The human genome project: Prospects and implications for clinical medicine

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

Green, E.D.; Waterston, R.H.

1991-10-09

The recently initiated human genome project is a large international effort to elucidate the genetic architecture of the genomes of man and several model organisms. The initial phases of this endeavor involve the establishment of rough blueprints (maps) of the genetic landscape of these genomes, with the long-term goal of determining their precise nucleotide sequences and identifying the genes. The knowledge gained by these studies will provide a vital tool for the study of many biologic processes and will have a profound impact on clinical medicine.

The organisational and human resource challenges facing primary care trusts: protocol of a multiple case study

PubMed Central

2001-01-01

Background The study is designed to assess the organisational and human resource challenges faced by Primary Care Trusts (PCTs). Its objectives are to: specify the organisational and human resources challenges faced by PCTs in fulfilling the roles envisaged in government and local policy; examine how PCTs are addressing these challenges, in particular, to describe the organisational forms they have adopted, and the OD/HR strategies and initiatives they have planned or in place; assess how effective these structures, strategies and initiatives have been in enabling the PCTs to meet the organisational and human resources challenges they face; identify the factors, both internal to the PCT and in the wider health community, which have contributed to the success or failure of different structures, strategies and initiatives. Methods The study will be undertaken in three stages. In Stage 1 the key literature on public sector and NHS organisational development and human resources management will be reviewed, and discussions will be held with key researchers and policy makers working in this area. Stage 2 will focus on detailed case studies in six PCTs designed to examine the organisational and human resources challenges they face. Data will be collected using semi-structured interviews, group discussion, site visits, observation of key meetings and examination of local documentation. The findings from the case study PCTs will be cross checked with a Reference Group of up to 20 other PCG/Ts, and key officers working in organisational development or primary care at local, regional and national level. In Stage 3 analysis of findings from the preparatory work, the case studies and the feedback from the Reference Group will be used to identify practical lessons for PCTs, key messages for policy makers, and contributions to further theoretical development. PMID:11737883

Evaluating mesenchymal stem cell therapy for sepsis with preclinical meta-analyses prior to initiating a first-in-human trial

PubMed Central

Lalu, Manoj M; Sullivan, Katrina J; Mei, Shirley HJ; Moher, David; Straus, Alexander; Fergusson, Dean A; Stewart, Duncan J; Jazi, Mazen; MacLeod, Malcolm; Winston, Brent; Marshall, John; Hutton, Brian; Walley, Keith R; McIntyre, Lauralyn

2016-01-01

Evaluation of preclinical evidence prior to initiating early-phase clinical studies has typically been performed by selecting individual studies in a non-systematic process that may introduce bias. Thus, in preparation for a first-in-human trial of mesenchymal stromal cells (MSCs) for septic shock, we applied systematic review methodology to evaluate all published preclinical evidence. We identified 20 controlled comparison experiments (980 animals from 18 publications) of in vivo sepsis models. Meta-analysis demonstrated that MSC treatment of preclinical sepsis significantly reduced mortality over a range of experimental conditions (odds ratio 0.27, 95% confidence interval 0.18–0.40, latest timepoint reported for each study). Risk of bias was unclear as few studies described elements such as randomization and no studies included an appropriately calculated sample size. Moreover, the presence of publication bias resulted in a ~30% overestimate of effect and threats to validity limit the strength of our conclusions. This novel prospective application of systematic review methodology serves as a template to evaluate preclinical evidence prior to initiating first-in-human clinical studies. DOI: http://dx.doi.org/10.7554/eLife.17850.001 PMID:27870924

Structural Basis of Mitochondrial Transcription Initiation.

PubMed

Hillen, Hauke S; Morozov, Yaroslav I; Sarfallah, Azadeh; Temiakov, Dmitry; Cramer, Patrick

2017-11-16

Transcription in human mitochondria is driven by a single-subunit, factor-dependent RNA polymerase (mtRNAP). Despite its critical role in both expression and replication of the mitochondrial genome, transcription initiation by mtRNAP remains poorly understood. Here, we report crystal structures of human mitochondrial transcription initiation complexes assembled on both light and heavy strand promoters. The structures reveal how transcription factors TFAM and TFB2M assist mtRNAP to achieve promoter-dependent initiation. TFAM tethers the N-terminal region of mtRNAP to recruit the polymerase to the promoter whereas TFB2M induces structural changes in mtRNAP to enable promoter opening and trapping of the DNA non-template strand. Structural comparisons demonstrate that the initiation mechanism in mitochondria is distinct from that in the well-studied nuclear, bacterial, or bacteriophage transcription systems but that similarities are found on the topological and conceptual level. These results provide a framework for studying the regulation of gene expression and DNA replication in mitochondria. Copyright © 2017 Elsevier Inc. All rights reserved.

Turnaround Arts Initiative: Final Evaluatiion Report

ERIC Educational Resources Information Center

Stoelinga, Sara Ray; Silk, Yael; Reddy, Prateek; Rahman, Nadiv

2015-01-01

The President's Committee on the Arts and the Humanities (PCAH) released the results of an independent study that shows substantial gains in student achievement at schools participating in its Turnaround Arts initiative. The eight schools' in the pilot phase of the initiative, showing increases in reading and math scores, as well as an increase in…

The value of case reports in human teratology.

PubMed

Goldberg, J D; Golbus, M S

1986-03-01

Birth defects caused by human teratogens are an important and potentially preventable cause of perinatal morbidity and mortality. Case reports provide an initial suggestion that a specific agent may be a human teratogen and provide the basis for further study. This review discusses the importance of case reports in human teratology and provides guidance in evaluating new case reports.

Reimagining the Role of Human Services Workers: Staff Experiences of a Social Change Initiative

ERIC Educational Resources Information Center

Spencer-Cavaliere, Nancy; Kingsley, Bethan C.; Norris, Carmen

2018-01-01

Despite recognition that social inclusion is a primary goal within the field of human services, people with disabilities continue to live lives of clienthood, marginalisation, and exclusion and human services staff struggle to make social inclusion a priority. The purpose of this study was to explore the perspectives of human services staff about…

Description of Campylobacter fetus subsp. testudinum subsp. nov., isolated from humans and reptiles

USDA-ARS?s Scientific Manuscript database

A polyphasic study was undertaken to determine the taxonomic position of 13 Campylobacter fetus-like isolates from humans (n=8) and reptiles (n=5). Phenotypic characterization, Genusgenus-specific and sap insertion-PCR initially identified all human isolates as type A Campylobacter fetus. Phylogenet...

ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling

PubMed Central

Goossens, Steven; Radaelli, Enrico; Blanchet, Odile; Durinck, Kaat; Van der Meulen, Joni; Peirs, Sofie; Taghon, Tom; Tremblay, Cedric S.; Costa, Magdaline; Ghahremani, Morvarid Farhang; De Medts, Jelle; Bartunkova, Sonia; Haigh, Katharina; Schwab, Claire; Farla, Natalie; Pieters, Tim; Matthijssens, Filip; Van Roy, Nadine; Best, J. Adam; Deswarte, Kim; Bogaert, Pieter; Carmichael, Catherine; Rickard, Adam; Suryani, Santi; Bracken, Lauryn S.; Alserihi, Raed; Canté-Barrett, Kirsten; Haenebalcke, Lieven; Clappier, Emmanuelle; Rondou, Pieter; Slowicka, Karolina; Huylebroeck, Danny; Goldrath, Ananda W.; Janzen, Viktor; McCormack, Matthew P.; Lock, Richard B.; Curtis, David J.; Harrison, Christine; Berx, Geert; Speleman, Frank; Meijerink, Jules P. P.; Soulier, Jean; Van Vlierberghe, Pieter; Haigh, Jody J.

2015-01-01

Early T-cell precursor leukaemia (ETP-ALL) is a high-risk subtype of human leukaemia that is poorly understood at the molecular level. Here we report translocations targeting the zinc finger E-box-binding transcription factor ZEB2 as a recurrent genetic lesion in immature/ETP-ALL. Using a conditional gain-of-function mouse model, we demonstrate that sustained Zeb2 expression initiates T-cell leukaemia. Moreover, Zeb2-driven mouse leukaemia exhibit some features of the human immature/ETP-ALL gene expression signature, as well as an enhanced leukaemia-initiation potential and activated Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signalling through transcriptional activation of IL7R. This study reveals ZEB2 as an oncogene in the biology of immature/ETP-ALL and paves the way towards pre-clinical studies of novel compounds for the treatment of this aggressive subtype of human T-ALL using our Zeb2-driven mouse model. PMID:25565005

From Hayflick to Walford: the role of T cell replicative senescence in human aging.

PubMed

Effros, Rita B

2004-06-01

The immunologic theory of aging, proposed more than 40 years ago by Roy Walford, suggests that the normal process of aging in man and in animals is pathogenetically related to faulty immunological processes. Since that time, research on immunological aging has undergone extraordinary expansion, leading to new information in areas spanning from molecular biology and cell signaling to large-scale clinical studies. Investigation in this area has also provided unexpected insights into HIV disease, many aspects of which represent accelerated immunological aging. This article describes the initial insights and vision of Roy Walford into one particular facet of human immunological aging, namely, the potential relevance of the well-studied human fibroblast replicative senescence model, initially developed by Leonard Hayflick, to cells of the immune system. Extensive research on T cell senescence in cell culture has now documented changes in vitro that closely mirror alterations occurring during in vivo aging in humans, underscoring the biological significance of T cell replicative senescence. Moreover, the inclusion of high proportions of putatively senescent T cells in the 'immune risk phenotype' that is associated with early mortality in octogenarians provides initial clinical confirmation of both the immunologic theory of aging and the role of the T cell Hayflick Limit in human aging, two areas of gerontological research pioneered by Roy Walford.

Making intelligent systems team players: Additional case studies

NASA Technical Reports Server (NTRS)

Malin, Jane T.; Schreckenghost, Debra L.; Rhoads, Ron W.

1993-01-01

Observations from a case study of intelligent systems are reported as part of a multi-year interdisciplinary effort to provide guidance and assistance for designers of intelligent systems and their user interfaces. A series of studies were conducted to investigate issues in designing intelligent fault management systems in aerospace applications for effective human-computer interaction. The results of the initial study are documented in two NASA technical memoranda: TM 104738 Making Intelligent Systems Team Players: Case Studies and Design Issues, Volumes 1 and 2; and TM 104751, Making Intelligent Systems Team Players: Overview for Designers. The objective of this additional study was to broaden the investigation of human-computer interaction design issues beyond the focus on monitoring and fault detection in the initial study. The results of this second study are documented which is intended as a supplement to the original design guidance documents. These results should be of interest to designers of intelligent systems for use in real-time operations, and to researchers in the areas of human-computer interaction and artificial intelligence.

Human Factors in Railroad Operations : Initial Studies

DOT National Transportation Integrated Search

1972-01-01

This report summarizes the progress of a year's work in providing support in human factors to the Federal Railroad Administration. The principal topics include: (a) a description of the locomotive engineer's job, particularly with regard to its inher...

Initiation of oncogenic transformation in human mammary epithelial cells by charged particles

NASA Technical Reports Server (NTRS)

Yang, T. C.; Georgy, K. A.; Craise, L. M.; Durante, M.

1997-01-01

Experimental studies have shown that high linear-energy transfer (LET) charged particles can be more effective than x-rays and gamma-rays in inducing oncogenic transformation in cultured cells and tumors in animals. Based on these results, experiments were designed and performed with an immortal human mammary epithelial cell line (H184B5), and several clones transformed by heavy ions were obtained. Cell fusion experiments were subsequently done, and results indicate that the transforming gene(s) is recessive. Chromosome analysis with fluorescence in situ hybridization (FISH) techniques also showed additional translocations in transformed human mammary epithelial cells. In addition, studies with these cell lines indicate that heavy ions can effectively induce deletion, break, and dicentrics. Deletion of tumor suppressor gene(s) and/or formation of translocation through DNA double strand breaks is a likely mechanism for the initiation of oncogenic transformation in human mammary epithelial cells.

Human Capital Planning in Higher Education Institutions: A Strategic Human Resource Development Initiative in Jordan

ERIC Educational Resources Information Center

Khasawneh, Samer

2011-01-01

Purpose: The primary purpose of this study is to determine the status of human capital planning in higher education institutions in Jordan. Design/methodology/approach: A random sample of 120 faculty members (in administrative positions) responded to a human capital planning (HCP) survey. The survey consisted of a pool of 38 items distributed over…

The Human Genome Initiative of the Department of Energy

DOE R&D Accomplishments Database

1988-01-01

The structural characterization of genes and elucidation of their encoded functions have become a cornerstone of modern health research, biology and biotechnology. A genome program is an organized effort to locate and identify the functions of all the genes of an organism. Beginning with the DOE-sponsored, 1986 human genome workshop at Santa Fe, the value of broadly organized efforts supporting total genome characterization became a subject of intensive study. There is now national recognition that benefits will rapidly accrue from an effective scientific infrastructure for total genome research. In the US genome research is now receiving dedicated funds. Several other nations are implementing genome programs. Supportive infrastructure is being improved through both national and international cooperation. The Human Genome Initiative of the Department of Energy (DOE) is a focused program of Resource and Technology Development, with objectives of speeding and bringing economies to the national human genome effort. This report relates the origins and progress of the Initiative.

Human Rights Education: Imaginative Possibilities for Creating Change

ERIC Educational Resources Information Center

Bajaj, Monisha

2015-01-01

Background/Context: Human rights education has proliferated in the past four decades and can be found in policy discussions, textbook reforms, and grassroots initiatives across the globe. This article specifically explores the role of creativity and imagination in human rights education (HRE) by focusing on a case study of one non-governmental…

Regulation of lipid synthesis genes and milk fat production in human mammary epithelial cells during secretory activation

USDA-ARS?s Scientific Manuscript database

Expression of genes for lipid biosynthetic enzymes during initiation of lactation in humans is unknown. Our objective was to study mRNA expression of lipid metabolic enzymes in human mammary epithelial cell (MEC) in conjunction with the measurement of milk fatty acid (FA) composition during secretor...

Adult Education & Human Resource Development: Overlapping and Disparate Fields

ERIC Educational Resources Information Center

Watkins, Karen E.; Marsick, Victoria J.

2014-01-01

Adult education and human resource development as fields of practice and study share some roots in common but have grown in different directions in their histories. Adult education's roots focused initially on citizenship for a democratic society, whereas human resource development's roots are in performance at work. While they have…

Automation and Robotics for Human Mars Exploration (AROMA)

NASA Technical Reports Server (NTRS)

Hofmann, Peter; von Richter, Andreas

2003-01-01

Automation and Robotics (A&R) systems are a key technology for Mars exploration. All over the world initiatives in this field aim at developing new A&R systems and technologies for planetary surface exploration. From December 2000 to February 2002 Kayser-Threde GmbH, Munich, Germany lead a study called AROMA (Automation and Robotics for Human Mars Exploration) under ESA contract in order to define a reference architecture of A&R elements in support of a human Mars exploration program. One of the goals of this effort is to initiate new developments and to maintain the competitiveness of European industry within this field. c2003 Published by Elsevier Science Ltd.

Automation and Robotics for Human Mars Exploration (AROMA).

PubMed

Hofmann, Peter; von Richter, Andreas

2003-01-01

Automation and Robotics (A&R) systems are a key technology for Mars exploration. All over the world initiatives in this field aim at developing new A&R systems and technologies for planetary surface exploration. From December 2000 to February 2002 Kayser-Threde GmbH, Munich, Germany lead a study called AROMA (Automation and Robotics for Human Mars Exploration) under ESA contract in order to define a reference architecture of A&R elements in support of a human Mars exploration program. One of the goals of this effort is to initiate new developments and to maintain the competitiveness of European industry within this field. c2003 Published by Elsevier Science Ltd.

Investigation of the Causes of Breast Cancer at the Cellular Level: Isolation of In Vivo Binding Sites of the Human Origin Recognition Complex

DTIC Science & Technology

2002-08-01

We study the process of DNA replication in proliferating human cells. Our efforts are directed to the identification and characterization of proteins...that promote DNA replication (initiators) as well as the DNA sequences recognized by them (replicators) . We have focused in a group of initiator...to be a critical factor for the coordination of DNA replication with the cell division cycle. hOrclp levels are higher between the exit of mitosis and

The role of free radicals in traumatic brain injury.

PubMed

O'Connell, Karen M; Littleton-Kearney, Marguerite T

2013-07-01

Traumatic brain injury (TBI) is a significant cause of death and disability in both the civilian and the military populations. The primary impact causes initial tissue damage, which initiates biochemical cascades, known as secondary injury, that expand the damage. Free radicals are implicated as major contributors to the secondary injury. Our review of recent rodent and human research reveals the prominent role of the free radicals superoxide anion, nitric oxide, and peroxynitrite in secondary brain injury. Much of our current knowledge is based on rodent studies, and the authors identified a gap in the translation of findings from rodent to human TBI. Rodent models are an effective method for elucidating specific mechanisms of free radical-induced injury at the cellular level in a well-controlled environment. However, human TBI does not occur in a vacuum, and variables controlled in the laboratory may affect the injury progression. Additionally, multiple experimental TBI models are accepted in rodent research, and no one model fully reproduces the heterogeneous injury seen in humans. Free radical levels are measured indirectly in human studies based on assumptions from the findings from rodent studies that use direct free radical measurements. Further study in humans should be directed toward large samples to validate the findings in rodent studies. Data obtained from these studies may lead to more targeted treatment to interrupt the secondary injury cascades.

A Human Factors Analysis of EVA Time Requirements

NASA Technical Reports Server (NTRS)

Pate, Dennis W.

1997-01-01

Human Factors Engineering (HFE) is a discipline whose goal is to engineer a safer, more efficient interface between humans and machines. HFE makes use of a wide range of tools and techniques to fulfill this goal. One of these tools is known as motion and time study, a technique used to develop time standards for given tasks. During the summer of 1995, a human factors motion and time study was initiated with the goals of developing a database of EVA task times and developing a method of utilizing the database to predict how long an EVA should take. Initial development relied on the EVA activities performed during the STS-61 (Hubble) mission. The first step of the study was to become familiar with EVA's, the previous task-time studies, and documents produced on EVA's. After reviewing these documents, an initial set of task primitives and task-time modifiers was developed. Data was collected from videotaped footage of two entire STS-61 EVA missions and portions of several others, each with two EVA astronauts. Feedback from the analysis of the data was used to further refine the primitives and modifiers used. The project was continued during the summer of 1996, during which data on human errors was also collected and analyzed. Additional data from the STS-71 mission was also collected. Analysis of variance techniques for categorical data was used to determine which factors may affect the primitive times and how much of an effect they have. Probability distributions for the various task were also generated. Further analysis of the modifiers and interactions is planned.

Re-Imagining Initial Multiracial Teacher Education (IMTE) Model through the ODL Philosophy: A Critical Qualitative Meta-Synthesis Study

ERIC Educational Resources Information Center

Nyoni, J.

2012-01-01

This article reports on a critical meta-analysis of empirical studies done by human sciences researchers on the initial multicultural teacher education (IMTE) models in multicultural post-colonial transitional societies with reference to sub-Saharan African states in general and South Africa in particular. Using a critical post-positivist…

Precise chronology of differentiation of developing human primary dentition.

PubMed

Hu, Xuefeng; Xu, Shan; Lin, Chensheng; Zhang, Lishan; Chen, YiPing; Zhang, Yanding

2014-02-01

While correlation of developmental stage with embryonic age of the human primary dentition has been well documented, the available information regarding the differentiation timing of the primary teeth was largely based on the observation of initial mineralization and varies significantly. In this study, we aimed to document precise differentiation timing of the developing human primary dentition. We systematically examined the expression of odontogenic differentiation markers along with the formation of mineralized tissue in each developing maxillary and mandibular teeth from human embryos with well-defined embryonic age. We show that, despite that all primary teeth initiate development at the same time, odontogenic differentiation begins in the maxillary incisors at the 15th week and in the mandibular incisors at the 16th week of gestation, followed by the canine, the first primary premolar, and the second primary premolar at a week interval sequentially. Despite that the mandibular primary incisors erupt earlier than the maxillary incisors, this distal to proximal sequential differentiation of the human primary dentition coincides in general with the sequence of tooth eruption. Our results provide an accurate chronology of odontogenic differentiation of the developing human primary dentition, which could be used as reference for future studies of human tooth development.

Consistent evolution in a pedestrian flow

NASA Astrophysics Data System (ADS)

Guan, Junbiao; Wang, Kaihua

2016-03-01

In this paper, pedestrian evacuation considering different human behaviors is studied by using a cellular automaton (CA) model combined with the snowdrift game theory. The evacuees are divided into two types, i.e. cooperators and defectors, and two different human behaviors, herding behavior and independent behavior, are investigated. It is found from a large amount of numerical simulations that the ratios of the corresponding evacuee clusters are evolved to consistent states despite 11 typically different initial conditions, which may largely owe to self-organization effect. Moreover, an appropriate proportion of initial defectors who are of herding behavior, coupled with an appropriate proportion of initial defectors who are of rationally independent thinking, are two necessary factors for short evacuation time.

A Matter of Discipline: Open Access, the Humanities, and Art History

ERIC Educational Resources Information Center

Tomlin, Patrick

2009-01-01

Recent events suggest that open access has gained new momentum in the humanities, but the slow and uneven development of open-access initiatives in humanist fields continues to hinder the consolidation of efforts across the university. Although various studies have traced the general origins of the humanities' reticence to embrace open access, few…

The effect of sodium pertechnetate human carbonic anhydrase I and II

NASA Astrophysics Data System (ADS)

Sahin, Ali; Senturk, Murat

2017-04-01

The inhibitory effects of Na99mTcO4 (Sodium pertechnetate) on human erythrocyte carbonic anhydrase I and II activity were investigated. For this purpose, hCA I was initially purified 114,29-fold at a yield of 69,19 % and hCA II was initially purified 710,82-fold at a yield of 71,72 % using sepharose 4B-tyrosine-sulfanilamide affinity gel chromatography. The in vitro effect of this compound on hCA I and II isoenzyme were studied. It was detected in in vitro studies that the hCA I and II enzymes are inhibited due to Na99mTcO4.

An Initial Model of Requirements Traceability an Empirical Study

DTIC Science & Technology

1992-09-22

procedures have been used extensively in the study of human problem-solving, including such areas as general problem-solving behavior, physics problem...heen doing unless you have traceability." " Humans don’t go back to the requirements enough." "Traceabi!ity should be extremely helpful with...by constraints on its usage: ("Traceability needs to be something that humans can work with, not just a whip held over people." "Traceability should

A coupling of homology modeling with multiple molecular dynamics simulation for identifying representative conformation of GPCR structures: a case study on human bombesin receptor subtype-3.

PubMed

Nowroozi, Amin; Shahlaei, Mohsen

2017-02-01

In this study, a computational pipeline was therefore devised to overcome homology modeling (HM) bottlenecks. The coupling of HM with molecular dynamics (MD) simulation is useful in that it tackles the sampling deficiency of dynamics simulations by providing good-quality initial guesses for the native structure. Indeed, HM also relaxes the severe requirement of force fields to explore the huge conformational space of protein structures. In this study, the interaction between the human bombesin receptor subtype-3 and MK-5046 was investigated integrating HM, molecular docking, and MD simulations. To improve conformational sampling in typical MD simulations of GPCRs, as in other biomolecules, multiple trajectories with different initial conditions can be employed rather than a single long trajectory. Multiple MD simulations of human bombesin receptor subtype-3 with different initial atomic velocities are applied to sample conformations in the vicinity of the structure generated by HM. The backbone atom conformational space distribution of replicates is analyzed employing principal components analysis. As a result, the averages of structural and dynamic properties over the twenty-one trajectories differ significantly from those obtained from individual trajectories.

A human factors analysis of EVA time requirements

NASA Technical Reports Server (NTRS)

Pate, D. W.

1996-01-01

Human Factors Engineering (HFE), also known as Ergonomics, is a discipline whose goal is to engineer a safer, more efficient interface between humans and machines. HFE makes use of a wide range of tools and techniques to fulfill this goal. One of these tools is known as motion and time study, a technique used to develop time standards for given tasks. A human factors motion and time study was initiated with the goal of developing a database of EVA task times and a method of utilizing the database to predict how long an ExtraVehicular Activity (EVA) should take. Initial development relied on the EVA activities performed during the STS-61 mission (Hubble repair). The first step of the analysis was to become familiar with EVAs and with the previous studies and documents produced on EVAs. After reviewing these documents, an initial set of task primitives and task time modifiers was developed. Videotaped footage of STS-61 EVAs were analyzed using these primitives and task time modifiers. Data for two entire EVA missions and portions of several others, each with two EVA astronauts, was collected for analysis. Feedback from the analysis of the data will be used to further refine the primitives and task time modifiers used. Analysis of variance techniques for categorical data will be used to determine which factors may, individually or by interactions, effect the primitive times and how much of an effect they have.

MECHANISMS OF ZN-INDUCED SIGNAL INITIATION THROUGH THE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR)

EPA Science Inventory

MECHANISMS OF Zn-INDUCED SIGNAL INITIATION THROUGH THE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR)
James M. Samet*, Lee M. Graves? and Weidong Wu?. *Human Studies Division, NHEERL, ORD, Research Triangle Park, NC 27711, and ?Center for Environmental Medicine, University of North C...

A new paradigm for transcription factor TFIIB functionality

PubMed Central

Gelev, Vladimir; Zabolotny, Janice M.; Lange, Martin; Hiromura, Makoto; Yoo, Sang Wook; Orlando, Joseph S.; Kushnir, Anna; Horikoshi, Nobuo; Paquet, Eric; Bachvarov, Dimcho; Schaffer, Priscilla A.; Usheva, Anny

2014-01-01

Experimental and bioinformatic studies of transcription initiation by RNA polymerase II (RNAP2) have revealed a mechanism of RNAP2 transcription initiation less uniform across gene promoters than initially thought. However, the general transcription factor TFIIB is presumed to be universally required for RNAP2 transcription initiation. Based on bioinformatic analysis of data and effects of TFIIB knockdown in primary and transformed cell lines on cellular functionality and global gene expression, we report that TFIIB is dispensable for transcription of many human promoters, but is essential for herpes simplex virus-1 (HSV-1) gene transcription and replication. We report a novel cell cycle TFIIB regulation and localization of the acetylated TFIIB variant on the transcriptionally silent mitotic chromatids. Taken together, these results establish a new paradigm for TFIIB functionality in human gene expression, which when downregulated has potent anti-viral effects. PMID:24441171

Climate Change: Modeling the Human Response

NASA Astrophysics Data System (ADS)

Oppenheimer, M.; Hsiang, S. M.; Kopp, R. E.

2012-12-01

Integrated assessment models have historically relied on forward modeling including, where possible, process-based representations to project climate change impacts. Some recent impact studies incorporate the effects of human responses to initial physical impacts, such as adaptation in agricultural systems, migration in response to drought, and climate-related changes in worker productivity. Sometimes the human response ameliorates the initial physical impacts, sometimes it aggravates it, and sometimes it displaces it onto others. In these arenas, understanding of underlying socioeconomic mechanisms is extremely limited. Consequently, for some sectors where sufficient data has accumulated, empirically based statistical models of human responses to past climate variability and change have been used to infer response sensitivities which may apply under certain conditions to future impacts, allowing a broad extension of integrated assessment into the realm of human adaptation. We discuss the insights gained from and limitations of such modeling for benefit-cost analysis of climate change.

The Contributions of Digital Communications Technology to Human Rights Education: A Case Study of Amnesty International

ERIC Educational Resources Information Center

Norlander, Rebecca Joy

2013-01-01

This dissertation addresses the need for critical assessment and evaluation of human rights education (HRE) programs and activities, especially newer initiatives that incorporate the use of digital information and communications technology (ICT). It provides an in-depth case study of the use of digital ICT in Amnesty International's HRE efforts,…

STRATEGIC PLAN FOR THE ANALYSIS OF THE NATIONAL HUMAN EXPOSURE ASSESSMENT SURVEY (NHEXAS) PILOT STUDY DATA

EPA Science Inventory

The Office of Research and Development (ORD) of the U.S. Environmental Protection Agency (EPA) initiated the National Human Exposure Assessment Survey (NHEXAS) in the early 1990's. It was a population-based pilot study of the exposure of over 500 people in three areas of the U....

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…

Prevalence and Duties of Collegiate Human Sexuality Peer Helpers: Results of a National Study

ERIC Educational Resources Information Center

Butler, Scott M.; Black, David R.

2011-01-01

The purpose of the present study is to assess human sexuality peer helper use among college student health centers nationwide. Results from 358 institutions indicate that 53.9% of centers use peers for educational programming, prevention efforts, and/or counseling initiatives. When adjusting for institutions that sponsor a program (n = 193), the M…

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

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

Post-approval monitoring and oversight of U.S.-initiated human subjects research in resource-constrained countries.

PubMed

Brown, Brandon; Kinsler, Janni; Folayan, Morenike O; Allen, Karen; Cáceres, Carlos F

2014-06-01

The history of human subjects research and controversial procedures in relation to it has helped form the field of bioethics. Ethically questionable elements may be identified during research design, research implementation, management at the study site, or actions by a study's investigator or other staff. Post-approval monitoring (PAM) may prevent violations from occurring or enable their identification at an early stage. In U.S.-initiated human subjects research taking place in resource-constrained countries with limited development of research regulatory structures, arranging a site visit from a U.S. research ethics committee (REC) becomes difficult, thus creating a potential barrier to regulatory oversight by the parent REC. However, this barrier may be overcome through the use of digital technologies, since much of the world has at least remote access to the Internet. Empirical research is needed to pilot test the use of these technologies for research oversight to ensure the protection of human subjects taking part in research worldwide.

Sensory gating for the initiation of the swing phase in different directions of human infant stepping.

PubMed

Pang, Marco Y C; Yang, Jaynie F

2002-07-01

Humans can make smooth, continuous transitions in walking direction from forward to backward. Thus, the processing of sensory input must allow a similar continuum of possibilities. Hip extension and reduced load are two important conditions that control the transition from the stance to swing phase during forward stepping in human infants. The purpose of this study was to determine whether the same factors also regulate the initiation of the swing phase in other directions of stepping. Thirty-seven infants between the ages of 5 and 13 months were studied during supported forward and sideways stepping on a treadmill. Disturbances were elicited by placing a piece of cardboard under the foot and pulling the cardboard in different directions. In this way, the leg was displaced in a particular direction and simultaneously unloaded. We observed whether the swing phase was immediately initiated after the application of disturbances in various directions. Electromyography, vertical ground reaction forces, and hip motion in frontal and sagittal planes were recorded. The results showed that the most potent sensory input to initiate the swing phase depends on the direction of stepping. Although low load was always necessary to initiate swing for all directions of walking, the preferred hip position was always one directly opposite the direction of walking. The results indicated the presence of selective gating of sensory input from the legs as a function of the direction of stepping.

Meta-Analysis: An Approach to Interview Success.

ERIC Educational Resources Information Center

McCaslin, Mark; Carlson, Nancy M.

An initial research step, developing an effective interview strategy, presents unique challenges for novice and master research alike. To focus qualitative research in the human ecology of the study, the strategy presented in this paper used an initial interview protocol and preanalysis process, called meta-analysis, prior to developing the formal…

INITIAL CHARACTERIZATION OF MONOCLONAL ANTIBODIES AGAINST THE FUNGAL HEMOLYSIN STACHYLYSIN FROM STACHYBOTRYS CHARTARUM

EPA Science Inventory

Stachybotrys chartarum is known to produce the hemolysin stachylysin and its detection in human serum has been proposed as a biomarker for exposure to the fungus. In this study we report the initial characterization of monoclonal antibodies (mAbs) against stachylysin and the dev...

Mapping Sustainability Initiatives across a Region: An Innovative Survey Approach

ERIC Educational Resources Information Center

Somerville, Margaret; Green, Monica

2012-01-01

The project of mapping sustainability initiatives across a region is part of a larger program of research about place and sustainability education for the Anthropocene, the new geological age of human-induced planetary changes (Zalasiewicz, Williams, Steffen, & Crutzen, 2010). The study investigated the location, nature and type of…

Thinking through the Body, Educating for the Humanities: A Plea for Somaesthetics

ERIC Educational Resources Information Center

Shusterman, Richard

2006-01-01

What are the humanities, and how should they be cultivated? With respect to this crucial question, opinions differ as to how widely the humanities should be construed and pursued. Initially connoting the study of Greek and Roman classics, the concept now more generally covers arts and letters, history, and philosophy. But does it also include the…

A Blueprint for Human Resource Development in the Third Decade of the Ontario Colleges of Applied Arts and Technology: Executive Summary.

ERIC Educational Resources Information Center

Giroux, Roy F.

In 1987, a review of Ontario's community college system was initiated to assess the system's present human resource development practices and plan future directions. A field-based study was conducted to identify and assess current human resource development efforts, identify areas for improvement, and suggest possible future directions. Through…

Normal and leukaemic human haemopoietic cells in diffusion chamber. A morphological and functional CFU-C study.

PubMed

Laurent, M; Clémancey-Marcille, G; Hollard, D

1980-03-01

Leukaemic human bone marrow and peripheral blood cells were cultured for 25 d in diffusion chambers implanted into cyclophosphamide treated mice. Normal bone marrow cells were cultured simultaneously. These cells were studied both morphologically and functionally (CFU-C). The leukaemic cells behaved heterogeneously, 2 groups being distinguishable in accordance with their initial in vitro growth pattern (1: no growth or microcluster growth. 2: macrocluster growth). Group I showed progressive cellular death with a diminution of granulocytic progenitors and the appearance of a predominantly macrophagic population. This behaviour resembled that of the control group. The initial microcluster growth pattern remained identical throughout the entire culture period. Group 2, after considerable cellular death up to d 5, showed an explosive proliferation of the granulocytic progenitors and incomplete differentiation (up to myelocyte). The initial macrocluster growth pattern remained identical.

Application of the accurate mass and time tag approach in studies of the human blood lipidome

PubMed Central

Ding, Jie; Sorensen, Christina M.; Jaitly, Navdeep; Jiang, Hongliang; Orton, Daniel J.; Monroe, Matthew E.; Moore, Ronald J.; Smith, Richard D.; Metz, Thomas O.

2008-01-01

We report a preliminary demonstration of the accurate mass and time (AMT) tag approach for lipidomics. Initial data-dependent LC-MS/MS analyses of human plasma, erythrocyte, and lymphocyte lipids were performed in order to identify lipid molecular species in conjunction with complementary accurate mass and isotopic distribution information. Identified lipids were used to populate initial lipid AMT tag databases containing 250 and 45 entries for those species detected in positive and negative electrospray ionization (ESI) modes, respectively. The positive ESI database was then utilized to identify human plasma, erythrocyte, and lymphocyte lipids in high-throughput LC-MS analyses based on the AMT tag approach. We were able to define the lipid profiles of human plasma, erythrocytes, and lymphocytes based on qualitative and quantitative differences in lipid abundance. PMID:18502191

Therapy-induced selective loss of leukemia-initiating activity in murine adult T cell leukemia

PubMed Central

El Hajj, Hiba; El-Sabban, Marwan; Hasegawa, Hideki; Zaatari, Ghazi; Ablain, Julien; Saab, Shahrazad T.; Janin, Anne; Mahfouz, Rami; Nasr, Rihab; Kfoury, Youmna; Nicot, Christophe; Hermine, Olivier; Hall, William

2010-01-01

Chronic HTLV-I (human T cell lymphotropic virus type I) infection may cause adult T cell leukemia/lymphoma (ATL), a disease with dismal long-term prognosis. The HTLV-I transactivator, Tax, initiates ATL in transgenic mice. In this study, we demonstrate that an As2O3 and IFN-α combination, known to trigger Tax proteolysis, cures Tax-driven ATL in mice. Unexpectedly, this combination therapy abrogated initial leukemia engraftment into secondary recipients, whereas the primary tumor bulk still grew in the primary hosts, only to ultimately abate later on. This loss of initial transplantability required proteasome function. A similar regimen recently yielded unprecedented disease control in human ATL. Our demonstration that this drug combination targeting Tax stability abrogates tumor cell immortality but not short-term growth may foretell a favorable long-term efficiency of this regimen in patients. PMID:21135137

Status of robotic mission studies for the Space Exploration Initiative - 1991

NASA Technical Reports Server (NTRS)

Bourke, Roger D.; Dias, William C.; Golombek, Matthew P.; Pivirotto, Donna L.; Sturms, Francis M.; Hubbard, G. S.

1991-01-01

Results of studies of robotic missions to the moon and Mars planned under the U.S. Space Exploration Initiative are summarized. First, an overall strategy for small robotic missions to accomplish the information gathering required by human missions is reviewed, and the principal robotic mission requirements are discussed. The discussion covers the following studies: the Lunar Observer, the Mars Environmental Survey mission, Mars Sample Return missions using microtechnology, and payloads.

Space transfer concepts and analysis for exploration missions

NASA Technical Reports Server (NTRS)

1991-01-01

A broad scoped and systematic study was made of space transfer concepts for human Lunar and Mars missions. Relevant space transportation studies were initiated to lead to further detailed activities in the following study period.

Cue-dependent memory-based smooth-pursuit in normal human subjects: importance of extra-retinal mechanisms for initial pursuit.

PubMed

Ito, Norie; Barnes, Graham R; Fukushima, Junko; Fukushima, Kikuro; Warabi, Tateo

2013-08-01

Using a cue-dependent memory-based smooth-pursuit task previously applied to monkeys, we examined the effects of visual motion-memory on smooth-pursuit eye movements in normal human subjects and compared the results with those of the trained monkeys. These results were also compared with those during simple ramp-pursuit that did not require visual motion-memory. During memory-based pursuit, all subjects exhibited virtually no errors in either pursuit-direction or go/no-go selection. Tracking eye movements of humans and monkeys were similar in the two tasks, but tracking eye movements were different between the two tasks; latencies of the pursuit and corrective saccades were prolonged, initial pursuit eye velocity and acceleration were lower, peak velocities were lower, and time to reach peak velocities lengthened during memory-based pursuit. These characteristics were similar to anticipatory pursuit initiated by extra-retinal components during the initial extinction task of Barnes and Collins (J Neurophysiol 100:1135-1146, 2008b). We suggest that the differences between the two tasks reflect differences between the contribution of extra-retinal and retinal components. This interpretation is supported by two further studies: (1) during popping out of the correct spot to enhance retinal image-motion inputs during memory-based pursuit, pursuit eye velocities approached those during simple ramp-pursuit, and (2) during initial blanking of spot motion during memory-based pursuit, pursuit components appeared in the correct direction. Our results showed the importance of extra-retinal mechanisms for initial pursuit during memory-based pursuit, which include priming effects and extra-retinal drive components. Comparison with monkey studies on neuronal responses and model analysis suggested possible pathways for the extra-retinal mechanisms.

Spatial Geometry of the Human Pelvis

DTIC Science & Technology

1982-03-01

ADA118238 Spatial Geometry of the Human Pelvis , FEDERAL AVIATION ADMINISTRATION WASHINGTON DC MAR 1982 Distribution Statement A: Approved for public...OF THE HUMAN PELVIS March 1982 6. Performing Orgaenizatin Cede S. Perlorming Organizetion Report No. 7. Autitrs) Herbert M. Reynolds, Clyde C. Snow...Tdd skeletal collection. Ibrk done on this study, initiated to define and describe the spatial geomtry of the adult pelvis , was sponsored by the

Undergraduate Research in the Human Sciences: Three Models

ERIC Educational Resources Information Center

Collins, Nina; Mitstifer, Dorothy I.; Nelson Goff, Briana S.; Hymon-Parker, Shirley

2009-01-01

Undergraduate research in the sciences has been shown by numerous studies to enhance the educational experience. The Undergraduate Research Community (URC) founded in 2001 supports several initiatives that promote research in human sciences/family and consumer sciences including an online peer-reviewed journal specifically for undergraduate work,…

Improving Human Papillomavirus Vaccination Uptake in College Students: A Socioecological Perspective

ERIC Educational Resources Information Center

Lanning, Beth; Golman, Mandy; Crosslin, Katie

2017-01-01

Background: Human papillomavirus (HPV) vaccination rates remain relatively low, despite new recommendations found in "Healthy People 2020." Purpose: The purpose of this study was to determine vaccination rates, identify factors that influenced initiation/continuance of HPV vaccine series, and identify levels of influence for HPV health…

48 CFR 1352.235-73 - Research involving human subjects-after initial contract award.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Research involving human... Provisions and Clauses 1352.235-73 Research involving human subjects—after initial contract award. As prescribed in 48 CFR 1335.006(d), insert the following clause: Research Involving Human Subjects—After...

48 CFR 1352.235-73 - Research involving human subjects-after initial contract award.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Research involving human... Provisions and Clauses 1352.235-73 Research involving human subjects—after initial contract award. As prescribed in 48 CFR 1335.006(d), insert the following clause: Research Involving Human Subjects—After...

48 CFR 1352.235-73 - Research involving human subjects-after initial contract award.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Research involving human... Provisions and Clauses 1352.235-73 Research involving human subjects—after initial contract award. As prescribed in 48 CFR 1335.006(d), insert the following clause: Research Involving Human Subjects—After...

Tumor initiation in human malignant melanoma and potential cancer therapies.

PubMed

Ma, Jie; Frank, Markus H

2010-02-01

Cancer stem cells (CSCs), also known as tumor-initiating cells, have been identified in several human malignancies, including human malignant melanoma. The frequency of malignant melanoma-initiating cells (MMICs), which are identified by their expression of ATP-binding cassette (ABC) family member ABCB5, correlates with disease progression in human patients. Furthermore, targeted MMIC ablation through ABCB5 inhibits tumor initiation and growth in preclinical xenotransplantation models, pointing to potential therapeutic promise of the CSC concept. Recent advances also show that CSCs can exert pro-angiogenic roles in tumor growth and serve immunomodulatory functions related to the evasion of host anti-tumor immunity. Thus, MMICs might initiate and sustain tumorigenic growth not only as a result of CSC-intrinsic self-renewal, differentiation and proliferative capacity, but also based on pro-tumorigenic interactions with the host environment.

Tumor Initiation in Human Malignant Melanoma and Potential Cancer Therapies

PubMed Central

Ma, Jie; Frank, Markus H.

2010-01-01

Cancer stem cells (CSCs), also known as tumor-initiating cells, have been identified in several human malignancies, including human malignant melanoma. The frequency of malignant melanoma-initiating cells (MMICs), which are identified by their expression of ATP-binding cassette (ABC) family member ABCB5, correlates with disease progression in human patients. Furthermore, targeted MMIC ablation through ABCB5 inhibits tumor initiation and growth in preclinical xenotransplantation models, pointing to potential therapeutic promise of the CSC concept. Recent advances also show that CSCs can exert pro-angiogenic roles in tumor growth and serve immunomodulatory functions related to the evasion of host anti-tumor immunity. Thus, MMICs might initiate and sustain tumorigenic growth not only as a result of CSC-intrinsic self-renewal, differentiation and proliferative capacity, but also based on pro-tumorigenic interactions with the host environment. PMID:20184545

Do infants perceive the social robot Keepon as a communicative partner?

PubMed

Peca, Andreea; Simut, Ramona; Cao, Hoang-Long; Vanderborght, Bram

2016-02-01

This study investigates if infants perceive an unfamiliar agent, such as the robot Keepon, as a social agent after observing an interaction between the robot and a human adult. 23 infants, aged 9-17 month, were exposed, in a first phase, to either a contingent interaction between the active robot and an active human adult, or to an interaction between an active human adult and the non-active robot, followed by a second phase, in which infants were offered the opportunity to initiate a turn-taking interaction with Keepon. The measured variables were: (1) the number of social initiations the infant directed toward the robot, and (2) the number of anticipatory orientations of attention to the agent that follows in the conversation. The results indicate a significant higher level of initiations in the interactive robot condition compared to the non-active robot condition, while the difference between the frequencies of anticipations of turn-taking behaviors was not significant. Copyright © 2015 Elsevier Inc. All rights reserved.

Determinants of initiation and progression of idiopathic pulmonary fibrosis

PubMed Central

Kottmann, Robert Matthew; Hogan, Christopher M.; Phipps, Richard P.; Sime, Patricia J.

2013-01-01

IPF is a devastating disease with few therapeutic options. The precise aetiology of IPF remains elusive. However, our understanding of the pathologic processes involved in the initiation and progression of this disease is improving. Data on the mechanisms underlying IPF have been generated from epidemiologic investigations as well as cellular and molecular studies of human tissues. Although no perfect animal model of human IPF exists, pre-clinical animal studies have helped define pathways which are likely important in human disease. Epithelial injury, fibroblast activation and repetitive cycles of injury and abnormal repair are almost certainly key events. Factors which have been associated with initiation and/or progression of IPF include viral infections, abnormal cytokine, chemokine and growth factor production, oxidant stress, autoimmunity, inhalational of toxicants and gastro-oesophageal reflux disease. Furthermore, recent evidence identifies a role for a variety of genetic and epigenetic abnormalities ranging from mutations in surfactant protein C to abnormalities in telomere length and telomerase activity. The challenge remains to identify additional inciting agents and key dysregulated pathways that lead to disease progression so that we can develop targeted therapies to treat or prevent this serious disease. PMID:19740254

Human support issues and systems for the space exploration initiative: Results from Project Outreach

NASA Technical Reports Server (NTRS)

Aroesty, J.; Zimmerman, R.; Logan, J.

1991-01-01

The analyses and evaluations of the Human Support panel are discussed. The Human Support panel is one of eight panels created by RAND to screen and analyze submissions to the Space Exploration Initiative (SEI) Outreach Program. Submissions to the Human Support panel were in the following areas: radiation protection; microgravity; life support systems; medical care; and human factors (behavior and performance).

Enteral Feeding With Human Milk Decreases Time to Discharge in Infants Following Gastroschisis Repair

PubMed Central

Gulack, Brian C.; Laughon, Matthew M.; Clark, Reese H.; Burgess, Terrance; Robinson, Sybil; Muhammad, Abdurrauf; Zhang, Angela; Davis, Adrienne; Morton, Robert; Chu, Vivian H.; Arnold, Christopher J.; Hornik, Christoph P.; Smith, P. Brian

2015-01-01

Objective We reviewed a multi-institutional database to assess the effect of enteral feeding with human milk on duration from initiation of feeds to discharge after gastroschisis repair. Study design Infants who had gastroschisis repair between 1997 and 2012 with data recorded in the Pediatrix Medical Group Clinical Data Warehouse were categorized into 4 groups based on the percentage of days they were fed human milk out of the number of days they were fed enterally. Cox proportional hazards regression modeling was performed to determine the adjusted effect of human milk on duration from initiation of feeds to discharge. Results Of 3082 infants, 659 (21%) were fed human milk on 0% of enteral feeding days, 766 (25%) on 1–50% of enteral feeding days, 725 (24%) on 51–99% of enteral feeding days, and 932 (30%) on 100% of enteral feeding days. Following adjustment, being fed human milk on 0% of enteral feeding days was associated with a significantly increased time to discharge compared with being fed human milk on 100% of enteral feeding days (HR for discharge per day: 0.46, 95% CI: 0.40–0.52). The same was found for infants fed human milk on 1–50% of enteral feeding days (HR: 0.37, 95% CI: 0.32–0.41) and for infants fed human milk on 51–99% of enteral feeding days (HR: 0.51, 95% CI: 0.46–0.57). Conclusion The use of human milk for enteral feeding of infants following repair of gastroschisis significantly reduces the time to discharge from initiation of feeds. PMID:26703875

Improving Dengue Virus Capture Rates in Humans and Vectors in Kamphaeng Phet Province, Thailand, Using an Enhanced Spatiotemporal Surveillance Strategy

PubMed Central

Thomas, Stephen J.; Aldstadt, Jared; Jarman, Richard G.; Buddhari, Darunee; Yoon, In-Kyu; Richardson, Jason H.; Ponlawat, Alongkot; Iamsirithaworn, Sopon; Scott, Thomas W.; Rothman, Alan L.; Gibbons, Robert V.; Lambrechts, Louis; Endy, Timothy P.

2015-01-01

Dengue is of public health importance in tropical and sub-tropical regions. Dengue virus (DENV) transmission dynamics was studied in Kamphaeng Phet Province, Thailand, using an enhanced spatiotemporal surveillance of 93 hospitalized subjects with confirmed dengue (initiates) and associated cluster individuals (associates) with entomologic sampling. A total of 438 associates were enrolled from 208 houses with household members with a history of fever, located within a 200-m radius of an initiate case. Of 409 associates, 86 (21%) had laboratory-confirmed DENV infection. A total of 63 (1.8%) of the 3,565 mosquitoes collected were dengue polymerase chain reaction positive (PCR+). There was a significant relationship between spatial proximity to the initiate case and likelihood of detecting DENV from associate cases and Aedes mosquitoes. The viral detection rate from human hosts and mosquito vectors in this study was higher than previously observed by the study team in the same geographic area using different methodologies. We propose that the sampling strategy used in this study could support surveillance of DENV transmission and vector interactions. PMID:25986580

Inter-lab proteomics: data mining in collaborative projects on the basis of the HUPO brain proteome project's pilot studies.

PubMed

Hamacher, Michael; Gröttrup, Bernd; Eisenacher, Martin; Marcus, Katrin; Park, Young Mok; Meyer, Helmut E; Kwon, Kyung-Hoon; Stephan, Christian

2011-01-01

Several projects were initiated by the Human Proteome Organisation (HUPO) focusing on the proteome analysis of distinct human organs. The initiative dedicated to the brain, its development and correlated diseases is the HUPO Brain Proteome Project (HUPO BPP). An objective data submission, storage, and reprocessing strategy have been established with the help of the results gained in a pilot study phase and within subsequent studies. The bioinformatic relevance of the data is drawn from the inter-laboratory comparisons as well as from the recalculation of all data sets submitted by the different groups. In the following, results of the single groups as well as the centralised reprocessing effort are summarised, demonstrating the added-value of this concerted work.

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.

Activation of human herpesvirus replication by apoptosis.

PubMed

Prasad, Alka; Remick, Jill; Zeichner, Steven L

2013-10-01

A central feature of herpesvirus biology is the ability of herpesviruses to remain latent within host cells. Classically, exposure to inducing agents, like activating cytokines or phorbol esters that stimulate host cell signal transduction events, and epigenetic agents (e.g., butyrate) was thought to end latency. We recently showed that Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus-8 [HHV-8]) has another, alternative emergency escape replication pathway that is triggered when KSHV's host cell undergoes apoptosis, characterized by the lack of a requirement for the replication and transcription activator (RTA) protein, accelerated late gene kinetics, and production of virus with decreased infectivity. Caspase-3 is necessary and sufficient to initiate the alternative replication program. HSV-1 was also recently shown to initiate replication in response to host cell apoptosis. These observations suggested that an alternative apoptosis-triggered replication program might be a general feature of herpesvirus biology and that apoptosis-initiated herpesvirus replication may have clinical implications, particularly for herpesviruses that almost universally infect humans. To explore whether an alternative apoptosis-initiated replication program is a common feature of herpesvirus biology, we studied cell lines latently infected with Epstein-Barr virus/HHV-4, HHV-6A, HHV-6B, HHV-7, and KSHV. We found that apoptosis triggers replication for each HHV studied, with caspase-3 being necessary and sufficient for HHV replication. An alternative apoptosis-initiated replication program appears to be a common feature of HHV biology. We also found that commonly used cytotoxic chemotherapeutic agents activate HHV replication, which suggests that treatments that promote apoptosis may lead to activation of latent herpesviruses, with potential clinical significance.

Activation of Human Herpesvirus Replication by Apoptosis

PubMed Central

Prasad, Alka; Remick, Jill

2013-01-01

A central feature of herpesvirus biology is the ability of herpesviruses to remain latent within host cells. Classically, exposure to inducing agents, like activating cytokines or phorbol esters that stimulate host cell signal transduction events, and epigenetic agents (e.g., butyrate) was thought to end latency. We recently showed that Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus-8 [HHV-8]) has another, alternative emergency escape replication pathway that is triggered when KSHV's host cell undergoes apoptosis, characterized by the lack of a requirement for the replication and transcription activator (RTA) protein, accelerated late gene kinetics, and production of virus with decreased infectivity. Caspase-3 is necessary and sufficient to initiate the alternative replication program. HSV-1 was also recently shown to initiate replication in response to host cell apoptosis. These observations suggested that an alternative apoptosis-triggered replication program might be a general feature of herpesvirus biology and that apoptosis-initiated herpesvirus replication may have clinical implications, particularly for herpesviruses that almost universally infect humans. To explore whether an alternative apoptosis-initiated replication program is a common feature of herpesvirus biology, we studied cell lines latently infected with Epstein-Barr virus/HHV-4, HHV-6A, HHV-6B, HHV-7, and KSHV. We found that apoptosis triggers replication for each HHV studied, with caspase-3 being necessary and sufficient for HHV replication. An alternative apoptosis-initiated replication program appears to be a common feature of HHV biology. We also found that commonly used cytotoxic chemotherapeutic agents activate HHV replication, which suggests that treatments that promote apoptosis may lead to activation of latent herpesviruses, with potential clinical significance. PMID:23885073

Human and Murine Innate Immune Cell Populations Display Common and Distinct Response Patterns during Their In Vitro Interaction with the Pathogenic Mold Aspergillus fumigatus.

PubMed

Hellmann, Anna-Maria; Lother, Jasmin; Wurster, Sebastian; Lutz, Manfred B; Schmitt, Anna Lena; Morton, Charles Oliver; Eyrich, Matthias; Czakai, Kristin; Einsele, Hermann; Loeffler, Juergen

2017-01-01

Aspergillus fumigatus is the main cause of invasive fungal infections occurring almost exclusively in immunocompromised patients. An improved understanding of the initial innate immune response is key to the development of better diagnostic tools and new treatment options. Mice are commonly used to study immune defense mechanisms during the infection of the mammalian host with A. fumigatus . However, little is known about functional differences between the human and murine immune response against this fungal pathogen. Thus, we performed a comparative functional analysis of human and murine dendritic cells (DCs), macrophages, and polymorphonuclear cells (PMNs) using standardized and reproducible working conditions, laboratory protocols, and readout assays. A. fumigatus did not provoke identical responses in murine and human immune cells but rather initiated relatively specific responses. While human DCs showed a significantly stronger upregulation of their maturation markers and major histocompatibility complex molecules and phagocytosed A. fumigatus more efficiently compared to their murine counterparts, murine PMNs and macrophages exhibited a significantly stronger release of reactive oxygen species after exposure to A. fumigatus . For all studied cell types, human and murine samples differed in their cytokine response to conidia or germ tubes of A. fumigatus . Furthermore, Dectin-1 showed inverse expression patterns on human and murine DCs after fungal stimulation. These specific differences should be carefully considered and highlight potential limitations in the transferability of murine host-pathogen interaction studies.

Human and Murine Innate Immune Cell Populations Display Common and Distinct Response Patterns during Their In Vitro Interaction with the Pathogenic Mold Aspergillus fumigatus

PubMed Central

Hellmann, Anna-Maria; Lother, Jasmin; Wurster, Sebastian; Lutz, Manfred B.; Schmitt, Anna Lena; Morton, Charles Oliver; Eyrich, Matthias; Czakai, Kristin; Einsele, Hermann; Loeffler, Juergen

2017-01-01

Aspergillus fumigatus is the main cause of invasive fungal infections occurring almost exclusively in immunocompromised patients. An improved understanding of the initial innate immune response is key to the development of better diagnostic tools and new treatment options. Mice are commonly used to study immune defense mechanisms during the infection of the mammalian host with A. fumigatus. However, little is known about functional differences between the human and murine immune response against this fungal pathogen. Thus, we performed a comparative functional analysis of human and murine dendritic cells (DCs), macrophages, and polymorphonuclear cells (PMNs) using standardized and reproducible working conditions, laboratory protocols, and readout assays. A. fumigatus did not provoke identical responses in murine and human immune cells but rather initiated relatively specific responses. While human DCs showed a significantly stronger upregulation of their maturation markers and major histocompatibility complex molecules and phagocytosed A. fumigatus more efficiently compared to their murine counterparts, murine PMNs and macrophages exhibited a significantly stronger release of reactive oxygen species after exposure to A. fumigatus. For all studied cell types, human and murine samples differed in their cytokine response to conidia or germ tubes of A. fumigatus. Furthermore, Dectin-1 showed inverse expression patterns on human and murine DCs after fungal stimulation. These specific differences should be carefully considered and highlight potential limitations in the transferability of murine host–pathogen interaction studies. PMID:29270175

Perceptions of nonhuman primates in human-wildlife conflict scenarios.

PubMed

Hill, Catherine M; Webber, Amanda D

2010-09-01

Nonhuman primates (referred to as primates in this study) are sometimes revered as gods, abhorred as evil spirits, killed for food because they damage crops, or butchered for sport. Primates' perceived similarity to humans places them in an anomalous position. While some human groups accept the idea that primates "straddle" the human-nonhuman boundary, for others this resemblance is a violation of the human-animal divide. In this study we use two case studies to explore how people's perceptions of primates are often influenced by these animals' apparent similarity to humans, creating expectations, founded within a "human morality" about how primates should interact with people. When animals transgress these social rules, they are measured against the same moral framework as humans. This has implications for how people view and respond to certain kinds of primate behaviors, their willingness to tolerate co-existence with primates and their likely support for primate conservation initiatives. 2010 Wiley-Liss, Inc.

Human Mars Entry, Descent, and Landing Architecture Study Overview

NASA Technical Reports Server (NTRS)

Cianciolo, Alicia D.; Polsgrove, Tara T.

2016-01-01

The Entry, Descent, and Landing (EDL) Architecture Study is a multi-NASA center activity to analyze candidate EDL systems as they apply to human Mars landing in the context of the Evolvable Mars Campaign. The study, led by the Space Technology Mission Directorate (STMD), is performed in conjunction with the NASA's Science Mission Directorate and the Human Architecture Team, sponsored by NASA's Human Exploration and Operations Mission Directorate. The primary objective is to prioritize future STMD EDL technology investments by (1) generating Phase A-level designs for selected concepts to deliver 20 t human class payloads, (2) developing a parameterized mass model for each concept capable of examining payloads between 5 and 40 t, and (3) evaluating integrated system performance using trajectory simulations. This paper summarizes the initial study results.

Functional characterization of individual human hematopoietic stem cells cultured at limiting dilution on supportive marrow stromal layers.

PubMed Central

Sutherland, H J; Lansdorp, P M; Henkelman, D H; Eaves, A C; Eaves, C J

1990-01-01

A major goal of current hematopoiesis research is to develop in vitro methods suitable for the measurement and characterization of stem cells with long-term in vivo repopulating potential. Previous studies from several centers have suggested the presence in normal human or murine marrow of a population of very primitive cells that are biologically, physically, and pharmacologically different from cells detectable by short-term colony assays and that can give rise to the latter in long-term cultures (LTCs) containing a competent stromal cell layer. In this report, we show that such cultures can be used to provide a quantitative assay for human "LTC-initiating cells" based on an assessment of the number of clonogenic cells present after 5-8 weeks. Production of derivative clonogenic cells is shown to be absolutely dependent on the presence of a stromal cell feeder. When this requirement is met, the clonogenic cell output (determined by assessment of 5-week-old cultures) is linearly related to the input cell number over a wide range of cell concentrations. Using limiting dilution analysis techniques, we have established the frequency of LTC-initiating cells in normal human marrow to be approximately 1 per 2 X 10(4) cells and in a highly purified CD34-positive subpopulation to be approximately 1 per 50-100 cells. The proliferative capacity exhibited by individual LTC-initiating cells cultured under apparently identical culture conditions was found to be highly variable. Values for the number of clonogenic cells per LTC-initiating cell in 5-week-old cultures ranged from 1 to 30 (the average being 4) with similar levels being detected in positive 8-week-old cultures. Some LTC-initiating cells are multipotent as evidenced by their generation of erythroid as well as granulopoietic progeny. The availability of a system for quantitative analysis of the proliferative and differentiative behavior of this newly defined compartment of primitive human hematopoietic cells should facilitate future studies of specific genetic or microenvironmental parameters involved in the regulation of these cells. Images PMID:2333304

Corneal collagen cross-linking: a confocal, electron, and light microscopy study of eye bank corneas.

PubMed

Dhaliwal, Jasmeet S; Kaufman, Stephen C

2009-01-01

The purpose of this study was to evaluate morphological changes induced by corneal collagen cross-linking in a human ex vivo cornea, using confocal, electron, and light microscopy. The central epithelium was partially removed from ex vivo human corneal buttons. Riboflavin 0.1% solution was applied before ultraviolet A light treatment and then for every 2 minutes for 30 minutes while the corneas were exposed to ultraviolet A light at a wavelength of 370 nm and intensity of 3 mW/cm(2). Each cornea was evaluated using confocal, electron, and light microscopy. Confocal microscopy demonstrated normal-appearing corneas on their initial pretreatment examination, with reduced stromal detail. After treatment, a superficial layer of highly reflective spherical structures (4-10 microm) was observed. Many of these hyperreflective structures appeared up to a depth of 300 microm. The remainder of the corneal stroma and endothelium appeared normal. Electron microscopy showed keratocyte apoptotic changes to a depth of 300 microm. No observable pathologic changes were seen on histology. Based on clinical studies, corneal cross-linking is a promising treatment that appears to be safe and to halt ectatic corneal disease progression. Initial European studies used animal models to extrapolate human protocols. In conjunction with clinical studies, we believe that human ex vivo corneal studies provide a means to evaluate the structural and morphological changes associated with this procedure, within human corneas, in a manner that cannot be accomplished in vivo.

"Detached concern" of medical students in a cadaver dissection course: A phenomenological study.

PubMed

Tseng, Wei-Ting; Lin, Ya-Ping

2016-05-06

The cadaver dissection course remains a time-honored tradition in medical education, partly because of its importance in cultivating professional attitudes in students. This study aims to investigate students' attitudes-specifically characterized as "detached concern"-in a cadaver dissection course. An interpretative phenomenological analysis was performed with semi-structured, focus group interviews among 12 third-year medical students from a Taiwanese medical school to reveal their perceptions and learning experiences regarding human cadaver dissection. Based on these interviews, four relevant categories of perspectives were delineated: (1) initial emotional impact, (2) human referents, (3) coping strategies, and (4) ways of perceiving cadavers. Students were divided into two groups based on these categories. Students in Group 1 developed mechanisms described as "detachment" to cope with their initial emotional reactions to cadaveric dissection, which was noted to have disruptive effects on their learning. They considered human referents to be learning obstacles and avoided contact with or thinking about the human referents while performing dissections. Some of them faced a conflict between perceiving the cadaver as a learning tool versus as a human being. This impasse could be resolved if they latently adopted a "perspective switch" between the concept of a learning tool (rational aspect) and a human being (sensitive aspect). The students in Group 2 had no obvious initial emotional reaction. For them, the human referents functioned as learning supports, and the cadavers were consistently perceived as humans. These students held the notion that "cadaver dissection is an act of love"; therefore, they did not experience any need to detach themselves from their feelings during dissection. This alternative attitude revealed that detached concern alone is not sufficient to describe the entire range of medical students' attitudes toward cadaver dissection. Anat Sci Educ 9: 265-271. © 2015 American Association of Anatomists. © 2015 American Association of Anatomists.

Social Learning as a Way to Overcome Choice-Induced Preferences? Insights from Humans and Rhesus Macaques

PubMed Central

Monfardini, Elisabetta; Gaveau, Valérie; Boussaoud, Driss; Hadj-Bouziane, Fadila; Meunier, Martine

2012-01-01

Much theoretical attention is currently devoted to social learning. Yet, empirical studies formally comparing its effectiveness relative to individual learning are rare. Here, we focus on free choice, which is at the heart of individual reward-based learning, but absent in social learning. Choosing among two equally valued options is known to create a preference for the selected option in both humans and monkeys. We thus surmised that social learning should be more helpful when choice-induced preferences retard individual learning than when they optimize it. To test this prediction, the same task requiring to find which among two items concealed a reward was applied to rhesus macaques and humans. The initial trial was individual or social, rewarded or unrewarded. Learning was assessed on the second trial. Choice-induced preference strongly affected individual learning. Monkeys and humans performed much more poorly after an initial negative choice than after an initial positive choice. Comparison with social learning verified our prediction. For negative outcome, social learning surpassed or at least equaled individual learning in all subjects. For positive outcome, the predicted superiority of individual learning did occur in a majority of subjects (5/6 monkeys and 6/12 humans). A minority kept learning better socially though, perhaps due to a more dominant/aggressive attitude toward peers. Poor learning from errors due to over-valuation of personal choices is among the decision-making biases shared by humans and animals. The present study suggests that choice-immune social learning may help curbing this potentially harmful tendency. Learning from successes is an easier path. The present data suggest that whether one tends to walk it alone or with a peer’s help might depend on the social dynamics within the actor/observer dyad. PMID:22969703

Experience is Instrumental in Tuning a Link Between Language and Cognition: Evidence from 6- to 7- Month-Old Infants' Object Categorization.

PubMed

Perszyk, Danielle R; Waxman, Sandra R

2017-04-19

At birth, infants not only prefer listening to human vocalizations, but also have begun to link these vocalizations to cognition: For infants as young as three months of age, listening to human language supports object categorization, a core cognitive capacity. This precocious link is initially broad: At 3 and 4 months, vocalizations of both humans and nonhuman primates support categorization. But by 6 months, infants have narrowed the link: Only human vocalizations support object categorization. Here we ask what guides infants as they tune their initially broad link to a more precise one, engaged only by the vocalizations of our species. Across three studies, we use a novel exposure paradigm to examine the effects of experience. We document that merely exposing infants to nonhuman primate vocalizations enables infants to preserve the early-established link between this signal and categorization. In contrast, exposing infants to backward speech - a signal that fails to support categorization at any age - offers no such advantage. Our findings reveal the power of early experience as infants specify which signals, from an initially broad set, they will continue to link to cognition.

Inhibition of human dendritic cell activation by hydroethanolic but not lipophilic extracts of turmeric (Curcuma longa).

PubMed

Krasovsky, Joseph; Chang, David H; Deng, Gary; Yeung, Simon; Lee, Mavis; Leung, Ping Chung; Cunningham-Rundles, Susanna; Cassileth, Barrie; Dhodapkar, Madhav V

2009-03-01

Turmeric has been extensively utilized in Indian and Chinese medicine for its immune-modulatory properties. Dendritic cells (DCs) are antigen-presenting cells specialized to initiate and regulate immunity. The ability of DCs to initiate immunity is linked to their activation status. The effects of turmeric on human DCs have not been studied. Here we show that hydroethanolic (HEE) but not lipophilic "supercritical" extraction (SCE) of turmeric inhibits the activation of human DCs in response to inflammatory cytokines. Treatment of DCs with HEE also inhibits the ability of DCs to stimulate the mixed lymphocyte reaction (MLR). Importantly, the lipophilic fraction does not synergize with the hydroethanolic fraction for the ability of inhibiting DC maturation. Rather, culturing of DCs with the combination of HEE and SCE leads to partial abrogation of the effects of HEE on the MLR initiated by DCs. These data provide a mechanism for the anti-inflammatory properties of turmeric. However, they suggest that these extracts are not synergistic and may contain components with mutually antagonistic effects on human DCs. Harnessing the immune effects of turmeric may benefit from specifically targeting the active fractions.

Inhibition of Human Dendritic Cell Activation by Hydroethanolic But Not Lipophilic Extracts of Turmeric (Curcuma longa)

PubMed Central

Krasovsky, Joseph; Chang, David H.; Deng, Gary; Yeung, Simon; Lee, Mavis; Leung, Ping Chung; Cunningham-Rundles, Susanna; Cassileth, Barrie; Dhodapkar, Madhav V.

2015-01-01

Turmeric has been extensively utilized in Indian and Chinese medicine for its immune-modulatory properties. Dendritic cells (DCs) are antigen-presenting cells specialized to initiate and regulate immunity. The ability of DCs to initiate immunity is linked to their activation status. The effects of turmeric on human DCs have not been studied. Here we show that hydroethanolic (HEE) but not lipophilic “supercritical” extraction (SCE) of turmeric inhibits the activation of human DCs in response to inflammatory cytokines. Treatment of DCs with HEE also inhibits the ability of DCs to stimulate the mixed lymphocyte reaction (MLR). Importantly, the lipophilic fraction does not synergize with the hydroethanolic fraction for the ability of inhibiting DC maturation. Rather, culturing of DCs with the combination of HEE and SCE leads to partial abrogation of the effects of HEE on the MLR initiated by DCs. These data provide a mechanism for the anti-inflammatory properties of turmeric. However, they suggest that these extracts are not synergistic and may contain components with mutually antagonistic effects on human DCs. Harnessing the immune effects of turmeric may benefit from specifically targeting the active fractions. PMID:19034830

Human rights education in patient care.

PubMed

Erdman, Joanna N

2017-01-01

This article explores how human rights education in the health professions can build knowledge, change culture, and empower advocacy. Through a study of educational initiatives in the field, the article analyzes different methods by which health professionals come to see the relevance of human rights norms for their work, to habituate these norms in everyday practice, and to espouse these norms in advocacy for social justice. The article seeks to show the transformative potential of education for human rights in patient care.

Controversies in cancer and the mind: effects of psychosocial support.

PubMed

Sampson, Wallace

2002-12-01

In the last decades of the twentieth century, interest in effects of consciousness on health and illness generated several lines of investigation into effects on cancer. Animal studies showed sensitivity of some cancers to hormonal and stressful influences. However, those findings did not translate into effects on humans, nor did they lead to advances in understanding of human cancer. The proposal that emotional state or stress, mediated through psycho-neuro-immunologic mechanisms would affect cancer generation or growth, resulted in conflicting information. Major surveys found no relationship. The proposal of a cancer personality (Type C) also was not confirmed. Initial observations that depression and stress affected human cancer seem to have best been explained by misinterpretations of cause and effect. By the mid 1990s, a remaining thesis--effect of psychosocial support on longevity and the course of cancer--was yet to be resolved. Initial positive results, especially findings in two popularly quoted studies, were not confirmed; they seem to have been due to inadequate numbers (chance) or to artifacts in study design or implementation. Psychosocial support may result in better adjustment and quality of life, but it does not directly affect the evolution of human cancer. Copyright 2002, Elsevier Science (USA). All rights reserved.

The lipid fraction of human milk initiates adipocyte differentiation in 3T3-L1 cells.

PubMed

Fujisawa, Yasuko; Yamaguchi, Rie; Nagata, Eiko; Satake, Eiichiro; Sano, Shinichiro; Matsushita, Rie; Kitsuta, Kazunobu; Nakashima, Shinichi; Nakanishi, Toshiki; Nakagawa, Yuichi; Ogata, Tsutomu

2013-09-01

The prevalence of childhood obesity has increased worldwide over the past decade. Despite evidence that human milk lowers the risk of childhood obesity, the mechanism is not fully understood. We investigated the direct effect of human milk on differentiation of 3T3-L1 preadipocytes. 3T3-L1 preadipocytes were treated with donated human milk only or the combination of the standard hormone mixture; insulin, dexamethasone (DEX), and 3-isobututyl-1-methylxanthine (IBMX). Furthermore, the induction of preadipocyte differentiation by extracted lipids from human milk was tested in comparison to the cells treated with lipid extracts from infant formula. Adipocyte differentiation, specific genes as well as formation of lipid droplets were examined. We clearly show that lipids present in human milk initiate 3T3-L1 preadipocyte differentiation. In contrast, this effect was not observed in response to lipids present in infant formula. The initiation of preadipocyte differentiation by human milk was enhanced by adding the adipogenic hormone, DEX or insulin. The expression of late adipocyte markers in Day 7 adipocytes that have been induced into differentiation with human milk lipid extracts was comparable to those in control cells initiated by a standard adipogenic hormone cocktail. These results demonstrate that human milk contains bioactive lipids that can initiate preadipocyte differentiation in the absence of the standard adipogenic compounds via a unique pathway. Copyright © 2013 Elsevier Ltd. All rights reserved.

Robot initiative in a team learning task increases the rhythm of interaction but not the perceived engagement.

PubMed

Ivaldi, Serena; Anzalone, Salvatore M; Rousseau, Woody; Sigaud, Olivier; Chetouani, Mohamed

2014-01-01

We hypothesize that the initiative of a robot during a collaborative task with a human can influence the pace of interaction, the human response to attention cues, and the perceived engagement. We propose an object learning experiment where the human interacts in a natural way with the humanoid iCub. Through a two-phases scenario, the human teaches the robot about the properties of some objects. We compare the effect of the initiator of the task in the teaching phase (human or robot) on the rhythm of the interaction in the verification phase. We measure the reaction time of the human gaze when responding to attention utterances of the robot. Our experiments show that when the robot is the initiator of the learning task, the pace of interaction is higher and the reaction to attention cues faster. Subjective evaluations suggest that the initiating role of the robot, however, does not affect the perceived engagement. Moreover, subjective and third-person evaluations of the interaction task suggest that the attentive mechanism we implemented in the humanoid robot iCub is able to arouse engagement and make the robot's behavior readable.

Robot initiative in a team learning task increases the rhythm of interaction but not the perceived engagement

PubMed Central

Ivaldi, Serena; Anzalone, Salvatore M.; Rousseau, Woody; Sigaud, Olivier; Chetouani, Mohamed

2014-01-01

We hypothesize that the initiative of a robot during a collaborative task with a human can influence the pace of interaction, the human response to attention cues, and the perceived engagement. We propose an object learning experiment where the human interacts in a natural way with the humanoid iCub. Through a two-phases scenario, the human teaches the robot about the properties of some objects. We compare the effect of the initiator of the task in the teaching phase (human or robot) on the rhythm of the interaction in the verification phase. We measure the reaction time of the human gaze when responding to attention utterances of the robot. Our experiments show that when the robot is the initiator of the learning task, the pace of interaction is higher and the reaction to attention cues faster. Subjective evaluations suggest that the initiating role of the robot, however, does not affect the perceived engagement. Moreover, subjective and third-person evaluations of the interaction task suggest that the attentive mechanism we implemented in the humanoid robot iCub is able to arouse engagement and make the robot's behavior readable. PMID:24596554

5 CFR 5502.107 - Supplemental disclosure of financial interests in substantially affected organizations applicable...

Code of Federal Regulations, 2010 CFR

2010-01-01

... clinical study involving human subjects under a clinical research protocol approved by an institutional review board. (2) Clinical research has the meaning set forth in 42 U.S.C. 284d(b). (3) Institutional... review a clinical research protocol and approve the initiation of biomedical research involving human...

Twenty-five years after "Wingspread"- Environmental endocrine disruptors (EDCs) and human health

EPA Science Inventory

The development of life-stage and tissue-specific AOPs for EDCs can reduce the uncertainty in extrapolating of the effects of EDCs from in vitro and in vivo studies in laboratory animals to humans. When the key events (KEs) and molecular initiating event (MIEs) in a pathway are...

SOX4 is essential for prostate tumorigenesis initiated by PTEN ablation | Office of Cancer Genomics

Cancer.gov

Understanding remains incomplete of the mechanisms underlying initiation and progression of prostate cancer, the most commonly diagnosed cancer in American men. The transcription factor SOX4 is overexpressed in many human cancers, including prostate cancer, suggesting it may participate in prostate tumorigenesis. In this study, we investigated this possibility by genetically deleting Sox4 in a mouse model of prostate cancer initiated by loss of the tumor suppressor Pten.

The initial changes of fat deposits during the decomposition of human and pig remains.

PubMed

Notter, Stephanie J; Stuart, Barbara H; Rowe, Rebecca; Langlois, Neil

2009-01-01

The early stages of adipocere formation in both pig and human adipose tissue in aqueous environments have been investigated. The aims were to determine the short-term changes occurring to fat deposits during decomposition and to ascertain the suitability of pigs as models for human decomposition. Subcutaneous adipose tissue from both species after immersion in distilled water for up to six months was compared using Fourier transform infrared spectroscopy, gas chromatography-mass spectrometry and inductively coupled plasma-mass spectrometry. Changes associated with decomposition were observed, but no adipocere was formed during the initial month of decomposition for either tissue type. Early-stage adipocere formation in pig samples during later months was detected. The variable time courses for adipose tissue decomposition were attributed to differences in the distribution of total fatty acids between species. Variations in the amount of sodium, potassium, calcium, and magnesium were also detected between species. The study shows that differences in total fatty acid composition between species need to be considered when interpreting results from experimental decomposition studies using pigs as human body analogs.

Ozone reaction with clothing and its initiated particle generation in an environmental chamber

NASA Astrophysics Data System (ADS)

Rai, Aakash C.; Guo, Bing; Lin, Chao-Hsin; Zhang, Jianshun; Pei, Jingjing; Chen, Qingyan

2013-10-01

Ozone-initiated chemistry in indoor air can produce sub-micron particles, which are potentially harmful for human health. Occupants in indoor spaces constitute potential sites for particle generation through ozone reactions with human skin and clothing. This investigation conducted chamber experiments to examine particle generation from ozone reactions with clothing (a T-shirt) under different indoor conditions. We studied the effect of various factors such as ozone concentration, relative humidity, soiling levels of T-shirt with human skin oils, and air change rate on particle generation. The results showed that ozone reactions with the T-shirt generated sub-micron particles, which were enhanced by the soiling of the T-shirt with human skin oils. In these reactions, a burst of ultrafine particles was observed about one hour after ozone injection, and then the particles grew to larger sizes. The particle generation from the ozone reactions with the soiled T-shirt was significantly affected by the different factors studied and these reactions were identified as another potential source for indoor ultrafine particles.

Automatic human body modeling for vision-based motion capture system using B-spline parameterization of the silhouette

NASA Astrophysics Data System (ADS)

Jaume-i-Capó, Antoni; Varona, Javier; González-Hidalgo, Manuel; Mas, Ramon; Perales, Francisco J.

2012-02-01

Human motion capture has a wide variety of applications, and in vision-based motion capture systems a major issue is the human body model and its initialization. We present a computer vision algorithm for building a human body model skeleton in an automatic way. The algorithm is based on the analysis of the human shape. We decompose the body into its main parts by computing the curvature of a B-spline parameterization of the human contour. This algorithm has been applied in a context where the user is standing in front of a camera stereo pair. The process is completed after the user assumes a predefined initial posture so as to identify the main joints and construct the human model. Using this model, the initialization problem of a vision-based markerless motion capture system of the human body is solved.

Predictors of Human Papillomavirus Vaccine Completion Among Female and Male Vaccine Initiators in Family Planning Centers.

PubMed

Simons, Hannah R; Unger, Zoe D; Lopez, Priscilla M; Kohn, Julia E

2015-12-01

We estimated human papillomavirus (HPV) vaccine series completion and examined predictors of completion among adolescents and young adults in a large family planning network. Our retrospective cohort study of vaccine completion within 12 months and time to completion used electronic health record data from 119 Planned Parenthood health centers in 11 US states for 9648 patients who initiated HPV vaccination between January 2011 and January 2013. Among vaccine initiators, 29% completed the series within 12 months. Patients who were male, younger than 22 years, or non-Hispanic Black or who had public insurance were less likely to complete within 12 months and completed more slowly than their counterparts. Gender appeared to modify the effect of public versus private insurance on completion (adjusted hazard ratio = 0.76 for women and 0.95 for men; relative excess risk due to interaction = 0.41; 95% confidence interval = 0.09, 0.73). Completion was low yet similar to previous studies conducted in safety net settings.

Volumetric integration of functions for a long term initial Mars habitat

NASA Astrophysics Data System (ADS)

Gutierrez, David John

Sucessfully planning a manned mission to Mars involves an extraordinary balance of resources, risk, technology development and innovation. The interdependency of these factors will ultimately drive out more feasible scenarios for supporting humans during three year, or longer, missions to the Mars surface and home to Earth. Based on a mission profile developed in the Exploration Programs Office at the Johnson Space Center, the Flight Crew Support division began developing conceptual Mars surface habitats to drive out the early human support issues and habitat development concerns. Following the completion of an analysis of a horizontally oriented and outfitted Initial Lunar Haitat (ILH), the decision was made to focus on a vertically oriented habitat as a comparative study. Drawing from the results of both KC-135 partial gravity locomotion testing and water immersion vertical translation studies, the Initial Mars Habitat (IMH), is an analysis of the habitat systems, volumes, and capabilities required to support the first crew of six on the surface of Mars for 500 to 600 days.

Fractionation and reconstitution of factors required for accurate transcription of mammalian ribosomal RNA genes: identification of a species-dependent initiation factor.

PubMed Central

Mishima, Y; Financsek, I; Kominami, R; Muramatsu, M

1982-01-01

Mouse and human cell extracts (S100) can support an accurate and efficient transcription initiation on homologous ribosomal RNA gene (rDNA) templates. The cell extracts were fractionated with the aid of a phosphocellulose column into four fractions (termed A, B, C and D), including one containing a major part of the RNA polymerase I activity. Various reconstitution experiments indicate that fraction D is an absolute requirement for the correct and efficient transcription initiation by RNA polymerase I on both mouse and human genes. Fraction B effectively suppresses random initiation on these templates. Fraction A appears to further enhance the transcription which takes place with fractions C and D. Although fractions A, B and C are interchangeable between mouse and human extracts, fraction D is not; i.e. initiation of transcription required the presence of a homologous fraction D for both templates. The factor(s) in fraction D, however, is not literally species-specific, since mouse D fraction is capable of supporting accurate transcription initiation on a rat rDNA template in the presence of all the other fractions from human cell extract under the conditions where human D fraction is unable to support it. We conclude from these experiments that a species-dependent factor in fraction D plays an important role in the initiation of rDNA transcription in each animal species. Images PMID:7177852

Cross-referencing yeast genetics and mammalian genomes

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

Hieter, P.; Basset, D.; Boguski, M.

1994-09-01

We have initiated a project that will systematically transfer information about yeast genes onto the genetic maps of mice and human beings. Rapidly expanding human EST data will serve as a source of candidate human homologs that will be repeatedly searched using yeast protein sequence queries. Search results will be automatically reported to participating labs. Human cDNA sequences from which the ESTs are derived will be mapped at high resolution in the human and mouse genomes. The comparative mapping information cross-references the genomic position of novel human cDNAs with functional information known about the cognate yeast genes. This should facilitatemore » the initial identification of genes responsible for mammalian mutant phenotypes, including human disease. In addition, the identification of mammalian homologs of yeast genes provides reagents for determining evolutionary conservation and for performing direct experiments in multicellular eukaryotes to enhance study of the yeast protein`s function. For example, ESTs homologous to CDC27 and CDC16 were identified, and the corresponding cDNA clones were obtained from ATTC, completely sequenced, and mapped on human and mouse chromosomes. In addition, the CDC17hs cDNA has been used to raise antisera to the CDC27Hs protein and used in subcellular localization experiments and junctional studies in mammalian cells. We have received funding from the National Center for Human Genome Research to provide a community resource which will establish comprehensive cross-referencing among yeast, human, and mouse loci. The project is set up as a service and information on how to communicate with this effort will be provided.« less

uAUG-mediated translational initiations are responsible for human mu opioid receptor gene expression

PubMed Central

Song, Kyu Young; Kim, Chun Sung; Hwang, Cheol Kyu; Choi, Hack Sun; Law, Ping-Yee; Wei, Li-Na; Loh, Horace H

2010-01-01

Abstract Mu opioid receptor (MOR) is the main site of interaction for major clinical analgesics, particularly morphine. MOR expression is regulated at the transcriptional and post-transcriptional levels. However, the protein expression of the MOR gene is relatively low and the translational control of MOR gene has not been well studied. The 5′-untranslated region (UTR) of the human MOR (OPRM1) mRNA contains four upstream AUG codons (uAUG) preceding the main translation initiation site. We mutated the four uAUGs individually and in combination. Mutations of the third uAUG, containing the same open reading frame, had the strongest inhibitory effect. The inhibitory effect caused by the third in-frame uAUG was confirmed by in vitro translation and receptor-binding assays. Toeprinting results showed that OPRM1 ribosomes initiated efficiently at the first uAUG, and subsequently re-initiated at the in-frame #3 uAUG and the physiological AUG site. This re-initiation resulted in negative expression of OPRM1 under normal conditions. These results indicate that re-initiation in MOR gene expression could play an important role in OPRM1 regulation. PMID:19438807

Is depressed myocyte contractility centrally involved in heart failure?

PubMed

Houser, Steven R; Margulies, Kenneth B

2003-03-07

This review examines the evidence for and against the hypothesis that abnormalities in cardiac contractility initiate the heart failure syndrome and drive its progression. There is substantial evidence that the contractility of failing human hearts is depressed and that abnormalities of basal Ca2+ regulation and adrenergic regulation of Ca2+ signaling are responsible. The cellular and molecular defects that cause depressed myocyte contractility are not well established but seem to culminate in abnormal sarcoplasmic reticulum uptake, storage, and release. There are also strong links between Ca2+ regulation, Ca2+ signaling pathways, hypertrophy, and heart failure that need to be more clearly delineated. There is not substantial direct evidence for a causative role for depressed contractility in the initiation and progression of human heart failure, and some studies show that heart failure can occur without depressed myocyte contractility. Stronger support for a causal role for depressed contractility in the initiation of heart failure comes from animal studies where maintaining or improving contractility can prevent heart failure. Recent clinical studies in humans also support the idea that beneficial heart failure treatments, such as beta-adrenergic antagonists, involve improved contractility. Current or previously used heart failure treatments that increase contractility, primarily by increasing cAMP, have generally increased mortality. Novel heart failure therapies that increase or maintain contractility or adrenergic signaling by selectively modulating specific molecules have produced promising results in animal experiments. How to reliably implement these potentially beneficial inotropic therapies in humans without introducing negative side effects is the major unanswered question in this field.

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

PubMed

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

2009-11-14

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

First Lunar Outpost support study

NASA Technical Reports Server (NTRS)

Bartz, Christopher; Cook, John; Rusingizandekwe, Jean-Luc

1993-01-01

The First Lunar Outpost (FLO) is the first manned step in the accomplishment of the Space Exploration Initiative, the Vice President's directive to NASA on the 20th anniversary of the Apollo moon landing. FLO's broad objectives are the establishment of a permanent human presence on the moon, supporting the utilization of extraterrestrial resources in a long-term, sustained program. The primary objective is to emplace and validate the first elements of a man tended outpost on the lunar surface to provide the basis for: (1) establishing, maintaining and expanding human activities and influence across the surface; (2) establishing, maintaining and enhancing human safety and productivity; (3) accommodating space transportation operations to and from the surface; (4) accommodating production of scientific information; (5) exploiting in-situ resources. Secondary objectives are: (1) to conduct local, small scale science (including life science); (2) In-situ resource utilization (ISRU) demonstrations; (3) engineering and operations tests; (4) to characterize the local environment; and (5) to explore locally. The current work is part of ongoing research at the Sasakawa International Center for Space Architecture supporting NASA's First Lunar Outpost initiative. Research at SICSA supporting the First Lunar Outpost initiative has been funded through the Space Exploration Initiatives office at Johnson Space Center. The objectives of the current study are to further develop a module concept from an evaluation of volumetric and programmatic requirements, and pursue a high fidelity design of this concept, with the intention of providing a high fidelity design mockup to research planetary design issues and evaluate future design concepts.

A personal history of the human exploration initiative with commentary on the pivotal role for life support research

NASA Technical Reports Server (NTRS)

Mendell, Wendell

1990-01-01

The author relates the history of the human exploration initiative from a personal perspective from the 1961 J. F. Kennedy initiative to land a man on the moon up to 1986 when a memo was circulated from NASA Headquarters to its employees which stated as a major goal the expansion of the human presence beyond Earth into the solar system. The pivotal role of life support research is woven into this personalized history.

Near-atomic resolution visualization of human transcription promoter opening

PubMed Central

He, Yuan; Yan, Chunli; Fang, Jie; Inouye, Carla; Tjian, Robert; Ivanov, Ivaylo; Nogales, Eva

2016-01-01

In eukaryotic transcription initiation, a large multi-subunit pre-initiation complex (PIC) that assembles at the core promoter is required for the opening of the duplex DNA and identification of the start site for transcription by RNA polymerase II. Here we use cryo-electron microscropy (cryo-EM) to determine near-atomic resolution structures of the human PIC in a closed state (engaged with duplex DNA), an open state (engaged with a transcription bubble), and an initially transcribing complex (containing six base pairs of DNA–RNA hybrid). Our studies provide structures for previously uncharacterized components of the PIC, such as TFIIE and TFIIH, and segments of TFIIA, TFIIB and TFIIF. Comparison of the different structures reveals the sequential conformational changes that accompany the transition from each state to the next throughout the transcription initiation process. This analysis illustrates the key role of TFIIB in transcription bubble stabilization and provides strong structural support for a translocase activity of XPB. PMID:27193682

The role of Space Station Freedom in the Human Exploration Initiative

NASA Technical Reports Server (NTRS)

Ahlf, P. R.; Saucillo, R. J.; Meredith, B. D.; Peach, L. L.

1990-01-01

Exploration accommodation requirements for Space Station Freedom (SSF) and mission-supporting capabilities have been studied. For supporting the Human Exploration Initiative (HEI), SSF will accommodate two functions with augmentations to the baseline Assembly Complete configuration. First, it will be an earth-orbiting transportation node providing facilities and resources (crew, power, communications) for space vehicle assembly, testing, processing and postflight servicing. Second, it will be an in-space laboratory for science research and technology development. The evolutionary design of SSF will allow the on-orbit addition of pressurized laboratory and habitation modules, power generation equipment, truss structure, and unpressurized vehicle processing platforms.

"Distance Learning" or "Learning at a Distance"? Case Study of an Education Initiative to Deliver an In-Service Bachelors Degree in Zambia

ERIC Educational Resources Information Center

Smith, Christopher J.

2010-01-01

In 1998, as part of what was then Zambia's Department of Technical Education and Vocational Training's (DTEVT) human resources capacity building initiative, under the Ministry of Science, Technology and Vocational Training (MSTVT), donor funding was secured to provide degree-level training for key teachers and managers within the technical…

Psychophysiology of Delayed Extinction and Reconsolidation in Humans

DTIC Science & Technology

2015-04-01

2013). Reconsolidation in a human fear conditioning study: a test of extinction as updating mechanism. Biological Psychology , 92(1), 43–50. doi...strengths of various pharmacological and behavioral, reconsolidation-blocking interventions could be tested . We completed testing for two...conductance, when assessing renewal and reinstatement. Mifepristone was tested as a second pharmacological intervention. After adjusting for initial

Indentation Damage and Crack Repair in Human Enamel*

PubMed Central

Rivera, C.; Arola, D.; Ossa, A.

2013-01-01

Tooth enamel is the hardest and most highly mineralized tissue in the human body. While there have been a number of studies aimed at understanding the hardness and crack growth resistance behavior of this tissue, no study has evaluated if cracks in this tissue undergo repair. In this investigation the crack repair characteristics of young human enamel were evaluated as a function of patient gender and as a function of the distance from the Dentin Enamel Junction (DEJ). Cracks were introduced via microindentation along the prism direction and evaluated as a function of time after the indentation. Microscopic observations indicated that the repair of cracks began immediately after crack initiation and reaches saturation after approximately 48 hours. During this process he crack length decreased up to 10% of the initial length, and the largest degree of reduction occurred in the deep enamel, nearest the DEJ. In addition, it was found that the degree of repair was significantly greater in the enamel of female patients. PMID:23541701

Indentation damage and crack repair in human enamel.

PubMed

Rivera, C; Arola, D; Ossa, A

2013-05-01

Tooth enamel is the hardest and most highly mineralized tissue in the human body. While there have been a number of studies aimed at understanding the hardness and crack growth resistance behavior of this tissue, no study has evaluated if cracks in this tissue undergo repair. In this investigation the crack repair characteristics of young human enamel were evaluated as a function of patient gender and as a function of the distance from the Dentin Enamel Junction (DEJ). Cracks were introduced via microindentation along the prism direction and evaluated as a function of time after the indentation. Microscopic observations indicated that the repair of cracks began immediately after crack initiation and reaches saturation after approximately 48 h. During this process he crack length decreased up to 10% of the initial length, and the largest degree of reduction occurred in the deep enamel, nearest the DEJ. In addition, it was found that the degree of repair was significantly greater in the enamel of female patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

Robonaut Mobile Autonomy: Initial Experiments

NASA Technical Reports Server (NTRS)

Diftler, M. A.; Ambrose, R. O.; Goza, S. M.; Tyree, K. S.; Huber, E. L.

2006-01-01

A mobile version of the NASA/DARPA Robonaut humanoid recently completed initial autonomy trials working directly with humans in cluttered environments. This compact robot combines the upper body of the Robonaut system with a Segway Robotic Mobility Platform yielding a dexterous, maneuverable humanoid ideal for interacting with human co-workers in a range of environments. This system uses stereovision to locate human teammates and tools and a navigation system that uses laser range and vision data to follow humans while avoiding obstacles. Tactile sensors provide information to grasping algorithms for efficient tool exchanges. The autonomous architecture utilizes these pre-programmed skills to form complex behaviors. The initial behavior demonstrates a robust capability to assist a human by acquiring a tool from a remotely located individual and then following the human in a cluttered environment with the tool for future use.

The Border Environmental Health Initiative-investigating the transboundary Santa Cruz watershed

USGS Publications Warehouse

Norman, Laura M.; Callegary, James; van Riper, Charles; Gray, Floyd

2010-01-01

In 2004 the U.S. Geological Survey (USGS) launched the Border Environmental Health Initiative (BEHI), a major project encompassing the entire U.S.-Mexico border region. In 2009, a study of the Santa Cruz River Watershed (SCW), located in the border region of Arizona and Sonora, Mexico, was initiated as part of the BEHI. In this borderland region of the desert Southwest, human health and the ecosystems on which humans rely depend critically on limited water resources. Surface water is scarce during much of the year, and groundwater is the primary source for industrial, agricultural, and domestic use. In order to identify risks to water resources in the SCW, and the potential consequences to riparian ecosystems and ultimately human health, the USGS is using an interdisciplinary and integrative approach that incorporates the expertise of geographers, hydrologists, biologists, and geologists to track organic and inorganic contaminants and their effects from sources to sinks in sediment, water, plants, and animals. Existing groundwater and surface-water models are being used and modified to assess contaminant and sediment transport.

Directed Evolution of a Cyclized Peptoid-Peptide Chimera against a Cell-Free Expressed Protein and Proteomic Profiling of the Interacting Proteins to Create a Protein-Protein Interaction Inhibitor.

PubMed

Kawakami, Takashi; Ogawa, Koji; Hatta, Tomohisa; Goshima, Naoki; Natsume, Tohru

2016-06-17

N-alkyl amino acids are useful building blocks for the in vitro display evolution of ribosomally synthesized peptides because they can increase the proteolytic stability and cell permeability of these peptides. However, the translation initiation substrate specificity of nonproteinogenic N-alkyl amino acids has not been investigated. In this study, we screened various N-alkyl amino acids and nonamino carboxylic acids for translation initiation with an Escherichia coli reconstituted cell-free translation system (PURE system) and identified those that efficiently initiated translation. Using seven of these efficiently initiating acids, we next performed in vitro display evolution of cyclized peptidomimetics against an arbitrarily chosen model human protein (β-catenin) cell-free expressed from its cloned cDNA (HUPEX) and identified a novel β-catenin-binding cyclized peptoid-peptide chimera. Furthermore, by a proteomic approach using direct nanoflow liquid chromatography-tandem mass spectrometry (DNLC-MS/MS), we successfully identified which protein-β-catenin interaction is inhibited by the chimera. The combination of in vitro display evolution of cyclized N-alkyl peptidomimetics and in vitro expression of human proteins would be a powerful approach for the high-speed discovery of diverse human protein-targeted cyclized N-alkyl peptidomimetics.

In-vitro study investigating influence of toothpaste containing green tea extract on the microhardness of demineralized human enamel

NASA Astrophysics Data System (ADS)

Febrian, K.; Triaminingsih, S.; Indrani, DJ

2017-08-01

The aim of this study was to analyze the influence of toothpaste containing green tea extract on the microhardness of demineralized enamel. Human tooth, which was demineralised in citric acid solution, had a toothpaste containing green tea extract of concentration of 5, 10 or 15% application. Microhardness measurement was carried out on each enamel surface of the teeth for initial, after the demineralization and after application of the tooth pastes. It showed that there was significant decrease between enamel microhardness of the teeth at the initial condition and after demineralization. After application of the toothpaste containing green tea extract of each concentration the microhardnss increased significantly. However, there the microhardness was insignificant between the applications of each green tea concentration.

Studies on the mechanism of endogenous pyrogen production. III. Human blood monocytes.

PubMed

Bodel, P

1974-10-01

The characteristics of pyrogen production and release by human blood monocytes were investigated. A dose-response assay of monocyte pyrogen in rabbits indicated a linear relationship of temperature elevation to dose of pyrogen at lower doses. Monocytes did not contain pyrogen when first obtained, nor did they release it spontaneously even after 5 days of incubation in vitro. Pyrogen production was apparent 4 h after stimulation by endotoxin or phagocytosis, and continued for 24 h or more. Puromycin, an inhibitor of protein synthesis, prevented both initiation and continuation of pyrogen production and release. Pyrogen-containing supernates retained most pyrogenic activity during overnight incubation even in the presence of activated cells. Lymphocytes appeared to play no role in either initiation or continuation of pyrogen production in these studies.

Demonstration of Human-Autonomy Teaming Principles

NASA Technical Reports Server (NTRS)

Shively, Robert Jay

2016-01-01

Known problems with automation include lack of mode awareness, automation brittleness, and risk of miscalibrated trust. Human-Autonomy Teaming (HAT) is essential for improving these problems. We have identified some critical components of HAT and ran a part-task study to introduce these components to a ground station that supports flight following of multiple aircraft. Our goal was to demonstrate, evaluate, and refine HAT principles. This presentation provides a brief summary of the study and initial findings.

The Mars imperative: Species survival and inspiring a globalized culture

NASA Astrophysics Data System (ADS)

Barker, Donald C.

2015-02-01

Humanity has crossed a unique technological threshold enabling self-guided survival, a first in the history of life on Earth. From a human perspective the Earth may be considered as a single interconnected ecosystem, and given our tenuous understanding and control over the environment as well as our own behaviors, ever-looming specters of social collapse or even extinction dictate enacting immediate off-world diversification and self-preservation efforts. Herein, Mars is touted as the most tenable and sustainable location in which to initiate such permanent diversification. Scientific curiosity alone cannot initiate nor drive such off-world settlement and concerted impetus and public support for such an endeavor is shown to be constrained by human attention span. Lastly, the initial act of settlement uniquely serves as humanities greatest globally inspiring self-initiated endeavor, a tangible benefit capable of inspiring generations, connecting cultures and motivating college enrollments and career path choices in science, technology, engineering and math (STEM) in a manner similar to the dawn of human space exploration.

Human Mars Lander Design for NASA's Evolvable Mars Campaign

NASA Technical Reports Server (NTRS)

Polsgrove, Tara; Chapman, Jack; Sutherlin, Steve; Taylor, Brian; Fabisinski, Leo; Collins, Tim; Cianciolo Dwyer, Alicia; Samareh, Jamshid; Robertson, Ed; Studak, Bill;

Protein crystallization studies

NASA Technical Reports Server (NTRS)

Lyne, James Evans

1996-01-01

The Structural Biology laboratory at NASA Marshall Spaceflight Center uses x-ray crystallographic techniques to conduct research into the three-dimensional structure of a wide variety of proteins. A major effort in the laboratory involves an ongoing study of human serum albumin (the principal protein in human plasma) and its interaction with various endogenous substances and pharmaceutical agents. Another focus is on antigenic and functional proteins from several pathogenic organisms including the human immunodeficiency virus (HIV) and the widespread parasitic genus, Schistosoma. My efforts this summer have been twofold: first, to identify clinically significant drug interactions involving albumin binding displacement and to initiate studies of the three-dimensional structure of albumin complexed with these agents, and secondly, to establish collaborative efforts to extend the lab's work on human pathogens.

Impact of Human Immunodeficiency Virus Infection on Survival and Acute Toxicities From Chemoradiation Therapy for Cervical Cancer Patients in a Limited-Resource Setting.

PubMed

Grover, Surbhi; Bvochora-Nsingo, Memory; Yeager, Alyssa; Chiyapo, Sebathu; Bhatia, Rohini; MacDuffie, Emily; Puri, Priya; Balang, Dawn; Ratcliffe, Sarah; Narasimhamurthy, Mohan; Gwangwava, Elliphine; Tsietso, Sylvia; Kayembe, Mukendi K A; Ramogola-Masire, Doreen; Dryden-Peterson, Scott; Mahantshetty, Umesh; Viswanathan, Akila N; Zetola, Nicola M; Lin, Lilie L

2018-05-01

To prospectively compare survival between human immunodeficiency virus (HIV)-infected versus HIV-uninfected cervical cancer patients who initiated curative chemoradiation therapy (CRT) in a limited-resource setting. Women with locally advanced cervical cancer with or without HIV infection initiating radical CRT in Botswana were enrolled in a prospective, observational, cohort study from July 2013 through January 2015. Of 182 women treated for cervical cancer during the study period, 143 women initiating curative CRT were included in the study. Eighty-five percent of the participants (122 of 143) had stage II/III cervical cancer, and 67% (96 of 143) were HIV-infected. All HIV-infected patients were receiving antiretroviral therapy (ART) at the time of curative cervical cancer treatment initiation. We found no difference in toxicities between HIV-infected and HIV-uninfected women. The 2-year overall survival (OS) rates were 65% for HIV-infected women (95% confidence interval [CI] 54%-74%) and 66% for HIV-uninfected women (95% CI 49%-79%) (P = .70). Factors associated with better 2-year OS on multivariate analyses included baseline hemoglobin >10 g/dL (hazard ratio [HR] 0.37, 95% CI 0.19-0.72, P = .003), total radiation dose ≥75 Gy (HR 0.52, 95% CI 0.27-0.97, P = .04), and age <40 years versus 40-59 years (HR 2.17, 95% CI 1.05-4.47, P = .03). Human immunodeficiency virus status had no effect on 2-year OS or on acute toxicities in women with well-managed HIV infection who initiated curative CRT in Botswana. In our cohort, we found that baseline hemoglobin levels, total radiation dose, and age were associated with survival, regardless of HIV status. Copyright © 2018 Elsevier Inc. All rights reserved.

Central Nervous System Control of Voice and Swallowing

PubMed Central

Ludlow, Christy L.

2015-01-01

This review of the central nervous control systems for voice and swallowing has suggested that the traditional concepts of a separation between cortical and limbic and brain stem control should be refined and more integrative. For voice production, a separation of the non-human vocalization system from the human learned voice production system has been posited based primarily on studies of non-human primates. However, recent humans studies of emotionally based vocalizations and human volitional voice production has shown more integration between these two systems than previously proposed. Recent human studies have shown that reflexive vocalization as well as learned voice production not involving speech, involve a common integrative system. On the other hand, recent studies of non-human primates have provided evidence of some cortical activity during vocalization and cortical changes with training during vocal behavior. For swallowing, evidence from the macaque and functional brain imaging in humans indicates that the control for the pharyngeal phase of swallowing is not primarily under brain stem mechanisms as previously proposed. Studies suggest that the initiation and patterning of swallowing for the pharyngeal phase is also under active cortical control for both spontaneous as well as volitional swallowing in awake humans and non-human primates. PMID:26241238

Advanced Active Thermal Control Systems Architecture Study

NASA Technical Reports Server (NTRS)

Hanford, Anthony J.; Ewert, Michael K.

1996-01-01

The Johnson Space Center (JSC) initiated a dynamic study to determine possible improvements available through advanced technologies (not used on previous or current human vehicles), identify promising development initiatives for advanced active thermal control systems (ATCS's), and help prioritize funding and personnel distribution among many research projects by providing a common basis to compare several diverse technologies. Some technologies included were two-phase thermal control systems, light-weight radiators, phase-change thermal storage, rotary fluid coupler, and heat pumps. JSC designed the study to estimate potential benefits from these various proposed and under-development thermal control technologies for five possible human missions early in the next century. The study compared all the technologies to a baseline mission using mass as a basis. Each baseline mission assumed an internal thermal control system; an external thermal control system; and aluminum, flow-through radiators. Solar vapor compression heat pumps and light-weight radiators showed the greatest promise as general advanced thermal technologies which can be applied across a range of missions. This initial study identified several other promising ATCS technologies which offer mass savings and other savings compared to traditional thermal control systems. Because the study format compares various architectures with a commonly defined baseline, it is versatile and expandable, and is expected to be updated as needed.

Aichi Virus in Sewage and Surface Water, the Netherlands

PubMed Central

Rutjes, Saskia A.; Takumi, Katsuhisa; Husman, Ana Maria de Roda

2013-01-01

Detection of Aichi virus in humans was initially reported in Japan in 1989. To establish a timeline for the prevalence of Aichi virus infection among humans in the Netherlands, we conducted molecular analysis of archival water samples from 1987–2000 and 2009–2012. Aichi virus RNA was detected in 100% (8/8) of sewage samples and 100% (7/7) of surface water samples collected during 1987–2000 and 100% (8/8) of sewage samples and 71% (5/7) of surface water samples collected during 2009–2012. Several genotype A and B Aichi virus lineages were observed over the 25-year period studied, but the time course of viral genetic diversity showed recent expansion of the genotype B population over genotype A. Our results show that Aichi virus has been circulating among the human population in the Netherlands since before its initial detection in humans was reported and that genotype B now predominates in this country. PMID:23876456

On random field Completely Automated Public Turing Test to Tell Computers and Humans Apart generation.

PubMed

Kouritzin, Michael A; Newton, Fraser; Wu, Biao

2013-04-01

Herein, we propose generating CAPTCHAs through random field simulation and give a novel, effective and efficient algorithm to do so. Indeed, we demonstrate that sufficient information about word tests for easy human recognition is contained in the site marginal probabilities and the site-to-nearby-site covariances and that these quantities can be embedded directly into certain conditional probabilities, designed for effective simulation. The CAPTCHAs are then partial random realizations of the random CAPTCHA word. We start with an initial random field (e.g., randomly scattered letter pieces) and use Gibbs resampling to re-simulate portions of the field repeatedly using these conditional probabilities until the word becomes human-readable. The residual randomness from the initial random field together with the random implementation of the CAPTCHA word provide significant resistance to attack. This results in a CAPTCHA, which is unrecognizable to modern optical character recognition but is recognized about 95% of the time in a human readability study.

78 FR 29371 - Eunice Kennedy Shriver National Institute of Child Health & Human Development; Notice of Closed...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-20

...: National Institute of Child Health and Human Development Initial Review Group; Population Sciences...: National Institute of Child Health and Human Development Initial Review Group; Biobehavioral and Behavioral Sciences Subcommittee. Date: June 27, 2013. Time: 9:00 a.m. to 5:00 p.m. Agenda: To review and evaluate...

40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated after...

40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated after...

Pedagogical Technology for Identifying the Level of Patriotism Formation in Senior School Students within Actualization of Social Commitment and Initiative

ERIC Educational Resources Information Center

Alieva, Sariyat A.; Bilalov, Magomed K.; Gadzhiev, Ramazan D.; Radzhabova, Raisa V.; Salmanova, Dzhamila A.

2018-01-01

The relevance of the problem under study stems from the new social and economic, moral and psychological situation in the society. In its development, the priority is currently given to both shared human values and national ones, to initiative and entrepreneurial spirit of the young people who can transform their homeland and improve Russia's life…

Analysis in Motion Initiative – Human Machine Intelligence

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

Blaha, Leslie

As computers and machines become more pervasive in our everyday lives, we are looking for ways for humans and machines to work more intelligently together. How can we help machines understand their users so the team can do smarter things together? The Analysis in Motion Initiative is advancing the science of human machine intelligence — creating human-machine teams that work better together to make correct, useful, and timely interpretations of data.

INDUCTION OF 6-THIOGUANINE RESISTANCE IN SYNTHRONIZED HUMAN FIBROBLAST CELLS TREATED WITH METHYL METHANESULFONATE, N-ACETOXY-2-ACETHYLAMINOFLUORENE AND N-METHYL-N'-NITRO-N-NITROSOGUANIDINE

EPA Science Inventory

Chemical induction of 6-thioguanine resistance was studied in synchronized human fibroblast cells. Cells initially grown in a medium lacking arginine and glutamine for 24 h ceased DNA synthesis and failed to enter the S phase. After introduction of complete medium, the cells prog...

Idiopathic Hypogonadotropic Hypogonadism Caused by Inactivating Mutations in SRA1

PubMed Central

Kotan, Leman Damla; Cooper, Charlton; Darcan, Şükran; Carr, Ian M.; Özen, Samim; Yan, Yi; Hamedani, Mohammad K.; Gürbüz, Fatih; Mengen, Eda; Turan, İhsan; Ulubay, Ayça; Akkuş, Gamze; Yüksel, Bilgin; Topaloğlu, A. Kemal; Leygue, Etienne

2016-01-01

Objective: What initiates the pubertal process in humans and other mammals is still unknown. We hypothesized that gene(s) taking roles in triggering human puberty may be identified by studying a cohort of idiopathic hypogonadotropic hypogonadism (IHH). Methods: A cohort of IHH cases was studied based on autozygosity mapping coupled with whole exome sequencing. Results: Our studies revealed three independent families in which IHH/delayed puberty is associated with inactivating SRA1 variants. SRA1 was the first gene to be identified to function through its protein as well as noncoding functional ribonucleic acid products. These products act as co-regulators of nuclear receptors including sex steroid receptors as well as SF-1 and LRH-1, the master regulators of steroidogenesis. Functional studies with a mutant SRA1 construct showed a reduced co-activation of ligand-dependent activity of the estrogen receptor alpha, as assessed by luciferase reporter assay in HeLa cells. Conclusion: Our findings strongly suggest that SRA1 gene function is required for initiation of puberty in humans. Furthermore, SRA1 with its alternative products and functionality may provide a potential explanation for the versatility and complexity of the pubertal process. PMID:27086651

Parkinson Patients' Initial Trust in Avatars: Theory and Evidence.

PubMed

Javor, Andrija; Ransmayr, Gerhard; Struhal, Walter; Riedl, René

2016-01-01

Parkinson's disease (PD) is a neurodegenerative disease that affects the motor system and cognitive and behavioral functions. Due to these impairments, PD patients also have problems in using the computer. However, using computers and the Internet could help these patients to overcome social isolation and enhance information search. Specifically, avatars (defined as virtual representations of humans) are increasingly used in online environments to enhance human-computer interaction by simulating face-to-face interaction. Our laboratory experiment investigated how PD patients behave in a trust game played with human and avatar counterparts, and we compared this behavior to the behavior of age, income, education and gender matched healthy controls. The results of our study show that PD patients trust avatar faces significantly more than human faces. Moreover, there was no significant difference between initial trust of PD patients and healthy controls in avatar faces, while PD patients trusted human faces significantly less than healthy controls. Our data suggests that PD patients' interaction with avatars may constitute an effective way of communication in situations in which trust is required (e.g., a physician recommends intake of medication). We discuss the implications of these results for several areas of human-computer interaction and neurological research.

Parkinson Patients’ Initial Trust in Avatars: Theory and Evidence

PubMed Central

Javor, Andrija; Ransmayr, Gerhard; Struhal, Walter; Riedl, René

2016-01-01

Parkinson’s disease (PD) is a neurodegenerative disease that affects the motor system and cognitive and behavioral functions. Due to these impairments, PD patients also have problems in using the computer. However, using computers and the Internet could help these patients to overcome social isolation and enhance information search. Specifically, avatars (defined as virtual representations of humans) are increasingly used in online environments to enhance human-computer interaction by simulating face-to-face interaction. Our laboratory experiment investigated how PD patients behave in a trust game played with human and avatar counterparts, and we compared this behavior to the behavior of age, income, education and gender matched healthy controls. The results of our study show that PD patients trust avatar faces significantly more than human faces. Moreover, there was no significant difference between initial trust of PD patients and healthy controls in avatar faces, while PD patients trusted human faces significantly less than healthy controls. Our data suggests that PD patients’ interaction with avatars may constitute an effective way of communication in situations in which trust is required (e.g., a physician recommends intake of medication). We discuss the implications of these results for several areas of human-computer interaction and neurological research. PMID:27820864

The impact of protease inhibitors on maternal serum screening analyte levels in pregnant women who are HIV positive.

PubMed

Einstein, Francine H; Wright, Rodney L; Trentacoste, Stephanie; Gross, Susan; Merkatz, Irwin R; Bernstein, Peter S

2004-09-01

The purpose of this study was to compare alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol levels in women who take protease inhibitors and those women who do not. This retrospective review from August 2000 to May 2003 was performed for maternal serum screen results, medication use, pregnancy, and perinatal outcomes. Thirty-nine women met study criteria. Sixteen women were treated with protease inhibitors, and 23 women were not treated with protease inhibitors. There was no difference in initial viral load or initial CD4 count between the groups. No difference was found for human chorionic gonadotropin and estriol levels; significantly lower alpha-fetoprotein multiples of the median were found for the women who were treated with protease inhibitors compared with the women who were not (0.97 +/- 0.32 [SD] MoM vs 1.2 +/- 0.4 MoM, respectively; P = .04). Six of 39 women (15%) had positive maternal serum screens. All the babies were normal at birth, and there were no cases of perinatal transmission of human immunodeficiency virus. Protease inhibitors are associated with lower alpha-fetoprotein levels in women who are infected with human immunodeficiency virus.

Role of Insulin-like growth factors in initiation of follicle growth in normal and polycystic human ovaries.

PubMed

Stubbs, Sharron A; Webber, Lisa J; Stark, Jaroslav; Rice, Suman; Margara, Raul; Lavery, Stuart; Trew, Geoffrey H; Hardy, Kate; Franks, Stephen

2013-08-01

Polycystic ovary syndrome (PCOS), the commonest cause of anovulatory infertility, is characterized by disordered follicle development including increased activation and accelerated growth of preantral follicles. Data from experimental animals and preliminary results from studies of human ovarian tissue suggest that IGFs affect preantral follicle development. Our objectives were to investigate the expression of the type-1 IGF receptor (IGFR-1) in the human ovary and to determine whether IGFs are involved in stimulating the transition of follicles from primordial to primary stage in normal and polycystic ovaries. We used archived ovarian tissue for protein expression studies and small cortical biopsies for follicle isolation and for tissue culture. This was a laboratory-based study, using clinical tissue samples. A total of 54 women, 33 with normal ovaries and 21 with polycystic ovaries, were classified by reference to menstrual cycle history and ultrasonography. We evaluated expression of IGFR-1 mRNA in isolated preantral follicles and of IGFR-1 protein in archived ovarian tissue samples from normal and polycystic ovaries and effects of exogenous IGF-1 on preantral follicle development and survival in cultured fragments of normal and polycystic ovaries. IGFR-1 mRNA and protein was expressed in preantral follicles at all stages of development and enhanced expression was noted in PCOS follicles during early preantral development. IGF-1 stimulated initiation of follicle growth in normal tissue but had little effect on preantral follicle growth in polycystic ovaries in which, characteristically, there was a higher proportion of follicles that had entered the growing phase even before culture. IGFs are plausible candidates in regulation of initiation of human follicle growth, and accelerated preantral follicle growth in PCOS may be due to increased activity of endogenous IGFs.

Hysteresis in simulations of malaria transmission

NASA Astrophysics Data System (ADS)

Yamana, Teresa K.; Qiu, Xin; Eltahir, Elfatih A. B.

2017-10-01

Malaria transmission is a complex system and in many parts of the world is closely related to climate conditions. However, studies on environmental determinants of malaria generally consider only concurrent climate conditions and ignore the historical or initial conditions of the system. Here, we demonstrate the concept of hysteresis in malaria transmission, defined as non-uniqueness of the relationship between malaria prevalence and concurrent climate conditions. We show the dependence of simulated malaria transmission on initial prevalence and the initial level of human immunity in the population. Using realistic time series of environmental variables, we quantify the effect of hysteresis in a modeled population. In a set of numerical experiments using HYDREMATS, a field-tested mechanistic model of malaria transmission, the simulated maximum malaria prevalence depends on both the initial prevalence and the initial level of human immunity in the population. We found the effects of initial conditions to be of comparable magnitude to the effects of interannual variability in environmental conditions in determining malaria prevalence. The memory associated with this hysteresis effect is longer in high transmission settings than in low transmission settings. Our results show that efforts to simulate and forecast malaria transmission must consider the exposure history of a location as well as the concurrent environmental drivers.

Identification of cells initiating human melanomas.

PubMed

Schatton, Tobias; Murphy, George F; Frank, Natasha Y; Yamaura, Kazuhiro; Waaga-Gasser, Ana Maria; Gasser, Martin; Zhan, Qian; Jordan, Stefan; Duncan, Lyn M; Weishaupt, Carsten; Fuhlbrigge, Robert C; Kupper, Thomas S; Sayegh, Mohamed H; Frank, Markus H

2008-01-17

Tumour-initiating cells capable of self-renewal and differentiation, which are responsible for tumour growth, have been identified in human haematological malignancies and solid cancers. If such minority populations are associated with tumour progression in human patients, specific targeting of tumour-initiating cells could be a strategy to eradicate cancers currently resistant to systemic therapy. Here we identify a subpopulation enriched for human malignant-melanoma-initiating cells (MMIC) defined by expression of the chemoresistance mediator ABCB5 (refs 7, 8) and show that specific targeting of this tumorigenic minority population inhibits tumour growth. ABCB5+ tumour cells detected in human melanoma patients show a primitive molecular phenotype and correlate with clinical melanoma progression. In serial human-to-mouse xenotransplantation experiments, ABCB5+ melanoma cells possess greater tumorigenic capacity than ABCB5- bulk populations and re-establish clinical tumour heterogeneity. In vivo genetic lineage tracking demonstrates a specific capacity of ABCB5+ subpopulations for self-renewal and differentiation, because ABCB5+ cancer cells generate both ABCB5+ and ABCB5- progeny, whereas ABCB5- tumour populations give rise, at lower rates, exclusively to ABCB5- cells. In an initial proof-of-principle analysis, designed to test the hypothesis that MMIC are also required for growth of established tumours, systemic administration of a monoclonal antibody directed at ABCB5, shown to be capable of inducing antibody-dependent cell-mediated cytotoxicity in ABCB5+ MMIC, exerted tumour-inhibitory effects. Identification of tumour-initiating cells with enhanced abundance in more advanced disease but susceptibility to specific targeting through a defining chemoresistance determinant has important implications for cancer therapy.

Properties of calcium-containing microparticles formed in the process of biomineralization of the human aortic wall

NASA Astrophysics Data System (ADS)

Zlatoustova, O. Yu; Vasilev, S. V.; Rudy, A. S.

2016-08-01

The results of the study of human aortic walls, subjected to different stages of mineralization are presented. By means of scanning electron microscopy and X-ray microanalysis the morphology, elemental composition and characteristics of the mineral component localization were investigated. The key differences in the initial, intermediate and final stages of pathological mineralization of the aorta wall were identified. The data obtained may be useful in describing the mechanism of biomineral deposits formation in human body.

[Short, medium and long-term benefits of human milk intake in very-low-birth-weight infants].

PubMed

Chinea Jiménez, Bibiana; Awad Parada, Yumana; Villarino Marín, Antonio; Sáenz de Pipaón Marcos, Miguel

2017-10-24

The aim of the present study is to evaluate the effect of human milk feeding during the first weeks of life in very low birth weight infants on weight gain at discharge, length of hospitalization, postmenstrual age at discharge and nutritional assessment, growth and neurodevelopment at two and five years. Longitudinal study of very-low-birth-weight infants (< 1,500 grams) admitted to the Neonatal Intensive Care Unit of La Paz University Hospital, from January 1st 2009 to December 31st 2009, followed in the follow-up clinic. Their parents agreed to perform a more exhaustive anthropometric study at five years, classified according to the type of feeding at the time of discharge (exclusive human milk, formula milk or mixed). Initial hospital duration and anthropometry at discharge were evaluated. At two years of age, anthropometric data (weight, height and head circumference) were collected and neurodevelopment was assessed according to the Bayley scale of child development. Data at five years were collected prospectively. Measurements of weight, height and head circumference, waist circumference, hip, relaxed and contracted arm, thigh and middle leg, bicipital, triceps, subscapular, suprailiac and leg skin folds were performed. For patients older than five years, the Kaufman test battery for children was used. The effect of human milk on the variables of interest was investigated using a multivariate analysis correcting for gestational age and weight at birth. One hundred and fifty-two infants born in 2009 were discharged from our unit: exclusive breast milk (59), formula (55) or mixed milk (38). More detailed follow-up was carried out for 61 of them. Human milk during the first admission decreases the initial hospital stay, and is associated with a higher head circumference at two and five years, and a better score in the global and verbal cognitive area at five years. Our results suggest that maternal milk feeding during initial admission should be encouraged because it can improve neurodevelopment at five years of age.

United Nations Human Space Technology Initiative (HSTI)

NASA Astrophysics Data System (ADS)

Ochiai, Mika; Niu, Aimin; Steffens, Heike; Balogh, Werner; Haubold, Hans; Othman, Mazlan; Doi, Takao

2014-11-01

The Human Space Technology Initiative was launched in 2010 within the framework of the United Nations Programme on Space Applications implemented by the Office for Outer Space Affairs of the United Nations. It aims to involve more countries in activities related to human spaceflight and space exploration and to increase the benefits from the outcome of such activities through international cooperation, to make space exploration a truly international effort. The role of the Initiative in these efforts is to provide a platform to exchange information, foster collaboration between partners from spacefaring and non-spacefaring countries, and encourage emerging and developing countries to take part in space research and benefit from space applications. The Initiative organizes expert meetings and workshops annually to raise awareness of the current status of space exploration activities as well as of the benefits of utilizing human space technology and its applications. The Initiative is also carrying out primary science activities including the Zero-Gravity Instrument Project and the Drop Tower Experiment Series aimed at promoting capacity-building activities in microgravity science and education, particularly in developing countries.

Plagiarized bacterial genes in the human book of life.

PubMed

Ponting, C P

2001-05-01

The initial analysis of the human genome draft sequence reveals that our 'book of life' is multi-authored. A small but significant proportion of our genes owes their heritage not to antecedent eukaryotes but instead to bacteria. The publicly funded Human Genome Project study indicates that about 0.5% of all human genes were copied into the genome from bacterial sources. Detailed sequence analyses point to these 'horizontal gene transfer' events having occurred relatively recently. So how did the human 'book of life' evolve to be a chimaera, part animal and part bacterium? And what was the probable evolutionary impact of such gene plagiarism?

Empirical analysis on the runners' velocity distribution in city marathons

NASA Astrophysics Data System (ADS)

Lin, Zhenquan; Meng, Fan

2018-01-01

In recent decades, much researches have been performed on human temporal activity and mobility patterns, while few investigations have been made to examine the features of the velocity distributions of human mobility patterns. In this paper, we investigated empirically the velocity distributions of finishers in New York City marathon, American Chicago marathon, Berlin marathon and London marathon. By statistical analyses on the datasets of the finish time records, we captured some statistical features of human behaviors in marathons: (1) The velocity distributions of all finishers and of partial finishers in the fastest age group both follow log-normal distribution; (2) In the New York City marathon, the velocity distribution of all male runners in eight 5-kilometer internal timing courses undergoes two transitions: from log-normal distribution at the initial stage (several initial courses) to the Gaussian distribution at the middle stage (several middle courses), and to log-normal distribution at the last stage (several last courses); (3) The intensity of the competition, which is described by the root-mean-square value of the rank changes of all runners, goes weaker from initial stage to the middle stage corresponding to the transition of the velocity distribution from log-normal distribution to Gaussian distribution, and when the competition gets stronger in the last course of the middle stage, there will come a transition from Gaussian distribution to log-normal one at last stage. This study may enrich the researches on human mobility patterns and attract attentions on the velocity features of human mobility.

A Preliminary Study of Peer-to-Peer Human-Robot Interaction

NASA Technical Reports Server (NTRS)

Fong, Terrence; Flueckiger, Lorenzo; Kunz, Clayton; Lees, David; Schreiner, John; Siegel, Michael; Hiatt, Laura M.; Nourbakhsh, Illah; Simmons, Reid; Ambrose, Robert

2006-01-01

The Peer-to-Peer Human-Robot Interaction (P2P-HRI) project is developing techniques to improve task coordination and collaboration between human and robot partners. Our work is motivated by the need to develop effective human-robot teams for space mission operations. A central element of our approach is creating dialogue and interaction tools that enable humans and robots to flexibly support one another. In order to understand how this approach can influence task performance, we recently conducted a series of tests simulating a lunar construction task with a human-robot team. In this paper, we describe the tests performed, discuss our initial results, and analyze the effect of intervention on task performance.

Toward 20 T magnetic resonance for human brain studies: opportunities for discovery and neuroscience rationale

PubMed Central

Bird, Mark D.; Frydman, Lucio; Long, Joanna R.; Mareci, Thomas H.; Rooney, William D.; Rosen, Bruce; Schenck, John F.; Schepkin, Victor D.; Sherry, A. Dean; Sodickson, Daniel K.; Springer, Charles S.; Thulborn, Keith R.; Uğurbil, Kamil; Wald, Lawrence L.

2017-01-01

An initiative to design and build magnetic resonance imaging (MRI) and spectroscopy (MRS) instruments at 14 T and beyond to 20 T has been underway since 2012. This initiative has been supported by 22 interested participants from the USA and Europe, of which 15 are authors of this review. Advances in high temperature superconductor materials, advances in cryocooling engineering, prospects for non-persistent mode stable magnets, and experiences gained from large-bore, high-field magnet engineering for the nuclear fusion endeavors support the feasibility of a human brain MRI and MRS system with 1 ppm homogeneity over at least a 16-cm diameter volume and a bore size of 68 cm. Twelve neuroscience opportunities are presented as well as an analysis of the biophysical and physiological effects to be investigated before exposing human subjects to the high fields of 14 T and beyond. PMID:27194154

The colibactin warhead crosslinks DNA

NASA Astrophysics Data System (ADS)

Vizcaino, Maria I.; Crawford, Jason M.

2015-05-01

Members of the human microbiota are increasingly being correlated to human health and disease states, but the majority of the underlying microbial metabolites that regulate host-microbe interactions remain largely unexplored. Select strains of Escherichia coli present in the human colon have been linked to the initiation of inflammation-induced colorectal cancer through an unknown small-molecule-mediated process. The responsible non-ribosomal peptide-polyketide hybrid pathway encodes ‘colibactin’, which belongs to a largely uncharacterized family of small molecules. Genotoxic small molecules from this pathway that are capable of initiating cancer formation have remained elusive due to their high instability. Guided by metabolomic analyses, here we employ a combination of NMR spectroscopy and bioinformatics-guided isotopic labelling studies to characterize the colibactin warhead, an unprecedented substituted spirobicyclic structure. The warhead crosslinks duplex DNA in vitro, providing direct experimental evidence for colibactin's DNA-damaging activity. The data support unexpected models for both colibactin biosynthesis and its mode of action.

Toward 20 T magnetic resonance for human brain studies: opportunities for discovery and neuroscience rationale.

PubMed

Budinger, Thomas F; Bird, Mark D; Frydman, Lucio; Long, Joanna R; Mareci, Thomas H; Rooney, William D; Rosen, Bruce; Schenck, John F; Schepkin, Victor D; Sherry, A Dean; Sodickson, Daniel K; Springer, Charles S; Thulborn, Keith R; Uğurbil, Kamil; Wald, Lawrence L

2016-06-01

An initiative to design and build magnetic resonance imaging (MRI) and spectroscopy (MRS) instruments at 14 T and beyond to 20 T has been underway since 2012. This initiative has been supported by 22 interested participants from the USA and Europe, of which 15 are authors of this review. Advances in high temperature superconductor materials, advances in cryocooling engineering, prospects for non-persistent mode stable magnets, and experiences gained from large-bore, high-field magnet engineering for the nuclear fusion endeavors support the feasibility of a human brain MRI and MRS system with 1 ppm homogeneity over at least a 16-cm diameter volume and a bore size of 68 cm. Twelve neuroscience opportunities are presented as well as an analysis of the biophysical and physiological effects to be investigated before exposing human subjects to the high fields of 14 T and beyond.

Effect of human pancreatic juice and bile on the tensile strength of suture materials.

PubMed

Muftuoglu, M A Tolga; Ozkan, Erkan; Saglam, Abdullah

2004-08-01

Several suture materials are used for pancreatojejunal anastomosis. In this study, we tested the durability of these suture materials in human pancreatic juice and bile. Plain and chromic catgut, polyglactin 910, polyglycolic acid, polydioxanone, polypropylene, and silk sutures were incubated in pancreatic juice and bile that was collected from patients. Fifteen samples of each type of suture material were placed in human juices for 1, 3, and 7 days. Tensile strengths were measured with a tensionmeter. Plain and chromic catgut disintegrated in pancreatic juice and pancreatic juice plus bile mixture. Polyglycolic acid and polyglactin 910 suture materials were vulnerable to pancreatic juice within 7 days. Polydioxanone retained most of its initial strength in pancreatic juice and bile. Polypropylene and silk retained 84% and 92% of their initial strength, respectively. We found that polidioxanone was the strongest suture material in pancreatic juice.

Are humans the initial source of canine mange?

PubMed

Andriantsoanirina, Valérie; Fang, Fang; Ariey, Frédéric; Izri, Arezki; Foulet, Françoise; Botterel, Françoise; Bernigaud, Charlotte; Chosidow, Olivier; Huang, Weiyi; Guillot, Jacques; Durand, Rémy

2016-03-25

Scabies, or mange as it is called in animals, is an ectoparasitic contagious infestation caused by the mite Sarcoptes scabiei. Sarcoptic mange is an important veterinary disease leading to significant morbidity and mortality in wild and domestic animals. A widely accepted hypothesis, though never substantiated by factual data, suggests that humans were the initial source of the animal contamination. In this study we performed phylogenetic analyses of populations of S. scabiei from humans and from canids to validate or not the hypothesis of a human origin of the mites infecting domestic dogs. Mites from dogs and foxes were obtained from three French sites and from other countries. A part of cytochrome c oxidase subunit 1 (cox1) gene was amplified and directly sequenced. Other sequences corresponding to mites from humans, raccoon dogs, foxes, jackal and dogs from various geographical areas were retrieved from GenBank. Phylogenetic analyses were performed using the Otodectes cynotis cox1 sequence as outgroup. Maximum Likelihood and Bayesian Inference analysis approaches were used. To visualize the relationship between the haplotypes, a median joining haplotype network was constructed using Network v4.6 according to host. Twenty-one haplotypes were observed among mites collected from five different host species, including humans and canids from nine geographical areas. The phylogenetic trees based on Maximum Likelihood and Bayesian Inference analyses showed similar topologies with few differences in node support values. The results were not consistent with a human origin of S. scabiei mites in dogs and, on the contrary, did not exclude the opposite hypothesis of a host switch from dogs to humans. Phylogenetic relatedness may have an impact in terms of epidemiological control strategy. Our results and other recent studies suggest to re-evaluate the level of transmission between domestic dogs and humans.

Updating histological data on crown initiation and crown completion ages in southern Africans.

PubMed

Reid, Donald J; Guatelli-Steinberg, Debbie

2017-04-01

To update histological data on crown initiation and completion ages in southern Africans. To evaluate implications of these data for studies that: (a) rely on these data to time linear enamel hypoplasias (LEHs), or, (b) use these data for comparison to fossil hominins. Initiation ages were calculated on 67 histological sections from southern Africans, with sample sizes ranging from one to 11 per tooth type. Crown completion ages for southern Africans were calculated in two ways. First, actual derived initiation ages were added to crown formation times for each histological section to obtain direct information on the crown completion ages of individuals. Second, average initiation ages from this study were added to average crown formation times of southern Africans from the Reid and coworkers previous studies that were based on larger samples. For earlier-initiating tooth types (all anterior teeth and first molars), there is little difference in ages of initiation and crown completion between this and previous studies. Differences increase as a function of initiation age, such that the greatest differences between this and previous studies for both initiation and crown completion ages are for the second and third molars. This study documents variation in initiation ages, particularly for later-initiating tooth types. It upholds the use of previously published histological aging charts for LEHs on anterior teeth. However, this study finds that ages of crown initiation and completion in second and third molars for this southern African sample are earlier than previously estimated. These earlier ages reduce differences between modern humans and fossil hominins for these developmental events in second and third molars. © 2017 Wiley Periodicals, Inc.

Human papillomavirus vaccination among adolescents in Georgia.

PubMed

Underwood, Natasha L; Weiss, Paul; Gargano, Lisa M; Seib, Katherine; Rask, Kimberly J; Morfaw, Christopher; Murray, Dennis; DiClemente, Ralph J; Hughes, James M; Sales, Jessica M

2015-01-01

Human papillomavirus (HPV) vaccination coverage for adolescent females and males remains low in the United States. We conducted a 3-arm randomized controlled trial (RCT) conducted in middle and high schools in eastern Georgia from 2011-2013 to determine the effect of 2 educational interventions used to increase adolescent vaccination coverage for the 4 recommended adolescent vaccines: Tdap, MCV4, HPV and influenza. As part of this RCT, this article focuses on: 1) describing initiation and completion of HPV vaccine series among a diverse population of male and female adolescents; 2) assessing parental attitudes toward HPV vaccine; and 3) examining correlates of HPV vaccine series initiation and completion. Parental attitude score was the strongest predictor of HPV vaccine initiation among adolescents (adjusted odds ratio (aOR): 2.08; 95% confidence interval (CI): 1.80, 2.39). Other correlates that significantly predicted HPV series initiation were gender, study year, and intervention arm. Parental attitudes remained a significant predictor of receipt of 3 doses of HPV vaccine along with gender, race, school type and insurance type. This study demonstrates that positive parental attitudes are important predictors of HPV vaccination and critical to increasing coverage rates. Our findings suggest that more research is needed to understand how parental attitudes are developed and evolve over time.

Exploring the Cytoskeleton During Intracytoplasmic Sperm Injection in Humans

NASA Astrophysics Data System (ADS)

Rawe, Vanesa Y.; Chemes, Héctor

Understanding the cellular events during fertilization in mammals is a major challenge that can contribute to the improvement of future infertility treatments in humans and reproductive performance in farm animals. Of special interest is the role of the oocyte and sperm cytoskeleton during the initial interaction between gametes. The aim of this chapter is to describe methods for studying cytoskeletal features during in vitro fertilization after intracytoplasmic sperm injection (ICSI) in humans. The following protocols will provide a detailed description of how to perform immunodetection and imaging of human eggs, zygotes, and sperm by fluorescence (confocal and epifluorescence) and electron microscopy.

Ambulatory Antibiotic Stewardship through a Human Factors Engineering Approach: A Systematic Review.

PubMed

Keller, Sara C; Tamma, Pranita D; Cosgrove, Sara E; Miller, Melissa A; Sateia, Heather; Szymczak, Julie; Gurses, Ayse P; Linder, Jeffrey A

2018-01-01

In the United States, most antibiotics are prescribed in ambulatory settings. Human factors engineering, which explores interactions between people and the place where they work, has successfully improved quality of care. However, human factors engineering models have not been explored to frame what is known about ambulatory antibiotic stewardship (AS) interventions and barriers and facilitators to their implementation. We conducted a systematic review and searched OVID MEDLINE, Embase, Scopus, Web of Science, and CINAHL to identify controlled interventions and qualitative studies of ambulatory AS and determine whether and how they incorporated principles from a human factors engineering model, the Systems Engineering Initiative for Patient Safety 2.0 model. This model describes how a work system (ambulatory clinic) contributes to a process (antibiotic prescribing) that leads to outcomes. The work system consists of 5 components, tools and technology, organization, person, tasks, and environment, within an external environment. Of 1,288 abstracts initially identified, 42 quantitative studies and 17 qualitative studies met inclusion criteria. Effective interventions focused on tools and technology (eg, clinical decision support and point-of-care testing), the person (eg, clinician education), organization (eg, audit and feedback and academic detailing), tasks (eg, delayed antibiotic prescribing), the environment (eg, commitment posters), and the external environment (media campaigns). Studies have not focused on clinic-wide approaches to AS. A human factors engineering approach suggests that investigating the role of the clinic's processes or physical layout or external pressures' role in antibiotic prescribing may be a promising way to improve ambulatory AS. © Copyright 2018 by the American Board of Family Medicine.

Determination of remodeling parameters for a strain-adaptive finite element model of the distal ulna.

PubMed

Neuert, Mark A C; Dunning, Cynthia E

2013-09-01

Strain energy-based adaptive material models are used to predict bone resorption resulting from stress shielding induced by prosthetic joint implants. Generally, such models are governed by two key parameters: a homeostatic strain-energy state (K) and a threshold deviation from this state required to initiate bone reformation (s). A refinement procedure has been performed to estimate these parameters in the femur and glenoid; this study investigates the specific influences of these parameters on resulting density distributions in the distal ulna. A finite element model of a human ulna was created using micro-computed tomography (µCT) data, initialized to a homogeneous density distribution, and subjected to approximate in vivo loading. Values for K and s were tested, and the resulting steady-state density distribution compared with values derived from µCT images. The sensitivity of these parameters to initial conditions was examined by altering the initial homogeneous density value. The refined model parameters selected were then applied to six additional human ulnae to determine their performance across individuals. Model accuracy using the refined parameters was found to be comparable with that found in previous studies of the glenoid and femur, and gross bone structures, such as the cortical shell and medullary canal, were reproduced. The model was found to be insensitive to initial conditions; however, a fair degree of variation was observed between the six specimens. This work represents an important contribution to the study of changes in load transfer in the distal ulna following the implementation of commercial orthopedic implants.

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

PubMed Central

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

2010-01-01

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

Human Cancer Models Initiative | Office of Cancer Genomics

Cancer.gov

The Human Cancer Models Initiative (HCMI) is an international consortium that is generating novel human tumor-derived culture models, which are annotated with genomic and clinical data. In an effort to advance cancer research and more fully understand how in vitro findings are related to clinical biology, HCMI-developed models and related data will be available as a community resource for cancer and other research.

Human Cancer Models Initiative | Office of Cancer Genomics

Cancer.gov

The Human Cancer Models Initiative (HCMI) is an international consortium that is generating novel human tumor-derived culture models, which are annotated with genomic and clinical data. In an effort to advance cancer research and more fully understand how in vitro findings are related to clinical biology, HCMI-developed models and related data will be available as a community resource for cancer research.

Field and laboratory comparison of the sensitivity and reliability of cocaine detection on currency using chemical sensors, humans, K-9s, and SPME/GC/MS/MS analysis

NASA Astrophysics Data System (ADS)

Furton, Kenneth G.; Hsu, Ya-Li; Luo, Tien-Ying; Norelus, Arnold; Rose, Stefan

1999-02-01

Reports that money in general circulation is contaminated with cocaine have resulted in contaminated money theories purporting that any person carrying currency could potentially initiate a drug dog alert. Field tests on dozens of different drug detector dogs with widely varying breeds, ages and training regimes show a consistent threshold level of 1 - 10 (mu) g of methyl benzoate spiked along with cocaine on U.S. currency or 0.1 - 1 ng/sec methyl benzoate diffusion required to initiate an alert. No other substance studied to data has initiated consistent responses by the drug dogs studied.

The Human Genome Initiative: First Steps.

ERIC Educational Resources Information Center

Newman, Alan R.

1990-01-01

Described is the basic biology involved in mapping chromosomes as presented at a symposium at a recent meeting of the American Chemical Association which focused on the Human Genome Initiative. Different types of gene maps and techniques used to produce gene maps are discussed. (CW)

5 CFR 9701.372 - Creating initial pay ranges.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Creating initial pay ranges. 9701.372 Section 9701.372 Administrative Personnel DEPARTMENT OF HOMELAND SECURITY HUMAN RESOURCES MANAGEMENT... HUMAN RESOURCES MANAGEMENT SYSTEM Pay and Pay Administration Transitional Provisions § 9701.372 Creating...

Contribution of the supplementary motor area and the cerebellum to the anticipatory postural adjustments and execution phases of human gait initiation.

PubMed

Richard, Aliénor; Van Hamme, Angèle; Drevelle, Xavier; Golmard, Jean-Louis; Meunier, Sabine; Welter, Marie-Laure

2017-09-01

Several brain structures including the brainstem, the cerebellum and the frontal cortico-basal ganglia network, with the primary and premotor areas have been shown to participate in the functional organization of gait initiation and postural control in humans, but their respective roles remain poorly understood. The aim of this study was to better understand the role of the supplementary motor area (SMA) and posterior cerebellum in the gait initiation process. Gait initiation parameters were recorded in 22 controls both before and after continuous theta burst transcranial stimulation (cTBS) of the SMA and cerebellum, and were compared to sham stimulation, using a randomized double-blind design study. The two phases of gait initiation process were analyzed: anticipatory postural adjustments (APAs) and execution, with recordings of soleus and tibialis anterior muscles. Functional inhibition of the SMA led to a shortened APA phase duration with advanced and increased muscle activity; during execution, it also advanced muscle co-activation and decreased the duration of stance soleus activity. Cerebellar functional inhibition did not influence the APA phase duration and amplitude but increased muscle co-activation, it decreased execution duration and showed a trend to increase velocity, with increased swing soleus muscle duration and activity. The results suggest that the SMA contributes to both the timing and amplitude of the APAs with no influence on step execution and the posterior cerebellum in the coupling between the APAs and execution phases and leg muscle activity pattern during gait initiation. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Longitudinal Psychosocial Adjustment of Women to Human Papillomavirus Infection.

PubMed

Hsu, Yu-Yun; Wang, Wei-Ming; Fetzer, Susan Jane; Cheng, Ya-Min; Hsu, Keng-Fu

2018-05-29

The aim of this study was to examine the psychosocial adjustment trajectory, focusing on psychological distress, sexual relationships and health care information, as well as factors which have an impact on adjustment on receiving a positive diagnosis of human papillomavirus infection. Human papillomavirus is a common sexually transmitted infection in females. To date, knowledge of the longitudinal psychosocial response to the diagnosis of human papillomavirus is limited. A prospective longitudinal design was conducted with a convenience sample. Women aged 20-65 years old were followed at one, 6 and 12 months after a diagnosis of HPV. Participants completed measures of initial emotional distress and followed-up psychosocial adjustment. A mixed-effects model was applied to analyze the longitudinal changes in psychosocial adjustment. Seventy human papillomavirus positive women participated in the study with nearly 20% of the women reporting emotional distress during their first visit. Mixed-effects model analyses showed that a trajectory of psychosocial adjustment in health care orientation, sexual relationship and psychosocial distress occur from one to 6 months after HPV diagnosis. However, a declining trend from 6-12 months was significant in health care orientation. Initial emotional distress was associated with changes in psychological adjustment. Psychosocial adjustment to human papillomavirus was worse at one month compared with 6 and 12 months after diagnosis. Healthcare providers should offer health information and psychosocial support to women according to their disease progression. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Dissecting Stages of Human Kidney Development and Tumorigenesis with Surface Markers Affords Simple Prospective Purification of Nephron Stem Cells.

PubMed

Pode-Shakked, Naomi; Pleniceanu, Oren; Gershon, Rotem; Shukrun, Rachel; Kanter, Itamar; Bucris, Efrat; Pode-Shakked, Ben; Tam, Gal; Tam, Hadar; Caspi, Revital; Pri-Chen, Sara; Vax, Einav; Katz, Guy; Omer, Dorit; Harari-Steinberg, Orit; Kalisky, Tomer; Dekel, Benjamin

2016-03-29

When assembling a nephron during development a multipotent stem cell pool becomes restricted as differentiation ensues. A faulty differentiation arrest in this process leads to transformation and initiation of a Wilms' tumor. Mapping these transitions with respective surface markers affords accessibility to specific cell subpopulations. NCAM1 and CD133 have been previously suggested to mark human renal progenitor populations. Herein, using cell sorting, RNA sequencing, in vitro studies with serum-free media and in vivo xenotransplantation we demonstrate a sequential map that links human kidney development and tumorigenesis; In nephrogenesis, NCAM1(+)CD133(-) marks SIX2(+) multipotent renal stem cells transiting to NCAM1(+)CD133(+) differentiating segment-specific SIX2(-) epithelial progenitors and NCAM1(-)CD133(+) differentiated nephron cells. In tumorigenesis, NCAM1(+)CD133(-) marks SIX2(+) blastema that includes the ALDH1(+) WT cancer stem/initiating cells, while NCAM1(+)CD133(+) and NCAM1(-)CD133(+) specifying early and late epithelial differentiation, are severely restricted in tumor initiation capacity and tumor self-renewal. Thus, negative selection for CD133 is required for defining NCAM1(+) nephron stem cells in normal and malignant nephrogenesis.

Nitric oxide production by cultured human aortic smooth muscle cells: stimulation by fluid flow

NASA Technical Reports Server (NTRS)

Papadaki, M.; Tilton, R. G.; Eskin, S. G.; McIntire, L. V.

1998-01-01

This study demonstrated that exposure of cultured human aortic smooth muscle cells (SMC) to fluid flow resulted in nitric oxide (NO) production, monitored by nitrite and guanosine 3',5'-cyclic monophosphate production. A rapid burst in nitrite production rate was followed by a more gradual increase throughout the period of flow exposure. Neither the initial burst nor the prolonged nitrite production was dependent on the level of shear stress in the range of 1.1-25 dyn/cm2. Repeated exposure to shear stress after a 30-min static period restimulated nitrite production similar to the initial burst. Ca(2+)-calmodulin antagonists blocked the initial burst in nitrite release. An inhibitor of nitric oxide synthase (NOS) blocked nitrite production, indicating that changes in nitrite reflect NO production. Treatment with dexamethasone or cycloheximide had no effect on nitrite production. Monoclonal antibodies directed against the inducible and endothelial NOS isoforms showed no immunoreactivity on Western blots, whereas monoclonal antibodies directed against the neuronal NOS gave specific products. These findings suggest that human aortic SMC express a constitutive neuronal NOS isoform, the enzymatic activity of which is modulated by flow.

The DNA Inflammasome in Human Myeloid Cells Is Initiated by a STING-Cell Death Program Upstream of NLRP3

PubMed Central

Gaidt, Moritz M.; Ebert, Thomas S.; Chauhan, Dhruv; Ramshorn, Katharina; Pinci, Francesca; Zuber, Sarah; O’Duill, Fionan; Schmid-Burgk, Jonathan L.; Hoss, Florian; Buhmann, Raymund; Wittmann, Georg; Latz, Eicke; Subklewe, Marion; Hornung, Veit

2018-01-01

Summary Detection of cytosolic DNA constitutes a central event in the context of numerous infectious and sterile inflammatory conditions. Recent studies have uncovered a bipartite mode of cytosolic DNA recognition, in which the cGAS-STING axis triggers antiviral immunity, whereas AIM2 triggers inflammasome activation. Here, we show that AIM2 is dispensable for DNA-mediated inflammasome activation in human myeloid cells. Instead, detection of cytosolic DNA by the cGAS-STING axis induces a cell death program initiating potassium efflux upstream of NLRP3. Forward genetics identified regulators of lysosomal trafficking to modulate this cell death program, and subsequent studies revealed that activated STING traffics to the lysosome, where it triggers membrane permeabilization and thus lysosomal cell death (LCD). Importantly, the cGAS-STING-NLRP3 pathway constitutes the default inflammasome response during viral and bacterial infections in human myeloid cells. We conclude that targeting the cGAS-STING-LCD-NLRP3 pathway will ameliorate pathology in inflammatory conditions that are associated with cytosolic DNA sensing. PMID:29033128

Effects of braiding on tensile properties of four-strand human hamstring tendon grafts.

PubMed

Millett, Peter J; Miller, Bruce S; Close, Matthew; Sterett, William I; Walsh, William; Hawkins, Richard J

2003-01-01

Anterior cruciate ligament reconstruction is commonly performed with autogenous hamstring tendon grafts. To ascertain the effects of braiding on ultimate tensile strength and stiffness of hamstring tendon graft. Controlled laboratory study. Sixteen fresh-frozen semitendinosus and gracilis tendons were harvested from eight matched (right and left) human cadaveric specimens. Both sets of hamstring tendons from each matched pair were doubled, creating a four-strand graft. Grafts were then randomized so that one graft from each matched pair was braided and the other remained unbraided. The diameter of each graft construct was recorded. Grafts were tested to failure on a materials testing machine. There were no significant differences in cross-sectional area before or after braiding. Fifteen of 16 tendons failed midsubstance; 1 failed at the lower clamp. Braiding reduced the initial tensile strength and stiffness of human hamstring tendon grafts in this study by 35.0% and 45.8%, respectively. Braiding may place the collagen fibers in a suboptimal orientation for loading that results in a weaker graft. We do not recommend the use of braiding if the strongest, stiffest initial graft is desired.

Identification of cells initiating human melanomas

PubMed Central

Schatton, Tobias; Murphy, George F.; Frank, Natasha Y.; Yamaura, Kazuhiro; Waaga-Gasser, Ana Maria; Gasser, Martin; Zhan, Qian; Jordan, Stefan; Duncan, Lyn M.; Weishaupt, Carsten; Fuhlbrigge, Robert C.; Kupper, Thomas S.; Sayegh, Mohamed H.; Frank, Markus H.

2012-01-01

Tumour-initiating cells capable of self-renewal and differentiation, which are responsible for tumour growth, have been identified in human haematological malignancies1,2 and solid cancers3–6. If such minority populations are associated with tumour progression in human patients, specific targeting of tumour-initiating cells could be a strategy to eradicate cancers currently resistant to systemic therapy. Here we identify a subpopulation enriched for human malignant-melanoma-initiating cells (MMIC) defined by expression of the chemoresistance mediator ABCB5 (refs 7, 8) and show that specific targeting of this tumorigenic minority population inhibits tumour growth. ABCB5+ tumour cells detected in human melanoma patients show a primitive molecular phenotype and correlate with clinical melanoma progression. In serial human-to-mouse xenotransplantation experiments, ABCB5+ melanoma cells possess greater tumorigenic capacity than ABCB5− bulk populations and re-establish clinical tumour heterogeneity. In vivo genetic lineage tracking demonstrates a specific capacity of ABCB5+ sub-populations for self-renewal and differentiation, because ABCB5+ cancer cells generate both ABCB5+ and ABCB5− progeny, whereas ABCB5− tumour populations give rise, at lower rates, exclusively to ABCB5− cells. In an initial proof-of-principle analysis, designed to test the hypothesis that MMIC are also required for growth of established tumours, systemic administration of a monoclonal antibody directed at ABCB5, shown to be capable of inducing antibody-dependent cell-mediated cytotoxicity in ABCB5+ MMIC, exerted tumour-inhibitory effects. Identification of tumour-initiating cells with enhanced abundance in more advanced disease but susceptibility to specific targeting through a defining chemoresistance determinant has important implications for cancer therapy. PMID:18202660

Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation

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

Meeran, Syed M.; Katiyar, Suchitra; Katiyar, Santosh K.

2008-05-15

Phytochemicals show promise as potential chemopreventive or chemotherapeutic agents against various cancers. Here we report the chemotherapeutic effects of berberine, a phytochemical, on human prostate cancer cells. The treatment of human prostate cancer cells (PC-3) with berberine induced dose-dependent apoptosis but this effect of berberine was not seen in non-neoplastic human prostate epithelial cells (PWR-1E). Berberine-induced apoptosis was associated with the disruption of the mitochondrial membrane potential, release of apoptogenic molecules (cytochrome c and Smac/DIABLO) from mitochondria and cleavage of caspase-9,-3 and PARP proteins. This effect of berberine on prostate cancer cells was initiated by the generation of reactive oxygenmore » species (ROS) irrespective of their androgen responsiveness, and the generation of ROS was through the increased induction of xanthine oxidase. Treatment of cells with allopurinol, an inhibitor of xanthine oxidase, inhibited berberine-induced oxidative stress in cancer cells. Berberine-induced apoptosis was blocked in the presence of antioxidant, N-acetylcysteine, through the prevention of disruption of mitochondrial membrane potential and subsequently release of cytochrome c and Smac/DIABLO. In conclusion, the present study reveals that the berberine-mediated cell death of human prostate cancer cells is regulated by reactive oxygen species, and therefore suggests that berberine may be considered for further studies as a promising therapeutic candidate for prostate cancer.« less

Contracting and Procurement for Evidence-Based Interventions in Public-Sector Human Services: A Case Study.

PubMed

Willging, Cathleen E; Aarons, Gregory A; Trott, Elise M; Green, Amy E; Finn, Natalie; Ehrhart, Mark G; Hecht, Debra B

2016-09-01

Sustainment of evidence-based interventions (EBIs) in human services depends on the inner context of community-based organizations (CBOs) that provide services and the outer context of their broader environment. Increasingly, public officials are experimenting with contracting models from for-profit industries to procure human services. In this case study, we conducted qualitative interviews with key government and CBO stakeholders to examine implementation of the Best Value-Performance Information Procurement System to contract for EBIs in a child welfare system. Findings suggest that stakeholder relationships may be compromised when procurement disregards local knowledge, communication, collaboration, and other factors supporting EBIs and public health initiatives.

Human Factors Planning Guidelines

DOT National Transportation Integrated Search

1996-01-01

To ensure human factors considerations are fully incorporated in the system : development, the Integrated Product Team (IPT) or Program Manager initiates a : Human Factors Program (HFP) that addresses the human performance and human : resource parame...

Human colonic myocytes are involved in postischemic inflammation through ADAM17-dependent TNFα production

PubMed Central

Jarry, Anne; Bach-Ngohou, Kalyane; Masson, Damien; Dejoie, Thomas; Lehur, Paul-Antoine; Mosnier, Jean-François; Denis, Marc G; Laboisse, Christian L

2005-01-01

The aim of this study was to identify human colonic resident cells able to initiate an inflammatory response in postischemic injury. Postischemic colonic injury, a condition relevant to various clinical settings, involves an inflammatory cascade in intestinal tissues through the recruitment of circulating inflammatory cells. However, there is no information on the nature of resident cells of the different intestinal layers able to initiate a postischemic inflammatory response. It is however an important issue in the context of a pharmacological approach of the early phase of intestinal ischemia. We reasoned that maintaining the different colonic layers as explant cultures in an oxygenated medium immediately after colonic resection, that is, after an ischemic period, would allow one to identify the resident cells able to initiate an inflammatory cascade, without interference of recruited inflammatory/immune cells. To this end, we designed an explant culture system that operationally defines three compartments in surgical specimens of the human colon, based on the microdissected layers, that is, mucosa, submucosa (containing muscularis mucosae) and muscularis propria. To validate the results obtained in explant cultures in the clinical setting of ischemic colitis, eight cases of sigmoid volvulus were examined. Only the myocytes-containing explants produced tumor necrosis factor alpha (TNFα), via an ADAM17 (a disintegrin and metalloproteinase-17)-dependent pathway, as shown by the abrogation of TNFα production by the inhibitor Tapi-2. Immunofluorescence studies identified nonvascular and vascular myocytes as resident cells coexpressing TNFα and ADAM17, both in our postischemic explant system and in surgical specimens from ischemic colitis patients. Finally, time-course experiments on explanted tissues showed that TNFα production by myocytes was an early event triggered by a postischemic oxidative stress involving nuclear factor kappa B (NF-κB). In conclusion, this study identifies human intestinal myocytes as resident cells able to initiate an inflammatory reaction through TNFα production in postischemic conditions, and delineates two points of control in TNFα production, NF-κB and ADAM17, which can be targeted by pharmacological manipulation. PMID:16273118

How do humans inspect BPMN models: an exploratory study.

PubMed

Haisjackl, Cornelia; Soffer, Pnina; Lim, Shao Yi; Weber, Barbara

2018-01-01

Even though considerable progress regarding the technical perspective on modeling and supporting business processes has been achieved, it appears that the human perspective is still often left aside. In particular, we do not have an in-depth understanding of how process models are inspected by humans, what strategies are taken, what challenges arise, and what cognitive processes are involved. This paper contributes toward such an understanding and reports an exploratory study investigating how humans identify and classify quality issues in BPMN process models. Providing preliminary answers to initial research questions, we also indicate other research questions that can be investigated using this approach. Our qualitative analysis shows that humans adapt different strategies on how to identify quality issues. In addition, we observed several challenges appearing when humans inspect process models. Finally, we present different manners in which classification of quality issues was addressed.

Personality Traits and Training Initiation Process: Intention, Planning, and Action Initiation

PubMed Central

Laguna, Mariola; Purc, Ewelina

2016-01-01

The article aims at investigating the role of personality traits in relation to training initiation. Training initiation is conceptualized as a goal realization process, and explained using goal theories. There are three stages of the process analyzed: intention to undertake training, plan formulation, and actual training undertaking. Two studies tested the relationships between five personality traits, defined according to the five factor model, and the stages of the goal realization process. In Study 1, which explains training intention and training plans’ formulation, 155 employees participated. In Study 2, which was time-lagged with two measurement points, and which explains intention, plans, and training actions undertaken, the data from 176 employees was collected at 3 month intervals. The results of these studies show that personality traits, mainly openness to experience, predict the training initiation process to some degree: intention, plans, and actual action initiation. The findings allow us to provide recommendations for practitioners responsible for human resource development. The assessment of openness to experience in employees helps predict their motivation to participate in training activities. To increase training motivation it is vital to strengthen intentions to undertake training, and to encourage training action planning. PMID:27909414

Personality Traits and Training Initiation Process: Intention, Planning, and Action Initiation.

PubMed

Laguna, Mariola; Purc, Ewelina

2016-01-01

The article aims at investigating the role of personality traits in relation to training initiation. Training initiation is conceptualized as a goal realization process, and explained using goal theories. There are three stages of the process analyzed: intention to undertake training, plan formulation, and actual training undertaking. Two studies tested the relationships between five personality traits, defined according to the five factor model, and the stages of the goal realization process. In Study 1, which explains training intention and training plans' formulation, 155 employees participated. In Study 2, which was time-lagged with two measurement points, and which explains intention, plans, and training actions undertaken, the data from 176 employees was collected at 3 month intervals. The results of these studies show that personality traits, mainly openness to experience, predict the training initiation process to some degree: intention, plans, and actual action initiation. The findings allow us to provide recommendations for practitioners responsible for human resource development. The assessment of openness to experience in employees helps predict their motivation to participate in training activities. To increase training motivation it is vital to strengthen intentions to undertake training, and to encourage training action planning.

ARE ENVIRONMENTAL EXPOSURES TO CHLOROPHENOXY HERBICIDES ASSOCIATED WITH AN INCREASE IN ADVERSE HUMAN HEALTH EFFECTS?

EPA Science Inventory

Background: Associations between adverse health effects and environmental exposures are difficult to study because exposures may be widespread, low-dose in nature, and common throughout the study population. Individual risk-factor epidemiology may not be able to initially ident...

Characterization of the human gene (TBXAS1) encoding thromboxane synthase.

PubMed

Miyata, A; Yokoyama, C; Ihara, H; Bandoh, S; Takeda, O; Takahashi, E; Tanabe, T

1994-09-01

The gene encoding human thromboxane synthase (TBXAS1) was isolated from a human EMBL3 genomic library using human platelet thromboxane synthase cDNA as a probe. Nucleotide sequencing revealed that the human thromboxane synthase gene spans more than 75 kb and consists of 13 exons and 12 introns, of which the splice donor and acceptor sites conform to the GT/AG rule. The exon-intron boundaries of the thromboxane synthase gene were similar to those of the human cytochrome P450 nifedipine oxidase gene (CYP3A4) except for introns 9 and 10, although the primary sequences of these enzymes exhibited 35.8% identity each other. The 1.2-kb of the 5'-flanking region sequence contained potential binding sites for several transcription factors (AP-1, AP-2, GATA-1, CCAAT box, xenobiotic-response element, PEA-3, LF-A1, myb, basic transcription element and cAMP-response element). Primer-extension analysis indicated the multiple transcription-start sites, and the major start site was identified as an adenine residue located 142 bases upstream of the translation-initiation site. However, neither a typical TATA box nor a typical CAAT box is found within the 100-b upstream of the translation-initiation site. Southern-blot analysis revealed the presence of one copy of the thromboxane synthase gene per haploid genome. Furthermore, a fluorescence in situ hybridization study revealed that the human gene for thromboxane synthase is localized to band q33-q34 of the long arm of chromosome 7. A tissue-distribution study demonstrated that thromboxane synthase mRNA is widely expressed in human tissues and is particularly abundant in peripheral blood leukocyte, spleen, lung and liver. The low but significant levels of mRNA were observed in kidney, placenta and thymus.

Characterization of 5' end of human thromboxane receptor gene. Organizational analysis and mapping of protein kinase C--responsive elements regulating expression in platelets.

PubMed

D'Angelo, D D; Davis, M G; Houser, W A; Eubank, J J; Ritchie, M E; Dorn, G W

1995-09-01

Platelet thromboxane receptors are acutely and reversibly upregulated after acute myocardial infarction. To determine if platelet thromboxane receptors are under transcriptional control, we isolated and characterized human genomic DNA clones containing the 5' flanking region of the thromboxane receptor gene. The exon-intron structure of the 5' portion of the thromboxane receptor gene was determined initially by comparing the nucleotide sequence of the 5' flanking genomic clone with that of a novel human uterine thromboxane receptor cDNA that extended the mRNA 141 bp further upstream than the previously identified human placental cDNA. A major transcription initiation site was located in three human tissues approximately 560 bp upstream from the translation initiation codon and 380 bp upstream from any previously identified transcription initiation site. The thromboxane receptor gene has neither a TATA nor a CAAT consensus site. Promoter function of the 5' flanking region of the thromboxane receptor gene was evaluated by transfection of thromboxane receptor gene promoter/chloramphenicol acetyltransferase (CAT) chimera plasmids into platelet-like K562 cells. Thromboxane receptor promoter activity, as assessed by CAT expression, was relatively weak but was significantly enhanced by phorbol ester treatment. Functional analysis of 5' deletion constructs in transfected K562 cells and gel mobility shift localized the major phorbol ester-responsive motifs in the thromboxane receptor gene promoter to a cluster of activator protein-2 (AP-2) binding consensus sites located approximately 1.8 kb 5' from the transcription initiation site. These studies are the first to determine the structure and organization of the 5' end of the thromboxane receptor gene and demonstrate that thromboxane receptor gene expression can be regulated by activation of protein kinase C via induction of an AP-2-like nuclear factor binding to upstream promoter elements. These findings strongly suggest that the mechanism for previously described upregulation of platelet thromboxane receptors after acute myocardial infarction is increased thromboxane receptor gene transcription in platelet-progenitor cells.

Development of a microplate coagulation assay for Factor V in human plasma.

PubMed

Tilley, Derek; Levit, Irina; Samis, John A

2011-06-28

Factor V (FV) in its activated form, FVa, is a critical regulator of thrombin generation during fibrin clot formation. There is a need of a simple, fast, and inexpensive microplate-based coagulation assay to measure the functional activity of FV in human plasma. The objective of this study was to develop a microplate-based assay that measures FV coagulation activity during clot formation in human plasma, which is currently not available. The FV assay requires a kinetic microplate reader to measure the change in absorbance at 405nm during fibrin formation in human plasma. The FV assay accurately measures the time, initial rate, and extent of fibrin clot formation in human plasma. The FV microplate assay is simple, fast, economical, sensitive to approx 24-80pM, and multiple samples may be analyzed simultaneously. All the required materials are commercially available. Standard curves of time or initial rate of fibrin clot formation vs FV activity in the 1-stage assay (Without activation by thrombin) may be used to measure FV activity in samples of human plasma. The assay was used to demonstrate that in nine patients with disseminated intravascular coagulation (DIC), the FV 1-stage, 2-stage (With activation by thrombin), and total (2-stage activity - 1-stage activity) activities were decreased, on average, by approximately 54%, 44%, and 42%, respectively, from prolonged clot times when compared to normal pooled human reference plasma (NHP). The results indicate that the FV in the DIC patient plasmas supported both a delayed and slower rate of fibrin clot formation compared with NHP; however, the extent of fibrin clot formation in the DIC patients remained largely unchanged from that observed with NHP. The FV microplate assay may be easily adapted to measure the activity of any coagulation factor using the appropriate factor-deficient plasma and clot initiating reagent. The microplate assay will find use in both research and clinical laboratories to provide measurement of the functional coagulation activity of FV in human plasma.

Structure of initial crystals formed during human amelogenesis

NASA Astrophysics Data System (ADS)

Cuisinier, F. J. G.; Voegel, J. C.; Yacaman, J.; Frank, R. M.

1992-02-01

X-ray diffraction analysis revealed only the existence of carbonated hydroxyapatite (c.HA) during amelogenesis, whereas conventional transmission electron microscopy investigations showed that developing enamel crystals have a ribbon-like habit. The described compositional changes could be an indication for the presence of minerals different from c.HA. However, the absence of identification of such a mineral shows the need of studies by high resolution electron microscopy (HREM) of initial formed human enamel crystals. We demonstrate the existence of two crystal families involved in the early stages of biomineralization: (a) nanometer-size particles which appeared as a precursor phase; (b) ribbon-like crystals, with a structure closely related to c.HA, which by a progressive thickening process tend to attain the mature enamel crystal habit.

Affordable Exploration of Mars: Recommendations from a Community Workshop on Sustainable Initial Human Missions

NASA Technical Reports Server (NTRS)

Thronson, Harley; Carberry, Chris; Cassady, R. J.; Cooke, Doug; Hopkins, Joshua; Perino, Maria A.; Kirkpatrick, Jim; Raftery, Michael; Westenberg, Artemis; Zucker, Richard

2013-01-01

There is a growing consensus that within two decades initial human missions to Mars are affordable under plausible budget assumptions and with sustained international participation. In response to this idea, a distinguished group of experts from the Mars exploration stakeholder communities attended the "Affording Mars" workshop at George Washington University in December, 2013. Participants reviewed and discussed scenarios for affordable and sustainable human and robotic exploration of Mars, the role of the International Space Station over the coming decade as the essential early step toward humans to Mars, possible "bridge" missions in the 2020s, key capabilities required for affordable initial missions, international partnerships, and a usable definition of affordability and sustainability. We report here the findings, observations, and recommendations that were agreed to at that workshop.

Randomized Controlled Trial on Effect of Intermittent Early Versus Late Kangaroo Mother Care on Human Milk Feeding in Low-Birth-Weight Neonates.

PubMed

Jayaraman, Dhaarani; Mukhopadhyay, Kanya; Bhalla, Anil Kumar; Dhaliwal, Lakhbir Kaur

2017-08-01

Breastfeeding at discharge among sick low-birth-weight (LBW) infants is low despite counseling and intervention like kangaroo mother care (KMC). Research aim: The aim was to study the effects of early initiation of KMC on exclusive human milk feeding, growth, mortality, and morbidities in LBW neonates compared with late initiation of KMC during the hospital stay and postdischarge. A randomized controlled trial was conducted in level 2 and 3 areas of a tertiary care neonatal unit over 15 months. Inborn neonates weighing 1 to 1.8 kg and hemodynamically stable were randomized to receive either early KMC, initiated within the first 4 days of life, or late KMC (off respiratory support and intravenous fluids). Follow-up was until 1 month postdischarge. Outcomes were proportion of infants achieving exclusive human milk feeding and direct breastfeeding, growth, mortality and morbidities during hospital stay, and postdischarge feeding and KMC practices until 1 month. The early KMC group ( n = 80) achieved significantly higher exclusive human milk feeding (86% vs. 45%, p < .001) and direct breastfeeding (49% vs. 30%, p = .021) in hospital and almost exclusive human milk feeding (73% vs. 36%, p < .001) until 1 month postdischarge than the late KMC group ( n = 80). The incidence of apnea (11.9% vs. 20%, p = .027) and recurrent apnea requiring ventilation (8.8% vs. 15%, p = .02) were significantly reduced in the early KMC group. There was no significant difference in mortality, morbidities, and growth during the hospital stay and postdischarge. Early KMC significantly increased exclusive human milk feeding and direct breastfeeding in LBW infants.

Behaviour of Solitary Adult Scandinavian Brown Bears (Ursus arctos) when Approached by Humans on Foot

PubMed Central

Moen, Gro Kvelprud; Støen, Ole-Gunnar; Sahlén, Veronica; Swenson, Jon E.

2012-01-01

Successful management has brought the Scandinavian brown bear (Ursus arctos L.) back from the brink of extinction, but as the population grows and expands the probability of bear-human encounters increases. More people express concerns about spending time in the forest, because of the possibility of encountering bears, and acceptance for the bear is decreasing. In this context, reliable information about the bear's normal behaviour during bear-human encounters is important. Here we describe the behaviour of brown bears when encountering humans on foot. During 2006–2009, we approached 30 adult (21 females, 9 males) GPS-collared bears 169 times during midday, using 1-minute positioning before, during and after the approach. Observer movements were registered with a handheld GPS. The approaches started 869±348 m from the bears, with the wind towards the bear when passing it at approximately 50 m. The bears were detected in 15% of the approaches, and none of the bears displayed any aggressive behaviour. Most bears (80%) left the initial site during the approach, going away from the observers, whereas some remained at the initial site after being approached (20%). Young bears left more often than older bears, possibly due to differences in experience, but the difference between ages decreased during the berry season compared to the pre-berry season. The flight initiation distance was longer for active bears (115±94 m) than passive bears (69±47 m), and was further affected by horizontal vegetation cover and the bear's age. Our findings show that bears try to avoid confrontations with humans on foot, and support the conclusions of earlier studies that the Scandinavian brown bear is normally not aggressive during encounters with humans. PMID:22363710

A case study: the initiative to improve RN scheduling at Hamilton Health Sciences.

PubMed

Wallace, Laurel-Anne; Pierson, Sharon

2008-01-01

In 2003, Hamilton Health Sciences embarked on an initiative to improve and standardize nursing schedules and scheduling practices. The scheduling project was one of several initiatives undertaken by a corporate-wide Nursing Resource Group established to enhance the work environment and patient care and to ensure appropriate utilization of nursing resources across the organization's five hospitals. This article focuses on major activities undertaken in the scheduling initiative. The step-by-step approach described, plus examples of the scheduling resources developed and samples of extended-tour schedules, will all provide insight, potential strategies and practical help for nursing administrators, human resources (HR) personnel and others interested in improving nurse scheduling.

Immunology in the clinic review series; focus on type 1 diabetes and viruses: the enterovirus link to type 1 diabetes: critical review of human studies

PubMed Central

Stene, L C; Rewers, M

2012-01-01

OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIES Metabolic diseases, host responses, cancer, autoinflammatory diseases, allergy. The hypothesis that under some circumstances enteroviral infections can lead to type 1 diabetes (T1D) was proposed several decades ago, based initially on evidence from animal studies and sero-epidemiology. Subsequently, enterovirus RNA has been detected more frequently in serum of patients than in control subjects, but such studies are susceptible to selection bias and reverse causality. Here, we review critically recent evidence from human studies, focusing on longitudinal studies with potential to demonstrate temporal association. Among seven longitudinal birth cohort studies, the evidence that enterovirus infections predict islet autoimmunity is quite inconsistent in our interpretation, due partially, perhaps, to heterogeneity in study design and a limited number of subjects studied. An association between enterovirus and rapid progression from autoimmunity to T1D was reported by one longitudinal study, but although consistent with evidence from animal models, this novel observation awaits replication. It is possible that a potential association with initiation and/or progression of islet autoimmunity can be ascribed to a subgroup of the many enterovirus serotypes, but this has still not been investigated properly. There is a need for larger studies with frequent sample intervals and collection of specimens of sufficient quality and quantity for detailed characterization of enterovirus. More research into the molecular epidemiology of enteroviruses and enterovirus immunity in human populations is also warranted. Ultimately, this knowledge may be used to devise strategies to reduce the risk of T1D in humans. PMID:22385232

Dollars and sense: the financial impact of Canadian wellness initiatives†.

PubMed

Wilkin, Christa L; Connelly, Catherine E

2015-09-01

The popular press reports anecdotal benefits of organizational initiatives that are designed to improve employees' work-life balance and wellness, but the long-term impact of these initiatives on firms' financial performance is unknown. Our longitudinal study of publicly traded Canadian organizations uses the strategic human resources management framework to explain why these initiatives may affect their financial performance. We use an exploratory factor analysis of three waves of archival data to identify two types of initiatives and regression to measure their impact on return on assets (ROA). Our findings suggest that, after 2 years, health promotion initiatives significantly decreased ROA, while work-life balance initiatives significantly increased it. Both effects became non-significant over the longer term. © The Author (2013). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Maternal and infant characteristics associated with human milk feeding in very low birth weight infants.

PubMed

Sisk, Paula M; Lovelady, Cheryl A; Dillard, Robert G; Gruber, Kenneth J; O'Shea, T Michael

2009-11-01

This study identified maternal and infant characteristics predicting human milk (HM) feeding in very low birth weight (VLBW) infants whose mothers (n = 184) participated in a study of lactation counseling and initiated milk expression. Data were collected prospectively, by maternal interview and medical record review. During hospitalization, 159 (86%) infants received at least 50% HM proportion of feedings in the first 2 weeks of life, and 114 (62%) received some HM until the day of hospital discharge. Analysis showed plan to breastfeed was the strongest predictor of initiation and duration of HM feeding. Greater than 12 years of education, respiratory distress syndrome, Apgar score >6, and female gender were significant predictors, and no perinatal hypertensive disorder, white race, and mechanical ventilation were marginal predictors of HM feeding. Women with a high-risk pregnancy should be provided education about the benefits of breastfeeding for infants who are likely to be born prematurely.

Faith-Based Human Services Initiatives: Considerations for Social Work Practice and Theory

ERIC Educational Resources Information Center

Tangenberg, Kathleen M.

2005-01-01

Faith-based human services initiatives present numerous challenges to professional social work. This article explores ways a theoretical integration of ecosystems and structuration perspectives may help social workers navigate complex ideological and practical implications of changing service delivery policies. The article highlights diversity…

Evidence for presence of nonesterified fatty acids as potential gustatory signaling molecules in humans.

PubMed

Kulkarni, Bhushan; Mattes, Richard

2013-02-01

Gustatory fatty acid signaling termed "fatty acid taste" is initiated when nonesterified fatty acids (NEFA) bind to putative fat receptors on taste receptor cells. However, the source and quantity of NEFA in the oral cavity of humans are unresolved. Dietary fat is comprised predominantly of triacylglycerol, and human lingual lipase is of questionable functionality. The objective of this study was to characterize the species of NEFA in saliva and quantify their individual concentrations during oral processing of high-fat foods. Participants chewed fixed amounts of almonds, coconut, walnuts, almond butter, and olive oil (stimuli that vary in physical state and fatty acid composition) for 1 min at the rate of 1 bite/s and expectorated. The salivary NEFA from the expectorant were quantitatively and qualitatively analyzed by gas chromatography-mass spectrometry. Palmitic, oleic, linoleic, and stearic acids were the 4 predominant salivary NEFA, reflecting their concentrations in the foods tested. Their significantly increased concentrations ranged from 20 to 60 µM. Previous animal electrophysiological studies suggest that these NEFA concentrations are sufficient to depolarize taste receptor cells. These data indicate NEFA concentrations likely to be sufficient to initiate gustatory signaling are present in the human oral cavity when masticating high-fat foods.

The Association of Peroxiredoxin 4 with the Initiation and Progression of Hepatocellular Carcinoma.

PubMed

Guo, Xin; Noguchi, Hirotsugu; Ishii, Naoki; Homma, Takujiro; Hamada, Taiji; Hiraki, Tsubasa; Zhang, Jing; Matsuo, Kei; Yokoyama, Seiya; Ishibashi, Hiroaki; Fukushige, Tomoko; Kanekura, Takuro; Fujii, Junichi; Uramoto, Hidetaka; Tanimoto, Akihide; Yamada, Sohsuke

2018-06-11

Peroxiredoxin 4 (PRDX4) is a member of the peroxiredoxin family of antioxidant enzymes. Previously, we reported that PRDX4 can restrain the initiation and progression of nonalcoholic steatohepatitis by reducing local and systemic reactive oxygen species (ROS) levels. Oxidative stress is recognized as a key factor in hepatocarcinogenesis, and a high ROS level has also been found in hepatocellular carcinoma (HCC). Here, our aim is to investigate roles of PRDX4 in the initiation and progression of HCC. In this study, for hepatocarcinogenesis, wild-type (WT), PRDX4 knockout (PRDX4 -/y ), and human PRDX4 transgenic (hPRDX4 +/+ ) mice were given a weekly intraperitoneal injection of diethylnitrosamine for 25 weeks. The HCC incidence was higher in PRDX4 -/y mice than in WT or hPRDX4 +/+ mice. Intrahepatic and circulating oxidative stress and inflammatory cell infiltration in the liver were obviously decreased in hPRDX4 +/+ mice, compared with WT mice. Furthermore, in our cohort study, human HCC specimens with low expression of PRDX4 had higher ROS levels and a highly malignant phenotype, which was associated with a reduced overall survival, compared with those with high PRDX4 expression. However, in human HCC cell lines, PRDX4 knockdown led to a rapidly increased intracellular ROS level and suppressed cell proliferation, inducing cell death. Innovation and Conclusion: Our results clearly indicate that PRDX4 has an inhibitory effect in the initiation of HCC, but a dual (inhibitory or promoting) role in the progression of HCC, suggesting the potential utility of PRDX4 activators or inhibitors as therapy for different stages and phenotypes of HCC. Antioxid. Redox Signal. 00, 000-000.

Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies

PubMed Central

Acland, Gregory M.

2014-01-01

Considerable clinical and molecular variations have been known in retinal blinding diseases in man and also in dogs. Different forms of retinal diseases occur in specific breed(s) caused by mutations segregating within each isolated breeding population. While molecular studies to find genes and mutations underlying retinal diseases in dogs have benefited largely from the phenotypic and genetic uniformity within a breed, within- and across-breed variations have often played a key role in elucidating the molecular basis. The increasing knowledge of phenotypic, allelic, and genetic heterogeneities in canine retinal degeneration has shown that the overall picture is rather more complicated than initially thought. Over the past 20 years, various approaches have been developed and tested to search for genes and mutations underlying genetic traits in dogs, depending on the availability of genetic tools and sample resources. Candidate gene, linkage analysis, and genome-wide association studies have so far identified 24 mutations in 18 genes underlying retinal diseases in at least 58 dog breeds. Many of these genes have been associated with retinal diseases in humans, thus providing opportunities to study the role in pathogenesis and in normal vision. Application in therapeutic interventions such as gene therapy has proven successful initially in a naturally occurring dog model followed by trials in human patients. Other genes whose human homologs have not been associated with retinal diseases are potential candidates to explain equivalent human diseases and contribute to the understanding of their function in vision. PMID:22065099

Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies.

PubMed

Miyadera, Keiko; Acland, Gregory M; Aguirre, Gustavo D

2012-02-01

Considerable clinical and molecular variations have been known in retinal blinding diseases in man and also in dogs. Different forms of retinal diseases occur in specific breed(s) caused by mutations segregating within each isolated breeding population. While molecular studies to find genes and mutations underlying retinal diseases in dogs have benefited largely from the phenotypic and genetic uniformity within a breed, within- and across-breed variations have often played a key role in elucidating the molecular basis. The increasing knowledge of phenotypic, allelic, and genetic heterogeneities in canine retinal degeneration has shown that the overall picture is rather more complicated than initially thought. Over the past 20 years, various approaches have been developed and tested to search for genes and mutations underlying genetic traits in dogs, depending on the availability of genetic tools and sample resources. Candidate gene, linkage analysis, and genome-wide association studies have so far identified 24 mutations in 18 genes underlying retinal diseases in at least 58 dog breeds. Many of these genes have been associated with retinal diseases in humans, thus providing opportunities to study the role in pathogenesis and in normal vision. Application in therapeutic interventions such as gene therapy has proven successful initially in a naturally occurring dog model followed by trials in human patients. Other genes whose human homologs have not been associated with retinal diseases are potential candidates to explain equivalent human diseases and contribute to the understanding of their function in vision.

Colon Cancer Tumorigenesis Initiated by the H1047R Mutant PI3K.

PubMed

Yueh, Alexander E; Payne, Susan N; Leystra, Alyssa A; Van De Hey, Dana R; Foley, Tyler M; Pasch, Cheri A; Clipson, Linda; Matkowskyj, Kristina A; Deming, Dustin A

2016-01-01

The phosphoinositide 3-kinase (PI3K) signaling pathway is critical for multiple important cellular functions, and is one of the most commonly altered pathways in human cancers. We previously developed a mouse model in which colon cancers were initiated by a dominant active PI3K p110-p85 fusion protein. In that model, well-differentiated mucinous adenocarcinomas developed within the colon and initiated through a non-canonical mechanism that is not dependent on WNT signaling. To assess the potential relevance of PI3K mutations in human cancers, we sought to determine if one of the common mutations in the human disease could also initiate similar colon cancers. Mice were generated expressing the Pik3caH1047R mutation, the analog of one of three human hotspot mutations in this gene. Mice expressing a constitutively active PI3K, as a result of this mutation, develop invasive adenocarcinomas strikingly similar to invasive adenocarcinomas found in human colon cancers. These tumors form without a polypoid intermediary and also lack nuclear CTNNB1 (β-catenin), indicating a non-canonical mechanism of tumor initiation mediated by the PI3K pathway. These cancers are sensitive to dual PI3K/mTOR inhibition indicating dependence on the PI3K pathway. The tumor tissue remaining after treatment demonstrated reduction in cellular proliferation and inhibition of PI3K signaling.

Colon Cancer Tumorigenesis Initiated by the H1047R Mutant PI3K

PubMed Central

Yueh, Alexander E.; Payne, Susan N.; Leystra, Alyssa A.; Van De Hey, Dana R.; Foley, Tyler M.; Pasch, Cheri A.; Clipson, Linda; Matkowskyj, Kristina A.; Deming, Dustin A.

2016-01-01

The phosphoinositide 3-kinase (PI3K) signaling pathway is critical for multiple important cellular functions, and is one of the most commonly altered pathways in human cancers. We previously developed a mouse model in which colon cancers were initiated by a dominant active PI3K p110-p85 fusion protein. In that model, well-differentiated mucinous adenocarcinomas developed within the colon and initiated through a non-canonical mechanism that is not dependent on WNT signaling. To assess the potential relevance of PI3K mutations in human cancers, we sought to determine if one of the common mutations in the human disease could also initiate similar colon cancers. Mice were generated expressing the Pik3caH1047R mutation, the analog of one of three human hotspot mutations in this gene. Mice expressing a constitutively active PI3K, as a result of this mutation, develop invasive adenocarcinomas strikingly similar to invasive adenocarcinomas found in human colon cancers. These tumors form without a polypoid intermediary and also lack nuclear CTNNB1 (β-catenin), indicating a non-canonical mechanism of tumor initiation mediated by the PI3K pathway. These cancers are sensitive to dual PI3K/mTOR inhibition indicating dependence on the PI3K pathway. The tumor tissue remaining after treatment demonstrated reduction in cellular proliferation and inhibition of PI3K signaling. PMID:26863299

An exclusive human milk-based diet in extremely premature infants reduces the probability of remaining on total parenteral nutrition: a reanalysis of the data.

PubMed

Ghandehari, Heli; Lee, Martin L; Rechtman, David J

2012-04-25

We have previously shown that an exclusively human milk-based diet is beneficial for extremely premature infants who are at risk for necrotizing enterocolitis (NEC). However, no significant difference in the other primary study endpoint, the length of time on total parenteral nutrition (TPN), was found. The current analysis re-evaluates these data from a different statistical perspective considering the probability or likelihood of needing TPN on any given day rather than the number of days on TPN. This study consisted of 207 premature infants randomized into three groups: one group receiving a control diet of human milk, formula and bovine-based fortifier ("control diet"), and the other two groups receiving only human milk and human milk-based fortifier starting at different times in the enteral feeding process (at feeding volumes of 40 or 100 mL/kg/day; "HM40" and "HM100", respectively). The counting process Cox proportional hazards survival model was used to determine the likelihood of needing TPN in each group. The two groups on the completely human-based diet had an 11-14 % reduction in the likelihood of needing nutrition via TPN when compared to infants on the control diet (p = 0.0001 and p = 0.001, respectively for the HM40 and HM100 groups, respectively). This was even more pronounced if the initial period of TPN was excluded (p < 0.0001 for both the HM40 and HM100 groups). A completely human milk-based diet significantly reduces the likelihood of TPN use for extremely premature infants when compared to a diet including cow-based products. This likelihood may be reduced even further when the human milk fortifier is initiated earlier in the feeding process. This study was registered at http://www.clinicaltrials.gov reg. # NCT00506584.

Anatomy and humanity: Examining the effects of a short documentary film and first anatomy laboratory experience on medical students.

PubMed

Dosani, Farah; Neuberger, Lindsay

2016-01-01

Medical students begin their education inside a laboratory dissecting cadavers to learn human gross anatomy. Many schools use the course experience as a way to instill empathy and some have begun integrating video and recorded interviews with body donors to humanize the experience, but their impact has yet to be measured. This study examines the effects of a brief documentary film and the initial cadaver encounter on student perceptions and attitudes towards the laboratory experience. A pre-test, exposure, post-test design was used with 77 first-year medical students at the University of Central Florida. A previously validated questionnaire was adapted to measure attitudes, emotions, initial reaction to cadaver, perception of the donor as a person, and impressions of the film. An online questionnaire was completed before the first day of laboratory, in which students watched the film Anatomy and Humanity and handled their respective cadavers (no dissection was performed). The post-test was administered immediately following the activities of the first laboratory day. Results indicate an increase in negative attitudes towards dissection, but a more positive initial reaction to the cadaver than originally anticipated. Students also experienced a decrease in emotions like sadness and guilt regarding anatomy laboratory and were less likely to view the cadaver as a once-living person. Findings suggest a higher comfort level, but also greater detachment toward the cadavers from day one despite the video intervention. These results provide novel insight that may aid other interventions aimed at promoting humanism in the anatomy laboratory experience. © 2015 American Association of Anatomists.

Lost in Translation: Bioinformatic Analysis of Variations Affecting the Translation Initiation Codon in the Human Genome.

PubMed

Abad, Francisco; de la Morena-Barrio, María Eugenia; Fernández-Breis, Jesualdo Tomás; Corral, Javier

2018-06-01

Translation is a key biological process controlled in eukaryotes by the initiation AUG codon. Variations affecting this codon may have pathological consequences by disturbing the correct initiation of translation. Unfortunately, there is no systematic study describing these variations in the human genome. Moreover, we aimed to develop new tools for in silico prediction of the pathogenicity of gene variations affecting AUG codons, because to date, these gene defects have been wrongly classified as missense. Whole-exome analysis revealed the mean of 12 gene variations per person affecting initiation codons, mostly with high (> 0:01) minor allele frequency (MAF). Moreover, analysis of Ensembl data (December 2017) revealed 11,261 genetic variations affecting the initiation AUG codon of 7,205 genes. Most of these variations (99.5%) have low or unknown MAF, probably reflecting deleterious consequences. Only 62 variations had high MAF. Genetic variations with high MAF had closer alternative AUG downstream codons than did those with low MAF. Besides, the high-MAF group better maintained both the signal peptide and reading frame. These differentiating elements could help to determine the pathogenicity of this kind of variation. Data and scripts in Perl and R are freely available at https://github.com/fanavarro/hemodonacion. jfernand@um.es. Supplementary data are available at Bioinformatics online.

The Isolation and Characterization of Human Prostate Cancer Stem Cells

DTIC Science & Technology

2012-02-01

established cell lines and primary patient samples) with human prostate fibroblasts hold promise as models of tumor initiation/cancer stem cell activity...We continue to optimize and validate our in vitro model of prostate cancer initiation to facilitate cancer stem cell discovery as well as drug targeting.

2009 Human Factors and Roadway Safety Workshop : Overviews of Safety Initiatives in Iowa [SD .WMV (720x480/29fps/80.2 MB)

DOT National Transportation Integrated Search

2009-11-05

Iowa Department of Transportation Research and Technology Bureau video presentation from the 2009 human factors and roadway safety workshop session titled: Overview of Safety Initiatives in Iowa : Tom Welch, Iowa DOT Highway Division Safety Engineer,...

Effects of Selected Task Performance Criteria at Initiating Adaptive Task Real locations

NASA Technical Reports Server (NTRS)

Montgomery, Demaris A.

2001-01-01

In the current report various performance assessment methods used to initiate mode transfers between manual control and automation for adaptive task reallocation were tested. Participants monitored two secondary tasks for critical events while actively controlling a process in a fictional system. One of the secondary monitoring tasks could be automated whenever operators' performance was below acceptable levels. Automation of the secondary task and transfer of the secondary task back to manual control were either human- or machine-initiated. Human-initiated transfers were based on the operator's assessment of the current task demands while machine-initiated transfers were based on the operators' performance. Different performance assessment methods were tested in two separate experiments.

Correlates of human papillomavirus vaccine coverage: a state-level analysis.

PubMed

Moss, Jennifer L; Reiter, Paul L; Brewer, Noel T

2015-02-01

We tested the hypothesis that states with higher rates of cancers associated with human papillomavirus (HPV) would have lower HPV vaccine coverage. We gathered state-level data on HPV-related cancer rates and HPV vaccine initiation coverage for girls and boys, separately, and HPV vaccine follow-through (i.e., receipt of 3 doses among those initiating the series) for girls only. In addition, we gathered state-level data on demographic composition and contact with the health care system. We calculated Pearson correlations for these ecological relationships. Human papillomavirus vaccine initiation among girls was lower in states with higher levels of cervical cancer incidence and mortality (r = -0.29 and -0.46, respectively). In addition, vaccine follow-through among girls was lower in states with higher levels of cervical cancer mortality (r = -0.30). Other cancer rates were associated with HPV vaccine initiation and follow-through among girls, but not among boys. Human papillomavirus vaccine initiation among girls was lower in states with higher proportions of non-Hispanic black residents and lower proportions of higher-income residents. Human papillomavirus vaccine follow-through was higher in states with greater levels of adolescents' contact with the health care system. Human papillomavirus vaccine coverage for girls was lower in states with higher HPV-related cancer rates. Public health efforts should concentrate on geographic areas with higher cancer rates. Strengthening adolescent preventive health care use may be particularly important to increase vaccine follow-through. Cost-effectiveness analyses may overestimate the benefits of current vaccination coverage and underestimate the benefits of increasing coverage.

Analysis of lung tumor initiation and progression in transgenic mice for Cre-inducible overexpression of Cul4A gene

DOE PAGES

Wang, Yang; Xu, Zhidong; Mao, Jian -Hua; ...

2015-06-08

Background: Lung cancer is the leading cause of morbidity and death worldwide. Although the available lung cancer animal models have been informative and further propel our understanding of human lung cancer, they still do not fully recapitulate the complexities of human lung cancer. The pathogenesis of lung cancer remains highly elusive because of its aggressive biologic nature and considerable heterogeneity, compared to other cancers. The association of Cul4A amplification with aggressive tumor growth and poor prognosis has been suggested. Our previous study suggested that Cul4A is oncogenic in vitro, but its oncogenic role in vivo has not been studied. Methods:more » Viral delivery approaches have been used extensively to model cancer in mouse models. In our experiments, we used Cre-recombinase induced overexpression of the Cul4A gene in transgenic mice to study the role of Cul4A on lung tumor initiation and progression and have developed a new model of lung tumor development in mice harboring a conditionally expressed allele of Cul4A. Results: Here we show that the use of a recombinant adenovirus expressing Cre-recombinase (“AdenoCre”) to induce Cul4A overexpression in the lungs of mice allows controls of the timing and multiplicity of tumor initiation. Following our mouse models, we are able to study the potential role of Cul4A in the development and progression in pulmonary adenocarcinoma as well. Conclusion: Our findings indicate that Cul4A is oncogenic in vivo, and this mouse model is a tool in understanding the mechanisms of Cul4A in human cancers and for testing experimental therapies targeting Cul4A.« less

Analysis of lung tumor initiation and progression in transgenic mice for Cre-inducible overexpression of Cul4A gene

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

Wang, Yang; Xu, Zhidong; Mao, Jian -Hua

Background: Lung cancer is the leading cause of morbidity and death worldwide. Although the available lung cancer animal models have been informative and further propel our understanding of human lung cancer, they still do not fully recapitulate the complexities of human lung cancer. The pathogenesis of lung cancer remains highly elusive because of its aggressive biologic nature and considerable heterogeneity, compared to other cancers. The association of Cul4A amplification with aggressive tumor growth and poor prognosis has been suggested. Our previous study suggested that Cul4A is oncogenic in vitro, but its oncogenic role in vivo has not been studied. Methods:more » Viral delivery approaches have been used extensively to model cancer in mouse models. In our experiments, we used Cre-recombinase induced overexpression of the Cul4A gene in transgenic mice to study the role of Cul4A on lung tumor initiation and progression and have developed a new model of lung tumor development in mice harboring a conditionally expressed allele of Cul4A. Results: Here we show that the use of a recombinant adenovirus expressing Cre-recombinase (“AdenoCre”) to induce Cul4A overexpression in the lungs of mice allows controls of the timing and multiplicity of tumor initiation. Following our mouse models, we are able to study the potential role of Cul4A in the development and progression in pulmonary adenocarcinoma as well. Conclusion: Our findings indicate that Cul4A is oncogenic in vivo, and this mouse model is a tool in understanding the mechanisms of Cul4A in human cancers and for testing experimental therapies targeting Cul4A.« less

Meta-analysis of human genome-microbiome association studies: the MiBioGen consortium initiative.

PubMed

Wang, Jun; Kurilshikov, Alexander; Radjabzadeh, Djawad; Turpin, Williams; Croitoru, Kenneth; Bonder, Marc Jan; Jackson, Matthew A; Medina-Gomez, Carolina; Frost, Fabian; Homuth, Georg; Rühlemann, Malte; Hughes, David; Kim, Han-Na; Spector, Tim D; Bell, Jordana T; Steves, Claire J; Timpson, Nicolas; Franke, Andre; Wijmenga, Cisca; Meyer, Katie; Kacprowski, Tim; Franke, Lude; Paterson, Andrew D; Raes, Jeroen; Kraaij, Robert; Zhernakova, Alexandra

2018-06-08

In recent years, human microbiota, especially gut microbiota, have emerged as an important yet complex trait influencing human metabolism, immunology, and diseases. Many studies are investigating the forces underlying the observed variation, including the human genetic variants that shape human microbiota. Several preliminary genome-wide association studies (GWAS) have been completed, but more are necessary to achieve a fuller picture. Here, we announce the MiBioGen consortium initiative, which has assembled 18 population-level cohorts and some 19,000 participants. Its aim is to generate new knowledge for the rapidly developing field of microbiota research. Each cohort has surveyed the gut microbiome via 16S rRNA sequencing and genotyped their participants with full-genome SNP arrays. We have standardized the analytical pipelines for both the microbiota phenotypes and genotypes, and all the data have been processed using identical approaches. Our analysis of microbiome composition shows that we can reduce the potential artifacts introduced by technical differences in generating microbiota data. We are now in the process of benchmarking the association tests and performing meta-analyses of genome-wide associations. All pipeline and summary statistics results will be shared using public data repositories. We present the largest consortium to date devoted to microbiota-GWAS. We have adapted our analytical pipelines to suit multi-cohort analyses and expect to gain insight into host-microbiota cross-talk at the genome-wide level. And, as an open consortium, we invite more cohorts to join us (by contacting one of the corresponding authors) and to follow the analytical pipeline we have developed.

Association of complementary and alternative medicine use with highly active antiretroviral therapy initiation.

PubMed

Merenstein, Daniel; Yang, Yang; Schneider, Michael F; Goparaju, Lakshmi; Weber, Kathleen; Sharma, Anjali; Levine, Alexandra M; Sharp, Gerald B; Gandhi, Monica; Liu, Chenglong

2008-01-01

To assess whether complementary and alternative medicine (CAM) use is associated with the timing of highly active antiretroviral therapy (HAART) initiation among human immunodeficiency virus (HIV)-infected participants of the Women's Interagency HIV Study. Prospective cohort study between January 1996 and March 2002. Differences in the cumulative incidence of HAART initiation were compared between CAM users and non-CAM users using a logrank test. Cox regression model was used to assess associations of CAM exposures with time to HAART initiation. MAIN OUTCOME AND EXPOSURES: Study outcome was time from January 1996 to initiation of HAART. Primary exposure was use of any CAM modality before January 1996, and secondary exposures included the number and type of CAM modalities used (ingestible CAM medication, body practice, or spiritual healing) during the same period. One thousand thirty-four HIV-infected women contributed a total of 4987 person-visits during follow-up. At any time point, the cumulative incidence of HAART initiation among CAM users was higher than that among non-CAM users. After adjustment for potential confounders, those reporting CAM use were 1.34 times (95% confidence interval: 1.09, 1.64) more likely to initiate HAART than non-CAM users. Female CAM users initiated HAART regimens earlier than non-CAM users. Initiation of HAART is an important clinical marker, but more research is needed to elucidate the role specific CAM modalities play in HIV disease progression.

Initial evaluation of the use of USPIO cell labeling and noninvasive MR monitoring of human tissue-engineered vascular grafts in vivo.

PubMed

Nelson, G N; Roh, J D; Mirensky, T L; Wang, Y; Yi, T; Tellides, G; Pober, J S; Shkarin, P; Shapiro, E M; Saltzman, W M; Papademetris, X; Fahmy, T M; Breuer, C K

2008-11-01

This pilot study examines noninvasive MR monitoring of tissue-engineered vascular grafts (TEVGs) in vivo using cells labeled with iron oxide nanoparticles. Human aortic smooth muscle cells (hASMCs) were labeled with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. The labeled hASMCs, along with human aortic endothelial cells, were incorporated into eight TEVGs and were then surgically implanted as aortic interposition grafts in a C.B-17 SCID/bg mouse host. USPIO-labeled hASMCs persisted in the grafts throughout a 3 wk observation period and allowed noninvasive MR imaging of the human TEVGs for real-time, serial monitoring of hASMC retention. This study demonstrates the feasibility of applying noninvasive imaging techniques for evaluation of in vivo TEVG performance.

An initial evaluation of newly proposed biomarker of zinc status in humans - linoleic acid: dihomo-γ-linolenic acid (LA:DGLA) ratio.

PubMed

Knez, Marija; Stangoulis, James C R; Zec, Manja; Debeljak-Martacic, Jasmina; Pavlovic, Zoran; Gurinovic, Mirjana; Glibetic, Maria

2016-10-01

Zinc is an essential micronutrient for humans with important physiological functions. A sensitive and specific biomarker for assessing Zn status is still needed. The major aim of this study was to examine if the changes in the content of plasma phospholipid LA, DGLA and LA: DGLA ratio can be used to efficiently predict the dietary Zn intake and plasma Zn status of humans. The study was performed on healthy human volunteers, 25-55 years of age. The dietary Zn intake was assessed using 24 h recall questionnaires. Plasma phospholipid fatty acid analysis was done by gas chromatography, and plasma analysis of minerals by atomic absorption spectrometry. Biochemical, anthropometrical and hematological parameters were assessed. No significant relationship was found between the dietary and plasma zinc status (r = 0.07; p = 0.6). There was a statistically significant correlation between DGLA and plasma Zn (r = 0.39, p = 0.00). No relationship was observed between the linoleic acid and plasma Zn, while there was a significant negative correlation between LA: DGLA ratio and plasma Zn status (r = -0.35, p = 0.01). Similarly, there were statistically significant difference in DGLA status (p = 0.004) and LA: DGLA ratio (p = 0.042) between the Zn formed groups. This study is an initial step in evaluating LA: DGLA ratio as a biomarker of Zn status in humans. The results are encouraging as they show that concentration of DGLA is decreased and LA: DGLA ratio increased in people with lower dietary Zn intake. However, additional studies are needed to fully examine the sensitivity of this biomarker. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Ozone reaction with clothing and its initiated VOC emissions in an environmental chamber.

PubMed

Rai, A C; Guo, B; Lin, C-H; Zhang, J; Pei, J; Chen, Q

2014-02-01

Human health is adversely affected by ozone and the volatile organic compounds (VOCs) produced from its reactions in the indoor environment. Hence, it is important to characterize the ozone-initiated reactive chemistry under indoor conditions and study the influence of different factors on these reactions. This investigation studied the ozone reactions with clothing through a series of experiments conducted in an environmental chamber under various conditions. The study found that the ozone reactions with a soiled (human-worn) T-shirt consumed ozone and generated VOCs. The ozone removal rate and deposition velocity for the T-shirt increased with the increasing soiling level and air change rate, decreased at high ozone concentrations, and were relatively unaffected by the humidity. The deposition velocity for the soiled T-shirt ranged from 0.15 to 0.29 cm/s. The ozone-initiated VOC emissions included C6-C10 straight-chain saturated aldehydes, acetone, and 4-OPA (4-oxopentanal). The VOC emissions were generally higher at higher ozone, humidity, soiling of T-shirt, and air change rate. The total molar yield was approximately 0.5 in most cases, which means that for every two moles of ozone removed by the T-shirt surface, one mole of VOCs was produced. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Computer simulations of the interaction of human immunodeficiency virus (HIV) aspartic protease with spherical gold nanoparticles: implications in acquired immunodeficiency syndrome (AIDS)

NASA Astrophysics Data System (ADS)

Whiteley, Chris G.; Lee, Duu-Jong

2016-09-01

The interaction of gold nanoparticles (AuNP) with human immune-deficiency virus aspartic protease (HIVPR) is modelled using a regime of molecular dynamics simulations. The simulations of the ‘docking’, first as a rigid-body complex, and eventually through flexible-fit analysis, creates 36 different complexes from four initial orientations of the nanoparticle strategically positioned around the surface of the enzyme. The structural deviations of the enzymes from the initial x-ray crystal structure during each docking simulation are assessed by comparative analysis of secondary structural elements, root mean square deviations, B-factors, interactive bonding energies, dihedral angles, radius of gyration (R g), circular dichroism (CD), volume occupied by C α , electrostatic potentials, solvation energies and hydrophobicities. Normalisation of the data narrows the selection from the initial 36 to one ‘final’ probable structure. It is concluded that, after computer simulations on each of the 36 initial complexes incorporating the 12 different biophysical techniques, the top five complexes are the same no matter which technique is explored. The significance of the present work is an expansion of an earlier study on the molecular dynamic simulation for the interaction of HIVPR with silver nanoparticles. This work is supported by experimental evidence since the initial ‘orientation’ of the AgNP with the enzyme is the same as the ‘final’ AuNP-HIVPR complex generated in the present study. The findings will provide insight into the forces of the binding of the HIVPR to AuNP. It is anticipated that the protocol developed in this study will act as a standard process for the interaction of any nanoparticle with any biomedical target.

Computer simulations of the interaction of human immunodeficiency virus (HIV) aspartic protease with spherical gold nanoparticles: implications in acquired immunodeficiency syndrome (AIDS).

PubMed

Whiteley, Chris G; Lee, Duu-Jong

2016-09-09

The interaction of gold nanoparticles (AuNP) with human immune-deficiency virus aspartic protease (HIVPR) is modelled using a regime of molecular dynamics simulations. The simulations of the 'docking', first as a rigid-body complex, and eventually through flexible-fit analysis, creates 36 different complexes from four initial orientations of the nanoparticle strategically positioned around the surface of the enzyme. The structural deviations of the enzymes from the initial x-ray crystal structure during each docking simulation are assessed by comparative analysis of secondary structural elements, root mean square deviations, B-factors, interactive bonding energies, dihedral angles, radius of gyration (R g), circular dichroism (CD), volume occupied by C α , electrostatic potentials, solvation energies and hydrophobicities. Normalisation of the data narrows the selection from the initial 36 to one 'final' probable structure. It is concluded that, after computer simulations on each of the 36 initial complexes incorporating the 12 different biophysical techniques, the top five complexes are the same no matter which technique is explored. The significance of the present work is an expansion of an earlier study on the molecular dynamic simulation for the interaction of HIVPR with silver nanoparticles. This work is supported by experimental evidence since the initial 'orientation' of the AgNP with the enzyme is the same as the 'final' AuNP-HIVPR complex generated in the present study. The findings will provide insight into the forces of the binding of the HIVPR to AuNP. It is anticipated that the protocol developed in this study will act as a standard process for the interaction of any nanoparticle with any biomedical target.

ASSOCIATION OF COMPLEMENTARY AND ALTERNATIVE MEDICINE USE WITH HIGHLY ACTIVE ANTIRETROVIRAL THERAPY INITIATION

PubMed Central

Merenstein, Daniel; Yang, Yang; Schneider, Michael F.; Goparaju, Lakshmi; Weber, Kathleen; Sharma, Anjali; Levine, Alexandra M.; Sharp, Gerald B.; Gandhi, Monica; Liu, Chenglong

2009-01-01

Objective To assess whether complementary and alternative medicine (CAM) use is associated with the timing of highly active antiretroviral therapy (HAART) initiation among human immunodeficiency virus (HIV)–infected participants of the Women’s Interagency HIV Study. Study Methods Prospective cohort study between January 1996 and March 2002. Differences in the cumulative incidence of HAART initiation were compared between CAM users and non–CAM users using a logrank test. Cox regression model was used to assess associations of CAM exposures with time to HAART initiation. Main Outcome and Exposures Study outcome was time from January 1996 to initiation of HAART. Primary exposure was use of any CAM modality before January 1996, and secondary exposures included the number and type of CAM modalities used (ingestible CAM medication, body practice, or spiritual healing) during the same period. Results One thousand thirty-four HIV-infected women contributed a total of 4987 person-visits during follow-up. At any time point, the cumulative incidence of HAART initiation among CAM users was higher than that among non–CAM users. After adjustment for potential confounders, those reporting CAM use were 1.34 times (95% confidence interval: 1.09, 1.64) more likely to initiate HAART than non–CAM users. Conclusion Female CAM users initiated HAART regimens earlier than non–CAM users. Initiation of HAART is an important clinical marker, but more research is needed to elucidate the role specific CAM modalities play in HIV disease progression. PMID:18780580

Initial description of a quantitative, cross-species (chimpanzee-human) social responsiveness measure

PubMed Central

Marrus, Natasha; Faughn, Carley; Shuman, Jeremy; Petersen, Steve; Constantino, John; Povinelli, Daniel; Pruett, John R.

2011-01-01

Objective Comparative studies of social responsiveness, an ability that is impaired in autistic spectrum disorders, can inform our understanding of both autism and the cognitive architecture of social behavior. Because there is no existing quantitative measure of social responsiveness in chimpanzees, we generated a quantitative, cross-species (human-chimpanzee) social responsiveness measure. Method We translated the Social Responsiveness Scale (SRS), an instrument that quantifies human social responsiveness, into an analogous instrument for chimpanzees. We then retranslated this "Chimp SRS" into a human "Cross-Species SRS" (XSRS). We evaluated three groups of chimpanzees (n=29) with the Chimp SRS and typical and autistic spectrum disorder (ASD) human children (n=20) with the XSRS. Results The Chimp SRS demonstrated strong inter-rater reliability at the three sites (ranges for individual ICCs: .534–.866 and mean ICCs: .851–.970). As has been observed in humans, exploratory principal components analysis of Chimp SRS scores supports a single factor underlying chimpanzee social responsiveness. Human subjects' XSRS scores were fully concordant with their SRS scores (r=.976, p=.001) and distinguished appropriately between typical and ASD subjects. One chimpanzee known for inappropriate social behavior displayed a significantly higher score than all other chimpanzees at its site, demonstrating the scale's ability to detect impaired social responsiveness in chimpanzees. Conclusion Our initial cross-species social responsiveness scale proved reliable and discriminated differences in social responsiveness across (in a relative sense) and within (in a more objectively quantifiable manner) humans and chimpanzees. PMID:21515200

National human genome projects: an update and an agenda.

PubMed

An, Joon Yong

2017-01-01

Population genetic and human genetic studies are being accelerated with genome technology and data sharing. Accordingly, in the past 10 years, several countries have initiated genetic research using genome technology and identified the genetic architecture of the ethnic groups living in the corresponding country or suggested the genetic foundation of a social phenomenon. Genetic research has been conducted from epidemiological studies that previously described the health or disease conditions in defined population. This perspective summarizes national genome projects conducted in the past 10 years and introduces case studies to utilize genomic data in genetic research.

Medical management of ectopic pregnancy with single-dose and 2-dose methotrexate protocols: human chorionic gonadotropin trends and patient outcomes.

PubMed

Mergenthal, Michelle C; Senapati, Suneeta; Zee, Jarcy; Allen-Taylor, Lynne; Whittaker, Paul G; Takacs, Peter; Sammel, Mary D; Barnhart, Kurt T

2016-11-01

Ectopic pregnancy, although rare, is an important cause of female morbidity and mortality and early, effective treatment is critical. Systemic methotrexate has become widely accepted as a safe and effective alternative to surgery in the stable patient. As the number and timing of methotrexate doses differ in the 3 main medical treatment regimens, one might expect trends in serum human chorionic gonadotropin and time to resolution to vary depending on protocol. Furthermore, human chorionic gonadotropin trends and time to resolution may predict ultimate treatment success. This study hypothesized that the 2-dose methotrexate protocol would be associated with a faster initial decline in serum human chorionic gonadotropin levels and a shorter time to resolution compared to the single-dose protocol. A prospective multicenter cohort study included clinical data from women who received medical management for ectopic pregnancy. Rates of human chorionic gonadotropin change and successful pregnancy resolution were assessed. Propensity score modeling addressed confounding by indication, the potential for differential assignment of patients with better prognosis to the single-dose methotrexate protocol. In all, 162 ectopic pregnancies were in the final analysis; 114 (70%) were treated with the single-dose methotrexate and 48 (30%) with the 2-dose protocol. Site, race, ethnicity, and reported pain level were associated with differential protocol allocation (P < .001, P = .011, P < .001, and P = .035, respectively). Women had similar initial human chorionic gonadotropin levels in either protocol but the mean rate of decline of human chorionic gonadotropin from day 0 (day of administration of first dose of methotrexate) to day 7 was significantly more rapid in women who received the single-dose protocol compared to those treated with the 2-dose protocol (mean change -31.3% vs -10.4%, P = .037, adjusted for propensity score and site). The 2 protocols had no significant differences in success rate or time to resolution. In a racially and geographically diverse group of women, the single- and double-dose methotrexate protocols had comparable outcomes. The more rapid human chorionic gonadotropin initial decline in the single-dose group suggested these patients were probably at lower risk for ectopic rupture than those getting the 2-dose protocol. A prospective randomized controlled design is needed to remove confounding by indication. Copyright © 2016 Elsevier Inc. All rights reserved.

Genital tract lesions in sexually mature Göttingen minipigs during the initial stages of experimental vaginal infection with Chlamydia trachomatis serovar D.

PubMed

Erneholm, Karin; Lorenzen, Emma; Bøje, Sarah; Olsen, Anja Weinreich; Andersen, Peter; Cassidy, Joseph P; Follmann, Frank; Jensen, Henrik E; Agerholm, Jørgen S

2016-09-10

Chlamydia is one of the most common sexually transmitted diseases in humans worldwide, causing chronic lesions in the reproductive tract. Due to its often asymptomatic course, there is limited knowledge about the initial changes in the genital tract following infection. This study employs a novel sexually mature minipig model to investigate the initial histopathological changes following vaginal infection with Chlamydia trachomatis serovar D. A vaginal inoculation resulted in an infection primarily affecting the lower genital tract. The histopathological changes were characterized by a subepithelial inflammation consisting of neutrophils and mononuclear cells, followed by an increase in the number of plasma cells within the sub-epithelial stroma of the vagina. Detection of Chlamydia was associated with expression of cyclooxygenase-2 and interleukin-8 by superficial epithelial cells. The infection was self-limiting, with a duration of 7 days. Neutrophils, plasma cells and IL-8 have been linked with Chlamydia genital infection of unknown duration in human patients. In this study, we observe a similar pattern of local immune response/inflammation following experimental inoculation suggesting this porcine model shows promise as a model for translational chlamydia research.

Stimulating collaboration between human and veterinary health care professionals.

PubMed

Eussen, Björn G M; Schaveling, Jaap; Dragt, Maria J; Blomme, Robert Jan

2017-06-13

Despite the need to control outbreaks of (emerging) zoonotic diseases and the need for added value in comparative/translational medicine, jointly addressed in the One Health approach [One health Initiative (n.d.a). About the One Health Initiative. http://www.onehealthinitiative.com/about.php . Accessed 13 September 2016], collaboration between human and veterinary health care professionals is limited. This study focuses on the social dilemma experienced by health care professionals and ways in which an interdisciplinary approach could be developed. Based on Gaertner and Dovidio's Common Ingroup Identity Model, a number of questionnaires were designed and tested; with PROGRESS, the relation between collaboration and common goal was assessed, mediated by decategorization, recategorization, mutual differentiation and knowledge sharing. This study confirms the Common Ingroup Identity Model stating that common goals stimulate collaboration. Decategorization and mutual differentiation proved to be significant in this relationship; recategorization and knowledge sharing mediate this relation. It can be concluded that the Common Ingroup Identity Model theory helps us to understand how health care professionals perceive the One Health initiative and how they can intervene in this process. In the One Health approach, professional associations could adopt a facilitating role.

Contracting and Procurement for Evidence-Based Interventions in Public-Sector Human Services: A Case Study

PubMed Central

Willging, Cathleen E.; Aarons, Gregory A.; Trott, Elise M.; Green, Amy E.; Finn, Natalie; Ehrhart, Mark G.; Hecht, Debra B.

2016-01-01

Sustainment of evidence-based interventions (EBIs) in human services depends on the inner context of community-based organizations (CBOs) that provide services and the outer context of their broader environment. Increasingly, public officials are experimenting with contracting models from for-profit industries to procure human services. In this case study, we conducted qualitative interviews with key government and CBO stakeholders to examine implementation of the Best Value-Performance Information Procurement System to contract for EBIs in a child welfare system. Findings suggest that stakeholder relationships may be compromised when procurement disregards local knowledge, communication, collaboration, and other factors supporting EBIs and public health initiatives. PMID:26386977

Pharmacokinetics of Snake Venom

PubMed Central

Sanhajariya, Suchaya; Duffull, Stephen B.

2018-01-01

Understanding snake venom pharmacokinetics is essential for developing risk assessment strategies and determining the optimal dose and timing of antivenom required to bind all venom in snakebite patients. This review aims to explore the current knowledge of snake venom pharmacokinetics in animals and humans. Literature searches were conducted using EMBASE (1974–present) and Medline (1946–present). For animals, 12 out of 520 initially identified studies met the inclusion criteria. In general, the disposition of snake venom was described by a two-compartment model consisting of a rapid distribution phase and a slow elimination phase, with half-lives of 5 to 48 min and 0.8 to 28 h, respectively, following rapid intravenous injection of the venoms or toxins. When the venoms or toxins were administered intramuscularly or subcutaneously, an initial absorption phase and slow elimination phase were observed. The bioavailability of venoms or toxins ranged from 4 to 81.5% following intramuscular administration and 60% following subcutaneous administration. The volume of distribution and the clearance varied between snake species. For humans, 24 out of 666 initially identified publications contained sufficient information and timed venom concentrations in the absence of antivenom therapy for data extraction. The data were extracted and modelled in NONMEM. A one-compartment model provided the best fit, with an elimination half-life of 9.71 ± 1.29 h. It is intended that the quantitative information provided in this review will provide a useful basis for future studies that address the pharmacokinetics of snakebite in humans. PMID:29414889

Cooperation in Human-Agent Systems to Support Resilience: A Microworld Experiment.

PubMed

Chiou, Erin K; Lee, John D

2016-09-01

This study uses a dyadic approach to understand human-agent cooperation and system resilience. Increasingly capable technology fundamentally changes human-machine relationships. Rather than reliance on or compliance with more or less reliable automation, we investigate interaction strategies with more or less cooperative agents. A joint-task microworld scenario was developed to explore the effects of agent cooperation on participant cooperation and system resilience. To assess the effects of agent cooperation on participant cooperation, 36 people coordinated with a more or less cooperative agent by requesting resources and responding to requests for resources in a dynamic task environment. Another 36 people were recruited to assess effects following a perturbation in their own hospital. Experiment 1 shows people reciprocated the cooperative behaviors of the agents; a low-cooperation agent led to less effective interactions and less resource sharing, whereas a high-cooperation agent led to more effective interactions and greater resource sharing. Experiment 2 shows that an initial fast-tempo perturbation undermined proactive cooperation-people tended to not request resources. However, the initial fast tempo had little effect on reactive cooperation-people tended to accept resource requests according to cooperation level. This study complements the supervisory control perspective of human-automation interaction by considering interdependence and cooperation rather than the more common focus on reliability and reliance. The cooperativeness of automated agents can influence the cooperativeness of human agents. Design and evaluation for resilience in teams involving increasingly autonomous agents should consider the cooperative behaviors of these agents. © 2016, Human Factors and Ergonomics Society.

Investigating RAS Signaling in Cancer | Office of Cancer Clinical Proteomics Research

Cancer.gov

CPTAC expertise has been charged to develop RAS specific targeted proteomic assays to study the important pathways of human cancer. The oncogene RAS is linked to 30 percent of human cancers, but the search for a targeted therapy for RAS has remained elusive. To advance our understanding of this oncogene and to develop improved targeted therapies against RAS pathway, the National Cancer Institute (NCI) has launched a RAS Initiative.

Signal Analysis of Visual Evoked Responses.

DTIC Science & Technology

1983-12-01

T-IE PRO3LEM The interest of the Air Force was in the study of: initially, animal VERs; and, later, human subject VERs. Fo,. obvious reasons, the...data re- oorded from human subjects were restricted to scalp electrode recordings. By ;ontrast, in the animal preparations, epitural bipolar electrode...left em sherechannel # 1 rigt hemisphere_______ _______ channel # 3 HP HPJ HP bT channel # 4 it 5 #t 6 Figure 6.4. Specification of channels. HP

Development of preference for conspecific faces in human infants.

PubMed

Sanefuji, Wakako; Wada, Kazuko; Yamamoto, Tomoka; Mohri, Ikuko; Taniike, Masako

2014-04-01

Previous studies have proposed that humans may be born with mechanisms that attend to conspecifics. However, as previous studies have relied on stimuli featuring human adults, it remains unclear whether infants attend only to adult humans or to the entire human species. We found that 1-month-old infants (n = 23) were able to differentiate between human and monkey infants' faces; however, they exhibited no preference for human infants' faces over monkey infants' faces (n = 24) and discriminated individual differences only within the category of human infants' faces (n = 30). We successfully replicated previous findings that 1-month-old infants (n = 42) preferred adult humans, even adults of other races, to adult monkeys. Further, by 3 months of age, infants (n = 55) preferred human faces to monkey faces with both infant and adult stimuli. Human infants' spontaneous preference for conspecific faces appears to be initially limited to conspecific adults and afterward extended to conspecific infants. Future research should attempt to determine whether preference for human adults results from some innate tendency to attend to conspecific adults or from the impact of early experiences with adults. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Deciphering DNA replication dynamics in eukaryotic cell populations in relation with their averaged chromatin conformations

NASA Astrophysics Data System (ADS)

Goldar, A.; Arneodo, A.; Audit, B.; Argoul, F.; Rappailles, A.; Guilbaud, G.; Petryk, N.; Kahli, M.; Hyrien, O.

2016-03-01

We propose a non-local model of DNA replication that takes into account the observed uncertainty on the position and time of replication initiation in eukaryote cell populations. By picturing replication initiation as a two-state system and considering all possible transition configurations, and by taking into account the chromatin’s fractal dimension, we derive an analytical expression for the rate of replication initiation. This model predicts with no free parameter the temporal profiles of initiation rate, replication fork density and fraction of replicated DNA, in quantitative agreement with corresponding experimental data from both S. cerevisiae and human cells and provides a quantitative estimate of initiation site redundancy. This study shows that, to a large extent, the program that regulates the dynamics of eukaryotic DNA replication is a collective phenomenon that emerges from the stochastic nature of replication origins initiation.

Cell of Origin: Exploring an Alternative Contributor to Ovarian Cancer

DTIC Science & Technology

2014-09-01

previously shown that DDX4 is expressed in ovarian carcinomas and its expression is associated with age and the serous histophenotype. Thus, we analyzed...oncogenic alleles of human TP53, AKT1, KRAS, and PIK3CA were constructed and initially validated in both a human endometrial cancer cell line and mouse...AKT1, KRAS, or PIK3CA were successfully constructed. 9. The viral constructs were initially validated in a human endometrial cancer cell line and

Signaling hierarchy regulating human endothelial cell development.

PubMed

Kelly, Melissa A; Hirschi, Karen K

2009-05-01

Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these studies. Using human embryonic stem cells as a model system, we were able to reproducibly and robustly generate differentiated endothelial cells via coculture on OP9 marrow stromal cells. We found that, in contrast to studies in the mouse, bFGF and VEGF had no specific effects on the initiation of human vasculogenesis. However, exogenous Ihh promoted endothelial cell differentiation, as evidenced by increased production of cells with cobblestone morphology that coexpress multiple endothelial-specific genes and proteins, form lumens, and exhibit DiI-AcLDL uptake. Inhibition of BMP signaling using Noggin or BMP4, specifically, using neutralizing antibodies suppressed endothelial cell formation; whereas, addition of rhBMP4 to cells treated with the hedgehog inhibitor cyclopamine rescued endothelial cell development. Our studies revealed that Ihh promoted human endothelial cell differentiation from pluripotent hES cells via BMP signaling, providing novel insights applicable to modulating human endothelial cell formation and vascular regeneration for human clinical therapies.

Dual Extended Kalman Filter for the Identification of Time-Varying Human Manual Control Behavior

NASA Technical Reports Server (NTRS)

Popovici, Alexandru; Zaal, Peter M. T.; Pool, Daan M.

2017-01-01

A Dual Extended Kalman Filter was implemented for the identification of time-varying human manual control behavior. Two filters that run concurrently were used, a state filter that estimates the equalization dynamics, and a parameter filter that estimates the neuromuscular parameters and time delay. Time-varying parameters were modeled as a random walk. The filter successfully estimated time-varying human control behavior in both simulated and experimental data. Simple guidelines are proposed for the tuning of the process and measurement covariance matrices and the initial parameter estimates. The tuning was performed on simulation data, and when applied on experimental data, only an increase in measurement process noise power was required in order for the filter to converge and estimate all parameters. A sensitivity analysis to initial parameter estimates showed that the filter is more sensitive to poor initial choices of neuromuscular parameters than equalization parameters, and bad choices for initial parameters can result in divergence, slow convergence, or parameter estimates that do not have a real physical interpretation. The promising results when applied to experimental data, together with its simple tuning and low dimension of the state-space, make the use of the Dual Extended Kalman Filter a viable option for identifying time-varying human control parameters in manual tracking tasks, which could be used in real-time human state monitoring and adaptive human-vehicle haptic interfaces.

Incorporating Human Readiness Levels at Sandia National Laboratories

DOE PAGES

See, Judi E.; Morris, Jason; Craft, Richard; ...

2018-01-24

Since 2010, the concept of human readiness levels has been under development as a possible supplement to the existing technology readiness level (TRL) scale. The intent is to provide a mechanism to address safety and performance risks associated with the human component in a system that parallels the TRL structure already familiar to the systems engineering community. Sandia National Laboratories in Albuquerque, New Mexico, initiated a study in 2015 to evaluate options to incorporate human readiness planning for Sandia processes and products. The study team has collected the majority of baseline assessment data and has conducted interviews to understand staffmore » perceptions of four different options for human readiness planning. Preliminary results suggest that all four options may have a vital role, depending on the type of work performed and the phase of product development. Upon completion of data collection, the utility of identified solutions will be assessed in one or more test cases.« less

Incorporating Human Readiness Levels at Sandia National Laboratories

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

See, Judi E.; Morris, Jason; Craft, Richard

Since 2010, the concept of human readiness levels has been under development as a possible supplement to the existing technology readiness level (TRL) scale. The intent is to provide a mechanism to address safety and performance risks associated with the human component in a system that parallels the TRL structure already familiar to the systems engineering community. Sandia National Laboratories in Albuquerque, New Mexico, initiated a study in 2015 to evaluate options to incorporate human readiness planning for Sandia processes and products. The study team has collected the majority of baseline assessment data and has conducted interviews to understand staffmore » perceptions of four different options for human readiness planning. Preliminary results suggest that all four options may have a vital role, depending on the type of work performed and the phase of product development. Upon completion of data collection, the utility of identified solutions will be assessed in one or more test cases.« less

The Best Possible Intentions Testing Prophylactic Approaches on Humans in Developing Countries

PubMed Central

2013-01-01

Debates on human experiments in developing countries focus on ethical principles such as informed consent, accountability, involvement of the concerned communities, and the improvement of local health services. Public health specialists who conducted human experiments in Rio de Janeiro (1902–1905) and in Guatemala (1947–1948) believed, however, that they were acting in the best interests of local populations, were aware of the importance of informed consent, were closely collaborating with local health professionals, and were contributing to the development of local health structures. Nevertheless, their investigations went dramatically wrong. An initial desire to conduct ethically and scientifically sound studies was undermined by pressure to obtain results and to save the researchers’ initial investment, the possibility of freely using hospitalized patients as experimental participants, uncritical help from local professional elites, and structural pitfalls of experimenting with severely deprived people. These elements can still be found in trials of preventive methods in the Global South. PMID:23237168

Development Education and Multi-Ethnic Education: Some Tensions. Development Education Paper No. 21.

ERIC Educational Resources Information Center

Storm, Michael

The document examines the relationships between multi-ethnic and development education in Great Britain. Multi-ethnic education, initially with a national focus, has a global dimension, and development education, initially with a global focus, has a national and even local dimension. A common interest in human diversity and human inequalities…

76 FR 28803 - Notice of Availability: Notice of Funding Availability (NOFA) for HUD's Fiscal Year (FY) 2011...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-18

... these funds at least $5 million shall be made available for rural capacity building activities. Purpose...), the Local Initiatives Support Corporation (LISC), and Habitat for Humanity International. Specifically... Initiatives Support Corporation, 501 Seventh Avenue, 7th Floor, New York, NY 10018. Habitat for Humanity...

Human liver proteome project: plan, progress, and perspectives.

PubMed

He, Fuchu

2005-12-01

The Human Liver Proteome Project is the first initiative of the human proteome project for human organs/tissues and aims at writing a modern Prometheus myth. Its global scientific objectives are to reveal the "solar system" of the human liver proteome, expression profiles, modification profiles, a protein linkage (protein-protein interaction) map, and a proteome localization map, and to define an ORFeome, physiome, and pathome. Since it was first proposed in April 2002, the Human Liver Proteome Project has attracted more than 100 laboratories from all over the world. In the ensuing 3 years, we set up a management infrastructure, identified reference laboratories, confirmed standard operating procedures, initiated international research collaborations, and finally achieved the first set of expression profile data.

Space Exploration Initiative: Chronology

NASA Technical Reports Server (NTRS)

McCurdy, Howard E.

1992-01-01

This chronology gives an overview of the human space exploration initiative from 1956 through 1989. Details are given for the political milestones of the initiative, including information on presidential mandates and NASA Administrator appointments.

The effect of simulator motion cues on initial training of airline pilots

DOT National Transportation Integrated Search

2005-08-15

Two earlier studies conducted in the framework of the Federal Aviation Administration/Volpe Flight Simulator Human Factors Program examining the effect of simulator motion on recurrent training and evaluation of airline pilots have found that in the ...

PROSPECTIVE PREGNANCY STUDY DESIGNS FOR ASSESSING REPRODUCTIVE AND DEVELOPMENTAL TOXICANTS

EPA Science Inventory

Of late, there is increasing recognition that exposures before, at or shortly after conception have life-long implications for human reproduction and development. Despite this evolving literature, few research initiatives have been designed to empirically evaluate exposures durin...

Origins of spatial, temporal and numerical cognition: Insights from comparative psychology.

PubMed

Haun, Daniel B M; Jordan, Fiona M; Vallortigara, Giorgio; Clayton, Nicky S

2010-12-01

Contemporary comparative cognition has a large repertoire of animal models and methods, with concurrent theoretical advances that are providing initial answers to crucial questions about human cognition. What cognitive traits are uniquely human? What are the species-typical inherited predispositions of the human mind? What is the human mind capable of without certain types of specific experiences with the surrounding environment? Here, we review recent findings from the domains of space, time and number cognition. These findings are produced using different comparative methodologies relying on different animal species, namely birds and non-human great apes. The study of these species not only reveals the range of cognitive abilities across vertebrates, but also increases our understanding of human cognition in crucial ways. Copyright © 2010 Elsevier Ltd. All rights reserved.

[The human variome project and its progress].

PubMed

Gao, Shan; Zhang, Ning; Zhang, Lei; Duan, Guang-You; Zhang, Tao

2010-11-01

The main goal of post genomics is to explain how the genome, the map of which has been constructed in the Human Genome Project, affacts activities of life. This leads to generate multiple "omics": structural genomics, functional genomics, proteomics, metabonomics, et al. In Jun. 2006, Melbourne, Australia, Human Genome Variation Society (HGVS) initiated the Human Variome Project (HVP) to collect all the sequence variation and polymorphism data worldwidely. HVP is to search and determine those mutations related with human diseases by association study between genetype and phenotype on the scale of genome level and other methods. Those results will be translated into clinical application. Considering the potential effects of this project on human health, this paper introduced its origin and main content in detail and discussed its meaning and prospect.

Sapovirus Translation Requires an Interaction between VPg and the Cap Binding Protein eIF4E

PubMed Central

Hosmillo, Myra; Chaudhry, Yasmin; Kim, Deok-Song

2014-01-01

ABSTRACT Sapoviruses of the Caliciviridae family of small RNA viruses are emerging pathogens that cause gastroenteritis in humans and animals. Molecular studies on human sapovirus have been hampered due to the lack of a cell culture system. In contrast, porcine sapovirus (PSaV) can be grown in cell culture, making it a suitable model for understanding the infectious cycle of sapoviruses and the related enteric caliciviruses. Caliciviruses are known to use a novel mechanism of protein synthesis that relies on the interaction of cellular translation initiation factors with the virus genome-encoded viral protein genome (VPg) protein, which is covalently linked to the 5′ end of the viral genome. Using PSaV as a representative member of the Sapovirus genus, we characterized the role of the viral VPg protein in sapovirus translation. As observed for other caliciviruses, the PSaV genome was found to be covalently linked to VPg, and this linkage was required for the translation and the infectivity of viral RNA. The PSaV VPg protein was associated with the 4F subunit of the eukaryotic translation initiation factor (eIF4F) complex in infected cells and bound directly to the eIF4E protein. As has been previously demonstrated for feline calicivirus, a member of the Vesivirus genus, PSaV translation required eIF4E and the interaction between eIF4E and eIF4G. Overall, our study provides new insights into the novel mechanism of sapovirus translation, suggesting that sapovirus VPg can hijack the cellular translation initiation mechanism by recruiting the eIF4F complex through a direct eIF4E interaction. IMPORTANCE Sapoviruses, which are members of the Caliciviridae family, are one of the causative agents of viral gastroenteritis in humans. However, human sapovirus remains noncultivable in cell culture, hampering the ability to characterize the virus infectious cycle. Here, we show that the VPg protein from porcine sapovirus, the only cultivatable sapovirus, is essential for viral translation and functions via a direct interaction with the cellular translation initiation factor eIF4E. This work provides new insights into the novel protein-primed mechanism of calicivirus VPg-dependent translation initiation. PMID:25142584

Sapovirus translation requires an interaction between VPg and the cap binding protein eIF4E.

PubMed

Hosmillo, Myra; Chaudhry, Yasmin; Kim, Deok-Song; Goodfellow, Ian; Cho, Kyoung-Oh

2014-11-01

Sapoviruses of the Caliciviridae family of small RNA viruses are emerging pathogens that cause gastroenteritis in humans and animals. Molecular studies on human sapovirus have been hampered due to the lack of a cell culture system. In contrast, porcine sapovirus (PSaV) can be grown in cell culture, making it a suitable model for understanding the infectious cycle of sapoviruses and the related enteric caliciviruses. Caliciviruses are known to use a novel mechanism of protein synthesis that relies on the interaction of cellular translation initiation factors with the virus genome-encoded viral protein genome (VPg) protein, which is covalently linked to the 5' end of the viral genome. Using PSaV as a representative member of the Sapovirus genus, we characterized the role of the viral VPg protein in sapovirus translation. As observed for other caliciviruses, the PSaV genome was found to be covalently linked to VPg, and this linkage was required for the translation and the infectivity of viral RNA. The PSaV VPg protein was associated with the 4F subunit of the eukaryotic translation initiation factor (eIF4F) complex in infected cells and bound directly to the eIF4E protein. As has been previously demonstrated for feline calicivirus, a member of the Vesivirus genus, PSaV translation required eIF4E and the interaction between eIF4E and eIF4G. Overall, our study provides new insights into the novel mechanism of sapovirus translation, suggesting that sapovirus VPg can hijack the cellular translation initiation mechanism by recruiting the eIF4F complex through a direct eIF4E interaction. Sapoviruses, which are members of the Caliciviridae family, are one of the causative agents of viral gastroenteritis in humans. However, human sapovirus remains noncultivable in cell culture, hampering the ability to characterize the virus infectious cycle. Here, we show that the VPg protein from porcine sapovirus, the only cultivatable sapovirus, is essential for viral translation and functions via a direct interaction with the cellular translation initiation factor eIF4E. This work provides new insights into the novel protein-primed mechanism of calicivirus VPg-dependent translation initiation. Copyright © 2014 Hosmillo et al.

Transient cardio-respiratory responses to visually induced tilt illusions

NASA Technical Reports Server (NTRS)

Wood, S. J.; Ramsdell, C. D.; Mullen, T. J.; Oman, C. M.; Harm, D. L.; Paloski, W. H.

2000-01-01

Although the orthostatic cardio-respiratory response is primarily mediated by the baroreflex, studies have shown that vestibular cues also contribute in both humans and animals. We have demonstrated a visually mediated response to illusory tilt in some human subjects. Blood pressure, heart and respiration rate, and lung volume were monitored in 16 supine human subjects during two types of visual stimulation, and compared with responses to real passive whole body tilt from supine to head 80 degrees upright. Visual tilt stimuli consisted of either a static scene from an overhead mirror or constant velocity scene motion along different body axes generated by an ultra-wide dome projection system. Visual vertical cues were initially aligned with the longitudinal body axis. Subjective tilt and self-motion were reported verbally. Although significant changes in cardio-respiratory parameters to illusory tilts could not be demonstrated for the entire group, several subjects showed significant transient decreases in mean blood pressure resembling their initial response to passive head-up tilt. Changes in pulse pressure and a slight elevation in heart rate were noted. These transient responses are consistent with the hypothesis that visual-vestibular input contributes to the initial cardiovascular adjustment to a change in posture in humans. On average the static scene elicited perceived tilt without rotation. Dome scene pitch and yaw elicited perceived tilt and rotation, and dome roll motion elicited perceived rotation without tilt. A significant correlation between the magnitude of physiological and subjective reports could not be demonstrated.

Size of clinical trials and Introductory prices of prophylactic vaccine series

PubMed Central

Weinberg, Steven H.; Butchart, Amy T.; Davis, Matthew M.

2012-01-01

Costs of completing the recommended immunization schedule have increased over the last decade. Access to prophylactic vaccines may become limited due to financing obstacles within current delivery systems. Vaccine prices reflect research and development expenses incurred by vaccine manufacturers, including costs associated with evaluating candidate vaccines in human subjects. If the number of subjects in clinical trials is increasing over time and associated with vaccine price, this may help explain increases in prices of vaccine series. We examined whether: (A) the initial public- and private-sector prices for recommended prophylactic vaccine series licensed and recommended in the US increased from 2000–2011, (B) the number of human subjects per licensed vaccine increased during the time period, and (C) the number of human subjects was associated with the initial public–and private–sector prices of the vaccine series. In regression analyses of 13 vaccines, approval year was not significantly associated with the number of human subjects, initial public-sector prices, or initial private-sector prices. While the number of phase II subjects was not significantly associated with prices, the numbers of phase III and combined late phase (phases II + III) subjects were significantly associated with initial public- and private-sector series prices (p < 0.05). The association between number of subjects and initial prices demonstrated diminishing marginal increases in price with increasing numbers of subjects. These findings may help guide the number of subjects required by the FDA in clinical trials, in order to reduce expenses for manufacturers and thereby help mitigate increases in initial vaccine series prices. PMID:22854668

Size of clinical trials and Introductory prices of prophylactic vaccine series.

PubMed

Weinberg, Steven H; Butchart, Amy T; Davis, Matthew M

2012-08-01

Costs of completing the recommended immunization schedule have increased over the last decade. Access to prophylactic vaccines may become limited due to financing obstacles within current delivery systems. Vaccine prices reflect research and development expenses incurred by vaccine manufacturers, including costs associated with evaluating candidate vaccines in human subjects. If the number of subjects in clinical trials is increasing over time and associated with vaccine price, this may help explain increases in prices of vaccine series. We examined whether: (A) the initial public- and private-sector prices for recommended prophylactic vaccine series licensed and recommended in the US increased from 2000-2011, (B) the number of human subjects per licensed vaccine increased during the time period, and (C) the number of human subjects was associated with the initial public-and private-sector prices of the vaccine series. In regression analyses of 13 vaccines, approval year was not significantly associated with the number of human subjects, initial public-sector prices, or initial private-sector prices. While the number of phase II subjects was not significantly associated with prices, the numbers of phase III and combined late phase (phases II + III) subjects were significantly associated with initial public- and private-sector series prices (p < 0.05). The association between number of subjects and initial prices demonstrated diminishing marginal increases in price with increasing numbers of subjects. These findings may help guide the number of subjects required by the FDA in clinical trials, in order to reduce expenses for manufacturers and thereby help mitigate increases in initial vaccine series prices.

Human Chorionic Gonadotrophin as a Possible Mediator of Leiomyoma Growth during Pregnancy: Molecular Mechanisms.

PubMed

Sarais, Veronica; Cermisoni, Greta Chiara; Schimberni, Matteo; Alteri, Alessandra; Papaleo, Enrico; Somigliana, Edgardo; Vigano', Paola

2017-09-20

Uterine fibroids are the most common gynecologic benign tumors. Studies supporting a strong pregnancy-related growth of leiomyomas generally claimed a crucial role of sex steroid hormones. However, sex steroids are unlikely the unique actors involved as estrogen and progesterone achieve a pick serum concentration in the last trimester while leiomyomas show a typical increase during the first trimester. Given the rapid exponential raise in serum human Chorionic Gonadotrophin (hCG) at the beginning of gestation, we conducted a review to assess the potential role of hCG in the striking growth of leiomyomas during initial pregnancy. Fibroid growth during initial pregnancy seems to correlate to the similar increase of serum hCG levels until 12 weeks of gestation. The presence of functional Luteinizing Hormone/human Chorionic Gonadotropin (LH/hCG) receptors was demonstrated on leiomyomas. In vitro treatment of leiomyoma cells with hCG determines an up to 500% increase in cell number after three days. Expression of cyclin E and cyclin-dependent kinase 1 was significantly increased in leiomyoma cells by hCG treatment. Moreover, upon binding to the receptor, hCG stimulates prolactin secretion in leiomyoma cells, promoting cell proliferation via the mitogen-activated protein kinase cascade. Fibroid enlargement during initial pregnancy may be regulated by serum hCG.

Human Chorionic Gonadotrophin as a Possible Mediator of Leiomyoma Growth during Pregnancy: Molecular Mechanisms

PubMed Central

Sarais, Veronica; Cermisoni, Greta Chiara; Schimberni, Matteo; Alteri, Alessandra; Papaleo, Enrico; Somigliana, Edgardo; Vigano’, Paola

2017-01-01

Uterine fibroids are the most common gynecologic benign tumors. Studies supporting a strong pregnancy-related growth of leiomyomas generally claimed a crucial role of sex steroid hormones. However, sex steroids are unlikely the unique actors involved as estrogen and progesterone achieve a pick serum concentration in the last trimester while leiomyomas show a typical increase during the first trimester. Given the rapid exponential raise in serum human Chorionic Gonadotrophin (hCG) at the beginning of gestation, we conducted a review to assess the potential role of hCG in the striking growth of leiomyomas during initial pregnancy. Fibroid growth during initial pregnancy seems to correlate to the similar increase of serum hCG levels until 12 weeks of gestation. The presence of functional Luteinizing Hormone/human Chorionic Gonadotropin (LH/hCG) receptors was demonstrated on leiomyomas. In vitro treatment of leiomyoma cells with hCG determines an up to 500% increase in cell number after three days. Expression of cyclin E and cyclin-dependent kinase 1 was significantly increased in leiomyoma cells by hCG treatment. Moreover, upon binding to the receptor, hCG stimulates prolactin secretion in leiomyoma cells, promoting cell proliferation via the mitogen-activated protein kinase cascade. Fibroid enlargement during initial pregnancy may be regulated by serum hCG. PMID:28930160

The Monty Hall dilemma in pigeons: effect of investment in initial choice.

PubMed

Stagner, Jessica P; Rayburn-Reeves, Rebecca; Zentall, Thomas R

2013-10-01

In the Monty Hall dilemma, humans are initially given a choice among three alternatives, one of which has a hidden prize. After choosing, but before it is revealed whether they have won the prize, they are shown that one of the remaining alternatives does not have the prize. They are then asked whether they want to stay with their original choice or switch to the remaining alternative. Although switching results in obtaining the prize two thirds of the time, humans consistently fail to adopt the optimal strategy of switching even after considerable training. Interestingly, there is evidence that pigeons show more optimal switching performance with this task than humans. Because humans often view even random choices already made as being more valuable than choices not made, we reasoned that if pigeons made a greater investment, it might produce an endowment or ownership effect resulting in more human-like suboptimal performance. On the other hand, the greater investment in the initial choice by the pigeons might facilitate switching behavior by helping them to better discriminate their staying versus switching behavior. In Experiment 1, we examined the effect of requiring pigeons to make a greater investment in their initial choice (20 pecks rather than the usual 1 peck). We found that the increased response requirement facilitated acquisition of the switching response. In Experiment 2, we showed that facilitation of switching due to the increased response requirement did not result from extinction of responding to the initially chosen location.

JSC Human Life Sciences Project

NASA Technical Reports Server (NTRS)

1998-01-01

This section of the Life and Microgravity Spacelab (LMS) publication includes articles entitled: (1) E029 - Magnetic Resonance Imaging after Exposure to Microgravity; (2) E030 - Extended Studies of Pulmonary Function in Weightlessness; (3) E074 - Direct Measurement of the Initial Bone Response to Spaceflight in Humans; (4) E401 - The Effects of Microgravity on Skeletal Muscle Contractile Properties; (5) E407 - Effects of Microgravity on the Biochemical and Bioenergetic Characteristics of Human Skeletal Muscle; (6) E410 - Torso Rotation Experiment; (7) E920 - Effect of Weightlessness on Human Single Muscle Fiber Function; (8) E948 - Human Sleep, Circadian Rhythms and Performance in Space; (9) E963 - Microgravity Effects on Standardized Cognitive Performance Measures; and (10) E971 - Measurement of Energy Expenditures During Spaceflight Using the Doubly Labeled Water Method

IVI human factors strategy

DOT National Transportation Integrated Search

1999-11-01

This document focuses on human factors research that supports the Intelligent Vehicle Initiative (IVI). The status of the problem areas within categories used often by the human factors community to organize human factors process is discussed. A simi...

Are chromosomal instabilities induced by exposure of cultured normal human cells to low- or high-LET radiation?

NASA Technical Reports Server (NTRS)

Dugan, Lawrence C.; Bedford, Joel S.

2003-01-01

Radiation-induced genomic instability has been proposed as a very early, if not an initiating, step in radiation carcinogenesis. Numerous studies have established the occurrence of radiation-induced chromosomal instability in various cells of both human and rodent origin. In many of these studies, however, the cells were not "normal" initially, and in many cases they involved tumor-derived cell lines. The phenomenon clearly would be of even greater interest if it were shown to occur generally in cells that are normal at the outset, rather than cells that may have been "selected" because of a pre-existing susceptibility to induced instability. As a test of the generality of the phenomenon, we studied low-passage normal diploid human fibroblasts (AG1521A) to determine whether they are susceptible to the induction of chromosomal instability in the progeny of surviving cells after exposure in G(0) to low- and high-LET radiation. Cytogenetic assays for instability were performed on both mixed populations of cells and clones of cells surviving exposure. We found no evidence for the induction of such instability as a result of radiation exposure, though we observed a senescence-related chromosomal instability in the progeny of both irradiated and unirradiated cell populations. Copyright 2003 by Radiation Research Society.

A Field Study of a Video Supported Seamless-Learning-Setting with Elementary Learners

ERIC Educational Resources Information Center

Fößl, Thomas; Ebner, Martin; Schön, Sandra; Holzinger, Andreas

2016-01-01

Seamless Learning shall initiate human learning processes that exceeds lesson and classroom limits. At the same time this approach fosters a self-regulated learning, by means of inspirational, open education settings. Advanced learning materials are easily accessible via mobile digital devices connected to the Internet. In this study it was…

Human Securitability: A Participatory Action Research Study Involving Novice Teachers and Youngsters

ERIC Educational Resources Information Center

Kravale-Paulina, Marite; Olehnovica, Eridiana

2015-01-01

Civic participation, initiative and interest in current events can bridge the alienation felt towards national and municipal institutions, thereby enabling individuals to improve their quality of life and contribute to all-round sustainable development of their resident state. This paper reports on a participatory action research study into civic…

77 FR 5026 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease... Series among Adolescent Females, IP12-004, and Intervention Study to Increase Use of Standing Orders... Series among Adolescent Females, FOA IP12-004; and Intervention Study to Increase Use of Standing Orders...

Ugly but tasty: A systematic review of possible human and animal health risks related to entomophagy.

PubMed

Testa, Marco; Stillo, Michela; Maffei, Giulia; Andriolo, Violetta; Gardois, Paolo; Zotti, Carla Maria

2017-11-22

According to many recent studies, the use of insects as food seems to be convenient, sustainable, economical and healthy. The objective of this study is to analyze the possible effects of insect consumption on human and animal health. A systematic review of the literature was performed using the PubMed, Scopus and CAB databases. Of the 6026 items initially retrieved, 70 were eligible for inclusion; 40 studies analyzed the use of insects in human foods or drugs, while 30 analyzed the use of insects in animal feed. In humans, the most commonly analyzed risks are nutrient malabsorption, growth alteration, chemical and microbiological contamination and allergy risk. Studies of animals focus on growth alteration, nutrient malabsorption and hematic and qualitative meat alteration. In recent years, researchers have shifted their focus from the possible use of edible insects in animal feed to their use as possible nutrient sources for humans. The results suggest that, if properly treated and preserved, products derived from insects are safe and efficient sources of nutrients for animals. Further studies are needed to evaluate the possible effects of prolonged insect consumption on human health.

Development of an orally-administrative MELK-targeting inhibitor that suppresses the growth of various types of human cancer.

PubMed

Chung, Suyoun; Suzuki, Hanae; Miyamoto, Takashi; Takamatsu, Naofumi; Tatsuguchi, Ayako; Ueda, Koji; Kijima, Kyoko; Nakamura, Yusuke; Matsuo, Yo

2012-12-01

We previously reported MELK (maternal embryonic leucine zipper kinase) as a novel therapeutic target for breast cancer. MELK was also reported to be highly upregulated in multiple types of human cancer. It was implied to play indispensable roles in cancer cell survival and indicated its involvement in the maintenance of tumor-initiating cells. We conducted a high-throughput screening of a compound library followed by structure-activity relationship studies, and successfully obtained a highly potent MELK inhibitor OTSSP167 with IC₅₀ of 0.41 nM. OTSSP167 inhibited the phosphorylation of PSMA1 (proteasome subunit alpha type 1) and DBNL (drebrin-like), which we identified as novel MELK substrates and are important for stem-cell characteristics and invasiveness. The compound suppressed mammosphere formation of breast cancer cells and exhibited significant tumor growth suppression in xenograft studies using breast, lung, prostate, and pancreas cancer cell lines in mice by both intravenous and oral administration. This MELK inhibitor should be a promising compound possibly to suppress the growth of tumor-initiating cells and be applied for treatment of a wide range of human cancer.

Dynamic interaction of Y RNAs with chromatin and initiation proteins during human DNA replication

PubMed Central

Zhang, Alice Tianbu; Langley, Alexander R.; Christov, Christo P.; Kheir, Eyemen; Shafee, Thomas; Gardiner, Timothy J.; Krude, Torsten

2011-01-01

Non-coding Y RNAs are required for the initiation of chromosomal DNA replication in mammalian cells. It is unknown how they perform this function or if they associate with a nuclear structure during DNA replication. Here, we investigate the association of Y RNAs with chromatin and their interaction with replication proteins during DNA replication in a human cell-free system. Our results show that fluorescently labelled Y RNAs associate with unreplicated euchromatin in late G1 phase cell nuclei before the initiation of DNA replication. Following initiation, Y RNAs are displaced locally from nascent and replicated DNA present in replication foci. In intact human cells, a substantial fraction of endogenous Y RNAs are associated with G1 phase nuclei, but not with G2 phase nuclei. Y RNAs interact and colocalise with the origin recognition complex (ORC), the pre-replication complex (pre-RC) protein Cdt1, and other proteins implicated in the initiation of DNA replication. These data support a molecular ‘catch and release’ mechanism for Y RNA function during the initiation of chromosomal DNA replication, which is consistent with Y RNAs acting as replication licensing factors. PMID:21610089

[Mechanisms of viral emergence and interspecies transmission: the exemple of simian foamy viruses in Central Africa].

PubMed

Gessain, Antoine

2013-12-01

A large proportion of viral pathogens that have emerged during the last decades in humans are considered to have originated from various animal species. This is well exemplified by several recent epidemics such as those of Nipah, Severe Acute Respiratory Syndrome, Avian flu, Ebola, Monkeypox, and Hantaviruses. After the initial interspecies transmission per se, the viruses can disseminate into the human population through various and distinct mechanisms. Some of them are well characterized and understood, thus allowing a certain level of risk control and prevention. Surprisingly and in contrast, the initial steps that lead to the emergence of several viruses, and of their associated diseases, remain still poorly understood. Epidemiological field studies conducted in certain specific high-risk populations are thus necessary to obtain new insights into the early events of this emergence process. Human infections by simian viruses represent increasing public health concerns. Indeed, by virtue of their genetic andphysiological similarities, non-human primates (NHPs) are considered to be likely the sources of viruses that can infect humans and thus may pose a significant threat to human population. This is well illustrated by retroviruses, which have the ability to cross species, adapt to a new host and sometimes spread within these new species. Sequence comparison and phylogenetic studies have thus clearly showed that the emergence of human immunodeficiency virus type 1 (HIV-1) and HIV-2 in humans have resulted from several independent interspecies transmissions of different SIV types from Chimpanzees and African monkeys (including sooty mangabeys), respectively, probably during the first part of the last century. The situation for Human T cell Lymphotropic virus type 1 (HTLV-1) is, for certain aspects, quite comparable. Indeed, the origin of most HTLV-1 subtypes appears to be linked to interspecies transmission between STLV-1-infected monkeys and humans, followed by variable periods of evolution in the human host. In this review, after an introduction on emerging viruses, we will briefly present the results of a large epidemiological study performed in groups of Bantus and Pygmies living in villages and settlements located in the rain forest of the South region of Cameroon. These populations are living nearby the habitats of several monkeys and apes, often naturally infected by different retroviruses including SIV, STLV and simianfoamy virus. Most of the persons included in this study were hunters of such NHPs, thus at high risk of contact with infected body fluids (blood, saliva,...) during hunting activities. After reviewing the current available data on the discovery, cross-species transmission from monkeys and apes to humans of the simian foamy retroviruses, we will report the results of our study. Such infection is a unique natural model to study the different mechanisms of restriction of retroviral emergence in Humans.

Dog Breed Differences in Visual Communication with Humans.

PubMed

Konno, Akitsugu; Romero, Teresa; Inoue-Murayama, Miho; Saito, Atsuko; Hasegawa, Toshikazu

2016-01-01

Domestic dogs (Canis familiaris) have developed a close relationship with humans through the process of domestication. In human-dog interactions, eye contact is a key element of relationship initiation and maintenance. Previous studies have suggested that canine ability to produce human-directed communicative signals is influenced by domestication history, from wolves to dogs, as well as by recent breed selection for particular working purposes. To test the genetic basis for such abilities in purebred dogs, we examined gazing behavior towards humans using two types of behavioral experiments: the 'visual contact task' and the 'unsolvable task'. A total of 125 dogs participated in the study. Based on the genetic relatedness among breeds subjects were classified into five breed groups: Ancient, Herding, Hunting, Retriever-Mastiff and Working). We found that it took longer time for Ancient breeds to make an eye-contact with humans, and that they gazed at humans for shorter periods of time than any other breed group in the unsolvable situation. Our findings suggest that spontaneous gaze behavior towards humans is associated with genetic similarity to wolves rather than with recent selective pressure to create particular working breeds.

Assessing university students' sexual risk behaviors as predictors of human papillomavirus (HPV) vaccine uptake behavior.

PubMed

Rohde, Rebecca L; Adjei Boakye, Eric; Christopher, Kara M; Geneus, Christian J; Walker, Ronald J; Varvares, Mark A; Osazuwa-Peters, Nosayaba

2018-06-14

There exists a significant gap in vaccine coverage of the human papillomavirus (HPV) among college-aged students. This study assessed sexual risk-taking behavior among university students and analyzed predictors of HPV vaccine initiation and completion in this population. Data (n = 746) were from an anonymous online, cross-sectional survey distributed to university students, between the ages of 19-26 years, at a private Midwestern university. Both chi-square and multivariable logistics regression models estimated the association between sociodemographic characteristics and sexual risk factors (including number of vaginal sexual partners, number of oral sexual partners, initiation of oral sex, and initiation of vaginal sex), with HPV vaccine initiation and completion. A significant number of participants (40%) had not received a single dose of the HPV vaccine series. Of those who initiated the series, more than half (51%) did not achieve completion. Additionally, a greater number of participants have had multiple (4 or more) oral sexual partners than vaginal sexual partners (25.7% vs. 20.3%). After adjusting for covariates, it was found that sexual risk factors were not significantly associated with HPV vaccine initiation or completion. HPV vaccine initiation and completion rates are suboptimal among university students. High levels of sexual-risk taking behaviors associated with HPV infection persist, yet are not significant predictors of HPV vaccine behaviors in this age group. To increase uptake among 18-26-year-old students, future public health interventions should focus on HPV vaccine education and uptake across the entire population, irrespective of sexual risk profile. Copyright © 2018 Elsevier Ltd. All rights reserved.

Space station crew safety alternatives study. Volume 3: Safety impact of human factors

NASA Technical Reports Server (NTRS)

Rockoff, L. A.; Raasch, R. F.; Peercy, R. L., Jr.

1985-01-01

The first 15 years of accumulated space station concepts for Initial Operational Capability (IOC) during the early 1990's was considered. Twenty-five threats to the space station are identified and selected threats addressed as impacting safety criteria, escape and rescue, and human factors safety concerns. Of the 25 threats identified, eight are discussed including strategy options for threat control: fire, biological or toxic contamination, injury/illness, explosion, loss of pressurization, radiation, meteoroid penetration and debris. Of particular interest here is volume three (of five volumes) pertaining to the safety impact of human factors.

Human Capital, (Human) Capabilities and Higher Education

ERIC Educational Resources Information Center

Le Grange, L.

2011-01-01

In this article I initiate a debate into the (de)merits of human capital theory and human capability theory and discuss implications of the debate for higher education. Human capital theory holds that economic growth depends on investment in education and that economic growth is the basis for improving the quality of human life. Human capable…

A MEG investigation of somatosensory processing in the rhesus monkey

PubMed Central

Wilson, Tony W.; Godwin, Dwayne W.; Czoty, Paul W.; Nader, Michael A.; Kraft, Robert A.; Buchheimer, Nancy C.; Daunais, James B.

2009-01-01

The use of minimally and non-invasive neuroimaging methods in animal models has sharply increased over the past decade. Such studies have enhanced understanding of the neural basis of the physical signals quantified by these tools, and have addressed an assortment of fundamental and otherwise intractable questions in neurobiology. To date, these studies have almost exclusively utilized positron-emission tomography or variants of magnetic resonance based imaging. These methods provide largely indirect measures of brain activity and are strongly reliant on intact vasculature and normal blood flow, which is known to be compromised in many clinical conditions. The current study provides the first demonstration of whole-head magnetoencephalography (MEG), a non-invasive and direct measure of neuronal activity, in a rhesus monkey, and in the process supplies the initial data on systems-level dynamics in somatosensory cortices. An adult rhesus monkey underwent three separate studies of tactile stimulation on the pad of the right second or fifth digit as whole-head MEG data were acquired. The neural generators of the primary neuromagnetic components were localized using an equivalent-current-dipole model. Second digit stimulation produced an initial cortical response peaking ∼16 ms after stimulus onset in the contralateral somatosensory cortices, with a later response at ∼96 ms in an overlapping or nearby neural area with a roughly orthogonal orientation. Stimulation of the fifth digit produced similar results, the main exception being a substantially weaker later response. We believe the 16ms response is likely the monkey homologue of the human M50 response, as both are the earliest cortical response and localize to the contralateral primary somatosensory area. Thus, these data suggest that mechanoreception in nonhuman primates operates substantially faster than that in adult humans. More broadly, these results demonstrate that it is feasible to use current human whole-head MEG instrumentation to record neuromagnetic responses in adult rhesus monkeys. Nonhuman primate models of human disease provide the closest phylogenetic link to humans. The present, non-invasive imaging study could promote exciting links between invasive animal studies and non-invasive human studies, allowing experimentally induced deficits and pharmacological treatments to be interpreted in light of resulting brain network interactions. PMID:19306931

A comprehensive framework to assess, model, and enhance the human role in conserving energy in commercial buildings

NASA Astrophysics Data System (ADS)

Azar, Elie

Energy conservation and sustainability are subjects of great interest today, especially in the commercial building sector which is witnessing a very high and growing demand for energy. Traditionally, efforts to reduce energy consumption in this sector consisted of researching and developing energy efficient building technologies and systems. On the other hand, recent studies indicate that human actions are major determinants of building energy performance and can lead to excessive energy use even in advanced low-energy buildings. As a result, it is essential to determine if the approach to future energy reduction initiatives should remain solely technology-focused, or if a human-focused approach is also needed to complement advancements in technology and improve building operation and performance. In practice, while technology-focused solutions have been extensively researched, promoted, and adopted in commercial buildings, research efforts on the role of human actions and energy use behaviors in energy conservation remain very limited. This study fills the missing gap in literature by presenting a comprehensive framework to (1) understand and quantify the influence of human actions on building energy performance, (2) model building occupants' energy use behaviors and account for potential changes in these behaviors over time, and (3) test and optimize different human-focused energy reduction interventions to increase their adoption in commercial buildings. Results are significant and prove that human actions have a major role to play in reducing the energy intensity of the commercial building sector. This sheds the light on the need for a shift in how people currently use and control different buildings systems, as this is crucial to ensure efficient building operation and to maximize the return on investment in energy-efficient technologies. Furthermore, this study proposes methods and tools that can be applied on any individual or groups of commercial buildings to evaluate the human impact on their energy performance. This is expected to boost research on the topic and promote the integration of human-focused interventions in large-scale energy reduction initiatives and policies. Finally, this dissertation presents a roadmap for the future challenges to energy conservation and the steps to take towards a more sustainable building sector and society.

Correlates of human papillomavirus vaccination rates in low-income, minority adolescents: a multicenter study.

PubMed

Perkins, Rebecca B; Brogly, Susan B; Adams, William G; Freund, Karen M

2012-08-01

Low rates of human papillomavirus (HPV) vaccination in low-income, minority adolescents may exacerbate racial disparities in cervical cancer incidence. Using electronic medical record data and chart abstraction, we examined correlates of HPV vaccine series initiation and completion among 7702 low-income and minority adolescents aged 11-21 receiving primary care at one of seven medical centers between May 1, 2007, and June 30, 2009. Our population included 61% African Americans, 13% Caucasians, 15% Latinas, and 11% other races; 90% receive public insurance (e.g., Medicaid). We used logistic regression to estimate the associations between vaccine initiation and completion and age, race/ethnicity, number of contacts with the healthcare system, provider documentation, and clinical site of care. Of the 41% of adolescent girls who initiated HPV vaccination, 20% completed the series. A higher proportion of girls aged 11-<13 (46%) and 13-<18 (47%) initiated vaccination than those aged 18-21 (28%). In adjusted analyses, receipt of other recommended adolescent vaccines was associated with vaccine initiation, and increased contact with the medical system was associated with both initiation and completion of the series. Conversely, provider failure to document risky health behaviors predicted nonvaccination. Manual review of a subset of unvaccinated patients' charts revealed no documentation of vaccine discussions in 67% of cases. Fewer than half of low-income and minority adolescents receiving health maintenance services initiated HPV vaccination, and only 20% completed the series. Provider failure to discuss vaccination with their patients appears to be an important contributor to nonvaccination. Future research should focus on improving both initiation and completion of HPV vaccination in high-risk adolescents.

Advances in technologies and study design

USDA-ARS?s Scientific Manuscript database

Completion of the initial draft sequence of the human genome was the proving ground for and has ushered in significant advancements in technology of increasing sophistication and ever increasing amounts of data. Often, this combination has a multiplicative effect of stimulating research groups to co...

An initial survey of national airspace system auditory alarm issues in terminal air traffic control.

DOT National Transportation Integrated Search

2003-04-01

A researcher from the Research Development & Human Factors Laboratory of the William J. Hughes Technical Center conducted an exploratory study to examine current National Airspace System (NAS) auditory alarm issues. The purpose was to identify proble...

The viability of establishing collaborative, reconfigurable research environments for the Human Performance Research Laboratory at NASA Ames

NASA Technical Reports Server (NTRS)

Clipson, Colin

1994-01-01

This paper will review and summarize research initiatives conducted between 1987 and 1992 at NASA Ames Research Center by a research team from the University of Michigan Architecture Research Laboratory. These research initiatives, funded by a NASA grant NAG2-635, examined the viability of establishing collaborative, reconfigurable research environments for the Human Performance Research Laboratory at NASA Ames in California. Collaborative Research Environments are envisioned as a way of enhancing the work of NASA research teams, optimizing the use of shared resources, and providing superior environments for housing research activities. The Integrated Simulation Project at NASA, Ames Human Performance Research Laboratory is one of the current realizations of this initiative.

Human Mars Ascent Vehicle Performance Sensitivities

NASA Technical Reports Server (NTRS)

Polsgrove, Tara P.; Thomas, Herbert D.

2016-01-01

Human Mars mission architecture studies have shown that the ascent vehicle mass drives performance requirements for the descent and in-space transportation elements. Understanding the sensitivity of Mars ascent vehicle (MAV) mass to various mission and vehicle design choices enables overall transportation system optimization. This paper presents the results of a variety of sensitivity trades affecting MAV performance including: landing site latitude, target orbit, initial thrust to weight ratio, staging options, specific impulse, propellant type and engine design.

RBE of Energetic Iron Ions for the Induction of Early and Late Chromosome Aberrations in Different Cell Types

NASA Technical Reports Server (NTRS)

Zhang, Ye; Yeshitla, Samrawit; Hada, Megumi; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

2015-01-01

Numerous published studies have reported the Relative Biological Effectiveness (RBE) values for chromosome aberrations induced by charged particles of different LET. The RBE for chromosome aberrations in human lymphocytes exposed ex vivo has been suggested to show a similar relationship as the quality factor for cancer induction. Therefore, increased chromosome aberrations in the astronauts' white blood cells post long-duration missions are used to determine the biological doses from exposures to space radiation. However, the RBE value is known to be very different for different types of cancer. Previously, we reported that, even though the RBE for initial chromosome damages was high in human lymphocytes exposed to Fe ions, the RBE was significantly reduced after multiple cell divisions post irradiation. To test the hypothesis that RBE values for chromosome aberrations are cell type dependent, and different between early and late damages, we exposed human lymphocytes ex vivo, and human mammary epithelial cells in vitro to various charged particles. Chromosome aberrations were quantified using the samples collected at first mitosis post irradiation for initial damages, and the samples collected after multiple generations for the remaining or late arising aberrations. Results of the study suggested that the effectiveness of high-LET charged particles for late chromosome aberrations may be cell type dependent, even though the RBE values are similar for early damages.

Human Finger-Prick Induced Pluripotent Stem Cells Facilitate the Development of Stem Cell Banking

PubMed Central

Tan, Hong-Kee; Toh, Cheng-Xu Delon; Ma, Dongrui; Yang, Binxia; Liu, Tong Ming; Lu, Jun; Wong, Chee-Wai; Tan, Tze-Kai; Li, Hu; Syn, Christopher; Tan, Eng-Lee; Lim, Bing; Lim, Yoon-Pin; Cook, Stuart A.

2014-01-01

Induced pluripotent stem cells (iPSCs) derived from somatic cells of patients can be a good model for studying human diseases and for future therapeutic regenerative medicine. Current initiatives to establish human iPSC (hiPSC) banking face challenges in recruiting large numbers of donors with diverse diseased, genetic, and phenotypic representations. In this study, we describe the efficient derivation of transgene-free hiPSCs from human finger-prick blood. Finger-prick sample collection can be performed on a “do-it-yourself” basis by donors and sent to the hiPSC facility for reprogramming. We show that single-drop volumes of finger-prick samples are sufficient for performing cellular reprogramming, DNA sequencing, and blood serotyping in parallel. Our novel strategy has the potential to facilitate the development of large-scale hiPSC banking worldwide. PMID:24646489

From wild animals to domestic pets, an evolutionary view of domestication.

PubMed

Driscoll, Carlos A; Macdonald, David W; O'Brien, Stephen J

2009-06-16

Artificial selection is the selection of advantageous natural variation for human ends and is the mechanism by which most domestic species evolved. Most domesticates have their origin in one of a few historic centers of domestication as farm animals. Two notable exceptions are cats and dogs. Wolf domestication was initiated late in the Mesolithic when humans were nomadic hunter-gatherers. Those wolves less afraid of humans scavenged nomadic hunting camps and over time developed utility, initially as guards warning of approaching animals or other nomadic bands and soon thereafter as hunters, an attribute tuned by artificial selection. The first domestic cats had limited utility and initiated their domestication among the earliest agricultural Neolithic settlements in the Near East. Wildcat domestication occurred through a self-selective process in which behavioral reproductive isolation evolved as a correlated character of assortative mating coupled to habitat choice for urban environments. Eurasian wildcats initiated domestication and their evolution to companion animals was initially a process of natural, rather than artificial, selection over time driven during their sympatry with forbear wildcats.

Operator performance-enhancing technologies to improve safety. A US DOT safety initiative for meeting the human-centered systems challenge.

DOT National Transportation Integrated Search

1999-11-01

The program implements DOT Human Factors Coordinating Committee (HFCC) recommendations for a coordinated Departmental Human Factors Research Program to advance the human-centered systems approach for enhancing transportation safety. Human error is a ...

48 CFR 1352.235-73 - Research involving human subjects-after initial contract award.

Code of Federal Regulations, 2012 CFR

2012-10-01

... the United States Department of Health and Human Services' Office for Human Research Protections... documentation may include: (1) Copies of the human subjects research protocol, advertisements, recruitment... human subjects research protocol, advertisements, recruitment material, and informed consent forms by...

76 FR 58023 - National Human Genome Research Institute; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Initial..., Scientific Review Officer, Office of Scientific Review, National Human Genome Research Institute, National...

77 FR 28888 - National Human Genome Research Institute Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Initial...: To review and evaluate grant applications. Place: National Human Genome Research Institute, 3635...

Feedbacks between conservation and social-ecological systems

PubMed Central

Miller, Brian W.; Caplow, Susan C.; Leslie, Paul W.

2012-01-01

Robust ways to meet objectives of environmental conservation and social and economic development remain elusive. This struggle may in part be related to insufficient understanding of the feedbacks between conservation initiatives and social-ecological systems, specifically, the ways in which conservation initiatives result in social changes that have secondary effects on the environments targeted by conservation. To explore this idea we sampled peer-reviewed articles addressing the social and environmental dimensions of conservation and coded each paper according to its research focus and characterization of these feedbacks. The majority of articles in our sample focused either on the effect of conservation initiatives on people (e.g., relocation, employment) or the effect of people on the environment (e.g., fragmentation, conservation efficacy of traditional management systems). Few studies in our sample empirically addressed both the social dynamics resulting from conservation initiatives and subsequent environmental effects. In many cases, one was measured and the other was discussed anecdotally. Among the studies that describe feedbacks between social and environmental variables, there was more evidence of positive (amplifying) feedbacks between social and environmental outcomes (i.e., undesirable social outcomes yielded undesirable environmental effects, and desirable social outcomes yielded desirable environmental effects). The major themes within the sampled literature include conflict between humans and wild animals, social movements, adaptive comanagement, loss of traditional management systems, traditional ecological knowledge, human displacement and risks to livelihoods, and conservation and development. The narratives associated with each theme can serve as hypotheses for facilitating further discussion about conservation issues and for catalyzing future studies of the feedbacks between conservation and social-ecological systems. PMID:22443128

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

Bernard, Eric; Hamel, Rodolphe; Neyret, Aymeric

Transmission of chikungunya virus (CHIKV) to humans is initiated by puncture of the skin by a blood-feeding Aedes mosquito. Despite the growing knowledge accumulated on CHIKV, the interplay between skin cells and CHIKV following inoculation still remains unclear. In this study we questioned the behavior of human keratinocytes, the predominant cell population in the skin, following viral challenge. We report that CHIKV rapidly elicits an innate immune response in these cells leading to the enhanced transcription of type I/II and type III interferon genes. Concomitantly, we show that despite viral particles internalization into Rab5-positive endosomes and efficient fusion of virusmore » and cell membranes, keratinocytes poorly replicate CHIKV as attested by absence of nonstructural proteins and genomic RNA synthesis. Accordingly, human keratinocytes behave as an antiviral defense against CHIKV infection rather than as a primary targets for initial replication. This picture significantly differs from that reported for Dengue and West Nile mosquito-borne viruses. - Highlights: • Human keratinocytes support endocytosis of CHIKV and fusion of viral membranes. • CHIKV replication is blocked at a post entry step in these cells. • Infection upregulates type-I, –II and –III IFN genes expression. • Keratinocytes behave as immune sentinels against CHIKV.« less

Human-animal relationships in zoo-housed orangutans (P. abelii) and gorillas (G. g. gorilla): the effects of familiarity.

PubMed

Smith, Joshua J

2014-10-01

I examined human-animal relationships (HARs) in zoo-housed orangutans (Pongo abelii) and gorillas (Gorilla gorilla gorilla) to see if they followed patterns similar to conspecific relationships in great apes and humans. Familiarity and social relationships guide humans' and great apes' behaviors with conspecifics. Inter-individual relationships, based on shared social history, and "generalized" relationships, based on a history of interactions with relevant classes of individuals, guide behavior with familiar and unfamiliar conspecifics, respectively. I examined whether both familiarity and social relationships similarly guides great apes' cross-species interactions with humans. I used repeated measures MANOVA to compare hourly rates and average durations of ape-initiated human-directed behaviors (HDBs) between familiar and unfamiliar humans and between great ape species. HDB patterns were consistent with familiarity-based HAR predictions, indicating more negative relationships with unfamiliar humans and more positive relationships with familiar humans. Findings for unfamiliar humans are consistent with negative effects of humans on apes' behavior reported in traditional visitor effect studies (VES). However, findings for familiar humans may be overlooked in VES due to pooling across levels of human familiarity or failure to consider humans other than primarily unfamiliar visitors. Additionally, species differences in apes' HDBs suggest that data pooling across species, common in many zoo studies, may mask important differences. These findings have important methodological implications for studies of human-animal interaction as well as for captive animal wellbeing. © 2014 Wiley Periodicals, Inc.

Insights from human studies into the host defense against candidiasis.

PubMed

Filler, Scott G

2012-04-01

Candida spp. are the most common cause of mucosal and disseminated fungal infections in humans. Studies using mutant strains of mice have provided initial information about the roles of dectin-1, CARD9, and Th17 cytokines in the host defense against candidiasis. Recent technological advances have resulted in the identification of mutations in specific genes that predispose humans to develop candidal infection. The analysis of individuals with these mutations demonstrates that dectin-1 is critical for the host defense against vulvovaginal candidiasis and candidal colonization of the gastrointestinal tract. They also indicate that CARD9 is important for preventing both mucosal and disseminated candidiasis, whereas the Th17 response is necessary for the defense against mucocutaneous candidiasis. This article reviews the recent studies of genetic defects in humans that result in an increased susceptibility to candidiasis and discusses how these studies provide new insight into the host defense against different types of candidal infections. Copyright © 2011 Elsevier Ltd. All rights reserved.

Human exposure assessment and the National Toxicology Program.

PubMed Central

Lucier, G W; Schecter, A

1998-01-01

The National Institute of Environmental Health Sciences/National Toxicology Program (NIEHS/NTP) is developing a new interagency initiative in exposure assessment. This initiative involves the NIEHS, the Centers for Disease Control and Prevention through its National Center for Environmental Health, the National Institute for Occupational Safety and Health, the EPA, and other participating institutes and agencies of the NTP. This initiative will benefit public health and priority setting in a number of ways. First, as discussed above, it will strengthen the scientific foundation for risk assessments by the development of more credible exposure/response relationships in people by improving cross-species extrapolation, the development of biologically based dose-response models, and the identification of sensitive subpopulations and for "margin of exposure" based estimates of risk. Second, it will provide the kind of information necessary for deciding which chemicals should be studied with the limited resources available for toxicological testing. For example, there are 85,000 chemicals in commerce today, and the NTP can only provide toxicological evaluations on 10-20 per year. Third, we would use the information obtained from the exposure initiative to focus our research on mixtures that are actually present in people's bodies. Fourth, we would obtain information on the kinds and amount of chemicals in children and other potentially sensitive subpopulations. Determinations of whether additional safety factors need to be applied to children must rest, in part, upon comparative exposure analyses between children and adults. Fifth, this initiative, taken together with the environmental genome initiative, will provide the science base essential for meaningful studies on gene/environment interactions, particularly for strengthening the evaluation of epidemiology studies. Sixth, efficacy of public health policies aimed at reducing human exposure to chemical agents could be evaluated in a more meaningful way if body burden data were available over time, including remediation around Superfund sites and efforts to achieve environmental justice. The exposure assessment initiative is needed to address public health needs. It is feasible because of recent advances in analytical technology and molecular biology, and it is an example of how different agencies can work together to better fulfill their respective missions. Images Figure 1 Figure 2 PMID:9755136

Initial description of a quantitative, cross-species (chimpanzee-human) social responsiveness measure.

PubMed

Marrus, Natasha; Faughn, Carley; Shuman, Jeremy; Petersen, Steve E; Constantino, John N; Povinelli, Daniel J; Pruett, John R

2011-05-01

Comparative studies of social responsiveness, an ability that is impaired in autism spectrum disorders, can inform our understanding of both autism and the cognitive architecture of social behavior. Because there is no existing quantitative measure of social responsiveness in chimpanzees, we generated a quantitative, cross-species (human-chimpanzee) social responsiveness measure. We translated the Social Responsiveness Scale (SRS), an instrument that quantifies human social responsiveness, into an analogous instrument for chimpanzees. We then retranslated this "Chimpanzee SRS" into a human "Cross-Species SRS" (XSRS). We evaluated three groups of chimpanzees (n = 29) with the Chimpanzee SRS and typical and human children with autism spectrum disorder (ASD; n = 20) with the XSRS. The Chimpanzee SRS demonstrated strong interrater reliability at the three sites (ranges for individual ICCs: 0.534 to 0.866; mean ICCs: 0.851 to 0.970). As has been observed in human beings, exploratory principal components analysis of Chimpanzee SRS scores supports a single factor underlying chimpanzee social responsiveness. Human subjects' XSRS scores were fully concordant with their SRS scores (r = 0.976, p = .001) and distinguished appropriately between typical and ASD subjects. One chimpanzee known for inappropriate social behavior displayed a significantly higher score than all other chimpanzees at its site, demonstrating the scale's ability to detect impaired social responsiveness in chimpanzees. Our initial cross-species social responsiveness scale proved reliable and discriminated differences in social responsiveness across (in a relative sense) and within (in a more objectively quantifiable manner) human beings and chimpanzees. Copyright © 2011 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Impact of blast induced transitory vibration and air-overpressure/noise on human brain--an experimental study.

PubMed

Raina, A K; Baheti, M; Haldar, A; Ramulu, M; Chakraborty, A K; Sahu, P B; Bandopadhayay, C

2004-04-01

Human response to blast induced ground vibration and air-overpressure/noise is a major concern of current mining activity. This is because the fact that mines are fast transgressing the habitats and people are getting educated. Consequently the response of humans is changing and expectedly will increase in days to come with no viable and economic alternative to blasting--an essential component of mining. The response of humans can be purely physiological or psychological in nature or combination of both depending upon the situation and conditions of mining. Where physiological response is documented in terms of effects on ears and lungs there is a meager amount or no literature available regarding effects of blasting on the brain. Moreover, the studies on transitory phenomenon like the effects of blasting on humans are rare in comparison to the whole body vibration studies. This study was designed to address the issues as a precursor to a major initiative. The preliminary investigations conducted with the monitoring of EEG responses of humans to vibration and air-overpressure/noise due to blasting revealed that there is no major response of the brain to transitory vibrations and noise.

Development of a microplate coagulation assay for Factor V in human plasma

PubMed Central

2011-01-01

Background Factor V (FV) in its activated form, FVa, is a critical regulator of thrombin generation during fibrin clot formation. There is a need of a simple, fast, and inexpensive microplate-based coagulation assay to measure the functional activity of FV in human plasma. The objective of this study was to develop a microplate-based assay that measures FV coagulation activity during clot formation in human plasma, which is currently not available. Methods The FV assay requires a kinetic microplate reader to measure the change in absorbance at 405nm during fibrin formation in human plasma. The FV assay accurately measures the time, initial rate, and extent of fibrin clot formation in human plasma. Results The FV microplate assay is simple, fast, economical, sensitive to approx 24-80pM, and multiple samples may be analyzed simultaneously. All the required materials are commercially available. Standard curves of time or initial rate of fibrin clot formation vs FV activity in the 1-stage assay (Without activation by thrombin) may be used to measure FV activity in samples of human plasma. The assay was used to demonstrate that in nine patients with disseminated intravascular coagulation (DIC), the FV 1-stage, 2-stage (With activation by thrombin), and total (2-stage activity - 1-stage activity) activities were decreased, on average, by approximately 54%, 44%, and 42%, respectively, from prolonged clot times when compared to normal pooled human reference plasma (NHP). The results indicate that the FV in the DIC patient plasmas supported both a delayed and slower rate of fibrin clot formation compared with NHP; however, the extent of fibrin clot formation in the DIC patients remained largely unchanged from that observed with NHP. Conclusions The FV microplate assay may be easily adapted to measure the activity of any coagulation factor using the appropriate factor-deficient plasma and clot initiating reagent. The microplate assay will find use in both research and clinical laboratories to provide measurement of the functional coagulation activity of FV in human plasma. PMID:21711555

Active numerical model of human body for reconstruction of falls from height.

PubMed

Milanowicz, Marcin; Kędzior, Krzysztof

2017-01-01

Falls from height constitute the largest group of incidents out of approximately 90,000 occupational accidents occurring each year in Poland. Reconstruction of the exact course of a fall from height is generally difficult due to lack of sufficient information from the accident scene. This usually results in several contradictory versions of an incident and impedes, for example, determination of the liability in a judicial process. In similar situations, in many areas of human activity, researchers apply numerical simulation. They use it to model physical phenomena to reconstruct their real course over time; e.g. numerical human body models are frequently used for investigation and reconstruction of road accidents. However, they are validated in terms of specific road traffic accidents and are considerably limited when applied to the reconstruction of other types of accidents. The objective of the study was to develop an active numerical human body model to be used for reconstruction of accidents associated with falling from height. Development of the model involved extension and adaptation of the existing Pedestrian human body model (available in the MADYMO package database) for the purposes of reconstruction of falls from height by taking into account the human reaction to the loss of balance. The model was developed by using the results of experimental tests of the initial phase of the fall from height. The active numerical human body model covering 28 sets of initial conditions related to various human reactions to the loss of balance was developed. The application of the model was illustrated by using it to reconstruct a real fall from height. From among the 28 sets of initial conditions, those whose application made it possible to reconstruct the most probable version of the incident was selected. The selection was based on comparison of the results of the reconstruction with information contained in the accident report. Results in the form of estimated injuries overlap with the real injuries sustained by the casualty. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

75 FR 26762 - National Human Genome Research Institute; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-12

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Initial... . (Catalogue of Federal Domestic Assistance Program Nos. 93.172, Human Genome Research, National Institutes of...

76 FR 3643 - National Human Genome Research Institute; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-20

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Initial... . (Catalogue of Federal Domestic Assistance Program Nos. 93.172, Human Genome Research, National Institutes of...

78 FR 24223 - National Human Genome Research Institute; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Initial...: To review and evaluate grant applications. Place: National Human Genome Research Institute, 3rd floor...

Double dynamic scaling in human communication dynamics

NASA Astrophysics Data System (ADS)

Wang, Shengfeng; Feng, Xin; Wu, Ye; Xiao, Jinhua

2017-05-01

In the last decades, human behavior has been deeply understanding owing to the huge quantities data of human behavior available for study. The main finding in human dynamics shows that temporal processes consist of high-activity bursty intervals alternating with long low-activity periods. A model, assuming the initiator of bursty follow a Poisson process, is widely used in the modeling of human behavior. Here, we provide further evidence for the hypothesis that different bursty intervals are independent. Furthermore, we introduce a special threshold to quantitatively distinguish the time scales of complex dynamics based on the hypothesis. Our results suggest that human communication behavior is a composite process of double dynamics with midrange memory length. The method for calculating memory length would enhance the performance of many sequence-dependent systems, such as server operation and topic identification.

SUBSTANCE ABUSE AND MENTAL HEALTH DATA ARCHIVE (SAMHDA)

EPA Science Inventory

The Substance Abuse and Mental Health Data Archive (SAMHDA) is an initiative of the Office of Applied Studies, Substance Abuse and Mental Health Services Administration (SAMHSA) of the United States Department of Health and Human Services. The goal of the archive is to provide re...

Summative Evaluation of the Learning Initiatives Program (LIP). Final Report

ERIC Educational Resources Information Center

Human Resources and Skills Development Canada, 2005

2005-01-01

The Learning Initiatives Program (LIP), formerly the Learning Initiatives Fund (LIF), is a contribution program which was established in 1994 to encourage and support initiatives that contribute to the development of a results-oriented, accessible, relevant and accountable learning system in Canada. Through this program, Human Resources and Skills…

45 CFR 79.37 - Initial decision.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Initial decision. 79.37 Section 79.37 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PROGRAM FRAUD CIVIL REMEDIES § 79.37 Initial decision. (a) The ALJ shall issue an initial decision based only on the record, which...

42 CFR 405.708 - Effect of initial determination.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Effect of initial determination. 405.708 Section 405.708 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... Under Medicare Part A § 405.708 Effect of initial determination. (a) The initial determination under...

42 CFR 405.806 - Effect of Initial Determination.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Effect of Initial Determination. 405.806 Section 405.806 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... Part B Program § 405.806 Effect of Initial Determination. The initial determination is binding upon all...

The human genetic history of the Americas: the final frontier.

PubMed

O'Rourke, Dennis H; Raff, Jennifer A

2010-02-23

The Americas, the last continents to be entered by modern humans, were colonized during the late Pleistocene via a land bridge across what is now the Bering strait. However, the timing and nature of the initial colonization events remain contentious. The Asian origin of the earliest Americans has been amply established by numerous classical marker studies of the mid-twentieth century. More recently, mtDNA sequences, Y-chromosome and autosomal marker studies have provided a higher level of resolution in confirming the Asian origin of indigenous Americans and provided more precise time estimates for the emergence of Native Americans. But these data raise many additional questions regarding source populations, number and size of colonizing groups and the points of entry to the Americas. Rapidly accumulating molecular data from populations throughout the Americas, increased use of demographic models to test alternative colonization scenarios, and evaluation of the concordance of archaeological, paleoenvironmental and genetic data provide optimism for a fuller understanding of the initial colonization of the Americas. Copyright 2010 Elsevier Ltd. All rights reserved.

Cancer Risk-Assessment of Radiation Damage in Ataxia Telangiectasia Heterozygous Human Breast Epithelial Cell Cultures

NASA Technical Reports Server (NTRS)

Applewhite, Lisa C.

2002-01-01

This paper describes the study of the markers of cellular changes that are found during the onset of carcinogenesis. Several of the biological factors are markers of stress response, oncoprotein expression, and differentiation factors. Oxidative stress response agents such as heat shock proteins (HSPs) protect cells from oxidative stresses such as ionizing radiation. The onocoprotein HER-2/neu, a specific breast cancer marker, indicates early onset of cancer. Additional structural and morphogenetic markers of differentiation were considered in order to determine initial cellular changes at the initial onset of cancer. As an additional consideration, all-trans retinoic acid (RA), a differentiation agent, was considered because of its known role in regulating normal differentiation and inhibiting tumor proliferation via specific nuclear receptors. This paper discusses study and results of the preliminary analyses of gamma irradiation of AT heterozygous human breast epithelial cells (WH). Comparisons are also made of the effects various RA concentrations post-irradiation.

Application of Faecalibacterium 16S rDNA genetic marker for accurate identification of duck faeces.

PubMed

Sun, Da; Duan, Chuanren; Shang, Yaning; Ma, Yunxia; Tan, Lili; Zhai, Jun; Gao, Xu; Guo, Jingsong; Wang, Guixue

2016-04-01

The aim of this study was to judge the legal duty of pollution liabilities by assessing a duck faeces-specific marker, which can exclude distractions of residual bacteria from earlier contamination accidents. With the gene sequencing technology and bioinformatics method, we completed the comparative analysis of Faecalibacterium sequences, which were associated with ducks and other animal species, and found the sequences unique to duck faeces. Polymerase chain reaction (PCR) and agarose gel electrophoresis techniques were used to verify the reliability of both human and duck faeces-specific primers. The duck faeces-specific primers generated an amplicon of 141 bp from 43.3 % of duck faecal samples, 0 % of control samples and 100 % of sewage wastewater samples that contained duck faeces. We present here the initial evidence of Faecalibacterium-based applicability as human faeces-specificity in China. Meanwhile, this study represents the initial report of a Faecalibacterium marker for duck faeces and suggests an independent or supplementary environmental biotechnology of microbial source tracking (MST).

Summary Report of Summer 2009 NGSI Human Capital Development Efforts at Lawrence Livermore National Laboratory

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

Dougan, A; Dreicer, M; Essner, J

2009-11-16

In 2009, Lawrence Livermore National Laboratory (LLNL) engaged in several activities to support NA-24's Next Generation Safeguards Initiative (NGSI). This report outlines LLNL's efforts to support Human Capital Development (HCD), one of five key components of NGSI managed by Dunbar Lockwood in the Office of International Regimes and Agreements (NA-243). There were five main LLNL summer safeguards HCD efforts sponsored by NGSI: (1) A joint Monterey Institute of International Studies/Center for Nonproliferation Studies-LLNL International Safeguards Policy and Information Analysis Course; (2) A Summer Safeguards Policy Internship Program at LLNL; (3) A Training in Environmental Sample Analysis for IAEA Safeguards Internship;more » (4) Safeguards Technology Internships; and (5) A joint LLNL-INL Summer Safeguards Lecture Series. In this report, we provide an overview of these five initiatives, an analysis of lessons learned, an update on the NGSI FY09 post-doc, and an update on students who participated in previous NGSI-sponsored LLNL safeguards HCD efforts.« less

Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon–independent apoptosis in human melanoma cells

PubMed Central

Besch, Robert; Poeck, Hendrik; Hohenauer, Tobias; Senft, Daniela; Häcker, Georg; Berking, Carola; Hornung, Veit; Endres, Stefan; Ruzicka, Thomas; Rothenfusser, Simon; Hartmann, Gunther

2009-01-01

The retinoic acid–inducible gene I (RIG-I) and melanoma differentiation–associated antigen 5 (MDA-5) helicases sense viral RNA in infected cells and initiate antiviral responses such as the production of type I IFNs. Here we have shown that RIG-I and MDA-5 also initiate a proapoptotic signaling pathway that is independent of type I IFNs. In human melanoma cells, this signaling pathway required the mitochondrial adapter Cardif (also known as IPS-1) and induced the proapoptotic BH3-only proteins Puma and Noxa. RIG-I– and MDA-5–initiated apoptosis required Noxa but was independent of the tumor suppressor p53. Triggering this pathway led to efficient activation of mitochondrial apoptosis, requiring caspase-9 and Apaf-1. Surprisingly, this proapoptotic signaling pathway was also active in nonmalignant cells, but these cells were much less sensitive to apoptosis than melanoma cells. Endogenous Bcl-xL rescued nonmalignant, but not melanoma, cells from RIG-I– and MDA-5–mediated apoptosis. In addition, we confirmed the results of the in vitro studies, demonstrating that RIG-I and MDA-5 ligands both reduced human tumor lung metastasis in immunodeficient NOD/SCID mice. These results identify an IFN-independent antiviral signaling pathway initiated by RIG-I and MDA-5 that activates proapoptotic signaling and, unless blocked by Bcl-xL, results in apoptosis. Due to their immunostimulatory and proapoptotic activity, RIG-I and MDA-5 ligands have therapeutic potential due to their ability to overcome the characteristic resistance of melanoma cells to apoptosis. PMID:19620789

Once More into the Breach: Examining the Human Capital Impact of a University Consolidation over Time

ERIC Educational Resources Information Center

Ribando, Saundra J.; Slade, Catherine P.; Fortner, C. Kevin

2017-01-01

Little research examines the sociocultural aspects of consolidating two post-secondary educational institutions. In a previous study we collected baseline data and reported on the initial impact of consolidation of a research-oriented, health sciences university with a teaching-oriented, comprehensive university. In the study we report here we…

NHEXAS PHASE I ARIZONA STUDY--STANDARD OPERATING PROCEDURE FOR PERFORMANCE OF COMPUTER SOFTWARE: VERIFICATION AND VALIDATION (UA-D-2.0)

EPA Science Inventory

The purpose of this SOP is to define the procedures used for the initial and periodic verification and validation of computer programs used during the Arizona NHEXAS project and the "Border" study. Keywords: Computers; Software; QA/QC.

The National Human Exposure Assessment Sur...

Human Capital--Economic Growth Nexus in the Former Soviet Bloc

ERIC Educational Resources Information Center

Osipian, Ararat L.

2007-01-01

This study analyses the role and impact of higher education on per capita economic growth in the Former Soviet Bloc. It attempts to estimate the significance of educational levels for initiating substantial economic growth that now takes place in these two countries. This study estimates a system of linear and log-linear equations that account for…

A goal and strategy for human exploration of the moon and Mars

NASA Technical Reports Server (NTRS)

Pivirotto, Donna Shirley

1990-01-01

Eventual settlement of the solar system, beginning with the moon and Mars, is proposed, and a strategy for the exploration of and initial settlement of the moon and Mars, based on the model of European settlement of the Americas, is discussed. Strategies suggest an allocation of functions between humans and telerobots to conduct the exploration and initial settlement.

Genetics and recent human evolution.

PubMed

Templeton, Alan R

2007-07-01

Starting with "mitochondrial Eve" in 1987, genetics has played an increasingly important role in studies of the last two million years of human evolution. It initially appeared that genetic data resolved the basic models of recent human evolution in favor of the "out-of-Africa replacement" hypothesis in which anatomically modern humans evolved in Africa about 150,000 years ago, started to spread throughout the world about 100,000 years ago, and subsequently drove to complete genetic extinction (replacement) all other human populations in Eurasia. Unfortunately, many of the genetic studies on recent human evolution have suffered from scientific flaws, including misrepresenting the models of recent human evolution, focusing upon hypothesis compatibility rather than hypothesis testing, committing the ecological fallacy, and failing to consider a broader array of alternative hypotheses. Once these flaws are corrected, there is actually little genetic support for the out-of-Africa replacement hypothesis. Indeed, when genetic data are used in a hypothesis-testing framework, the out-of-Africa replacement hypothesis is strongly rejected. The model of recent human evolution that emerges from a statistical hypothesis-testing framework does not correspond to any of the traditional models of human evolution, but it is compatible with fossil and archaeological data. These studies also reveal that any one gene or DNA region captures only a small part of human evolutionary history, so multilocus studies are essential. As more and more loci became available, genetics will undoubtedly offer additional insights and resolutions of human evolution.

The human secretome atlas initiative: Implications in health and disease conditions

PubMed Central

Brown, Kristy J; Seol, Haeri; Pillai, Dinesh K; Sankoorikal, Binu-John; Formolo, Catherine A; Mac, Jenny; Edwards, Nathan J.; Rose, Mary C; Hathout, Yetrib

2013-01-01

Proteomic analysis of human body fluids is highly challenging, therefore many researchers are redirecting efforts towards secretome profiling. The goal is to define potential biomarkers and therapeutic targets in the secretome that can be traced back in accessible human body fluids. However, currently there is a lack of secretome profiles of normal human primary cells making it difficult to assess the biological meaning of current findings. In this study we sought to establish secretome profiles of human primary cells obtained from healthy donors with the goal of building a human secretome atlas. Such an atlas can be used as a reference for discovery of potential disease associated biomarkers and eventually novel therapeutic targets. As a preliminary study, secretome profiles were established for six different types of human primary cell cultures and checked for overlaps with the three major human body fluids including plasma, cerebrospinal fluid and urine. About 67% of the 1054 identified proteins in the secretome of these primary cells occurred in at least one body fluid. Furthermore, comparison of the secretome profiles of two human glioblastoma cell lines to this new human secretome atlas enabled unambiguous identification of potential brain tumor biomarkers. These biomarkers can be easily monitored in different body fluids using stable isotope labeled standard proteins. The long term goal of this study is to establish a comprehensive online human secretome atlas for future use as a reference for any disease related secretome study. PMID:23603790

New Strategy for Exploration Technology Development: The Human Exploration and Development of Space (HEDS) Exploration/Commercialization Technology Initiative

NASA Technical Reports Server (NTRS)

Mankins, John C.

2000-01-01

In FY 2001, NASA will undertake a new research and technology program supporting the goals of human exploration: the Human Exploration and Development of Space (HEDS) Exploration/Commercialization Technology Initiative (HTCI). The HTCI represents a new strategic approach to exploration technology, in which an emphasis will be placed on identifying and developing technologies for systems and infrastructures that may be common among exploration and commercial development of space objectives. A family of preliminary strategic research and technology (R&T) road maps have been formulated that address "technology for human exploration and development of space (THREADS). These road maps frame and bound the likely content of the HTCL Notional technology themes for the initiative include: (1) space resources development, (2) space utilities and power, (3) habitation and bioastronautics, (4) space assembly, inspection and maintenance, (5) exploration and expeditions, and (6) space transportation. This paper will summarize the results of the THREADS road mapping process and describe the current status and content of the HTCI within that framework. The paper will highlight the space resources development theme within the Initiative and will summarize plans for the coming year.

The Virtual Physiological Human - a European initiative for in silico human modelling -.

PubMed

Viceconti, Marco; Clapworthy, Gordon; Van Sint Jan, Serge

2008-12-01

The Virtual Physiological Human (VPH) is an initiative, strongly supported by the European Commission (EC), that seeks to develop an integrated model of human physiology at multiple scales from the whole body through the organ, tissue, cell and molecular levels to the genomic level. VPH had its beginnings in 2005 with informal discussions amongst like-minded scientists which led to the STEP project, a Coordination Action funded by the EC that began in early 2006. The STEP project greatly accelerated the progress of the VPH and proved to be a catalyst for wide-ranging discussions within Europe and for outreach activities designed to develop a broad international approach to the huge scientific and technological challenges involved in this area. This paper provides an overview of the VPH and the developments it has engendered in the rapidly expanding worldwide activities associated with the physiome. It then uses one particular project, the Living Human Project, to illustrate the type of advances that are taking place to further the aims of the VPH and similar initiatives worldwide.

The First New Zealanders: Patterns of Diet and Mobility Revealed through Isotope Analysis

PubMed Central

Kinaston, Rebecca L.; Walter, Richard K.; Jacomb, Chris; Brooks, Emma; Tayles, Nancy; Halcrow, Sian E.; Stirling, Claudine; Reid, Malcolm; Gray, Andrew R.; Spinks, Jean; Shaw, Ben; Fyfe, Roger; Buckley, Hallie R.

2013-01-01

Direct evidence of the environmental impact of human colonization and subsequent human adaptational responses to new environments is extremely rare anywhere in the world. New Zealand was the last Polynesian island group to be settled by humans, who arrived around the end of the 13th century AD. Little is known about the nature of human adaptation and mobility during the initial phase of colonization. We report the results of the isotopic analysis (carbon, nitrogen and strontium) of the oldest prehistoric skeletons discovered in New Zealand to assess diet and migration patterns. The isotope data show that the culturally distinctive burials, Group 1, had similar diets and childhood origins, supporting the assertion that this group was distinct from Group 2/3 and may have been part of the initial colonizing population at the site. The Group 2/3 individuals displayed highly variable diets and likely lived in different regions of the country before their burial at Wairau Bar, supporting the archaeological evidence that people were highly mobile in New Zealand since the initial phase of human settlement. PMID:23691250

Viruses and Human Cancer: From Detection to Causality

PubMed Central

Sarid, Ronit; Gao, Shou-Jiang

2010-01-01

The study of cancer is incomplete without taking into consideration of tumorigenic viruses. Initially, searches for human cancer viruses were fruitless despite an expansion of our knowledge in the same period concerning acute-transforming retroviruses in animals. However, over the last 40 years, we have witnessed rapid progress in the tumor virology field. Currently, acknowledged human cancer viruses include Epstein-Barr virus, Hepatitis B virus, Hepatitis C virus, High-risk human papilloma viruses, Human T-cell lymphotropic virus type 1 and Kaposi’s sarcoma-associated herpesvirus. Extensive epidemiological and mechanistic studies have led to the development of novel preventive and therapeutic approaches for managing some of these infections and associated cancers. In addition, recent advances in molecular technologies have enabled the discovery of a new potential human tumor virus, Merkel cell polyomavirus, but its association with cancer remains to be validated. It is anticipated that in the next few decades many additional human cancer viruses will be discovered and the mechanisms underlying viral oncogenesis delineated. Thus, it can be expected that better tools for preventing and treating virus-associated cancer will be available in the near future. PMID:20971551

Enteral Feeding with Human Milk Decreases Time to Discharge in Infants following Gastroschisis Repair.

PubMed

Gulack, Brian C; Laughon, Matthew M; Clark, Reese H; Burgess, Terrance; Robinson, Sybil; Muhammad, Abdurrauf; Zhang, Angela; Davis, Adrienne; Morton, Robert; Chu, Vivian H; Arnold, Christopher J; Hornik, Christoph P; Smith, P Brian

2016-03-01

To assess the effect of enteral feeding with human milk on the time from initiation of feeds to discharge after gastroschisis repair through review of a multi-institutional database. Infants who underwent gastroschisis repair between 1997 and 2012 with data recorded in the Pediatrix Medical Group Clinical Data Warehouse were categorized into 4 groups based on the percentage of days fed human milk out of the number of days fed enterally. Cox proportional hazards regression modeling was performed to determine the adjusted effect of human milk on the time from initiation of feeds to discharge. Among 3082 infants, 659 (21%) were fed human milk on 0% of enteral feeding days, 766 (25%) were fed human milk on 1%-50% of enteral feeding days, 725 (24%) were fed human milk on 51%-99% of enteral feeding days, and 932 (30%) were fed human milk on 100% of enteral feeding days. Following adjustment, being fed human milk on 0% of enteral feeding days was associated with a significantly increased time to discharge compared with being fed human milk on 100% of enteral feeding days (hazard ratio [HR] for discharge per day, 0.46; 95% CI, 0.40-0.52). The same was found for infants fed human milk on 1%-50% of enteral feeding days (HR, 0.37; 95% CI, 0.32-0.41) and for infants fed human milk on 51%-99% of enteral feeding days (HR, 0.51; 95% CI, 0.46-0.57). The use of human milk for enteral feeding of infants following repair of gastroschisis significantly reduces the time to discharge from initiation of feeds. Copyright © 2016 Elsevier Inc. All rights reserved.

A methodology to condition distorted acoustic emission signals to identify fracture timing from human cadaver spine impact tests.

PubMed

Arun, Mike W J; Yoganandan, Narayan; Stemper, Brian D; Pintar, Frank A

2014-12-01

While studies have used acoustic sensors to determine fracture initiation time in biomechanical studies, a systematic procedure is not established to process acoustic signals. The objective of the study was to develop a methodology to condition distorted acoustic emission data using signal processing techniques to identify fracture initiation time. The methodology was developed from testing a human cadaver lumbar spine column. Acoustic sensors were glued to all vertebrae, high-rate impact loading was applied, load-time histories were recorded (load cell), and fracture was documented using CT. Compression fracture occurred to L1 while other vertebrae were intact. FFT of raw voltage-time traces were used to determine an optimum frequency range associated with high decibel levels. Signals were bandpass filtered in this range. Bursting pattern was found in the fractured vertebra while signals from other vertebrae were silent. Bursting time was associated with time of fracture initiation. Force at fracture was determined using this time and force-time data. The methodology is independent of selecting parameters a priori such as fixing a voltage level(s), bandpass frequency and/or using force-time signal, and allows determination of force based on time identified during signal processing. The methodology can be used for different body regions in cadaver experiments. Copyright © 2014 Elsevier Ltd. All rights reserved.

Initial Investigation into the Psychoacoustic Properties of Small Unmanned Aerial System Noise

NASA Technical Reports Server (NTRS)

Christian, Andrew; Cabell, Randolph

2017-01-01

For the past several years, researchers at NASA Langley have been engaged in a series of projects to study the degree to which existing facilities and capabilities, originally created for work on full-scale aircraft, are extensible to smaller scales --those of the small unmanned aerial systems (sUAS, also UAVs and, colloquially, `drones') that have been showing up in the nation's airspace of late. This paper follows an e ort that has led to an initial human{subject psychoacoustic test regarding the annoyance generated by sUAS noise. This e ort spans three phases: 1. The collection of the sounds through field recordings. 2. The formulation and execution of a psychoacoustic test using those recordings. 3. The initial analysis of the data from that test. The data suggests a lack of parity between the noise of the recorded sUAS and that of a set of road vehicles that were also recorded and included in the test, as measured by a set of contemporary noise metrics. Future work, including the possibility of further human subject testing, is discussed in light of this suggestion.

Regulated expression of the MRP8 and MRP14 genes during terminal differentiation of human promyelocytic leukemic HL-60 cells

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

Warner-Bartnicki, A.L.; Murao, S.; Collart, F.R.

1992-02-14

The calcium-binding proteins MRP8 and MRP14 are induced during monomyelocytic cell maturation and may mediate the growth arrest in differentiating HL-60 cells. We determined the levels of a protein complex (PC) containing MRP8 and MRP14 and investigated the mechanism by which the genes encoding these proteins are regulated in HL-60 cells treated with the differentiation-inducing agent mycophenolic acid. Elevated levels of the PC were found to directly parallel gains in the steady-state levels of MRP8 and MRP14 mRNA. Transcription studies with the use of nuclear run-on experiments revealed increased transcription initiation at the MRP8 and MRP14 promoters after MPA treatment.more » 1{alpha},25-Dihydroxyvitamin D{sub 3}, which induces HL-60 cell differentiation by another mechanism, was also found to increase transcription initiation at the MRP8 and MRP14 promoters, suggesting that this initiation is the major control of MRP8 and MRP14 gene expression during terminal differentiation of human promyelocytic cells.« less

Biological Effects of Activating Distinct ErbB Receptor Dimers in Polarized Growth Arrested Epithelia

DTIC Science & Technology

2006-09-01

deregulating the function of Par protein complex, we made the unexpected observation that overexpression of Par6 induced growth- factor independent...predisposition factors for human cancer [8] and the human papillomavirus protein E6, targets scribble for degradation[9]. It has also been shown that Par6...vivo and thus is an excellent model to study the important factors in the initiation of the oncogenic process. However, activation of ErbB1 does not

Identification of Early Response Genes in Human Peripheral Leukocytes Infected with Orientia tsutsugamushi: The Emergent of a Unique Gene Expression Profile for Diagnosis of O. tsutsugamush Infection

DTIC Science & Technology

2010-01-01

dynein to move from the cell periphery to the microtubule organizing center [22]. Therefore, the initial interactions between host and intracellular...used to study host-pathogen interactions , mainly by identifying genes from pathogens that may be involved in pathogenecity and by surveying the scope...toward understanding the host-Orientia tsutsugamushi interaction at the molecular level, we used human cDNA microarray technology to examine in detail

Developing Novel Therapeutic Approaches in Small Cell Lung Carcinoma Using Genetically Engineered Mouse Models and Human Circulating Tumor Cells

DTIC Science & Technology

2016-12-01

developed expertise in live animal imaging to enable monitoring to tumors over time in these models. We have initiated treatment studies with chemotherapy...requested on 9/22/14 and reported in our first annual report. Significant changes in use or care of human subjects, vertebrate animals ...biohazards and/or select agents We have no additional changes to make in use of vertebrate animals , biohazards and/or select reagents beyond what was

Identification of a sulfate metabolite of PCB 11 in human serum

PubMed Central

Grimm, Fabian A.; Lehmler, Hans-Joachim; Koh, Wen Xin; DeWall, Jeanne; Teesch, Lynn M.; Hornbuckle, Keri C.; Thorne, Peter S.; Robertson, Larry W.; Duffel, Michael W.

2016-01-01

Despite increasing evidence for a major role for sulfation in the metabolism of lower-chlorinated polychlorinated biphenyls in vitro and in vivo, and initial evidence for potential bioactivities of the resulting sulfate ester metabolites, the formation of PCB sulfates in PCB exposed human populations had not been explored. The primary goal of this study was to determine if PCB sulfates, and potentially other conjugated PCB derivatives, are relevant classes of PCB metabolites in the serum of humans with known exposures to PCBs. In order to detect and quantify dichlorinated PCB sulfates in serum samples of 46 PCB-exposed individuals from either rural or urban communities, we developed a high-resolution mass spectrometry-based protocol using 4-PCB 11 sulfate as a model compound. The method also allowed the preliminary analysis of these 46 human serum extracts for the presence of other metabolites, such as glucuronic acid conjugates and hydroxylated PCBs. Sulfate ester metabolites derived from dichlorinated PCBs were detectable and quantifiable in more than 20 % of analyzed serum samples. Moreover, we were able to utilize this method to detect PCB glucuronides and hydroxylated PCBs, albeit at lower frequencies than PCB sulfates. Altogether, our results provide initial evidence for the presence of PCB sulfates in human serum. Considering the inability of previously employed analytical protocols for PCBs to extract these sulfate ester metabolites and the concentrations of these metabolites observed in our current study, our data support the hypothesis that total serum levels of PCB metabolites in exposed individuals may have been underestimated in the past. PMID:27816204

Identification of a sulfate metabolite of PCB 11 in human serum.

PubMed

Grimm, Fabian A; Lehmler, Hans-Joachim; Koh, Wen Xin; DeWall, Jeanne; Teesch, Lynn M; Hornbuckle, Keri C; Thorne, Peter S; Robertson, Larry W; Duffel, Michael W

2017-01-01

Despite increasing evidence for a major role for sulfation in the metabolism of lower-chlorinated polychlorinated biphenyls in vitro and in vivo, and initial evidence for potential bioactivities of the resulting sulfate ester metabolites, the formation of PCB sulfates in PCB exposed human populations had not been explored. The primary goal of this study was to determine if PCB sulfates, and potentially other conjugated PCB derivatives, are relevant classes of PCB metabolites in the serum of humans with known exposures to PCBs. In order to detect and quantify dichlorinated PCB sulfates in serum samples of 46 PCB-exposed individuals from either rural or urban communities, we developed a high-resolution mass spectrometry-based protocol using 4-PCB 11 sulfate as a model compound. The method also allowed the preliminary analysis of these 46 human serum extracts for the presence of other metabolites, such as glucuronic acid conjugates and hydroxylated PCBs. Sulfate ester metabolites derived from dichlorinated PCBs were detectable and quantifiable in more than 20% of analyzed serum samples. Moreover, we were able to utilize this method to detect PCB glucuronides and hydroxylated PCBs, albeit at lower frequencies than PCB sulfates. Altogether, our results provide initial evidence for the presence of PCB sulfates in human serum. Considering the inability of previously employed analytical protocols for PCBs to extract these sulfate ester metabolites and the concentrations of these metabolites observed in our current study, our data support the hypothesis that total serum levels of PCB metabolites in exposed individuals may have been underestimated in the past. Copyright © 2016 Elsevier Ltd. All rights reserved.

Strategic research in the social sciences

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

Bainbridge, W.S.

1995-12-31

The federal government has identified a number of multi-agency funding initiatives for science in strategic areas, such as the initiatives on global environmental change and high performance computing, that give some role to the social sciences. Seven strategic areas for social science research are given with potential for federal funding: (1) Democratization. (2) Human Capital. (3) Administrative Science. (4) Cognitive Science. (5) High Performance Computing and Digital Libraries. (6) Human Dimensions of Environmental Change. and (7) Human Genetic Diversity. The first two are addressed in detail and the remainder as a group. 10 refs.

Architecture of human translation initiation factor 3

PubMed Central

Querol-Audi, Jordi; Sun, Chaomin; Vogan, Jacob M.; Smith, Duane; Gu, Yu; Cate, Jamie; Nogales, Eva

2013-01-01

SUMMARY Eukaryotic translation initiation factor 3 (eIF3) plays a central role in protein synthesis by organizing the formation of the 43S preinitiation complex. Using genetic tag visualization by electron microscopy, we reveal the molecular organization of ten human eIF3 subunits, including an octameric core. The structure of eIF3 bears a close resemblance to that of the proteasome lid, with a conserved spatial organization of eight core subunits containing PCI and MPN domains that coordinate functional interactions in both complexes. We further show that eIF3 subunits a and c interact with initiation factors eIF1 and eIF1A, which control the stringency of start codon selection. Finally, we find that subunit j, which modulates messenger RNA interactions with the small ribosomal subunit, makes multiple independent interactions with the eIF3 octameric core. These results highlight the conserved architecture of eIF3 and how it scaffolds key factors that control translation initiation in higher eukaryotes, including humans. PMID:23623729

Comparison of minipig, dog, monkey and human drug metabolism and disposition.

PubMed

Dalgaard, Lars

2015-01-01

This article gives an overview of the drug metabolism and disposition (ADME) characteristics of the most common non-rodent species used in toxicity testing of drugs (minipigs, dogs, and monkeys) and compares these to human characteristics with regard to enzymes mediating the metabolism of drugs and the transport proteins which contribute to the absorption, distribution and excretion of drugs. Literature on ADME and regulatory guidelines of relevance in drug development of small molecules has been gathered. Non-human primates (monkeys) are the species that is closest to humans in terms of genetic homology. Dogs have an advantage due to the ready availability of comprehensive background data for toxicological safety assessment and dogs are easy to handle. Pigs have been used less than dogs and monkeys as a model in safety assessment of drug candidates. However, when a drug candidate is metabolised by aldehyde oxidase (AOX1), N-acetyltransferases (NAT1 and NAT2) or cytochrome (CYP2C9-like) enzymes which are not expressed in dogs, but are present in pigs, this species may be a better choice than dogs, provided that adequate exposure can be obtained in pigs. Conversely, pigs might not be the right choice if sulfation, involving 3-phospho-adenosyl-5-phosphosulphate sulphotransferase (PAPS) is an important pathway in the human metabolism of a drug candidate. In general, the species selection should be based on comparison between in vitro studies with human cell-based systems and animal-cell-based systems. Results from pharmacokinetic studies are also important for decision-making by establishing the obtainable exposure level in the species. Access to genetically humanized mouse models and highly sensitive analytical methods (accelerator mass spectrometry) makes it possible to improve the chance of finding all metabolites relevant for humans before clinical trials have been initiated and, if necessary, to include another animal species before long term toxicity studies are initiated. In conclusion, safety testing can be optimized by applying knowledge about species ADME differences and utilising advanced analytical techniques. Copyright © 2014 Elsevier Inc. All rights reserved.

The Robot in the Crib: A Developmental Analysis of Imitation Skills in Infants and Robots.

PubMed

Demiris, Yiannis; Meltzoff, Andrew

2008-01-01

Interesting systems, whether biological or artificial, develop. Starting from some initial conditions, they respond to environmental changes, and continuously improve their capabilities. Developmental psychologists have dedicated significant effort to studying the developmental progression of infant imitation skills, because imitation underlies the infant's ability to understand and learn from his or her social environment. In a converging intellectual endeavour, roboticists have been equipping robots with the ability to observe and imitate human actions because such abilities can lead to rapid teaching of robots to perform tasks. We provide here a comparative analysis between studies of infants imitating and learning from human demonstrators, and computational experiments aimed at equipping a robot with such abilities. We will compare the research across the following two dimensions: (a) initial conditions-what is innate in infants, and what functionality is initially given to robots, and (b) developmental mechanisms-how does the performance of infants improve over time, and what mechanisms are given to robots to achieve equivalent behaviour. Both developmental science and robotics are critically concerned with: (a) how their systems can and do go 'beyond the stimulus' given during the demonstration, and (b) how the internal models used in this process are acquired during the lifetime of the system.

The Dynamics of Initiative in Communication Networks.

PubMed

Mollgaard, Anders; Mathiesen, Joachim

2016-01-01

Human social interaction is often intermittent. Two acquainted persons can have extended periods without social interaction punctuated by periods of repeated interaction. In this case, the repeated interaction can be characterized by a seed initiative by either of the persons and a number of follow-up interactions. The tendency to initiate social interaction plays an important role in the formation of social networks and is in general not symmetric between persons. In this paper, we study the dynamics of initiative by analysing and modeling a detailed call and text message network sampled from a group of 700 individuals. We show that in an average relationship between two individuals, one part is almost twice as likely to initiate communication compared to the other part. The asymmetry has social consequences and ultimately might lead to the discontinuation of a relationship. We explain the observed asymmetry by a positive feedback mechanism where individuals already taking initiative are more likely to take initiative in the future. In general, people with many initiatives receive attention from a broader spectrum of friends than people with few initiatives. Lastly, we compare the likelihood of taking initiative with the basic personality traits of the five factor model.

Human ribosomal RNA gene: nucleotide sequence of the transcription initiation region and comparison of three mammalian genes.

PubMed Central

Financsek, I; Mizumoto, K; Mishima, Y; Muramatsu, M

1982-01-01

The transcription initiation site of the human ribosomal RNA gene (rDNA) was located by using the single-strand specific nuclease protection method and by determining the first nucleotide of the in vitro capped 45S preribosomal RNA. The sequence of 1,211 nucleotides surrounding the initiation site was determined. The sequenced region was found to consist of 75% G and C and to contain a number of short direct and inverted repeats and palindromes. By comparison of the corresponding initiation regions of three mammalian species, several conserved sequences were found upstream and downstream from the transcription starting point. Two short A + T-rich sequences are present on human, mouse, and rat ribosomal RNA genes between the initiation site and 40 nucleotides upstream, and a C + T cluster is located at a position around -60. At and downstream from the initiation site, a common sequence, T-AG-C-T-G-A-C-A-C-G-C-T-G-T-C-C-T-CT-T, was found in the three genes from position -1 through +18. The strong conservation of these sequences suggests their functional significance in rDNA. The S1 nuclease protection experiments with cloned rDNA fragments indicated the presence in human 45S RNA of molecules several hundred nucleotides shorter than the supposed primary transcript. The first 19 nucleotides of these molecules appear identical--except for one mismatch--to the nucleotide sequence of the 5' end of a supposed early processing product of the mouse 45S RNA. Images PMID:6954460

The human milk project: a quality improvement initiative to increase human milk consumption in very low birth weight infants.

PubMed

Ward, Laura; Auer, Christine; Smith, Carrie; Schoettker, Pamela J; Pruett, Raymond; Shah, Nilesh Y; Kotagal, Uma R

2012-08-01

Human milk has well-established health benefits for preterm infants. We conducted a multidisciplinary quality improvement effort aimed at providing at least 500 mL of human milk/kg in the first 14 days of life to very low birth weight (VLBW) (< 1,500 g) infants in the neonatal intensive care unit. Improvement activities included antenatal consults with at-risk mothers, staff and parent education, a breast pump loaner program for uninsured/underinsured mothers, pump logs, establishment of a donor milk program, and twice-daily physician evaluation of infants' ability to tolerate feedings. The number of infants receiving at least 500 mL of human milk/kg in their first 14 days of life increased from 50% to 80% within 11 months of implementation, and this increase has been sustained for 4 years. Infants who met the feeding goal because they received donor milk increased each year. Since September 2007, infants have received, on average, 1,111 mL of human milk/kg. Approximately 4% of infants did not receive any human milk. Respiratory instability was the most frequent physiological reason given by clinicians for not initiating or advancing feedings in the first 14 days of life. Our quality improvement initiative resulted in a higher consumption of human milk in VLBW infants in the first 14 days of life. Other clinicians can use these described quality improvement methods and techniques to improve their VLBW babies' consumption of human milk.

Application of “Systems Vaccinology” to Evaluate Inflammation and Reactogenicity of Adjuvanted Preventative Vaccines

PubMed Central

Lewis, David J. M.; Lythgoe, Mark P.

2015-01-01

Advances in “omics” technology (transcriptomics, proteomics, metabolomics, genomics/epigenomics, etc.) allied with statistical and bioinformatics tools are providing insights into basic mechanisms of vaccine and adjuvant efficacy or inflammation/reactogenicity. Predictive biomarkers of relatively frequent inflammatory reactogenicity may be identified in systems vaccinology studies involving tens or hundreds of participants and used to screen new vaccines and adjuvants in in vitro, ex vivo, animal, or human models. The identification of rare events (such as those observed with initial rotavirus vaccine or suspected autoimmune complications) will require interrogation of large data sets and population-based research before application of systems vaccinology. The Innovative Medicine Initiative funded public-private project BIOVACSAFE is an initial attempt to systematically identify biomarkers of relatively common inflammatory events after adjuvanted immunization using human, animal, and population-based models. Discriminatory profiles or biomarkers are being identified, which require validation in large trials involving thousands of participants before they can be generalized. Ultimately, it is to be hoped that the knowledge gained from such initiatives will provide tools to the industry, academia, and regulators to select optimal noninflammatory but immunogenic and effective vaccine adjuvant combinations, thereby shortening product development cycles and identifying unsuitable vaccine candidates that would fail in expensive late stage development or postmarketing. PMID:26380327

Human Mitochondrial Transcription Factor B2 Is Required for Promoter Melting during Initiation of Transcription.

PubMed

Posse, Viktor; Gustafsson, Claes M

2017-02-17

The mitochondrial transcription initiation machinery in humans consists of three proteins: the RNA polymerase (POLRMT) and two accessory factors, transcription factors A and B2 (TFAM and TFB2M, respectively). This machinery is required for the expression of mitochondrial DNA and the biogenesis of the oxidative phosphorylation system. Previous experiments suggested that TFB2M is required for promoter melting, but conclusive experimental proof for this effect has not been presented. Moreover, the role of TFB2M in promoter unwinding has not been discriminated from that of TFAM. Here we used potassium permanganate footprinting, DNase I footprinting, and in vitro transcription from the mitochondrial light-strand promoter to study the role of TFB2M in transcription initiation. We demonstrate that a complex composed of TFAM and POLRMT was readily formed at the promoter but alone was insufficient for promoter melting, which only occurred when TFB2M joined the complex. We also show that mismatch bubble templates could circumvent the requirement of TFB2M, but TFAM was still required for efficient initiation. Our findings support a model in which TFAM first recruits POLRMT to the promoter, followed by TFB2M binding and induction of promoter melting. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

The difference in LET and ion species dependence for induction of initially measured and non-rejoined chromatin breaks in normal human fibroblasts.

PubMed

Tsuruoka, Chizuru; Suzuki, Masao; Hande, M Prakash; Furusawa, Yoshiya; Anzai, Kazunori; Okayasu, Ryuichi

2008-08-01

We studied the LET and ion species dependence of the induction of chromatin breaks measured immediately after irradiation as initially measured breaks and after 24 h postirradiation incubation (37 degrees C) as non-rejoined breaks in normal human fibroblasts with different heavy ions, such as carbon, neon, silicon and iron, generated by the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Science (NIRS). Chromatin breaks were measured as an excess number of fragments of prematurely condensed chromosomes using premature chromosome condensation (PCC). The results showed that the number of excess fragments per cell per Gy for initially measured chromatin breaks was dependent on LET in the range from 13.3 to 113.1 keV/mum but was not dependent on ion species. On the other hand, the number of non-rejoined chromatin breaks detected after 24 h postirradiation incubation was clearly dependent on both LET and ion species. No significant difference was observed in the cross section for initially measured breaks, but a statistically significant difference was observed in the cross section for non-rejoined breaks among carbon, neon, silicon and iron ions. This suggests that the LET-dependent structure in the biological effects is reflected in biological consequences of repair processes.

Prognostic factors in pemphigus vulgaris and pemphigus foliaceus.

PubMed

Saha, M; Bhogal, B; Black, M M; Cooper, D; Vaughan, R W; Groves, R W

2014-01-01

Pemphigus typically has a chronic course, although there is great variability in disease duration (DD) and time taken to disease remission (DR) between individuals with the disease. The reasons for this are unclear. To explore the prognostic influence of epidemiological, clinical, immunological and genetic factors on disease course and remission in pemphigus vulgaris (PV) and pemphigus foliaceus (PF). This was a retrospective study of patients with PV and PF, recruited from a single UK centre. Direct and indirect immunofluorescence and enzyme-linked immunosorbent assay studies for antidesmoglein (Dsg) antibodies were used to assess immunological factors. Polymerase chain reaction with sequence specific primers (PCR-SSP) was used to assess the Class II human leukocyte antigen status of patients. Prognostic endpoints investigated were time to initial first DR and total DD. Ninety-five patients were recruited (79 PV and 16 PF). Patients of Indo-Asian origin were significantly associated with longer DD than White-British patients (P = 0.029). In addition, younger age at onset was associated with a worse prognosis in terms of DD: the mean age at presentation of patients with DD of < 5 years was 49 years (SEM = 3.4) compared with 40 years (SEM = 1.9) in those with DD > 5 years (P = 0.039). A higher initial intercellular antibody titre on normal human skin substrate was associated with a greater time to initial DR (P = 0.007) and high anti-Dsg 3 levels at baseline were associated with a longer total DD (P = 0.03). Ethnic group, age at presentation, initial intercellular antibody titre and initial Dsg 3 antibody levels all had a significant impact on prognosis of pemphigus. © 2013 British Association of Dermatologists.

Differences in Human Papillomavirus Vaccination Among Adolescent Girls in Metropolitan Versus Non-metropolitan Areas: Considering the Moderating Roles of Maternal Socioeconomic Status and Health Care Access.

PubMed

Monnat, Shannon M; Rhubart, Danielle C; Wallington, Sherrie Flynt

2016-02-01

This study is among the first to examine metropolitan status differences in human papillomavirus (HPV) vaccine initiation and completion among United States adolescent girls and is unique in its focus on how maternal socioeconomic status and health care access moderate metropolitan status differences in HPV vaccination. Using cross-sectional data from 3573 girls aged 12-17 in the U.S. from the 2008-2010 Behavioral Risk Factor Surveillance System, we estimate main and interaction effects from binary logistic regression models to identify subgroups of girls for which there are metropolitan versus non-metropolitan differences in HPV vaccination. Overall 34 % of girls initiated vaccination, and 19 % completed all three shots. On average, there were no metropolitan status differences in vaccination odds. However, there were important subgroup differences. Among low-income girls and girls whose mothers did not complete high school, those in non-metropolitan areas had significantly higher probability of vaccine initiation than those in metropolitan areas. Among high-income girls and girls whose mothers completed college, those in metropolitan areas had significantly higher odds of vaccine initiation than those in non-metropolitan areas. Moreover, among girls whose mothers experienced a medical cost barrier, non-metropolitan girls were less likely to initiate vaccination compared to metropolitan girls. Mothers remain essential targets for public health efforts to increase HPV vaccination and combat cervical cancer. Public health experts who study barriers to HPV vaccination and physicians who come into contact with mothers should be aware of group-specific barriers to vaccination and employ more tailored efforts to increase vaccination.

75 FR 17411 - Submission for OMB Review; Comment Request; Women's Health Initiative Observational Study

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Submission for OMB Review... of Management and Budget (OMB) a request for review and approval of the information collection listed... assessments of historical, physical, psychosocial, and physiologic characteristics. In addition, the...

Development of Methodologies, Metrics, and Tools for Investigating Human-Robot Interaction in Space Robotics

NASA Technical Reports Server (NTRS)

Ezer, Neta; Zumbado, Jennifer Rochlis; Sandor, Aniko; Boyer, Jennifer

2011-01-01

Human-robot systems are expected to have a central role in future space exploration missions that extend beyond low-earth orbit [1]. As part of a directed research project funded by NASA s Human Research Program (HRP), researchers at the Johnson Space Center have started to use a variety of techniques, including literature reviews, case studies, knowledge capture, field studies, and experiments to understand critical human-robot interaction (HRI) variables for current and future systems. Activities accomplished to date include observations of the International Space Station s Special Purpose Dexterous Manipulator (SPDM), Robonaut, and Space Exploration Vehicle (SEV), as well as interviews with robotics trainers, robot operators, and developers of gesture interfaces. A survey of methods and metrics used in HRI was completed to identify those most applicable to space robotics. These methods and metrics included techniques and tools associated with task performance, the quantification of human-robot interactions and communication, usability, human workload, and situation awareness. The need for more research in areas such as natural interfaces, compensations for loss of signal and poor video quality, psycho-physiological feedback, and common HRI testbeds were identified. The initial findings from these activities and planned future research are discussed. Human-robot systems are expected to have a central role in future space exploration missions that extend beyond low-earth orbit [1]. As part of a directed research project funded by NASA s Human Research Program (HRP), researchers at the Johnson Space Center have started to use a variety of techniques, including literature reviews, case studies, knowledge capture, field studies, and experiments to understand critical human-robot interaction (HRI) variables for current and future systems. Activities accomplished to date include observations of the International Space Station s Special Purpose Dexterous Manipulator (SPDM), Robonaut, and Space Exploration Vehicle (SEV), as well as interviews with robotics trainers, robot operators, and developers of gesture interfaces. A survey of methods and metrics used in HRI was completed to identify those most applicable to space robotics. These methods and metrics included techniques and tools associated with task performance, the quantification of human-robot interactions and communication, usability, human workload, and situation awareness. The need for more research in areas such as natural interfaces, compensations for loss of signal and poor video quality, psycho-physiological feedback, and common HRI testbeds were identified. The initial findings from these activities and planned future research are discussed.

Identification of prefrontal cortex (BA10) activation while performing Stroop test using diffuse optical tomography

NASA Astrophysics Data System (ADS)

Khadka, Sabin; Chityala, Srujan R.; Tian, Fenghua; Liu, Hanli

2011-03-01

Stroop test is commonly used as a behavior-testing tool for psychological examinations that are related to attention and cognitive control of the human brain. Studies have shown activations in Broadmann area 10 (BA10) of prefrontal cortex (PFC) during attention and cognitive process. The use of diffuse optical tomography (DOT) for human brain mapping is becoming more prevalent. In this study we expect to find neural correlates between the performed cognitive tasks and hemodynamic signals detected by a DOT system. Our initial observation showed activation of oxy-hemoglobin concentration in BA 10, which is consistent with some results seen by positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Our study demonstrates the possibility of combining DOT with Stroop test to quantitatively investigate cognitive functions of the human brain at the prefrontal cortex.

Getting the point across: exploring the effects of dynamic virtual humans in an interactive museum exhibit on user perceptions.

PubMed

Rivera-Gutierrez, Diego; Ferdig, Rick; Li, Jian; Lok, Benjamin

2014-04-01

We have created “You, M.D.”, an interactive museum exhibit in which users learn about topics in public health literacy while interacting with virtual humans. You, M.D. is equipped with a weight sensor, a height sensor and a Microsoft Kinect that gather basic user information. Conceptually, You, M.D. could use this user information to dynamically select the appearance of the virtual humans in the interaction attempting to improve learning outcomes and user perception for each particular user. For this concept to be possible, a better understanding of how different elements of the visual appearance of a virtual human affects user perceptions is required. In this paper, we present the results of an initial user study with a large sample size (n =333) ran using You, M.D. The study measured users’ reactions based on the user’s gender and body-mass index (BMI) when facing virtual humans with BMI either concordant or discordant from the user’s BMI. The results of the study indicate that concordance between the users’ BMI and the virtual human’s BMI affects male and female users differently. The results also show that female users rate virtual humans as more knowledgeable than male users rate the same virtual humans.

Stem-Cell-Based Tumorigenesis in Adult Drosophila.

PubMed

Hou, S X; Singh, S R

2017-01-01

Recent studies suggest that a small subset of cells within a tumor, the so-called cancer stem cells (CSCs), are responsible for tumor propagation, relapse, and the eventual death of most cancer patients. CSCs may derive from a few tumor-initiating cells, which are either transformed normal stem cells or reprogrammed differentiated cells after acquiring initial cancer-causing mutations. CSCs and normal stem cells share some properties, but CSCs differ from normal stem cells in their tumorigenic ability. Notably, CSCs are usually resistant to chemo- and radiation therapies. Despite the apparent roles of CSCs in human cancers, the biology underlying their behaviors remains poorly understood. Over the past few years, studies in Drosophila have significantly contributed to this new frontier of cancer research. Here, we first review how stem-cell tumors are initiated and propagated in Drosophila, through niche appropriation in the posterior midgut and through stem-cell competition for niche occupancy in the testis. We then discuss the differences between normal and tumorigenic stem cells, revealed by studying Ras V12 -transformed stem-cell tumors in the Drosophila kidney. Finally, we review the biology behind therapy resistance, which has been elucidated through studies of stem-cell resistance and sensitivity to death inducers using female germline stem cells and intestinal stem cells of the posterior midgut. We expect that screens using adult Drosophila neoplastic stem-cell tumor models will be valuable for identifying novel and effective compounds for treating human cancers. © 2017 Elsevier Inc. All rights reserved.

Review and standardization of cell phone exposure calculations using the SAM phantom and anatomically correct head models.

PubMed

Beard, Brian B; Kainz, Wolfgang

2004-10-13

We reviewed articles using computational RF dosimetry to compare the Specific Anthropomorphic Mannequin (SAM) to anatomically correct models of the human head. Published conclusions based on such comparisons have varied widely. We looked for reasons that might cause apparently similar comparisons to produce dissimilar results. We also looked at the information needed to adequately compare the results of computational RF dosimetry studies. We concluded studies were not comparable because of differences in definitions, models, and methodology. Therefore we propose a protocol, developed by an IEEE standards group, as an initial step in alleviating this problem. The protocol calls for a benchmark validation study comparing the SAM phantom to two anatomically correct models of the human head. It also establishes common definitions and reporting requirements that will increase the comparability of all computational RF dosimetry studies of the human head.

Review and standardization of cell phone exposure calculations using the SAM phantom and anatomically correct head models

PubMed Central

Beard, Brian B; Kainz, Wolfgang

2004-01-01

We reviewed articles using computational RF dosimetry to compare the Specific Anthropomorphic Mannequin (SAM) to anatomically correct models of the human head. Published conclusions based on such comparisons have varied widely. We looked for reasons that might cause apparently similar comparisons to produce dissimilar results. We also looked at the information needed to adequately compare the results of computational RF dosimetry studies. We concluded studies were not comparable because of differences in definitions, models, and methodology. Therefore we propose a protocol, developed by an IEEE standards group, as an initial step in alleviating this problem. The protocol calls for a benchmark validation study comparing the SAM phantom to two anatomically correct models of the human head. It also establishes common definitions and reporting requirements that will increase the comparability of all computational RF dosimetry studies of the human head. PMID:15482601

SOX2 regulates self-renewal and tumorigenicity of human melanoma-initiating cells.

PubMed

Santini, R; Pietrobono, S; Pandolfi, S; Montagnani, V; D'Amico, M; Penachioni, J Y; Vinci, M C; Borgognoni, L; Stecca, B

2014-09-18

Melanoma is one of the most aggressive types of human cancer, characterized by enhanced heterogeneity and resistance to conventional therapy at advanced stages. We and others have previously shown that HEDGEHOG-GLI (HH-GLI) signaling is required for melanoma growth and for survival and expansion of melanoma-initiating cells (MICs). Recent reports indicate that HH-GLI signaling regulates a set of genes typically expressed in embryonic stem cells, including SOX2 (sex-determining region Y (SRY)-Box2). Here we address the function of SOX2 in human melanomas and MICs and its interaction with HH-GLI signaling. We find that SOX2 is highly expressed in melanoma stem cells. Knockdown of SOX2 sharply decreases self-renewal in melanoma spheres and in putative melanoma stem cells with high aldehyde dehydrogenase activity (ALDH(high)). Conversely, ectopic expression of SOX2 in melanoma cells enhances their self-renewal in vitro. SOX2 silencing also inhibits cell growth and induces apoptosis in melanoma cells. In addition, depletion of SOX2 progressively abrogates tumor growth and leads to a significant decrease in tumor-initiating capability of ALDH(high) MICs upon xenotransplantation, suggesting that SOX2 is required for tumor initiation and for continuous tumor growth. We show that SOX2 is regulated by HH signaling and that the transcription factors GLI1 and GLI2, the downstream effectors of HH-GLI signaling, bind to the proximal promoter region of SOX2 in primary melanoma cells. In functional studies, we find that SOX2 function is required for HH-induced melanoma cell growth and MIC self-renewal in vitro. Thus SOX2 is a critical factor for self-renewal and tumorigenicity of MICs and an important mediator of HH-GLI signaling in melanoma. These findings could provide the basis for novel therapeutic strategies based on the inhibition of SOX2 for the treatment of a subset of human melanomas.

21 CFR 570.15 - Adoption of regulation on initiative of Commissioner.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Adoption of regulation on initiative of Commissioner. 570.15 Section 570.15 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Adoption of regulation on initiative of Commissioner. (a) The Commissioner upon his own initiative may...

21 CFR 170.15 - Adoption of regulation on initiative of Commissioner.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Adoption of regulation on initiative of Commissioner. 170.15 Section 170.15 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Adoption of regulation on initiative of Commissioner. (a) The Commissioner upon his own initiative may...

Dynamic resetting of the human circadian pacemaker by intermittent bright light

NASA Technical Reports Server (NTRS)

Rimmer, D. W.; Boivin, D. B.; Shanahan, T. L.; Kronauer, R. E.; Duffy, J. F.; Czeisler, C. A.

2000-01-01

In humans, experimental studies of circadian resetting typically have been limited to lengthy episodes of exposure to continuous bright light. To evaluate the time course of the human endogenous circadian pacemaker's resetting response to brief episodes of intermittent bright light, we studied 16 subjects assigned to one of two intermittent lighting conditions in which the subjects were presented with intermittent episodes of bright-light exposure at 25- or 90-min intervals. The effective duration of bright-light exposure was 31% or 63% compared with a continuous 5-h bright-light stimulus. Exposure to intermittent bright light elicited almost as great a resetting response compared with 5 h of continuous bright light. We conclude that exposure to intermittent bright light produces robust phase shifts of the endogenous circadian pacemaker. Furthermore, these results demonstrate that humans, like other species, exhibit an enhanced sensitivity to the initial minutes of bright-light exposure.

Lunar and Mars missions - Challenges for advanced life support

NASA Technical Reports Server (NTRS)

Duke, Michael B.

1988-01-01

The development of a suite of scenarios is a prerequisite to the studies that will enable an informed decision by the United States on a program to meet the recently announced space policy goal to expand human presence beyond earth orbit. NASA's Office of Exploration is currently studying a range of initiative options that would extend the sphere of human activity in space to Mars and include permanent bases or outposts on the moon and on Mars. This paper describes the evolutionary lunar base and the Mars expedition scenarios in some detail so that an evaluation can be made from the point of view of human support and opportunities. Alternative approaches in the development of lunar outposts are outlined along with Mars expeditionary scenarios. Human environmental issues are discussed, including: closed loop life support systems; EVA systems; mobility systems; and medical support, physiological deconditioning, and psychological effects associated with long-duration missions.

Human responses to bright light of different durations.

PubMed

Chang, Anne-Marie; Santhi, Nayantara; St Hilaire, Melissa; Gronfier, Claude; Bradstreet, Dayna S; Duffy, Jeanne F; Lockley, Steven W; Kronauer, Richard E; Czeisler, Charles A

2012-07-01

Light exposure in the early night induces phase delays of the circadian rhythm in melatonin in humans. Previous studies have investigated the effect of timing, intensity, wavelength, history and pattern of light stimuli on the human circadian timing system. We present results from a study of the duration–response relationship to phase-delaying bright light. Thirty-nine young healthy participants (16 female; 22.18±3.62 years) completed a 9-day inpatient study. Following three baseline days, participants underwent an initial circadian phase assessment procedure in dim light (<3 lux), and were then randomized for exposure to a bright light pulse (∼10,000 lux) of 0.2 h, 1.0 h, 2.5 h or 4.0 h duration during a 4.5 h controlled-posture episode centred in a 16 h wake episode. After another 8 h sleep episode, participants completed a second circadian phase assessment. Phase shifts were calculated from the difference in the clock time of the dim light melatonin onset (DLMO) between the initial and final phase assessments. Exposure to varying durations of bright light reset the circadian pacemaker in a dose-dependent, non-linear manner. Per minute of exposure, the 0.2 h duration was over 5 times more effective at phase delaying the circadian pacemaker (1.07±0.36 h) as compared with the 4.0 h duration (2.65±0.24 h). Acute melatonin suppression and subjective sleepiness also had a dose-dependent response to light exposure duration. These results provide strong evidence for a non-linear resetting response of the human circadian pacemaker to light duration.

Pathway Based Toxicology and Fit-for-Purpose Assays.

PubMed

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

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

Centromere reference models for human chromosomes X and Y satellite arrays

PubMed Central

Miga, Karen H.; Newton, Yulia; Jain, Miten; Altemose, Nicolas; Willard, Huntington F.; Kent, W. James

2014-01-01

The human genome sequence remains incomplete, with multimegabase-sized gaps representing the endogenous centromeres and other heterochromatic regions. Available sequence-based studies within these sites in the genome have demonstrated a role in centromere function and chromosome pairing, necessary to ensure proper chromosome segregation during cell division. A common genomic feature of these regions is the enrichment of long arrays of near-identical tandem repeats, known as satellite DNAs, which offer a limited number of variant sites to differentiate individual repeat copies across millions of bases. This substantial sequence homogeneity challenges available assembly strategies and, as a result, centromeric regions are omitted from ongoing genomic studies. To address this problem, we utilize monomer sequence and ordering information obtained from whole-genome shotgun reads to model two haploid human satellite arrays on chromosomes X and Y, resulting in an initial characterization of 3.83 Mb of centromeric DNA within an individual genome. To further expand the utility of each centromeric reference sequence model, we evaluate sites within the arrays for short-read mappability and chromosome specificity. Because satellite DNAs evolve in a concerted manner, we use these centromeric assemblies to assess the extent of sequence variation among 366 individuals from distinct human populations. We thus identify two satellite array variants in both X and Y centromeres, as determined by array length and sequence composition. This study provides an initial sequence characterization of a regional centromere and establishes a foundation to extend genomic characterization to these sites as well as to other repeat-rich regions within complex genomes. PMID:24501022

The benefits of 'One Health' for pastoralists in Africa.

PubMed

Greter, Helena; Jean-Richard, Vreni; Crump, Lisa; Béchir, Mahamat; Alfaroukh, Idriss O; Schelling, Esther; Bonfoh, Bassirou; Zinsstag, Jakob

2014-04-23

'One health' is particularly suited to serve mobile pastoralists. Dinka pastoralists in Sudan inspired Calvin Schwabe to coin the term 'one medicine', indicating that there is no difference in paradigm between human and veterinary medicine. Our contemporary definition of 'one health' is any added value in terms of improved health of humans and animals or financial savings or environmental services resulting from a closer cooperation of human and animal health sectors. Here we present a summary of 'one health' studies with mobile pastoralists in Africa which were done in research partnership, demonstrating such an added value. Initial joint human and animal health studies revealed higher livestock vaccination coverage than in the pastoralist community, leading to joint animal and human vaccination intervention studies which demonstrated a better access to primary health care services for pastoralists in Chad. Further simultaneous animal and human serological studies showed that camel breeding was associated with human Q-fever seropositivity. In Borana communities in Ethiopia, human cases of Mycobacterium bovis infection could be related to strains isolated from cattle. A challenge remained with regard to how to assess vaccination coverage in mobile populations. With the advent of mobile phones, health and demographic surveillance could be established for mobile pastoralists and their animals. This presents vast possibilities for surveillance and control of human and animal diseases. Pastoralists prefer a 'one health' approach and therefore contribute toward the validation of this concept by showing real added value of the cooperation between human and animal health services.

78 FR 20664 - 2013 Medical Countermeasures Initiative Regulatory Science Symposium

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] 2013 Medical Countermeasures Initiative Regulatory Science Symposium AGENCY: Food and Drug... following meeting: 2013 Medical Countermeasures initiative (MCMi) Regulatory Science Symposium. The...

The potential influence of radiation-induced microenvironments in neoplastic progression

NASA Technical Reports Server (NTRS)

Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

1998-01-01

Ionizing radiation is a complete carcinogen, able both to initiate and promote neoplastic progression and is a known carcinogen of human and murine mammary gland. Tissue response to radiation is a composite of genetic damage, cell death and induction of new gene expression patterns. Although DNA damage is believed to initiate carcinogenesis, the contribution of these other aspects of radiation response are beginning to be explored. Our studies demonstrate that radiation elicits rapid and persistent global alterations in the mammary gland microenvironment. We postulate that radiation-induced microenvironments may affect epithelial cells neoplastic transformation by altering their number or susceptibility. Alternatively, radiation induced microenvironments may exert a selective force on initiated cells and/or be conducive to progression. A key impetus for these studies is the possibility that blocking these events could be a strategy to interrupt neoplastic progression.

Demographic and health attributes of the Nahua, initial contact population of the Peruvian Amazon.

PubMed

Culqui, Dante R; Ayuso-Alvarez, Ana; Munayco, Cesar V; Quispe-Huaman, Carlos; Mayta-Tristán, Percy; Campos, Juan de Mata Donado

2016-01-01

We present the case of the Nahua population of Santa Rosa de Serjali, Peruvian Amazon's population, considered of initial contact. This population consists of human groups that for a long time decided to live in isolation, but lately have begun living a more sedentary lifestyle and in contact with Western populations. There are two fully identified initial contact groups in Peru: the Nahua and the Nanti. The health statistics of the Nahua are scarce. This study offers an interpretation of demographic and epidemiological indicators of the Nahua people, trying to identify if a certain degree of health vulnerability exists. We performed a cross sectional study, and after analyzing their health indicators, as well as the supplemental qualitative analysis of the population, brought us to conclude that in 2006, the Nahua, remained in a state of health vulnerability.

Engineering of Surface Functionality onto Polystyrene Microcarriers for the Attachment and Growth of Human Endothelial Cells

NASA Astrophysics Data System (ADS)

Xiong, Gordon M.; Foord, John S.; Griffiths, Jon-Paul; Parker, Emily M.; Moloney, Mark G.; Choong, Cleo

2014-08-01

This work reports the effects of introducing diverse chemical functionalities onto the surface of polystyrene microcarrier beads on their ability to function as injectable cell carriers. Cellular adhesion and proliferation, as well as cellular outgrowths from microcarrier surfaces, using human umbilical vein endothelial cells (HUVECs), were examined in detail. It was observed that initial cell adhesion appeared to be most significantly decreased by hydrophobicity, whilst cell proliferation appeared to be improved in most chemical functional groups over unmodified polystyrene. Overall, our study highlights the importance of surface chemistry in directing the growth and function of human endothelial cells.

Human Exploration Framework Team: Strategy and Status

NASA Technical Reports Server (NTRS)

Muirhead, Brian K.; Sherwood, Brent; Olson, John

2011-01-01

Human Exploration Framework Team (HEFT) was formulated to create a decision framework for human space exploration that drives out the knowledge, capabilities and infrastructure NASA needs to send people to explore multiple destinations in the Solar System in an efficient, sustainable way. The specific goal is to generate an initial architecture that can evolve into a long term, enterprise-wide architecture that is the basis for a robust human space flight enterprise. This paper will discuss the initial HEFT activity which focused on starting up the cross-agency team, getting it functioning, developing a comprehensive development and analysis process and conducting multiple iterations of the process. The outcome of this process will be discussed including initial analysis of capabilities and missions for at least two decades, keeping Mars as the ultimate destination. Details are provided on strategies that span a broad technical and programmatic trade space, are analyzed against design reference missions and evaluated against a broad set of figures of merit including affordability, operational complexity, and technical and programmatic risk.

Pilot interaction with automated airborne decision making systems

NASA Technical Reports Server (NTRS)

Rouse, W. B.; Chu, Y. Y.; Greenstein, J. S.; Walden, R. S.

1976-01-01

An investigation was made of interaction between a human pilot and automated on-board decision making systems. Research was initiated on the topic of pilot problem solving in automated and semi-automated flight management systems and attempts were made to develop a model of human decision making in a multi-task situation. A study was made of allocation of responsibility between human and computer, and discussed were various pilot performance parameters with varying degrees of automation. Optimal allocation of responsibility between human and computer was considered and some theoretical results found in the literature were presented. The pilot as a problem solver was discussed. Finally the design of displays, controls, procedures, and computer aids for problem solving tasks in automated and semi-automated systems was considered.

Cloning and characterization of the human 5,10-methenyltetrahydrofolate synthetase-encoding cDNA.

PubMed

Dayan, A; Bertrand, R; Beauchemin, M; Chahla, D; Mamo, A; Filion, M; Skup, D; Massie, B; Jolivet, J

1995-11-20

Methenyltetrahydrofolate synthetase (MTHFS) catalyses the obligatory initial metabolic step in the intracellular conversion of 5-formyltetrahydrofolate to other reduced folates. We have isolated and sequenced a human MTHFS cDNA which is 872-bp long and codes for a 203-amino-acid protein of 23,229 Da. Escherichia coli BL21(DE3), transfected with pET11c plasmids containing an open reading frame encoding MTHFS, showed a 100-fold increase in MTHFS activity in bacterial extracts after IPTG induction. Northern blot studies of human tissues determined that the MTHFS mRNA was expressed preferentially in the liver and Southern blot analysis of human genomic DNA suggested the presence of a single-copy gene.

Human papillomavirus vaccine use among adolescent girls and young adult women: an analysis of the 2007 California Health Interview Survey.

PubMed

Tiro, Jasmin A; Tsui, Jennifer; Bauer, Heidi M; Yamada, Eileen; Kobrin, Sarah; Breen, Nancy

2012-06-01

Administration of the human papillomavirus (HPV) vaccine is recommended for adolescent girls and young adult women. Little is known about the factors associated with vaccination. This study examined prevalence and correlates of HPV vaccine initiation (≥1 dose) among a statewide representative sample of adolescent and young adult females living in California. HPV vaccination data on 3615 parents of adolescent girls aged 12-17 and 2068 young adult women aged 18-27 from the 2007 California Health Interview Survey (CHIS) were examined by sociodemographic, healthcare access, and health behavior factors using chi-square and multivariable logistic regression models. Nineteen percent of adolescent girls and 11% of young adult women had initiated the HPV vaccine series. In both groups, lower educational attainment (parental/own) was associated with lack of vaccine initiation. For adolescents, vaccine initiation was also significantly lower among those whose parents had low incomes or no usual source of care. For young adults, initiation was lower among the older group and those who spent less time in the United States, had public insurance, had no recent provider visit, or had fewer sexual partners. In a statewide representative sample, different correlates of early initiation of HPV vaccination emerged for Californian adolescent girls and young adult women. These different patterns may be due to differential access to programs that provide free or low-cost HPV vaccines. Because several of these factors are associated with disparities in use of Pap tests, disparities will persist or even worsen unless greater effort is placed on vaccinating populations at highest risk for cervical cancer.

Effect of Abdominal Loading Location on Liver Motion: Experimental Assessment using Ultrafast Ultrasound Imaging and Simulation with a Human Body Model.

PubMed

Le Ruyet, Anicet; Berthet, Fabien; Rongiéras, Frédéric; Beillas, Philippe

2016-11-01

A protocol based on ultrafast ultrasound imaging was applied to study the in situ motion of the liver while the abdomen was subjected to compressive loading at 3 m/s by a hemispherical impactor or a seatbelt. The loading was applied to various locations between the lower abdomen and the mid thorax while feature points inside the liver were followed on the ultrasound movie (2000 frames per second). Based on tests performed on five post mortem human surrogates (including four tested in the current study), trends were found between the loading location and feature point trajectory parameters such as the initial angle of motion or the peak displacement in the direction of impact. The impactor tests were then simulated using the GHBMC M50 human body model that was globally scaled to the dimensions of each surrogate. Some of the experimental trends observed could be reproduced in the simulations (e.g. initial angle) while others differed more widely (e.g. final caudal motion). The causes for the discrepancies need to be further investigated. The liver strain energy density predicted by the model was also widely affected by the impact location. Experimental and simulation results both highlight the importance of the liver position with respect to the impactor when studying its response in situ.

An analysis of nitrification during the aerobic digestion of secondary sludges.

PubMed

Bhargava, D S; Datar, M T

1989-01-01

Investigations were undertaken to study the occurrence and progress of nitrification during aerobic digestion of activated sludge in a wide range of initial concentrations of total solids (1000 to 80 000 mg litre(-1), initial pH range of 4.5 to 10.4 and digestion temperature range of 5 degrees to 60 degrees C. Batch aerobic digestion studies on activated sludge grown on wastewater (enriched with organic solids from human excretal material) indicate that almost complete elimination of the 'biodegradable' matter of the activated sludge was one of the essential prerequisites to initiate nitrification. Favourable ranges of temperature and pH for nitrification were observed to be 25 degrees to 30 degrees C and 6.0 to 8.3, respectively. With all favourable conditions, a minimum period of about 2 days was necessary for population build-up of genera Nitrosomonas and Nitrobacter, and to initiate nitrification. Nitrate formation invariably lagged behind nitrite formation, but under certain conditions both phases of nitrification were observed to progress hand in hand.

[Expression of matrix metalloproteinase-19 in the human cornea. Wound healing in the MMP-19 knock-out mouse model].

PubMed

Treumer, F; Flöhr, C; Klettner, A; Nölle, B; Roider, J

2010-07-01

At present there are no data in the literature on the expression of matrix metalloprotein-19 in the human cornea. The aim of this study was to analyze the expression of matrix metalloproteinase-19 in the human cornea and to investigate its potential role in corneal wound healing using a MMP-19 knock-out mouse model. A method with Western blotting and immunohistological staining for MMP-19 was performed using paraffin embedded human corneas. Excimer laser keratectomy was performed in wild type (wt) and MMP-19 knock-out (ko) mice and the rate of re-epithelialization was analyzed after 8 h and 18 h. MMP-19 was strongly expressed in the human corneal epithelium mainly in the basal cell layer. MMP-19 was not expressed in the corneal stroma. In the mouse model the size of the corneal lesion after 8 h was 83% (wt) and 89.9% (ko) of the initial area (p=0.09). After 18 h the lesion was 17% (wt) and 13.3% (ko) of the initial area (p=0.01). Laminin-5 was expressed in the migrating epithelial cells with no differences between wild type and knock-out mouse. MMP-19 showed a strong expression in the basal cells of the human corneal epithelium. Corneal re-epithelialization was slightly faster in the MMP-19 knock-out mouse. No differences in the expression of laminin-5 could be detected.

Panta Rhei-Everything flows: Global Hotspots of Human-Water Interactions

NASA Astrophysics Data System (ADS)

Di Baldassarre, G.; Srinivasan, V.; Tian, F.; Mohamed, Y.; Krueger, T.; Kreibich, H.; Liu, J.; Troy, T. J.; AghaKouchak, A.

2017-12-01

Panta Rhei-Everything Flows is the scientific decade (2013-2022) of the International Association of Hydrological Sciences (IAHS). This initiative aims to reach an improved interpretation of the processes governing the water cycle by focusing on their changing dynamics in connection with rapidly changing human systems (Montanari et al., 2013; McMillan et al., 2016). More than 400 water scientists have been involved in Panta Rhei so far, and several working groups have produced significant outcomes. In this presentation, we first summarize some key achievements of this initiative by showing how they have advanced our understanding of the way in which humans impact on, and respond to, hydrological change. Then, we suggest simple indicators to characterize interactions between water and human systems. These indicators aim to capture the relevance of human-water interactions and their potential to generate negative effects, such as water crises or unintended consequences. Finally, we show an application of these indicators to global hotspots, i.e. contrasting case studies from around the world. Our goal is to facilitate a community-wide effort in collecting and sharing essential data to map the role of human-water interactions across social and hydrological conditions. ReferencesMontanari et al. (2013) Panta Rhei—Everything Flows: Change in hydrology and society—The IAHS Scientific Decade 2013-2022, Hydrological Sciences Journal, 58(6), 1256-1275. McMillan et al. (2016) Panta Rhei 2013-2015: Global perspectives on hydrology, society and change. Hydrological sciences journal 61(7), 1174-1191.

Generation of mature T cells from human hematopoietic stem and progenitor cells in artificial thymic organoids.

PubMed

Seet, Christopher S; He, Chongbin; Bethune, Michael T; Li, Suwen; Chick, Brent; Gschweng, Eric H; Zhu, Yuhua; Kim, Kenneth; Kohn, Donald B; Baltimore, David; Crooks, Gay M; Montel-Hagen, Amélie

2017-05-01

Studies of human T cell development require robust model systems that recapitulate the full span of thymopoiesis, from hematopoietic stem and progenitor cells (HSPCs) through to mature T cells. Existing in vitro models induce T cell commitment from human HSPCs; however, differentiation into mature CD3 + TCR-αβ + single-positive CD8 + or CD4 + cells is limited. We describe here a serum-free, artificial thymic organoid (ATO) system that supports efficient and reproducible in vitro differentiation and positive selection of conventional human T cells from all sources of HSPCs. ATO-derived T cells exhibited mature naive phenotypes, a diverse T cell receptor (TCR) repertoire and TCR-dependent function. ATOs initiated with TCR-engineered HSPCs produced T cells with antigen-specific cytotoxicity and near-complete lack of endogenous TCR Vβ expression, consistent with allelic exclusion of Vβ-encoding loci. ATOs provide a robust tool for studying human T cell differentiation and for the future development of stem-cell-based engineered T cell therapies.

Generation of mature T cells from human hematopoietic stem/progenitor cells in artificial thymic organoids

PubMed Central

Seet, Christopher S.; He, Chongbin; Bethune, Michael T.; Li, Suwen; Chick, Brent; Gschweng, Eric H.; Zhu, Yuhua; Kim, Kenneth; Kohn, Donald B.; Baltimore, David; Crooks, Gay M.; Montel-Hagen, Amélie

2017-01-01

Studies of human T cell development require robust model systems that recapitulate the full span of thymopoiesis, from hematopoietic stem and progenitor cells (HSPCs) through to mature T cells. Existing in vitro models induce T cell commitment from human HSPCs; however, differentiation into mature CD3+TCRab+ single positive (SP) CD8+ or CD4+ cells is limited. We describe here a serum-free, artificial thymic organoid (ATO) system that supports highly efficient and reproducible in vitro differentiation and positive selection of conventional human T cells from all sources of HSPCs. ATO-derived T cells exhibited mature naïve phenotypes, a diverse TCR repertoire, and TCR-dependent function. ATOs initiated with TCR-engineered HSPCs produced T cells with antigen specific cytotoxicity and near complete lack of endogenous TCR Vβ expression, consistent with allelic exclusion of Vβ loci. ATOs provide a robust tool for studying human T cell development and stem cell based approaches to engineered T cell therapies. PMID:28369043

Dopamine in the medial amygdala network mediates human bonding.

PubMed

Atzil, Shir; Touroutoglou, Alexandra; Rudy, Tali; Salcedo, Stephanie; Feldman, Ruth; Hooker, Jacob M; Dickerson, Bradford C; Catana, Ciprian; Barrett, Lisa Feldman

2017-02-28

Research in humans and nonhuman animals indicates that social affiliation, and particularly maternal bonding, depends on reward circuitry. Although numerous mechanistic studies in rodents demonstrated that maternal bonding depends on striatal dopamine transmission, the neurochemistry supporting maternal behavior in humans has not been described so far. In this study, we tested the role of central dopamine in human bonding. We applied a combined functional MRI-PET scanner to simultaneously probe mothers' dopamine responses to their infants and the connectivity between the nucleus accumbens (NAcc), the amygdala, and the medial prefrontal cortex (mPFC), which form an intrinsic network (referred to as the "medial amygdala network") that supports social functioning. We also measured the mothers' behavioral synchrony with their infants and plasma oxytocin. The results of this study suggest that synchronous maternal behavior is associated with increased dopamine responses to the mother's infant and stronger intrinsic connectivity within the medial amygdala network. Moreover, stronger network connectivity is associated with increased dopamine responses within the network and decreased plasma oxytocin. Together, these data indicate that dopamine is involved in human bonding. Compared with other mammals, humans have an unusually complex social life. The complexity of human bonding cannot be fully captured in nonhuman animal models, particularly in pathological bonding, such as that in autistic spectrum disorder or postpartum depression. Thus, investigations of the neurochemistry of social bonding in humans, for which this study provides initial evidence, are warranted.

Our Mission to Planet Earth: A guide to teaching Earth system science

NASA Technical Reports Server (NTRS)

1994-01-01

Volcanic eruptions, hurricanes, floods, and El Nino are naturally occurring events over which humans have no control. But can human activities cause additional environmental change? Can scientists predict the global impacts of increased levels of pollutants in the atmosphere? Will the planet warm because increased levels of greenhouse gases, produced by the burning of fossil fuels, trap heat and prevent it from being radiated back into space? Will the polar ice cap melt, causing massive coastal flooding? Have humans initiated wholesale climatic change? These are difficult questions, with grave implications. Predicting global change and understanding the relationships among earth's components have increased in priority for the nation. The National Aeronautics and Space Administration (NASA), along with many other government agencies, has initiated long-term studies of earth's atmosphere, oceans, and land masses using observations from satellite, balloon, and aircraft-borne instruments. NASA calls its research program Mission to Planet Earth. Because NASA can place scientific instruments far above earth's surface, the program allows scientists to explore earth's components and their interactions on a global scale.

Structural impact detection with vibro-haptic interfaces

NASA Astrophysics Data System (ADS)

Jung, Hwee-Kwon; Park, Gyuhae; Todd, Michael D.

2016-07-01

This paper presents a new sensing paradigm for structural impact detection using vibro-haptic interfaces. The goal of this study is to allow humans to ‘feel’ structural responses (impact, shape changes, and damage) and eventually determine health conditions of a structure. The target applications for this study are aerospace structures, in particular, airplane wings. Both hardware and software components are developed to realize the vibro-haptic-based impact detection system. First, L-shape piezoelectric sensor arrays are deployed to measure the acoustic emission data generated by impacts on a wing. Unique haptic signals are then generated by processing the measured acoustic emission data. These haptic signals are wirelessly transmitted to human arms, and with vibro-haptic interface, human pilots could identify impact location, intensity and possibility of subsequent damage initiation. With the haptic interface, the experimental results demonstrate that human could correctly identify such events, while reducing false indications on structural conditions by capitalizing on human’s classification capability. Several important aspects of this study, including development of haptic interfaces, design of optimal human training strategies, and extension of the haptic capability into structural impact detection are summarized in this paper.

AIDS research in developing countries: do the ends justify the means?

PubMed

Clark, Peter A

2002-09-01

Concrete ethical standards for human research are clearly stipulated in both international and national codes of ethics, and are meant to protect human subjects, especially the most vulnerable. A recent clinical study conducted from 1994 to 1997 by Dr. Thomas C, Quinn, M.D. has fueled the debate raging in the scientific community regarding the ethics of clinical AIDS research in developing countries. Quinn's conducted a community-based, randomized, controlled study of 15,127 rural Ugandans to determine whether intermittent antibiotic treatment to reduce the prevalence of other sexually transmitted diseases would also reduce the rate of HIV transmission. Subsequently, the study identified 415 couples in which one partner was HIV positive and one was initially HIV negative and followed them prospectively for up to 30 months. Researchers were not permitted to inform the seronegative partner of the HIV status of the other partner. As a result, 90 of the initially HIV negative partners (21.7%) seroconverted during a follow-up period of 30 months. To allow for research studies in developing countries that are not permitted in the United States appears to make the Third World equivalent to a 'research sweat shop'. Developing nations offer easy access to patients, reduced costs, and less stringent regulations. This appears to create a double standard for medical research that is both ethically and humanly unacceptable, especially when other viable option exist. To allow relativism to seep into the international and national ethical standards will open the door to an idea that condones the possible abuse of those least able to protect themselves. Researchers have an ethical responsibility to uphold the integrity of these ethical standards. Failure to do so today may have a devastating impact on humanity in the future.

Identifying the links between violence against women and HIV/AIDS: ecosocial and human rights frameworks offer insight into U.S. prevention policies.

PubMed

Teti, Michelle; Chilton, Mariana; Lloyd, Linda; Rubinstein, Susan

2006-01-01

While US government-sponsored HIV prevention initiatives have achieved notable successes, challenges remain to serving women effectively. Intimate partner violence hinders women's efforts to decrease their HIV risk behaviors. The global HIV/AIDS epidemic is often viewed as a human rights crisis. An analysis of US HIV prevention strategies based on ecosocial and health and human rights frameworks clarifies women's HIV risk practices and suggests opportunities for progress. These two frameworks help to (1) demonstrate how HIV/AIDS is a clinical manifestation of violence against women, (2) identify safety from violence as a human right necessary for well-being, and (3) suggest ways in which HIV prevention initiatives can more effectively improve women's health and fulfill their basic human rights.

[Impact of health care reform on human resources and employment management].

PubMed

Brito Quintana, P E

2000-01-01

According to those in charge of health sector reform, human resources are the key component of health sector reform processes and offer health services their greatest competitive advantage. With the help of the Observatory for Human Resources within Health Sector Reform promoted by the Pan American Health Organization and other groups, countries of the Region of the Americas have now begun to gather, in a methodical fashion, tangible evidence of the decisive importance of human resources within health sector reform initiatives and particularly of the impact of these initiatives on health personnel. This mutual influence is the main theme of this article, which explores the most disturbing aspects of health sector reform from a human resources perspective, including job instability and conflicting interests of employers and employees.

Human exploration and settlement of Mars - The roles of humans and robots

NASA Technical Reports Server (NTRS)

Duke, Michael B.

1991-01-01

The scientific objectives and strategies for human settlement on Mars are examined in the context of the Space Exploration Initiative (SEI). An integrated strategy for humans and robots in the exploration and settlement of Mars is examined. Such an effort would feature robotic, telerobotic, and human-supervised robotic phases.

Human Rights and Foreign Policy. Headline Series 241.

ERIC Educational Resources Information Center

Frankel, Charles

A discussion is presented of the meaning of human rights, implications of human rights for foreign policy, and obstacles to its realization on a global scale. Chapter I identifies human rights as a critical issue, commends President Carter's initiative in this area, and points out difficulties of implementing a human rights policy. Chapter II…

A nonlinear dynamics of trunk kinematics during manual lifting tasks.

PubMed

Khalaf, Tamer; Karwowski, Waldemar; Sapkota, Nabin

2015-01-01

Human responses at work may exhibit nonlinear properties where small changes in the initial task conditions can lead to large changes in system behavior. Therefore, it is important to study such nonlinearity to gain a better understanding of human performance under a variety of physical, perceptual, and cognitive tasks conditions. The main objective of this study was to investigate whether the human trunk kinematics data during a manual lifting task exhibits nonlinear behavior in terms of determinist chaos. Data related to kinematics of the trunk with respect to the pelvis were collected using Industrial Lumbar Motion Monitor (ILMM), and analyzed applying the nonlinear dynamical systems methodology. Nonlinear dynamics quantifiers of Lyapunov exponents and Kaplan-Yorke dimensions were calculated and analyzed under different task conditions. The study showed that human trunk kinematics during manual lifting exhibits chaotic behavior in terms of trunk sagittal angular displacement, velocity and acceleration. The findings support the importance of accounting for nonlinear dynamical properties of biomechanical responses to lifting tasks.

Prophylaxis with human serum butyrylcholinesterase protects guinea pigs exposed to multiple lethal doses of soman or VX.

PubMed

Saxena, Ashima; Sun, Wei; Fedorko, James M; Koplovitz, Irwin; Doctor, Bhupendra P

2011-01-01

Human serum butyrylcholinesterase (Hu BChE) is currently under advanced development as a bioscavenger for the prophylaxis of organophosphorus (OP) nerve agent toxicity in humans. It is estimated that a dose of 200mg will be required to protect a human against 2×LD(50) of soman. To provide data for initiating an investigational new drug application for the use of this enzyme as a bioscavenger in humans, we purified enzyme from Cohn fraction IV-4 paste and initiated safety and efficacy evaluations in mice, guinea pigs, and non-human primates. In mice, we demonstrated that a single dose of enzyme that is 30 times the therapeutic dose circulated in blood for at least four days and did not cause any clinical pathology in these animals. In this study, we report the results of safety and efficacy evaluations conducted in guinea pigs. Various doses of Hu BChE delivered by i.m. injections peaked at ∼24h and had a mean residence time of 78-103h. Hu BChE did not exhibit any toxicity in guinea pigs as measured by general observation, serum chemistry, hematology, and gross and histological tissue changes. Efficacy evaluations showed that Hu BChE protected guinea pigs from an exposure of 5.5×LD(50) of soman or 8×LD(50) of VX. These results provide convincing data for the development of Hu BChE as a bioscavenger that can protect humans against all OP nerve agents. Published by Elsevier Inc.

Dog Breed Differences in Visual Communication with Humans

PubMed Central

Konno, Akitsugu; Romero, Teresa; Inoue-Murayama, Miho; Saito, Atsuko; Hasegawa, Toshikazu

2016-01-01

Domestic dogs (Canis familiaris) have developed a close relationship with humans through the process of domestication. In human-dog interactions, eye contact is a key element of relationship initiation and maintenance. Previous studies have suggested that canine ability to produce human-directed communicative signals is influenced by domestication history, from wolves to dogs, as well as by recent breed selection for particular working purposes. To test the genetic basis for such abilities in purebred dogs, we examined gazing behavior towards humans using two types of behavioral experiments: the ‘visual contact task’ and the ‘unsolvable task’. A total of 125 dogs participated in the study. Based on the genetic relatedness among breeds subjects were classified into five breed groups: Ancient, Herding, Hunting, Retriever-Mastiff and Working). We found that it took longer time for Ancient breeds to make an eye-contact with humans, and that they gazed at humans for shorter periods of time than any other breed group in the unsolvable situation. Our findings suggest that spontaneous gaze behavior towards humans is associated with genetic similarity to wolves rather than with recent selective pressure to create particular working breeds. PMID:27736990

Comparative genome map of human and cattle

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

Solinas-Toldo, S.; Fries, R.; Lengauer, C.

Chromosomal homologies between individual human chromosomes and the bovine karyotype have been established by using a new approach termed Zoo-FISH. Labeled DNA libraries from flow-sorted human chromosomes were used as probes for fluorescence in situ hybridization on cattle chromosomes. All human DNA libraries, except the Y chromosome library, hybridized to one or more cattle chromosomes, identifying and delineating 50 segments of homology, most of them corresponding to the regions of homology as identified by the previous mapping of individual conserved loci. However, Zoo-FISH refines the comparative maps constructed by molecular gene mapping of individual loci by providing information on themore » boundaries of conserved regions in the absence of obvious cytogenetic homologies of human and bovine chromosomes. It allows study of karyotypic evolution and opens new avenues for genomic analysis by facilitating the extrapolation of results from the human genome initiative. 50 refs., 3 figs., 1 tab.« less

Effects of pill burden on discontinuation of the initial HAART regimen in minority female patients prescribed 1 pill/day versus any other pill burden.

PubMed

Hill, Seth; Kavookjian, Jan; Qian, Jingjing; Chung, Allison; Vandewaa, John

2014-01-01

Highly active antiretroviral therapy (HAART) is a mainstay of treatment for patients with Human Immunodeficiency Virus (HIV). Since second line HAART therapies can be costlier and less effective, it is essential to understand the duration of initial HAART therapies. The overall aim of this study was to estimate the effects of daily pill burden on the time to discontinuation of the initial HAART regimen. Patients were initially identified through the clinic's CAREWARE database. A chart review was conducted for data collection, where only adult, female, HIV-positive patients initiating therapy at the study clinic between 1 January 2001 and 31 December 2011 were included. All study subjects were followed up from the initiation of HAART to treatment discontinuation. A Kaplan-Meier curve was generated to describe time to discontinuation by regimens, and a Cox proportional hazards model was developed to assess the impact of different regimen and patient demographic characteristics on the hazard of discontinuation of the initial regimen. A total of 498 charts were initially reviewed. After assessment of these patients for inclusion criteria, a cohort of 115 adult female patients who initiated HAART at the study clinic was included. Patients treated with 1 pill/day regimen had a significantly longer time to discontinuation than regimens of >1 pills/day (mean duration of initial therapy was 1062.56 days vs. 631.70 days, respectively, p = 0.003). Compared to 1 pill/day regimens, >1 pills/day regimens were associated with a higher hazard of discontinuation (hazard ratio (HR) =3.44 with 95% confidence interval (CI) = 1.25, 9.48). A higher viral load and patients without insurance were also found to be significantly associated with increased hazards of discontinuation. Overall, female HIV patients initiating therapy with the 1 pill/day HAART regimen were less likely to discontinue their treatment compared to patients initiating with >1 pills/day HAART regimen.

Phage lytic enzymes: a history.

PubMed

Trudil, David

2015-02-01

There are many recent studies regarding the efficacy of bacteriophage-related lytic enzymes: the enzymes of 'bacteria-eaters' or viruses that infect bacteria. By degrading the cell wall of the targeted bacteria, these lytic enzymes have been shown to efficiently lyse Gram-positive bacteria without affecting normal flora and non-related bacteria. Recent studies have suggested approaches for lysing Gram-negative bacteria as well (Briersa Y, et al., 2014). These enzymes include: phage-lysozyme, endolysin, lysozyme, lysin, phage lysin, phage lytic enzymes, phageassociated enzymes, enzybiotics, muralysin, muramidase, virolysin and designations such as Ply, PAE and others. Bacteriophages are viruses that kill bacteria, do not contribute to antimicrobial resistance, are easy to develop, inexpensive to manufacture and safe for humans, animals and the environment. The current focus on lytic enzymes has been on their use as anti-infectives in humans and more recently in agricultural research models. The initial translational application of lytic enzymes, however, was not associated with treating or preventing a specific disease but rather as an extraction method to be incorporated in a rapid bacterial detection assay (Bernstein D, 1997).The current review traces the translational history of phage lytic enzymes-from their initial discovery in 1986 for the rapid detection of group A streptococcus in clinical specimens to evolving applications in the detection and prevention of disease in humans and in agriculture.

Synthesis of three novel fluorine-18 labeled analogues of L-deprenyl for positron emission tomography (PET) studies of monoamine oxidase B (MAO-B).

PubMed

Nag, Sangram; Lehmann, Lutz; Heinrich, Tobias; Thiele, Andrea; Kettschau, Georg; Nakao, Ryuji; Gulyás, Balázs; Halldin, Christer

2011-10-27

The aim in this project was to synthesize and to study fluorine-18 labeled analogues of l-deprenyl which bind selectively to the enzyme monoamine oxidase B (MAO-B). Three fluorinated l-deprenyl analogues have been generated in multistep organic syntheses. The most promising fluorine-18 compound N-[(2S)-1-[(18)F]fluoro-3-phenylpropan-2-yl]-N-methylprop-2-yn-1-amine (4c) was synthesized by a one-step fluorine-18 nucleophilic substitution reaction. Autoradiography on human brain tissue sections demonstrated specific binding for compound 4c to brain regions known to have a high content of MAO-B. In addition, the corresponding nonradioactive fluorine-19 compound (13) inhibited recombinant human MAO-B with an IC(50) of 170.5 ± 29 nM but did not inhibit recombinant human MAO-A (IC(50) > 2000 nM), demonstrating its specificity. Biodistribution of 4c in mice showed high initial brain uptake leveling at 5.2 ± 0.04%ID/g after 2 min post injection. In conclusion, compound 4c is a specific inhibitor of MAO-B with high initial brain uptake in mice and is, therefore, a candidate for further investigation in PET.

Elongin B-mediated epigenetic alteration of viral chromatin correlates with efficient human cytomegalovirus gene expression and replication.

PubMed

Hwang, Jiwon; Saffert, Ryan T; Kalejta, Robert F

2011-01-01

Elongins B and C are members of complexes that increase the efficiency of transcriptional elongation by RNA polymerase II (RNAPII) and enhance the monoubiquitination of histone H2B, an epigenetic mark of actively transcribed genes. Here we show that, in addition to its role in facilitating transcription of the cellular genome, elongin B also enhances gene expression from the double-stranded DNA genome of human cytomegalovirus (HCMV), a pathogenic herpesvirus. Reducing the level of elongin B by small interfering RNA- or short hairpin RNA-mediated knockdown decreased viral mRNA expression, viral protein accumulation, viral DNA replication, and infectious virion production. Chromatin immunoprecipitation analysis indicated viral genome occupancy of the elongating form of RNAPII, and monoubiquitinated histone H2B was reduced in elongin B-deficient cells. These data suggest that, in addition to the previously documented epigenetic regulation of transcriptional initiation, HCMV also subverts cellular elongin B-mediated epigenetic mechanisms for enhancing transcriptional elongation to enhance viral gene expression and virus replication. The genetic and epigenetic control of transcription initiation at both cellular and viral promoters is well documented. Recently, the epigenetic modification of histone H2B monoubiquitination throughout the bodies of cellular genes has been shown to enhance the elongation of RNA polymerase II-initiated transcripts. Mechanisms that might control the elongation of viral transcripts are less well studied. Here we show that, as with cellular genes, elongin B-mediated monoubiquitination of histone H2B also facilitates the transcriptional elongation of human cytomegalovirus genes. This and perhaps other epigenetic markings of actively transcribed regions may help in identifying viral genes expressed during in vitro latency or during natural infections of humans. Furthermore, this work identifies a novel, tractable model system to further study the regulation of transcriptional elongation in living cells.

Advances in Retinal Prosthetic Research: A Systematic Review of Engineering and Clinical Characteristics of Current Prosthetic Initiatives.

PubMed

Cheng, Derrick L; Greenberg, Paul B; Borton, David A

2017-03-01

To date, reviews of retinal prostheses have focused primarily on devices undergoing human trials in the Western Hemisphere and fail to capture significant advances in materials and engineering research in countries such as Japan and Korea, as well as projects in early stages of development. To address these gaps, this systematic review examines worldwide advances in retinal prosthetic research, evaluates engineering characteristics and clinical progress of contemporary device initiatives, and identifies potential directions for future research in the field of retinal prosthetics. A literature search using PubMed, Google Scholar, and IEEExplore was conducted following the PRISMA Guidelines for Systematic Review. Inclusion criteria were peer-reviewed papers demonstrating progress in human or animal trials and papers discussing the prosthetic engineering design. For each initiative, a description of the device, its engineering considerations, and recent clinical results were provided. Ten prosthetic initiatives met our inclusion criteria and were organized by stimulation location. Of these initiatives, four have recently completed human trials, three are undergoing multi- or single-center human trials, and three are undergoing preclinical animal testing. Only the Argus II (FDA 2013, CE 2011) has obtained FDA approval for use in the United States; the Alpha-IMS (CE 2013) has achieved the highest visual acuity using a Landolt-C test to date and is the only device presently undergoing a multicenter clinical trial. Several distinct approaches to retinal stimulation have been successful in eliciting visual precepts in animals and/or humans. However, many clinical needs are still not met and engineering challenges must be addressed before a retinal prosthesis with the capability to fully and safely restore functional vision can be realized.

Success factors for strategic change initiatives: a qualitative study of healthcare administrators' perspectives.

PubMed

Kash, Bita Arbab; Spaulding, Aaron; Johnson, Christopher E; Gamm, Larry

2014-01-01

Success factors related to the implementation of change initiatives are well documented and discussed in the management literature, but they are seldom studied in healthcare organizations engaged in multiple strategic change initiatives. The purpose of this study was to identify key success factors related to implementation of change initiatives based on rich qualitative data gathered from health leader interviews at two large health systems implementing multiple change initiatives. In-depth personal interviews with 61 healthcare leaders in the two large systems were conducted and inductive qualitative analysis was employed to identify success factors associated with 13 change initiatives. Results from this analysis were compared to success factors identified in the literature, and generalizations were drawn that add significantly to the management literature, especially to that in the healthcare sector. Ten specific success factors were identified for the implementation of change initiatives. The top three success factors were (1) culture and values, (2) business processes, and (3) people and engagement. Two of the identified success factors are unique to the healthcare sector and not found in the literature on change models: service quality and client satisfaction (ranked fourth of 10) and access to information (ranked ninth). Results demonstrate the importance of human resource functions, alignment of culture and values with change, and business processes that facilitate effective communication and access to information to achieve many change initiatives. The responses also suggest opportunities for leaders of healthcare organizations to more formally recognize the degree to which various change initiatives are dependent on one another.

The Effects of a Midbrain Glioma on Memory and Other Functions: A Longitudinal Single Case Study

ERIC Educational Resources Information Center

Weddell, Rodger A.

2008-01-01

Our understanding of the effects of midbrain damage on cognition is largely based on animal studies, though there have been occasional investigations of the effects of human midbrain lesions on cognition. This investigation of a rare case of a glioma initially confined to the dorsal midbrain explores the effects of disease progression on IQ,…

Organizational strategy and diversity management: diversity-sensitive orientation as a moderating influence.

PubMed

Dansky, Kathryn H; Weech-Maldonado, Robert; De Souza, Gita; Dreachslin, Janice L

2003-01-01

Empirical studies on diversity suggest that health care organizations have been slow to embrace diversity management. We propose that sensitivity to diversity, at the corporate level, moderates strategic decision making, which influences human resource management practices such as diversity initiatives. This study of 203 hospitals explored the relationships among organizational strategy, organizational sensitivity to diversity, and diversity management practices.

Initial Description of a Quantitative, Cross-Species (Chimpanzee-Human) Social Responsiveness Measure

ERIC Educational Resources Information Center

Marrus, Natasha; Faughn, Carley; Shuman, Jeremy; Petersen, Steve E.; Constantino, John N.; Povinelli, Daniel J.; Pruett, John R., Jr.

2011-01-01

Objective: Comparative studies of social responsiveness, an ability that is impaired in autism spectrum disorders, can inform our understanding of both autism and the cognitive architecture of social behavior. Because there is no existing quantitative measure of social responsiveness in chimpanzees, we generated a quantitative, cross-species…

77 FR 3269 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Data...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-23

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention (CDC) Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Data Coordinating Center for Autism and Other Developmental Disabilities Research and Epidemiologic Studies, RFA DD12-001, Initial...

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…

PARTICLE NUMBER AND SURFACE CHARGE PREDICT THE BIOLOGICAL ACTIVATION OF HUMAN BRONCHIAL EPITHELIAL CELLS EXPOSED TO PARTICULATE MATTER.

EPA Science Inventory

Exposure to particulate matter (PM) produces a uniform degree of mortality in exposed populations, in spite of its diverse sources. This suggests a common mechanism of action to explain its initial toxicity. The present study relates certain physicochemical characteristics (i.e.,...

Correlations of SELENOF and SELENOP genotypes with serum selenium levels and prostate cancer

USDA-ARS?s Scientific Manuscript database

Studies were conducted in order to investigate whether there were relationships among the genotype of selenoproteins implicated in increased cancer risk, selenium status and race. Initial efforts focused on the SELENOF protein which is cytoplasmic in human prostate cancer cell lines and tumor tissue...

DIFFERENTIAL GENE EXPRESSION BY CHAPEL HILL FINE PARTICLES IN HUMAN ALVEOLAR MACHROPHAGES

EPA Science Inventory

Pollutant particles (PM) induce systemic and lung inflammation. Alveolar macrophages (AM) are one of the lung cells directly exposed to PM that may initiate these responses. In this study, we determined the gene expression profile induced by Chapel Hill fine particles (PM2.5) in ...

An Intelligent Tutor for Basic Algebra.

ERIC Educational Resources Information Center

McArthur, David; Stasz, Cathleen

The stated goal of Individual Computer-Assisted Instruction (ICAI) research is the development of computer software that combines much of the subject matter being studied, any particular student's learning schema, and the pedagogical knowledge of human tutors into a powerful one-to-one learning environment. This report describes the initial steps…

77 FR 21785 - Medical Countermeasures Initiative Regulatory Science Symposium

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-11

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Medical Countermeasures Initiative Regulatory Science Symposium AGENCY: Food and Drug Administration, HHS...: Medical Countermeasures Initiative Regulatory Science Symposium. The symposium is intended to provide a...

Reminiscences of a journeyman scientist: studies of thermoregulation in non-human primates and humans.

PubMed

Adair, Eleanor Reed

2008-12-01

After graduating from Mount Holyoke College in 1948 where I majored in experimental psychology I worked at the College for 2 years with the Johns Hopkins Thermophysiological Unit. My graduate work later at the University of Wisconsin, centering on sensory psychology, culminated in my 1955 PhD thesis on human dark adaptation. I continued work in sensory psychology later with Neal Miller at Yale and then moved to the John B. Pierce Foundation--a Yale affiliate--where I began the studies of thermoregulation that constitute the center of my scientific career. Those studies were largely--later wholly--conducted using microwave energy as a thermal load and were thus published in Bioelectromagnetics even as I played an active role in the Bioelectromagnetics Society. In the beginning this work was centered on the responses of Squirrel Monkeys to thermal loads. Later, serving as Senior Scientist at the Air Force Research Laboratory at San Antonio, I completed an extensive analysis of thermal regulation in humans. I consider this work of special note inasmuch as the extraordinary human thermoregulatory ability was surely among the attributes that were paramount in initially separating humans from the other anthropoid primates.

In vitro and in vivo antiproliferative activity of metformin on stem-like cells isolated from spontaneous canine mammary carcinomas: translational implications for human tumors.

PubMed

Barbieri, Federica; Thellung, Stefano; Ratto, Alessandra; Carra, Elisa; Marini, Valeria; Fucile, Carmen; Bajetto, Adriana; Pattarozzi, Alessandra; Würth, Roberto; Gatti, Monica; Campanella, Chiara; Vito, Guendalina; Mattioli, Francesca; Pagano, Aldo; Daga, Antonio; Ferrari, Angelo; Florio, Tullio

2015-04-07

Cancer stem cells (CSCs) are considered the cell subpopulation responsible for breast cancer (BC) initiation, growth, and relapse. CSCs are identified as self-renewing and tumor-initiating cells, conferring resistance to chemo- and radio-therapy to several neoplasias. Nowadays, th (about 10mM)e pharmacological targeting of CSCs is considered an ineludible therapeutic goal. The antidiabetic drug metformin was reported to suppress in vitro and in vivo CSC survival in different tumors and, in particular, in BC preclinical models. However, few studies are available on primary CSC cultures derived from human postsurgical BC samples, likely because of the limited amount of tissue available after surgery. In this context, comparative oncology is acquiring a relevant role in cancer research, allowing the analysis of larger samples from spontaneous pet tumors that represent optimal models for human cancer. Isolation of primary canine mammary carcinoma (CMC) cells and enrichment in stem-like cell was carried out from fresh tumor specimens by culturing cells in stem-permissive conditions. Phenotypic and functional characterization of CMC-derived stem cells was performed in vitro, by assessment of self-renewal, long-lasting proliferation, marker expression, and drug sensitivity, and in vivo, by tumorigenicity experiments. Corresponding cultures of differentiated CMC cells were used as internal reference. Metformin efficacy on CMC stem cell viability was analyzed both in vitro and in vivo. We identified a subpopulation of CMC cells showing human breast CSC features, including expression of specific markers (i.e. CD44, CXCR4), growth as mammospheres, and tumor-initiation in mice. These cells show resistance to doxorubicin but were highly sensitive to metformin in vitro. Finally, in vivo metformin administration significantly impaired CMC growth in NOD-SCID mice, associated with a significant depletion of CSCs. Similarly to the human counterpart, CMCs contain stem-like subpopulations representing, in a comparative oncology context, a valuable translational model for human BC, and, in particular, to predict the efficacy of antitumor drugs. Moreover, metformin represents a potential CSC-selective drug for BC, as effective (neo-)adjuvant therapy to eradicate CSC in mammary carcinomas of humans and animals.

Harmonisation of seven common enzyme results through EQA.

PubMed

Weykamp, Cas; Franck, Paul; Gunnewiek, Jacqueline Klein; de Jonge, Robert; Kuypers, Aldy; van Loon, Douwe; Steigstra, Herman; Cobbaert, Christa

2014-11-01

Equivalent results between different laboratories enable optimal patient care and can be achieved with harmonisation. We report on EQA-initiated national harmonisation of seven enzymes using commutable samples. EQA samples were prepared from human serum spiked with human recombinant enzymes. Target values were assigned with the IFCC Reference Measurement Procedures. The same samples were included at four occasions in the EQA programmes of 2012 and 2013. Laboratories were encouraged to report IFCC traceable results. A parallel study was done to confirm commutability of the samples. Of the 223 participating laboratories, 95% reported IFCC traceable results, ranging from 98% (ASAT) to 87% (amylase). Users of Roche and Siemens (97%) more frequently reported in IFCC traceable results than users of Abbott (91%), Beckman (90%), and Olympus (87%). The success of harmonisation, expressed as the recovery of assigned values and the inter-laboratory CV was: ALAT (recovery 100%; inter-lab CV 4%), ASAT (102%; 4%), LD (98%; 3%), CK (101%; 5%), GGT (98%; 4%), AP (96%; 6%), amylase (99%; 4%). There were no significant differences between the manufacturers. Commutability was demonstrated in the parallel study. Equal results in the same sample in the 2012 and 2013 EQA programmes demonstrated stability of the samples. The EQA-initiated national harmonisation of seven enzymes, using stable, commutable human serum samples, spiked with human recombinant enzymes, and targeted with the IFCC Reference Measurement Procedures, was successful in terms of implementation of IFCC traceable results (95%), recovery of the target (99%), and inter-laboratory CV (4%).

Cell Adhesion Minimization by a Novel Mesh Culture Method Mechanically Directs Trophoblast Differentiation and Self-Assembly Organization of Human Pluripotent Stem Cells.

PubMed

Okeyo, Kennedy Omondi; Kurosawa, Osamu; Yamazaki, Satoshi; Oana, Hidehiro; Kotera, Hidetoshi; Nakauchi, Hiromitsu; Washizu, Masao

2015-10-01

Mechanical methods for inducing differentiation and directing lineage specification will be instrumental in the application of pluripotent stem cells. Here, we demonstrate that minimization of cell-substrate adhesion can initiate and direct the differentiation of human pluripotent stem cells (hiPSCs) into cyst-forming trophoblast lineage cells (TLCs) without stimulation with cytokines or small molecules. To precisely control cell-substrate adhesion area, we developed a novel culture method where cells are cultured on microstructured mesh sheets suspended in a culture medium such that cells on mesh are completely out of contact with the culture dish. We used microfabricated mesh sheets that consisted of open meshes (100∼200 μm in pitch) with narrow mesh strands (3-5 μm in width) to provide support for initial cell attachment and growth. We demonstrate that minimization of cell adhesion area achieved by this culture method can trigger a sequence of morphogenetic transformations that begin with individual hiPSCs attached on the mesh strands proliferating to form cell sheets by self-assembly organization and ultimately differentiating after 10-15 days of mesh culture to generate spherical cysts that secreted human chorionic gonadotropin (hCG) hormone and expressed caudal-related homeobox 2 factor (CDX2), a specific marker of trophoblast lineage. Thus, this study demonstrates a simple and direct mechanical approach to induce trophoblast differentiation and generate cysts for application in the study of early human embryogenesis and drug development and screening.

Metformin selectively affects human glioblastoma tumor-initiating cell viability

PubMed Central

Würth, Roberto; Pattarozzi, Alessandra; Gatti, Monica; Bajetto, Adirana; Corsaro, Alessandro; Parodi, Alessia; Sirito, Rodolfo; Massollo, Michela; Marini, Cecilia; Zona, Gianluigi; Fenoglio, Daniela; Sambuceti, Gianmario; Filaci, Gilberto; Daga, Antonio; Barbieri, Federica; Florio, Tullio

2013-01-01

Cancer stem cell theory postulates that a small population of tumor-initiating cells is responsible for the development, progression and recurrence of several malignancies, including glioblastoma. In this perspective, tumor-initiating cells represent the most relevant target to obtain effective cancer treatment. Metformin, a first-line drug for type II diabetes, was reported to possess anticancer properties affecting the survival of cancer stem cells in breast cancer models. We report that metformin treatment reduced the proliferation rate of tumor-initiating cell-enriched cultures isolated from four human glioblastomas. Metformin also impairs tumor-initiating cell spherogenesis, indicating a direct effect on self-renewal mechanisms. Interestingly, analyzing by FACS the antiproliferative effects of metformin on CD133-expressing subpopulation, a component of glioblastoma cancer stem cells, a higher reduction of proliferation was observed as compared with CD133-negative cells, suggesting a certain degree of cancer stem cell selectivity in its effects. In fact, glioblastoma cell differentiation strongly reduced sensitivity to metformin treatment. Metformin effects in tumor-initiating cell-enriched cultures were associated with a powerful inhibition of Akt-dependent cell survival pathway, while this pathway was not affected in differentiated cells. The specificity of metformin antiproliferative effects toward glioblastoma tumor-initiating cells was confirmed by the lack of significant inhibition of normal human stem cells (umbilical cord-derived mesenchymal stem cells) in vitro proliferation after metformin exposure. Altogether, these data clearly suggest that metformin exerts antiproliferative activity on glioblastoma cells, showing a higher specificity toward tumor-initiating cells, and that the inhibition of Akt pathway may represent a possible intracellular target of this effect. PMID:23255107

Nuclear health and safety

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

Glenn, J.

1991-02-01

There has been concern over the Department of Energy's (DOE) dual role of producing nuclear weapons and assessing the potential health hazards associated with operating its facilities has raised questions about DOE's ability to effectively manage its health and health effects (epidemiology) research programs. In March 1990, the secrecy of Energy announced several initiatives to address these concerns. These initiatives include, among others, the development of an occupational health and epidemiology program, the transfer of long-term health effects' studies to the Department of Health and Human Services (HHS), the establishment of an advisory committee to oversee DOE's environmental, safety, andmore » health activities, and the design of a data base to store and retrieve health data. This paper provides a brief description of DOE's initiatives, including their status as of December 1990 and general observations of these initiatives.« less

The right way to kiss: directionality bias in head-turning during kissing.

PubMed

Karim, A K M Rezaul; Proulx, Michael J; de Sousa, Alexandra A; Karmaker, Chhanda; Rahman, Arifa; Karim, Fahria; Nigar, Naima

2017-07-14

Humans have a bias for turning to the right in a number of settings. Here we document a bias in head-turning to the right in adult humans, as tested in the act of kissing. We investigated head-turning bias in both kiss initiators and kiss recipients for lip kissing, and took into consideration differences due to sex and handedness, in 48 Bangladeshi heterosexual married couples. We report a significant male bias in the initiation of kissing and a significant bias in head-turning to the right in both kiss initiators and kiss recipients, with a tendency among kiss recipients to match their partners' head-turning direction. These interesting outcomes are explained by the influences of societal learning or cultural norms and the potential neurophysiological underpinnings which together offer novel insights about the mechanisms underlying behavioral laterality in humans.

Medications Development for the Treatment of Alcohol Use Disorder: Insights into the Predictive Value of Animal and Human Laboratory Models

PubMed Central

Yardley, Megan M.; Ray, Lara A.

2016-01-01

Development of effective treatments for alcohol use disorder (AUD) represents an important public health goal. This review provides a summary of completed preclinical and clinical studies testing pharmacotherapies for treatment of AUD. We discuss opportunities for improving the translation from preclinical findings to clinical trial outcomes, focusing on the validity and predictive value of animal and human laboratory models of AUD. Specifically, while preclinical studies of medications development have offered important insights into the neurobiology of the disorder and alcohol's molecular targets, limitations include the lack of standardized methods and streamlined processes whereby animal studies can readily inform human studies. Behavioral pharmacology studies provide a less expensive and valuable opportunity to assess the feasibility of a pharmacotherapy prior to initiating larger scale clinical trials by providing insights into the mechanism of the drug, which can then inform recruitment, analyses, and assessments. Summary tables are provided to illustrate the wide range of preclinical, human laboratory, and clinical studies of medications development for alcoholism. Taken together, this review highlights the challenges associated with animal paradigms, human laboratory studies and clinical trials with the overarching goal of advancing treatment development and highlighting opportunities to bridge the gap between preclinical and clinical research. PMID:26833803

Stepping responses to treadmill perturbations vary with severity of motor deficits in human SCI.

PubMed

Chu, Virginia Way Tong; Hornby, T George; Schmit, Brian D

2018-04-18

In this study, we investigated the responses to tread perturbations during human stepping on a treadmill. Our approach was to test the effects of perturbations to a single leg using a split-belt treadmill in healthy participants and in participants with varying severity of spinal cord injury (SCI). We recruited 11 people with incomplete SCI and 5 noninjured participants. As participants walked on an instrumented treadmill, the belt on one side was stopped or accelerated briefly during mid to late stance. A majority of participants initiated an unnecessary swing when the treadmill was stopped in mid stance, although the likelihood of initiating a step was decreased in participants with more severe SCI. Accelerating or decelerating one belt of the treadmill during stance altered the characteristics of swing. We observed delayed swing initiation when the belt was decelerated (i.e. the hip was in a more flexed position at time of swing) and advanced swing initiation with acceleration (i.e. hip extended at swing initiation). Further, the timing and leg posture of heel strike appeared to remain constant, reflected by a sagittal plane hip angle at heel strike that remained the same regardless of the perturbation. In summary, our results supported the current understanding of the role of sensory feedback and central drive in the control of stepping in participants with incomplete SCI and noninjured participants. In particular, the observation of unnecessary swing during a stop perturbation highlights the interdependence of central and sensory drive in walking control.

Self-Powered Human-Interactive Transparent Nanopaper Systems.

PubMed

Zhong, Junwen; Zhu, Hongli; Zhong, Qize; Dai, Jiaqi; Li, Wenbo; Jang, Soo-Hwan; Yao, Yonggang; Henderson, Doug; Hu, Qiyi; Hu, Liangbing; Zhou, Jun

2015-07-28

Self-powered human-interactive but invisible electronics have many applications in anti-theft and anti-fake systems for human society. In this work, for the first time, we demonstrate a transparent paper-based, self-powered, and human-interactive flexible system. The system is based on an electrostatic induction mechanism with no extra power system appended. The self-powered, transparent paper device can be used for a transparent paper-based art anti-theft system in museums or for a smart mapping anti-fake system in precious packaging and documents, by virtue of the advantages of adding/removing freely, having no impairment on the appearance of the protected objects, and being easily mass manufactured. This initial study bridges the transparent nanopaper with a self-powered and human-interactive electronic system, paving the way for the development of smart transparent paper electronics.

The Initial Inflammatory Response to Bioactive Implants Is Characterized by NETosis

PubMed Central

Stoiber, Walter; Hannig, Matthias; Klappacher, Michaela; Hartl, Dominik

2015-01-01

Implants trigger an inflammatory response, which is important for osseointegration. Here we studied neutrophil extracellular trap (NET) release of human neutrophils in response to sandblasted large-grit acid etched (SLA) implants using fluorescent, confocal laser scanning and scanning electron microscopy. Our studies demonstrate that human neutrophils rapidly adhered to SLA surfaces, which triggered histone citrullination and NET release. Further studies showed that albumin or acetylsalicylic acid had no significant effects on the inflammatory response to SLA surfaces. In contrast to bioinert materials, which do not osseointegrate, the bioactivity of SLA surfaces is coupled with the ability to release NETs. Further investigations are necessary for clarifying the role of NETosis for osseointegration. PMID:25798949

Organizational change for services integration in public human service organizations: experiences in seven counties.

PubMed

Packard, Thomas; Patti, Rino; Daly, Donna; Tucker-Tatlow, Jennifer

2012-01-01

This is a study of organizational change strategies employed in seven county human service agencies to improve the coordination of services through the structural integration of previously free standing organizations or the development of voluntary interagency collaborative service delivery systems. The central question involves the identification of organizational change tactics which contributed to the success of the organizational change initiatives. The literature on organizational change is reviewed, with particular attention to a framework developed by Fernandez and Rainey based on their extensive review and synthesis of the research on successful change strategies in the public and business sectors. Qualitative and quantitative data were gathered from over 250 individuals and from agency documents. Findings are compared with the success factors identified by Fernandez and Rainey, and refinements to their propositions are suggested. More precise methods for measuring successful and unsuccessful change initiatives are suggested. Implications for practice and research are presented.

Metabolism of 20-Hydroxyvitamin D3 and 20,23-Dihydroxyvitamin D3 by Rat and Human CYP24A1

PubMed Central

Tieu, Elaine W.; Li, Wei; Chen, Jianjun; Kim, Tae-Kang; Ma, Dejian; Slominski, Andrzej T.; Tuckey, Robert C.

2015-01-01

CYP11A1 hydroxylates vitamin D3 producing 20S-hydroxyvitamin D3 [20(OH)D3] and 20S,23-dihydroxyvitamin D3 [20,23(OH)2D3] as the major and most characterized metabolites. Both display immuno-regulatory and anti-cancer properties while being non-calcemic. A previous study indicated 20(OH)D3 can be metabolized by rat CYP24A1 to products including 20S,24-dihydroxyvitamin D3 [20,24(OH)2D3] and 20S,25-dihydroxyvitamin D3, with both producing greater inhibition of melanoma colony formation than 20(OH)D3. The aim of this study was to characterize the ability of rat and human CYP24A1 to metabolize 20(OH)D3 and 20,23(OH)2D3. Both isoforms metabolized 20(OH)D3 to the same dihydroxyvitamin D species with no secondary metabolites being observed. Hydroxylation at C24 produced both enantiomers of 20,24(OH)2D3. For rat CYP24A1 the preferred initial site of hydroxylation was at C24 whereas the human enzyme preferred C25. 20,23(OH)2D3 was initially metabolized to 20S,23,24-trihydroxyvitamin D3 and 20S,23,25-trihydroxyvitamin D3 by rat and human CYP24A1 as determined by NMR, with both isoforms showing a preference for initial hydroxylation at C25. CYP24A1 was able to further oxidize these metabolites in a series of reactions which included the cleavage of C23-C24 bond, as indicated by high resolution mass spectrometry of the products, analogous to the catabolism of 1,25(OH)2D3 via the C24-oxidation pathway. Similar catalytic efficiencies were observed for the metabolism of 20(OH)D3 and 20,23(OH)2D3 by human CYP24A1 and were lower than for the metabolism of 1,25(OH)2D3. We conclude that rat and human CYP24A1 metabolizes 20(OH)D3 producing only dihydroxyvitamin D3 species as products which retain biological activity, whereas 20,23(OH)2D3 undergoes multiple oxidations which include cleavage of the side chain. PMID:25727742

"Democratic and Humanistic/Humane Paideia in the Euro-Cypriot Polity--Prospects for Reconstruction and Modernization": A Biographical Sociological Analysis of A Reform Initiative in a (De-)Globalizing World

ERIC Educational Resources Information Center

Klerides, Eleftherios

2018-01-01

In 2004, a reform report entitled "Democratic and Humanistic/ Humane Paideia in the Euro-Cypriot Polity: Prospects for Reconstruction and Modernization" was published by the Ministry of Education and Culture in the Republic of Cyprus. Professor Andreas M. Kazamias is held to have been the driving force behind this initiative, shaping…

Model systems for defining initiation, promotion, and progression of skin neoplasms.

PubMed

Boutwell, R K

1989-01-01

A number of items that must be considered in designing and choosing a suitable model for initiation and promotion testing have been described. Although these items may seem complex, tests for initiation and promotion are, in reality, quite simple and provide a rational approach to carcinogen testing. Several tests have been described here and Eastin, elsewhere in this book, describes the validation of a simple and highly recommended test. The processes involved in initiation and promotion are qualitatively different. The criteria for concern about possible human hazards as well as for regulation of initiators and promoters should be based on these qualitative differences. Realistic appraisal of the risk must be based on the level and nature of the potential hazard. In particular, it must be recognized that promoting action is reversible, that a threshold exists, and that promotion is readily inhibited. Therefore, animal tests that differentiate between potential initiators and promoters are essential to enable a logical assessment of human risk and the implementation of appropriate protective measures based on scientific facts.

Replication landscape of the human genome

PubMed Central

Petryk, Nataliya; Kahli, Malik; d'Aubenton-Carafa, Yves; Jaszczyszyn, Yan; Shen, Yimin; Silvain, Maud; Thermes, Claude; Chen, Chun-Long; Hyrien, Olivier

2016-01-01

Despite intense investigation, human replication origins and termini remain elusive. Existing data have shown strong discrepancies. Here we sequenced highly purified Okazaki fragments from two cell types and, for the first time, quantitated replication fork directionality and delineated initiation and termination zones genome-wide. Replication initiates stochastically, primarily within non-transcribed, broad (up to 150 kb) zones that often abut transcribed genes, and terminates dispersively between them. Replication fork progression is significantly co-oriented with the transcription. Initiation and termination zones are frequently contiguous, sometimes separated by regions of unidirectional replication. Initiation zones are enriched in open chromatin and enhancer marks, even when not flanked by genes, and often border ‘topologically associating domains' (TADs). Initiation zones are enriched in origin recognition complex (ORC)-binding sites and better align to origins previously mapped using bubble-trap than λ-exonuclease. This novel panorama of replication reveals how chromatin and transcription modulate the initiation process to create cell-type-specific replication programs. PMID:26751768

Initial eye movements during face identification are optimal and similar across cultures

PubMed Central

Or, Charles C.-F.; Peterson, Matthew F.; Eckstein, Miguel P.

2015-01-01

Culture influences not only human high-level cognitive processes but also low-level perceptual operations. Some perceptual operations, such as initial eye movements to faces, are critical for extraction of information supporting evolutionarily important tasks such as face identification. The extent of cultural effects on these crucial perceptual processes is unknown. Here, we report that the first gaze location for face identification was similar across East Asian and Western Caucasian cultural groups: Both fixated a featureless point between the eyes and the nose, with smaller between-group than within-group differences and with a small horizontal difference across cultures (8% of the interocular distance). We also show that individuals of both cultural groups initially fixated at a slightly higher point on Asian faces than on Caucasian faces. The initial fixations were found to be both fundamental in acquiring the majority of information for face identification and optimal, as accuracy deteriorated when observers held their gaze away from their preferred fixations. An ideal observer that integrated facial information with the human visual system's varying spatial resolution across the visual field showed a similar information distribution across faces of both races and predicted initial human fixations. The model consistently replicated the small vertical difference between human fixations to Asian and Caucasian faces but did not predict the small horizontal leftward bias of Caucasian observers. Together, the results suggest that initial eye movements during face identification may be driven by brain mechanisms aimed at maximizing accuracy, and less influenced by culture. The findings increase our understanding of the interplay between the brain's aims to optimally accomplish basic perceptual functions and to respond to sociocultural influences. PMID:26382003

Propagation of normal human epithelial cell populations using an in vivo culture system. Description and applications.

PubMed Central

Klein-Szanto, A. J.; Terzaghi, M.; Mirkin, L. D.; Martin, D.; Shiba, M.

1982-01-01

A new model using xenotransplanted human epithelia was developed for the study of toxic and carcinogenic effects of chemicals. Epithelial cells from the respiratory tract of 4 male and 3 female premature and fullterm fetuses were enzymatically removed and inoculated into deepithelialized rat tracheas. These were sealed at both ends and transplanted subcutaneously into nude mice. After 3-4 weeks, a normal mucociliary epithelium covered the tracheal lumen. At this stage the epithelial cells could be isolated again and transplanted into new denuded rat tracheas. This passaging could be repeated up to six times, each permitting an amplification factor of approximately 3. Tracheal transplants containing cells of human origin (in vivo Passages 2-4) were treated with 7,12-dimethylbenz(a)anthracene. Hyperplasias, squamous metaplasias, and dysplasias were seen 1-8 weeks after initiation of treatment, indicating that the responses of human and rodent epithelial cells to polycyclic aromatic hydrocarbons are similar. Initial experiments with skin and esophageal epithelia suggest that other covering epithelia could also be used in this fashion for evaluation of toxicants and carcinogens that are likely to come into contact with these tissues. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:6821529

Drug development and nonclinical to clinical translational databases: past and current efforts.

PubMed

Monticello, Thomas M

2015-01-01

The International Consortium for Innovation and Quality (IQ) in Pharmaceutical Development is a science-focused organization of pharmaceutical and biotechnology companies. The mission of the Preclinical Safety Leadership Group (DruSafe) of the IQ is to advance science-based standards for nonclinical development of pharmaceutical products and to promote high-quality and effective nonclinical safety testing that can enable human risk assessment. DruSafe is creating an industry-wide database to determine the accuracy with which the interpretation of nonclinical safety assessments in animal models correctly predicts human risk in the early clinical development of biopharmaceuticals. This initiative aligns with the 2011 Food and Drug Administration strategic plan to advance regulatory science and modernize toxicology to enhance product safety. Although similar in concept to the initial industry-wide concordance data set conducted by International Life Sciences Institute's Health and Environmental Sciences Institute (HESI/ILSI), the DruSafe database will proactively track concordance, include exposure data and large and small molecules, and will continue to expand with longer duration nonclinical and clinical study comparisons. The output from this work will help identify actual human and animal adverse event data to define both the reliability and the potential limitations of nonclinical data and testing paradigms in predicting human safety in phase 1 clinical trials. © 2014 by The Author(s).

Exploding the Myths: Caregiving in America. A Study by the Subcommittee on Human Services of the Select Committee on Aging. House of Representatives, Second Session.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Select Committee on Aging.

The purpose of this Congressional study is to underscore the continuing contribution of the family in providing care to the frail and disabled elderly. This study has been developed to distill information that currently exists, to provide new data based on national estimates and to highlight both public and private sector initiatives targeted at…

Moving Forward with Computational Red Teaming

DTIC Science & Technology

2011-03-01

Within DSTO, his experience lies in the conduct of studies and analysis falling within the needs phase of the capability development cycle for...procedures, and doctrines that each UNCLASSIFIED UNCLASSIFIED of the blue and red teams need to obey are all studied . Domain experts are drawn from...entities including human. See [Bui, Abbass and Bender, 2010] for an initial study on evolving stories for scenarios. Computations: Once a context is

Implantation of GL261 neurospheres into C57/BL6 mice: a more reliable syngeneic graft model for research on glioma-initiating cells.

PubMed

Yi, Liang; Zhou, Chun; Wang, Bing; Chen, Tunan; Xu, Minhui; Xu, Lunshan; Feng, Hua

2013-08-01

Recent studies have demonstrated that inflammatory cells and inflammatory mediators are indispensable components of the tumor-initiating cell (TIC) niche and regulate the malignant behavior of TICs. However, conventional animal models for glioma-initiating cell (GIC) studies are based on the implantation of GICs from human glioblastoma (GBM) into immunodeficient mice without the regulation of immune system. Whether animal models can mimic the cellular microenvironment of malignancy and evaluate the biological features of GICs accurately is unclear. Here, we detected the biological features of neurosphere-like tumor cells derived from the murine GBM cell line GL261 (GL261-NS) and from primary human GBM (PGBM-NS) in vitro, injected GL261-NS into syngeneic C57/BL6 mouse brain and injected PGBM-NS into NOD/SCID mouse brain, respectively. The tumorigenic characteristics of the two different orthotopic transplantation models were analyzed and the histological discrepancy between grafts and human primary GBM was compared. We found that GICs enriched in GL261-NS, GL261-NS and PGBM-NS exhibited increased GIC potential and enhanced chemoresistance in vitro. GL261-NS was significantly more aggressive compared to GL261 adhesive cells (GL261-AC) in vivo and the enhanced aggression was more significant in syngeneic mice compared to immunodeficient mice. The discrepancy of tumorigenicity between GL261-NS and GL261-AC in C57/BL6 mice was also larger compared to that between PGBM-NS and PGBM-AC in immunodeficient mice. Syngrafts derived from GL261-NS in C57/BL6 mice corresponded to the human GBM histologically better, compared with xenografts derived from PGBM-NS in NOD/SCID mice, which lack inflammatory cells and inflammatory mediators. We conclude that the inflammatory niche is involved in the tumorigenicity of GICs and implantation of GL261-NS into C57/BL6 mice is a more reliable syngeneic graft model for in vivo study on GICs relative to the immunodeficiency model.

77 FR 8271 - Eunice Kennedy Shriver National Institute of Child Health & Human Development; Notice of Closed...

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2013-05-30

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76 FR 6808 - Eunice Kennedy Shriver National Institute of Child Health & Human Development; Notice of Closed...

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2011-02-08

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40 CFR 26.1101 - To what does this subpart apply?

Code of Federal Regulations, 2012 CFR

2012-07-01

... HUMAN SUBJECTS Basic Ethical Requirements for Third-Party Human Research for Pesticides Involving... initiated after April 7, 2006 involving intentional exposure of a human subject if, at any time prior to... additional protections for human subjects. (e) This subpart does not affect any State or local laws or...

40 CFR 26.1101 - To what does this subpart apply?

Code of Federal Regulations, 2011 CFR

2011-07-01

... HUMAN SUBJECTS Basic Ethical Requirements for Third-Party Human Research for Pesticides Involving... initiated after April 7, 2006 involving intentional exposure of a human subject if, at any time prior to... additional protections for human subjects. (e) This subpart does not affect any State or local laws or...

76 FR 5594 - Eunice Kennedy Shriver National Institute of Child Health & Human Development; Notice of Closed...

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2011-02-01

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2011-09-27

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2013-09-11

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2012-10-12

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2013-02-13

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2012-05-16

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2011-05-19

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2012-10-09

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Evaluation of potential severe accidents during low power and shutdown operations at Surry, Unit 1. Volume 5: Analysis of core damage frequency from seismic events during mid-loop operations

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

Budnitz, R.J.; Davis, P.R.; Ravindra, M.K.

1994-08-01

In 1989 the US Nuclear Regulatory Commission (NRC) initiated an extensive program to examine carefully the potential risks during low-power and shutdown operations. The program included two parallel projects, one at Brookhaven National Laboratory studying a pressurized water reactor (Surry Unit 1) and the other at Sandia National Laboratories studying a boiling water reactor (Grand Gulf). Both the Brookhaven and Sandia projects have examined only accidents initiated by internal plant faults--so-called ``internal initiators.`` This project, which has explored the likelihood of seismic-initiated core damage accidents during refueling shutdown conditions, is complementary to the internal-initiator analyses at Brookhaven and Sandia. Thismore » report covers the seismic analysis at Surry Unit 1. All of the many systems modeling assumptions, component non-seismic failure rates, and human error rates that were used in the internal-initiator study at Surry have been adopted here, so that the results of the two studies can be as comparable as possible. Both the Brookhaven study and this study examine only two shutdown plant operating states (POSs) during refueling outages at Surry, called POS 6 and POS 10, which represent mid-loop operation before and after refueling, respectively. This analysis has been limited to work analogous to a level-1 seismic PRA, in which estimates have been developed for the core-damage frequency from seismic events during POSs 6 and 10. The results of the analysis are that the core-damage frequency of earthquake-initiated accidents during refueling outages in POS 6 and POS 10 is found to be low in absolute terms, less than 10{sup {minus}6}/year.« less

Evaluation of potential severe accidents during low power and shutdown operations at Grand Gulf, Unit 1. Volume 5: Analysis of core damage frequency from seismic events for plant operational state 5 during a refueling outage

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

Budnitz, R.J.; Davis, P.R.; Ravindra, M.K.

In 1989 the US Nuclear Regulatory Commission (NRC) initiated an extensive program to examine carefully the potential risks during low-power and shutdown operations. The program included two parallel projects, one at Sandia National Laboratories studying a boiling water reactor (Grand Gulf), and the other at Brookhaven National Laboratory studying a pressurized water reactor (Surry Unit 1). Both the Sandia and Brookhaven projects have examined only accidents initiated by internal plant faults---so-called ``internal initiators.`` This project, which has explored the likelihood of seismic-initiated core damage accidents during refueling outage conditions, is complementary to the internal-initiator analyses at Brookhaven and Sandia. Thismore » report covers the seismic analysis at Grand Gulf. All of the many systems modeling assumptions, component non-seismic failure rates, and human effort rates that were used in the internal-initiator study at Grand Gulf have been adopted here, so that the results of the study can be as comparable as possible. Both the Sandia study and this study examine only one shutdown plant operating state (POS) at Grand Gulf, namely POS 5 representing cold shutdown during a refueling outage. This analysis has been limited to work analogous to a level-1 seismic PRA, in which estimates have been developed for the core-damage frequency from seismic events during POS 5. The results of the analysis are that the core-damage frequency for earthquake-initiated accidents during refueling outages in POS 5 is found to be quite low in absolute terms, less than 10{sup {minus}7}/year.« less

75 FR 39031 - Eunice Kennedy Shriver National Institute of Child Health and Human Development; Notice of Closed...

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2010-07-07

... National Institute of Child Health and Human Development; Notice of Closed Meeting Pursuant to section 10(d... Institute of Child Health and Human Development Special Emphasis Panel, Initiation of Human Labor... Human Development, 6100 Executive Boulevard, Room 5B01, Bethesda, MD 20892-7510, (301) 435- 6902, peter...

Human Rights Engagement and Exposure: New Scales to Challenge Social Work Education

ERIC Educational Resources Information Center

McPherson, Jane; Abell, Neil

2012-01-01

Objectives: Advancing human rights is a core competency of U.S. social work education; yet, human rights attitudes and behaviors have never been measured in the social work literature. Thus, this article describes the development and initial validation of two scales, Human Rights Engagement in Social Work (HRESW) and Human Rights Exposure in…

PESP Landscaping Initiative

EPA Pesticide Factsheets

Landscaping practices can positively or negatively affect local environments and human health. The Landscaping Initiative seeks to enhance benefits of landscaping while reducing need for pesticides, fertilizers, etc., by working with partners.

Perceptions of human papillomavirus vaccination of adolescent schoolgirls in western Uganda and their implications for acceptability of HPV vaccination: a qualitative study.

PubMed

Turiho, Andrew Kampikaho; Okello, Elialilia Sarikieli; Muhwezi, Wilson Winstons; Katahoire, Anne Ruhweza

2017-08-30

Human papillomavirus (HPV) vaccination has been perceived in diverse ways some of which encourage its uptake while others could potentially deter its acceptability. This study explored community member's perceptions about HPV vaccination in Ibanda district and the implications of the perceptions for acceptability of HPV vaccination. The study was conducted following initial vaccination of adolescent schoolgirls in the district between 2008 and 2011. This qualitative study employed focus group discussions (FGDs) and key informant interviews (KIIs). FGDs were conducted with schoolgirls and parents/guardians and KIIs were conducted with school teachers, health workers and community leaders. Transcripts from the FGDs and KIIs were coded and analyzed thematically using ATLAS.ti (v. 6). The HPV vaccination was understood to safely prevent cervical cancer, which was perceived to be a severe incurable disease. Vaccinations were perceived as protection against diseases like measles and polio that were known to kill children. These were major motivations for girls' and parents' acceptance of HPV vaccination. Parents' increased awareness that HPV is sexually transmitted encouraged their support for vaccination of their adolescent daughters against HPV. There were reports however of some initial fears and misconceptions about HPV vaccination especially during its introduction. These initially discouraged some parents and girls but over the years with no major side effects reported, girls reported that they were willing to recommend the vaccination to others and parents also reported their willingness to get their daughters vaccinated without fear. Health workers and teachers interviewed however explained that, some concerns stilled lingered in the communities. The perceived benefits and safety of HPV vaccination enhanced girls' and parents' acceptability of HPV vaccination. The initial rumors, fears and concerns about HPV vaccination that reportedly discouraged some girls and parents, seemed to have waned with time giving way to more favourable perceptions regarding HPV vaccination although the study still found that a few concerns still lingered on and these have implications for HPV vaccination acceptability.

Metabolic changes in humans following total body irradiation. Report for February 1960-October 1961

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

Not Available

These studies are designed to obtain new information about the metabolic effects of total body and partial body irradiation so as to have a better understanding of the acute and subacute effects of irradiation in the human. The initial studies are pointed toward the elucidation of biological indicators of radiation effects in humans. The major parameters being investigated at present are urinary amino aciduria and alterations in immunological patterns. Certain other parameters such as creatine and creatinine excretion and hematological effects are also being followed. The long-term program envisions carrying out the various observations at dose levels of 100 radmore » and gradually increasing the dose to 150, 200, 250 and 300 rad. Eventually doses up to 600 rad are anticipated. Also comparison of effects of radiomimetic drugs with total body radiation will be studied.« less

Deliberate or unintended: Intentions modulate empathic responses to others' economic payoffs in social interactions.

PubMed

Ma, Qingguo; Meng, Liang; Shen, Qiang

2017-12-01

Previous studies examining empathy have revealed the neural substrates of how the physical pain of others is represented in the human brain. However, little is known about the empathic modulation of behavioral and neural responses to others' economic payoffs, especially in the social context. In the present study, we engaged participants in a revised Dictator Game as observers who observe the powerless players receiving varied offers proposed by the dominant players, establishing the link between empathy and fairness perception. Results showed that unfair division schemes elicited a more pronounced FRN than fair ones only if a human agent proposed the initial offer. In addition, observers sacrificed their own payments to adjust unfair proposals, especially when a human agent proposed the offer. Thus, results of the current study demonstrated that perceived intention modulates behavioral and neural responses to others' economic payoffs in social interactions.

Posttraumatic Stress Disorder: An Immunological Disorder?

PubMed Central

Wang, Zhewu; Caughron, Blaine; Young, M. Rita I.

2017-01-01

Patients with posttraumatic stress disorder (PTSD) exhibit an increased state of inflammation. Various animal models for PTSD have shown some of the same immune imbalances as have been shown in human subjects with PTSD, and some of these studies are discussed in this review. However, animal studies can only indirectly implicate immune involvement in PTSD in humans. This review of mainly studies with human subjects focuses on dissecting the immunological role in the pathogenesis of PTSD following initial trauma exposure. It addresses both the inflammatory state associated with PTSD and the immune imbalance between stimulatory and inhibitory immune mediators, as well as variables that can lead to discrepancies between analyses. The concept of immunological treatment approaches is proposed for PTSD, as new treatments are needed for this devastating disorder that is affecting unprecedented numbers of Veterans from the long-standing wars in the Middle East and which affects civilians following severe trauma. PMID:29163241

Viruses in diarrhoeic dogs include novel kobuviruses and sapoviruses.

PubMed

Li, Linlin; Pesavento, Patricia A; Shan, Tongling; Leutenegger, Christian M; Wang, Chunlin; Delwart, Eric

2011-11-01

The close interactions of dogs with humans and surrounding wildlife provide frequent opportunities for cross-species virus transmissions. In order to initiate an unbiased characterization of the eukaryotic viruses in the gut of dogs, this study used deep sequencing of partially purified viral capsid-protected nucleic acids from the faeces of 18 diarrhoeic dogs. Known canine parvoviruses, coronaviruses and rotaviruses were identified, and the genomes of the first reported canine kobuvirus and sapovirus were characterized. Canine kobuvirus, the first sequenced canine picornavirus and the closest genetic relative of the diarrhoea-causing human Aichi virus, was detected at high frequency in the faeces of both healthy and diarrhoeic dogs. Canine sapovirus constituted a novel genogroup within the genus Sapovirus, a group of viruses also associated with human and animal diarrhoea. These results highlight the high frequency of new virus detection possible even in extensively studied animal species using metagenomics approaches, and provide viral genomes for further disease-association studies.

Distinct Neural Activities in Premotor Cortex during Natural Vocal Behaviors in a New World Primate, the Common Marmoset (Callithrix jacchus).

PubMed

Roy, Sabyasachi; Zhao, Lingyun; Wang, Xiaoqin

2016-11-30

Although evidence from human studies has long indicated the crucial role of the frontal cortex in speech production, it has remained uncertain whether the frontal cortex in nonhuman primates plays a similar role in vocal communication. Previous studies of prefrontal and premotor cortices of macaque monkeys have found neural signals associated with cue- and reward-conditioned vocal production, but not with self-initiated or spontaneous vocalizations (Coudé et al., 2011; Hage and Nieder, 2013), which casts doubt on the role of the frontal cortex of the Old World monkeys in vocal communication. A recent study of marmoset frontal cortex observed modulated neural activities associated with self-initiated vocal production (Miller et al., 2015), but it did not delineate whether these neural activities were specifically attributed to vocal production or if they may result from other nonvocal motor activity such as orofacial motor movement. In the present study, we attempted to resolve these issues and examined single neuron activities in premotor cortex during natural vocal exchanges in the common marmoset (Callithrix jacchus), a highly vocal New World primate. Neural activation and suppression were observed both before and during self-initiated vocal production. Furthermore, by comparing neural activities between self-initiated vocal production and nonvocal orofacial motor movement, we identified a subpopulation of neurons in marmoset premotor cortex that was activated or suppressed by vocal production, but not by orofacial movement. These findings provide clear evidence of the premotor cortex's involvement in self-initiated vocal production in natural vocal behaviors of a New World primate. Human frontal cortex plays a crucial role in speech production. However, it has remained unclear whether the frontal cortex of nonhuman primates is involved in the production of self-initiated vocalizations during natural vocal communication. Using a wireless multichannel neural recording technique, we observed in the premotor cortex neural activation and suppression both before and during self-initiated vocalizations when marmosets, a highly vocal New World primate species, engaged in vocal exchanges with conspecifics. A novel finding of the present study is the discovery of a subpopulation of premotor cortex neurons that was activated by vocal production, but not by orofacial movement. These observations provide clear evidence of the premotor cortex's involvement in vocal production in a New World primate species. Copyright © 2016 the authors 0270-6474/16/3612168-12$15.00/0.

Two-decade reconstruction of algal blooms in China's Lake Taihu.

PubMed

Duan, Hongtao; Ma, Ronghua; Xu, Xiaofeng; Kong, Fanxiang; Zhang, Shouxuan; Kong, Weijuan; Hao, Jingyan; Shang, Linlin

2009-05-15

The algal blooming in the inland lakes has become a critically important issue for its impacts not only on local natural and social environments, but also on global human community. However, the occurrences of blooming on larger spatial scale and longer time scale have rarely been studied. As the third largest freshwater lake in China, Lake Taihu has drawn increasing attention from both public and scientific communities concerning its degradation. Using available satellite images, we reconstructed the spatial and temporal patterns of algal blooms in Lake Taihu through the pasttwo decades. The blooming characteristics over the past two decades were examined with the dynamic of initial blooming date being highlighted. The initial blooming dates were gradually becoming later and later from 1987 to 1997. Since 1998, however, the initial blooming date came earlier and earlier year by year, with approximately 11.42 days advancement per year. From 1987 to 2007, the annual duration of algal blooms lengthened year by year, in line with the substantial increases in the occurrences of algal blooms in spring and summer months. The algal blooms usually occur in northern bays and spread to center and south parts of Lake Taihu. The increases in previous winter's mean daily minimum temperature partially contributed to the earlier blooming onset. However, human activities, expressed as total gross domestic product (GDP) and population, outweighed the climatic contribution on the initial blooming date and blooming duration. This study may provide insights for the policy makers who try to curb the algal blooming and improve the water quality of inland freshwater lakes.

Mitochondrial diversity in human head louse populations across the Americas.

PubMed

Ascunce, Marina S; Fane, Jackie; Kassu, Gebreyes; Toloza, Ariel C; Picollo, Maria I; González-Oliver, Angélica; Reed, David L

2013-09-01

Anthropological studies suggest that the genetic makeup of human populations in the Americas is the result of diverse processes including the initial colonization of the continent by the first people plus post-1492 European migrations. Because of the recent nature of some of these events, understanding the geographical origin of American human diversity is challenging. However, human parasites have faster evolutionary rates and larger population sizes allowing them to maintain greater levels of genetic diversity than their hosts. Thus, we can use human parasites to provide insights into some aspects of human evolution that may be unclear from direct evidence. In this study, we analyzed mitochondrial DNA (mtDNA) sequences from 450 head lice in the Americas. Haplotypes clustered into two well-supported haplogroups, known as A and B. Haplogroup frequencies differ significantly among North, Central and South America. Within each haplogroup, we found evidence of demographic expansions around 16,000 and 20,000 years ago, which correspond broadly with those estimated for Native Americans. The parallel timing of demographic expansions of human lice and Native Americans plus the contrasting pattern between the distribution of haplogroups A and B through the Americas suggests that human lice can provide additional evidence about the human colonization of the New World. Copyright © 2013 Wiley Periodicals, Inc.

Complete Plasmodium falciparum liver-stage development in liver-chimeric mice

PubMed Central

Vaughan, Ashley M.; Mikolajczak, Sebastian A.; Wilson, Elizabeth M.; Grompe, Markus; Kaushansky, Alexis; Camargo, Nelly; Bial, John; Ploss, Alexander; Kappe, Stefan H.I.

2012-01-01

Plasmodium falciparum, which causes the most lethal form of human malaria, replicates in the host liver during the initial stage of infection. However, in vivo malaria liver-stage (LS) studies in humans are virtually impossible, and in vitro models of LS development do not reconstitute relevant parasite growth conditions. To overcome these obstacles, we have adopted a robust mouse model for the study of P. falciparum LS in vivo: the immunocompromised and fumarylacetoacetate hydrolase–deficient mouse (Fah–/–, Rag2–/–, Il2rg–/–, termed the FRG mouse) engrafted with human hepatocytes (FRG huHep). FRG huHep mice supported vigorous, quantifiable P. falciparum LS development that culminated in complete maturation of LS at approximately 7 days after infection, providing a relevant model for LS development in humans. The infections allowed observations of previously unknown expression of proteins in LS, including P. falciparum translocon of exported proteins 150 (PTEX150) and exported protein-2 (EXP-2), components of a known parasite protein export machinery. LS schizonts exhibited exoerythrocytic merozoite formation and merosome release. Furthermore, FRG mice backcrossed to the NOD background and repopulated with huHeps and human red blood cells supported reproducible transition from LS infection to blood-stage infection. Thus, these mice constitute reliable models to study human LS directly in vivo and demonstrate utility for studies of LS–to–blood-stage transition of a human malaria parasite. PMID:22996664

Complete Plasmodium falciparum liver-stage development in liver-chimeric mice.

PubMed

Vaughan, Ashley M; Mikolajczak, Sebastian A; Wilson, Elizabeth M; Grompe, Markus; Kaushansky, Alexis; Camargo, Nelly; Bial, John; Ploss, Alexander; Kappe, Stefan H I

2012-10-01

Plasmodium falciparum, which causes the most lethal form of human malaria, replicates in the host liver during the initial stage of infection. However, in vivo malaria liver-stage (LS) studies in humans are virtually impossible, and in vitro models of LS development do not reconstitute relevant parasite growth conditions. To overcome these obstacles, we have adopted a robust mouse model for the study of P. falciparum LS in vivo: the immunocompromised and fumarylacetoacetate hydrolase-deficient mouse (Fah-/-, Rag2-/-, Il2rg-/-, termed the FRG mouse) engrafted with human hepatocytes (FRG huHep). FRG huHep mice supported vigorous, quantifiable P. falciparum LS development that culminated in complete maturation of LS at approximately 7 days after infection, providing a relevant model for LS development in humans. The infections allowed observations of previously unknown expression of proteins in LS, including P. falciparum translocon of exported proteins 150 (PTEX150) and exported protein-2 (EXP-2), components of a known parasite protein export machinery. LS schizonts exhibited exoerythrocytic merozoite formation and merosome release. Furthermore, FRG mice backcrossed to the NOD background and repopulated with huHeps and human red blood cells supported reproducible transition from LS infection to blood-stage infection. Thus, these mice constitute reliable models to study human LS directly in vivo and demonstrate utility for studies of LS-to-blood-stage transition of a human malaria parasite.

Advances in the role of oxytocin receptors in human parturition.

PubMed

Kim, Sung Hye; Bennett, Phillip R; Terzidou, Vasso

2017-07-05

Oxytocin (OT) is a neurohypophysial hormone which has been found to play a central role in the regulation of human parturition. The most established role of oxytocin/oxytocin receptor (OT/OTR) system in human parturition is the initiation of uterine contractions, however, recent evidence have demonstrated that it may have a more complex role including initiation of inflammation, regulation of miRNA expression, as well as mediation of other non-classical oxytocin actions via receptor crosstalk with other G protein-coupled receptors (GPCRs). In this review we highlight both established and newly emerging roles of OT/OTR system in human parturition and discuss the expanding potential for OTRs as pharmacological targets in the management of preterm labour. Copyright © 2017. Published by Elsevier B.V.

Space Station life sciences guidelines for nonhuman experiment accommodation

NASA Technical Reports Server (NTRS)

Arno, R.; Hilchey, J.

1985-01-01

Life scientists will utilize one of four habitable modules which constitute the initial Space Station configuration. This module will be initially employed for studies related to nonhuman and human life sciences. At a later date, a new module, devoted entirely to nonhuman life sciences will be launched. This report presents a description of the characteristics of a Space Station laboratory facility from the standpoint of nonhuman research requirements. Attention is given to the science rationale for experiments which support applied medical research and basic gravitational biology, mission profiles and typical equipment and subsystem descriptions, issues associated with the accommodation of nonhuman life sciences on the Space Station, and conceptual designs for the initial operational capability configuration and later Space Station life-sciences research facilities.

Maine Tidal Power Initiative: Environmental Impact Protocols For Tidal Power

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

Peterson, Michael Leroy; Zydlewski, Gayle Barbin; Xue, Huijie

2014-02-02

The Maine Tidal Power Initiative (MTPI), an interdisciplinary group of engineers, biologists, oceanographers, and social scientists, has been conducting research to evaluate tidal energy resources and better understand the potential effects and impacts of marine hydro-kinetic (MHK) development on the environment and local community. Project efforts include: 1) resource assessment, 2) development of initial device design parameters using scale model tests, 3) baseline environmental studies and monitoring, and 4) human and community responses. This work included in-situ measurement of the environmental and social response to the pre-commercial Turbine Generator Unit (TGU®) developed by Ocean Renewable Power Company (ORPC) as wellmore » as considering the path forward for smaller community scale projects.« less

Development of protective immunity to Salmonella, a mucosal pathogen with a systemic agenda

PubMed Central

Griffin, Amanda J.; McSorley, Stephen J.

2014-01-01

Salmonella infections can cause a range of intestinal and systemic disease in human and animal hosts. While some Salmonella serovars initiate a localized intestinal inflammatory response, others use the intestine as a portal of entry to initiate a systemic infection. Considerable progress has been made in understanding bacterial invasion and dissemination strategies and the nature of the Salmonella-specific immune response to oral infection. Innate and adaptive immunity are rapidly initiated after oral infection but these effector responses can also be hindered by bacterial evasion strategies. Furthermore, although Salmonella resides within intramacrophage phagosomes, recent studies highlight a surprising collaboration of CD4 Th1, Th17, and B cell responses in mediating resistance to Salmonella infection. PMID:21307847

Space and Ground Trades for Human Exploration and Wearable Computing

NASA Technical Reports Server (NTRS)

Lupisella, Mark; Donohue, John; Mandl, Dan; Ly, Vuong; Graves, Corey; Heimerdinger, Dan; Studor, George; Saiz, John; DeLaune, Paul; Clancey, William

2006-01-01

Human exploration of the Moon and Mars will present unique trade study challenges as ground system elements shift to planetary bodies and perhaps eventually to the bodies of human explorers in the form of wearable computing technologies. This presentation will highlight some of the key space and ground trade issues that will face the Exploration Initiative as NASA begins designing systems for the sustained human exploration of the Moon and Mars, with an emphasis on wearable computing. We will present some preliminary test results and scenarios that demonstrate how wearable computing might affect the trade space noted below. We will first present some background on wearable computing and its utility to NASA's Exploration Initiative. Next, we will discuss three broad architectural themes, some key ground and space trade issues within those themes and how they relate to wearable computing. Lastly, we will present some preliminary test results and suggest guidance for proceeding in the assessment and creation of a value-added role for wearable computing in the Exploration Initiative. The three broad ground-space architectural trade themes we will discuss are: 1. Functional Shift and Distribution: To what extent, if any, should traditional ground system functionality be shifted to, and distributed among, the Earth, Moon/Mars, and the human. explorer? 2. Situational Awareness and Autonomy: How much situational awareness (e.g. environmental conditions, biometrics, etc.) and autonomy is required and desired, and where should these capabilities reside? 3. Functional Redundancy: What functions (e.g. command, control, analysis) should exist simultaneously on Earth, the Moon/Mars, and the human explorer? These three themes can serve as the axes of a three-dimensional trade space, within which architectural solutions reside. We will show how wearable computers can fit into this trade space and what the possible implications could be for the rest of the ground and space architecture(s). We intend this to be an example of explorer-centric thinking in a fully integrated explorer paradigm, where integrated explorer refers to a human explorer having instant access to all relevant data, knowledge of the environment, science models, health and safety-related events, and other tools and information via wearable computing technologies. The trade study approach will include involvement from the relevant stakeholders (Constellation Systems, CCCI, EVA Project Office, Astronaut office, Mission Operations, Space Life Sciences, etc.) to develop operations concepts (and/or operations scenarios) from which a basic high-level set of requirements could be extracted. This set of requirements could serve as a foundation (along with stakeholder buy-in) that would help define the trade space and assist in identifying candidate technologies for further study and evolution to higher-level technology readiness levels.

Cell-autonomous intracellular androgen receptor signaling drives the growth of human prostate cancer initiating cells.

PubMed

Vander Griend, Donald J; D'Antonio, Jason; Gurel, Bora; Antony, Lizamma; Demarzo, Angelo M; Isaacs, John T

2010-01-01

The lethality of prostate cancer is due to the continuous growth of cancer initiating cells (CICs) which are often stimulated by androgen receptor (AR) signaling. However, the underlying molecular mechanism(s) for such AR-mediated growth stimulation are not fully understood. Such mechanisms may involve cancer cell-dependent induction of tumor stromal cells to produce paracrine growth factors or could involve cancer cell autonomous autocrine and/or intracellular AR signaling pathways. We utilized clinical samples, animal models and a series of AR-positive human prostate cancer cell lines to evaluate AR-mediated growth stimulation of prostate CICs. The present studies document that stromal AR expression is not required for prostate cancer growth, since tumor stroma surrounding AR-positive human prostate cancer metastases (N = 127) are characteristically AR-negative. This lack of a requirement for AR expression in tumor stromal cells is also documented by the fact that human AR-positive prostate cancer cells grow equally well when xenografted in wild-type versus AR-null nude mice. AR-dependent growth stimulation was documented to involve secretion, extracellular binding, and signaling by autocrine growth factors. Orthotopic xenograft animal studies documented that the cellautonomous autocrine growth factors which stimulate prostate CIC growth are not the andromedins secreted by normal prostate stromal cells. Such cell autonomous and extracellular autocrine signaling is necessary but not sufficient for the optimal growth of prostate CICs based upon the response to anti-androgen plus/or minus preconditioned media. AR-induced growth stimulation of human prostate CICs requires AR-dependent intracellular pathways. The identification of such AR-dependent intracellular pathways offers new leads for the development of effective therapies for prostate cancer. (c) 2009 Wiley-Liss, Inc.

First-in-human Phase 1 CRISPR Gene Editing Cancer Trials: Are We Ready?

PubMed

Baylis, Francoise; McLeod, Marcus

2017-01-01

A prospective first-in-human Phase 1 CRISPR gene editing trial in the United States for patients with melanoma, synovial sarcoma, and multiple myeloma offers hope that gene editing tools may usefully treat human disease. An overarching ethical challenge with first-in-human Phase 1 clinical trials, however, is knowing when it is ethically acceptable to initiate such trials on the basis of safety and efficacy data obtained from pre-clinical studies. If the pre-clinical studies that inform trial design are themselves poorly designed - as a result of which the quality of pre-clinical evidence is deficient - then the ethical requirement of scientific validity for clinical research may not be satisfied. In turn, this could mean that the Phase 1 clinical trial will be unsafe and that trial participants will be exposed to risk for no potential benefit. To assist sponsors, researchers, clinical investigators and reviewers in deciding when it is ethically acceptable to initiate first-in-human Phase 1 CRISPR gene editing clinical trials, structured processes have been developed to assess and minimize translational distance between pre-clinical and clinical research. These processes draw attention to various features of internal validity, construct validity, and external validity. As well, the credibility of supporting evidence is to be critically assessed with particular attention to optimism bias, financial conflicts of interest and publication bias. We critically examine the pre-clinical evidence used to justify the first-inhuman Phase 1 CRISPR gene editing cancer trial in the United States using these tools. We conclude that the proposed trial cannot satisfy the ethical requirement of scientific validity because the supporting pre-clinical evidence used to inform trial design is deficient. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Alteration of Cell Cycle Mediated by Zinc in Human Bronchial ...

EPA Pesticide Factsheets

Zinc (Zn2+), a ubiquitous ambient air contaminant, presents an oxidant challenge to the human lung and is linked to adverse human health effects. To further elucidate the adaptive and apoptotic cellular responses of human airway cells to Zn2+, we performed pilot studies to examine cell cycle perturbation upon exposure using a normal human bronchial epithelial cell culture (BEAS-2B). BEAS-2B cells were treated with low (0, 1, 2 µM) and apoptotic (3 µM) doses of Zn2+ plus 1 µM pyrithione, a Zn2+-specific ionophore facilitating cellular uptake, for up to 24 h. Fixed cells were then stained with propidium iodine (PI) and cell cycle phase was determined by fluorescent image cytometry. Initial results report the percentage of cells in the S phase after 18 h exposure to 1, 2, and 3 µM Zn2+ were similar (8%, 7%, and 12%, respectively) compared with 7% in controls. Cells exposed to 3 µM Zn2+ increased cell populations in G2/M phase (76% versus 68% in controls). Interestingly, exposure to 1 µM Zn2+ resulted in decreased (59%) cells in G2/M. While preliminary, these pilot studies suggest Zn2+ alters cell cycle in BEAS-2B cells, particularly in the G2/M phase. The G2/M checkpoint maintains DNA integrity by enabling initiation of DNA repair or apoptosis. Our findings suggest that the adaptive and apoptotic responses to Zn2+ exposure may be mediated via perturbation of the cell cycle at the G2/M checkpoint. This work was a collaborative summer student project. The st

Innovative problem solving by wild spotted hyenas

PubMed Central

Benson-Amram, Sarah; Holekamp, Kay E.

2012-01-01

Innovative animals are those able to solve novel problems or invent novel solutions to existing problems. Despite the important ecological and evolutionary consequences of innovation, we still know very little about the traits that vary among individuals within a species to make them more or less innovative. Here we examine innovative problem solving by spotted hyenas (Crocuta crocuta) in their natural habitat, and demonstrate for the first time in a non-human animal that those individuals exhibiting a greater diversity of initial exploratory behaviours are more successful problem solvers. Additionally, as in earlier work, we found that neophobia was a critical inhibitor of problem-solving success. Interestingly, although juveniles and adults were equally successful in solving the problem, juveniles were significantly more diverse in their initial exploratory behaviours, more persistent and less neophobic than were adults. We found no significant effects of social rank or sex on success, the diversity of initial exploratory behaviours, behavioural persistence or neophobia. Our results suggest that the diversity of initial exploratory behaviours, akin to some measures of human creativity, is an important, but largely overlooked, determinant of problem-solving success in non-human animals. PMID:22874748

I Got 99 Problems, and eHealth Is One.

PubMed

Wass, Sofie; Vimarlund, Vivian

2017-01-01

Many eHealth initiatives are never implemented or merely end as pilot projects. Previous studies report that organisational, technical and human issues need to be properly taken into consideration if such initiatives are to be successful. The aim of this paper is to explore whether previously identified challenges within the area have remained in the Swedish eHealth setting or whether they have changed. After interviewing experts in eHealth, we present a classification of areas of concern. Recurrence of previously identified challenges was found, but also new issues were identified. The results of the study indicate that there is a need to consider organisational and semantic issues on both national and international levels. Legal and technical challenges still exist but it seems even more important to support eHealth initiatives financially, increase practitioners' knowledge in health informatics and manage new expectations from patients.

Viruses and human cancer: from detection to causality.

PubMed

Sarid, Ronit; Gao, Shou-Jiang

2011-06-28

The study of cancer is incomplete without taking into consideration of tumorigenic viruses. Initially, searches for human cancer viruses were fruitless despite an expansion of our knowledge in the same period concerning acute-transforming retroviruses in animals. However, over the last 40 years, we have witnessed rapid progress in the tumor virology field. Currently, acknowledged human cancer viruses include Epstein-Barr virus, hepatitis B virus, hepatitis C virus, high-risk human papilloma viruses, human T-cell lymphotropic virus type 1 and Kaposi's sarcoma-associated herpesvirus. Extensive epidemiological and mechanistic studies have led to the development of novel preventive and therapeutic approaches for managing some of these infections and associated cancers. In addition, recent advances in molecular technologies have enabled the discovery of a new potential human tumor virus, Merkel cell polyomavirus, but its association with cancer remains to be validated. It is anticipated that in the next few decades many additional human cancer viruses will be discovered and the mechanisms underlying viral oncogenesis delineated. Thus, it can be expected that better tools for preventing and treating virus-associated cancer will be available in the near future. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Direct measurement of time-dependent anesthetized in vivo human pulp temperature.

PubMed

Runnacles, Patrício; Arrais, Cesar Augusto Galvão; Pochapski, Marcia Thais; dos Santos, Fábio André; Coelho, Ulisses; Gomes, João Carlos; De Goes, Mário Fernando; Gomes, Osnara Maria Mongruel; Rueggeberg, Frederick Allen

2015-01-01

Human intrapupal tooth temperature is considered to be similar to that of the body (≈37 °C), although the actual temperature has never been measured. This study evaluated the in vivo, human, basal, coronal intrapulpal temperature of anesthetized upper first premolars. After approval of the local Ethics Committee was obtained (protocol no. 255,945), upper right and left first premolars requiring extraction for orthodontic reasons from 8 volunteers, ranging from 12 to 30 years old, received infiltrative and intraligamental anesthesia. The teeth (n=15) were isolated using rubber dam and a small, occlusal preparation was made using high-speed handpiece, under constant air-water spray, until a minute pulp exposure was attained. The sterile probe from a wireless, NIST-traceable, temperature acquisition system (Thermes WFI) was inserted directly into the coronal pulp. Once the probe was properly positioned and stable, real-time temperature data were continuously acquired for approximately 25 min. Data (°C) were subjected to 2-tailed, paired t-test (α=0.05), and the 95% confidence intervals for the initial and 25-min mean temperatures were also determined. The initial pulp temperature value (31.8±1.5 °C) was significantly lower than after 25-min (35.3±0.7 °C) (p<0.05). The 95% confidence interval for the initial temperature ranged from 31.0 to 32.6 °C and from 35.0 to 35.7 °C after 25 min. A slow, gradual temperature increase was observed after probe insertion until the pulp temperature reached a plateau, usually after 15 min. Consistent coronal, human, in vivo temperature values were observed and were slightly, but significantly below that of body core temperature. Copyright © 2014 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Geographic Factors and Human Papillomavirus (HPV) Vaccination Initiation among Adolescent Girls in the United States.

PubMed

Henry, Kevin A; Stroup, Antoinette M; Warner, Echo L; Kepka, Deanna

2016-02-01

This study is among the first to explore geographic factors that may be associated with human papillomavirus (HPV) vaccine uptake in the United States. Data from the 2011 and 2012 National Immunization Survey-Teen for 20,565 female adolescents aged 13 to 17 years were analyzed to examine associations of HPV vaccine initiation (receipt of at least one dose) with ZIP code-level geographic factors. Logistic regression including individual and geographic factors was used to estimate the odds of HPV vaccine initiation. Approximately 53% of girls initiated the HPV vaccine in both years. Girls in high poverty communities had higher HPV vaccine initiation compared with those in low poverty communities [61.1% vs. 52.4%; adjusted OR (AOR), 1.18; 95% confidence intervals (CI), 1.04-1.33]. Initiation was higher among girls in communities where the majority of the population was Hispanic (69.0% vs. 49.9%; AOR, 1.64; 95% CI, 1.43-1.87) or non-Hispanic mixed race (60.4% vs. 49.9%; AOR, 1.30; 95% CI, 1.17-1.44) compared with majority non-Hispanic white communities. Interactions between individual-level race/ethnicity and community racial-ethnic composition indicated significantly higher odds of initiation among Hispanic girls living in Hispanic communities compared with Hispanic girls living in predominantly non-Hispanic White (NHW) (AOR, 2.23; 95% CI, 1.87-2.65) or non-Hispanic Black (NHB) (AOR, 1.90; 95% CI, 1.20-3.04) communities, respectively. Initiation rates of HPV vaccination among teen girls were highest in the poorest communities and among Hispanics living in communities where the racial-ethnic composition was predominantly Hispanic or mixed race. Given low HPV vaccination rates in the United States, these results provide important evidence to inform public health interventions to increase HPV vaccination. ©2016 American Association for Cancer Research.

Biomechanics of Step Initiation After Balance Recovery With Implications for Humanoid Robot Locomotion.

PubMed

Miller Buffinton, Christine; Buffinton, Elise M; Bieryla, Kathleen A; Pratt, Jerry E

2016-03-01

Balance-recovery stepping is often necessary for both a human and humanoid robot to avoid a fall by taking a single step or multiple steps after an external perturbation. The determination of where to step to come to a complete stop has been studied, but little is known about the strategy for initiation of forward motion from the static position following such a step. The goal of this study was to examine the human strategy for stepping by moving the back foot forward from a static, double-support position, comparing parameters from normal step length (SL) to those from increasing SLs to the point of step failure, to provide inspiration for a humanoid control strategy. Healthy young adults instrumented with joint reflective markers executed a prescribed-length step from rest while marker positions and ground reaction forces (GRFs) were measured. The participants were scaled to the Gait2354 model in opensim software to calculate body kinematic and joint kinetic parameters, with further post-processing in matlab. With increasing SL, participants reduced both static and push-off back-foot GRF. Body center of mass (CoM) lowered and moved forward, with additional lowering at the longer steps, and followed a path centered within the initial base of support (BoS). Step execution was successful if participants gained enough forward momentum at toe-off to move the instantaneous capture point (ICP) to within the BoS defined by the final position of both feet on the front force plate. All lower extremity joint torques increased with SL except ankle joint. Front knee work increased dramatically with SL, accompanied by decrease in back-ankle work. As SL increased, the human strategy changed, with participants shifting their CoM forward and downward before toe-off, thus gaining forward momentum, while using less propulsive work from the back ankle and engaging the front knee to straighten the body. The results have significance for human motion, suggesting the upper limit of the SL that can be completed with back-ankle push-off before additional knee flexion and torque is needed. For biped control, the results support stability based on capture-point dynamics and suggest strategy for center-of-mass trajectory and distribution of ground force reactions that can be compared with robot controllers for initiation of gait after recovery steps.

The initial antibody response to HIV-1: induction of ineffective early B cell responses against GP41 by the transmitted/founder virus

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

Chavez, Leslie L; Perelson, Alan

2008-01-01

A window of opportunity for immune responses to extinguish HIV -1 exists from the moment of transmission through establishment of the latent pool of HIV -I-infected cells. A critical time to study the initial immune responses to the transmitted/founder virus is the eclipse phase of HIV-1 infection (time from transmission to the first appearance of plasma virus) but, to date, this period has been logistically difficult to analyze. Studies in non-human primates challenged with chimeric simianhuman immunodeficiency virus have shown that neutralizing antibodies, when present at the time of infection, can prevent virus infection.

Tissue engineering in urethral reconstruction—an update

PubMed Central

Mangera, Altaf; Chapple, Christopher R

2013-01-01

The field of tissue engineering is rapidly progressing. Much work has gone into developing a tissue engineered urethral graft. Current grafts, when long, can create initial donor site morbidity. In this article, we evaluate the progress made in finding a tissue engineered substitute for the human urethra. Researchers have investigated cell-free and cell-seeded grafts. We discuss different approaches to developing these grafts and review their reported successes in human studies. With further work, tissue engineered grafts may facilitate the management of lengthy urethral strictures requiring oral mucosa substitution urethroplasty. PMID:23042444

EPM - The European Facility for human physiology research on ISS.

PubMed

Rieschel, Mats; Nasca, Rosario; Junk, Peter; Gerhard, Ingo

2002-07-01

The European Physiology Modules (EPM) Facility is one of the four major Space Station facilities being developed within the framework of ESA's Microgravity Facilities for Columbus (MFC) programme. In order to allow a wide spectrum of physiological studies in weightlessness conditions, the facility provides the infrastructure to accommodate a variable set of scientific equipment. The initial EPM configuration supports experiments in the fields of neuroscience, bone & muscle research, cardiovascular research and metabolism. The International Space Life Science Working Group (ISLSWG) has recommended co-locating EPM with the 2 NASA Human Research Facility racks.

Modeling human infertility with pluripotent stem cells.

PubMed

Chen, Di; Gell, Joanna J; Tao, Yu; Sosa, Enrique; Clark, Amander T

2017-05-01

Human fertility is dependent upon the correct establishment and differentiation of the germline. This is because no other cell type in the body is capable of passing a genome and epigenome from parent to child. Terminally differentiated germline cells in the adult testis and ovary are called gametes. However, the initial specification of germline cells occurs in the embryo around the time of gastrulation. Most of our knowledge regarding the cell and molecular events that govern human germline specification involves extrapolating scientific principles from model organisms, most notably the mouse. However, recent work using next generation sequencing, gene editing and differentiation of germline cells from pluripotent stem cells has revealed that the core molecular mechanisms that regulate human germline development are different from rodents. Here, we will discuss the major molecular pathways required for human germline differentiation and how pluripotent stem cells have revolutionized our ability to study the earliest steps in human embryonic lineage specification in order to understand human fertility. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Planning the Human Variome Project: The Spain Report†

PubMed Central

Kaput, Jim; Cotton, Richard G. H.; Hardman, Lauren; Al Aqeel, Aida I.; Al-Aama, Jumana Y.; Al-Mulla, Fahd; Aretz, Stefan; Auerbach, Arleen D.; Axton, Myles; Bapat, Bharati; Bernstein, Inge T.; Bhak, Jong; Bleoo, Stacey L.; Blöcker, Helmut; Brenner, Steven E.; Burn, John; Bustamante, Mariona; Calzone, Rita; Cambon-Thomsen, Anne; Cargill, Michele; Carrera, Paola; Cavedon, Lawrence; Cho, Yoon Shin; Chung, Yeun-Jun; Claustres, Mireille; Cutting, Garry; Dalgleish, Raymond; den Dunnen, Johan T.; Díaz, Carlos; Dobrowolski, Steven; dos Santos, M. Rosário N.; Ekong, Rosemary; Flanagan, Simon B.; Flicek, Paul; Furukawa, Yoichi; Genuardi, Maurizio; Ghang, Ho; Golubenko, Maria V.; Greenblatt, Marc S.; Hamosh, Ada; Hancock, John M.; Hardison, Ross; Harrison, Terence M.; Hoffmann, Robert; Horaitis, Rania; Howard, Heather J.; Barash, Carol Isaacson; Izagirre, Neskuts; Jung, Jongsun; Kojima, Toshio; Laradi, Sandrine; Lee, Yeon-Su; Lee, Jong-Young; Gil-da-Silva-Lopes, Vera L.; Macrae, Finlay A.; Maglott, Donna; Marafie, Makia J.; Marsh, Steven G.E.; Matsubara, Yoichi; Messiaen, Ludwine M.; Möslein, Gabriela; Netea, Mihai G.; Norton, Melissa L.; Oefner, Peter J.; Oetting, William S.; O’Leary, James C.; de Ramirez, Ana Maria Oller; Paalman, Mark H.; Parboosingh, Jillian; Patrinos, George P.; Perozzi, Giuditta; Phillips, Ian R.; Povey, Sue; Prasad, Suyash; Qi, Ming; Quin, David J.; Ramesar, Rajkumar S.; Richards, C. Sue; Savige, Judith; Scheible, Dagmar G.; Scott, Rodney J.; Seminara, Daniela; Shephard, Elizabeth A.; Sijmons, Rolf H.; Smith, Timothy D.; Sobrido, María-Jesús; Tanaka, Toshihiro; Tavtigian, Sean V.; Taylor, Graham R.; Teague, Jon; Töpel, Thoralf; Ullman-Cullere, Mollie; Utsunomiya, Joji; van Kranen, Henk J.; Vihinen, Mauno; Watson, Michael; Webb, Elizabeth; Weber, Thomas K.; Yeager, Meredith; Yeom, Young I.; Yim, Seon-Hee; Yoo, Hyang-Sook

2018-01-01

The remarkable progress in characterizing the human genome sequence, exemplified by the Human Genome Project and the HapMap Consortium, has led to the perception that knowledge and the tools (e.g., microarrays) are sufficient for many if not most biomedical research efforts. A large amount of data from diverse studies proves this perception inaccurate at best, and at worst, an impediment for further efforts to characterize the variation in the human genome. Since variation in genotype and environment are the fundamental basis to understand phenotypic variability and heritability at the population level, identifying the range of human genetic variation is crucial to the development of personalized nutrition and medicine. The Human Variome Project (HVP; http://www.humanvariomeproject.org/) was proposed initially to systematically collect mutations that cause human disease and create a cyber infrastructure to link locus specific databases (LSDB). We report here the discussions and recommendations from the 2008 HVP planning meeting held in San Feliu de Guixols, Spain, in May 2008. PMID:19306394

Planning the human variome project: the Spain report.

PubMed

Kaput, Jim; Cotton, Richard G H; Hardman, Lauren; Watson, Michael; Al Aqeel, Aida I; Al-Aama, Jumana Y; Al-Mulla, Fahd; Alonso, Santos; Aretz, Stefan; Auerbach, Arleen D; Bapat, Bharati; Bernstein, Inge T; Bhak, Jong; Bleoo, Stacey L; Blöcker, Helmut; Brenner, Steven E; Burn, John; Bustamante, Mariona; Calzone, Rita; Cambon-Thomsen, Anne; Cargill, Michele; Carrera, Paola; Cavedon, Lawrence; Cho, Yoon Shin; Chung, Yeun-Jun; Claustres, Mireille; Cutting, Garry; Dalgleish, Raymond; den Dunnen, Johan T; Díaz, Carlos; Dobrowolski, Steven; dos Santos, M Rosário N; Ekong, Rosemary; Flanagan, Simon B; Flicek, Paul; Furukawa, Yoichi; Genuardi, Maurizio; Ghang, Ho; Golubenko, Maria V; Greenblatt, Marc S; Hamosh, Ada; Hancock, John M; Hardison, Ross; Harrison, Terence M; Hoffmann, Robert; Horaitis, Rania; Howard, Heather J; Barash, Carol Isaacson; Izagirre, Neskuts; Jung, Jongsun; Kojima, Toshio; Laradi, Sandrine; Lee, Yeon-Su; Lee, Jong-Young; Gil-da-Silva-Lopes, Vera L; Macrae, Finlay A; Maglott, Donna; Marafie, Makia J; Marsh, Steven G E; Matsubara, Yoichi; Messiaen, Ludwine M; Möslein, Gabriela; Netea, Mihai G; Norton, Melissa L; Oefner, Peter J; Oetting, William S; O'Leary, James C; de Ramirez, Ana Maria Oller; Paalman, Mark H; Parboosingh, Jillian; Patrinos, George P; Perozzi, Giuditta; Phillips, Ian R; Povey, Sue; Prasad, Suyash; Qi, Ming; Quin, David J; Ramesar, Rajkumar S; Richards, C Sue; Savige, Judith; Scheible, Dagmar G; Scott, Rodney J; Seminara, Daniela; Shephard, Elizabeth A; Sijmons, Rolf H; Smith, Timothy D; Sobrido, María-Jesús; Tanaka, Toshihiro; Tavtigian, Sean V; Taylor, Graham R; Teague, Jon; Töpel, Thoralf; Ullman-Cullere, Mollie; Utsunomiya, Joji; van Kranen, Henk J; Vihinen, Mauno; Webb, Elizabeth; Weber, Thomas K; Yeager, Meredith; Yeom, Young I; Yim, Seon-Hee; Yoo, Hyang-Sook

2009-04-01

The remarkable progress in characterizing the human genome sequence, exemplified by the Human Genome Project and the HapMap Consortium, has led to the perception that knowledge and the tools (e.g., microarrays) are sufficient for many if not most biomedical research efforts. A large amount of data from diverse studies proves this perception inaccurate at best, and at worst, an impediment for further efforts to characterize the variation in the human genome. Because variation in genotype and environment are the fundamental basis to understand phenotypic variability and heritability at the population level, identifying the range of human genetic variation is crucial to the development of personalized nutrition and medicine. The Human Variome Project (HVP; http://www.humanvariomeproject.org/) was proposed initially to systematically collect mutations that cause human disease and create a cyber infrastructure to link locus specific databases (LSDB). We report here the discussions and recommendations from the 2008 HVP planning meeting held in San Feliu de Guixols, Spain, in May 2008. (c) 2009 Wiley-Liss, Inc.

Human Transportation System (HTS) study: Executive summary

NASA Technical Reports Server (NTRS)

Lance, N.; Geyer, M. S.; Gaunce, M. T.

1993-01-01

Work completed under the Human Transportation System Study is summarized. This study was conducted by the New Initiatives Office at JSC with the technical support of Boeing, General Dynamics, Lockheed, McDonnell-Douglas, Martin Marietta, and Rockwell. The study was designed to generate information on determining the appropriate path to follow for new system development to meet the Nation's space transportation needs. The study evaluates 18 transportation architecture options using a parametric set of mission requirements. These options include use of current systems as well as proposed systems to assess the impact of various considerations, such as the cost of alternate access, or the benefit of separating people and cargo. The architecture options are compared to each other with six measurable evaluation criteria or attributes. They are the following: funding profile, human safety, probability of mission success, architecture cost risk, launch schedule confidence, and environmental impact. Values for these attributes are presented for the architecture options, with pertinent conclusions and recommendations.

Human Transportation System (HTS) study, volume 2

NASA Technical Reports Server (NTRS)

Lance, N.; Geyer, M. S.; Gaunce, M. T.

1993-01-01

This report summarizes work completed under the Human Transportation System Study. This study was conducted by the New Initiatives Office at JSC with the technical support of Boeing, General Dynamics, Lockheed, McDonnell-Douglas, Martin Marietta, and Rockwell. The study was designed to generate information on determining the appropriate path to follow for new system development to meet the Nation's space transportation needs. The study evaluates 18 transportation architecture options using a parametric set of mission requirements. These options include use of current systems (e.g., Shuttle, Titan, etc. ) as well as proposed systems (e.g., PLS, Single-Stage-to-Orbit, etc.) to assess the impact of various considerations, such as the cost of alternate access, or the benefit of separating people and cargo. The architecture options are compared to each other with six measurable evaluation criteria or attributes. They are: funding profile, human safety, probability of mission success, architecture cost risk, launch schedule confidence, and environmental impact. Values for these attributes are presented for the architecture options, with pertinent conclusions and recommendations.

Human Transportation System (HTS) study, volume 1

NASA Technical Reports Server (NTRS)

Lance, N.; Geyer, M. S.; Gaunce, M. T.

1993-01-01

Work completed under the Human Transportation System Study is summarized. This study was conducted by the New Initiatives Office at JSC with the technical support of Boeing, General Dynamics, Lockheed, McDonnell-Douglas, Martin Marietta, and Rockwell. The study was designed to generate information on determining the appropriate path to follow for new system development to meet the Nation's space transportation needs. The study evaluates 18 transportation architecture options using a parametric set of mission requirements. These options include use of current systems as well as proposed systems to assess the impact of various considerations, such as the cost of alternate access, or the benefit of separating people and cargo. The architecture options are compared to each other with six measurable evaluation criteria or attributes. They are the following: funding profile, human safety, probability of mission success, architecture cost risk, launch schedule confidence, and environmental impact. Values for these attributes are presented for the architecture options, with pertinent conclusions and recommendations.

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

Wheeler, F.; Wessol, D.; Atkinson, C.

During the past few years, murine and large animal research, as well as human studies have provided data to the point where human clinical trials have been initiated at the BMRR using BPA-F for gliomas and at the Massachusetts Institute of Technology Reactor (MITR) using BPA for melanomas of the extremeties. It is expected that glioma trials using BSH will proceed soon at the Petten High Flux Reactor (HFR) in the Netherlands. The first human glioma epithermal boron neutron capture therapy application was performed at the BMRR in the fall of 1994. This was a collaborative effort by BNL, Bethmore » Israel Manhattan hospital, and INEL. The INEL planning system was chosen to perform dose predictions for this application.« less

The dietary intake of wheat and other cereal grains and their role in inflammation.

PubMed

de Punder, Karin; Pruimboom, Leo

2013-03-12

Wheat is one of the most consumed cereal grains worldwide and makes up a substantial part of the human diet. Although government-supported dietary guidelines in Europe and the U.S.A advise individuals to eat adequate amounts of (whole) grain products per day, cereal grains contain "anti-nutrients," such as wheat gluten and wheat lectin, that in humans can elicit dysfunction and disease. In this review we discuss evidence from in vitro, in vivo and human intervention studies that describe how the consumption of wheat, but also other cereal grains, can contribute to the manifestation of chronic inflammation and autoimmune diseases by increasing intestinal permeability and initiating a pro-inflammatory immune response.

Borrelia miyamotoi: a widespread tick-borne relapsing fever spirochete.

PubMed

Wagemakers, Alex; Staarink, Pieter J; Sprong, Hein; Hovius, Joppe W R

2015-06-01

Borrelia miyamotoi is a relapsing fever spirochete that has only recently been identified as a human pathogen. Borrelia miyamotoi is genetically and ecologically distinct from Borrelia burgdorferi sensu lato, while both are present in Ixodes ticks. Over 50 patients with an acute febrile illness have been described with a B. miyamotoi infection, and two infected immunocompromised patients developed a meningoencephalitis. Seroprevalence studies indicate exposure in the general population and in specific risk groups, such as patients initially suspected of having human granulocytic anaplasmosis. Here, we review the available literature on B. miyamotoi, describing its presence in ticks, reservoir hosts, and humans, and discussing its potential impact on public health. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pathology as the enabler of human research.

PubMed

Crawford, James M; Tykocinski, Mark L

2005-09-01

Academic Pathology is a key player in human molecular science and in the powerful initiatives of the National Institutes of Health. Pathologists generate data crucial to virtually every molecular study of human tissue, and have the necessary skills and authority to oversee processing of human tissues for research analysis. We advocate that Academic Pathology is optimally positioned to drive the molecular revolution in study of human disease, through human tissue collection, analysis, and databasing. This can be achieved through playing a major role in human tissue procurement and management; establishing high-quality 'Pathology Resource Laboratories'; providing the scientific expertise for pathology data sharing; and recruiting and training physician scientists. Pathology should position itself to be the local institutional driver of technology implementation and development, by operating the resource laboratories, providing the expertise for technical and conceptual design of research projects, maintaining the databases that link molecular and morphological information on human tissues with the requisite clinical databases, providing education and mentorship of technology users, and nurturing new research through the development of preliminary data. We also consider that outstanding pathology journals are available for the publication of research emanating from such studies, to the benefit of the pathology profession as an academic enterprise. It is our earnest hope that Academic Pathology can play a leading role in the remarkable advances to be made as the 21st century unfolds.

Genome-wide uniformity of human ‘open’ pre-initiation complexes

PubMed Central

Lai, William K.M.; Pugh, B. Franklin

2017-01-01

Transcription of protein-coding and noncoding DNA occurs pervasively throughout the mammalian genome. Their sites of initiation are generally inferred from transcript 5′ ends and are thought to be either locally dispersed or focused. How these two modes of initiation relate is unclear. Here, we apply permanganate treatment and chromatin immunoprecipitation (PIP-seq) of initiation factors to identify the precise location of melted DNA separately associated with the preinitiation complex (PIC) and the adjacent paused complex (PC). This approach revealed the two known modes of transcription initiation. However, in contrast to prevailing views, they co-occurred within the same promoter region: initiation originating from a focused PIC, and broad nucleosome-linked initiation. PIP-seq allowed transcriptional orientation of Pol II to be determined, which may be useful near promoters where sufficient sense/anti-sense transcript mapping information is lacking. PIP-seq detected divergently oriented Pol II at both coding and noncoding promoters, as well as at enhancers. Their occupancy levels were not necessarily coupled in the two orientations. DNA sequence and shape analysis of initiation complex sites suggest that both sequence and shape contribute to specificity, but in a context-restricted manner. That is, initiation sites have the locally “best” initiator (INR) sequence and/or shape. These findings reveal a common core to pervasive Pol II initiation throughout the human genome. PMID:27927716

Exercise-induced ischemia initiates the second window of protection in humans independent of collateral recruitment.

PubMed

Lambiase, Pier D; Edwards, Richard J; Cusack, Michael R; Bucknall, Clifford A; Redwood, Simon R; Marber, Michael S

2003-04-02

This study was designed to examine if exercise-induced ischemia initiated late preconditioning in humans that becomes manifest during subsequent exercise and serial balloon occlusion of the left anterior descending coronary artery (LAD). The existence of late preconditioning in humans is controversial. We therefore compared myocardial responses to exercise-induced and intracoronary balloon inflation-induced ischemia in two groups of patients subjected to different temporal patterns of ischemia. Thirty patients with stable angina secondary to single-vessel LAD disease underwent percutaneous coronary intervention (PCI) after two separate exercise tolerance test (ETT) protocols designed to investigate isolated early preconditioning (IEP) alone or the second window of protection (SWOP). The IEP subjects underwent three sequential ETTs at least two weeks before PCI. The SWOP subjects underwent five sequential ETTs commencing 24 h before PCI. During PCI there was no significant difference in intracoronary pressure-derived collateral flow index (CFI) between groups (IEP = 0.15 +/- 0.13, SWOP = 0.19 +/- 0.15). In SWOP patients, compared with the initial ETT, the ETT performed 24 h later had a 40% (p < 0.001) increase in time to 0.1-mV ST depression and a 60% (p < 0.05) decrease in ventricular ectopic frequency. During the first balloon inflation, peak ST elevation was reduced by 49% (p < 0.05) in the SWOP versus the IEP group, and the dependence on CFI observed in the IEP group was abolished (analysis of covariance, p < 0.05). The significant attenuation of ST elevation (47%, p < 0.005) seen at the time of the second inflation in the IEP patients was not seen in the SWOP patients. Exercise-induced ischemia triggers late preconditioning in humans, which becomes manifest during exercise and PCI. This is the first evidence that ischemia induced by coronary occlusion is attenuated in humans by a late preconditioning effect induced by exercise.

The Liberal Arts in Anglophone Africa

ERIC Educational Resources Information Center

Lilford, Grant

2012-01-01

In 2009 and 2010, the author was involved in two University of Botswana initiatives on graduate employability. The first was a university-wide task force exploring the attitudes of students and staff and recommending reforms both in learning and teaching and in support services for students. The second was a Faculty of Humanities tracer study, in…

MUTAGENIC AND CARCINOGENIC POTENCY OF EXTRACTS OF DIESEL AND RELATED ENVIRONMENTAL EMISSIONS: STUDY DESIGN, SAMPLE GENERATION, COLLECTION, AND PREPARATION (JOURNAL VERSION)

EPA Science Inventory

A major diesel emissions research program has been initiated by the US Environmental Protection Agency to assess the human health risk associated with increased use of diesel automobiles. This program is intended to establish the mutagenic and carcinogenic potency of complex orga...

Competency-Based Hiring Interviews and University Teaching Performance

ERIC Educational Resources Information Center

Ellis, Jerald K.

2014-01-01

The purpose of this study was to determine if a pre-hire structured interview with competency-based behavioral questions can be linked to the teaching performance ratings of faculty at member institutions of the Florida State University System (SUS). Insights gained from this investigation can support the initiative for a proactive Human Resource…

Innovations in Higher Education. Singapore at the Competitive Edge. World Bank Technical Paper No. 222.

ERIC Educational Resources Information Center

Selvaratnam, Viswanathan

This report provides an overview of Singapore's strategy for human resource development and the country's concerted effort to successfully orchestrate the many separate initiatives between 1960s to 1980s into an effective market-driven, three-tiered higher education system emphasizing technology and modernization. The study highlights the…

Learning about Life and Death in Early Childhood

ERIC Educational Resources Information Center

Slaughter, Virginia; Lyons, Michelle

2003-01-01

Inagaki and Hatano (2002) have argued that young children initially understand biological phenomena in terms of vitalism, a mode of construal in which "life" or "life-force" is the central causal-explanatory concept. This study investigated the development of vitalistic reasoning in young children's concepts of life, the human body and death.…

A Phenomenological Study of Student Engagement at a For-Profit, Online College

ERIC Educational Resources Information Center

Alward, Thomas S.

2012-01-01

As college enrollment continues to increase, there is greater need to understand how students remain engaged in their courses and throughout their program. Colleges are investing financial and human resources on understanding how student engagement initiatives impact retention and completion efforts, yet little research has been conducted on…

Gendering Corporal Punishment: Beyond the Discourse of Human Rights

ERIC Educational Resources Information Center

Humphreys, Sara

2008-01-01

In the last few years the Global Initiative to End All Corporal Punishment of Children has been gathering momentum, with a submission to "The United Nations Secretary General's study on violence against children" the most recent addition to the cause. Nevertheless, corporal punishment in schools is still condoned in many countries and…

Conjugative type IVb pilus recognizes lipopolysaccharide of recipient cells to initiate PAPI-1 pathogenicity island transfer in Pseudomonas aeruginosa

USDA-ARS?s Scientific Manuscript database

Pseudomonas aeruginosa pathogenicity island 1 (PAPI-1) is one of the largest genomic islands of this important opportunistic human pathogen. Previous studies have shown that PAPI-1 encodes several putative virulence factors, a major regulator of biofilm formation, and antibiotic-resistance traits, a...

21 CFR 312.82 - Early consultation.

Code of Federal Regulations, 2013 CFR

2013-04-01

... meeting is to review and reach agreement on the design of animal studies needed to initiate human testing... goal that such testing will be adequate to provide sufficient data on the drug's safety and... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Early consultation. 312.82 Section 312.82 Food and...

21 CFR 312.82 - Early consultation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... meeting is to review and reach agreement on the design of animal studies needed to initiate human testing... goal that such testing will be adequate to provide sufficient data on the drug's safety and... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Early consultation. 312.82 Section 312.82 Food and...

21 CFR 312.82 - Early consultation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... meeting is to review and reach agreement on the design of animal studies needed to initiate human testing... goal that such testing will be adequate to provide sufficient data on the drug's safety and... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Early consultation. 312.82 Section 312.82 Food and...

21 CFR 312.82 - Early consultation.

Code of Federal Regulations, 2014 CFR

2014-04-01

... meeting is to review and reach agreement on the design of animal studies needed to initiate human testing... goal that such testing will be adequate to provide sufficient data on the drug's safety and... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Early consultation. 312.82 Section 312.82 Food and...

21 CFR 312.82 - Early consultation.

Code of Federal Regulations, 2012 CFR

2012-04-01

... meeting is to review and reach agreement on the design of animal studies needed to initiate human testing... goal that such testing will be adequate to provide sufficient data on the drug's safety and... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Early consultation. 312.82 Section 312.82 Food and...

The Prussian Academy of Sciences and Humanities during the Weimar Republic

ERIC Educational Resources Information Center

Hardtwig, Wolfgang

2004-01-01

The German Revolution of November 1918 dramatically altered the Academy's view of its relationship with government. In particular, the Academy's Prussian tradition had to be rethought. From initial wariness to grudging acceptance, the Academy came to accept the Weimar regime. This paper studies the politics of the Academy, uncovers factions and…

Association between Human Body Composition and Periodontal Disease.

PubMed

Salekzamani, Yagoub; Shirmohammadi, Adileh; Rahbar, Mohammad; Shakouri, Seyed-Kazem; Nayebi, Farough

2011-01-01

Obesity in humans might increase the risk of periodontitis. The aim of the present study was to examine the relationship between body composition of males and their periodontal status. AS total of 150 males (aged 30-60) were selected: 31 were periodontally healthy, 45 had gingivitis, 39 had initial periodontitis, and 35 suffered from established periodontitis. BMI (body mass index), WC (waist circumference), and body composition parameters (consisting of body water, body fat, and skeletal muscle and bone mass) were measured. After adjusting for age, history of diabetes, smoking, physical activity status, and socioeconomic status, statistically significant correlations were found between periodontitis and BMI, WC, and body composition. There was only a statistically significant difference between the periodontal health and established periodontitis; that is, periodontal disease in mild forms (gingivitis) and initial periodontitis do not influence these variables (BMI, WC, and body composition parameters) and only the severe form of the disease influences the variables. These data suggest that there is a considerable association between severe forms of periodontal disease in males and their body composition, but this preliminary finding needs to be confirmed in more extensive studies.

Phase Transformations in a Human Tooth Tissue at the Initial Stage of Caries

PubMed Central

Prutskij, Tatiana; Ippolitov, Yury

2015-01-01

The aim of the paper is to study phase transformations in solid tissues of the human teeth during the development of fissure caries by Raman and fluorescence microspectroscopy. The study of the areas with fissure caries confirmed the assumption of the formation of a weak interaction between phosphate apatite enamel and organic acids (products of microorganisms). The experimental results obtained with by Raman microspectroscopy showed the formation of dicalcium phosphate dihydrate - CaHPO4-2H2O in the area of mural demineralization of carious fissure. A comparative analysis of structural and spectroscopic data for the intact and carious enamel shows that emergence of a more soluble phase - carbonate-substituted hydroxyapatite - is typical for the initial stage of caries. It is shown that microareas of dental hard tissues in the carious fissure due to an emerging misorientation of apatite crystals have a higher fluorescence yield than the area of the intact enamel. These areas can be easily detected even prior to a deep demineralization (white spot stage) for the case of irreversibly changed organomineral complex and intensive removal of the mineral component. PMID:25901743

Structural technology challenges for evolutionary growth of Space Station Freedom

NASA Technical Reports Server (NTRS)

Doiron, Harold H.

1990-01-01

A proposed evolutionary growth scenario for Space Station Freedom was defined recently by a NASA task force created to study requirements for a Human Exploration Initiative. The study was an initial response to President Bush's July 20, 1989 proposal to begin a long range program of human exploration of space including a permanently manned lunar base and a manned mission to Mars. This growth scenario evolves Freedom into a critical transportation node to support lunar and Mars missions. The growth scenario begins with the Assembly Complete configuration and adds structure, power, and facilities to support a Lunar Transfer Vehicle (LTV) verification flight. Evolutionary growth continues to support expendable, then reusable LTV operations, and finally, LTV and Mars Transfer Vehicle (MTV) operations. The significant structural growth and additional operations creating new loading conditions will present new technological and structural design challenges in addition to the considerable technology requirements of the baseline Space Station Freedom program. Several structural design and technology issues of the baseline program are reviewed and related technology development required by the growth scenario is identified.

76 FR 28437 - Disease, Disability, and Injury Prevention and Control Special Interest Project (SIP): Initial...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Interest Project (SIP): Initial Review The meeting... Disease or Treated by Assisted Reproductive Technology, SIP11-048, Panel F,'' initial review In accordance...