Extraction, integration and analysis of alternative splicing and protein structure distributed information

PubMed Central

D'Antonio, Matteo; Masseroli, Marco

2009-01-01

Background Alternative splicing has been demonstrated to affect most of human genes; different isoforms from the same gene encode for proteins which differ for a limited number of residues, thus yielding similar structures. This suggests possible correlations between alternative splicing and protein structure. In order to support the investigation of such relationships, we have developed the Alternative Splicing and Protein Structure Scrutinizer (PASS), a Web application to automatically extract, integrate and analyze human alternative splicing and protein structure data sparsely available in the Alternative Splicing Database, Ensembl databank and Protein Data Bank. Primary data from these databases have been integrated and analyzed using the Protein Identifier Cross-Reference, BLAST, CLUSTALW and FeatureMap3D software tools. Results A database has been developed to store the considered primary data and the results from their analysis; a system of Perl scripts has been implemented to automatically create and update the database and analyze the integrated data; a Web interface has been implemented to make the analyses easily accessible; a database has been created to manage user accesses to the PASS Web application and store user's data and searches. Conclusion PASS automatically integrates data from the Alternative Splicing Database with protein structure data from the Protein Data Bank. Additionally, it comprehensively analyzes the integrated data with publicly available well-known bioinformatics tools in order to generate structural information of isoform pairs. Further analysis of such valuable information might reveal interesting relationships between alternative splicing and protein structure differences, which may be significantly associated with different functions. PMID:19828075

OAS :: Our Structure

Science.gov Websites

General Assembly Governance H Human Development Human Rights I Indigenous Peoples Integral Development Scholarships School of Governance Science and Technology Social Development Summits of the Americas Sustainable

The Human Thalamus Is an Integrative Hub for Functional Brain Networks

PubMed Central

Bertolero, Maxwell A.

2017-01-01

The thalamus is globally connected with distributed cortical regions, yet the functional significance of this extensive thalamocortical connectivity remains largely unknown. By performing graph-theoretic analyses on thalamocortical functional connectivity data collected from human participants, we found that most thalamic subdivisions display network properties that are capable of integrating multimodal information across diverse cortical functional networks. From a meta-analysis of a large dataset of functional brain-imaging experiments, we further found that the thalamus is involved in multiple cognitive functions. Finally, we found that focal thalamic lesions in humans have widespread distal effects, disrupting the modular organization of cortical functional networks. This converging evidence suggests that the human thalamus is a critical hub region that could integrate diverse information being processed throughout the cerebral cortex as well as maintain the modular structure of cortical functional networks. SIGNIFICANCE STATEMENT The thalamus is traditionally viewed as a passive relay station of information from sensory organs or subcortical structures to the cortex. However, the thalamus has extensive connections with the entire cerebral cortex, which can also serve to integrate information processing between cortical regions. In this study, we demonstrate that multiple thalamic subdivisions display network properties that are capable of integrating information across multiple functional brain networks. Moreover, the thalamus is engaged by tasks requiring multiple cognitive functions. These findings support the idea that the thalamus is involved in integrating information across cortical networks. PMID:28450543

Fragmentation of Thinking Structure's Students to Solving the Problem of Application Definite Integral in Area

ERIC Educational Resources Information Center

Wibawa, Kadek Adi; Nusantara, Toto; Subanji; Parta, I. Nengah

2017-01-01

This study aims to reveal the fragmentation of thinking structure's students in solving the problems of application definite integral in area. Fragmentation is a term on the computer (storage) that is highly relevant correlated with theoretical constructions that occur in the human brain (memory). Almost every student has a different way to…

Structure Learning in Bayesian Sensorimotor Integration

PubMed Central

Genewein, Tim; Hez, Eduard; Razzaghpanah, Zeynab; Braun, Daniel A.

2015-01-01

Previous studies have shown that sensorimotor processing can often be described by Bayesian learning, in particular the integration of prior and feedback information depending on its degree of reliability. Here we test the hypothesis that the integration process itself can be tuned to the statistical structure of the environment. We exposed human participants to a reaching task in a three-dimensional virtual reality environment where we could displace the visual feedback of their hand position in a two dimensional plane. When introducing statistical structure between the two dimensions of the displacement, we found that over the course of several days participants adapted their feedback integration process in order to exploit this structure for performance improvement. In control experiments we found that this adaptation process critically depended on performance feedback and could not be induced by verbal instructions. Our results suggest that structural learning is an important meta-learning component of Bayesian sensorimotor integration. PMID:26305797

Atrial fibrillation driver mechanisms: Insight from the isolated human heart.

PubMed

Csepe, Thomas A; Hansen, Brian J; Fedorov, Vadim V

2017-01-01

Although there have been great technological advances in the treatment of atrial fibrillation (AF), current therapies remain limited due to a narrow understanding of AF mechanisms in the human heart. This review will highlight our recent studies on explanted human hearts where we developed and employed a novel functional-structural mapping approach by integrating high-resolution simultaneous endo-epicardial and panoramic optical mapping with 3D gadolinium-enhanced MRI to define the spatiotemporal characteristics of AF drivers and their structural substrates. The results allow us to postulate that the primary mechanism of AF maintenance in human hearts is a limited number of localized intramural microanatomic reentrant AF drivers anchored to heart-specific 3D fibrotically insulated myobundle tracks, which may remain hidden to clinical single-surface electrode mapping. We suggest that ex vivo human heart studies, by using an integrated 3D functional and structural mapping approach, will help to reveal defining features of AF drivers as well as validate and improve clinical approaches to detect and target these AF drivers in patients with cardiac diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

A 3D bioprinting system to produce human-scale tissue constructs with structural integrity.

PubMed

Kang, Hyun-Wook; Lee, Sang Jin; Ko, In Kap; Kengla, Carlos; Yoo, James J; Atala, Anthony

2016-03-01

A challenge for tissue engineering is producing three-dimensional (3D), vascularized cellular constructs of clinically relevant size, shape and structural integrity. We present an integrated tissue-organ printer (ITOP) that can fabricate stable, human-scale tissue constructs of any shape. Mechanical stability is achieved by printing cell-laden hydrogels together with biodegradable polymers in integrated patterns and anchored on sacrificial hydrogels. The correct shape of the tissue construct is achieved by representing clinical imaging data as a computer model of the anatomical defect and translating the model into a program that controls the motions of the printer nozzles, which dispense cells to discrete locations. The incorporation of microchannels into the tissue constructs facilitates diffusion of nutrients to printed cells, thereby overcoming the diffusion limit of 100-200 μm for cell survival in engineered tissues. We demonstrate capabilities of the ITOP by fabricating mandible and calvarial bone, cartilage and skeletal muscle. Future development of the ITOP is being directed to the production of tissues for human applications and to the building of more complex tissues and solid organs.

ESTIMATING SUSTAINABILITY OF A SIMPLE HUMAN SOCIETY AND ITS ASSOCIATED ECOSYSTEM USING RESILIENCE AND FISHER INFORMATION

EPA Science Inventory

Sustainability applies to integrated systems comprising humans and the rest of nature. To be considered sustainable, human components (society, economy, law, etc.) that interact with ecosystems cannot decrease the resilience of ecosystem structures and functions (trophic linkage...

Information Structure, Information Technology, and the Human Services Organizational Environment.

ERIC Educational Resources Information Center

Semke, Jeanette I.; Nurius, Paula S.

1991-01-01

Examines current trends in data collection and information use in human services organizations. Describes issues for managers who are planning information systems, including practitioner resistance to automation. Proposes that conceptual integration of agendas for human services automation, practice evaluation, and service effectiveness enables…

ESTIMATING SUSTAINABILITY OF A SIMPLE HUMAN SOCIETY AND ITS ASSOCIATED ECOSYTEM USING RESILIENCE AND FISHER INFORMATION

EPA Science Inventory

Sustainability applies to integrated systems comprising humans and the rest of nature. To be considered sustainable, human components (society, economy, law, etc.) that interact with ecosystems cannot decrease the resilience of ecosystem structures and functions (trophic linkages...

Patterns of craniofacial integration in extant Homo, Pan, and Gorilla.

PubMed

Polanski, Joshua M; Franciscus, Robert G

2006-09-01

Brain size increased greatly during Pleistocene human evolution, while overall facial and dentognathic size decreased markedly. This mosaic pattern is due to either selective forces that acted uniquely on each functional unit in a modularized, developmentally uncoupled craniofacial complex, or alternatively, selection that acted primarily on one unit, with the other responding passively as part of a coevolved set of ontogenetically and evolutionarily integrated structures. Using conditional independence modeling on homologous linear measurements of the height, breadth, and depth of the cranium in Pan (n = 95), Gorilla (n = 102), and recent Homo (n = 120), we reject the null hypothesis of equal levels of overall cranial integration. While all three groups share the pattern of greater neurocranial integration with distinct separation between the face and neurocranium (modularization), family differences do exist. The apes are more integrated in their entire crania, but display a particularly strong pattern of integration within the facial complex related to prognathism. Modern humans display virtually no facial integration, a pattern which is likely related to their markedly decreased facial projection. Modern humans also differ from their great ape counterparts in being more integrated within the breadth dimension of the cranial vault, likely tied to the increase in brain size and eventual globularity seen in human evolution. That the modern human integration pattern differs from the ancestral African great ape pattern along the inverse neurocranial-facial trend seen in human evolution indicates that this shift in the pattern of integration is evolutionarily significant, and may help to clarify aspects of the current debate over defining modern humans. 2006 Wiley-Liss, Inc.

Aeronautics Technology Possibilities for 2000: Report of a Workshop

NASA Technical Reports Server (NTRS)

1984-01-01

Topics discussed include: Aerodynamics; Propulsion; Structural Analysis and Design Technology; Materials for Structural Members, Propulsion Systems, and Subsystems; Guidance, Navigation, and Control; Computer and Information Technology; Human Factors Engineering; Systems Integration.

Human Systems Integration in Practice: Constellation Lessons Learned

NASA Technical Reports Server (NTRS)

Zumbado, Jennifer Rochlis

2012-01-01

NASA's Constellation program provided a unique testbed for Human Systems Integration (HSI) as a fundamental element of the Systems Engineering process. Constellation was the first major program to have HSI mandated by NASA's Human Rating document. Proper HSI is critical to the success of any project that relies on humans to function as operators, maintainers, or controllers of a system. HSI improves mission, system and human performance, significantly reduces lifecycle costs, lowers risk and minimizes re-design. Successful HSI begins with sufficient project schedule dedicated to the generation of human systems requirements, but is by no means solely a requirements management process. A top-down systems engineering process that recognizes throughout the organization, human factors as a technical discipline equal to traditional engineering disciplines with authority for the overall system. This partners with a bottoms-up mechanism for human-centered design and technical issue resolution. The Constellation Human Systems Integration Group (HSIG) was a part of the Systems Engineering and Integration (SE&I) organization within the program office, and existed alongside similar groups such as Flight Performance, Environments & Constraints, and Integrated Loads, Structures and Mechanisms. While the HSIG successfully managed, via influence leadership, a down-and-in Community of Practice to facilitate technical integration and issue resolution, it lacked parallel top-down authority to drive integrated design. This presentation will discuss how HSI was applied to Constellation, the lessons learned and best practices it revealed, and recommendations to future NASA program and project managers. This presentation will discuss how Human Systems Integration (HSI) was applied to NASA's Constellation program, the lessons learned and best practices it revealed, and recommendations to future NASA program and project managers on how to accomplish this critical function.

Autonomous Assembly of Modular Structures in Space and on Extraterrestrial Locations

NASA Astrophysics Data System (ADS)

Alhorn, Dean C.

2005-02-01

The new U.S. National Vision for Space Exploration requires many new enabling technologies to accomplish the goals of space commercialization and returning humans to the moon and extraterrestrial environments. Traditionally, flight elements are complete sub-systems requiring humans to complete the integration and assembly. These bulky structures also require the use of heavy launch vehicles to send the units to a desired location. This philosophy necessitates a high degree of safety, numerous space walks at a significant cost. Future space mission costs must be reduced and safety increased to reasonably achieve exploration goals. One proposed concept is the autonomous assembly of space structures. This concept is an affordable, reliable solution to in-space and extraterrestrial assembly. Assembly is autonomously performed when two components join after determining that specifications are correct. Local sensors continue monitor joint integrity post assembly, which is critical for safety and structural reliability. Achieving this concept requires a change in space structure design philosophy and the development of innovative technologies to perform autonomous assembly. Assembly of large space structures will require significant numbers of integrity sensors. Thus simple, low-cost sensors are integral to the success of this concept. This paper addresses these issues and proposes a novel concept for assembling space structures autonomously. Core technologies required to achieve in space assembly are presented. These core technologies are critical to the goal of utilizing space in a cost efficient and safe manner. Additionally, these novel technologies can be applied to other systems both on earth and extraterrestrial environments.

Autonomous Assembly of Modular Structures in Space and on Extraterrestrial Locations

NASA Technical Reports Server (NTRS)

Alhorn, Dean C.

2005-01-01

The new U.S. National Vision for Space Exploration requires many new enabling technologies to accomplish the goals of space commercialization and returning humans to the moon and extraterrestrial environments. Traditionally, flight elements are complete subsystems requiring humans to complete the integration and assembly. These bulky structures also require the use of heavy launch vehicles to send the units to a desired location. This philosophy necessitates a high degree of safety, numerous space walks at a significant cost. Future space mission costs must be reduced and safety increased to reasonably achieve exploration goals. One proposed concept is the autonomous assembly of space structures. This concept is an affordable, reliable solution to in-space and extraterrestrial assembly. Assembly is autonomously performed when two components join after determining that specifications are correct. Local sensors continue monitor joint integrity post assembly, which is critical for safety and structural reliability. Achieving this concept requires a change in space structure design philosophy and the development of innovative technologies to perform autonomous assembly. Assembly of large space structures will require significant numbers of integrity sensors. Thus simple, low-cost sensors are integral to the success of this concept. This paper addresses these issues and proposes a novel concept for assembling space structures autonomously. Core technologies required to achieve in space assembly are presented. These core technologies are critical to the goal of utilizing space in a cost efficient and safe manner. Additionally, these novel technologies can be applied to other systems both on earth and extraterrestrial environments.

Learning to Lead: Self- and Peer Evaluation of Team Leaders in the Human Structure Didactic Block

ERIC Educational Resources Information Center

Chen, Laura P.; Gregory, Jeremy K.; Camp, Christopher L.; Juskewitch, Justin E.; Pawlina, Wojciech; Lachman, Nirusha

2009-01-01

Increasing emphasis on leadership in medical education has created a need for developing accurate evaluations of team leaders. Our study aimed to compare the accuracy of self- and peer evaluation of student leaders in the first-year Human Structure block (integrated gross anatomy, embryology, and radiology). Forty-nine first-year medical students…

Integrative Annotation of 21,037 Human Genes Validated by Full-Length cDNA Clones

PubMed Central

Imanishi, Tadashi; Itoh, Takeshi; Suzuki, Yutaka; O'Donovan, Claire; Fukuchi, Satoshi; Koyanagi, Kanako O; Barrero, Roberto A; Tamura, Takuro; Yamaguchi-Kabata, Yumi; Tanino, Motohiko; Yura, Kei; Miyazaki, Satoru; Ikeo, Kazuho; Homma, Keiichi; Kasprzyk, Arek; Nishikawa, Tetsuo; Hirakawa, Mika; Thierry-Mieg, Jean; Thierry-Mieg, Danielle; Ashurst, Jennifer; Jia, Libin; Nakao, Mitsuteru; Thomas, Michael A; Mulder, Nicola; Karavidopoulou, Youla; Jin, Lihua; Kim, Sangsoo; Yasuda, Tomohiro; Lenhard, Boris; Eveno, Eric; Suzuki, Yoshiyuki; Yamasaki, Chisato; Takeda, Jun-ichi; Gough, Craig; Hilton, Phillip; Fujii, Yasuyuki; Sakai, Hiroaki; Tanaka, Susumu; Amid, Clara; Bellgard, Matthew; Bonaldo, Maria de Fatima; Bono, Hidemasa; Bromberg, Susan K; Brookes, Anthony J; Bruford, Elspeth; Carninci, Piero; Chelala, Claude; Couillault, Christine; de Souza, Sandro J.; Debily, Marie-Anne; Devignes, Marie-Dominique; Dubchak, Inna; Endo, Toshinori; Estreicher, Anne; Eyras, Eduardo; Fukami-Kobayashi, Kaoru; R. Gopinath, Gopal; Graudens, Esther; Hahn, Yoonsoo; Han, Michael; Han, Ze-Guang; Hanada, Kousuke; Hanaoka, Hideki; Harada, Erimi; Hashimoto, Katsuyuki; Hinz, Ursula; Hirai, Momoki; Hishiki, Teruyoshi; Hopkinson, Ian; Imbeaud, Sandrine; Inoko, Hidetoshi; Kanapin, Alexander; Kaneko, Yayoi; Kasukawa, Takeya; Kelso, Janet; Kersey, Paul; Kikuno, Reiko; Kimura, Kouichi; Korn, Bernhard; Kuryshev, Vladimir; Makalowska, Izabela; Makino, Takashi; Mano, Shuhei; Mariage-Samson, Regine; Mashima, Jun; Matsuda, Hideo; Mewes, Hans-Werner; Minoshima, Shinsei; Nagai, Keiichi; Nagasaki, Hideki; Nagata, Naoki; Nigam, Rajni; Ogasawara, Osamu; Ohara, Osamu; Ohtsubo, Masafumi; Okada, Norihiro; Okido, Toshihisa; Oota, Satoshi; Ota, Motonori; Ota, Toshio; Otsuki, Tetsuji; Piatier-Tonneau, Dominique; Poustka, Annemarie; Ren, Shuang-Xi; Saitou, Naruya; Sakai, Katsunaga; Sakamoto, Shigetaka; Sakate, Ryuichi; Schupp, Ingo; Servant, Florence; Sherry, Stephen; Shiba, Rie; Shimizu, Nobuyoshi; Shimoyama, Mary; Simpson, Andrew J; Soares, Bento; Steward, Charles; Suwa, Makiko; Suzuki, Mami; Takahashi, Aiko; Tamiya, Gen; Tanaka, Hiroshi; Taylor, Todd; Terwilliger, Joseph D; Unneberg, Per; Veeramachaneni, Vamsi; Watanabe, Shinya; Wilming, Laurens; Yasuda, Norikazu; Yoo, Hyang-Sook; Stodolsky, Marvin; Makalowski, Wojciech; Go, Mitiko; Nakai, Kenta; Takagi, Toshihisa; Kanehisa, Minoru; Sakaki, Yoshiyuki; Quackenbush, John; Okazaki, Yasushi; Hayashizaki, Yoshihide; Hide, Winston; Chakraborty, Ranajit; Nishikawa, Ken; Sugawara, Hideaki; Tateno, Yoshio; Chen, Zhu; Oishi, Michio; Tonellato, Peter; Apweiler, Rolf; Okubo, Kousaku; Wagner, Lukas; Wiemann, Stefan; Strausberg, Robert L; Isogai, Takao; Auffray, Charles; Nomura, Nobuo; Sugano, Sumio

2004-01-01

The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology. PMID:15103394

Microwave non-contact imaging of subcutaneous human body tissues.

PubMed

Kletsov, Andrey; Chernokalov, Alexander; Khripkov, Alexander; Cho, Jaegeol; Druchinin, Sergey

2015-10-01

A small-size microwave sensor is developed for non-contact imaging of a human body structure in 2D, enabling fitness and health monitoring using mobile devices. A method for human body tissue structure imaging is developed and experimentally validated. Subcutaneous fat tissue reconstruction depth of up to 70 mm and maximum fat thickness measurement error below 2 mm are demonstrated by measurements with a human body phantom and human subjects. Electrically small antennas are developed for integration of the microwave sensor into a mobile device. Usability of the developed microwave sensor for fitness applications, healthcare, and body weight management is demonstrated.

On the Problems of Cracking and the Question of Structural Integrity of Engineering Composite Materials

NASA Astrophysics Data System (ADS)

Beaumont, Peter W. R.

2014-02-01

Predicting precisely where a crack will develop in a material under stress and exactly when in time catastrophic fracture of the component will occur is one the oldest unsolved mysteries in the design and building of large engineering structures. Where human life depends upon engineering ingenuity, the burden of testing to prove a "fracture safe design" is immense. For example, when human life depends upon structural integrity as an essential design requirement, it takes ten thousand material test coupons per composite laminate configuration to evaluate an airframe plus loading to ultimate failure tails, wing boxes, and fuselages to achieve a commercial aircraft airworthiness certification. Fitness considerations for long-life implementation of aerospace composites include understanding phenomena such as impact, fatigue, creep, and stress corrosion cracking that affect reliability, life expectancy, and durability of structure. Structural integrity analysis treats the design, the materials used, and figures out how best components and parts can be joined. Furthermore, SI takes into account service duty. However, there are conflicting aims in the complete design process of designing simultaneously for high efficiency and safety assurance throughout an economically viable lifetime with an acceptable level of risk.

Understanding Learner Strengths and Weaknesses: Assessing Performance on an Integrated Writing Task

ERIC Educational Resources Information Center

Sawaki, Yasuyo; Quinlan, Thomas; Lee, Yong-Won

2013-01-01

The present study examined the factor structures across features of 446 examinees' responses to a writing task that integrates reading and listening modalities as well as reading and listening comprehension items of the TOEFL iBT[R] (Internet-based test). Both human and automated scores obtained for the integrated essays were utilized. Based on a…

Beyond the Cognitive and the Virtue Approaches to Moral Education: Some Theoretical Foundations for an Integrated Account of Moral Education.

ERIC Educational Resources Information Center

Roh, Young-Ran

2000-01-01

Explores theoretical foundation for integrated approach to moral education; discusses rational choice and moral action within human reflective structure; investigates moral values required for integrative approach to moral education; discusses content of moral motivation, including role of emotion and reason. (Contains 15 references.) (PKP)

Integrating Informational, Social, and Behavioral Exchanges Between Humans, Urban Centers, and the Internet

DTIC Science & Technology

2014-06-01

against measures of effectiveness to help discern how to better utilize physical structures and human activities to create a more effective and...behaviors were solely enacted within the physical bounds of an urban center- mall, outdoor shopping plaza, or downtown, to name a few. The Internet has...is the effective integration of these components to enact city functions, plans, and is realized in physical design. City functions are: production

Pervasive genetic integration directs the evolution of human skull shape.

PubMed

Martínez-Abadías, Neus; Esparza, Mireia; Sjøvold, Torstein; González-José, Rolando; Santos, Mauro; Hernández, Miquel; Klingenberg, Christian Peter

2012-04-01

It has long been unclear whether the different derived cranial traits of modern humans evolved independently in response to separate selection pressures or whether they resulted from the inherent morphological integration throughout the skull. In a novel approach to this issue, we combine evolutionary quantitative genetics and geometric morphometrics to analyze genetic and phenotypic integration in human skull shape. We measured human skulls in the ossuary of Hallstatt (Austria), which offer a unique opportunity because they are associated with genealogical data. Our results indicate pronounced covariation of traits throughout the skull. Separate simulations of selection for localized shape changes corresponding to some of the principal derived characters of modern human skulls produced outcomes that were similar to each other and involved a joint response in all of these traits. The data for both genetic and phenotypic shape variation were not consistent with the hypothesis that the face, cranial base, and cranial vault are completely independent modules but relatively strongly integrated structures. These results indicate pervasive integration in the human skull and suggest a reinterpretation of the selective scenario for human evolution where the origin of any one of the derived characters may have facilitated the evolution of the others. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

Genetic effect of MTHFR C677T polymorphism on the structural covariance network and white-matter integrity in Alzheimer's disease.

PubMed

Chang, Yu-Tzu; Hsu, Shih-Wei; Tsai, Shih-Jen; Chang, Ya-Ting; Huang, Chi-Wei; Liu, Mu-En; Chen, Nai-Ching; Chang, Wen-Neng; Hsu, Jung-Lung; Lee, Chen-Chang; Chang, Chiung-Chih

2017-06-01

The 677 C to T transition in the MTHFR gene is a genetic determinant for hyperhomocysteinemia. We investigated whether this polymorphism modulates gray matter (GM) structural covariance networks independently of white-matter integrity in patients with Alzheimer's disease (AD). GM structural covariance networks were constructed by 3D T1-magnetic resonance imaging and seed-based analysis. The patients were divided into two genotype groups: C homozygotes (n = 73) and T carriers (n = 62). Using diffusion tensor imaging and white-matter parcellation, 11 fiber bundle integrities were compared between the two genotype groups. Cognitive test scores were the major outcome factors. The T carriers had higher homocysteine levels, lower posterior cingulate cortex GM volume, and more clusters in the dorsal medial lobe subsystem showing stronger covariance strength. Both posterior cingulate cortex seed and interconnected peak cluster volumes predicted cognitive test scores, especially in the T carriers. There were no between-group differences in fiber tract diffusion parameters. The MTHFR 677T polymorphism modulates posterior cingulate cortex-anchored structural covariance strength independently of white matter integrities. Hum Brain Mapp 38:3039-3051, 2017. © 2017 The Authors Human Brain Mapping Published Wiley by Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published Wiley by Periodicals, Inc.

Uberon, an integrative multi-species anatomy ontology

PubMed Central

2012-01-01

We present Uberon, an integrated cross-species ontology consisting of over 6,500 classes representing a variety of anatomical entities, organized according to traditional anatomical classification criteria. The ontology represents structures in a species-neutral way and includes extensive associations to existing species-centric anatomical ontologies, allowing integration of model organism and human data. Uberon provides a necessary bridge between anatomical structures in different taxa for cross-species inference. It uses novel methods for representing taxonomic variation, and has proved to be essential for translational phenotype analyses. Uberon is available at http://uberon.org PMID:22293552

Integration of genomic and medical data into a 3D atlas of human anatomy.

PubMed

Turinsky, Andrei L; Fanea, Elena; Trinh, Quang; Dong, Xiaoli; Stromer, Julie N; Shu, Xueling; Wat, Stephen; Hallgrímsson, Benedikt; Hill, Jonathan W; Edwards, Carol; Grosenick, Brenda; Yajima, Masumi; Sensen, Christoph W

2008-01-01

We have developed a framework for the visual integration and exploration of multi-scale biomedical data, which includes anatomical and molecular components. We have also created a Java-based software system that integrates molecular information, such as gene expression data, into a three-dimensional digital atlas of the male adult human anatomy. Our atlas is structured according to the Terminologia Anatomica. The underlying data-indexing mechanism uses open standards and semantic ontology-processing tools to establish the associations between heterogeneous data types. The software system makes an extensive use of virtual reality visualization.

Anti-infectious drug repurposing using an integrated chemical genomics and structural systems biology approach.

PubMed

Ng, Clara; Hauptman, Ruth; Zhang, Yinliang; Bourne, Philip E; Xie, Lei

2014-01-01

The emergence of multi-drug and extensive drug resistance of microbes to antibiotics poses a great threat to human health. Although drug repurposing is a promising solution for accelerating the drug development process, its application to anti-infectious drug discovery is limited by the scope of existing phenotype-, ligand-, or target-based methods. In this paper we introduce a new computational strategy to determine the genome-wide molecular targets of bioactive compounds in both human and bacterial genomes. Our method is based on the use of a novel algorithm, ligand Enrichment of Network Topological Similarity (ligENTS), to map the chemical universe to its global pharmacological space. ligENTS outperforms the state-of-the-art algorithms in identifying novel drug-target relationships. Furthermore, we integrate ligENTS with our structural systems biology platform to identify drug repurposing opportunities via target similarity profiling. Using this integrated strategy, we have identified novel P. falciparum targets of drug-like active compounds from the Malaria Box, and suggest that a number of approved drugs may be active against malaria. This study demonstrates the potential of an integrative chemical genomics and structural systems biology approach to drug repurposing.

DNA methylation at hepatitis B viral integrants is associated with methylation at flanking human genomic sequences

PubMed Central

Watanabe, Yoshiyuki; Yamamoto, Hiroyuki; Oikawa, Ritsuko; Toyota, Minoru; Yamamoto, Masakazu; Kokudo, Norihiro; Tanaka, Shinji; Arii, Shigeki; Yotsuyanagi, Hiroshi; Koike, Kazuhiko; Itoh, Fumio

2015-01-01

Integration of DNA viruses into the human genome plays an important role in various types of tumors, including hepatitis B virus (HBV)–related hepatocellular carcinoma. However, the molecular details and clinical impact of HBV integration on either human or HBV epigenomes are unknown. Here, we show that methylation of the integrated HBV DNA is related to the methylation status of the flanking human genome. We developed a next-generation sequencing-based method for structural methylation analysis of integrated viral genomes (denoted G-NaVI). This method is a novel approach that enables enrichment of viral fragments for sequencing using unique baits based on the sequence of the HBV genome. We detected integrated HBV sequences in the genome of the PLC/PRF/5 cell line and found variable levels of methylation within the integrated HBV genomes. Allele-specific methylation analysis revealed that the HBV genome often became significantly methylated when integrated into highly methylated host sites. After integration into unmethylated human genome regions such as promoters, however, the HBV DNA remains unmethylated and may eventually play an important role in tumorigenesis. The observed dynamic changes in DNA methylation of the host and viral genomes may functionally affect the biological behavior of HBV. These findings may impact public health given that millions of people worldwide are carriers of HBV. We also believe our assay will be a powerful tool to increase our understanding of the various types of DNA virus-associated tumorigenesis. PMID:25653310

Ecosystems and Human Health: Meeting Challenges through Integrated Research and Policy

EPA Science Inventory

Human activity is transforming the structure and function of Earth’s natural systems including its land cover, rivers, oceans, biogeochemical cycles, and climate system.  As this transformation accelerates, there is growing evidence that changes in the state of natural...

Microwave non-contact imaging of subcutaneous human body tissues

PubMed Central

Chernokalov, Alexander; Khripkov, Alexander; Cho, Jaegeol; Druchinin, Sergey

2015-01-01

A small-size microwave sensor is developed for non-contact imaging of a human body structure in 2D, enabling fitness and health monitoring using mobile devices. A method for human body tissue structure imaging is developed and experimentally validated. Subcutaneous fat tissue reconstruction depth of up to 70 mm and maximum fat thickness measurement error below 2 mm are demonstrated by measurements with a human body phantom and human subjects. Electrically small antennas are developed for integration of the microwave sensor into a mobile device. Usability of the developed microwave sensor for fitness applications, healthcare, and body weight management is demonstrated. PMID:26609415

DSSTox EPA Integrated Risk Information System Structure-Index Locator File: SDF File and Documentation

EPA Science Inventory

EPA's Integrated Risk Information System (IRIS) database was developed and is maintained by EPA's Office of Research and Developement, National Center for Environmental Assessment. IRIS is a database of human health effects that may result from exposure to various substances fou...

Establishment of the Northeast Coastal Watershed Geospatial Data Network (NECWGDN)

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

Hannigan, Robyn

The goals of NECWGDN were to establish integrated geospatial databases that interfaced with existing open-source (water.html) environmental data server technologies (e.g., HydroDesktop) and included ecological and human data to enable evaluation, prediction, and adaptation in coastal environments to climate- and human-induced threats to the coastal marine resources within the Gulf of Maine. We have completed the development and testing of a "test bed" architecture that is compatible with HydroDesktop and have identified key metadata structures that will enable seamless integration and delivery of environmental, ecological, and human data as well as models to predict threats to end-users. Uniquely this databasemore » integrates point as well as model data and so offers capacities to end-users that are unique among databases. Future efforts will focus on the development of integrated environmental-human dimension models that can serve, in near real time, visualizations of threats to coastal resources and habitats.« less

Micro-structural integrity of dental enamel subjected to two tooth whitening regimes.

PubMed

Tanaka, Reina; Shibata, Yo; Manabe, Atsufumi; Miyazaki, Takashi

2010-04-01

Colour modification of tooth enamel has proven successful, but it is unclear how various bleaching applications affect micro-structural integrity of the whitened enamel. To investigate the internal structural integrity of human intact tooth enamel with the application of two commonly used whitening regimes (in-office power bleaching with 35% hydrogen peroxide and home bleaching with 10% carbamide peroxide), evaluations were performed on teeth of identical colour classification. After the bleaching applications, the enamel mineral density was quantified and visualised with micro-computed tomography. The micro-structural differences between the whitened tooth enamel samples were distinctive, though the colour parameter changes within the samples were equivalent. Home bleaching achieved colour modification by demineralisation, whereas in-office bleaching depended on redistribution of the minerals after treatment and subsequent enhanced mineralisation.

Brain/MINDS: brain-mapping project in Japan

PubMed Central

Okano, Hideyuki; Miyawaki, Atsushi; Kasai, Kiyoto

2015-01-01

There is an emerging interest in brain-mapping projects in countries across the world, including the USA, Europe, Australia and China. In 2014, Japan started a brain-mapping project called Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS). Brain/MINDS aims to map the structure and function of neuronal circuits to ultimately understand the vast complexity of the human brain, and takes advantage of a unique non-human primate animal model, the common marmoset (Callithrix jacchus). In Brain/MINDS, the RIKEN Brain Science Institute acts as a central institute. The objectives of Brain/MINDS can be categorized into the following three major subject areas: (i) structure and functional mapping of a non-human primate brain (the marmoset brain); (ii) development of innovative neurotechnologies for brain mapping; and (iii) human brain mapping; and clinical research. Brain/MINDS researchers are highly motivated to identify the neuronal circuits responsible for the phenotype of neurological and psychiatric disorders, and to understand the development of these devastating disorders through the integration of these three subject areas. PMID:25823872

Monogamy, strongly bonded groups, and the evolution of human social structure.

PubMed

Chapais, Bernard

2013-01-01

Human social evolution has most often been treated in a piecemeal fashion, with studies focusing on the evolution of specific components of human society such as pair-bonding, cooperative hunting, male provisioning, grandmothering, cooperative breeding, food sharing, male competition, male violence, sexual coercion, territoriality, and between-group conflicts. Evolutionary models about any one of those components are usually concerned with two categories of questions, one relating to the origins of the component and the other to its impact on the evolution of human cognition and social life. Remarkably few studies have been concerned with the evolution of the entity that integrates all components, the human social system itself. That social system has as its core feature human social structure, which I define here as the common denominator of all human societies in terms of group composition, mating system, residence patterns, and kinship structures. The paucity of information on the evolution of human social structure poses substantial problems because that information is useful, if not essential, to assess both the origins and impact of any particular aspect of human society. Copyright © 2013 Wiley Periodicals, Inc.

Integration of faces and vocalizations in ventral prefrontal cortex: Implications for the evolution of audiovisual speech

PubMed Central

Romanski, Lizabeth M.

2012-01-01

The integration of facial gestures and vocal signals is an essential process in human communication and relies on an interconnected circuit of brain regions, including language regions in the inferior frontal gyrus (IFG). Studies have determined that ventral prefrontal cortical regions in macaques [e.g., the ventrolateral prefrontal cortex (VLPFC)] share similar cytoarchitectonic features as cortical areas in the human IFG, suggesting structural homology. Anterograde and retrograde tracing studies show that macaque VLPFC receives afferents from the superior and inferior temporal gyrus, which provide complex auditory and visual information, respectively. Moreover, physiological studies have shown that single neurons in VLPFC integrate species-specific face and vocal stimuli. Although bimodal responses may be found across a wide region of prefrontal cortex, vocalization responsive cells, which also respond to faces, are mainly found in anterior VLPFC. This suggests that VLPFC may be specialized to process and integrate social communication information, just as the IFG is specialized to process and integrate speech and gestures in the human brain. PMID:22723356

Retained structural integrity of collagen and elastin within cryopreserved human heart valve tissue as detected by two-photon laser scanning confocal microscopy.

PubMed

Gerson, Cindy J; Goldstein, Steven; Heacox, Albert E

2009-10-01

Cryopreservation is commonly used for the long-term storage of heart valve allografts. Despite the excellent hemodynamic performance and durability of cryopreserved allografts, reports have questioned whether cryopreservation affects the valvular structural proteins, collagen and elastin. This study uses two-photon laser scanning confocal microscopy (LSCM) to evaluate the effect of cryopreservation on collagen and elastin integrity within the leaflet and conduit of aortic and pulmonary human heart valves. To permit pairwise comparisons of fresh and cryopreserved tissue, test valves were bisected longitudinally with one segment imaged fresh and the other imaged after cryopreservation and brief storage in liquid nitrogen. Collagen was detected by second harmonic generation (SHG) stimulation and elastin by autofluorescence excitation. Qualitative analysis of all resultant images indicated the maintenance of collagen and elastin structure within leaflet and conduit post-cryopreservation. Analysis of the optimized percent laser transmission (OPLT) required for full dynamic range imaging of collagen and elastin showed that OPLT observations were highly variable among both fresh and cryopreserved samples. Changes in donor-specific average OPLT in response to cryopreservation exhibited no consistent directional trend. The donor-aggregated results predominantly showed no statistically significant change in collagen and elastin average OPLT due to cryopreservation. Since OPLT has an inverse relationship with structural signal intensity, these results indicate that there was largely no statistical difference in collagen and elastin signal strength between fresh and cryopreserved tissue. Overall, this study indicates that the conventional cryopreservation of human heart valve allografts does not detrimentally affect their collagen and elastin structural integrity.

The Human-Robot Interaction Operating System

NASA Technical Reports Server (NTRS)

Fong, Terrence; Kunz, Clayton; Hiatt, Laura M.; Bugajska, Magda

2006-01-01

In order for humans and robots to work effectively together, they need to be able to converse about abilities, goals and achievements. Thus, we are developing an interaction infrastructure called the "Human-Robot Interaction Operating System" (HRI/OS). The HRI/OS provides a structured software framework for building human-robot teams, supports a variety of user interfaces, enables humans and robots to engage in task-oriented dialogue, and facilitates integration of robots through an extensible API.

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…

Rendezvous Integration Complexities of NASA Human Flight Vehicles

NASA Technical Reports Server (NTRS)

Brazzel, Jack P.; Goodman, John L.

2009-01-01

Propellant-optimal trajectories, relative sensors and navigation, and docking/capture mechanisms are rendezvous disciplines that receive much attention in the technical literature. However, other areas must be considered. These include absolute navigation, maneuver targeting, attitude control, power generation, software development and verification, redundancy management, thermal control, avionics integration, robotics, communications, lighting, human factors, crew timeline, procedure development, orbital debris risk mitigation, structures, plume impingement, logistics, and in some cases extravehicular activity. While current and future spaceflight programs will introduce new technologies and operations concepts, the complexity of integrating multiple systems on multiple spacecraft will remain. The systems integration task may become more difficult as increasingly complex software is used to meet current and future automation, autonomy, and robotic operation requirements.

HHV-6A/B Integration and the Pathogenesis Associated with the Reactivation of Chromosomally Integrated HHV-6A/B.

PubMed

Collin, Vanessa; Flamand, Louis

2017-06-26

Unlike other human herpesviruses, human herpesvirus 6A and 6B (HHV-6A/B) infection can lead to integration of the viral genome in human chromosomes. When integration occurs in germinal cells, the integrated HHV-6A/B genome can be transmitted to 50% of descendants. Such individuals, carrying one copy of the HHV-6A/B genome in every cell, are referred to as having inherited chromosomally-integrated HHV-6A/B (iciHHV-6) and represent approximately 1% of the world's population. Interestingly, HHV-6A/B integrate their genomes in a specific region of the chromosomes known as telomeres. Telomeres are located at chromosomes' ends and play essential roles in chromosomal stability and the long-term proliferative potential of cells. Considering that the integrated HHV-6A/B genome is mostly intact without any gross rearrangements or deletions, integration is likely used for viral maintenance into host cells. Knowing the roles played by telomeres in cellular homeostasis, viral integration in such structure is not likely to be without consequences. At present, the mechanisms and factors involved in HHV-6A/B integration remain poorly defined. In this review, we detail the potential biological and medical impacts of HHV-6A/B integration as well as the possible chromosomal integration and viral excision processes.

Multi-scale integration and predictability in resting state brain activity

PubMed Central

Kolchinsky, Artemy; van den Heuvel, Martijn P.; Griffa, Alessandra; Hagmann, Patric; Rocha, Luis M.; Sporns, Olaf; Goñi, Joaquín

2014-01-01

The human brain displays heterogeneous organization in both structure and function. Here we develop a method to characterize brain regions and networks in terms of information-theoretic measures. We look at how these measures scale when larger spatial regions as well as larger connectome sub-networks are considered. This framework is applied to human brain fMRI recordings of resting-state activity and DSI-inferred structural connectivity. We find that strong functional coupling across large spatial distances distinguishes functional hubs from unimodal low-level areas, and that this long-range functional coupling correlates with structural long-range efficiency on the connectome. We also find a set of connectome regions that are both internally integrated and coupled to the rest of the brain, and which resemble previously reported resting-state networks. Finally, we argue that information-theoretic measures are useful for characterizing the functional organization of the brain at multiple scales. PMID:25104933

Temporal Structure and Complexity Affect Audio-Visual Correspondence Detection

PubMed Central

Denison, Rachel N.; Driver, Jon; Ruff, Christian C.

2013-01-01

Synchrony between events in different senses has long been considered the critical temporal cue for multisensory integration. Here, using rapid streams of auditory and visual events, we demonstrate how humans can use temporal structure (rather than mere temporal coincidence) to detect multisensory relatedness. We find psychophysically that participants can detect matching auditory and visual streams via shared temporal structure for crossmodal lags of up to 200 ms. Performance on this task reproduced features of past findings based on explicit timing judgments but did not show any special advantage for perfectly synchronous streams. Importantly, the complexity of temporal patterns influences sensitivity to correspondence. Stochastic, irregular streams – with richer temporal pattern information – led to higher audio-visual matching sensitivity than predictable, rhythmic streams. Our results reveal that temporal structure and its complexity are key determinants for human detection of audio-visual correspondence. The distinctive emphasis of our new paradigms on temporal patterning could be useful for studying special populations with suspected abnormalities in audio-visual temporal perception and multisensory integration. PMID:23346067

Organizing human functioning and rehabilitation research into distinct scientific fields. Part I: Developing a comprehensive structure from the cell to society.

PubMed

Stucki, Gerold; Grimby, Gunnar

2007-05-01

There is a need to organize rehabilitation and related research into distinct scientific fields in order to overcome the current limitations of rehabilitation research. Based on the general distinction in basic, applied and professional sciences applicable to research in general, and the rehabilitation relevant distinction between the comprehensive perspective based on WHO's integrative model of human functioning (ICF) and the partial perspective focusing on the biomedical aspects of functioning, it is possible to identify 5 distinct scientific fields of human functioning and rehabilitation research. These are the emerging human functioning sciences and integrative rehabilitation sciences from the comprehensive perspective, the established biosciences and biomedical rehabilitation sciences and engineering from the partial perspective, and the professional rehabilitation sciences at the cutting edge of research and practice. The human functioning sciences aim to understand human functioning and to identify targets for comprehensive interventions, with the goal of contributing to the minimization of the experience of disability in the population. The biosciences in rehabilitation aim to explain body injury and repair and to identify targets for biomedical interventions. The integrative rehabilitation sciences design and study comprehensive assessments and interventions that integrate biomedical, personal factor and environmental approaches suited to optimize people's performance. The biomedical rehabilitation sciences and engineering study diagnostic measures and interventions suitable to minimize impairment, including symptom control, and to optimize people's capacity. The professional rehabilitation sciences study how to provide best care with the goal of enabling people with health conditions experiencing or likely to experience disability to achieve and maintain optimal functioning in interaction with the environment. The organization of human functioning and rehabilitation research into the 5 distinct scientific fields facilitates the development of academic training programs and career building as well as the development of research structures dedicated to human functioning and rehabilitation research.

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

PubMed

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

2012-10-01

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

The structure of distractor-response bindings: Conditions for configural and elemental integration.

PubMed

Moeller, Birte; Frings, Christian; Pfister, Roland

2016-04-01

Human action control is influenced by bindings between perceived stimuli and responses carried out in their presence. Notably, responses given to a target stimulus can also be integrated with additional response-irrelevant distractor stimuli that accompany the target (distractor-response binding). Subsequently reencountering such a distractor then retrieves the associated response. Although a large body of evidence supports the existence of this effect, the specific structure of distractor-response bindings is still unclear. Here, we test the predictions derived from 2 possible assumptions about the structure of bindings between distractors and responses. According to a configural approach, the entire distractor object is integrated with a response, and only upon repetition of the entire distractor object the associated response would be retrieved. According to an elemental approach, one would predict integration of individual distractor features with the response and retrieval due to the repetition of an individual distractor feature. Four experiments indicate that both, configural and elemental bindings exist and specify boundary conditions for each type of binding. These findings provide detailed insights into the architecture of bindings between response-irrelevant stimuli and actions and thus allow for specifying how distractor stimuli influence human behavior. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Integration of Histology Lectures and Practical Teaching in China

ERIC Educational Resources Information Center

Lu, Xiaoye; Cheng, Xin; Li, Ke; Lee, Kenneth Ka Ho; Yang, Xuesong

2016-01-01

Objectives: Human histology is a discipline concerning the study of microscopic structures of human tissues and organs--with the aid of light or electron microscopes. Traditional teaching of histology is composed of two separated components, theory and practice. The main disadvantage with traditional histology teaching is the detachment of theory…

Ecosystem Services Connect Environmental Change to Human Health Outcomes

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

Bayles, Brett R.; Brauman, Kate A.; Adkins, Joshua N.

Global environmental change, driven in large part by human activities, profoundly impacts the structure and functioning of Earth’s ecosystems (Millennium Ecosystem Assessment 2005). We are beginning to push beyond planetary boundaries (Steffan et al. 2015), and the consequences for human health remain largely unknown (Myers et al. 2013). Growing evidence suggests that ecological transformations can dramatically affect human health in ways that are both obvious and obscure (Myers and Patz 2009; Myers et al. 2013). The framework of ecosystem services, designed to evaluate the benefits that people derive from ecosystem products and processes, provides a compelling framework for integrating themore » many factors that influence the human health response to global change, as well as for integrating health impacts into broader analyses of the impacts of this change« less

A Neural Network Model of the Structure and Dynamics of Human Personality

ERIC Educational Resources Information Center

Read, Stephen J.; Monroe, Brian M.; Brownstein, Aaron L.; Yang, Yu; Chopra, Gurveen; Miller, Lynn C.

2010-01-01

We present a neural network model that aims to bridge the historical gap between dynamic and structural approaches to personality. The model integrates work on the structure of the trait lexicon, the neurobiology of personality, temperament, goal-based models of personality, and an evolutionary analysis of motives. It is organized in terms of two…

Human Chromosome 7: DNA Sequence and Biology

PubMed Central

Scherer, Stephen W.; Cheung, Joseph; MacDonald, Jeffrey R.; Osborne, Lucy R.; Nakabayashi, Kazuhiko; Herbrick, Jo-Anne; Carson, Andrew R.; Parker-Katiraee, Layla; Skaug, Jennifer; Khaja, Razi; Zhang, Junjun; Hudek, Alexander K.; Li, Martin; Haddad, May; Duggan, Gavin E.; Fernandez, Bridget A.; Kanematsu, Emiko; Gentles, Simone; Christopoulos, Constantine C.; Choufani, Sanaa; Kwasnicka, Dorota; Zheng, Xiangqun H.; Lai, Zhongwu; Nusskern, Deborah; Zhang, Qing; Gu, Zhiping; Lu, Fu; Zeesman, Susan; Nowaczyk, Malgorzata J.; Teshima, Ikuko; Chitayat, David; Shuman, Cheryl; Weksberg, Rosanna; Zackai, Elaine H.; Grebe, Theresa A.; Cox, Sarah R.; Kirkpatrick, Susan J.; Rahman, Nazneen; Friedman, Jan M.; Heng, Henry H. Q.; Pelicci, Pier Giuseppe; Lo-Coco, Francesco; Belloni, Elena; Shaffer, Lisa G.; Pober, Barbara; Morton, Cynthia C.; Gusella, James F.; Bruns, Gail A. P.; Korf, Bruce R.; Quade, Bradley J.; Ligon, Azra H.; Ferguson, Heather; Higgins, Anne W.; Leach, Natalia T.; Herrick, Steven R.; Lemyre, Emmanuelle; Farra, Chantal G.; Kim, Hyung-Goo; Summers, Anne M.; Gripp, Karen W.; Roberts, Wendy; Szatmari, Peter; Winsor, Elizabeth J. T.; Grzeschik, Karl-Heinz; Teebi, Ahmed; Minassian, Berge A.; Kere, Juha; Armengol, Lluis; Pujana, Miguel Angel; Estivill, Xavier; Wilson, Michael D.; Koop, Ben F.; Tosi, Sabrina; Moore, Gudrun E.; Boright, Andrew P.; Zlotorynski, Eitan; Kerem, Batsheva; Kroisel, Peter M.; Petek, Erwin; Oscier, David G.; Mould, Sarah J.; Döhner, Hartmut; Döhner, Konstanze; Rommens, Johanna M.; Vincent, John B.; Venter, J. Craig; Li, Peter W.; Mural, Richard J.; Adams, Mark D.; Tsui, Lap-Chee

2010-01-01

DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism. PMID:12690205

Bridging the Gap between Human Judgment and Automated Reasoning in Predictive Analytics

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

Sanfilippo, Antonio P.; Riensche, Roderick M.; Unwin, Stephen D.

2010-06-07

Events occur daily that impact the health, security and sustainable growth of our society. If we are to address the challenges that emerge from these events, anticipatory reasoning has to become an everyday activity. Strong advances have been made in using integrated modeling for analysis and decision making. However, a wider impact of predictive analytics is currently hindered by the lack of systematic methods for integrating predictive inferences from computer models with human judgment. In this paper, we present a predictive analytics approach that supports anticipatory analysis and decision-making through a concerted reasoning effort that interleaves human judgment and automatedmore » inferences. We describe a systematic methodology for integrating modeling algorithms within a serious gaming environment in which role-playing by human agents provides updates to model nodes and the ensuing model outcomes in turn influence the behavior of the human players. The approach ensures a strong functional partnership between human players and computer models while maintaining a high degree of independence and greatly facilitating the connection between model and game structures.« less

Stabilization of Telomere G-Quadruplexes Interferes with Human Herpesvirus 6A Chromosomal Integration.

PubMed

Gilbert-Girard, Shella; Gravel, Annie; Artusi, Sara; Richter, Sara N; Wallaschek, Nina; Kaufer, Benedikt B; Flamand, Louis

2017-07-15

Human herpesviruses 6A and 6B (HHV-6A/B) can integrate their genomes into the telomeres of human chromosomes using a mechanism that remains poorly understood. To achieve a better understanding of the HHV-6A/B integration mechanism, we made use of BRACO-19, a compound that stabilizes G-quadruplex secondary structures and prevents telomere elongation by the telomerase complex. First, we analyzed the folding of telomeric sequences into G-quadruplex structures and their binding to BRACO-19 using G-quadruplex-specific antibodies and surface plasmon resonance. Circular dichroism studies indicate that BRACO-19 modifies the conformation and greatly stabilizes the G-quadruplexes formed in G-rich telomeric DNA. Subsequently we assessed the effects of BRACO-19 on the HHV-6A initial phase of infection. Our results indicate that BRACO-19 does not affect entry of HHV-6A DNA into cells. We next investigated if stabilization of G-quadruplexes by BRACO-19 affected HHV-6A's ability to integrate its genome into host chromosomes. Incubation of telomerase-expressing cells with BRACO-19, such as HeLa and MCF-7, caused a significant reduction in the HHV-6A integration frequency ( P < 0.002); in contrast, BRACO-19 had no effect on HHV-6 integration frequency in U2OS cells that lack telomerase activity and elongate their telomeres through alternative lengthening mechanisms. Our data suggest that the fluidity of telomeres is important for efficient chromosomal integration of HHV-6A and that interference with telomerase activity negatively affects the generation of cellular clones containing integrated HHV-6A. IMPORTANCE HHV-6A/B can integrate their genomes into the telomeres of infected cells. Telomeres consist of repeated hexanucleotides (TTAGGG) of various lengths (up to several kilobases) and end with a single-stranded 3' extension. To avoid recognition and induce a DNA damage response, the single-stranded overhang folds back on itself and forms a telomeric loop (T-loop) or adopts a tertiary structure, referred to as a G-quadruplex. In the current study, we have examined the effects of a G-quadruplex binding and stabilizing agent, BRACO-19, on HHV-6A chromosomal integration. By stabilizing G-quadruplex structures, BRACO-19 affects the ability of the telomerase complex to elongate telomeres. Our results indicate that BRACO-19 reduces the number of clones harboring integrated HHV-6A. This study is the first of its kind and suggests that telomerase activity is essential to restore a functional telomere of adequate length following HHV-6A integration. Copyright © 2017 American Society for Microbiology.

Structural integrity of engineering composite materials: a cracking good yarn.

PubMed

Beaumont, Peter W R; Soutis, Costas

2016-07-13

Predicting precisely where a crack will develop in a material under stress and exactly when in time catastrophic fracture of the component will occur is one the oldest unsolved mysteries in the design and building of large-scale engineering structures. Where human life depends upon engineering ingenuity, the burden of testing to prove a 'fracture safe design' is immense. Fitness considerations for long-life implementation of large composite structures include understanding phenomena such as impact, fatigue, creep and stress corrosion cracking that affect reliability, life expectancy and durability of structure. Structural integrity analysis treats the design, the materials used, and figures out how best components and parts can be joined, and takes service duty into account. However, there are conflicting aims in the complete design process of designing simultaneously for high efficiency and safety assurance throughout an economically viable lifetime with an acceptable level of risk. This article is part of the themed issue 'Multiscale modelling of the structural integrity of composite materials'. © 2016 The Author(s).

Functional connectivity-based parcellation and connectome of cortical midline structures in the mouse: a perfusion autoradiography study

PubMed Central

Holschneider, Daniel P.; Wang, Zhuo; Pang, Raina D.

2014-01-01

Rodent cortical midline structures (CMS) are involved in emotional, cognitive and attentional processes. Tract tracing has revealed complex patterns of structural connectivity demonstrating connectivity-based integration and segregation for the prelimbic, cingulate area 1, retrosplenial dysgranular cortices dorsally, and infralimbic, cingulate area 2, and retrosplenial granular cortices ventrally. Understanding of CMS functional connectivity (FC) remains more limited. Here we present the first subregion-level FC analysis of the mouse CMS, and assess whether fear results in state-dependent FC changes analogous to what has been reported in humans. Brain mapping using [14C]-iodoantipyrine was performed in mice during auditory-cued fear conditioned recall and in controls. Regional cerebral blood flow (CBF) was analyzed in 3-D images reconstructed from brain autoradiographs. Regions-of-interest were selected along the CMS anterior-posterior and dorsal-ventral axes. In controls, pairwise correlation and graph theoretical analyses showed strong FC within each CMS structure, strong FC along the dorsal-ventral axis, with segregation of anterior from posterior structures. Seed correlation showed FC of anterior regions to limbic/paralimbic areas, and FC of posterior regions to sensory areas–findings consistent with functional segregation noted in humans. Fear recall increased FC between the cingulate and retrosplenial cortices, but decreased FC between dorsal and ventral structures. In agreement with reports in humans, fear recall broadened FC of anterior structures to the amygdala and to somatosensory areas, suggesting integration and processing of both limbic and sensory information. Organizational principles learned from animal models at the mesoscopic level (brain regions and pathways) will not only critically inform future work at the microscopic (single neurons and synapses) level, but also have translational value to advance our understanding of human brain architecture. PMID:24966831

Functional connectivity-based parcellation and connectome of cortical midline structures in the mouse: a perfusion autoradiography study.

PubMed

Holschneider, Daniel P; Wang, Zhuo; Pang, Raina D

2014-01-01

Rodent cortical midline structures (CMS) are involved in emotional, cognitive and attentional processes. Tract tracing has revealed complex patterns of structural connectivity demonstrating connectivity-based integration and segregation for the prelimbic, cingulate area 1, retrosplenial dysgranular cortices dorsally, and infralimbic, cingulate area 2, and retrosplenial granular cortices ventrally. Understanding of CMS functional connectivity (FC) remains more limited. Here we present the first subregion-level FC analysis of the mouse CMS, and assess whether fear results in state-dependent FC changes analogous to what has been reported in humans. Brain mapping using [(14)C]-iodoantipyrine was performed in mice during auditory-cued fear conditioned recall and in controls. Regional cerebral blood flow (CBF) was analyzed in 3-D images reconstructed from brain autoradiographs. Regions-of-interest were selected along the CMS anterior-posterior and dorsal-ventral axes. In controls, pairwise correlation and graph theoretical analyses showed strong FC within each CMS structure, strong FC along the dorsal-ventral axis, with segregation of anterior from posterior structures. Seed correlation showed FC of anterior regions to limbic/paralimbic areas, and FC of posterior regions to sensory areas-findings consistent with functional segregation noted in humans. Fear recall increased FC between the cingulate and retrosplenial cortices, but decreased FC between dorsal and ventral structures. In agreement with reports in humans, fear recall broadened FC of anterior structures to the amygdala and to somatosensory areas, suggesting integration and processing of both limbic and sensory information. Organizational principles learned from animal models at the mesoscopic level (brain regions and pathways) will not only critically inform future work at the microscopic (single neurons and synapses) level, but also have translational value to advance our understanding of human brain architecture.

Reconstruction of the experimentally supported human protein interactome: what can we learn?

PubMed

Klapa, Maria I; Tsafou, Kalliopi; Theodoridis, Evangelos; Tsakalidis, Athanasios; Moschonas, Nicholas K

2013-10-02

Understanding the topology and dynamics of the human protein-protein interaction (PPI) network will significantly contribute to biomedical research, therefore its systematic reconstruction is required. Several meta-databases integrate source PPI datasets, but the protein node sets of their networks vary depending on the PPI data combined. Due to this inherent heterogeneity, the way in which the human PPI network expands via multiple dataset integration has not been comprehensively analyzed. We aim at assembling the human interactome in a global structured way and exploring it to gain insights of biological relevance. First, we defined the UniProtKB manually reviewed human "complete" proteome as the reference protein-node set and then we mined five major source PPI datasets for direct PPIs exclusively between the reference proteins. We updated the protein and publication identifiers and normalized all PPIs to the UniProt identifier level. The reconstructed interactome covers approximately 60% of the human proteome and has a scale-free structure. No apparent differentiating gene functional classification characteristics were identified for the unrepresented proteins. The source dataset integration augments the network mainly in PPIs. Polyubiquitin emerged as the highest-degree node, but the inclusion of most of its identified PPIs may be reconsidered. The high number (>300) of connections of the subsequent fifteen proteins correlates well with their essential biological role. According to the power-law network structure, the unrepresented proteins should mainly have up to four connections with equally poorly-connected interactors. Reconstructing the human interactome based on the a priori definition of the protein nodes enabled us to identify the currently included part of the human "complete" proteome, and discuss the role of the proteins within the network topology with respect to their function. As the network expansion has to comply with the scale-free theory, we suggest that the core of the human interactome has essentially emerged. Thus, it could be employed in systems biology and biomedical research, despite the considerable number of currently unrepresented proteins. The latter are probably involved in specialized physiological conditions, justifying the scarcity of related PPI information, and their identification can assist in designing relevant functional experiments and targeted text mining algorithms.

Visual Narrative Structure

ERIC Educational Resources Information Center

Cohn, Neil

2013-01-01

Narratives are an integral part of human expression. In the graphic form, they range from cave paintings to Egyptian hieroglyphics, from the Bayeux Tapestry to modern day comic books (Kunzle, 1973; McCloud, 1993). Yet not much research has addressed the structure and comprehension of narrative images, for example, how do people create meaning out…

Hirarchical emotion calculation model for virtual human modellin - biomed 2010.

PubMed

Zhao, Yue; Wright, David

2010-01-01

This paper introduces a new emotion generation method for virtual human modelling. The method includes a novel hierarchical emotion structure, a group of emotion calculation equations and a simple heuristics decision making mechanism, which enables virtual humans to perform emotionally in real-time according to their internal and external factors. Emotion calculation equations used in this research were derived from psychologic emotion measurements. Virtual humans can utilise the information in virtual memory and emotion calculation equations to generate their own numerical emotion states within the hierarchical emotion structure. Those emotion states are important internal references for virtual humans to adopt appropriate behaviours and also key cues for their decision making. A simple heuristics theory is introduced and integrated into decision making process in order to make the virtual humans decision making more like a real human. A data interface which connects the emotion calculation and the decision making structure together has also been designed and simulated to test the method in Virtools environment.

Human Factors Interface with Systems Engineering for NASA Human Spaceflights

NASA Technical Reports Server (NTRS)

Wong, Douglas T.

2009-01-01

This paper summarizes the past and present successes of the Habitability and Human Factors Branch (HHFB) at NASA Johnson Space Center s Space Life Sciences Directorate (SLSD) in including the Human-As-A-System (HAAS) model in many NASA programs and what steps to be taken to integrate the Human-Centered Design Philosophy (HCDP) into NASA s Systems Engineering (SE) process. The HAAS model stresses systems are ultimately designed for the humans; the humans should therefore be considered as a system within the systems. Therefore, the model places strong emphasis on human factors engineering. Since 1987, the HHFB has been engaging with many major NASA programs with much success. The HHFB helped create the NASA Standard 3000 (a human factors engineering practice guide) and the Human Systems Integration Requirements document. These efforts resulted in the HAAS model being included in many NASA programs. As an example, the HAAS model has been successfully introduced into the programmatic and systems engineering structures of the International Space Station Program (ISSP). Success in the ISSP caused other NASA programs to recognize the importance of the HAAS concept. Also due to this success, the HHFB helped update NASA s Systems Engineering Handbook in December 2007 to include HAAS as a recommended practice. Nonetheless, the HAAS model has yet to become an integral part of the NASA SE process. Besides continuing in integrating HAAS into current and future NASA programs, the HHFB will investigate incorporating the Human-Centered Design Philosophy (HCDP) into the NASA SE Handbook. The HCDP goes further than the HAAS model by emphasizing a holistic and iterative human-centered systems design concept.

Autonomous Assembly of Modular Structures in Space and on Extraterrestrial Locations

NASA Technical Reports Server (NTRS)

Alhorn, Dean C.

2005-01-01

The fulfillment of the new US. National Vision for Space Exploration requires many new enabling technologies to accomplish the goal of utilizing space for commercial activities and for returning humans to the moon and extraterrestrial environments. Traditionally, flight structures are manufactured as complete systems and require humans to complete the integration and assembly in orbit. These structures are bulky and require the use of heavy launch vehicles to send the units to the desired location, e.g. International Space Station (ISS). This method requires a high degree of safety, numerous space walks and significant cost for the humans to perform the assembly in orbit. For example, for assembly and maintenance of the ISS, 52 Extravehicular Activities (EVA's) have been performed so far with a total EVA time of approximately 322 hours. Sixteen (16) shuttle flights haw been to the ISS to perform these activities with an approximate cost of $450M per mission. For future space missions, costs have to be reduced to reasonably achieve the exploration goals. One concept that has been proposed is the autonomous assembly of space structures. This concept is an affordable, reliable solution to in-space and extraterrestrial assembly operations. Assembly is autonomously performed when two components containing onboard electronics join after recognizing that the joint is appropriate and in the precise position and orientation required for assembly. The mechanism only activates when the specifications are correct and m a nominal range. After assembly, local sensors and electronics monitor the integrity of the joint for feedback to a master controller. To achieve this concept will require a shift in the methods for designing space structures. In addition, innovative techniques will be required to perform the assembly autonomously. Monitoring of the assembled joint will be necessary for safety and structural integrity. If a very large structure is to be assembled in orbit, then the number of integrity sensors will be significant. Thus simple, low cost sensors are integral to the success of this concept. This paper will address these issues and will propose a novel concept for assembling space structures autonomously. The paper will present Several autonomous assembly methods. Core technologies required to achieve in space assembly will be discussed and novel techniques for communicating, sensing, docking and assembly will be detailed. These core technologies are critical to the goal of utilizing space in a cost efficient and safe manner. Finally, these technologies can also be applied to other systems both on earth and extraterrestrial environments.

Role of innovative institutional structures in integrated governance. A case study of integrating health and nutrition programs in Chhattisgarh, India.

PubMed

Kalita, Anuska; Mondal, Shinjini

2012-01-01

The aim of this paper is to highlight the significance of integrated governance in bringing about community participation, improved service delivery, accountability of public systems and human resource rationalisation. It discusses the strategies of innovative institutional structures in translating such integration in the areas of public health and nutrition for poor communities. The paper draws on experience of initiating integrated governance through innovations in health and nutrition programming in the resource-poor state of Chhattisgarh, India, at different levels of governance structures--hamlets, villages, clusters, blocks, districts and at the state. The study uses mixed methods--i.e. document analysis, interviews, discussions and quantitative data from facilities surveys--to present a case study analyzing the process and outcome of integration. The data indicate that integrated governance initiatives improved convergence between health and nutrition departments of the state at all levels. Also, innovative structures are important to implement the idea of integration, especially in contexts that do not have historical experience of such partnerships. Integration also contributed towards improved participation of communities in self-governance, community monitoring of government programs, and therefore, better services. As governments across the world, especially in developing countries, struggle towards achieving better governance, integration can serve as a desirable process to address this. Integration can affect the decentralisation of power, inclusion, efficiency, accountability and improved service quality in government programs. The institutional structures detailed in this paper can provide models for replication in other similar contexts for translating and sustaining the idea of integrated governance. This paper is one of the few to investigate innovative public institutions of a and community mobilisation to explore this important, and under-researched, topic.

Natural Biology vs. Cultural Structures: Art and Child Development in Education

ERIC Educational Resources Information Center

Burrill, Rebecca R.

2005-01-01

Art in Education is generally considered a sideline, a secondary specialty, or something to be integrated into the primary curriculum, i.e. literacy and arts integration. But art is not secondary; it is primary in learning and in human development. Art is, in fact, necessary and optimal for learning to write, read, and perform arithmetic. This…

Midsagittal brain variation and MRI shape analysis of the precuneus in adult individuals.

PubMed

Bruner, Emiliano; Rangel de Lázaro, Gizéh; de la Cuétara, José Manuel; Martín-Loeches, Manuel; Colom, Roberto; Jacobs, Heidi I L

2014-04-01

Recent analyses indicate that the precuneus is one of the main centres of integration in terms of functional and structural processes within the human brain. This neuroanatomical element is formed by different subregions, involved in visuo-spatial integration, memory and self-awareness. We analysed the midsagittal brain shape in a sample of adult humans (n = 90) to evidence the patterns of variability and geometrical organization of this area. Interestingly, the major brain covariance pattern within adult humans is strictly associated with the relative proportions of the precuneus. Its morphology displays a marked individual variation, both in terms of geometry (mostly in its longitudinal dimensions) and anatomy (patterns of convolution). No patent differences are evident between males and females, and the allometric effect of size is minimal. However, in terms of morphology, the precuneus does not represent an individual module, being influenced by different neighbouring structures. Taking into consideration the apparent involvement of the precuneus in higher-order human brain functions and evolution, its wide variation further stresses the important role of these deep parietal areas in modern neuroanatomical organization. © 2014 Anatomical Society.

Using structural equation modeling to link human activities to wetland ecological integrity

USGS Publications Warehouse

Schweiger, E. William; Grace, James B.; Cooper, David; Bobowski, Ben; Britten, Mike

2016-01-01

The integrity of wetlands is of global concern. A common approach to evaluating ecological integrity involves bioassessment procedures that quantify the degree to which communities deviate from historical norms. While helpful, bioassessment provides little information about how altered conditions connect to community response. More detailed information is needed for conservation and restoration. We have illustrated an approach to addressing this challenge using structural equation modeling (SEM) and long-term monitoring data from Rocky Mountain National Park (RMNP). Wetlands in RMNP are threatened by a complex history of anthropogenic disturbance including direct alteration of hydrologic regimes; elimination of elk, wolves, and grizzly bears; reintroduction of elk (absent their primary predators); and the extirpation of beaver. More recently, nonnative moose were introduced to the region and have expanded into the park. Bioassessment suggests that up to half of the park's wetlands are not in reference condition. We developed and evaluated a general hypothesis about how human alterations influence wetland integrity and then develop a specific model using RMNP wetlands. Bioassessment revealed three bioindicators that appear to be highly sensitive to human disturbance (HD): (1) conservatism, (2) degree of invasion, and (3) cover of native forbs. SEM analyses suggest several ways human activities have impacted wetland integrity and the landscape of RMNP. First, degradation is highest where the combined effects of all types of direct HD have been the greatest (i.e., there is a general, overall effect). Second, specific HDs appear to create a “mixed-bag” of complex indirect effects, including reduced invasion and increased conservatism, but also reduced native forb cover. Some of these effects are associated with alterations to hydrologic regimes, while others are associated with altered shrub production. Third, landscape features created by historical beaver activity continue to influence wetland integrity years after beavers have abandoned sites via persistent landforms and reduced biomass of tall shrubs. Our model provides a system-level perspective on wetland integrity and provides a context for future evaluations and investigations. It also suggests scientifically supported natural resource management strategies that can assist in the National Park Service mission of maintaining or, when indicated, restoring ecological integrity “unimpaired for future generations.”

Human health benefits and burdens of a pharmaceutical treatment: Discussion of a conceptual integrated approach.

PubMed

Debaveye, Sam; De Soete, Wouter; De Meester, Steven; Vandijck, Dominique; Heirman, Bert; Kavanagh, Shane; Dewulf, Jo

2016-01-01

The effects of a pharmaceutical treatment have until now been evaluated by the field of Health Economics on the patient health benefits, expressed in Quality-Adjusted Life Years (QALYs) versus the monetary costs. However, there is also a Human Health burden associated with this process, resulting from emissions that originate from the pharmaceutical production processes, Use Phase and End of Life (EoL) disposal of the medicine. This Human Health burden is evaluated by the research field of Life Cycle Assessment (LCA) and expressed in Disability-Adjusted Life Years (DALYs), a metric similar to the QALY. The need for a new framework presents itself in which both the positive and negative health effects of a pharmaceutical treatment are integrated into a net Human Health effect. To do so, this article reviews the methodologies of both Health Economics and the area of protection Human Health of the LCA methodology and proposes a conceptual framework on which to base an integration of both health effects. Methodological issues such as the inclusion of future costs and benefits, discounting and age weighting are discussed. It is suggested to use the structure of an LCA as a backbone to cover all methodological challenges involved in the integration. The possibility of monetizing both Human Health benefits and burdens is explored. The suggested approach covers the main methodological aspects that should be considered in an integrated assessment of the health effects of a pharmaceutical treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

Atomic scale chemical tomography of human bone

NASA Astrophysics Data System (ADS)

Langelier, Brian; Wang, Xiaoyue; Grandfield, Kathryn

2017-01-01

Human bone is a complex hierarchical material. Understanding bone structure and its corresponding composition at the nanometer scale is critical for elucidating mechanisms of biomineralization under healthy and pathological states. However, the three-dimensional structure and chemical nature of bone remains largely unexplored at the nanometer scale due to the challenges associated with characterizing both the structural and chemical integrity of bone simultaneously. Here, we use correlative transmission electron microscopy and atom probe tomography for the first time, to our knowledge, to reveal structures in human bone at the atomic level. This approach provides an overlaying chemical map of the organic and inorganic constituents of bone on its structure. This first use of atom probe tomography on human bone reveals local gradients, trace element detection of Mg, and the co-localization of Na with the inorganic-organic interface of bone mineral and collagen fibrils, suggesting the important role of Na-rich organics in the structural connection between mineral and collagen. Our findings provide the first insights into the hierarchical organization and chemical heterogeneity in human bone in three-dimensions at its smallest length scale - the atomic level. We demonstrate that atom probe tomography shows potential for new insights in biomineralization research on bone.

Human factors in operations design

NASA Technical Reports Server (NTRS)

Chafin, R. L.

1982-01-01

The manner in which organizations develop their organizational structure is considered, taking into account an example in which the environment changes for an older organization. In such cases, it would be preferable to have some theoretical foundation on which to base the restructuring of the organization to meet new environmental needs. A description is given of a theoretic foundation based on the principles of Differentiation/Integration and Procedural/Knowledge based operations. The organizational design principle of Differentiation and Integration has been presented by Lawrence and Lorsch (1969). The differentiation/integration processes are related to the organizational structures presented in studies concerning NASA Deep Space Network (DSN) operations. The principles presented provide valuable tools for analyzing operations organization.

Electromechanical integration of cardiomyocytes derived from human embryonic stem cells.

PubMed

Kehat, Izhak; Khimovich, Leonid; Caspi, Oren; Gepstein, Amira; Shofti, Rona; Arbel, Gil; Huber, Irit; Satin, Jonathan; Itskovitz-Eldor, Joseph; Gepstein, Lior

2004-10-01

Cell therapy is emerging as a promising strategy for myocardial repair. This approach is hampered, however, by the lack of sources for human cardiac tissue and by the absence of direct evidence for functional integration of donor cells into host tissues. Here we investigate whether cells derived from human embryonic stem (hES) cells can restore myocardial electromechanical properties. Cardiomyocyte cell grafts were generated from hES cells in vitro using the embryoid body differentiating system. This tissue formed structural and electromechanical connections with cultured rat cardiomyocytes. In vivo integration was shown in a large-animal model of slow heart rate. The transplanted hES cell-derived cardiomyocytes paced the hearts of swine with complete atrioventricular block, as assessed by detailed three-dimensional electrophysiological mapping and histopathological examination. These results demonstrate the potential of hES-cell cardiomyocytes to act as a rate-responsive biological pacemaker and for future myocardial regeneration strategies.

Common fragile sites (CFS) and extremely large CFS genes are targets for human papillomavirus integrations and chromosome rearrangements in oropharyngeal squamous cell carcinoma.

PubMed

Gao, Ge; Johnson, Sarah H; Vasmatzis, George; Pauley, Christina E; Tombers, Nicole M; Kasperbauer, Jan L; Smith, David I

2017-01-01

Common fragile sites (CFS) are chromosome regions that are prone to form gaps or breaks in response to DNA replication stress. They are often found as hotspots for sister chromatid exchanges, deletions, and amplifications in different cancers. Many of the CFS regions are found to span genes whose genomic sequence is greater than 1 Mb, some of which have been demonstrated to function as important tumor suppressors. CFS regions are also hotspots for human papillomavirus (HPV) integrations in cervical cancer. We used mate-pair sequencing to examine HPV integration events and chromosomal structural variations in 34 oropharyngeal squamous cell carcinoma (OPSCC). We used endpoint PCR and Sanger sequencing to validate each HPV integration event and found HPV integrations preferentially occurred within CFS regions similar to what is observed in cervical cancer. We also found that many of the chromosomal alterations detected also occurred at or near the cytogenetic location of CFSs. Several large genes were also found to be recurrent targets of rearrangements, independent of HPV integrations, including CSMD1 (2.1Mb), LRP1B (1.9Mb), and LARGE1 (0.7Mb). Sanger sequencing revealed that the nucleotide sequences near to identified junction sites contained repetitive and AT-rich sequences that were shown to have the potential to form stem-loop DNA secondary structures that might stall DNA replication fork progression during replication stress. This could then cause increased instability in these regions which could lead to cancer development in human cells. Our findings suggest that CFSs and some specific large genes appear to play important roles in OPSCC. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Scavenging energy from human motion with tubular dielectric polymer

NASA Astrophysics Data System (ADS)

Jean-Mistral, Claire; Basrour, Skandar

2010-04-01

Scavenging energy from human motion is a challenge to supply low consumption systems for sport or medical applications. A promising solution is to use electroactive polymers and especially dielectric polymers to scavenge mechanical energy during walk. In this paper, we present a tubular dielectric generator which is the first step toward an integration of these structures into textiles. For a 10cm length and under a strain of 100%, the structure is able to scavenge 1.5μJ for a poling voltage of 200V and up to 40μJ for a poling voltage of 1000V. A 30cm length structure is finally compared to our previous planar structure, and the power management module for those structures is discussed.

Expression of recombinant glycoproteins in mammalian cells: towards an integrative approach to structural biology.

PubMed

Aricescu, A Radu; Owens, Raymond J

2013-06-01

Mammalian cells are rapidly becoming the system of choice for the production of recombinant glycoproteins for structural biology applications. Their use has enabled the structural investigation of a whole new set of targets including large, multi-domain and highly glycosylated eukaryotic cell surface receptors and their supra-molecular assemblies. We summarize the technical advances that have been made in mammalian expression technology and highlight some of the structural insights that have been obtained using these methods. Looking forward, it is clear that mammalian cell expression will provide exciting and unique opportunities for an integrative approach to the structural study of proteins, especially of human origin and medically relevant, by bridging the gap between the purified state and the cellular context. Copyright © 2013 Elsevier Ltd. All rights reserved.

In Search of a Unified Theory of Biological Organization: What Does the Motor System of a Sea Slug Tell Us About Human Motor Integration?

DTIC Science & Technology

1992-04-07

integrated activity of large numbers of neurons might arise from interactions occurring localy between indi- vidual neurons. Thanks to the work of Rene ... Descartes and Euclid wouid like us to believe. the possibility of high-dimensiona space. of noniinearities. and of the dialectic be- tween structure

The retromer subunit Vps26 has an arrestin fold and binds Vps35 through its C-terminal domain.

PubMed

Shi, Hang; Rojas, Raul; Bonifacino, Juan S; Hurley, James H

2006-06-01

The mammalian retromer complex consists of SNX1, SNX2, Vps26, Vps29 and Vps35, and retrieves lysosomal enzyme receptors from endosomes to the trans-Golgi network. The structure of human Vps26A at 2.1-A resolution reveals two curved beta-sandwich domains connected by a polar core and a flexible linker. Vps26 has an unpredicted structural relationship to arrestins. The Vps35-binding site on Vps26 maps to a mobile loop spanning residues 235-246, near the tip of the C-terminal domain. The loop is phylogenetically conserved and provides a mechanism for Vps26 integration into the complex that leaves the rest of the structure free for engagements with membranes and for conformational changes. Hydrophobic residues and a glycine in this loop are required for integration into the retromer complex and endosomal localization of human Vps26, and for the function of yeast Vps26 in carboxypeptidase Y sorting.

Bionic Nanosystems

NASA Astrophysics Data System (ADS)

Sebastian Mannoor, Manu

Direct multidimensional integration of functional electronics and mechanical elements with viable biological systems could allow for the creation of bionic systems and devices possessing unique and advanced capabilities. For example, the ability to three dimensionally integrate functional electronic and mechanical components with biological cells and tissue could enable the creation of bionic systems that can have tremendous impact in regenerative medicine, prosthetics, and human-machine interfaces. However, as a consequence of the inherent dichotomy in material properties and limitations of conventional fabrication methods, the attainment of truly seamless integration of electronic and/or mechanical components with biological systems has been challenging. Nanomaterials engineering offers a general route for overcoming these dichotomies, primarily due to the existence of a dimensional compatibility between fundamental biological functional units and abiotic nanomaterial building blocks. One area of compelling interest for bionic systems is in the field of biomedical sensing, where the direct interfacing of nanosensors onto biological tissue or the human body could stimulate exciting opportunities such as on-body health quality monitoring and adaptive threat detection. Further, interfacing of antimicrobial peptide based bioselective probes onto the bionic nanosensors could offer abilities to detect pathogenic bacteria with bio-inspired selectivity. Most compellingly, when paired with additive manufacturing techniques such as 3D printing, these characteristics enable three dimensional integration and merging of a variety of functional materials including electronic, structural and biomaterials with viable biological cells, in the precise anatomic geometries of human organs, to form three dimensionally integrated, multi-functional bionic hybrids and cyborg devices with unique capabilities. In this thesis, we illustrate these approaches using three representative bionic systems: 1) Bionic Nanosensors: featuring bio-integrated graphene nanosensors for ubiquitous sensing, 2) Bionic Organs: featuring 3D printed bionic ears with three dimensionally integrated electronics and 3) Bionic Leaves: describing ongoing work in the direction of the creation of a bionic leaf enabled by the integration of plant derived photosynthetic functional units with electronic materials and components into a leaf-shaped hierarchical structure for harvesting photosynthetic bioelectricity.

Generating action descriptions from statistically integrated representations of human motions and sentences.

PubMed

Takano, Wataru; Kusajima, Ikuo; Nakamura, Yoshihiko

2016-08-01

It is desirable for robots to be able to linguistically understand human actions during human-robot interactions. Previous research has developed frameworks for encoding human full body motion into model parameters and for classifying motion into specific categories. For full understanding, the motion categories need to be connected to the natural language such that the robots can interpret human motions as linguistic expressions. This paper proposes a novel framework for integrating observation of human motion with that of natural language. This framework consists of two models; the first model statistically learns the relations between motions and their relevant words, and the second statistically learns sentence structures as word n-grams. Integration of these two models allows robots to generate sentences from human motions by searching for words relevant to the motion using the first model and then arranging these words in appropriate order using the second model. This allows making sentences that are the most likely to be generated from the motion. The proposed framework was tested on human full body motion measured by an optical motion capture system. In this, descriptive sentences were manually attached to the motions, and the validity of the system was demonstrated. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Basic Science Curriculum in the 21st Century: What Needs to Be Changed?

ERIC Educational Resources Information Center

Garant, Philias R.

1986-01-01

The basic science curriculum in dental education could be improved by adopting a curriculum containing only two integrated required science courses about (1) the structure and function of the human body and (2) disease and reaction to disease in the human body. Elective graduate-level predoctoral courses would allow specialization. (MSE)

Distributed multifunctional sensor network for composite structural state sensing

NASA Astrophysics Data System (ADS)

Qing, Xinlin P.; Wang, Yishou; Gao, Limin; Kumar, Amrita

2012-04-01

Advanced fiber reinforced composite materials are becoming the main structural materials of next generation of aircraft because of their high strength and stiffness to weight ratios, and strong designability. In order to take full advantages of composite materials, there is a need to develop an embeddable multifunctional sensing system to allow a structure to "feel" and "think" its structural state. In this paper, the concept of multifunctional sensor network integrated with a structure, similar to the human nervous system, has been developed. Different types of network sensors are permanently integrated within a composite structure to sense structural strain, temperature, moisture, aerodynamic pressure; monitor external impact on the structure; and detect structural damages. Utilizing this revolutionary concept, future composite structures can be designed and manufactured to provide multiple modes of information, so that the structures have the capabilities for intelligent sensing, environmental adaptation and multi-functionality. The challenges for building such a structural state sensing system and some solutions to address the challenges are also discussed in the paper.

Evaluation of optimal control type models for the human gunner in an Anti-Aircraft Artillery (AAA) system

NASA Technical Reports Server (NTRS)

Phatak, A. V.; Kessler, K. M.

1975-01-01

The selection of the structure of optimal control type models for the human gunner in an anti aircraft artillery system is considered. Several structures within the LQG framework may be formulated. Two basic types are considered: (1) kth derivative controllers; and (2) proportional integral derivative (P-I-D) controllers. It is shown that a suitable criterion for model structure determination can be based on the ensemble statistics of the tracking error. In the case when the ensemble tracking steady state error is zero, it is suggested that a P-I-D controller formulation be used in preference to the kth derivative controller.

Symbolic modeling of human anatomy for visualization and simulation

NASA Astrophysics Data System (ADS)

Pommert, Andreas; Schubert, Rainer; Riemer, Martin; Schiemann, Thomas; Tiede, Ulf; Hoehne, Karl H.

1994-09-01

Visualization of human anatomy in a 3D atlas requires both spatial and more abstract symbolic knowledge. Within our 'intelligent volume' model which integrates these two levels, we developed and implemented a semantic network model for describing human anatomy. Concepts for structuring (abstraction levels, domains, views, generic and case-specific modeling, inheritance) are introduced. Model, tools for generation and exploration and applications in our 3D anatomical atlas are presented and discussed.

Web-based Three-dimensional Virtual Body Structures: W3D-VBS

PubMed Central

Temkin, Bharti; Acosta, Eric; Hatfield, Paul; Onal, Erhan; Tong, Alex

2002-01-01

Major efforts are being made to improve the teaching of human anatomy to foster cognition of visuospatial relationships. The Visible Human Project of the National Library of Medicine makes it possible to create virtual reality-based applications for teaching anatomy. Integration of traditional cadaver and illustration-based methods with Internet-based simulations brings us closer to this goal. Web-based three-dimensional Virtual Body Structures (W3D-VBS) is a next-generation immersive anatomical training system for teaching human anatomy over the Internet. It uses Visible Human data to dynamically explore, select, extract, visualize, manipulate, and stereoscopically palpate realistic virtual body structures with a haptic device. Tracking user’s progress through evaluation tools helps customize lesson plans. A self-guided “virtual tour” of the whole body allows investigation of labeled virtual dissections repetitively, at any time and place a user requires it. PMID:12223495

Web-based three-dimensional Virtual Body Structures: W3D-VBS.

PubMed

Temkin, Bharti; Acosta, Eric; Hatfield, Paul; Onal, Erhan; Tong, Alex

2002-01-01

Major efforts are being made to improve the teaching of human anatomy to foster cognition of visuospatial relationships. The Visible Human Project of the National Library of Medicine makes it possible to create virtual reality-based applications for teaching anatomy. Integration of traditional cadaver and illustration-based methods with Internet-based simulations brings us closer to this goal. Web-based three-dimensional Virtual Body Structures (W3D-VBS) is a next-generation immersive anatomical training system for teaching human anatomy over the Internet. It uses Visible Human data to dynamically explore, select, extract, visualize, manipulate, and stereoscopically palpate realistic virtual body structures with a haptic device. Tracking user's progress through evaluation tools helps customize lesson plans. A self-guided "virtual tour" of the whole body allows investigation of labeled virtual dissections repetitively, at any time and place a user requires it.

Structure of neuro-endocrine and neuro-epithelial interactions in human foetal pancreas.

PubMed

Krivova, Yuliya; Proshchina, Alexandra; Barabanov, Valeriy; Leonova, Olga; Saveliev, Sergey

2016-12-01

In the pancreas of many mammals including humans, endocrine islet cells can be integrated with the nervous system components into neuro-insular complexes. The mechanism of the formation of such complexes is not clearly understood. The present study evaluated the interactions between the nervous system components, epithelial cells and endocrine cells in the human pancreas. Foetal pancreas, gestational age 19-23 weeks (13 cases) and 30-34 weeks (7 cases), were studied using double immunohistochemical labeling with neural markers (S100 protein and beta III tubulin), epithelial marker (cytokeratin 19 (CK19)) and antibodies to insulin and glucagon. We first analyse the structure of neuro-insular complexes using confocal microscopy and provide immunohistochemical evidences of the presence of endocrine cells within the ganglia or inside the nerve bundles. We showed that the nervous system components contact with the epithelial cells located in ducts or in clusters outside the ductal epithelium and form complexes with separate epithelial cells. We observed CK19-positive cells inside the ganglia and nerve bundles which were located separately or were integrated with the islets. Therefore, we conclude that neuro-insular complexes may forms as a result of integration between epithelial cells and nervous system components at the initial stages of islets formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

An integrated environmental and health performance quantification model for pre-occupancy phase of buildings in China

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

Li, Xiaodong, E-mail: eastdawn@tsinghua.edu.cn; Su, Shu, E-mail: sushuqh@163.com; Zhang, Zhihui, E-mail: zhzhg@tsinghua.edu.cn

To comprehensively pre-evaluate the damages to both the environment and human health due to construction activities in China, this paper presents an integrated building environmental and health performance (EHP) assessment model based on the Building Environmental Performance Analysis System (BEPAS) and the Building Health Impact Analysis System (BHIAS) models and offers a new inventory data estimation method. The new model follows the life cycle assessment (LCA) framework and the inventory analysis step involves bill of quantity (BOQ) data collection, consumption data formation, and environmental profile transformation. The consumption data are derived from engineering drawings and quotas to conduct the assessmentmore » before construction for pre-evaluation. The new model classifies building impacts into three safeguard areas: ecosystems, natural resources and human health. Thus, this model considers environmental impacts as well as damage to human wellbeing. The monetization approach, distance-to-target method and panel method are considered as optional weighting approaches. Finally, nine residential buildings of different structural types are taken as case studies to test the operability of the integrated model through application. The results indicate that the new model can effectively pre-evaluate building EHP and the structure type significantly affects the performance of residential buildings.« less

Everyday robotic action: lessons from human action control

PubMed Central

de Kleijn, Roy; Kachergis, George; Hommel, Bernhard

2014-01-01

Robots are increasingly capable of performing everyday human activities such as cooking, cleaning, and doing the laundry. This requires the real-time planning and execution of complex, temporally extended sequential actions under high degrees of uncertainty, which provides many challenges to traditional approaches to robot action control. We argue that important lessons in this respect can be learned from research on human action control. We provide a brief overview of available psychological insights into this issue and focus on four principles that we think could be particularly beneficial for robot control: the integration of symbolic and subsymbolic planning of action sequences, the integration of feedforward and feedback control, the clustering of complex actions into subcomponents, and the contextualization of action-control structures through goal representations. PMID:24672474

Display integration for ground combat vehicles

NASA Astrophysics Data System (ADS)

Busse, David J.

1998-09-01

The United States Army's requirement to employ high resolution target acquisition sensors and information warfare to increase its dominance over enemy forces has led to the need to integrate advanced display devices into ground combat vehicle crew stations. The Army's force structure require the integration of advanced displays on both existing and emerging ground combat vehicle systems. The fielding of second generation target acquisition sensors, color digital terrain maps and high volume digital command and control information networks on these platforms define display performance requirements. The greatest challenge facing the system integrator is the development and integration of advanced displays that meet operational, vehicle and human computer interface performance requirements for the ground combat vehicle fleet. The subject of this paper is to address those challenges: operational and vehicle performance, non-soldier centric crew station configurations, display performance limitations related to human computer interfaces and vehicle physical environments, display technology limitations and the Department of Defense (DOD) acquisition reform initiatives. How the ground combat vehicle Program Manager and system integrator are addressing these challenges are discussed through the integration of displays on fielded, current and future close combat vehicle applications.

Bryostatin and its synthetic analog, picolog rescue dermal fibroblasts from prolonged stress and contribute to survival and rejuvenation of human skin equivalents.

PubMed

Khan, Tapan K; Wender, Paul A; Alkon, Daniel L

2018-02-01

Skin health is associated with the day-to-day activity of fibroblasts. The primary function of fibroblasts is to synthesize structural proteins, such as collagen, extracellular matrix proteins, and other proteins that support the structural integrity of the skin and are associated with younger, firmer, and more elastic skin that is better able to resist and recover from injury. At sub-nanomolar concentrations (0.03-0.3 nM), bryostatin-1 and its synthetic analog, picolog (0.1-10 nM) sustained the survival and activation of human dermal fibroblasts cultured under the stressful condition of prolonged serum deprivation. Bryostatin-1 treatment stabilized human skin equivalents (HSEs), a bioengineered combination of primary human skin cells (keratinocytes and dermal fibroblasts) on an extracellular matrix composed of mainly collagen. Fibroblasts activated by bryostatin-1 protected the structural integrity of HSEs. Bryostatin-1 and picolog prolonged activation of Erk in fibroblasts to promote cell survival. Chronic stress promotes the progression of apoptosis. Dermal fibroblasts constitutively express all components of Fas associated apoptosis, including caspase-8, an initiator enzyme of apoptosis. Prolong bryostatin-1 treatment reduced apoptosis by decreasing caspase-8 and protected dermal fibroblasts. Our data suggest that bryostatin-1 and picolog could be useful in anti-aging skincare, and could have applications in tissue engineering and regenerative medicine. © 2017 Wiley Periodicals, Inc.

Integration sites of Epstein-Barr virus genome on chromosomes of human lymphoblastoid cell lines

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

Wuu, K.D.; Chen, Y.J.; Wang-Wuu, S.

1994-09-01

Epstein-Barr virus (EBV) is the pathogen of infectious mononucleosis. The viral genome is present in more than 95% of the African cases of Burkitt lymphoma and it is usually maintained in episomal form in the tumor cells. Viral integration has been described only for Nanalwa which is a Burkitt lymphoma cell line lacking episomes. In order to examine the role of EBV in the immortalization of human Blymphocytes, we investigated whether the EBV integration into the human genome is essential. If the integration does occur, we would like to know whether the integration is randomly distributed or whether the viralmore » DNA integrates preferentially at certain sites. Fourteen in vitro immortalized human lymphoblastoid cell lines (LCLs) were examined by fluorescence in situ hybridization (FISH) with a biotinylated EBV BamHI w DNA fragment as probe. The episomal form of EBV DNA was found in all cells of these cell lines, while only about 65% of the cells have the integrated viral DNA. This might suggest that integration is not a pre-requisite for cell immortalization. Although all chromosomes, except Y, have been found with integrated viral genome, chromsomes 1 and 5 are the most frequent EBV DNA carrier (p<0.05). Nine chromosome bands, namely, 1p31, 1q31, 2q32, 3q13, 3q26, 5q14, 6q24, 7q31 and 12q21, are preferential targets for EBV integration (p<0.001). Eighty percent of the total 938 EBV hybridization signals were found to be at G-band-positive area. This suggests that the mechanism of EBV integration might be different from that of the retroviruses, which specifically integrate to G-band-negative areas. Thus, we conclude that the integration of EBV to host genome is non-random and it may have something to do with the structure of chromosome and DNA sequences.« less

The Naturalistic Flight Deck System: An Integrated System Concept for Improved Single-Pilot Operations

NASA Technical Reports Server (NTRS)

Schutte, Paul C.; Goodrich, Kenneth H.; Cox, David E.; Jackson, Bruce; Palmer, Michael T.; Pope, Alan T.; Schlecht, Robin W.; Tedjojuwono, Ken K.; Trujillo, Anna C.; Williams, Ralph A.;

Integrated mobile robot control

NASA Technical Reports Server (NTRS)

Amidi, Omead; Thorpe, Charles

1991-01-01

This paper describes the structure, implementation, and operation of a real-time mobile robot controller which integrates capabilities such as: position estimation, path specification and tracking, human interfaces, fast communication, and multiple client support. The benefits of such high-level capabilities in a low-level controller was shown by its implementation for the Navlab autonomous vehicle. In addition, performance results from positioning and tracking systems are reported and analyzed.

Early brain development toward shaping of human mind: an integrative psychoneurodevelopmental model in prenatal and perinatal medicine.

PubMed

Hruby, Radovan; Maas, Lili M; Fedor-Freybergh, P G

2013-01-01

The article introduces an integrative psychoneurodevelopmental model of complex human brain and mind development based on the latest findings in prenatal and perinatal medicine in terms of integrative neuroscience. The human brain development is extraordinarily complex set of events and could be influenced by a lot of factors. It is supported by new insights into the early neuro-ontogenic processes with the help of structural 3D magnetic resonance imaging or diffusion tensor imaging of fetal human brain. Various factors and targets for neural development including birth weight variability, fetal and early-life programming, fetal neurobehavioral states and fetal behavioral responses to various stimuli and others are discussed. Molecular biology reveals increasing sets of genes families as well as transcription and neurotropic factors together with critical epigenetic mechanisms to be deeply employed in the crucial neurodevelopmental events. Another field of critical importance is psychoimmuno-neuroendocrinology. Various effects of glucocorticoids as well as other hormones, prenatal stress and fetal HPA axis modulation are thought to be of special importance for brain development. The early postnatal period is characterized by the next intense shaping of complex competences, induced mainly by the very unique mother - newborn´s interactions and bonding. All these mechanisms serve to shape individual human mind with complex abilities and neurobehavioral strategies. Continuous research elucidating these special competences of human fetus and newborn/child supports integrative neuroscientific approach to involve various scientific disciplines for the next progress in human brain and mind research, and opens new scientific challenges and philosophic attitudes. New findings and approaches in this field could establish new methods in science, in primary prevention and treatment strategies, and markedly contribute to the development of modern integrative and personalized medicine.

Army-NASA aircrew/aircraft integration program: Phase 4 A(3)I Man-Machine Integration Design and Analysis System (MIDAS) software detailed design document

NASA Technical Reports Server (NTRS)

Banda, Carolyn; Bushnell, David; Chen, Scott; Chiu, Alex; Constantine, Betsy; Murray, Jerry; Neukom, Christian; Prevost, Michael; Shankar, Renuka; Staveland, Lowell

1991-01-01

The Man-Machine Integration Design and Analysis System (MIDAS) is an integrated suite of software components that constitutes a prototype workstation to aid designers in applying human factors principles to the design of complex human-machine systems. MIDAS is intended to be used at the very early stages of conceptual design to provide an environment wherein designers can use computational representations of the crew station and operator, instead of hardware simulators and man-in-the-loop studies, to discover problems and ask 'what if' questions regarding the projected mission, equipment, and environment. This document is the Software Product Specification for MIDAS. Introductory descriptions of the processing requirements, hardware/software environment, structure, I/O, and control are given in the main body of the document for the overall MIDAS system, with detailed discussion of the individual modules included in Annexes A-J.

Reconstruction of the experimentally supported human protein interactome: what can we learn?

PubMed Central

2013-01-01

Background Understanding the topology and dynamics of the human protein-protein interaction (PPI) network will significantly contribute to biomedical research, therefore its systematic reconstruction is required. Several meta-databases integrate source PPI datasets, but the protein node sets of their networks vary depending on the PPI data combined. Due to this inherent heterogeneity, the way in which the human PPI network expands via multiple dataset integration has not been comprehensively analyzed. We aim at assembling the human interactome in a global structured way and exploring it to gain insights of biological relevance. Results First, we defined the UniProtKB manually reviewed human “complete” proteome as the reference protein-node set and then we mined five major source PPI datasets for direct PPIs exclusively between the reference proteins. We updated the protein and publication identifiers and normalized all PPIs to the UniProt identifier level. The reconstructed interactome covers approximately 60% of the human proteome and has a scale-free structure. No apparent differentiating gene functional classification characteristics were identified for the unrepresented proteins. The source dataset integration augments the network mainly in PPIs. Polyubiquitin emerged as the highest-degree node, but the inclusion of most of its identified PPIs may be reconsidered. The high number (>300) of connections of the subsequent fifteen proteins correlates well with their essential biological role. According to the power-law network structure, the unrepresented proteins should mainly have up to four connections with equally poorly-connected interactors. Conclusions Reconstructing the human interactome based on the a priori definition of the protein nodes enabled us to identify the currently included part of the human “complete” proteome, and discuss the role of the proteins within the network topology with respect to their function. As the network expansion has to comply with the scale-free theory, we suggest that the core of the human interactome has essentially emerged. Thus, it could be employed in systems biology and biomedical research, despite the considerable number of currently unrepresented proteins. The latter are probably involved in specialized physiological conditions, justifying the scarcity of related PPI information, and their identification can assist in designing relevant functional experiments and targeted text mining algorithms. PMID:24088582

Spider-web inspired multi-resolution graphene tactile sensor.

PubMed

Liu, Lu; Huang, Yu; Li, Fengyu; Ma, Ying; Li, Wenbo; Su, Meng; Qian, Xin; Ren, Wanjie; Tang, Kanglai; Song, Yanlin

2018-05-08

Multi-dimensional accurate response and smooth signal transmission are critical challenges in the advancement of multi-resolution recognition and complex environment analysis. Inspired by the structure-activity relationship between discrepant microstructures of the spiral and radial threads in a spider web, we designed and printed graphene with porous and densely-packed microstructures to integrate into a multi-resolution graphene tactile sensor. The three-dimensional (3D) porous graphene structure performs multi-dimensional deformation responses. The laminar densely-packed graphene structure contributes excellent conductivity with flexible stability. The spider-web inspired printed pattern inherits orientational and locational kinesis tracking. The multi-structure construction with homo-graphene material can integrate discrepant electronic properties with remarkable flexibility, which will attract enormous attention for electronic skin, wearable devices and human-machine interactions.

Human-Automation Integration: Principle and Method for Design and Evaluation

NASA Technical Reports Server (NTRS)

Billman, Dorrit; Feary, Michael

2012-01-01

Future space missions will increasingly depend on integration of complex engineered systems with their human operators. It is important to ensure that the systems that are designed and developed do a good job of supporting the needs of the work domain. Our research investigates methods for needs analysis. We included analysis of work products (plans for regulation of the space station) as well as work processes (tasks using current software), in a case study of Attitude Determination and Control Officers (ADCO) planning work. This allows comparing how well different designs match the structure of the work to be supported. Redesigned planning software that better matches the structure of work was developed and experimentally assessed. The new prototype enabled substantially faster and more accurate performance in plan revision tasks. This success suggests the approach to needs assessment and use in design and evaluation is promising, and merits investigatation in future research.

Flexible and Stretchable Physical Sensor Integrated Platforms for Wearable Human-Activity Monitoringand Personal Healthcare.

PubMed

Trung, Tran Quang; Lee, Nae-Eung

2016-06-01

Flexible and stretchable physical sensors that can measure and quantify electrical signals generated by human activities are attracting a great deal of attention as they have unique characteristics, such as ultrathinness, low modulus, light weight, high flexibility, and stretchability. These flexible and stretchable physical sensors conformally attached on the surface of organs or skin can provide a new opportunity for human-activity monitoring and personal healthcare. Consequently, in recent years there has been considerable research effort devoted to the development of flexible and stretchable physical sensors to fulfill the requirements of future technology, and much progress has been achieved. Here, the most recent developments of flexible and stretchable physical sensors are described, including temperature, pressure, and strain sensors, and flexible and stretchable sensor-integrated platforms. The latest successful examples of flexible and stretchable physical sensors for the detection of temperature, pressure, and strain, as well as their novel structures, technological innovations, and challenges, are reviewed first. In the next section, recent progress regarding sensor-integrated wearable platforms is overviewed in detail. Some of the latest achievements regarding self-powered sensor-integrated wearable platform technologies are also reviewed. Further research direction and challenges are also proposed to develop a fully sensor-integrated wearable platform for monitoring human activity and personal healthcare in the near future. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Medial temporal lobe roles in human path integration.

PubMed

Yamamoto, Naohide; Philbeck, John W; Woods, Adam J; Gajewski, Daniel A; Arthur, Joeanna C; Potolicchio, Samuel J; Levy, Lucien; Caputy, Anthony J

2014-01-01

Path integration is a process in which observers derive their location by integrating self-motion signals along their locomotion trajectory. Although the medial temporal lobe (MTL) is thought to take part in path integration, the scope of its role for path integration remains unclear. To address this issue, we administered a variety of tasks involving path integration and other related processes to a group of neurosurgical patients whose MTL was unilaterally resected as therapy for epilepsy. These patients were unimpaired relative to neurologically intact controls in many tasks that required integration of various kinds of sensory self-motion information. However, the same patients (especially those who had lesions in the right hemisphere) walked farther than the controls when attempting to walk without vision to a previewed target. Importantly, this task was unique in our test battery in that it allowed participants to form a mental representation of the target location and anticipate their upcoming walking trajectory before they began moving. Thus, these results put forth a new idea that the role of MTL structures for human path integration may stem from their participation in predicting the consequences of one's locomotor actions. The strengths of this new theoretical viewpoint are discussed.

Medial Temporal Lobe Roles in Human Path Integration

PubMed Central

Yamamoto, Naohide; Philbeck, John W.; Woods, Adam J.; Gajewski, Daniel A.; Arthur, Joeanna C.; Potolicchio, Samuel J.; Levy, Lucien; Caputy, Anthony J.

2014-01-01

Path integration is a process in which observers derive their location by integrating self-motion signals along their locomotion trajectory. Although the medial temporal lobe (MTL) is thought to take part in path integration, the scope of its role for path integration remains unclear. To address this issue, we administered a variety of tasks involving path integration and other related processes to a group of neurosurgical patients whose MTL was unilaterally resected as therapy for epilepsy. These patients were unimpaired relative to neurologically intact controls in many tasks that required integration of various kinds of sensory self-motion information. However, the same patients (especially those who had lesions in the right hemisphere) walked farther than the controls when attempting to walk without vision to a previewed target. Importantly, this task was unique in our test battery in that it allowed participants to form a mental representation of the target location and anticipate their upcoming walking trajectory before they began moving. Thus, these results put forth a new idea that the role of MTL structures for human path integration may stem from their participation in predicting the consequences of one's locomotor actions. The strengths of this new theoretical viewpoint are discussed. PMID:24802000

Neurobehavioral Integrity of Chimpanzee Newborns: Comparisons across groups and across species reveal gene-environment interaction effects

PubMed Central

Bard, Kim A.; Brent, Linda; Lester, Barry; Worobey, John; Suomi, Stephen J.

2014-01-01

The aims of this article are to describe the neurobehavioral integrity of chimpanzee newborns, to investigate how early experiences affect the neurobehavioral organization of chimpanzees, and to explore species differences by comparing chimpanzee newborns to a group of typically developing human newborns. Neurobehavioral integrity related to orientation, motor performance, arousal, and state regulation of 55 chimpanzee (raised in four different settings) and 42 human newborns was measured with the Neonatal Behavioral Assessment Scale (NBAS) a semi-structured 25-minute interactive assessment. Thirty-eight chimpanzees were tested every other day from birth, and analyses revealed significant developmental changes in 19 of 27 NBAS scores. The cross-group and cross-species comparisons were conducted at 2 and 30 days of age. Among the 4 chimpanzee groups, significant differences were found in 23 of 24 NBAS scores. Surprisingly, the cross-species comparisons revealed that the human group was distinct in only 1 of 25 NBAS scores (the human group had significantly less muscle tone than all the chimpanzee groups). The human group was indistinguishable from at least one of the chimpanzee groups in the remaining 24 of 25 NBAS scores. The results of this study support the conclusion that the interplay between genes and environment, rather than genes alone or environment alone, accounts for phenotypic expressions of newborn neurobehavioral integrity in hominids. PMID:25110465

A Human Systems Integration Approach to Energy Efficiency in Ground Transportation

DTIC Science & Technology

2015-12-01

Granite Construction Organizational Structure .........................................53 Figure 7. A Comparison of USMC Structure to Granite Construction...Caterpillar Corporation and the implementation and use of their telematics systems within a company called Granite Construction. Granite Construction...profit over 250 million dollars annually. In addition, similar to the USMC, Granite Construction handles both large and small scale projects in a

Evolutionary, structural and biochemical evidence for a new interaction site of the leptin obesity protein

NASA Technical Reports Server (NTRS)

Gaucher, Eric A.; Miyamoto, Michael M.; Benner, Steven A.

2003-01-01

The Leptin protein is central to the regulation of energy metabolism in mammals. By integrating evolutionary, structural, and biochemical information, a surface segment, outside of its known receptor contacts, is predicted as a second interaction site that may help to further define its roles in energy balance and its functional differences between humans and other mammals.

Linkages among Education, Health, and Social Services Systems in States That Are Creating New Governance Structures.

ERIC Educational Resources Information Center

Mutchler, Sue E.; Pollard, Joyce S.

As they work to develop integrated, community-driven service systems that meet the constellation of needs of children and families, several states are beginning to develop new governance structures at the local level. This paper describes the ways in which states are creating or supporting linkages among education, health, and human services. A…

Access to justice: evaluating law, health and human rights programmes in Kenya

PubMed Central

Gruskin, Sofia; Safreed-Harmon, Kelly; Ezer, Tamar; Gathumbi, Anne; Cohen, Jonathan; Kameri-Mbote, Patricia

2013-01-01

Introduction In Kenya, human rights violations have a marked impact on the health of people living with HIV. Integrating legal literacy and legal services into healthcare appears to be an effective strategy to empower vulnerable groups and address underlying determinants of health. Methods We carried out an evaluation to collect evidence about the impact of legal empowerment programmes on health and human rights. The evaluation focused on Open Society Foundation-supported legal integration activities at four sites: the Academic Model of Providing Access to Healthcare (AMPATH) facility, where the Legal Aid Centre of Eldoret (LACE) operates, in Eldoret; Kenyatta National Hospital's Gender-based Violence Recovery Centre, which hosts the COVAW legal integration program; and Christian Health Association of Kenya (CHAK) facilities in Mombasa and Naivasha. In consultation with the organizations implementing the programs, we designed a conceptual logic model grounded in human rights principles, identified relevant indicators and then coded structure, process and outcome indicators for the rights-related principles they reflect. The evaluation included a resource assessment questionnaire, a review of program records and routine data, and semi-structured interviews and focus group discussions with clients and service providers. Data were collected in May–August 2010 and April–June 2011. Results Clients showed a notable increase in practical knowledge and awareness about how to access legal aid and claim their rights, as well as an enhanced ability to communicate with healthcare providers and to improve their access to healthcare and justice. In turn, providers became more adept at identifying human rights violations and other legal difficulties, which enabled them to give clients basic information about their rights, refer them to legal aid and assist them in accessing needed support. Methodological challenges in evaluating such activities point to the need to strengthen rights-oriented evaluation methods. Conclusions Legal empowerment programmes have the potential to promote accountability, reduce stigma and discrimination and contribute to altering unjust structures and systems. Given their apparent value as a health and human rights intervention, particularly for marginalized populations, further rigorous evaluations are called for to support the scale-up of such programmes. PMID:24242267

Access to justice: evaluating law, health and human rights programmes in Kenya.

PubMed

Gruskin, Sofia; Safreed-Harmon, Kelly; Ezer, Tamar; Gathumbi, Anne; Cohen, Jonathan; Kameri-Mbote, Patricia

2013-11-13

In Kenya, human rights violations have a marked impact on the health of people living with HIV. Integrating legal literacy and legal services into healthcare appears to be an effective strategy to empower vulnerable groups and address underlying determinants of health. We carried out an evaluation to collect evidence about the impact of legal empowerment programmes on health and human rights. The evaluation focused on Open Society Foundation-supported legal integration activities at four sites: the Academic Model of Providing Access to Healthcare (AMPATH) facility, where the Legal Aid Centre of Eldoret (LACE) operates, in Eldoret; Kenyatta National Hospital's Gender-based Violence Recovery Centre, which hosts the COVAW legal integration program; and Christian Health Association of Kenya (CHAK) facilities in Mombasa and Naivasha. In consultation with the organizations implementing the programs, we designed a conceptual logic model grounded in human rights principles, identified relevant indicators and then coded structure, process and outcome indicators for the rights-related principles they reflect. The evaluation included a resource assessment questionnaire, a review of program records and routine data, and semi-structured interviews and focus group discussions with clients and service providers. Data were collected in May-August 2010 and April-June 2011. Clients showed a notable increase in practical knowledge and awareness about how to access legal aid and claim their rights, as well as an enhanced ability to communicate with healthcare providers and to improve their access to healthcare and justice. In turn, providers became more adept at identifying human rights violations and other legal difficulties, which enabled them to give clients basic information about their rights, refer them to legal aid and assist them in accessing needed support. Methodological challenges in evaluating such activities point to the need to strengthen rights-oriented evaluation methods. Legal empowerment programmes have the potential to promote accountability, reduce stigma and discrimination and contribute to altering unjust structures and systems. Given their apparent value as a health and human rights intervention, particularly for marginalized populations, further rigorous evaluations are called for to support the scale-up of such programmes.

A combined computational and structural model of the full-length human prolactin receptor

PubMed Central

Bugge, Katrine; Papaleo, Elena; Haxholm, Gitte W.; Hopper, Jonathan T. S.; Robinson, Carol V.; Olsen, Johan G.; Lindorff-Larsen, Kresten; Kragelund, Birthe B.

2016-01-01

The prolactin receptor is an archetype member of the class I cytokine receptor family, comprising receptors with fundamental functions in biology as well as key drug targets. Structurally, each of these receptors represent an intriguing diversity, providing an exceptionally challenging target for structural biology. Here, we access the molecular architecture of the monomeric human prolactin receptor by combining experimental and computational efforts. We solve the NMR structure of its transmembrane domain in micelles and collect structural data on overlapping fragments of the receptor with small-angle X-ray scattering, native mass spectrometry and NMR spectroscopy. Along with previously published data, these are integrated by molecular modelling to generate a full receptor structure. The result provides the first full view of a class I cytokine receptor, exemplifying the architecture of more than 40 different receptor chains, and reveals that the extracellular domain is merely the tip of a molecular iceberg. PMID:27174498

Nurses' human dignity in education and practice: An integrated literature review.

PubMed

Parandeh, Akram; Khaghanizade, Morteza; Mohammadi, Eesa; Mokhtari-Nouri, Jamileh

2016-01-01

Human dignity, as a fundamental human right and a moral obligation, has been emphasized in different fields of nursing. The aim of the present integrative review was to explore the nature of nurses' human dignity in educational and clinical settings. A literature review was conducted on quantitative and qualitative research papers in English and Persian using the PubMed, ProQuest, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Google Scholar, SID, and Irandoc databases from the year 2000 to 2013. Keywords for the search included dignity, nursing, faculty, nurse clinicians, nursing student, and humanism. In total, 12 research papers met the inclusion criteria for the integrative review. From this review, four key themes emerged. The themes consisted of concept of human dignity (it was as an expression of the professional value in nursing settings), factors affecting human dignity (including respect, communication, autonomy and power, competency and ability, structure of the workplace, and value-based education), dimensions of human dignity (including intrinsic and professional domains), and consequences of human dignity [positive (individual and professional growth and caring professional behavior) and negative (loss of motivation, intention to leave the profession, and non-professional image of nursing in the minds of people)]. The small number of studies found for the review indicates the need for further research in the field of nurses' dignity. Recognizing nurses' dignity can help to improve the nursing practice and provide them a dignified workplace.

Nurses’ human dignity in education and practice: An integrated literature review

PubMed Central

Parandeh, Akram; Khaghanizade, Morteza; Mohammadi, Eesa; Mokhtari-Nouri, Jamileh

2016-01-01

Background: Human dignity, as a fundamental human right and a moral obligation, has been emphasized in different fields of nursing. The aim of the present integrative review was to explore the nature of nurses’ human dignity in educational and clinical settings. Materials and Methods: A literature review was conducted on quantitative and qualitative research papers in English and Persian using the PubMed, ProQuest, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Google Scholar, SID, and Irandoc databases from the year 2000 to 2013. Keywords for the search included dignity, nursing, faculty, nurse clinicians, nursing student, and humanism. In total, 12 research papers met the inclusion criteria for the integrative review. Results: From this review, four key themes emerged. The themes consisted of concept of human dignity (it was as an expression of the professional value in nursing settings), factors affecting human dignity (including respect, communication, autonomy and power, competency and ability, structure of the workplace, and value-based education), dimensions of human dignity (including intrinsic and professional domains), and consequences of human dignity [positive (individual and professional growth and caring professional behavior) and negative (loss of motivation, intention to leave the profession, and non-professional image of nursing in the minds of people)]. Conclusions: The small number of studies found for the review indicates the need for further research in the field of nurses’ dignity. Recognizing nurses’ dignity can help to improve the nursing practice and provide them a dignified workplace. PMID:26985216

Structural Biology of Proteins of the Multi-enzyme Assembly Human Pyruvate Dehydrogenase Complex

NASA Technical Reports Server (NTRS)

2003-01-01

Objectives and research challenges of this effort include: 1. Need to establish Human Pyruvate Dehydrogenase Complex protein crystals; 2. Need to test value of microgravity for improving crystal quality of Human Pyruvate Dehydrogenase Complex protein crystals; 3. Need to improve flight hardware in order to control and understand the effects of microgravity on crystallization of Human Pyruvate Dehydrogenase Complex proteins; 4. Need to integrate sets of national collaborations with the restricted and specific requirements of flight experiments; 5. Need to establish a highly controlled experiment in microgravity with a rigor not yet obtained; 6. Need to communicate both the rigor of microgravity experiments and the scientific value of results obtained from microgravity experiments to the national community; and 7. Need to advance the understanding of Human Pyruvate Dehydrogenase Complex structures so that scientific and commercial advance is identified for these proteins.

Knowledge acquisition from natural language for expert systems based on classification problem-solving methods

NASA Technical Reports Server (NTRS)

Gomez, Fernando

1989-01-01

It is shown how certain kinds of domain independent expert systems based on classification problem-solving methods can be constructed directly from natural language descriptions by a human expert. The expert knowledge is not translated into production rules. Rather, it is mapped into conceptual structures which are integrated into long-term memory (LTM). The resulting system is one in which problem-solving, retrieval and memory organization are integrated processes. In other words, the same algorithm and knowledge representation structures are shared by these processes. As a result of this, the system can answer questions, solve problems or reorganize LTM.

The hippocampus is an integral part of the temporal limbic system during emotional processing. Comment on "The quartet theory of human emotions: An integrative and neurofunctional model" by S. Koelsch et al.

NASA Astrophysics Data System (ADS)

Trost, Wiebke; Frühholz, Sascha

2015-06-01

The proposed quartet theory of human emotions by Koelsch and colleagues [1] identifies four different affect systems to be involved in the processing of particular types of emotions. Moreover, the theory integrates both basic emotions and more complex emotion concepts, which include also aesthetic emotions such as musical emotions. The authors identify a particular brain system for each kind of emotion type, also by contrasting them to brain structures that are generally involved in emotion processing irrespective of the type of emotion. A brain system that has been less regarded in emotion theories, but which represents one of the four systems of the quartet to induce attachment related emotions, is the hippocampus.

Bridging animal and human models of exercise-induced brain plasticity

PubMed Central

Voss, Michelle W.; Vivar, Carmen; Kramer, Arthur F.; van Praag, Henriette

2015-01-01

Significant progress has been made in understanding the neurobiological mechanisms through which exercise protects and restores the brain. In this feature review, we integrate animal and human research, examining physical activity effects across multiple levels of description (neurons up to inter-regional pathways). We evaluate the influence of exercise on hippocampal structure and function, addressing common themes such as spatial memory and pattern separation, brain structure and plasticity, neurotrophic factors, and vasculature. Areas of research focused more within species, such as hippocampal neurogenesis in rodents, also provide crucial insight into the protective role of physical activity. Overall, converging evidence suggests exercise benefits brain function and cognition across the mammalian lifespan, which may translate into reduced risk for Alzheimer’s disease (AD) in humans. PMID:24029446

Process Integrated Mechanism for Human-Computer Collaboration and Coordination

DTIC Science & Technology

2012-09-12

system we implemented the TAFLib library that provides the communication with TAF . The data received from the TAF server is collected in a data structure...send new commands and flight plans for the UAVs to the TAF server. Test scenarios Several scenarios have been implemented to test and prove our...areas. Shooting Enemies The basic scenario proved the successful integration of PIM and the TAF simulation environment. Subsequently we improved the CP

INTEGRATING GENETIC AND STRUCTURAL DATA ON HUMAN PROTEIN KINOME IN NETWORK-BASED MODELING OF KINASE SENSITIVITIES AND RESISTANCE TO TARGETED AND PERSONALIZED ANTICANCER DRUGS.

PubMed

Verkhivker, Gennady M

2016-01-01

The human protein kinome presents one of the largest protein families that orchestrate functional processes in complex cellular networks, and when perturbed, can cause various cancers. The abundance and diversity of genetic, structural, and biochemical data underlies the complexity of mechanisms by which targeted and personalized drugs can combat mutational profiles in protein kinases. Coupled with the evolution of system biology approaches, genomic and proteomic technologies are rapidly identifying and charactering novel resistance mechanisms with the goal to inform rationale design of personalized kinase drugs. Integration of experimental and computational approaches can help to bring these data into a unified conceptual framework and develop robust models for predicting the clinical drug resistance. In the current study, we employ a battery of synergistic computational approaches that integrate genetic, evolutionary, biochemical, and structural data to characterize the effect of cancer mutations in protein kinases. We provide a detailed structural classification and analysis of genetic signatures associated with oncogenic mutations. By integrating genetic and structural data, we employ network modeling to dissect mechanisms of kinase drug sensitivities to oncogenic EGFR mutations. Using biophysical simulations and analysis of protein structure networks, we show that conformational-specific drug binding of Lapatinib may elicit resistant mutations in the EGFR kinase that are linked with the ligand-mediated changes in the residue interaction networks and global network properties of key residues that are responsible for structural stability of specific functional states. A strong network dependency on high centrality residues in the conformation-specific Lapatinib-EGFR complex may explain vulnerability of drug binding to a broad spectrum of mutations and the emergence of drug resistance. Our study offers a systems-based perspective on drug design by unravelling complex relationships between robustness of targeted kinase genes and binding specificity of targeted kinase drugs. We discuss how these approaches can exploit advances in chemical biology and network science to develop novel strategies for rationally tailored and robust personalized drug therapies.

Cognitive structure, flexibility, and plasticity in human multitasking-An integrative review of dual-task and task-switching research.

PubMed

Koch, Iring; Poljac, Edita; Müller, Hermann; Kiesel, Andrea

2018-06-01

Numerous studies showed decreased performance in situations that require multiple tasks or actions relative to appropriate control conditions. Because humans often engage in such multitasking activities, it is important to understand how multitasking affects performance. In the present article, we argue that research on dual-task interference and sequential task switching has proceeded largely separately using different experimental paradigms and methodology. In our article we aim at organizing this complex set of research in terms of three complementary research perspectives on human multitasking. One perspective refers to structural accounts in terms of cognitive bottlenecks (i.e., critical processing stages). A second perspective refers to cognitive flexibility in terms of the underlying cognitive control processes. A third perspective emphasizes cognitive plasticity in terms of the influence of practice on human multitasking abilities. With our review article we aimed at highlighting the value of an integrative position that goes beyond isolated consideration of a single theoretical research perspective and that broadens the focus from single experimental paradigms (dual task and task switching) to favor instead a view that emphasizes the fundamental similarity of the underlying cognitive mechanisms across multitasking paradigms. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Columba: an integrated database of proteins, structures, and annotations.

PubMed

Trissl, Silke; Rother, Kristian; Müller, Heiko; Steinke, Thomas; Koch, Ina; Preissner, Robert; Frömmel, Cornelius; Leser, Ulf

2005-03-31

Structural and functional research often requires the computation of sets of protein structures based on certain properties of the proteins, such as sequence features, fold classification, or functional annotation. Compiling such sets using current web resources is tedious because the necessary data are spread over many different databases. To facilitate this task, we have created COLUMBA, an integrated database of annotations of protein structures. COLUMBA currently integrates twelve different databases, including PDB, KEGG, Swiss-Prot, CATH, SCOP, the Gene Ontology, and ENZYME. The database can be searched using either keyword search or data source-specific web forms. Users can thus quickly select and download PDB entries that, for instance, participate in a particular pathway, are classified as containing a certain CATH architecture, are annotated as having a certain molecular function in the Gene Ontology, and whose structures have a resolution under a defined threshold. The results of queries are provided in both machine-readable extensible markup language and human-readable format. The structures themselves can be viewed interactively on the web. The COLUMBA database facilitates the creation of protein structure data sets for many structure-based studies. It allows to combine queries on a number of structure-related databases not covered by other projects at present. Thus, information on both many and few protein structures can be used efficiently. The web interface for COLUMBA is available at http://www.columba-db.de.

Label-free specific detection of femtomolar cardiac troponin using an integrated nanoslit array fluidic diode.

PubMed

Liu, Yifan; Yobas, Levent

2014-12-10

We demonstrate here for the first time the utility of an integrated nanofluidic diode for detecting and quantifying physiologically relevant macromolecules. Troponin T, a key human cardiac protein biomarker, was selectively and rapidly detected free of labels for concentrations down to 10 fg/mL (∼ 0.3 fM) in buffer as well as 10 pg/mL (∼ 300 fM) in untreated human serum. This ultrasensitive detection arises from monolithic integration of a unique nanofluidic diode structure that is highly robust and amenable to site-specific surface modification. The structure features a planar nanoslit array where each nanoslit is defined at a nominal width of 70 nm over a micrometer-scale silicon trench without the use of high-resolution patterning techniques. Through vapor deposition, a glass layer is placed at a nonuniform thickness, tapering the trench profile upward and contributing to the triangular nanoslit structure. This asymmetric profile is essential for ionic current rectification noted here at various pH values, ionic strengths, and captured target species, which modulate the surface-charge density within the sensitive region of the nanoslit. The nanoslit, unlike nanopores, offers only 1D confinement, which appears to be adequate for reasonable rectification. The measurements are found in quantitative agreement with the diode simulations for the first time based on a pH- and salt-dependent surface-charge model.

A promising biodegradable magnesium alloy suitable for clinical vascular stent application

PubMed Central

Mao, Lin; shen, Li; Chen, Jiahui; Zhang, Xiaobo; Kwak, Minsuk; Wu, Yu; Fan, Rong; Zhang, Lei; Pei, Jia; Yuan, Guangyin; Song, Chengli; Ge, Junbo; Ding, Wenjiang

2017-01-01

We report a Mg alloy Mg-2.2Nd-0.1Zn-0.4Zr (wt.%, denoted as JDBM-2) showing great potential in clinical vascular stent application by integrating the advantages of traditional medical stainless steel and polymer. This alloy exhibits high yield strength and elongation of 276 ± 6 MPa and 34.3 ± 3.4% respectively. The JDBM-2 with a stable degradation surface results in a highly homogeneous degradation mechanism and long-term structural and mechanical durability. In vitro cytotoxicity test of the Mg extract via human vascular endothelial cells (HUVECs) indicates that the corrosion products are well tolerated by the tested cells and potentially negligible toxic effect on arterial vessel walls. This alloy also exhibits compromised foreign body response (FBR) determined by human peripheral blood derived macrophage adhesion, foreign body giant cell (FBGC) formation and inflammatory cytokine and chemokine secretion. Finally, vascular stents manufactured from the JDBM-2 were implanted into rabbits for long-term evaluation. The results confirm excellent tissue compatibility and up to 6-month structural and mechanical integrity of the stent in vivo. Thus, the JDBM-2 stent with up to 6-month structural and mechanical integrity and excellent tissue compatibility represents a major breakthrough in this field and a promising alternative to traditional medical stainless steel and polymer for the clinical application. PMID:28397881

Human Autoantibodies Reveal Titin as a Chromosomal Protein

PubMed Central

Machado, Cristina; Sunkel, Claudio E.; Andrew, Deborah J.

1998-01-01

Assembly of the higher-order structure of mitotic chromosomes is a prerequisite for proper chromosome condensation, segregation and integrity. Understanding the details of this process has been limited because very few proteins involved in the assembly of chromosome structure have been discovered. Using a human autoimmune scleroderma serum that identifies a chromosomal protein in human cells and Drosophila embryos, we cloned the corresponding Drosophila gene that encodes the homologue of vertebrate titin based on protein size, sequence similarity, developmental expression and subcellular localization. Titin is a giant sarcomeric protein responsible for the elasticity of striated muscle that may also function as a molecular scaffold for myofibrillar assembly. Molecular analysis and immunostaining with antibodies to multiple titin epitopes indicates that the chromosomal and muscle forms of titin may vary in their NH2 termini. The identification of titin as a chromosomal component provides a molecular basis for chromosome structure and elasticity. PMID:9548712

Brain-mapping projects using the common marmoset.

PubMed

Okano, Hideyuki; Mitra, Partha

2015-04-01

Globally, there is an increasing interest in brain-mapping projects, including the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative project in the USA, the Human Brain Project (HBP) in Europe, and the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) project in Japan. These projects aim to map the structure and function of neuronal circuits to ultimately understand the vast complexity of the human brain. Brain/MINDS is focused on structural and functional mapping of the common marmoset (Callithrix jacchus) brain. This non-human primate has numerous advantages for brain mapping, including a well-developed frontal cortex and a compact brain size, as well as the availability of transgenic technologies. In the present review article, we discuss strategies for structural and functional mapping of the marmoset brain and the relation of the common marmoset to other animals models. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Combining cognitive engineering and information fusion architectures to build effective joint systems

NASA Astrophysics Data System (ADS)

Sliva, Amy L.; Gorman, Joe; Voshell, Martin; Tittle, James; Bowman, Christopher

2016-05-01

The Dual Node Decision Wheels (DNDW) architecture concept was previously described as a novel approach toward integrating analytic and decision-making processes in joint human/automation systems in highly complex sociotechnical settings. In this paper, we extend the DNDW construct with a description of components in this framework, combining structures of the Dual Node Network (DNN) for Information Fusion and Resource Management with extensions on Rasmussen's Decision Ladder (DL) to provide guidance on constructing information systems that better serve decision-making support requirements. The DNN takes a component-centered approach to system design, decomposing each asset in terms of data inputs and outputs according to their roles and interactions in a fusion network. However, to ensure relevancy to and organizational fitment within command and control (C2) processes, principles from cognitive systems engineering emphasize that system design must take a human-centered systems view, integrating information needs and decision making requirements to drive the architecture design and capabilities of network assets. In the current work, we present an approach for structuring and assessing DNDW systems that uses a unique hybrid DNN top-down system design with a human-centered process design, combining DNN node decomposition with artifacts from cognitive analysis (i.e., system abstraction decomposition models, decision ladders) to provide work domain and task-level insights at different levels in an example intelligence, surveillance, and reconnaissance (ISR) system setting. This DNDW structure will ensure not only that the information fusion technologies and processes are structured effectively, but that the resulting information products will align with the requirements of human decision makers and be adaptable to different work settings .

Ethnicity and Population Structure in Personal Naming Networks

PubMed Central

Mateos, Pablo; Longley, Paul A.; O'Sullivan, David

2011-01-01

Personal naming practices exist in all human groups and are far from random. Rather, they continue to reflect social norms and ethno-cultural customs that have developed over generations. As a consequence, contemporary name frequency distributions retain distinct geographic, social and ethno-cultural patterning that can be exploited to understand population structure in human biology, public health and social science. Previous attempts to detect and delineate such structure in large populations have entailed extensive empirical analysis of naming conventions in different parts of the world without seeking any general or automated methods of population classification by ethno-cultural origin. Here we show how ‘naming networks’, constructed from forename-surname pairs of a large sample of the contemporary human population in 17 countries, provide a valuable representation of cultural, ethnic and linguistic population structure around the world. This innovative approach enriches and adds value to automated population classification through conventional national data sources such as telephone directories and electoral registers. The method identifies clear social and ethno-cultural clusters in such naming networks that extend far beyond the geographic areas in which particular names originated, and that are preserved even after international migration. Moreover, one of the most striking findings of this approach is that these clusters simply ‘emerge’ from the aggregation of millions of individual decisions on parental naming practices for their children, without any prior knowledge introduced by the researcher. Our probabilistic approach to community assignment, both at city level as well as at a global scale, helps to reveal the degree of isolation, integration or overlap between human populations in our rapidly globalising world. As such, this work has important implications for research in population genetics, public health, and social science adding new understandings of migration, identity, integration and social interaction across the world. PMID:21909399

Clinical trials bureaucracy: unintended consequences of well-intentioned policy.

PubMed

Califf, Robert M

2006-01-01

As randomized controlled trials have become the 'gold standard' for medical research, a complex regulatory structure for the conduct of clinical trials has emerged. However, this structure has not been adequately assessed to ensure that regulations governing human subjects research actually produce the desired effects. Our purpose is to identify some of the major shortcomings in the current regulatory system of human clinical trials oversight, and to propose some potential solutions to these problems. We discuss the evolution of the current US regulatory environment and its application in the context of several widely-used drug therapies. Despite numerous randomized controlled trials, performed within a structure of extensive documentation and data collection, serious shortcomings in a number of pharmaceutical therapies were not detected until after the drugs were approved and widely adopted by clinicians. The current system of regulatory bureaucracy in clinical trials has led to an extremely expensive research paradigm that, in spite of complex systems of oversight and exhaustive data collection, cannot be shown to adequately ensure the integrity of the research process and the protection of human research subjects. Some parts of the system, including Research Ethics Review Boards, may not be well-suited to carrying out their core mission of overseeing research conduct, and other aspects of clinical trials regulatory structure, such as monitoring/auditing review and adverse event reporting, may constitute a waste of money and resources. Misdirected data collection and adverse events reporting divert valuable resources and hamper development of large, simple clinical trials powered to definitively answer important research questions. Careful scrutiny of the utility of current or proposed regulatory schemes is required to ensure the integrity of human subjects research and to enhance the effectiveness of research dollars.

HESTIA Commodities Exchange Pallet and Sounding Rocket Test Stand

NASA Technical Reports Server (NTRS)

Chaparro, Javier

2013-01-01

During my Spring 2016 internship, my two major contributions were the design of the Commodities Exchange Pallet and the design of a test stand for a 100 pounds-thrust sounding rocket. The Commodities Exchange Pallet is a prototype developed for the Human Exploration Spacecraft Testbed for Integration and Advancement (HESTIA) program. Under the HESTIA initiative the Commodities Exchange Pallet was developed as a method for demonstrating multi-system integration thru the transportation of In-Situ Resource Utilization produced oxygen and water to a human habitat. Ultimately, this prototype's performance will allow for future evaluation of integration, which may lead to the development of a flight capable pallet for future deep-space exploration missions. For HESTIA, my main task was to design the Commodities Exchange Pallet system to be used for completing an integration demonstration. Under the guidance of my mentor, I designed, both, the structural frame and fluid delivery system for the commodities pallet. The fluid delivery system includes a liquid-oxygen to gaseous-oxygen system, a water delivery system, and a carbon-dioxide compressors system. The structural frame is designed to meet safety and transportation requirements, as well as the ability to interface with the ER division's Portable Utility Pallet. The commodities pallet structure also includes independent instrumentation oxygen/water panels for operation and system monitoring. My major accomplishments for the commodities exchange pallet were the completion of the fluid delivery systems and the structural frame designs. In addition, parts selection was completed in order to expedite construction of the prototype, scheduled to begin in May of 2016. Once the commodities pallet is assembled and tested it is expected to complete a fully integrated transfer demonstration with the ISRU unit and the Environmental Control and Life Support System test chamber in September of 2016. In addition to the development of the Commodities Exchange Pallet, I also assisted in preparation for testing the upper stage of a sounding rocket developed as a Center Innovation Fund project. The main objective of this project is to demonstrate the integration between a propulsion system and a solid oxide fuel cell (SOFC). The upper stage and SOFC are scheduled to complete an integrated test in August of 2016. As part of preparation for scheduled testing, I was responsible for designing the upper stage's test stand/support structure and main engine plume deflector to be used during hot-fire testing (fig. 3). The structural components of the test stand need to meet safety requirements for operation of the propulsion system, which consist of a 100 pounds-thrust main engine and two 15 pounds-thrust reaction control thrusters. My main accomplishment for this project was the completion of the design and the parts selection for construction of the structure, scheduled to begin late April of 2016.

Characterizing and Mapping of Ecosystem Services (CMESs) Literature Database Version 1.0

EPA Science Inventory

Ecosystem services (ESs) represent an ecosystem’s capacity for satisfying essential human needs, directly or indirectly, above that required to maintain ecosystem integrity (structure, function and processes). The spatial characterization and mapping of ESs is an essential first ...

In vitro cell transformation assays for an integrated, alternative assessment of carcinogenicity: a data-based analysis.

PubMed

Benigni, Romualdo; Bossa, Cecilia; Tcheremenskaia, Olga

2013-01-01

The study of the chemical carcinogenesis mechanisms and the design of efficient prevention strategies and measures are of crucial importance to protect human health. The long-term carcinogenesis bioassays have played a central role in protecting human health, but for ethical and practical reasons their use is dramatically diminishing, and the genotoxicity short-term tests have taken the pivotal role in the pre-screening of carcinogenicity. However, there is evidence that this strategy is not sensitive enough to detect all genotoxic carcinogens and it cannot detect nongenotoxic carcinogens. In a previous article, we have shown that an integrated strategy consisting of the in vitro Ames and Syrian Hamster Embryo cells transformation assays, combined with structure-activity relationships, is a valid alternative to the present pre-screening strategies. Here, we expand the previous investigation by (i) including results of cell transformation assays on inorganics, together with an additional assay (Bhas 42), and (ii) considering new structural alerts for nongenotoxic carcinogenicity. We also present a new analysis on global relationships between toxicological endpoints. The new results confirm that the previously proposed integrated, alternative strategy is an efficient tool to identify both genotoxic and nongenotoxic carcinogens, with an estimated 90-95% sensitivity.

Structural characterisation of medically relevant protein assemblies by integrating mass spectrometry with computational modelling.

PubMed

Politis, Argyris; Schmidt, Carla

2018-03-20

Structural mass spectrometry with its various techniques is a powerful tool for the structural elucidation of medically relevant protein assemblies. It delivers information on the composition, stoichiometries, interactions and topologies of these assemblies. Most importantly it can deal with heterogeneous mixtures and assemblies which makes it universal among the conventional structural techniques. In this review we summarise recent advances and challenges in structural mass spectrometric techniques. We describe how the combination of the different mass spectrometry-based methods with computational strategies enable structural models at molecular levels of resolution. These models hold significant potential for helping us in characterizing the function of protein assemblies related to human health and disease. In this review we summarise the techniques of structural mass spectrometry often applied when studying protein-ligand complexes. We exemplify these techniques through recent examples from literature that helped in the understanding of medically relevant protein assemblies. We further provide a detailed introduction into various computational approaches that can be integrated with these mass spectrometric techniques. Last but not least we discuss case studies that integrated mass spectrometry and computational modelling approaches and yielded models of medically important protein assembly states such as fibrils and amyloids. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Emulation as an Integrating Principle for Cognition

PubMed Central

Colder, Brian

2011-01-01

Emulations, defined as ongoing internal representations of potential actions and the futures those actions are expected to produce, play a critical role in directing human bodily activities. Studies of gross motor behavior, perception, allocation of attention, response to errors, interoception, and homeostatic activities, and higher cognitive reasoning suggest that the proper execution of all these functions relies on emulations. Further evidence supports the notion that reinforcement learning in humans is aimed at updating emulations, and that action selection occurs via the advancement of preferred emulations toward realization of their action and environmental prediction. Emulations are hypothesized to exist as distributed active networks of neurons in cortical and sub-cortical structures. This manuscript ties together previously unrelated theories of the role of prediction in different aspects of human information processing to create an integrated framework for cognition. PMID:21660288

Neuromandibular integration in humans and chimpanzees: Implications for dental and mandibular reduction in Homo.

PubMed

Veneziano, Alessio; Meloro, Carlo; Irish, Joel D; Stringer, Chris; Profico, Antonio; De Groote, Isabelle

2018-05-08

Although the evolution of the hominin masticatory apparatus has been linked to diet and food processing, the physical connection between neurocranium and lower jaw suggests a role of encephalization in the trend of dental and mandibular reduction. Here, the hypothesis that tooth size and mandibular robusticity are influenced by morphological changes in the neurocranium was tested. Three-dimensional landmarks, alveolar lengths, and mandibular robusticity data were recorded on a sample of chimpanzee and human skulls. The morphological integration between the neurocranium and the lower jaw was analyzed by means of Singular Warps Analysis. Redundancy Analysis was performed to understand if the pattern of neuromandibular integration affects tooth size and mandibular robusticity. There is significant morphological covariation between neurocranium and lower jaw in both chimpanzees and humans. In humans, changes in the temporal fossa seem to produce alterations of the relative orientation of jaw parts, while the influence of similar neurocranial changes in chimpanzees are more localized. In both species, postcanine alveolar lengths and mandibular robusticity are associated with shape changes of the temporal fossa. The results of this study support the hypothesis that the neurocranium is able to affect the evolution and development of the lower jaw, although most likely through functional integration of mandible, teeth, and muscles within the masticatory apparatus. This study highlights the relative influence of structural constraints and adaptive factors in the evolution of the human skull. © 2018 Wiley Periodicals, Inc.

The RCSB protein data bank: integrative view of protein, gene and 3D structural information

PubMed Central

Rose, Peter W.; Prlić, Andreas; Altunkaya, Ali; Bi, Chunxiao; Bradley, Anthony R.; Christie, Cole H.; Costanzo, Luigi Di; Duarte, Jose M.; Dutta, Shuchismita; Feng, Zukang; Green, Rachel Kramer; Goodsell, David S.; Hudson, Brian; Kalro, Tara; Lowe, Robert; Peisach, Ezra; Randle, Christopher; Rose, Alexander S.; Shao, Chenghua; Tao, Yi-Ping; Valasatava, Yana; Voigt, Maria; Westbrook, John D.; Woo, Jesse; Yang, Huangwang; Young, Jasmine Y.; Zardecki, Christine; Berman, Helen M.; Burley, Stephen K.

2017-01-01

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB, http://rcsb.org), the US data center for the global PDB archive, makes PDB data freely available to all users, from structural biologists to computational biologists and beyond. New tools and resources have been added to the RCSB PDB web portal in support of a ‘Structural View of Biology.’ Recent developments have improved the User experience, including the high-speed NGL Viewer that provides 3D molecular visualization in any web browser, improved support for data file download and enhanced organization of website pages for query, reporting and individual structure exploration. Structure validation information is now visible for all archival entries. PDB data have been integrated with external biological resources, including chromosomal position within the human genome; protein modifications; and metabolic pathways. PDB-101 educational materials have been reorganized into a searchable website and expanded to include new features such as the Geis Digital Archive. PMID:27794042

Reverse engineering the cooperative machinery of human hemoglobin.

PubMed

Ren, Zhong

2013-01-01

Hemoglobin transports molecular oxygen from the lungs to all human tissues for cellular respiration. Its α2β2 tetrameric assembly undergoes cooperative binding and releasing of oxygen for superior efficiency and responsiveness. Over past decades, hundreds of hemoglobin structures were determined under a wide range of conditions for investigation of molecular mechanism of cooperativity. Based on a joint analysis of hemoglobin structures in the Protein Data Bank (Ren, companion article), here I present a reverse engineering approach to elucidate how two subunits within each dimer reciprocate identical motions that achieves intradimer cooperativity, how ligand-induced structural signals from two subunits are integrated to drive quaternary rotation, and how the structural environment at the oxygen binding sites alter their binding affinity. This mechanical model reveals the intricate design that achieves the cooperative mechanism and has previously been masked by inconsistent structural fluctuations. A number of competing theories on hemoglobin cooperativity and broader protein allostery are reconciled and unified.

Measuring changes in chemistry, composition, and molecular structure within hair fibers by infrared and Raman spectroscopic imaging.

PubMed

Zhang, Guojin; Senak, Laurence; Moore, David J

2011-05-01

Spatially resolved infrared (IR) and Raman images are acquired from human hair cross sections or intact hair fibers. The full informational content of these spectra are spatially correlated to hair chemistry, anatomy, and structural organization through univariate and multivariate data analysis. Specific IR and Raman images from untreated human hair describing the spatial dependence of lipid and protein distribution, protein secondary structure, lipid chain conformational order, and distribution of disulfide cross-links in hair protein are presented in this study. Factor analysis of the image plane acquired with IR microscopy in hair sections, permits delineation of specific micro-regions within the hair. These data indicate that both IR and Raman imaging of molecular structural changes in a specific region of hair will prove to be valuable tools in the understanding of hair structure, physiology, and the effect of various stresses upon its integrity.

Radiation-Shielding Polymer/Soil Composites

NASA Technical Reports Server (NTRS)

Sen, Subhayu

2007-01-01

It has been proposed to fabricate polymer/ soil composites primarily from extraterrestrial resources, using relatively low-energy processes, with the original intended application being that habitat structures constructed from such composites would have sufficient structural integrity and also provide adequate radiation shielding for humans and sensitive electronic equipment against the radiation environment on the Moon and Mars. The proposal is a response to the fact that it would be much less expensive to fabricate such structures in situ as opposed to transporting them from Earth.

Effect of biocompatible polymers on the structural integrity of lipid bilayers under external stimuli

NASA Astrophysics Data System (ADS)

Wang, Jia-Yu; Kausik, Ravinath; Chen, Chi-Yuan; Han, Song-I.; Marks, Jeremy; Lee, Ka Yee

2010-03-01

Cell membrane dysfunction due to loss of structural integrity is the pathology of tissue death in trauma and common diseases. It is now established that certain biocompatible polymers, such as Poloxamer 188, Poloxamine 1107 and polyethylene glycol (PEG), are effective in sealing of injured cell membranes, and able to prevent acute necrosis. Despite these broad applications of these polymers for human health, the fundamental mechanisms by which these polymers interact with cell membranes are still under debate. Here, the effects of a group of biocompatible polymers on phospholipid membrane integrity under osmotic and oxidative stress were explored using giant unilamellar vesicles as model cell membranes. Our results suggest that the adsorption of the polymers on the membrane surface is responsible for the cell membrane resealing process due to its capability of slowing down the surface hydration dynamics.

Causal learning and inference as a rational process: the new synthesis.

PubMed

Holyoak, Keith J; Cheng, Patricia W

2011-01-01

Over the past decade, an active line of research within the field of human causal learning and inference has converged on a general representational framework: causal models integrated with bayesian probabilistic inference. We describe this new synthesis, which views causal learning and inference as a fundamentally rational process, and review a sample of the empirical findings that support the causal framework over associative alternatives. Causal events, like all events in the distal world as opposed to our proximal perceptual input, are inherently unobservable. A central assumption of the causal approach is that humans (and potentially nonhuman animals) have been designed in such a way as to infer the most invariant causal relations for achieving their goals based on observed events. In contrast, the associative approach assumes that learners only acquire associations among important observed events, omitting the representation of the distal relations. By incorporating bayesian inference over distributions of causal strength and causal structures, along with noisy-logical (i.e., causal) functions for integrating the influences of multiple causes on a single effect, human judgments about causal strength and structure can be predicted accurately for relatively simple causal structures. Dynamic models of learning based on the causal framework can explain patterns of acquisition observed with serial presentation of contingency data and are consistent with available neuroimaging data. The approach has been extended to a diverse range of inductive tasks, including category-based and analogical inferences.

The Added Value of Integrating Emergy into LCA

EPA Science Inventory

Life Cycle Assessment (LCA) has become a standard procedure to investigate the environmental performance of human-dominated products and processes. It is meant to capture the overall impact of a product or service along its lifetime and supply chain, and it is structured in four ...

Graph Learning in Knowledge Bases

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

Goldberg, Sean; Wang, Daisy Zhe

The amount of text data has been growing exponentially in recent years, giving rise to automatic information extraction methods that store text annotations in a database. The current state-of-theart structured prediction methods, however, are likely to contain errors and it’s important to be able to manage the overall uncertainty of the database. On the other hand, the advent of crowdsourcing has enabled humans to aid machine algorithms at scale. As part of this project we introduced pi-CASTLE , a system that optimizes and integrates human and machine computing as applied to a complex structured prediction problem involving conditional random fieldsmore » (CRFs). We proposed strategies grounded in information theory to select a token subset, formulate questions for the crowd to label, and integrate these labelings back into the database using a method of constrained inference. On both a text segmentation task over academic citations and a named entity recognition task over tweets we showed an order of magnitude improvement in accuracy gain over baseline methods.« less

Anatomically correct visualization of the human upper airway using a high-speed long range optical coherence tomography system with an integrated positioning sensor

NASA Astrophysics Data System (ADS)

Jing, Joseph C.; Chou, Lidek; Su, Erica; Wong, Brian J. F.; Chen, Zhongping

2016-12-01

The upper airway is a complex tissue structure that is prone to collapse. Current methods for studying airway obstruction are inadequate in safety, cost, or availability, such as CT or MRI, or only provide localized qualitative information such as flexible endoscopy. Long range optical coherence tomography (OCT) has been used to visualize the human airway in vivo, however the limited imaging range has prevented full delineation of the various shapes and sizes of the lumen. We present a new long range OCT system that integrates high speed imaging with a real-time position tracker to allow for the acquisition of an accurate 3D anatomical structure in vivo. The new system can achieve an imaging range of 30 mm at a frame rate of 200 Hz. The system is capable of generating a rapid and complete visualization and quantification of the airway, which can then be used in computational simulations to determine obstruction sites.

Student-centered integrated anatomy resource sessions at Alfaisal University.

PubMed

Cowan, Michèle; Arain, Nasir Nisar; Assale, Tawfic Samer Abu; Assi, Abdulelah Hassan; Albar, Raed Alwai; Ganguly, Paul K

2010-01-01

Alfaisal University is a new medical school in Riyadh, Kingdom of Saudi Arabia that matriculates eligible students directly from high school and requires them to participate in a hybrid problem-based learning (PBL) curriculum. PBL is a well-established student-centered approach, and the authors have sought to examine if a student-centered, integrated approach to learn human structures leads to positive perceptions of learning outcomes. Ten students were divided into four groups to rotate through wet and dry laboratory stations (integrated resource sessions, IRSs) that engaged them in imaging techniques, embryology, histology, gross anatomy (dissections and prosections), surface anatomy, and self-directed learning questions. All IRSs were primarily directed by students. During two second-semester organ system blocks, forty students responded to a structured questionnaire designed to poll students' perceptions of changes in their knowledge, skills, and attitudes as a result of IRS. The majority (60%) of students felt that the student-centered approach to learning enhanced their medical knowledge. Most students also felt that the IRS approach was advantageous for formulating clear learning objectives (55%) and in preparing for examinations (65%). Despite their positive feelings toward IRS, students did not view this learning approach as an adequate replacement for the knowledge gained from lectures and textbooks. Students' performance on objective structured practical examinations improved significantly for the two curricular blocks that included IRS compared with earlier non-IRS blocks. A student-centered approach to teach human structure in a hybrid PBL curriculum may enhance understanding of the basic sciences in first-year medical students.

Complete Genome Sequence of Germline Chromosomally Integrated Human Herpesvirus 6A and Analyses Integration Sites Define a New Human Endogenous Virus with Potential to Reactivate as an Emerging Infection.

PubMed

Tweedy, Joshua; Spyrou, Maria Alexandra; Pearson, Max; Lassner, Dirk; Kuhl, Uwe; Gompels, Ursula A

2016-01-15

Human herpesvirus-6A and B (HHV-6A, HHV-6B) have recently defined endogenous genomes, resulting from integration into the germline: chromosomally-integrated "CiHHV-6A/B". These affect approximately 1.0% of human populations, giving potential for virus gene expression in every cell. We previously showed that CiHHV-6A was more divergent than CiHHV-6B by examining four genes in 44 European CiHHV-6A/B cardiac/haematology patients. There was evidence for gene expression/reactivation, implying functional non-defective genomes. To further define the relationship between HHV-6A and CiHHV-6A we used next-generation sequencing to characterize genomes from three CiHHV-6A cardiac patients. Comparisons to known exogenous HHV-6A showed CiHHV-6A genomes formed a separate clade; including all 85 non-interrupted genes and necessary cis-acting signals for reactivation as infectious virus. Greater single nucleotide polymorphism (SNP) density was defined in 16 genes and the direct repeats (DR) terminal regions. Using these SNPs, deep sequencing analyses demonstrated superinfection with exogenous HHV-6A in two of the CiHHV-6A patients with recurrent cardiac disease. Characterisation of the integration sites in twelve patients identified the human chromosome 17p subtelomere as a prevalent site, which had specific repeat structures and phylogenetically related CiHHV-6A coding sequences indicating common ancestral origins. Overall CiHHV-6A genomes were similar, but distinct from known exogenous HHV-6A virus, and have the capacity to reactivate as emerging virus infections.

Complete Genome Sequence of Germline Chromosomally Integrated Human Herpesvirus 6A and Analyses Integration Sites Define a New Human Endogenous Virus with Potential to Reactivate as an Emerging Infection

PubMed Central

Tweedy, Joshua; Spyrou, Maria Alexandra; Pearson, Max; Lassner, Dirk; Kuhl, Uwe; Gompels, Ursula A.

2016-01-01

Human herpesvirus-6A and B (HHV-6A, HHV-6B) have recently defined endogenous genomes, resulting from integration into the germline: chromosomally-integrated “CiHHV-6A/B”. These affect approximately 1.0% of human populations, giving potential for virus gene expression in every cell. We previously showed that CiHHV-6A was more divergent than CiHHV-6B by examining four genes in 44 European CiHHV-6A/B cardiac/haematology patients. There was evidence for gene expression/reactivation, implying functional non-defective genomes. To further define the relationship between HHV-6A and CiHHV-6A we used next-generation sequencing to characterize genomes from three CiHHV-6A cardiac patients. Comparisons to known exogenous HHV-6A showed CiHHV-6A genomes formed a separate clade; including all 85 non-interrupted genes and necessary cis-acting signals for reactivation as infectious virus. Greater single nucleotide polymorphism (SNP) density was defined in 16 genes and the direct repeats (DR) terminal regions. Using these SNPs, deep sequencing analyses demonstrated superinfection with exogenous HHV-6A in two of the CiHHV-6A patients with recurrent cardiac disease. Characterisation of the integration sites in twelve patients identified the human chromosome 17p subtelomere as a prevalent site, which had specific repeat structures and phylogenetically related CiHHV-6A coding sequences indicating common ancestral origins. Overall CiHHV-6A genomes were similar, but distinct from known exogenous HHV-6A virus, and have the capacity to reactivate as emerging virus infections. PMID:26784220

Rapid assessment of the antigenic integrity of tetrameric HLA complexes by human monoclonal HLA antibodies.

PubMed

Eijsink, Chantal; Kester, Michel G D; Franke, Marry E I; Franken, Kees L M C; Heemskerk, Mirjam H M; Claas, Frans H J; Mulder, Arend

2006-08-31

The ability of tetrameric major histocompatibility complex (MHC) class I-peptide complexes (tetramers) to detect antigen-specific T lymphocyte responses has yielded significant information about the generation of in vivo immunity in numerous antigenic systems. Here we present a novel method for rapid validation of tetrameric HLA molecules based on the presence of allodeterminants. Human monoclonal antibodies (mAbs) recognizing polymorphic determinants on HLA class I were immobilized on polystyrene microparticles and used to probe the structural integrity of tetrameric HLA class I molecules by flow cytometry. A total of 22 tetramers, based on HLA-A1, A2, A3, A24, B7 and B8 were reactive with their counterpart mAbs, thus confirming their antigenic integrity. A positive outcome of this mAb test ensures that tetrameric HLA class I can be used with greater confidence in subsequent functional assays.

Seeking Synthesis: The Integrative Problem in Understanding Language and Its Evolution.

PubMed

Dale, Rick; Kello, Christopher T; Schoenemann, P Thomas

2016-04-01

We discuss two problems for a general scientific understanding of language, sequences and synergies: how language is an intricately sequenced behavior and how language is manifested as a multidimensionally structured behavior. Though both are central in our understanding, we observe that the former tends to be studied more than the latter. We consider very general conditions that hold in human brain evolution and its computational implications, and identify multimodal and multiscale organization as two key characteristics of emerging cognitive function in our species. This suggests that human brains, and cognitive function specifically, became more adept at integrating diverse information sources and operating at multiple levels for linguistic performance. We argue that framing language evolution, learning, and use in terms of synergies suggests new research questions, and it may be a fruitful direction for new developments in theory and modeling of language as an integrated system. Copyright © 2016 Cognitive Science Society, Inc.

Marrying Hydrological Modelling and Integrated Assessment for the needs of Water Resource Management

NASA Astrophysics Data System (ADS)

Croke, B. F. W.; Blakers, R. S.; El Sawah, S.; Fu, B.; Guillaume, J. H. A.; Kelly, R. A.; Patrick, M. J.; Ross, A.; Ticehurst, J.; Barthel, R.; Jakeman, A. J.

2014-09-01

This paper discusses the integration of hydrology with other disciplines using an Integrated Assessment (IA) and modelling approach to the management and allocation of water resources. Recent developments in the field of socio-hydrology aim to develop stronger relationships between hydrology and the human dimensions of Water Resource Management (WRM). This should build on an existing wealth of knowledge and experience of coupled human-water systems. To further strengthen this relationship and contribute to this broad body of knowledge, we propose a strong and durable "marriage" between IA and hydrology. The foundation of this marriage requires engagement with appropriate concepts, model structures, scales of analyses, performance evaluation and communication - and the associated tools and models that are needed for pragmatic deployment or operation. To gain insight into how this can be achieved, an IA case study in water allocation in the Lower Namoi catchment, NSW, Australia is presented.

Space Structure Development

NASA Technical Reports Server (NTRS)

Smith, Thomas

2015-01-01

The duration of my Summer 2015 Internship Tour at NASA's Johnson Space Center was spent working in the Structural Engineering Division's Structures Branch. One of the two main roles of the Structures Branch, ES2, is to ensure the structural integrity of spacecraft vehicles and the structural subsystems needed to support those vehicles. The other main objective of this branch is to develop the lightweight structures that are necessary to take humans beyond Low-Earth Orbit. Within ES2, my four projects involved inflatable space structure air bladder material testing; thermal and impact material testing for spacecraft windows; structural analysis on a joint used in the Boeing CST-100 airbag system; and an additive manufacturing design project.

Nondestructive cryomicro-CT imaging enables structural and molecular analysis of human lung tissue.

PubMed

Vasilescu, Dragoş M; Phillion, André B; Tanabe, Naoya; Kinose, Daisuke; Paige, David F; Kantrowitz, Jacob J; Liu, Gang; Liu, Hanqiao; Fishbane, Nick; Verleden, Stijn E; Vanaudenaerde, Bart M; Lenburg, Marc; Stevenson, Christopher S; Spira, Avrum; Cooper, Joel D; Hackett, Tillie-Louise; Hogg, James C

2017-01-01

Micro-computed tomography (CT) enables three-dimensional (3D) imaging of complex soft tissue structures, but current protocols used to achieve this goal preclude cellular and molecular phenotyping of the tissue. Here we describe a radiolucent cryostage that permits micro-CT imaging of unfixed frozen human lung samples at an isotropic voxel size of (11 µm) 3 under conditions where the sample is maintained frozen at -30°C during imaging. The cryostage was tested for thermal stability to maintain samples frozen up to 8 h. This report describes the methods used to choose the materials required for cryostage construction and demonstrates that whole genome mRNA integrity and expression are not compromised by exposure to micro-CT radiation and that the tissue can be used for immunohistochemistry. The new cryostage provides a novel method enabling integration of 3D tissue structure with cellular and molecular analysis to facilitate the identification of molecular determinants of disease. The described micro-CT cryostage provides a novel way to study the three-dimensional lung structure preserved without the effects of fixatives while enabling subsequent studies of the cellular matrix composition and gene expression. This approach will, for the first time, enable researchers to study structural changes of lung tissues that occur with disease and correlate them with changes in gene or protein signatures. Copyright © 2017 the American Physiological Society.

An Adaptive Complex Network Model for Brain Functional Networks

PubMed Central

Gomez Portillo, Ignacio J.; Gleiser, Pablo M.

2009-01-01

Brain functional networks are graph representations of activity in the brain, where the vertices represent anatomical regions and the edges their functional connectivity. These networks present a robust small world topological structure, characterized by highly integrated modules connected sparsely by long range links. Recent studies showed that other topological properties such as the degree distribution and the presence (or absence) of a hierarchical structure are not robust, and show different intriguing behaviors. In order to understand the basic ingredients necessary for the emergence of these complex network structures we present an adaptive complex network model for human brain functional networks. The microscopic units of the model are dynamical nodes that represent active regions of the brain, whose interaction gives rise to complex network structures. The links between the nodes are chosen following an adaptive algorithm that establishes connections between dynamical elements with similar internal states. We show that the model is able to describe topological characteristics of human brain networks obtained from functional magnetic resonance imaging studies. In particular, when the dynamical rules of the model allow for integrated processing over the entire network scale-free non-hierarchical networks with well defined communities emerge. On the other hand, when the dynamical rules restrict the information to a local neighborhood, communities cluster together into larger ones, giving rise to a hierarchical structure, with a truncated power law degree distribution. PMID:19738902

Conceptual framework for a Danish human biomonitoring program

PubMed Central

Thomsen, Marianne; Knudsen, Lisbeth E; Vorkamp, Katrin; Frederiksen, Marie; Bach, Hanne; Bonefeld-Jorgensen, Eva Cecilie; Rastogi, Suresch; Fauser, Patrik; Krongaard, Teddy; Sorensen, Peter Borgen

2008-01-01

The aim of this paper is to present the conceptual framework for a Danish human biomonitoring (HBM) program. The EU and national science-policy interface, that is fundamental for a realization of the national and European environment and human health strategies, is discussed, including the need for a structured and integrated environmental and human health surveillance program at national level. In Denmark, the initiative to implement such activities has been taken. The proposed framework of the Danish monitoring program constitutes four scientific expert groups, i.e. i. Prioritization of the strategy for the monitoring program, ii. Collection of human samples, iii. Analysis and data management and iv. Dissemination of results produced within the program. This paper presents the overall framework for data requirements and information flow in the integrated environment and health surveillance program. The added value of an HBM program, and in this respect the objectives of national and European HBM programs supporting environmental health integrated policy-decisions and human health targeted policies, are discussed. In Denmark environmental monitoring has been prioritized by extensive surveillance systems of pollution in oceans, lakes and soil as well as ground and drinking water. Human biomonitoring has only taken place in research programs and few incidences of e.g. lead contamination. However an arctic program for HBM has been in force for decades and from the preparations of the EU-pilot project on HBM increasing political interest in a Danish program has developed. PMID:18541069

Ultra-Structure database design methodology for managing systems biology data and analyses

PubMed Central

Maier, Christopher W; Long, Jeffrey G; Hemminger, Bradley M; Giddings, Morgan C

2009-01-01

Background Modern, high-throughput biological experiments generate copious, heterogeneous, interconnected data sets. Research is dynamic, with frequently changing protocols, techniques, instruments, and file formats. Because of these factors, systems designed to manage and integrate modern biological data sets often end up as large, unwieldy databases that become difficult to maintain or evolve. The novel rule-based approach of the Ultra-Structure design methodology presents a potential solution to this problem. By representing both data and processes as formal rules within a database, an Ultra-Structure system constitutes a flexible framework that enables users to explicitly store domain knowledge in both a machine- and human-readable form. End users themselves can change the system's capabilities without programmer intervention, simply by altering database contents; no computer code or schemas need be modified. This provides flexibility in adapting to change, and allows integration of disparate, heterogenous data sets within a small core set of database tables, facilitating joint analysis and visualization without becoming unwieldy. Here, we examine the application of Ultra-Structure to our ongoing research program for the integration of large proteomic and genomic data sets (proteogenomic mapping). Results We transitioned our proteogenomic mapping information system from a traditional entity-relationship design to one based on Ultra-Structure. Our system integrates tandem mass spectrum data, genomic annotation sets, and spectrum/peptide mappings, all within a small, general framework implemented within a standard relational database system. General software procedures driven by user-modifiable rules can perform tasks such as logical deduction and location-based computations. The system is not tied specifically to proteogenomic research, but is rather designed to accommodate virtually any kind of biological research. Conclusion We find Ultra-Structure offers substantial benefits for biological information systems, the largest being the integration of diverse information sources into a common framework. This facilitates systems biology research by integrating data from disparate high-throughput techniques. It also enables us to readily incorporate new data types, sources, and domain knowledge with no change to the database structure or associated computer code. Ultra-Structure may be a significant step towards solving the hard problem of data management and integration in the systems biology era. PMID:19691849

Massive integration of diverse protein quality assessment methods to improve template based modeling in CASP11

PubMed Central

Cao, Renzhi; Bhattacharya, Debswapna; Adhikari, Badri; Li, Jilong; Cheng, Jianlin

2015-01-01

Model evaluation and selection is an important step and a big challenge in template-based protein structure prediction. Individual model quality assessment methods designed for recognizing some specific properties of protein structures often fail to consistently select good models from a model pool because of their limitations. Therefore, combining multiple complimentary quality assessment methods is useful for improving model ranking and consequently tertiary structure prediction. Here, we report the performance and analysis of our human tertiary structure predictor (MULTICOM) based on the massive integration of 14 diverse complementary quality assessment methods that was successfully benchmarked in the 11th Critical Assessment of Techniques of Protein Structure prediction (CASP11). The predictions of MULTICOM for 39 template-based domains were rigorously assessed by six scoring metrics covering global topology of Cα trace, local all-atom fitness, side chain quality, and physical reasonableness of the model. The results show that the massive integration of complementary, diverse single-model and multi-model quality assessment methods can effectively leverage the strength of single-model methods in distinguishing quality variation among similar good models and the advantage of multi-model quality assessment methods of identifying reasonable average-quality models. The overall excellent performance of the MULTICOM predictor demonstrates that integrating a large number of model quality assessment methods in conjunction with model clustering is a useful approach to improve the accuracy, diversity, and consequently robustness of template-based protein structure prediction. PMID:26369671

High Fidelity Additive Manufacturing of Optically Transparent Glass Structures

NASA Astrophysics Data System (ADS)

Inamura, Chikara

Glass has been an integral part of human civilization with expressions across scales and disciplines: from the microscope to the telescope, from fiber optics to mobile interface, and from the petri dish to a building envelope. Such a diverse range of applications is enabled by the inherent material properties including mechanical strength, optical transparency and chemical inertness. Additive manufacturing provides opportunities for integrating the unique properties of glass to engineer novel structures that are functionary graded through precise spatiotemporal deposition of molten glass. This talk presents the Mediated Matter Group's latest development of a novel additive manufacturing platform, and related processes, for 3D Printing optically transparent glass for architectural scale applications.

The functional and structural asymmetries of the superior temporal sulcus.

PubMed

Specht, Karsten; Wigglesworth, Philip

2018-02-01

The superior temporal sulcus (STS) is an anatomical structure that increasingly interests researchers. This structure appears to receive multisensory input and is involved in several perceptual and cognitive core functions, such as speech perception, audiovisual integration, (biological) motion processing and theory of mind capacities. In addition, the superior temporal sulcus is not only one of the longest sulci of the brain, but it also shows marked functional and structural asymmetries, some of which have only been found in humans. To explore the functional-structural relationships of these asymmetries in more detail, this study combines functional and structural magnetic resonance imaging. Using a speech perception task, an audiovisual integration task, and a theory of mind task, this study again demonstrated an involvement of the STS in these processes, with an expected strong leftward asymmetry for the speech perception task. Furthermore, this study confirmed the earlier described, human-specific asymmetries, namely that the left STS is longer than the right STS and that the right STS is deeper than the left STS. However, this study did not find any relationship between these structural asymmetries and the detected brain activations or their functional asymmetries. This can, on the other hand, give further support to the notion that the structural asymmetry of the STS is not directly related to the functional asymmetry of the speech perception and the language system as a whole, but that it may have other causes and functions. © 2018 The Authors. Scandinavian Journal of Psychology published by Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Integrated Environmental Modelling: Human decisions, human challenges

USGS Publications Warehouse

Glynn, Pierre D.

2015-01-01

Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

Loss of Neuronal Integrity During Progressive HIV-1 Infection of Humanized Mice

PubMed Central

Dash, Prasanta K.; Gorantla, Santhi; Gendelman, Howard E; Knibbe, Jaclyn; Casale, George P; Makarov, Edward; Epstein, Adrian A; Gelbard, Harris A; Boska, Michael D; Poluektova, Larisa Y

2011-01-01

Neuronal damage induced by ongoing HIV-1 infection was investigated in humanized NOD/scid-IL-2Rgcnull mice transplanted at birth with human CD34-positive hematopoietic stem cells. Mice infected at 5 months of age and followed for up to 15 weeks maintained significant plasma viral loads and showed reduced numbers of CD4+ T cells. Prospective serial proton magnetic resonance spectroscopy tests showed selective reductions in cortical N-acetyl aspartate in infected animals. Diffusion tensor imaging revealed structural changes in cortical gray matter. Postmortem immunofluorescence brain tissue examinations for neuronal and glial markers, captured by multispectral imaging microscopy and quantified by morphometric and fluorescence emission, showed regional reduction of neuronal soma and synaptic architectures. This was evidenced by loss of microtubule-associated protein 2, synaptophysin and neurofilament antigens. This study is the first, to our knowledge, demonstrating lost neuronal integrity following HIV-1 infection in humanized mice. As such, the model permits studies of the relationships between ongoing viral replication and virus-associated neurodegeneration. PMID:21368026

A Progression of Static Equilibrium Laboratory Exercises

ERIC Educational Resources Information Center

Kutzner, Mickey; Kutzner, Andrew

2013-01-01

Although simple architectural structures like bridges, catwalks, cantilevers, and Stonehenge have been integral in human societies for millennia, as have levers and other simple tools, modern students of introductory physics continue to grapple with Newton's conditions for static equilibrium. As formulated in typical introductory physics…

The "Science of HRD Research": Reshaping HRD Research through Scientometrics

ERIC Educational Resources Information Center

Wang, Greg G.; Gilley, Jerry W.; Sun, Judy Y.

2012-01-01

We explore opportunities for assessing and advancing Human Resource Development (HRD) research through an integrative literature review of scientometric theories and methods. Known as the "science of science," scientometrics is concerned with the quantitative study of scholarly communications, disciplinary structure and assessment and measurement…

Using model order tests to determine sensory inputs in a motion study

NASA Technical Reports Server (NTRS)

Repperger, D. W.; Junker, A. M.

1977-01-01

In the study of motion effects on tracking performance, a problem of interest is the determination of what sensory inputs a human uses in controlling his tracking task. In the approach presented here a simple canonical model (FID or a proportional, integral, derivative structure) is used to model the human's input-output time series. A study of significant changes in reduction of the output error loss functional is conducted as different permutations of parameters are considered. Since this canonical model includes parameters which are related to inputs to the human (such as the error signal, its derivatives and integration), the study of model order is equivalent to the study of which sensory inputs are being used by the tracker. The parameters are obtained which have the greatest effect on reducing the loss function significantly. In this manner the identification procedure converts the problem of testing for model order into the problem of determining sensory inputs.

Do anesthetics harm the developing human brain? An integrative analysis of animal and human studies.

PubMed

Lin, Erica P; Lee, Jeong-Rim; Lee, Christopher S; Deng, Meng; Loepke, Andreas W

Anesthetics that permit surgical procedures and stressful interventions have been found to cause structural brain abnormalities and functional impairment in immature animals, generating extensive concerns among clinicians, parents, and government regulators regarding the safe use of these drugs in young children. Critically important questions remain, such as the exact age at which the developing brain is most vulnerable to the effects of anesthetic exposure, whether a particular age exists beyond which anesthetics are devoid of long-term effects on the brain, and whether any specific exposure duration exists that does not lead to deleterious effects. Accordingly, the present analysis attempts to put the growing body of animal studies, which we identified to include >440 laboratory studies to date, into a translational context, by integrating the preclinical data on brain structure and function with clinical results attained from human neurocognitive studies, which currently exceed 30 studies. Our analysis demonstrated no clear exposure duration threshold below which no structural injury or subsequent cognitive abnormalities occurred. Animal data did not clearly identify a specific age beyond which anesthetic exposure did not cause any structural or functional abnormalities. Several potential mitigating strategies were found, however, no general anesthetic was identified that consistently lacked neurodegenerative properties and could be recommended over other anesthetics. It therefore is imperative, to expand efforts to devise safer anesthetic techniques and mitigating strategies, even before long-term alterations in brain development are unequivocally confirmed to occur in millions of young children undergoing anesthesia every year. Copyright © 2016 Elsevier Inc. All rights reserved.

Structure Shapes Dynamics and Directionality in Diverse Brain Networks: Mathematical Principles and Empirical Confirmation in Three Species

NASA Astrophysics Data System (ADS)

Moon, Joon-Young; Kim, Junhyeok; Ko, Tae-Wook; Kim, Minkyung; Iturria-Medina, Yasser; Choi, Jee-Hyun; Lee, Joseph; Mashour, George A.; Lee, Uncheol

2017-04-01

Identifying how spatially distributed information becomes integrated in the brain is essential to understanding higher cognitive functions. Previous computational and empirical studies suggest a significant influence of brain network structure on brain network function. However, there have been few analytical approaches to explain the role of network structure in shaping regional activities and directionality patterns. In this study, analytical methods are applied to a coupled oscillator model implemented in inhomogeneous networks. We first derive a mathematical principle that explains the emergence of directionality from the underlying brain network structure. We then apply the analytical methods to the anatomical brain networks of human, macaque, and mouse, successfully predicting simulation and empirical electroencephalographic data. The results demonstrate that the global directionality patterns in resting state brain networks can be predicted solely by their unique network structures. This study forms a foundation for a more comprehensive understanding of how neural information is directed and integrated in complex brain networks.

Cranial airways and the integration between the inner and outer facial skeleton in humans.

PubMed

Bastir, Markus; Rosas, Antonio

2013-10-01

The cranial airways are in the center of the human face. Therefore variation in the size and shape of these central craniofacial structures could have important consequences for the surrounding midfacial morphology during development and evolution. Yet such interactions are unclear because one school of thought, based on experimental and developmental evidence, suggests a relative independence (modularity) of these two facial compartments, whereas another one assumes tight morphological integration. This study uses geometric morphometrics of modern humans (N = 263) and 40 three-dimensional-landmarks of the skeletal nasopharynx and nasal cavity and outer midfacial skeleton to analyze these questions in terms of modularity. The sizes of all facial compartments were all strongly correlated. Shape integration was high between the cranial airways and the outer midfacial skeleton and between the latter and the anterior airway openings (skeletal regions close to and including piriform aperture). However, no shape integration was detected between outer midface and posterior airway openings (nasopharynx and choanae). Similarly, no integration was detected between posterior and anterior airway openings. This may reflect functional modularization of nasal cavity compartments related to respiratory physiology and differential developmental interactions with the face. Airway size likely relates to the energetics of the organism, whereas airways shape might be more indicative of respiratory physiology and climate. Although this hypothesis should be addressed in future steps, here we suggest that selection on morphofunctional characteristics of the cranial airways could have cascading effects for the variation, development, and evolution of the human face. Copyright © 2013 Wiley Periodicals, Inc.

The Zebrafish Model Organism Database: new support for human disease models, mutation details, gene expression phenotypes and searching

PubMed Central

Howe, Douglas G.; Bradford, Yvonne M.; Eagle, Anne; Fashena, David; Frazer, Ken; Kalita, Patrick; Mani, Prita; Martin, Ryan; Moxon, Sierra Taylor; Paddock, Holly; Pich, Christian; Ramachandran, Sridhar; Ruzicka, Leyla; Schaper, Kevin; Shao, Xiang; Singer, Amy; Toro, Sabrina; Van Slyke, Ceri; Westerfield, Monte

2017-01-01

The Zebrafish Model Organism Database (ZFIN; http://zfin.org) is the central resource for zebrafish (Danio rerio) genetic, genomic, phenotypic and developmental data. ZFIN curators provide expert manual curation and integration of comprehensive data involving zebrafish genes, mutants, transgenic constructs and lines, phenotypes, genotypes, gene expressions, morpholinos, TALENs, CRISPRs, antibodies, anatomical structures, models of human disease and publications. We integrate curated, directly submitted, and collaboratively generated data, making these available to zebrafish research community. Among the vertebrate model organisms, zebrafish are superbly suited for rapid generation of sequence-targeted mutant lines, characterization of phenotypes including gene expression patterns, and generation of human disease models. The recent rapid adoption of zebrafish as human disease models is making management of these data particularly important to both the research and clinical communities. Here, we describe recent enhancements to ZFIN including use of the zebrafish experimental conditions ontology, ‘Fish’ records in the ZFIN database, support for gene expression phenotypes, models of human disease, mutation details at the DNA, RNA and protein levels, and updates to the ZFIN single box search. PMID:27899582

Segregation and Integration of Auditory Streams when Listening to Multi-Part Music

PubMed Central

Ragert, Marie; Fairhurst, Merle T.; Keller, Peter E.

2014-01-01

In our daily lives, auditory stream segregation allows us to differentiate concurrent sound sources and to make sense of the scene we are experiencing. However, a combination of segregation and the concurrent integration of auditory streams is necessary in order to analyze the relationship between streams and thus perceive a coherent auditory scene. The present functional magnetic resonance imaging study investigates the relative role and neural underpinnings of these listening strategies in multi-part musical stimuli. We compare a real human performance of a piano duet and a synthetic stimulus of the same duet in a prioritized integrative attention paradigm that required the simultaneous segregation and integration of auditory streams. In so doing, we manipulate the degree to which the attended part of the duet led either structurally (attend melody vs. attend accompaniment) or temporally (asynchronies vs. no asynchronies between parts), and thus the relative contributions of integration and segregation used to make an assessment of the leader-follower relationship. We show that perceptually the relationship between parts is biased towards the conventional structural hierarchy in western music in which the melody generally dominates (leads) the accompaniment. Moreover, the assessment varies as a function of both cognitive load, as shown through difficulty ratings and the interaction of the temporal and the structural relationship factors. Neurally, we see that the temporal relationship between parts, as one important cue for stream segregation, revealed distinct neural activity in the planum temporale. By contrast, integration used when listening to both the temporally separated performance stimulus and the temporally fused synthetic stimulus resulted in activation of the intraparietal sulcus. These results support the hypothesis that the planum temporale and IPS are key structures underlying the mechanisms of segregation and integration of auditory streams, respectively. PMID:24475030

Segregation and integration of auditory streams when listening to multi-part music.

PubMed

Ragert, Marie; Fairhurst, Merle T; Keller, Peter E

2014-01-01

In our daily lives, auditory stream segregation allows us to differentiate concurrent sound sources and to make sense of the scene we are experiencing. However, a combination of segregation and the concurrent integration of auditory streams is necessary in order to analyze the relationship between streams and thus perceive a coherent auditory scene. The present functional magnetic resonance imaging study investigates the relative role and neural underpinnings of these listening strategies in multi-part musical stimuli. We compare a real human performance of a piano duet and a synthetic stimulus of the same duet in a prioritized integrative attention paradigm that required the simultaneous segregation and integration of auditory streams. In so doing, we manipulate the degree to which the attended part of the duet led either structurally (attend melody vs. attend accompaniment) or temporally (asynchronies vs. no asynchronies between parts), and thus the relative contributions of integration and segregation used to make an assessment of the leader-follower relationship. We show that perceptually the relationship between parts is biased towards the conventional structural hierarchy in western music in which the melody generally dominates (leads) the accompaniment. Moreover, the assessment varies as a function of both cognitive load, as shown through difficulty ratings and the interaction of the temporal and the structural relationship factors. Neurally, we see that the temporal relationship between parts, as one important cue for stream segregation, revealed distinct neural activity in the planum temporale. By contrast, integration used when listening to both the temporally separated performance stimulus and the temporally fused synthetic stimulus resulted in activation of the intraparietal sulcus. These results support the hypothesis that the planum temporale and IPS are key structures underlying the mechanisms of segregation and integration of auditory streams, respectively.

Medical Humanities Teaching in North American Allopathic and Osteopathic Medical Schools.

PubMed

Klugman, Craig M

2017-11-07

Although the AAMC requires annual reporting of medical humanities teaching, most literature is based on single-school case reports and studies using information reported on schools' websites. This study sought to discover what medical humanities is offered in North American allopathic and osteopathic undergraduate medical schools. An 18-question, semi-structured survey was distributed to all 146 (as of June 2016) member schools of the American Association of Medical Colleges and the American Association of Colleges of Osteopathic Medicine. The survey sought information on required and elective humanities content, hours of humanities instruction, types of disciplines, participation rates, and humanities administrative structure. The survey was completed by 134 schools (145 AAMC; 31 AACOM). 70.8% of schools offered required and 80.6% offered electives in humanities. Global health and writing were the most common disciplines. Schools required 43.9 mean (MD 45.4; DO 37.1) and 30 (MD 29; DO 37.5) median hours in humanities. In the first two years, most humanities are integrated into other course work; most electives are offered as stand-alone classes. 50.0% of schools report only 0-25% of students participating in humanities electives. Presence of a certificate, concentration or arts journal increased likelihood of humanities content but decreased mean hours. Schools with a medical humanities MA had a higher number of required humanities hours. Medical humanities content in undergraduate curriculum is lower than is indicated in the AAMC annual report. Schools with a formal structure have a greater humanities presence in the curriculum and are taken by more students.

Convergence of Human Genetics and Animal Studies: Gene Therapy for X-Linked Retinoschisis

PubMed Central

Bush, Ronald A.; Wei, Lisa L.; Sieving, Paul A.

2015-01-01

Retinoschisis is an X-linked recessive genetic disease that leads to vision loss in males. X-linked retinoschisis (XLRS) typically affects young males; however, progressive vision loss continues throughout life. Although discovered in 1898 by Haas in two brothers, the underlying biology leading to blindness has become apparent only in the last 15 years with the advancement of human genetic analyses, generation of XLRS animal models, and the development of ocular monitoring methods such as the electroretinogram and optical coherence tomography. It is now recognized that retinoschisis results from cyst formations within the retinal layers that interrupt normal visual neurosignaling and compromise structural integrity. Mutations in the human retinoschisin gene have been correlated with disease severity of the human XLRS phenotype. Introduction of a normal human retinoschisin cDNA into retinoschisin knockout mice restores retinal structure and improves neural function, providing proof-of-concept that gene replacement therapy is a plausible treatment for XLRS. PMID:26101206

Chemical Speciation and Metallomics.

PubMed

de Jesus, Jemmyson Romário; da Costa, Luana Ferreira; Lehmann, Eraldo Luiz; Galazzi, Rodrigo Moretto; Madrid, Katherine Chacón; Arruda, Marco Aurélio Zezzi

2018-01-01

Chemical speciation approaches is an inherent part of metallomics, once metals/metalloids and organic structures need to be currently evaluated for attaining metallomics studies. Then, this chapter focuses on the applications of the chemical speciation applied to the human health risk, food and human diet, drugs, forensic, nanoscience, and geological metallomics, also pointing out the advances in such area. Some aspects regarding sample preparation is commented along this chapter, and some strategies for maintaining the integrity of the metallomics information are also emphasized.

Design for an integrated discipline operations control center for Space Station Freedom

NASA Technical Reports Server (NTRS)

Haines, Richard F.

1993-01-01

This paper presents selected features of a human factors oriented plan for a Space Station Freedom (SSF) ground Discipline Operations Center (DOC) that is integrated with other work areas used by multidisciplinary life scientists. This combined facility is referred to as an integrated DOC or IDOC. This plan is based upon the assumption that there will be a constantly changing array of specialized equipment and procedures used by life sciences principal investigators (PI) on the ground which must be linked to SSF through various DOC systems. Other sites will also be able to communicate with SSF (Anon., 1992). It is also assumed that cost reduction will be a major design consideration and that one integrated structure will be less expensive to build and operate than two separate ones. Since both the DOC personnel and PIs will need to communicate with the flight crew aboard SSF, the general interconnect architecture of the PIs' communication linkage is considered here. Key human factor design elements of this plan include: a candidate facility layout which accommodates three (3), multipurpose, rapidly reconfigurable work areas (suites) and consequent user traffic flow considerations, a multimedia telecommunications support capability, functional (human) traffic flow, optimized internal illumination and acoustics requirements, selected volumetric and safety requirements, and other architectural design parameters.

Vocal learning in the functionally referential food grunts of chimpanzees.

PubMed

Watson, Stuart K; Townsend, Simon W; Schel, Anne M; Wilke, Claudia; Wallace, Emma K; Cheng, Leveda; West, Victoria; Slocombe, Katie E

2015-02-16

One standout feature of human language is our ability to reference external objects and events with socially learned symbols, or words. Exploring the phylogenetic origins of this capacity is therefore key to a comprehensive understanding of the evolution of language. While non-human primates can produce vocalizations that refer to external objects in the environment, it is generally accepted that their acoustic structure is fixed and a product of arousal states. Indeed, it has been argued that the apparent lack of flexible control over the structure of referential vocalizations represents a key discontinuity with language. Here, we demonstrate vocal learning in the acoustic structure of referential food grunts in captive chimpanzees. We found that, following the integration of two groups of adult chimpanzees, the acoustic structure of referential food grunts produced for a specific food converged over 3 years. Acoustic convergence arose independently of preference for the food, and social network analyses indicated this only occurred after strong affiliative relationships were established between the original subgroups. We argue that these data represent the first evidence of non-human animals actively modifying and socially learning the structure of a meaningful referential vocalization from conspecifics. Our findings indicate that primate referential call structure is not simply determined by arousal and that the socially learned nature of referential words in humans likely has ancient evolutionary origins. Copyright © 2015 Elsevier Ltd. All rights reserved.

An Integrative Breakage Model of genome architecture, reshuffling and evolution: The Integrative Breakage Model of genome evolution, a novel multidisciplinary hypothesis for the study of genome plasticity.

PubMed

Farré, Marta; Robinson, Terence J; Ruiz-Herrera, Aurora

2015-05-01

Our understanding of genomic reorganization, the mechanics of genomic transmission to offspring during germ line formation, and how these structural changes contribute to the speciation process, and genetic disease is far from complete. Earlier attempts to understand the mechanism(s) and constraints that govern genome remodeling suffered from being too narrowly focused, and failed to provide a unified and encompassing view of how genomes are organized and regulated inside cells. Here, we propose a new multidisciplinary Integrative Breakage Model for the study of genome evolution. The analysis of the high-level structural organization of genomes (nucleome), together with the functional constrains that accompany genome reshuffling, provide insights into the origin and plasticity of genome organization that may assist with the detection and isolation of therapeutic targets for the treatment of complex human disorders. © 2015 WILEY Periodicals, Inc.

The Landscape Framework for the Spatial Characterization and Mapping of Ecosystem Services: What is the State of the Science?

EPA Science Inventory

Ecosystem services (ESS) represent an ecosystems capacity for satisfying essential human needs, directly or indirectly, above that required to maintain ecosystem integrity (structure, function and processes). The spatial characterization and mapping of ESS is an essential first s...

The Role of Information about "Convention," "Design," and "Goal" in Representing Artificial Kinds

ERIC Educational Resources Information Center

German, Tim P.; Truxaw, Danielle; Defeyter, Margaret Anne

2007-01-01

Artifact knowledge requires integration of information from different areas of human commonsense knowledge--our everyday understanding of object mechanics and our everyday psychology. Here, we address the question of artifact conceptual structure, outlining evidence from tasks involving categorization, function judgments, and problem solving.

Projecting wildfire emissions over the south-eastern United States to mid-century

Treesearch

Uma Shankar; Jeffrey Prestemon; Donald McKenzie; Kevin Talgo; Aijun Xiu; Mohammad Omary; Bok Haeng Baek; Dongmei Yang; William Vizuete

2018-01-01

Wildfires can impair human health because of the toxicity of emitted pollutants, and threaten communities, structures and the integrity of ecosystems sensitive to disturbance. Climate and socioeconomic factors (e.g. population and income growth) are known regional drivers of wildfires. Reflecting changes in these factors in wildfire...

EVALUATION OF ANEUPLOIDY AND DNA DAMAGE IN HUMAN SPERMATOZOA: APPLICATIONS IN FIELD STUDIES

EPA Science Inventory

With the goal of incorporating measures of sperm nuclear integrity in an epidemiology study, semen samples from young Czech men were analyzed for sperm anueploidy and sperm chromatin structure in addition to routine measures of sperm production and quality. The exposure in ques...

The Value of Significant Learning Strategies in Undergraduate Education

ERIC Educational Resources Information Center

Coco, Charles M.

2012-01-01

Learning taxonomies can assist faculty in developing course structures that promote enhanced student learning in the cognitive and affective domains. Significant Learning is one approach to course design that allows for development in six key areas: Foundational Knowledge, Application, Integration, Human Dimension, Caring, and Learning How to…

Integrating PM2.5 Observations, Model Estimates and Satellite Signals for the Eastern United States by Projection onto Latent Structures

EPA Science Inventory

Detailed, time-varying spatial fields of air contaminant concentrations are valuable to public health professionals seeking to identify relationships between human health and ambient air quality, and policy makers interested in assessing compliance with air quality regulations. ...

Speech Motor Development: Integrating Muscles, Movements, and Linguistic Units

ERIC Educational Resources Information Center

Smith, Anne

2006-01-01

A fundamental problem for those interested in human communication is to determine how ideas and the various units of language structure are communicated through speaking. The physiological concepts involved in the control of muscle contraction and movement are theoretically distant from the processing levels and units postulated to exist in…

Art Therapy and Social Action: A Transpersonal Framework

ERIC Educational Resources Information Center

Hocoy, Dan

2005-01-01

This article introduces a conceptual framework that integrates art therapy and social action. The author uses a transpersonal model of the human psyche and an interdependent paradigm of the self and views personal psychological experiences and external societal structures as entwined in a cocreative, mutually dependent relationship. From this…

The Intellectual Assembly Line is Already Here

ERIC Educational Resources Information Center

Vanderburg, Willem H.

2004-01-01

The universal attempt to link computers by means of business process reengineering, enterprise integration, and the management of technology is creating large systems that structure and control the flows of information within institutions. Human work associated with these systems must be reorganized in the image of these technologies. The…

Evolving marine biomimetics for regenerative dentistry.

PubMed

Green, David W; Lai, Wing-Fu; Jung, Han-Sung

2014-05-13

New products that help make human tissue and organ regeneration more effective are in high demand and include materials, structures and substrates that drive cell-to-tissue transformations, orchestrate anatomical assembly and tissue integration with biology. Marine organisms are exemplary bioresources that have extensive possibilities in supporting and facilitating development of human tissue substitutes. Such organisms represent a deep and diverse reserve of materials, substrates and structures that can facilitate tissue reconstruction within lab-based cultures. The reason is that they possess sophisticated structures, architectures and biomaterial designs that are still difficult to replicate using synthetic processes, so far. These products offer tantalizing pre-made options that are versatile, adaptable and have many functions for current tissue engineers seeking fresh solutions to the deficiencies in existing dental biomaterials, which lack the intrinsic elements of biofunctioning, structural and mechanical design to regenerate anatomically correct dental tissues both in the culture dish and in vivo.

Evolving Marine Biomimetics for Regenerative Dentistry

PubMed Central

Green, David W.; Lai, Wing-Fu; Jung, Han-Sung

2014-01-01

New products that help make human tissue and organ regeneration more effective are in high demand and include materials, structures and substrates that drive cell-to-tissue transformations, orchestrate anatomical assembly and tissue integration with biology. Marine organisms are exemplary bioresources that have extensive possibilities in supporting and facilitating development of human tissue substitutes. Such organisms represent a deep and diverse reserve of materials, substrates and structures that can facilitate tissue reconstruction within lab-based cultures. The reason is that they possess sophisticated structures, architectures and biomaterial designs that are still difficult to replicate using synthetic processes, so far. These products offer tantalizing pre-made options that are versatile, adaptable and have many functions for current tissue engineers seeking fresh solutions to the deficiencies in existing dental biomaterials, which lack the intrinsic elements of biofunctioning, structural and mechanical design to regenerate anatomically correct dental tissues both in the culture dish and in vivo. PMID:24828293

Innovation in Evaluating the Impact of Integrated Service-Delivery: The Integra Indexes of HIV and Reproductive Health Integration.

PubMed

Mayhew, Susannah H; Ploubidis, George B; Sloggett, Andy; Church, Kathryn; Obure, Carol D; Birdthistle, Isolde; Sweeney, Sedona; Warren, Charlotte E; Watts, Charlotte; Vassall, Anna

2016-01-01

The body of knowledge on evaluating complex interventions for integrated healthcare lacks both common definitions of 'integrated service delivery' and standard measures of impact. Using multiple data sources in combination with statistical modelling the aim of this study is to develop a measure of HIV-reproductive health (HIV-RH) service integration that can be used to assess the degree of service integration, and the degree to which integration may have health benefits to clients, or reduce service costs. Data were drawn from the Integra Initiative's client flow (8,263 clients in Swaziland and 25,539 in Kenya) and costing tools implemented between 2008-2012 in 40 clinics providing RH services in Kenya and Swaziland. We used latent variable measurement models to derive dimensions of HIV-RH integration using these data, which quantified the extent and type of integration between HIV and RH services in Kenya and Swaziland. The modelling produced two clear and uncorrelated dimensions of integration at facility level leading to the development of two sub-indexes: a Structural Integration Index (integrated physical and human resource infrastructure) and a Functional Integration Index (integrated delivery of services to clients). The findings highlight the importance of multi-dimensional assessments of integration, suggesting that structural integration is not sufficient to achieve the integrated delivery of care to clients--i.e. "functional integration". These Indexes are an important methodological contribution for evaluating complex multi-service interventions. They help address the need to broaden traditional evaluations of integrated HIV-RH care through the incorporation of a functional integration measure, to avoid misleading conclusions on its 'impact' on health outcomes. This is particularly important for decision-makers seeking to promote integration in resource constrained environments.

Different integrated geophysical approaches to investigate archaeological sites in urban and suburban area.

NASA Astrophysics Data System (ADS)

Piro, Salvatore; Papale, Enrico; Zamuner, Daniela

2016-04-01

Geophysical methods are frequently used in archaeological prospection in order to provide detailed information about the presence of structures in the subsurface as well as their position and their geometrical reconstruction, by measuring variations of some physical properties. Often, due to the limited size and depth of an archaeological structure, it may be rather difficult to single out its position and extent because of the generally low signal-to-noise ratio. This problem can be overcome by improving data acquisition, processing techniques and by integrating different geophysical methods. In this work, two sites of archaeological interest, were investigated employing several methods (Ground Penetrating Radar (GPR), Electrical Resistivity Tomography (ERT), Fluxgate Differential Magnetic) to obtain precise and detailed maps of subsurface bodies. The first site, situated in a suburban area between Itri and Fondi, in the Aurunci Natural Regional Park (Central Italy), is characterized by the presence of remains of past human activity dating from the third century B.C. The second site, is instead situated in an urban area in the city of Rome (Basilica di Santa Balbina), where historical evidence is also present. The methods employed, allowed to determine the position and the geometry of some structures in the subsurface related to this past human activity. To have a better understanding of the subsurface, we then performed a qualitative and quantitative integration of this data, which consists in fusing the data from all the methods used, to have a complete visualization of the investigated area. Qualitative integration consists in graphically overlaying the maps obtained by the single methods; this method yields only images, not new data that may be subsequently analyzed. Quantitative integration is instead performed by mathematical and statistical solutions, which allows to have a more accurate reconstruction of the subsurface and generates new data with high information content.

Genic insights from integrated human proteomics in GeneCards.

PubMed

Fishilevich, Simon; Zimmerman, Shahar; Kohn, Asher; Iny Stein, Tsippi; Olender, Tsviya; Kolker, Eugene; Safran, Marilyn; Lancet, Doron

2016-01-01

GeneCards is a one-stop shop for searchable human gene annotations (http://www.genecards.org/). Data are automatically mined from ∼120 sources and presented in an integrated web card for every human gene. We report the application of recent advances in proteomics to enhance gene annotation and classification in GeneCards. First, we constructed the Human Integrated Protein Expression Database (HIPED), a unified database of protein abundance in human tissues, based on the publically available mass spectrometry (MS)-based proteomics sources ProteomicsDB, Multi-Omics Profiling Expression Database, Protein Abundance Across Organisms and The MaxQuant DataBase. The integrated database, residing within GeneCards, compares favourably with its individual sources, covering nearly 90% of human protein-coding genes. For gene annotation and comparisons, we first defined a protein expression vector for each gene, based on normalized abundances in 69 normal human tissues. This vector is portrayed in the GeneCards expression section as a bar graph, allowing visual inspection and comparison. These data are juxtaposed with transcriptome bar graphs. Using the protein expression vectors, we further defined a pairwise metric that helps assess expression-based pairwise proximity. This new metric for finding functional partners complements eight others, including sharing of pathways, gene ontology (GO) terms and domains, implemented in the GeneCards Suite. In parallel, we calculated proteome-based differential expression, highlighting a subset of tissues that overexpress a gene and subserving gene classification. This textual annotation allows users of VarElect, the suite's next-generation phenotyper, to more effectively discover causative disease variants. Finally, we define the protein-RNA expression ratio and correlation as yet another attribute of every gene in each tissue, adding further annotative information. The results constitute a significant enhancement of several GeneCards sections and help promote and organize the genome-wide structural and functional knowledge of the human proteome. Database URL:http://www.genecards.org/. © The Author(s) 2016. Published by Oxford University Press.

MitBASE : a comprehensive and integrated mitochondrial DNA database. The present status

PubMed Central

Attimonelli, M.; Altamura, N.; Benne, R.; Brennicke, A.; Cooper, J. M.; D’Elia, D.; Montalvo, A. de; Pinto, B. de; De Robertis, M.; Golik, P.; Knoop, V.; Lanave, C.; Lazowska, J.; Licciulli, F.; Malladi, B. S.; Memeo, F.; Monnerot, M.; Pasimeni, R.; Pilbout, S.; Schapira, A. H. V.; Sloof, P.; Saccone, C.

2000-01-01

MitBASE is an integrated and comprehensive database of mitochondrial DNA data which collects, under a single interface, databases for Plant, Vertebrate, Invertebrate, Human, Protist and Fungal mtDNA and a Pilot database on nuclear genes involved in mitochondrial biogenesis in Saccharomyces cerevisiae. MitBASE reports all available information from different organisms and from intraspecies variants and mutants. Data have been drawn from the primary databases and from the literature; value adding information has been structured, e.g., editing information on protist mtDNA genomes, pathological information for human mtDNA variants, etc. The different databases, some of which are structured using commercial packages (Microsoft Access, File Maker Pro) while others use a flat-file format, have been integrated under ORACLE. Ad hoc retrieval systems have been devised for some of the above listed databases keeping into account their peculiarities. The database is resident at the EBI and is available at the following site: http://www3.ebi.ac.uk/Research/Mitbase/mitbase.pl . The impact of this project is intended for both basic and applied research. The study of mitochondrial genetic diseases and mitochondrial DNA intraspecies diversity are key topics in several biotechnological fields. The database has been funded within the EU Biotechnology programme. PMID:10592207

A structure- and chemical genomics-based approach for repositioning of drugs against VCP/p97 ATPase.

PubMed

Segura-Cabrera, Aldo; Tripathi, Reshmi; Zhang, Xiaoyi; Gui, Lin; Chou, Tsui-Fen; Komurov, Kakajan

2017-03-21

Valosin-containing protein (VCP/p97) ATPase (a.k.a. Cdc48) is a key member of the ER-associated protein degradation (ERAD) pathway. ERAD and VCP/p97 have been implicated in a multitude of human diseases, such as neurodegenerative diseases and cancer. Inhibition of VCP/p97 induces proteotoxic ER stress and cell death in cancer cells, making it an attractive target for cancer treatment. However, no drugs exist against this protein in the market. Repositioning of drugs towards new indications is an attractive alternative to the de novo drug development due to the potential for significantly shorter time to clinical translation. Here, we employed an integrative strategy for the repositioning of drugs as novel inhibitors of the VCP/p97 ATPase. We integrated structure-based virtual screening with the chemical genomics analysis of drug molecular signatures, and identified several candidate inhibitors of VCP/p97 ATPase. Importantly, experimental validation with cell-based and in vitro ATPase assays confirmed three (ebastine, astemizole and clotrimazole) out of seven tested candidates (~40% true hit rate) as direct inhibitors of VCP/p97 and ERAD. This study introduces an effective integrative strategy for drug repositioning, and identified new drugs against the VCP/p97/ERAD pathway in human diseases.

Functional Coupling between HIV-1 Integrase and the SWI/SNF Chromatin Remodeling Complex for Efficient in vitro Integration into Stable Nucleosomes

PubMed Central

Lesbats, Paul; Botbol, Yair; Chevereau, Guillaume; Vaillant, Cédric; Calmels, Christina; Arneodo, Alain; Andreola, Marie-Line; Lavigne, Marc; Parissi, Vincent

2011-01-01

Establishment of stable HIV-1 infection requires the efficient integration of the retroviral genome into the host DNA. The molecular mechanism underlying the control of this process by the chromatin structure has not yet been elucidated. We show here that stably associated nucleosomes strongly inhibit in vitro two viral-end integration by decreasing the accessibility of DNA to integrase. Remodeling of the chromatinized template by the SWI/SNF complex, whose INI1 major component interacts with IN, restores and redirects the full-site integration into the stable nucleosome region. These effects are not observed after remodeling by other human remodeling factors such as SNF2H or BRG1 lacking the integrase binding protein INI1. This suggests that the restoration process depends on the direct interaction between IN and the whole SWI/SNF complex, supporting a functional coupling between the remodeling and integration complexes. Furthermore, in silico comparison between more than 40,000 non-redundant cellular integration sites selected from literature and nucleosome occupancy predictions also supports that HIV-1 integration is promoted in the genomic region of weaker intrinsic nucleosome density in the infected cell. Our data indicate that some chromatin structures can be refractory for integration and that coupling between nucleosome remodeling and HIV-1 integration is required to overcome this natural barrier. PMID:21347347

Innovation in Evaluating the Impact of Integrated Service-Delivery: The Integra Indexes of HIV and Reproductive Health Integration

PubMed Central

Mayhew, Susannah H.; Ploubidis, George B.; Sloggett, Andy; Church, Kathryn; Obure, Carol D.; Birdthistle, Isolde; Sweeney, Sedona; Warren, Charlotte E.; Watts, Charlotte; Vassall, Anna

2016-01-01

Background The body of knowledge on evaluating complex interventions for integrated healthcare lacks both common definitions of ‘integrated service delivery’ and standard measures of impact. Using multiple data sources in combination with statistical modelling the aim of this study is to develop a measure of HIV-reproductive health (HIV-RH) service integration that can be used to assess the degree of service integration, and the degree to which integration may have health benefits to clients, or reduce service costs. Methods and Findings Data were drawn from the Integra Initiative’s client flow (8,263 clients in Swaziland and 25,539 in Kenya) and costing tools implemented between 2008–2012 in 40 clinics providing RH services in Kenya and Swaziland. We used latent variable measurement models to derive dimensions of HIV-RH integration using these data, which quantified the extent and type of integration between HIV and RH services in Kenya and Swaziland. The modelling produced two clear and uncorrelated dimensions of integration at facility level leading to the development of two sub-indexes: a Structural Integration Index (integrated physical and human resource infrastructure) and a Functional Integration Index (integrated delivery of services to clients). The findings highlight the importance of multi-dimensional assessments of integration, suggesting that structural integration is not sufficient to achieve the integrated delivery of care to clients—i.e. “functional integration”. Conclusions These Indexes are an important methodological contribution for evaluating complex multi-service interventions. They help address the need to broaden traditional evaluations of integrated HIV-RH care through the incorporation of a functional integration measure, to avoid misleading conclusions on its ‘impact’ on health outcomes. This is particularly important for decision-makers seeking to promote integration in resource constrained environments. PMID:26800517

Integrating the genomic architecture of human nucleolar organizer regions with the biophysical properties of nucleoli.

PubMed

Mangan, Hazel; Gailín, Michael Ó; McStay, Brian

2017-12-01

Nucleoli are the sites of ribosome biogenesis and the largest membraneless subnuclear structures. They are intimately linked with growth and proliferation control and function as sensors of cellular stress. Nucleoli form around arrays of ribosomal gene (rDNA) repeats also called nucleolar organizer regions (NORs). In humans, NORs are located on the short arms of all five human acrocentric chromosomes. Multiple NORs contribute to the formation of large heterochromatin-surrounded nucleoli observed in most human cells. Here we will review recent findings about their genomic architecture. The dynamic nature of nucleoli began to be appreciated with the advent of photodynamic experiments using fluorescent protein fusions. We review more recent data on nucleoli in Xenopus germinal vesicles (GVs) which has revealed a liquid droplet-like behavior that facilitates nucleolar fusion. Further analysis in both XenopusGVs and Drosophila embryos indicates that the internal organization of nucleoli is generated by a combination of liquid-liquid phase separation and active processes involving rDNA. We will attempt to integrate these recent findings with the genomic architecture of human NORs to advance our understanding of how nucleoli form and respond to stress in human cells. © 2017 Federation of European Biochemical Societies.

Susceptibility to mountain hazards in Austria - paradigms of vulnerability revisited

NASA Astrophysics Data System (ADS)

Fuchs, Sven

2010-05-01

The concept of vulnerability is pillared by multiple disciplinary theories underpinning either a technical or a social origin of the concept and resulting in a range of paradigms for either a qualitative or quantitative assessment of vulnerability. However, efforts to reduce susceptibility to hazards and to create disaster-resilient communities require intersections among these theories, since human activity cannot be seen independently from the environmental setting. Acknowledging different roots of disciplinary paradigms, issues determining structural, economic, institutional and social vulnerability are discussed with respect to mountain hazards in Austria. The underlying idea of taking such an integrative viewpoint was the cognition that human action in mountain environments affects the state of vulnerability, and the state of vulnerability in turn shapes the possibilities of human action. It is argued that structural vulnerability as originator results in considerable economic vulnerability, generated by the institutional settings of dealing with natural hazards and shaped by the overall societal framework. Hence, the vulnerability of a specific location and within a considered point of time is triggered by the hazardous event and the related physical susceptibility of structures, such as buildings located on a torrent fan. Depending on the specific institutional settings, economic vulnerability of individuals or of the society results, above all with respect to imperfect loss compensation mechanisms in the areas under investigation. While this potential for harm can be addressed as social vulnerability, the concept of institutional vulnerability has been developed with respect to the overall political settings of governmental risk management. As a result, the concept of vulnerability, as being used in natural sciences, can be extended by integration of possible reasons why such physical susceptibility of structures exists, and by integration of compensation mechanisms and coping strategies being developed within social sciences. If vulnerability and its counterpart, resilience, is analysed and evaluated by using a comprehensive approach, a better understanding of the vulnerability-influencing parameters could be achieved, taking into account the interdependencies and interactions between the disciplinary foci. Thereby the overall aim of this work is not to develop another integrative approach for vulnerability assessment, different approaches are rather applied by using a vulnerability-of-place criterion, and key issues of vulnerability are reconsidered aiming at a general illustration of the situation in a densely populated mountain region of Europe.

Medical Systems Engineering to Support Mars Mission Crew Autonomy

NASA Technical Reports Server (NTRS)

Antonsen, Erik; Mindock, Jennifer

2017-01-01

Human spaceflight missions to Mars face exceptionally challenging resource limitations that far exceed those faced before. Increasing transit times, decreasing opportunity for resupply, communications challenges, and extended time to evacuate a crew to definitive medical care dictate a level of crew autonomy in medical care that is beyond the current medical model. To approach this challenge, a medical systems engineering approach is proposed that relies on a clearly articulated Concept of Operations and risk analysis tools that are in development at NASA. This paper proposes an operational clinical model with key terminology and concepts translated to a controls theory paradigm to frame a common language between clinical and engineering teams. This common language will be used for design and validation of an exploration medical system that is fully integrated into a Mars transit vehicle. This approach merges medical simulation, human factors evaluation techniques, and human-in-the-loop testing in ground based analogs to tie medical hardware and software subsystem performance and overall medical system functionality to metrics of operational medical autonomy. Merging increases in operational clinical autonomy with a more restricted vehicle system resource scenario in interplanetary spaceflight will require an unprecedented level of medical and engineering integration. Full integration of medical capabilities into a Mars vehicle system may require a new approach to integrating medical system design and operations into the vehicle Program structure. Prior to the standing-up of a Mars Mission Program, proof of concept is proposed through the Human Research Program.

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.

Small-world human brain networks: Perspectives and challenges.

PubMed

Liao, Xuhong; Vasilakos, Athanasios V; He, Yong

2017-06-01

Modelling the human brain as a complex network has provided a powerful mathematical framework to characterize the structural and functional architectures of the brain. In the past decade, the combination of non-invasive neuroimaging techniques and graph theoretical approaches enable us to map human structural and functional connectivity patterns (i.e., connectome) at the macroscopic level. One of the most influential findings is that human brain networks exhibit prominent small-world organization. Such a network architecture in the human brain facilitates efficient information segregation and integration at low wiring and energy costs, which presumably results from natural selection under the pressure of a cost-efficiency balance. Moreover, the small-world organization undergoes continuous changes during normal development and ageing and exhibits dramatic alterations in neurological and psychiatric disorders. In this review, we survey recent advances regarding the small-world architecture in human brain networks and highlight the potential implications and applications in multidisciplinary fields, including cognitive neuroscience, medicine and engineering. Finally, we highlight several challenging issues and areas for future research in this rapidly growing field. Copyright © 2017 Elsevier Ltd. All rights reserved.

Organizational and Clinical Implications of Integrating an Alcohol Screening and Brief Intervention Within Non-Substance Abuse Serving Agencies

PubMed Central

PATTERSON, DAVID A.; WOLF (ADELV UNEGV WAYA), SILVER; McKIERNAN, PATRICK M.

2012-01-01

Although there have been efforts to advance evidenced-based practices into community-based organizations the limited successes of dissemination and poor implementation of efficacious treatments within these organizations are beginning to be documented. This article builds on the knowledge gained from organizational research and those internal structures (e.g., culture and climate), which possibly impede or enhance evidenced-based practice implementation within community-based organizations. While there are many evidenced-based practices available to human services organizations, there seems to be a gap between research and the implementation of these clinical practices. Recommendations are provided to better enable community-based organizations to integrate evidenced-based practice into its existing service structures. PMID:20799131

Organizational and clinical implications of integrating an alcohol screening and brief intervention within non-substance abuse serving agencies.

PubMed

Patterson, David A; Wolf Adelv Unegv Waya, Silver; McKiernan, Patrick M

2010-07-01

Although there have been efforts to advance evidenced-based practices into community-based organizations the limited successes of dissemination and poor implementation of efficacious treatments within these organizations are beginning to be documented. This article builds on the knowledge gained from organizational research and those internal structures (e.g., culture and climate), which possibly impede or enhance evidenced-based practice implementation within community-based organizations. While there are many evidenced-based practices available to human services organizations, there seems to be a gap between research and the implementation of these clinical practices. Recommendations are provided to better enable community-based organizations to integrate evidenced-based practice into its existing service structures.

The nuclear envelope as an integrator of nuclear and cytoplasmic architecture.

PubMed

Crisp, Melissa; Burke, Brian

2008-06-18

Initially perceived as little more than a container for the genome, our view of the nuclear envelope (NE) and its role in defining global nuclear architecture has evolved significantly in recent years. The recognition that certain human diseases arise from defects in NE components has provided new insight into its structural and regulatory functions. In particular, NE defects associated with striated muscle disease have been shown to cause structural perturbations not just of the nucleus itself but also of the cytoplasm. It is now becoming increasingly apparent that these two compartments display co-dependent mechanical properties. The identification of cytoskeletal binding complexes that localize to the NE now reveals a molecular framework that can seamlessly integrate nuclear and cytoplasmic architecture.

DigitalHuman (DH): An Integrative Mathematical Model ofHuman Physiology

NASA Technical Reports Server (NTRS)

Hester, Robert L.; Summers, Richard L.; lIescu, Radu; Esters, Joyee; Coleman, Thomas G.

2010-01-01

Mathematical models and simulation are important tools in discovering the key causal relationships governing physiological processes and improving medical intervention when physiological complexity is a central issue. We have developed a model of integrative human physiology called DigitalHuman (DH) consisting of -5000 variables modeling human physiology describing cardiovascular, renal, respiratory, endocrine, neural and metabolic physiology. Users can view time-dependent solutions and interactively introduce perturbations by altering numerical parameters to investigate new hypotheses. The variables, parameters and quantitative relationships as well as all other model details are described in XML text files. All aspects of the model, including the mathematical equations describing the physiological processes are written in XML open source, text-readable files. Model structure is based upon empirical data of physiological responses documented within the peer-reviewed literature. The model can be used to understand proposed physiological mechanisms and physiological interactions that may not be otherwise intUitively evident. Some of the current uses of this model include the analyses of renal control of blood pressure, the central role of the liver in creating and maintaining insulin resistance, and the mechanisms causing orthostatic hypotension in astronauts. Additionally the open source aspect of the modeling environment allows any investigator to add detailed descriptions of human physiology to test new concepts. The model accurately predicts both qualitative and more importantly quantitative changes in clinically and experimentally observed responses. DigitalHuman provides scientists a modeling environment to understand the complex interactions of integrative physiology. This research was supported by.NIH HL 51971, NSF EPSCoR, and NASA

Massive integration of diverse protein quality assessment methods to improve template based modeling in CASP11.

PubMed

Cao, Renzhi; Bhattacharya, Debswapna; Adhikari, Badri; Li, Jilong; Cheng, Jianlin

2016-09-01

Model evaluation and selection is an important step and a big challenge in template-based protein structure prediction. Individual model quality assessment methods designed for recognizing some specific properties of protein structures often fail to consistently select good models from a model pool because of their limitations. Therefore, combining multiple complimentary quality assessment methods is useful for improving model ranking and consequently tertiary structure prediction. Here, we report the performance and analysis of our human tertiary structure predictor (MULTICOM) based on the massive integration of 14 diverse complementary quality assessment methods that was successfully benchmarked in the 11th Critical Assessment of Techniques of Protein Structure prediction (CASP11). The predictions of MULTICOM for 39 template-based domains were rigorously assessed by six scoring metrics covering global topology of Cα trace, local all-atom fitness, side chain quality, and physical reasonableness of the model. The results show that the massive integration of complementary, diverse single-model and multi-model quality assessment methods can effectively leverage the strength of single-model methods in distinguishing quality variation among similar good models and the advantage of multi-model quality assessment methods of identifying reasonable average-quality models. The overall excellent performance of the MULTICOM predictor demonstrates that integrating a large number of model quality assessment methods in conjunction with model clustering is a useful approach to improve the accuracy, diversity, and consequently robustness of template-based protein structure prediction. Proteins 2016; 84(Suppl 1):247-259. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Embodied niche construction in the hominin lineage: semiotic structure and sustained attention in human embodied cognition

PubMed Central

Stutz, Aaron J.

2014-01-01

Human evolution unfolded through a rather distinctive, dynamically constructed ecological niche. The human niche is not only generally terrestrial in habitat, while being flexibly and extensively heterotrophic in food-web connections. It is also defined by semiotically structured and structuring embodied cognitive interfaces, connecting the individual organism with the wider environment. The embodied dimensions of niche-population co-evolution have long involved semiotic system construction, which I hypothesize to be an evolutionarily primitive aspect of learning and higher-level cognitive integration and attention in the great apes and humans alike. A clearly pre-linguistic form of semiotic cognitive structuration is suggested to involve recursively learned and constructed object icons. Higher-level cognitive iconic representation of visually, auditorily, or haptically perceived extrasomatic objects would be learned and evoked through indexical connections to proprioceptive and affective somatic states. Thus, private cognitive signs would be defined, not only by their learned and perceived extrasomatic referents, but also by their associations to iconically represented somatic states. This evolutionary modification of animal associative learning is suggested to be adaptive in ecological niches occupied by long-lived, large-bodied ape species, facilitating memory construction and recall in highly varied foraging and social contexts, while sustaining selective attention during goal-directed behavioral sequences. The embodied niche construction (ENC) hypothesis of human evolution posits that in the early hominin lineage, natural selection further modified the ancestral ape semiotic adaptations, favoring the recursive structuration of concise iconic narratives of embodied interaction with the environment. PMID:25136323

Embodied niche construction in the hominin lineage: semiotic structure and sustained attention in human embodied cognition.

PubMed

Stutz, Aaron J

2014-01-01

Human evolution unfolded through a rather distinctive, dynamically constructed ecological niche. The human niche is not only generally terrestrial in habitat, while being flexibly and extensively heterotrophic in food-web connections. It is also defined by semiotically structured and structuring embodied cognitive interfaces, connecting the individual organism with the wider environment. The embodied dimensions of niche-population co-evolution have long involved semiotic system construction, which I hypothesize to be an evolutionarily primitive aspect of learning and higher-level cognitive integration and attention in the great apes and humans alike. A clearly pre-linguistic form of semiotic cognitive structuration is suggested to involve recursively learned and constructed object icons. Higher-level cognitive iconic representation of visually, auditorily, or haptically perceived extrasomatic objects would be learned and evoked through indexical connections to proprioceptive and affective somatic states. Thus, private cognitive signs would be defined, not only by their learned and perceived extrasomatic referents, but also by their associations to iconically represented somatic states. This evolutionary modification of animal associative learning is suggested to be adaptive in ecological niches occupied by long-lived, large-bodied ape species, facilitating memory construction and recall in highly varied foraging and social contexts, while sustaining selective attention during goal-directed behavioral sequences. The embodied niche construction (ENC) hypothesis of human evolution posits that in the early hominin lineage, natural selection further modified the ancestral ape semiotic adaptations, favoring the recursive structuration of concise iconic narratives of embodied interaction with the environment.

Benefits from a geographers' perspective on human-water systems - the waterscape concept

NASA Astrophysics Data System (ADS)

Evers, Mariele; Höllermann, Britta; Almoradie, Adrian; Taft, Linda

2016-04-01

Recently a couple of theoretical foundations and concepts were developed such as hydro-sociology, hydro-economics and integrated water resources management in order to structure and process parameterizations of hydrological research and reflect human-water-interrelations. However, a remaining challenge in human-water-system research is that approaches like socio-hydrology still struggle to formalize hypotheses which are capable to capture the basic driving mechanisms of the dynamic human-water system beyond optimizing algorithms or the principle of optimality or entropy as the societal values and experiences may unfold diverging policy and society responses (cf. Troy et al. 2015). Another challenge that we see is the integration of physical and social sciences with regard to the different epistemologies and perspectives: positivist thinking common in natural sciences and engineering and constructivist conceptualisation common in the social sciences. Here, geographic research seeks to acknowledge multi-spatial perspectives of the different actors and entities and their integration into the physical system that needs mutual recognition of natural and social sciences concepts, theories and methods. We suggest for human-water system research a more geographic perspective, which we call waterscape concept. Water can be regarded as a key structuring element for landscape and its management and, hence, from our perspective, the dynamics in water resources and interrelation of actors and entities in its management also helps to better understand current landscape patterns, their developments and interrelations, respectively. By our definition, a waterscape includes sources and users of water, their interactions, feedbacks and external influencing factors. It is therefore not only the physical space but rather includes the arena of actors and entities interacting. Against this understanding, waterscapes are defined by reciprocal boundary conditions which allow integrating the knowledge of natural and social sciences by acknowledging their different epistemologies, concepts and methods at the same time, hereby, fostering a true integration of the disciplines. Space and time and feedback loops are the three key factors to understand human-water interactions. Especially, by recognizing the degree of feedback sensitive system parameters can be detected and allow for emerging a set of multiple framings and possible development paths. Therefore, the geographical perspective on the waterscape concept proposes a search apart from one solution or best practice as, in our assumption, there are no single best answers because the human dimension and their action and reaction are guided also beyond perceptions, preferences, benefits and costs. Our waterscape concept allows a multi-spatial and multi-disciplinary perspective on water and its projection into space by acknowledging multiple meanings, alternative framings and possible development paths, hence fostering an integrative perspective on human-water systems. It further provides a fruitful framework for transdisciplinary research approaches since it is open and supports societal co-production and reframing of knowledge and policies. Troy, T. J., Pavao-Zuckerman, M., and Evans, T. P.: Debates Perspectives on socio-hydrology: Socio-hydrologic modeling: Tradeoffs, hypothesis testing, and validation, Water Resour Res, 51, 4806-4814, 10.1002/2015WR017046, 2015

A structurally decoupled mechanism for measuring wrist torque in three degrees of freedom

NASA Astrophysics Data System (ADS)

Pan, Lizhi; Yang, Zhen; Zhang, Dingguo

2015-10-01

The wrist joint is a critical part of the human body for movement. Measuring the torque of the wrist with three degrees of freedom (DOFs) is important in some fields, including rehabilitation, biomechanics, ergonomics, and human-machine interfacing. However, the particular structure of the wrist joint makes it difficult to measure the torque in all three directions simultaneously. This work develops a structurally decoupled instrument for measuring and improving the measurement accuracy of 3-DOF wrist torque during isometric contraction. Three single-axis torque sensors were embedded in a customized mechanical structure. The dimensions and components of the instrument were designed based on requirement of manufacturability. A prototype of the instrument was machined, assembled, integrated, and tested. The results show that the structurally decoupled mechanism is feasible for acquiring wrist torque data in three directions either independently or simultaneously. As a case study, we use the device to measure wrist torques concurrently with electromyography signal acquisition in preparation for simultaneous and proportional myoelectric control of prostheses.

GPCR-I-TASSER: A hybrid approach to G protein-coupled receptor structure modeling and the application to the human genome

PubMed Central

Zhang, Jian; Yang, Jianyi; Jang, Richard; Zhang, Yang

2015-01-01

SUMMARY Experimental structure determination remains very difficult for G protein-coupled receptors (GPCRs). We propose a new hybrid protocol to construct GPCR structure models that integrates experimental mutagenesis data with ab initio transmembrane (TM) helix assembly simulations. The method was tested on 24 known GPCRs where the ab initio TM-helix assembly procedure constructed the correct fold for 20 cases. When combined with weak-homology and sparse mutagenesis restraints, the method generated correct folds for all the tested cases with an average C-alpha RMSD 2.4 Å in the TM-regions. The new hybrid protocol was applied to model all 1026 GPCRs in the human genome, where 923 have a high confidence score that are expected to have correct folds; these contain many pharmaceutically important families with no previously solved structures, including Trace amine, Prostanoids, Releasing hormones, Melanocortins, Vasopressin and Neuropeptide Y receptors. The results demonstrate new progress on genome-wide structure modeling of transmembrane proteins. PMID:26190572

A structurally decoupled mechanism for measuring wrist torque in three degrees of freedom.

PubMed

Pan, Lizhi; Yang, Zhen; Zhang, Dingguo

2015-10-01

The wrist joint is a critical part of the human body for movement. Measuring the torque of the wrist with three degrees of freedom (DOFs) is important in some fields, including rehabilitation, biomechanics, ergonomics, and human-machine interfacing. However, the particular structure of the wrist joint makes it difficult to measure the torque in all three directions simultaneously. This work develops a structurally decoupled instrument for measuring and improving the measurement accuracy of 3-DOF wrist torque during isometric contraction. Three single-axis torque sensors were embedded in a customized mechanical structure. The dimensions and components of the instrument were designed based on requirement of manufacturability. A prototype of the instrument was machined, assembled, integrated, and tested. The results show that the structurally decoupled mechanism is feasible for acquiring wrist torque data in three directions either independently or simultaneously. As a case study, we use the device to measure wrist torques concurrently with electromyography signal acquisition in preparation for simultaneous and proportional myoelectric control of prostheses.

Mapping population-based structural connectomes.

PubMed

Zhang, Zhengwu; Descoteaux, Maxime; Zhang, Jingwen; Girard, Gabriel; Chamberland, Maxime; Dunson, David; Srivastava, Anuj; Zhu, Hongtu

2018-05-15

Advances in understanding the structural connectomes of human brain require improved approaches for the construction, comparison and integration of high-dimensional whole-brain tractography data from a large number of individuals. This article develops a population-based structural connectome (PSC) mapping framework to address these challenges. PSC simultaneously characterizes a large number of white matter bundles within and across different subjects by registering different subjects' brains based on coarse cortical parcellations, compressing the bundles of each connection, and extracting novel connection weights. A robust tractography algorithm and streamline post-processing techniques, including dilation of gray matter regions, streamline cutting, and outlier streamline removal are applied to improve the robustness of the extracted structural connectomes. The developed PSC framework can be used to reproducibly extract binary networks, weighted networks and streamline-based brain connectomes. We apply the PSC to Human Connectome Project data to illustrate its application in characterizing normal variations and heritability of structural connectomes in healthy subjects. Copyright © 2018 Elsevier Inc. All rights reserved.

Morphological evolution through integration: a quantitative study of cranial integration in Homo, Pan, Gorilla and Pongo.

PubMed

Singh, Nandini; Harvati, Katerina; Hublin, Jean-Jacques; Klingenberg, Christian P

2012-01-01

Morphological integration refers to coordinated variation among traits that are closely related in development and/or function. Patterns of integration can offer important insight into the structural relationship between phenotypic units, providing a framework to address questions about phenotypic evolvability and constraints. Integrative features of the primate cranium have recently become a popular subject of study. However, an important question that still remains under-investigated is: what is the pattern of cranial shape integration among closely related hominoids? To address this question, we conducted a Procrustes-based geometric morphometrics study to quantify and analyze shape covariation patterns between different cranial regions in Homo, Pan, Gorilla and Pongo. A total of fifty-six 3D landmarks were collected on 407 adult individuals. We then sub-divided the landmarks corresponding to cranial units as outlined in the 'functional matrix hypothesis.' Sub-dividing the cranium in this manner allowed us to explore patterns of covariation between the face, basicranium and cranial vault, using the two-block partial least squares approach. Our results suggest that integrated shape changes in the hominoid cranium are complex, but that the overall pattern of integration is similar among human and non-human apes. Thus, despite having very distinct morphologies the way in which the face, basicranium and cranial vault covary is shared among these taxa. These results imply that the pattern of cranial integration among hominoids is conserved. Copyright © 2011 Elsevier Ltd. All rights reserved.

Proteomic characterization of the nucleolar linker histone H1 interaction network

PubMed Central

Szerlong, Heather J.; Herman, Jacob A.; Krause, Christine M.; DeLuca, Jennifer G.; Skoultchi, Arthur; Winger, Quinton A.; Prenni, Jessica E.; Hansen, Jeffrey C.

2015-01-01

To investigate the relationship between linker histone H1 and protein-protein interactions in the nucleolus, biochemical and proteomics approaches were used to characterize nucleoli purified from cultured human and mouse cells. Mass spectrometry identified 175 proteins in human T-cell nucleolar extracts that bound to sepharose-immobilized H1 in vitro. Gene ontology analysis found significant enrichment for H1 binding proteins with functions related to nucleolar chromatin structure and RNA polymerase I transcription regulation, rRNA processing, and mRNA splicing. Consistent with the affinity binding results, H1 existed in large (400 to >650 kDa) macromolecular complexes in human T cell nucleolar extracts. To complement the biochemical experiments, the effects of in vivo H1 depletion on protein content and structural integrity of the nucleolus were investigated using the H1 triple isoform knock out (H1ΔTKO) mouse embryonic stem cell (mESC) model system. Proteomic profiling of purified wild type mESC nucleoli identified a total of 613 proteins, only ~60% of which were detected in the H1 mutant nucleoli. Within the affected group, spectral counting analysis quantitated 135 specific nucleolar proteins whose levels were significantly altered in H1ΔTKO mESC. Importantly, the functions of the affected proteins in mESC closely overlapped with those of the human T cell nucleolar H1 binding proteins. Immunofluorescence microscopy of intact H1ΔTKO mESC demonstrated both a loss of nucleolar RNA content and altered nucleolar morphology resulting from in vivo H1 depletion. We conclude that H1 organizes and maintains an extensive protein-protein interaction network in the nucleolus required for nucleolar structure and integrity. PMID:25584861

Combined spectrophotometry and tensile measurements of human connective tissues: potentials and limitations.

PubMed

Ernstberger, Markus; Sichting, Freddy; Baselt, Tobias; Hartmann, Peter; Aust, Gabriela; Hammer, Niels

2013-06-01

Strain-dependent transmission data of nine iliotibial tract specimens are determined using a custom-built optical setup with a halogen light source and an industrial norm material testing machine. Polarized light microscopy and hematoxylin-eosin staining indicated that lateral contraction of collagen structures is responsible for total intensity variations during a 20-cycle preconditioning and a 5-cycle tensile test. Tensile force progress is opposite to total transmission progress. Due to dehydration, wavelength-specific radiation intensity shifting is determined during the test, primarily noticeable in a water absorption band between 1400 and 1500 nm. The results show the capability of integrating spectrophotometry technology into biomechanics for determining structural alterations of human collagen due to applied strain. Being more sensitive to drying, spectrophotometry may likely serve as a quality control in stress-strain testing of biological structures.

Biomechanical behavior of muscle-tendon complex during dynamic human movements.

PubMed

Fukashiro, Senshi; Hay, Dean C; Nagano, Akinori

2006-05-01

This paper reviews the research findings regarding the force and length changes of the muscle-tendon complex during dynamic human movements, especially those using ultrasonography and computer simulation. The use of ultrasonography demonstrated that the tendinous structures of the muscle-tendon complex are compliant enough to influence the biomechanical behavior (length change, shortening velocity, and so on) of fascicles substantially. It was discussed that the fascicles are a force generator rather than a work generator; the tendinous structures function not only as an energy re-distributor but also as a power amplifier, and the interaction between fascicles and tendinous structures is essential for generating higher joint power outputs during the late pushoff phase in human vertical jumping. This phenomenon could be explained based on the force-length/velocity relationships of each element (contractile and series elastic elements) in the muscle-tendon complex during movements. Through computer simulation using a Hill-type muscle-tendon complex model, the benefit of making a countermovement was examined in relation to the compliance of the muscle-tendon complex and the length ratio between the contractile and series elastic elements. Also, the integral roles of the series elastic element were simulated in a cyclic human heel-raise exercise. It was suggested that the storage and reutilization of elastic energy by the tendinous structures play an important role in enhancing work output and movement efficiency in many sorts of human movements.

Evaluate the application of modal test and analysis processes to structural fault detection in MSFC - STS project elements

NASA Technical Reports Server (NTRS)

Springer, William T.

1987-01-01

The Space Transportation System (STS) is a complex and expensive flight system intended to carry unique payloads into low Earth orbit and return. A catastrophic failure, such as STS 51-L, resulted in the loss of both human life as well as expensive and unique hardware. The impact of this incident reaffirms the need to do everything possible to ensure the integrity and reliability of STS. One means of achieving this goal is to expand the number of inspection technologies available. Reported here is the evaluation of the use of modal analysis and test techniques for the purpose of assessing the structural integrity of STS components for which Marshall Space Flight Center has responsibility. This entailed reviewing existing literature and developing a low-level experimental program determine the feasibility of using this technology for structural fault detection.

[Landscape classification: research progress and development trend].

PubMed

Liang, Fa-Chao; Liu, Li-Ming

2011-06-01

Landscape classification is the basis of the researches on landscape structure, process, and function, and also, the prerequisite for landscape evaluation, planning, protection, and management, directly affecting the precision and practicability of landscape research. This paper reviewed the research progress on the landscape classification system, theory, and methodology, and summarized the key problems and deficiencies of current researches. Some major landscape classification systems, e. g. , LANMAP and MUFIC, were introduced and discussed. It was suggested that a qualitative and quantitative comprehensive classification based on the ideology of functional structure shape and on the integral consideration of landscape classification utility, landscape function, landscape structure, physiogeographical factors, and human disturbance intensity should be the major research directions in the future. The integration of mapping, 3S technology, quantitative mathematics modeling, computer artificial intelligence, and professional knowledge to enhance the precision of landscape classification would be the key issues and the development trend in the researches of landscape classification.

Genomic deletions created upon LINE-1 retrotransposition.

PubMed

Gilbert, Nicolas; Lutz-Prigge, Sheila; Moran, John V

2002-08-09

LINE-1 (L1) retrotransposition continues to impact the human genome, yet little is known about how L1 integrates into DNA. Here, we developed a plasmid-based rescue system and have used it to recover 37 new L1 retrotransposition events from cultured human cells. Sequencing of the insertions revealed the usual L1 structural hallmarks; however, in four instances, retrotransposition generated large target site deletions. Remarkably, three of those resulted in the formation of chimeric L1s, containing the 5' end of an endogenous L1 fused precisely to our engineered L1. Thus, our data demonstrate multiple pathways for L1 integration in cultured cells, and show that L1 is not simply an insertional mutagen, but that its retrotransposition can result in significant deletions of genomic sequence.

Structural basis for spectrin recognition by ankyrin.

PubMed

Ipsaro, Jonathan J; Mondragón, Alfonso

2010-05-20

Maintenance of membrane integrity and organization in the metazoan cell is accomplished through intracellular tethering of membrane proteins to an extensive, flexible protein network. Spectrin, the principal component of this network, is anchored to membrane proteins through the adaptor protein ankyrin. To elucidate the atomic basis for this interaction, we determined a crystal structure of human betaI-spectrin repeats 13 to 15 in complex with the ZU5-ANK domain of human ankyrin R. The structure reveals the role of repeats 14 to 15 in binding, the electrostatic and hydrophobic contributions along the interface, and the necessity for a particular orientation of the spectrin repeats. Using structural and biochemical data as a guide, we characterized the individual proteins and their interactions by binding and thermal stability analyses. In addition to validating the structural model, these data provide insight into the nature of some mutations associated with cell morphology defects, including those found in human diseases such as hereditary spherocytosis and elliptocytosis. Finally, analysis of the ZU5 domain suggests it is a versatile protein-protein interaction module with distinct interaction surfaces. The structure represents not only the first of a spectrin fragment in complex with its binding partner, but also that of an intermolecular complex involving a ZU5 domain.

Integration of MSFC Usability Lab with Usability Testing

NASA Technical Reports Server (NTRS)

Cheng, Yiwei; Richardson, Sally

2010-01-01

As part of the Stage Analysis Branch, human factors engineering plays an important role in relating humans to the systems of hardware and structure designs of the new launch vehicle. While many branches are involved in the technical aspects of creating a launch vehicle, human factors connects humans to the scientific systems with the goal of improving operational performance and safety while reducing operational error and damage to the hardware. Human factors engineers use physical and computerized models to visualize possible areas for improvements to ensure human accessibility to components requiring maintenance and that the necessary maintenance activities can be accomplished with minimal risks to human and hardware. Many methods of testing are used to fulfill this goal, such as physical mockups, computerized visualization, and usability testing. In this analysis, a usability test is conducted to test how usable a website is to users who are and are not familiar with it. The testing is performed using participants and Morae software to record and analyze the results. This analysis will be a preliminary test of the usability lab in preparation for use in new spacecraft programs, NASA Enterprise, or other NASA websites. The usability lab project is divided into two parts: integration of the usability lab and a preliminary test of the usability lab.

CAVEman: Standardized Anatomical Context for Biomedical Data Mapping

ERIC Educational Resources Information Center

Turinsky, Andrei L.; Fanea, Elena; Trinh, Quang; Wat, Stephen; Hallgrimsson, Benedikt; Dong, Xiaoli; Shu, Xueling; Stromer, Julie N.; Hill, Jonathan W.; Edwards, Carol; Grosenick, Brenda; Yajima, Masumi; Sensen, Christoph W.

2008-01-01

The authors have created a software system called the CAVEman, for the visual integration and exploration of heterogeneous anatomical and biomedical data. The CAVEman can be applied for both education and research tasks. The main component of the system is a three-dimensional digital atlas of the adult male human anatomy, structured according to…

Integrating Outer Space Design into Design Curriculum

ERIC Educational Resources Information Center

Wilsing, Markus; Akpinar-Wilsing, Nil

2004-01-01

The imagination of human beings and the exploration of novel ideas have always contributed to developments in science. These developments lead us to re-examine the existing structures in our environment and society so that they can be further improved. The review of literature regarding science fiction and its place in education also highlights…

Human Processing of Knowledge from Texts: Acquisition, Integration, and Reasoning.

ERIC Educational Resources Information Center

Thorndyke, Perry W.; Hayes-Roth, Barbara

This report documents a series of studies on how undergraduate students learn from and reason with textual information. The studies described were undertaken to produce models that could serve as the basis for designing computer systems capable of structuring and presenting text material in optimal formats. Divided into sections, the report…

Under Your Skin

ERIC Educational Resources Information Center

Corsino, Janet

2012-01-01

A traditional understanding in art is that, in order to draw the human figure, the artist must first understand its structure and inner workings. This project was first developed for middle-school art students in an attempt to help them better understand figure drawing. In subsequent years, it has been amended and adapted to integrate with other…

Integrated studies of Azraq Basin in Jordan

Treesearch

Mohammed Shahbaz; B. Sunna

2000-01-01

Many historical indications of the eastern Mediterranean Basin exhibit climatic changes or alterations effecting the status of water resources, hence, effecting human-kind and the quality of life. It is essential to deeply understand the nature of climates and geological structures employing state of the art techniques to assess rainfall, runoff, and floods that...

Multi-Filter String Matching and Human-Centric Entity Matching for Information Extraction

ERIC Educational Resources Information Center

Sun, Chong

2012-01-01

More and more information is being generated in text documents, such as Web pages, emails and blogs. To effectively manage this unstructured information, one broadly used approach includes locating relevant content in documents, extracting structured information and integrating the extracted information for querying, mining or further analysis. In…

Alaska's Copper River: humankind in a changing world.

Treesearch

Harriet H. Christensen; J. Louise Mastrantonio; John C. Gordon; Bernard T. Bormann

2000-01-01

Opportunities for natural and social science research were assessed in the Copper River ecosystem including long-term, integrated studies of ecosystem structure and function. The ecosystem is one where change, often rapid, cataclysmic change, is the rule rather than the exception. The ecosystem also contains a variety of people pursuing various human purposes. Although...

Conceptual ecological models to guide integrated landscape monitoring of the Great Basin

USGS Publications Warehouse

Miller, D.M.; Finn, S.P.; Woodward, Andrea; Torregrosa, Alicia; Miller, M.E.; Bedford, D.R.; Brasher, A.M.

2010-01-01

The Great Basin Integrated Landscape Monitoring Pilot Project was developed in response to the need for a monitoring and predictive capability that addresses changes in broad landscapes and waterscapes. Human communities and needs are nested within landscapes formed by interactions among the hydrosphere, geosphere, and biosphere. Understanding the complex processes that shape landscapes and deriving ways to manage them sustainably while meeting human needs require sophisticated modeling and monitoring. This document summarizes current understanding of ecosystem structure and function for many of the ecosystems within the Great Basin using conceptual models. The conceptual ecosystem models identify key ecological components and processes, identify external drivers, develop a hierarchical set of models that address both site and landscape attributes, inform regional monitoring strategy, and identify critical gaps in our knowledge of ecosystem function. The report also illustrates an approach for temporal and spatial scaling from site-specific models to landscape models and for understanding cumulative effects. Eventually, conceptual models can provide a structure for designing monitoring programs, interpreting monitoring and other data, and assessing the accuracy of our understanding of ecosystem functions and processes.

A tale of two species: neural integration in zebrafish and monkeys

PubMed Central

Joshua, Mati; Lisberger, Stephen G.

2014-01-01

Selection of a model organism creates a tension between competing constraints. The recent explosion of modern molecular techniques has revolutionized the analysis of neural systems in organisms that are amenable to genetic techniques. Yet, the non-human primate remains the gold-standard for the analysis of the neural basis of behavior, and as a bridge to the operation of the human brain. The challenge is to generalize across species in a way that exposes the operation of circuits as well as the relationship of circuits to behavior. Eye movements provide an opportunity to cross the bridge from mechanism to behavior through research on diverse species. Here, we review experiments and computational studies on a circuit function called “neural integration” that occurs in the brainstems of larval zebrafish, non-human primates, and species “in between”. We show that analysis of circuit structure using modern molecular and imaging approaches in zebrafish has remarkable explanatory power for the details of the responses of integrator neurons in the monkey. The combination of research from the two species has led to a much stronger hypothesis for the implementation of the neural integrator than could have been achieved using either species alone. PMID:24797331

Human glucose-6-phosphate dehydrogenase: the crystal structure reveals a structural NADP(+) molecule and provides insights into enzyme deficiency.

PubMed

Au, S W; Gover, S; Lam, V M; Adams, M J

2000-03-15

Glucose-6-phosphate dehydrogenase (G6PD) catalyses the first committed step in the pentose phosphate pathway; the generation of NADPH by this enzyme is essential for protection against oxidative stress. The human enzyme is in a dimer<-->tetramer equilibrium and its stability is dependent on NADP(+) concentration. G6PD deficiency results from many different point mutations in the X-linked gene encoding G6PD and is the most common human enzymopathy. Severe deficiency causes chronic non-spherocytic haemolytic anaemia; the usual symptoms are neonatal jaundice, favism and haemolytic anaemia. We have determined the first crystal structure of a human G6PD (the mutant Canton, Arg459-->Leu) at 3 A resolution. The tetramer is a dimer of dimers. Despite very similar dimer topology, there are two major differences from G6PD of Leuconostoc mesenteroides: a structural NADP(+) molecule, close to the dimer interface but integral to the subunit, is visible in all subunits of the human enzyme; and an intrasubunit disulphide bond tethers the otherwise disordered N-terminal segment. The few dimer-dimer contacts making the tetramer are charge-charge interactions. The importance of NADP(+) for stability is explained by the structural NADP(+) site, which is not conserved in prokaryotes. The structure shows that point mutations causing severe deficiency predominate close to the structural NADP(+) and the dimer interface, primarily affecting the stability of the molecule. They also indicate that a stable dimer is essential to retain activity in vivo. As there is an absolute requirement for some G6PD activity, residues essential for coenzyme or substrate binding are rarely modified.

Considerations in representing human individuals in social ecological models

USGS Publications Warehouse

Manfredo, Michael J.; Teel, Tara L.; Gavin, Michael C.; Fulton, David C.

2017-01-01

In this chapter we focus on how to integrate the human individual into social-ecological systems analysis, and how to improve research on individual thought and action regarding the environment by locating it within the broader social-ecological context. We discuss three key questions as considerations for future research: (1) is human thought conceptualized as a dynamic and adaptive process, (2) is the individual placed in a multi-level context (including within-person levels, person-group interactions, and institutional and structural factors), and (3) is human thought seen as mutually constructed with the social and natural environment. Increased emphasis on the individual will be essential if we are to understand agency, innovation, and adaptation in social-ecological systems.

Framework for Infectious Disease Analysis: A comprehensive and integrative multi-modeling approach to disease prediction and management.

PubMed

Erraguntla, Madhav; Zapletal, Josef; Lawley, Mark

2017-12-01

The impact of infectious disease on human populations is a function of many factors including environmental conditions, vector dynamics, transmission mechanics, social and cultural behaviors, and public policy. A comprehensive framework for disease management must fully connect the complete disease lifecycle, including emergence from reservoir populations, zoonotic vector transmission, and impact on human societies. The Framework for Infectious Disease Analysis is a software environment and conceptual architecture for data integration, situational awareness, visualization, prediction, and intervention assessment. Framework for Infectious Disease Analysis automatically collects biosurveillance data using natural language processing, integrates structured and unstructured data from multiple sources, applies advanced machine learning, and uses multi-modeling for analyzing disease dynamics and testing interventions in complex, heterogeneous populations. In the illustrative case studies, natural language processing from social media, news feeds, and websites was used for information extraction, biosurveillance, and situation awareness. Classification machine learning algorithms (support vector machines, random forests, and boosting) were used for disease predictions.

Enteric nervous system abnormalities are present in human necrotizing enterocolitis: potential neurotransplantation therapy

PubMed Central

2013-01-01

Introduction Intestinal dysmotility following human necrotizing enterocolitis suggests that the enteric nervous system is injured during the disease. We examined human intestinal specimens to characterize the enteric nervous system injury that occurs in necrotizing enterocolitis, and then used an animal model of experimental necrotizing enterocolitis to determine whether transplantation of neural stem cells can protect the enteric nervous system from injury. Methods Human intestinal specimens resected from patients with necrotizing enterocolitis (n = 18), from control patients with bowel atresia (n = 8), and from necrotizing enterocolitis and control patients undergoing stoma closure several months later (n = 14 and n = 6 respectively) were subjected to histologic examination, immunohistochemistry, and real-time reverse-transcription polymerase chain reaction to examine the myenteric plexus structure and neurotransmitter expression. In addition, experimental necrotizing enterocolitis was induced in newborn rat pups and neurotransplantation was performed by administration of fluorescently labeled neural stem cells, with subsequent visualization of transplanted cells and determination of intestinal integrity and intestinal motility. Results There was significant enteric nervous system damage with increased enteric nervous system apoptosis, and decreased neuronal nitric oxide synthase expression in myenteric ganglia from human intestine resected for necrotizing enterocolitis compared with control intestine. Structural and functional abnormalities persisted months later at the time of stoma closure. Similar abnormalities were identified in rat pups exposed to experimental necrotizing enterocolitis. Pups receiving neural stem cell transplantation had improved enteric nervous system and intestinal integrity, differentiation of transplanted neural stem cells into functional neurons, significantly improved intestinal transit, and significantly decreased mortality compared with control pups. Conclusions Significant injury to the enteric nervous system occurs in both human and experimental necrotizing enterocolitis. Neural stem cell transplantation may represent a novel future therapy for patients with necrotizing enterocolitis. PMID:24423414

Wikidata as a semantic framework for the Gene Wiki initiative.

PubMed

Burgstaller-Muehlbacher, Sebastian; Waagmeester, Andra; Mitraka, Elvira; Turner, Julia; Putman, Tim; Leong, Justin; Naik, Chinmay; Pavlidis, Paul; Schriml, Lynn; Good, Benjamin M; Su, Andrew I

2016-01-01

Open biological data are distributed over many resources making them challenging to integrate, to update and to disseminate quickly. Wikidata is a growing, open community database which can serve this purpose and also provides tight integration with Wikipedia. In order to improve the state of biological data, facilitate data management and dissemination, we imported all human and mouse genes, and all human and mouse proteins into Wikidata. In total, 59,721 human genes and 73,355 mouse genes have been imported from NCBI and 27,306 human proteins and 16,728 mouse proteins have been imported from the Swissprot subset of UniProt. As Wikidata is open and can be edited by anybody, our corpus of imported data serves as the starting point for integration of further data by scientists, the Wikidata community and citizen scientists alike. The first use case for these data is to populate Wikipedia Gene Wiki infoboxes directly from Wikidata with the data integrated above. This enables immediate updates of the Gene Wiki infoboxes as soon as the data in Wikidata are modified. Although Gene Wiki pages are currently only on the English language version of Wikipedia, the multilingual nature of Wikidata allows for usage of the data we imported in all 280 different language Wikipedias. Apart from the Gene Wiki infobox use case, a SPARQL endpoint and exporting functionality to several standard formats (e.g. JSON, XML) enable use of the data by scientists. In summary, we created a fully open and extensible data resource for human and mouse molecular biology and biochemistry data. This resource enriches all the Wikipedias with structured information and serves as a new linking hub for the biological semantic web. Database URL: https://www.wikidata.org/. © The Author(s) 2016. Published by Oxford University Press.

Disruption of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Integrity Contributes to Muscle Insulin Resistance in Mice and Humans.

PubMed

Tubbs, Emily; Chanon, Stéphanie; Robert, Maud; Bendridi, Nadia; Bidaux, Gabriel; Chauvin, Marie-Agnès; Ji-Cao, Jingwei; Durand, Christine; Gauvrit-Ramette, Daphné; Vidal, Hubert; Lefai, Etienne; Rieusset, Jennifer

2018-04-01

Modifications of the interactions between endoplasmic reticulum (ER) and mitochondria, defined as mitochondria-associated membranes (MAMs), were recently shown to be involved in the control of hepatic insulin action and glucose homeostasis, but with conflicting results. Whereas skeletal muscle is the primary site of insulin-mediated glucose uptake and the main target for alterations in insulin-resistant states, the relevance of MAM integrity in muscle insulin resistance is unknown. Deciphering the importance of MAMs on muscle insulin signaling could help to clarify this controversy. Here, we show in skeletal muscle of different mice models of obesity and type 2 diabetes (T2D) a marked disruption of ER-mitochondria interactions as an early event preceding mitochondrial dysfunction and insulin resistance. Furthermore, in human myotubes, palmitate-induced insulin resistance is associated with a reduction of structural and functional ER-mitochondria interactions. Importantly, experimental increase of ER-mitochondria contacts in human myotubes prevents palmitate-induced alterations of insulin signaling and action, whereas disruption of MAM integrity alters the action of the hormone. Lastly, we found an association between altered insulin signaling and ER-mitochondria interactions in human myotubes from obese subjects with or without T2D compared with healthy lean subjects. Collectively, our data reveal a new role of MAM integrity in insulin action of skeletal muscle and highlight MAM disruption as an essential subcellular alteration associated with muscle insulin resistance in mice and humans. Therefore, reduced ER-mitochondria coupling could be a common alteration of several insulin-sensitive tissues playing a key role in altered glucose homeostasis in the context of obesity and T2D. © 2018 by the American Diabetes Association.

Humanization of work circumstances in dialog communication using data display devices, volume 1

NASA Astrophysics Data System (ADS)

Graunke, H.; Julich, H.; Petersen, H. C.; Schaefer, H.; Strupp, K.

1982-11-01

The effects of data display on working places was investigated. Data processing by data display devices is not considered. Important criteria for job contentment is the integration into complex job structures. Corresponding to this principle of organization is team work with a flexible way of labor division which provides the chance and the motivation for a cooperative self controlled working process which give strain caused by data display devices. It is found that in public administration a team with an institutional leadership with primarily social integrative functions is appreciated most.

Metagenomic systems biology and metabolic modeling of the human microbiome: from species composition to community assembly rules.

PubMed

Levy, Roie; Borenstein, Elhanan

2014-01-01

The human microbiome is a key contributor to health and development. Yet little is known about the ecological forces that are at play in defining the composition of such host-associated communities. Metagenomics-based studies have uncovered clear patterns of community structure but are often incapable of distinguishing alternative structuring paradigms. In a recent study, we integrated metagenomic analysis with a systems biology approach, using a reverse ecology framework to model numerous human microbiota species and to infer metabolic interactions between species. Comparing predicted interactions with species composition data revealed that the assembly of the human microbiome is dominated at the community level by habitat filtering. Furthermore, we demonstrated that this habitat filtering cannot be accounted for by known host phenotypes or by the metabolic versatility of the various species. Here we provide a summary of our findings and offer a brief perspective on related studies and on future approaches utilizing this metagenomic systems biology framework.

From confluent human iPS cells to self-forming neural retina and retinal pigmented epithelium

PubMed Central

Reichman, Sacha; Terray, Angélique; Slembrouck, Amélie; Nanteau, Céline; Orieux, Gaël; Habeler, Walter; Nandrot, Emeline F.; Sahel, José-Alain; Monville, Christelle; Goureau, Olivier

2014-01-01

Progress in retinal-cell therapy derived from human pluripotent stem cells currently faces technical challenges that require the development of easy and standardized protocols. Here, we developed a simple retinal differentiation method, based on confluent human induced pluripotent stem cells (hiPSC), bypassing embryoid body formation and the use of exogenous molecules, coating, or Matrigel. In 2 wk, we generated both retinal pigmented epithelial cells and self-forming neural retina (NR)-like structures containing retinal progenitor cells (RPCs). We report sequential differentiation from RPCs to the seven neuroretinal cell types in maturated NR-like structures as floating cultures, thereby revealing the multipotency of RPCs generated from integration-free hiPSCs. Furthermore, Notch pathway inhibition boosted the generation of photoreceptor precursor cells, crucial in establishing cell therapy strategies. This innovative process proposed here provides a readily efficient and scalable approach to produce retinal cells for regenerative medicine and for drug-screening purposes, as well as an in vitro model of human retinal development and disease. PMID:24912154

Toward Developmental Connectomics of the Human Brain

PubMed Central

Cao, Miao; Huang, Hao; Peng, Yun; Dong, Qi; He, Yong

2016-01-01

Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying structural and functional connectivity patterns of the developing brain. Normal brain development is characterized by continuous and significant network evolution throughout infancy, childhood, and adolescence, following specific maturational patterns. Disruption of these normal changes is associated with neuropsychiatric developmental disorders, such as autism spectrum disorders or attention-deficit hyperactivity disorder. In this review, we focused on the recent progresses regarding typical and atypical development of human brain networks from birth to early adulthood, using a connectomic approach. Specifically, by the time of birth, structural networks already exhibit adult-like organization, with global efficient small-world and modular structures, as well as hub regions and rich-clubs acting as communication backbones. During development, the structure networks are fine-tuned, with increased global integration and robustness and decreased local segregation, as well as the strengthening of the hubs. In parallel, functional networks undergo more dramatic changes during maturation, with both increased integration and segregation during development, as brain hubs shift from primary regions to high order functioning regions, and the organization of modules transitions from a local anatomical emphasis to a more distributed architecture. These findings suggest that structural networks develop earlier than functional networks; meanwhile functional networks demonstrate more dramatic maturational changes with the evolution of structural networks serving as the anatomical backbone. In this review, we also highlighted topologically disorganized characteristics in structural and functional brain networks in several major developmental neuropsychiatric disorders (e.g., autism spectrum disorders, attention-deficit hyperactivity disorder and developmental dyslexia). Collectively, we showed that delineation of the brain network from a connectomics perspective offers a unique and refreshing view of both normal development and neuropsychiatric disorders. PMID:27064378

Crystal Structure of the FERM-SH2 Module of Human Jak2.

PubMed

McNally, Randall; Toms, Angela V; Eck, Michael J

2016-01-01

Jak-family tyrosine kinases mediate signaling from diverse cytokine receptors. Binding of Jaks to their cognate receptors is mediated by their N-terminal region, which contains FERM and SH2 domains. Here we describe the crystal structure of the FERM-SH2 region of Jak2 at 3.0Å resolution. The structure reveals that these domains and their flanking linker segments interact intimately to form an integrated structural module. The Jak2 FERM-SH2 structure closely resembles that recently described for Tyk2, another member of the Jak family. While the overall architecture and interdomain orientations are preserved between Jak2 and Tyk2, we identify residues in the putative receptor-binding groove that differ between the two and may contribute to the specificity of receptor recognition. Analysis of Jak mutations that are reported to disrupt receptor binding reveals that they lie in the hydrophobic core of the FERM domain, and are thus expected to compromise the structural integrity of the FERM-SH2 unit. Similarly, analysis of mutations in Jak3 that are associated with severe combined immunodeficiency suggests that they compromise Jak3 function by destabilizing the FERM-SH2 structure.

StrAuto: automation and parallelization of STRUCTURE analysis.

PubMed

Chhatre, Vikram E; Emerson, Kevin J

2017-03-24

Population structure inference using the software STRUCTURE has become an integral part of population genetic studies covering a broad spectrum of taxa including humans. The ever-expanding size of genetic data sets poses computational challenges for this analysis. Although at least one tool currently implements parallel computing to reduce computational overload of this analysis, it does not fully automate the use of replicate STRUCTURE analysis runs required for downstream inference of optimal K. There is pressing need for a tool that can deploy population structure analysis on high performance computing clusters. We present an updated version of the popular Python program StrAuto, to streamline population structure analysis using parallel computing. StrAuto implements a pipeline that combines STRUCTURE analysis with the Evanno Δ K analysis and visualization of results using STRUCTURE HARVESTER. Using benchmarking tests, we demonstrate that StrAuto significantly reduces the computational time needed to perform iterative STRUCTURE analysis by distributing runs over two or more processors. StrAuto is the first tool to integrate STRUCTURE analysis with post-processing using a pipeline approach in addition to implementing parallel computation - a set up ideal for deployment on computing clusters. StrAuto is distributed under the GNU GPL (General Public License) and available to download from http://strauto.popgen.org .

Integration and long distance axonal regeneration in the central nervous system from transplanted primitive neural stem cells.

PubMed

Zhao, Jiagang; Sun, Woong; Cho, Hyo Min; Ouyang, Hong; Li, Wenlin; Lin, Ying; Do, Jiun; Zhang, Liangfang; Ding, Sheng; Liu, Yizhi; Lu, Paul; Zhang, Kang

2013-01-04

Spinal cord injury (SCI) results in devastating motor and sensory deficits secondary to disrupted neuronal circuits and poor regenerative potential. Efforts to promote regeneration through cell extrinsic and intrinsic manipulations have met with limited success. Stem cells represent an as yet unrealized therapy in SCI. Recently, we identified novel culture methods to induce and maintain primitive neural stem cells (pNSCs) from human embryonic stem cells. We tested whether transplanted human pNSCs can integrate into the CNS of the developing chick neural tube and injured adult rat spinal cord. Following injection of pNSCs into the developing chick CNS, pNSCs integrated into the dorsal aspects of the neural tube, forming cell clusters that spontaneously differentiated into neurons. Furthermore, following transplantation of pNSCs into the lesioned rat spinal cord, grafted pNSCs survived, differentiated into neurons, and extended long distance axons through the scar tissue at the graft-host interface and into the host spinal cord to form terminal-like structures near host spinal neurons. Together, these findings suggest that pNSCs derived from human embryonic stem cells differentiate into neuronal cell types with the potential to extend axons that associate with circuits of the CNS and, more importantly, provide new insights into CNS integration and axonal regeneration, offering hope for repair in SCI.

Central mechanisms for force and motion--towards computational synthesis of human movement.

PubMed

Hemami, Hooshang; Dariush, Behzad

2012-12-01

Anatomical, physiological and experimental research on the human body can be supplemented by computational synthesis of the human body for all movement: routine daily activities, sports, dancing, and artistic and exploratory involvements. The synthesis requires thorough knowledge about all subsystems of the human body and their interactions, and allows for integration of known knowledge in working modules. It also affords confirmation and/or verification of scientific hypotheses about workings of the central nervous system (CNS). A simple step in this direction is explored here for controlling the forces of constraint. It requires co-activation of agonist-antagonist musculature. The desired trajectories of motion and the force of contact have to be provided by the CNS. The spinal control involves projection onto a muscular subset that induces the force of contact. The projection of force in the sensory motor cortex is implemented via a well-defined neural population unit, and is executed in the spinal cord by a standard integral controller requiring input from tendon organs. The sensory motor cortex structure is extended to the case for directing motion via two neural population units with vision input and spindle efferents. Digital computer simulations show the feasibility of the system. The formulation is modular and can be extended to multi-link limbs, robot and humanoid systems with many pairs of actuators or muscles. It can be expanded to include reticular activating structures and learning. Copyright © 2012 Elsevier Ltd. All rights reserved.

NASA Human Integration Design Handbook (HIDH): Revitalization of Space-Related Human Factors, Environmental, and Habitability Data and Design Guidance

NASA Technical Reports Server (NTRS)

Stroud, Kenneth; Pickett, Lynn; Tillman, Barry

2008-01-01

This poster presentation reviews the Human Integration Design Handbook (HIDH). It provides guidance and data to aid vehicle / habitat designers in human-system integration It also aids requirements writers in development of human-system integration requirements from SFHSS Standards

Reflexive aerostructures: increased vehicle survivability

NASA Astrophysics Data System (ADS)

Margraf, Thomas W.; Hemmelgarn, Christopher D.; Barnell, Thomas J.; Franklin, Mark A.

2007-04-01

Aerospace systems stand to benefit significantly from the advancement of reflexive aerostructure technologies for increased vehicle survivability. Cornerstone Research Group Inc. (CRG) is developing lightweight, healable composite systems for use as primary load-bearing aircraft components. The reflexive system is comprised of piezoelectric structural health monitoring systems, localized thermal activation systems, and lightweight, healable composite structures. The reflexive system is designed to mimic the involuntary human response to damage. Upon impact, the structural health monitoring system will identify the location and magnitude of the damage, sending a signal to a discrete thermal activation control system to resistively heat the shape memory polymer (SMP) matrix composite above activation temperature, resulting in localized shape recovery and healing of the damaged areas. CRG has demonstrated SMP composites that can recover 90 percent of flexural yield stress and modulus after postfailure healing. During the development, CRG has overcome issues of discrete activation, structural health monitoring integration, and healable resin systems. This paper will address the challenges associated with development of a reflexive aerostructure, including integration of structural health monitoring, discrete healing, and healable shape memory resin systems.

Medical humanities and their discontents: definitions, critiques, and implications.

PubMed

Shapiro, Johanna; Coulehan, Jack; Wear, Delese; Montello, Martha

2009-02-01

The humanities offer great potential for enhancing professional and humanistic development in medical education. Yet, although many students report benefit from exposure to the humanities in their medical education, they also offer consistent complaints and skepticism. The authors offer a pedagogical definition of the medical humanities, linking it to medicine as a practice profession. They then explore three student critiques of medical humanities curricula: (1) the content critique, examining issues of perceived relevance and intellectual bait-and-switch, (2) the teaching critique, which examines instructor trustworthiness and perceived personal intrusiveness, and (3) the structural/placement critique, or how and when medical humanities appear in the curriculum. Next, ways are suggested to tailor medical humanities to better acknowledge and reframe the needs of medical students. These include ongoing cross-disciplinary reflective practices in which intellectual tools of the humanities are incorporated into educational activities to help students examine and, at times, contest the process, values, and goals of medical practice. This systematic, pervasive reflection will organically lead to meaningful contributions from the medical humanities in three specific areas of great interest to medical educators: professionalism, "narrativity," and educational competencies. Regarding pedagogy, the implications of this approach are an integrated required curriculum and innovative concepts such as "applied humanities scholars." In turn, systematic integration of humanities perspectives and ways of thinking into clinical training will usefully expand the range of metaphors and narratives available to reflect on medical practice and offer possibilities for deepening and strengthening professional education.

Lineage-specific expansions of retroviral insertions within the genomes of African great apes but not humans and orangutans.

PubMed

Yohn, Chris T; Jiang, Zhaoshi; McGrath, Sean D; Hayden, Karen E; Khaitovich, Philipp; Johnson, Matthew E; Eichler, Marla Y; McPherson, John D; Zhao, Shaying; Pääbo, Svante; Eichler, Evan E

2005-04-01

Retroviral infections of the germline have the potential to episodically alter gene function and genome structure during the course of evolution. Horizontal transmissions between species have been proposed, but little evidence exists for such events in the human/great ape lineage of evolution. Based on analysis of finished BAC chimpanzee genome sequence, we characterize a retroviral element (Pan troglodytes endogenous retrovirus 1 [PTERV1]) that has become integrated in the germline of African great ape and Old World monkey species but is absent from humans and Asian ape genomes. We unambiguously map 287 retroviral integration sites and determine that approximately 95.8% of the insertions occur at non-orthologous regions between closely related species. Phylogenetic analysis of the endogenous retrovirus reveals that the gorilla and chimpanzee elements share a monophyletic origin with a subset of the Old World monkey retroviral elements, but that the average sequence divergence exceeds neutral expectation for a strictly nuclear inherited DNA molecule. Within the chimpanzee, there is a significant integration bias against genes, with only 14 of these insertions mapping within intronic regions. Six out of ten of these genes, for which there are expression data, show significant differences in transcript expression between human and chimpanzee. Our data are consistent with a retroviral infection that bombarded the genomes of chimpanzees and gorillas independently and concurrently, 3-4 million years ago. We speculate on the potential impact of such recent events on the evolution of humans and great apes.

[Research of joint-robotics-based design of biomechanics testing device on human spine].

PubMed

Deng, Guoyong; Tian, Lianfang; Mao, Zongyuan

2009-12-01

This paper introduces the hardware and software of a biomechanical robot-based testing device. The bottom control orders, posture and torque data transmission, and the control algorithms are integrated in a unified visual control platform by Visual C+ +, with easy control and management. By using hybrid force-displacement control method to load the human spine, we can test the organizational structure and the force state of the FSU (Functional spinal unit) well, which overcomes the shortcomings due to the separation of the force and displacement measurement, thus greatly improves the measurement accuracy. Also it is esay to identify the spinal degeneration and the load-bearing impact on the organizational structure of the FSU after various types of surgery.

The Ecology of Seamounts: Structure, Function, and Human Impacts

NASA Astrophysics Data System (ADS)

Clark, Malcolm R.; Rowden, Ashley A.; Schlacher, Thomas; Williams, Alan; Consalvey, Mireille; Stocks, Karen I.; Rogers, Alex D.; O'Hara, Timothy D.; White, Martin; Shank, Timothy M.; Hall-Spencer, Jason M.

2010-01-01

In this review of seamount ecology, we address a number of key scientific issues concerning the structure and function of benthic communities, human impacts, and seamount management and conservation. We consider whether community composition and diversity differ between seamounts and continental slopes, how important dispersal capabilities are in seamount connectivity, what environmental factors drive species composition and diversity, whether seamounts are centers of enhanced biological productivity, and whether they have unique trophic architecture. We discuss how vulnerable seamount communities are to fishing and mining, and how we can balance exploitation of resources and conservation of habitat. Despite considerable advances in recent years, there remain many questions about seamount ecosystems that need closer integration of molecular, oceanographic, and ecological research.

Architecture of the Human and Yeast General Transcription and DNA Repair Factor TFIIH.

PubMed

Luo, Jie; Cimermancic, Peter; Viswanath, Shruthi; Ebmeier, Christopher C; Kim, Bong; Dehecq, Marine; Raman, Vishnu; Greenberg, Charles H; Pellarin, Riccardo; Sali, Andrej; Taatjes, Dylan J; Hahn, Steven; Ranish, Jeff

2015-09-03

TFIIH is essential for both RNA polymerase II transcription and DNA repair, and mutations in TFIIH can result in human disease. Here, we determine the molecular architecture of human and yeast TFIIH by an integrative approach using chemical crosslinking/mass spectrometry (CXMS) data, biochemical analyses, and previously published electron microscopy maps. We identified four new conserved "topological regions" that function as hubs for TFIIH assembly and more than 35 conserved topological features within TFIIH, illuminating a network of interactions involved in TFIIH assembly and regulation of its activities. We show that one of these conserved regions, the p62/Tfb1 Anchor region, directly interacts with the DNA helicase subunit XPD/Rad3 in native TFIIH and is required for the integrity and function of TFIIH. We also reveal the structural basis for defects in patients with xeroderma pigmentosum and trichothiodystrophy, with mutations found at the interface between the p62 Anchor region and the XPD subunit. Copyright © 2015 Elsevier Inc. All rights reserved.

Architecture of the human and yeast general transcription and DNA repair factor TFIIH

PubMed Central

Luo, Jie; Cimermancic, Peter; Viswanath, Shruthi; Ebmeier, Christopher C.; Kim, Bong; Dehecq, Marine; Raman, Vishnu; Greenberg, Charles H.; Pellarin, Riccardo; Sali, Andrej; Taatjes, Dylan J.; Hahn, Steven; Ranish, Jeff

2015-01-01

Summary TFIIH is essential for both RNA polymerase II transcription and DNA repair, and mutations in TFIIH can result in human disease. Here, we determine the molecular architecture of human and yeast TFIIH by an integrative approach using chemical crosslinking/mass spectrometry (CXMS) data, biochemical analyses, and previously published electron microscopy maps. We identified four new conserved “topological regions” that function as hubs for TFIIH assembly and more than 35 conserved topological features within TFIIH, illuminating a network of interactions involved in TFIIH assembly and regulation of its activities. We show that one of these conserved regions, the p62/Tfb1 Anchor region, directly interacts with the DNA helicase subunit XPD/Rad3 in native TFIIH and is required for the integrity and function of TFIIH. We also reveal the structural basis for defects in patients with Xeroderma pigmentosum and Trichothiodystrophy, with mutations found at the interface between the p62 Anchor region and the XPD subunit. PMID:26340423

Structural health monitoring and impact detection for primary aircraft structures

NASA Astrophysics Data System (ADS)

Kosters, Eric; van Els, Thomas J.

2010-04-01

The increasing use of thermoplastic carbon fiber-reinforced plastic (CFRP) materials in the aerospace industry for primary aircraft structures, such as wing leading-edge surfaces and fuselage sections, has led to rapid growth in the field of structural health monitoring (SHM). Impact, vibration, and load can all cause failure, such as delamination and matrix cracking, in composite materials. Moreover, the internal material damage can occur without being visible to the human eye, making inspection of and clear insight into structural integrity difficult using currently available evaluation methods. Here, we describe the detection of impact and its localization in materials and structures by high-speed interrogation of multiple-fiber Bragg grating (FBG) sensors mounted on a composite aircraft component.

Connectome Signatures of Neurocognitive Abnormalities in Euthymic Bipolar I Disorder

PubMed Central

Ajilore, Olusola; Vizueta, Nathalie; Walshaw, Patricia; Zhan, Liang; Leow, Alex; Altshuler, Lori L.

2015-01-01

Objectives Connectomics have allowed researchers to study integrative patterns of neural connectivity in humans. Yet, it is unclear how connectomics may elucidate structure-function relationships in bipolar I disorder (BPI). Expanding on our previous structural connectome study, here we used an overlapping sample with additional psychometric and fMRI data to relate structural connectome properties to both fMRI signals and cognitive performance. Methods 42 subjects completed a neuropsychological (NP) battery covering domains of processing speed, verbal memory, working memory, and cognitive flexibility. 32 subjects also had fMRI data performing a Go/NoGo task. Results Bipolar participants had lower NP performance across all domains, but only working memory reached statistical significance. In BPI participants, processing speed was significantly associated with both white matter integrity (WMI) in the corpus callosum and interhemispheric network integration. Mediation models further revealed that the relationship between interhemispheric integration and processing speed was mediated by WMI, and processing speed mediated the relationship between WMI and working memory. Bipolar subjects had significantly decreased BA47 activation during NoGo vs. Go. Significant predictors of BA47 fMRI activations during the Go/NoGo task were its nodal path length (left hemisphere) and its nodal clustering coefficient (right hemisphere). Conclusions This study suggests that structural connectome changes underlie abnormalities in fMRI activation and cognitive performance in euthymic BPI subjects. Results support that BA47 structural connectome changes may be a trait marker for BPI. Future studies are needed to determine if these “connectome signatures” may also confer a biological risk and/or serve as predictors of relapse. PMID:26228398

Evaluation of the integrated clinic model for HIV/AIDS services in Ho Chi Minh City, Viet Nam, 2013-2014.

PubMed

Hung, V; Nguyen, S T; Tieu, V T T; Nguyen, T T T; Duong, T H; Lyss, S; Oeltmann, J E

2016-12-21

Setting: Ho Chi Minh City (HCMC), Viet Nam. Objective: To evaluate a new integrated service model for human immunodeficiency virus/acquired immune-deficiency syndrome (HIV/AIDS) care. Design: In HCMC, co-located services, including voluntary HIV counseling and testing (VCT), HIV treatment at out-patient clinics (OPC), and methadone maintenance therapy (MMT) for persons who inject drugs, have operated under different administrative structures. In the context of decreasing international financial support, integration of these services into one administrative structure with reduced staff occurred in seven districts in HCMC between October 2013 and June 2014. We used a pre-post study design to compare service-related outcomes from routinely collected data at health facilities 6 months before and 6 months after integration. Results: The proportion of HIV-infected persons linked from VCT to OPCs was unchanged or increased following integration. A higher percentage of patients eligible for antiretroviral therapy (ART) were started on ART. The proportion of ART patients lost to follow-up remained unchanged. The proportions of MMT patients who tested positive for heroin or other substances decreased or were unchanged. Conclusions: VCT, OPC and MMT service delivery quality remained the same or improved during the 6 months following the integration. Expansion of the integrated model should be considered for HIV-related services.

Laser Direct Writing and Selective Metallization of Metallic Circuits for Integrated Wireless Devices.

PubMed

Cai, Jinguang; Lv, Chao; Watanabe, Akira

2018-01-10

Portable and wearable devices have attracted wide research attention due to their intimate relations with human daily life. As basic structures in the devices, the preparation of high-conductive metallic circuits or micro-circuits on flexible substrates should be facile, cost-effective, and easily integrated with other electronic units. In this work, high-conductive carbon/Ni composite structures were prepared by using a facile laser direct writing method, followed by an electroless Ni plating process, which exhibit a 3-order lower sheet resistance of less than 0.1 ohm/sq compared to original structures before plating, showing the potential for practical use. The carbon/Ni composite structures exhibited a certain flexibility and excellent anti-scratch property due to the tight deposition of Ni layers on carbon surfaces. On the basis of this approach, a wireless charging and storage device on a polyimide film was demonstrated by integrating an outer rectangle carbon/Ni composite coil for harvesting electromagnetic waves and an inner carbon micro-supercapacitor for energy storage, which can be fast charged wirelessly by a commercial wireless charger. Furthermore, a near-field communication (NFC) tag was prepared by combining a carbon/Ni composite coil for harvesting signals and a commercial IC chip for data storage, which can be used as an NFC tag for practical application.

The structural and functional brain networks that support human social networks.

PubMed

Noonan, M P; Mars, R B; Sallet, J; Dunbar, R I M; Fellows, L K

2018-02-20

Social skills rely on a specific set of cognitive processes, raising the possibility that individual differences in social networks are related to differences in specific brain structural and functional networks. Here, we tested this hypothesis with multimodality neuroimaging. With diffusion MRI (DMRI), we showed that differences in structural integrity of particular white matter (WM) tracts, including cingulum bundle, extreme capsule and arcuate fasciculus were associated with an individual's social network size (SNS). A voxel-based morphology analysis demonstrated correlations between gray matter (GM) volume and SNS in limbic and temporal lobe regions. These structural changes co-occured with functional network differences. As a function of SNS, dorsomedial and dorsolateral prefrontal cortex showed altered resting-state functional connectivity with the default mode network (DMN). Finally, we integrated these three complementary methods, interrogating the relationship between social GM clusters and specific WM and resting-state networks (RSNs). Probabilistic tractography seeded in these GM nodes utilized the SNS-related WM pathways. Further, the spatial and functional overlap between the social GM clusters and the DMN was significantly closer than other control RSNs. These integrative analyses provide convergent evidence of the role of specific circuits in SNS, likely supporting the adaptive behavior necessary for success in extensive social environments. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Social cognitive theory of gender development and differentiation.

PubMed

Bussey, K; Bandura, A

1999-10-01

Human differentiation on the basis of gender is a fundamental phenomenon that affects virtually every aspect of people's daily lives. This article presents the social cognitive theory of gender role development and functioning. It specifies how gender conceptions are constructed from the complex mix of experiences and how they operate in concert with motivational and self-regulatory mechanisms to guide gender-linked conduct throughout the life course. The theory integrates psychological and sociostructural determinants within a unified conceptual structure. In this theoretical perspective, gender conceptions and roles are the product of a broad network of social influences operating interdependently in a variety of societal subsystems. Human evolution provides bodily structures and biological potentialities that permit a range of possibilities rather than dictate a fixed type of gender differentiation. People contribute to their self-development and bring about social changes that define and structure gender relationships through their agentic actions within the interrelated systems of influence.

Frontostriatal white matter integrity mediates adult age differences in probabilistic reward learning.

PubMed

Samanez-Larkin, Gregory R; Levens, Sara M; Perry, Lee M; Dougherty, Robert F; Knutson, Brian

2012-04-11

Frontostriatal circuits have been implicated in reward learning, and emerging findings suggest that frontal white matter structural integrity and probabilistic reward learning are reduced in older age. This cross-sectional study examined whether age differences in frontostriatal white matter integrity could account for age differences in reward learning in a community life span sample of human adults. By combining diffusion tensor imaging with a probabilistic reward learning task, we found that older age was associated with decreased reward learning and decreased white matter integrity in specific pathways running from the thalamus to the medial prefrontal cortex and from the medial prefrontal cortex to the ventral striatum. Further, white matter integrity in these thalamocorticostriatal paths could statistically account for age differences in learning. These findings suggest that the integrity of frontostriatal white matter pathways critically supports reward learning. The findings also raise the possibility that interventions that bolster frontostriatal integrity might improve reward learning and decision making.

Decision support for integrated landscape evaluation and restoration planning.

Treesearch

Keith M. Reynolds; Paul F. Hessburg

2005-01-01

The historical patterns of Inland Northwest United States forests have been dramatically altered by a little more than two centuries of human settlement and land use. Spatial patterns of forest structural conditions, tree species composition, snags and down wood, and temporal variation in these patterns, have been altered to such an extent that the natural ebb and flow...

Utilizing Human Patient Simulators (HPS) to Meet Learning Objectives across Concurrent Core Nursing Courses: A Pilot Study

ERIC Educational Resources Information Center

Miller, Charman L.; Leadingham, Camille; Vance, Ronald

2010-01-01

Associate Degree Nursing (ADN) faculty are challenged by the monumental responsibility of preparing students to function as safe, professional nurses in a two year course of study. Advances in computer technology and emphasis on integrating technology and active learning strategies into existing course structures have prompted many nurse educators…

Holocaust Youth and Creativity.

ERIC Educational Resources Information Center

Clark, Joanna

As Holocaust study for youth becomes integrated into the U.S. educational structure, educators throughout the country are going to need resources that combine history and humanity to convey to young people the impact of tragedy and violence that World War II and the Holocaust had on the youth of a particular time in the 20th century. This paper…

Theorising big IT programmes in healthcare: strong structuration theory meets actor-network theory.

PubMed

Greenhalgh, Trisha; Stones, Rob

2010-05-01

The UK National Health Service is grappling with various large and controversial IT programmes. We sought to develop a sharper theoretical perspective on the question "What happens - at macro-, meso- and micro-level - when government tries to modernise a health service with the help of big IT?" Using examples from data fragments at the micro-level of clinical work, we considered how structuration theory and actor-network theory (ANT) might be combined to inform empirical investigation. Giddens (1984) argued that social structures and human agency are recursively linked and co-evolve. ANT studies the relationships that link people and technologies in dynamic networks. It considers how discourses become inscribed in data structures and decision models of software, making certain network relations irreversible. Stones' (2005) strong structuration theory (SST) is a refinement of Giddens' work, systematically concerned with empirical research. It views human agents as linked in dynamic networks of position-practices. A quadripartite approcach considers [a] external social structures (conditions for action); [b] internal social structures (agents' capabilities and what they 'know' about the social world); [c] active agency and actions and [d] outcomes as they feed back on the position-practice network. In contrast to early structuration theory and ANT, SST insists on disciplined conceptual methodology and linking this with empirical evidence. In this paper, we adapt SST for the study of technology programmes, integrating elements from material interactionism and ANT. We argue, for example, that the position-practice network can be a socio-technical one in which technologies in conjunction with humans can be studied as 'actants'. Human agents, with their complex socio-cultural frames, are required to instantiate technology in social practices. Structurally relevant properties inscribed and embedded in technological artefacts constrain and enable human agency. The fortunes of healthcare IT programmes might be studied in terms of the interplay between these factors. Copyright 2010 Elsevier Ltd. All rights reserved.

Computer-Based Learning: Graphical Integration of Whole and Sectional Neuroanatomy Improves Long-Term Retention

PubMed Central

Naaz, Farah; Chariker, Julia H.; Pani, John R.

2013-01-01

A study was conducted to test the hypothesis that instruction with graphically integrated representations of whole and sectional neuroanatomy is especially effective for learning to recognize neural structures in sectional imagery (such as MRI images). Neuroanatomy was taught to two groups of participants using computer graphical models of the human brain. Both groups learned whole anatomy first with a three-dimensional model of the brain. One group then learned sectional anatomy using two-dimensional sectional representations, with the expectation that there would be transfer of learning from whole to sectional anatomy. The second group learned sectional anatomy by moving a virtual cutting plane through the three-dimensional model. In tests of long-term retention of sectional neuroanatomy, the group with graphically integrated representation recognized more neural structures that were known to be challenging to learn. This study demonstrates the use of graphical representation to facilitate a more elaborated (deeper) understanding of complex spatial relations. PMID:24563579

Structural Insights into the Assembly of the Adeno-associated Virus Type 2 Rep68 Protein on the Integration Site AAVS1*

PubMed Central

Musayev, Faik N.; Zarate-Perez, Francisco; Bishop, Clayton; Burgner, John W.; Escalante, Carlos R.

2015-01-01

Adeno-associated virus (AAV) is the only eukaryotic virus with the property of establishing latency by integrating site-specifically into the human genome. The integration site known as AAVS1 is located in chromosome 19 and contains multiple GCTC repeats that are recognized by the AAV non-structural Rep proteins. These proteins are multifunctional, with an N-terminal origin-binding domain (OBD) and a helicase domain joined together by a short linker. As a first step to understand the process of site-specific integration, we proceeded to characterize the recognition and assembly of Rep68 onto the AAVS1 site. We first determined the x-ray structure of AAV-2 Rep68 OBD in complex with the AAVS1 DNA site. Specificity is achieved through the interaction of a glycine-rich loop that binds the major groove and an α-helix that interacts with a downstream minor groove on the same face of the DNA. Although the structure shows a complex with three OBD molecules bound to the AAVS1 site, we show by using analytical centrifugation and electron microscopy that the full-length Rep68 forms a heptameric complex. Moreover, we determined that a minimum of two direct repeats is required to form a stable complex and to melt DNA. Finally, we show that although the individual domains bind DNA poorly, complex assembly requires oligomerization and cooperation between its OBD, helicase, and the linker domains. PMID:26370092

Thermal denaturation of the BRCT tandem repeat region of human tumour suppressor gene product BRCA1.

PubMed

Pyrpassopoulos, Serapion; Ladopoulou, Angela; Vlassi, Metaxia; Papanikolau, Yannis; Vorgias, Constantinos E; Yannoukakos, Drakoulis; Nounesis, George

2005-04-01

Reduced stability of the tandem BRCT domains of human BReast CAncer 1 (BRCA1) due to missense mutations may be critical for loss of function in DNA repair and damage-induced checkpoint control. In the present thermal denaturation study of the BRCA1 BRCT region, high-precision differential scanning calorimetry (DSC) and circular dichroism (CD) spectroscopy provide evidence for the existence of a denatured state that is structurally very similar to the native. Consistency between theoretical structure-based estimates of the enthalpy (DeltaH) and heat capacity change (DeltaCp) and the calorimetric results is obtained when considering partial thermal unfolding contained in the region of the conserved hydrophobic pocket formed at the interface of the two BRCT repeats. The structural integrity of this region has been shown to be crucial for the interaction of BRCA1 with phosphorylated peptides. In addition, cancer-causing missense mutations located at the inter-BRCT-repeat interface have been linked to the destabilization of the tandem BRCT structure.

Mechanistic insights into the active site and allosteric communication pathways in human nonmuscle myosin-2C

PubMed Central

Preller, Matthias

2017-01-01

Despite a generic, highly conserved motor domain, ATP turnover kinetics and their activation by F-actin vary greatly between myosin-2 isoforms. Here, we present a 2.25 Å pre-powerstroke state (ADP⋅VO4) crystal structure of the human nonmuscle myosin-2C motor domain, one of the slowest myosins characterized. In combination with integrated mutagenesis, ensemble-solution kinetics, and molecular dynamics simulation approaches, the structure reveals an allosteric communication pathway that connects the distal end of the motor domain with the active site. Disruption of this pathway by mutation of hub residue R788, which forms the center of a cluster of interactions connecting the converter, the SH1-SH2 helix, the relay helix, and the lever, abolishes nonmuscle myosin-2 specific kinetic signatures. Our results provide insights into structural changes in the myosin motor domain that are triggered upon F-actin binding and contribute critically to the mechanochemical behavior of stress fibers, actin arcs, and cortical actin-based structures. PMID:29256864

Crystal Structure of the Human, FIC-Domain Containing Protein HYPE and Implications for Its Functions

PubMed Central

Bunney, Tom D.; Cole, Ambrose R.; Broncel, Malgorzata; Esposito, Diego; Tate, Edward W.; Katan, Matilda

2014-01-01

Summary Protein AMPylation, the transfer of AMP from ATP to protein targets, has been recognized as a new mechanism of host-cell disruption by some bacterial effectors that typically contain a FIC-domain. Eukaryotic genomes also encode one FIC-domain protein, HYPE, which has remained poorly characterized. Here we describe the structure of human HYPE, solved by X-ray crystallography, representing the first structure of a eukaryotic FIC-domain protein. We demonstrate that HYPE forms stable dimers with structurally and functionally integrated FIC-domains and with TPR-motifs exposed for protein-protein interactions. As HYPE also uniquely possesses a transmembrane helix, dimerization is likely to affect its positioning and function in the membrane vicinity. The low rate of autoAMPylation of the wild-type HYPE could be due to autoinhibition, consistent with the mechanism proposed for a number of putative FIC AMPylators. Our findings also provide a basis to further consider possible alternative cofactors of HYPE and distinct modes of target-recognition. PMID:25435325

Crystal structure of the human, FIC-domain containing protein HYPE and implications for its functions.

PubMed

Bunney, Tom D; Cole, Ambrose R; Broncel, Malgorzata; Esposito, Diego; Tate, Edward W; Katan, Matilda

2014-12-02

Protein AMPylation, the transfer of AMP from ATP to protein targets, has been recognized as a new mechanism of host-cell disruption by some bacterial effectors that typically contain a FIC-domain. Eukaryotic genomes also encode one FIC-domain protein,HYPE, which has remained poorly characterized.Here we describe the structure of human HYPE, solved by X-ray crystallography, representing the first structure of a eukaryotic FIC-domain protein. We demonstrate that HYPE forms stable dimers with structurally and functionally integrated FIC-domains and with TPR-motifs exposed for protein-protein interactions. As HYPE also uniquely possesses a transmembrane helix, dimerization is likely to affect its positioning and function in the membrane vicinity. The low rate of auto AMPylation of the wild-type HYPE could be due to autoinhibition, consistent with the mechanism proposed for a number of putative FIC AMPylators. Our findings also provide a basis to further consider possible alternative cofactors of HYPE and distinct modes of target-recognition.

Comprehensive cellular‐resolution atlas of the adult human brain

PubMed Central

Royall, Joshua J.; Sunkin, Susan M.; Ng, Lydia; Facer, Benjamin A.C.; Lesnar, Phil; Guillozet‐Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A.; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A.; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L.; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A.; Koch, Christof; Phillips, John W.; Sestan, Nenad; Wohnoutka, Paul; Zielke, H. Ronald; Hohmann, John G.; Jones, Allan R.; Bernard, Amy; Hawrylycz, Michael J.; Hof, Patrick R.; Fischl, Bruce

2016-01-01

ABSTRACT Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole‐brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high‐resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion‐weighted imaging (DWI), and 1,356 large‐format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto‐ and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127–3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:27418273

Integrated endoscopic OCT system and in-vivo images of human internal organs

NASA Astrophysics Data System (ADS)

Sergeev, Alexander M.; Gelikonov, Valentin M.; Gelikonov, Grigory V.; Feldchtein, Felix I.; Kuranov, Roman V.; Gladkova, Natalia D.; Shakhova, Natalia M.; Snopova, Ludmila; Shakhov, Andrei; Kuznetzova, Irina N.; Denisenko, Arkady; Pochinko, Vitaly; Chumakov, Yuri; Almasov, Valentin

1998-04-01

First results of endoscopic applications of optical coherence tomography (OCT) for in vivo studies of human mucosa in respiratory, gastrointestinal, urinary and genital tracts are presented. A novel endoscopic OCT (EOCT) system has been created that is based on the integration of a sampling arm of an all-optical-fiber interferometer into standard endoscopic devices using their biopsy channel to transmit low-coherence radiation to investigated tissue. We have studied mucous membranes of esophagus, larynx, stomach, urinary bladder, uterine cervix and endometrium as typical localization for carcinomatous processes. Images of tumor tissues versus healthy tissues have been recorded and analyzed. Violations of well-defined stratified healthy mucosa structure in cancered tissue is distinctly seen by EOCT, thus making this technique promising for early diagnosis of tumors and precise guiding of excisional biopsy.

Human Eye Development Is Characterized by Coordinated Expression of Fibrillin Isoforms

PubMed Central

Hubmacher, Dirk; Reinhardt, Dieter P.; Plesec, Thomas; Schenke-Layland, Katja; Apte, Suneel S.

2014-01-01

Purpose. Mutations in human fibrillin-1 and -2, which are major constituents of tissue microfibrils, can affect multiple ocular components, including the ciliary zonule, lens, drainage apparatus, cornea, and retina. However, the expression pattern of the three human fibrillins and an integral microfibrillar component, MAGP1, during human eye development is not known. Methods. We analyzed sections from human eyes at gestational weeks (GWs) 6, 8, and 11 and at 1 and 3 years of age with antibodies specific for each human fibrillin isoform or MAGP1, using immunofluorescence microscopy. Results. During embryonic development, each fibrillin isoform was detected in vascular structures bridging the ciliary body and the developing lens, hyaloid vasculature, and retina. In addition, they were present in the developing corneal basement membranes and lens capsule. MAGP1 codistributed with the fibrillin isoforms. In contrast, the juvenile zonule was composed of fibrillin-1 microfibrils containing MAGP1, but fibrillin-2 was absent and fibrillin-3 was only sparsely detected. Conclusions. Fibrillin-1, -2, and, unique to humans, fibrillin-3 are found in various ocular structures during human embryonic eye development, whereas fibrillin-1 dominates the postnatal zonule. We speculate that vasculature spanning the ciliary body and lens, which elaborates fibrillin-2 and -3, may provide an initial scaffold for fibrillin assembly and zonule formation. PMID:25406291

Integration methods for thermosensitive gel systems in garments

NASA Astrophysics Data System (ADS)

Reich, A.; Rödel, H.; Stoll, A.; Liske, A.; Zehm, D.

2017-10-01

Humans live and work under severe thermophysiological conditions, which are characterized by extreme temperatures and humidities. Furthermore, additional burdens can arise from physical activities of the human body or the work conditions (resulting in psychological stress) [1]. The thermoregulation of the human body compensates such situations and maintains the core body temperature at 37°C (98,6 °F). The currently used systems for supporting human thermoregulation, such as PCM-equipped surface structures or mobile water-based cooling units have the disadvantage that the running cooling process is neither switchable nor reversible. Another promising possibility for a personal cooling is the use of temperature-dependent superabsorbers (so-called LCST and UCST) in garments, which absorb the human sweat and transmit it to the environment by evaporation. Cooling during evaporation results in heat transfer from the human body.

Human albumin solders for clinical application during laser tissue welding.

PubMed

Poppas, D P; Wright, E J; Guthrie, P D; Shlahet, L T; Retik, A B

1996-01-01

Fifty percent human albumin solder significantly improves weld strength when compared to lower concentrations [Wright et al., ASLMS meeting, April, 1995]. We developed a method for preparing 50% human albumin that may be considered compatible for clinical applications. Fifty percent human albumin solder was prepared from 25% commercially available human albumin using a lyophilization technique. Assessment of sterility, viscosity, pH, and peak absorption wavelength were performed. This report describes the methodology used to prepare a 50% human albumin solder that is compatible with clinical use. Maintenance of the structural integrity of the albumin was confirmed by polyacrylamide gel electrophoresis. This solder preparation can be used alone or with the addition of exogenous chromophores. The final product is sterile, incorporates viral free protocols, maintains high viscosity, and can be applied easily during open or laparoscopic procedures.

A tale of two species: Neural integration in zebrafish and monkeys.

PubMed

Joshua, M; Lisberger, S G

2015-06-18

Selection of a model organism creates tension between competing constraints. The recent explosion of modern molecular techniques has revolutionized the analysis of neural systems in organisms that are amenable to genetic techniques. Yet, the non-human primate remains the gold-standard for the analysis of the neural basis of behavior, and as a bridge to the operation of the human brain. The challenge is to generalize across species in a way that exposes the operation of circuits as well as the relationship of circuits to behavior. Eye movements provide an opportunity to cross the bridge from mechanism to behavior through research on diverse species. Here, we review experiments and computational studies on a circuit function called "neural integration" that occurs in the brainstems of larval zebrafish, primates, and species "in between". We show that analysis of circuit structure using modern molecular and imaging approaches in zebrafish has remarkable explanatory power for details of the responses of integrator neurons in the monkey. The combination of research from the two species has led to a much stronger hypothesis for the implementation of the neural integrator than could have been achieved using either species alone. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Human-Systems Integration (HSI) and the Network Integration Evaluations (NIEs), Part 3: Mitigating Cognitive Load in Network-Enabled Mission Command

DTIC Science & Technology

2016-06-01

ARL-TR-7698 ● JUNE 2016 US Army Research Laboratory Human -Systems Integration (HSI) and the Network Integration Evaluations...ARL-TR-7698 ● JUNE 2016 US Army Research Laboratory Human -Systems Integration (HSI) and the Network Integration Evaluations (NIEs), Part 3...Mitigating Cognitive Load in Network-Enabled Mission Command by John K Hawley Human Research and Engineering Directorate, ARL Michael W

Concepts to Support HRP Integration Using Publications and Modeling

NASA Technical Reports Server (NTRS)

Mindock, J.; Lumpkins, S.; Shelhamer, M.

2014-01-01

Initial efforts are underway to enhance the Human Research Program (HRP)'s identification and support of potential cross-disciplinary scientific collaborations. To increase the emphasis on integration in HRP's science portfolio management, concepts are being explored through the development of a set of tools. These tools are intended to enable modeling, analysis, and visualization of the state of the human system in the spaceflight environment; HRP's current understanding of that state with an indication of uncertainties; and how that state changes due to HRP programmatic progress and design reference mission definitions. In this talk, we will discuss proof-of-concept work performed using a subset of publications captured in the HRP publications database. The publications were tagged in the database with words representing factors influencing health and performance in spaceflight, as well as with words representing the risks HRP research is reducing. Analysis was performed on the publication tag data to identify relationships between factors and between risks. Network representations were then created as one type of visualization of these relationships. This enables future analyses of the structure of the networks based on results from network theory. Such analyses can provide insights into HRP's current human system knowledge state as informed by the publication data. The network structure analyses can also elucidate potential improvements by identifying network connections to establish or strengthen for maximized information flow. The relationships identified in the publication data were subsequently used as inputs to a model captured in the Systems Modeling Language (SysML), which functions as a repository for relationship information to be gleaned from multiple sources. Example network visualization outputs from a simple SysML model were then also created to compare to the visualizations based on the publication data only. We will also discuss ideas for building upon this proof-of-concept work to further support an integrated approach to human spaceflight risk reduction.

Suppression of HPV E6 and E7 expression by BAF53 depletion in cervical cancer cells

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

Lee, Kiwon; Lee, Ah-Young; Kwon, Yunhee Kim

Highlights: {yields} Integration of HPV into host genome critical for activation of E6 and E7 oncogenes. {yields} BAF53 is essential for higher-order chromatin structure. {yields} BAF53 knockdown suppresses E6 and E7 from HPV integrants, but not from episomal HPVs. {yields} BAF53 knockdown decreases H3K9Ac and H4K12Ac on P105 promoter of integrated HPV 18. {yields} BAF53 knockdown restores the p53-dependent signaling pathway in HeLa and SiHa cells. -- Abstract: Deregulation of the expression of human papillomavirus (HPV) oncogenes E6 and E7 plays a pivotal role in cervical carcinogenesis because the E6 and E7 proteins neutralize p53 and Rb tumor suppressor pathways,more » respectively. In approximately 90% of all cervical carcinomas, HPVs are found to be integrated into the host genome. Following integration, the core-enhancer element and P105 promoter that control expression of E6 and E7 adopt a chromatin structure that is different from that of episomal HPV, and this has been proposed to contribute to activation of E6 and E7 expression. However, the molecular basis underlying this chromatin structural change remains unknown. Previously, BAF53 has been shown to be essential for the integrity of higher-order chromatin structure and interchromosomal interactions. Here, we examined whether BAF53 is required for activated expression of E6 and E7 genes. We found that BAF53 knockdown led to suppression of expression of E6 and E7 genes from HPV integrants in cervical carcinoma cell lines HeLa and SiHa. Conversely, expression of transiently transfected HPV18-LCR-Luciferase was not suppressed by BAF53 knockdown. The level of the active histone marks H3K9Ac and H4K12Ac on the P105 promoter of integrated HPV 18 was decreased in BAF53 knockdown cells. BAF53 knockdown restored the p53-dependent signaling pathway in HeLa and SiHa cells. These results suggest that activated expression of the E6 and E7 genes of integrated HPV is dependent on BAF53-dependent higher-order chromatin structure or nuclear motor activity.« less

Human Tau Isoforms Assemble into Ribbon-like Fibrils That Display Polymorphic Structure and Stability*

PubMed Central

Wegmann, Susanne; Jung, Yu Jin; Chinnathambi, Subashchandrabose; Mandelkow, Eva-Maria; Mandelkow, Eckhard; Muller, Daniel J.

2010-01-01

Fibrous aggregates of Tau protein are characteristic features of Alzheimer disease. We applied high resolution atomic force and EM microscopy to study fibrils assembled from different human Tau isoforms and domains. All fibrils reveal structural polymorphism; the “thin twisted” and “thin smooth” fibrils resemble flat ribbons (cross-section ∼10 × 15 nm) with diverse twist periodicities. “Thick fibrils” show periodicities of ∼65–70 nm and thicknesses of ∼9–18 nm such as routinely reported for “paired helical filaments” but structurally resemble heavily twisted ribbons. Therefore, thin and thick fibrils assembled from different human Tau isoforms challenge current structural models of paired helical filaments. Furthermore, all Tau fibrils reveal axial subperiodicities of ∼17–19 nm and, upon exposure to mechanical stress or hydrophobic surfaces, disassemble into uniform fragments that remain connected by thin thread-like structures (∼2 nm). This hydrophobically induced disassembly is inhibited at enhanced electrolyte concentrations, indicating that the fragments resemble structural building blocks and the fibril integrity depends largely on hydrophobic and electrostatic interactions. Because full-length Tau and repeat domain constructs assemble into fibrils of similar thickness, the “fuzzy coat” of Tau protein termini surrounding the fibril axis is nearly invisible for atomic force microscopy and EM, presumably because of its high flexibility. PMID:20566652

Corticosteroid-Binding Globulin: Structure-Function Implications from Species Differences

PubMed Central

Gardill, Bernd R.; Vogl, Michael R.; Lin, Hai-Yan; Hammond, Geoffrey L.; Muller, Yves A.

2012-01-01

Corticosteroid-binding globulin (CBG) transports glucocorticoids and progesterone in the blood and thereby modulates the tissue availability of these hormones. As a member of the serine protease inhibitor (SERPIN) family, CBG displays a reactive center loop (RCL) that is targeted by proteinases. Cleavage of the RCL is thought to trigger a SERPIN-typical stressed-to-relaxed (S-to-R) transition that leads to marked structural rearrangements and a reduced steroid-binding affinity. To characterize structure-function relationships in CBG we studied various conformational states of E. coli-produced rat and human CBG. In the 2.5 Å crystal structure of human CBG in complex with progesterone, the RCL is cleaved at a novel site that differs from the known human neutrophil elastase recognition site. Although the cleaved RCL segment is five residues longer than anticipated, it becomes an integral part of β-sheet A as a result of the S-to-R transition. The atomic interactions observed between progesterone and CBG explain the lower affinity of progesterone in comparison to corticosteroids. Surprisingly, CD measurements in combination with thermal unfolding experiments show that rat CBG fails to undergo an S-to-R transition upon proteolytic cleavage of the RCL hinting that the S-to-R transition observed in human CBG is not a prerequisite for CBG function in rat. This observation cautions against drawing general conclusions about molecular mechanisms by comparing and merging structural data from different species. PMID:23300763

Human 60-kDa Lysophospholipase Contains an N-terminal l-Asparaginase Domain That Is Allosterically Regulated by l-Asparagine*

PubMed Central

Karamitros, Christos S.; Konrad, Manfred

2014-01-01

The structural and functional characterization of human enzymes that are of potential medical and therapeutic interest is of prime significance for translational research. One of the most notable examples of a therapeutic enzyme is l-asparaginase, which has been established as an antileukemic protein drug for more than four decades. Up until now, only bacterial enzymes have been used in therapy despite a plethora of undesired side effects mainly attributed to the bacterial origins of these enzymes. Therefore, the replacement of the currently approved bacterial drugs by human homologs aiming at the elimination of adverse effects is of great importance. Recently, we structurally and biochemically characterized the enzyme human l-asparaginase 3 (hASNase3), which possesses l-asparaginase activity and belongs to the N-terminal nucleophile superfamily of enzymes. Inspired by the necessity for the development of a protein drug of human origin, in the present study, we focused on the characterization of another human l-asparaginase, termed hASNase1. This bacterial-type cytoplasmic l-asparaginase resides in the N-terminal subdomain of an overall 573-residue protein previously reported to function as a lysophospholipase. Our kinetic, mutagenesis, structural modeling, and fluorescence labeling data highlight allosteric features of hASNase1 that are similar to those of its Escherichia coli homolog, EcASNase1. Differential scanning fluorometry and urea denaturation experiments demonstrate the impact of particular mutations on the structural and functional integrity of the l-asparaginase domain and provide a direct comparison of sites critical for the conformational stability of the human and E. coli enzymes. PMID:24657844

W(h)ither the Oracle? Cognitive biases and other human challenges of integrated environmental modeling

USGS Publications Warehouse

Glynn, Pierre D.; Ames, D.P.; Quinn, N. W. T.; Rizzoli, A.E.

2014-01-01

Integrated environmental modeling (IEM) can organize and increase our knowledge of the complex, dynamic ecosystems that house our natural resources and control the quality of our environments. Human behavior, however, must be taken into account. Human biases/heuristics reflect adaptation over our evolutionary past to frequently experienced situations that affected our survival and that provided sharply distinguished feedbacks at the level of the individual. Unfortunately, human behavior is not adapted to the more diffusely experienced, less frequently encountered, problems and issues that IEM typically seeks to address in the simulation of natural resources and environments. While seeking inspiration from the prophetic traditions of the Oracle of Delphi, several human biases are identified that may affect how the science base of IEM is assembled, and how IEM results are interpreted and used. These biases are supported by personal observations, and by the findings of behavioral scientists. A process for critical analysis is proposed that solicits explicit accounting and cognizance of potential human biases. A number of suggestions are made to address the human challenges of IEM, in addition to maintaining attitudes of watchful humility, open-mindedness, honesty, and transparent accountability. These include creating a new area of study in the behavioral biogeosciences, using structured processes for engaging the modeling and stakeholder community in IEM, and using “red teams” to increase resilience of IEM constructs and use.

Multilevel depth and image fusion for human activity detection.

PubMed

Ni, Bingbing; Pei, Yong; Moulin, Pierre; Yan, Shuicheng

2013-10-01

Recognizing complex human activities usually requires the detection and modeling of individual visual features and the interactions between them. Current methods only rely on the visual features extracted from 2-D images, and therefore often lead to unreliable salient visual feature detection and inaccurate modeling of the interaction context between individual features. In this paper, we show that these problems can be addressed by combining data from a conventional camera and a depth sensor (e.g., Microsoft Kinect). We propose a novel complex activity recognition and localization framework that effectively fuses information from both grayscale and depth image channels at multiple levels of the video processing pipeline. In the individual visual feature detection level, depth-based filters are applied to the detected human/object rectangles to remove false detections. In the next level of interaction modeling, 3-D spatial and temporal contexts among human subjects or objects are extracted by integrating information from both grayscale and depth images. Depth information is also utilized to distinguish different types of indoor scenes. Finally, a latent structural model is developed to integrate the information from multiple levels of video processing for an activity detection. Extensive experiments on two activity recognition benchmarks (one with depth information) and a challenging grayscale + depth human activity database that contains complex interactions between human-human, human-object, and human-surroundings demonstrate the effectiveness of the proposed multilevel grayscale + depth fusion scheme. Higher recognition and localization accuracies are obtained relative to the previous methods.

Geoparsing text for characterizing urban operational environments through machine learning techniques

NASA Astrophysics Data System (ADS)

Garfinkle, Noah W.; Selig, Lucas; Perkins, Timothy K.; Calfas, George W.

2017-05-01

Increasing worldwide internet connectivity and access to sources of print and open social media has increased near realtime availability of textual information. Capabilities to structure and integrate textual data streams can contribute to more meaningful representations of operational environment factors (i.e., Political, Military, Economic, Social, Infrastructure, Information, Physical Environment, and Time [PMESII-PT]) and tactical civil considerations (i.e., Areas, Structures, Capabilities, Organizations, People and Events [ASCOPE]). However, relying upon human analysts to encode this information as it arrives quickly proves intractable. While human analysts possess an ability to comprehend context in unstructured text far beyond that of computers, automated geoparsing (the extraction of locations from unstructured text) can empower analysts to automate sifting through datasets for areas of interest. This research evaluates existing approaches to geoprocessing as well as initiating the research and development of locally-improved methods of tagging parts of text as possible locations, resolving possible locations into coordinates, and interfacing such results with human analysts. The objective of this ongoing research is to develop a more contextually-complete picture of an area of interest (AOI) including human-geographic context for events. In particular, our research is working to make improvements to geoparsing (i.e., the extraction of spatial context from documents), which requires development, integration, and validation of named-entity recognition (NER) tools, gazetteers, and entity-attribution. This paper provides an overview of NER models and methodologies as applied to geoparsing, explores several challenges encountered, presents preliminary results from the creation of a flexible geoparsing research pipeline, and introduces ongoing and future work with the intention of contributing to the efficient geocoding of information containing valuable insights into human activities in space.

Structural mechanism of ligand activation in human calcium-sensing receptor

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

Geng, Yong; Mosyak, Lidia; Kurinov, Igor

2016-07-19

Human calcium-sensing receptor (CaSR) is a G-protein-coupled receptor (GPCR) that maintains extracellular Ca 2+homeostasis through the regulation of parathyroid hormone secretion. It functions as a disulfide-tethered homodimer composed of three main domains, the Venus Flytrap module, cysteine-rich domain, and seven-helix transmembrane region. Here, we present the crystal structures of the entire extracellular domain of CaSR in the resting and active conformations. We provide direct evidence that L-amino acids are agonists of the receptor. In the active structure, L-Trp occupies the orthosteric agonist-binding site at the interdomain cleft and is primarily responsible for inducing extracellular domain closure to initiate receptor activation.more » Our structures reveal multiple binding sites for Ca 2+and PO 4 3-ions. Both ions are crucial for structural integrity of the receptor. While Ca 2+ions stabilize the active state, PO 4 3-ions reinforce the inactive conformation. The activation mechanism of CaSR involves the formation of a novel dimer interface between subunits.« less

GPCR-I-TASSER: A Hybrid Approach to G Protein-Coupled Receptor Structure Modeling and the Application to the Human Genome.

PubMed

Zhang, Jian; Yang, Jianyi; Jang, Richard; Zhang, Yang

2015-08-04

Experimental structure determination remains difficult for G protein-coupled receptors (GPCRs). We propose a new hybrid protocol to construct GPCR structure models that integrates experimental mutagenesis data with ab initio transmembrane (TM) helix assembly simulations. The method was tested on 24 known GPCRs where the ab initio TM-helix assembly procedure constructed the correct fold for 20 cases. When combined with weak homology and sparse mutagenesis restraints, the method generated correct folds for all the tested cases with an average Cα root-mean-square deviation 2.4 Å in the TM regions. The new hybrid protocol was applied to model all 1,026 GPCRs in the human genome, where 923 have a high confidence score and are expected to have correct folds; these contain many pharmaceutically important families with no previously solved structures, including Trace amine, Prostanoids, Releasing hormones, Melanocortins, Vasopressin, and Neuropeptide Y receptors. The results demonstrate new progress on genome-wide structure modeling of TM proteins. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Model for Professional Education in the 21st Century: Integrating Humanities and Engineering through Writing.

ERIC Educational Resources Information Center

Olds, Barbara M.; Miller, Ronald L.

The "HumEn" (Humanities/Engineering Integration) program developed at the Colorado School of Mines integrates humanities and engineering through reading and writing. Through integrative reading and writing engineering students are led to make appropriate connections between the humanities and their technical work, connections that will…

Human mitochondrial NDUFS3 protein bearing Leigh syndrome mutation is more prone to aggregation than its wild-type.

PubMed

Jaokar, Tulika M; Patil, Deepak P; Shouche, Yogesh S; Gaikwad, Sushama M; Suresh, C G

2013-12-01

NDUFS3 is an integral subunit of the Q module of the mitochondrial respiratory Complex-I. The combined mutation (T145I + R199W) in the subunit is reported to cause optic atrophy and Leigh syndrome accompanied by severe Complex-I deficiency. In the present study, we have cloned and overexpressed the human NDUFS3 subunit and its double mutant in a soluble form in Escherichia coli. The wild-type (w-t) and mutant proteins were purified to homogeneity through a serial two-step chromatographic purification procedure of anion exchange followed by size exclusion chromatography. The integrity and purity of the purified proteins was confirmed by Western blot analysis and MALDI-TOF/TOF. The conformational transitions of the purified subunits were studied through steady state as well as time resolved fluorescence and CD spectroscopy under various denaturing conditions. The mutant protein showed altered polarity around tryptophan residues, changed quenching parameters and also noticeably altered secondary and tertiary structure compared to the w-t protein. Mutant also exhibited a higher tendency than the w-t protein for aggregation which was examined using fluorescent (Thioflavin-T) and spectroscopic (Congo red) dye binding techniques. The pH stability of the w-t and mutant proteins varied at extreme acidic pH and the molten globule like structure of w-t at pH1 was absent in case of the mutant protein. Both the w-t and mutant proteins showed multi-step thermal and Gdn-HCl induced unfolding. Thus, the results provide insight into the alterations of NDUFS3 protein structure caused by the mutations, affecting the overall integrity of the protein and finally leading to disruption of Complex-I assembly. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Detection of a novel, integrative aging process suggests complex physiological integration.

PubMed

Cohen, Alan A; Milot, Emmanuel; Li, Qing; Bergeron, Patrick; Poirier, Roxane; Dusseault-Bélanger, Francis; Fülöp, Tamàs; Leroux, Maxime; Legault, Véronique; Metter, E Jeffrey; Fried, Linda P; Ferrucci, Luigi

2015-01-01

Many studies of aging examine biomarkers one at a time, but complex systems theory and network theory suggest that interpretations of individual markers may be context-dependent. Here, we attempted to detect underlying processes governing the levels of many biomarkers simultaneously by applying principal components analysis to 43 common clinical biomarkers measured longitudinally in 3694 humans from three longitudinal cohort studies on two continents (Women's Health and Aging I & II, InCHIANTI, and the Baltimore Longitudinal Study on Aging). The first axis was associated with anemia, inflammation, and low levels of calcium and albumin. The axis structure was precisely reproduced in all three populations and in all demographic sub-populations (by sex, race, etc.); we call the process represented by the axis "integrated albunemia." Integrated albunemia increases and accelerates with age in all populations, and predicts mortality and frailty--but not chronic disease--even after controlling for age. This suggests a role in the aging process, though causality is not yet clear. Integrated albunemia behaves more stably across populations than its component biomarkers, and thus appears to represent a higher-order physiological process emerging from the structure of underlying regulatory networks. If this is correct, detection of this process has substantial implications for physiological organization more generally.

[Network structures in biological systems].

PubMed

Oleskin, A V

2013-01-01

Network structures (networks) that have been extensively studied in the humanities are characterized by cohesion, a lack of a central control unit, and predominantly fractal properties. They are contrasted with structures that contain a single centre (hierarchies) as well as with those whose elements predominantly compete with one another (market-type structures). As far as biological systems are concerned, their network structures can be subdivided into a number of types involving different organizational mechanisms. Network organization is characteristic of various structural levels of biological systems ranging from single cells to integrated societies. These networks can be classified into two main subgroups: (i) flat (leaderless) network structures typical of systems that are composed of uniform elements and represent modular organisms or at least possess manifest integral properties and (ii) three-dimensional, partly hierarchical structures characterized by significant individual and/or intergroup (intercaste) differences between their elements. All network structures include an element that performs structural, protective, and communication-promoting functions. By analogy to cell structures, this element is denoted as the matrix of a network structure. The matrix includes a material and an immaterial component. The material component comprises various structures that belong to the whole structure and not to any of its elements per se. The immaterial (ideal) component of the matrix includes social norms and rules regulating network elements' behavior. These behavioral rules can be described in terms of algorithms. Algorithmization enables modeling the behavior of various network structures, particularly of neuron networks and their artificial analogs.

Alteration of gene expression in human hepatocellular carcinoma with integrated hepatitis B virus DNA.

PubMed

Tamori, Akihiro; Yamanishi, Yoshihiro; Kawashima, Shuichi; Kanehisa, Minoru; Enomoto, Masaru; Tanaka, Hiromu; Kubo, Shoji; Shiomi, Susumu; Nishiguchi, Shuhei

2005-08-15

Integration of hepatitis B virus (HBV) DNA into the human genome is one of the most important steps in HBV-related carcinogenesis. This study attempted to find the link between HBV DNA, the adjoining cellular sequence, and altered gene expression in hepatocellular carcinoma (HCC) with integrated HBV DNA. We examined 15 cases of HCC infected with HBV by cassette ligation-mediated PCR. The human DNA adjacent to the integrated HBV DNA was sequenced. Protein coding sequences were searched for in the human sequence. In five cases with HBV DNA integration, from which good quality RNA was extracted, gene expression was examined by cDNA microarray analysis. The human DNA sequence successive to integrated HBV DNA was determined in the 15 HCCs. Eight protein-coding regions were involved: ras-responsive element binding protein 1, calmodulin 1, mixed lineage leukemia 2 (MLL2), FLJ333655, LOC220272, LOC255345, LOC220220, and LOC168991. The MLL2 gene was expressed in three cases with HBV DNA integrated into exon 3 of MLL2 and in one case with HBV DNA integrated into intron 3 of MLL2. Gene expression analysis suggested that two HCCs with HBV integrated into MLL2 had similar patterns of gene expression compared with three HCCs with HBV integrated into other loci of human chromosomes. HBV DNA was integrated at random sites of human DNA, and the MLL2 gene was one of the targets for integration. Our results suggest that HBV DNA might modulate human genes near integration sites, followed by integration site-specific expression of such genes during hepatocarcinogenesis.

The NATO Unmanned Aircraft System Human Systems Integration Guidebook

DTIC Science & Technology

2012-11-01

Stakeholders HSI Management Activity Goals Project SMEs HCR Acceptance Methods & Criteria Figure 2. Overarching HSI Goal Structure ...88ABW Clear 10/21/2013; 88ABW-2013-4442 55 N NATO North Atlantic Treaty Organisation NTSB National Transportation Safety Board S SME Subject...support the organisation Personnel trained to support safety Operational Concepts HSI Technical Activity Goals Allocation of Functions

Children's Representation and Imitation of Events: How Goal Organization Influences 3-Year-Old Children's Memory for Action Sequences

ERIC Educational Resources Information Center

Loucks, Jeff; Mutschler, Christina; Meltzoff, Andrew N.

2017-01-01

Children's imitation of adults plays a prominent role in human cognitive development. However, few studies have investigated how children represent the complex structure of observed actions which underlies their imitation. We integrate theories of action segmentation, memory, and imitation to investigate whether children's event representation is…

The influence of the visual modality on language structure and conventionalization: insights from sign language and gesture.

PubMed

Perniss, Pamela; Özyürek, Asli; Morgan, Gary

2015-01-01

For humans, the ability to communicate and use language is instantiated not only in the vocal modality but also in the visual modality. The main examples of this are sign languages and (co-speech) gestures. Sign languages, the natural languages of Deaf communities, use systematic and conventionalized movements of the hands, face, and body for linguistic expression. Co-speech gestures, though non-linguistic, are produced in tight semantic and temporal integration with speech and constitute an integral part of language together with speech. The articles in this issue explore and document how gestures and sign languages are similar or different and how communicative expression in the visual modality can change from being gestural to grammatical in nature through processes of conventionalization. As such, this issue contributes to our understanding of how the visual modality shapes language and the emergence of linguistic structure in newly developing systems. Studying the relationship between signs and gestures provides a new window onto the human ability to recruit multiple levels of representation (e.g., categorical, gradient, iconic, abstract) in the service of using or creating conventionalized communicative systems. Copyright © 2015 Cognitive Science Society, Inc.

Development of Human System Integration at NASA

NASA Technical Reports Server (NTRS)

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

2012-01-01

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

Integrating national community-based health worker programmes into health systems: a systematic review identifying lessons learned from low-and middle-income countries.

PubMed

Zulu, Joseph Mumba; Kinsman, John; Michelo, Charles; Hurtig, Anna-Karin

2014-09-22

Despite the development of national community-based health worker (CBHW) programmes in several low- and middle-income countries, their integration into health systems has not been optimal. Studies have been conducted to investigate the factors influencing the integration processes, but systematic reviews to provide a more comprehensive understanding are lacking. We conducted a systematic review of published research to understand factors that may influence the integration of national CBHW programmes into health systems in low- and middle-income countries. To be included in the study, CBHW programmes should have been developed by the government and have standardised training, supervision and incentive structures. A conceptual framework on the integration of health innovations into health systems guided the review. We identified 3410 records, of which 36 were finally selected, and on which an analysis was conducted concerning the themes and pathways associated with different factors that may influence the integration process. Four programmes from Brazil, Ethiopia, India and Pakistan met the inclusion criteria. Different aspects of each of these programmes were integrated in different ways into their respective health systems. Factors that facilitated the integration process included the magnitude of countries' human resources for health problems and the associated discourses about how to address these problems; the perceived relative advantage of national CBHWs with regard to delivering health services over training and retaining highly skilled health workers; and the participation of some politicians and community members in programme processes, with the result that they viewed the programmes as legitimate, credible and relevant. Finally, integration of programmes within the existing health systems enhanced programme compatibility with the health systems' governance, financing and training functions. Factors that inhibited the integration process included a rapid scale-up process; resistance from other health workers; discrimination of CBHWs based on social, gender and economic status; ineffective incentive structures; inadequate infrastructure and supplies; and hierarchical and parallel communication structures. CBHW programmes should design their scale-up strategy differently based on current contextual factors. Further, adoption of a stepwise approach to the scale-up and integration process may positively shape the integration process of CBHW programmes into health systems.

Structure and dynamics of human communication at the beginning of life.

PubMed

Papousek, H; Papousek, M

1986-01-01

Although the beginning of postpartum social integration and communication has been long viewed as relevant to psychiatric theories, early parent-infant communication has become a matter of scientific investigation only recently. The present survey explains the significance of an approach based upon the general systems theory and explores to what extent the early parent-infant interaction can function as a didactic system to support the development of thought and speech. Evidence of this function has been found in those forms of parental behavior that escape the parent's conscious awareness and control, as exemplified in the vocal communication with presyllabic infants. Parents unknowingly adjust the structure and dynamics of speech to the constraints of infant capacities, detach prosodic musicality from lexical structure, and use it in particularly expressive forms for the delivery of the first prototypical messages. In this and other similar ways, parents offer an abundance of learning situations in which infants can try out various integrative operations. A biological rather than cultural provenience of the support of communicative development indicates a potential relevance for the interpretation of speech evolution. In addition to qualities of the vocal tract and to complex symbolic capacities in humans, the early intuitive support of communicative development and its playful character are suggested as species-specific determinants of speech evolution. Implications for clinical research are suggested.

Methodological Problems on the Way to Integrative Human Neuroscience.

PubMed

Kotchoubey, Boris; Tretter, Felix; Braun, Hans A; Buchheim, Thomas; Draguhn, Andreas; Fuchs, Thomas; Hasler, Felix; Hastedt, Heiner; Hinterberger, Thilo; Northoff, Georg; Rentschler, Ingo; Schleim, Stephan; Sellmaier, Stephan; Tebartz Van Elst, Ludger; Tschacher, Wolfgang

2016-01-01

Neuroscience is a multidisciplinary effort to understand the structures and functions of the brain and brain-mind relations. This effort results in an increasing amount of data, generated by sophisticated technologies. However, these data enhance our descriptive knowledge , rather than improve our understanding of brain functions. This is caused by methodological gaps both within and between subdisciplines constituting neuroscience, and the atomistic approach that limits the study of macro- and mesoscopic issues. Whole-brain measurement technologies do not resolve these issues, but rather aggravate them by the complexity problem. The present article is devoted to methodological and epistemic problems that obstruct the development of human neuroscience. We neither discuss ontological questions (e.g., the nature of the mind) nor review data, except when it is necessary to demonstrate a methodological issue. As regards intradisciplinary methodological problems, we concentrate on those within neurobiology (e.g., the gap between electrical and chemical approaches to neurophysiological processes) and psychology (missing theoretical concepts). As regards interdisciplinary problems, we suggest that core disciplines of neuroscience can be integrated using systemic concepts that also entail human-environment relations. We emphasize the necessity of a meta-discussion that should entail a closer cooperation with philosophy as a discipline of systematic reflection. The atomistic reduction should be complemented by the explicit consideration of the embodiedness of the brain and the embeddedness of humans. The discussion is aimed at the development of an explicit methodology of integrative human neuroscience , which will not only link different fields and levels, but also help in understanding clinical phenomena.

Methodological Problems on the Way to Integrative Human Neuroscience

PubMed Central

Kotchoubey, Boris; Tretter, Felix; Braun, Hans A.; Buchheim, Thomas; Draguhn, Andreas; Fuchs, Thomas; Hasler, Felix; Hastedt, Heiner; Hinterberger, Thilo; Northoff, Georg; Rentschler, Ingo; Schleim, Stephan; Sellmaier, Stephan; Tebartz Van Elst, Ludger; Tschacher, Wolfgang

2016-01-01

Neuroscience is a multidisciplinary effort to understand the structures and functions of the brain and brain-mind relations. This effort results in an increasing amount of data, generated by sophisticated technologies. However, these data enhance our descriptive knowledge, rather than improve our understanding of brain functions. This is caused by methodological gaps both within and between subdisciplines constituting neuroscience, and the atomistic approach that limits the study of macro- and mesoscopic issues. Whole-brain measurement technologies do not resolve these issues, but rather aggravate them by the complexity problem. The present article is devoted to methodological and epistemic problems that obstruct the development of human neuroscience. We neither discuss ontological questions (e.g., the nature of the mind) nor review data, except when it is necessary to demonstrate a methodological issue. As regards intradisciplinary methodological problems, we concentrate on those within neurobiology (e.g., the gap between electrical and chemical approaches to neurophysiological processes) and psychology (missing theoretical concepts). As regards interdisciplinary problems, we suggest that core disciplines of neuroscience can be integrated using systemic concepts that also entail human-environment relations. We emphasize the necessity of a meta-discussion that should entail a closer cooperation with philosophy as a discipline of systematic reflection. The atomistic reduction should be complemented by the explicit consideration of the embodiedness of the brain and the embeddedness of humans. The discussion is aimed at the development of an explicit methodology of integrative human neuroscience, which will not only link different fields and levels, but also help in understanding clinical phenomena. PMID:27965548

An Integrated and Interdisciplinary Model for Predicting the Risk of Injury and Death in Future Earthquakes.

PubMed

Shapira, Stav; Novack, Lena; Bar-Dayan, Yaron; Aharonson-Daniel, Limor

2016-01-01

A comprehensive technique for earthquake-related casualty estimation remains an unmet challenge. This study aims to integrate risk factors related to characteristics of the exposed population and to the built environment in order to improve communities' preparedness and response capabilities and to mitigate future consequences. An innovative model was formulated based on a widely used loss estimation model (HAZUS) by integrating four human-related risk factors (age, gender, physical disability and socioeconomic status) that were identified through a systematic review and meta-analysis of epidemiological data. The common effect measures of these factors were calculated and entered to the existing model's algorithm using logistic regression equations. Sensitivity analysis was performed by conducting a casualty estimation simulation in a high-vulnerability risk area in Israel. the integrated model outcomes indicated an increase in the total number of casualties compared with the prediction of the traditional model; with regard to specific injury levels an increase was demonstrated in the number of expected fatalities and in the severely and moderately injured, and a decrease was noted in the lightly injured. Urban areas with higher populations at risk rates were found more vulnerable in this regard. The proposed model offers a novel approach that allows quantification of the combined impact of human-related and structural factors on the results of earthquake casualty modelling. Investing efforts in reducing human vulnerability and increasing resilience prior to an occurrence of an earthquake could lead to a possible decrease in the expected number of casualties.

Evaluate the application of modal test and analysis processes to structural fault detection in MSFC-STS project elements

NASA Technical Reports Server (NTRS)

Springer, William T.

1988-01-01

The Space Transportation System (STS) is a very complex and expensive flight system which is intended to carry payloads into low Earth orbit and return. A catastrophic failure of the STS (such as experienced in the 51-L incident) results in the loss of both human life as well as very expensive hardware. One impact of this incident was to reaffirm the need to do everything possible to insure the integrity and reliability of the STS is sufficient to produce a safe flight. One means of achieving this goal is to expand the number of inspection technologies available for use on the STS. The purpose was to begin to evaluate the possible use of assessing the structural integrity of STS components for which Marshall Space Flight Center (MSFC) has responsibility. This entailed reviewing the available literature and determining a low-level experimental program which could be performed by MSFC and would help establish the feasibility of using this technology for structural fault detection.

Making psycholinguistics musical: Self-paced reading time evidence for shared processing of linguistic and musical syntax

PubMed Central

Robert Slevc, L.; Rosenberg, Jason C.; Patel, Aniruddh D.

2009-01-01

Linguistic processing–especially syntactic processing–is often considered a hallmark of human cognition, thus the domain-specificity or domain-generality of syntactic processing has attracted considerable debate. These experiments address this issue by simultaneously manipulating syntactic processing demands in language and music. Participants performed self-paced reading of garden-path sentences in which structurally unexpected words cause temporary syntactic processing difficulty. A musical chord accompanied each sentence segment, with the resulting sequence forming a coherent chord progression. When structurally unexpected words were paired with harmonically unexpected chords, participants showed substantially enhanced garden-path effects. No such interaction was observed when the critical words violated semantic expectancy, nor when the critical chords violated timbral expectancy. These results support a prediction of the shared syntactic integration resource hypothesis (SSIRH, Patel, 2003), which suggests that music and language draw on a common pool of limited processing resources for integrating incoming elements into syntactic structures. PMID:19293110

HEMD: an integrated tool of human epigenetic enzymes and chemical modulators for therapeutics.

PubMed

Huang, Zhimin; Jiang, Haiming; Liu, Xinyi; Chen, Yingyi; Wong, Jiemin; Wang, Qi; Huang, Wenkang; Shi, Ting; Zhang, Jian

2012-01-01

Epigenetic mechanisms mainly include DNA methylation, post-translational modifications of histones, chromatin remodeling and non-coding RNAs. All of these processes are mediated and controlled by enzymes. Abnormalities of the enzymes are involved in a variety of complex human diseases. Recently, potent natural or synthetic chemicals are utilized to establish the quantitative contributions of epigenetic regulation through the enzymes and provide novel insight for developing new therapeutics. However, the development of more specific and effective epigenetic therapeutics requires a more complete understanding of the chemical epigenomic landscape. Here, we present a human epigenetic enzyme and modulator database (HEMD), the database which provides a central resource for the display, search, and analysis of the structure, function, and related annotation for human epigenetic enzymes and chemical modulators focused on epigenetic therapeutics. Currently, HEMD contains 269 epigenetic enzymes and 4377 modulators in three categories (activators, inhibitors, and regulators). Enzymes are annotated with detailed description of epigenetic mechanisms, catalytic processes, and related diseases, and chemical modulators with binding sites, pharmacological effect, and therapeutic uses. Integrating the information of epigenetic enzymes in HEMD should allow for the prediction of conserved features for proteins and could potentially classify them as ideal targets for experimental validation. In addition, modulators curated in HEMD can be used to investigate potent epigenetic targets for the query compound and also help chemists to implement structural modifications for the design of novel epigenetic drugs. HEMD could be a platform and a starting point for biologists and medicinal chemists for furthering research on epigenetic therapeutics. HEMD is freely available at http://mdl.shsmu.edu.cn/HEMD/.

An Asymmetrical Look at Air Force Human Capital Management: More Emphasis on Qualifications and Less on Rank

DTIC Science & Technology

2006-03-01

will need to become integrated organizations if they expect to make the most of the knowledge, skills, and abilities of their people . (GAO 2000: 7 ...Case – 316 Rank – E- 7 Comment – It is extremely difficult to seperate rank within the structure of the enlisted/officer structures. People look for...is a life long joyful battle but get’s put aside to easily for convenience. 154 Case – 317 Rank – E- 7 Comment – The majority of Highly

Modeling the spatial spread of infectious diseases: the GLobal Epidemic and Mobility computational model

PubMed Central

Balcan, Duygu; Gonçalves, Bruno; Hu, Hao; Ramasco, José J.; Colizza, Vittoria

2010-01-01

Here we present the Global Epidemic and Mobility (GLEaM) model that integrates sociodemographic and population mobility data in a spatially structured stochastic disease approach to simulate the spread of epidemics at the worldwide scale. We discuss the flexible structure of the model that is open to the inclusion of different disease structures and local intervention policies. This makes GLEaM suitable for the computational modeling and anticipation of the spatio-temporal patterns of global epidemic spreading, the understanding of historical epidemics, the assessment of the role of human mobility in shaping global epidemics, and the analysis of mitigation and containment scenarios. PMID:21415939

Age-related changes in the topological organization of the white matter structural connectome across the human lifespan.

PubMed

Zhao, Tengda; Cao, Miao; Niu, Haijing; Zuo, Xi-Nian; Evans, Alan; He, Yong; Dong, Qi; Shu, Ni

2015-10-01

Lifespan is a dynamic process with remarkable changes in brain structure and function. Previous neuroimaging studies have indicated age-related microstructural changes in specific white matter tracts during development and aging. However, the age-related alterations in the topological architecture of the white matter structural connectome across the human lifespan remain largely unknown. Here, a cohort of 113 healthy individuals (ages 9-85) with both diffusion and structural MRI acquisitions were examined. For each participant, the high-resolution white matter structural networks were constructed by deterministic fiber tractography among 1024 parcellation units and were quantified with graph theoretical analyses. The global network properties, including network strength, cost, topological efficiency, and robustness, followed an inverted U-shaped trajectory with a peak age around the third decade. The brain areas with the most significantly nonlinear changes were located in the prefrontal and temporal cortices. Different brain regions exhibited heterogeneous trajectories: the posterior cingulate and lateral temporal cortices displayed prolonged maturation/degeneration compared with the prefrontal cortices. Rich-club organization was evident across the lifespan, whereas hub integration decreased linearly with age, especially accompanied by the loss of frontal hubs and their connections. Additionally, age-related changes in structural connections were predominantly located within and between the prefrontal and temporal modules. Finally, based on the graph metrics of structural connectome, accurate predictions of individual age were obtained (r = 0.77). Together, the data indicated a dynamic topological organization of the brain structural connectome across human lifespan, which may provide possible structural substrates underlying functional and cognitive changes with age. © 2015 Wiley Periodicals, Inc.

Human-technology Integration

NASA Astrophysics Data System (ADS)

Mullen, Katharine M.

Human-technology integration is the replacement of human parts and extension of human capabilities with engineered devices and substrates. Its result is hybrid biological-artificial systems. We discuss here four categories of products furthering human-technology integration: wearable computers, pervasive computing environments, engineered tissues and organs, and prosthetics, and introduce examples of currently realized systems in each category. We then note that realization of a completely artificial sytem via the path of human-technology integration presents the prospect of empirical confirmation of an aware artificially embodied system.

Design and development an insect-inspired humanoid gripper that is structurally sound, yet very flexible

NASA Astrophysics Data System (ADS)

Hajjaj, S.; Pun, N.

2013-06-01

One of the biggest challenges in mechanical robotics design is the balance between structural integrity and flexibility. An industrial robotic gripper could be technically advanced, however it contains only 1 Degree of Freedom (DOF). If one is to add more DOFs the design would become complex. On the other hand, the human wrist and fingers contain 23 DOFs, and is very lightweight and highly flexible. Robotics are becoming more and more part of our social life, they are more and more being incorporated in social, medical, and personal application. Therefore, for such robots to be effective, they need to mimic human performance, both in performance as well as in mechanical design. In this work, a Humanoid Gripper is designed and built to mimic a simplified version of a human wrist and fingers. This is attempted by mimicking insect and human designs of grippes. The main challenge was to insure that the gripper is structurally sound, but at the same time flexible and lightweight. A combination of light weight material and a unique design of finger actuators were applied. The gripper is controlled by a PARALLAX servo controller 28823 (PSCI), which mounted on the assembly itself. At the end, a 6 DOF humanoid gripper made of lightweight material, similar in size to the human arm, and is able to carry a weight of 1 Kg has been designed and built.

Evidence-based ergonomics: a model and conceptual structure proposal.

PubMed

Silveira, Dierci Marcio

2012-01-01

In Human Factors and Ergonomics Science (HFES), it is difficult to identify what is the best approach to tackle the workplace and systems design problems which needs to be solved, and it has been also advocated as transdisciplinary and multidisciplinary the issue of "How to solve the human factors and ergonomics problems that are identified?". The proposition on this study is to combine the theoretical approach for Sustainability Science, the Taxonomy of the Human Factors and Ergonomics (HFE) discipline and the framework for Evidence-Based Medicine in an attempt to be applied in Human Factors and Ergonomics. Applications of ontologies are known in the field of medical research and computer science. By scrutinizing the key requirements for the HFES structuring of knowledge, it was designed a reference model, First, it was identified the important requirements for HFES Concept structuring, as regarded by Meister. Second, it was developed an evidence-based ergonomics framework as a reference model composed of six levels based on these requirements. Third, it was devised a mapping tool using linguistic resources to translate human work, systems environment and the complexities inherent to their hierarchical relationships to support future development at Level 2 of the reference model and for meeting the two major challenges for HFES, namely, identifying what problems should be addressed in HFE as an Autonomous Science itself and proposing solutions by integrating concepts and methods applied in HFES for those problems.

Case Study: Organotypic human in vitro models of embryonic ...

EPA Pesticide Factsheets

Morphogenetic fusion of tissues is a common event in embryonic development and disruption of fusion is associated with birth defects of the eye, heart, neural tube, phallus, palate, and other organ systems. Embryonic tissue fusion requires precise regulation of cell-cell and cell-matrix interactions that drive proliferation, differentiation, and morphogenesis. Chemical low-dose exposures can disrupt morphogenesis across space and time by interfering with key embryonic fusion events. The Morphogenetic Fusion Task uses computer and in vitro models to elucidate consequences of developmental exposures. The Morphogenetic Fusion Task integrates multiple approaches to model responses to chemicals that leaad to birth defects, including integrative mining on ToxCast DB, ToxRefDB, and chemical structures, advanced computer agent-based models, and human cell-based cultures that model disruption of cellular and molecular behaviors including mechanisms predicted from integrative data mining and agent-based models. The purpose of the poster is to indicate progress on the CSS 17.02 Virtual Tissue Models Morphogenesis Task 1 products for the Board of Scientific Counselors meeting on Nov 16-17.

Deformable devices with integrated functional nanomaterials for wearable electronics.

PubMed

Kim, Jaemin; Lee, Jongsu; Son, Donghee; Choi, Moon Kee; Kim, Dae-Hyeong

2016-01-01

As the market and related industry for wearable electronics dramatically expands, there are continuous and strong demands for flexible and stretchable devices to be seamlessly integrated with soft and curvilinear human skin or clothes. However, the mechanical mismatch between the rigid conventional electronics and the soft human body causes many problems. Therefore, various prospective nanomaterials that possess a much lower flexural rigidity than their bulk counterparts have rapidly established themselves as promising electronic materials replacing rigid silicon and/or compound semiconductors in next-generation wearable devices. Many hybrid structures of multiple nanomaterials have been also developed to pursue both high performance and multifunctionality. Here, we provide an overview of state-of-the-art wearable devices based on one- or two-dimensional nanomaterials (e.g., carbon nanotubes, graphene, single-crystal silicon and oxide nanomembranes, organic nanomaterials and their hybrids) in combination with zero-dimensional functional nanomaterials (e.g., metal/oxide nanoparticles and quantum dots). Starting from an introduction of materials strategies, we describe device designs and the roles of individual ones in integrated systems. Detailed application examples of wearable sensors/actuators, memories, energy devices, and displays are also presented.

International Space Station USOS Waste and Hygiene Compartment Development

NASA Technical Reports Server (NTRS)

Link, Dwight E., Jr.; Broyan, James Lee, Jr.; Gelmis, Karen; Philistine, Cynthia; Balistreri, Steven

2007-01-01

The International Space Station (ISS) currently provides human waste collection and hygiene facilities in the Russian Segment Service Module (SM) which supports a three person crew. Additional hardware is planned for the United States Operational Segment (USOS) to support expansion of the crew to six person capability. The additional hardware will be integrated in an ISS standard equipment rack structure that was planned to be installed in the Node 3 element; however, the ISS Program Office recently directed implementation of the rack, or Waste and Hygiene Compartment (WHC), into the U.S. Laboratory element to provide early operational capability. In this configuration, preserved urine from the WHC waste collection system can be processed by the Urine Processor Assembly (UPA) in either the U.S. Lab or Node 3 to recover water for crew consumption or oxygen production. The human waste collection hardware is derived from the Service Module system and is provided by RSC-Energia. This paper describes the concepts, design, and integration of the WHC waste collection hardware into the USOS including integration with U.S. Lab and Node 3 systems.

What is the effect of fasting on the lifespan of neurons?

PubMed

Kalsi, Dilraj S

2015-11-01

Medical advancements have increased life expectancy but have consequently increased the incidence of age-related disease. Fasting or dietary restriction (DR) can help prevent these via anti-ageing effects; however, these effects in neurons are less well characterized. Here, a series of animal and human studies of the effects of DR on the structural and functional integrity of neurons and the underlying mechanisms are analyzed. DR improves the integrity of animal neurons via a wide range of possible mechanisms including changes in metabolism, oxidative damage, stress responses, growth factors, and gene expression. These mechanisms are extensively interlinked and point to an optimum range of calorie intake, above calorie deprivation and below burdensome calorie excess. Human studies also suggest that DR improves neuron integrity; however, due to ethical and methodological limitations, the most conclusive data on DR hinge upon on-going life-long monkey experiments. Rather than developing pharmacological mimetics of DR, our focus should be on educating the public about DR in order to minimize age-related disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Deformable devices with integrated functional nanomaterials for wearable electronics

NASA Astrophysics Data System (ADS)

Kim, Jaemin; Lee, Jongsu; Son, Donghee; Choi, Moon Kee; Kim, Dae-Hyeong

2016-03-01

As the market and related industry for wearable electronics dramatically expands, there are continuous and strong demands for flexible and stretchable devices to be seamlessly integrated with soft and curvilinear human skin or clothes. However, the mechanical mismatch between the rigid conventional electronics and the soft human body causes many problems. Therefore, various prospective nanomaterials that possess a much lower flexural rigidity than their bulk counterparts have rapidly established themselves as promising electronic materials replacing rigid silicon and/or compound semiconductors in next-generation wearable devices. Many hybrid structures of multiple nanomaterials have been also developed to pursue both high performance and multifunctionality. Here, we provide an overview of state-of-the-art wearable devices based on one- or two-dimensional nanomaterials (e.g., carbon nanotubes, graphene, single-crystal silicon and oxide nanomembranes, organic nanomaterials and their hybrids) in combination with zero-dimensional functional nanomaterials (e.g., metal/oxide nanoparticles and quantum dots). Starting from an introduction of materials strategies, we describe device designs and the roles of individual ones in integrated systems. Detailed application examples of wearable sensors/actuators, memories, energy devices, and displays are also presented.

Large-scale brain networks in affective and social neuroscience: Towards an integrative functional architecture of the brain

PubMed Central

Barrett, Lisa Feldman; Satpute, Ajay

2013-01-01

Understanding how a human brain creates a human mind ultimately depends on mapping psychological categories and concepts to physical measurements of neural response. Although it has long been assumed that emotional, social, and cognitive phenomena are realized in the operations of separate brain regions or brain networks, we demonstrate that it is possible to understand the body of neuroimaging evidence using a framework that relies on domain general, distributed structure-function mappings. We review current research in affective and social neuroscience and argue that the emerging science of large-scale intrinsic brain networks provides a coherent framework for a domain-general functional architecture of the human brain. PMID:23352202

Innovation leadership: new perspectives for new work.

PubMed

Malloch, Kathy

2010-03-01

The industrial age command and control leadership style and supporting infrastructure are ineffective in meeting the challenges of the increased availability and sharing of information, the media used for knowledge transfer, the changing range and types of relationships between individuals, and the time required to transfer and share information. What has not changed is the need for effective personal relationships in the evaluation and selection of new technologies; human to human sensitivity, acknowledgment, and respect for the patient care experience. As individuals embrace these new technologies, the essence of the innovation leader emerges to purposefully guide, assess, integrate, and synthesize technology into the human work of patient care. Building organizational infrastructures with openness for technology and innovations to enhance effective patient care relationships now requires an innovation skill set that understands and integrates human needs with the best of technology. In this article a brief description of innovation leadership is presented as the backdrop for change along with 4 significant changes in work processes that have irreversibly altered health care work, the trimodal organizational structure to accommodate operations, innovation, and transition between the 2, and finally, individual and team behaviors that emphasize the work of innovation. Copyright 2010 Elsevier Inc. All rights reserved.

AnnoLnc: a web server for systematically annotating novel human lncRNAs.

PubMed

Hou, Mei; Tang, Xing; Tian, Feng; Shi, Fangyuan; Liu, Fenglin; Gao, Ge

2016-11-16

Long noncoding RNAs (lncRNAs) have been shown to play essential roles in almost every important biological process through multiple mechanisms. Although the repertoire of human lncRNAs has rapidly expanded, their biological function and regulation remain largely elusive, calling for a systematic and integrative annotation tool. Here we present AnnoLnc ( http://annolnc.cbi.pku.edu.cn ), a one-stop portal for systematically annotating novel human lncRNAs. Based on more than 700 data sources and various tool chains, AnnoLnc enables a systematic annotation covering genomic location, secondary structure, expression patterns, transcriptional regulation, miRNA interaction, protein interaction, genetic association and evolution. An intuitive web interface is available for interactive analysis through both desktops and mobile devices, and programmers can further integrate AnnoLnc into their pipeline through standard JSON-based Web Service APIs. To the best of our knowledge, AnnoLnc is the only web server to provide on-the-fly and systematic annotation for newly identified human lncRNAs. Compared with similar tools, the annotation generated by AnnoLnc covers a much wider spectrum with intuitive visualization. Case studies demonstrate the power of AnnoLnc in not only rediscovering known functions of human lncRNAs but also inspiring novel hypotheses.

Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project.

PubMed

Birney, Ewan; Stamatoyannopoulos, John A; Dutta, Anindya; Guigó, Roderic; Gingeras, Thomas R; Margulies, Elliott H; Weng, Zhiping; Snyder, Michael; Dermitzakis, Emmanouil T; Thurman, Robert E; Kuehn, Michael S; Taylor, Christopher M; Neph, Shane; Koch, Christoph M; Asthana, Saurabh; Malhotra, Ankit; Adzhubei, Ivan; Greenbaum, Jason A; Andrews, Robert M; Flicek, Paul; Boyle, Patrick J; Cao, Hua; Carter, Nigel P; Clelland, Gayle K; Davis, Sean; Day, Nathan; Dhami, Pawandeep; Dillon, Shane C; Dorschner, Michael O; Fiegler, Heike; Giresi, Paul G; Goldy, Jeff; Hawrylycz, Michael; Haydock, Andrew; Humbert, Richard; James, Keith D; Johnson, Brett E; Johnson, Ericka M; Frum, Tristan T; Rosenzweig, Elizabeth R; Karnani, Neerja; Lee, Kirsten; Lefebvre, Gregory C; Navas, Patrick A; Neri, Fidencio; Parker, Stephen C J; Sabo, Peter J; Sandstrom, Richard; Shafer, Anthony; Vetrie, David; Weaver, Molly; Wilcox, Sarah; Yu, Man; Collins, Francis S; Dekker, Job; Lieb, Jason D; Tullius, Thomas D; Crawford, Gregory E; Sunyaev, Shamil; Noble, William S; Dunham, Ian; Denoeud, France; Reymond, Alexandre; Kapranov, Philipp; Rozowsky, Joel; Zheng, Deyou; Castelo, Robert; Frankish, Adam; Harrow, Jennifer; Ghosh, Srinka; Sandelin, Albin; Hofacker, Ivo L; Baertsch, Robert; Keefe, Damian; Dike, Sujit; Cheng, Jill; Hirsch, Heather A; Sekinger, Edward A; Lagarde, Julien; Abril, Josep F; Shahab, Atif; Flamm, Christoph; Fried, Claudia; Hackermüller, Jörg; Hertel, Jana; Lindemeyer, Manja; Missal, Kristin; Tanzer, Andrea; Washietl, Stefan; Korbel, Jan; Emanuelsson, Olof; Pedersen, Jakob S; Holroyd, Nancy; Taylor, Ruth; Swarbreck, David; Matthews, Nicholas; Dickson, Mark C; Thomas, Daryl J; Weirauch, Matthew T; Gilbert, James; Drenkow, Jorg; Bell, Ian; Zhao, XiaoDong; Srinivasan, K G; Sung, Wing-Kin; Ooi, Hong Sain; Chiu, Kuo Ping; Foissac, Sylvain; Alioto, Tyler; Brent, Michael; Pachter, Lior; Tress, Michael L; Valencia, Alfonso; Choo, Siew Woh; Choo, Chiou Yu; Ucla, Catherine; Manzano, Caroline; Wyss, Carine; Cheung, Evelyn; Clark, Taane G; Brown, James B; Ganesh, Madhavan; Patel, Sandeep; Tammana, Hari; Chrast, Jacqueline; Henrichsen, Charlotte N; Kai, Chikatoshi; Kawai, Jun; Nagalakshmi, Ugrappa; Wu, Jiaqian; Lian, Zheng; Lian, Jin; Newburger, Peter; Zhang, Xueqing; Bickel, Peter; Mattick, John S; Carninci, Piero; Hayashizaki, Yoshihide; Weissman, Sherman; Hubbard, Tim; Myers, Richard M; Rogers, Jane; Stadler, Peter F; Lowe, Todd M; Wei, Chia-Lin; Ruan, Yijun; Struhl, Kevin; Gerstein, Mark; Antonarakis, Stylianos E; Fu, Yutao; Green, Eric D; Karaöz, Ulaş; Siepel, Adam; Taylor, James; Liefer, Laura A; Wetterstrand, Kris A; Good, Peter J; Feingold, Elise A; Guyer, Mark S; Cooper, Gregory M; Asimenos, George; Dewey, Colin N; Hou, Minmei; Nikolaev, Sergey; Montoya-Burgos, Juan I; Löytynoja, Ari; Whelan, Simon; Pardi, Fabio; Massingham, Tim; Huang, Haiyan; Zhang, Nancy R; Holmes, Ian; Mullikin, James C; Ureta-Vidal, Abel; Paten, Benedict; Seringhaus, Michael; Church, Deanna; Rosenbloom, Kate; Kent, W James; Stone, Eric A; Batzoglou, Serafim; Goldman, Nick; Hardison, Ross C; Haussler, David; Miller, Webb; Sidow, Arend; Trinklein, Nathan D; Zhang, Zhengdong D; Barrera, Leah; Stuart, Rhona; King, David C; Ameur, Adam; Enroth, Stefan; Bieda, Mark C; Kim, Jonghwan; Bhinge, Akshay A; Jiang, Nan; Liu, Jun; Yao, Fei; Vega, Vinsensius B; Lee, Charlie W H; Ng, Patrick; Shahab, Atif; Yang, Annie; Moqtaderi, Zarmik; Zhu, Zhou; Xu, Xiaoqin; Squazzo, Sharon; Oberley, Matthew J; Inman, David; Singer, Michael A; Richmond, Todd A; Munn, Kyle J; Rada-Iglesias, Alvaro; Wallerman, Ola; Komorowski, Jan; Fowler, Joanna C; Couttet, Phillippe; Bruce, Alexander W; Dovey, Oliver M; Ellis, Peter D; Langford, Cordelia F; Nix, David A; Euskirchen, Ghia; Hartman, Stephen; Urban, Alexander E; Kraus, Peter; Van Calcar, Sara; Heintzman, Nate; Kim, Tae Hoon; Wang, Kun; Qu, Chunxu; Hon, Gary; Luna, Rosa; Glass, Christopher K; Rosenfeld, M Geoff; Aldred, Shelley Force; Cooper, Sara J; Halees, Anason; Lin, Jane M; Shulha, Hennady P; Zhang, Xiaoling; Xu, Mousheng; Haidar, Jaafar N S; Yu, Yong; Ruan, Yijun; Iyer, Vishwanath R; Green, Roland D; Wadelius, Claes; Farnham, Peggy J; Ren, Bing; Harte, Rachel A; Hinrichs, Angie S; Trumbower, Heather; Clawson, Hiram; Hillman-Jackson, Jennifer; Zweig, Ann S; Smith, Kayla; Thakkapallayil, Archana; Barber, Galt; Kuhn, Robert M; Karolchik, Donna; Armengol, Lluis; Bird, Christine P; de Bakker, Paul I W; Kern, Andrew D; Lopez-Bigas, Nuria; Martin, Joel D; Stranger, Barbara E; Woodroffe, Abigail; Davydov, Eugene; Dimas, Antigone; Eyras, Eduardo; Hallgrímsdóttir, Ingileif B; Huppert, Julian; Zody, Michael C; Abecasis, Gonçalo R; Estivill, Xavier; Bouffard, Gerard G; Guan, Xiaobin; Hansen, Nancy F; Idol, Jacquelyn R; Maduro, Valerie V B; Maskeri, Baishali; McDowell, Jennifer C; Park, Morgan; Thomas, Pamela J; Young, Alice C; Blakesley, Robert W; Muzny, Donna M; Sodergren, Erica; Wheeler, David A; Worley, Kim C; Jiang, Huaiyang; Weinstock, George M; Gibbs, Richard A; Graves, Tina; Fulton, Robert; Mardis, Elaine R; Wilson, Richard K; Clamp, Michele; Cuff, James; Gnerre, Sante; Jaffe, David B; Chang, Jean L; Lindblad-Toh, Kerstin; Lander, Eric S; Koriabine, Maxim; Nefedov, Mikhail; Osoegawa, Kazutoyo; Yoshinaga, Yuko; Zhu, Baoli; de Jong, Pieter J

2007-06-14

We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.

The social neuroscience and the theory of integrative levels.

PubMed

Bello-Morales, Raquel; Delgado-García, José María

2015-01-01

The theory of integrative levels provides a general description of the evolution of matter through successive orders of complexity and integration. Along its development, material forms pass through different levels of organization, such as physical, chemical, biological or sociological. The appearance of novel structures and dynamics during this process of development of matter in complex systems has been called emergence. Social neuroscience (SN), an interdisciplinary field that aims to investigate the biological mechanisms that underlie social structures, processes, and behavior and the influences between social and biological levels of organization, has affirmed the necessity for including social context as an essential element to understand the human behavior. To do this, SN proposes a multilevel integrative approach by means of three principles: multiple determinism, nonadditive determinism and reciprocal determinism. These theoretical principles seem to share the basic tenets of the theory of integrative levels but, in this paper, we aim to reveal the differences among both doctrines. First, SN asserts that combination of neural and social variables can produce emergent phenomena that would not be predictable from a neuroscientific or social psychological analysis alone; SN also suggests that to achieve a complete understanding of social structures we should use an integrative analysis that encompasses levels of organization ranging from the genetic level to the social one; finally, SN establishes that there can be mutual influences between biological and social factors in determining behavior, accepting, therefore, a double influence, upward from biology to social level, and downward, from social level to biology. In contrast, following the theory of integrative levels, emergent phenomena are not produced by the combination of variables from two levels, but by the increment of complexity at one level. In addition, the social behavior and structures might be contemplated not as the result of mixing or summing social and biological influences, but as emergent phenomena that should be described with its own laws. Finally, following the integrative levels view, influences upward, from biology to social level, and downward, from social level to biology, might not be equivalent, since the bottom-up processes are emergent and the downward causation (DC) is not.

The social neuroscience and the theory of integrative levels

PubMed Central

Bello-Morales, Raquel; Delgado-García, José María

2015-01-01

The theory of integrative levels provides a general description of the evolution of matter through successive orders of complexity and integration. Along its development, material forms pass through different levels of organization, such as physical, chemical, biological or sociological. The appearance of novel structures and dynamics during this process of development of matter in complex systems has been called emergence. Social neuroscience (SN), an interdisciplinary field that aims to investigate the biological mechanisms that underlie social structures, processes, and behavior and the influences between social and biological levels of organization, has affirmed the necessity for including social context as an essential element to understand the human behavior. To do this, SN proposes a multilevel integrative approach by means of three principles: multiple determinism, nonadditive determinism and reciprocal determinism. These theoretical principles seem to share the basic tenets of the theory of integrative levels but, in this paper, we aim to reveal the differences among both doctrines. First, SN asserts that combination of neural and social variables can produce emergent phenomena that would not be predictable from a neuroscientific or social psychological analysis alone; SN also suggests that to achieve a complete understanding of social structures we should use an integrative analysis that encompasses levels of organization ranging from the genetic level to the social one; finally, SN establishes that there can be mutual influences between biological and social factors in determining behavior, accepting, therefore, a double influence, upward from biology to social level, and downward, from social level to biology. In contrast, following the theory of integrative levels, emergent phenomena are not produced by the combination of variables from two levels, but by the increment of complexity at one level. In addition, the social behavior and structures might be contemplated not as the result of mixing or summing social and biological influences, but as emergent phenomena that should be described with its own laws. Finally, following the integrative levels view, influences upward, from biology to social level, and downward, from social level to biology, might not be equivalent, since the bottom-up processes are emergent and the downward causation (DC) is not. PMID:26578909

An in vivo model of functional and vascularized human brain organoids.

PubMed

Mansour, Abed AlFatah; Gonçalves, J Tiago; Bloyd, Cooper W; Li, Hao; Fernandes, Sarah; Quang, Daphne; Johnston, Stephen; Parylak, Sarah L; Jin, Xin; Gage, Fred H

2018-06-01

Differentiation of human pluripotent stem cells to small brain-like structures known as brain organoids offers an unprecedented opportunity to model human brain development and disease. To provide a vascularized and functional in vivo model of brain organoids, we established a method for transplanting human brain organoids into the adult mouse brain. Organoid grafts showed progressive neuronal differentiation and maturation, gliogenesis, integration of microglia, and growth of axons to multiple regions of the host brain. In vivo two-photon imaging demonstrated functional neuronal networks and blood vessels in the grafts. Finally, in vivo extracellular recording combined with optogenetics revealed intragraft neuronal activity and suggested graft-to-host functional synaptic connectivity. This combination of human neural organoids and an in vivo physiological environment in the animal brain may facilitate disease modeling under physiological conditions.

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.

Hemispheric Asymmetry of Human Brain Anatomical Network Revealed by Diffusion Tensor Tractography

PubMed Central

Liu, Yaou; Duan, Yunyun; Li, Kuncheng

2015-01-01

The topological architecture of the cerebral anatomical network reflects the structural organization of the human brain. Recently, topological measures based on graph theory have provided new approaches for quantifying large-scale anatomical networks. However, few studies have investigated the hemispheric asymmetries of the human brain from the perspective of the network model, and little is known about the asymmetries of the connection patterns of brain regions, which may reflect the functional integration and interaction between different regions. Here, we utilized diffusion tensor imaging to construct binary anatomical networks for 72 right-handed healthy adult subjects. We established the existence of structural connections between any pair of the 90 cortical and subcortical regions using deterministic tractography. To investigate the hemispheric asymmetries of the brain, statistical analyses were performed to reveal the brain regions with significant differences between bilateral topological properties, such as degree of connectivity, characteristic path length, and betweenness centrality. Furthermore, local structural connections were also investigated to examine the local asymmetries of some specific white matter tracts. From the perspective of both the global and local connection patterns, we identified the brain regions with hemispheric asymmetries. Combined with the previous studies, we suggested that the topological asymmetries in the anatomical network may reflect the functional lateralization of the human brain. PMID:26539535

[Anatomical discoveries and concept of human body structure in Nan-jing (Classic of Questioning)].

PubMed

Yang, Shi-zhe

2006-04-01

What Nan-jing (Classic of Questioning) contributes to the anatomical discoveries and concepts of human body structure in TCM is that it clarifies the concept, function and anatomical essence of viscera and bowels. It is the first. book that clearly defines the triple jiao as a "qi bowel", This statement is a typical example of Chinese dualistic system of its view on the human body, consisting of physical and spiritual components. This has stirred up confusion for modern interpretation and, as a result, some thought the visceral theory in the book is not based on substantial basis of anatomy. However, the Forty-second Question in Nan-jing not only carries the contents about Wei (stomach), Xiaochang (small intestine), Huichang (large intestine) and Guangchang (anus) in the chapter of "Intestine and Stomach" in Lingshu Jing (Miraculous Pivot), but also changes these names to those we actually use today in the latter chapters; and it also records the gross anatomical shape and size of gall bladder, urinary bladder and all the five viscerae. So, Nan-jing discusses the structure of human body in ancient times, and is equivalent to an integrated science of modern physiology and anatomy, and establishes a solid basis for the fundamental theory of TCM.

Glycerophospholipid Supplementation as a Potential Intervention for Supporting Cerebral Structure in Older Adults

PubMed Central

Reddan, Jeffery M.; White, David J.; Macpherson, Helen; Scholey, Andrew; Pipingas, Andrew

2018-01-01

Modifying nutritional intake through supplementation may be efficacious for altering the trajectory of cerebral structural decline evident with increasing age. To date, there have been a number of clinical trials in older adults whereby chronic supplementation with B vitamins, omega-3 fatty acids, or resveratrol, has been observed to either slow the rate of decline or repair cerebral tissue. There is also some evidence from animal studies indicating that supplementation with glycerophospholipids (GPL) may benefit cerebral structure, though these effects have not yet been investigated in adult humans. Despite this paucity of research, there are a number of factors predicting poorer cerebral structure in older humans, which GPL supplementation appears to beneficially modify or protect against. These include elevated concentrations of homocysteine, unbalanced activity of reactive oxygen species both increasing the risk of oxidative stress, increased concentrations of pro-inflammatory messengers, as well as poorer cardio- and cerebrovascular function. As such, it is hypothesized that GPL supplementation will support cerebral structure in older adults. These cerebral effects may influence cognitive function. The current review aims to provide a theoretical basis for future clinical trials investigating the effects of GPL supplementation on cerebral structural integrity in older adults. PMID:29563868

Aging and inhibitory control of action: cortico-subthalamic connection strength predicts stopping performance.

PubMed

Coxon, James P; Van Impe, Annouchka; Wenderoth, Nicole; Swinnen, Stephan P

2012-06-13

Diffusion weighted imaging (DWI) studies in humans have shown that seniors exhibit reduced white matter integrity compared with young adults, with the most pronounced change occurring in frontal white matter. It is generally assumed that this structural deterioration underlies inhibitory control deficits in old age, but specific evidence from a structural neuroscience perspective is lacking. Cognitive action control is thought to rely on an interconnected network consisting of right inferior frontal cortex (r-IFC), pre-supplementary motor area (preSMA), and the subthalamic nucleus (STN). Here we performed probabilistic DWI tractography to delineate this cognitive control network and had the same individuals (20 young, 20 older adults) perform a task probing both response inhibition and action reprogramming. We hypothesized that structural integrity (fractional anisotropy) and connection strength within this network would be predictive of individual and age-related differences in task performance. We show that the integrity of r-IFC white matter is an age-independent predictor of stop-signal reaction time (SSRT). We further provide evidence that the integrity of white matter projecting to STN predicts both outright stopping (SSRT) and transient braking of response initiation to buy time for action reprogramming (stopping interference effects). These associations remain even after controlling for Go task performance, demonstrating specificity to the Stop component of this task. Finally, a multiple regression analysis reveals bilateral preSMA-STN tract strength as a significant predictor of SSRT in older adults. Our data link age-related decline in inhibitory control with structural decline of STN projections.

Modeling a flexible representation machinery of human concept learning.

PubMed

Matsuka, Toshihiko; Sakamoto, Yasuaki; Chouchourelou, Arieta

2008-01-01

It is widely acknowledged that categorically organized abstract knowledge plays a significant role in high-order human cognition. Yet, there are many unknown issues about the nature of how categories are internally represented in our mind. Traditionally, it has been considered that there is a single innate internal representation system for categorical knowledge, such as Exemplars, Prototypes, or Rules. However, results of recent empirical and computational studies collectively suggest that the human internal representation system is apparently capable of exhibiting behaviors consistent with various types of internal representation schemes. We, then, hypothesized that humans' representational system as a dynamic mechanism, capable of selecting a representation scheme that meets situational characteristics, including complexities of category structure. The present paper introduces a framework for a cognitive model that integrates robust and flexible internal representation machinery. Three simulation studies were conducted. The results showed that SUPERSET, our new model, successfully exhibited cognitive behaviors that are consistent with three main theories of the human internal representation system. Furthermore, a simulation study on social cognitive behaviors showed that the model was capable of acquiring knowledge with high commonality, even for a category structure with numerous valid conceptualizations.

Helicoidal multi-lamellar features of RGD-functionalized silk biomaterials for corneal tissue engineering.

PubMed

Gil, Eun Seok; Mandal, Biman B; Park, Sang-Hyug; Marchant, Jeffrey K; Omenetto, Fiorenzo G; Kaplan, David L

2010-12-01

RGD-coupled silk protein-biomaterial lamellar systems were prepared and studied with human cornea fibroblasts (hCFs) to match functional requirements. A strategy for corneal tissue engineering was pursued to replicate the structural hierarchy of human corneal stroma within thin stacks of lamellae-like tissues, in this case constructed from scaffolds constructed with RGD-coupled, patterned, porous, mechanically robust and transparent silk films. The influence of RGD-coupling on the orientation, proliferation, ECM organization, and gene expression of hCFs was assessed. RGD surface modification enhanced cell attachment, proliferation, alignment and expression of both collagens (type I and V) and proteoglycans (decorin and biglycan). Confocal and histological images of the lamellar systems revealed that the bio-functionalized silk human cornea 3D constructs exhibited integrated corneal stroma tissue with helicoidal multi-lamellar alignment of collagen-rich and proteoglycan-rich extracellular matrix, with transparency of the construct. This biomimetic approach to replicate corneal stromal tissue structural hierarchy and architecture demonstrates a useful strategy for engineering human cornea. Further, this approach can be exploited for other tissue systems due to the pervasive nature of such helicoids in most human tissues. Copyright © 2010 Elsevier Ltd. All rights reserved.

Bacteria-Human Somatic Cell Lateral Gene Transfer Is Enriched in Cancer Samples

PubMed Central

Robinson, Kelly M.; White, James Robert; Ganesan, Ashwinkumar; Nourbakhsh, Syrus; Dunning Hotopp, Julie C.

2013-01-01

There are 10× more bacterial cells in our bodies from the microbiome than human cells. Viral DNA is known to integrate in the human genome, but the integration of bacterial DNA has not been described. Using publicly available sequence data from the human genome project, the 1000 Genomes Project, and The Cancer Genome Atlas (TCGA), we examined bacterial DNA integration into the human somatic genome. Here we present evidence that bacterial DNA integrates into the human somatic genome through an RNA intermediate, and that such integrations are detected more frequently in (a) tumors than normal samples, (b) RNA than DNA samples, and (c) the mitochondrial genome than the nuclear genome. Hundreds of thousands of paired reads support random integration of Acinetobacter-like DNA in the human mitochondrial genome in acute myeloid leukemia samples. Numerous read pairs across multiple stomach adenocarcinoma samples support specific integration of Pseudomonas-like DNA in the 5′-UTR and 3′-UTR of four proto-oncogenes that are up-regulated in their transcription, consistent with conversion to an oncogene. These data support our hypothesis that bacterial integrations occur in the human somatic genome and may play a role in carcinogenesis. We anticipate that the application of our approach to additional cancer genome projects will lead to the more frequent detection of bacterial DNA integrations in tumors that are in close proximity to the human microbiome. PMID:23840181

Morphomics: An integral part of systems biology of the human placenta.

PubMed

Mayhew, T M

2015-04-01

The placenta is a transient organ the functioning of which has health consequences far beyond the embryo/fetus. Understanding the biology of any system (organ, organism, single cell, etc) requires a comprehensive and inclusive approach which embraces all the biomedical disciplines and 'omic' technologies and then integrates information obtained from all of them. Among the latest 'omics' is morphomics. The terms morphome and morphomics have been applied incoherently in biology and biomedicine but, recently, they have been given clear and widescale definitions. Morphomics is placed in the context of other 'omics' and its pertinent technologies and tools for sampling and quantitation are reviewed. Emphasis is accorded to the importance of random sampling principles in systems biology and the value of combining 3D quantification with alternative imaging techniques to advance knowledge and understanding of the human placental morphome. By analogy to other 'omes', the morphome is the totality of morphological features within a system and morphomics is the systematic study of those structures. Information about structure is required at multiple levels of resolution in order to understand better the processes by which a given system alters with time, experimental treatment or environmental insult. Therefore, morphomics research includes all imaging techniques at all levels of achievable resolution from gross anatomy and medical imaging, via optical and electron microscopy, to molecular characterisation. Quantification is an important element of all 'omics' studies and, because biological systems exist and operate in 3-dimensional (3D) space, precise descriptions of form, content and spatial relationships require the quantification of structure in 3D. These considerations are relevant to future study contributions to the Human Placenta Project. Copyright © 2015 Elsevier Ltd. All rights reserved.

Development of an artificial neural network model for risk assessment of skin sensitization using human cell line activation test, direct peptide reactivity assay, KeratinoSens™ and in silico structure alert parameter.

PubMed

Hirota, Morihiko; Ashikaga, Takao; Kouzuki, Hirokazu

2018-04-01

It is important to predict the potential of cosmetic ingredients to cause skin sensitization, and in accordance with the European Union cosmetic directive for the replacement of animal tests, several in vitro tests based on the adverse outcome pathway have been developed for hazard identification, such as the direct peptide reactivity assay, KeratinoSens™ and the human cell line activation test. Here, we describe the development of an artificial neural network (ANN) prediction model for skin sensitization risk assessment based on the integrated testing strategy concept, using direct peptide reactivity assay, KeratinoSens™, human cell line activation test and an in silico or structure alert parameter. We first investigated the relationship between published murine local lymph node assay EC3 values, which represent skin sensitization potency, and in vitro test results using a panel of about 134 chemicals for which all the required data were available. Predictions based on ANN analysis using combinations of parameters from all three in vitro tests showed a good correlation with local lymph node assay EC3 values. However, when the ANN model was applied to a testing set of 28 chemicals that had not been included in the training set, predicted EC3s were overestimated for some chemicals. Incorporation of an additional in silico or structure alert descriptor (obtained with TIMES-M or Toxtree software) in the ANN model improved the results. Our findings suggest that the ANN model based on the integrated testing strategy concept could be useful for evaluating the skin sensitization potential. Copyright © 2017 John Wiley & Sons, Ltd.

Image-guided feedback for ophthalmic microsurgery using multimodal intraoperative swept-source spectrally encoded scanning laser ophthalmoscopy and optical coherence tomography

NASA Astrophysics Data System (ADS)

Li, Jianwei D.; Malone, Joseph D.; El-Haddad, Mohamed T.; Arquitola, Amber M.; Joos, Karen M.; Patel, Shriji N.; Tao, Yuankai K.

2017-02-01

Surgical interventions for ocular diseases involve manipulations of semi-transparent structures in the eye, but limited visualization of these tissue layers remains a critical barrier to developing novel surgical techniques and improving clinical outcomes. We addressed limitations in image-guided ophthalmic microsurgery by using microscope-integrated multimodal intraoperative swept-source spectrally encoded scanning laser ophthalmoscopy and optical coherence tomography (iSS-SESLO-OCT). We previously demonstrated in vivo human ophthalmic imaging using SS-SESLO-OCT, which enabled simultaneous acquisition of en face SESLO images with every OCT cross-section. Here, we integrated our new 400 kHz iSS-SESLO-OCT, which used a buffered Axsun 1060 nm swept-source, with a surgical microscope and TrueVision stereoscopic viewing system to provide image-based feedback. In vivo human imaging performance was demonstrated on a healthy volunteer, and simulated surgical maneuvers were performed in ex vivo porcine eyes. Denselysampled static volumes and volumes subsampled at 10 volumes-per-second were used to visualize tissue deformations and surgical dynamics during corneal sweeps, compressions, and dissections, and retinal sweeps, compressions, and elevations. En face SESLO images enabled orientation and co-registration with the widefield surgical microscope view while OCT imaging enabled depth-resolved visualization of surgical instrument positions relative to anatomic structures-of-interest. TrueVision heads-up display allowed for side-by-side viewing of the surgical field with SESLO and OCT previews for real-time feedback, and we demonstrated novel integrated segmentation overlays for augmented-reality surgical guidance. Integration of these complementary imaging modalities may benefit surgical outcomes by enabling real-time intraoperative visualization of surgical plans, instrument positions, tissue deformations, and image-based surrogate biomarkers correlated with completion of surgical goals.

Terra Populus and DataNet Collaboration

NASA Astrophysics Data System (ADS)

Kugler, T.; Ruggles, S.; Fitch, C. A.; Clark, P. D.; Sobek, M.; Van Riper, D.

2012-12-01

Terra Populus, part of NSF's new DataNet initiative, is developing organizational and technical infrastructure to integrate, preserve, and disseminate data describing changes in the human population and environment over time. Terra Populus will incorporate large microdata and aggregate census datasets from the United States and around the world, as well as land use, land cover, climate and other environmental datasets. These data are widely dispersed, exist in a variety of data structures, have incompatible or inadequate metadata, and have incompatible geographic identifiers. Terra Populus is developing methods of integrating data from different domains and translating across data structures based on spatio-temporal linkages among data contents. The new infrastructure will enable researchers to identify and merge data from heterogeneous sources to study the relationships between human behavior and the natural world. Terra Populus will partner with data archives, data producers, and data users to create a sustainable international organization that will guarantee preservation and access over multiple decades. Terra Populus is also collaborating with the other projects in the DataNet initiative - DataONE, the DataNet Federation Consortium (DFC) and Sustainable Environment-Actionable Data (SEAD). Taken together, the four projects address aspects of the entire data lifecycle, including planning, collection, documentation, discovery, integration, curation, preservation, and collaboration; and encompass a wide range of disciplines including earth sciences, ecology, social sciences, hydrology, oceanography, and engineering. The four projects are pursuing activities to share data, tools, and expertise between pairs of projects as well as collaborating across the DataNet program on issues of cyberinfrastructure and community engagement. Topics to be addressed through program-wide collaboration include technical, organizational, and financial sustainability; semantic integration; data management training and education; and cross-disciplinary awareness of data resources.

Developing an integrated framework of problem-based learning and coaching psychology for medical education: a participatory research.

PubMed

Wang, Qing; Li, Huiping; Pang, Weiguo; Liang, Shuo; Su, Yiliang

2016-01-05

Medical schools have been making efforts to develop their own problem-based learning (PBL) approaches based on their educational conditions, human resources and existing curriculum structures. This study aimed to explore a new framework by integrating the essential features of PBL and coaching psychology applicable to the undergraduate medical education context. A participatory research design was employed. Four educational psychology researchers, eight undergraduate medical school students and two accredited PBL tutors participated in a four-month research programme. Data were collected through participatory observation, focus groups, semi-structured interviews, workshop documents and feedback surveys and then subjected to thematic content analysis. The triangulation of sources and member checking were used to ensure the credibility and trustworthiness of the research process. Five themes emerged from the analysis: current experience of PBL curriculum; the roles of and relationships between tutors and students; student group dynamics; development of self-directed learning; and coaching in PBL facilitation. On the basis of this empirical data, a systematic model of PBL and coaching psychology was developed. The findings highlighted that coaching psychology could be incorporated into the facilitation system in PBL. The integrated framework of PBL and coaching psychology in undergraduate medical education has the potential to promote the development of the learning goals of cultivating clinical reasoning ability, lifelong learning capacities and medical humanity. Challenges, benefits and future directions for implementing the framework are discussed in this paper.

Structural insights into NHEJ: building up an integrated picture of the dynamic DSB repair super complex, one component and interaction at a time

PubMed Central

Williams, Gareth J.; Hammel, Michal; Radhakrishnan, Sarvan Kumar; Ramsden, Dale; Lees-Miller, Susan P.; Tainer, John A.

2014-01-01

Non-homologous end joining (NHEJ) is the major pathway for repair of DNA double-strand breaks (DSBs) in human cells. NHEJ is also needed for V(D)J recombination and the development of T and B cells in vertebrate immune systems, and acts in both the generation and prevention of non-homologous chromosomal translocations, a hallmark of genomic instability and many human cancers. X-ray crystal structures, cryo-electron microscopy envelopes, and small angle X-ray scattering (SAXS) solution conformations and assemblies are defining most of the core protein components for NHEJ: Ku70/Ku80 heterodimer; the DNA dependent protein kinase catalytic subunit (DNA-PKcs); the structure-specific endonuclease Artemis along with polynucleotide kinase/phosphatase (PNKP), aprataxin and PNKP related protein (APLF); the scaffolding proteins XRCC4 and XLF (XRCC4-like factor); DNA polymerases, and DNA ligase IV (Lig IV). The dynamic assembly of multi-protein NHEJ complexes at DSBs is regulated in part by protein phosphorylation. The basic steps of NHEJ have been biochemically defined to require: 1) DSB detection by the Ku heterodimer with subsequent DNA-PKcs tethering to form the DNA-PKcs-Ku-DNA complex (termed DNA-PK), 2) lesion processing, and 3) DNA end ligation by Lig IV, which functions in complex with XRCC4 and XLF. The current integration of structures by combined methods is resolving puzzles regarding the mechanisms, coordination and regulation of these three basic steps. Overall, structural results suggest the NHEJ system forms a flexing scaffold with the DNA-PKcs HEAT repeats acting as compressible macromolecular springs suitable to store and release conformational energy to apply forces to regulate NHEJ complexes and the DNA substrate for DNA end protection, processing, and ligation. PMID:24656613

Maturation status of sarcomere structure and function in human iPSC-derived cardiac myocytes.

PubMed

Bedada, Fikru B; Wheelwright, Matthew; Metzger, Joseph M

2016-07-01

Human heart failure due to myocardial infarction is a major health concern. The paucity of organs for transplantation limits curative approaches for the diseased and failing adult heart. Human induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs) have the potential to provide a long-term, viable, regenerative-medicine alternative. Significant progress has been made with regard to efficient cardiac myocyte generation from hiPSCs. However, directing hiPSC-CMs to acquire the physiological structure, gene expression profile and function akin to mature cardiac tissue remains a major obstacle. Thus, hiPSC-CMs have several hurdles to overcome before they find their way into translational medicine. In this review, we address the progress that has been made, the void in knowledge and the challenges that remain. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Human effects on ecological connectivity in aquatic ecosystems: Integrating scientific approaches to support management and mitigation.

PubMed

Crook, David A; Lowe, Winsor H; Allendorf, Frederick W; Erős, Tibor; Finn, Debra S; Gillanders, Bronwyn M; Hadwen, Wade L; Harrod, Chris; Hermoso, Virgilio; Jennings, Simon; Kilada, Raouf W; Nagelkerken, Ivan; Hansen, Michael M; Page, Timothy J; Riginos, Cynthia; Fry, Brian; Hughes, Jane M

2015-11-15

Understanding the drivers and implications of anthropogenic disturbance of ecological connectivity is a key concern for the conservation of biodiversity and ecosystem processes. Here, we review human activities that affect the movements and dispersal of aquatic organisms, including damming of rivers, river regulation, habitat loss and alteration, human-assisted dispersal of organisms and climate change. Using a series of case studies, we show that the insight needed to understand the nature and implications of connectivity, and to underpin conservation and management, is best achieved via data synthesis from multiple analytical approaches. We identify four key knowledge requirements for progressing our understanding of the effects of anthropogenic impacts on ecological connectivity: autecology; population structure; movement characteristics; and environmental tolerance/phenotypic plasticity. Structuring empirical research around these four broad data requirements, and using this information to parameterise appropriate models and develop management approaches, will allow for mitigation of the effects of anthropogenic disturbance on ecological connectivity in aquatic ecosystems. Copyright © 2015 Elsevier B.V. All rights reserved.

Mechanisms of hemispheric lateralization: Asymmetric interhemispheric recruitment in the face perception network.

PubMed

Frässle, Stefan; Paulus, Frieder Michel; Krach, Sören; Schweinberger, Stefan Robert; Stephan, Klaas Enno; Jansen, Andreas

2016-01-01

Perceiving human faces constitutes a fundamental ability of the human mind, integrating a wealth of information essential for social interactions in everyday life. Neuroimaging studies have unveiled a distributed neural network consisting of multiple brain regions in both hemispheres. Whereas the individual regions in the face perception network and the right-hemispheric dominance for face processing have been subject to intensive research, the functional integration among these regions and hemispheres has received considerably less attention. Using dynamic causal modeling (DCM) for fMRI, we analyzed the effective connectivity between the core regions in the face perception network of healthy humans to unveil the mechanisms underlying both intra- and interhemispheric integration. Our results suggest that the right-hemispheric lateralization of the network is due to an asymmetric face-specific interhemispheric recruitment at an early processing stage - that is, at the level of the occipital face area (OFA) but not the fusiform face area (FFA). As a structural correlate, we found that OFA gray matter volume was correlated with this asymmetric interhemispheric recruitment. Furthermore, exploratory analyses revealed that interhemispheric connection asymmetries were correlated with the strength of pupil constriction in response to faces, a measure with potential sensitivity to holistic (as opposed to feature-based) processing of faces. Overall, our findings thus provide a mechanistic description for lateralized processes in the core face perception network, point to a decisive role of interhemispheric integration at an early stage of face processing among bilateral OFA, and tentatively indicate a relation to individual variability in processing strategies for faces. These findings provide a promising avenue for systematic investigations of the potential role of interhemispheric integration in future studies. Copyright © 2015 Elsevier Inc. All rights reserved.

A Flexible and Wearable Human Stress Monitoring Patch

PubMed Central

Yoon, Sunghyun; Sim, Jai Kyoung; Cho, Young-Ho

2016-01-01

A human stress monitoring patch integrates three sensors of skin temperature, skin conductance, and pulsewave in the size of stamp (25 mm × 15 mm × 72 μm) in order to enhance wearing comfort with small skin contact area and high flexibility. The skin contact area is minimized through the invention of an integrated multi-layer structure and the associated microfabrication process; thus being reduced to 1/125 of that of the conventional single-layer multiple sensors. The patch flexibility is increased mainly by the development of flexible pulsewave sensor, made of a flexible piezoelectric membrane supported by a perforated polyimide membrane. In the human physiological range, the fabricated stress patch measures skin temperature with the sensitivity of 0.31 Ω/°C, skin conductance with the sensitivity of 0.28 μV/0.02 μS, and pulse wave with the response time of 70 msec. The skin-attachable stress patch, capable to detect multimodal bio-signals, shows potential for application to wearable emotion monitoring. PMID:27004608

Handedness- and brain size-related efficiency differences in small-world brain networks: a resting-state functional magnetic resonance imaging study.

PubMed

Li, Meiling; Wang, Junping; Liu, Feng; Chen, Heng; Lu, Fengmei; Wu, Guorong; Yu, Chunshui; Chen, Huafu

2015-05-01

The human brain has been described as a complex network, which integrates information with high efficiency. However, the relationships between the efficiency of human brain functional networks and handedness and brain size remain unclear. Twenty-one left-handed and 32 right-handed healthy subjects underwent a resting-state functional magnetic resonance imaging scan. The whole brain functional networks were constructed by thresholding Pearson correlation matrices of 90 cortical and subcortical regions. Graph theory-based methods were employed to further analyze their topological properties. As expected, all participants demonstrated small-world topology, suggesting a highly efficient topological structure. Furthermore, we found that smaller brains showed higher local efficiency, whereas larger brains showed higher global efficiency, reflecting a suitable efficiency balance between local specialization and global integration of brain functional activity. Compared with right-handers, significant alterations in nodal efficiency were revealed in left-handers, involving the anterior and median cingulate gyrus, middle temporal gyrus, angular gyrus, and amygdala. Our findings indicated that the functional network organization in the human brain was associated with handedness and brain size.

Estimation of skeletal movement of human locomotion from body surface shapes using dynamic spatial video camera (DSVC) and 4D human model.

PubMed

Saito, Toshikuni; Suzuki, Naoki; Hattori, Asaki; Suzuki, Shigeyuki; Hayashibe, Mitsuhiro; Otake, Yoshito

2006-01-01

We have been developing a DSVC (Dynamic Spatial Video Camera) system to measure and observe human locomotion quantitatively and freely. A 4D (four-dimensional) human model with detailed skeletal structure, joint, muscle, and motor functionality has been built. The purpose of our research was to estimate skeletal movements from body surface shapes using DSVC and the 4D human model. For this purpose, we constructed a body surface model of a subject and resized the standard 4D human model to match with geometrical features of the subject's body surface model. Software that integrates the DSVC system and the 4D human model, and allows dynamic skeletal state analysis from body surface movement data was also developed. We practically applied the developed system in dynamic skeletal state analysis of a lower limb in motion and were able to visualize the motion using geometrically resized standard 4D human model.

Development of an Integrated Human Factors Toolkit

NASA Technical Reports Server (NTRS)

Resnick, Marc L.

2003-01-01

An effective integration of human abilities and limitations is crucial to the success of all NASA missions. The Integrated Human Factors Toolkit facilitates this integration by assisting system designers and analysts to select the human factors tools that are most appropriate for the needs of each project. The HF Toolkit contains information about a broad variety of human factors tools addressing human requirements in the physical, information processing and human reliability domains. Analysis of each tool includes consideration of the most appropriate design stage, the amount of expertise in human factors that is required, the amount of experience with the tool and the target job tasks that are needed, and other factors that are critical for successful use of the tool. The benefits of the Toolkit include improved safety, reliability and effectiveness of NASA systems throughout the agency. This report outlines the initial stages of development for the Integrated Human Factors Toolkit.

Identification of human papillomavirus (HPV) 16 DNA integration and the ensuing patterns of methylation in HPV-associated head and neck squamous cell carcinoma cell lines.

PubMed

Hatano, Takashi; Sano, Daisuke; Takahashi, Hideaki; Hyakusoku, Hiroshi; Isono, Yasuhiro; Shimada, Shoko; Sawakuma, Kae; Takada, Kentaro; Oikawa, Ritsuko; Watanabe, Yoshiyuki; Yamamoto, Hiroyuki; Itoh, Fumio; Myers, Jeffrey N; Oridate, Nobuhiko

2017-04-01

Recent studies showed that human papillomavirus (HPV) integration contributes to the genomic instability seen in HPV-associated head and neck squamous cell carcinoma (HPV-HNSCC). However, the epigenetic alterations induced after HPV integration remains unclear. To identify the molecular details of HPV16 DNA integration and the ensuing patterns of methylation in HNSCC, we performed next-generation sequencing using a target-enrichment method for the effective identification of HPV16 integration breakpoints as well as the characterization of genomic sequences adjacent to HPV16 integration breakpoints with three HPV16-related HNSCC cell lines. The DNA methylation levels of the integrated HPV16 genome and that of the adjacent human genome were also analyzed by bisulfite pyrosequencing. We found various integration loci, including novel integration sites. Integration loci were located predominantly in the intergenic region, with a significant enrichment of the microhomologous sequences between the human and HPV16 genomes at the integration breakpoints. Furthermore, various levels of methylation within both the human genome and the integrated HPV genome at the integration breakpoints in each integrant were observed. Allele-specific methylation analysis suggested that the HPV16 integrants remained hypomethylated when the flanking host genome was hypomethylated. After integration into highly methylated human genome regions, however, the HPV16 DNA became methylated. In conclusion, we found novel integration sites and methylation patterns in HPV-HNSCC using our unique method. These findings may provide insights into understanding of viral integration mechanism and virus-associated carcinogenesis of HPV-HNSCC. © 2016 UICC.

Delivery of Functionality in Complex Food Systems: Physically Inspired Approaches from Nanoscale to Microscale, Wageningen 18–21 October 2009

PubMed Central

Ubbink, Job; Duchateau, Guus

2010-01-01

The Wageningen Delivery of Functionality symposium covered all aspects involved with food structural design to arrive at high-quality foods which meet demanding customer expectations and regulatory requirements. The symposium integrated aspects from the structural organization of foods at molecular and supramolecular scales to dedicated techniques required to describe and visualize such structures, the gastro-intestinal events and how to model these in a laboratory setting, and finally the impact those food structures and ingredients have on the consumer’s physiology and on the human perception. As an interdisciplinary platform, bringing together more than 160 researchers from academia and industry, the symposium meanwhile fulfills an important role in the food science community. PMID:21125000

The Proteome Folding Project: Proteome-scale prediction of structure and function

PubMed Central

Drew, Kevin; Winters, Patrick; Butterfoss, Glenn L.; Berstis, Viktors; Uplinger, Keith; Armstrong, Jonathan; Riffle, Michael; Schweighofer, Erik; Bovermann, Bill; Goodlett, David R.; Davis, Trisha N.; Shasha, Dennis; Malmström, Lars; Bonneau, Richard

2011-01-01

The incompleteness of proteome structure and function annotation is a critical problem for biologists and, in particular, severely limits interpretation of high-throughput and next-generation experiments. We have developed a proteome annotation pipeline based on structure prediction, where function and structure annotations are generated using an integration of sequence comparison, fold recognition, and grid-computing-enabled de novo structure prediction. We predict protein domain boundaries and three-dimensional (3D) structures for protein domains from 94 genomes (including human, Arabidopsis, rice, mouse, fly, yeast, Escherichia coli, and worm). De novo structure predictions were distributed on a grid of more than 1.5 million CPUs worldwide (World Community Grid). We generated significant numbers of new confident fold annotations (9% of domains that are otherwise unannotated in these genomes). We demonstrate that predicted structures can be combined with annotations from the Gene Ontology database to predict new and more specific molecular functions. PMID:21824995

Human Behavioral Representations with Realistic Personality and Cultural Characteristics

DTIC Science & Technology

2005-06-01

personality factors as customizations to an underlying formally rational symbolic architecture, PAC uses dimensions of personality, emotion , and culture as...foundations for the cognitive process. The structure of PAC allows it to function as a personality/ emotional layer that can be used stand-alone or...integrated with existing constrained- rationality cognitive architectures. In addition, a set of tools was developed to support the authoring

The 2.6 Angstrom Crystal Structure of a Human A[subscript 2A] Adenosine Receptor Bound to an Antagonist

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

Jaakola, Veli-Pekka; Griffith, Mark T.; Hanson, Michael A.

2009-01-15

The adenosine class of heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) mediates the important role of extracellular adenosine in many physiological processes and is antagonized by caffeine. We have determined the crystal structure of the human A{sub 2A} adenosine receptor, in complex with a high-affinity subtype-selective antagonist, ZM241385, to 2.6 angstrom resolution. Four disulfide bridges in the extracellular domain, combined with a subtle repacking of the transmembrane helices relative to the adrenergic and rhodopsin receptor structures, define a pocket distinct from that of other structurally determined GPCRs. The arrangement allows for the binding of the antagonist in an extendedmore » conformation, perpendicular to the membrane plane. The binding site highlights an integral role for the extracellular loops, together with the helical core, in ligand recognition by this class of GPCRs and suggests a role for ZM241385 in restricting the movement of a tryptophan residue important in the activation mechanism of the class A receptors.« less

The Molecular Structure of Human Red Blood Cell Membranes from Highly Oriented, Solid Supported Multi-Lamellar Membranes

PubMed Central

Himbert, Sebastian; Alsop, Richard J.; Rose, Markus; Hertz, Laura; Dhaliwal, Alexander; Moran-Mirabal, Jose M.; Verschoor, Chris P.; Bowdish, Dawn M. E.; Kaestner, Lars; Wagner, Christian; Rheinstädter, Maikel C.

2017-01-01

We prepared highly oriented, multi-lamellar stacks of human red blood cell (RBC) membranes applied on silicon wafers. RBC ghosts were prepared by hemolysis and applied onto functionalized silicon chips and annealed into multi-lamellar RBC membranes. High resolution X-ray diffraction was used to determine the molecular structure of the stacked membranes. We present direct experimental evidence that these RBC membranes consist of nanometer sized domains of integral coiled-coil peptides, as well as liquid ordered (lo) and liquid disordered (ld) lipids. Lamellar spacings, membrane and hydration water layer thicknesses, areas per lipid tail and domain sizes were determined. The common drug aspirin was added to the RBC membranes and found to interact with RBC membranes and preferably partition in the head group region of the lo domain leading to a fluidification of the membranes, i.e., a thinning of the bilayers and an increase in lipid tail spacing. Our results further support current models of RBC membranes as patchy structures and provide unprecedented structural details of the molecular organization in the different domains. PMID:28045119

The Molecular Structure of Human Red Blood Cell Membranes from Highly Oriented, Solid Supported Multi-Lamellar Membranes

NASA Astrophysics Data System (ADS)

Himbert, Sebastian; Alsop, Richard J.; Rose, Markus; Hertz, Laura; Dhaliwal, Alexander; Moran-Mirabal, Jose M.; Verschoor, Chris P.; Bowdish, Dawn M. E.; Kaestner, Lars; Wagner, Christian; Rheinstädter, Maikel C.

2017-01-01

We prepared highly oriented, multi-lamellar stacks of human red blood cell (RBC) membranes applied on silicon wafers. RBC ghosts were prepared by hemolysis and applied onto functionalized silicon chips and annealed into multi-lamellar RBC membranes. High resolution X-ray diffraction was used to determine the molecular structure of the stacked membranes. We present direct experimental evidence that these RBC membranes consist of nanometer sized domains of integral coiled-coil peptides, as well as liquid ordered (lo) and liquid disordered (ld) lipids. Lamellar spacings, membrane and hydration water layer thicknesses, areas per lipid tail and domain sizes were determined. The common drug aspirin was added to the RBC membranes and found to interact with RBC membranes and preferably partition in the head group region of the lo domain leading to a fluidification of the membranes, i.e., a thinning of the bilayers and an increase in lipid tail spacing. Our results further support current models of RBC membranes as patchy structures and provide unprecedented structural details of the molecular organization in the different domains.

Positive Disintegration as a Process of Symmetry Breaking.

PubMed

Laycraft, Krystyna

2017-04-01

This article presents an analysis of the positive disintegration as a process of symmetry breaking. Symmetry breaking plays a major role in self-organized patterns formation and correlates directly to increasing complexity and function specialization. According to Dabrowski, a creator of the Theory of Positive Disintegration, the change from lower to higher levels of human development requires a major restructuring of an individual's psychological makeup. Each level of human development is a relatively stable and coherent configuration of emotional-cognitive patterns called developmental dynamisms. Their main function is to restructure a mental structure by breaking the symmetry of a low level and bringing differentiation and then integration to higher levels. The positive disintegration is then the process of transitions from a lower level of high symmetry and low complexity to higher levels of low symmetry and high complexity of mental structure.

Topologically Diverse Human Membrane Proteins Partition to Liquid-Disordered Domains in Phase-Separated Lipid Vesicles.

PubMed

Schlebach, Jonathan P; Barrett, Paul J; Day, Charles A; Kim, Ji Hun; Kenworthy, Anne K; Sanders, Charles R

2016-02-23

The integration of membrane proteins into "lipid raft" membrane domains influences many biochemical processes. The intrinsic structural properties of membrane proteins are thought to mediate their partitioning between membrane domains. However, whether membrane topology influences the targeting of proteins to rafts remains unclear. To address this question, we examined the domain preference of three putative raft-associated membrane proteins with widely different topologies: human caveolin-3, C99 (the 99 residue C-terminal domain of the amyloid precursor protein), and peripheral myelin protein 22. We find that each of these proteins are excluded from the ordered domains of giant unilamellar vesicles containing coexisting liquid-ordered and liquid-disordered phases. Thus, the intrinsic structural properties of these three topologically distinct disease-linked proteins are insufficient to confer affinity for synthetic raft-like domains.

Interlaced photoacoustic and ultrasound imaging system with real-time coregistration for ovarian tissue characterization

NASA Astrophysics Data System (ADS)

Alqasemi, Umar; Li, Hai; Yuan, Guangqian; Kumavor, Patrick; Zanganeh, Saeid; Zhu, Quing

2014-07-01

Coregistered ultrasound (US) and photoacoustic imaging are emerging techniques for mapping the echogenic anatomical structure of tissue and its corresponding optical absorption. We report a 128-channel imaging system with real-time coregistration of the two modalities, which provides up to 15 coregistered frames per second limited by the laser pulse repetition rate. In addition, the system integrates a compact transvaginal imaging probe with a custom-designed fiber optic assembly for in vivo detection and characterization of human ovarian tissue. We present the coregistered US and photoacoustic imaging system structure, the optimal design of the PC interfacing software, and the reconfigurable field programmable gate array operation and optimization. Phantom experiments of system lateral resolution and axial sensitivity evaluation, examples of the real-time scanning of a tumor-bearing mouse, and ex vivo human ovaries studies are demonstrated.

Electron microscopic observations of human sperm whole-mounts after extraction for nuclear matrix and intermediate filaments (NM-IF).

PubMed

Markova, Maya Dyankova

2004-10-01

The extraction for nuclear matrix and intermediate filaments (NM-IF) is used to reveal, isolate and study these highly resistant structures in different cell types. We applied for the first time this chemical dissection to human spermatozoa and observed them as whole-mounts by unembedded electron microscopy. The general appearance of NM-IF extracted sperm cells was preserved, showing the intermediate filament-like properties of their cytoskeletal components. In most heads, a network was observed in subacrosomal position, consisting of hubs interconnected by filaments. It seemed to be overlaid on another, finer network. The neck retained its integrity, allowing observations of the three-dimensional structure of the segmented columns. More distally, axoneme and outer dense fibres were covered by submitochondrial cytoskeleton in the middle piece and fibrous sheath in the principal piece, with the annulus usually detached from the fibrous sheath. End piece microtubules were retained in most cells and showed a tendency of cohesion, remaining in a parallel bundle or forming flat sheets. In conclusion, our results provided additional structural details of human sperm cytoskeleton and demonstrated the advantages of combining different methodological approaches in ultrastructural research.

Structural Integration and Control of Peerless Human-like Prosthetic Hand

NASA Astrophysics Data System (ADS)

Dave, Ankit; Muthu, P.; Karthikraj, V.; Latha, S.

2018-04-01

Limb damage can create severe disturbance in movement and operative abilities wherein the prosthetic rehabilitation has the potential to replace function and enhance the quality of life. This paper presents a humanlike prosthetic hand using such unique design concept of hand model using artificial bones, ligaments, and tendons controlled using Arduino. Amongst various platforms available, Arduino is known for its adaptability, adoration and low cost. The design of prosthetic hand has a unique structure with all carpal, metacarpal, and phalanges which are bones of the hand. These bones are attached to each other following the pattern of human hand using the polymeric rubber as a functioning ligament. Furthermore, this structure of finger is driven by tendons attached to all fingers and passes through the ligaments working as pulley resulting in more degrees of freedom. The motor can twitch the tendons to achieve the action of fingers. Thus the servos, controlled by an Arduino, are used to regulate the movement mechanism of the prosthetic hand.

Discovery of the Highly Potent PI3K/mTOR Dual Inhibitor PF-04979064 through Structure-Based Drug Design

PubMed Central

2012-01-01

PI3K, AKT, and mTOR are key kinases from PI3K signaling pathway being extensively pursued to treat a variety of cancers in oncology. To search for a structurally differentiated back-up candidate to PF-04691502, which is currently in phase I/II clinical trials for treating solid tumors, a lead optimization effort was carried out with a tricyclic imidazo[1,5]naphthyridine series. Integration of structure-based drug design and physical properties-based optimization yielded a potent and selective PI3K/mTOR dual kinase inhibitor PF-04979064. This manuscript discusses the lead optimization for the tricyclic series, which both improved the in vitro potency and addressed a number of ADMET issues including high metabolic clearance mediated by both P450 and aldehyde oxidase (AO), poor permeability, and poor solubility. An empirical scaling tool was developed to predict human clearance from in vitro human liver S9 assay data for tricyclic derivatives that were AO substrates. PMID:24900568

APPRIS: annotation of principal and alternative splice isoforms

PubMed Central

Rodriguez, Jose Manuel; Maietta, Paolo; Ezkurdia, Iakes; Pietrelli, Alessandro; Wesselink, Jan-Jaap; Lopez, Gonzalo; Valencia, Alfonso; Tress, Michael L.

2013-01-01

Here, we present APPRIS (http://appris.bioinfo.cnio.es), a database that houses annotations of human splice isoforms. APPRIS has been designed to provide value to manual annotations of the human genome by adding reliable protein structural and functional data and information from cross-species conservation. The visual representation of the annotations provided by APPRIS for each gene allows annotators and researchers alike to easily identify functional changes brought about by splicing events. In addition to collecting, integrating and analyzing reliable predictions of the effect of splicing events, APPRIS also selects a single reference sequence for each gene, here termed the principal isoform, based on the annotations of structure, function and conservation for each transcript. APPRIS identifies a principal isoform for 85% of the protein-coding genes in the GENCODE 7 release for ENSEMBL. Analysis of the APPRIS data shows that at least 70% of the alternative (non-principal) variants would lose important functional or structural information relative to the principal isoform. PMID:23161672

The role of temporal structure in human vision.

PubMed

Blake, Randolph; Lee, Sang-Hun

2005-03-01

Gestalt psychologists identified several stimulus properties thought to underlie visual grouping and figure/ground segmentation, and among those properties was common fate: the tendency to group together individual objects that move together in the same direction at the same speed. Recent years have witnessed an upsurge of interest in visual grouping based on other time-dependent sources of visual information, including synchronized changes in luminance, in motion direction, and in figure/ ground relations. These various sources of temporal grouping information can be subsumed under the rubric temporal structure. In this article, the authors review evidence bearing on the effectiveness of temporal structure in visual grouping. They start with an overview of evidence bearing on temporal acuity of human vision, covering studies dealing with temporal integration and temporal differentiation. They then summarize psychophysical studies dealing with figure/ground segregation based on temporal phase differences in deterministic and stochastic events. The authors conclude with a brief discussion of neurophysiological implications of these results.

Structural centrosome aberrations favor proliferation by abrogating microtubule-dependent tissue integrity of breast epithelial mammospheres

PubMed Central

Schnerch, D; Nigg, E A

2016-01-01

Structural centrosome aberrations are frequently observed in early stage carcinomas, but their role in malignant transformation is poorly understood. Here, we examined the impact of overexpression of Ninein-like protein (Nlp) on the architecture of polarized epithelia in three-dimensional mammospheres. When Nlp was overexpressed to levels resembling those seen in human tumors, it formed striking centrosome-related bodies (CRBs), which sequestered Ninein and affected the kinetics of microtubule (MT) nucleation and release. In turn, the profound reorganization of the MT cytoskeleton resulted in mislocalization of several adhesion and junction proteins as well as the tumor suppressor Scribble, resulting in the disruption of epithelial polarity, cell-cell interactions and mammosphere architecture. Remarkably, cells harboring Nlp-CRBs displayed an enhanced proliferative response to epidermal growth factor. These results demonstrate that structural centrosome aberrations cause not only the disruption of epithelial polarity but also favor overproliferation, two phenotypes typically associated with human carcinomas. PMID:26364601

Fracture modes in human teeth.

PubMed

Lee, J J-W; Kwon, J-Y; Chai, H; Lucas, P W; Thompson, V P; Lawn, B R

2009-03-01

The structural integrity of teeth under stress is vital to functional longevity. We tested the hypothesis that this integrity is limited by fracture of the enamel. Experiments were conducted on molar teeth, with a metal rod loaded onto individual cusps. Fracture during testing was tracked with a video camera. Two longitudinal modes of cracking were observed: median cracking from the contact zone, and margin cracking along side walls. Median cracks initiated from plastic damage at the contact site, at first growing slowly and then accelerating to the tooth margin. Margin cracks appeared to originate from the cemento-enamel junction, and traversed the tooth wall adjacent to the loaded cusp from the gingival to the occlusal surface. All cracks remained confined within the enamel shell up to about 550 N. At higher loads, additional crack modes--such as enamel chipping and delamination--began to manifest themselves, leading to more comprehensive failure of the tooth structure.

Formation of Micro- and Nanostructures on the Nanotitanium Surface by Chemical Etching and Deposition of Titania Films by Atomic Layer Deposition (ALD)

PubMed Central

Nazarov, Denis V.; Zemtsova, Elena G.; Valiev, Ruslan Z.; Smirnov, Vladimir M.

2015-01-01

In this study, an integrated approach was used for the preparation of a nanotitanium-based bioactive material. The integrated approach included three methods: severe plastic deformation (SPD), chemical etching and atomic layer deposition (ALD). For the first time, it was experimentally shown that the nature of the etching medium (acidic or basic Piranha solutions) and the etching time have a significant qualitative impact on the nanotitanium surface structure both at the nano- and microscale. The etched samples were coated with crystalline biocompatible TiO2 films with a thickness of 20 nm by Atomic Layer Deposition (ALD). Comparative study of the adhesive and spreading properties of human osteoblasts MG-63 has demonstrated that presence of nano- and microscale structures and crystalline titanium oxide on the surface of nanotitanium improve bioactive properties of the material. PMID:28793716

Assurance Technology Challenges of Advanced Space Systems

NASA Technical Reports Server (NTRS)

Chern, E. James

2004-01-01

The initiative to explore space and extend a human presence across our solar system to revisit the moon and Mars post enormous technological challenges to the nation's space agency and aerospace industry. Key areas of technology development needs to enable the endeavor include advanced materials, structures and mechanisms; micro/nano sensors and detectors; power generation, storage and management; advanced thermal and cryogenic control; guidance, navigation and control; command and data handling; advanced propulsion; advanced communication; on-board processing; advanced information technology systems; modular and reconfigurable systems; precision formation flying; solar sails; distributed observing systems; space robotics; and etc. Quality assurance concerns such as functional performance, structural integrity, radiation tolerance, health monitoring, diagnosis, maintenance, calibration, and initialization can affect the performance of systems and subsystems. It is thus imperative to employ innovative nondestructive evaluation methodologies to ensure quality and integrity of advanced space systems. Advancements in integrated multi-functional sensor systems, autonomous inspection approaches, distributed embedded sensors, roaming inspectors, and shape adaptive sensors are sought. Concepts in computational models for signal processing and data interpretation to establish quantitative characterization and event determination are also of interest. Prospective evaluation technologies include ultrasonics, laser ultrasonics, optics and fiber optics, shearography, video optics and metrology, thermography, electromagnetics, acoustic emission, x-ray, data management, biomimetics, and nano-scale sensing approaches for structural health monitoring.

A computer-aided movement analysis system.

PubMed

Fioretti, S; Leo, T; Pisani, E; Corradini, M L

1990-08-01

Interaction with biomechanical data concerning human movement analysis implies the adoption of various experimental equipments and the choice of suitable models, data processing, and graphical data restitution techniques. The integration of measurement setups with the associated experimental protocols and the relative software procedures constitutes a computer-aided movement analysis (CAMA) system. In the present paper such integration is mapped onto the causes that limit the clinical acceptance of movement analysis methods. The structure of the system is presented. A specific CAMA system devoted to posture analysis is described in order to show the attainable features. Scientific results obtained with the support of the described system are also reported.

Human rights barriers for displaced persons in southern Sudan.

PubMed

Pavlish, Carol; Ho, Anita

2009-01-01

This community-based research explores community perspectives on human rights barriers that women encounter in a postconflict setting of southern Sudan. An ethnographic design was used to guide data collection in five focus groups with community members and during in-depth interviews with nine key informants. A constant comparison method of data analysis was used. Atlas.ti data management software facilitated the inductive coding and sorting of data. Participants identified three formal and one set of informal community structures for human rights. Human rights barriers included shifting legal frameworks, doubt about human rights, weak government infrastructure, and poverty. The evolving government infrastructure cannot currently provide adequate human rights protection, especially for women. The nature of living in poverty without development opportunities includes human rights abuses. Good governance, protection, and human development opportunities were emphasized as priority human rights concerns. Human rights framework could serve as a powerful integrator of health and development work with community-based organizations. Results help nurses understand the intersection between health and human rights as well as approaches to advancing rights in a culturally attuned manner.

Multidisciplinary team of intensive therapy: humanization and fragmentation of the work process.

PubMed

Evangelista, Viviane Canhizares; Domingos, Thiago da Silva; Siqueira, Fernanda Paula Cerântola; Braga, Eliana Mara

2016-01-01

to understand the meaning of humanized care in intensive care units considering the experience of the multidisciplinary team. descriptive and exploratory qualitative research. For this purpose, we conducted semi-structured interviews with 24 professionals of the heath-care team, and, after transcription, we organized the qualitative data according to content analysis. from two main categories, we were able to understand that humanized care is characterized in the actions of health-care: effective communication, team work, empathy, singularity, and integrality; and mischaracterized in the management processes, specifically in the fragmentation of the work process and health-care, in the precarious work conditions, and in differing conceptual aspects of the political proposal of humanization. care activities in intensive therapy are guided by the humanization of care and corroborate the hospital management as a challenge to be overcome to boost advances in the operationalization of this Brazilian policy.

High volume hydraulic fracturing operations: potential impacts on surface water and human health.

PubMed

Mrdjen, Igor; Lee, Jiyoung

2016-08-01

High volume, hydraulic fracturing (HVHF) processes, used to extract natural gas and oil from underground shale deposits, pose many potential hazards to the environment and human health. HVHF can negatively affect the environment by contaminating soil, water, and air matrices with potential pollutants. Due to the relatively novel nature of the process, hazards to surface waters and human health are not well known. The purpose of this article is to link the impacts of HVHF operations on surface water integrity, with human health consequences. Surface water contamination risks include: increased structural failure rates of unconventional wells, issues with wastewater treatment, and accidental discharge of contaminated fluids. Human health risks associated with exposure to surface water contaminated with HVHF chemicals include increased cancer risk and turbidity of water, leading to increased pathogen survival time. Future research should focus on modeling contamination spread throughout the environment, and minimizing occupational exposure to harmful chemicals.

Morphological integration in the gorilla, chimpanzee, and human neck.

PubMed

Arlegi, Mikel; Gómez-Robles, Aida; Gómez-Olivencia, Asier

2018-06-01

Although integration studies are important to understand the evolution of organisms' traits across phylogenies, vertebral integration in primates is still largely unexplored. Here we describe and quantify patterns of morphological integration and modularity in the subaxial cervical vertebrae (C3-C7) in extant hominines incorporating the potential influence of size. Three-dimensional landmarks were digitized on 546 subaxial cervical vertebrae from 141 adult individuals of Gorilla gorilla, Pan troglodytes, and Homo sapiens. Integration and modularity, and the influence of size effects, were quantified using geometric morphometric approaches. All subaxial cervical vertebrae from the three species show a strong degree of integration. Gorillas show the highest degree of integration; conversely, humans have the lowest degree of integration. Analyses of allometric regression residuals show that size is an important factor promoting integration in gorillas, with lesser influence in chimpanzees and almost no effect in humans. Results point to a likely ancestral pattern of integration in non-human hominines, whereby the degree of integration decreases from cranial to caudal positions. Humans deviate from this pattern in the cranialmost (C3) and, to a lesser extent, in the caudalmost (C7) vertebrae, which are less integrated. These differences can be tentatively related to the emergence of bipedalism due to the presence of modern human-like C3 in australopiths, which still preserve a more chimpanzee-like C7. © 2018 Wiley Periodicals, Inc.

Morphological Integration of the Modern Human Mandible during Ontogeny

PubMed Central

Polanski, Joshua M.

2011-01-01

Craniofacial integration is prevalent in anatomical modernity research. Little investigation has been done on mandibular integration. Integration patterns were quantified in a longitudinal modern human sample of mandibles. This integration pattern is one of modularization between the alveolar and muscle attachment regions, but with age-specific differences. The ascending ramus and nonalveolar portions of the corpus remain integrated throughout ontogeny. The alveolar region is dynamic, becoming modularized according to the needs of the mandible at a particular developmental stage. Early in ontogeny, this modularity reflects the need for space for the developing dentition; later, modularity is more reflective of mastication. The overall pattern of modern human mandibular integration follows the integration pattern seen in other mammals, including chimpanzees. Given the differences in craniofacial integration patterns between humans and chimpanzees, but the similarities in mandibular integration, it is likely that the mandible has played the more passive role in hominin skull evolution. PMID:21716741

Effects of amyloid and small vessel disease on white matter network disruption.

PubMed

Kim, Hee Jin; Im, Kiho; Kwon, Hunki; Lee, Jong Min; Ye, Byoung Seok; Kim, Yeo Jin; Cho, Hanna; Choe, Yearn Seong; Lee, Kyung Han; Kim, Sung Tae; Kim, Jae Seung; Lee, Jae Hong; Na, Duk L; Seo, Sang Won

2015-01-01

There is growing evidence that the human brain is a large scale complex network. The structural network is reported to be disrupted in cognitively impaired patients. However, there have been few studies evaluating the effects of amyloid and small vessel disease (SVD) markers, the common causes of cognitive impairment, on structural networks. Thus, we evaluated the association between amyloid and SVD burdens and structural networks using diffusion tensor imaging (DTI). Furthermore, we determined if network parameters predict cognitive impairments. Graph theoretical analysis was applied to DTI data from 232 cognitively impaired patients with varying degrees of amyloid and SVD burdens. All patients underwent Pittsburgh compound-B (PiB) PET to detect amyloid burden, MRI to detect markers of SVD, including the volume of white matter hyperintensities and the number of lacunes, and detailed neuropsychological testing. The whole-brain network was assessed by network parameters of integration (shortest path length, global efficiency) and segregation (clustering coefficient, transitivity, modularity). PiB retention ratio was not associated with any white matter network parameters. Greater white matter hyperintensity volumes or lacunae numbers were significantly associated with decreased network integration (increased shortest path length, decreased global efficiency) and increased network segregation (increased clustering coefficient, increased transitivity, increased modularity). Decreased network integration or increased network segregation were associated with poor performances in attention, language, visuospatial, memory, and frontal-executive functions. Our results suggest that SVD alters white matter network integration and segregation, which further predicts cognitive dysfunction.

Linking structural biology with genome research: Beamlines for the Berlin ``Protein Structure Factory'' initiative

NASA Astrophysics Data System (ADS)

Illing, Gerd; Saenger, Wolfram; Heinemann, Udo

2000-06-01

The Protein Structure Factory will be established to characterize proteins encoded by human genes or cDNAs, which will be selected by criteria of potential structural novelty or medical or biotechnological usefulness. It represents an integrative approach to structure analysis combining bioinformatics techniques, automated gene expression and purification of gene products, generation of a biophysical fingerprint of the proteins and the determination of their three-dimensional structures either by NMR spectroscopy or by X-ray diffraction. The use of synchrotron radiation will be crucial to the Protein Structure Factory: high brilliance and tunable wavelengths are prerequisites for fast data collection, the use of small crystals and multiwavelength anomalous diffraction (MAD) phasing. With the opening of BESSY II, direct access to a third-generation XUV storage ring source with excellent conditions is available nearby. An insertion device with two MAD beamlines and one constant energy station will be set up until 2001.

Prospects of a mathematical theory of human behavior in complex man-machine systems tasks. [time sharing computer analogy of automobile driving

NASA Technical Reports Server (NTRS)

Johannsen, G.; Rouse, W. B.

1978-01-01

A hierarchy of human activities is derived by analyzing automobile driving in general terms. A structural description leads to a block diagram and a time-sharing computer analogy. The range of applicability of existing mathematical models is considered with respect to the hierarchy of human activities in actual complex tasks. Other mathematical tools so far not often applied to man machine systems are also discussed. The mathematical descriptions at least briefly considered here include utility, estimation, control, queueing, and fuzzy set theory as well as artificial intelligence techniques. Some thoughts are given as to how these methods might be integrated and how further work might be pursued.

Anatomical Network Comparison of Human Upper and Lower, Newborn and Adult, and Normal and Abnormal Limbs, with Notes on Development, Pathology and Limb Serial Homology vs. Homoplasy

PubMed Central

Diogo, Rui; Esteve-Altava, Borja; Smith, Christopher; Boughner, Julia C.; Rasskin-Gutman, Diego

2015-01-01

How do the various anatomical parts (modules) of the animal body evolve into very different integrated forms (integration) yet still function properly without decreasing the individual’s survival? This long-standing question remains unanswered for multiple reasons, including lack of consensus about conceptual definitions and approaches, as well as a reasonable bias toward the study of hard tissues over soft tissues. A major difficulty concerns the non-trivial technical hurdles of addressing this problem, specifically the lack of quantitative tools to quantify and compare variation across multiple disparate anatomical parts and tissue types. In this paper we apply for the first time a powerful new quantitative tool, Anatomical Network Analysis (AnNA), to examine and compare in detail the musculoskeletal modularity and integration of normal and abnormal human upper and lower limbs. In contrast to other morphological methods, the strength of AnNA is that it allows efficient and direct empirical comparisons among body parts with even vastly different architectures (e.g. upper and lower limbs) and diverse or complex tissue composition (e.g. bones, cartilages and muscles), by quantifying the spatial organization of these parts—their topological patterns relative to each other—using tools borrowed from network theory. Our results reveal similarities between the skeletal networks of the normal newborn/adult upper limb vs. lower limb, with exception to the shoulder vs. pelvis. However, when muscles are included, the overall musculoskeletal network organization of the upper limb is strikingly different from that of the lower limb, particularly that of the more proximal structures of each limb. Importantly, the obtained data provide further evidence to be added to the vast amount of paleontological, gross anatomical, developmental, molecular and embryological data recently obtained that contradicts the long-standing dogma that the upper and lower limbs are serial homologues. In addition, the AnNA of the limbs of a trisomy 18 human fetus strongly supports Pere Alberch's ill-named "logic of monsters" hypothesis, and contradicts the commonly accepted idea that birth defects often lead to lower integration (i.e. more parcellation) of anatomical structures. PMID:26452269

Anatomical Network Comparison of Human Upper and Lower, Newborn and Adult, and Normal and Abnormal Limbs, with Notes on Development, Pathology and Limb Serial Homology vs. Homoplasy.

PubMed

Diogo, Rui; Esteve-Altava, Borja; Smith, Christopher; Boughner, Julia C; Rasskin-Gutman, Diego

2015-01-01

How do the various anatomical parts (modules) of the animal body evolve into very different integrated forms (integration) yet still function properly without decreasing the individual's survival? This long-standing question remains unanswered for multiple reasons, including lack of consensus about conceptual definitions and approaches, as well as a reasonable bias toward the study of hard tissues over soft tissues. A major difficulty concerns the non-trivial technical hurdles of addressing this problem, specifically the lack of quantitative tools to quantify and compare variation across multiple disparate anatomical parts and tissue types. In this paper we apply for the first time a powerful new quantitative tool, Anatomical Network Analysis (AnNA), to examine and compare in detail the musculoskeletal modularity and integration of normal and abnormal human upper and lower limbs. In contrast to other morphological methods, the strength of AnNA is that it allows efficient and direct empirical comparisons among body parts with even vastly different architectures (e.g. upper and lower limbs) and diverse or complex tissue composition (e.g. bones, cartilages and muscles), by quantifying the spatial organization of these parts-their topological patterns relative to each other-using tools borrowed from network theory. Our results reveal similarities between the skeletal networks of the normal newborn/adult upper limb vs. lower limb, with exception to the shoulder vs. pelvis. However, when muscles are included, the overall musculoskeletal network organization of the upper limb is strikingly different from that of the lower limb, particularly that of the more proximal structures of each limb. Importantly, the obtained data provide further evidence to be added to the vast amount of paleontological, gross anatomical, developmental, molecular and embryological data recently obtained that contradicts the long-standing dogma that the upper and lower limbs are serial homologues. In addition, the AnNA of the limbs of a trisomy 18 human fetus strongly supports Pere Alberch's ill-named "logic of monsters" hypothesis, and contradicts the commonly accepted idea that birth defects often lead to lower integration (i.e. more parcellation) of anatomical structures.

Bringing the Pieces Together – Placing Core Facilities at the Core of Universities and Institutions: Lessons from Mergers, Acquisitions and Consolidations

PubMed Central

Mundoma, Claudius

2013-01-01

As organizations expand and grow, the core facilities have become more dispersed disconnected. This is happening at a time when collaborations within the organization is a driver to increased productivity. Stakeholders are looking at the best way to bring the pieces together. It is inevitable that core facilities at universities and research institutes have to be integrated in order to streamline services and facilitate ease of collaboration. The path to integration often goes through consolidation, merging and shedding of redundant services. Managing this process requires a delicate coordination of two critical factors: the human (lab managers) factor and the physical assets factor. Traditionally more emphasis has been placed on reorganizing the physical assets without paying enough attention to the professionals who have been managing the assets for years, if not decades. The presentation focuses on how a systems approach can be used to effect a smooth core facility integration process. Managing the human element requires strengthening existing channels of communication and if necessary, creating new ones throughout the organization to break cultural and structural barriers. Managing the physical assets requires a complete asset audit and this requires direct input from the administration as well as the facility managers. Organizations can harness the power of IT to create asset visibility. Successfully managing the physical assets and the human assets increases productivity and efficiency within the organization.

Using a fuzzy comprehensive evaluation method to determine product usability: A proposed theoretical framework.

PubMed

Zhou, Ronggang; Chan, Alan H S

2017-01-01

In order to compare existing usability data to ideal goals or to that for other products, usability practitioners have tried to develop a framework for deriving an integrated metric. However, most current usability methods with this aim rely heavily on human judgment about the various attributes of a product, but often fail to take into account of the inherent uncertainties in these judgments in the evaluation process. This paper presents a universal method of usability evaluation by combining the analytic hierarchical process (AHP) and the fuzzy evaluation method. By integrating multiple sources of uncertain information during product usability evaluation, the method proposed here aims to derive an index that is structured hierarchically in terms of the three usability components of effectiveness, efficiency, and user satisfaction of a product. With consideration of the theoretical basis of fuzzy evaluation, a two-layer comprehensive evaluation index was first constructed. After the membership functions were determined by an expert panel, the evaluation appraisals were computed by using the fuzzy comprehensive evaluation technique model to characterize fuzzy human judgments. Then with the use of AHP, the weights of usability components were elicited from these experts. Compared to traditional usability evaluation methods, the major strength of the fuzzy method is that it captures the fuzziness and uncertainties in human judgments and provides an integrated framework that combines the vague judgments from multiple stages of a product evaluation process.

An Integrated and Interdisciplinary Model for Predicting the Risk of Injury and Death in Future Earthquakes

PubMed Central

Shapira, Stav; Novack, Lena; Bar-Dayan, Yaron; Aharonson-Daniel, Limor

2016-01-01

Background A comprehensive technique for earthquake-related casualty estimation remains an unmet challenge. This study aims to integrate risk factors related to characteristics of the exposed population and to the built environment in order to improve communities’ preparedness and response capabilities and to mitigate future consequences. Methods An innovative model was formulated based on a widely used loss estimation model (HAZUS) by integrating four human-related risk factors (age, gender, physical disability and socioeconomic status) that were identified through a systematic review and meta-analysis of epidemiological data. The common effect measures of these factors were calculated and entered to the existing model’s algorithm using logistic regression equations. Sensitivity analysis was performed by conducting a casualty estimation simulation in a high-vulnerability risk area in Israel. Results the integrated model outcomes indicated an increase in the total number of casualties compared with the prediction of the traditional model; with regard to specific injury levels an increase was demonstrated in the number of expected fatalities and in the severely and moderately injured, and a decrease was noted in the lightly injured. Urban areas with higher populations at risk rates were found more vulnerable in this regard. Conclusion The proposed model offers a novel approach that allows quantification of the combined impact of human-related and structural factors on the results of earthquake casualty modelling. Investing efforts in reducing human vulnerability and increasing resilience prior to an occurrence of an earthquake could lead to a possible decrease in the expected number of casualties. PMID:26959647

The medical humanities and the perils of curricular integration.

PubMed

Chiavaroli, Neville; Ellwood, Constance

2012-12-01

The advent of integration as a feature of contemporary medical curricula can be seen as an advantage for the medical humanities in that it provides a clear implementation strategy for the inclusion of medical humanities content and/or perspectives, while also making its relevance to medical education more apparent. This paper discusses an example of integration of humanities content into a graduate medical course, raises questions about the desirability of an exclusively integrated approach, and argues for the value of retaining a discrete and coherent disciplinary presence for the medical humanities in medical curricula.

[Human body meridian spatial decision support system for clinical treatment and teaching of acupuncture and moxibustion].

PubMed

Wu, Dehua

2016-01-01

The spatial position and distribution of human body meridian are expressed limitedly in the decision support system (DSS) of acupuncture and moxibustion at present, which leads to the failure to give the effective quantitative analysis on the spatial range and the difficulty for the decision-maker to provide a realistic spatial decision environment. Focusing on the limit spatial expression in DSS of acupuncture and moxibustion, it was proposed that on the basis of the geographic information system, in association of DSS technology, the design idea was developed on the human body meridian spatial DSS. With the 4-layer service-oriented architecture adopted, the data center integrated development platform was taken as the system development environment. The hierarchical organization was done for the spatial data of human body meridian via the directory tree. The structured query language (SQL) server was used to achieve the unified management of spatial data and attribute data. The technologies of architecture, configuration and plug-in development model were integrated to achieve the data inquiry, buffer analysis and program evaluation of the human body meridian spatial DSS. The research results show that the human body meridian spatial DSS could reflect realistically the spatial characteristics of the spatial position and distribution of human body meridian and met the constantly changeable demand of users. It has the powerful spatial analysis function and assists with the scientific decision in clinical treatment and teaching of acupuncture and moxibustion. It is the new attempt to the informatization research of human body meridian.

QSAR modeling of cumulative environmental end-points for the prioritization of hazardous chemicals.

PubMed

Gramatica, Paola; Papa, Ester; Sangion, Alessandro

2018-01-24

The hazard of chemicals in the environment is inherently related to the molecular structure and derives simultaneously from various chemical properties/activities/reactivities. Models based on Quantitative Structure Activity Relationships (QSARs) are useful to screen, rank and prioritize chemicals that may have an adverse impact on humans and the environment. This paper reviews a selection of QSAR models (based on theoretical molecular descriptors) developed for cumulative multivariate endpoints, which were derived by mathematical combination of multiple effects and properties. The cumulative end-points provide an integrated holistic point of view to address environmentally relevant properties of chemicals.

The optical antenna system design research on earth integrative network laser link in the future

NASA Astrophysics Data System (ADS)

Liu, Xianzhu; Fu, Qiang; He, Jingyi

2014-11-01

Earth integrated information network can be real-time acquisition, transmission and processing the spatial information with the carrier based on space platforms, such as geostationary satellites or in low-orbit satellites, stratospheric balloons or unmanned and manned aircraft, etc. It is an essential infrastructure for China to constructed earth integrated information network. Earth integrated information network can not only support the highly dynamic and the real-time transmission of broadband down to earth observation, but the reliable transmission of the ultra remote and the large delay up to the deep space exploration, as well as provide services for the significant application of the ocean voyage, emergency rescue, navigation and positioning, air transportation, aerospace measurement or control and other fields.Thus the earth integrated information network can expand the human science, culture and productive activities to the space, ocean and even deep space, so it is the global research focus. The network of the laser communication link is an important component and the mean of communication in the earth integrated information network. Optimize the structure and design the system of the optical antenna is considered one of the difficulty key technologies for the space laser communication link network. Therefore, this paper presents an optical antenna system that it can be used in space laser communication link network.The antenna system was consisted by the plurality mirrors stitched with the rotational paraboloid as a substrate. The optical system structure of the multi-mirror stitched was simulated and emulated by the light tools software. Cassegrain form to be used in a relay optical system. The structural parameters of the relay optical system was optimized and designed by the optical design software of zemax. The results of the optimal design and simulation or emulation indicated that the antenna system had a good optical performance and a certain reference value in engineering. It can provide effective technical support to realize interconnection of earth integrated laser link information network in the future.

Human Rights Education Can Be Integrated throughout the School Day

ERIC Educational Resources Information Center

Childhood Education, 2005

2005-01-01

Research indicates that few state departments of education have actually mandated human rights education in their schools. Clearly, individual teachers will need to take responsibility for the integration of peace education and human rights education. By integrating human rights education and peace education into the daily fabric of the school…

The Importance of Primary Martian Surface and Airfall Dust Sample Return for Toxicological Hazard Evaluations for Human Exploration

NASA Technical Reports Server (NTRS)

Harrington, A. D.; McCubbin, F. M.

2018-01-01

Manned missions to the Moon highlight a major hazard for future human exploration of the Moon and beyond: surface dust. Not only did the dust cause mechanical and structural integrity issues with the suits, the dust 'storm' generated upon reentrance into the crew cabin caused "lunar hay fever" and "almost blindness" . It was further reported that the allergic response to the dust worsened with each exposure. Due to the prevalence of these high exposures, the Human Research Roadmap developed by NASA identifies the Risk of Adverse Health and Performance Effects of Celestial Dust Exposure as an area of concern. Extended human exploration will further increase the probability of inadvertent and repeated exposures to celestial dusts. Going forward, hazard assessments of celestial dusts will be determined through sample return efforts prior to astronaut deployment.

An integrative architecture for a sensor-supported trust management system.

PubMed

Trček, Denis

2012-01-01

Trust plays a key role not only in e-worlds and emerging pervasive computing environments, but also already for millennia in human societies. Trust management solutions that have being around now for some fifteen years were primarily developed for the above mentioned cyber environments and they are typically focused on artificial agents, sensors, etc. However, this paper presents extensions of a new methodology together with architecture for trust management support that is focused on humans and human-like agents. With this methodology and architecture sensors play a crucial role. The architecture presents an already deployable tool for multi and interdisciplinary research in various areas where humans are involved. It provides new ways to obtain an insight into dynamics and evolution of such structures, not only in pervasive computing environments, but also in other important areas like management and decision making support.

Structure-Based Sequence Alignment of the Transmembrane Domains of All Human GPCRs: Phylogenetic, Structural and Functional Implications

PubMed Central

Cvicek, Vaclav; Goddard, William A.; Abrol, Ravinder

2016-01-01

The understanding of G-protein coupled receptors (GPCRs) is undergoing a revolution due to increased information about their signaling and the experimental determination of structures for more than 25 receptors. The availability of at least one receptor structure for each of the GPCR classes, well separated in sequence space, enables an integrated superfamily-wide analysis to identify signatures involving the role of conserved residues, conserved contacts, and downstream signaling in the context of receptor structures. In this study, we align the transmembrane (TM) domains of all experimental GPCR structures to maximize the conserved inter-helical contacts. The resulting superfamily-wide GpcR Sequence-Structure (GRoSS) alignment of the TM domains for all human GPCR sequences is sufficient to generate a phylogenetic tree that correctly distinguishes all different GPCR classes, suggesting that the class-level differences in the GPCR superfamily are encoded at least partly in the TM domains. The inter-helical contacts conserved across all GPCR classes describe the evolutionarily conserved GPCR structural fold. The corresponding structural alignment of the inactive and active conformations, available for a few GPCRs, identifies activation hot-spot residues in the TM domains that get rewired upon activation. Many GPCR mutations, known to alter receptor signaling and cause disease, are located at these conserved contact and activation hot-spot residue positions. The GRoSS alignment places the chemosensory receptor subfamilies for bitter taste (TAS2R) and pheromones (Vomeronasal, VN1R) in the rhodopsin family, known to contain the chemosensory olfactory receptor subfamily. The GRoSS alignment also enables the quantification of the structural variability in the TM regions of experimental structures, useful for homology modeling and structure prediction of receptors. Furthermore, this alignment identifies structurally and functionally important residues in all human GPCRs. These residues can be used to make testable hypotheses about the structural basis of receptor function and about the molecular basis of disease-associated single nucleotide polymorphisms. PMID:27028541

Biorecognition Element Design and Characterization for Human Performance Biomarkers Sensing

DTIC Science & Technology

2015-07-16

immobilize aptamers and peptides on the AuNP surface. The parameters optimized in this work included reaction times, ligand ratio (PEG-OH vs PEG- COOH...instructions for performing peptides and aptamers surface immobilization were provided to collaborators in order to create nanoprobes that were integrated...with sequences made of less than 20 amino acids) and DNA aptamers (via on-off structural switching properties) are appealing BREs for new sensors

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

Nose, Y.

Methods were developed for generating an integrated, statistical model of the anatomical structures within the human thorax relevant to radioisotope powered artificial heart implantation. These methods involve measurement and analysis of anatomy in four areas: chest wall, pericardium, vascular connections, and great vessels. A model for the prediction of thorax outline from radiograms was finalized. These models were combined with 100 radiograms to arrive at a size distribution representing the adult male and female populations. (CH)

Control of Cellular Structural Networks Through Unstructured Protein Domains

DTIC Science & Technology

2016-07-01

stem cells (hPSCs), including embryonic and induced pluripotent stem cells . We had a third paper accepted to Scientific Reports in which we showed...2012 Stem Cells Young Investigator Award. We then had a followup paper accepted to Integrative Biology extending these ideas to human pluripotent ...morphology, mechanics, and neurogenesis in neural stem cells ; (3) To develop and use multiscale computational 1. REPORT DATE (DD-MM-YYYY) 4. TITLE AND

Porous biodegradable lumbar interbody fusion cage design and fabrication using integrated global-local topology optimization with laser sintering.

PubMed

Kang, Heesuk; Hollister, Scott J; La Marca, Frank; Park, Paul; Lin, Chia-Ying

2013-10-01

Biodegradable cages have received increasing attention for their use in spinal procedures involving interbody fusion to resolve complications associated with the use of nondegradable cages, such as stress shielding and long-term foreign body reaction. However, the relatively weak initial material strength compared to permanent materials and subsequent reduction due to degradation may be problematic. To design a porous biodegradable interbody fusion cage for a preclinical large animal study that can withstand physiological loads while possessing sufficient interconnected porosity for bony bridging and fusion, we developed a multiscale topology optimization technique. Topology optimization at the macroscopic scale provides optimal structural layout that ensures mechanical strength, while optimally designed microstructures, which replace the macroscopic material layout, ensure maximum permeability. Optimally designed cages were fabricated using solid, freeform fabrication of poly(ε-caprolactone) mixed with hydroxyapatite. Compression tests revealed that the yield strength of optimized fusion cages was two times that of typical human lumbar spine loads. Computational analysis further confirmed the mechanical integrity within the human lumbar spine, although the pore structure locally underwent higher stress than yield stress. This optimization technique may be utilized to balance the complex requirements of load-bearing, stress shielding, and interconnected porosity when using biodegradable materials for fusion cages.

Cardiomyocytes from human pluripotent stem cells: From laboratory curiosity to industrial biomedical platform.

PubMed

Denning, Chris; Borgdorff, Viola; Crutchley, James; Firth, Karl S A; George, Vinoj; Kalra, Spandan; Kondrashov, Alexander; Hoang, Minh Duc; Mosqueira, Diogo; Patel, Asha; Prodanov, Ljupcho; Rajamohan, Divya; Skarnes, William C; Smith, James G W; Young, Lorraine E

2016-07-01

Cardiomyocytes from human pluripotent stem cells (hPSCs-CMs) could revolutionise biomedicine. Global burden of heart failure will soon reach USD $90bn, while unexpected cardiotoxicity underlies 28% of drug withdrawals. Advances in hPSC isolation, Cas9/CRISPR genome engineering and hPSC-CM differentiation have improved patient care, progressed drugs to clinic and opened a new era in safety pharmacology. Nevertheless, predictive cardiotoxicity using hPSC-CMs contrasts from failure to almost total success. Since this likely relates to cell immaturity, efforts are underway to use biochemical and biophysical cues to improve many of the ~30 structural and functional properties of hPSC-CMs towards those seen in adult CMs. Other developments needed for widespread hPSC-CM utility include subtype specification, cost reduction of large scale differentiation and elimination of the phenotyping bottleneck. This review will consider these factors in the evolution of hPSC-CM technologies, as well as their integration into high content industrial platforms that assess structure, mitochondrial function, electrophysiology, calcium transients and contractility. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Differential sensitivity of Chironomus and human hemoglobin to gamma radiation

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

Gaikwad, Pallavi S.; Molecular Biology Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085; Panicker, Lata

Chironomus ramosus is known to tolerate high doses of gamma radiation exposure. Larvae of this insect possess more than 95% of hemoglobin (Hb) in its circulatory hemolymph. This is a comparative study to see effect of gamma radiation on Hb of Chironomus and humans, two evolutionarily diverse organisms one having extracellular and the other intracellular Hb respectively. Stability and integrity of Chironomus and human Hb to gamma radiation was compared using biophysical techniques like Dynamic Light Scattering (DLS), UV-visible spectroscopy, fluorescence spectrometry and CD spectroscopy after exposure of whole larvae, larval hemolymph, human peripheral blood, purified Chironomus and human Hb.more » Sequence- and structure-based bioinformatics methods were used to analyze the sequence and structural similarities or differences in the heme pockets of respective Hbs. Resistivity of Chironomus Hb to gamma radiation is remarkably higher than human Hb. Human Hb exhibited loss of heme iron at a relatively low dose of gamma radiation exposure as compared to Chironomus Hb. Unlike human Hb, the heme pocket of Chironomus Hb is rich in aromatic amino acids. Higher hydophobicity around heme pocket confers stability of Chironomus Hb compared to human Hb. Previously reported gamma radiation tolerance of Chironomus can be largely attributed to its evolutionarily ancient form of extracellular Hb as evident from the present study. -- Highlights: •Comparison of radiation tolerant Chironomus Hb and radiation sensitive Human Hb. •Amino acid composition of midge and human heme confer differential hydrophobicity. •Heme pocket of evolutionarily ancient midge Hb provide gamma radiation resistivity.« less

Integrating ambient noise with GIS for a new perspective on volcano imaging and monitoring: The case study of Mt. Etna

NASA Astrophysics Data System (ADS)

Guardo, R.; De Siena, L.

2017-11-01

The timely estimation of short- and long-term volcanic hazard relies on the availability of detailed 3D geophysical images of volcanic structures. High-resolution seismic models of the absorbing uppermost conduit systems and highly-heterogeneous shallowest volcanic layers, while particularly challenging to obtain, provide important data to locate feasible eruptive centres and forecast flank collapses and lava ascending paths. Here, we model the volcanic structures of Mt. Etna (Sicily, Italy) and its outskirts using the Horizontal to Vertical Spectral Ratio method, generally applied to industrial and engineering settings. The integration of this technique with Web-based Geographic Information System improves precision during the acquisition phase. It also integrates geological and geophysical visualization of 3D surface and subsurface structures in a queryable environment representing their exact three-dimensional geographic position, enhancing interpretation. The results show high-resolution 3D images of the shallowest volcanic and feeding systems, which complement (1) deeper seismic tomography imaging and (2) the results of recent remote sensing imaging. The study recovers a vertical structure that divides the pre-existing volcanic complexes of Ellittico and Cuvigghiuni. This could be interpreted as a transitional phase between the two systems. A comparison with recent remote sensing and geological results, however, shows that anomalies are generally related to volcano-tectonic structures active during the last 17 years. We infer that seismic noise measurements from miniaturized instruments, when combined with remote sensing techniques, represent an important resource to monitor volcanoes in unrest, reducing the risk of loss of human lives and instrumentation.

Structural variants in genes associated with human Williams-Beuren syndrome underlie stereotypical hypersociability in domestic dogs.

PubMed

vonHoldt, Bridgett M; Shuldiner, Emily; Koch, Ilana Janowitz; Kartzinel, Rebecca Y; Hogan, Andrew; Brubaker, Lauren; Wanser, Shelby; Stahler, Daniel; Wynne, Clive D L; Ostrander, Elaine A; Sinsheimer, Janet S; Udell, Monique A R

2017-07-01

Although considerable progress has been made in understanding the genetic basis of morphologic traits (for example, body size and coat color) in dogs and wolves, the genetic basis of their behavioral divergence is poorly understood. An integrative approach using both behavioral and genetic data is required to understand the molecular underpinnings of the various behavioral characteristics associated with domestication. We analyze a 5-Mb genomic region on chromosome 6 previously found to be under positive selection in domestic dog breeds. Deletion of this region in humans is linked to Williams-Beuren syndrome (WBS), a multisystem congenital disorder characterized by hypersocial behavior. We associate quantitative data on behavioral phenotypes symptomatic of WBS in humans with structural changes in the WBS locus in dogs. We find that hypersociability, a central feature of WBS, is also a core element of domestication that distinguishes dogs from wolves. We provide evidence that structural variants in GTF2I and GTF2IRD1 , genes previously implicated in the behavioral phenotype of patients with WBS and contained within the WBS locus, contribute to extreme sociability in dogs. This finding suggests that there are commonalities in the genetic architecture of WBS and canine tameness and that directional selection may have targeted a unique set of linked behavioral genes of large phenotypic effect, allowing for rapid behavioral divergence of dogs and wolves, facilitating coexistence with humans.

Development and characterization of a eukaryotic expression system for human type II procollagen.

PubMed

Wieczorek, Andrew; Rezaei, Naghmeh; Chan, Clara K; Xu, Chuan; Panwar, Preety; Brömme, Dieter; Merschrod S, Erika F; Forde, Nancy R

2015-12-15

Triple helical collagens are the most abundant structural protein in vertebrates and are widely used as biomaterials for a variety of applications including drug delivery and cellular and tissue engineering. In these applications, the mechanics of this hierarchically structured protein play a key role, as does its chemical composition. To facilitate investigation into how gene mutations of collagen lead to disease as well as the rational development of tunable mechanical and chemical properties of this full-length protein, production of recombinant expressed protein is required. Here, we present a human type II procollagen expression system that produces full-length procollagen utilizing a previously characterized human fibrosarcoma cell line for production. The system exploits a non-covalently linked fluorescence readout for gene expression to facilitate screening of cell lines. Biochemical and biophysical characterization of the secreted, purified protein are used to demonstrate the proper formation and function of the protein. Assays to demonstrate fidelity include proteolytic digestion, mass spectrometric sequence and posttranslational composition analysis, circular dichroism spectroscopy, single-molecule stretching with optical tweezers, atomic-force microscopy imaging of fibril assembly, and transmission electron microscopy imaging of self-assembled fibrils. Using a mammalian expression system, we produced full-length recombinant human type II procollagen. The integrity of the collagen preparation was verified by various structural and degradation assays. This system provides a platform from which to explore new directions in collagen manipulation.

Structural and Functional Analysis of an mRNP Complex That Mediates the High Stability of Human β-Globin mRNA

PubMed Central

Yu, Jia; Russell, J. Eric

2001-01-01

Human globins are encoded by mRNAs exhibiting high stabilities in transcriptionally silenced erythrocyte progenitors. Unlike α-globin mRNA, whose stability is enhanced by assembly of a specific messenger RNP (mRNP) α complex on its 3′ untranslated region (UTR), neither the structure(s) nor the mechanism(s) that effects the high-level stability of human β-globin mRNA has been identified. The present work describes an mRNP complex assembling on the 3′ UTR of the β-globin mRNA that exhibits many of the properties of the stability-enhancing α complex. The β-globin mRNP complex is shown to contain one or more factors homologous to αCP, a 39-kDa RNA-binding protein that is integral to α-complex assembly. Sequence analysis implicates a specific 14-nucleotide pyrimidine-rich track within its 3′ UTR as the site of β-globin mRNP assembly. The importance of this track to mRNA stability is subsequently verified in vivo using mice expressing human β-globin transgenes that contain informative mutations in this region. In combination, the in vitro and in vivo analyses indicate that the high stabilities of the α- and β-globin mRNAs are maintained through related mRNP complexes that may share a common regulatory pathway. PMID:11486027

A survey of molecular details in the human pineal gland in the light of phylogeny, structure, function and chronobiological diseases.

PubMed

Stehle, Jörg H; Saade, Anastasia; Rawashdeh, Oliver; Ackermann, Katrin; Jilg, Antje; Sebestény, Tamás; Maronde, Erik

2011-08-01

The human pineal gland is a neuroendocrine transducer that forms an integral part of the brain. Through the nocturnally elevated synthesis and release of the neurohormone melatonin, the pineal gland encodes and disseminates information on circadian time, thus coupling the outside world to the biochemical and physiological internal demands of the body. Approaches to better understand molecular details behind the rhythmic signalling in the human pineal gland are limited but implicitly warranted, as human chronobiological dysfunctions are often associated with alterations in melatonin synthesis. Current knowledge on melatonin synthesis in the human pineal gland is based on minimally invasive analyses, and by the comparison of signalling events between different vertebrate species, with emphasis put on data acquired in sheep and other primates. Together with investigations using autoptic pineal tissue, a remnant silhouette of premortem dynamics within the hormone's biosynthesis pathway can be constructed. The detected biochemical scenario behind the generation of dynamics in melatonin synthesis positions the human pineal gland surprisingly isolated. In this neuroendocrine brain structure, protein-protein interactions and nucleo-cytoplasmic protein shuttling indicate furthermore a novel twist in the molecular dynamics in the cells of this neuroendocrine brain structure. These findings have to be seen in the light that an impaired melatonin synthesis is observed in elderly and/or demented patients, in individuals affected by Alzheimer's disease, Smith-Magenis syndrome, autism spectrum disorder and sleep phase disorders. Already, recent advances in understanding signalling dynamics in the human pineal gland have significantly helped to counteract chronobiological dysfunctions through a proper restoration of the nocturnal melatonin surge. © 2011 John Wiley & Sons A/S.

Structural characterization and mutational assessment of podocin - a novel drug target to nephrotic syndrome - an in silico approach.

PubMed

Tabassum, Asra; Rajeshwari, Tadigadapa; Soni, Nidhi; Raju, D S B; Yadav, Mukesh; Nayarisseri, Anuraj; Jahan, Parveen

2014-03-01

Non-synonymous single nucleotide changes (nSNC) are coding variants that introduce amino acid changes in their corresponding proteins. They can affect protein function; they are believed to have the largest impact on human health compared with SNCs in other regions of the genome. Such a sequence alteration directly affects their structural stability through conformational changes. Presence of these conformational changes near catalytic site or active site may alter protein function and as a consequence receptor-ligand complex interactions. The present investigation includes assessment of human podocin mutations (G92C, P118L, R138Q, and D160G) on its structure. Podocin is an important glomerular integral membrane protein thought to play a key role in steroid resistant nephrotic syndrome. Podocin has a hairpin like structure with 383 amino acids, it is an integral protein homologous to stomatin, and acts as a molecular link in a stretch-sensitive system. We modeled 3D structure of podocin by means of Modeller and validated via PROCHECK to get a Ramachandran plot (88.5% in most favored region), main chain, side chain, bad contacts, gauche and pooled standard deviation. Further, a protein engineering tool Triton was used to induce mutagenesis corresponding to four variants G92C, P118L, R138Q and D160G in the wild type. Perusal of energies of wild and mutated type of podocin structures confirmed that mutated structures were thermodynamically more stable than wild type and therefore biological events favored synthesis of mutated forms of podocin than wild type. As a conclusive part, two mutations G92C (-8179.272 kJ/mol) and P118L (-8136.685 kJ/mol) are more stable and probable to take place in podocin structure over wild podocin structure (-8105.622 kJ/mol). Though there is lesser difference in mutated and wild type (approximately, 74 and 35 kJ/mol), it may play a crucial role in deciding why mutations are favored and occur at the genetic level.

Integrated Testing Approaches for the NASA Ares I Crew Launch Vehicle

NASA Technical Reports Server (NTRS)

Taylor, James L.; Cockrell, Charles E.; Tuma, Margaret L.; Askins, Bruce R.; Bland, Jeff D.; Davis, Stephan R.; Patterson, Alan F.; Taylor, Terry L.; Robinson, Kimberly L.

2008-01-01

The Ares I crew launch vehicle is being developed by the U.S. National Aeronautics and Space Administration (NASA) to provide crew and cargo access to the International Space Station (ISS) and, together with the Ares V cargo launch vehicle, serves as a critical component of NASA's future human exploration of the Moon. During the preliminary design phase, NASA defined and began implementing plans for integrated ground and flight testing necessary to achieve the first human launch of Ares I. The individual Ares I flight hardware elements - including the first stage five segment booster (FSB), upper stage, and J-2X upper stage engine - will undergo extensive development, qualification, and certification testing prior to flight. Key integrated system tests include the upper stage Main Propulsion Test Article (MPTA), acceptance tests of the integrated upper stage and upper stage engine assembly, a full-scale integrated vehicle ground vibration test (IVGVT), aerodynamic testing to characterize vehicle performance, and integrated testing of the avionics and software components. The Ares I-X development flight test will provide flight data to validate engineering models for aerodynamic performance, stage separation, structural dynamic performance, and control system functionality. The Ares I-Y flight test will validate ascent performance of the first stage, stage separation functionality, validate the ability of the upper stage to manage cryogenic propellants to achieve upper stage engine start conditions, and a high-altitude demonstration of the launch abort system (LAS) following stage separation. The Orion 1 flight test will be conducted as a full, un-crewed, operational flight test through the entire ascent flight profile prior to the first crewed launch.

Integrated System Test Approaches for the NASA Ares I Crew Launch Vehicle

NASA Technical Reports Server (NTRS)

Cockrell, Charles E., Jr.; Askins, Bruce R.; Bland, Jeffrey; Davis, Stephan; Holladay, Jon B.; Taylor, James L.; Taylor, Terry L.; Robinson, Kimberly F.; Roberts, Ryan E.; Tuma, Margaret

2007-01-01

The Ares I Crew Launch Vehicle (CLV) is being developed by the U.S. National Aeronautics and Space Administration (NASA) to provide crew access to the International Space Station (ISS) and, together with the Ares V Cargo Launch Vehicle (CaLV), serves as one component of a future launch capability for human exploration of the Moon. During the system requirements definition process and early design cycles, NASA defined and began implementing plans for integrated ground and flight testing necessary to achieve the first human launch of Ares I. The individual Ares I flight hardware elements: the first stage five segment booster (FSB), upper stage, and J-2X upper stage engine, will undergo extensive development, qualification, and certification testing prior to flight. Key integrated system tests include the Main Propulsion Test Article (MPTA), acceptance tests of the integrated upper stage and upper stage engine assembly, a full-scale integrated vehicle dynamic test (IVDT), aerodynamic testing to characterize vehicle performance, and integrated testing of the avionics and software components. The Ares I-X development flight test will provide flight data to validate engineering models for aerodynamic performance, stage separation, structural dynamic performance, and control system functionality. The Ares I-Y flight test will validate ascent performance of the first stage, stage separation functionality, and a highaltitude actuation of the launch abort system (LAS) following separation. The Orion-1 flight test will be conducted as a full, un-crewed, operational flight test through the entire ascent flight profile prior to the first crewed launch.

Transforming educational accountability in medical ethics and humanities education toward professionalism.

PubMed

Doukas, David J; Kirch, Darrell G; Brigham, Timothy P; Barzansky, Barbara M; Wear, Stephen; Carrese, Joseph A; Fins, Joseph J; Lederer, Susan E

2015-06-01

Effectively developing professionalism requires a programmatic view on how medical ethics and humanities should be incorporated into an educational continuum that begins in premedical studies, stretches across medical school and residency, and is sustained throughout one's practice. The Project to Rebalance and Integrate Medical Education National Conference on Medical Ethics and Humanities in Medical Education (May 2012) invited representatives from the three major medical education and accreditation organizations to engage with an expert panel of nationally known medical educators in ethics, history, literature, and the visual arts. This article, based on the views of these representatives and their respondents, offers a future-tense account of how professionalism can be incorporated into medical education.The themes that are emphasized herein include the need to respond to four issues. The first theme highlights how ethics and humanities can provide a response to the dissonance that occurs in current health care delivery. The second theme focuses on how to facilitate preprofessional readiness for applicants through reform of the medical school admission process. The third theme emphasizes the importance of integrating ethics and humanities into the medical school administrative structure. The fourth theme underscores how outcomes-based assessment should reflect developmental milestones for professional attributes and conduct. The participants emphasized that ethics and humanities-based knowledge, skills, and conduct that promote professionalism should be taught with accountability, flexibility, and the premise that all these traits are essential to the formation of a modern professional physician.

Integration of ecological-biological thresholds in conservation decision making.

PubMed

Mavrommati, Georgia; Bithas, Kostas; Borsuk, Mark E; Howarth, Richard B

2016-12-01

In the Anthropocene, coupled human and natural systems dominate and only a few natural systems remain relatively unaffected by human influence. On the one hand, conservation criteria based on areas of minimal human impact are not relevant to much of the biosphere. On the other hand, conservation criteria based on economic factors are problematic with respect to their ability to arrive at operational indicators of well-being that can be applied in practice over multiple generations. Coupled human and natural systems are subject to economic development which, under current management structures, tends to affect natural systems and cross planetary boundaries. Hence, designing and applying conservation criteria applicable in real-world systems where human and natural systems need to interact and sustainably coexist is essential. By recognizing the criticality of satisfying basic needs as well as the great uncertainty over the needs and preferences of future generations, we sought to incorporate conservation criteria based on minimal human impact into economic evaluation. These criteria require the conservation of environmental conditions such that the opportunity for intergenerational welfare optimization is maintained. Toward this end, we propose the integration of ecological-biological thresholds into decision making and use as an example the planetary-boundaries approach. Both conservation scientists and economists must be involved in defining operational ecological-biological thresholds that can be incorporated into economic thinking and reflect the objectives of conservation, sustainability, and intergenerational welfare optimization. © 2016 Society for Conservation Biology.

Dynamical Integration of Language and Behavior in a Recurrent Neural Network for Human-Robot Interaction.

PubMed

Yamada, Tatsuro; Murata, Shingo; Arie, Hiroaki; Ogata, Tetsuya

2016-01-01

To work cooperatively with humans by using language, robots must not only acquire a mapping between language and their behavior but also autonomously utilize the mapping in appropriate contexts of interactive tasks online. To this end, we propose a novel learning method linking language to robot behavior by means of a recurrent neural network. In this method, the network learns from correct examples of the imposed task that are given not as explicitly separated sets of language and behavior but as sequential data constructed from the actual temporal flow of the task. By doing this, the internal dynamics of the network models both language-behavior relationships and the temporal patterns of interaction. Here, "internal dynamics" refers to the time development of the system defined on the fixed-dimensional space of the internal states of the context layer. Thus, in the execution phase, by constantly representing where in the interaction context it is as its current state, the network autonomously switches between recognition and generation phases without any explicit signs and utilizes the acquired mapping in appropriate contexts. To evaluate our method, we conducted an experiment in which a robot generates appropriate behavior responding to a human's linguistic instruction. After learning, the network actually formed the attractor structure representing both language-behavior relationships and the task's temporal pattern in its internal dynamics. In the dynamics, language-behavior mapping was achieved by the branching structure. Repetition of human's instruction and robot's behavioral response was represented as the cyclic structure, and besides, waiting to a subsequent instruction was represented as the fixed-point attractor. Thanks to this structure, the robot was able to interact online with a human concerning the given task by autonomously switching phases.

Making psycholinguistics musical: self-paced reading time evidence for shared processing of linguistic and musical syntax.

PubMed

Slevc, L Robert; Rosenberg, Jason C; Patel, Aniruddh D

2009-04-01

Linguistic processing, especially syntactic processing, is often considered a hallmark of human cognition; thus, the domain specificity or domain generality of syntactic processing has attracted considerable debate. The present experiments address this issue by simultaneously manipulating syntactic processing demands in language and music. Participants performed self-paced reading of garden path sentences, in which structurally unexpected words cause temporary syntactic processing difficulty. A musical chord accompanied each sentence segment, with the resulting sequence forming a coherent chord progression. When structurally unexpected words were paired with harmonically unexpected chords, participants showed substantially enhanced garden path effects. No such interaction was observed when the critical words violated semantic expectancy or when the critical chords violated timbral expectancy. These results support a prediction of the shared syntactic integration resource hypothesis (Patel, 2003), which suggests that music and language draw on a common pool of limited processing resources for integrating incoming elements into syntactic structures. Notations of the stimuli from this study may be downloaded from pbr.psychonomic-journals.org/content/supplemental.

Target-Pathogen: a structural bioinformatic approach to prioritize drug targets in pathogens

PubMed Central

Sosa, Ezequiel J; Burguener, Germán; Lanzarotti, Esteban; Radusky, Leandro; Pardo, Agustín M; Marti, Marcelo

2018-01-01

Abstract Available genomic data for pathogens has created new opportunities for drug discovery and development to fight them, including new resistant and multiresistant strains. In particular structural data must be integrated with both, gene information and experimental results. In this sense, there is a lack of an online resource that allows genome wide-based data consolidation from diverse sources together with thorough bioinformatic analysis that allows easy filtering and scoring for fast target selection for drug discovery. Here, we present Target-Pathogen database (http://target.sbg.qb.fcen.uba.ar/patho), designed and developed as an online resource that allows the integration and weighting of protein information such as: function, metabolic role, off-targeting, structural properties including druggability, essentiality and omic experiments, to facilitate the identification and prioritization of candidate drug targets in pathogens. We include in the database 10 genomes of some of the most relevant microorganisms for human health (Mycobacterium tuberculosis, Mycobacterium leprae, Klebsiella pneumoniae, Plasmodium vivax, Toxoplasma gondii, Leishmania major, Wolbachia bancrofti, Trypanosoma brucei, Shigella dysenteriae and Schistosoma Smanosoni) and show its applicability. New genomes can be uploaded upon request. PMID:29106651

Reward Dependent Invigoration Relates to Theta Oscillations and Is Predicted by Dopaminergic Midbrain Integrity in Healthy Elderly.

PubMed

Steiger, Tineke K; Bunzeck, Nico

2017-01-01

Motivation can have invigorating effects on behavior via dopaminergic neuromodulation. While this relationship has mainly been established in theoretical models and studies in younger subjects, the impact of structural declines of the dopaminergic system during healthy aging remains unclear. To investigate this issue, we used electroencephalography (EEG) in healthy young and elderly humans in a reward-learning paradigm. Specifically, scene images were initially encoded by combining them with cues predicting monetary reward (high vs. low reward). Subsequently, recognition memory for the scenes was tested. As a main finding, we can show that response times (RTs) during encoding were faster for high reward predicting images in the young but not elderly participants. This pattern was resembled in power changes in the theta-band (4-7 Hz). Importantly, analyses of structural MRI data revealed that individual reward-related differences in the elderlies' response time could be predicted by the structural integrity of the dopaminergic substantia nigra (SN; as measured by magnetization transfer (MT)). These findings suggest a close relationship between reward-based invigoration, theta oscillations and age-dependent changes of the dopaminergic system.

Exploration Medical Capability System Engineering Introduction and Vision

NASA Technical Reports Server (NTRS)

Mindock, J.; Reilly, J.

2017-01-01

Human exploration missions to beyond low Earth orbit destinations such as Mars will require more autonomous capability compared to current low Earth orbit operations. For the medical system, lack of consumable resupply, evacuation opportunities, and real-time ground support are key drivers toward greater autonomy. Recognition of the limited mission and vehicle resources available to carry out exploration missions motivates the Exploration Medical Capability (ExMC) Element's approach to enabling the necessary autonomy. The Element's work must integrate with the overall exploration mission and vehicle design efforts to successfully provide exploration medical capabilities. ExMC is applying systems engineering principles and practices to accomplish its integrative goals. This talk will briefly introduce the discipline of systems engineering and key points in its application to exploration medical capability development. It will elucidate technical medical system needs to be met by the systems engineering work, and the structured and integrative science and engineering approach to satisfying those needs, including the development of shared mental and qualitative models within and external to the human health and performance community. These efforts are underway to ensure relevancy to exploration system maturation and to establish medical system development that is collaborative with vehicle and mission design and engineering efforts.

Distribution of glycolipid and unsaturated fatty acids in human hair.

PubMed

Takahashi, Toshie; Yoshida, Satoshi

2014-09-01

It has been recognized that human hair lipids play crucial roles in the integrity of cells and matrices, while the details of distribution and structure of the minor lipids are hardly known. Here we investigated the lipids at the hair surface, at the interface between cuticle and cortex and in the interior of hair (cortex, medulla and melanin granules). Hair lipids and fatty acids and their metabolites were detected and characterized by using infrared spectroscopy and several mass spectrometry techniques (FTIR, ToF-SIMS, GCMS, and ESI-MS). As a result, it was found that unsaturated fatty acids were present more in the cortex of hair than at the hair surface. At the interface between cuticle and cortex, it is suggested that steryl glycoside-like lipids containing N-acetylglucosamine were present, and contributing to the adhesion between the cuticle and cortex of hair. Oxidative metabolites derived from integral fatty acids such as linoleic and alpha-linolenic acids were found in the hair bulb and melanin granules. Especially the oxidative metabolites of alpha-linolenic acid were integrated into the lipids non-covalently and tightly bound to melanin granules (namely, melanin lipids) and suggested as being involved in the biosynthetic processes of melanosome.

Dispositional empathy and the hierarchical structure of personality.

PubMed

Mooradian, Todd A; Davis, Mark; Matzler, Kurt

2011-01-01

Personality psychology has recognized a fundamental 5-factor structure that has integrated and organized theory and research. Nevertheless, personality-like differences beyond that structure have been identified. In heretofore unrelated research, dispositional empathy has been an essential construct in understanding human development, behavior, and interpersonal relationships. Addressing a gap in the literature, we map multidimensional dispositional empathy into 2 versions of the 5-factor space. Empathic concern is closely related to agreeableness, and personal distress is closely related to neuroticism. Perspective taking has complex, interstitial relationships with the 5 factors. In contrast, fantasy is not well explained by the 5 factors. We discuss the implications of these findings for understanding dispositional empathy and for understanding the 5-factor structure, its correlates in emotional processes and experiences, and its limits.

A Systems Biology Approach for Identifying Hepatotoxicant Groups Based on Similarity in Mechanisms of Action and Chemical Structure.

PubMed

Hebels, Dennie G A J; Rasche, Axel; Herwig, Ralf; van Westen, Gerard J P; Jennen, Danyel G J; Kleinjans, Jos C S

2016-01-01

When evaluating compound similarity, addressing multiple sources of information to reach conclusions about common pharmaceutical and/or toxicological mechanisms of action is a crucial strategy. In this chapter, we describe a systems biology approach that incorporates analyses of hepatotoxicant data for 33 compounds from three different sources: a chemical structure similarity analysis based on the 3D Tanimoto coefficient, a chemical structure-based protein target prediction analysis, and a cross-study/cross-platform meta-analysis of in vitro and in vivo human and rat transcriptomics data derived from public resources (i.e., the diXa data warehouse). Hierarchical clustering of the outcome scores of the separate analyses did not result in a satisfactory grouping of compounds considering their known toxic mechanism as described in literature. However, a combined analysis of multiple data types may hypothetically compensate for missing or unreliable information in any of the single data types. We therefore performed an integrated clustering analysis of all three data sets using the R-based tool iClusterPlus. This indeed improved the grouping results. The compound clusters that were formed by means of iClusterPlus represent groups that show similar gene expression while simultaneously integrating a similarity in structure and protein targets, which corresponds much better with the known mechanism of action of these toxicants. Using an integrative systems biology approach may thus overcome the limitations of the separate analyses when grouping liver toxicants sharing a similar mechanism of toxicity.

Patient-tailored multimodal neuroimaging, visualization and quantification of human intra-cerebral hemorrhage

NASA Astrophysics Data System (ADS)

Goh, Sheng-Yang M.; Irimia, Andrei; Vespa, Paul M.; Van Horn, John D.

2016-03-01

In traumatic brain injury (TBI) and intracerebral hemorrhage (ICH), the heterogeneity of lesion sizes and types necessitates a variety of imaging modalities to acquire a comprehensive perspective on injury extent. Although it is advantageous to combine imaging modalities and to leverage their complementary benefits, there are difficulties in integrating information across imaging types. Thus, it is important that efforts be dedicated to the creation and sustained refinement of resources for multimodal data integration. Here, we propose a novel approach to the integration of neuroimaging data acquired from human patients with TBI/ICH using various modalities; we also demonstrate the integrated use of multimodal magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) data for TBI analysis based on both visual observations and quantitative metrics. 3D models of healthy-appearing tissues and TBIrelated pathology are generated, both of which are derived from multimodal imaging data. MRI volumes acquired using FLAIR, SWI, and T2 GRE are used to segment pathology. Healthy tissues are segmented using user-supervised tools, and results are visualized using a novel graphical approach called a `connectogram', where brain connectivity information is depicted within a circle of radially aligned elements. Inter-region connectivity and its strength are represented by links of variable opacities drawn between regions, where opacity reflects the percentage longitudinal change in brain connectivity density. Our method for integrating, analyzing and visualizing structural brain changes due to TBI and ICH can promote knowledge extraction and enhance the understanding of mechanisms underlying recovery.

Patterns of morphological variation in enamel–dentin junction and outer enamel surface of human molars

PubMed Central

Morita, Wataru; Yano, Wataru; Nagaoka, Tomohito; Abe, Mikiko; Ohshima, Hayato; Nakatsukasa, Masato

2014-01-01

Tooth crown patterning is governed by the growth and folding of the inner enamel epithelium (IEE) and the following enamel deposition forms outer enamel surface (OES). We hypothesized that overall dental crown shape and covariation structure are determined by processes that configurate shape at the enamel–dentine junction (EDJ), the developmental vestige of IEE. This this hypothesis was tested by comparing patterns of morphological variation between EDJ and OES in human permanent maxillary first molar (UM1) and deciduous second molar (um2). Using geometric morphometric methods, we described morphological variation and covariation between EDJ and OES, and evaluated the strength of two components of phenotypic variability, canalization and morphological integration, in addition to the relevant evolutionary flexibility, i.e. the ability to respond to selective pressure. The strength of covariation between EDJ and OES was greater in um2 than in UM1, and the way that multiple traits covary between EDJ and OES was different between these teeth. The variability analyses showed that EDJ had less shape variation and a higher level of morphological integration than OES, which indicated that canalization and morphological integration acted as developmental constraints. These tendencies were greater in UM1 than in um2. On the other hand, EDJ and OES had a comparable level of evolvability in these teeth. Amelogenesis could play a significant role in tooth shape and covariation structure, and its influence was not constant among teeth, which may be responsible for the differences in the rate and/or period of enamel formation. PMID:24689536

ESA Human rating Requirements:Status

NASA Astrophysics Data System (ADS)

Trujillo, M.; Sgobba, T.

2012-01-01

The European Space Agency (ESA) human rating safety requirements are based on heritage requirements of the International Space Station as well as the knowledge and experience derived from European participation on international partnerships. This expertise in conjunction with recommendations derived from past accidents (i.e.: Columbia) and lessons learned have led to the identification of m inimum core safety tech nical requirements for hum an rated space syst ems. These requirements apply to th e crewed space vehicle, integrated space system (i.e.: cre wed vehicle on its launcher) and its interfaces with control centres, la unch pad, etc. In 2009, a first draft was issued. Then, in the summer of 2010, ESA established a working group comprised of more than twenty experts (from disciplines including propulsion, pyrotechnics, structures, avionics, human factors and life support among others) across the Agency to review this draft. This paper provides an overview of ESA "Safety technical re quirements for human rated s pace systems" document, its scope a nd structure, as well as the planned steps for verification of these requirements in term s of achieving the identified safety objectives for crew safety in t erms of a quantitative risk evaluation.

Learning collaborative teamwork: an argument for incorporating the humanities.

PubMed

Hall, Pippa; Brajtman, Susan; Weaver, Lynda; Grassau, Pamela Anne; Varpio, Lara

2014-11-01

A holistic, collaborative interprofessional team approach, which includes patients and families as significant decision-making members, has been proposed to address the increasing burden being placed on the health-care system. This project hypothesized that learning activities related to the humanities during clinical placements could enhance interprofessional teamwork. Through an interprofessional team of faculty, clinical staff, students, and patient representatives, we developed and piloted the self-learning module, "interprofessional education for collaborative person-centred practice through the humanities". The module was designed to provide learners from different professions and educational levels with a clinical placement/residency experience that would enable them, through a lens of the humanities, to better understand interprofessional collaborative person-centred care without structured interprofessional placement activities. Learners reported the self-paced and self-directed module to be a satisfactory learning experience in all four areas of care at our institution, and certain attitudes and knowledge were significantly and positively affected. The module's evaluation resulted in a revised edition providing improved structure and instruction for students with no experience in self-directed learning. The module was recently adapted into an interactive bilingual (French and English) online e-learning module to facilitate its integration into the pre-licensure curriculum at colleges and universities.

Conceptualizing a Human Right to Prevention in Global HIV/AIDS Policy

PubMed Central

Meier, Benjamin Mason; Brugh, Kristen Nichole; Halima, Yasmin

2012-01-01

Given current constraints on universal treatment campaigns, recent advances in public health prevention initiatives have revitalized efforts to stem the tide of HIV transmission. Yet, despite a growing imperative for prevention—supported by the promise of behavioral, structural and biomedical approaches to lower the incidence of HIV—human rights frameworks remain limited in addressing collective prevention policy through global health governance. Assessing the evolution of rights-based approaches to global HIV/AIDS policy, this review finds that human rights have shifted from collective public health to individual treatment access. While the advent of the HIV/AIDS pandemic gave meaning to rights in framing global health policy, the application of rights in treatment access litigation came at the expense of public health prevention efforts. Where the human rights framework remains limited to individual rights enforced against a state duty bearer, such rights have faced constrained application in framing population-level policy to realize the public good of HIV prevention. Concluding that human rights frameworks must be developed to reflect the complementarity of individual treatment and collective prevention, this article conceptualizes collective rights to public health, structuring collective combination prevention to alleviate limitations on individual rights frameworks and frame rights-based global HIV/AIDS policy to assure research expansion, prevention access and health system integration. PMID:23226723

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

Brandriff, B.F.; Gordon, L.A.

Human reproductive wastage is known to be a common event. One major cause of embryonic and fetal losses is chromosomal aberrations, identified by karyotyping spontaneous abortion material and in vitro fertilized human embryos. Karyotyping of human gametes has made it possible to document types and frequencies of chromosomal aberrations directly in eggs and sperm themselves. Our studies with human sperm from normal, healthy men support the view that chromosome-specific aneuploidy does in fact occur, and that frequencies of structural chromosomal aberrations appear to be person specific and stable over time. The types of structural aberrations identified suggest that normal humanmore » spermiogenesis may be vulnerable to breakage events or precursor lesions leading to such breakage events. After entry into egg cytoplasm and preceding the formation of first-cleavage mitotic chromosomes, the male as well as the female genome replicate their DNA in a pattern qualitatively similar to that in somatic cells. However, at present it is not known what relationship exists between spontaneous chromosome breaks seen at first cleavage and DNA replication activities. Limited data on survivors of radiotherapy lend support to the view that long-term effects on sperm chromosomal integrity can be identified. Studies on sperm cytogenetics thus have the potential for identifying adverse environmental effects on human spermatogenesis as monitored by this well-defined endpoint. 32 refs., 2 figs., 1 tab.« less

Functional Connectivity Mapping in the Animal Model: Principles and Applications of Resting-State fMRI

PubMed Central

Gorges, Martin; Roselli, Francesco; Müller, Hans-Peter; Ludolph, Albert C.; Rasche, Volker; Kassubek, Jan

2017-01-01

“Resting-state” fMRI has substantially contributed to the understanding of human and non-human functional brain organization by the analysis of correlated patterns in spontaneous activity within dedicated brain systems. Spontaneous neural activity is indirectly measured from the blood oxygenation level-dependent signal as acquired by echo planar imaging, when subjects quietly “resting” in the scanner. Animal models including disease or knockout models allow a broad spectrum of experimental manipulations not applicable in humans. The non-invasive fMRI approach provides a promising tool for cross-species comparative investigations. This review focuses on the principles of “resting-state” functional connectivity analysis and its applications to living animals. The translational aspect from in vivo animal models toward clinical applications in humans is emphasized. We introduce the fMRI-based investigation of the non-human brain’s hemodynamics, the methodological issues in the data postprocessing, and the functional data interpretation from different abstraction levels. The longer term goal of integrating fMRI connectivity data with structural connectomes obtained with tracing and optical imaging approaches is presented and will allow the interrogation of fMRI data in terms of directional flow of information and may identify the structural underpinnings of observed functional connectivity patterns. PMID:28539914

Mesenchymal Stem Cell-Mediated Functional Tooth Regeneration in Swine

PubMed Central

Fang, Dianji; Yamaza, Takayoshi; Seo, Byoung-Moo; Zhang, Chunmei; Liu, He; Gronthos, Stan; Wang, Cun-Yu; Shi, Songtao; Wang, Songlin

2006-01-01

Mesenchymal stem cell-mediated tissue regeneration is a promising approach for regenerative medicine for a wide range of applications. Here we report a new population of stem cells isolated from the root apical papilla of human teeth (SCAP, stem cells from apical papilla). Using a minipig model, we transplanted both human SCAP and periodontal ligament stem cells (PDLSCs) to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. This work integrates a stem cell-mediated tissue regeneration strategy, engineered materials for structure, and current dental crown technologies. This hybridized tissue engineering approach led to recovery of tooth strength and appearance. PMID:17183711

Development of an Integrated Metabolomic Profiling Approach for Infectious Diseases Research

PubMed Central

Lv, Haitao; Hung, Chia S.; Chaturvedi, Kaveri S.; Hooton, Thomas M.; Henderson, Jeffrey P.

2013-01-01

Metabolomic profiling offers direct insights into the chemical environment and metabolic pathway activities at sites of human disease. During infection, this environment may receive important contributions from both host and pathogen. Here we apply untargeted metabolomics approach to identify compounds associated with an E. coli urinary tract infection population. Correlative and structural data from minimally processed samples were obtained using an optimized LC-MS platform capable of resolving ∼2300 molecular features. Principal components analysis readily distinguished patient groups and multiple supervised chemometric analyses resolved robust metabolomic shifts between groups. These analyses revealed nine compounds whose provisional structures suggest candidate infection-associated endocrine, catabolic, and lipid pathways. Several of these metabolite signatures may derive from microbial processing of host metabolites. Overall, this study highlights the ability of metabolomic approaches to directly identify compounds encountered by, and produced from, bacterial pathogens within human hosts. PMID:21922104

Structure-based design of novel quinoxaline-2-carboxylic acids and analogues as Pim-1 inhibitors.

PubMed

Oyallon, Bruno; Brachet-Botineau, Marie; Logé, Cédric; Bonnet, Pascal; Souab, Mohamed; Robert, Thomas; Ruchaud, Sandrine; Bach, Stéphane; Berthelot, Pascal; Gouilleux, Fabrice; Viaud-Massuard, Marie-Claude; Denevault-Sabourin, Caroline

2018-05-11

We identified a new series of quinoxaline-2-carboxylic acid derivatives, targeting the human proviral integration site for Moloney murine leukemia virus-1 (HsPim-1) kinase. Seventeen analogues were synthesized providing useful insight into structure-activity relationships studied. Docking studies realized in the ATP pocket of HsPim-1 are consistent with an unclassical binding mode of these inhibitors. The lead compound 1 was able to block HsPim-1 enzymatic activity at nanomolar concentrations (IC 50 of 74 nM), with a good selectivity profile against a panel of mammalian protein kinases. In vitro studies on the human chronic myeloid leukemia cell line KU812 showed an antitumor activity at micromolar concentrations. As a result, compound 1 represents a promising lead for the design of novel anticancer targeted therapies. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A high-quality human reference panel reveals the complexity and distribution of genomic structural variants.

PubMed

Hehir-Kwa, Jayne Y; Marschall, Tobias; Kloosterman, Wigard P; Francioli, Laurent C; Baaijens, Jasmijn A; Dijkstra, Louis J; Abdellaoui, Abdel; Koval, Vyacheslav; Thung, Djie Tjwan; Wardenaar, René; Renkens, Ivo; Coe, Bradley P; Deelen, Patrick; de Ligt, Joep; Lameijer, Eric-Wubbo; van Dijk, Freerk; Hormozdiari, Fereydoun; Uitterlinden, André G; van Duijn, Cornelia M; Eichler, Evan E; de Bakker, Paul I W; Swertz, Morris A; Wijmenga, Cisca; van Ommen, Gert-Jan B; Slagboom, P Eline; Boomsma, Dorret I; Schönhuth, Alexander; Ye, Kai; Guryev, Victor

2016-10-06

Structural variation (SV) represents a major source of differences between individual human genomes and has been linked to disease phenotypes. However, the majority of studies provide neither a global view of the full spectrum of these variants nor integrate them into reference panels of genetic variation. Here, we analyse whole genome sequencing data of 769 individuals from 250 Dutch families, and provide a haplotype-resolved map of 1.9 million genome variants across 9 different variant classes, including novel forms of complex indels, and retrotransposition-mediated insertions of mobile elements and processed RNAs. A large proportion are previously under reported variants sized between 21 and 100 bp. We detect 4 megabases of novel sequence, encoding 11 new transcripts. Finally, we show 191 known, trait-associated SNPs to be in strong linkage disequilibrium with SVs and demonstrate that our panel facilitates accurate imputation of SVs in unrelated individuals.

Thin Films and Inflatable Applications in Exploration Habitat Structures

NASA Technical Reports Server (NTRS)

Frazier, Donald O.; Paley, Mark S.; Strong, Janet D.

2005-01-01

NASA's vision to return to the Moon and then extend human exploration to Mars will benefit from human habitat technology development using new and creative applications of polymer materials and concepts. Thin Film and Inflatable (TFVI) materials are particularly interesting for exploration applications due to their light weight and low volume. Whereas TF/I materials can be launched and carried from Earth to multiple and distant exploration sites without the constraints of upmass limitations, eventually, with recycling and reclamation efforts, these materials may be developed using in-situ resources. These materials can be useful for fabricating, patching and repairing vehicles, replacement parts and even habitat structures, as well as for developing stand-alone habitat structure technologies and for nested and integrated applications. TF/Is can also be ideal environmental containment vessels within lunar or Martian regolith walls or as liners inside caves or raw regolith exterior structures for the provisions of atmosphere containment, debris protection and cleanliness. Further, TFOs can be specialized and matured for various and diverse applications. The desired range of applications will require materials specification for such properties as transparency, elasticity, thermal conductivity, mechanical strength, heat capacity, chemical resistance, and permeability. This paper will discuss Marshall Space Flight Center's plans to analyze and prioritize TF/I materials properties and classifications and to develop applications for these highly desirable materials in human habitat construction projects on the Moon and Mars.

Human Systems Integration in the Federal Government

NASA Technical Reports Server (NTRS)

Jones, Patricia M.; Graves, Gaye L.; Allard, Terry; Blackhurst, Jack; Fitts, David J.; Peters, Sean; Piccione, Dino; Shattuck, Lawrence G.

2010-01-01

Human Systems Integration principles and methods can be used to help integrate people, technology, and organizations in an effective and efficient manner. Over the past decade, a wide range of tools, techniques, and technologies have been developed by federal agencies to achieve significant cost and performance benefits. In this discussion, we will explore trends in military human systems integration and learn about the critical role being played by human performance and effectiveness research. We will also examine case studies on the planning and design of future human space flight vehicles, the national air space system and the first nuclear reactors to be built in the United States in over 30 years. And with an eye toward sustaining the discipline s principles and methods, we ll take a look at educating and training the next generation of human systems integration practitioners.

Early life stress-induced alterations in rat brain structures measured with high resolution MRI.

PubMed

Sarabdjitsingh, R Angela; Loi, Manila; Joëls, Marian; Dijkhuizen, Rick M; van der Toorn, Annette

2017-01-01

Adverse experiences early in life impair cognitive function both in rodents and humans. In humans this increases the vulnerability to develop mental illnesses while in the rodent brain early life stress (ELS) abnormalities are associated with changes in synaptic plasticity, excitability and microstructure. Detailed information on the effects of ELS on rodent brain structural integrity at large and connectivity within the brain is currently lacking; this information is highly relevant for understanding the mechanism by which early life stress predisposes to mental illnesses. Here, we exposed rats to 24 hours of maternal deprivation (MD) at postnatal day 3, a paradigm known to increase corticosterone levels and thereby activate glucocorticoid receptors in the brain. Using structural magnetic resonance imaging we examined: i) volumetric changes and white/grey matter properties of the whole cerebrum and of specific brain areas; and ii) whether potential alterations could be normalized by blocking glucocorticoid receptors with mifepristone during the critical developmental window of early adolescence, i.e. between postnatal days 26 and 28. The results show that MD caused a volumetric reduction of the prefrontal cortex, particularly the ventromedial part, and the orbitofrontal cortex. Within the whole cerebrum, white (relative to grey) matter volume was decreased and region-specifically in prefrontal cortex and dorsomedial striatum following MD. A trend was found for the hippocampus. Grey matter fractions were not affected. Treatment with mifepristone did not normalize these changes. This study indicates that early life stress in rodents has long lasting consequences for the volume and structural integrity of the brain. However, changes were relatively modest and-unlike behavior- not mitigated by blockade of glucocorticoid receptors during a critical developmental period.

Integrated In Silico-In Vitro Identification and Characterization of the SH3-Mediated Interaction between Human PTTG and its Cognate Partners in Medulloblastoma.

PubMed

Liu, Jiangang; Wang, Dapeng; Li, Yanyan; Yao, Hui; Zhang, Nan; Zhang, Xuewen; Zhong, Fangping; Huang, Yulun

2018-06-01

The human pituitary tumor-transforming gene is an oncogenic protein which serves as a central hub in the cellular signaling network of medulloblastoma. The protein contains two vicinal PxxP motifs at its C terminus that are potential binding sites of peptide-recognition SH3 domains. Here, a synthetic protocol that integrated in silico analysis and in vitro assay was described to identify the SH3-binding partners of pituitary tumor-transforming gene in the gene expression profile of medulloblastoma. In the procedure, a variety of structurally diverse, non-redundant SH3 domains with high gene expression in medulloblastoma were compiled, and their three-dimensional structures were either manually retrieved from the protein data bank database or computationally modeled through bioinformatics technique. The binding capability of these domains towards the two PxxP-containing peptides m1p: 161 LGPPSPVK 168 and m2p: 168 KMPSPPWE 175 of pituitary tumor-transforming gene were ranked by structure-based scoring and fluorescence-based assay. Consequently, a number of SH3 domains, including MAP3K and PI3K, were found to have moderate or high affinity for m1p and/or m2p. Interestingly, the two overlapping peptides exhibits a distinct binding profile to these identified domain partners, suggesting that the binding selectivity of m1p and m2p is optimized across the medulloblastoma expression spectrum by competing for domain candidates. In addition, two redesigned versions of m1p peptide ware obtained via a structure-based rational mutation approach, which exhibited an increased affinity for the domain as compared to native peptide.

Characterization of Equine Infectious Anemia Virus Integration in the Horse Genome.

PubMed

Liu, Qiang; Wang, Xue-Feng; Ma, Jian; He, Xi-Jun; Wang, Xiao-Jun; Zhou, Jian-Hua

2015-06-19

Human immunodeficiency virus (HIV)-1 has a unique integration profile in the human genome relative to murine and avian retroviruses. Equine infectious anemia virus (EIAV) is another well-studied lentivirus that can also be used as a promising retro-transfection vector, but its integration into its native host has not been characterized. In this study, we mapped 477 integration sites of the EIAV strain EIAVFDDV13 in fetal equine dermal (FED) cells during in vitro infection. Published integration sites of EIAV and HIV-1 in the human genome were also analyzed as references. Our results demonstrated that EIAVFDDV13 tended to integrate into genes and AT-rich regions, and it avoided integrating into transcription start sites (TSS), which is consistent with EIAV and HIV-1 integration in the human genome. Notably, the integration of EIAVFDDV13 favored long interspersed elements (LINEs) and DNA transposons in the horse genome, whereas the integration of HIV-1 favored short interspersed elements (SINEs) in the human genome. The chromosomal environment near LINEs or DNA transposons potentially influences viral transcription and may be related to the unique EIAV latency states in equids. The data on EIAV integration in its natural host will facilitate studies on lentiviral infection and lentivirus-based therapeutic vectors.

Characterization of Equine Infectious Anemia Virus Integration in the Horse Genome

PubMed Central

Liu, Qiang; Wang, Xue-Feng; Ma, Jian; He, Xi-Jun; Wang, Xiao-Jun; Zhou, Jian-Hua

2015-01-01

Human immunodeficiency virus (HIV)-1 has a unique integration profile in the human genome relative to murine and avian retroviruses. Equine infectious anemia virus (EIAV) is another well-studied lentivirus that can also be used as a promising retro-transfection vector, but its integration into its native host has not been characterized. In this study, we mapped 477 integration sites of the EIAV strain EIAVFDDV13 in fetal equine dermal (FED) cells during in vitro infection. Published integration sites of EIAV and HIV-1 in the human genome were also analyzed as references. Our results demonstrated that EIAVFDDV13 tended to integrate into genes and AT-rich regions, and it avoided integrating into transcription start sites (TSS), which is consistent with EIAV and HIV-1 integration in the human genome. Notably, the integration of EIAVFDDV13 favored long interspersed elements (LINEs) and DNA transposons in the horse genome, whereas the integration of HIV-1 favored short interspersed elements (SINEs) in the human genome. The chromosomal environment near LINEs or DNA transposons potentially influences viral transcription and may be related to the unique EIAV latency states in equids. The data on EIAV integration in its natural host will facilitate studies on lentiviral infection and lentivirus-based therapeutic vectors. PMID:26102582

An Overview of the Human Systems Integration Division

NASA Technical Reports Server (NTRS)

Gore, Brian F.

2015-01-01

This presentation will provide an overview of the Human Systems Integration Division, and will highlight some of the human performance modeling efforts undertaken in previously presented MIDAS human performance modeling efforts.

Unmanned tactical autonomous control and collaboration (utacc) human machine integration measures of performance and measures of effectiveness

DTIC Science & Technology

2017-06-01

AUTONOMOUS CONTROL AND COLLABORATION (UTACC) HUMAN-MACHINE INTEGRATION MEASURES OF PERFORMANCE AND MEASURES OF EFFECTIVENESS by Thomas A...TACTICAL AUTONOMOUS CONTROL AND COLLABORATION (UTACC) HUMAN-MACHINE INTEGRATION MEASURES OF PERFORMANCE AND MEASURES OF EFFECTIVENESS 5. FUNDING...Tactical Autonomous Control and Collaboration (UTACC) program seeks to integrate Marines and autonomous machines to address the challenges encountered in

Ontological modelling of knowledge management for human-machine integrated design of ultra-precision grinding machine

NASA Astrophysics Data System (ADS)

Hong, Haibo; Yin, Yuehong; Chen, Xing

2016-11-01

Despite the rapid development of computer science and information technology, an efficient human-machine integrated enterprise information system for designing complex mechatronic products is still not fully accomplished, partly because of the inharmonious communication among collaborators. Therefore, one challenge in human-machine integration is how to establish an appropriate knowledge management (KM) model to support integration and sharing of heterogeneous product knowledge. Aiming at the diversity of design knowledge, this article proposes an ontology-based model to reach an unambiguous and normative representation of knowledge. First, an ontology-based human-machine integrated design framework is described, then corresponding ontologies and sub-ontologies are established according to different purposes and scopes. Second, a similarity calculation-based ontology integration method composed of ontology mapping and ontology merging is introduced. The ontology searching-based knowledge sharing method is then developed. Finally, a case of human-machine integrated design of a large ultra-precision grinding machine is used to demonstrate the effectiveness of the method.

VCP-dependent muscle degeneration is linked to defects in a dynamic tubular lysosomal network in vivo

PubMed Central

Johnson, Alyssa E; Shu, Huidy; Hauswirth, Anna G; Tong, Amy; Davis, Graeme W

2015-01-01

Lysosomes are classically viewed as vesicular structures to which cargos are delivered for degradation. Here, we identify a network of dynamic, tubular lysosomes that extends throughout Drosophila muscle, in vivo. Live imaging reveals that autophagosomes merge with tubular lysosomes and that lysosomal membranes undergo extension, retraction, fusion and fission. The dynamics and integrity of this tubular lysosomal network requires VCP, an AAA-ATPase that, when mutated, causes degenerative diseases of muscle, bone and neurons. We show that human VCP rescues the defects caused by loss of Drosophila VCP and overexpression of disease relevant VCP transgenes dismantles tubular lysosomes, linking tubular lysosome dysfunction to human VCP-related diseases. Finally, disruption of tubular lysosomes correlates with impaired autophagosome-lysosome fusion, increased cytoplasmic poly-ubiquitin aggregates, lipofuscin material, damaged mitochondria and impaired muscle function. We propose that VCP sustains sarcoplasmic proteostasis, in part, by controlling the integrity of a dynamic tubular lysosomal network. DOI: http://dx.doi.org/10.7554/eLife.07366.001 PMID:26167652

Organ-on-a-Chip Systems: Microengineering to Biomimic Living Systems.

PubMed

Zheng, Fuyin; Fu, Fanfan; Cheng, Yao; Wang, Chunyan; Zhao, Yuanjin; Gu, Zhongze

2016-05-01

"Organ-on-a-chip" systems integrate microengineering, microfluidic technologies, and biomimetic principles to create key aspects of living organs faithfully, including critical microarchitecture, spatiotemporal cell-cell interactions, and extracellular microenvironments. This creative platform and its multiorgan integration recapitulating organ-level structures and functions can bring unprecedented benefits to a diversity of applications, such as developing human in vitro models for healthy or diseased organs, enabling the investigation of fundamental mechanisms in disease etiology and organogenesis, benefiting drug development in toxicity screening and target discovery, and potentially serving as replacements for animal testing. Recent advances in novel designs and examples for developing organ-on-a-chip platforms are reviewed. The potential for using this emerging technology in understanding human physiology including mechanical, chemical, and electrical signals with precise spatiotemporal controls are discussed. The current challenges and future directions that need to be pursued for these proof-of-concept studies are also be highlighted. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Integration of fMRI, NIROT and ERP for studies of human brain function.

PubMed

Gore, John C; Horovitz, Silvina G; Cannistraci, Christopher J; Skudlarski, Pavel

2006-05-01

Different methods of assessing human brain function possess specific advantages and disadvantages compared to others, but it is believed that combining different approaches will provide greater information than can be obtained from each alone. For example, functional magnetic resonance imaging (fMRI) has good spatial resolution but poor temporal resolution, whereas the converse is true for electrophysiological recordings (event-related potentials or ERPs). In this review of recent work, we highlight a novel approach to combining these modalities in a manner designed to increase information on the origins and locations of the generators of specific ERPs and the relationship between fMRI and ERP signals. Near infrared imaging techniques have also been studied as alternatives to fMRI and can be readily integrated with simultaneous electrophysiological recordings. Each of these modalities may in principle be also used in so-called steady-state acquisitions in which the correlational structure of signals from the brain may be analyzed to provide new insights into brain function.

Integration of human factors and ergonomics during medical device design and development: it's all about communication.

PubMed

Vincent, Christopher James; Li, Yunqiu; Blandford, Ann

2014-05-01

Manufacturers of interactive medical devices, such as infusion pumps, need to ensure that devices minimise the risk of unintended harm during use. However, development teams face challenges in incorporating Human Factors. The aim of the research reported here was to better understand the constraints under which medical device design and development take place. We report the results of a qualitative study based on 19 semi-structured interviews with professionals involved in the design, development and deployment of interactive medical devices. A thematic analysis was conducted. Multiple barriers to designing for safety and usability were identified. In particular, we identified barriers to communication both between the development organisation and the intended users and between different teams within the development organisation. We propose the use of mediating representations. Artefacts such as personas and scenarios, known to provide integration across multiple perspectives, are an essential component of designing for safety and usability. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Effects of human dynamics on epidemic spreading in Côte d'Ivoire

NASA Astrophysics Data System (ADS)

Li, Ruiqi; Wang, Wenxu; Di, Zengru

2017-02-01

Understanding and predicting outbreaks of contagious diseases are crucial to the development of society and public health, especially for underdeveloped countries. However, challenging problems are encountered because of complex epidemic spreading dynamics influenced by spatial structure and human dynamics (including both human mobility and human interaction intensity). We propose a systematical model to depict nationwide epidemic spreading in Côte d'Ivoire, which integrates multiple factors, such as human mobility, human interaction intensity, and demographic features. We provide insights to aid in modeling and predicting the epidemic spreading process by data-driven simulation and theoretical analysis, which is otherwise beyond the scope of local evaluation and geometrical views. We show that the requirement that the average local basic reproductive number to be greater than unity is not necessary for outbreaks of epidemics. The observed spreading phenomenon can be roughly explained as a heterogeneous diffusion-reaction process by redefining mobility distance according to the human mobility volume between nodes, which is beyond the geometrical viewpoint. However, the heterogeneity of human dynamics still poses challenges to precise prediction.

Human-Robot Interaction in High Vulnerability Domains

NASA Technical Reports Server (NTRS)

Gore, Brian F.

2016-01-01

Future NASA missions will require successful integration of the human with highly complex systems. Highly complex systems are likely to involve humans, automation, and some level of robotic assistance. The complex environments will require successful integration of the human with automation, with robots, and with human-automation-robot teams to accomplish mission critical goals. Many challenges exist for the human performing in these types of operational environments with these kinds of systems. Systems must be designed to optimally integrate various levels of inputs and outputs based on the roles and responsibilities of the human, the automation, and the robots; from direct manual control, shared human-robotic control, or no active human control (i.e. human supervisory control). It is assumed that the human will remain involved at some level. Technologies that vary based on contextual demands and on operator characteristics (workload, situation awareness) will be needed when the human integrates into these systems. Predictive models that estimate the impact of the technologies on the system performance and the on the human operator are also needed to meet the challenges associated with such future complex human-automation-robot systems in extreme environments.

Demonstrating Acquisition of Real-Time Thermal Data Over Fires Utilizing UAVs

NASA Technical Reports Server (NTRS)

Ambrosia, Vincent G.; Wegener, Steven S.; Brass, James A.; Buechel, Sally W.; Peterson, David L. (Technical Monitor)

2002-01-01

A disaster mitigation demonstration, designed to integrate remote-piloted aerial platforms, a thermal infrared imaging payload, over-the-horizon (OTH) data telemetry and advanced image geo-rectification technologies was initiated in 2001. Project FiRE incorporates the use of a remotely piloted Uninhabited Aerial Vehicle (UAV), thermal imagery, and over-the-horizon satellite data telemetry to provide geo-corrected data over a controlled burn, to a fire management community in near real-time. The experiment demonstrated the use of a thermal multi-spectral scanner, integrated on a large payload capacity UAV, distributing data over-the-horizon via satellite communication telemetry equipment, and precision geo-rectification of the resultant data on the ground for data distribution to the Internet. The use of the UAV allowed remote-piloted flight (thereby reducing the potential for loss of human life during hazardous missions), and the ability to "finger and stare" over the fire for extended periods of time (beyond the capabilities of human-pilot endurance). Improved bit-rate capacity telemetry capabilities increased the amount, structure, and information content of the image data relayed to the ground. The integration of precision navigation instrumentation allowed improved accuracies in geo-rectification of the resultant imagery, easing data ingestion and overlay in a GIS framework. We focus on these technological advances and demonstrate how these emerging technologies can be readily integrated to support disaster mitigation and monitoring strategies regionally and nationally.

Audio-tactile integration and the influence of musical training.

PubMed

Kuchenbuch, Anja; Paraskevopoulos, Evangelos; Herholz, Sibylle C; Pantev, Christo

2014-01-01

Perception of our environment is a multisensory experience; information from different sensory systems like the auditory, visual and tactile is constantly integrated. Complex tasks that require high temporal and spatial precision of multisensory integration put strong demands on the underlying networks but it is largely unknown how task experience shapes multisensory processing. Long-term musical training is an excellent model for brain plasticity because it shapes the human brain at functional and structural levels, affecting a network of brain areas. In the present study we used magnetoencephalography (MEG) to investigate how audio-tactile perception is integrated in the human brain and if musicians show enhancement of the corresponding activation compared to non-musicians. Using a paradigm that allowed the investigation of combined and separate auditory and tactile processing, we found a multisensory incongruency response, generated in frontal, cingulate and cerebellar regions, an auditory mismatch response generated mainly in the auditory cortex and a tactile mismatch response generated in frontal and cerebellar regions. The influence of musical training was seen in the audio-tactile as well as in the auditory condition, indicating enhanced higher-order processing in musicians, while the sources of the tactile MMN were not influenced by long-term musical training. Consistent with the predictive coding model, more basic, bottom-up sensory processing was relatively stable and less affected by expertise, whereas areas for top-down models of multisensory expectancies were modulated by training.

Bridging the engineering gap: integrated systems thinking

NASA Astrophysics Data System (ADS)

Weintré, J. R.; Delfi, M.

2017-09-01

On visits to rural Indonesia it is apparent that the advances made possible by technical engineered solutions, are rarely at the same pace as the human captivation of technical development. This uneven pace has limited the application of labour-saving equipment and efficiency. It is suggested to be of primary importance to advance technical application skills among communities as part of the continuous advancement cycle in our human environment. A creative approach to inclusive technology and internal transfer of equipment knowledge in society, reduces barriers and could diminish structural or societal undesired situations. Earlier theoretical concepts provide us a lens for describing the practices of habitus, conceptualization of social capital and integrated systems thinking. The interrelationship and complexities in technical and social systems requires to be investigated. This paper aims to describe those, combined with technological applications in an empirical ethnographic approach. The study analyses the negotiations of community members with the available technology. It intends to foster a better understanding of the various cultural-economic values by exploring the systems thinking theory, with a focus on rice cultivation in Indonesia, Japan and Australia. This research suggests that cultural, economic and technical advances vary considerably and human expectations are strongly influenced by local culture.

Vaccinia virus, herpes simplex virus, and carcinogens induce DNA amplification in a human cell line and support replication of a helpervirus dependent parvovirus

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

Schlehofer, J.R.; Ehrbar, M.; zur Hausen, H.

1986-07-15

The SV40-transformed human kidney cell line, NB-E, amplifies integrated as well as episomal SV40 DNA upon treatment with chemical (DMBA) or physical (uv irradiation) carcinogens (initiators) as well as after infection with herpes simplex virus (HSV) type 1 or with vaccinia virus. In addition it is shown that vaccinia virus induces SV40 DNA amplification also in the SV40-transformed Chinese hamster embryo cell line, CO631. These findings demonstrate that human cells similar to Chinese hamster cells amplify integrated DNA sequences after treatment with carcinogens or infection with specific viruses. Furthermore, a poxvirus--vaccinia virus--similar to herpes group viruses induces DNA amplification. Asmore » reported for other systems, the vaccinia virus-induced DNA amplification in NB-E cells is inhibited by coinfection with adeno-associated virus (AAV) type 5. This is in line with previous studies on inhibition of carcinogen- or HSV-induced DNA amplification in CO631 cells. The experiments also demonstrate that vaccinia virus, in addition to herpes and adenoviruses acts as a helper virus for replication and structural antigen synthesis of AAV-5 in NB-E cells.« less

Human Ageing Genomic Resources: Integrated databases and tools for the biology and genetics of ageing

PubMed Central

Tacutu, Robi; Craig, Thomas; Budovsky, Arie; Wuttke, Daniel; Lehmann, Gilad; Taranukha, Dmitri; Costa, Joana; Fraifeld, Vadim E.; de Magalhães, João Pedro

2013-01-01

The Human Ageing Genomic Resources (HAGR, http://genomics.senescence.info) is a freely available online collection of research databases and tools for the biology and genetics of ageing. HAGR features now several databases with high-quality manually curated data: (i) GenAge, a database of genes associated with ageing in humans and model organisms; (ii) AnAge, an extensive collection of longevity records and complementary traits for >4000 vertebrate species; and (iii) GenDR, a newly incorporated database, containing both gene mutations that interfere with dietary restriction-mediated lifespan extension and consistent gene expression changes induced by dietary restriction. Since its creation about 10 years ago, major efforts have been undertaken to maintain the quality of data in HAGR, while further continuing to develop, improve and extend it. This article briefly describes the content of HAGR and details the major updates since its previous publications, in terms of both structure and content. The completely redesigned interface, more intuitive and more integrative of HAGR resources, is also presented. Altogether, we hope that through its improvements, the current version of HAGR will continue to provide users with the most comprehensive and accessible resources available today in the field of biogerontology. PMID:23193293

Bridges to sustainable tropical health

PubMed Central

Singer, Burton H.; de Castro, Marcia Caldas

2007-01-01

Ensuring sustainable health in the tropics will require bridge building between communities that currently have a limited track record of interaction. It will also require new organizational innovation if much of the negative health consequences of large-scale economic development projects are to be equitably mitigated, if not prevented. We focus attention on three specific contexts: (i) forging linkages between the engineering and health communities to implement clean water and sanitation on a broad scale to prevent reworming, after the current deworming-only programs, of people by diverse intestinal parasites; (ii) building integrated human and animal disease surveillance infrastructure and technical capacity in tropical countries on the reporting and scientific evidence requirements of the sanitary and phytosanitary agreement under the World Trade Organization; and (iii) developing an independent and equitable organizational structure for health impact assessments as well as monitoring and mitigation of health consequences of economic development projects. Effective global disease surveillance and timely early warning of new outbreaks will require a far closer integration of veterinary and human medicine than heretofore. Many of the necessary surveillance components exist within separate animal- and human-oriented organizations. The challenge is to build the necessary bridges between them. PMID:17913894

Near-optimal integration of facial form and motion.

PubMed

Dobs, Katharina; Ma, Wei Ji; Reddy, Leila

2017-09-08

Human perception consists of the continuous integration of sensory cues pertaining to the same object. While it has been fairly well shown that humans use an optimal strategy when integrating low-level cues proportional to their relative reliability, the integration processes underlying high-level perception are much less understood. Here we investigate cue integration in a complex high-level perceptual system, the human face processing system. We tested cue integration of facial form and motion in an identity categorization task and found that an optimal model could successfully predict subjects' identity choices. Our results suggest that optimal cue integration may be implemented across different levels of the visual processing hierarchy.

Brain and Social Networks: Fundamental Building Blocks of Human Experience.

PubMed

Falk, Emily B; Bassett, Danielle S

2017-09-01

How do brains shape social networks, and how do social ties shape the brain? Social networks are complex webs by which ideas spread among people. Brains comprise webs by which information is processed and transmitted among neural units. While brain activity and structure offer biological mechanisms for human behaviors, social networks offer external inducers or modulators of those behaviors. Together, these two axes represent fundamental contributors to human experience. Integrating foundational knowledge from social and developmental psychology and sociology on how individuals function within dyads, groups, and societies with recent advances in network neuroscience can offer new insights into both domains. Here, we use the example of how ideas and behaviors spread to illustrate the potential of multilayer network models. Copyright © 2017 Elsevier Ltd. All rights reserved.

Distinct functions of human RecQ helicases during DNA replication.

PubMed

Urban, Vaclav; Dobrovolna, Jana; Janscak, Pavel

2017-06-01

DNA replication is the most vulnerable process of DNA metabolism in proliferating cells and therefore it is tightly controlled and coordinated with processes that maintain genomic stability. Human RecQ helicases are among the most important factors involved in the maintenance of replication fork integrity, especially under conditions of replication stress. RecQ helicases promote recovery of replication forks being stalled due to different replication roadblocks of either exogenous or endogenous source. They prevent generation of aberrant replication fork structures and replication fork collapse, and are involved in proper checkpoint signaling. The essential role of human RecQ helicases in the genome maintenance during DNA replication is underlined by association of defects in their function with cancer predisposition. Copyright © 2016 Elsevier B.V. All rights reserved.

Structural basis of O-GlcNAc recognition by mammalian 14-3-3 proteins.

PubMed

Toleman, Clifford A; Schumacher, Maria A; Yu, Seok-Ho; Zeng, Wenjie; Cox, Nathan J; Smith, Timothy J; Soderblom, Erik J; Wands, Amberlyn M; Kohler, Jennifer J; Boyce, Michael

2018-06-05

O-GlcNAc is an intracellular posttranslational modification that governs myriad cell biological processes and is dysregulated in human diseases. Despite this broad pathophysiological significance, the biochemical effects of most O-GlcNAcylation events remain uncharacterized. One prevalent hypothesis is that O-GlcNAc moieties may be recognized by "reader" proteins to effect downstream signaling. However, no general O-GlcNAc readers have been identified, leaving a considerable gap in the field. To elucidate O-GlcNAc signaling mechanisms, we devised a biochemical screen for candidate O-GlcNAc reader proteins. We identified several human proteins, including 14-3-3 isoforms, that bind O-GlcNAc directly and selectively. We demonstrate that 14-3-3 proteins bind O-GlcNAc moieties in human cells, and we present the structures of 14-3-3β/α and γ bound to glycopeptides, providing biophysical insights into O-GlcNAc-mediated protein-protein interactions. Because 14-3-3 proteins also bind to phospho-serine and phospho-threonine, they may integrate information from O-GlcNAc and O-phosphate signaling pathways to regulate numerous physiological functions.

Mechanism of mismatch recognition revealed by human MutSβ bound to unpaired DNA loops

PubMed Central

Gupta, Shikha; Gellert, Martin; Yang, Wei

2011-01-01

DNA mismatch repair corrects replication errors, thus reducing mutation rates and microsatellite instability. Genetic defects in this pathway cause Lynch Syndrome and various cancers in humans. Binding of a mispaired or unpaired base by bacterial MutS and eukaryotic MutSα is well characterized. We report here crystal structures of human MutSβ complexed with DNA containing insertion-deletion loops (IDL) of 2, 3, 4, or 6 unpaired nucleotides. In contrast to eukaryotic MutSα and bacterial MutS, which bind the base of a mismatched nucleotide, MutSβ binds three phosphates in an IDL. DNA is severely bent at the IDL; unpaired bases are flipped out into the major groove and partially exposed to solvent. A normal downstream basepair can become unpaired; thereby a single unpaired base can be converted to an IDL of 2 nucleotides and recognized by MutSβ. The C-terminal dimerization domains form an integral part of the MutS structure and coordinate asymmetrical ATP hydrolysis by Msh2 and Msh3 with mismatch binding to signal for repair. PMID:22179786

RTEL1: functions of a disease-associated helicase.

PubMed

Vannier, Jean-Baptiste; Sarek, Grzegorz; Boulton, Simon J

2014-07-01

DNA secondary structures that arise during DNA replication, repair, and recombination (3R) must be processed correctly to prevent genetic instability. Regulator of telomere length 1 (RTEL1) is an essential DNA helicase that disassembles a variety of DNA secondary structures to facilitate 3R processes and to maintain telomere integrity. The past few years have witnessed the emergence of RTEL1 variants that confer increased susceptibility to high-grade glioma, astrocytomas, and glioblastomas. Mutations in RTEL1 have also been implicated in Hoyeraal-Hreidarsson syndrome, a severe form of the bone-marrow failure and cancer predisposition disorder, dyskeratosis congenita. We review these recent findings and highlight its crucial link between DNA secondary-structure metabolism and human disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

Orchestrating emotion and action in an evolutionary framework. Comment on "The quartet theory of human emotions: An integrative and neurofunctional model" by S. Koelsch et al.

NASA Astrophysics Data System (ADS)

Arbib, Michael A.

2015-06-01

The lead author of the Quartet Theory [10] is, appropriately enough, an expert on the neuroscience linking music and emotion, and examples of this linkage are a welcome feature of the article. Actually, the article charts two quartets: A structural quartet of affect systems centered on (i) brainstem, (ii) diencephalon, (iii) hippocampus and (iv) orbitofrontal cortex.

Human Structure in Six and One-Half Weeks: One Approach to Providing Foundational Anatomical Competency in an Era of Compressed Medical School Anatomy Curricula

ERIC Educational Resources Information Center

Halliday, Nancy; O'Donoghue, Daniel; Klump, Kathryn E.; Thompson, Britta

2015-01-01

The University of Oklahoma College of Medicine reduced gross anatomy from a full semester, 130-hour course to a six and one-half week, 105-hour course as part of a new integrated systems-based pre-clinical curriculum. In addition to the reduction in contact hours, content from embryology, histology, and radiology were added into the course. The…

Technical Basis and Implementation Guidelines for a Technique for Human Event Analysis (ATHEANA)

DTIC Science & Technology

2000-05-01

posted at NRC’s Web site address www.nrc.gov/NRC/NUREGS/indexnum.html are updated regularly and may differ from the last printed version. Non-NRC...distinctly different in that it provides structured search schemes for finding such EFCs, by using and integrating knowledge and experience in...Learned from Serious Accidents The record of significant incidents in nuclear power plant NPP operations shows a substantially different picture of

Structural and mechanistic insights into human splicing factor SF3b complex derived using an integrated approach guided by the cryo-EM density maps

PubMed Central

Rakesh, Ramachandran; Joseph, Agnel Praveen; Bhaskara, Ramachandra M.; Srinivasan, Narayanaswamy

2016-01-01

ABSTRACT Pre-mRNA splicing in eukaryotes is performed by the spliceosome, a highly complex macromolecular machine. SF3b is a multi-protein complex which recognizes the branch point adenosine of pre-mRNA as part of a larger U2 snRNP or U11/U12 di-snRNP in the dynamic spliceosome machinery. Although a cryo-EM map is available for human SF3b complex, the structure and relative spatial arrangement of all components in the complex are not yet known. We have recognized folds of domains in various proteins in the assembly and generated comparative models. Using an integrative approach involving structural and other experimental data, guided by the available cryo-EM density map, we deciphered a pseudo-atomic model of the closed form of SF3b which is found to be a “fuzzy complex” with highly flexible components and multiplicity of folds. Further, the model provides structural information for 5 proteins (SF3b10, SF3b155, SF3b145, SF3b130 and SF3b14b) and localization information for 4 proteins (SF3b10, SF3b145, SF3b130 and SF3b14b) in the assembly for the first time. Integration of this model with the available U11/U12 di-snRNP cryo-EM map enabled elucidation of an open form. This now provides new insights on the mechanistic features involved in the transition between closed and open forms pivoted by a hinge region in the SF3b155 protein that also harbors cancer causing mutations. Moreover, the open form guided model of the 5′ end of U12 snRNA, which includes the branch point duplex, shows that the architecture of SF3b acts as a scaffold for U12 snRNA: pre-mRNA branch point duplex formation with potential implications for branch point adenosine recognition fidelity. PMID:27618338

Career Education for Mental Health Workers. Integrative Seminar in Human Service. Human Service Instructional Series. Module No. 5.

ERIC Educational Resources Information Center

Redcay, Shirley

This module on an integrative seminar in human service is one of a set of six developed to prepare human services workers for the changing mental health service delivery system. A total of eight objectives are included to help students integrate previously learned knowledge and skills into a process of assessing service need, developing treatment…

What We Know About the Brain Structure-Function Relationship.

PubMed

Batista-García-Ramó, Karla; Fernández-Verdecia, Caridad Ivette

2018-04-18

How the human brain works is still a question, as is its implication with brain architecture: the non-trivial structure–function relationship. The main hypothesis is that the anatomic architecture conditions, but does not determine, the neural network dynamic. The functional connectivity cannot be explained only considering the anatomical substrate. This involves complex and controversial aspects of the neuroscience field and that the methods and methodologies to obtain structural and functional connectivity are not always rigorously applied. The goal of the present article is to discuss about the progress made to elucidate the structure–function relationship of the Central Nervous System, particularly at the brain level, based on results from human and animal studies. The current novel systems and neuroimaging techniques with high resolutive physio-structural capacity have brought about the development of an integral framework of different structural and morphometric tools such as image processing, computational modeling and graph theory. Different laboratories have contributed with in vivo, in vitro and computational/mathematical models to study the intrinsic neural activity patterns based on anatomical connections. We conclude that multi-modal techniques of neuroimaging are required such as an improvement on methodologies for obtaining structural and functional connectivity. Even though simulations of the intrinsic neural activity based on anatomical connectivity can reproduce much of the observed patterns of empirical functional connectivity, future models should be multifactorial to elucidate multi-scale relationships and to infer disorder mechanisms.

Oculometric Screening for Traumatic Brain Injury in Veterans

DTIC Science & Technology

2017-06-01

Durso, F., & Lee, J. (2015). APA handbook of human systems integration . Washington, DC: The American Psychological Association. Brain Injury Association...Submitted in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE IN HUMAN SYSTEMS INTEGRATION from the NAVAL POSTGRADUATE...PURPOSE ...................................................................................................3 C. HUMAN SYSTEMS INTEGRATION CONSIDERATIONS

Crystal structures of a rat anti-CD52 (CAMPATH-1) therapeutic antibody Fab fragment and its humanized counterpart.

PubMed

Cheetham, G M; Hale, G; Waldmann, H; Bloomer, A C

1998-11-20

The CAMPATH-1 family of antibodies are able systematically to lyse human lymphocytes with human complement by targeting the small cell-surface glycoprotein CD52, commonly called the CAMPATH-1 antigen. These antibodies have been used clinically for several years, providing therapy for patients with a variety of immunologically mediated diseases. We report here the first X-ray crystallographic analyses of a Fab fragment from a rat antibody, the original therapeutic monoclonal CAMPATH-1G and its humanized counterpart CAMPATH-1H, into which the six complementarity-determining regions of the rat antibody have been introduced. These structures have been refined at 2.6 A and 3.25 A resolution, respectively. The VL domains of adjacent molecules of CAMPATH-1H form a symmetric dimer within the crystals with an inter-molecular extended beta-sheet as seen in light chain dimers of the kappa class. Crystals of CAMPATH-1G have translational pseudo-symmetry. Within the antibody-combining sites, which are dominated by the protrusion of LysH52b and LysH53 from hypervariable loop H2, the charge distribution and overall integrity are highly conserved, but large changes in the position of loop H1 are observed and an altered conformation of loop H2. The major determinants of this are framework residues H71 and H24, whose identity differs in these two antibodies. These structures provide a detailed structural insight into the transplantation of an intact antibody-combining site between a rodent and a human framework, and provide an increased understanding of the specificity and antigen affinity of this pair of CAMPATH-1 antibodies for CD52. This study forms the structural basis for future modification and design of more effective antibodies to this important antigen. Copyright 1998 Academic Press

An Integrative Architecture for a Sensor-Supported Trust Management System

PubMed Central

Trček, Denis

2012-01-01

Trust plays a key role not only in e-worlds and emerging pervasive computing environments, but also already for millennia in human societies. Trust management solutions that have being around now for some fifteen years were primarily developed for the above mentioned cyber environments and they are typically focused on artificial agents, sensors, etc. However, this paper presents extensions of a new methodology together with architecture for trust management support that is focused on humans and human-like agents. With this methodology and architecture sensors play a crucial role. The architecture presents an already deployable tool for multi and interdisciplinary research in various areas where humans are involved. It provides new ways to obtain an insight into dynamics and evolution of such structures, not only in pervasive computing environments, but also in other important areas like management and decision making support. PMID:23112628

Restructuring a basic science course for core competencies: an example from anatomy teaching.

PubMed

Gregory, Jeremy K; Lachman, Nirusha; Camp, Christopher L; Chen, Laura P; Pawlina, Wojciech

2009-09-01

Medical schools revise their curricula in order to develop physicians best skilled to serve the public's needs. To ensure a smooth transition to residency programs, undergraduate medical education is often driven by the six core competencies endorsed by the Accreditation Council for Graduate Medical Education (ACGME): patient care, medical knowledge, practice-based learning, interpersonal skills, professionalism, and systems-based practice. Recent curricular redesign at Mayo Medical School provided an opportunity to restructure anatomy education and integrate radiology with first-year gross and developmental anatomy. The resulting 6-week (120-contact-hour) human structure block provides students with opportunities to learn gross anatomy through dissection, radiologic imaging, and embryologic correlation. We report more than 20 educational interventions from the human structure block that may serve as a model for incorporating the ACGME core competencies into basic science and early medical education. The block emphasizes clinically-oriented anatomy, invites self- and peer-evaluation, provides daily formative feedback through an audience response system, and employs team-based learning. The course includes didactic briefing sessions and roles for students as teachers, leaders, and collaborators. Third-year medical students serve as teaching assistants. With its clinical focus and competency-based design, the human structure block connects basic science with best-practice clinical medicine.

Response of SCP-2L domain of human MFE-2 to ligand removal: binding site closure and burial of peroxisomal targeting signal.

PubMed

Lensink, M F; Haapalainen, A M; Hiltunen, J K; Glumoff, T; Juffer, A H

2002-10-11

In the study of the structure and function relationship of human MFE-2, we have investigated the dynamics of human MFE-2SCP-2L (hSCP-2L) and its response to ligand removal. A comparison was made with homologous rabbit SCP-2. Breathing and a closing motion are found, identifiable with an adjustment in size and a closing off of the binding pocket. Crucial residues for structural integrity have been identified. Particularly mobile areas of the protein are loop 1 that is connecting helices A and C in space, and helix D, next to the entrance of the pocket. In hSCP-2L, the binding pocket gets occupied by Phe93, which is making a tight hydrophobic contact with Trp36. In addition, it is found that the C-terminal peroxisomal targeting signal (PTS1) that is solvent exposed in the complexed structure becomes buried when no ligand is present. Moreover, an anti-correlation exists between burial of PTS1 and the size of the binding pocket. The results are in accordance with plant nsLTPs, where a similar accommodation of binding pocket size was found after ligand binding/removal. Furthermore, the calculations support the suggestion of a ligand-assisted targeting mechanism.

A high-throughput approach to profile RNA structure.

PubMed

Delli Ponti, Riccardo; Marti, Stefanie; Armaos, Alexandros; Tartaglia, Gian Gaetano

2017-03-17

Here we introduce the Computational Recognition of Secondary Structure (CROSS) method to calculate the structural profile of an RNA sequence (single- or double-stranded state) at single-nucleotide resolution and without sequence length restrictions. We trained CROSS using data from high-throughput experiments such as Selective 2΄-Hydroxyl Acylation analyzed by Primer Extension (SHAPE; Mouse and HIV transcriptomes) and Parallel Analysis of RNA Structure (PARS; Human and Yeast transcriptomes) as well as high-quality NMR/X-ray structures (PDB database). The algorithm uses primary structure information alone to predict experimental structural profiles with >80% accuracy, showing high performances on large RNAs such as Xist (17 900 nucleotides; Area Under the ROC Curve AUC of 0.75 on dimethyl sulfate (DMS) experiments). We integrated CROSS in thermodynamics-based methods to predict secondary structure and observed an increase in their predictive power by up to 30%. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Integrated care reform in urban China: a qualitative study on design, supporting environment and implementation.

PubMed

Qian, Yi; Hou, Zhiyuan; Wang, Wei; Zhang, Donglan; Yan, Fei

2017-10-25

Initiatives on integrated care between hospitals and community health centers (CHCs) have been introduced to transform the current fragmented health care delivery system into an integrated system in China. Up to date no research has analyzed in-depth the experiences of these initiatives based on perspectives from various stakeholders. This study analyzed the integrated care pilot in Hangzhou City by investigating stakeholders' perspectives on its design features and supporting environment, their acceptability of this pilot, and further identifying the enabling and constraining factors that may influence the implementation of the integrated care reform. The qualitative study was carried out based on in-depth interviews and focus group discussions with 50 key informants who were involved in the policy-making process and implementation. Relevant policy documents were also collected for analysis. The pilot in Hangzhou was established as a CHC-led delivery system based on cooperation agreement between CHCs and hospitals to deliver primary and specialty care together for patients with chronic diseases. An innovative learning-from-practice mentorship system between specialists and general practitioners was also introduced to solve the poor capacity of general practitioners. The design of the pilot, its governance and organizational structure and human resources were enabling factors, which facilitated the integrated care reform. However, the main constraining factors were a lack of an integrated payment mechanism from health insurance and a lack of tailored information system to ensure its sustainability. The integrated care pilot in Hangzhou enabled CHCs to play as gate-keeper and care coordinator for the full continuum of services across the health care providers. The government put integrated care a priority, and constructed an efficient design, governance and organizational structure to enable its implementation. Health insurance should play a proactive role, and adopt a shared financial incentive system to support integrated care across providers in the future.

The Conjugative Relaxase TrwC Promotes Integration of Foreign DNA in the Human Genome.

PubMed

González-Prieto, Coral; Gabriel, Richard; Dehio, Christoph; Schmidt, Manfred; Llosa, Matxalen

2017-06-15

Bacterial conjugation is a mechanism of horizontal DNA transfer. The relaxase TrwC of the conjugative plasmid R388 cleaves one strand of the transferred DNA at the oriT gene, covalently attaches to it, and leads the single-stranded DNA (ssDNA) into the recipient cell. In addition, TrwC catalyzes site-specific integration of the transferred DNA into its target sequence present in the genome of the recipient bacterium. Here, we report the analysis of the efficiency and specificity of the integrase activity of TrwC in human cells, using the type IV secretion system of the human pathogen Bartonella henselae to introduce relaxase-DNA complexes. Compared to Mob relaxase from plasmid pBGR1, we found that TrwC mediated a 10-fold increase in the rate of plasmid DNA transfer to human cells and a 100-fold increase in the rate of chromosomal integration of the transferred DNA. We used linear amplification-mediated PCR and plasmid rescue to characterize the integration pattern in the human genome. DNA sequence analysis revealed mostly reconstituted oriT sequences, indicating that TrwC is active and recircularizes transferred DNA in human cells. One TrwC-mediated site-specific integration event was detected, proving that TrwC is capable of mediating site-specific integration in the human genome, albeit with very low efficiency compared to the rate of random integration. Our results suggest that TrwC may stabilize the plasmid DNA molecules in the nucleus of the human cell, probably by recircularization of the transferred DNA strand. This stabilization would increase the opportunities for integration of the DNA by the host machinery. IMPORTANCE Different biotechnological applications, including gene therapy strategies, require permanent modification of target cells. Long-term expression is achieved either by extrachromosomal persistence or by integration of the introduced DNA. Here, we studied the utility of conjugative relaxase TrwC, a bacterial protein with site-specific integrase activity in bacteria, as an integrase in human cells. Although it is not efficient as a site-specific integrase, we found that TrwC is active in human cells and promotes random integration of the transferred DNA in the human genome, probably acting as a DNA chaperone until it is integrated by host mechanisms. TrwC-DNA complexes can be delivered to human cells through a type IV secretion system involved in pathogenesis. Thus, TrwC could be used in vivo to transfer the DNA of interest into the appropriate cell and promote its integration. If used in combination with a site-specific nuclease, it could lead to site-specific integration of the incoming DNA by homologous recombination. Copyright © 2017 American Society for Microbiology.

The Conjugative Relaxase TrwC Promotes Integration of Foreign DNA in the Human Genome

PubMed Central

González-Prieto, Coral; Gabriel, Richard; Dehio, Christoph; Schmidt, Manfred

2017-01-01

ABSTRACT Bacterial conjugation is a mechanism of horizontal DNA transfer. The relaxase TrwC of the conjugative plasmid R388 cleaves one strand of the transferred DNA at the oriT gene, covalently attaches to it, and leads the single-stranded DNA (ssDNA) into the recipient cell. In addition, TrwC catalyzes site-specific integration of the transferred DNA into its target sequence present in the genome of the recipient bacterium. Here, we report the analysis of the efficiency and specificity of the integrase activity of TrwC in human cells, using the type IV secretion system of the human pathogen Bartonella henselae to introduce relaxase-DNA complexes. Compared to Mob relaxase from plasmid pBGR1, we found that TrwC mediated a 10-fold increase in the rate of plasmid DNA transfer to human cells and a 100-fold increase in the rate of chromosomal integration of the transferred DNA. We used linear amplification-mediated PCR and plasmid rescue to characterize the integration pattern in the human genome. DNA sequence analysis revealed mostly reconstituted oriT sequences, indicating that TrwC is active and recircularizes transferred DNA in human cells. One TrwC-mediated site-specific integration event was detected, proving that TrwC is capable of mediating site-specific integration in the human genome, albeit with very low efficiency compared to the rate of random integration. Our results suggest that TrwC may stabilize the plasmid DNA molecules in the nucleus of the human cell, probably by recircularization of the transferred DNA strand. This stabilization would increase the opportunities for integration of the DNA by the host machinery. IMPORTANCE Different biotechnological applications, including gene therapy strategies, require permanent modification of target cells. Long-term expression is achieved either by extrachromosomal persistence or by integration of the introduced DNA. Here, we studied the utility of conjugative relaxase TrwC, a bacterial protein with site-specific integrase activity in bacteria, as an integrase in human cells. Although it is not efficient as a site-specific integrase, we found that TrwC is active in human cells and promotes random integration of the transferred DNA in the human genome, probably acting as a DNA chaperone until it is integrated by host mechanisms. TrwC-DNA complexes can be delivered to human cells through a type IV secretion system involved in pathogenesis. Thus, TrwC could be used in vivo to transfer the DNA of interest into the appropriate cell and promote its integration. If used in combination with a site-specific nuclease, it could lead to site-specific integration of the incoming DNA by homologous recombination. PMID:28411218

Critical interactions between the Global Fund-supported HIV programs and the health system in Ghana.

PubMed

Atun, Rifat; Pothapregada, Sai Kumar; Kwansah, Janet; Degbotse, D; Lazarus, Jeffrey V

2011-08-01

The support of global health initiatives in recipient countries has been vigorously debated. Critics are concerned that disease-specific programs may be creating vertical and parallel service delivery structures that to some extent undermine health systems. This case study of Ghana aimed to explore how the Global Fund-supported HIV program interacts with the health system there and to map the extent and nature of integration of the national disease program across 6 key health systems functions. Qualitative interviews of national stakeholders were conducted to understand the perceptions of the strengths and weaknesses of the relationship between Global Fund-supported activities and the health system and to identify positive synergies and unintended consequences of integration. Ghana has a well-functioning sector-wide approach to financing its health system, with a strong emphasis on integrated care delivery. Ghana has benefited from US $175 million of approved Global Fund support to address the HIV epidemic, accounting for almost 85% of the National AIDS Control Program budget. Investments in infrastructure, human resources, and commodities have enabled HIV interventions to increase exponentially. Global Fund-supported activities have been well integrated into key health system functions to strengthen them, especially financing, planning, service delivery, and demand generation. Yet, with governance and monitoring and evaluation functions, parallel structures to national systems have emerged, leading to inefficiencies. This case study demonstrates that interactions and integration are highly varied across different health system functions, and strong government leadership has facilitated the integration of Global Fund-supported activities within national programs.

Human homolog of the mouse sperm receptor

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

Chamberlin, M.E.; Dean, J.

1990-08-01

The human zona pellucida, composed of three glycoproteins (ZP1, ZP2, and ZP3), forms an extracellular matrix that surrounds ovulated eggs and mediates species-specific fertilization. The genes that code for at least two of the zona proteins (ZP2 and ZP3) cross-hybridize with other mammalian DNA. The recently characterized mouse sperm receptor gene (Zp-3) was used to isolate its human homolog. The human homolog spans {approx}18.3 kilobase pairs (kbp) (compared to 8.6 kbp for the mouse gene) and contains eight exons, the sizes of which are strictly conserved between the two species. Four short (8-15 bp) sequences within the first 250 bpmore » of the 5{prime} flanking region in the human Zp-3 homolog are also present upstream of mouse Zp-3. These elements may modulate oocyte-specific gene expression. By using the polymerase chain reaction, a full-length cDNA of human ZP3 was isolated from human ovarian poly(A){sup +} RNA and used to deduce the structure of human ZP3 mRNA. Certain features of the human and mouse ZP3 transcripts are conserved. Both have unusually short 5{prime} and 3{prime} untranslated regions, both contain a single open reading frame that is 74% identical, and both code for 424 amino acid polypeptides that are 67% the same. The similarity between the two proteins may define domains that are important in maintaining the structural integrity of the zona pellucida, while the differences may play a role in mediating the species-specific events of mammalian fertilization.« less

Reducing the Risk of Human Space Missions with INTEGRITY

NASA Technical Reports Server (NTRS)

Jones, Harry W.; Dillon-Merill, Robin L.; Tri, Terry O.; Henninger, Donald L.

2003-01-01

The INTEGRITY Program will design and operate a test bed facility to help prepare for future beyond-LEO missions. The purpose of INTEGRITY is to enable future missions by developing, testing, and demonstrating advanced human space systems. INTEGRITY will also implement and validate advanced management techniques including risk analysis and mitigation. One important way INTEGRITY will help enable future missions is by reducing their risk. A risk analysis of human space missions is important in defining the steps that INTEGRITY should take to mitigate risk. This paper describes how a Probabilistic Risk Assessment (PRA) of human space missions will help support the planning and development of INTEGRITY to maximize its benefits to future missions. PRA is a systematic methodology to decompose the system into subsystems and components, to quantify the failure risk as a function of the design elements and their corresponding probability of failure. PRA provides a quantitative estimate of the probability of failure of the system, including an assessment and display of the degree of uncertainty surrounding the probability. PRA provides a basis for understanding the impacts of decisions that affect safety, reliability, performance, and cost. Risks with both high probability and high impact are identified as top priority. The PRA of human missions beyond Earth orbit will help indicate how the risk of future human space missions can be reduced by integrating and testing systems in INTEGRITY.

Enigmatic insight into collagen

PubMed Central

Deshmukh, Shrutal Narendra; Dive, Alka M; Moharil, Rohit; Munde, Prashant

2016-01-01

Collagen is a unique, triple helical molecule which forms the major part of extracellular matrix. It is the most abundant protein in the human body, representing 30% of its dry weight. It is the fibrous structural protein that makes up the white fibers (collagen fibers) of skin, tendons, bones, cartilage and all other connective tissues. Collagens are not only essential for the mechanical resistance and resilience of multicellular organisms, but are also signaling molecules defining cellular shape and behavior. The human body has at least 16 types of collagen, but the most prominent types are I, II and III. Collagens are produced by several cell types and are distinguishable by their molecular compositions, morphologic characteristics, distribution, functions and pathogenesis. This is the major fibrous glycoprotein present in the extracellular matrix and in connective tissue and helps in maintaining the structural integrity of these tissues. It has a triple helical structure. Various studies have proved that mutations that modify folding of the triple helix result in identifiable genetic disorders. Collagen diseases share certain similarities with autoimmune diseases, because autoantibodies specific to each collagen disease are produced. Therefore, this review highlights the role of collagen in normal health and also the disorders associated with structural and functional defects in collagen. PMID:27601823

Determination of Death: A Scientific Perspective on Biological Integration

PubMed Central

Condic, Maureen L.

2016-01-01

Human life is operationally defined by the onset and cessation of organismal function. At postnatal stages of life, organismal integration critically and uniquely requires a functioning brain. In this article, a distinction is drawn between integrated and coordinated biologic activities. While communication between cells can provide a coordinated biologic response to specific signals, it does not support the integrated function that is characteristic of a living human being. Determining the loss of integrated function can be complicated by medical interventions (i.e., “life support”) that uncouple elements of the natural biologic hierarchy underlying our intuitive understanding of death. Such medical interventions can allow living human beings who are no longer able to function in an integrated manner to be maintained in a living state. In contrast, medical intervention can also allow the cells and tissues of an individual who has died to be maintained in a living state. To distinguish between a living human being and living human cells, two criteria are proposed: either the persistence of any form of brain function or the persistence of autonomous integration of vital functions. Either of these criteria is sufficient to determine a human being is alive. PMID:27075193

Forming of science teacher thinking through integrated laboratory exercises

NASA Astrophysics Data System (ADS)

Horváthová, Daniela; Rakovská, Mária; Zelenický, Ľubomír

2017-01-01

Within the three-semester optional course Science we have also included into curricula the subject entitled Science Practicum consisting of laboratory exercises of complementary natural scientific disciplines whose content exceeds the boundaries of relevant a scientific discipline (physics, biology, …). The paper presents the structure and selected samples of laboratory exercises of physical part of Science Practicum in which we have processed in an integrated way the knowledge of physics and biology at secondary grammar school. When planning the exercises we have proceeded from those areas of mentioned disciplines in which we can appropriately apply integration of knowledge and where the measurement methods are used. We have focused on the integration of knowledge in the field of human sensory organs (eye, ear), dolphins, bats (spatial orientation) and bees (ommatidium of faceted eye) and their modelling. Laboratory exercises are designed in such a way that they would motivate future teachers of natural scientific subjects to work independently with specialized literature of the mentioned natural sciences and ICT.

Integrity of Induced Pluripotent Stem Cell (iPSC) Derived Megakaryocytes as Assessed by Genetic and Transcriptomic Analysis

PubMed Central

Kammers, Kai; Taub, Margaret A.; Ruczinski, Ingo; Martin, Joshua; Yanek, Lisa R.; Frazee, Alyssa; Gao, Yongxing; Hoyle, Dixie; Faraday, Nauder; Becker, Diane M.; Cheng, Linzhao; Wang, Zack Z.; Leek, Jeff T.; Becker, Lewis C.; Mathias, Rasika A.

2017-01-01

Previously, we have described our feeder-free, xeno-free approach to generate megakaryocytes (MKs) in culture from human induced pluripotent stem cells (iPSCs). Here, we focus specifically on the integrity of these MKs using: (1) genotype discordance between parent cell DNA to iPSC cell DNA and onward to the differentiated MK DNA; (2) genomic structural integrity using copy number variation (CNV); and (3) transcriptomic signatures of the derived MK lines compared to the iPSC lines. We detected a very low rate of genotype discordance; estimates were 0.0001%-0.01%, well below the genotyping error rate for our assay (0.37%). No CNVs were generated in the iPSCs that were subsequently passed on to the MKs. Finally, we observed highly biologically relevant gene sets as being upregulated in MKs relative to the iPSCs: platelet activation, blood coagulation, megakaryocyte development, platelet formation, platelet degranulation, and platelet aggregation. These data strongly support the integrity of the derived MK lines. PMID:28107356

Beyond DSM-5 and IQ Scores: Integrating the Four Pillars to Forensic Evaluations.

PubMed

Delgado, Sergio V; Barzman, Drew H

2017-03-01

The current adult and child forensic psychiatrist is well trained, familiar, and comfortable with the use of the semi-structured Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, APA 2013 (DSM-5) [In APA, 2003] interview style. The author's assertion is not that this method is invalid or unreliable; rather, that it can be complemented by integrating elements of the defendant's four pillar assessment. Assessing the four pillars expands on the information provided by a semi-structured DSM-5-style interview in psychiatry. The four pillars are the foundation of a person's personality; temperament, cognition (learning abilities or weaknesses), cognitive flexibility (theory of mind) and internal working models of attachment, within the backdrop of the family and of the social and cultural environment in which they have lived. The importance of the study of four pillars is based on the understanding that human behavior and psychopathology as a complex and multifaceted process that includes the level of social-emotional maturity and cognitive abilities (In Delgado et al. Contemporary Psychodynamic Psychotherapy for Children and Adolescents: Integrating Intersubjectivity and Neuroscience. Springer, Berlin, 2015). The four pillars are not new concepts, rather they had been studied by separate non-clinical disciplines, and had not been integrated to the clinical practice. As far as we know, it wasn't until Delgado et al. (Contemporary Psychodynamic Psychotherapy for Children and Adolescents: Integrating Intersubjectivity and Neuroscience. Springer, Berlin, 2015) incorporated the four pillars in a user-friendly manner to clinical practice.

A Quantitative Human Spacecraft Design Evaluation Model for Assessing Crew Accommodation and Utilization

NASA Astrophysics Data System (ADS)

Fanchiang, Christine

Crew performance, including both accommodation and utilization factors, is an integral part of every human spaceflight mission from commercial space tourism, to the demanding journey to Mars and beyond. Spacecraft were historically built by engineers and technologists trying to adapt the vehicle into cutting edge rocketry with the assumption that the astronauts could be trained and will adapt to the design. By and large, that is still the current state of the art. It is recognized, however, that poor human-machine design integration can lead to catastrophic and deadly mishaps. The premise of this work relies on the idea that if an accurate predictive model exists to forecast crew performance issues as a result of spacecraft design and operations, it can help designers and managers make better decisions throughout the design process, and ensure that the crewmembers are well-integrated with the system from the very start. The result should be a high-quality, user-friendly spacecraft that optimizes the utilization of the crew while keeping them alive, healthy, and happy during the course of the mission. Therefore, the goal of this work was to develop an integrative framework to quantitatively evaluate a spacecraft design from the crew performance perspective. The approach presented here is done at a very fundamental level starting with identifying and defining basic terminology, and then builds up important axioms of human spaceflight that lay the foundation for how such a framework can be developed. With the framework established, a methodology for characterizing the outcome using a mathematical model was developed by pulling from existing metrics and data collected on human performance in space. Representative test scenarios were run to show what information could be garnered and how it could be applied as a useful, understandable metric for future spacecraft design. While the model is the primary tangible product from this research, the more interesting outcome of this work is the structure of the framework and what it tells future researchers in terms of where the gaps and limitations exist for developing a better framework. It also identifies metrics that can now be collected as part of future validation efforts for the model.

A flexible pressure responsive device based on the interaction between silver nanoparticles and an aluminum reflector

NASA Astrophysics Data System (ADS)

Rankin, Alasdair; McGarry, Steven

2018-01-01

The unique and tunable optical properties of metal nanoparticles have attracted intense and sustained academic attention in recent years. In tandem with the demand for low-cost responsive materials, one particular topic of interest is the development of mechanically responsive device structures. This work describes the design, fabrication, and testing of a mechanically responsive plasmonic device structure that has been integrated onto a standard commercial plastic substrate. With a low actuation force and a visually perceivable color shift, this device would be attractive for applications requiring responsive features that can be activated by the human hand.

Rights to food with a human face in the global south.

PubMed

Rahim, Aminur

2011-01-01

This article seeks to dispel the popular myth surrounding the food crises which precipitated food riots in the global South in 2008. Arguing from a structural and historical perspective, the article suggests that global hunger is a deep-rooted crisis that is embedded in the social and structural variables associated within the nation-state that places a restraint on the self-regulating capacity of nation-states in the South. Internationalizing the food crisis, however, will do more harm to the south’s agricultural transformation and rural development. The article argues for integrated rural development that will increase output growth through an institutional, technological, and marketing strategy.

Integrating global health with medical education.

PubMed

Aulakh, Alex; Tweed, Sam; Moore, Jolene; Graham, Wendy

2017-04-01

Globalisation has implications for the next generation of doctors, and thus for medical education. Increasingly, global health is being taught in medical schools, although its incorporation into an already full curriculum presents challenges. Global health was introduced into the MBChB curriculum at the University of Aberdeen through a student-selected component (SSC) as part of an existing medical humanities block. The Global Health and Humanities (GHH) module was first delivered in the autumn of 2013 and will shortly enter its third year. This student-led study used quantitative and qualitative methods to assess the module's appropriateness and effectiveness for strengthening learning on global health, consisting of online surveys for course participants and semi-structured interviews with faculty members. Integrating global health into the undergraduate medical curriculum by way of an SSC was regarded by teaching staff as an effective and realistic approach. A recognised strength of delivering global health as part of the medical humanities block was the opportunity to expose students to the social determinants of health through interdisciplinary teaching. Participating students all agreed that the learning approach strengthened both their knowledge of global health and a range of generic skills. SSCs are, by definition, self-selecting, and will have a tendency to attract students already with an interest in a topic - here global health. A wide range of learning opportunities is needed to integrate global health throughout medical curricula, and to reach all students. © 2016 John Wiley & Sons Ltd.

Using a fuzzy comprehensive evaluation method to determine product usability: A proposed theoretical framework

PubMed Central

Zhou, Ronggang; Chan, Alan H. S.

2016-01-01

BACKGROUND: In order to compare existing usability data to ideal goals or to that for other products, usability practitioners have tried to develop a framework for deriving an integrated metric. However, most current usability methods with this aim rely heavily on human judgment about the various attributes of a product, but often fail to take into account of the inherent uncertainties in these judgments in the evaluation process. OBJECTIVE: This paper presents a universal method of usability evaluation by combining the analytic hierarchical process (AHP) and the fuzzy evaluation method. By integrating multiple sources of uncertain information during product usability evaluation, the method proposed here aims to derive an index that is structured hierarchically in terms of the three usability components of effectiveness, efficiency, and user satisfaction of a product. METHODS: With consideration of the theoretical basis of fuzzy evaluation, a two-layer comprehensive evaluation index was first constructed. After the membership functions were determined by an expert panel, the evaluation appraisals were computed by using the fuzzy comprehensive evaluation technique model to characterize fuzzy human judgments. Then with the use of AHP, the weights of usability components were elicited from these experts. RESULTS AND CONCLUSIONS: Compared to traditional usability evaluation methods, the major strength of the fuzzy method is that it captures the fuzziness and uncertainties in human judgments and provides an integrated framework that combines the vague judgments from multiple stages of a product evaluation process. PMID:28035943

Crystal structure of mitochondrial respiratory membrane protein complex II.

PubMed

Sun, Fei; Huo, Xia; Zhai, Yujia; Wang, Aojin; Xu, Jianxing; Su, Dan; Bartlam, Mark; Rao, Zihe

2005-07-01

The mitochondrial respiratory Complex II or succinate:ubiquinone oxidoreductase (SQR) is an integral membrane protein complex in both the tricarboxylic acid cycle and aerobic respiration. Here we report the first crystal structure of Complex II from porcine heart at 2.4 A resolution and its complex structure with inhibitors 3-nitropropionate and 2-thenoyltrifluoroacetone (TTFA) at 3.5 A resolution. Complex II is comprised of two hydrophilic proteins, flavoprotein (Fp) and iron-sulfur protein (Ip), and two transmembrane proteins (CybL and CybS), as well as prosthetic groups required for electron transfer from succinate to ubiquinone. The structure correlates the protein environments around prosthetic groups with their unique midpoint redox potentials. Two ubiquinone binding sites are discussed and elucidated by TTFA binding. The Complex II structure provides a bona fide model for study of the mitochondrial respiratory system and human mitochondrial diseases related to mutations in this complex.

Organization of Synthetic Alphoid DNA Array in Human Artificial Chromosome (HAC) with a Conditional Centromere

PubMed Central

Kouprina, Natalay; Samoshkin, Alexander; Erliandri, Indri; Nakano, Megumi; Lee, Hee-Sheung; Fu, Haiging; Iida, Yuichi; Aladjem, Mirit; Oshimura, Mitsuo; Masumoto, Hiroshi; Earnshaw, William C.; Larionov, Vladimir

2012-01-01

Human artificial chromosomes (HACs) represent a novel promising episomal system for functional genomics, gene therapy and synthetic biology. HACs are engineered from natural and synthetic alphoid DNA arrays upon transfection into human cells. The use of HACs for gene expression studies requires the knowledge of their structural organization. However, none of de novo HACs constructed so far has been physically mapped in detail. Recently we constructed a synthetic alphoidtetO-HAC that was successfully used for expression of full-length genes to correct genetic deficiencies in human cells. The HAC can be easily eliminated from cell populations by inactivation of its conditional kinetochore. This unique feature provides a control for phenotypic changes attributed to expression of HAC-encoded genes. This work describes organization of a megabase-size synthetic alphoid DNA array in the alphoidtetO-HAC that has been formed from a ~50 kb synthetic alphoidtetO-construct. Our analysis showed that this array represents a 1.1 Mb continuous sequence assembled from multiple copies of input DNA, a significant part of which was rearranged before assembling. The tandem and inverted alphoid DNA repeats in the HAC range in size from 25 to 150 kb. In addition, we demonstrated that the structure and functional domains of the HAC remains unchanged after several rounds of its transfer into different host cells. The knowledge of the alphoidtetO-HAC structure provides a tool to control HAC integrity during different manipulations. Our results also shed light on a mechanism for de novo HAC formation in human cells. PMID:23411994

Contact structure, mobility, environmental impact and behaviour: the importance of social forces to infectious disease dynamics and disease ecology

PubMed Central

Gurley, Emily S.

2017-01-01

Human factors, including contact structure, movement, impact on the environment and patterns of behaviour, can have significant influence on the emergence of novel infectious diseases and the transmission and amplification of established ones. As anthropogenic climate change alters natural systems and global economic forces drive land-use and land-cover change, it becomes increasingly important to understand both the ecological and social factors that impact infectious disease outcomes for human populations. While the field of disease ecology explicitly studies the ecological aspects of infectious disease transmission, the effects of the social context on zoonotic pathogen spillover and subsequent human-to-human transmission are comparatively neglected in the literature. The social sciences encompass a variety of disciplines and frameworks for understanding infectious diseases; however, here we focus on four primary areas of social systems that quantitatively and qualitatively contribute to infectious diseases as social–ecological systems. These areas are social mixing and structure, space and mobility, geography and environmental impact, and behaviour and behaviour change. Incorporation of these social factors requires empirical studies for parametrization, phenomena characterization and integrated theoretical modelling of social–ecological interactions. The social–ecological system that dictates infectious disease dynamics is a complex system rich in interacting variables with dynamically significant heterogeneous properties. Future discussions about infectious disease spillover and transmission in human populations need to address the social context that affects particular disease systems by identifying and measuring qualitatively important drivers. This article is part of the themed issue ‘Opening the black box: re-examining the ecology and evolution of parasite transmission’. PMID:28289265

Predicting protein structures with a multiplayer online game.

PubMed

Cooper, Seth; Khatib, Firas; Treuille, Adrien; Barbero, Janos; Lee, Jeehyung; Beenen, Michael; Leaver-Fay, Andrew; Baker, David; Popović, Zoran; Players, Foldit

2010-08-05

People exert large amounts of problem-solving effort playing computer games. Simple image- and text-recognition tasks have been successfully 'crowd-sourced' through games, but it is not clear if more complex scientific problems can be solved with human-directed computing. Protein structure prediction is one such problem: locating the biologically relevant native conformation of a protein is a formidable computational challenge given the very large size of the search space. Here we describe Foldit, a multiplayer online game that engages non-scientists in solving hard prediction problems. Foldit players interact with protein structures using direct manipulation tools and user-friendly versions of algorithms from the Rosetta structure prediction methodology, while they compete and collaborate to optimize the computed energy. We show that top-ranked Foldit players excel at solving challenging structure refinement problems in which substantial backbone rearrangements are necessary to achieve the burial of hydrophobic residues. Players working collaboratively develop a rich assortment of new strategies and algorithms; unlike computational approaches, they explore not only the conformational space but also the space of possible search strategies. The integration of human visual problem-solving and strategy development capabilities with traditional computational algorithms through interactive multiplayer games is a powerful new approach to solving computationally-limited scientific problems.

Differentially categorized structural brain hubs are involved in different microstructural, functional, and cognitive characteristics and contribute to individual identification.

PubMed

Wang, Xindi; Lin, Qixiang; Xia, Mingrui; He, Yong

2018-04-01

Very little is known regarding whether structural hubs of human brain networks that enable efficient information communication may be classified into different categories. Using three multimodal neuroimaging data sets, we construct individual structural brain networks and further identify hub regions based on eight widely used graph-nodal metrics, followed by comprehensive characteristics and reproducibility analyses. We show the three categories of structural hubs in the brain network, namely, aggregated, distributed, and connector hubs. Spatially, these distinct categories of hubs are primarily located in the default-mode system and additionally in the visual and limbic systems for aggregated hubs, in the frontoparietal system for distributed hubs, and in the sensorimotor and ventral attention systems for connector hubs. These categorized hubs exhibit various distinct characteristics to support their differentiated roles, involving microstructural organization, wiring costs, topological vulnerability, functional modular integration, and cognitive flexibility; moreover, these characteristics are better in the hubs than nonhubs. Finally, all three categories of hubs display high across-session spatial similarities and act as structural fingerprints with high predictive rates (100%, 100%, and 84.2%) for individual identification. Collectively, we highlight three categories of brain hubs with differential microstructural, functional and, cognitive associations, which shed light on topological mechanisms of the human connectome. © 2018 Wiley Periodicals, Inc.

The role of the human pulvinar in visual attention and action: evidence from temporal-order judgment, saccade decision, and antisaccade tasks.

PubMed

Arend, Isabel; Machado, Liana; Ward, Robert; McGrath, Michelle; Ro, Tony; Rafal, Robert D

2008-01-01

The pulvinar nucleus of the thalamus has been considered as a key structure for visual attention functions (Grieve, K.L. et al. (2000). Trends Neurosci., 23: 35-39; Shipp, S. (2003). Philos. Trans. R. Soc. Lond. B Biol. Sci., 358(1438): 1605-1624). During the past several years, we have studied the role of the human pulvinar in visual attention and oculomotor behaviour by testing a small group of patients with unilateral pulvinar lesions. Here we summarize some of these findings, and present new evidence for the role of this structure in both eye movements and visual attention through two versions of a temporal-order judgment task and an antisaccade task. Pulvinar damage induces an ipsilesional bias in perceptual temporal-order judgments and in saccadic decision, and also increases the latency of antisaccades away from contralesional targets. The demonstration that pulvinar damage affects both attention and oculomotor behaviour highlights the role of this structure in the integration of visual and oculomotor signals and, more generally, its role in flexibly linking visual stimuli with context-specific motor responses.

Describing sequencing results of structural chromosome rearrangements with a suggested next-generation cytogenetic nomenclature.

PubMed

Ordulu, Zehra; Wong, Kristen E; Currall, Benjamin B; Ivanov, Andrew R; Pereira, Shahrin; Althari, Sara; Gusella, James F; Talkowski, Michael E; Morton, Cynthia C

2014-05-01

With recent rapid advances in genomic technologies, precise delineation of structural chromosome rearrangements at the nucleotide level is becoming increasingly feasible. In this era of "next-generation cytogenetics" (i.e., an integration of traditional cytogenetic techniques and next-generation sequencing), a consensus nomenclature is essential for accurate communication and data sharing. Currently, nomenclature for describing the sequencing data of these aberrations is lacking. Herein, we present a system called Next-Gen Cytogenetic Nomenclature, which is concordant with the International System for Human Cytogenetic Nomenclature (2013). This system starts with the alignment of rearrangement sequences by BLAT or BLAST (alignment tools) and arrives at a concise and detailed description of chromosomal changes. To facilitate usage and implementation of this nomenclature, we are developing a program designated BLA(S)T Output Sequence Tool of Nomenclature (BOSToN), a demonstrative version of which is accessible online. A standardized characterization of structural chromosomal rearrangements is essential both for research analyses and for application in the clinical setting. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Structural characterization and chromosomal location of the mouse macrophage migration inhibitory factor gene and pseudogenes

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

Bozza, M.; Gerard, C.; Kolakowski, L.F. Jr.

1995-06-10

Macrophage migration inhibitory factor, MIF, is a cytokine released by T-lymphocytes, macrophages, and the pituitary gland that serves to integrate peripheral and central inflammatory responses. Ubiquitous expression and developmental regulation suggest that MIF may have additional roles outside of the immune system. Here we report the structure and chromosomal location of the mouse Mif gene and the partial characterization of five Mif pseudogenes. The mouse Mif gene spans less than 0.7 kb of chromosomal DNA and is composed of three exons. A comparison between the mouse and the human genes shows a similar gene structure and common regulatory elements inmore » both promoter regions. The mouse Mif gene maps to the middle region of chromosome 10, between Bcr and S100b, which have been mapped to human chromosomes 22q11 and 21q22.3, respectively. The entire sequence of two pseudogenes demonstrates the absence of introns, the presence of the 5{prime} untranslated region of the cDNA, a 3{prime} poly(A) tail, and the lack of sequence similarity with untranscribed regions of the gene. The five pseudogenes are highly homologous to the cDNA, but contain a variable number of mutations that would produce mutated or truncated MIF-like proteins. Phylogenetic analyses of MIF genes and pseudogenes indicate several independent genetic events that can account for multiple genomic integrations. Three of the Mif pseudogenes were also mapped by interspecific backcross to chromosomes 1, 9, and 17. These results suggest that Mif pseudogenes originated by retrotransposition. 46 refs., 5 figs., 1 tab.« less

Human due diligence.

PubMed

Harding, David; Rouse, Ted

2007-04-01

Most companies do a thorough job of financial due diligence when they acquire other companies. But all too often, deal makers simply ignore or underestimate the significance of people issues in mergers and acquisitions. The consequences are severe. Most obviously, there's a high degree of talent loss after a deal's announcement. To make matters worse, differences in decision-making styles lead to infighting; integration stalls; and productivity declines. The good news is that human due diligence can help companies avoid these problems. Done early enough, it helps acquirers decide whether to embrace or kill a deal and determine the price they are willing to pay. It also lays the groundwork for smooth integration. When acquirers have done their homework, they can uncover capability gaps, points of friction, and differences in decision making. Even more important, they can make the critical "people" decisions-who stays, who goes, who runs the combined business, what to do with the rank and file-at the time the deal is announced or shortly thereafter. Making such decisions within the first 30 days is critical to the success of a deal. Hostile situations clearly make things more difficult, but companies can and must still do a certain amount of human due diligence to reduce the inevitable fallout from the acquisition process and smooth the integration. This article details the steps involved in conducting human due diligence. The approach is structured around answering five basic questions: Who is the cultural acquirer? What kind of organization do you want? Will the two cultures mesh? Who are the people you most want to retain? And how will rank-and-file employees react to the deal? Unless an acquiring company has answered these questions to its satisfaction, the acquisition it is making will be very likely to end badly.

Integrative network alignment reveals large regions of global network similarity in yeast and human.

PubMed

Kuchaiev, Oleksii; Przulj, Natasa

2011-05-15

High-throughput methods for detecting molecular interactions have produced large sets of biological network data with much more yet to come. Analogous to sequence alignment, efficient and reliable network alignment methods are expected to improve our understanding of biological systems. Unlike sequence alignment, network alignment is computationally intractable. Hence, devising efficient network alignment heuristics is currently a foremost challenge in computational biology. We introduce a novel network alignment algorithm, called Matching-based Integrative GRAph ALigner (MI-GRAAL), which can integrate any number and type of similarity measures between network nodes (e.g. proteins), including, but not limited to, any topological network similarity measure, sequence similarity, functional similarity and structural similarity. Hence, we resolve the ties in similarity measures and find a combination of similarity measures yielding the largest contiguous (i.e. connected) and biologically sound alignments. MI-GRAAL exposes the largest functional, connected regions of protein-protein interaction (PPI) network similarity to date: surprisingly, it reveals that 77.7% of proteins in the baker's yeast high-confidence PPI network participate in such a subnetwork that is fully contained in the human high-confidence PPI network. This is the first demonstration that species as diverse as yeast and human contain so large, continuous regions of global network similarity. We apply MI-GRAAL's alignments to predict functions of un-annotated proteins in yeast, human and bacteria validating our predictions in the literature. Furthermore, using network alignment scores for PPI networks of different herpes viruses, we reconstruct their phylogenetic relationship. This is the first time that phylogeny is exactly reconstructed from purely topological alignments of PPI networks. Supplementary files and MI-GRAAL executables: http://bio-nets.doc.ic.ac.uk/MI-GRAAL/.

Ultra-structural time-course study in the C. elegans model for Duchenne muscular dystrophy highlights a crucial role for sarcomere-anchoring structures and sarcolemma integrity in the earliest steps of the muscle degeneration process.

PubMed

Brouilly, Nicolas; Lecroisey, Claire; Martin, Edwige; Pierson, Laura; Mariol, Marie-Christine; Qadota, Hiroshi; Labouesse, Michel; Streichenberger, Nathalie; Mounier, Nicole; Gieseler, Kathrin

2015-11-15

Duchenne muscular dystrophy (DMD) is a genetic disease characterized by progressive muscle degeneration due to mutations in the dystrophin gene. In spite of great advances in the design of curative treatments, most patients currently receive palliative therapies with steroid molecules such as prednisone or deflazacort thought to act through their immunosuppressive properties. These molecules only slightly slow down the progression of the disease and lead to severe side effects. Fundamental research is still needed to reveal the mechanisms involved in the disease that could be exploited as therapeutic targets. By studying a Caenorhabditis elegans model for DMD, we show here that dystrophin-dependent muscle degeneration is likely to be cell autonomous and affects the muscle cells the most involved in locomotion. We demonstrate that muscle degeneration is dependent on exercise and force production. Exhaustive studies by electron microscopy allowed establishing for the first time the chronology of subcellular events occurring during the entire process of muscle degeneration. This chronology highlighted the crucial role for dystrophin in stabilizing sarcomeric anchoring structures and the sarcolemma. Our results suggest that the disruption of sarcomeric anchoring structures and sarcolemma integrity, observed at the onset of the muscle degeneration process, triggers subcellular consequences that lead to muscle cell death. An ultra-structural analysis of muscle biopsies from DMD patients suggested that the chronology of subcellular events established in C. elegans models the pathogenesis in human. Finally, we found that the loss of sarcolemma integrity was greatly reduced after prednisone treatment suggesting a role for this molecule in plasma membrane stabilization. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Comprehensiveness and humanization of nursing care management in the Intensive Care Unit.

PubMed

Medeiros, Adriane Calvetti de; Siqueira, Hedi Crecencia Heckler de; Zamberlan, Claudia; Cecagno, Diana; Nunes, Simone Dos Santos; Thurow, Mara Regina Bergmann

2016-01-01

Identifying the elements that promote comprehensiveness and humanization of nursing care management in the Intensive Care Unit, with an ecosystemic approach. A documentary qualitative study. The method of documentary analysis was used for data analysis. Four pre-established categories were identified - Technical; Organizational; Technological; and Humanizing Dimensions. Data resulted in forming two sub-categories that integrate the humanizing dimension category, namely 'Comprehensiveness in healthcare actions' and 'Integrating processes and promoters of humanization,' bringing forth implications and challenges in forms of managing health work processes, enabling organizational, structural and managerial changes to the provided healthcare. It was considered that all structural elements in managing nursing care with a focus on the needs of users should be in line with public policies and the principles of comprehensiveness and humanization, thus possessing strong potential for transforming health practices. Identificar os elementos capazes de promover a integralidade e a humanização na gestão do cuidado de enfermagem na Unidade de Terapia Intensiva, com enfoque ecossistêmico. Pesquisa documental, de natureza qualitativa. Para a análise dos dados utilizou-se do método da análise documental. SForam identificadas quatro categorias preestabelecidas ‒ Dimensões: Técnica; Organizacional; Tecnológica e Humanizadora. Os dados resultantes das duas subcategorias que integraram a categoria Dimensão Humanizadora, Integralidade nas ações do cuidado e Processos integradores e promotores de humanização, trazem implicações e desafios nos modos de gerir os processos de trabalho em saúde, o que possibilita transformações organizacionais, estruturais e gerenciais na produção do cuidado. Considera-se que na gestão do cuidado de enfermagem todos os elementos estruturantes, com enfoque nas necessidades dos usuários, devem estar em consonância com as políticas públicas e os princípios da integralidade e da humanização e possuir forte potencial para a transformação das práticas em saúde.

Self-organizing ontology of biochemically relevant small molecules

PubMed Central

2012-01-01

Background The advent of high-throughput experimentation in biochemistry has led to the generation of vast amounts of chemical data, necessitating the development of novel analysis, characterization, and cataloguing techniques and tools. Recently, a movement to publically release such data has advanced biochemical structure-activity relationship research, while providing new challenges, the biggest being the curation, annotation, and classification of this information to facilitate useful biochemical pattern analysis. Unfortunately, the human resources currently employed by the organizations supporting these efforts (e.g. ChEBI) are expanding linearly, while new useful scientific information is being released in a seemingly exponential fashion. Compounding this, currently existing chemical classification and annotation systems are not amenable to automated classification, formal and transparent chemical class definition axiomatization, facile class redefinition, or novel class integration, thus further limiting chemical ontology growth by necessitating human involvement in curation. Clearly, there is a need for the automation of this process, especially for novel chemical entities of biological interest. Results To address this, we present a formal framework based on Semantic Web technologies for the automatic design of chemical ontology which can be used for automated classification of novel entities. We demonstrate the automatic self-assembly of a structure-based chemical ontology based on 60 MeSH and 40 ChEBI chemical classes. This ontology is then used to classify 200 compounds with an accuracy of 92.7%. We extend these structure-based classes with molecular feature information and demonstrate the utility of our framework for classification of functionally relevant chemicals. Finally, we discuss an iterative approach that we envision for future biochemical ontology development. Conclusions We conclude that the proposed methodology can ease the burden of chemical data annotators and dramatically increase their productivity. We anticipate that the use of formal logic in our proposed framework will make chemical classification criteria more transparent to humans and machines alike and will thus facilitate predictive and integrative bioactivity model development. PMID:22221313

Deep biomarkers of human aging: Application of deep neural networks to biomarker development

PubMed Central

Putin, Evgeny; Mamoshina, Polina; Aliper, Alexander; Korzinkin, Mikhail; Moskalev, Alexey; Kolosov, Alexey; Ostrovskiy, Alexander; Cantor, Charles; Vijg, Jan; Zhavoronkov, Alex

2016-01-01

One of the major impediments in human aging research is the absence of a comprehensive and actionable set of biomarkers that may be targeted and measured to track the effectiveness of therapeutic interventions. In this study, we designed a modular ensemble of 21 deep neural networks (DNNs) of varying depth, structure and optimization to predict human chronological age using a basic blood test. To train the DNNs, we used over 60,000 samples from common blood biochemistry and cell count tests from routine health exams performed by a single laboratory and linked to chronological age and sex. The best performing DNN in the ensemble demonstrated 81.5 % epsilon-accuracy r = 0.90 with R2 = 0.80 and MAE = 6.07 years in predicting chronological age within a 10 year frame, while the entire ensemble achieved 83.5% epsilon-accuracy r = 0.91 with R2 = 0.82 and MAE = 5.55 years. The ensemble also identified the 5 most important markers for predicting human chronological age: albumin, glucose, alkaline phosphatase, urea and erythrocytes. To allow for public testing and evaluate real-life performance of the predictor, we developed an online system available at http://www.aging.ai. The ensemble approach may facilitate integration of multi-modal data linked to chronological age and sex that may lead to simple, minimally invasive, and affordable methods of tracking integrated biomarkers of aging in humans and performing cross-species feature importance analysis. PMID:27191382

Deep biomarkers of human aging: Application of deep neural networks to biomarker development.

PubMed

Putin, Evgeny; Mamoshina, Polina; Aliper, Alexander; Korzinkin, Mikhail; Moskalev, Alexey; Kolosov, Alexey; Ostrovskiy, Alexander; Cantor, Charles; Vijg, Jan; Zhavoronkov, Alex

2016-05-01

One of the major impediments in human aging research is the absence of a comprehensive and actionable set of biomarkers that may be targeted and measured to track the effectiveness of therapeutic interventions. In this study, we designed a modular ensemble of 21 deep neural networks (DNNs) of varying depth, structure and optimization to predict human chronological age using a basic blood test. To train the DNNs, we used over 60,000 samples from common blood biochemistry and cell count tests from routine health exams performed by a single laboratory and linked to chronological age and sex. The best performing DNN in the ensemble demonstrated 81.5 % epsilon-accuracy r = 0.90 with R(2) = 0.80 and MAE = 6.07 years in predicting chronological age within a 10 year frame, while the entire ensemble achieved 83.5% epsilon-accuracy r = 0.91 with R(2) = 0.82 and MAE = 5.55 years. The ensemble also identified the 5 most important markers for predicting human chronological age: albumin, glucose, alkaline phosphatase, urea and erythrocytes. To allow for public testing and evaluate real-life performance of the predictor, we developed an online system available at http://www.aging.ai. The ensemble approach may facilitate integration of multi-modal data linked to chronological age and sex that may lead to simple, minimally invasive, and affordable methods of tracking integrated biomarkers of aging in humans and performing cross-species feature importance analysis.

High-Throughput Sequencing Reveals Principles of Adeno-Associated Virus Serotype 2 Integration

PubMed Central

Janovitz, Tyler; Klein, Isaac A.; Oliveira, Thiago; Mukherjee, Piali; Nussenzweig, Michel C.; Sadelain, Michel

2013-01-01

Viral integrations are important in human biology, yet genome-wide integration profiles have not been determined for many viruses. Adeno-associated virus (AAV) infects most of the human population and is a prevalent gene therapy vector. AAV integrates into the human genome with preference for a single locus, termed AAVS1. However, the genome-wide integration of AAV has not been defined, and the principles underlying this recombination remain unclear. Using a novel high-throughput approach, integrant capture sequencing, nearly 12 million AAV junctions were recovered from a human cell line, providing five orders of magnitude more data than were previously available. Forty-five percent of integrations occurred near AAVS1, and several thousand novel integration hotspots were identified computationally. Most of these occurred in genes, with dozens of hotspots targeting known oncogenes. Viral replication protein binding sites (RBS) and transcriptional activity were major factors favoring integration. In a first for eukaryotic viruses, the data reveal a unique asymmetric integration profile with distinctive directional orientation of viral genomes. These studies provide a new understanding of AAV integration biology through the use of unbiased high-throughput data acquisition and bioinformatics. PMID:23720718

Evidence for expansion of the precuneus in human evolution.

PubMed

Bruner, Emiliano; Preuss, Todd M; Chen, Xu; Rilling, James K

2017-03-01

The evolution of neurocranial morphology in Homo sapiens is characterized by bulging of the parietal region, a feature unique to our species. In modern humans, expansion of the parietal surface occurs during the first year of life, in a morphogenetic stage which is absent in chimpanzees and Neandertals. A similar variation in brain shape among living adult humans is associated with expansion of the precuneus. Using MRI-derived structural brain templates, we compare medial brain morphology between humans and chimpanzees through shape analysis and geometrical modeling. We find that the main spatial difference is a prominent expansion of the precuneus in our species, providing further evidence of evolutionary changes associated with this area. The precuneus is a major hub of brain organization, a central node of the default-mode network, and plays an essential role in visuospatial integration. Together, the comparative neuroanatomical and paleontological evidence suggest that precuneus expansion is a neurological specialization of H. sapiens that evolved in the last 150,000 years that may be associated with recent human cognitive specializations.