Wi-Fi access point and a laptop with dedicated software as a receiver. Simple detection strategies tailored for real-time operation are implemented to process the received signal strength measurements. The achieved results confirm the potentialities of the simple system here proposed to reliably detect human motion in operational conditions.

  1. Experimental econophysics: Complexity, self-organization, and emergent properties

    NASA Astrophysics Data System (ADS)

    Huang, J. P.

    2015-03-01

    Experimental econophysics is concerned with statistical physics of humans in the laboratory, and it is based on controlled human experiments developed by physicists to study some problems related to economics or finance. It relies on controlled human experiments in the laboratory together with agent-based modeling (for computer simulations and/or analytical theory), with an attempt to reveal the general cause-effect relationship between specific conditions and emergent properties of real economic/financial markets (a kind of complex adaptive systems). Here I review the latest progress in the field, namely, stylized facts, herd behavior, contrarian behavior, spontaneous cooperation, partial information, and risk management. Also, I highlight the connections between such progress and other topics of traditional statistical physics. The main theme of the review is to show diverse emergent properties of the laboratory markets, originating from self-organization due to the nonlinear interactions among heterogeneous humans or agents (complexity).

  2. In vitro experimental investigation of voice production

    PubMed Central

    Horáčcek, Jaromír; Brücker, Christoph; Becker, Stefan

    2012-01-01

    The process of human phonation involves a complex interaction between the physical domains of structural dynamics, fluid flow, and acoustic sound production and radiation. Given the high degree of nonlinearity of these processes, even small anatomical or physiological disturbances can significantly affect the voice signal. In the worst cases, patients can lose their voice and hence the normal mode of speech communication. To improve medical therapies and surgical techniques it is very important to understand better the physics of the human phonation process. Due to the limited experimental access to the human larynx, alternative strategies, including artificial vocal folds, have been developed. The following review gives an overview of experimental investigations of artificial vocal folds within the last 30 years. The models are sorted into three groups: static models, externally driven models, and self-oscillating models. The focus is on the different models of the human vocal folds and on the ways in which they have been applied. PMID:23181007

  3. A dynamic human water and electrolyte balance model for verification and optimization of life support systems in space flight applications

    NASA Astrophysics Data System (ADS)

    Hager, P.; Czupalla, M.; Walter, U.

    2010-11-01

    In this paper we report on the development of a dynamic MATLAB SIMULINK® model for the water and electrolyte balance inside the human body. This model is part of an environmentally sensitive dynamic human model for the optimization and verification of environmental control and life support systems (ECLSS) in space flight applications. An ECLSS provides all vital supplies for supporting human life on board a spacecraft. As human space flight today focuses on medium- to long-term missions, the strategy in ECLSS is shifting to closed loop systems. For these systems the dynamic stability and function over long duration are essential. However, the only evaluation and rating methods for ECLSS up to now are either expensive trial and error breadboarding strategies or static and semi-dynamic simulations. In order to overcome this mismatch the Exploration Group at Technische Universität München (TUM) is developing a dynamic environmental simulation, the "Virtual Habitat" (V-HAB). The central element of this simulation is the dynamic and environmentally sensitive human model. The water subsystem simulation of the human model discussed in this paper is of vital importance for the efficiency of possible ECLSS optimizations, as an over- or under-scaled water subsystem would have an adverse effect on the overall mass budget. On the other hand water has a pivotal role in the human organism. Water accounts for about 60% of the total body mass and is educt and product of numerous metabolic reactions. It is a transport medium for solutes and, due to its high evaporation enthalpy, provides the most potent medium for heat load dissipation. In a system engineering approach the human water balance was worked out by simulating the human body's subsystems and their interactions. The body fluids were assumed to reside in three compartments: blood plasma, interstitial fluid and intracellular fluid. In addition, the active and passive transport of water and solutes between those compartments was modeled dynamically. A kidney model regulates the electrolyte concentration in body fluids (osmolality) in narrow confines and a thirst mechanism models the urge to ingest water. A controlled exchange of water and electrolytes with other human subsystems, as well as with the environment, is implemented. Finally, the changes in body composition due to muscle growth are accounted for. The outcome of this is a dynamic water and electrolyte balance, which is capable of representing body reactions like thirst and headaches, as well as heat stroke and collapse, as a response to its work load and environment.

  4. An Argument against Using Standardized Test Scores for Placement of International Undergraduate Students in English as a Second Language (ESL) Courses

    ERIC Educational Resources Information Center

    Kokhan, Kateryna

    2013-01-01

    Development and administration of institutional ESL placement tests require a great deal of financial and human resources. Due to a steady increase in the number of international students studying in the United States, some US universities have started to consider using standardized test scores for ESL placement. The English Placement Test (EPT)…

  5. Nesting pair density and abundance of ferruginous hawks (Buteo regalis) and golden eagles (Aquila chrysaetos) from aerial surveys in Wyoming

    Treesearch

    Lucretia E. Olson; Robert J. Oakleaf; John R. Squires; Zachary P. Wallace; Patricia L. Kennedy

    2015-01-01

    Raptors that inhabit sagebrush steppe and grassland ecosystems in the western United States may be threatened by continued loss and modification of their habitat due to energy development, conversion to agriculture, and human encroachment. Actions to protect these species are hampered by a lack of reliable data on such basic information as population size and...

  6. A noninvasive tool to assess the distribution of Pacific lamprey (Entosphenus tridentatus) in the Columbia River basin

    Treesearch

    Kellie J. Carim; J. Caleb Dysthe; Michael K. Young; Kevin S. McKelvey; Michael K. Schwartz

    2017-01-01

    The Pacific lamprey (Entosphenus tridentatus) is an anadromous fish once abundant throughout coastal basins of western North America that has suffered dramatic declines in the last century due primarily to human activities. Here, we describe the development of an environmental DNA (eDNA) assay to detect Pacific lamprey in the Columbia River basin. The eDNA assay...

  7. Water yield responses to climate change and variability across the North–South Transect of Eastern China (NSTEC)

    Treesearch

    Nan Lu; Ge Sun; Xiaoming Feng; Bojie Fu

    2013-01-01

    China is facing a growing water crisis due to climate and land use change, and rise in human water demand across this rapidly developing country. Understanding the spatial and temporal ecohydrologic responses to climate change is critical to sustainable water resource management. We investigated water yield (WY) responses to historical (1981–2000) and projected...

  8. Development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis.

    PubMed

    De Benedictis, Paola; Minola, Andrea; Rota Nodari, Elena; Aiello, Roberta; Zecchin, Barbara; Salomoni, Angela; Foglierini, Mathilde; Agatic, Gloria; Vanzetta, Fabrizia; Lavenir, Rachel; Lepelletier, Anthony; Bentley, Emma; Weiss, Robin; Cattoli, Giovanni; Capua, Ilaria; Sallusto, Federica; Wright, Edward; Lanzavecchia, Antonio; Bourhy, Hervé; Corti, Davide

    2016-04-01

    Currently available rabies post-exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad-spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non-RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20-RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post-vaccination antibody response. © 2016 Humabs BioMed SA Published under the terms of the CC BY 4.0 license.

  9. Classification of deaths in women with human immunodeficiency virus/acquired immunodeficiency syndrome in pregnancy and childbirth.

    PubMed

    Brayner, Manuella Coutinho; Alves, Sandra Valongueiro

    2017-01-01

    To reclassify deaths of women infected with the human immunodeficiency virus/acquired immunodeficiency syndrome in pregnancy and childbirth in the State of Pernambuco, Brazil, from 2000 to 2010. A descriptive exploratory study, developed from the following steps: translation to Portuguese of the item "HIV and aids" of the United Nations document "The WHO application of ICD-10 to deaths during pregnancy, childbirth and the puerperium: DCI MM 2012"; development of a classification algorithm of deaths of women living with the human immunodeficiency virus/acquired immunodeficiency syndrome in pregnancy and childbirth; and reclassification of deaths by a group of experts. Among the 25 reclassified deaths, 12 were due to human immunodeficiency virus/acquired immunodeficiency syndrome, and pregnancy condition was coexisting; 9 were reclassified as indirect maternal death, with O98.7 code, proposed by the World Health Organization; 2 as direct/indirect maternal death; and 2 were considered indeterminate. The reclassification showed a possible pattern of change in maternal mortality, since most of the deaths were attributed to the virus and may lead to a reduction in deaths from maternal causes. The algorithm will subsidize the use of the new classification of maternal death and human immunodeficiency virus/acquired immunodeficiency syndrome.

  10. Vulnerability assessment of atmospheric environment driven by human impacts.

    PubMed

    Zhang, Yang; Shen, Jing; Ding, Feng; Li, Yu; He, Li

    2016-11-15

    Atmospheric environment quality worsening is a substantial threat to public health worldwide, and in many places, air pollution due to the intensification of the human activity is increasing dramatically. However, no studies have been investigated the integration of vulnerability assessment and atmospheric environment driven by human impacts. The objective of this study was to identify and prioritize the undesirable environmental changes as an early warning system for environment managers and decision makers in term of human, atmospheric environment, and social economic elements. We conduct a vulnerability assessment method of atmospheric environment associated with human impact, this method integrates spatial context of Geographic Information System (GIS) tool, multi-criteria decision analysis (MCDA) method, ordered weighted averaging (OWA) operators under the Exposure-Sensitivity- Adaptive Capacity (ESA) framework. Decision makers can find out relevant vulnerability assessment results with different vulnerable attitudes. In the Beijing-Tianjin-Hebei (BTH) region, China, we further applied this developed method and proved it to be reliable and consistent with the China Environmental Status Bulletin. Results indicate that the vulnerability of atmospheric environment in the BTH region is not optimistic, and environment managers should do more about air pollution. Thus, the most appropriate strategic decision and development program of city or state can be picked out assisting by the vulnerable results. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Manipulation of Metabolic Pathways to Develop Vitamin-Enriched Crops for Human Health

    PubMed Central

    Jiang, Ling; Wang, Weixuan; Lian, Tong; Zhang, Chunyi

    2017-01-01

    Vitamin deficiencies are major forms of micronutrient deficiencies, and are associated with huge economic losses as well as severe physical and intellectual damages to humans. Much evidence has demonstrated that biofortification plays an important role in combating vitamin deficiencies due to its economical and effective delivery of nutrients to populations in need. Biofortification enables food plants to be enriched with vitamins through conventional breeding and/or biotechnology. Here, we focus on the progress in the manipulation of the vitamin metabolism, an essential part of biofortification, by the genetic modification or by the marker-assisted selection to understand mechanisms underlying metabolic improvement in food plants. We also propose to integrate new breeding technologies with metabolic pathway modification to facilitate biofortification in food plants and, thereby, to benefit human health. PMID:28634484

  12. Platelet bioreactor-on-a-chip

    PubMed Central

    Mazutis, Linas; Wu, Stephen; Sylman, Joanna L.; Ehrlicher, Allen; Machlus, Kellie R.; Feng, Qiang; Lu, Shijiang; Lanza, Robert; Neeves, Keith B.; Weitz, David A.; Italiano, Joseph E.

    2014-01-01

    Platelet transfusions total >2.17 million apheresis-equivalent units per year in the United States and are derived entirely from human donors, despite clinically significant immunogenicity, associated risk of sepsis, and inventory shortages due to high demand and 5-day shelf life. To take advantage of known physiological drivers of thrombopoiesis, we have developed a microfluidic human platelet bioreactor that recapitulates bone marrow stiffness, extracellular matrix composition, micro-channel size, hemodynamic vascular shear stress, and endothelial cell contacts, and it supports high-resolution live-cell microscopy and quantification of platelet production. Physiological shear stresses triggered proplatelet initiation, reproduced ex vivo bone marrow proplatelet production, and generated functional platelets. Modeling human bone marrow composition and hemodynamics in vitro obviates risks associated with platelet procurement and storage to help meet growing transfusion needs. PMID:25606631

  13. Variation is the universal: making cultural evolution work in developmental psychology.

    PubMed

    Kline, Michelle Ann; Shamsudheen, Rubeena; Broesch, Tanya

    2018-04-05

    Culture is a human universal, yet it is a source of variation in human psychology, behaviour and development. Developmental researchers are now expanding the geographical scope of research to include populations beyond relatively wealthy Western communities. However, culture and context still play a secondary role in the theoretical grounding of developmental psychology research, far too often. In this paper, we highlight four false assumptions that are common in psychology, and that detract from the quality of both standard and cross-cultural research in development. These assumptions are: (i) the universality assumption , that empirical uniformity is evidence for universality, while any variation is evidence for culturally derived variation; (ii) the Western centrality assumption , that Western populations represent a normal and/or healthy standard against which development in all societies can be compared; (iii) the deficit assumption , that population-level differences in developmental timing or outcomes are necessarily due to something lacking among non-Western populations; and (iv) the equivalency assumption , that using identical research methods will necessarily produce equivalent and externally valid data, across disparate cultural contexts. For each assumption, we draw on cultural evolutionary theory to critique and replace the assumption with a theoretically grounded approach to culture in development. We support these suggestions with positive examples drawn from research in development. Finally, we conclude with a call for researchers to take reasonable steps towards more fully incorporating culture and context into studies of development, by expanding their participant pools in strategic ways. This will lead to a more inclusive and therefore more accurate description of human development.This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'. © 2018 The Author(s).

  14. Lectins in human pathogenic fungi.

    PubMed

    Gallegos, Belém; Martínez, Ruth; Pérez, Laura; Del Socorro Pina, María; Perez, Eduardo; Hernández, Pedro

    2014-01-01

    Lectins are carbohydrate-binding proteins widely distributed in nature. They constitute a highly diverse group of proteins consisting of many different protein families that are, in general, structurally unrelated. In the last few years, mushroom and other fungal lectins have attracted wide attention due to their antitumour, antiproliferative and immunomodulatory activities. The present mini-review provides concise information about recent developments in understanding lectins from human pathogenic fungi. A bibliographic search was performed in the Science Direct and PubMed databases, using the following keywords "lectin", "fungi", "human" and "pathogenic". Lectins present in fungi have been classified; however, the role played by lectins derived from human pathogenic fungi in infectious processes remains uncertain; thus, this is a scientific field requiring more research. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

  15. Challenges to Sierra Nevada forests and their local communities: An observational and modeling perspective

    NASA Astrophysics Data System (ADS)

    Schmidt, Cynthia L.

    Global forests are experiencing dramatic changes due to changes in climate as well as anthropogenic activities. Increased warming is causing the advancement of some species upslope and northward, while it is also causing widespread mortality due to increased drought conditions. In addition, increasing human population in mountain regions is resulting in elevated risk of human life and property loss due to larger and more severe wildfires. My research focuses on assessing the current vulnerability of forests and their communities in the Sierra Nevada, and how forests are projected to change in the future based on different climate change scenarios. In the first chapter I use Landsat satellite imagery to identify and attribute cause of forest disturbance between 1985 and 2011, primarily focusing on disturbances due to insect, diseases and drought. The change-detection algorithm, Landtrendr, was successfully used to identify forest disturbance, but identifying cause of disturbance was challenging due to the spectral similarities between disturbance types. Landtrendr was most successful in identifying disturbance due to insect, disease and drought in the San Bernardino National Forest, where there is little forest management activity. In the second chapter, I assess whether state or local land use policies in high-fire prone regions exist to reduce the vulnerability of residential developments to wildfire. Three specific land-use tools associated with reducing wildfire vulnerability are identified: (1) buffers around developments; (2) clustered developments; (3) restricting construction on slopes greater than 25%. The study also determines whether demographic and physical characteristics of selected California counties were related to implementing land use policies related to reducing wildfire vulnerability. Results indicate that land use policies related to preventing wildfire-related losses focus on building materials, road access, water availability and vegetation management, not the three identified land-use tools. San Diego County, the county that has experienced the most devastating fires, had the highest percentage of residential developments with both clustering and buffering. The third chapter focuses on future forest conditions. I used a Dynamic Global Vegetation Model (DGVM) to assess future vegetation dynamics and productivity under changing climate and atmospheric CO2 concentrations in the Sierra Nevada. Model results suggest that Temperate Broadleaved Evergreen Plant Functional Types (PFTs) will move upslope and eastward, replacing Temperate Needleleaved PFTs. Boreal Needleleaved Evergreen PFTs, found primarily at higher elevations, will decline dramatically as temperatures continue to increase. Gross Primary Productivity (GPP) will increase as atmospheric CO2 concentration increases, due primarily to the increase in the more productive broadleaved PFTs. Forest ecosystems play an important role in maintaining climate stability at the regional and global scales as a vital carbon sink, so understanding the role of disturbance and climate change will be vital to both scientists and policy makers in the future.

  16. Evaluating the Human Damage of Tsunami at Each Time Frame in Aggregate Units Based on GPS data

    NASA Astrophysics Data System (ADS)

    Ogawa, Y.; Akiyama, Y.; Kanasugi, H.; Shibasaki, R.; Kaneda, H.

    2016-06-01

    Assessments of the human damage caused by the tsunami are required in order to consider disaster prevention at such a regional level. Hence, there is an increasing need for the assessments of human damage caused by earthquakes. However, damage assessments in japan currently usually rely on static population distribution data, such as statistical night time population data obtained from national census surveys. Therefore, human damage estimation that take into consideration time frames have not been assessed yet. With these backgrounds, the objectives of this study are: to develop a method for estimating the population distribution of the for each time frame, based on location positioning data observed with mass GPS loggers of mobile phones, to use a evacuation and casualties models for evaluating human damage due to the tsunami, and evaluate each time frame by using the data developed in the first objective, and 3) to discuss the factors which cause the differences in human damage for each time frame. By visualizing the results, we clarified the differences in damage depending on time frame, day and area. As this study enables us to assess damage for any time frame in and high resolution, it will be useful to consider provision for various situations when an earthquake may hit, such as during commuting hours or working hours and week day or holiday.

  17. The role of associative and non-associative learning in the training of horses and implications for the welfare (a review).

    PubMed

    Baragli, Paolo; Padalino, Barbara; Telatin, Angelo

    2015-01-01

    Horses were domesticated 6000 years ago and since then different types of approaches have been developed to enhance the horse's wellbeing and the human-horse relationship. Even though horse training is an increasingly important research area and many articles have been published on the subject, equitation is still the sport with the highest rate of human injuries, and a significant percentage of horses are sold or slaughtered due to behavioral problems. One explanation for this data is that the human-horse relationship is complex and the communication between humans and horses has not yet been accurately developed. Thus, this review addresses correct horse training based on scientific knowledge in animal learning and psychology. Specifically, it starts from the basic communication between humans and horses and then focuses on associative and non-associative learning, with many practical outcomes in horse management from the ground and under saddle. Finally, it highlights the common mistakes in the use of negative reinforcement, as well as all the implications that improper training could have on horse welfare. Increased levels of competence in horse training could be useful for equine technicians, owners, breeders, veterinarians, and scientists, in order to safeguard horse welfare, and also to reduce the number of human injuries and economic loss for civil society and the public health system.

  18. Reducing Human Radiation Risks on Deep Space Missions

    DTIC Science & Technology

    2017-09-01

    Roadmap (2016). .........................................................108 Figure 53. Risk Assessment for Acute Radiation Syndrome Due to SPEs...Risk of Acute Radiation Syndromes Due to Solar Particle Events Figure 53 highlights the fact that acute radiation syndrome is a short-term risk...acceptable for long-term missions. Figure 53. Risk Assessment for Acute Radiation Syndrome Due to SPEs. Source: NASA Human Research Roadmap (2016

  19. Digenic retinitis pigmentosa due to mutations at the unlinked peripherin/RDS and ROM1 loci

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

    Kajiwara, K.; Berson, E.L.; Dryja, T.P.

    1994-06-10

    In spite of recent advances in identifying genes causing monogenic human disease, very little is known about the genes involved in polygenic disease. Three families were identified with mutations in the unlinked photoreceptor-specific genes ROM 1 and peripherin/RDS, in which only double heterozygotes develop retinitis pigmentosa (RP). These findings indicate that the allelic and nonallelic heterogeneity known to be a feature of monogenic RP is complicated further by interactions between unlinked mutations causing digenic RP. Recognition of the inheritance pattern exemplified by these three families might facilitate the identification of other examples of digenic inheritance in human disease.

  20. Developmental and morphological studies in Japanese medaka with ultra-high resolution optical coherence tomography

    PubMed Central

    Gladys, Fanny Moses; Matsuda, Masaru; Lim, Yiheng; Jackin, Boaz Jessie; Imai, Takuto; Otani, Yukitoshi; Yatagai, Toyohiko; Cense, Barry

    2015-01-01

    We propose ultra-high resolution optical coherence tomography to study the morphological development of internal organs in medaka fish in the post-embryonic stages at micrometer resolution. Different stages of Japanese medaka were imaged after hatching in vivo with an axial resolution of 2.8 µm in tissue. Various morphological structures and organs identified in the OCT images were then compared with the histology. Due to the medaka’s close resemblance to vertebrates, including humans, these morphological features play an important role in morphogenesis and can be used to study diseases that also occur in humans. PMID:25780725

  1. Freestanding triboelectric-layer-based nanogenerators for harvesting energy from a moving object or human motion in contact and non-contact modes.

    PubMed

    Wang, Sihong; Xie, Yannan; Niu, Simiao; Lin, Long; Wang, Zhong Lin

    2014-05-01

    For versatile mechanical energy harvesting from arbitrary moving objects such as humans, a new mode of triboelectric nanogenerator is developed based on the sliding of a freestanding triboelectric-layer between two stationary electrodes on the same plane. With two electrodes alternatively approached by the tribo-charges on the sliding layer, electricity is effectively generated due to electrostatic induction. A unique feature of this nanogenerator is that it can operate in non-contact sliding mode, which greatly increases the lifetime and the efficiency of such devices. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Ethics of paid organ donation.

    PubMed

    Phadke, Kishore D; Anandh, Urmila

    2002-05-01

    As the waiting list of patients requiring organ transplantation grows, there is a subtle but noticeable shift in society towards accepting organs as a commodity which can be paid for. Although nowhere is the organ trade legal, the commerce of organs goes on in different parts of the world, especially in developing countries such as India. This is largely due to societal and governmental failure to implement the existing "transplant laws". It is high time the medical profession ceased being an accomplice to this unscrupulous trade, which exploits the poor, deters altruism retarding the living-related and cadaver transplant programs, commercializes the human body and jeopardizes human dignity.

  3. [Update on cutaneous dirofilariasis].

    PubMed

    Benzaquen, M; Marmottant, E; Parola, P; Berbis, P

    2017-10-01

    Dirofilariasis is a worldwide zoonotic infection that rarely affects humans and is caused by filarial nematodes of the genus Diroflaria transmitted by mosquitoes. Cutaneous dirofilariasis, due to D. repens, presents as inflammatory lesions that develop into subcutaneous nodules. These clinical symptoms may be consistent with Wells' cellulitis. Diagnosis of dirofilariasis involves demonstration of the presence of the nematode during skin biopsy and identification of the worm through macroscopic, histological and PCR analysis. Surgical resection of the nodule remains the gold standard treatment. The number of cases of human cutaneous dirofilariasis has increased in the recent years and the disease must not be misdiagnosed. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Fascioliasis: An Ongoing Zoonotic Trematode Infection

    PubMed Central

    Nyindo, Mramba; Lukambagire, Abdul-Hamid

    2015-01-01

    Zoonotic trematode infections are an area of the neglected tropical diseases that have become of major interest to global and public health due to their associated morbidity. Human fascioliasis is a trematode zoonosis of interest in public health. It affects approximately 50 million people worldwide and over 180 million are at risk of infection in both developed and underdeveloped countries. The one health paradigm is an area that seeks to address the problem of zoonotic infections through a comprehensive and sustainable approach. This review attempts to address the major challenges in managing human and animal fascioliasis with valuable insights gained from the one health paradigm to global health and multidisciplinary integration. PMID:26417603

  5. Fascioliasis: An Ongoing Zoonotic Trematode Infection.

    PubMed

    Nyindo, Mramba; Lukambagire, Abdul-Hamid

    2015-01-01

    Zoonotic trematode infections are an area of the neglected tropical diseases that have become of major interest to global and public health due to their associated morbidity. Human fascioliasis is a trematode zoonosis of interest in public health. It affects approximately 50 million people worldwide and over 180 million are at risk of infection in both developed and underdeveloped countries. The one health paradigm is an area that seeks to address the problem of zoonotic infections through a comprehensive and sustainable approach. This review attempts to address the major challenges in managing human and animal fascioliasis with valuable insights gained from the one health paradigm to global health and multidisciplinary integration.

  6. Xpert Flu for point-of-care diagnosis of human influenza in industrialized countries.

    PubMed

    Salez, Nicolas; Nougairede, Antoine; Ninove, Laetitia; Zandotti, Christine; de Lamballerie, Xavier; Charrel, Rémi N

    2014-05-01

    Respiratory infections, particularly those caused by influenza viruses, represent the third-most important cause of death in the world due to infectious diseases. Nevertheless, despite the enormous publicity attracted by epidemics due to these viruses, laboratory diagnosis, documentation and recording of respiratory diseases is still unsatisfactory. Available diagnostic tests capable of providing results rapidly are either limited and insufficiently sensitive or highly sensitive and specific but insufficiently rapid. Considerable investment and research efforts have been made towards the development of new diagnostics for influenza A and B viruses and the Xpert(®) Flu assay (Cepheid(®), CA, USA) has emerged as one of the most promising. In this article, we review current knowledge of the Xpert Flu test, discuss its potential value as a point-of-care test and outline the potential leads for future development.

  7. Physical changes of the environment and health effects with special reference to water pollution and sanitation in Malaysia.

    PubMed

    Sekarajasekaran, I A

    1979-12-01

    Development of a human community are not without changes in its environment. Such changes result in either beneficial or adverse effects on human health. In Malaysia, in the wake of the New Economic Policy aimed at the redressing of the poor population and income distribution, development of the nation has brought about various changes in the environment. Some of these changes have elevated basic public health problems, while others, particularly new agricultural practices and industrialisation programmes with urbanisation trends, have brought a new set of problems due to water pollution and sanitation. Various measures are being taken to protect and to improve the environment so that progress can be realised with minimum adverse effects. This also calls for assistance from international sources, in terms of expertise, training and funds.

  8. [The activity of drug addiction service of the Russian Federation: an assessment of statistical parameters and an analysis of results].

    PubMed

    Koshkina, E A; Kirzhanova, V V; Babicheva, L P; Mugantseva, L A

    2013-01-01

    The authors studied changes in the structure of drug addiction services, the dynamics of outpatient and inpatient referrals for drug addiction treatment and effectiveness of drug addiction services in 2011 compared to the preceding period. There was a reduction of availability of drug treatment services due to the reduction of the number of drug addiction units and the depletion of human resource potential. The lack of structural development of rehabilitation sector of drug care services and low rates of its development as well as the decrease in the number of patients seeking treatment are highlighted. It has been concluded that the drug addiction services require reorganization of its regulatory and legal framework and need innovative organizational and management decisions and human resources trained in innovative thinking and technologies.

  9. Acute occupational poisoning by octogen: first case report.

    PubMed

    Testud, François; Descotes, Jacques; Le Meur, Brigitte

    2006-01-01

    Octogen (HMX) is a polynitramine explosive closely related to hexogen, a known occupational toxin in military munitions plants. No acute human poisoning with octogen has ever been reported. A 28-year-old man with no history of epilepsy was admitted to the Emergency Department for seizures that had developed during the night after a full working day when he manually sieved large amounts of dry octogen. On admission, the clinical examination was normal and all other examinations could not substantiate the development of essential or secondary epilepsy. Elevated octogen concentrations were measured in his plasma, which confirmed occupational exposure to the explosive. The rarity of acute human poisonings by octogen is due to the infrequent use of this explosive and, more importantly, its very low oral bioavailability. However, acute poisoning can occur, but should be easily avoided by implementing adequate preventive measures.

  10. Recent developments in trans-sialidase inhibitors of Trypanosoma cruzi.

    PubMed

    Kashif, Muhammad; Moreno-Herrera, Antonio; Lara-Ramirez, Edgar E; Ramírez-Moreno, Esther; Bocanegra-García, Virgilio; Ashfaq, Muhammad; Rivera, Gildardo

    2017-07-01

    Chagas is a lethal chronic disease that currently affects 8-10 million people worldwide, primarily in South and Central America. Trypanosoma cruzi trans-sialidase is an enzyme that is of vital importance for the survival of the parasite due to its key role in the transfer of sialic acid from the host to the parasite surface and it also helps the parasite combat the host's immune system. This enzyme has no equivalent human enzyme; thus, it has become an interesting target for the development of inhibitors that combat the parasite. In this review, we summarize three classes of inhibitors (acceptor, donor and unrelated) with their inhibition values and their mode of action against this enzyme. Based on molecular docking, molecular dynamics and structure-activity relationship studies, it has been discovered that the molecules with -NH 2 , -OH and -COOH groups on an aromatic ring could be used as a scaffold for the development of new and potent trans-sialidase inhibitors due to their key interaction with active enzyme sites. In particular, carboxylic acid derivatives have importance over the sugar moiety due to their ease of synthesis and unique structure-activity relationship.

  11. Emergence of scaling in human-interest dynamics

    PubMed Central

    Zhao, Zhi-Dan; Yang, Zimo; Zhang, Zike; Zhou, Tao; Huang, Zi-Gang; Lai, Ying-Cheng

    2013-01-01

    Human behaviors are often driven by human interests. Despite intense recent efforts in exploring the dynamics of human behaviors, little is known about human-interest dynamics, partly due to the extreme difficulty in accessing the human mind from observations. However, the availability of large-scale data, such as those from e-commerce and smart-phone communications, makes it possible to probe into and quantify the dynamics of human interest. Using three prototypical “Big Data” sets, we investigate the scaling behaviors associated with human-interest dynamics. In particular, from the data sets we uncover fat-tailed (possibly power-law) distributions associated with the three basic quantities: (1) the length of continuous interest, (2) the return time of visiting certain interest, and (3) interest ranking and transition. We argue that there are three basic ingredients underlying human-interest dynamics: preferential return to previously visited interests, inertial effect, and exploration of new interests. We develop a biased random-walk model, incorporating the three ingredients, to account for the observed fat-tailed distributions. Our study represents the first attempt to understand the dynamical processes underlying human interest, which has significant applications in science and engineering, commerce, as well as defense, in terms of specific tasks such as recommendation and human-behavior prediction. PMID:24326949

  12. Chimeric mice with humanized liver: Application in drug metabolism and pharmacokinetics studies for drug discovery.

    PubMed

    Naritomi, Yoichi; Sanoh, Seigo; Ohta, Shigeru

    2018-02-01

    Predicting human drug metabolism and pharmacokinetics (PK) is key to drug discovery. In particular, it is important to predict human PK, metabolite profiles and drug-drug interactions (DDIs). Various methods have been used for such predictions, including in vitro metabolic studies using human biological samples, such as hepatic microsomes and hepatocytes, and in vivo studies using experimental animals. However, prediction studies using these methods are often inconclusive due to discrepancies between in vitro and in vivo results, and interspecies differences in drug metabolism. Further, the prediction methods have changed from qualitative to quantitative to solve these issues. Chimeric mice with humanized liver have been developed, in which mouse liver cells are mostly replaced with human hepatocytes. Since human drug metabolizing enzymes are expressed in the liver of these mice, they are regarded as suitable models for mimicking the drug metabolism and PK observed in humans; therefore, these mice are useful for predicting human drug metabolism and PK. In this review, we discuss the current state, issues, and future directions of predicting human drug metabolism and PK using chimeric mice with humanized liver in drug discovery. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  13. Recommendations for genetic variation data capture in developing countries to ensure a comprehensive worldwide data collection.

    PubMed

    Patrinos, George P; Al Aama, Jumana; Al Aqeel, Aida; Al-Mulla, Fahd; Borg, Joseph; Devereux, Andrew; Felice, Alex E; Macrae, Finlay; Marafie, Makia J; Petersen, Michael B; Qi, Ming; Ramesar, Rajkumar S; Zlotogora, Joel; Cotton, Richard G H

    2011-01-01

    Developing countries have significantly contributed to the elucidation of the genetic basis of both common and rare disorders, providing an invaluable resource of cases due to large family sizes, consanguinity, and potential founder effects. Moreover, the recognized depth of genomic variation in indigenous African populations, reflecting the ancient origins of humanity on the African continent, and the effect of selection pressures on the genome, will be valuable in understanding the range of both pathological and nonpathological variations. The involvement of these populations in accurately documenting the extant genetic heterogeneity is more than essential. Developing nations are regarded as key contributors to the Human Variome Project (HVP; http://www.humanvariomeproject.org), a major effort to systematically collect mutations that contribute to or cause human disease and create a cyber infrastructure to tie databases together. However, biomedical research has not been the primary focus in these countries even though such activities are likely to produce economic and health benefits for all. Here, we propose several recommendations and guidelines to facilitate participation of developing countries in genetic variation data documentation, ensuring an accurate and comprehensive worldwide data collection. We also summarize a few well-coordinated genetic data collection initiatives that would serve as paradigms for similar projects.

  14. Catchment scale assessment of risk posed by traffic generated heavy metals and polycyclic aromatic hydrocarbons.

    PubMed

    Ma, Yukun; McGree, James; Liu, An; Deilami, Kaveh; Egodawatta, Prasanna; Goonetilleke, Ashantha

    2017-10-01

    Heavy metals (HMs) and polycyclic aromatic hydrocarbons (PAHs) are among the most toxic chemical pollutants present in urban stormwater. Consequently, urban stormwater reuse is constrained due to the human health risk posed by these pollutants. This study developed a scientifically robust approach to assess the risk to human health posed by HMs and PAHs in urban stormwater in order to enhance its reuse. Accordingly, an innovative methodology was created consisting of four stages: quantification of traffic and land use parameters; estimation of pollutant concentrations for model development; risk assessment, and risk map presentation. This methodology will contribute to catchment scale assessment of the risk associated with urban stormwater and for risk mitigation. The risk map developed provides a simple and efficient approach to identify the critical areas within a large catchment. The study also found that heavy molecular weight PAHs (PAHs with 5-6 benzene rings) in urban stormwater pose higher risk to human health compared to light molecular PAHs (PAHs with 2-4 benzene rings). These outcomes will facilitate the development of practical approaches for applying appropriate mitigation measures for the safe management of urban stormwater pollution and for the identification of enhanced reuse opportunities. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Discovery of specific ligands for oral squamous carcinoma to develop anti-cancer drug loaded precise targeting nanotherapeutics.

    PubMed

    Yang, Fan; Liu, Ruiwu; Kramer, Randall; Xiao, Wenwu; Jordan, Richard; Lam, Kit S

    2012-12-01

    Oral squamous cell carcinoma has a low five-year survival rate, which may be due to late detection and a lack of effective tumor-specific therapies. Using a high throughput drug discovery strategy termed one-bead one-compound combinatorial library, the authors identified six compounds with high binding affinity to different human oral squamous cell carcinoma cell lines but not to normal cells. Current work is under way to develop these ligands to oral squamous cell carcinoma specific imaging probes or therapeutic agents.

  16. The human factor in mining reclamation

    USGS Publications Warehouse

    Arbogast, Belinda F.; Knepper, Daniel H.; Langer, William H.

    2000-01-01

    Rapid urbanization of the landscape results in less space available for wildlife habitat, agriculture, and recreation. Mineral resources (especially nonmetallic construction materials) become unrecoverable due to inaccessibility caused by development. This report both describes mine sites with serious problems and draws attention to thoughtful reclamation projects for better future management. It presents information from selected sites in terms of their history, landform, design approach, and visual discernment. Examples from Colorado are included to introduce the broader issue of regions soundly developing mining sites, permitting the best utilization of natural resources, and respecting the landscape.

  17. Shrimp viral diseases, import risk assessment and international trade.

    PubMed

    Karunasagar, Iddya; Ababouch, Lahsen

    2012-09-01

    Shrimp is an important commodity in international trade accounting for 15 % in terms of value of internationally traded seafood products which reached $102.00 billion in 2008. Aquaculture contributes to over 50 % of global shrimp production. One of the major constraints faced by shrimp aquaculture is the loss due to viral diseases like white spot syndrome, yellow head disease, and Taura syndrome. There are several examples of global spread of shrimp diseases due to importation of live shrimp for aquaculture. Though millions of tonnes of frozen or processed shrimp have been traded internationally during the last two decades despite prevalence of viral diseases in shrimp producing areas in Asia and the Americas, there is no evidence of diseases having been transmitted through shrimp imported for human consumption. The guidelines developed by the World Animal Health Organisation for movement of live animals for aquaculture, frozen crustaceans for human consumption, and the regulations implemented by some shrimp importing regions in the world are reviewed.

  18. Galactosaminogalactan, a New Immunosuppressive Polysaccharide of Aspergillus fumigatus

    PubMed Central

    Simenel, Catherine; Coddeville, Bernadette; van Vliet, Sandra J.; van Kooyk, Yvette; Bozza, Silvia; Moretti, Silvia; Schwarz, Flavio; Trichot, Coline; Aebi, Markus; Delepierre, Muriel; Elbim, Carole; Romani, Luigina; Latgé, Jean-Paul

    2011-01-01

    A new polysaccharide secreted by the human opportunistic fungal pathogen Aspergillus fumigatus has been characterized. Carbohydrate analysis using specific chemical degradations, mass spectrometry, 1H and 13C nuclear magnetic resonance showed that this polysaccharide is a linear heterogeneous galactosaminogalactan composed of α1-4 linked galactose and α1-4 linked N-acetylgalactosamine residues where both monosacharides are randomly distributed and where the percentage of galactose per chain varied from 15 to 60%. This polysaccharide is antigenic and is recognized by a majority of the human population irrespectively of the occurrence of an Aspergillus infection. GalNAc oligosaccharides are an essential epitope of the galactosaminogalactan that explains the universal antibody reaction due to cross reactivity with other antigenic molecules containing GalNAc stretches such as the N-glycans of Campylobacter jejuni. The galactosaminogalactan has no protective effect during Aspergillus infections. Most importantly, the polysaccharide promotes fungal development in immunocompetent mice due to its immunosuppressive activity associated with disminished neutrophil infiltrates. PMID:22102815

  19. Dynamics of the brain: Mathematical models and non-invasive experimental studies

    NASA Astrophysics Data System (ADS)

    Toronov, V.; Myllylä, T.; Kiviniemi, V.; Tuchin, V. V.

    2013-10-01

    Dynamics is an essential aspect of the brain function. In this article we review theoretical models of neural and haemodynamic processes in the human brain and experimental non-invasive techniques developed to study brain functions and to measure dynamic characteristics, such as neurodynamics, neurovascular coupling, haemodynamic changes due to brain activity and autoregulation, and cerebral metabolic rate of oxygen. We focus on emerging theoretical biophysical models and experimental functional neuroimaging results, obtained mostly by functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS). We also included our current results on the effects of blood pressure variations on cerebral haemodynamics and simultaneous measurements of fast processes in the brain by near-infrared spectroscopy and a very novel functional MRI technique called magnetic resonance encephalography. Based on a rapid progress in theoretical and experimental techniques and due to the growing computational capacities and combined use of rapidly improving and emerging neuroimaging techniques we anticipate during next decade great achievements in the overall knowledge of the human brain.

  20. Being stressed outside the park—conservation of African elephants (Loxodonta africana) in Namibia

    PubMed Central

    Ringstad, Iris H; Jackson, Craig R; May, Roel; Fossøy, Frode; Uiseb, Kenneth; Killian, Werner; Palme, Rupert; Røskaft, Eivin

    2017-01-01

    Abstract The conservation of the African savanna elephant (Loxodonta africana) is of prime importance for many African countries. Interactions between elephants and humans are known to induce stress and thereby have the potential to affect elephants’ fitness. In Namibia, anthropogenic disturbances are increasing due to increasing human population size and development, particularly near protected areas, such as national parks. In this study, we investigated elephant stress levels in relation to their land use, specifically their protection status, comparing elephants within Etosha National Park in Namibia with elephants residing outside the park. We noninvasively collected dung samples of 91 elephants and determined the concentration of faecal glucocorticoid metabolites (fGCM), an indicator of physiological stress. Elephants outside the park (N = 35) had significantly higher concentrations of fGCM than those inside ENP (N = 56), suggesting that, despite including community-based conservancies, unprotected areas are more stressful for elephants than protected areas, most likely due to increased interactions with humans. We also found that males had lower fGCM concentrations than females, but no significant effect of age, body size or group size was detected. Additionally, herd sizes were significantly smaller and calf recruitment was potentially lower in unprotected areas. These findings underpin the importance of protected areas such as ENP, while encouraging decision-makers to continue reducing and mitigating potential human-induced disturbances. PMID:29270294

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