Potentials of single-cell biology in identification and validation of disease biomarkers.

PubMed

Niu, Furong; Wang, Diane C; Lu, Jiapei; Wu, Wei; Wang, Xiangdong

2016-09-01

Single-cell biology is considered a new approach to identify and validate disease-specific biomarkers. However, the concern raised by clinicians is how to apply single-cell measurements for clinical practice, translate the message of single-cell systems biology into clinical phenotype or explain alterations of single-cell gene sequencing and function in patient response to therapies. This study is to address the importance and necessity of single-cell gene sequencing in the identification and development of disease-specific biomarkers, the definition and significance of single-cell biology and single-cell systems biology in the understanding of single-cell full picture, the development and establishment of whole-cell models in the validation of targeted biological function and the figure and meaning of single-molecule imaging in single cell to trace intra-single-cell molecule expression, signal, interaction and location. We headline the important role of single-cell biology in the discovery and development of disease-specific biomarkers with a special emphasis on understanding single-cell biological functions, e.g. mechanical phenotypes, single-cell biology, heterogeneity and organization of genome function. We have reason to believe that such multi-dimensional, multi-layer, multi-crossing and stereoscopic single-cell biology definitely benefits the discovery and development of disease-specific biomarkers. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Gene network biological validity based on gene-gene interaction relevance.

PubMed

Gómez-Vela, Francisco; Díaz-Díaz, Norberto

2014-01-01

In recent years, gene networks have become one of the most useful tools for modeling biological processes. Many inference gene network algorithms have been developed as techniques for extracting knowledge from gene expression data. Ensuring the reliability of the inferred gene relationships is a crucial task in any study in order to prove that the algorithms used are precise. Usually, this validation process can be carried out using prior biological knowledge. The metabolic pathways stored in KEGG are one of the most widely used knowledgeable sources for analyzing relationships between genes. This paper introduces a new methodology, GeneNetVal, to assess the biological validity of gene networks based on the relevance of the gene-gene interactions stored in KEGG metabolic pathways. Hence, a complete KEGG pathway conversion into a gene association network and a new matching distance based on gene-gene interaction relevance are proposed. The performance of GeneNetVal was established with three different experiments. Firstly, our proposal is tested in a comparative ROC analysis. Secondly, a randomness study is presented to show the behavior of GeneNetVal when the noise is increased in the input network. Finally, the ability of GeneNetVal to detect biological functionality of the network is shown.

Semantically enabled and statistically supported biological hypothesis testing with tissue microarray databases

PubMed Central

2011-01-01

Background Although many biological databases are applying semantic web technologies, meaningful biological hypothesis testing cannot be easily achieved. Database-driven high throughput genomic hypothesis testing requires both of the capabilities of obtaining semantically relevant experimental data and of performing relevant statistical testing for the retrieved data. Tissue Microarray (TMA) data are semantically rich and contains many biologically important hypotheses waiting for high throughput conclusions. Methods An application-specific ontology was developed for managing TMA and DNA microarray databases by semantic web technologies. Data were represented as Resource Description Framework (RDF) according to the framework of the ontology. Applications for hypothesis testing (Xperanto-RDF) for TMA data were designed and implemented by (1) formulating the syntactic and semantic structures of the hypotheses derived from TMA experiments, (2) formulating SPARQLs to reflect the semantic structures of the hypotheses, and (3) performing statistical test with the result sets returned by the SPARQLs. Results When a user designs a hypothesis in Xperanto-RDF and submits it, the hypothesis can be tested against TMA experimental data stored in Xperanto-RDF. When we evaluated four previously validated hypotheses as an illustration, all the hypotheses were supported by Xperanto-RDF. Conclusions We demonstrated the utility of high throughput biological hypothesis testing. We believe that preliminary investigation before performing highly controlled experiment can be benefited. PMID:21342584

Twelve testable hypotheses on the geobiology of weathering

Treesearch

S.L. Brantley; J.P. Megonigal; F.N. Scatena; Z. Balogh-Brunstad; R.T. Barnes; M.A. Bruns; P. van Cappelen; K. Dontsova; H.E. Hartnett; A.S. Hartshorn; A. Heimsath; E. Herndon; L. Jin; C.K. Keller; J.R. Leake; W.H. McDowell; F.C. Meinzer; T.J. Mozdzer; S. Petsch; J. Pett-Ridge; K.S. Pretziger; P.A. Raymond; C.S. Riebe; K. Shumaker; A. Sutton-Grier; R. Walter; K. Yoo

2011-01-01

Critical Zone (CZ) research investigates the chemical, physical, and biological processes that modulate the Earth's surface. Here, we advance 12 hypotheses that must be tested to improve our understanding of the CZ: (1) Solar-to-chemical conversion of energy by plants regulates flows of carbon, water, and nutrients through plant-microbe soil networks, thereby...

Validation of Procedures for Monitoring Crewmember Immune Function - Short Duration Biological Investigation

NASA Technical Reports Server (NTRS)

Sams, Clarence; Crucian, Brian; Stowe, Raymond; Pierson, Duane; Mehta, Satish; Morukov, Boris; Uchakin, Peter; Nehlsen-Cannarella, Sandra

2008-01-01

Validation of Procedures for Monitoring Crew Member Immune Function - Short Duration Biological Investigation (Integrated Immune-SDBI) will assess the clinical risks resulting from the adverse effects of space flight on the human immune system and will validate a flightcompatible immune monitoring strategy. Immune system changes will be monitored by collecting and analyzing blood, urine and saliva samples from crewmembers before, during and after space flight.

A Review of Hypothesized Determinants Associated with Bighorn Sheep (Ovis canadensis) Die-Offs

PubMed Central

Miller, David S.; Hoberg, Eric; Weiser, Glen; Aune, Keith; Atkinson, Mark; Kimberling, Cleon

2012-01-01

Multiple determinants have been hypothesized to cause or favor disease outbreaks among free-ranging bighorn sheep (Ovis canadensis) populations. This paper considered direct and indirect causes of mortality, as well as potential interactions among proposed environmental, host, and agent determinants of disease. A clear, invariant relationship between a single agent and field outbreaks has not yet been documented, in part due to methodological limitations and practical challenges associated with developing rigorous study designs. Therefore, although there is a need to develop predictive models for outbreaks and validated mitigation strategies, uncertainty remains as to whether outbreaks are due to endemic or recently introduced agents. Consequently, absence of established and universal explanations for outbreaks contributes to conflict among wildlife and livestock stakeholders over land use and management practices. This example illustrates the challenge of developing comprehensive models for understanding and managing wildlife diseases in complex biological and sociological environments. PMID:22567546

Relations between Intuitive Biological Thinking and Biological Misconceptions in Biology Majors and Nonmajors

PubMed Central

Coley, John D.; Tanner, Kimberly

2015-01-01

Research and theory development in cognitive psychology and science education research remain largely isolated. Biology education researchers have documented persistent scientifically inaccurate ideas, often termed misconceptions, among biology students across biological domains. In parallel, cognitive and developmental psychologists have described intuitive conceptual systems—teleological, essentialist, and anthropocentric thinking—that humans use to reason about biology. We hypothesize that seemingly unrelated biological misconceptions may have common origins in these intuitive ways of knowing, termed cognitive construals. We presented 137 undergraduate biology majors and nonmajors with six biological misconceptions. They indicated their agreement with each statement, and explained their rationale for their response. Results indicate frequent agreement with misconceptions, and frequent use of construal-based reasoning among both biology majors and nonmajors in their written explanations. Moreover, results also show associations between specific construals and the misconceptions hypothesized to arise from those construals. Strikingly, such associations were stronger among biology majors than nonmajors. These results demonstrate important linkages between intuitive ways of thinking and misconceptions in discipline-based reasoning, and raise questions about the origins, persistence, and generality of relations between intuitive reasoning and biological misconceptions. PMID:25713093

Ancestral state reconstructions require biological evidence to test evolutionary hypotheses: A case study examining the evolution of reproductive mode in squamate reptiles.

PubMed

Griffith, Oliver W; Blackburn, Daniel G; Brandley, Matthew C; Van Dyke, James U; Whittington, Camilla M; Thompson, Michael B

2015-09-01

To understand evolutionary transformations it is necessary to identify the character states of extinct ancestors. Ancestral character state reconstruction is inherently difficult because it requires an accurate phylogeny, character state data, and a statistical model of transition rates and is fundamentally constrained by missing data such as extinct taxa. We argue that model based ancestral character state reconstruction should be used to generate hypotheses but should not be considered an analytical endpoint. Using the evolution of viviparity and reversals to oviparity in squamates as a case study, we show how anatomical, physiological, and ecological data can be used to evaluate hypotheses about evolutionary transitions. The evolution of squamate viviparity requires changes to the timing of reproductive events and the successive loss of features responsible for building an eggshell. A reversal to oviparity requires that those lost traits re-evolve. We argue that the re-evolution of oviparity is inherently more difficult than the reverse. We outline how the inviability of intermediate phenotypes might present physiological barriers to reversals from viviparity to oviparity. Finally, we show that ecological data supports an oviparous ancestral state for squamates and multiple transitions to viviparity. In summary, we conclude that the first squamates were oviparous, that frequent transitions to viviparity have occurred, and that reversals to oviparity in viviparous lineages either have not occurred or are exceedingly rare. As this evidence supports conclusions that differ from previous ancestral state reconstructions, our paper highlights the importance of incorporating biological evidence to evaluate model-generated hypotheses. © 2015 Wiley Periodicals, Inc.

Validation of an Instrument for Assessing Conceptual Change with Respect to the Theory of Evolution by Secondary Biology Students

NASA Astrophysics Data System (ADS)

Goff, Kevin David

This pilot study evaluated the validity of a new quantitative, closed-response instrument for assessing student conceptual change regarding the theory of evolution. The instrument has two distinguishing design features. First, it is designed not only to gauge student mastery of the scientific model of evolution, but also to elicit a trio of deeply intuitive tendencies that are known to compromise many students' understanding: the projection of intentional agency, teleological directionality, and immutable essences onto biological phenomena. Second, in addition to a section of conventional multiple choice questions, the instrument contains a series of items where students may simultaneously endorse both scientifically normative propositions and intuitively appealing yet unscientific propositions, without having to choose between them. These features allow for the hypothesized possibility that the three intuitions are partly innate, themselves products of cognitive evolution in our hominin ancestors, and thus may continue to inform students' thinking even after instruction and conceptual change. The test was piloted with 340 high school students from diverse schools and communities. Confirmatory factor analysis and other statistical methods provided evidence that the instrument already has strong potential for validly distinguishing students who hold a correct scientific understanding from those who do not, but that revision and retesting are needed to render it valid for gauging students' adherence to intuitive misconceptions. Ultimately the instrument holds promise as a tool for classroom intervention studies by conceptual change researchers, for diagnostic testing and data gathering by instructional leaders, and for provoking classroom dialogue and debate by science teachers.

Systems biology-embedded target validation: improving efficacy in drug discovery.

PubMed

Vandamme, Drieke; Minke, Benedikt A; Fitzmaurice, William; Kholodenko, Boris N; Kolch, Walter

2014-01-01

The pharmaceutical industry is faced with a range of challenges with the ever-escalating costs of drug development and a drying out of drug pipelines. By harnessing advances in -omics technologies and moving away from the standard, reductionist model of drug discovery, there is significant potential to reduce costs and improve efficacy. Embedding systems biology approaches in drug discovery, which seek to investigate underlying molecular mechanisms of potential drug targets in a network context, will reduce attrition rates by earlier target validation and the introduction of novel targets into the currently stagnant market. Systems biology approaches also have the potential to assist in the design of multidrug treatments and repositioning of existing drugs, while stratifying patients to give a greater personalization of medical treatment. © 2013 Wiley Periodicals, Inc.

Testing evolutionary hypotheses for phenotypic divergence using landscape genetics.

PubMed

Funk, W Chris; Murphy, Melanie A

2010-02-01

Understanding the evolutionary causes of phenotypic variation among populations has long been a central theme in evolutionary biology. Several factors can influence phenotypic divergence, including geographic isolation, genetic drift, divergent natural or sexual selection, and phenotypic plasticity. But the relative importance of these factors in generating phenotypic divergence in nature is still a tantalizing and unresolved problem in evolutionary biology. The origin and maintenance of phenotypic divergence is also at the root of many ongoing debates in evolutionary biology, such as the extent to which gene flow constrains adaptive divergence (Garant et al. 2007) and the relative importance of genetic drift, natural selection, and sexual selection in initiating reproductive isolation and speciation (Coyne & Orr 2004). In this issue, Wang & Summers (2010) test the causes of one of the most fantastic examples of phenotypic divergence in nature: colour pattern divergence among populations of the strawberry poison frog (Dendrobates pumilio) in Panama and Costa Rica (Fig. 1). This study provides a beautiful example of the use of the emerging field of landscape genetics to differentiate among hypotheses for phenotypic divergence. Using landscape genetic analyses, Wang & Summers were able to reject the hypotheses that colour pattern divergence is due to isolation-by-distance (IBD) or landscape resistance. Instead, the hypothesis left standing is that colour divergence is due to divergent selection, in turn driving reproductive isolation among populations with different colour morphs. More generally, this study provides a wonderful example of how the emerging field of landscape genetics, which has primarily been applied to questions in conservation and ecology, now plays an essential role in evolutionary research.

Ecosystem functioning and maximum entropy production: a quantitative test of hypotheses.

PubMed

Meysman, Filip J R; Bruers, Stijn

2010-05-12

The idea that entropy production puts a constraint on ecosystem functioning is quite popular in ecological thermodynamics. Yet, until now, such claims have received little quantitative verification. Here, we examine three 'entropy production' hypotheses that have been forwarded in the past. The first states that increased entropy production serves as a fingerprint of living systems. The other two hypotheses invoke stronger constraints. The state selection hypothesis states that when a system can attain multiple steady states, the stable state will show the highest entropy production rate. The gradient response principle requires that when the thermodynamic gradient increases, the system's new stable state should always be accompanied by a higher entropy production rate. We test these three hypotheses by applying them to a set of conventional food web models. Each time, we calculate the entropy production rate associated with the stable state of the ecosystem. This analysis shows that the first hypothesis holds for all the food webs tested: the living state shows always an increased entropy production over the abiotic state. In contrast, the state selection and gradient response hypotheses break down when the food web incorporates more than one trophic level, indicating that they are not generally valid.

Twelve testable hypotheses on the geobiology of weathering.

PubMed

Brantley, S L; Megonigal, J P; Scatena, F N; Balogh-Brunstad, Z; Barnes, R T; Bruns, M A; Van Cappellen, P; Dontsova, K; Hartnett, H E; Hartshorn, A S; Heimsath, A; Herndon, E; Jin, L; Keller, C K; Leake, J R; McDowell, W H; Meinzer, F C; Mozdzer, T J; Petsch, S; Pett-Ridge, J; Pregitzer, K S; Raymond, P A; Riebe, C S; Shumaker, K; Sutton-Grier, A; Walter, R; Yoo, K

2011-03-01

Critical Zone (CZ) research investigates the chemical, physical, and biological processes that modulate the Earth's surface. Here, we advance 12 hypotheses that must be tested to improve our understanding of the CZ: (1) Solar-to-chemical conversion of energy by plants regulates flows of carbon, water, and nutrients through plant-microbe soil networks, thereby controlling the location and extent of biological weathering. (2) Biological stoichiometry drives changes in mineral stoichiometry and distribution through weathering. (3) On landscapes experiencing little erosion, biology drives weathering during initial succession, whereas weathering drives biology over the long term. (4) In eroding landscapes, weathering-front advance at depth is coupled to surface denudation via biotic processes. (5) Biology shapes the topography of the Critical Zone. (6) The impact of climate forcing on denudation rates in natural systems can be predicted from models incorporating biogeochemical reaction rates and geomorphological transport laws. (7) Rising global temperatures will increase carbon losses from the Critical Zone. (8) Rising atmospheric P(CO2) will increase rates and extents of mineral weathering in soils. (9) Riverine solute fluxes will respond to changes in climate primarily due to changes in water fluxes and secondarily through changes in biologically mediated weathering. (10) Land use change will impact Critical Zone processes and exports more than climate change. (11) In many severely altered settings, restoration of hydrological processes is possible in decades or less, whereas restoration of biodiversity and biogeochemical processes requires longer timescales. (12) Biogeochemical properties impart thresholds or tipping points beyond which rapid and irreversible losses of ecosystem health, function, and services can occur. © 2011 Blackwell Publishing Ltd.

Systems Biology-Driven Hypotheses Tested In Vivo: The Need to Advancing Molecular Imaging Tools.

PubMed

Verma, Garima; Palombo, Alessandro; Grigioni, Mauro; La Monaca, Morena; D'Avenio, Giuseppe

2018-01-01

Processing and interpretation of biological images may provide invaluable insights on complex, living systems because images capture the overall dynamics as a "whole." Therefore, "extraction" of key, quantitative morphological parameters could be, at least in principle, helpful in building a reliable systems biology approach in understanding living objects. Molecular imaging tools for system biology models have attained widespread usage in modern experimental laboratories. Here, we provide an overview on advances in the computational technology and different instrumentations focused on molecular image processing and analysis. Quantitative data analysis through various open source software and algorithmic protocols will provide a novel approach for modeling the experimental research program. Besides this, we also highlight the predictable future trends regarding methods for automatically analyzing biological data. Such tools will be very useful to understand the detailed biological and mathematical expressions under in-silico system biology processes with modeling properties.

Transfer factor - hypotheses for its structure and function.

PubMed

Shifrine, M; Scibienski, R

1975-01-01

Transfer factor (TF) is a dialyzable extract from primed lymphocytes that is able to transfer specific delayed hypersensitivity from one animal to another. On the basis of available data we suggest that TF is a polypeptide with a molecular weight below 15,000 daltons. We hypothesize that TF is the variable light or heavy chain domain of immunoglobulin: such a molecule conforms with the accepted properties of TF and also has the necessary specificity requirements. We also hypothesize that TF is part of a receptor site. beta-2-microglobulin, a molecule that is an integral part of cell surfaces, could be the anchor for TF. beta-2-microglobulin has homologies with the constant portion of immunoglobulin light or heavy chain and thus would combine with the variable domain (TF) to form a complete receptor site for a specific antigen. The properties of TF suggest its mode of action, which is discussed in detail in the text. The biologic advantages of TF is its ability to confer immediate (immunologie specific) protection while the 'normal' immune response develops.

Relations between intuitive biological thinking and biological misconceptions in biology majors and nonmajors.

PubMed

Coley, John D; Tanner, Kimberly

2015-03-02

Research and theory development in cognitive psychology and science education research remain largely isolated. Biology education researchers have documented persistent scientifically inaccurate ideas, often termed misconceptions, among biology students across biological domains. In parallel, cognitive and developmental psychologists have described intuitive conceptual systems--teleological, essentialist, and anthropocentric thinking--that humans use to reason about biology. We hypothesize that seemingly unrelated biological misconceptions may have common origins in these intuitive ways of knowing, termed cognitive construals. We presented 137 undergraduate biology majors and nonmajors with six biological misconceptions. They indicated their agreement with each statement, and explained their rationale for their response. Results indicate frequent agreement with misconceptions, and frequent use of construal-based reasoning among both biology majors and nonmajors in their written explanations. Moreover, results also show associations between specific construals and the misconceptions hypothesized to arise from those construals. Strikingly, such associations were stronger among biology majors than nonmajors. These results demonstrate important linkages between intuitive ways of thinking and misconceptions in discipline-based reasoning, and raise questions about the origins, persistence, and generality of relations between intuitive reasoning and biological misconceptions. © 2015 J. D. Coley and K. Tanner. CBE—Life Sciences Education © 2015 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

cellPACK: A Virtual Mesoscope to Model and Visualize Structural Systems Biology

PubMed Central

Johnson, Graham T.; Autin, Ludovic; Al-Alusi, Mostafa; Goodsell, David S.; Sanner, Michel F.; Olson, Arthur J.

2014-01-01

cellPACK assembles computational models of the biological mesoscale, an intermediate scale (10−7–10−8m) between molecular and cellular biology. cellPACK’s modular architecture unites existing and novel packing algorithms to generate, visualize and analyze comprehensive 3D models of complex biological environments that integrate data from multiple experimental systems biology and structural biology sources. cellPACK is currently available as open source code, with tools for validation of models and with recipes and models for five biological systems: blood plasma, cytoplasm, synaptic vesicles, HIV and a mycoplasma cell. We have applied cellPACK to model distributions of HIV envelope protein to test several hypotheses for consistency with experimental observations. Biologists, educators, and outreach specialists can interact with cellPACK models, develop new recipes and perform packing experiments through scripting and graphical user interfaces at http://cellPACK.org. PMID:25437435

Robotics-inspired biology.

PubMed

Gravish, Nick; Lauder, George V

2018-03-29

For centuries, designers and engineers have looked to biology for inspiration. Biologically inspired robots are just one example of the application of knowledge of the natural world to engineering problems. However, recent work by biologists and interdisciplinary teams have flipped this approach, using robots and physical models to set the course for experiments on biological systems and to generate new hypotheses for biological research. We call this approach robotics-inspired biology; it involves performing experiments on robotic systems aimed at the discovery of new biological phenomena or generation of new hypotheses about how organisms function that can then be tested on living organisms. This new and exciting direction has emerged from the extensive use of physical models by biologists and is already making significant advances in the areas of biomechanics, locomotion, neuromechanics and sensorimotor control. Here, we provide an introduction and overview of robotics-inspired biology, describe two case studies and suggest several directions for the future of this exciting new research area. © 2018. Published by The Company of Biologists Ltd.

An automation-assisted generic approach for biological sample preparation and LC-MS/MS method validation.

PubMed

Zhang, Jie; Wei, Shimin; Ayres, David W; Smith, Harold T; Tse, Francis L S

2011-09-01

Although it is well known that automation can provide significant improvement in the efficiency of biological sample preparation in quantitative LC-MS/MS analysis, it has not been widely implemented in bioanalytical laboratories throughout the industry. This can be attributed to the lack of a sound strategy and practical procedures in working with robotic liquid-handling systems. Several comprehensive automation assisted procedures for biological sample preparation and method validation were developed and qualified using two types of Hamilton Microlab liquid-handling robots. The procedures developed were generic, user-friendly and covered the majority of steps involved in routine sample preparation and method validation. Generic automation procedures were established as a practical approach to widely implement automation into the routine bioanalysis of samples in support of drug-development programs.

Development of the biology card sorting task to measure conceptual expertise in biology.

PubMed

Smith, Julia I; Combs, Elijah D; Nagami, Paul H; Alto, Valerie M; Goh, Henry G; Gourdet, Muryam A A; Hough, Christina M; Nickell, Ashley E; Peer, Adrian G; Coley, John D; Tanner, Kimberly D

2013-01-01

There are widespread aspirations to focus undergraduate biology education on teaching students to think conceptually like biologists; however, there is a dearth of assessment tools designed to measure progress from novice to expert biological conceptual thinking. We present the development of a novel assessment tool, the Biology Card Sorting Task, designed to probe how individuals organize their conceptual knowledge of biology. While modeled on tasks from cognitive psychology, this task is unique in its design to test two hypothesized conceptual frameworks for the organization of biological knowledge: 1) a surface feature organization focused on organism type and 2) a deep feature organization focused on fundamental biological concepts. In this initial investigation of the Biology Card Sorting Task, each of six analytical measures showed statistically significant differences when used to compare the card sorting results of putative biological experts (biology faculty) and novices (non-biology major undergraduates). Consistently, biology faculty appeared to sort based on hypothesized deep features, while non-biology majors appeared to sort based on either surface features or nonhypothesized organizational frameworks. Results suggest that this novel task is robust in distinguishing populations of biology experts and biology novices and may be an adaptable tool for tracking emerging biology conceptual expertise.

Development of the Biology Card Sorting Task to Measure Conceptual Expertise in Biology

PubMed Central

Smith, Julia I.; Combs, Elijah D.; Nagami, Paul H.; Alto, Valerie M.; Goh, Henry G.; Gourdet, Muryam A. A.; Hough, Christina M.; Nickell, Ashley E.; Peer, Adrian G.; Coley, John D.; Tanner, Kimberly D.

2013-01-01

There are widespread aspirations to focus undergraduate biology education on teaching students to think conceptually like biologists; however, there is a dearth of assessment tools designed to measure progress from novice to expert biological conceptual thinking. We present the development of a novel assessment tool, the Biology Card Sorting Task, designed to probe how individuals organize their conceptual knowledge of biology. While modeled on tasks from cognitive psychology, this task is unique in its design to test two hypothesized conceptual frameworks for the organization of biological knowledge: 1) a surface feature organization focused on organism type and 2) a deep feature organization focused on fundamental biological concepts. In this initial investigation of the Biology Card Sorting Task, each of six analytical measures showed statistically significant differences when used to compare the card sorting results of putative biological experts (biology faculty) and novices (non–biology major undergraduates). Consistently, biology faculty appeared to sort based on hypothesized deep features, while non–biology majors appeared to sort based on either surface features or nonhypothesized organizational frameworks. Results suggest that this novel task is robust in distinguishing populations of biology experts and biology novices and may be an adaptable tool for tracking emerging biology conceptual expertise. PMID:24297290

Use of a validated algorithm to estimate the annual cost of effective biologic treatment for rheumatoid arthritis.

PubMed

Curtis, Jeffrey R; Schabert, Vernon F; Yeaw, Jason; Korn, Jonathan R; Quach, Caroleen; Harrison, David J; Yun, Huifeng; Joseph, George J; Collier, David

2014-08-01

To estimate biologic cost per effectively treated patient with rheumatoid arthritis (RA) using a claims-based algorithm for effectiveness. Patients with RA aged 18-63 years in the IMS PharMetrics Plus database were categorized as effectively treated if they met all six criteria: (1) a medication possession ratio ≥80% (subcutaneous) or at least as many infusions as specified in US labeling (intravenous); (2) no biologic dose increase; (3) no biologic switch; (4) no new non-biologic disease-modifying anti-rheumatic drug; (5) no new or increased oral glucocorticoid; and (6) ≤1 glucocorticoid injection. Biologic cost per effectively treated patient was defined as total cost of the index biologic (drug plus intravenous administration) divided by the number of patients categorized by the algorithm as effectively treated. Similar methods were used for the index biologic in the second year and for a second biologic after a switch. Rates that the index biologic was categorized as effective in the first year were 31.0% etanercept (2243/7247), 28.6% adalimumab (1426/4991), 28.6% abatacept (332/1160), 27.2% golimumab (71/261), and 20.2% infliximab (474/2352). Mean biologic cost per effectively treated patient, per the algorithm, was $50,141 etanercept, $53,386 golimumab, $56,942 adalimumab, $73,516 abatacept, and $114,089 infliximab. Biologic cost per effectively treated patient, using this algorithm, was lower for patients who continued the index biologic in the second year and higher after switching. When a claims-based algorithm was applied to a large commercial claims database, etanercept was categorized as the most effective and had the lowest estimated 1-year biologic cost per effectively treated patient. This proxy for effectiveness from claims databases was validated against a clinical effectiveness scale, but analyses of the second year or the year after a biologic switch were not included in the validation. Costs of other medications were not included in cost

Perceptions as Hypotheses

NASA Astrophysics Data System (ADS)

Gregory, R. L.

1980-07-01

Perceptions may be compared with hypotheses in science. The methods of acquiring scientific knowledge provide a working paradigm for investigating processes of perception. Much as the information channels of instruments, such as radio telescopes, transmit signals which are processed according to various assumptions to give useful data, so neural signals are processed to give data for perception. To understand perception, the signal codes and the stored knowledge or assumptions used for deriving perceptual hypotheses must be discovered. Systematic perceptual errors are important clues for appreciating signal channel limitations, and for discovering hypothesis-generating procedures. Although this distinction between `physiological' and `cognitive' aspects of perception may be logically clear, it is in practice surprisingly difficult to establish which are responsible even for clearly established phenomena such as the classical distortion illusions. Experimental results are presented, aimed at distinguishing between and discovering what happens when there is mismatch with the neural signal channel, and when neural signals are processed inappropriately for the current situation. This leads us to make some distinctions between perceptual and scientific hypotheses, which raise in a new form the problem: What are `objects'?

Preliminary testing of flow-ecology hypotheses developed for the GCP LCC region

USGS Publications Warehouse

Brewer, Shannon K.; Davis, Mary

2014-01-01

The Ecological Limits of Hydrological Alteration (ELOHA) framework calls for the development of flow-ecology hypotheses to support protection of the flow regime from ecologically harmful alteration due to human activities. As part of a larger instream flow project for the Gulf Coast Prairie Landscape Conservation Cooperative (GCP LCC), regional flow-ecology hypotheses were developed for fish, mussels, birds, and riparian vegetation (Davis and Brewer 20141). The objective of this study was to assess the usefulness of existing ecological and hydrological data to test these hypotheses or others that may be developed in the future. Several databases related to biological collections and hydrologic data from Oklahoma, Texas, and Louisiana were compiled. State fish-community data from Oklahoma and Louisiana were summarized and paired with existing USGS gage data having at least a 40-year period of record that could be separated into reference and current conditions for comparison. The objective of this study was not to conduct exhaustive analyses of these data, the hypotheses, or analyses interpretation, but rather to use these data to determine if existing data were adequate to statistically test the regional flow-ecology hypotheses. The regional flow-ecology hypotheses were developed for the GCP LCC by a committee chaired by Shannon Brewer and Mary Davis (Davis and Brewer 2014). Existing data were useful for informing the hypotheses and suggest support for some hypotheses, but also highlight the need for additional testing and development as some results contradicted hypotheses. Results presented here suggest existing data are adequate to support some flow-ecology hypotheses; however, lack of sampling effort reported with the fish collections and the need for ecoregion-specific analyses suggest more data would be beneficial to analyses in some ecoregions. Additional fish sampling data from Texas and Louisiana will be available for future analyses and may ameliorate

Testing multiple statistical hypotheses resulted in spurious associations: a study of astrological signs and health.

PubMed

Austin, Peter C; Mamdani, Muhammad M; Juurlink, David N; Hux, Janet E

2006-09-01

To illustrate how multiple hypotheses testing can produce associations with no clinical plausibility. We conducted a study of all 10,674,945 residents of Ontario aged between 18 and 100 years in 2000. Residents were randomly assigned to equally sized derivation and validation cohorts and classified according to their astrological sign. Using the derivation cohort, we searched through 223 of the most common diagnoses for hospitalization until we identified two for which subjects born under one astrological sign had a significantly higher probability of hospitalization compared to subjects born under the remaining signs combined (P<0.05). We tested these 24 associations in the independent validation cohort. Residents born under Leo had a higher probability of gastrointestinal hemorrhage (P=0.0447), while Sagittarians had a higher probability of humerus fracture (P=0.0123) compared to all other signs combined. After adjusting the significance level to account for multiple comparisons, none of the identified associations remained significant in either the derivation or validation cohort. Our analyses illustrate how the testing of multiple, non-prespecified hypotheses increases the likelihood of detecting implausible associations. Our findings have important implications for the analysis and interpretation of clinical studies.

Discovery-based studies of schistosome diversity stimulate new hypotheses about parasite biology

PubMed Central

Brant, Sara V.; Loker, Eric S.

2013-01-01

This review provides an update of ongoing efforts to expand our understanding of the diversity inherent within the Schistosomatidae, the parasites responsible for causing schistosomiasis and cercarial dermatitis. By revealing more of the species present, particularly among under-studied avian schistosomes, we gain increased understanding of patterns of schistosome diversification, and their abilities to colonize new hosts and habitats. Schistosomes reveal a surprising ability to switch into new snail and vertebrate host species, into new intra-host habitats, and may adopt novel body forms in the process. Often these changes are not associated with deep splits or long branches in their phylogeny, suggesting they are of relatively recent origin. Several hypotheses prompted by the new observations are discussed, helping to focus thinking on processes influencing not only schistosome diversification, but also their pathogenicity and abundance. PMID:23849836

A method to identify and analyze biological programs through automated reasoning

PubMed Central

Yordanov, Boyan; Dunn, Sara-Jane; Kugler, Hillel; Smith, Austin; Martello, Graziano; Emmott, Stephen

2016-01-01

Predictive biology is elusive because rigorous, data-constrained, mechanistic models of complex biological systems are difficult to derive and validate. Current approaches tend to construct and examine static interaction network models, which are descriptively rich, but often lack explanatory and predictive power, or dynamic models that can be simulated to reproduce known behavior. However, in such approaches implicit assumptions are introduced as typically only one mechanism is considered, and exhaustively investigating all scenarios is impractical using simulation. To address these limitations, we present a methodology based on automated formal reasoning, which permits the synthesis and analysis of the complete set of logical models consistent with experimental observations. We test hypotheses against all candidate models, and remove the need for simulation by characterizing and simultaneously analyzing all mechanistic explanations of observed behavior. Our methodology transforms knowledge of complex biological processes from sets of possible interactions and experimental observations to precise, predictive biological programs governing cell function. PMID:27668090

Chemometric and biological validation of a capillary electrophoresis metabolomic experiment of Schistosoma mansoni infection in mice.

PubMed

Garcia-Perez, Isabel; Angulo, Santiago; Utzinger, Jürg; Holmes, Elaine; Legido-Quigley, Cristina; Barbas, Coral

2010-07-01

Metabonomic and metabolomic studies are increasingly utilized for biomarker identification in different fields, including biology of infection. The confluence of improved analytical platforms and the availability of powerful multivariate analysis software have rendered the multiparameter profiles generated by these omics platforms a user-friendly alternative to the established analysis methods where the quality and practice of a procedure is well defined. However, unlike traditional assays, validation methods for these new multivariate profiling tools have yet to be established. We propose a validation for models obtained by CE fingerprinting of urine from mice infected with the blood fluke Schistosoma mansoni. We have analysed urine samples from two sets of mice infected in an inter-laboratory experiment where different infection methods and animal husbandry procedures were employed in order to establish the core biological response to a S. mansoni infection. CE data were analysed using principal component analysis. Validation of the scores consisted of permutation scrambling (100 repetitions) and a manual validation method, using a third of the samples (not included in the model) as a test or prediction set. The validation yielded 100% specificity and 100% sensitivity, demonstrating the robustness of these models with respect to deciphering metabolic perturbations in the mouse due to a S. mansoni infection. A total of 20 metabolites across the two experiments were identified that significantly discriminated between S. mansoni-infected and noninfected control samples. Only one of these metabolites, allantoin, was identified as manifesting different behaviour in the two experiments. This study shows the reproducibility of CE-based metabolic profiling methods for disease characterization and screening and highlights the importance of much needed validation strategies in the emerging field of metabolomics.

Impact of biology knowledge on the conservation and management of large pelagic sharks.

PubMed

Yokoi, Hiroki; Ijima, Hirotaka; Ohshimo, Seiji; Yokawa, Kotaro

2017-09-06

Population growth rate, which depends on several biological parameters, is valuable information for the conservation and management of pelagic sharks, such as blue and shortfin mako sharks. However, reported biological parameters for estimating the population growth rates of these sharks differ by sex and display large variability. To estimate the appropriate population growth rate and clarify relationships between growth rate and relevant biological parameters, we developed a two-sex age-structured matrix population model and estimated the population growth rate using combinations of biological parameters. We addressed elasticity analysis and clarified the population growth rate sensitivity. For the blue shark, the estimated median population growth rate was 0.384 with a range of minimum and maximum values of 0.195-0.533, whereas those values of the shortfin mako shark were 0.102 and 0.007-0.318, respectively. The maturity age of male sharks had the largest impact for blue sharks, whereas that of female sharks had the largest impact for shortfin mako sharks. Hypotheses for the survival process of sharks also had a large impact on the population growth rate estimation. Both shark maturity age and survival rate were based on ageing validation data, indicating the importance of validating the quality of these data for the conservation and management of large pelagic sharks.

A novel cell culture model as a tool for forensic biology experiments and validations.

PubMed

Feine, Ilan; Shpitzen, Moshe; Roth, Jonathan; Gafny, Ron

2016-09-01

To improve and advance DNA forensic casework investigation outcomes, extensive field and laboratory experiments are carried out in a broad range of relevant branches, such as touch and trace DNA, secondary DNA transfer and contamination confinement. Moreover, the development of new forensic tools, for example new sampling appliances, by commercial companies requires ongoing validation and assessment by forensic scientists. A frequent challenge in these kinds of experiments and validations is the lack of a stable, reproducible and flexible biological reference material. As a possible solution, we present here a cell culture model based on skin-derived human dermal fibroblasts. Cultured cells were harvested, quantified and dried on glass slides. These slides were used in adhesive tape-lifting experiments and tests of DNA crossover confinement by UV irradiation. The use of this model enabled a simple and concise comparison between four adhesive tapes, as well as a straightforward demonstration of the effect of UV irradiation intensities on DNA quantity and degradation. In conclusion, we believe this model has great potential to serve as an efficient research tool in forensic biology. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Implementing the Science Assessment Standards: Developing and validating a set of laboratory assessment tasks in high school biology

NASA Astrophysics Data System (ADS)

Saha, Gouranga Chandra

Very often a number of factors, especially time, space and money, deter many science educators from using inquiry-based, hands-on, laboratory practical tasks as alternative assessment instruments in science. A shortage of valid inquiry-based laboratory tasks for high school biology has been cited. Driven by this need, this study addressed the following three research questions: (1) How can laboratory-based performance tasks be designed and developed that are doable by students for whom they are designed/written? (2) Do student responses to the laboratory-based performance tasks validly represent at least some of the intended process skills that new biology learning goals want students to acquire? (3) Are the laboratory-based performance tasks psychometrically consistent as individual tasks and as a set? To answer these questions, three tasks were used from the six biology tasks initially designed and developed by an iterative process of trial testing. Analyses of data from 224 students showed that performance-based laboratory tasks that are doable by all students require careful and iterative process of development. Although the students demonstrated more skill in performing than planning and reasoning, their performances at the item level were very poor for some items. Possible reasons for the poor performances have been discussed and suggestions on how to remediate the deficiencies have been made. Empirical evidences for validity and reliability of the instrument have been presented both from the classical and the modern validity criteria point of view. Limitations of the study have been identified. Finally implications of the study and directions for further research have been discussed.

Gene Function Hypotheses for the Campylobacter jejuni Glycome Generated by a Logic-Based Approach

PubMed Central

Sternberg, Michael J.E.; Tamaddoni-Nezhad, Alireza; Lesk, Victor I.; Kay, Emily; Hitchen, Paul G.; Cootes, Adrian; van Alphen, Lieke B.; Lamoureux, Marc P.; Jarrell, Harold C.; Rawlings, Christopher J.; Soo, Evelyn C.; Szymanski, Christine M.; Dell, Anne; Wren, Brendan W.; Muggleton, Stephen H.

2013-01-01

Increasingly, experimental data on biological systems are obtained from several sources and computational approaches are required to integrate this information and derive models for the function of the system. Here, we demonstrate the power of a logic-based machine learning approach to propose hypotheses for gene function integrating information from two diverse experimental approaches. Specifically, we use inductive logic programming that automatically proposes hypotheses explaining the empirical data with respect to logically encoded background knowledge. We study the capsular polysaccharide biosynthetic pathway of the major human gastrointestinal pathogen Campylobacter jejuni. We consider several key steps in the formation of capsular polysaccharide consisting of 15 genes of which 8 have assigned function, and we explore the extent to which functions can be hypothesised for the remaining 7. Two sources of experimental data provide the information for learning—the results of knockout experiments on the genes involved in capsule formation and the absence/presence of capsule genes in a multitude of strains of different serotypes. The machine learning uses the pathway structure as background knowledge. We propose assignments of specific genes to five previously unassigned reaction steps. For four of these steps, there was an unambiguous optimal assignment of gene to reaction, and to the fifth, there were three candidate genes. Several of these assignments were consistent with additional experimental results. We therefore show that the logic-based methodology provides a robust strategy to integrate results from different experimental approaches and propose hypotheses for the behaviour of a biological system. PMID:23103756

Gene function hypotheses for the Campylobacter jejuni glycome generated by a logic-based approach.

PubMed

Sternberg, Michael J E; Tamaddoni-Nezhad, Alireza; Lesk, Victor I; Kay, Emily; Hitchen, Paul G; Cootes, Adrian; van Alphen, Lieke B; Lamoureux, Marc P; Jarrell, Harold C; Rawlings, Christopher J; Soo, Evelyn C; Szymanski, Christine M; Dell, Anne; Wren, Brendan W; Muggleton, Stephen H

2013-01-09

Increasingly, experimental data on biological systems are obtained from several sources and computational approaches are required to integrate this information and derive models for the function of the system. Here, we demonstrate the power of a logic-based machine learning approach to propose hypotheses for gene function integrating information from two diverse experimental approaches. Specifically, we use inductive logic programming that automatically proposes hypotheses explaining the empirical data with respect to logically encoded background knowledge. We study the capsular polysaccharide biosynthetic pathway of the major human gastrointestinal pathogen Campylobacter jejuni. We consider several key steps in the formation of capsular polysaccharide consisting of 15 genes of which 8 have assigned function, and we explore the extent to which functions can be hypothesised for the remaining 7. Two sources of experimental data provide the information for learning-the results of knockout experiments on the genes involved in capsule formation and the absence/presence of capsule genes in a multitude of strains of different serotypes. The machine learning uses the pathway structure as background knowledge. We propose assignments of specific genes to five previously unassigned reaction steps. For four of these steps, there was an unambiguous optimal assignment of gene to reaction, and to the fifth, there were three candidate genes. Several of these assignments were consistent with additional experimental results. We therefore show that the logic-based methodology provides a robust strategy to integrate results from different experimental approaches and propose hypotheses for the behaviour of a biological system. Copyright © 2012 Elsevier Ltd. All rights reserved.

Biology of Consciousness

PubMed Central

Edelman, Gerald M.; Gally, Joseph A.; Baars, Bernard J.

2010-01-01

The Dynamic Core and Global Workspace hypotheses were independently put forward to provide mechanistic and biologically plausible accounts of how brains generate conscious mental content. The Dynamic Core proposes that reentrant neural activity in the thalamocortical system gives rise to conscious experience. Global Workspace reconciles the limited capacity of momentary conscious content with the vast repertoire of long-term memory. In this paper we show the close relationship between the two hypotheses. This relationship allows for a strictly biological account of phenomenal experience and subjectivity that is consistent with mounting experimental evidence. We examine the constraints on causal analyses of consciousness and suggest that there is now sufficient evidence to consider the design and construction of a conscious artifact. PMID:21713129

An integrative systems biology approach to understanding pulmonary diseases.

PubMed

Auffray, Charles; Adcock, Ian M; Chung, Kian Fan; Djukanovic, Ratko; Pison, Christophe; Sterk, Peter J

2010-06-01

Chronic inflammatory pulmonary diseases such as COPD and asthma are highly prevalent and associated with a major health burden worldwide. Despite a wealth of biologic and clinical information on normal and pathologic airway structure and function, the primary causes and mechanisms of disease remain to a large extent unknown, preventing the development of more efficient diagnosis and treatment. We propose to overcome these limitations through an integrative systems biology research strategy designed to identify the functional and regulatory pathways that play central roles in respiratory pathophysiology, starting with severe asthma. This approach relies on global genome, transcriptome, proteome, and metabolome data sets collected in cross-sectional patient cohorts with high-throughput measurement platforms and integrated with biologic and clinical data to inform predictive multiscale models ranging from the molecular to the organ levels. Working hypotheses formulated on the mechanisms and pathways involved in various disease states are tested through perturbation experiments using model simulation combined with targeted and global technologies in cellular and animal models. The responses observed are compared with those predicted by the initial models, which are refined to account better for the results. Novel perturbation experiments are designed and tested both computationally and experimentally to arbitrate between competing hypotheses. The process is iterated until the derived knowledge allows a better classification and subphenotyping of severe asthma using complex biomarkers, which will facilitate the development of novel diagnostic and therapeutic interventions targeting multiple components of the molecular and cellular pathways involved. This can be tested and validated in prospective clinical trials.

Applicability of computational systems biology in toxicology.

PubMed

Kongsbak, Kristine; Hadrup, Niels; Audouze, Karine; Vinggaard, Anne Marie

2014-07-01

Systems biology as a research field has emerged within the last few decades. Systems biology, often defined as the antithesis of the reductionist approach, integrates information about individual components of a biological system. In integrative systems biology, large data sets from various sources and databases are used to model and predict effects of chemicals on, for instance, human health. In toxicology, computational systems biology enables identification of important pathways and molecules from large data sets; tasks that can be extremely laborious when performed by a classical literature search. However, computational systems biology offers more advantages than providing a high-throughput literature search; it may form the basis for establishment of hypotheses on potential links between environmental chemicals and human diseases, which would be very difficult to establish experimentally. This is possible due to the existence of comprehensive databases containing information on networks of human protein-protein interactions and protein-disease associations. Experimentally determined targets of the specific chemical of interest can be fed into these networks to obtain additional information that can be used to establish hypotheses on links between the chemical and human diseases. Such information can also be applied for designing more intelligent animal/cell experiments that can test the established hypotheses. Here, we describe how and why to apply an integrative systems biology method in the hypothesis-generating phase of toxicological research. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Deformational plagiocephaly in normal infants: a systematic review of causes and hypotheses.

PubMed

De Bock, Freia; Braun, Volker; Renz-Polster, Herbert

2017-06-01

Deformational plagiocephaly (DP) is one of the most prevalent abnormal findings in infants and a frequent reason for parents to seek paediatric advice. To systematically review the literature and identify evidence and hypotheses on the aetiology and determinants of DP in otherwise healthy infants. Systematic keyword search in all major biomedical databases to identify peer-reviewed publications reporting (a) empirical research or (b) hypotheses on the aetiology of DP in healthy, term infants. 3150 studies published between 1985 and 2016 and containing relevant keywords were screened. In a two-pronged approach, results were summarised separately for the body of empirical work (22 studies) and the body of hypotheses (110 articles). Only a few empirical studies have examined risk factors in non-selected patient populations on a higher grade methodological level. The most commonly reported risk factors were: male gender, supine sleep position, limited neck rotation or preference in head position, first-born child, lower level of activity and lack of tummy time. Agreement between empirical studies was poor for most exposures, including supine sleep position, tummy time and use of car seats. The articles reporting hypotheses on the aetiology of DP cover a wide field of environmental and biological factors, but include little suggestions as to the potential influence of the everyday care environment of the baby. The evidence on the aetiology of DP is fragmentary and heterogeneous. In addition, factors possibly relevant to the development of DP have not been appreciated in the scientific discussion. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Fostering synergy between cell biology and systems biology.

PubMed

Eddy, James A; Funk, Cory C; Price, Nathan D

2015-08-01

In the shared pursuit of elucidating detailed mechanisms of cell function, systems biology presents a natural complement to ongoing efforts in cell biology. Systems biology aims to characterize biological systems through integrated and quantitative modeling of cellular information. The process of model building and analysis provides value through synthesizing and cataloging information about cells and molecules, predicting mechanisms and identifying generalizable themes, generating hypotheses and guiding experimental design, and highlighting knowledge gaps and refining understanding. In turn, incorporating domain expertise and experimental data is crucial for building towards whole cell models. An iterative cycle of interaction between cell and systems biologists advances the goals of both fields and establishes a framework for mechanistic understanding of the genome-to-phenome relationship. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Homework Stress: Construct Validation of a Measure

ERIC Educational Resources Information Center

Katz, Idit; Buzukashvili, Tamara; Feingold, Liat

2012-01-01

This article presents 2 studies aimed at validating a measure of stress experienced by children and parents around the issue of homework, applying Benson's program of validation (Benson, 1998). Study 1 provides external validity of the measure by supporting hypothesized relations between stress around homework and students' and parents' positive…

Seed dormancy and germination—emerging mechanisms and new hypotheses

PubMed Central

Nonogaki, Hiroyuki

2014-01-01

Seed dormancy has played a significant role in adaptation and evolution of seed plants. While its biological significance is clear, molecular mechanisms underlying seed dormancy induction, maintenance and alleviation still remain elusive. Intensive efforts have been made to investigate gibberellin and abscisic acid metabolism in seeds, which greatly contributed to the current understanding of seed dormancy mechanisms. Other mechanisms, which might be independent of hormones, or specific to the seed dormancy pathway, are also emerging from genetic analysis of “seed dormancy mutants.” These studies suggest that chromatin remodeling through histone ubiquitination, methylation and acetylation, which could lead to transcription elongation or gene silencing, may play a significant role in seed dormancy regulation. Small interfering RNA and/or long non-coding RNA might be a trigger of epigenetic changes at the seed dormancy or germination loci, such as DELAY OF GERMINATION1. While new mechanisms are emerging from genetic studies of seed dormancy, novel hypotheses are also generated from seed germination studies with high throughput gene expression analysis. Recent studies on tissue-specific gene expression in tomato and Arabidopsis seeds, which suggested possible “mechanosensing” in the regulatory mechanisms, advanced our understanding of embryo-endosperm interaction and have potential to re-draw the traditional hypotheses or integrate them into a comprehensive scheme. The progress in basic seed science will enable knowledge translation, another frontier of research to be expanded for food and fuel production. PMID:24904627

Current hypotheses for the evolution of sex and recombination.

PubMed

Hartfield, Matthew; Keightley, Peter D

2012-06-01

The evolution of sex is one of the most important and controversial problems in evolutionary biology. Although sex is almost universal in higher animals and plants, its inherent costs have made its maintenance difficult to explain. The most famous of these is the twofold cost of males, which can greatly reduce the fecundity of a sexual population, compared to a population of asexual females. Over the past century, multiple hypotheses, along with experimental evidence to support these, have been put forward to explain widespread costly sex. In this review, we outline some of the most prominent theories, along with the experimental and observational evidence supporting these. Historically, there have been 4 classes of theories: the ability of sex to fix multiple novel advantageous mutants (Fisher-Muller hypothesis); sex as a mechanism to stop the build-up of deleterious mutations in finite populations (Muller's ratchet); recombination creating novel genotypes that can resist infection by parasites (Red Queen hypothesis); and the ability of sex to purge bad genomes if deleterious mutations act synergistically (mutational deterministic hypothesis). Current theoretical and experimental evidence seems to favor the hypothesis that sex breaks down selection interference between new mutants, or it acts as a mechanism to shuffle genotypes in order to repel parasitic invasion. However, there is still a need to collect more data from natural populations and experimental studies, which can be used to test different hypotheses. © 2012 ISZS, Blackwell Publishing and IOZ/CAS.

Predictive hypotheses are ineffectual in resolving complex biochemical systems.

PubMed

Fry, Michael

2018-03-20

Scientific hypotheses may either predict particular unknown facts or accommodate previously-known data. Although affirmed predictions are intuitively more rewarding than accommodations of established facts, opinions divide whether predictive hypotheses are also epistemically superior to accommodation hypotheses. This paper examines the contribution of predictive hypotheses to discoveries of several bio-molecular systems. Having all the necessary elements of the system known beforehand, an abstract predictive hypothesis of semiconservative mode of DNA replication was successfully affirmed. However, in defining the genetic code whose biochemical basis was unclear, hypotheses were only partially effective and supplementary experimentation was required for its conclusive definition. Markedly, hypotheses were entirely inept in predicting workings of complex systems that included unknown elements. Thus, hypotheses did not predict the existence and function of mRNA, the multiple unidentified components of the protein biosynthesis machinery, or the manifold unknown constituents of the ubiquitin-proteasome system of protein breakdown. Consequently, because of their inability to envision unknown entities, predictive hypotheses did not contribute to the elucidation of cation theories remained the sole instrument to explain complex bio-molecular systems, the philosophical question of alleged advantage of predictive over accommodative hypotheses became inconsequential.

Linking Microbiota to Human Diseases: A Systems Biology Perspective.

PubMed

Wu, Hao; Tremaroli, Valentina; Bäckhed, Fredrik

2015-12-01

The human gut microbiota encompasses a densely populated ecosystem that provides essential functions for host development, immune maturation, and metabolism. Alterations to the gut microbiota have been observed in numerous diseases, including human metabolic diseases such as obesity, type 2 diabetes (T2D), and irritable bowel syndrome, and some animal experiments have suggested causality. However, few studies have validated causality in humans and the underlying mechanisms remain largely to be elucidated. We discuss how systems biology approaches combined with new experimental technologies may disentangle some of the mechanistic details in the complex interactions of diet, microbiota, and host metabolism and may provide testable hypotheses for advancing our current understanding of human-microbiota interaction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy.

PubMed

Hollyman, Daniel; Stefanski, Jolanta; Przybylowski, Mark; Bartido, Shirley; Borquez-Ojeda, Oriana; Taylor, Clare; Yeh, Raymond; Capacio, Vanessa; Olszewska, Malgorzata; Hosey, James; Sadelain, Michel; Brentjens, Renier J; Rivière, Isabelle

2009-01-01

On the basis of promising preclinical data demonstrating the eradication of systemic B-cell malignancies by CD19-targeted T lymphocytes in vivo in severe combined immunodeficient-beige mouse models, we are launching phase I clinical trials in patients with chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia. We present here the validation of the bioprocess which we developed for the production and expansion of clinical grade autologous T cells derived from patients with CLL. We demonstrate that T cells genetically modified with a replication-defective gammaretroviral vector derived from the Moloney murine leukemia virus encoding a chimeric antigen receptor (CAR) targeted to CD19 (1928z) can be expanded with Dynabeads CD3/CD28. This bioprocess allows us to generate clinical doses of 1928z+ T cells in approximately 2 to 3 weeks in a large-scale semiclosed culture system using the Wave Bioreactor. These 1928z+ T cells remain biologically functional not only in vitro but also in severe combined immunodeficient-beige mice bearing disseminated tumors. The validation requirements in terms of T-cell expansion, T-cell transduction with the 1928z CAR, biologic activity, quality control testing, and release criteria were met for all 4 validation runs using apheresis products from patients with CLL. Additionally, after expansion of the T cells, the diversity of the skewed Vbeta T-cell receptor repertoire was significantly restored. This validated process will be used in phase I clinical trials in patients with chemorefractory CLL and in patients with relapsed acute lymphoblastic leukemia. It can also be adapted for other clinical trials involving the expansion and transduction of patient or donor T cells using any CAR or T-cell receptor.

Hypothesizing dopaminergic genetic antecedents in schizophrenia and substance seeking behavior.

PubMed

Blum, Kenneth; Oscar-Berman, Marlene; Badgaiyan, Rajendra D; Palomo, Tomas; Gold, Mark S

2014-05-01

The dopamine system has been implicated in both substance use disorder (SUD) and schizophrenia. A recent meta-analysis suggests that A1 allele of the DRD2 gene imposes genetic risk for SUD, especially alcoholism and has been implicated in Reward Deficiency Syndrome (RDS). We hypothesize that dopamine D2 receptor (DRD2) gene Taq1 A2 allele is associated with a subtype of non-SUD schizophrenics and as such may act as a putative protective agent against the development of addiction to alcohol or other drugs of abuse. Schizophrenics with SUD may be carriers of the DRD2 Taq1 A1 allele, and/or other RDS reward polymorphisms and have hypodopaminergic reward function. One plausible mechanism for alcohol seeking in schizophrenics with SUD, based on previous research, may be a deficiency of gamma type endorphins that has been linked to schizophrenic type psychosis. We also propose that alcohol seeking behavior in schizophrenics, may serve as a physiological self-healing process linked to the increased function of the gamma endorphins, thereby reducing abnormal dopaminergic activity at the nucleus accumbens (NAc). These hypotheses warrant further investigation and cautious interpretation. We, therefore, encourage research involving neuroimaging, genome wide association studies (GWAS), and epigenetic investigation into the relationship between neurogenetics and systems biology to unravel the role of dopamine in psychiatric illness and SUD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hypothesizing Dopaminergic Genetic Antecedents in Schizophrenia and Substance Seeking Behavior

PubMed Central

Blum, Kenneth; Oscar-Berman, Marlene; Badgaiyan, Rajendra; Palomo, Tomas; Gold, Mark S.

2014-01-01

The dopamine system has been implicated in both substance use disorder (SUD) and schizophrenia. A recent meta- analysis suggests that A1 allele of the DRD2 gene imposes genetic risk for SUD, especially alcoholism and has been implicated in Reward Deficiency Syndrome (RDS). We hypothesize that dopamine D2 receptor (DRD2) gene Taq1 A2 allele is associated with a subtype of non- SUD schizophrenics and as such may act as a putative protective agent against the development of addiction to alcohol or other drugs of abuse. Schizophrenics with SUD may be carriers of the DRD2 Taq1 A1 allele, and/or other RDS reward polymorphisms and have hypodopaminergic reward function. One plausible mechanism for alcohol seeking in schizophrenics with SUD, based on previous research, may be a deficiency of gamma type endorphins that has been linked to schizophrenic type psychosis.. We also propose that alcohol seeking behavior in schizophrenics, may serve as a physiological self-healing process linked to the increased function of the gamma endorphins, thereby reducing abnormal dopaminergic activity at the nucleus accumbens (NAc). These hypotheses warrant further investigation and cautious interpretation. We, therefore, encourage research involving neuroimaging, genome wide association studies (GWAS), and epigenetic investigation into the relationship between neurogenetics and systems biology to unravel the role of dopamine in psychiatric illness and SUD. PMID:24636783

The validation of forensic DNA extraction systems to utilize soil contaminated biological evidence.

PubMed

Kasu, Mohaimin; Shires, Karen

2015-07-01

The production of full DNA profiles from biological evidence found in soil has a high failure rate due largely to the inhibitory substance humic acid (HA). Abundant in various natural soils, HA co-extracts with DNA during extraction and inhibits DNA profiling by binding to the molecular components of the genotyping assay. To successfully utilize traces of soil contaminated evidence, such as that found at many murder and rape crime scenes in South Africa, a reliable HA removal extraction system would often be selected based on previous validation studies. However, for many standard forensic DNA extraction systems, peer-reviewed publications detailing the efficacy on soil evidence is either lacking or is incomplete. Consequently, these sample types are often not collected or fail to yield suitable DNA material due to the use of unsuitable methodology. The aim of this study was to validate the common forensic DNA collection and extraction systems used in South Africa, namely DNA IQ, FTA elute and Nucleosave for processing blood and saliva contaminated with HA. A forensic appropriate volume of biological evidence was spiked with HA (0, 0.5, 1.5 and 2.5 mg/ml) and processed through each extraction protocol for the evaluation of HA removal using QPCR and STR-genotyping. The DNA IQ magnetic bead system effectively removed HA from highly contaminated blood and saliva, and generated consistently acceptable STR profiles from both artificially spiked samples and crude soil samples. This system is highly recommended for use on soil-contaminated evidence over the cellulose card-based systems currently being preferentially used for DNA sample collection. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A review of active learning approaches to experimental design for uncovering biological networks

PubMed Central

2017-01-01

Various types of biological knowledge describe networks of interactions among elementary entities. For example, transcriptional regulatory networks consist of interactions among proteins and genes. Current knowledge about the exact structure of such networks is highly incomplete, and laboratory experiments that manipulate the entities involved are conducted to test hypotheses about these networks. In recent years, various automated approaches to experiment selection have been proposed. Many of these approaches can be characterized as active machine learning algorithms. Active learning is an iterative process in which a model is learned from data, hypotheses are generated from the model to propose informative experiments, and the experiments yield new data that is used to update the model. This review describes the various models, experiment selection strategies, validation techniques, and successful applications described in the literature; highlights common themes and notable distinctions among methods; and identifies likely directions of future research and open problems in the area. PMID:28570593

Evaluation of Metabolic and Synaptic Dysfunction Hypotheses of Alzheimer's Disease (AD): A Meta-Analysis of CSF Markers.

PubMed

Manyevitch, Roni; Protas, Matthew; Scarpiello, Sean; Deliso, Marisa; Bass, Brittany; Nanajian, Anthony; Chang, Matthew; Thompson, Stefani M; Khoury, Neil; Gonnella, Rachel; Trotz, Margit; Moore, D Blaine; Harms, Emily; Perry, George; Clunes, Lucy; Ortiz, Angelica; Friedrich, Jan O; Murray, Ian V J

2018-01-01

Alzheimer's disease (AD) is currently incurable and a majority of investigational drugs have failed clinical trials. One explanation for this failure may be the invalidity of hypotheses focusing on amyloid to explain AD pathogenesis. Recently, hypotheses which are centered on synaptic and metabolic dysfunction are increasingly implicated in AD. Evaluate AD hypotheses by comparing neurotransmitter and metabolite marker concentrations in normal versus AD CSF. Meta-analysis allows for statistical comparison of pooled, existing cerebrospinal fluid (CSF) marker data extracted from multiple publications, to obtain a more reliable estimate of concentrations. This method also provides a unique opportunity to rapidly validate AD hypotheses using the resulting CSF concentration data. Hubmed, Pubmed and Google Scholar were comprehensively searched for published English articles, without date restrictions, for the keywords "AD", "CSF", and "human" plus markers selected for synaptic and metabolic pathways. Synaptic markers were acetylcholine, gamma-aminobutyric acid (GABA), glutamine, and glycine. Metabolic markers were glutathione, glucose, lactate, pyruvate, and 8 other amino acids. Only studies that measured markers in AD and controls (Ctl), provided means, standard errors/deviation, and subject numbers were included. Data were extracted by six authors and reviewed by two others for accuracy. Data were pooled using ratio of means (RoM of AD/Ctl) and random effects meta-analysis using Cochrane Collaboration's Review Manager software. Of the 435 identified publications, after exclusion and removal of duplicates, 35 articles were included comprising a total of 605 AD patients and 585 controls. The following markers of synaptic and metabolic pathways were significantly changed in AD/controls: acetylcholine (RoM 0.36, 95% CI 0.24-0.53, p<0.00001), GABA (0.74, 0.58-0.94, p<0.01), pyruvate (0.48, 0.24-0.94, p=0.03), glutathione (1.11, 1.01- 1.21, p=0.03), alanine (1.10, 0

Reconciling Mechanistic Hypotheses About Rhizosphere Priming

NASA Astrophysics Data System (ADS)

Cheng, W.

2016-12-01

Rhizosphere priming on soil organic matter decomposition has emerged as a key mechanism regulating biogeochemnical cycling of carbon, nitrogen and other elements from local to global scales. The level of the rhizosphere priming effect on decomposition rates can be comparable to the levels of controls from soil temperature and moisture conditions. However, our understanding on mechanisms responsible for rhizosphere priming remains rudimentary and controversial. The following individual hypotheses have been postulated in the published literature: (1) microbial activation, (2) microbial community succession, (3) aggregate turnover, (4) nitrogen mining, (5) nutrient competition, (6) preferential substrate utilization, and (7) drying-rewetting. Meshing these hypotheses with existing empirical evidence tends to support a general conclusion: each of these 7 hypotheses represents an aspect of the overall rhizosphere priming complex while the relative contribution by each individual aspect varies depending on the actual plant-soil conditions across time and space.

Validation of Radio Frequency Telemetry Concept in the Presence of Biological Tissue-Like Stratified Media

NASA Technical Reports Server (NTRS)

Miranda, Felix A.; Simons, Rainee N.; Haal, David G.

2004-01-01

In this paper we discuss a novel radio frequency (RF) telemetry concept for biomedical applications. The concept consists of a miniaturized spiral inductor/antenna for bio-MEMS sensors and an external pick-up antenna integrated into a handheld device. The measured relative signal strength in the presence of biological phantoms ranged from 5.9 to 7.5 dB for antenna separations of 5 and 10 cm. These relative signal strengths are easily measurable, therefore validating the RF telemetry concept for biomedical applications.

Genetics and biology of pancreatic ductal adenocarcinoma

PubMed Central

Ying, Haoqiang; Dey, Prasenjit; Yao, Wantong; Kimmelman, Alec C.; Draetta, Giulio F.; Maitra, Anirban; DePinho, Ronald A.

2016-01-01

With 5-year survival rates remaining constant at 6% and rising incidences associated with an epidemic in obesity and metabolic syndrome, pancreatic ductal adenocarcinoma (PDAC) is on track to become the second most common cause of cancer-related deaths by 2030. The high mortality rate of PDAC stems primarily from the lack of early diagnosis and ineffective treatment for advanced tumors. During the past decade, the comprehensive atlas of genomic alterations, the prominence of specific pathways, the preclinical validation of such emerging targets, sophisticated preclinical model systems, and the molecular classification of PDAC into specific disease subtypes have all converged to illuminate drug discovery programs with clearer clinical path hypotheses. A deeper understanding of cancer cell biology, particularly altered cancer cell metabolism and impaired DNA repair processes, is providing novel therapeutic strategies that show strong preclinical activity. Elucidation of tumor biology principles, most notably a deeper understanding of the complexity of immune regulation in the tumor microenvironment, has provided an exciting framework to reawaken the immune system to attack PDAC cancer cells. While the long road of translation lies ahead, the path to meaningful clinical progress has never been clearer to improve PDAC patient survival. PMID:26883357

A systems biology-led insight into the role of the proteome in neurodegenerative diseases.

PubMed

Fasano, Mauro; Monti, Chiara; Alberio, Tiziana

2016-09-01

Multifactorial disorders are the result of nonlinear interactions of several factors; therefore, a reductionist approach does not appear to be appropriate. Proteomics is a global approach that can be efficiently used to investigate pathogenetic mechanisms of neurodegenerative diseases. Here, we report a general introduction about the systems biology approach and mechanistic insights recently obtained by over-representation analysis of proteomics data of cellular and animal models of Alzheimer's disease, Parkinson's disease and other neurodegenerative disorders, as well as of affected human tissues. Expert commentary: As an inductive method, proteomics is based on unbiased observations that further require validation of generated hypotheses. Pathway databases and over-representation analysis tools allow researchers to assign an expectation value to pathogenetic mechanisms linked to neurodegenerative diseases. The systems biology approach based on omics data may be the key to unravel the complex mechanisms underlying neurodegeneration.

Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy

PubMed Central

Hollyman, Daniel; Stefanski, Jolanta; Przybylowski, Mark; Bartido, Shirley; Borquez-Ojeda, Oriana; Taylor, Clare; Yeh, Raymond; Capacio, Vanessa; Olszewska, Malgorzata; Hosey, James; Sadelain, Michel; Brentjens, Renier J.; Rivière, Isabelle

2009-01-01

Summary Based on promising pre-clinical data demonstrating the eradication of systemic B cell malignancies by CD19-targeted T lymphocytes in vivo in SCID beige mouse models, we are launching Phase 1 clinical trials in patients with chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL). We present here the validation of the bioprocess we developed for the production and expansion of clinical grade autologous T cells derived from patients with CLL. We demonstrate that T cells genetically modified with a replication-defective gammaretroviral vector derived from the Moloney murine leukemia virus encoding a chimeric antigen receptor (CAR) targeted to CD19 (1928z) can be expanded with Dynabeads® CD3/CD28. This bioprocess allows us to generate clinical doses of 1928z+ T cells in approximately 2 to 3 weeks in a large-scale semi-closed culture system using the Wave bioreactor. These 1928z+ T cells remain biologically functional not only in vitro but also in SCID beige mice bearing disseminated tumors. The validation requirements in terms of T cell expansion, T cell transduction with the 1928z CAR, biological activity, quality control testing and release criteria were met for all four validation runs using apheresis products from patients with CLL. Additionally, following expansion of the T cells, the diversity of the skewed Vβ T cell receptor repertoire was significantly restored. This validated process will be used in phase I clinical trials in patients with chemo-refractory CLL and in patients with relapsed ALL. It can also be adapted for other clinical trials involving the expansion and transduction of patient or donor T cells using any chimeric antigen receptor or T cell receptor. PMID:19238016

Plant reproduction systems in microgravity: experimental data and hypotheses

NASA Astrophysics Data System (ADS)

Kordyum, E. L.

Elucidation of the possibilities for higher plants to realize complete ontogenesis, from seed to seed, and to propagate by seeds in microgravity, is a fundamental task of space biology connected with the working of the CELSS program. At present, there are results of only 6 spaceflight experiments with Arabidopsis thaliana, an ephemeral plant which will flower and fruit in orbit. Morphogenesis of generative organs occurs normally in microgravity, but unlike the ground control, buds and flowers mainly contain sterile elements of the androecium and gynoecium which degenerate at different stages of development in microgravity. Cytological peculiarities of male and female sterility in microgravity are similar to those occurring naturally during sexual differentiation. Many of the seed formed in microgravity are: 1) nutritional deficiency, 2) insufficient light, 3) intensification of the influence of the above-mentioned factors by microgravity, 4) disturbances of a hormonal nature, and 5) the absence of pollination and fertilization. Possible ways for testing these hypotheses and obtaining viable seeds in microgravity are discussed.

Evaluation of Metabolic and Synaptic Dysfunction Hypotheses of Alzheimer’s Disease (AD): A Meta-Analysis of CSF Markers

PubMed Central

Manyevitch, Roni; Protas, Matthew; Scarpiello, Sean; Deliso, Marisa; Bass, Brittany; Nanajian, Anthony; Chang, Matthew; Thompson, Stefani M.; Khoury, Neil; Gonnella, Rachel; Trotz, Margit; Moore, D. Blaine; Harms, Emily; Perry, George; Clunes, Lucy; Ortiz, Angélica; Friedrich, Jan O.; Murray, Ian V.J.

2018-01-01

Background: Alzheimer’s disease (AD) is currently incurable and a majority of investigational drugs have failed clinical trials. One explanation for this failure may be the invalidity of hypotheses focus-ing on amyloid to explain AD pathogenesis. Recently, hypotheses which are centered on synaptic and met-abolic dysfunction are increasingly implicated in AD. Objective: Evaluate AD hypotheses by comparing neurotransmitter and metabolite marker concentrations in normal versus AD CSF. Methods: Meta-analysis allows for statistical comparison of pooled, existing cerebrospinal fluid (CSF) marker data extracted from multiple publications, to obtain a more reliable estimate of concentrations. This method also provides a unique opportunity to rapidly validate AD hypotheses using the resulting CSF con-centration data. Hubmed, Pubmed and Google Scholar were comprehensively searched for published Eng-lish articles, without date restrictions, for the keywords “AD”, “CSF”, and “human” plus markers selected for synaptic and metabolic pathways. Synaptic markers were acetylcholine, gamma-aminobutyric acid (GABA), glutamine, and glycine. Metabolic markers were glutathione, glucose, lactate, pyruvate, and 8 other amino acids. Only studies that measured markers in AD and controls (Ctl), provided means, standard er-rors/deviation, and subject numbers were included. Data were extracted by six authors and reviewed by two others for accuracy. Data were pooled using ratio of means (RoM of AD/Ctl) and random effects meta-analysis using Cochrane Collaboration’s Review Manager software. Results: Of the 435 identified publications, after exclusion and removal of duplicates, 35 articles were in-cluded comprising a total of 605 AD patients and 585 controls. The following markers of synaptic and met-abolic pathways were significantly changed in AD/controls: acetylcholine (RoM 0.36, 95% CI 0.24-0.53, p<0.00001), GABA (0.74, 0.58-0.94, p<0.01), pyruvate (0.48, 0.24-0.94, p=0

A survey of etiologic hypotheses among testicular cancer researchers.

PubMed

Stang, A; Trabert, B; Rusner, C; Poole, C; Almstrup, K; Rajpert-De Meyts, E; McGlynn, K A

2015-01-01

Basic research results can provide new ideas and hypotheses to be examined in epidemiological studies. We conducted a survey among testicular cancer researchers on hypotheses concerning the etiology of this malignancy. All researchers on the mailing list of Copenhagen Testis Cancer Workshops and corresponding authors of PubMed-indexed articles identified by the search term 'testicular cancer' and published within 10 years (in total 2750 recipients) were invited to respond to an e-mail-based survey. Participants of the 8th Copenhagen Testis Cancer Workshop in May 2014 were subsequently asked to rate the plausibility of the suggested etiologic hypotheses on a scale of 1 (very implausible) to 10 (very plausible). This report describes the methodology of the survey, the score distributions by individual hypotheses, hypothesis group, and the participants' major research fields, and discuss the hypotheses that scored as most plausible. We also present plans for improving the survey that may be repeated at a next international meeting of experts in testicular cancer. Overall 52 of 99 (53%) registered participants of the 8th Copenhagen Testis Cancer Workshop submitted the plausibility rating form. Fourteen of 27 hypotheses were related to exposures during pregnancy. Hypotheses with the highest mean plausibility ratings were either related to pre-natal exposures or exposures that might have an effect during pregnancy and in post-natal life. The results of the survey may be helpful for triggering more specific etiologic hypotheses that include factors related to endocrine disruption, DNA damage, inflammation, and nutrition during pregnancy. The survey results may stimulate a multidisciplinary discussion about new etiologic hypotheses of testicular cancer. Published 2014. This article is a U. S. Government work and is in the public domain in the USA.

A method for validating Rent's rule for technological and biological networks.

PubMed

Alcalde Cuesta, Fernando; González Sequeiros, Pablo; Lozano Rojo, Álvaro

2017-07-14

Rent's rule is empirical power law introduced in an effort to describe and optimize the wiring complexity of computer logic graphs. It is known that brain and neuronal networks also obey Rent's rule, which is consistent with the idea that wiring costs play a fundamental role in brain evolution and development. Here we propose a method to validate this power law for a certain range of network partitions. This method is based on the bifurcation phenomenon that appears when the network is subjected to random alterations preserving its degree distribution. It has been tested on a set of VLSI circuits and real networks, including biological and technological ones. We also analyzed the effect of different types of random alterations on the Rentian scaling in order to test the influence of the degree distribution. There are network architectures quite sensitive to these randomization procedures with significant increases in the values of the Rent exponents.

Teaching the Fluctuation Test "In Silico" by Using Mutate: A Program to Distinguish between the Adaptive and Spontaneous Mutation Hypotheses

ERIC Educational Resources Information Center

Carvajal-Rodriguez, Antonio

2012-01-01

Mutate is a program developed for teaching purposes to impart a virtual laboratory class for undergraduate students of Genetics in Biology. The program emulates the so-called fluctuation test whose aim is to distinguish between spontaneous and adaptive mutation hypotheses in bacteria. The plan is to train students in certain key multidisciplinary…

A statistical approach to selecting and confirming validation targets in -omics experiments

PubMed Central

2012-01-01

Background Genomic technologies are, by their very nature, designed for hypothesis generation. In some cases, the hypotheses that are generated require that genome scientists confirm findings about specific genes or proteins. But one major advantage of high-throughput technology is that global genetic, genomic, transcriptomic, and proteomic behaviors can be observed. Manual confirmation of every statistically significant genomic result is prohibitively expensive. This has led researchers in genomics to adopt the strategy of confirming only a handful of the most statistically significant results, a small subset chosen for biological interest, or a small random subset. But there is no standard approach for selecting and quantitatively evaluating validation targets. Results Here we present a new statistical method and approach for statistically validating lists of significant results based on confirming only a small random sample. We apply our statistical method to show that the usual practice of confirming only the most statistically significant results does not statistically validate result lists. We analyze an extensively validated RNA-sequencing experiment to show that confirming a random subset can statistically validate entire lists of significant results. Finally, we analyze multiple publicly available microarray experiments to show that statistically validating random samples can both (i) provide evidence to confirm long gene lists and (ii) save thousands of dollars and hundreds of hours of labor over manual validation of each significant result. Conclusions For high-throughput -omics studies, statistical validation is a cost-effective and statistically valid approach to confirming lists of significant results. PMID:22738145

The use of analysis of variance procedures in biological studies

USGS Publications Warehouse

Williams, B.K.

1987-01-01

The analysis of variance (ANOVA) is widely used in biological studies, yet there remains considerable confusion among researchers about the interpretation of hypotheses being tested. Ambiguities arise when statistical designs are unbalanced, and in particular when not all combinations of design factors are represented in the data. This paper clarifies the relationship among hypothesis testing, statistical modelling and computing procedures in ANOVA for unbalanced data. A simple two-factor fixed effects design is used to illustrate three common parametrizations for ANOVA models, and some associations among these parametrizations are developed. Biologically meaningful hypotheses for main effects and interactions are given in terms of each parametrization, and procedures for testing the hypotheses are described. The standard statistical computing procedures in ANOVA are given along with their corresponding hypotheses. Throughout the development unbalanced designs are assumed and attention is given to problems that arise with missing cells.

Risk assessment paradigm: an opportunity for rationalizing the choice of biological indicator during the validation of isolator biodecontamination cycles.

PubMed

Sansoë-Bourget, Emmanuelle

2006-01-01

The use of biological indicators is integral to the validation of isolator decontamination cycles. The difficulty in setting up the initial qualification of the decontamination cycle and especially the successive requalifications may vary as a function of not only the installation to be qualified and the sterilizing agent and generator used, but also as a function of the type of biological indicators used. In this article the manufacture and control of biological indicators are analyzed using the hazard analysis and critical control point (HACCP) approach. The HACCP risk analysis, which must take into account the application of the isolator being qualified or requalified, is an efficient simplification tool for performing a decontamination cycle using either hydrogen peroxide gas or peracetic acid in a reliable, economical, and reproducible way.

Formulating appropriate statistical hypotheses for treatment comparison in clinical trial design and analysis.

PubMed

Huang, Peng; Ou, Ai-hua; Piantadosi, Steven; Tan, Ming

2014-11-01

We discuss the problem of properly defining treatment superiority through the specification of hypotheses in clinical trials. The need to precisely define the notion of superiority in a one-sided hypothesis test problem has been well recognized by many authors. Ideally designed null and alternative hypotheses should correspond to a partition of all possible scenarios of underlying true probability models P={P(ω):ω∈Ω} such that the alternative hypothesis Ha={P(ω):ω∈Ωa} can be inferred upon the rejection of null hypothesis Ho={P(ω):ω∈Ω(o)} However, in many cases, tests are carried out and recommendations are made without a precise definition of superiority or a specification of alternative hypothesis. Moreover, in some applications, the union of probability models specified by the chosen null and alternative hypothesis does not constitute a completed model collection P (i.e., H(o)∪H(a) is smaller than P). This not only imposes a strong non-validated assumption of the underlying true models, but also leads to different superiority claims depending on which test is used instead of scientific plausibility. Different ways to partition P fro testing treatment superiority often have different implications on sample size, power, and significance in both efficacy and comparative effectiveness trial design. Such differences are often overlooked. We provide a theoretical framework for evaluating the statistical properties of different specification of superiority in typical hypothesis testing. This can help investigators to select proper hypotheses for treatment comparison inclinical trial design. Copyright © 2014 Elsevier Inc. All rights reserved.

Not just a theory--the utility of mathematical models in evolutionary biology.

PubMed

Servedio, Maria R; Brandvain, Yaniv; Dhole, Sumit; Fitzpatrick, Courtney L; Goldberg, Emma E; Stern, Caitlin A; Van Cleve, Jeremy; Yeh, D Justin

2014-12-01

Progress in science often begins with verbal hypotheses meant to explain why certain biological phenomena exist. An important purpose of mathematical models in evolutionary research, as in many other fields, is to act as “proof-of-concept” tests of the logic in verbal explanations, paralleling the way in which empirical data are used to test hypotheses. Because not all subfields of biology use mathematics for this purpose, misunderstandings of the function of proof-of-concept modeling are common. In the hope of facilitating communication, we discuss the role of proof-of-concept modeling in evolutionary biology.

Empirical agreement in model validation.

PubMed

Jebeile, Julie; Barberousse, Anouk

2016-04-01

Empirical agreement is often used as an important criterion when assessing the validity of scientific models. However, it is by no means a sufficient criterion as a model can be so adjusted as to fit available data even though it is based on hypotheses whose plausibility is known to be questionable. Our aim in this paper is to investigate into the uses of empirical agreement within the process of model validation. Copyright © 2015 Elsevier Ltd. All rights reserved.

About hypotheses and paradigms: exploring the Discreetness-Chance Paradigm.

PubMed

Kaellis, Eugene

2006-01-01

Hypotheses generally conform to paradigms which, over time, change, usually tardily, after they have become increasingly difficult to sustain under the impact of non-conforming evidence and alternative hypotheses, but more important, when they no longer are comfortably ensconced in the surrounding social-economic-political-cultural milieu. It is asserted that this milieu is the most important factor in shaping scientific theorizing. Some examples are cited: the rejection of the evidence that the world orbits around the sun (suspected by Pythagoras) in favor of centuries-long firm adherence to the Ptolemaic geocentric system; the early acceptance of Natural Selection in spite of its tautological essence and only conjectural supporting evidence, because it justified contemporaneous social-political ideologies as typified by, e.g., Spencer and Malthus. Economic, social, and cultural factors are cited as providing the ground, i.e., ideational substrate, for what is cited as the Discreetness-Chance Paradigm (DCP), that has increasingly dominated physics, biology, and medicine for over a century and which invokes small, discrete packets of energy/matter (quanta, genes, microorganisms, aberrant cells) functioning within an environment of statistical, not determined, causality. There is speculation on a possible paradigmatic shift from the DCP, which has fostered the proliferation, parallel with ("splitting") taxonomy, of alleged individual disease entities, their diagnoses, and, when available, their specific remedies, something particularly prominent in, e.g., psychiatry's Diagnostic and Statistical Manual, a codified compendium of alleged mental and behavioral disorders, but evident in any textbook of diagnosis and treatment of physical ailments. This presumed paradigm shift may be reflected in Western medicine, presently increasingly empirical and atomized, towards a growing acceptance of a more generalized, subject-oriented, approach to health and disease, a non

Testing hypotheses for differences between linear regression lines

Treesearch

Stanley J. Zarnoch

2009-01-01

Five hypotheses are identified for testing differences between simple linear regression lines. The distinctions between these hypotheses are based on a priori assumptions and illustrated with full and reduced models. The contrast approach is presented as an easy and complete method for testing for overall differences between the regressions and for making pairwise...

Recommendations for the validation of cell-based assays used for the detection of neutralizing antibody immune responses elicited against biological therapeutics.

PubMed

Gupta, Shalini; Devanarayan, Viswanath; Finco, Deborah; Gunn, George R; Kirshner, Susan; Richards, Susan; Rup, Bonita; Song, An; Subramanyam, Meena

2011-07-15

The administration of biological therapeutics may result in the development of anti-drug antibodies (ADAs) in treated subjects. In some cases, ADA responses may result in the loss of therapeutic efficacy due to the formation of neutralizing ADAs (NAbs). An important characteristic of anti-drug NAbs is their direct inhibitory effect on the pharmacological activity of the therapeutic. Neutralizing antibody responses are of particular concern for biologic products with an endogenous homolog whose activity can be potentially dampened or completely inhibited by the NAbs leading to an autoimmune-type deficiency syndrome. Therefore, it is important that ADAs are detected and characterized appropriately using sensitive and reliable methods. The design, development and optimization of cell-based assays used for detection of NAbs have been published previously by Gupta et al. 2007 [1]. This paper provides recommendations on best practices for the validation of cell-based NAb assay and suggested validation parameters based on the experience of the authors. Copyright © 2011 Elsevier B.V. All rights reserved.

Keeping an eye on the biology

USDA-ARS?s Scientific Manuscript database

Genomic data sets offer remarkable opportunities for students to explore hypotheses and generate original findings without expensive laboratory equipment and supplies, scaling the benefits of traditional undergraduate research experiences to classrooms. Yet, biology students can become frustrated wi...

The Use of Bayesian Methods for Uncertainty Analysis and Evaluation of Biological Hypotheses in PBPK Models

EPA Science Inventory

Physiologically based pharmacokinetic (PBPK) models are compartmental models that describe the uptake and distribution of drugs and chemicals throughout the body. They can be structured so that model parameters (i.e., physiological and chemical-specific) reflect biological charac...

Hypotheses about the psychological benefits of horses.

PubMed

Kendall, Elizabeth; Maujean, Annick; Pepping, Christopher A; Wright, John J

2014-01-01

In the last few decades, therapeutic horse-riding has become recognized as a progressive form of therapy, particularly for people with disabilities. Although there is a substantial amount of literature that supports the physical benefit of therapeutic riding, only anecdotal evidence exists in relation to its psychological benefits. The purpose of this article is to develop hypotheses about the mechanisms by which therapeutic riding might have a beneficial psychological effect. These hypotheses can then be tested, leading to a more detailed knowledge base. PsychINFO, MEDLINE, PROQUEST, Scopus, Web of Science, and CINAHL. Data sources were searched for studies that (a) were related to the psychological effects of therapeutic horse-riding, (b) focused exclusively on therapeutic horse-riding, (c) described, explicitly or implicitly, the mechanism by which therapeutic riding had a beneficial psychological effect. Studies were limited to those published between 2008 and 2012. Data were extracted by two authors independently. Thirty articles met the inclusion criteria. Three potential hypotheses emerged from the literature, namely, (1) the psychological benefits of therapeutic riding are actually unrelated to the horse, (2) the horse provides a particularly positive context within which psychological gains are facilitated, and (3) the horse itself has specific therapeutic qualities that bring about unique changes not otherwise likely to occur. The challenge for researchers in this area is to design studies that adequately test these competing hypotheses. Copyright © 2014 Elsevier Inc. All rights reserved.

Discovery informatics in biological and biomedical sciences: research challenges and opportunities.

PubMed

Honavar, Vasant

2015-01-01

New discoveries in biological, biomedical and health sciences are increasingly being driven by our ability to acquire, share, integrate and analyze, and construct and simulate predictive models of biological systems. While much attention has focused on automating routine aspects of management and analysis of "big data", realizing the full potential of "big data" to accelerate discovery calls for automating many other aspects of the scientific process that have so far largely resisted automation: identifying gaps in the current state of knowledge; generating and prioritizing questions; designing studies; designing, prioritizing, planning, and executing experiments; interpreting results; forming hypotheses; drawing conclusions; replicating studies; validating claims; documenting studies; communicating results; reviewing results; and integrating results into the larger body of knowledge in a discipline. Against this background, the PSB workshop on Discovery Informatics in Biological and Biomedical Sciences explores the opportunities and challenges of automating discovery or assisting humans in discovery through advances (i) Understanding, formalization, and information processing accounts of, the entire scientific process; (ii) Design, development, and evaluation of the computational artifacts (representations, processes) that embody such understanding; and (iii) Application of the resulting artifacts and systems to advance science (by augmenting individual or collective human efforts, or by fully automating science).

Cancer risks near nuclear facilities: the importance of research design and explicit study hypotheses.

PubMed

Wing, Steve; Richardson, David B; Hoffmann, Wolfgang

2011-04-01

In April 2010, the U.S. Nuclear Regulatory Commission asked the National Academy of Sciences to update a 1990 study of cancer risks near nuclear facilities. Prior research on this topic has suffered from problems in hypothesis formulation and research design. We review epidemiologic principles used in studies of generic exposure-response associations and in studies of specific sources of exposure. We then describe logical problems with assumptions, formation of testable hypotheses, and interpretation of evidence in previous research on cancer risks near nuclear facilities. Advancement of knowledge about cancer risks near nuclear facilities depends on testing specific hypotheses grounded in physical and biological mechanisms of exposure and susceptibility while considering sample size and ability to adequately quantify exposure, ascertain cancer cases, and evaluate plausible confounders. Next steps in advancing knowledge about cancer risks near nuclear facilities require studies of childhood cancer incidence, focus on in utero and early childhood exposures, use of specific geographic information, and consideration of pathways for transport and uptake of radionuclides. Studies of cancer mortality among adults, cancers with long latencies, large geographic zones, and populations that reside at large distances from nuclear facilities are better suited for public relations than for scientific purposes.

Evaluation of Criterion Validity for Scales with Congeneric Measures

ERIC Educational Resources Information Center

Raykov, Tenko

2007-01-01

A method for estimating criterion validity of scales with homogeneous components is outlined. It accomplishes point and interval estimation of interrelationship indices between composite scores and criterion variables and is useful for testing hypotheses about criterion validity of measurement instruments. The method can also be used with missing…

Identifying World Views Projected by Science Teaching Materials: A Case Study Using Pepper's WORLD HYPOTHESES to Analyze a Biology Textbook.

ERIC Educational Resources Information Center

Kilbourn, Brent

The purpose of this study is to develop and demonstrate the use of a conceptual framework for assessing the potential of "world view" as a concept for understanding important issues in science education. The framework is based on Stephen C. Pepper's treatment of six world hypotheses (animism, mysticism, formism, mechansim, contextualism, and…

Teaching Rival Hypotheses in Experimental Psychology.

ERIC Educational Resources Information Center

Howard, George S.; Engelhardt, Jean L.

1984-01-01

Students critiqued research contained in the book "Rival Hypotheses" (Huck and Sandler, 1979), which contains studies dealing with knowledge claims of practical importance, e.g., the evidence that saccharine causes cancer. (RM)

Finite element analysis of dental implants with validation: to what extent can we expect the model to predict biological phenomena? A literature review and proposal for classification of a validation process.

PubMed

Chang, Yuanhan; Tambe, Abhijit Anil; Maeda, Yoshinobu; Wada, Masahiro; Gonda, Tomoya

2018-03-08

A literature review of finite element analysis (FEA) studies of dental implants with their model validation process was performed to establish the criteria for evaluating validation methods with respect to their similarity to biological behavior. An electronic literature search of PubMed was conducted up to January 2017 using the Medical Subject Headings "dental implants" and "finite element analysis." After accessing the full texts, the context of each article was searched using the words "valid" and "validation" and articles in which these words appeared were read to determine whether they met the inclusion criteria for the review. Of 601 articles published from 1997 to 2016, 48 that met the eligibility criteria were selected. The articles were categorized according to their validation method as follows: in vivo experiments in humans (n = 1) and other animals (n = 3), model experiments (n = 32), others' clinical data and past literature (n = 9), and other software (n = 2). Validation techniques with a high level of sufficiency and efficiency are still rare in FEA studies of dental implants. High-level validation, especially using in vivo experiments tied to an accurate finite element method, needs to become an established part of FEA studies. The recognition of a validation process should be considered when judging the practicality of an FEA study.

Studying Biological Responses to Global Change in Atmospheric Oxygen

PubMed Central

Powell, Frank L.

2010-01-01

A popular book recently hypothesized that change in atmospheric oxygen over geological time is the most important physical factor in the evolution of many fundamental characteristics of modern terrestrial animals. This hypothesis is generated primarily using fossil data but the present paper considers how modern experimental biology can be used to test it. Comparative physiology and experimental evolution clearly show that changes in atmospheric O2 over the ages had the potential to drive evolution, assuming the physiological O2-sensitivity of animals today is similar to the past. Established methods, such as phylogenetically independent contrasts, as well new approaches, such as adding environmental history to phylogenetic analyses or modeling interactions between environmental stresses and biological responses with different rate constants, may be useful for testing (disproving) hypotheses about biological adaptations to changes in atmospheric O2. PMID:20385257

25 Low-Cost Biology Investigations.

ERIC Educational Resources Information Center

Beller, Joel

This book is a compilation of biology labs that are safe, simple, dependable, economical, and diverse. Some of the 25 investigations contained within this book involve organisms that are free for the taking and returned to the environment unharmed following the investigations. Students gain experience in making observations, forming hypotheses,…

Validation through Understanding Test-Taking Strategies: An Illustration With the CELPIP-General Reading Pilot Test Using Structural Equation Modeling

ERIC Educational Resources Information Center

Wu, Amery D.; Stone, Jake E.

2016-01-01

This article explores an approach for test score validation that examines test takers' strategies for taking a reading comprehension test. The authors formulated three working hypotheses about score validity pertaining to three types of test-taking strategy (comprehending meaning, test management, and test-wiseness). These hypotheses were…

Covariance hypotheses for LANDSAT data

NASA Technical Reports Server (NTRS)

Decell, H. P.; Peters, C.

1983-01-01

Two covariance hypotheses are considered for LANDSAT data acquired by sampling fields, one an autoregressive covariance structure and the other the hypothesis of exchangeability. A minimum entropy approximation of the first structure by the second is derived and shown to have desirable properties for incorporation into a mixture density estimation procedure. Results of a rough test of the exchangeability hypothesis are presented.

New hypotheses regarding the Danish health puzzle.

PubMed

Bakah, May; Raphael, Dennis

2017-12-01

Nordic welfare states have achieved admirable population health profiles as a result of public policies that provide economic and social security across the life course. Denmark has been an exception to this rule, as its life expectancies and infant mortality rates since the mid-1970s have lagged behind the other Nordic nations and, in the case of life expectancy, behind most Organisation for Economic Co-operation and Development nations. In this review paper, we identify a number of new hypotheses for why this may be the case. These hypotheses concern the health effects of neo-liberal restructuring of the economy and its institutions, the institution of flexi-security in Denmark's labour market and the influence of Denmark's tobacco and alcohol industries. Also of note is that Denmark experienced higher unemployment rates during its initial period of health stagnation, as well as its treatment of non-Western immigrants and high wealth inequality and, until recently, the fact that Denmark did not systematically address the issue of health inequalities. These hypotheses may serve as covering explanations for the usually provided accounts of elevated behavioural risks and psychosocial stress as being responsible for Denmark's health profile.

Integrating cell biology and proteomic approaches in plants.

PubMed

Takáč, Tomáš; Šamajová, Olga; Šamaj, Jozef

2017-10-03

Significant improvements of protein extraction, separation, mass spectrometry and bioinformatics nurtured advancements of proteomics during the past years. The usefulness of proteomics in the investigation of biological problems can be enhanced by integration with other experimental methods from cell biology, genetics, biochemistry, pharmacology, molecular biology and other omics approaches including transcriptomics and metabolomics. This review aims to summarize current trends integrating cell biology and proteomics in plant science. Cell biology approaches are most frequently used in proteomic studies investigating subcellular and developmental proteomes, however, they were also employed in proteomic studies exploring abiotic and biotic stress responses, vesicular transport, cytoskeleton and protein posttranslational modifications. They are used either for detailed cellular or ultrastructural characterization of the object subjected to proteomic study, validation of proteomic results or to expand proteomic data. In this respect, a broad spectrum of methods is employed to support proteomic studies including ultrastructural electron microscopy studies, histochemical staining, immunochemical localization, in vivo imaging of fluorescently tagged proteins and visualization of protein-protein interactions. Thus, cell biological observations on fixed or living cell compartments, cells, tissues and organs are feasible, and in some cases fundamental for the validation and complementation of proteomic data. Validation of proteomic data by independent experimental methods requires development of new complementary approaches. Benefits of cell biology methods and techniques are not sufficiently highlighted in current proteomic studies. This encouraged us to review most popular cell biology methods used in proteomic studies and to evaluate their relevance and potential for proteomic data validation and enrichment of purely proteomic analyses. We also provide examples of

Introducing First-Year Medical Students to Early Diagnostic Hypotheses

ERIC Educational Resources Information Center

Taylor, P. J.; And Others

1978-01-01

A method of instruction in gynecology is described that encouraged the formulation of early diagnostic hypotheses, an important part of clinical problem-solving. Students were given a set of clinical clues to help them make broad diagnostic hypotheses. Student ability, results, and student perceptions of the course are provided. (Author/LBH)

The revelation effect: A meta-analytic test of hypotheses.

PubMed

Aßfalg, André; Bernstein, Daniel M; Hockley, William

2017-12-01

Judgments can depend on the activity directly preceding them. An example is the revelation effect whereby participants are more likely to claim that a stimulus is familiar after a preceding task, such as solving an anagram, than without a preceding task. We test conflicting predictions of four revelation-effect hypotheses in a meta-analysis of 26 years of revelation-effect research. The hypotheses' predictions refer to three subject areas: (1) the basis of judgments that are subject to the revelation effect (recollection vs. familiarity vs. fluency), (2) the degree of similarity between the task and test item, and (3) the difficulty of the preceding task. We use a hierarchical multivariate meta-analysis to account for dependent effect sizes and variance in experimental procedures. We test the revelation-effect hypotheses with a model selection procedure, where each model corresponds to a prediction of a revelation-effect hypothesis. We further quantify the amount of evidence for one model compared to another with Bayes factors. The results of this analysis suggest that none of the extant revelation-effect hypotheses can fully account for the data. The general vagueness of revelation-effect hypotheses and the scarcity of data were the major limiting factors in our analyses, emphasizing the need for formalized theories and further research into the puzzling revelation effect.

Validation of an entirely in vitro approach for rapid prototyping of DNA regulatory elements for synthetic biology

PubMed Central

Chappell, James; Jensen, Kirsten; Freemont, Paul S.

2013-01-01

A bottleneck in our capacity to rationally and predictably engineer biological systems is the limited number of well-characterized genetic elements from which to build. Current characterization methods are tied to measurements in living systems, the transformation and culturing of which are inherently time-consuming. To address this, we have validated a completely in vitro approach for the characterization of DNA regulatory elements using Escherichia coli extract cell-free systems. Importantly, we demonstrate that characterization in cell-free systems correlates and is reflective of performance in vivo for the most frequently used DNA regulatory elements. Moreover, we devise a rapid and completely in vitro method to generate DNA templates for cell-free systems, bypassing the need for DNA template generation and amplification from living cells. This in vitro approach is significantly quicker than current characterization methods and is amenable to high-throughput techniques, providing a valuable tool for rapidly prototyping libraries of DNA regulatory elements for synthetic biology. PMID:23371936

Review of stochastic hybrid systems with applications in biological systems modeling and analysis.

PubMed

Li, Xiangfang; Omotere, Oluwaseyi; Qian, Lijun; Dougherty, Edward R

2017-12-01

Stochastic hybrid systems (SHS) have attracted a lot of research interests in recent years. In this paper, we review some of the recent applications of SHS to biological systems modeling and analysis. Due to the nature of molecular interactions, many biological processes can be conveniently described as a mixture of continuous and discrete phenomena employing SHS models. With the advancement of SHS theory, it is expected that insights can be obtained about biological processes such as drug effects on gene regulation. Furthermore, combining with advanced experimental methods, in silico simulations using SHS modeling techniques can be carried out for massive and rapid verification or falsification of biological hypotheses. The hope is to substitute costly and time-consuming in vitro or in vivo experiments or provide guidance for those experiments and generate better hypotheses.

Cancer Risks near Nuclear Facilities: The Importance of Research Design and Explicit Study Hypotheses

PubMed Central

Wing, Steve; Richardson, David B.; Hoffmann, Wolfgang

2011-01-01

Background In April 2010, the U.S. Nuclear Regulatory Commission asked the National Academy of Sciences to update a 1990 study of cancer risks near nuclear facilities. Prior research on this topic has suffered from problems in hypothesis formulation and research design. Objectives We review epidemiologic principles used in studies of generic exposure–response associations and in studies of specific sources of exposure. We then describe logical problems with assumptions, formation of testable hypotheses, and interpretation of evidence in previous research on cancer risks near nuclear facilities. Discussion Advancement of knowledge about cancer risks near nuclear facilities depends on testing specific hypotheses grounded in physical and biological mechanisms of exposure and susceptibility while considering sample size and ability to adequately quantify exposure, ascertain cancer cases, and evaluate plausible confounders. Conclusions Next steps in advancing knowledge about cancer risks near nuclear facilities require studies of childhood cancer incidence, focus on in utero and early childhood exposures, use of specific geographic information, and consideration of pathways for transport and uptake of radionuclides. Studies of cancer mortality among adults, cancers with long latencies, large geographic zones, and populations that reside at large distances from nuclear facilities are better suited for public relations than for scientific purposes. PMID:21147606

Revisiting the environmental Kuznets curve and pollution haven hypotheses: MIKTA sample.

PubMed

Bakirtas, Ibrahim; Cetin, Mumin Atalay

2017-08-01

This study aims to examine the validity of the environmental Kuznets curve (EKC) and pollution haven hypotheses in Mexico, Indonesia, South Korea, Turkey, and Australia (MIKTA) countries from 1982 to 2011 by using a panel vector auto regressive (PVAR) model. Empirical findings imply that the EKC hypothesis is rejected by the MIKTA sample. However, PVAR estimations reveal Granger causality from income level, foreign direct investment (FDI) inward, and energy consumption to CO 2 emissions. Orthogonalized impulse-response functions are derived from PVAR estimations. According to the analysis results, the response of CO 2 emissions to a shock on FDI is positive. These results assert that FDI has a detrimental effect on environmental quality in MIKTA countries which means the pollution haven hypothesis is confirmed by the MIKTA sample. Therefore, MIKTA countries should revise their current economic growth plans to provide sustainable development and also re-organize their legal infrastructure to induce usage of renewable energy sources.

Topic modeling for cluster analysis of large biological and medical datasets

PubMed Central

2014-01-01

Background The big data moniker is nowhere better deserved than to describe the ever-increasing prodigiousness and complexity of biological and medical datasets. New methods are needed to generate and test hypotheses, foster biological interpretation, and build validated predictors. Although multivariate techniques such as cluster analysis may allow researchers to identify groups, or clusters, of related variables, the accuracies and effectiveness of traditional clustering methods diminish for large and hyper dimensional datasets. Topic modeling is an active research field in machine learning and has been mainly used as an analytical tool to structure large textual corpora for data mining. Its ability to reduce high dimensionality to a small number of latent variables makes it suitable as a means for clustering or overcoming clustering difficulties in large biological and medical datasets. Results In this study, three topic model-derived clustering methods, highest probable topic assignment, feature selection and feature extraction, are proposed and tested on the cluster analysis of three large datasets: Salmonella pulsed-field gel electrophoresis (PFGE) dataset, lung cancer dataset, and breast cancer dataset, which represent various types of large biological or medical datasets. All three various methods are shown to improve the efficacy/effectiveness of clustering results on the three datasets in comparison to traditional methods. A preferable cluster analysis method emerged for each of the three datasets on the basis of replicating known biological truths. Conclusion Topic modeling could be advantageously applied to the large datasets of biological or medical research. The three proposed topic model-derived clustering methods, highest probable topic assignment, feature selection and feature extraction, yield clustering improvements for the three different data types. Clusters more efficaciously represent truthful groupings and subgroupings in the data than

Topic modeling for cluster analysis of large biological and medical datasets.

PubMed

Zhao, Weizhong; Zou, Wen; Chen, James J

2014-01-01

The big data moniker is nowhere better deserved than to describe the ever-increasing prodigiousness and complexity of biological and medical datasets. New methods are needed to generate and test hypotheses, foster biological interpretation, and build validated predictors. Although multivariate techniques such as cluster analysis may allow researchers to identify groups, or clusters, of related variables, the accuracies and effectiveness of traditional clustering methods diminish for large and hyper dimensional datasets. Topic modeling is an active research field in machine learning and has been mainly used as an analytical tool to structure large textual corpora for data mining. Its ability to reduce high dimensionality to a small number of latent variables makes it suitable as a means for clustering or overcoming clustering difficulties in large biological and medical datasets. In this study, three topic model-derived clustering methods, highest probable topic assignment, feature selection and feature extraction, are proposed and tested on the cluster analysis of three large datasets: Salmonella pulsed-field gel electrophoresis (PFGE) dataset, lung cancer dataset, and breast cancer dataset, which represent various types of large biological or medical datasets. All three various methods are shown to improve the efficacy/effectiveness of clustering results on the three datasets in comparison to traditional methods. A preferable cluster analysis method emerged for each of the three datasets on the basis of replicating known biological truths. Topic modeling could be advantageously applied to the large datasets of biological or medical research. The three proposed topic model-derived clustering methods, highest probable topic assignment, feature selection and feature extraction, yield clustering improvements for the three different data types. Clusters more efficaciously represent truthful groupings and subgroupings in the data than traditional methods, suggesting

Identification and validation of distinct biological phenotypes in patients with acute respiratory distress syndrome by cluster analysis.

PubMed

Bos, L D; Schouten, L R; van Vught, L A; Wiewel, M A; Ong, D S Y; Cremer, O; Artigas, A; Martin-Loeches, I; Hoogendijk, A J; van der Poll, T; Horn, J; Juffermans, N; Calfee, C S; Schultz, M J

2017-10-01

We hypothesised that patients with acute respiratory distress syndrome (ARDS) can be clustered based on concentrations of plasma biomarkers and that the thereby identified biological phenotypes are associated with mortality. Consecutive patients with ARDS were included in this prospective observational cohort study. Cluster analysis of 20 biomarkers of inflammation, coagulation and endothelial activation provided the phenotypes in a training cohort, not taking any outcome data into account. Logistic regression with backward selection was used to select the most predictive biomarkers, and these predicted phenotypes were validated in a separate cohort. Multivariable logistic regression was used to quantify the independent association with mortality. Two phenotypes were identified in 454 patients, which we named 'uninflamed' (N=218) and 'reactive' (N=236). A selection of four biomarkers (interleukin-6, interferon gamma, angiopoietin 1/2 and plasminogen activator inhibitor-1) could be used to accurately predict the phenotype in the training cohort (area under the receiver operating characteristics curve: 0.98, 95% CI 0.97 to 0.99). Mortality rates were 15.6% and 36.4% (p<0.001) in the training cohort and 13.6% and 37.5% (p<0.001) in the validation cohort (N=207). The 'reactive phenotype' was independent from confounders associated with intensive care unit mortality (training cohort: OR 1.13, 95% CI 1.04 to 1.23; validation cohort: OR 1.18, 95% CI 1.06 to 1.31). Patients with ARDS can be clustered into two biological phenotypes, with different mortality rates. Four biomarkers can be used to predict the phenotype with high accuracy. The phenotypes were very similar to those found in cohorts derived from randomised controlled trials, and these results may improve patient selection for future clinical trials targeting host response in patients with ARDS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please

Revising Segmentation Hypotheses in First and Second Language Listening

ERIC Educational Resources Information Center

Field, John

2008-01-01

Any on-line processing that takes place while an utterance is unfolding is extremely tentative, with early-formed hypotheses having to be revised as the utterance proceeds. The hypotheses in question relate not only to the words that are present but also to where their boundaries fall. This study examines how first and second language listeners…

Supporting cognition in systems biology analysis: findings on users' processes and design implications.

PubMed

Mirel, Barbara

2009-02-13

Current usability studies of bioinformatics tools suggest that tools for exploratory analysis support some tasks related to finding relationships of interest but not the deep causal insights necessary for formulating plausible and credible hypotheses. To better understand design requirements for gaining these causal insights in systems biology analyses a longitudinal field study of 15 biomedical researchers was conducted. Researchers interacted with the same protein-protein interaction tools to discover possible disease mechanisms for further experimentation. Findings reveal patterns in scientists' exploratory and explanatory analysis and reveal that tools positively supported a number of well-structured query and analysis tasks. But for several of scientists' more complex, higher order ways of knowing and reasoning the tools did not offer adequate support. Results show that for a better fit with scientists' cognition for exploratory analysis systems biology tools need to better match scientists' processes for validating, for making a transition from classification to model-based reasoning, and for engaging in causal mental modelling. As the next great frontier in bioinformatics usability, tool designs for exploratory systems biology analysis need to move beyond the successes already achieved in supporting formulaic query and analysis tasks and now reduce current mismatches with several of scientists' higher order analytical practices. The implications of results for tool designs are discussed.

Validation of a Fecal Glucocorticoid Assay to Assess Adrenocortical Activity in Meerkats Using Physiological and Biological Stimuli

PubMed Central

Heistermann, Michael; Santema, Peter; Dantzer, Ben; Mausbach, Jelena; Ganswindt, Andre; Manser, Marta B.

2016-01-01

In mammals, glucocorticoid (i.e. GC) levels have been associated with specific life-history stages and transitions, reproductive strategies, and a plethora of behaviors. Assessment of adrenocortical activity via measurement of glucocorticoid metabolites in feces (FGCM) has greatly facilitated data collection from wild animals, due to its non-invasive nature, and thus has become an established tool in behavioral ecology and conservation biology. The aim of our study was to validate a fecal glucocorticoid assay for assessing adrenocortical activity in meerkats (Suricata suricatta), by comparing the suitability of three GC enzyme immunoassays (corticosterone, 11β-hydroxyetiocholanolone and 11oxo-etiocholanolone) in detecting FGCM increases in adult males and females following a pharmacological challenge with adrenocorticotropic hormone (ACTH) and biological stimuli. In addition, we investigated the time course characterizing FGCM excretion, the effect of age, sex and time of day on FGCM levels and assessed the potential effects of soil contamination (sand) on FGCM patterns. Our results show that the group specific 11β-hydroxyetiocholanolone assay was most sensitive to FGCM alterations, detecting significant and most distinctive elevations in FGCM levels around 25 h after ACTH administration. We found no age and sex differences in basal FGCM or on peak response levels to ACTH, but a marked diurnal pattern, with FGCM levels being substantially higher in the morning than later during the day. Soil contamination did not significantly affect FGCM patterns. Our results emphasize the importance of conducting assay validations to characterize species-specific endocrine excretion patterns, a crucial step to all animal endocrinology studies using a non-invasive approach. PMID:27077741

Experimenting with Mathematical Biology

ERIC Educational Resources Information Center

Sanft, Rebecca; Walter, Anne

2016-01-01

St. Olaf College recently added a Mathematical Biology concentration to its curriculum. The core course, Mathematics of Biology, was redesigned to include a wet laboratory. The lab classes required students to collect data and implement the essential modeling techniques of formulation, implementation, validation, and analysis. The four labs…

Understanding Variables & Hypotheses in Scientific Research.

ERIC Educational Resources Information Center

Charters, W. W., Jr.

The hypothesis is the device scientists use to translate questions, theories, or proposed explanations into a form amenable to empirical research. This edition of W. W. Charter's treatise on clear, conceptual definitions and precise operational hypotheses, which was originally developed to assist students in educational policy and management…

Testing Pattern Hypotheses for Correlation Matrices

ERIC Educational Resources Information Center

McDonald, Roderick P.

1975-01-01

The treatment of covariance matrices given by McDonald (1974) can be readily modified to cover hypotheses prescribing zeros and equalities in the correlation matrix rather than the covariance matrix, still with the convenience of the closed-form Least Squares solution and the classical Newton method. (Author/RC)

NASA Biological Specimen Repository

NASA Technical Reports Server (NTRS)

Pietrzyk, Robert; McMonigal, K. A.; Sams, C. F.; Johnson, M. A.

2009-01-01

The NASA Biological Specimen Repository (NBSR) has been established to collect, process, annotate, store, and distribute specimens under the authority of the NASA/JSC Committee for the Protection of Human Subjects. The International Space Station (ISS) provides a platform to investigate the effects of microgravity on human physiology prior to lunar and exploration class missions. The NBSR is a secure controlled storage facility that is used to maintain biological specimens over extended periods of time, under well-controlled conditions, for future use in approved human spaceflight-related research protocols. The repository supports the Human Research Program, which is charged with identifying and investigating physiological changes that occur during human spaceflight, and developing and implementing effective countermeasures when necessary. The storage of crewmember samples from many different ISS flights in a single repository will be a valuable resource with which researchers can validate clinical hypotheses, study space-flight related changes, and investigate physiological markers All samples collected require written informed consent from each long duration crewmember. The NBSR collects blood and urine samples from all participating long duration ISS crewmembers. These biological samples are collected pre-flight at approximately 45 days prior to launch, during flight on flight days 15, 30, 60 120 and within 2 weeks of landing. Postflight sessions are conducted 3 and 30 days following landing. The number of inflight sessions is dependent on the duration of the mission. Operations began in 2007 and as of October 2009, 23 USOS crewmembers have completed or agreed to participate in this project. As currently planned, these human biological samples will be collected from crewmembers covering multiple ISS missions until the end of U.S. presence on the ISS or 2017. The NBSR will establish guidelines for sample distribution that are consistent with ethical principles

Testing co-evolutionary hypotheses over geological timescales: interactions between Mesozoic non-avian dinosaurs and cycads.

PubMed

Butler, Richard J; Barrett, Paul M; Kenrick, Paul; Penn, Malcolm G

2009-02-01

The significance of co-evolution over ecological timescales is well established, yet it remains unclear to what extent co-evolutionary processes contribute to driving large-scale evolutionary and ecological changes over geological timescales. Some of the most intriguing and pervasive long-term co-evolutionary hypotheses relate to proposed interactions between herbivorous non-avian dinosaurs and Mesozoic plants, including cycads. Dinosaurs have been proposed as key dispersers of cycad seeds during the Mesozoic, and temporal variation in cycad diversity and abundance has been linked to dinosaur faunal changes. Here we assess the evidence for proposed hypotheses of trophic and evolutionary interactions between these two groups using diversity analyses, a new database of Cretaceous dinosaur and plant co-occurrence data, and a geographical information system (GIS) as a visualisation tool. Phylogenetic evidence suggests that the origins of several key biological properties of cycads (e.g. toxins, bright-coloured seeds) likely predated the origin of dinosaurs. Direct evidence of dinosaur-cycad interactions is lacking, but evidence from extant ecosystems suggests that dinosaurs may plausibly have acted as seed dispersers for cycads, although it is likely that other vertebrate groups (e.g. birds, early mammals) also played a role. Although the Late Triassic radiations of dinosaurs and cycads appear to have been approximately contemporaneous, few significant changes in dinosaur faunas coincide with the late Early Cretaceous cycad decline. No significant spatiotemporal associations between particular dinosaur groups and cycads can be identified - GIS visualisation reveals disparities between the spatiotemporal distributions of some dinosaur groups (e.g. sauropodomorphs) and cycads that are inconsistent with co-evolutionary hypotheses. The available data provide no unequivocal support for any of the proposed co-evolutionary interactions between cycads and herbivorous dinosaurs

Applications of CRISPR genome editing technology in drug target identification and validation.

PubMed

Lu, Quinn; Livi, George P; Modha, Sundip; Yusa, Kosuke; Macarrón, Ricardo; Dow, David J

2017-06-01

The analysis of pharmaceutical industry data indicates that the major reason for drug candidates failing in late stage clinical development is lack of efficacy, with a high proportion of these due to erroneous hypotheses about target to disease linkage. More than ever, there is a requirement to better understand potential new drug targets and their role in disease biology in order to reduce attrition in drug development. Genome editing technology enables precise modification of individual protein coding genes, as well as noncoding regulatory sequences, enabling the elucidation of functional effects in human disease relevant cellular systems. Areas covered: This article outlines applications of CRISPR genome editing technology in target identification and target validation studies. Expert opinion: Applications of CRISPR technology in target validation studies are in evidence and gaining momentum. Whilst technical challenges remain, we are on the cusp of CRISPR being applied in complex cell systems such as iPS derived differentiated cells and stem cell derived organoids. In the meantime, our experience to date suggests that precise genome editing of putative targets in primary cell systems is possible, offering more human disease relevant systems than conventional cell lines.

Validity and Reliability of Psychosocial Factors Related to Breast Cancer Screening.

ERIC Educational Resources Information Center

Zapka, Jane G.; And Others

1991-01-01

The construct validity of hypothesized survey items and data reduction procedures for selected psychosocial constructs frequently used in breast cancer screening research were investigated in telephone interviews with randomly selected samples of 1,184 and 903 women and a sample of 169 Hispanic clinic clients. Validity of the constructs is…

Biological validation of physical coastal waters classification along the NE Atlantic region based on rocky macroalgae distribution

NASA Astrophysics Data System (ADS)

Ramos, Elvira; Puente, Araceli; Juanes, José Antonio; Neto, João M.; Pedersen, Are; Bartsch, Inka; Scanlan, Clare; Wilkes, Robert; Van den Bergh, Erika; Ar Gall, Erwan; Melo, Ricardo

2014-06-01

A methodology to classify rocky shores along the North East Atlantic (NEA) region was developed. Previously, biotypes and the variability of environmental conditions within these were recognized based on abiotic data. A biological validation was required in order to support the ecological meaning of the physical typologies obtained. A database of intertidal macroalgae species occurring in the coastal area between Norway and the South Iberian Peninsula was generated. Semi-quantitative abundance data of the most representative macroalgal taxa were collected in three levels: common, rare or absent. Ordination and classification multivariate analyses revealed a clear latitudinal gradient in the distribution of macroalgae species resulting in two distinct groups: one northern and one southern group, separated at the coast of Brittany (France). In general, the results based on biological data coincided with the results based on physical characteristics. The ecological meaning of the coastal waters classification at a broad scale shown in this work demonstrates that it can be valuable as a practical tool for conservation and management purposes.

Biology Curriculum Reform in Venezuela.

ERIC Educational Resources Information Center

Rondon, Leonor Mariasole

2001-01-01

Describes science in the Venezuelan school system which reflects on the process of development followed to design and validate the Biology Study Programs (BSP) with the emphasis on the relevance of curricular changes proposed in biological science for secondary education. (Contains 19 references.) (ASK)

Testing hypotheses of velocity and celerity at the catchment scale using ensemble hydrograph separation

NASA Astrophysics Data System (ADS)

Kirchner, James

2017-04-01

linear regression equation that quantifies the fraction of current rainfall in streamflow across ensembles of precipitation events. These ensembles can be selected to represent different discharge ranges, different precipitation intensities, or different levels of antecedent moisture, thus quantifying how the fraction of "new water" in streamflow varies with forcings such as these. This approach can be generalized to determine the contributions of precipitation inputs to streamflow across a range of time lags. In this way the short-term tail of the transit time distribution can be directly quantified for an ensemble of precipitation events, for direct comparison with the unit hydrograph, which quantifies the distribution of hydraulic celerities. High-frequency tracer time series from several experimental catchments will be used to demonstrate how this approach can be used to generate distinctive signatures of catchment behavior for testing model hypotheses. Kirchner, J.W., R.P. Hooper, C. Kendall, C. Neal, and G. Leavesley, Testing and validating environmental models, Science of the Total Environment, 183, 33-47, 1996. Kirchner, J.W., A double paradox in catchment hydrology and geochemistry, Hydrological Processes, 17, 871-874, 2003. Kirchner, J.W., Getting the right answers for the right reasons: linking measurements, analyses, and models to advance the science of hydrology, Water Resources Research, 42, Art. No. WR004362, 2006.

XML-based data model and architecture for a knowledge-based grid-enabled problem-solving environment for high-throughput biological imaging.

PubMed

Ahmed, Wamiq M; Lenz, Dominik; Liu, Jia; Paul Robinson, J; Ghafoor, Arif

2008-03-01

High-throughput biological imaging uses automated imaging devices to collect a large number of microscopic images for analysis of biological systems and validation of scientific hypotheses. Efficient manipulation of these datasets for knowledge discovery requires high-performance computational resources, efficient storage, and automated tools for extracting and sharing such knowledge among different research sites. Newly emerging grid technologies provide powerful means for exploiting the full potential of these imaging techniques. Efficient utilization of grid resources requires the development of knowledge-based tools and services that combine domain knowledge with analysis algorithms. In this paper, we first investigate how grid infrastructure can facilitate high-throughput biological imaging research, and present an architecture for providing knowledge-based grid services for this field. We identify two levels of knowledge-based services. The first level provides tools for extracting spatiotemporal knowledge from image sets and the second level provides high-level knowledge management and reasoning services. We then present cellular imaging markup language, an extensible markup language-based language for modeling of biological images and representation of spatiotemporal knowledge. This scheme can be used for spatiotemporal event composition, matching, and automated knowledge extraction and representation for large biological imaging datasets. We demonstrate the expressive power of this formalism by means of different examples and extensive experimental results.

Integrative Systems Biology for Data Driven Knowledge Discovery

PubMed Central

Greene, Casey S.; Troyanskaya, Olga G.

2015-01-01

Integrative systems biology is an approach that brings together diverse high throughput experiments and databases to gain new insights into biological processes or systems at molecular through physiological levels. These approaches rely on diverse high-throughput experimental techniques that generate heterogeneous data by assaying varying aspects of complex biological processes. Computational approaches are necessary to provide an integrative view of these experimental results and enable data-driven knowledge discovery. Hypotheses generated from these approaches can direct definitive molecular experiments in a cost effective manner. Using integrative systems biology approaches, we can leverage existing biological knowledge and large-scale data to improve our understanding of yet unknown components of a system of interest and how its malfunction leads to disease. PMID:21044756

The Biology of Trauma: Implications for Treatment

ERIC Educational Resources Information Center

Solomon, Eldra P.; Heide, Kathleen M.

2005-01-01

During the past 20 years, the development of brain imaging techniques and new biochemical approaches has led to increased understanding of the biological effects of psychological trauma. New hypotheses have been generated about brain development and the roots of antisocial behavior. We now understand that psychological trauma disrupts homeostasis…

Landscape moderation of biodiversity patterns and processes - eight hypotheses.

PubMed

Tscharntke, Teja; Tylianakis, Jason M; Rand, Tatyana A; Didham, Raphael K; Fahrig, Lenore; Batáry, Péter; Bengtsson, Janne; Clough, Yann; Crist, Thomas O; Dormann, Carsten F; Ewers, Robert M; Fründ, Jochen; Holt, Robert D; Holzschuh, Andrea; Klein, Alexandra M; Kleijn, David; Kremen, Claire; Landis, Doug A; Laurance, William; Lindenmayer, David; Scherber, Christoph; Sodhi, Navjot; Steffan-Dewenter, Ingolf; Thies, Carsten; van der Putten, Wim H; Westphal, Catrin

2012-08-01

Understanding how landscape characteristics affect biodiversity patterns and ecological processes at local and landscape scales is critical for mitigating effects of global environmental change. In this review, we use knowledge gained from human-modified landscapes to suggest eight hypotheses, which we hope will encourage more systematic research on the role of landscape composition and configuration in determining the structure of ecological communities, ecosystem functioning and services. We organize the eight hypotheses under four overarching themes. Section A: 'landscape moderation of biodiversity patterns' includes (1) the landscape species pool hypothesis-the size of the landscape-wide species pool moderates local (alpha) biodiversity, and (2) the dominance of beta diversity hypothesis-landscape-moderated dissimilarity of local communities determines landscape-wide biodiversity and overrides negative local effects of habitat fragmentation on biodiversity. Section B: 'landscape moderation of population dynamics' includes (3) the cross-habitat spillover hypothesis-landscape-moderated spillover of energy, resources and organisms across habitats, including between managed and natural ecosystems, influences landscape-wide community structure and associated processes and (4) the landscape-moderated concentration and dilution hypothesis-spatial and temporal changes in landscape composition can cause transient concentration or dilution of populations with functional consequences. Section C: 'landscape moderation of functional trait selection' includes (5) the landscape-moderated functional trait selection hypothesis-landscape moderation of species trait selection shapes the functional role and trajectory of community assembly, and (6) the landscape-moderated insurance hypothesis-landscape complexity provides spatial and temporal insurance, i.e. high resilience and stability of ecological processes in changing environments. Section D: 'landscape constraints on

The Math–Biology Values Instrument: Development of a Tool to Measure Life Science Majors’ Task Values of Using Math in the Context of Biology

PubMed Central

Andrews, Sarah E.; Runyon, Christopher; Aikens, Melissa L.

2017-01-01

In response to calls to improve the quantitative training of undergraduate biology students, there have been increased efforts to better integrate math into biology curricula. One challenge of such efforts is negative student attitudes toward math, which are thought to be particularly prevalent among biology students. According to theory, students’ personal values toward using math in a biological context will influence their achievement and behavioral outcomes, but a validated instrument is needed to determine this empirically. We developed the Math–Biology Values Instrument (MBVI), an 11-item college-level self-­report instrument grounded in expectancy-value theory, to measure life science students’ interest in using math to understand biology, the perceived usefulness of math to their life science career, and the cost of using math in biology courses. We used a process that integrates multiple forms of validity evidence to show that scores from the MBVI can be used as a valid measure of a student’s value of math in the context of biology. The MBVI can be used by instructors and researchers to help identify instructional strategies that influence math–biology values and understand how math–biology values are related to students’ achievement and decisions to pursue more advanced quantitative-based courses. PMID:28747355

Exploring hypotheses in attitude control fault diagnosis

NASA Technical Reports Server (NTRS)

Bell, Benjamin

1987-01-01

A system which analyzes telemetry and evaluates hypotheses to explain any anomalies that are observed is described. Results achieved from a sample set of failure cases are presented, followed by a brief discussion of the benefits derived from this approach.

Systems analysis of transcriptome data provides new hypotheses about Arabidopsis root response to nitrate treatments

PubMed Central

Canales, Javier; Moyano, Tomás C.; Villarroel, Eva; Gutiérrez, Rodrigo A.

2014-01-01

Nitrogen (N) is an essential macronutrient for plant growth and development. Plants adapt to changes in N availability partly by changes in global gene expression. We integrated publicly available root microarray data under contrasting nitrate conditions to identify new genes and functions important for adaptive nitrate responses in Arabidopsis thaliana roots. Overall, more than 2000 genes exhibited changes in expression in response to nitrate treatments in Arabidopsis thaliana root organs. Global regulation of gene expression by nitrate depends largely on the experimental context. However, despite significant differences from experiment to experiment in the identity of regulated genes, there is a robust nitrate response of specific biological functions. Integrative gene network analysis uncovered relationships between nitrate-responsive genes and 11 highly co-expressed gene clusters (modules). Four of these gene network modules have robust nitrate responsive functions such as transport, signaling, and metabolism. Network analysis hypothesized G2-like transcription factors are key regulatory factors controlling transport and signaling functions. Our meta-analysis highlights the role of biological processes not studied before in the context of the nitrate response such as root hair development and provides testable hypothesis to advance our understanding of nitrate responses in plants. PMID:24570678

Bioculture System Validation

NASA Technical Reports Server (NTRS)

Sato, Kevin Y.

2012-01-01

The Bioculture System first flight will be to validate the performance of the hardware and its automated and manual operational capabilities in the space flight environment of the International Space Station. Biology, Engineering, and Operations tests will be conducted in the Bioculture System fully characterize its automated and manual functions to support cell culturing for short and long durations. No hypothesis-driven research will be conducted with biological sample, and the science leads have all provided their concurrence that none of the data they collect will be considered as proprietary and can be free distributed to the science community. The outcome of the validation flight will be to commission the hardware for use by the science community. This presentation will provide non-proprietary details about the Bioculture System and information about the activities for the first flight.

Pectus excavatum: history, hypotheses and treatment options

PubMed Central

Brochhausen, Christoph; Turial, Salmai; Müller, Felix K.P.; Schmitt, Volker H.; Coerdt, Wiltrud; Wihlm, Jean-Marie; Schier, Felix; Kirkpatrick, C. James

2012-01-01

Pectus excavatum and pectus carinatum represent the most frequent chest wall deformations. However, the pathogenesis is still poorly understood and research results remain inconsistent. To focus on the recent state of knowledge, we summarize and critically discuss the pathological concepts based on the history of these entities, beginning with the first description in the sixteenth century. Based on the early clinical descriptions, we review and discuss the different pathogenetic hypotheses. To open new perspectives for the potential pathomechanisms, the embryonic and foetal development of the ribs and the sternum is highlighted following the understanding that the origin of these deformities is given by the disruption in the maturation of the parasternal region. In the second, different therapeutical techniques are highlighted and based on the pathogenetic hypotheses and the embryological knowledge potential new biomaterial-based perspectives with interesting insights for tissue engineering-based treatment options are presented. PMID:22394989

[Witch hunt and hypotheses loss].

PubMed

Köhler, Dieter

2015-12-01

At this time randomized controlled studies (RCT) in clinical trials usually have high quality. But this quality is only true for the included patients (intrinsic validity). It is common to generalize the results to more or less similar patients. This inductive method is prohibited in epistemology what is known for 250 years (D Hume, K R Popper). Therefore the external validity for the data of RCT is low. To solve this problem additional clinical and pathophysiological based data are necessary to generalize the results. Unfortunately RCT show less quality in their premises. This is partly due to the influence of the pharmaceutical industry. A loss of universality of the hypothesis for RCT decreases basically the extrinsic validity. The articles describe this problem with examples. © Georg Thieme Verlag KG Stuttgart · New York.

Nearly complete 28S rRNA gene sequences confirm new hypotheses of sponge evolution.

PubMed

Thacker, Robert W; Hill, April L; Hill, Malcolm S; Redmond, Niamh E; Collins, Allen G; Morrow, Christine C; Spicer, Lori; Carmack, Cheryl A; Zappe, Megan E; Pohlmann, Deborah; Hall, Chelsea; Diaz, Maria C; Bangalore, Purushotham V

2013-09-01

The highly collaborative research sponsored by the NSF-funded Assembling the Porifera Tree of Life (PorToL) project is providing insights into some of the most difficult questions in metazoan systematics. Our understanding of phylogenetic relationships within the phylum Porifera has changed considerably with increased taxon sampling and data from additional molecular markers. PorToL researchers have falsified earlier phylogenetic hypotheses, discovered novel phylogenetic alliances, found phylogenetic homes for enigmatic taxa, and provided a more precise understanding of the evolution of skeletal features, secondary metabolites, body organization, and symbioses. Some of these exciting new discoveries are shared in the papers that form this issue of Integrative and Comparative Biology. Our analyses of over 300 nearly complete 28S ribosomal subunit gene sequences provide specific case studies that illustrate how our dataset confirms new hypotheses of sponge evolution. We recovered monophyletic clades for all 4 classes of sponges, as well as the 4 major clades of Demospongiae (Keratosa, Myxospongiae, Haploscleromorpha, and Heteroscleromorpha), but our phylogeny differs in several aspects from traditional classifications. In most major clades of sponges, families within orders appear to be paraphyletic. Although additional sampling of genes and taxa are needed to establish whether this pattern results from a lack of phylogenetic resolution or from a paraphyletic classification system, many of our results are congruent with those obtained from 18S ribosomal subunit gene sequences and complete mitochondrial genomes. These data provide further support for a revision of the traditional classification of sponges.

Approximated adjusted fractional Bayes factors: A general method for testing informative hypotheses.

PubMed

Gu, Xin; Mulder, Joris; Hoijtink, Herbert

2018-05-01

Informative hypotheses are increasingly being used in psychological sciences because they adequately capture researchers' theories and expectations. In the Bayesian framework, the evaluation of informative hypotheses often makes use of default Bayes factors such as the fractional Bayes factor. This paper approximates and adjusts the fractional Bayes factor such that it can be used to evaluate informative hypotheses in general statistical models. In the fractional Bayes factor a fraction parameter must be specified which controls the amount of information in the data used for specifying an implicit prior. The remaining fraction is used for testing the informative hypotheses. We discuss different choices of this parameter and present a scheme for setting it. Furthermore, a software package is described which computes the approximated adjusted fractional Bayes factor. Using this software package, psychological researchers can evaluate informative hypotheses by means of Bayes factors in an easy manner. Two empirical examples are used to illustrate the procedure. © 2017 The British Psychological Society.

Effective use of latent semantic indexing and computational linguistics in biological and biomedical applications.

PubMed

Chen, Hongyu; Martin, Bronwen; Daimon, Caitlin M; Maudsley, Stuart

2013-01-01

Text mining is rapidly becoming an essential technique for the annotation and analysis of large biological data sets. Biomedical literature currently increases at a rate of several thousand papers per week, making automated information retrieval methods the only feasible method of managing this expanding corpus. With the increasing prevalence of open-access journals and constant growth of publicly-available repositories of biomedical literature, literature mining has become much more effective with respect to the extraction of biomedically-relevant data. In recent years, text mining of popular databases such as MEDLINE has evolved from basic term-searches to more sophisticated natural language processing techniques, indexing and retrieval methods, structural analysis and integration of literature with associated metadata. In this review, we will focus on Latent Semantic Indexing (LSI), a computational linguistics technique increasingly used for a variety of biological purposes. It is noted for its ability to consistently outperform benchmark Boolean text searches and co-occurrence models at information retrieval and its power to extract indirect relationships within a data set. LSI has been used successfully to formulate new hypotheses, generate novel connections from existing data, and validate empirical data.

Bayesian meta-analysis of Cronbach's coefficient alpha to evaluate informative hypotheses.

PubMed

Okada, Kensuke

2015-12-01

This paper proposes a new method to evaluate informative hypotheses for meta-analysis of Cronbach's coefficient alpha using a Bayesian approach. The coefficient alpha is one of the most widely used reliability indices. In meta-analyses of reliability, researchers typically form specific informative hypotheses beforehand, such as 'alpha of this test is greater than 0.8' or 'alpha of one form of a test is greater than the others.' The proposed method enables direct evaluation of these informative hypotheses. To this end, a Bayes factor is calculated to evaluate the informative hypothesis against its complement. It allows researchers to summarize the evidence provided by previous studies in favor of their informative hypothesis. The proposed approach can be seen as a natural extension of the Bayesian meta-analysis of coefficient alpha recently proposed in this journal (Brannick and Zhang, 2013). The proposed method is illustrated through two meta-analyses of real data that evaluate different kinds of informative hypotheses on superpopulation: one is that alpha of a particular test is above the criterion value, and the other is that alphas among different test versions have ordered relationships. Informative hypotheses are supported from the data in both cases, suggesting that the proposed approach is promising for application. Copyright © 2015 John Wiley & Sons, Ltd.

The Molecular Biology Capstone Assessment: A Concept Assessment for Upper-Division Molecular Biology Students

PubMed Central

Couch, Brian A.; Wood, William B.; Knight, Jennifer K.

2015-01-01

Measuring students’ conceptual understandings has become increasingly important to biology faculty members involved in evaluating and improving departmental programs. We developed the Molecular Biology Capstone Assessment (MBCA) to gauge comprehension of fundamental concepts in molecular and cell biology and the ability to apply these concepts in novel scenarios. Targeted at graduating students, the MBCA consists of 18 multiple-true/false (T/F) questions. Each question consists of a narrative stem followed by four T/F statements, which allows a more detailed assessment of student understanding than the traditional multiple-choice format. Questions were iteratively developed with extensive faculty and student feedback, including validation through faculty reviews and response validation through student interviews. The final assessment was taken online by 504 students in upper-division courses at seven institutions. Data from this administration indicate that the MBCA has acceptable levels of internal reliability (α = 0.80) and test–retest stability (r = 0.93). Students achieved a wide range of scores with a 67% overall average. Performance results suggest that students have an incomplete understanding of many molecular biology concepts and continue to hold incorrect conceptions previously documented among introductory-level students. By pinpointing areas of conceptual difficulty, the MBCA can provide faculty members with guidance for improving undergraduate biology programs. PMID:25713098

Estimating the proportion of true null hypotheses when the statistics are discrete.

PubMed

Dialsingh, Isaac; Austin, Stefanie R; Altman, Naomi S

2015-07-15

In high-dimensional testing problems π0, the proportion of null hypotheses that are true is an important parameter. For discrete test statistics, the P values come from a discrete distribution with finite support and the null distribution may depend on an ancillary statistic such as a table margin that varies among the test statistics. Methods for estimating π0 developed for continuous test statistics, which depend on a uniform or identical null distribution of P values, may not perform well when applied to discrete testing problems. This article introduces a number of π0 estimators, the regression and 'T' methods that perform well with discrete test statistics and also assesses how well methods developed for or adapted from continuous tests perform with discrete tests. We demonstrate the usefulness of these estimators in the analysis of high-throughput biological RNA-seq and single-nucleotide polymorphism data. implemented in R. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Bayesian Meta-Analysis of Cronbach's Coefficient Alpha to Evaluate Informative Hypotheses

ERIC Educational Resources Information Center

Okada, Kensuke

2015-01-01

This paper proposes a new method to evaluate informative hypotheses for meta-analysis of Cronbach's coefficient alpha using a Bayesian approach. The coefficient alpha is one of the most widely used reliability indices. In meta-analyses of reliability, researchers typically form specific informative hypotheses beforehand, such as "alpha of…

76 FR 4360 - Guidance for Industry on Process Validation: General Principles and Practices; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-25

... elements of process validation for the manufacture of human and animal drug and biological products... process validation for the manufacture of human and animal drug and biological products, including APIs. This guidance describes process validation activities in three stages: In Stage 1, Process Design, the...

Causes of bat fatalities at wind turbines: Hypotheses and predictions

USGS Publications Warehouse

Cryan, P.M.; Barclay, R.M.R.

2009-01-01

Thousands of industrial-scale wind turbines are being built across the world each year to meet the growing demand for sustainable energy. Bats of certain species are dying at wind turbines in unprecedented numbers. Species of bats consistently affected by turbines tend to be those that rely on trees as roosts and most migrate long distances. Although considerable progress has been made in recent years toward better understanding the problem, the causes of bat fatalities at turbines remain unclear. In this synthesis, we review hypothesized causes of bat fatalities at turbines. Hypotheses of cause fall into 2 general categoriesproximate and ultimate. Proximate causes explain the direct means by which bats die at turbines and include collision with towers and rotating blades, and barotrauma. Ultimate causes explain why bats come close to turbines and include 3 general types: random collisions, coincidental collisions, and collisions that result from attraction of bats to turbines. The random collision hypothesis posits that interactions between bats and turbines are random events and that fatalities are representative of the bats present at a site. Coincidental hypotheses posit that certain aspects of bat distribution or behavior put them at risk of collision and include aggregation during migration and seasonal increases in flight activity associated with feeding or mating. A surprising number of attraction hypotheses suggest that bats might be attracted to turbines out of curiosity, misperception, or as potential feeding, roosting, flocking, and mating opportunities. Identifying, prioritizing, and testing hypothesized causes of bat collisions with wind turbines are vital steps toward developing practical solutions to the problem. ?? 2009 American Society of Mammalogists.

Validating the Riverside Acculturation Stress Inventory with Asian Americans.

PubMed

Miller, Matthew J; Kim, Jungeun; Benet-Martínez, Verónica

2011-06-01

An emerging body of empirical research highlights the impact of acculturative stress in the lives of culturally diverse populations. Therefore, to facilitate future research in this area, we conducted 3 studies to examine the psychometric properties of the Riverside Acculturation Stress Inventory (RASI; Benet-Martínez & Haritatos, 2005) and its 5 subscales in a total sample of 793 self-identified Asian American participants. The reliability and validity of RASI scores and the hypothesized 1-factor higher order model (with 1st-order factors Language Skills, Work Challenges, Intercultural Relations, Discrimination, and Cultural Isolation) of the RASI were examined in Study 1. The RASI higher order structure and score validity and reliability were examined across different generational groups in Study 2. The stability of RASI scores over a 3-week period was examined in Study 3. Overall, findings from these studies support the hypothesized structure of the RASI and indicate that this brief instrument provides reliable and valid acculturative stress scores. In addition, results suggest that RASI items are interpreted in an equivalent manner across different generations of Asian American individuals. Implications for research and assessment are discussed. 2011 APA, all rights reserved

The effects of message recipients' power before and after persuasion: a self-validation analysis.

PubMed

Briñol, Pablo; Petty, Richard E; Valle, Carmen; Rucker, Derek D; Becerra, Alberto

2007-12-01

In the present research, the authors examined the effect of a message recipient's power on attitude change and introduced a new mechanism by which power can affect social judgment. In line with prior research that suggested a link between power and approach tendencies, the authors hypothesized that having power increases confidence relative to being powerless. After demonstrating this link in Experiment 1, in 4 additional studies, they examined the role of power in persuasion as a function of when power is infused into the persuasion process. On the basis of the idea that power validates whatever mental content is accessible, they hypothesized that power would have different effects on persuasion depending on when power was induced. Specifically, the authors predicted that making people feel powerful prior to a message would validate their existing views and thus reduce the perceived need to attend to subsequent information. However, it was hypothesized that inducing power after a message has been processed would validate one's recently generated thoughts and thus influence the extent to which people rely upon their thoughts in determining their attitudes. (c) 2007 APA, all rights reserved.

Fuzzy method of recognition of high molecular substances in evidence-based biology

NASA Astrophysics Data System (ADS)

Olevskyi, V. I.; Smetanin, V. T.; Olevska, Yu. B.

2017-10-01

Nowadays modern requirements to achieving reliable results along with high quality of researches put mathematical analysis methods of results at the forefront. Because of this, evidence-based methods of processing experimental data have become increasingly popular in the biological sciences and medicine. Their basis is meta-analysis, a method of quantitative generalization of a large number of randomized trails contributing to a same special problem, which are often contradictory and performed by different authors. It allows identifying the most important trends and quantitative indicators of the data, verification of advanced hypotheses and discovering new effects in the population genotype. The existing methods of recognizing high molecular substances by gel electrophoresis of proteins under denaturing conditions are based on approximate methods for comparing the contrast of electrophoregrams with a standard solution of known substances. We propose a fuzzy method for modeling experimental data to increase the accuracy and validity of the findings of the detection of new proteins.

How biological background assumptions influence scientific risk evaluation of stacked genetically modified plants: an analysis of research hypotheses and argumentations.

PubMed

Rocca, Elena; Andersen, Fredrik

2017-08-14

Scientific risk evaluations are constructed by specific evidence, value judgements and biological background assumptions. The latter are the framework-setting suppositions we apply in order to understand some new phenomenon. That background assumptions co-determine choice of methodology, data interpretation, and choice of relevant evidence is an uncontroversial claim in modern basic science. Furthermore, it is commonly accepted that, unless explicated, disagreements in background assumptions can lead to misunderstanding as well as miscommunication. Here, we extend the discussion on background assumptions from basic science to the debate over genetically modified (GM) plants risk assessment. In this realm, while the different political, social and economic values are often mentioned, the identity and role of background assumptions at play are rarely examined. We use an example from the debate over risk assessment of stacked genetically modified plants (GM stacks), obtained by applying conventional breeding techniques to GM plants. There are two main regulatory practices of GM stacks: (i) regulate as conventional hybrids and (ii) regulate as new GM plants. We analyzed eight papers representative of these positions and found that, in all cases, additional premises are needed to reach the stated conclusions. We suggest that these premises play the role of biological background assumptions and argue that the most effective way toward a unified framework for risk analysis and regulation of GM stacks is by explicating and examining the biological background assumptions of each position. Once explicated, it is possible to either evaluate which background assumptions best reflect contemporary biological knowledge, or to apply Douglas' 'inductive risk' argument.

Formative Assessment Probes: To Hypothesize or Not

ERIC Educational Resources Information Center

Keeley, Page

2010-01-01

Formative assessment probes are used not only to uncover the ideas students bring to their learning, they can also be used to reveal teachers' common misconceptions. Consider a process widely used in inquiry science--developing hypotheses. In this article, the author features the probe "Is It a Hypothesis?", which serves as an example of how…

Biomaterial science meets computational biology.

PubMed

Hutmacher, Dietmar W; Little, J Paige; Pettet, Graeme J; Loessner, Daniela

2015-05-01

There is a pressing need for a predictive tool capable of revealing a holistic understanding of fundamental elements in the normal and pathological cell physiology of organoids in order to decipher the mechanoresponse of cells. Therefore, the integration of a systems bioengineering approach into a validated mathematical model is necessary to develop a new simulation tool. This tool can only be innovative by combining biomaterials science with computational biology. Systems-level and multi-scale experimental data are incorporated into a single framework, thus representing both single cells and collective cell behaviour. Such a computational platform needs to be validated in order to discover key mechano-biological factors associated with cell-cell and cell-niche interactions.

A systems biology strategy to identify molecular mechanisms of action and protein indicators of traumatic brain injury.

PubMed

Yu, Chenggang; Boutté, Angela; Yu, Xueping; Dutta, Bhaskar; Feala, Jacob D; Schmid, Kara; Dave, Jitendra; Tawa, Gregory J; Wallqvist, Anders; Reifman, Jaques

2015-02-01

The multifactorial nature of traumatic brain injury (TBI), especially the complex secondary tissue injury involving intertwined networks of molecular pathways that mediate cellular behavior, has confounded attempts to elucidate the pathology underlying the progression of TBI. Here, systems biology strategies are exploited to identify novel molecular mechanisms and protein indicators of brain injury. To this end, we performed a meta-analysis of four distinct high-throughput gene expression studies involving different animal models of TBI. By using canonical pathways and a large human protein-interaction network as a scaffold, we separately overlaid the gene expression data from each study to identify molecular signatures that were conserved across the different studies. At 24 hr after injury, the significantly activated molecular signatures were nonspecific to TBI, whereas the significantly suppressed molecular signatures were specific to the nervous system. In particular, we identified a suppressed subnetwork consisting of 58 highly interacting, coregulated proteins associated with synaptic function. We selected three proteins from this subnetwork, postsynaptic density protein 95, nitric oxide synthase 1, and disrupted in schizophrenia 1, and hypothesized that their abundance would be significantly reduced after TBI. In a penetrating ballistic-like brain injury rat model of severe TBI, Western blot analysis confirmed our hypothesis. In addition, our analysis recovered 12 previously identified protein biomarkers of TBI. The results suggest that systems biology may provide an efficient, high-yield approach to generate testable hypotheses that can be experimentally validated to identify novel mechanisms of action and molecular indicators of TBI. © 2014 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

Revisiting Preschoolers' Living Things Concept: A Microgenetic Analysis of Conceptual Change in Basic Biology

ERIC Educational Resources Information Center

Opfer, John E.; Siegler, Robert S.

2004-01-01

Many preschoolers know that plants and animals share basic biological properties, but this knowledge does not usually lead them to conclude that plants, like animals, are living things. To resolve this seeming paradox, we hypothesized that preschoolers largely base their judgments of life status on a biological property, capacity for teleological…

Pickles and ice cream! Food cravings in pregnancy: hypotheses, preliminary evidence, and directions for future research

PubMed Central

Orloff, Natalia C.; Hormes, Julia M.

2014-01-01

Women in the United States experience an increase in food cravings at two specific times during their life, (1) perimenstrually and (2) prenatally. The prevalence of excess gestational weight gain (GWG) is a growing concern due to its association with adverse health outcomes in both mothers and children. To the extent that prenatal food cravings may be a determinant of energy intake in pregnancy, a better understanding of craving etiology could be crucial in addressing the issue of excessive GWG. This paper reviews the available literature to corroborate and/or dispute some of the most commonly accepted hypotheses regarding the causes of food cravings during pregnancy, including a role of (1) hormonal changes, (2) nutritional deficits, (3) pharmacologically active ingredients in the desired foods, and (4) cultural and psychosocial factors. An existing model of perimenstrual chocolate craving etiology serves to structure the discussion of these hypotheses. The main hypotheses discussed receive little support, with the notable exception of a postulated role of cultural and psychosocial factors. The presence of cravings during pregnancy is a common phenomenon across different cultures, but the types of foods desired and the adverse impact of cravings on health may be culture-specific. Various psychosocial factors appear to correlate with excess GWG, including the presence of restrained eating. Findings strongly suggest that more research be conducted in this area. We propose that future investigations fall into one of the four following categories: (1) validation of food craving and eating-related measures specifically in pregnant populations, (2) use of ecological momentary assessment to obtain real time data on cravings during pregnancy, (3) implementation of longitudinal studies to address causality between eating disorder symptoms, food cravings, and GWG, and (4) development of interventions to ensure proper prenatal nutrition and prevent excess GWG. PMID:25295023

Validation of N-myristoyltransferase as an antimalarial drug target using an integrated chemical biology approach

NASA Astrophysics Data System (ADS)

Wright, Megan H.; Clough, Barbara; Rackham, Mark D.; Rangachari, Kaveri; Brannigan, James A.; Grainger, Munira; Moss, David K.; Bottrill, Andrew R.; Heal, William P.; Broncel, Malgorzata; Serwa, Remigiusz A.; Brady, Declan; Mann, David J.; Leatherbarrow, Robin J.; Tewari, Rita; Wilkinson, Anthony J.; Holder, Anthony A.; Tate, Edward W.

2014-02-01

Malaria is an infectious disease caused by parasites of the genus Plasmodium, which leads to approximately one million deaths per annum worldwide. Chemical validation of new antimalarial targets is urgently required in view of rising resistance to current drugs. One such putative target is the enzyme N-myristoyltransferase, which catalyses the attachment of the fatty acid myristate to protein substrates (N-myristoylation). Here, we report an integrated chemical biology approach to explore protein myristoylation in the major human parasite P. falciparum, combining chemical proteomic tools for identification of the myristoylated and glycosylphosphatidylinositol-anchored proteome with selective small-molecule N-myristoyltransferase inhibitors. We demonstrate that N-myristoyltransferase is an essential and chemically tractable target in malaria parasites both in vitro and in vivo, and show that selective inhibition of N-myristoylation leads to catastrophic and irreversible failure to assemble the inner membrane complex, a critical subcellular organelle in the parasite life cycle. Our studies provide the basis for the development of new antimalarials targeting N-myristoyltransferase.

Nearly Complete 28S rRNA Gene Sequences Confirm New Hypotheses of Sponge Evolution

PubMed Central

Thacker, Robert W.; Hill, April L.; Hill, Malcolm S.; Redmond, Niamh E.; Collins, Allen G.; Morrow, Christine C.; Spicer, Lori; Carmack, Cheryl A.; Zappe, Megan E.; Pohlmann, Deborah; Hall, Chelsea; Diaz, Maria C.; Bangalore, Purushotham V.

2013-01-01

The highly collaborative research sponsored by the NSF-funded Assembling the Porifera Tree of Life (PorToL) project is providing insights into some of the most difficult questions in metazoan systematics. Our understanding of phylogenetic relationships within the phylum Porifera has changed considerably with increased taxon sampling and data from additional molecular markers. PorToL researchers have falsified earlier phylogenetic hypotheses, discovered novel phylogenetic alliances, found phylogenetic homes for enigmatic taxa, and provided a more precise understanding of the evolution of skeletal features, secondary metabolites, body organization, and symbioses. Some of these exciting new discoveries are shared in the papers that form this issue of Integrative and Comparative Biology. Our analyses of over 300 nearly complete 28S ribosomal subunit gene sequences provide specific case studies that illustrate how our dataset confirms new hypotheses of sponge evolution. We recovered monophyletic clades for all 4 classes of sponges, as well as the 4 major clades of Demospongiae (Keratosa, Myxospongiae, Haploscleromorpha, and Heteroscleromorpha), but our phylogeny differs in several aspects from traditional classifications. In most major clades of sponges, families within orders appear to be paraphyletic. Although additional sampling of genes and taxa are needed to establish whether this pattern results from a lack of phylogenetic resolution or from a paraphyletic classification system, many of our results are congruent with those obtained from 18S ribosomal subunit gene sequences and complete mitochondrial genomes. These data provide further support for a revision of the traditional classification of sponges. PMID:23748742

Integrating ecosystem studies: A Bayesian comparison of hypotheses

USGS Publications Warehouse

Adkison, Milo D.; Ballachey, Brenda E.; Bodkin, James L.; Holland-Bartels, Leslie E.; Funk, F.; Quinn, T.J.; Heifetz, J.; Ianelli, J.N.; Powers, J.E.; Schweigert, J.F.; Sullivan, P.J.; Zhang, C.-I.

1998-01-01

Ecosystem studies are difficult to interpret because of the complexity and number of pathways that may affect a phenomenon of interest. It is not possible to study all aspects of a problem; thus subjective judgment is required to weigh what has been observed in the context of components that were not studied but may have been important. This subjective judgment is usually a poorly documented and ad hoc addendum to a statistical analysis of the data. We present a Bayesian methodology for documenting, quantifying, and incorporating these necessary subjective elements into an ecosystem study. The end product of this methodology is the probability of each of the competing hypotheses. As an example, this method is applied to an ecosystem study designed to discriminate among competing hypotheses for a low abundance of sea otters at a previously oiled site in Prince William Sound, Alaska.

NASA Developmental Biology Workshop: A summary

NASA Technical Reports Server (NTRS)

Souza, K. A. (Editor); Halstead, T. W. (Editor)

1985-01-01

The Life Sciences Division of the National Aeronautics and Space Administration (NASA) as part of its continuing assessment of its research program, convened a workshop on Developmental Biology to determine whether there are important scientific studies in this area which warrant continued or expanded NASA support. The workshop consisted of six panels, each of which focused on a single major phylogenetic group. The objectives of each panel were to determine whether gravity plays a role in the ontogeny of their subject group, to determine whether the microgravity of spaceflight can be used to help understand fundamental problems in developmental biology, to develop the rationale and hypotheses for conducting NASA-relevant research in development biology both on the ground and in space, and to identify any unique equipment and facilities that would be required to support both ground-based and spaceflight experiments.

A novel approach to generating CER hypotheses based on mining clinical data.

PubMed

Zhang, Shuo; Li, Lin; Yu, Yiqin; Sun, Xingzhi; Xu, Linhao; Zhao, Wei; Teng, Xiaofei; Pan, Yue

2013-01-01

Comparative effectiveness research (CER) is a scientific method of investigating the effectiveness of alternative intervention methods. In a CER study, clinical researchers typically start with a CER hypothesis, and aim to evaluate it by applying a series of medical statistical methods. Traditionally, the CER hypotheses are defined manually by clinical researchers. This makes the task of hypothesis generation very time-consuming and the quality of hypothesis heavily dependent on the researchers' skills. Recently, with more electronic medical data being collected, it is highly promising to apply the computerized method for discovering CER hypotheses from clinical data sets. In this poster, we proposes a novel approach to automatically generating CER hypotheses based on mining clinical data, and presents a case study showing that the approach can facilitate clinical researchers to identify potentially valuable hypotheses and eventually define high quality CER studies.

Translation and Validation of the Dutch Western Ontario Meniscal Evaluation Tool.

PubMed

van der Wal, Robert J P; Heemskerk, Bastiaan T J; van Arkel, Ewoud R A; Mokkink, Lidwine B; Thomassen, Bregje J W

2017-05-01

The aim of this study was to translate the Western Ontario Meniscal Evaluation Tool (WOMET) into Dutch, to evaluate the content validity, construct validity, reliability, and responsiveness, and to determine the minimal important change (MIC) of the Dutch version. The WOMET was translated into Dutch according to a standardized forward-backward translation protocol. A total of 86 patients (51 males, 35 females, median age 52 years [interquartile range, 43-60 years]) with isolated meniscal pathology were included. The WOMET was completed three times; at baseline, around 2 weeks, and after 3 months from the baseline. Knee injury and osteoarthritis outcome score, International Knee Documentation Committee subjective knee form, short-form 36, and an anchor question were also answered. There were good results for content validity (floor and ceiling effects [< 15%]), construct validity (79% of the predefined hypotheses were confirmed), internal consistency (Cronbach α = 0.87, 0.79, and 0.86 for each subscale score), test-retest reliability (intraclass correlation coefficient = 0.78 for total WOMET score), and responsiveness (79% of the predefined hypotheses were confirmed). The smallest detectable change and MIC for the Dutch WOMET are 20.5 and 14.7, respectively. The Dutch version of the WOMET is valid and reliable for assessing health-related quality of life in patients with meniscal pathology. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Math-Biology Values Instrument: Development of a Tool to Measure Life Science Majors' Task Values of Using Math in the Context of Biology.

PubMed

Andrews, Sarah E; Runyon, Christopher; Aikens, Melissa L

2017-01-01

In response to calls to improve the quantitative training of undergraduate biology students, there have been increased efforts to better integrate math into biology curricula. One challenge of such efforts is negative student attitudes toward math, which are thought to be particularly prevalent among biology students. According to theory, students' personal values toward using math in a biological context will influence their achievement and behavioral outcomes, but a validated instrument is needed to determine this empirically. We developed the Math-Biology Values Instrument (MBVI), an 11-item college-level self--report instrument grounded in expectancy-value theory, to measure life science students' interest in using math to understand biology, the perceived usefulness of math to their life science career, and the cost of using math in biology courses. We used a process that integrates multiple forms of validity evidence to show that scores from the MBVI can be used as a valid measure of a student's value of math in the context of biology. The MBVI can be used by instructors and researchers to help identify instructional strategies that influence math-biology values and understand how math-biology values are related to students' achievement and decisions to pursue more advanced quantitative-based courses. © 2017 S. E. Andrews et al. CBE—Life Sciences Education © 2017 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Testing hypotheses of bat baculum function with 3D models derived from microCT

PubMed Central

Herdina, Anna Nele; Kelly, Diane A; Jahelková, Helena; Lina, Peter H C; Horáček, Ivan; Metscher, Brian D

2015-01-01

The baculum (os penis) has been extensively studied as a taxon-specific character in bats and other mammals but its mechanical function is still unclear. There is a wide consensus in the literature that the baculum is probably a sexually selected character. Using a novel approach combining postmortem manipulation and three-dimensional (3D) imaging, we tested two functional hypotheses in the common noctule bat Nyctalus noctula, the common pipistrelle Pipistrellus pipistrellus, and Nathusius’ pipistrelle Pipistrellus nathusii: (i) whether the baculum can protect the distal urethra and urethral opening from compression during erection and copulation; and (ii) whether the baculum and corpora cavernosa form a functional unit to support both the penile shaft and the more distal glans tip. In freshly dead or frozen and thawed bats, we compared flaccid penises with artificially ‘erect’ penises that were inflated with 10% formalin. Penises were stained with alcoholic iodine and imaged with a lab-based high-resolution x-ray microtomography system. Analysis of the 3D images enabled us to compare the changes in relative positions of the baculum, corpora cavernosa, urethra, and corpus spongiosum with one another between flaccid and ‘erect’ penises. Our results support both functional hypotheses, indicating that the baculum probably performs two different roles during erection. Our approach should prove valuable for comparing and testing the functions of different baculum morphologies in bats and other mammals. Moreover, we have validated an essential component of the groundwork necessary to extend this approach with finite element analysis for quantitative 3D biomechanical modeling of penis function. PMID:25655647

A Validation Study of Student Differentiation between Computing Disciplines

ERIC Educational Resources Information Center

Battig, Michael; Shariq, Muhammad

2011-01-01

Using a previously published study of how students differentiate between computing disciplines, this study attempts to validate the original research and add additional hypotheses regarding the type of institution that the student resides. Using the identical survey instrument from the original study, students in smaller colleges and in different…

Preschool Temperament Assessment: A Quantitative Assessment of the Validity of Behavioral Style Questionnaire Data

ERIC Educational Resources Information Center

Huelsman, Timothy J.; Gagnon, Sandra Glover; Kidder-Ashley, Pamela; Griggs, Marissa Swaim

2014-01-01

Research Findings: Child temperament is an important construct, but its measurement has been marked by a number of weaknesses that have diminished the frequency with which it is assessed in practice. We address this problem by presenting the results of a quantitative construct validation study. We calculated validity indices by hypothesizing the…

Validation of a Computerized Cognitive Assessment System for Persons with Stroke: A Pilot Study

ERIC Educational Resources Information Center

Yip, Chi Kwong; Man, David W. K.

2009-01-01

This study investigates the validity of a newly developed computerized cognitive assessment system (CCAS) that is equipped with rich multimedia to generate simulated testing situations and considers both test item difficulty and the test taker's ability. It is also hypothesized that better predictive validity of the CCAS in self-care of persons…

The nucleic acid revolution continues - will forensic biology become forensic molecular biology?

PubMed

Gunn, Peter; Walsh, Simon; Roux, Claude

2014-01-01

Molecular biology has evolved far beyond that which could have been predicted at the time DNA identity testing was established. Indeed we should now perhaps be referring to "forensic molecular biology." Aside from DNA's established role in identifying the "who" in crime investigations, other developments in medical and developmental molecular biology are now ripe for application to forensic challenges. The impact of DNA methylation and other post-fertilization DNA modifications, plus the emerging role of small RNAs in the control of gene expression, is re-writing our understanding of human biology. It is apparent that these emerging technologies will expand forensic molecular biology to allow for inferences about "when" a crime took place and "what" took place. However, just as the introduction of DNA identity testing engendered many challenges, so the expansion of molecular biology into these domains will raise again the issues of scientific validity, interpretation, probative value, and infringement of personal liberties. This Commentary ponders some of these emerging issues, and presents some ideas on how they will affect the conduct of forensic molecular biology in the foreseeable future.

Compatible ecological niche signals between biological and archaeological datasets for late-surviving Neandertals.

PubMed

Bible, Rachael C; Peterson, A Townsend

2018-04-17

To assess ecological niche similarity for biological and archaeological samples representing late-surviving Neandertals in Europe to evaluate the validity of combining these two types of data in ecological niche modeling analyses. Tests of niche conservatism were used to assess niche similarity and niche identity of samples of morphologically diagnostic Neandertal remains and Middle Paleolithic (MP) archaeological sites dating to the time period leading up to Neandertal extinction. Paleoenvironmental reconstructions for the Pre-H4 (43.3-40.2 ky cal BP) were used as environmental space analyses. Null hypotheses of niche similarity and identity of the two types of samples could not be rejected. As primary and secondary evidence of Neandertal occurrence during the Pre-H4 show high levels of niche similarity and identity, combining the two types of occurrence data to create larger samples for niche analyses is justified without the concern that different environmental signals could complicate future research. © 2018 Wiley Periodicals, Inc.

3D tooth microwear texture analysis in fishes as a test of dietary hypotheses of durophagy

NASA Astrophysics Data System (ADS)

Purnell, Mark A.; Darras, Laurent P. G.

2016-03-01

An understanding of how extinct animals functioned underpins our understanding of past evolutionary events, including adaptive radiations, and the role of functional innovation and adaptation as drivers of both micro- and macroevolution. Yet analysis of function in extinct animals is fraught with difficulty. Hypotheses that interpret molariform teeth in fishes as evidence of durophagous (shell-crushing) diets provide a good example of the particular problems inherent in the methods of functional morphology. This is because the assumed close coupling of form and function upon which the approach is based is weakened by, among other things, behavioural flexibility and the absence of a clear one to one relationship between structures and functions. Here we show that ISO 25178-2 standard parameters for surface texture, derived from analysis of worn surfaces of molariform teeth of fishes, vary significantly between species that differ in the amount of hard-shelled prey they consume. Two populations of the Sheepshead Seabream (Archosargus probatocephalus) were studied. This fish is not a dietary specialist, and one of the populations is known to consume more vegetation and less hard-shelled prey than the other; this is reflected in significant differences in their microwear textures. The Archosargus populations differ significantly in their microwear from the specialist shell-crusher Anarhichas lupus (the Atlantic Wolffish). Multivariate analysis of these three groups of fishes lends further support to the relationship between diet and tooth microwear, and provides robust validation of the approach. Application of the multivariate models derived from microwear texture in Archosargus and Anarhichas to a third fish species—the cichlid Astatoreochromis alluaudi—successfully separates wild caught fish that ate hard-shelled prey from lab-raised fish that did not. This cross-taxon validation demonstrates that quantitative analysis of tooth microwear texture can

The molecular biology capstone assessment: a concept assessment for upper-division molecular biology students.

PubMed

Couch, Brian A; Wood, William B; Knight, Jennifer K

2015-03-02

Measuring students' conceptual understandings has become increasingly important to biology faculty members involved in evaluating and improving departmental programs. We developed the Molecular Biology Capstone Assessment (MBCA) to gauge comprehension of fundamental concepts in molecular and cell biology and the ability to apply these concepts in novel scenarios. Targeted at graduating students, the MBCA consists of 18 multiple-true/false (T/F) questions. Each question consists of a narrative stem followed by four T/F statements, which allows a more detailed assessment of student understanding than the traditional multiple-choice format. Questions were iteratively developed with extensive faculty and student feedback, including validation through faculty reviews and response validation through student interviews. The final assessment was taken online by 504 students in upper-division courses at seven institutions. Data from this administration indicate that the MBCA has acceptable levels of internal reliability (α=0.80) and test-retest stability (r=0.93). Students achieved a wide range of scores with a 67% overall average. Performance results suggest that students have an incomplete understanding of many molecular biology concepts and continue to hold incorrect conceptions previously documented among introductory-level students. By pinpointing areas of conceptual difficulty, the MBCA can provide faculty members with guidance for improving undergraduate biology programs. © 2015 B. A. Couch et al. CBE—Life Sciences Education © 2015 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Why are we not evaluating multiple competing hypotheses in ecology and evolution?

PubMed Central

Avgar, Tal; Fryxell, John M.

2017-01-01

The use of multiple working hypotheses to gain strong inference is widely promoted as a means to enhance the effectiveness of scientific investigation. Only 21 of 100 randomly selected studies from the ecological and evolutionary literature tested more than one hypothesis and only eight tested more than two hypotheses. The surprising rarity of application of multiple working hypotheses suggests that this gap between theory and practice might reflect some fundamental issues. Here, we identify several intellectual and practical barriers that discourage us from using multiple hypotheses in our scientific investigation. While scientists have developed a number of ways to avoid biases, such as the use of double-blind controls, we suspect that few scientists are fully aware of the potential influence of cognitive bias on their decisions and they have not yet adopted many techniques available to overcome intellectual and practical barriers in order to improve scientific investigation. PMID:28280578

Can Scientifically Useful Hypotheses Be Tested with Correlations?

ERIC Educational Resources Information Center

Bentler, Peter M.

2007-01-01

Historically, interesting psychological theories have been phrased in terms of correlation coefficients, which are standardized covariances, and various statistics derived from them. Methodological practice over the last 40 years, however, has suggested it is necessary to transform such theories into hypotheses on covariances and statistics…

Severe and acute complications of biologics in psoriasis.

PubMed

Oussedik, Elias; Patel, Nupur U; Cash, Devin R; Gupta, Angela S; Feldman, Steven R

2017-12-01

Biologic therapies have revolutionized the approach to immune-mediated diseases such as psoriasis. Due to their favorable safety profiles and excellent efficacy, biologic agents are considered the gold standard for moderate-to-severe psoriasis. The aim of this paper is to saliently review the severe and acute complications of the Food and Drug Administration (FDA) approved biologic agents for psoriasis. Reviewed agents include tumor necrosis factor alpha inhibitors (etanercept, infliximab, and adalimumab), interleukin 12/23 inhibitors (ustekinumab), and interleukin 17 (IL-17) inhibitors (secukinumab and ixekizumab). While malignancies, serious infections, and major adverse cardiovascular events have been reported, their association with biologic therapy are not hypothesized as causal. However, IL-17 inhibitors appear to cause exacerbations and new cases of inflammatory bowel disease. While more long-term studies are warranted in understanding the biologic's long-term side effect profile, short-term studies have confirmed that the biologics are some of the safest treatment options for psoriasis. Nevertheless, certain populations yield higher risk to acute complications with the biologics than others - physicians must use their judgement and vigilance when monitoring and treating patients undergoing therapy with biological agents.

Life History theory hypotheses on child growth: Potential implications for short and long-term child growth, development and health.

PubMed

Said-Mohamed, Rihlat; Pettifor, John M; Norris, Shane A

2018-01-01

Life history theory integrates ecological, physiological, and molecular layers within an evolutionary framework to understand organisms' strategies to optimize survival and reproduction. Two life history hypotheses and their implications for child growth, development, and health (illustrated in the South African context) are reviewed here. One hypothesis suggests that there is an energy trade-off between linear growth and brain growth. Undernutrition in infancy and childhood may trigger adaptive physiological mechanisms prioritizing the brain at the expense of body growth. Another hypothesis is that the period from conception to infancy is a critical window of developmental plasticity of linear growth, the duration of which may vary between and within populations. The transition from infancy to childhood may mark the end of a critical window of opportunity for improving child growth. Both hypotheses emphasize the developmental plasticity of linear growth and the potential determinants of growth variability (including the role of parent-offspring conflict in maternal resources allocation). Implications of these hypotheses in populations with high burdens of undernutrition and infections are discussed. In South Africa, HIV/AIDS during pregnancy (associated with adverse birth outcomes, short duration of breastfeeding, and social consequences) may lead to a shortened window of developmental plasticity of growth. Furthermore, undernutrition and infectious diseases in children living in South Africa, a country undergoing a rapid nutrition transition, may have adverse consequences on individuals' cognitive abilities and risks of cardio-metabolic diseases. Studies are needed to identify physiological mechanisms underlying energy allocation between biological functions and their potential impacts on health. © 2017 Wiley Periodicals, Inc.

Service-based analysis of biological pathways

PubMed Central

Zheng, George; Bouguettaya, Athman

2009-01-01

Background Computer-based pathway discovery is concerned with two important objectives: pathway identification and analysis. Conventional mining and modeling approaches aimed at pathway discovery are often effective at achieving either objective, but not both. Such limitations can be effectively tackled leveraging a Web service-based modeling and mining approach. Results Inspired by molecular recognitions and drug discovery processes, we developed a Web service mining tool, named PathExplorer, to discover potentially interesting biological pathways linking service models of biological processes. The tool uses an innovative approach to identify useful pathways based on graph-based hints and service-based simulation verifying user's hypotheses. Conclusion Web service modeling of biological processes allows the easy access and invocation of these processes on the Web. Web service mining techniques described in this paper enable the discovery of biological pathways linking these process service models. Algorithms presented in this paper for automatically highlighting interesting subgraph within an identified pathway network enable the user to formulate hypothesis, which can be tested out using our simulation algorithm that are also described in this paper. PMID:19796403

What Is the Problem of Ad Hoc Hypotheses?

ERIC Educational Resources Information Center

Bamford, Greg

1999-01-01

Philosophers' attempts to convincingly explicate the received view of an ad hoc hypothesis--that it accounts for only the observations it was designed to account for--have been unsuccessful. Familiar and firmer criteria for evaluating the hypotheses or modified theories so classified are characteristically available. Contains 41 references.…

Sex, Drugs, and Rock ‘N’ Roll: Hypothesizing Common Mesolimbic Activation as a Function of Reward Gene Polymorphisms

PubMed Central

Blum, Kenneth; Werner, Tonia; Carnes, Stefanie; Carnes, Patrick; Bowirrat, Abdalla; Giordano, John; Marlene-Oscar-Berman; Gold, Mark

2014-01-01

The nucleus accumbens, a site within the ventral striatum, plays a prominent role in mediating the reinforcing effects of drugs of abuse, food, sex, and other addictions. Indeed, it is generally believed that this structure mandates motivated behaviors such as eating, drinking, and sexual activity, which are elicited by natural rewards and other strong incentive stimuli. This article focuses on sex addiction, but we hypothesize that there is a common underlying mechanism of action for the powerful effects that all addictions have on human motivation. That is, biological drives may have common molecular genetic antecedents, which if impaired, lead to aberrant behaviors. Based on abundant scientific support, we further hypothesize that dopaminergic genes, and possibly other candidate neurotransmitter-related gene polymorphisms, affect both hedonic and anhedonic behavioral outcomes. Genotyping studies already have linked gene polymorphic associations with alcohol and drug addictions and obesity, and we anticipate that future genotyping studies of sex addicts will provide evidence for polymorphic associations with specific clustering of sexual typologies based on clinical instrument assessments. We recommend that scientists and clinicians embark on research coupling the use of neuroimaging tools with dopaminergic agonistic agents to target specific gene polymorphisms systematically for normalizing hyper- or hypo-sexual behaviors. PMID:22641964

Construct Validity and Scoring Methods of the World Health Organization: Health and Work Performance Questionnaire Among Workers With Arthritis and Rheumatological Conditions.

PubMed

AlHeresh, Rawan; LaValley, Michael P; Coster, Wendy; Keysor, Julie J

2017-06-01

To evaluate construct validity and scoring methods of the world health organization-health and work performance questionnaire (HPQ) for people with arthritis. Construct validity was examined through hypothesis testing using the recommended guidelines of the consensus-based standards for the selection of health measurement instruments (COSMIN). The HPQ using the absolute scoring method showed moderate construct validity as four of the seven hypotheses were met. The HPQ using the relative scoring method had weak construct validity as only one of the seven hypotheses were met. The absolute scoring method for the HPQ is superior in construct validity to the relative scoring method in assessing work performance among people with arthritis and related rheumatic conditions; however, more research is needed to further explore other psychometric properties of the HPQ.

Selection of biological indicator for validating microwave heating sterilization.

PubMed

Sasaki, K; Mori, Y; Honda, W; Miyake, Y

1998-01-01

For the purpose of selecting an appropriate biological indicator for evaluation of the effects of microwave heating sterilization, we examined aerobic bacterial spores to determine whether microwaves have non-thermal sterilization effects. After microwave irradiation on dry bacterial spores (three species), none of the bacterial spores were killed. The survival rate of the spores after microwave irradiation of spore suspensions (twelve species) was compared with that after heating by a conventional method. The order of heat resistance in the bacterial species was similar between the two heating methods. Bacillus stearothermophilus spores were the most heat-resistant. These results suggest that microwaves have no non-thermal sterilization effects on bacterial spores, the specific resistant spores to microwave heating, and microwave heating sterilization can be evaluated in the same way as for conventional heating sterilization. As a biological indicator for evaluation of overkill sterilization, B. stearothermophilus spores may be appropriate for microwave heating sterilization as well as steam sterilization.

Novel insights into embryonic stem cell self-renewal revealed through comparative human and mouse systems biology networks.

PubMed

Dowell, Karen G; Simons, Allen K; Bai, Hao; Kell, Braden; Wang, Zack Z; Yun, Kyuson; Hibbs, Matthew A

2014-05-01

Embryonic stem cells (ESCs), characterized by their ability to both self-renew and differentiate into multiple cell lineages, are a powerful model for biomedical research and developmental biology. Human and mouse ESCs share many features, yet have distinctive aspects, including fundamental differences in the signaling pathways and cell cycle controls that support self-renewal. Here, we explore the molecular basis of human ESC self-renewal using Bayesian network machine learning to integrate cell-type-specific, high-throughput data for gene function discovery. We integrated high-throughput ESC data from 83 human studies (~1.8 million data points collected under 1,100 conditions) and 62 mouse studies (~2.4 million data points collected under 1,085 conditions) into separate human and mouse predictive networks focused on ESC self-renewal to analyze shared and distinct functional relationships among protein-coding gene orthologs. Computational evaluations show that these networks are highly accurate, literature validation confirms their biological relevance, and reverse transcriptase polymerase chain reaction (RT-PCR) validation supports our predictions. Our results reflect the importance of key regulatory genes known to be strongly associated with self-renewal and pluripotency in both species (e.g., POU5F1, SOX2, and NANOG), identify metabolic differences between species (e.g., threonine metabolism), clarify differences between human and mouse ESC developmental signaling pathways (e.g., leukemia inhibitory factor (LIF)-activated JAK/STAT in mouse; NODAL/ACTIVIN-A-activated fibroblast growth factor in human), and reveal many novel genes and pathways predicted to be functionally associated with self-renewal in each species. These interactive networks are available online at www.StemSight.org for stem cell researchers to develop new hypotheses, discover potential mechanisms involving sparsely annotated genes, and prioritize genes of interest for experimental validation

Scanning transmission ion microscopy mass measurements for quantitative trace element analysis within biological samples and validation using atomic force microscopy thickness measurements

NASA Astrophysics Data System (ADS)

Devès, Guillaume; Cohen-Bouhacina, Touria; Ortega, Richard

2004-10-01

We used the nuclear microprobe techniques, micro-PIXE (particle-induced X-ray emission), micro-RBS (Rutherford backscattering spectrometry) and scanning transmission ion microscopy (STIM) in order to perform the characterization of trace element content and spatial distribution within biological samples (dehydrated cultured cells, tissues). The normalization of PIXE results was usually expressed in terms of sample dry mass as determined by micro-RBS recorded simultaneously to micro-PIXE. However, the main limit of RBS mass measurement is the sample mass loss occurring during irradiation and which could be up to 30% of the initial sample mass. We present here a new methodology for PIXE normalization and quantitative analysis of trace element within biological samples based on dry mass measurement performed by mean of STIM. The validation of STIM cell mass measurements was obtained in comparison with AFM sample thickness measurements. Results indicated the reliability of STIM mass measurement performed on biological samples and suggested that STIM should be performed for PIXE normalization. Further information deriving from direct confrontation of AFM and STIM analysis could as well be obtained, like in situ measurements of cell specific gravity within cells compartment (nucleolus and cytoplasm).

Optimization and validation of a label-free MRM method for the quantification of cytochrome P450 isoforms in biological samples.

PubMed

Al Ali, Ahmad; Touboul, David; Le Caër, Jean-Pierre; Schmitz-Afonso, Isabelle; Flinois, Jean-Pierre; Marchetti, Catherine; De Waziers, Isabelle; Brunelle, Alain; Laprévote, Olivier; Beaune, Philippe

2014-08-01

Cytochromes P450 (CYPs) play critical roles in oxidative metabolism of many endogenous and exogenous compounds. Protein expression levels of CYPs in liver provide relevant information for a better understanding of the importance of CYPs in pharmacology and toxicology. This work aimed at establishing a simple method to quantify six CYPs (CYP3A4, CYP3A5, CYP1A2, CYP2D6, CYP2C9, and CYP2J2) in various biological samples without isotopic labeling. The biological matrix was spiked with the standard peptides prior to the digestion step to realize a label-free quantification by mass spectrometry. The method was validated and applied to quantify these six isoforms in both human liver microsomes and mitochondria, but also in recombinant expression systems such as baculosomes and the HepG2 cell line. The results showed intra-assay and interassay accuracy and precision within 16 % and 5 %, respectively, at the low quality control level, and demonstrated the advantages of the method in terms of reproducibility and cost.

Nestedness across biological scales

PubMed Central

Marquitti, Flavia M. D.; Raimundo, Rafael L. G.; Sebastián-González, Esther; Coltri, Patricia P.; Perez, S. Ivan; Brandt, Débora Y. C.; Nunes, Kelly; Daura-Jorge, Fábio G.; Floeter, Sergio R.; Guimarães, Paulo R.

2017-01-01

Biological networks pervade nature. They describe systems throughout all levels of biological organization, from molecules regulating metabolism to species interactions that shape ecosystem dynamics. The network thinking revealed recurrent organizational patterns in complex biological systems, such as the formation of semi-independent groups of connected elements (modularity) and non-random distributions of interactions among elements. Other structural patterns, such as nestedness, have been primarily assessed in ecological networks formed by two non-overlapping sets of elements; information on its occurrence on other levels of organization is lacking. Nestedness occurs when interactions of less connected elements form proper subsets of the interactions of more connected elements. Only recently these properties began to be appreciated in one-mode networks (where all elements can interact) which describe a much wider variety of biological phenomena. Here, we compute nestedness in a diverse collection of one-mode networked systems from six different levels of biological organization depicting gene and protein interactions, complex phenotypes, animal societies, metapopulations, food webs and vertebrate metacommunities. Our findings suggest that nestedness emerge independently of interaction type or biological scale and reveal that disparate systems can share nested organization features characterized by inclusive subsets of interacting elements with decreasing connectedness. We primarily explore the implications of a nested structure for each of these studied systems, then theorize on how nested networks are assembled. We hypothesize that nestedness emerges across scales due to processes that, although system-dependent, may share a general compromise between two features: specificity (the number of interactions the elements of the system can have) and affinity (how these elements can be connected to each other). Our findings suggesting occurrence of nestedness

Bayes Factor Approaches for Testing Interval Null Hypotheses

ERIC Educational Resources Information Center

Morey, Richard D.; Rouder, Jeffrey N.

2011-01-01

Psychological theories are statements of constraint. The role of hypothesis testing in psychology is to test whether specific theoretical constraints hold in data. Bayesian statistics is well suited to the task of finding supporting evidence for constraint, because it allows for comparing evidence for 2 hypotheses against each another. One issue…

Optimization and validation of spectrophotometric methods for determination of finasteride in dosage and biological forms

PubMed Central

Amin, Alaa S.; Kassem, Mohammed A.

2012-01-01

Aim and Background: Three simple, accurate and sensitive spectrophotometric methods for the determination of finasteride in pure, dosage and biological forms, and in the presence of its oxidative degradates were developed. Materials and Methods: These methods are indirect, involve the addition of excess oxidant potassium permanganate for method A; cerric sulfate [Ce(SO4)2] for methods B; and N-bromosuccinimide (NBS) for method C of known concentration in acid medium to finasteride, and the determination of the unreacted oxidant by measurement of the decrease in absorbance of methylene blue for method A, chromotrope 2R for method B, and amaranth for method C at a suitable maximum wavelength, λmax: 663, 528, and 520 nm, for the three methods, respectively. The reaction conditions for each method were optimized. Results: Regression analysis of the Beer plots showed good correlation in the concentration ranges of 0.12–3.84 μg mL–1 for method A, and 0.12–3.28 μg mL–1 for method B and 0.14 – 3.56 μg mL–1 for method C. The apparent molar absorptivity, Sandell sensitivity, detection and quantification limits were evaluated. The stoichiometric ratio between the finasteride and the oxidant was estimated. The validity of the proposed methods was tested by analyzing dosage forms and biological samples containing finasteride with relative standard deviation ≤ 0.95. Conclusion: The proposed methods could successfully determine the studied drug with varying excess of its oxidative degradation products, with recovery between 99.0 and 101.4, 99.2 and 101.6, and 99.6 and 101.0% for methods A, B, and C, respectively. PMID:23781478

Black/White Differences in Adolescent Drug Use: A Test of Six Hypotheses

ERIC Educational Resources Information Center

Rote, Sunshine M.; Taylor, John

2014-01-01

Six specific hypotheses have been developed to account for why Caucasians have higher rates of drug use compared to African-Americans. This article utilizes data from a South Florida-based community study of 893 young adults (1998-2002) to test these hypotheses. Specifically, Caucasians (1) initiate drug use at younger ages than African-Americans…

Nanoparticle-based biologic mimetics

PubMed Central

Cliffel, David E.; Turner, Brian N.; Huffman, Brian J.

2009-01-01

Centered on solid chemistry foundations, biology and materials science have reached a crossroad where bottom-up designs of new biologically important nanomaterials are a reality. The topics discussed here present the interdisciplinary field of creating biological mimics. Specifically, this discussion focuses on mimics that are developed using various types of metal nanoparticles (particularly gold) through facile synthetic methods. These methods conjugate biologically relevant molecules, e.g., small molecules, peptides, proteins, and carbohydrates, in conformationally favorable orientations on the particle surface. These new products provide stable, safe, and effective substitutes for working with potentially hazardous biologicals for applications such as drug targeting, immunological studies, biosensor development, and biocatalysis. Many standard bioanalytical techniques can be used to characterize and validate the efficacy of these new materials, including quartz crystal microbalance (QCM), surface plasmon resonance (SPR), and enzyme-linked immunosorbent assay (ELISA). Metal nanoparticle–based biomimetics continue to be developed as potential replacements for the native biomolecule in applications of immunoassays and catalysis. PMID:20049778

A Diagnostic Assessment for Introductory Molecular and Cell Biology

PubMed Central

Wood, William B.; Martin, Jennifer M.; Guild, Nancy A.; Vicens, Quentin; Knight, Jennifer K.

2010-01-01

We have developed and validated a tool for assessing understanding of a selection of fundamental concepts and basic knowledge in undergraduate introductory molecular and cell biology, focusing on areas in which students often have misconceptions. This multiple-choice Introductory Molecular and Cell Biology Assessment (IMCA) instrument is designed for use as a pre- and posttest to measure student learning gains. To develop the assessment, we first worked with faculty to create a set of learning goals that targeted important concepts in the field and seemed likely to be emphasized by most instructors teaching these subjects. We interviewed students using open-ended questions to identify commonly held misconceptions, formulated multiple-choice questions that included these ideas as distracters, and reinterviewed students to establish validity of the instrument. The assessment was then evaluated by 25 biology experts and modified based on their suggestions. The complete revised assessment was administered to more than 1300 students at three institutions. Analysis of statistical parameters including item difficulty, item discrimination, and reliability provides evidence that the IMCA is a valid and reliable instrument with several potential uses in gauging student learning of key concepts in molecular and cell biology. PMID:21123692

Improving the Validity of Quantitative Measures in Applied Linguistics Research

ERIC Educational Resources Information Center

Purpura, James E.; Brown, James Dean; Schoonen, Rob

2015-01-01

In empirical applied linguistics research it is essential that the key variables are operationalized in a valid and reliable way, and that the scores are treated appropriately, allowing for a proper testing of the hypotheses under investigation. The current article addresses several theoretical and practical issues regarding the use of measurement…

Gravitational Biology Facility on Space Station: Meeting the needs of space biology

NASA Technical Reports Server (NTRS)

Allen, Katherine; Wade, Charles

1992-01-01

The Gravitational Biology Facility (GBF) is a set of generic laboratory equipment needed to conduct research on Space Station Freedom (SSF), focusing on Space Biology Program science (Cell and Developmental Biology and Plant Biology). The GBF will be functional from the earliest utilization flights through the permanent manned phase. Gravitational biology research will also make use of other Life Sciences equipment on the space station as well as existing equipment developed for the space shuttle. The facility equipment will be developed based on requirements derived from experiments proposed by the scientific community to address critical questions in the Space Biology Program. This requires that the facility have the ability to house a wide variety of species, various methods of observation, and numerous methods of sample collection, preservation, and storage. The selection of the equipment will be done by the members of a scientific working group (5 members representing cell biology, 6 developmental biology, and 6 plant biology) who also provide requirements to design engineers to ensure that the equipment will meet scientific needs. All equipment will undergo extensive ground based experimental validation studies by various investigators addressing a variety of experimental questions. Equipment will be designed to be adaptable to other space platforms. The theme of the Gravitational Biology Facility effort is to provide optimal and reliable equipment to answer the critical questions in Space Biology as to the effects of gravity on living systems.

Hypothesized predictors of patient–physician trust and distrust in the elderly: implications for health and disease management

PubMed Central

Mascarenhas, Oswald AJ; Cardozo, Lavoisier J; Afonso, Nelia M; Siddique, Mohamed; Steinberg, Joel; Lepczyk, Marybeth; Aranha, Anil NF

2006-01-01

This study notes the differences between trust and distrust perceptions by the elderly as compared with younger populations. Given the importance of trust and distrust in compliance, changing behaviors, and forming partnerships for both health and disease management, it is necessary to be able to measure patient–doctor trust and distrust (PDTD). Following recent conceptualizations on trust and distrust as coexistent states, this study hypothesizes predictors of PDTD. We are proposing that these predictors form the basis for designing, developing and validating a PDTD scale (PDTDS). It is important to capture the trust–distrust perceptions of older patients as they confront the complexities and vulnerabilities of the modern healthcare delivery system. This is necessary if we are to design interventions to change behaviors of both the healthcare provider and the older patient. PMID:18044114

MotiveValidator: interactive web-based validation of ligand and residue structure in biomolecular complexes.

PubMed

Vařeková, Radka Svobodová; Jaiswal, Deepti; Sehnal, David; Ionescu, Crina-Maria; Geidl, Stanislav; Pravda, Lukáš; Horský, Vladimír; Wimmerová, Michaela; Koča, Jaroslav

2014-07-01

Structure validation has become a major issue in the structural biology community, and an essential step is checking the ligand structure. This paper introduces MotiveValidator, a web-based application for the validation of ligands and residues in PDB or PDBx/mmCIF format files provided by the user. Specifically, MotiveValidator is able to evaluate in a straightforward manner whether the ligand or residue being studied has a correct annotation (3-letter code), i.e. if it has the same topology and stereochemistry as the model ligand or residue with this annotation. If not, MotiveValidator explicitly describes the differences. MotiveValidator offers a user-friendly, interactive and platform-independent environment for validating structures obtained by any type of experiment. The results of the validation are presented in both tabular and graphical form, facilitating their interpretation. MotiveValidator can process thousands of ligands or residues in a single validation run that takes no more than a few minutes. MotiveValidator can be used for testing single structures, or the analysis of large sets of ligands or fragments prepared for binding site analysis, docking or virtual screening. MotiveValidator is freely available via the Internet at http://ncbr.muni.cz/MotiveValidator. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Development of working hypotheses linking management of the Missouri River to population dynamics of Scaphirhynchus albus (pallid sturgeon)

USGS Publications Warehouse

Jacobson, Robert B.; Parsley, Michael J.; Annis, Mandy L.; Colvin, Michael E.; Welker, Timothy L.; James, Daniel A.

2016-01-20

The initial set of candidate hypotheses provides a useful starting point for quantitative modeling and adaptive management of the river and species. We anticipate that hypotheses will change from the set of working management hypotheses as adaptive management progresses. More importantly, hypotheses that have been filtered out of our multistep process are still being considered. These filtered hypotheses are archived and if existing hypotheses are determined to be inadequate to explain observed population dynamics, new hypotheses can be created or filtered hypotheses can be reinstated.

Auditory biological marker of concussion in children

PubMed Central

Kraus, Nina; Thompson, Elaine C.; Krizman, Jennifer; Cook, Katherine; White-Schwoch, Travis; LaBella, Cynthia R.

2016-01-01

Concussions carry devastating potential for cognitive, neurologic, and socio-emotional disease, but no objective test reliably identifies a concussion and its severity. A variety of neurological insults compromise sound processing, particularly in complex listening environments that place high demands on brain processing. The frequency-following response captures the high computational demands of sound processing with extreme granularity and reliably reveals individual differences. We hypothesize that concussions disrupt these auditory processes, and that the frequency-following response indicates concussion occurrence and severity. Specifically, we hypothesize that concussions disrupt the processing of the fundamental frequency, a key acoustic cue for identifying and tracking sounds and talkers, and, consequently, understanding speech in noise. Here we show that children who sustained a concussion exhibit a signature neural profile. They have worse representation of the fundamental frequency, and smaller and more sluggish neural responses. Neurophysiological responses to the fundamental frequency partially recover to control levels as concussion symptoms abate, suggesting a gain in biological processing following partial recovery. Neural processing of sound correctly identifies 90% of concussion cases and clears 95% of control cases, suggesting this approach has practical potential as a scalable biological marker for sports-related concussion and other types of mild traumatic brain injuries. PMID:28005070

Prequels to Synthetic Biology: From Candidate Gene Identification and Validation to Enzyme Subcellular Localization in Plant and Yeast Cells.

PubMed

Foureau, E; Carqueijeiro, I; Dugé de Bernonville, T; Melin, C; Lafontaine, F; Besseau, S; Lanoue, A; Papon, N; Oudin, A; Glévarec, G; Clastre, M; St-Pierre, B; Giglioli-Guivarc'h, N; Courdavault, V

2016-01-01

Natural compounds extracted from microorganisms or plants constitute an inexhaustible source of valuable molecules whose supply can be potentially challenged by limitations in biological sourcing. The recent progress in synthetic biology combined to the increasing access to extensive transcriptomics and genomics data now provide new alternatives to produce these molecules by transferring their whole biosynthetic pathway in heterologous production platforms such as yeasts or bacteria. While the generation of high titer producing strains remains per se an arduous field of investigation, elucidation of the biosynthetic pathways as well as characterization of their complex subcellular organization are essential prequels to the efficient development of such bioengineering approaches. Using examples from plants and yeasts as a framework, we describe potent methods to rationalize the study of partially characterized pathways, including the basics of computational applications to identify candidate genes in transcriptomics data and the validation of their function by an improved procedure of virus-induced gene silencing mediated by direct DNA transfer to get around possible resistance to Agrobacterium-delivery of viral vectors. To identify potential alterations of biosynthetic fluxes resulting from enzyme mislocalizations in reconstituted pathways, we also detail protocols aiming at characterizing subcellular localizations of protein in plant cells by expression of fluorescent protein fusions through biolistic-mediated transient transformation, and localization of transferred enzymes in yeast using similar fluorescence procedures. Albeit initially developed for the Madagascar periwinkle, these methods may be applied to other plant species or organisms in order to establish synthetic biology platform. © 2016 Elsevier Inc. All rights reserved.

The nucleic acid revolution continues – will forensic biology become forensic molecular biology?

PubMed Central

Gunn, Peter; Walsh, Simon; Roux, Claude

2014-01-01

Molecular biology has evolved far beyond that which could have been predicted at the time DNA identity testing was established. Indeed we should now perhaps be referring to “forensic molecular biology.” Aside from DNA’s established role in identifying the “who” in crime investigations, other developments in medical and developmental molecular biology are now ripe for application to forensic challenges. The impact of DNA methylation and other post-fertilization DNA modifications, plus the emerging role of small RNAs in the control of gene expression, is re-writing our understanding of human biology. It is apparent that these emerging technologies will expand forensic molecular biology to allow for inferences about “when” a crime took place and “what” took place. However, just as the introduction of DNA identity testing engendered many challenges, so the expansion of molecular biology into these domains will raise again the issues of scientific validity, interpretation, probative value, and infringement of personal liberties. This Commentary ponders some of these emerging issues, and presents some ideas on how they will affect the conduct of forensic molecular biology in the foreseeable future. PMID:24634675

Poisson's ratio over two centuries: challenging hypotheses

PubMed Central

Greaves, G. Neville

2013-01-01

This article explores Poisson's ratio, starting with the controversy concerning its magnitude and uniqueness in the context of the molecular and continuum hypotheses competing in the development of elasticity theory in the nineteenth century, moving on to its place in the development of materials science and engineering in the twentieth century, and concluding with its recent re-emergence as a universal metric for the mechanical performance of materials on any length scale. During these episodes France lost its scientific pre-eminence as paradigms switched from mathematical to observational, and accurate experiments became the prerequisite for scientific advance. The emergence of the engineering of metals followed, and subsequently the invention of composites—both somewhat separated from the discovery of quantum mechanics and crystallography, and illustrating the bifurcation of technology and science. Nowadays disciplines are reconnecting in the face of new scientific demands. During the past two centuries, though, the shape versus volume concept embedded in Poisson's ratio has remained invariant, but its application has exploded from its origins in describing the elastic response of solids and liquids, into areas such as materials with negative Poisson's ratio, brittleness, glass formation, and a re-evaluation of traditional materials. Moreover, the two contentious hypotheses have been reconciled in their complementarity within the hierarchical structure of materials and through computational modelling. PMID:24687094

Contemporary Test Validity in Theory and Practice: A Primer for Discipline-Based Education Researchers.

PubMed

Reeves, Todd D; Marbach-Ad, Gili

2016-01-01

Most discipline-based education researchers (DBERs) were formally trained in the methods of scientific disciplines such as biology, chemistry, and physics, rather than social science disciplines such as psychology and education. As a result, DBERs may have never taken specific courses in the social science research methodology--either quantitative or qualitative--on which their scholarship often relies so heavily. One particular aspect of (quantitative) social science research that differs markedly from disciplines such as biology and chemistry is the instrumentation used to quantify phenomena. In response, this Research Methods essay offers a contemporary social science perspective on test validity and the validation process. The instructional piece explores the concepts of test validity, the validation process, validity evidence, and key threats to validity. The essay also includes an in-depth example of a validity argument and validation approach for a test of student argument analysis. In addition to DBERs, this essay should benefit practitioners (e.g., lab directors, faculty members) in the development, evaluation, and/or selection of instruments for their work assessing students or evaluating pedagogical innovations. © 2016 T. D. Reeves and G. Marbach-Ad. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Inter-institutional Development of a Poster-Based Cancer Biology Learning Tool

PubMed Central

Andraos-Selim, Cecile; Modzelewski, Ruth A.; Steinman, Richard A.

2010-01-01

There is a paucity of African-American Cancer researchers. To help address this, an educational collaboration was developed between a Comprehensive Cancer Center and a distant undergraduate biology department at a minority institution that sought to teach students introductory cancer biology while modeling research culture. A student-centered active learning curriculum was established that incorporated scientific poster presentations and simulated research exercises to foster learning of cancer biology. Students successfully mined primary literature for supportive data to test cancer-related hypotheses. Student feedback indicated that the poster project substantially enhanced depth of understanding of cancer biology and laid the groundwork for subsequent laboratory work. This inter-institutional collaboration modeled the research process while conveying facts and concepts about cancer. PMID:20237886

Landscape moderation of biodiversity patterns and processes - eight hypotheses

USDA-ARS?s Scientific Manuscript database

Understanding how landscape characteristics affect local biodiversity patterns and ecological processes is critical for mitigating effects of global environmental change. In this review, we use knowledge gained from human-modified landscapes to suggest the following seven hypotheses, which we hope w...

Advancing Biological Understanding and Therapeutics Discovery with Small Molecule Probes

PubMed Central

Schreiber, Stuart L.; Kotz, Joanne D.; Li, Min; Aubé, Jeffrey; Austin, Christopher P.; Reed, John C.; Rosen, Hugh; White, E. Lucile; Sklar, Larry A.; Lindsley, Craig W.; Alexander, Benjamin R.; Bittker, Joshua A.; Clemons, Paul A.; de Souza, Andrea; Foley, Michael A.; Palmer, Michelle; Shamji, Alykhan F.; Wawer, Mathias J.; McManus, Owen; Wu, Meng; Zou, Beiyan; Yu, Haibo; Golden, Jennifer E.; Schoenen, Frank J.; Simeonov, Anton; Jadhav, Ajit; Jackson, Michael R.; Pinkerton, Anthony B.; Chung, Thomas D.Y.; Griffin, Patrick R.; Cravatt, Benjamin F.; Hodder, Peter S.; Roush, William R.; Roberts, Edward; Chung, Dong-Hoon; Jonsson, Colleen B.; Noah, James W.; Severson, William E.; Ananthan, Subramaniam; Edwards, Bruce; Oprea, Tudor I.; Conn, P. Jeffrey; Hopkins, Corey R.; Wood, Michael R.; Stauffer, Shaun R.; Emmitte, Kyle A.

2015-01-01

Small-molecule probes can illuminate biological processes and aid in the assessment of emerging therapeutic targets by perturbing biological systems in a manner distinct from other experimental approaches. Despite the tremendous promise of chemical tools for investigating biology and disease, small-molecule probes were unavailable for most targets and pathways as recently as a decade ago. In 2005, the U.S. National Institutes of Health launched the decade-long Molecular Libraries Program with the intent of innovating in and broadening access to small-molecule science. This Perspective describes how novel small-molecule probes identified through the program are enabling the exploration of biological pathways and therapeutic hypotheses not otherwise testable. These experiences illustrate how small-molecule probes can help bridge the chasm between biological research and the development of medicines, but also highlight the need to innovate the science of therapeutic discovery. PMID:26046436

Towards sound epistemological foundations of statistical methods for high-dimensional biology.

PubMed

Mehta, Tapan; Tanik, Murat; Allison, David B

2004-09-01

A sound epistemological foundation for biological inquiry comes, in part, from application of valid statistical procedures. This tenet is widely appreciated by scientists studying the new realm of high-dimensional biology, or 'omic' research, which involves multiplicity at unprecedented scales. Many papers aimed at the high-dimensional biology community describe the development or application of statistical techniques. The validity of many of these is questionable, and a shared understanding about the epistemological foundations of the statistical methods themselves seems to be lacking. Here we offer a framework in which the epistemological foundation of proposed statistical methods can be evaluated.

Instructional Interactions of Kindergarten Mathematics Classrooms: Validating a Direct Observation Instrument

ERIC Educational Resources Information Center

Doabler, Christian; Smolkowski, Keith; Fien, Hank; Kosty, Derek B.; Cary, Mari Strand

2010-01-01

In this paper, the authors report research focused directly on the validation of the Coding of Academic Teacher-Student interactions (CATS) direct observation instrument. They use classroom information gathered by the CATS instrument to better understand the potential mediating variables hypothesized to influence student achievement. Their study's…

Toward University Modeling Instruction—Biology: Adapting Curricular Frameworks from Physics to Biology

PubMed Central

Manthey, Seth; Brewe, Eric

2013-01-01

University Modeling Instruction (UMI) is an approach to curriculum and pedagogy that focuses instruction on engaging students in building, validating, and deploying scientific models. Modeling Instruction has been successfully implemented in both high school and university physics courses. Studies within the physics education research (PER) community have identified UMI's positive impacts on learning gains, equity, attitudinal shifts, and self-efficacy. While the success of this pedagogical approach has been recognized within the physics community, the use of models and modeling practices is still being developed for biology. Drawing from the existing research on UMI in physics, we describe the theoretical foundations of UMI and how UMI can be adapted to include an emphasis on models and modeling for undergraduate introductory biology courses. In particular, we discuss our ongoing work to develop a framework for the first semester of a two-semester introductory biology course sequence by identifying the essential basic models for an introductory biology course sequence. PMID:23737628

Toward university modeling instruction--biology: adapting curricular frameworks from physics to biology.

PubMed

Manthey, Seth; Brewe, Eric

2013-06-01

University Modeling Instruction (UMI) is an approach to curriculum and pedagogy that focuses instruction on engaging students in building, validating, and deploying scientific models. Modeling Instruction has been successfully implemented in both high school and university physics courses. Studies within the physics education research (PER) community have identified UMI's positive impacts on learning gains, equity, attitudinal shifts, and self-efficacy. While the success of this pedagogical approach has been recognized within the physics community, the use of models and modeling practices is still being developed for biology. Drawing from the existing research on UMI in physics, we describe the theoretical foundations of UMI and how UMI can be adapted to include an emphasis on models and modeling for undergraduate introductory biology courses. In particular, we discuss our ongoing work to develop a framework for the first semester of a two-semester introductory biology course sequence by identifying the essential basic models for an introductory biology course sequence.

The water balance of the urban Salt Lake Valley: a multiple-box model validated by observations

NASA Astrophysics Data System (ADS)

Stwertka, C.; Strong, C.

2012-12-01

A main focus of the recently awarded National Science Foundation (NSF) EPSCoR Track-1 research project "innovative Urban Transitions and Arid-region Hydro-sustainability (iUTAH)" is to quantify the primary components of the water balance for the Wasatch region, and to evaluate their sensitivity to climate change and projected urban development. Building on the multiple-box model that we developed and validated for carbon dioxide (Strong et al 2011), mass balance equations for water in the atmosphere and surface are incorporated into the modeling framework. The model is used to determine how surface fluxes, ground-water transport, biological fluxes, and meteorological processes regulate water cycling within and around the urban Salt Lake Valley. The model is used to evaluate the hypotheses that increased water demand associated with urban growth in Salt Lake Valley will (1) elevate sensitivity to projected climate variability and (2) motivate more attentive management of urban water use and evaporative fluxes.

The Synthetic Biology Open Language (SBOL) provides a community standard for communicating designs in synthetic biology.

PubMed

Galdzicki, Michal; Clancy, Kevin P; Oberortner, Ernst; Pocock, Matthew; Quinn, Jacqueline Y; Rodriguez, Cesar A; Roehner, Nicholas; Wilson, Mandy L; Adam, Laura; Anderson, J Christopher; Bartley, Bryan A; Beal, Jacob; Chandran, Deepak; Chen, Joanna; Densmore, Douglas; Endy, Drew; Grünberg, Raik; Hallinan, Jennifer; Hillson, Nathan J; Johnson, Jeffrey D; Kuchinsky, Allan; Lux, Matthew; Misirli, Goksel; Peccoud, Jean; Plahar, Hector A; Sirin, Evren; Stan, Guy-Bart; Villalobos, Alan; Wipat, Anil; Gennari, John H; Myers, Chris J; Sauro, Herbert M

2014-06-01

The re-use of previously validated designs is critical to the evolution of synthetic biology from a research discipline to an engineering practice. Here we describe the Synthetic Biology Open Language (SBOL), a proposed data standard for exchanging designs within the synthetic biology community. SBOL represents synthetic biology designs in a community-driven, formalized format for exchange between software tools, research groups and commercial service providers. The SBOL Developers Group has implemented SBOL as an XML/RDF serialization and provides software libraries and specification documentation to help developers implement SBOL in their own software. We describe early successes, including a demonstration of the utility of SBOL for information exchange between several different software tools and repositories from both academic and industrial partners. As a community-driven standard, SBOL will be updated as synthetic biology evolves to provide specific capabilities for different aspects of the synthetic biology workflow.

PASTIS: Bayesian extrasolar planet validation - I. General framework, models, and performance

NASA Astrophysics Data System (ADS)

Díaz, R. F.; Almenara, J. M.; Santerne, A.; Moutou, C.; Lethuillier, A.; Deleuil, M.

2014-06-01

A large fraction of the smallest transiting planet candidates discovered by the Kepler and CoRoT space missions cannot be confirmed by a dynamical measurement of the mass using currently available observing facilities. To establish their planetary nature, the concept of planet validation has been advanced. This technique compares the probability of the planetary hypothesis against that of all reasonably conceivable alternative false positive (FP) hypotheses. The candidate is considered as validated if the posterior probability of the planetary hypothesis is sufficiently larger than the sum of the probabilities of all FP scenarios. In this paper, we present PASTIS, the Planet Analysis and Small Transit Investigation Software, a tool designed to perform a rigorous model comparison of the hypotheses involved in the problem of planet validation, and to fully exploit the information available in the candidate light curves. PASTIS self-consistently models the transit light curves and follow-up observations. Its object-oriented structure offers a large flexibility for defining the scenarios to be compared. The performance is explored using artificial transit light curves of planets and FPs with a realistic error distribution obtained from a Kepler light curve. We find that data support the correct hypothesis strongly only when the signal is high enough (transit signal-to-noise ratio above 50 for the planet case) and remain inconclusive otherwise. PLAnetary Transits and Oscillations of stars (PLATO) shall provide transits with high enough signal-to-noise ratio, but to establish the true nature of the vast majority of Kepler and CoRoT transit candidates additional data or strong reliance on hypotheses priors is needed.

Elaboration of Cognitive Knowledge of Biology from Childhood to Adulthood.

ERIC Educational Resources Information Center

Fisher, Kathleen M.

Word association techniques were used to examine the growth of biological knowledge over a period of years, from fourth-grade to college students. Results were analyzed by classifying stimulus-response word pairs according to the nature of the relationship between the words in each pair. Three hypotheses were tested: (1) the proportion of enactive…

Multidisciplinary approaches to understanding collective cell migration in developmental biology.

PubMed

Schumacher, Linus J; Kulesa, Paul M; McLennan, Rebecca; Baker, Ruth E; Maini, Philip K

2016-06-01

Mathematical models are becoming increasingly integrated with experimental efforts in the study of biological systems. Collective cell migration in developmental biology is a particularly fruitful application area for the development of theoretical models to predict the behaviour of complex multicellular systems with many interacting parts. In this context, mathematical models provide a tool to assess the consistency of experimental observations with testable mechanistic hypotheses. In this review, we showcase examples from recent years of multidisciplinary investigations of neural crest cell migration. The neural crest model system has been used to study how collective migration of cell populations is shaped by cell-cell interactions, cell-environmental interactions and heterogeneity between cells. The wide range of emergent behaviours exhibited by neural crest cells in different embryonal locations and in different organisms helps us chart out the spectrum of collective cell migration. At the same time, this diversity in migratory characteristics highlights the need to reconcile or unify the array of currently hypothesized mechanisms through the next generation of experimental data and generalized theoretical descriptions. © 2016 The Authors.

Effects of Developed Electronic Instructional Medium on Students' Achievement in Biology

ERIC Educational Resources Information Center

Chinna, Nsofor Caroline; Dada, Momoh Gabriel

2013-01-01

The study investigated the effects of developed electronic instructional medium (video DVD instructional package) on students' achievement in Biology. It was guided by two research questions and two hypotheses, using a quasi-experimental, pretest-postest control group design. The sample comprised of 180 senior secondary, year two students from six…

Statistical Selection of Biological Models for Genome-Wide Association Analyses.

PubMed

Bi, Wenjian; Kang, Guolian; Pounds, Stanley B

2018-05-24

Genome-wide association studies have discovered many biologically important associations of genes with phenotypes. Typically, genome-wide association analyses formally test the association of each genetic feature (SNP, CNV, etc) with the phenotype of interest and summarize the results with multiplicity-adjusted p-values. However, very small p-values only provide evidence against the null hypothesis of no association without indicating which biological model best explains the observed data. Correctly identifying a specific biological model may improve the scientific interpretation and can be used to more effectively select and design a follow-up validation study. Thus, statistical methodology to identify the correct biological model for a particular genotype-phenotype association can be very useful to investigators. Here, we propose a general statistical method to summarize how accurately each of five biological models (null, additive, dominant, recessive, co-dominant) represents the data observed for each variant in a GWAS study. We show that the new method stringently controls the false discovery rate and asymptotically selects the correct biological model. Simulations of two-stage discovery-validation studies show that the new method has these properties and that its validation power is similar to or exceeds that of simple methods that use the same statistical model for all SNPs. Example analyses of three data sets also highlight these advantages of the new method. An R package is freely available at www.stjuderesearch.org/site/depts/biostats/maew. Copyright © 2018. Published by Elsevier Inc.

Collection of biological and non-biological particles by new and used filters made from glass and electrostatically charged synthetic fibers.

PubMed

Raynor, P C; Kim, B G; Ramachandran, G; Strommen, M R; Horns, J H; Streifel, A J

2008-02-01

Synthetic filters made from fibers carrying electrostatic charges and fiberglass filters that do not carry electrostatic charges are both utilized commonly in heating, ventilating, and air-conditioning (HVAC) systems. The pressure drop and efficiency of a bank of fiberglass filters and a bank of electrostatically charged synthetic filters were measured repeatedly for 13 weeks in operating HVAC systems at a hospital. Additionally, the efficiency with which new and used fiberglass and synthetic filters collected culturable biological particles was measured in a test apparatus. Pressure drop measurements adjusted to equivalent flows indicated that the synthetic filters operated with a pressure drop less than half that of the fiberglass filters throughout the test. When measured using total ambient particles, synthetic filter efficiency decreased during the test period for all particle diameters. For particles 0.7-1.0 mum in diameter, efficiency decreased from 92% to 44%. It is hypothesized that this reduction in collection efficiency may be due to charge shielding. Efficiency did not change significantly for the fiberglass filters during the test period. However, when measured using culturable biological particles in the ambient air, efficiency was essentially the same for new filters and filters used for 13 weeks in the hospital for both the synthetic and fiberglass filters. It is hypothesized that the lack of efficiency reduction for culturable particles may be due to their having higher charge than non-biological particles, allowing them to overcome the effects of charge shielding. The type of particles requiring capture may be an important consideration when comparing the relative performance of electrostatically charged synthetic and fiberglass filters. Electrostatically charged synthetic filters with high initial efficiency can frequently replace traditional fiberglass filters with lower efficiency in HVAC systems because properly designed synthetic filters

Biologically optimized helium ion plans: calculation approach and its in vitro validation

NASA Astrophysics Data System (ADS)

Mairani, A.; Dokic, I.; Magro, G.; Tessonnier, T.; Kamp, F.; Carlson, D. J.; Ciocca, M.; Cerutti, F.; Sala, P. R.; Ferrari, A.; Böhlen, T. T.; Jäkel, O.; Parodi, K.; Debus, J.; Abdollahi, A.; Haberer, T.

2016-06-01

Treatment planning studies on the biological effect of raster-scanned helium ion beams should be performed, together with their experimental verification, before their clinical application at the Heidelberg Ion Beam Therapy Center (HIT). For this purpose, we introduce a novel calculation approach based on integrating data-driven biological models in our Monte Carlo treatment planning (MCTP) tool. Dealing with a mixed radiation field, the biological effect of the primary 4He ion beams, of the secondary 3He and 4He (Z  =  2) fragments and of the produced protons, deuterons and tritons (Z  =  1) has to be taken into account. A spread-out Bragg peak (SOBP) in water, representative of a clinically-relevant scenario, has been biologically optimized with the MCTP and then delivered at HIT. Predictions of cell survival and RBE for a tumor cell line, characterized by {{(α /β )}\\text{ph}}=5.4 Gy, have been successfully compared against measured clonogenic survival data. The mean absolute survival variation ({μΔ \\text{S}} ) between model predictions and experimental data was 5.3%  ±  0.9%. A sensitivity study, i.e. quantifying the variation of the estimations for the studied plan as a function of the applied phenomenological modelling approach, has been performed. The feasibility of a simpler biological modelling based on dose-averaged LET (linear energy transfer) has been tested. Moreover, comparisons with biophysical models such as the local effect model (LEM) and the repair-misrepair-fixation (RMF) model were performed. {μΔ \\text{S}} values for the LEM and the RMF model were, respectively, 4.5%  ±  0.8% and 5.8%  ±  1.1%. The satisfactorily agreement found in this work for the studied SOBP, representative of clinically-relevant scenario, suggests that the introduced approach could be applied for an accurate estimation of the biological effect for helium ion radiotherapy.

Design and validation of diffusion MRI models of white matter

NASA Astrophysics Data System (ADS)

Jelescu, Ileana O.; Budde, Matthew D.

2017-11-01

Diffusion MRI is arguably the method of choice for characterizing white matter microstructure in vivo. Over the typical duration of diffusion encoding, the displacement of water molecules is conveniently on a length scale similar to that of the underlying cellular structures. Moreover, water molecules in white matter are largely compartmentalized which enables biologically-inspired compartmental diffusion models to characterize and quantify the true biological microstructure. A plethora of white matter models have been proposed. However, overparameterization and mathematical fitting complications encourage the introduction of simplifying assumptions that vary between different approaches. These choices impact the quantitative estimation of model parameters with potential detriments to their biological accuracy and promised specificity. First, we review biophysical white matter models in use and recapitulate their underlying assumptions and realms of applicability. Second, we present up-to-date efforts to validate parameters estimated from biophysical models. Simulations and dedicated phantoms are useful in assessing the performance of models when the ground truth is known. However, the biggest challenge remains the validation of the “biological accuracy” of estimated parameters. Complementary techniques such as microscopy of fixed tissue specimens have facilitated direct comparisons of estimates of white matter fiber orientation and densities. However, validation of compartmental diffusivities remains challenging, and complementary MRI-based techniques such as alternative diffusion encodings, compartment-specific contrast agents and metabolites have been used to validate diffusion models. Finally, white matter injury and disease pose additional challenges to modeling, which are also discussed. This review aims to provide an overview of the current state of models and their validation and to stimulate further research in the field to solve the remaining open

Design and validation of diffusion MRI models of white matter

PubMed Central

Jelescu, Ileana O.; Budde, Matthew D.

2018-01-01

Diffusion MRI is arguably the method of choice for characterizing white matter microstructure in vivo. Over the typical duration of diffusion encoding, the displacement of water molecules is conveniently on a length scale similar to that of the underlying cellular structures. Moreover, water molecules in white matter are largely compartmentalized which enables biologically-inspired compartmental diffusion models to characterize and quantify the true biological microstructure. A plethora of white matter models have been proposed. However, overparameterization and mathematical fitting complications encourage the introduction of simplifying assumptions that vary between different approaches. These choices impact the quantitative estimation of model parameters with potential detriments to their biological accuracy and promised specificity. First, we review biophysical white matter models in use and recapitulate their underlying assumptions and realms of applicability. Second, we present up-to-date efforts to validate parameters estimated from biophysical models. Simulations and dedicated phantoms are useful in assessing the performance of models when the ground truth is known. However, the biggest challenge remains the validation of the “biological accuracy” of estimated parameters. Complementary techniques such as microscopy of fixed tissue specimens have facilitated direct comparisons of estimates of white matter fiber orientation and densities. However, validation of compartmental diffusivities remains challenging, and complementary MRI-based techniques such as alternative diffusion encodings, compartment-specific contrast agents and metabolites have been used to validate diffusion models. Finally, white matter injury and disease pose additional challenges to modeling, which are also discussed. This review aims to provide an overview of the current state of models and their validation and to stimulate further research in the field to solve the remaining open

Good reliability and validity for a new utility instrument measuring the birth experience, the Labor and Delivery Index.

PubMed

Gärtner, Fania R; de Miranda, Esteriek; Rijnders, Marlies E; Freeman, Liv M; Middeldorp, Johanna M; Bloemenkamp, Kitty W M; Stiggelbout, Anne M; van den Akker-van Marle, M Elske

2015-10-01

To validate the Labor and Delivery Index (LADY-X), a new delivery-specific utility measure. In a test-retest design, women were surveyed online, 6 to 8 weeks postpartum and again 1 to 2 weeks later. For reliability testing, we assessed the standard error of measurement (S.E.M.) and the intraclass correlation coefficient (ICC). For construct validity, we tested hypotheses on the association with comparison instruments (Mackey Childbirth Satisfaction Rating Scale and Wijma Delivery Experience Questionnaire), both on domain and total score levels. We assessed known-group differences using eight obstetrical indicators: method and place of birth, induction, transfer, control over pain medication, complications concerning mother and child, and experienced control. The questionnaire was completed by 308 women, 257 (83%) completed the retest. The distribution of LADY-X scores was skewed. The reliability was good, as the ICC exceeded 0.80 and the S.E.M. was 0.76. Requirements for good construct validity were fulfilled: all hypotheses for convergent and divergent validity were confirmed, and six of eight hypotheses for known-group differences were confirmed as all differences were statistically significant (P-values: <0.001-0.023), but for two tests, difference scores did not exceed the S.E.M. The LADY-X demonstrates good reliability and construct validity. Despite its skewed distribution, the LADY-X can discriminate between groups. With the preference weights available, the LADY-X might fulfill the need for a utility measure for cost-effectiveness studies for perinatal care interventions. Copyright © 2015 Elsevier Inc. All rights reserved.

Development and initial validation of a cognitive-based work-nonwork conflict scale.

PubMed

Ezzedeen, Souha R; Swiercz, Paul M

2007-06-01

Current research related to work and life outside work specifies three types of work-nonwork conflict: time, strain, and behavior-based. Overlooked in these models is a cognitive-based type of conflict whereby individuals experience work-nonwork conflict from cognitive preoccupation with work. Four studies on six different groups (N=549) were undertaken to develop and validate an initial measure of this construct. Structural equation modeling confirmed a two-factor, nine-item scale. Hypotheses regarding cognitive-based conflict's relationship with life satisfaction, work involvement, work-nonwork conflict, and work hours were supported. The relationship with knowledge work was partially supported in that only the cognitive dimension of cognitive-based conflict was related to extent of knowledge work. Hypotheses regarding cognitive-based conflict's relationship with family demands were rejected in that the cognitive dimension correlated positively rather than negatively with number of dependent children and perceived family demands. The study provides encouraging preliminary evidence of scale validity.

Advancing the literature on designing audit and feedback interventions: identifying theory-informed hypotheses.

PubMed

Colquhoun, Heather L; Carroll, Kelly; Eva, Kevin W; Grimshaw, Jeremy M; Ivers, Noah; Michie, Susan; Sales, Anne; Brehaut, Jamie C

2017-09-29

Audit and feedback (A&F) is a common strategy for helping health providers to implement evidence into practice. Despite being extensively studied, health care A&F interventions remain variably effective, with overall effect sizes that have not improved since 2003. Contributing to this stagnation is the fact that most health care A&F interventions have largely been designed without being informed by theoretical understanding from the behavioral and social sciences. To determine if the trend can be improved, the objective of this study was to develop a list of testable, theory-informed hypotheses about how to design more effective A&F interventions. Using purposive sampling, semi-structured 60-90-min telephone interviews were conducted with experts in theories related to A&F from a range of fields (e.g., cognitive, health and organizational psychology, medical decision-making, economics). Guided by detailed descriptions of A&F interventions from the health care literature, interviewees described how they would approach the problem of designing improved A&F interventions. Specific, theory-informed hypotheses about the conditions for effective design and delivery of A&F interventions were elicited from the interviews. The resulting hypotheses were assigned by three coders working independently into themes, and categories of themes, in an iterative process. We conducted 28 interviews and identified 313 theory-informed hypotheses, which were placed into 30 themes. The 30 themes included hypotheses related to the following five categories: A&F recipient (seven themes), content of the A&F (ten themes), process of delivery of the A&F (six themes), behavior that was the focus of the A&F (three themes), and other (four themes). We have identified a set of testable, theory-informed hypotheses from a broad range of behavioral and social science that suggest conditions for more effective A&F interventions. This work demonstrates the breadth of perspectives about A&F from non

High Cholesterol/Low Cholesterol: Effects in Biological Membranes: A Review.

PubMed

Subczynski, Witold K; Pasenkiewicz-Gierula, Marta; Widomska, Justyna; Mainali, Laxman; Raguz, Marija

2017-12-01

Lipid composition determines membrane properties, and cholesterol plays a major role in this determination as it regulates membrane fluidity and permeability, as well as induces the formation of coexisting phases and domains in the membrane. Biological membranes display a very diverse lipid composition, the lateral organization of which plays a crucial role in regulating a variety of membrane functions. We hypothesize that, during biological evolution, membranes with a particular cholesterol content were selected to perform certain functions in the cells of eukaryotic organisms. In this review, we discuss the major membrane properties induced by cholesterol, and their relationship to certain membrane functions.

Computational protein design-the next generation tool to expand synthetic biology applications.

PubMed

Gainza-Cirauqui, Pablo; Correia, Bruno Emanuel

2018-05-02

One powerful approach to engineer synthetic biology pathways is the assembly of proteins sourced from one or more natural organisms. However, synthetic pathways often require custom functions or biophysical properties not displayed by natural proteins, limitations that could be overcome through modern protein engineering techniques. Structure-based computational protein design is a powerful tool to engineer new functional capabilities in proteins, and it is beginning to have a profound impact in synthetic biology. Here, we review efforts to increase the capabilities of synthetic biology using computational protein design. We focus primarily on computationally designed proteins not only validated in vitro, but also shown to modulate different activities in living cells. Efforts made to validate computational designs in cells can illustrate both the challenges and opportunities in the intersection of protein design and synthetic biology. We also highlight protein design approaches, which although not validated as conveyors of new cellular function in situ, may have rapid and innovative applications in synthetic biology. We foresee that in the near-future, computational protein design will vastly expand the functional capabilities of synthetic cells. Copyright © 2018. Published by Elsevier Ltd.

Development and Validation of the Masculine Attributes Questionnaire

PubMed Central

Cho, Junhan; Kogan, Steven M.

2017-01-01

The present study describes the development and validation of the Masculine Attributes Questionnaire (MAQ). The purpose of this study was to develop a theoretically and empirically grounded measure of masculine attributes for sexual health research with African American young men. Consistent with Whitehead’s theory, the MAQ items were hypothesized to comprise two components representing reputation-based and respect-based attributes. The sample included 505 African American men aged 19 to 22 years (M = 20.29, SD = 1.10) living in resource-poor communities in the rural South. Convergent and discriminant validity of the MAQ were assessed by examining the associations of masculinity attributes with psychosocial factors. Criterion validity was assessed by examining the extent to which the MAQ subscales predicted sexual risk behavior outcomes. Consistent with study hypotheses, the MAQ was composed of (a) reputation-based attributes oriented toward sexual prowess, toughness, and authority-defying behavior and (b) respect-based attributes oriented toward economic independence, socially approved levels of hard work and education, and committed romantic relationships. Reputation-based attributes were associated positively with street code and negatively related to academic orientation, vocational engagement, and self-regulation, whereas respect-based attributes were associated positively with academic and vocational orientations and self-regulation. Finally, reputation-based attributes predicted sexual risk behaviors including concurrent sexual partnerships, multiple sexual partners, marijuana use, and incarceration, net of the influence of respect-based attributes. The development of the MAQ provides a new measure that permits systematic quantitative investigation of the associations between African American men’s masculinity ideology and sexual risk behavior. PMID:28413906

Development and Validation of the Masculine Attributes Questionnaire.

PubMed

Cho, Junhan; Kogan, Steven M

2017-07-01

The present study describes the development and validation of the Masculine Attributes Questionnaire (MAQ). The purpose of this study was to develop a theoretically and empirically grounded measure of masculine attributes for sexual health research with African American young men. Consistent with Whitehead's theory, the MAQ items were hypothesized to comprise two components representing reputation-based and respect-based attributes. The sample included 505 African American men aged 19 to 22 years ( M = 20.29, SD = 1.10) living in resource-poor communities in the rural South. Convergent and discriminant validity of the MAQ were assessed by examining the associations of masculinity attributes with psychosocial factors. Criterion validity was assessed by examining the extent to which the MAQ subscales predicted sexual risk behavior outcomes. Consistent with study hypotheses, the MAQ was composed of (a) reputation-based attributes oriented toward sexual prowess, toughness, and authority-defying behavior and (b) respect-based attributes oriented toward economic independence, socially approved levels of hard work and education, and committed romantic relationships. Reputation-based attributes were associated positively with street code and negatively related to academic orientation, vocational engagement, and self-regulation, whereas respect-based attributes were associated positively with academic and vocational orientations and self-regulation. Finally, reputation-based attributes predicted sexual risk behaviors including concurrent sexual partnerships, multiple sexual partners, marijuana use, and incarceration, net of the influence of respect-based attributes. The development of the MAQ provides a new measure that permits systematic quantitative investigation of the associations between African American men's masculinity ideology and sexual risk behavior.

Validation of World Health Organization Assessment Schedule 2.0 in specialized somatic rehabilitation services in Norway.

PubMed

Moen, Vegard Pihl; Drageset, Jorunn; Eide, Geir Egil; Klokkerud, Mari; Gjesdal, Sturla

2017-02-01

The World Health Organization Disability Assessment Schedule (WHODAS) 2.0 is a generic instrument to assess disability covering six domains. The purpose of this study was to investigate the potential of the instrument for monitoring disability in specialized somatic rehabilitation by testing reliability, construct validity and responsiveness of WHODAS 2.0, Norwegian version, among patients with various health conditions. For taxonomy, terminology and definitions, the Consensus-based Standards for the Selection of Health Measurement Instruments were followed. Reproducibility was investigated by the intra-class correlation coefficient (ICC) in a randomly selected sample. Internal consistency was assessed by Cronbach's alpha. Construct validity was evaluated by correlations between WHODAS 2.0 and the Medical Outcomes Study 36-item Short Form, and fit of the hypothesized structure using confirmatory factor analysis (CFA). Responsiveness was evaluated in another randomly selected sample by testing a priori formulated hypotheses. Nine hundred seventy patients were included in the study. Reproducibility and responsiveness were evaluated in 53 and 104 patients, respectively. The ICC for the WHODAS 2.0 domains ranged from 0.63 to 0.84 and was 0.87 for total score. Cronbach's alpha for domains ranged from 0.75 to 0.94 and was 0.93 for total score. For construct validity, 6 of 12 expected correlations were confirmed and CFA did not achieve satisfactory fit indices. For responsiveness, 3 of 8 hypotheses were confirmed. The Norwegian version of WHODAS 2.0 showed moderate to satisfactory reliability and moderate validity in rehabilitation patients. However, the present study indicated possible limitations in terms of responsiveness.

A Diagnostic Assessment for Introductory Molecular and Cell Biology

ERIC Educational Resources Information Center

Shi, Jia; Wood, William B.; Martin, Jennifer M.; Guild, Nancy A.; Vicens, Quentin; Knight, Jennifer K.

2010-01-01

We have developed and validated a tool for assessing understanding of a selection of fundamental concepts and basic knowledge in undergraduate introductory molecular and cell biology, focusing on areas in which students often have misconceptions. This multiple-choice Introductory Molecular and Cell Biology Assessment (IMCA) instrument is designed…

The Development and Validation of a Learning Progression for Argumentation in Science

ERIC Educational Resources Information Center

Osborne, Jonathan F.; Henderson, J. Bryan; MacPherson, Anna; Szu, Evan; Wild, Andrew; Yao, Shi-Ying

2016-01-01

Given the centrality of argumentation in the Next Generation Science Standards, there is an urgent need for an empirically validated learning progression of this core practice and the development of high-quality assessment items. Here, we introduce a hypothesized three-tiered learning progression for scientific argumentation. The learning…

Automatic Bayes Factors for Testing Equality- and Inequality-Constrained Hypotheses on Variances.

PubMed

Böing-Messing, Florian; Mulder, Joris

2018-05-03

In comparing characteristics of independent populations, researchers frequently expect a certain structure of the population variances. These expectations can be formulated as hypotheses with equality and/or inequality constraints on the variances. In this article, we consider the Bayes factor for testing such (in)equality-constrained hypotheses on variances. Application of Bayes factors requires specification of a prior under every hypothesis to be tested. However, specifying subjective priors for variances based on prior information is a difficult task. We therefore consider so-called automatic or default Bayes factors. These methods avoid the need for the user to specify priors by using information from the sample data. We present three automatic Bayes factors for testing variances. The first is a Bayes factor with equal priors on all variances, where the priors are specified automatically using a small share of the information in the sample data. The second is the fractional Bayes factor, where a fraction of the likelihood is used for automatic prior specification. The third is an adjustment of the fractional Bayes factor such that the parsimony of inequality-constrained hypotheses is properly taken into account. The Bayes factors are evaluated by investigating different properties such as information consistency and large sample consistency. Based on this evaluation, it is concluded that the adjusted fractional Bayes factor is generally recommendable for testing equality- and inequality-constrained hypotheses on variances.

Development and validity of the Emotion and Motivation Self-regulation Questionnaire (EMSR-Q).

PubMed

Alonso-Tapia, Jesús; Panadero Calderón, Ernesto; Díaz Ruiz, Miguel A

2014-07-15

This study has two objectives, first, to develop and validate the "Emotion and Motivation Self-regulation Questionnaire" (EMSR-Q), and second, to analyze (in the context of the questionnaire validation process) the relationships between self-regulation styles (SRS) rooted in goal orientations, and classroom motivational climate (CMC). A total of 664 Secondary Education students from Madrid (Spain) formed the sample of the study. It was divided randomly in two groups to perform confirmatory factor analysis and to cross-validate the results. Both analyses supported a five first-order factor structure, organized around two second-order factors, "Learning self-regulation style" (LSR) and "Avoidance self-regulation style" (ASR): (χ 2 /df = 2.71; GFI = .89; IFI = .84; CFI = .84; RMSEA = .07). Hypotheses concerning the relationships between SRS, goal orientations and expectancies are supported by additional correlation and factor analyses. Moreover, several regression analyses supported for the most part of the remaining hypotheses concerning the role of self-regulation styles as predictors of classroom motivational climate (CMC) perception, of change in self-regulation attributed to teacher work, and of students' satisfaction with this same work. Theoretical and practical implications are discussed.

Validation of the Work-Life Balance Culture Scale (WLBCS).

PubMed

Nitzsche, Anika; Jung, Julia; Kowalski, Christoph; Pfaff, Holger

2014-01-01

The purpose of this paper is to describe the theoretical development and initial validation of the newly developed Work-Life Balance Culture Scale (WLBCS), an instrument for measuring an organizational culture that promotes the work-life balance of employees. In Study 1 (N=498), the scale was developed and its factorial validity tested through exploratory factor analyses. In Study 2 (N=513), confirmatory factor analysis (CFA) was performed to examine model fit and retest the dimensional structure of the instrument. To assess construct validity, a priori hypotheses were formulated and subsequently tested using correlation analyses. Exploratory and confirmatory factor analyses revealed a one-factor model. Results of the bivariate correlation analyses may be interpreted as preliminary evidence of the scale's construct validity. The five-item WLBCS is a new and efficient instrument with good overall quality. Its conciseness makes it particularly suitable for use in employee surveys to gain initial insight into a company's perceived work-life balance culture.

Validity and reliability of a pictorial instrument for assessing perceived motor competence in Portuguese children.

PubMed

Lopes, V P; Barnett, L M; Saraiva, L; Gonçalves, C; Bowe, S J; Abbott, G; Rodrigues, L P

2016-09-01

It is important to assess young children's perceived Fundamental Movement Skill (FMS) competence in order to examine the role of perceived FMS competence in motivation toward physical activity. Children's perceptions of motor competence may vary according to the culture/country of origin; therefore, it is also important to measure perceptions in different cultural contexts. The purpose was to assess the face validity, internal consistency, test-retest reliability and construct validity of the 12 FMS items in the Pictorial Scale for Perceived Movement Skill Competence for Young Children (PMSC) in a Portuguese sample. Two hundred one Portuguese children (girls, n = 112), 5 to 10 years of age (7.6 ± 1.4), participated. All children completed the PMSC once. Ordinal alpha assessed internal consistency. A random subsamples (n = 47) were reassessed one week later to determine test-retest reliability with Bland-Altman method. Children were asked questions after the second administration to determine face validity. Construct validity was assessed on the whole sample with a Bayesian Structural Equation Modelling (BSEM) approach. The hypothesized theoretical model used the 12 items and two hypothesized factors: object control and locomotor skills. The majority of children correctly identified the skills and could understand most of the pictures. Test-retest reliability analysis was good, with an agreement ration between 0.99 and 1.02. Ordinal alpha values ranged from acceptable (object control 0.73, locomotor 0.68) to good (all FMS 0.81). The hypothesized BSEM model had an adequate fit. The PMSC can be used to investigate perceptions of children's FMS competence. This instrument can also be satisfactorily used among Portuguese children. © 2016 John Wiley & Sons Ltd.

Review of surface steam sterilization for validation purposes.

PubMed

van Doornmalen, Joost; Kopinga, Klaas

2008-03-01

Sterilization is an essential step in the process of producing sterile medical devices. To guarantee sterility, the process of sterilization must be validated. Because there is no direct way to measure sterility, the techniques applied to validate the sterilization process are based on statistical principles. Steam sterilization is the most frequently applied sterilization method worldwide and can be validated either by indicators (chemical or biological) or physical measurements. The steam sterilization conditions are described in the literature. Starting from these conditions, criteria for the validation of steam sterilization are derived and can be described in terms of physical parameters. Physical validation of steam sterilization appears to be an adequate and efficient validation method that could be considered as an alternative for indicator validation. Moreover, physical validation can be used for effective troubleshooting in steam sterilizing processes.

Deficiency in the Opioid Hypotheses of Self-Injurious Behavior.

ERIC Educational Resources Information Center

King, Bryan H.; And Others

1991-01-01

This commentary critiques two papers by Curt Sandman, pointing out interpretive problems in models explaining self-injurious behavior in terms of opioids. Withdrawal effects are emphasized as an alternative to hypotheses asserting congenital opioid excess as a cause of sensory depression or an addiction to a relative excess of opioid activity in…

S-Nitrosothiol measurements in biological systems⋄

PubMed Central

Gow, Andrew; Doctor, Allan; Mannick, Joan; Gaston, Benjamin

2007-01-01

S-Nitrosothiol (SNO) cysteine modifications are regulated signaling reactions that dramatically affect, and are affected by, protein conformation. The lability of the S-NO bond can make SNO-modified proteins cumbersome to measure accurately. Here, we review methodologies for detecting SNO modifications in biology. There are three caveats. 1) Many assays for biological SNOs are used near the limit of detection: standard curves must be in the biologically relevant concentration range. 2) The assays that are most reliable are those that modify SNO protein or peptide chemistry the least. 3) Each result should be quantitatively validated using more than one assay. Improved assays are needed and are in development. PMID:17379583

Exaptation in human evolution: how to test adaptive vs exaptive evolutionary hypotheses.

PubMed

Pievani, Telmo; Serrelli, Emanuele

2011-01-01

Palaeontologists, Stephen J. Gould and Elisabeth Vrba, introduced the term "ex-aptation" with the aim of improving and enlarging the scientific language available to researchers studying the evolution of any useful character, instead of calling it an "adaptation" by default, coming up with what Gould named an "extended taxonomy of fitness". With the extension to functional co-optations from non-adaptive structures ("spandrels"), the notion of exaptation expanded and revised the neo-Darwinian concept of "pre-adaptation" (which was misleading, for Gould and Vrba, suggesting foreordination). Exaptation is neither a "saltationist" nor an "anti-Darwinian" concept and, since 1982, has been adopted by many researchers in evolutionary and molecular biology, and particularly in human evolution. Exaptation has also been contested. Objections include the "non-operationality objection".We analyze the possible operationalization of this concept in two recent studies, and identify six directions of empirical research, which are necessary to test "adaptive vs. exaptive" evolutionary hypotheses. We then comment on a comprehensive survey of literature (available online), and on the basis of this we make a quantitative and qualitative evaluation of the adoption of the term among scientists who study human evolution. We discuss the epistemic conditions that may have influenced the adoption and appropriate use of exaptation, and comment on the benefits of an "extended taxonomy of fitness" in present and future studies concerning human evolution.

Efficiently Photocontrollable or not? Biological Activity of Photoisomerizable Diarylethenes.

PubMed

Komarov, Igor V; Afonin, Sergii; Babii, Oleg; Schober, Tim; Ulrich, Anne S

2018-04-06

Diarylethene derivatives, whose biological activity can be reversibly changed by irradiation with light of different wavelengths, have shown promise as scientific tools and as candidates for photocontrollable drugs. However, examples demonstrating efficient photocontrol of their biological activity are still relatively rare. This concept article discusses the possible reasons for this situation and presents a critical analysis of existing data and hypotheses in this field, in order to extract the design principles enabling the construction of efficient photocontrollable diarylethene-based molecules. Papers addressing biologically relevant interactions between diarylethenes and biomolecules are analyzed; however, in most published cases, the efficiency of photocontrol in living systems remains to be demonstrated. We hope that this article will encourage further discussion of design principles, primarily among pharmacologists and synthetic and medicinal chemists. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The KUPNetViz: a biological network viewer for multiple -omics datasets in kidney diseases.

PubMed

Moulos, Panagiotis; Klein, Julie; Jupp, Simon; Stevens, Robert; Bascands, Jean-Loup; Schanstra, Joost P

2013-07-24

Constant technological advances have allowed scientists in biology to migrate from conventional single-omics to multi-omics experimental approaches, challenging bioinformatics to bridge this multi-tiered information. Ongoing research in renal biology is no exception. The results of large-scale and/or high throughput experiments, presenting a wealth of information on kidney disease are scattered across the web. To tackle this problem, we recently presented the KUPKB, a multi-omics data repository for renal diseases. In this article, we describe KUPNetViz, a biological graph exploration tool allowing the exploration of KUPKB data through the visualization of biomolecule interactions. KUPNetViz enables the integration of multi-layered experimental data over different species, renal locations and renal diseases to protein-protein interaction networks and allows association with biological functions, biochemical pathways and other functional elements such as miRNAs. KUPNetViz focuses on the simplicity of its usage and the clarity of resulting networks by reducing and/or automating advanced functionalities present in other biological network visualization packages. In addition, it allows the extrapolation of biomolecule interactions across different species, leading to the formulations of new plausible hypotheses, adequate experiment design and to the suggestion of novel biological mechanisms. We demonstrate the value of KUPNetViz by two usage examples: the integration of calreticulin as a key player in a larger interaction network in renal graft rejection and the novel observation of the strong association of interleukin-6 with polycystic kidney disease. The KUPNetViz is an interactive and flexible biological network visualization and exploration tool. It provides renal biologists with biological network snapshots of the complex integrated data of the KUPKB allowing the formulation of new hypotheses in a user friendly manner.

The KUPNetViz: a biological network viewer for multiple -omics datasets in kidney diseases

PubMed Central

2013-01-01

Background Constant technological advances have allowed scientists in biology to migrate from conventional single-omics to multi-omics experimental approaches, challenging bioinformatics to bridge this multi-tiered information. Ongoing research in renal biology is no exception. The results of large-scale and/or high throughput experiments, presenting a wealth of information on kidney disease are scattered across the web. To tackle this problem, we recently presented the KUPKB, a multi-omics data repository for renal diseases. Results In this article, we describe KUPNetViz, a biological graph exploration tool allowing the exploration of KUPKB data through the visualization of biomolecule interactions. KUPNetViz enables the integration of multi-layered experimental data over different species, renal locations and renal diseases to protein-protein interaction networks and allows association with biological functions, biochemical pathways and other functional elements such as miRNAs. KUPNetViz focuses on the simplicity of its usage and the clarity of resulting networks by reducing and/or automating advanced functionalities present in other biological network visualization packages. In addition, it allows the extrapolation of biomolecule interactions across different species, leading to the formulations of new plausible hypotheses, adequate experiment design and to the suggestion of novel biological mechanisms. We demonstrate the value of KUPNetViz by two usage examples: the integration of calreticulin as a key player in a larger interaction network in renal graft rejection and the novel observation of the strong association of interleukin-6 with polycystic kidney disease. Conclusions The KUPNetViz is an interactive and flexible biological network visualization and exploration tool. It provides renal biologists with biological network snapshots of the complex integrated data of the KUPKB allowing the formulation of new hypotheses in a user friendly manner. PMID:23883183

Interinstrument Variability and Validation Study for the XMX/2L-MIL Biological Air Sampler

DTIC Science & Technology

2012-07-13

fixed final nozzle orientation. Three XMXs were operated in a 12-m3 aerosol test chamber (ATC) in which a Bacillus globigii (Bg) aerosol was...impactor, aerosol, biological aerosol, collection media, biological agent, Remel M5®, PBS solution, Bacillus globigii, male-specific 2 bacteriophage, MS2...Edmonton AB, Canada. The performance of the XMX was evaluated using two biological agents, spore-forming bacteria Bacillus globigii (Bg) and viral

Furious Frederich: Nietzsche's neurosyphilis diagnosis and new hypotheses.

PubMed

André, Charles; Rios, André Rangel

2015-12-01

The causes of Friedrich Nietzsche's mental breakdown in early 1889 and of the subsequent slow decay to end-stage dementia along ten years will possibly remain open to debate. The diagnosis of syphilitic dementia paralytica, based only on medical anamnesis and physical examination, was considered indisputable by Otto Binswanger. On the other hand, taking into account recently described diseases, selectively collected evidence lend some support to alternative hypotheses: basal forebrain meningioma, CADASIL, MELAS and frontotemporal dementia.

Leveraging contemporary species introductions to test phylogenetic hypotheses of trait evolution.

PubMed

Lu-Irving, Patricia; Marx, Hannah E; Dlugosch, Katrina M

2018-05-10

Plant trait evolution is a topic of interest across disciplines and scales. Phylogenetic studies are powerful for generating hypotheses about the mechanisms that have shaped plant traits and their evolution. Introduced plants are a rich source of data on contemporary trait evolution. Introductions could provide especially useful tests of a variety of evolutionary hypotheses because the environments selecting on evolving traits are still present. We review phylogenetic and contemporary studies of trait evolution and identify areas of overlap and areas for further integration. Emerging tools which can promote integration include broadly focused repositories of trait data, and comparative models of trait evolution that consider both intra and interspecific variation. Copyright © 2018 Elsevier Ltd. All rights reserved.

The emerging molecular biology toolbox for the study of long noncoding RNA biology.

PubMed

Fok, Ezio T; Scholefield, Janine; Fanucchi, Stephanie; Mhlanga, Musa M

2017-10-01

Long noncoding RNAs (lncRNAs) have been implicated in many biological processes. However, due to the unique nature of lncRNAs and the consequential difficulties associated with their characterization, there is a growing disparity between the rate at which lncRNAs are being discovered and the assignment of biological function to these transcripts. Here we present a molecular biology toolbox equipped to help dissect aspects of lncRNA biology and reveal functionality. We outline an approach that begins with a broad survey of genome-wide, high-throughput datasets to identify potential lncRNA candidates and then narrow the focus on specific methods that are well suited to interrogate the transcripts of interest more closely. This involves the use of imaging-based strategies to validate these candidates and observe the behaviors of these transcripts at single molecule resolution in individual cells. We also describe the use of gene editing tools and interactome capture techniques to interrogate functionality and infer mechanism, respectively. With the emergence of lncRNAs as important molecules in healthy and diseased cellular function, it remains crucial to deepen our understanding of their biology.

Comparison for aphasic and control subjects of eye movements hypothesized in neurolinguistic programming.

PubMed

Dooley, K O; Farmer, A

1988-08-01

Neurolinguistic programming's hypothesized eye movements were measured independently using videotapes of 10 nonfluent aphasic and 10 control subjects matched for age and sex. Chi-squared analysis indicated that eye-position responses were significantly different for the groups. Although earlier research has not supported the hypothesized eye positions for normal subjects, the present findings support the contention that eye-position responses may differ between neurologically normal and aphasic individuals.

Psychometric Properties and Validation of the Arabic Social Media Addiction Scale.

PubMed

Al-Menayes, Jamal

2015-01-01

This study investigated the psychometric properties of the Arabic version of the SMAS. SMAS is a variant of IAT customized to measure addiction to social media instead of the Internet as a whole. Using a self-report instrument on a cross-sectional sample of undergraduate students, the results revealed the following. First, the exploratory factor analysis showed that a three-factor model fits the data well. Second, concurrent validity analysis showed the SMAS to be a valid measure of social media addiction. However, further studies and data should verify the hypothesized model. Finally, this study showed that the Arabic version of the SMAS is a valid and reliable instrument for use in measuring social media addiction in the Arab world.

Psychometric Properties and Validation of the Arabic Social Media Addiction Scale

PubMed Central

Al-Menayes, Jamal

2015-01-01

This study investigated the psychometric properties of the Arabic version of the SMAS. SMAS is a variant of IAT customized to measure addiction to social media instead of the Internet as a whole. Using a self-report instrument on a cross-sectional sample of undergraduate students, the results revealed the following. First, the exploratory factor analysis showed that a three-factor model fits the data well. Second, concurrent validity analysis showed the SMAS to be a valid measure of social media addiction. However, further studies and data should verify the hypothesized model. Finally, this study showed that the Arabic version of the SMAS is a valid and reliable instrument for use in measuring social media addiction in the Arab world. PMID:26347848

A framework for evolutionary systems biology

PubMed Central

Loewe, Laurence

2009-01-01

Background Many difficult problems in evolutionary genomics are related to mutations that have weak effects on fitness, as the consequences of mutations with large effects are often simple to predict. Current systems biology has accumulated much data on mutations with large effects and can predict the properties of knockout mutants in some systems. However experimental methods are too insensitive to observe small effects. Results Here I propose a novel framework that brings together evolutionary theory and current systems biology approaches in order to quantify small effects of mutations and their epistatic interactions in silico. Central to this approach is the definition of fitness correlates that can be computed in some current systems biology models employing the rigorous algorithms that are at the core of much work in computational systems biology. The framework exploits synergies between the realism of such models and the need to understand real systems in evolutionary theory. This framework can address many longstanding topics in evolutionary biology by defining various 'levels' of the adaptive landscape. Addressed topics include the distribution of mutational effects on fitness, as well as the nature of advantageous mutations, epistasis and robustness. Combining corresponding parameter estimates with population genetics models raises the possibility of testing evolutionary hypotheses at a new level of realism. Conclusion EvoSysBio is expected to lead to a more detailed understanding of the fundamental principles of life by combining knowledge about well-known biological systems from several disciplines. This will benefit both evolutionary theory and current systems biology. Understanding robustness by analysing distributions of mutational effects and epistasis is pivotal for drug design, cancer research, responsible genetic engineering in synthetic biology and many other practical applications. PMID:19239699

Bridging the gap between biologic, individual, and macroenvironmental factors in cancer: a multilevel approach.

PubMed

Lynch, Shannon M; Rebbeck, Timothy R

2013-04-01

To address the complex nature of cancer occurrence and outcomes, approaches have been developed to simultaneously assess the role of two or more etiologic agents within hierarchical levels including the: (i) macroenvironment level (e.g., health care policy, neighborhood, or family structure); (ii) individual level (e.g., behaviors, carcinogenic exposures, socioeconomic factors, and psychologic responses); and (iii) biologic level (e.g., cellular biomarkers and inherited susceptibility variants). Prior multilevel approaches tend to focus on social and environmental hypotheses, and are thus limited in their ability to integrate biologic factors into a multilevel framework. This limited integration may be related to the limited translation of research findings into the clinic. We propose a "Multi-level Biologic and Social Integrative Construct" (MBASIC) to integrate macroenvironment and individual factors with biology. The goal of this framework is to help researchers identify relationships among factors that may be involved in the multifactorial, complex nature of cancer etiology, to aid in appropriate study design, to guide the development of statistical or mechanistic models to study these relationships, and to position the results of these studies for improved intervention, translation, and implementation. MBASIC allows researchers from diverse fields to develop hypotheses of interest under a common conceptual framework, to guide transdisciplinary collaborations, and to optimize the value of multilevel studies for clinical and public health activities.

Biological pathways and genetic mechanisms involved in social functioning.

PubMed

Ordoñana, Juan R; Bartels, Meike; Boomsma, Dorret I; Cella, David; Mosing, Miriam; Oliveira, Joao R; Patrick, Donald L; Veenhoven, Ruut; Wagner, Gert G; Sprangers, Mirjam A G

2013-08-01

To describe the major findings in the literature regarding associations between biological and genetic factors and social functioning, paying special attention to: (1) heritability studies on social functioning and related concepts; (2) hypothesized biological pathways and genetic variants that could be involved in social functioning, and (3) the implications of these results for quality-of-life research. A search of Web of Science and PubMed databases was conducted using combinations of the following keywords: genetics, twins, heritability, social functioning, social adjustment, social interaction, and social dysfunction. Variability in the definitions and measures of social functioning was extensive. Moderate to high heritability was reported for social functioning and related concepts, including prosocial behavior, loneliness, and extraversion. Disorders characterized by impairments in social functioning also show substantial heritability. Genetic variants hypothesized to be involved in social functioning are related to the network of brain structures and processes that are known to affect social cognition and behavior. Better knowledge and understanding about the impact of genetic factors on social functioning is needed to help us to attain a more comprehensive view of health-related quality-of-life (HRQOL) and will ultimately enhance our ability to identify those patients who are vulnerable to poor social functioning.

Epidemiology and biology of physical activity and cancer recurrence.

PubMed

Friedenreich, Christine M; Shaw, Eileen; Neilson, Heather K; Brenner, Darren R

2017-10-01

Physical activity is emerging from epidemiologic research as a lifestyle factor that may improve survival from colorectal, breast, and prostate cancers. However, there is considerably less evidence relating physical activity to cancer recurrence and the biologic mechanisms underlying this association remain unclear. Cancer patients are surviving longer than ever before, and fear of cancer recurrence is an important concern. Herein, we provide an overview of the current epidemiologic evidence relating physical activity to cancer recurrence. We review the biologic mechanisms most commonly researched in the context of physical activity and cancer outcomes, and, using the example of colorectal cancer, we explore hypothesized mechanisms through which physical activity might intervene in the colorectal recurrence pathway. Our review highlights the importance of considering pre-diagnosis and post-diagnosis activity, as well as cancer stage and timing of recurrence, in epidemiologic studies. In addition, more epidemiologic research is needed with cancer recurrence as a consistently defined outcome studied separately from survival. Future mechanistic research using randomized controlled trials, specifically those demonstrating the exercise responsiveness of hypothesized mechanisms in early stages of carcinogenesis, are needed to inform recommendations about when to exercise and to anticipate additive or synergistic effects with other preventive behaviors or treatments.

Evaluation of seven hypotheses for metamemory performance in rhesus monkeys

PubMed Central

Basile, Benjamin M.; Schroeder, Gabriel R.; Brown, Emily Kathryn; Templer, Victoria L.; Hampton, Robert R.

2014-01-01

Knowing the extent to which nonhumans and humans share mechanisms for metacognition will advance our understanding of cognitive evolution and will improve selection of model systems for biomedical research. Some nonhuman species avoid difficult cognitive tests, seek information when ignorant, or otherwise behave in ways consistent with metacognition. There is agreement that some nonhuman animals “succeed” in these metacognitive tasks, but little consensus about the cognitive mechanisms underlying performance. In one paradigm, rhesus monkeys visually searched for hidden food when ignorant of the location of the food, but acted immediately when knowledgeable. This result has been interpreted as evidence that monkeys introspectively monitored their memory to adaptively control information seeking. However, convincing alternative hypotheses have been advanced that might also account for the adaptive pattern of visual searching. We evaluated seven hypotheses using a computerized task in which monkeys chose either to take memory tests immediately or to see the answer again before proceeding to the test. We found no evidence to support the hypotheses of behavioral cue association, rote response learning, expectancy violation, response competition, generalized search strategy, or postural mediation. In contrast, we repeatedly found evidence to support the memory monitoring hypothesis. Monkeys chose to see the answer when memory was poor, either from natural variation or experimental manipulation. We found limited evidence that monkeys also monitored the fluency of memory access. Overall, the evidence indicates that rhesus monkeys can use memory strength as a discriminative cue for information seeking, consistent with introspective monitoring of explicit memory. PMID:25365530

An exploratory study into the effect of time-restricted internet access on face-validity, construct validity and reliability of postgraduate knowledge progress testing

PubMed Central

2013-01-01

Background Yearly formative knowledge testing (also known as progress testing) was shown to have a limited construct-validity and reliability in postgraduate medical education. One way to improve construct-validity and reliability is to improve the authenticity of a test. As easily accessible internet has become inseparably linked to daily clinical practice, we hypothesized that allowing internet access for a limited amount of time during the progress test would improve the perception of authenticity (face-validity) of the test, which would in turn improve the construct-validity and reliability of postgraduate progress testing. Methods Postgraduate trainees taking the yearly knowledge progress test were asked to participate in a study where they could access the internet for 30 minutes at the end of a traditional pen and paper test. Before and after the test they were asked to complete a short questionnaire regarding the face-validity of the test. Results Mean test scores increased significantly for all training years. Trainees indicated that the face-validity of the test improved with internet access and that they would like to continue to have internet access during future testing. Internet access did not improve the construct-validity or reliability of the test. Conclusion Improving the face-validity of postgraduate progress testing, by adding the possibility to search the internet for a limited amount of time, positively influences test performance and face-validity. However, it did not change the reliability or the construct-validity of the test. PMID:24195696

Developing risk hypotheses and selecting species for assessing non-target impacts of GM trees with novel traits: the case of altered-lignin pine trees.

PubMed

Malone, Louise A; Todd, Jacqui H; Burgess, Elisabeth P J; Walter, Christian; Wagner, Armin; Barratt, Barbara I P

2010-01-01

A procedure is presented for developing environmental risk hypotheses associated with the deployment of forest trees genetically modified to have altered wood properties and for selecting non-target species to test these hypotheses. Altered-lignin Pinus radiata trees intended for use in New Zealand are used as a hypothetical case study to illustrate our approach. Firstly, environmental management goals (such as wood production, flood control or preservation of biodiversity) were identified and linked to the forest attributes they require. Necessary conditions for each attribute were listed and appropriate assessment endpoints for them developed. For example, biological control of pests may be one condition necessary for a forest to have healthy trees, and the diversity and abundance of natural enemy species in the forest could be an appropriate assessment endpoint for measuring this condition. A conceptual model describing the relationships between an altered-lignin GM pine tree and potentially affected invertebrates and micro-organisms in a plantation forest was used to develop a set of risk hypotheses describing how the GM trees might affect each assessment endpoint. Because purified lignin does not represent the properties it imparts to wood, maximum hazard dose tests with non-target organisms, as are used to inform toxin risk assessment, cannot be conducted. Alternative experiments, based on current knowledge of the responses of organisms to lignin, must be designed. A screening method was adapted and applied to a database of invertebrate species known to inhabit New Zealand pine forests to identify and prioritize non-target invertebrate species that could be used as experimental subjects for examining these hypotheses. The screening model and its application are presented, along with a set of recommendations for pre-release tests with GM pines and potentially affected invertebrates and micro-organisms. © ISBR, EDP Sciences, 2011.

Confirmatory and Competitive Evaluation of Alternative Gene-Environment Interaction Hypotheses

ERIC Educational Resources Information Center

Belsky, Jay; Pluess, Michael; Widaman, Keith F.

2013-01-01

Background: Most gene-environment interaction (GXE) research, though based on clear, vulnerability-oriented hypotheses, is carried out using exploratory rather than hypothesis-informed statistical tests, limiting power and making formal evaluation of competing GXE propositions difficult. Method: We present and illustrate a new regression technique…

Differential invasion success of salmonids in southern Chile: patterns and hypotheses

USGS Publications Warehouse

Arismendi, Ivan; Penaluna, Brooke E.; Dunham, Jason B.; García de Leaniz, Carlos; Soto, Doris; Fleming, Ian A.; Gomez-Uchidam, Daniel; Gajardo, Gonzalo; Vargas, Pamela V.; León-Muñoz, Jorge

2014-01-01

Biological invasions create complex ecological and societal issues worldwide. Most of the knowledge about invasions comes only from successful invaders, but less is known about which processes determine the differential success of invasions. In this review, we develop a framework to identify the main dimensions driving the success and failure of invaders, including human influences, characteristics of the invader, and biotic interactions. We apply this framework by contrasting hypotheses and available evidence to explain variability in invasion success for 12 salmonids introduced to Chile. The success of Oncorhynchus mykiss and Salmo trutta seems to be influenced by a context-specific combination of their phenotypic plasticity, low ecosystem resistance, and propagule pressure. These well-established invaders may limit the success of subsequently introduced salmonids, with the possible exception of O. tshawytscha, which has a short freshwater residency and limited spatial overlap with trout. Although propagule pressure is high for O. kisutch and S. salar due to their intensive use in aquaculture, their lack of success in Chile may be explained by environmental resistance, including earlier spawning times than in their native ranges, and interactions with previously established and resident Rainbow Trout. Other salmonids have also failed to establish, and they exhibit a suite of ecological traits, environmental resistance, and limited propagule pressure that are variably associated with their lack of success. Collectively, understanding how the various drivers of invasion success interact may explain the differential success of invaders and provide key guidance for managing both positive and negative outcomes associated with their presence.

Measuring the Effect of Tourism Services on Travelers' Quality of Life: Further Validation.

ERIC Educational Resources Information Center

Neal, Janet D.; Sirgy, M. Joseph; Uysal, Muzaffer

2004-01-01

lication and extension study provided additional validational support of the original tourism services satisfaction measure in relation to QOL-related measures.Neal, Sirgy and Uysal (1999) developed a model and a measure to capture the effect of tourism services on travelers' quality of life (QOL). They hypothesized that travelers' overall life…

Cell and molecular biology of the spiny dogfish Squalus acanthias and little skate Leucoraja erinacea: insights from in vitro cultured cells.

PubMed

Barnes, D W

2012-04-01

Two of the most commonly used elasmobranch experimental model species are the spiny dogfish Squalus acanthias and the little skate Leucoraja erinacea. Comparative biology and genomics with these species have provided useful information in physiology, pharmacology, toxicology, immunology, evolutionary developmental biology and genetics. A wealth of information has been obtained using in vitro approaches to study isolated cells and tissues from these organisms under circumstances in which the extracellular environment can be controlled. In addition to classical work with primary cell cultures, continuously proliferating cell lines have been derived recently, representing the first cell lines from cartilaginous fishes. These lines have proved to be valuable tools with which to explore functional genomic and biological questions and to test hypotheses at the molecular level. In genomic experiments, complementary (c)DNA libraries have been constructed, and c. 8000 unique transcripts identified, with over 3000 representing previously unknown gene sequences. A sub-set of messenger (m)RNAs has been detected for which the 3' untranslated regions show elements that are remarkably well conserved evolutionarily, representing novel, potentially regulatory gene sequences. The cell culture systems provide physiologically valid tools to study functional roles of these sequences and other aspects of elasmobranch molecular cell biology and physiology. Information derived from the use of in vitro cell cultures is valuable in revealing gene diversity and information for genomic sequence assembly, as well as for identification of new genes and molecular markers, construction of gene-array probes and acquisition of full-length cDNA sequences. © 2012 The Author. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.

Agent-Based Modeling in Molecular Systems Biology.

PubMed

Soheilypour, Mohammad; Mofrad, Mohammad R K

2018-07-01

Molecular systems orchestrating the biology of the cell typically involve a complex web of interactions among various components and span a vast range of spatial and temporal scales. Computational methods have advanced our understanding of the behavior of molecular systems by enabling us to test assumptions and hypotheses, explore the effect of different parameters on the outcome, and eventually guide experiments. While several different mathematical and computational methods are developed to study molecular systems at different spatiotemporal scales, there is still a need for methods that bridge the gap between spatially-detailed and computationally-efficient approaches. In this review, we summarize the capabilities of agent-based modeling (ABM) as an emerging molecular systems biology technique that provides researchers with a new tool in exploring the dynamics of molecular systems/pathways in health and disease. © 2018 WILEY Periodicals, Inc.

Conceptual dissonance: evaluating the efficacy of natural language processing techniques for validating translational knowledge constructs.

PubMed

Payne, Philip R O; Kwok, Alan; Dhaval, Rakesh; Borlawsky, Tara B

2009-03-01

The conduct of large-scale translational studies presents significant challenges related to the storage, management and analysis of integrative data sets. Ideally, the application of methodologies such as conceptual knowledge discovery in databases (CKDD) provides a means for moving beyond intuitive hypothesis discovery and testing in such data sets, and towards the high-throughput generation and evaluation of knowledge-anchored relationships between complex bio-molecular and phenotypic variables. However, the induction of such high-throughput hypotheses is non-trivial, and requires correspondingly high-throughput validation methodologies. In this manuscript, we describe an evaluation of the efficacy of a natural language processing-based approach to validating such hypotheses. As part of this evaluation, we will examine a phenomenon that we have labeled as "Conceptual Dissonance" in which conceptual knowledge derived from two or more sources of comparable scope and granularity cannot be readily integrated or compared using conventional methods and automated tools.

Contemporary Test Validity in Theory and Practice: A Primer for Discipline-Based Education Researchers

PubMed Central

Reeves, Todd D.; Marbach-Ad, Gili

2016-01-01

Most discipline-based education researchers (DBERs) were formally trained in the methods of scientific disciplines such as biology, chemistry, and physics, rather than social science disciplines such as psychology and education. As a result, DBERs may have never taken specific courses in the social science research methodology—either quantitative or qualitative—on which their scholarship often relies so heavily. One particular aspect of (quantitative) social science research that differs markedly from disciplines such as biology and chemistry is the instrumentation used to quantify phenomena. In response, this Research Methods essay offers a contemporary social science perspective on test validity and the validation process. The instructional piece explores the concepts of test validity, the validation process, validity evidence, and key threats to validity. The essay also includes an in-depth example of a validity argument and validation approach for a test of student argument analysis. In addition to DBERs, this essay should benefit practitioners (e.g., lab directors, faculty members) in the development, evaluation, and/or selection of instruments for their work assessing students or evaluating pedagogical innovations. PMID:26903498

Freshwater ecosystems and aquatic insects: a paradox in biological invasions.

PubMed

Fenoglio, Stefano; Bonada, Núria; Guareschi, Simone; López-Rodríguez, Manuel J; Millán, Andrés; Tierno de Figueroa, J Manuel

2016-04-01

Biological invasions have increased significantly in response to global change and constitute one of the major causes of biodiversity loss. Insects make up a large fraction of invasive species, in general, and freshwaters are among the most invaded ecosystems on our planet. However, even though aquatic insects dominate most inland waters, have unparalleled taxonomic diversity and occupy nearly all trophic niches, there are almost no invasive insects in freshwaters. We present some hypotheses regarding why aquatic insects are not common among aquatic invasive organisms, suggesting that it may be the result of a suite of biological, ecological and anthropogenic factors. Such specific knowledge introduces a paradox in the current scientific discussion on invasive species; therefore, a more in-depth understanding could be an invaluable aid to disentangling how and why biological invasions occur. © 2016 The Author(s).

Breath-giving cooperation: critical review of origin of mitochondria hypotheses : Major unanswered questions point to the importance of early ecology.

PubMed

Zachar, István; Szathmáry, Eörs

2017-08-14

The origin of mitochondria is a unique and hard evolutionary problem, embedded within the origin of eukaryotes. The puzzle is challenging due to the egalitarian nature of the transition where lower-level units took over energy metabolism. Contending theories widely disagree on ancestral partners, initial conditions and unfolding of events. There are many open questions but there is no comparative examination of hypotheses. We have specified twelve questions about the observable facts and hidden processes leading to the establishment of the endosymbiont that a valid hypothesis must address. We have objectively compared contending hypotheses under these questions to find the most plausible course of events and to draw insight on missing pieces of the puzzle. Since endosymbiosis borders evolution and ecology, and since a realistic theory has to comply with both domains' constraints, the conclusion is that the most important aspect to clarify is the initial ecological relationship of partners. Metabolic benefits are largely irrelevant at this initial phase, where ecological costs could be more disruptive. There is no single theory capable of answering all questions indicating a severe lack of ecological considerations. A new theory, compliant with recent phylogenomic results, should adhere to these criteria. This article was reviewed by Michael W. Gray, William F. Martin and Purificación López-García.

Assessing hypotheses about nesting site occupancy dynamics

USGS Publications Warehouse

Bled, Florent; Royle, J. Andrew; Cam, Emmanuelle

2011-01-01

Hypotheses about habitat selection developed in the evolutionary ecology framework assume that individuals, under some conditions, select breeding habitat based on expected fitness in different habitat. The relationship between habitat quality and fitness may be reflected by breeding success of individuals, which may in turn be used to assess habitat quality. Habitat quality may also be assessed via local density: if high-quality sites are preferentially used, high density may reflect high-quality habitat. Here we assessed whether site occupancy dynamics vary with site surrogates for habitat quality. We modeled nest site use probability in a seabird subcolony (the Black-legged Kittiwake, Rissa tridactyla) over a 20-year period. We estimated site persistence (an occupied site remains occupied from time t to t + 1) and colonization through two subprocesses: first colonization (site creation at the timescale of the study) and recolonization (a site is colonized again after being deserted). Our model explicitly incorporated site-specific and neighboring breeding success and conspecific density in the neighborhood. Our results provided evidence that reproductively "successful'' sites have a higher persistence probability than "unsuccessful'' ones. Analyses of site fidelity in marked birds and of survival probability showed that high site persistence predominantly reflects site fidelity, not immediate colonization by new owners after emigration or death of previous owners. There is a negative quadratic relationship between local density and persistence probability. First colonization probability decreases with density, whereas recolonization probability is constant. This highlights the importance of distinguishing initial colonization and recolonization to understand site occupancy. All dynamics varied positively with neighboring breeding success. We found evidence of a positive interaction between site-specific and neighboring breeding success. We addressed local

Self-preservation relation to the Kolmogorov similarity hypotheses

NASA Astrophysics Data System (ADS)

Djenidi, Lyazid; Antonia, Robert A.; Danaila, Luminita

2017-05-01

The relation between self-preservation (SP) and the Kolmogorov similarity hypotheses (Kolmogorov, The local structure of turbulence in incompressible viscous fluid for very large Reynolds numbers, Dokl. Akad. Nauk SSSR 30, 301 (1941) [Proc. R. Soc. London A 434, 9 (1991), 10.1098/rspa.1991.0075]) is investigated through the transport equations for the second- and third-order moments of the longitudinal velocity increments [ δ u (r ,t )=u (x ,t )-u (x +r ,t ) , where x ,t , and r are the spatial point and the time and longitudinal separation between two points, respectively]. It is shown that the fluid viscosity ν and the mean turbulent kinetic energy dissipation rate ɛ ¯ (the overbar represents an ensemble average) emerge naturally from the equations of motion as controlling parameters for the velocity increment moments when SP is assumed. Consequently, the Kolmogorov length scale η [≡(ν3/ɛ¯) 1 /4] and velocity scale vK [≡(νɛ ¯) 1 /4] also emerge as natural scaling parameters in conformity with SP, indicating that Kolmogorov's first hypothesis is subsumed under the more general hypothesis of SP. Further, the requirement for a very large Reynolds number is also relaxed, at least for the first similarity hypothesis. This requirement however is still necessary to derive the two-thirds law (or the four-fifths law) from the analysis. These analytical results are supported by experimental data in wake, jet, and grid turbulence. An expression for the fourth-order moment of the longitudinal velocity increments (δu ) 4¯ is derived from the analysis carried out in the inertial range. The expression, which involves the product of (δu ) 2 and ∂ δ p /∂ x , does not require the use the volume-averaged dissipation ɛ¯r, introduced by Oboukhov [Oboukhov, Some specific features of atmospheric turbulence, J. Fluid Mech. 13, 77 (1962), 10.1017/S0022112062000506] on a phenomenological basis and used by Kolmogorov to derive his refined similarity hypotheses

ONR Tropical Cyclone Motion Research Initiative; First-Year Review, Discussion and Tentative Hypotheses.

DTIC Science & Technology

1988-02-01

Pacific Network should have 3 to 4 levels of flight level observations and dropwindsonde from research aircraft. An outer box roughly 500 km2 should also...Motion Research Initiative: First. Year Review, Discussion and Tentative Hypotheses : ’ so A.t’oR’,S) Russell L. Elsberry *3j 0V R.OQ 2 ’ 3 .) T’E...Abstract 2 1. Introduction 3 2. Discussion Sessions 5 3 . Tentative Hypotheses 18 4. Preliminary field experiment design considerations 27 5

Action-related auditory ERP attenuation: Paradigms and hypotheses.

PubMed

Horváth, János

2015-11-11

A number studies have shown that the auditory N1 event-related potential (ERP) is attenuated when elicited by self-induced or self-generated sounds. Because N1 is a correlate of auditory feature- and event-detection, it was generally assumed that N1-attenuation reflected the cancellation of auditory re-afference, enabled by the internal forward modeling of the predictable sensory consequences of the given action. Focusing on paradigms utilizing non-speech actions, the present review summarizes recent progress on action-related auditory attenuation. Following a critical analysis of the most widely used, contingent paradigm, two further hypotheses on the possible causes of action-related auditory ERP attenuation are presented. The attention hypotheses suggest that auditory ERP attenuation is brought about by a temporary division of attention between the action and the auditory stimulation. The pre-activation hypothesis suggests that the attenuation is caused by the activation of a sensory template during the initiation of the action, which interferes with the incoming stimulation. Although each hypothesis can account for a number of findings, none of them can accommodate the whole spectrum of results. It is suggested that a better understanding of auditory ERP attenuation phenomena could be achieved by systematic investigations of the types of actions, the degree of action-effect contingency, and the temporal characteristics of action-effect contingency representation-buildup and -deactivation. This article is part of a Special Issue entitled SI: Prediction and Attention. Copyright © 2015. Published by Elsevier B.V.

Biological control of aragonite formation in stony corals

NASA Astrophysics Data System (ADS)

Von Euw, Stanislas; Zhang, Qihong; Manichev, Viacheslav; Murali, Nagarajan; Gross, Juliane; Feldman, Leonard C.; Gustafsson, Torgny; Flach, Carol; Mendelsohn, Richard; Falkowski, Paul G.

2017-06-01

Little is known about how stony corals build their calcareous skeletons. There are two prevailing hypotheses: that it is a physicochemically dominated process and that it is a biologically mediated one. Using a combination of ultrahigh-resolution three-dimensional imaging and two-dimensional solid-state nuclear magnetic resonance (NMR) spectroscopy, we show that mineral deposition is biologically driven. Randomly arranged, amorphous nanoparticles are initially deposited in microenvironments enriched in organic material; they then aggregate and form ordered aragonitic structures through crystal growth by particle attachment. Our NMR results are consistent with heterogeneous nucleation of the solid mineral phase driven by coral acid-rich proteins. Such a mechanism suggests that stony corals may be able to sustain calcification even under lower pH conditions that do not favor the inorganic precipitation of aragonite.

Global mtDNA genetic structure and hypothesized invasion history of a major pest of citrus, Diaphorina citri (Hemiptera: Liviidae).

PubMed

Luo, Yufa; Agnarsson, Ingi

2018-01-01

The Asian citrus psyllid Diaphorina citri Kuwayama is a key pest of citrus as the vector of the bacterium causing the "huanglongbing" disease (HLB). To assess the global mtDNA population genetic structure, and possible dispersal history of the pest, we investigated genetic variation at the COI gene collating newly collected samples with all previously published data. Our dataset consists of 356 colonies from 106 geographic sites worldwide. High haplotype diversity (H-mean = 0.702 ± 0.017), low nucleotide diversity (π-mean = 0.003), and significant positive selection (Ka/Ks = 32.92) were observed. Forty-four haplotypes (Hap) were identified, clustered into two matrilines: Both occur in southeastern and southern Asia, North and South America, and Africa; lineages A and B also occur in eastern and western Asia, respectively. The most abundant haplotypes were Hap4 in lineage A (35.67%), and Hap9 in lineage B (41.29%). The haplotype network identified them as the ancestral haplotypes within their respective lineages. Analysis of molecular variance showed significant genetic structure ( F ST  = 0.62, p  < .0001) between the lineages, and population genetic analysis suggests geographic structuring. We hypothesize a southern and/or southeastern Asia origin, three dispersal routes, and parallel expansions of two lineages. The hypothesized first route involved the expansion of lineage B from southern Asia into North America via West Asia. The second, the expansion of some lineage A individuals from Southeast Asia into East Asia, and the third involved both lineages from Southeast Asia spreading westward into Africa and subsequently into South America. To test these hypotheses and gain a deeper understanding of the global history of D. citri , more data-rich approaches will be necessary from the ample toolkit of next-generation sequencing (NGS). However, this study may serve to guide such sampling and in the development of biological control programs against

Real-time remote scientific model validation

NASA Technical Reports Server (NTRS)

Frainier, Richard; Groleau, Nicolas

1994-01-01

This paper describes flight results from the use of a CLIPS-based validation facility to compare analyzed data from a space life sciences (SLS) experiment to an investigator's preflight model. The comparison, performed in real-time, either confirms or refutes the model and its predictions. This result then becomes the basis for continuing or modifying the investigator's experiment protocol. Typically, neither the astronaut crew in Spacelab nor the ground-based investigator team are able to react to their experiment data in real time. This facility, part of a larger science advisor system called Principal Investigator in a Box, was flown on the space shuttle in October, 1993. The software system aided the conduct of a human vestibular physiology experiment and was able to outperform humans in the tasks of data integrity assurance, data analysis, and scientific model validation. Of twelve preflight hypotheses associated with investigator's model, seven were confirmed and five were rejected or compromised.

Vaccines and Autism: A Tale of Shifting Hypotheses

PubMed Central

Gerber, Jeffrey S.; Offit, Paul A.

2010-01-01

Although child vaccination rates remain high, some parental concern persists that vaccines might cause autism. Three specific hypotheses have been proposed: (1) the combination measles-mumps-rubella vaccine causes autism by damaging the intestinal lining, which allows the entrance of encephalopathic proteins; (2) thimerosal, an ethylmercury-containing preservative in some vaccines, is toxic to the central nervous system; and (3) the simultaneous administration of multiple vaccines overwhelms or weakens the immune system. We will discuss the genesis of each of these theories and review the relevant epidemiological evidence. PMID:19128068

Vaccines and autism: a tale of shifting hypotheses.

PubMed

Gerber, Jeffrey S; Offit, Paul A

2009-02-15

Although child vaccination rates remain high, some parental concern persists that vaccines might cause autism. Three specific hypotheses have been proposed: (1) the combination measles-mumps-rubella vaccine causes autism by damaging the intestinal lining, which allows the entrance of encephalopathic proteins; (2) thimerosal, an ethylmercury-containing preservative in some vaccines, is toxic to the central nervous system; and (3) the simultaneous administration of multiple vaccines overwhelms or weakens the immune system. We will discuss the genesis of each of these theories and review the relevant epidemiological evidence.

Pathogenesis of Bacterial Vaginosis: Discussion of Current Hypotheses

PubMed Central

Muzny, Christina A.; Schwebke, Jane R.

2016-01-01

In April 2015, the Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases hosted an experts technical consultation on bacterial vaginosis (BV), where data regarding controversies over the pathogenesis of BV were discussed. The discussion on the epidemiology and pathogenesis of BV is presented here, and several hypotheses on its pathogenesis are critiqued. Rigorous hypothesis-driven studies are needed to ultimately determine the cause of BV. This information is vital for the prevention and control of this important infection and its adverse public health consequences. PMID:27449868

Modelling Analysis of Students' Processes of Generating Scientific Explanatory Hypotheses

ERIC Educational Resources Information Center

Park, Jongwon

2006-01-01

It has recently been determined that generating an explanatory hypothesis to explain a discrepant event is important for students' conceptual change. The purpose of this study is to investigate how students' generate new explanatory hypotheses. To achieve this goal, questions are used to identify students prior ideas related to electromagnetic…

Qualification of a rapid readout biological indicator with moist heat sterilization.

PubMed

McCormick, Patrick; Finocchario, Catherine; Manchester, Robert; Glasgow, Louis; Costanzo, Stephen

2003-01-01

Biological indicators are recognized as an important component in the validation and routine monitoring of moist heat (steam) sterilization processes. Due to the need to allow for the recovery and outgrowth of test organisms that may have been sub-lethally injured, between 2-5 days of incubation are typically required before the outcome of sterilization processing can be reliably interpreted. Rapid readout biological indicators that incorporate the response of a heat resistant enzyme provide a means for assessing the efficacy of moist heat sterilization within hours of processing. This study describes the qualification of the 3M Attest 1292 Rapid Readout Biological Indicator with moist heat sterilization according to the procedures described in the PDA Technical Report No. 33, "Evaluation, Validation and Implementation of New Microbiological Testing Methods".

Reliability and validity of a new HIV-specific questionnaire with adults living with HIV in Canada and Ireland: the HIV Disability Questionnaire (HDQ).

PubMed

O'Brien, Kelly K; Solomon, Patricia; Bergin, Colm; O'Dea, Siobhán; Stratford, Paul; Iku, Nkem; Bayoumi, Ahmed M

2015-08-12

Our aim was to assess internal consistency reliability, construct validity, and test-retest reliability of the HDQ with adults living with HIV in Canada and Ireland. We recruited adults 18 years of age or older living with HIV from hospital clinics and AIDS service organizations in Canada and Ireland. We administered the HDQ paired with reference measures (World Health Organization Disability Assessment Schedule, SF-36 Questionnaire, Medical Outcomes Study Social Support Survey), and a demographic questionnaire. We calculated HDQ disability presence, severity and episodic scores (scored from 0-100). We calculated Cronbach's alpha and Intraclass Correlation Coefficients (ICC) (Canada only) for the disability severity and episodic scores and considered coefficients >0.80 and >0.70 as acceptable, respectively. To assess construct validity, we tested 40 a priori hypotheses of correlations between scores on the HDQ and reference measures and two known group hypotheses comparing HDQ presence and severity scores based on age and comorbidity. We considered acceptance of at least 75% of hypotheses as demonstrating support for construct validity. Of the 235 participants (139 Canada; 96 Ireland), the majority were men (74% Ireland; 82% Canada) and were taking antiretroviral therapy (88% Ireland; 91% Canada). Compared with Irish participants, Canadian participants were older (median age: 48 versus 41 years) and reported living with a higher median number of comorbidities (4 versus 1). Cronbach's alpha for Irish and Canadian participants were 0.97 (95% confidence interval (CI): 0.97-0.98) and 0.96 (95 % CI: 0.95-0.98), respectively, for the severity scale and 0.98 (95 % CI: 0.97-0.98) and 0.96 (95 % CI: 0.95-0.98), respectively, for the episodic scale. Of the 40 construct validity correlation hypotheses, 32 (80%) and 22 (55%) were supported among the Canadian and Irish samples respectively; both (100%) known group hypotheses were also supported. ICC values for Canadian

Biological evolution and statistical physics

NASA Astrophysics Data System (ADS)

Drossel, Barbara

2001-03-01

This review is an introduction to theoretical models and mathematical calculations for biological evolution, aimed at physicists. The methods in the field are naturally very similar to those used in statistical physics, although the majority of publications have appeared in biology journals. The review has three parts, which can be read independently. The first part deals with evolution in fitness landscapes and includes Fisher's theorem, adaptive walks, quasispecies models, effects of finite population sizes, and neutral evolution. The second part studies models of coevolution, including evolutionary game theory, kin selection, group selection, sexual selection, speciation, and coevolution of hosts and parasites. The third part discusses models for networks of interacting species and their extinction avalanches. Throughout the review, attention is paid to giving the necessary biological information, and to pointing out the assumptions underlying the models, and their limits of validity.

Serial Learning Process: Test of Chaining, Position, and Dual-Process Hypotheses

ERIC Educational Resources Information Center

Giurintano, S. L.

1973-01-01

The chaining, position, and dual-process hypotheses of serial learning (SL) as well as serial recall, reordering, and relearning of paired-associate learning were examined to establish learning patterns. Results provide evidence for dual-process hypothesis. (DS)

Mechanisms of bacterial morphogenesis: evolutionary cell biology approaches provide new insights.

PubMed

Jiang, Chao; Caccamo, Paul D; Brun, Yves V

2015-04-01

How Darwin's "endless forms most beautiful" have evolved remains one of the most exciting questions in biology. The significant variety of bacterial shapes is most likely due to the specific advantages they confer with respect to the diverse environments they occupy. While our understanding of the mechanisms generating relatively simple shapes has improved tremendously in the last few years, the molecular mechanisms underlying the generation of complex shapes and the evolution of shape diversity are largely unknown. The emerging field of bacterial evolutionary cell biology provides a novel strategy to answer this question in a comparative phylogenetic framework. This relatively novel approach provides hypotheses and insights into cell biological mechanisms, such as morphogenesis, and their evolution that would have been difficult to obtain by studying only model organisms. We discuss the necessary steps, challenges, and impact of integrating "evolutionary thinking" into bacterial cell biology in the genomic era. © 2015 WILEY Periodicals, Inc.

Head and neck cancer-specific quality of life: instrument validation.

PubMed

Terrell, J E; Nanavati, K A; Esclamado, R M; Bishop, J K; Bradford, C R; Wolf, G T

1997-10-01

The disfigurement and dysfunction associated with head and neck cancer affect emotional well-being and some of the most basic functions of life. Most cancer-specific quality-of-life assessments give a single composite score for head and neck cancer-related quality of life. To develop and evaluate an improved multidimensional instrument to assess head and neck cancer-related functional status and well-being. The item selection process included literature review, interviews with health care workers, and patient surveys. A survey with 37 disease-specific questions and the SF-12 survey were administered to 253 patients in 3 large medical centers. Factor analysis was performed to identify disease-specific domains. Domain scores were calculated as the standardized score of the component items. These domains were assessed for construct validity based on clinical hypotheses and test-retest reliability. Four relevant domains were identified: Eating (6 items), Communication (4 items), Pain (4 items), and Emotion (6 items). Each had an internal consistency (Cronbach alpha value) of greater than 0.80. Construct validity was demonstrated by moderate correlations with the SF-12 Physical and Mental component scores (r=0.43-0.60). Test-retest reliability for each domain demonstrated strong reliability between the 2 time points. Correlations were strong for each individual question, ranging from 0.53 to 0.93. Construct validity testing demonstrated that the direction of differences for each domain were as hypothesized. The Head and Neck Quality of Life questionnaire is a promising multidimensional tool with which to assess head and neck cancer-specific quality of life.

[Validation of two indices of biological integrity (IBI) for the Angulo River subbasin in Central Mexico].

PubMed

Ramírez-Herrejón, Juan Pablo; Mercado-Silva, Norman; Medina-Nava, Martina; Domínguez-Domínguez, Omar

2012-12-01

Efforts to halt freshwater ecosystem degradation in central Mexico can benefit from using bio-monitoring tools that reflect the condition of their biotic integrity. We analyzed the applicability of two fish-based indices of biotic integrity using data from lotic and lentic systems in the Angulo River subbasin (Lerma-Chapala basin). Both independent data from our own collections during two consecutive years, and existing information detailing the ecological attributes of each species, were used to calculate indices of biological integrity for 16 sites in lotic and lentic habitats. We assessed environmental quality by combining independent evaluations water and habitat quality for each site. We found sites with poor, regular and good biotic integrity. Our study did not find sites with good environmental quality. Fish-based IBI scores were strongly and significantly correlated with scores from independent environmental assessment techniques. IBI scores were adequate at representing environmental conditions in most study sites. These results expand the area where a lotic system fish-based IBI can be used, and constitute an initial validation of a lentic system fish-based IBI. Our results suggest that these bio-monitoring tools can be used in future conservation efforts in freshwater ecosystems in the Middle Lerma Basin.

On Nomological Validity and Auxiliary Assumptions: The Importance of Simultaneously Testing Effects in Social Cognitive Theories Applied to Health Behavior and Some Guidelines

PubMed Central

Hagger, Martin S.; Gucciardi, Daniel F.; Chatzisarantis, Nikos L. D.

2017-01-01

Tests of social cognitive theories provide informative data on the factors that relate to health behavior, and the processes and mechanisms involved. In the present article, we contend that tests of social cognitive theories should adhere to the principles of nomological validity, defined as the degree to which predictions in a formal theoretical network are confirmed. We highlight the importance of nomological validity tests to ensure theory predictions can be disconfirmed through observation. We argue that researchers should be explicit on the conditions that lead to theory disconfirmation, and identify any auxiliary assumptions on which theory effects may be conditional. We contend that few researchers formally test the nomological validity of theories, or outline conditions that lead to model rejection and the auxiliary assumptions that may explain findings that run counter to hypotheses, raising potential for ‘falsification evasion.’ We present a brief analysis of studies (k = 122) testing four key social cognitive theories in health behavior to illustrate deficiencies in reporting theory tests and evaluations of nomological validity. Our analysis revealed that few articles report explicit statements suggesting that their findings support or reject the hypotheses of the theories tested, even when findings point to rejection. We illustrate the importance of explicit a priori specification of fundamental theory hypotheses and associated auxiliary assumptions, and identification of the conditions which would lead to rejection of theory predictions. We also demonstrate the value of confirmatory analytic techniques, meta-analytic structural equation modeling, and Bayesian analyses in providing robust converging evidence for nomological validity. We provide a set of guidelines for researchers on how to adopt and apply the nomological validity approach to testing health behavior models. PMID:29163307

Biological Insights From 108 Schizophrenia-Associated Genetic Loci

PubMed Central

Ripke, Stephan; Neale, Benjamin M; Corvin, Aiden; Walters, James TR; Farh, Kai-How; Holmans, Peter A; Lee, Phil; Bulik-Sullivan, Brendan; Collier, David A; Huang, Hailiang; Pers, Tune H; Agartz, Ingrid; Agerbo, Esben; Albus, Margot; Alexander, Madeline; Amin, Farooq; Bacanu, Silviu A; Begemann, Martin; Belliveau, Richard A; Bene, Judit; Bergen, Sarah E; Bevilacqua, Elizabeth; Bigdeli, Tim B; Black, Donald W; Bruggeman, Richard; Buccola, Nancy G; Buckner, Randy L; Byerley, William; Cahn, Wiepke; Cai, Guiqing; Campion, Dominique; Cantor, Rita M; Carr, Vaughan J; Carrera, Noa; Catts, Stanley V; Chambert, Kimberley D; Chan, Raymond CK; Chan, Ronald YL; Chen, Eric YH; Cheng, Wei; Cheung, Eric FC; Chong, Siow Ann; Cloninger, C Robert; Cohen, David; Cohen, Nadine; Cormican, Paul; Craddock, Nick; Crowley, James J; Curtis, David; Davidson, Michael; Davis, Kenneth L; Degenhardt, Franziska; Del Favero, Jurgen; Demontis, Ditte; Dikeos, Dimitris; Dinan, Timothy; Djurovic, Srdjan; Donohoe, Gary; Drapeau, Elodie; Duan, Jubao; Dudbridge, Frank; Durmishi, Naser; Eichhammer, Peter; Eriksson, Johan; Escott-Price, Valentina; Essioux, Laurent; Fanous, Ayman H; Farrell, Martilias S; Frank, Josef; Franke, Lude; Freedman, Robert; Freimer, Nelson B; Friedl, Marion; Friedman, Joseph I; Fromer, Menachem; Genovese, Giulio; Georgieva, Lyudmila; Giegling, Ina; Giusti-Rodríguez, Paola; Godard, Stephanie; Goldstein, Jacqueline I; Golimbet, Vera; Gopal, Srihari; Gratten, Jacob; de Haan, Lieuwe; Hammer, Christian; Hamshere, Marian L; Hansen, Mark; Hansen, Thomas; Haroutunian, Vahram; Hartmann, Annette M; Henskens, Frans A; Herms, Stefan; Hirschhorn, Joel N; Hoffmann, Per; Hofman, Andrea; Hollegaard, Mads V; Hougaard, David M; Ikeda, Masashi; Joa, Inge; Julià, Antonio; Kahn, René S; Kalaydjieva, Luba; Karachanak-Yankova, Sena; Karjalainen, Juha; Kavanagh, David; Keller, Matthew C; Kennedy, James L; Khrunin, Andrey; Kim, Yunjung; Klovins, Janis; Knowles, James A; Konte, Bettina; Kucinskas, Vaidutis; Kucinskiene, Zita Ausrele; Kuzelova-Ptackova, Hana; Kähler, Anna K; Laurent, Claudine; Lee, Jimmy; Lee, S Hong; Legge, Sophie E; Lerer, Bernard; Li, Miaoxin; Li, Tao; Liang, Kung-Yee; Lieberman, Jeffrey; Limborska, Svetlana; Loughland, Carmel M; Lubinski, Jan; Lönnqvist, Jouko; Macek, Milan; Magnusson, Patrik KE; Maher, Brion S; Maier, Wolfgang; Mallet, Jacques; Marsal, Sara; Mattheisen, Manuel; Mattingsdal, Morten; McCarley, Robert W; McDonald, Colm; McIntosh, Andrew M; Meier, Sandra; Meijer, Carin J; Melegh, Bela; Melle, Ingrid; Mesholam-Gately, Raquelle I; Metspalu, Andres; Michie, Patricia T; Milani, Lili; Milanova, Vihra; Mokrab, Younes; Morris, Derek W; Mors, Ole; Murphy, Kieran C; Murray, Robin M; Myin-Germeys, Inez; Müller-Myhsok, Bertram; Nelis, Mari; Nenadic, Igor; Nertney, Deborah A; Nestadt, Gerald; Nicodemus, Kristin K; Nikitina-Zake, Liene; Nisenbaum, Laura; Nordin, Annelie; O’Callaghan, Eadbhard; O’Dushlaine, Colm; O’Neill, F Anthony; Oh, Sang-Yun; Olincy, Ann; Olsen, Line; Van Os, Jim; Pantelis, Christos; Papadimitriou, George N; Papiol, Sergi; Parkhomenko, Elena; Pato, Michele T; Paunio, Tiina; Pejovic-Milovancevic, Milica; Perkins, Diana O; Pietiläinen, Olli; Pimm, Jonathan; Pocklington, Andrew J; Powell, John; Price, Alkes; Pulver, Ann E; Purcell, Shaun M; Quested, Digby; Rasmussen, Henrik B; Reichenberg, Abraham; Reimers, Mark A; Richards, Alexander L; Roffman, Joshua L; Roussos, Panos; Ruderfer, Douglas M; Salomaa, Veikko; Sanders, Alan R; Schall, Ulrich; Schubert, Christian R; Schulze, Thomas G; Schwab, Sibylle G; Scolnick, Edward M; Scott, Rodney J; Seidman, Larry J; Shi, Jianxin; Sigurdsson, Engilbert; Silagadze, Teimuraz; Silverman, Jeremy M; Sim, Kang; Slominsky, Petr; Smoller, Jordan W; So, Hon-Cheong; Spencer, Chris C A; Stahl, Eli A; Stefansson, Hreinn; Steinberg, Stacy; Stogmann, Elisabeth; Straub, Richard E; Strengman, Eric; Strohmaier, Jana; Stroup, T Scott; Subramaniam, Mythily; Suvisaari, Jaana; Svrakic, Dragan M; Szatkiewicz, Jin P; Söderman, Erik; Thirumalai, Srinivas; Toncheva, Draga; Tosato, Sarah; Veijola, Juha; Waddington, John; Walsh, Dermot; Wang, Dai; Wang, Qiang; Webb, Bradley T; Weiser, Mark; Wildenauer, Dieter B; Williams, Nigel M; Williams, Stephanie; Witt, Stephanie H; Wolen, Aaron R; Wong, Emily HM; Wormley, Brandon K; Xi, Hualin Simon; Zai, Clement C; Zheng, Xuebin; Zimprich, Fritz; Wray, Naomi R; Stefansson, Kari; Visscher, Peter M; Adolfsson, Rolf; Andreassen, Ole A; Blackwood, Douglas HR; Bramon, Elvira; Buxbaum, Joseph D; Børglum, Anders D; Cichon, Sven; Darvasi, Ariel; Domenici, Enrico; Ehrenreich, Hannelore; Esko, Tõnu; Gejman, Pablo V; Gill, Michael; Gurling, Hugh; Hultman, Christina M; Iwata, Nakao; Jablensky, Assen V; Jönsson, Erik G; Kendler, Kenneth S; Kirov, George; Knight, Jo; Lencz, Todd; Levinson, Douglas F; Li, Qingqin S; Liu, Jianjun; Malhotra, Anil K; McCarroll, Steven A; McQuillin, Andrew; Moran, Jennifer L; Mortensen, Preben B; Mowry, Bryan J; Nöthen, Markus M; Ophoff, Roel A; Owen, Michael J; Palotie, Aarno; Pato, Carlos N; Petryshen, Tracey L; Posthuma, Danielle; Rietschel, Marcella; Riley, Brien P; Rujescu, Dan; Sham, Pak C; Sklar, Pamela; St Clair, David; Weinberger, Daniel R; Wendland, Jens R; Werge, Thomas; Daly, Mark J; Sullivan, Patrick F; O’Donovan, Michael C

2014-01-01

Summary Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here, we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain providing biological plausibility for the findings. Many findings have the potential to provide entirely novel insights into aetiology, but associations at DRD2 and multiple genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that play important roles in immunity, providing support for the hypothesized link between the immune system and schizophrenia. PMID:25056061

Biology is only part of the story ...

PubMed

Read, Dwight; van der Leeuw, Sander

2008-06-12

The origins and development of human cognition constitute one of the most interesting questions to which archaeology can contribute today. In this paper, we do so by presenting an overview of the evolution of artefact technology from the maker's point of view, and linking that development to some hypotheses on the evolution of human cognitive capacity. Our main hypothesis is that these data indicate that, in the first part of the trajectory, biological limits to cognitive capacity were a major constraint that limited technology, whereas, in the second part, this biological constraint seems to have been lifted and others have come in its place. But these are modifiable by means of conceptual frameworks that facilitate concept innovation and therefore enable learning, thereby permitting acceleration in the pace of change in technology. In the last part of the paper, we elaborate on some of the consequences of that acceleration.

Call transmission efficiency in native and invasive anurans: competing hypotheses of divergence in acoustic signals.

PubMed

Llusia, Diego; Gómez, Miguel; Penna, Mario; Márquez, Rafael

2013-01-01

Invasive species are a leading cause of the current biodiversity decline, and hence examining the major traits favouring invasion is a key and long-standing goal of invasion biology. Despite the prominent role of the advertisement calls in sexual selection and reproduction, very little attention has been paid to the features of acoustic communication of invasive species in nonindigenous habitats and their potential impacts on native species. Here we compare for the first time the transmission efficiency of the advertisement calls of native and invasive species, searching for competitive advantages for acoustic communication and reproduction of introduced taxa, and providing insights into competing hypotheses in evolutionary divergence of acoustic signals: acoustic adaptation vs. morphological constraints. Using sound propagation experiments, we measured the attenuation rates of pure tones (0.2-5 kHz) and playback calls (Lithobates catesbeianus and Pelophylax perezi) across four distances (1, 2, 4, and 8 m) and over two substrates (water and soil) in seven Iberian localities. All factors considered (signal type, distance, substrate, and locality) affected transmission efficiency of acoustic signals, which was maximized with lower frequency sounds, shorter distances, and over water surface. Despite being broadcast in nonindigenous habitats, the advertisement calls of invasive L. catesbeianus were propagated more efficiently than those of the native species, in both aquatic and terrestrial substrates, and in most of the study sites. This implies absence of optimal relationship between native environments and propagation of acoustic signals in anurans, in contrast to what predicted by the acoustic adaptation hypothesis, and it might render these vertebrates particularly vulnerable to intrusion of invasive species producing low frequency signals, such as L. catesbeianus. Our findings suggest that mechanisms optimizing sound transmission in native habitat can play a less

Call Transmission Efficiency in Native and Invasive Anurans: Competing Hypotheses of Divergence in Acoustic Signals

PubMed Central

Llusia, Diego; Gómez, Miguel; Penna, Mario; Márquez, Rafael

2013-01-01

Invasive species are a leading cause of the current biodiversity decline, and hence examining the major traits favouring invasion is a key and long-standing goal of invasion biology. Despite the prominent role of the advertisement calls in sexual selection and reproduction, very little attention has been paid to the features of acoustic communication of invasive species in nonindigenous habitats and their potential impacts on native species. Here we compare for the first time the transmission efficiency of the advertisement calls of native and invasive species, searching for competitive advantages for acoustic communication and reproduction of introduced taxa, and providing insights into competing hypotheses in evolutionary divergence of acoustic signals: acoustic adaptation vs. morphological constraints. Using sound propagation experiments, we measured the attenuation rates of pure tones (0.2–5 kHz) and playback calls (Lithobates catesbeianus and Pelophylax perezi) across four distances (1, 2, 4, and 8 m) and over two substrates (water and soil) in seven Iberian localities. All factors considered (signal type, distance, substrate, and locality) affected transmission efficiency of acoustic signals, which was maximized with lower frequency sounds, shorter distances, and over water surface. Despite being broadcast in nonindigenous habitats, the advertisement calls of invasive L. catesbeianus were propagated more efficiently than those of the native species, in both aquatic and terrestrial substrates, and in most of the study sites. This implies absence of optimal relationship between native environments and propagation of acoustic signals in anurans, in contrast to what predicted by the acoustic adaptation hypothesis, and it might render these vertebrates particularly vulnerable to intrusion of invasive species producing low frequency signals, such as L. catesbeianus. Our findings suggest that mechanisms optimizing sound transmission in native habitat can play a

Head size, weaponry, and cervical adaptation: Testing craniocervical evolutionary hypotheses in Ceratopsia.

PubMed

VanBuren, Collin S; Campione, Nicolás E; Evans, David C

2015-07-01

The anterior cervical vertebrae form the skeletal connection between the cranial and postcranial skeletons in higher tetrapods. As a result, the morphology of the atlas-axis complex is likely to be shaped by selection pressures acting on either the head or neck. The neoceratopsian (Reptilia:Dinosauria) syncervical represents one of the most highly modified atlas-axis regions in vertebrates, being formed by the complete coalescence of the three most anterior cervical vertebrae. In ceratopsids, the syncervical has been hypothesized to be an adaptation to support a massive skull, or to act as a buttress during intraspecific head-to-head combat. Here, we test these functional/adaptive hypotheses within a phylogenetic framework and critically examine the previously proposed methods for quantifying relative head size in the fossil record for the first time. Results indicate that neither the evolution of cranial weaponry nor large head size correlates with the origin of cervical fusion in ceratopsians, and we, therefore, reject both adaptive hypotheses for the origin of the syncervical. Anterior cervical fusion has evolved independently in a number of amniote clades, and further research on extant groups with this peculiar anatomy is needed to understand the evolutionary basis for cervical fusion in Neoceratopsia. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

Targeted Therapy Database (TTD): A Model to Match Patient's Molecular Profile with Current Knowledge on Cancer Biology

PubMed Central

Mocellin, Simone; Shrager, Jeff; Scolyer, Richard; Pasquali, Sandro; Verdi, Daunia; Marincola, Francesco M.; Briarava, Marta; Gobbel, Randy; Rossi, Carlo; Nitti, Donato

2010-01-01

Background The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. Objective To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. Methods To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. Results and Conclusions We created a manually annotated database (Targeted Therapy Database, TTD) where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method developed to fully exploit

Targeted Therapy Database (TTD): a model to match patient's molecular profile with current knowledge on cancer biology.

PubMed

Mocellin, Simone; Shrager, Jeff; Scolyer, Richard; Pasquali, Sandro; Verdi, Daunia; Marincola, Francesco M; Briarava, Marta; Gobbel, Randy; Rossi, Carlo; Nitti, Donato

2010-08-10

The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. We created a manually annotated database (Targeted Therapy Database, TTD) where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method developed to fully exploit the available knowledge on cancer biology with the

Discovery and validation of a glioblastoma co-expressed gene module

PubMed Central

Dunwoodie, Leland J.; Poehlman, William L.; Ficklin, Stephen P.; Feltus, Frank Alexander

2018-01-01

Tumors exhibit complex patterns of aberrant gene expression. Using a knowledge-independent, noise-reducing gene co-expression network construction software called KINC, we created multiple RNAseq-based gene co-expression networks relevant to brain and glioblastoma biology. In this report, we describe the discovery and validation of a glioblastoma-specific gene module that contains 22 co-expressed genes. The genes are upregulated in glioblastoma relative to normal brain and lower grade glioma samples; they are also hypo-methylated in glioblastoma relative to lower grade glioma tumors. Among the proneural, neural, mesenchymal, and classical glioblastoma subtypes, these genes are most-highly expressed in the mesenchymal subtype. Furthermore, high expression of these genes is associated with decreased survival across each glioblastoma subtype. These genes are of interest to glioblastoma biology and our gene interaction discovery and validation workflow can be used to discover and validate co-expressed gene modules derived from any co-expression network. PMID:29541392

Discovery and validation of a glioblastoma co-expressed gene module.

PubMed

Dunwoodie, Leland J; Poehlman, William L; Ficklin, Stephen P; Feltus, Frank Alexander

2018-02-16

Tumors exhibit complex patterns of aberrant gene expression. Using a knowledge-independent, noise-reducing gene co-expression network construction software called KINC, we created multiple RNAseq-based gene co-expression networks relevant to brain and glioblastoma biology. In this report, we describe the discovery and validation of a glioblastoma-specific gene module that contains 22 co-expressed genes. The genes are upregulated in glioblastoma relative to normal brain and lower grade glioma samples; they are also hypo-methylated in glioblastoma relative to lower grade glioma tumors. Among the proneural, neural, mesenchymal, and classical glioblastoma subtypes, these genes are most-highly expressed in the mesenchymal subtype. Furthermore, high expression of these genes is associated with decreased survival across each glioblastoma subtype. These genes are of interest to glioblastoma biology and our gene interaction discovery and validation workflow can be used to discover and validate co-expressed gene modules derived from any co-expression network.

Teaching the fluctuation test in silico by using mutate: a program to distinguish between the adaptive and spontaneous mutation hypotheses.

PubMed

Carvajal-Rodríguez, Antonio

2012-07-01

Mutate is a program developed for teaching purposes to impart a virtual laboratory class for undergraduate students of Genetics in Biology. The program emulates the so-called fluctuation test whose aim is to distinguish between spontaneous and adaptive mutation hypotheses in bacteria. The plan is to train students in certain key multidisciplinary aspects of current genetics such as sequence databases, DNA mutations, and hypothesis testing, while introducing the fluctuation test. This seminal experiment was originally performed studying Escherichia coli resistance to the infection by bacteriophage T1. The fluctuation test initiated the modern bacterial genetics that 25 years later ushered in the era of the recombinant DNA. Nowadays we know that some deletions in fhuA, the gene responsible for E. coli membrane receptor of T1, could cause the E. coli resistance to this phage. For the sake of simplicity, we will introduce the assumption that a single mutation generates the resistance to T1. During the practical, the students use the program to download some fhuA gene sequences, manually introduce some stop codon mutations, and design a fluctuation test to obtain data for distinguishing between preadaptative (spontaneous) and induced (adaptive) mutation hypotheses. The program can be launched from a browser or, if preferred, its executable file can be downloaded from http://webs.uvigo.es/acraaj/MutateWeb/Mutate.html. It requires the Java 5.0 (or higher) Runtime Environment (freely available at http://www.java.com). Copyright © 2012 Wiley Periodicals, Inc.

[Validity of the axis "conflicts" of the Operationalized Psychodynamic Diagnostics (OPD)].

PubMed

Pieh, Christoph; Frisch, Martin; Meyer, Nicole; Loew, Thomas; Lahmann, Claas

2009-01-01

This clinical trial is concerned with controlling the validity of unconscious conflicts within the OPD by verifying the hypotheses by means of psychometric analysis. Unconscious conflicts were determined by use of the OPD as well as by psychometric tests (GT, IIP, RQ-2) for patients in treatment in a psychosomatic hospital; they were divided into an explorative (n=1377) and a confirmative (n=1380) sample. Using the Mann-Whitney U-test, we investigated the connection between the main conflicts according to OPD-1 and the psychometric findings. For seven of most frequently chosen conflict types, a great coherence was found. For the others the results were inconsistent. Concerning the seven most frequently chosen conflict types, the OPD is a valid diagnose tool. As to the other conflicts, this study cannot clear up open questions concerning validity.

Biological control of aragonite formation in stony corals.

PubMed

Von Euw, Stanislas; Zhang, Qihong; Manichev, Viacheslav; Murali, Nagarajan; Gross, Juliane; Feldman, Leonard C; Gustafsson, Torgny; Flach, Carol; Mendelsohn, Richard; Falkowski, Paul G

2017-06-02

Little is known about how stony corals build their calcareous skeletons. There are two prevailing hypotheses: that it is a physicochemically dominated process and that it is a biologically mediated one. Using a combination of ultrahigh-resolution three - dimensional imaging and two-dimensional solid-state nuclear magnetic resonance (NMR) spectroscopy, we show that mineral deposition is biologically driven. Randomly arranged, amorphous nanoparticles are initially deposited in microenvironments enriched in organic material; they then aggregate and form ordered aragonitic structures through crystal growth by particle attachment. Our NMR results are consistent with heterogeneous nucleation of the solid mineral phase driven by coral acid-rich proteins. Such a mechanism suggests that stony corals may be able to sustain calcification even under lower pH conditions that do not favor the inorganic precipitation of aragonite. Copyright © 2017, American Association for the Advancement of Science.

[Again on language of biology].

PubMed

Morchio, di Renzo

2004-01-01

Some time ago I proposed in an Editorial in this journal some considerations on the language of biology. I concluded that, to realize an autonomy of such a language (and therefore of biology), we have to develop a valid language for biology. In such a context, it seemed to me that the term "metaphors" referred to the concepts concerning the information carried by genetic code, was a reasonable one. However, Barbieri's article in this issue of Rivista di Biologia / Biology Forum calls for a reply. Of course, we do not know very much in this field, even if we have some evidence that a sequence of bases on a DNA is not determined only by chance. In any case we can exclude that nature in this occasion has "invented" a code. Nature doesn't "invent" anything: it only follows its rules, that we name "laws of nature". Barbieri quotes the Morse code, but forgets to say that such a code is "conventional" in the sense that it is valid only because it is the result of an "agreement" between Morse and the users of that code. There is nothing more unnatural than a "code": with whom nature should actually have to "reach an agreement"? As a matter of fact, we interpret as "information" what happens by law of nature. Also Barbieri's thesis that genes and proteins are molecular artifacts, assembled by external agents, whereas generally molecules are determined by their bonds, i.e. by internal factors, is a disputable one. It is examined how much an external structure plays a role in ordinary chemical reactions. The "information" of physics is not a semantic information. For such information we can refer to history of literature, telegraphic offices, genetics or biochemistry.

Using potential performance theory to test five hypotheses about meta-attribution.

PubMed

Trafimow, David; Hunt, Gayle; Rice, Stephen; Geels, Kasha

2011-01-01

Based on I. Kant's (1991) distinction between perfect and imperfect duties and the attribution literature pertaining to that distinction, the authors proposed and tested 5 hypotheses about meta-attribution. More specifically, violations of perfect duties have been shown to arouse both more negative affect and stronger correspondent inferences than do violations of imperfect duties (e.g., D. Trafimow, I. K. Bromgard, K. A. Finlay, & T. Ketelaar, 2005). But when it comes to making meta-attributions-that is, guessing the attributions others would make-is the affect differential an advantage or a disadvantage? In addition to the null hypothesis of no effect, the authors proposed and tested additional hypotheses about how negative affect might increase or decrease the effectiveness of people's meta-attribution strategies and how even if there is no effect on strategy effectiveness, negative affect could increase or decrease the consistencies with which these strategies could be used.

Testing hypotheses of earthquake occurrence

NASA Astrophysics Data System (ADS)

Kagan, Y. Y.; Jackson, D. D.; Schorlemmer, D.; Gerstenberger, M.

2003-12-01

We present a relatively straightforward likelihood method for testing those earthquake hypotheses that can be stated as vectors of earthquake rate density in defined bins of area, magnitude, and time. We illustrate the method as it will be applied to the Regional Earthquake Likelihood Models (RELM) project of the Southern California Earthquake Center (SCEC). Several earthquake forecast models are being developed as part of this project, and additional contributed forecasts are welcome. Various models are based on fault geometry and slip rates, seismicity, geodetic strain, and stress interactions. We would test models in pairs, requiring that both forecasts in a pair be defined over the same set of bins. Thus we offer a standard "menu" of bins and ground rules to encourage standardization. One menu category includes five-year forecasts of magnitude 5.0 and larger. Forecasts would be in the form of a vector of yearly earthquake rates on a 0.05 degree grid at the beginning of the test. Focal mechanism forecasts, when available, would be also be archived and used in the tests. The five-year forecast category may be appropriate for testing hypotheses of stress shadows from large earthquakes. Interim progress will be evaluated yearly, but final conclusions would be made on the basis of cumulative five-year performance. The second category includes forecasts of earthquakes above magnitude 4.0 on a 0.05 degree grid, evaluated and renewed daily. Final evaluation would be based on cumulative performance over five years. Other types of forecasts with different magnitude, space, and time sampling are welcome and will be tested against other models with shared characteristics. All earthquakes would be counted, and no attempt made to separate foreshocks, main shocks, and aftershocks. Earthquakes would be considered as point sources located at the hypocenter. For each pair of forecasts, we plan to compute alpha, the probability that the first would be wrongly rejected in favor of

Molecular engineering and measurements to test hypothesized mechanisms in single molecule conductance switching.

PubMed

Moore, Amanda M; Dameron, Arrelaine A; Mantooth, Brent A; Smith, Rachel K; Fuchs, Daniel J; Ciszek, Jacob W; Maya, Francisco; Yao, Yuxing; Tour, James M; Weiss, Paul S

2006-02-15

Six customized phenylene-ethynylene-based oligomers have been studied for their electronic properties using scanning tunneling microscopy to test hypothesized mechanisms of stochastic conductance switching. Previously suggested mechanisms include functional group reduction, functional group rotation, backbone ring rotation, neighboring molecule interactions, bond fluctuations, and hybridization changes. Here, we test these hypotheses experimentally by varying the molecular designs of the switches; the ability of the molecules to switch via each hypothetical mechanism is selectively engineered into or out of each molecule. We conclude that hybridization changes at the molecule-surface interface are responsible for the switching we observe.

Hypotheses of Spatial Stock Structure in Orange Roughy Hoplostethus atlanticus Inferred from Diet, Feeding, Condition, and Reproductive Activity

PubMed Central

Dunn, Matthew R.; Forman, Jeffrey S.

2011-01-01

We evaluate hypotheses for meso-scale spatial structure in an orange roughy (Hoplostethus atlanticus) stock using samples collected during research trawl surveys off the east coast of New Zealand. Distance-based linear models and generalised additive models were used to identify the most significant biological, environmental, and temporal predictors of variability in diet, proportion of stomachs containing prey, standardised weight of prey, fish somatic weight, fish total weight, and reproductive activity. The diet was similar to that observed elsewhere, and varied with ontogeny, depth, and surface water temperature. Smaller sized and female orange roughy in warmer bottom water were most likely to contain food. Fish condition and reproductive activity were highest at distances more than 20 km from the summit of the hills. Trawl survey catches indicated greater orange roughy densities in hill strata, suggesting hill habitat was favoured. However, analyses of feeding, condition, and reproductive activity indicated hill fish were not superior, despite fish densities on hills being reduced by fishing which, in principle, should have reduced intra-specific competition for food and other resources. Hypotheses for this result include: (1) fish in relatively poor condition visit hills to feed and regain condition and then leave, or (2) commercial fishing has disturbed feeding aggregations and/or caused habitat damage, making fished hills less productive. Mature orange roughy were observed on both flat and hill habitat during periods outside of spawning, and if this spatial structure was persistent then a proportion of the total spawning stock biomass would remain unavailable to fisheries targeting hills. Orange roughy stock assessments informed only by data from hills may well be misleading. PMID:22069464

[Cooperations between biology laboratories of the establishments of healthcare].

PubMed

Burnat, Pascal; Payen, Catherine; Mérens, Audrey; Ceppa, Franck; Renard, Christophe

2013-01-01

In France, the cooperations between biological laboratories of the healthcare establishments increased after those realized in the private laboratories. The biologists are confronted with various hypotheses of organization. They are often complex because they may preserve the quality of the care and their continuity while realizing financial economies. These economies are mostly based on the global reduction in the staff and in the equipments by mutualising the biological tests with varying degrees. We describe the various elements to be taken into account (staff, activities, budget, quality, transport, materials) and propose many scenarios of cooperations, from a unique central shape to the transfer of very specialized tests, with their advantages and their inconveniences. The management of human aspects in these cooperations is determining to facilitate their success as well as a reliable preliminary inventory of fixtures.

How a visual surveillance system hypothesizes how you behave.

PubMed

Micheloni, C; Piciarelli, C; Foresti, G L

2006-08-01

In the last few years, the installation of a large number of cameras has led to a need for increased capabilities in video surveillance systems. It has, indeed, been more and more necessary for human operators to be helped in the understanding of ongoing activities in real environments. Nowadays, the technology and the research in the machine vision and artificial intelligence fields allow one to expect a new generation of completely autonomous systems able to reckon the behaviors of entities such as pedestrians, vehicles, and so forth. Hence, whereas the sensing aspect of these systems has been the issue considered the most so far, research is now focused mainly on more newsworthy problems concerning understanding. In this article, we present a novel method for hypothesizing the evolution of behavior. For such purposes, the system is required to extract useful information by means of low-level techniques for detecting and maintaining track of moving objects. The further estimation of performed trajectories, together with objects classification, enables one to compute the probability distribution of the normal activities (e.g., trajectories). Such a distribution is defined by means of a novel clustering technique. The resulting clusters are used to estimate the evolution of objects' behaviors and to speculate about any intention to act dangerously. The provided solution for hypothesizing behaviors occurring in real environments was tested in the context of an outdoor parking lot

Are evolutionary hypotheses for motion sickness "just-so" stories?

PubMed

Oman, Charles M

2012-01-01

Vertebrates have evolved rapidly conditionable nausea and vomiting reflexes mediated by gut and brainstem receptors, clearly as a defense against neurotoxin ingestion. In 1977 Treisman proposed that sensory orientation linkages to emetic centers evolved for the same reason, and that motion sickness was an accidental byproduct. It was an "adaptationist" explanation for motion sickness, since it assumed that evolution has shaped all phenotypic traits for survival advantage. Treisman's "poison" theory is plausible, and frequently cited as the accepted scientific explanation for motion sickness. However, alternative explanations have been proposed. The creation of hypotheses is an essential part of science - provided they are testable. This paper reviews the evidence for the Poison theory and several other adaptationist explanations. These hypotheses are certainly not "just-so stories", but supporting evidence is equivocal, and contradictory evidence exists Parsimony suggests an alternative "pluralistic" view: The vertebrate reticular formation maintains oxygenated blood flow to the brain, discriminates unexpected sensory stimuli- including postural disturbances, and detects and expels ingested neurotoxins. The three systems share neuroarchitectural elements but normally function independently. Brainstem sensory conflict neurons normally discriminate brief postural disturbances, but can be abnormally stimulated during prolonged passive transport (e.g. by boat, beginning about 150-200 generations ago). Sensory conflict signals cross couple into the neurotoxin expulsion and avoidance system, producing an arguably maladaptive emetic phenotype.

The Strengths and Difficulties Questionnaire (SDQ): The Factor Structure and Scale Validation in U.S. Adolescents

ERIC Educational Resources Information Center

He, Jian-Ping; Burstein, Marcy; Schmitz, Anja; Merikangas, Kathleen R.

2013-01-01

The Strengths and Difficulties Questionnaire (SDQ) is one of the most commonly used instruments for screening psychopathology in children and adolescents. This study evaluated the hypothesized five-factor structure of the SDQ and examined its convergent validity against comprehensive clinical diagnostic assessments. Data were derived from the…

Portuguese Version of the Pain Beliefs and Perceptions Inventory: A Multicenter Validation Study.

PubMed

Azevedo, Luís Filipe; Sampaio, Rute; Camila Dias, Cláudia; Romão, José; Lemos, Laurinda; Agualusa, Luís; Vaz-Serra, Sílvia; Patto, Teresa; Costa-Pereira, Altamiro; Castro-Lopes, José Manuel

2017-07-01

We aimed to perform the translation, cultural adaptation, and validation of the Pain Beliefs and Perceptions Inventory (PBPI) for the European Portuguese language and chronic pain population. This is a longitudinal multicenter validation study. A Portuguese version of the PBPI (PBPI-P) was created through a process of translation, back translation, and expert panel evaluation. The PBPI-P was administered to a total of 122 patients from 13 chronic pain clinics in Portugal, at baseline and after 7 days. Internal consistency and test-retest reliability were assessed by Cronbach's alpha (α) and intraclass correlation coefficient (ICC). Construct (convergent and discriminant) validity was assessed based on a set of previously developed theoretical hypotheses about interrelations between the PBPI-P and other measures. Exploratory and confirmatory factor analyses were performed to test the theoretical structure of the PBPI-P. The internal consistency and test-retest reliability coefficients for each respective subscale were α = 0.620 and ICC = 0.801 for mystery; α = 0.744 and ICC = 0.841 for permanence; α = 0.778 and ICC = 0.791 for constancy; and α = 0.764 and ICC = 0.881 for self-blame. Exploratory and confirmatory factor analysis revealed a four-factor structure (performance, constancy, self-blame, and mystery) that explained 63% of the variance. The construct validity of the PBPI-P was shown to be adequate, with more than 90% of the previously defined hypotheses regarding interrelations with other measures confirmed. The PBPI-P has been shown to be adequate and to have excellent reliability, internal consistency, and validity. It may contribute to a better pain assessment and is suitable for research and clinical use. © 2016 World Institute of Pain.

Introduction to the Special Issue: Advances in island plant biology since Sherwin Carlquist's Island Biology

PubMed Central

Traveset, Anna; Fernández-Palacios, José María; Kueffer, Christoph; Bellingham, Peter J.; Morden, Clifford; Drake, Donald R.

2016-01-01

Sherwin Carlquist's seminal publications—in particular his classic Island Biology, published in 1974—formulated hypotheses specific to island biology that remain valuable today. This special issue brings together some of the most interesting contributions presented at the First Island Biology Symposium hosted in Honolulu on 7–11 July 2014. We compiled a total of 18 contributions that present data from multiple archipelagos across the world and from different disciplines within the plant sciences. In this introductory paper, we first provide a short overview of Carlquist's life and work and then summarize the main findings of the collated papers. A first group of papers deals with issues to which Carlquist notably contributed: long-distance dispersal, adaptive radiation and plant reproductive biology. The findings of such studies demonstrate the extent to which the field has advanced thanks to (i) the increasing availability and richness of island data, covering many taxonomic groups and islands; (ii) new information from the geosciences, phylogenetics and palaeoecology, which allows us a more realistic understanding of the geological and biological development of islands and their biotas; and (iii) the new theoretical and methodological advances that allow us to assess patterns of abundance, diversity and distribution of island biota over large spatial scales. Most other papers in the issue cover a range of topics related to plant conservation on islands, such as causes and consequences of mutualistic disruptions (due to pollinator or disperser losses, introduction of alien predators, etc.). Island biologists are increasingly considering reintroducing ecologically important species to suitable habitats within their historic range and to neighbouring islands with depauperate communities of vertebrate seed dispersers, and an instructive example is given here. Finally, contributions on ecological networks demonstrate the usefulness of this methodological tool to

A test of biological and behavioral explanations for gender differences in telomere length: the multi-ethnic study of atherosclerosis.

PubMed

Needham, Belinda L; Diez Roux, Ana V; Bird, Chloe E; Bradley, Ryan; Fitzpatrick, Annette L; Jacobs, David R; Ouyang, Pamela; Seeman, Teresa E; Thurston, Rebecca C; Vaidya, Dhananjay; Wang, Steven

2014-01-01

The purpose of this study was to examine biological and behavioral explanations for gender differences in leukocyte telomere length (LTL), a biomarker of cell aging that has been hypothesized to contribute to women's greater longevity. Data are from a subsample (n = 851) of the Multi-Ethnic Study of Atherosclerosis, a population-based study of women and men aged 45 to 84. Mediation models were used to examine study hypotheses. We found that women had longer LTL than men, but the gender difference was smaller at older ages. Gender differences in smoking and processed meat consumption partially mediated gender differences in telomere length, whereas gender differences in estradiol, total testosterone, oxidative stress, and body mass index did not. Neither behavioral nor biological factors explained why the gender difference in LTL was smaller at older ages. Longitudinal studies are needed to assess gender differences in the rate of change in LTL over time; to identify the biological, behavioral, and psychosocial factors that contribute to these differences throughout the life course; and to determine whether gender differences in LTL explain the gender gap in longevity.

Delinquency and Peer Acceptance in Adolescence: A Within-Person Test of Moffitt’s Hypotheses

PubMed Central

Rulison, Kelly L; Kreager, Derek A.; Osgood, D. Wayne

2015-01-01

We tested two hypotheses derived from Moffitt’s (1993) taxonomic theory of antisocial behavior, both of which are central to her explanation for the rise in delinquency during adolescence. Specifically, we tested whether persistently delinquent individuals become more accepted by their peers during adolescence and whether individuals who abstain from delinquent behavior become less accepted. Participants were 4,359 adolescents from 14 communities in the PROSPER study, which assessed friendship networks and delinquency from 6th (M = 11.8 years) to 9th (M = 15.3 years) grade. We operationalized peer acceptance as: number of nominations received (indegree centrality), attractiveness as a friend (adjusted indegree centrality), and network bridging potential (betweenness centrality) and tested the hypotheses using multilevel modeling. Contrary to Moffitt’s hypothesis, persistently delinquent youth did not become more accepted between early and middle adolescence, and although abstainers were less accepted in early adolescence, they became more accepted over time. Results were similar for boys and girls; when differences occurred, they provided no support for Moffitt’s hypotheses for boys and were opposite of her hypotheses for girls. Sensitivity analyses using alternative strategies and additional data to identify persistently delinquent adolescents produced similar results. We explore the implications of these results for Moffitt’s assertions that social mimicry of persistently antisocial adolescents leads to increases in delinquency and that social isolation leads to abstention. PMID:25243328

Assessment of the benefits and impacts in the U.S. Nuclear Power Industry of hypothesized lower occupational dose limits

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

Andersen, R.L.; Schmitt, J.F.

1995-03-01

The International Commission on Radiological Protection and the National Council on Radiation Protection and Measurements have issued recommendations that would limit occupational exposure of individuals to doses lower than regulatory limits contained in the Nuclear Regulatory Commission`s 10 CFR Part 20, {open_quotes}Standards for Protection Against Radiation{close_quotes}. Because of this situation, there is interest in the potential benefits and impacts that would be associated with movement of the NRC regulatory limits toward the advisory bodies recommendations. The records of occupational worker doses in the U.S. commercial nuclear power industry show that the vast majority of these workers have doses that aremore » significantly below the regulatory limit of 50 mSv (5 rem) per year. Some workers doses do approach the limits, however. This is most common in the case of specially skilled workers, especially those with skills utilized in support of plant outage work. Any consideration of the potential benefits and impacts of hypothesized lower dose limits must address these workers as an important input to the overall assessment. There are also, of course, many other areas in which the benefits and impacts must be evaluated. To prepare to provide valid, constructive input on this matter, the U.S. nuclear power industry is undertaking an assessment, facilitated by the Nuclear Energy Institute (NEI), of the potential benefits and impacts at its facilities associated with hypothesized lower occupational dose limits. Some preliminary results available to date from this assessment are provided.« less

Repurposing High-Throughput Image Assays Enables Biological Activity Prediction for Drug Discovery.

PubMed

Simm, Jaak; Klambauer, Günter; Arany, Adam; Steijaert, Marvin; Wegner, Jörg Kurt; Gustin, Emmanuel; Chupakhin, Vladimir; Chong, Yolanda T; Vialard, Jorge; Buijnsters, Peter; Velter, Ingrid; Vapirev, Alexander; Singh, Shantanu; Carpenter, Anne E; Wuyts, Roel; Hochreiter, Sepp; Moreau, Yves; Ceulemans, Hugo

2018-05-17

In both academia and the pharmaceutical industry, large-scale assays for drug discovery are expensive and often impractical, particularly for the increasingly important physiologically relevant model systems that require primary cells, organoids, whole organisms, or expensive or rare reagents. We hypothesized that data from a single high-throughput imaging assay can be repurposed to predict the biological activity of compounds in other assays, even those targeting alternate pathways or biological processes. Indeed, quantitative information extracted from a three-channel microscopy-based screen for glucocorticoid receptor translocation was able to predict assay-specific biological activity in two ongoing drug discovery projects. In these projects, repurposing increased hit rates by 50- to 250-fold over that of the initial project assays while increasing the chemical structure diversity of the hits. Our results suggest that data from high-content screens are a rich source of information that can be used to predict and replace customized biological assays. Copyright © 2018 Elsevier Ltd. All rights reserved.

The acquisition of biological knowledge during childhood: Cognitive conflict or tabula rasa?

NASA Astrophysics Data System (ADS)

Lawson, Anton E.

Clinical interviews were conducted with three elementary school children, who varied in age but not in family or school environment, to determine the extent to which they held naive misconceptions about important biological topics and to determine agewise trends in the development of biological knowledge. Does early biological knowledge acquisition follow a pattern of spontaneous naive theory construction and cognitive conflict or does it follow a pattern of gradual accretion to an initially blank slate? Contrary to findings in the physical sciences, little evidence was found for biological misconceptions as knowledge acquisition appeared to more directly follow the gradual accretion hypothesis with the primary source of that knowledge adult authority rather than personal experience. However, conceptual change teaching is still advocated due to its ability to provoke students to consider and test alternative conceptions (even if they are not their own) as a means of encouraging the development of important general reasoning patterns utilized in the testing of causal hypotheses.

Experienced physicians benefit from analyzing initial diagnostic hypotheses

PubMed Central

Bass, Adam; Geddes, Colin; Wright, Bruce; Coderre, Sylvain; Rikers, Remy; McLaughlin, Kevin

2013-01-01

Background Most incorrect diagnoses involve at least one cognitive error, of which premature closure is the most prevalent. While metacognitive strategies can mitigate premature closure in inexperienced learners, these are rarely studied in experienced physicians. Our objective here was to evaluate the effect of analytic information processing on diagnostic performance of nephrologists and nephrology residents. Methods We asked nine nephrologists and six nephrology residents at the University of Calgary and Glasgow University to diagnose ten nephrology cases. We provided presenting features along with contextual information, after which we asked for an initial diagnosis. We then primed participants to use either hypothetico-deductive reasoning or scheme-inductive reasoning to analyze the remaining case data and generate a final diagnosis. Results After analyzing initial hypotheses, both nephrologists and residents improved the accuracy of final diagnoses (31.1% vs. 65.6%, p < 0.001, and 40.0% vs. 70.0%, p < 0.001, respectively). We found a significant interaction between experience and analytic processing strategy (p = 0.02): nephrology residents had significantly increased odds of diagnostic success when using scheme-inductive reasoning (odds ratio [95% confidence interval] 5.69 [1.59, 20.33], p = 0.07), whereas the performance of experienced nephrologists did not differ between strategies (odds ratio 0.57 [0.23, 1.39], p = 0.20). Discussion Experienced nephrologists and nephrology residents can improve their performance by analyzing initial diagnostic hypotheses. The explanation of the interaction between experience and the effect of different reasoning strategies is unclear, but may relate to preferences in reasoning strategy, or the changes in knowledge structure with experience. PMID:26451203

Hypothesizing the body's genius to trigger and self-organize its healing: 25 years using a standardized neurophysics therapy

PubMed Central

Ross, Sara N.; Ware, Ken

2013-01-01

We aim for this contribution to operate bi-directionally, both as a “bedside to bench” reverse-translational fractal physiological hypothesis and as a methodological innovation to inform clinical practice. In 25 years using gym equipment therapeutically in non-research settings, the standardized therapy is consistently observed to trigger universal responses of micro to macro waves of system transition dynamics in the human nervous system. These are associated with observably desirable impacts on disorders, injuries, diseases, and athletic performance. Requisite conditions are therapeutic coaching, erect posture, extremely slow movements in mild resistance exercises, and executive control over arousal and attention. To motivate research into the physiological improvements and in validation studies, we integrate from across disciplines to hypothesize explanations for the relationships among the methods, the system dynamics, and evident results. Key hypotheses include: (1) Correctly-directed system efforts may reverse a system's heretofore misdirected efforts, restoring healthier neurophysiology. (2) The enhanced information processing accompanying good posture is an essential initial condition. (3) Behaviors accompanying exercises performed with few degrees of freedom amplify information processing, triggering destabilization and transition dynamics. (4) Executive control over arousal and attention is essential to release system constraints, amplifying and complexifying information. (5) The dynamics create necessary and in many cases evidently sufficient conditions for the body to resolve or improve its own conditions within often short time periods. Literature indicates how the human system possesses material self-awareness. A broad explanation for the nature and effects of the therapy appears rooted in the cascading recursions of the systems' dynamics, which appear to trigger health-fostering self-reorganizing processes when this therapy provides catalytic

The Internalized Homophobia Scale for Vietnamese Sexual Minority Women: Conceptualization, Factor Structure, Reliability, and Associations With Hypothesized Correlates.

PubMed

Nguyen, Trang Quynh; Poteat, Tonia; Bandeen-Roche, Karen; German, Danielle; Nguyen, Yen Hai; Vu, Loan Kieu-Chau; Nguyen, Nam Thi-Thu; Knowlton, Amy R

2016-08-01

We developed the first Vietnamese Internalized Homophobia (IH) scale for use with Vietnamese sexual minority women (SMW). Drawing from existing IH scales in the international literature and based on prior qualitative research about SMW in the Viet Nam context, the scale covers two domains: self-stigma (negative attitudes toward oneself as a sexual minority person) and sexual prejudice (negative attitudes toward homosexuality/same-sex relations in general). Scale items, including items borrowed from existing scales and items based on local expressions, were reviewed and confirmed by members of the target population. Quantitative evaluation used data from an anonymous web-based survey of Vietnamese SMW, including those who identified as lesbian (n = 1187), or as bisexual (n = 641) and those who were unsure about their sexual identity (n = 353). The scale was found to consist of two highly correlated factors reflecting self-stigma (not normal/wholesome and self-reproach and wishing away same-sex sexuality) and one factor reflecting sexual prejudice, and to have excellent internal consistency. Construct validity was evidenced by subscale associations with a wide range of hypothesized correlates, including perceived sexual stigma, outness, social support, connection to other SMW, relationship quality, psychological well-being, anticipation of heterosexual marriage, and endorsement of same-sex marriage legalization. Self-stigma was more strongly associated with psychosocial correlates, and sexual prejudice was more associated with endorsement of legal same-sex marriage. The variations in these associations across the hypothesized correlates and across sexual identity groups were consistent with the minority stress model and the IH literature, and exhibited context-specific features, which are discussed.

ENFIN a network to enhance integrative systems biology.

PubMed

Kahlem, Pascal; Birney, Ewan

2007-12-01

Integration of biological data of various types and development of adapted bioinformatics tools represent critical objectives to enable research at the systems level. The European Network of Excellence ENFIN is engaged in developing both an adapted infrastructure to connect databases and platforms to enable the generation of new bioinformatics tools as well as the experimental validation of computational predictions. We will give an overview of the projects tackled within ENFIN and discuss the challenges associated with integration for systems biology.

Unifying Quantum Physics with Biology

NASA Astrophysics Data System (ADS)

Goradia, Shantilal

2014-09-01

We find that the natural logarithm of the age of the universe in quantum mechanical units is close to 137. Since science is not religion, it is our moral duty to recognize the importance of this finding on the following ground. The experimentally obtained number 137 is a mystical number in science, as if written by the hand of God. It is found in cosmology; unlike other theories, it works in biology too. A formula by Boltzmann also works in both: biology and physics, as if it is in the heart of God. His formula simply leads to finding the logarithm of microstates. One of the two conflicting theories of physics (1) Einstein's theory of General Relativity and (2) Quantum Physics, the first applies only in cosmology, but the second applies in biology too. Since we have to convert the age of the universe, 13 billion years, into 1,300,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000 Planck times to get close to 137, quantum physics clearly shows the characteristics of unifying with biology. The proof of its validity also lies in its ability to extend information system observed in biology.

Macroevolutionary developmental biology: Embryos, fossils, and phylogenies.

PubMed

Organ, Chris L; Cooper, Lisa Noelle; Hieronymus, Tobin L

2015-10-01

The field of evolutionary developmental biology is broadly focused on identifying the genetic and developmental mechanisms underlying morphological diversity. Connecting the genotype with the phenotype means that evo-devo research often considers a wide range of evidence, from genetics and morphology to fossils. In this commentary, we provide an overview and framework for integrating fossil ontogenetic data with developmental data using phylogenetic comparative methods to test macroevolutionary hypotheses. We survey the vertebrate fossil record of preserved embryos and discuss how phylogenetic comparative methods can integrate data from developmental genetics and paleontology. Fossil embryos provide limited, yet critical, developmental data from deep time. They help constrain when developmental innovations first appeared during the history of life and also reveal the order in which related morphologies evolved. Phylogenetic comparative methods provide a powerful statistical approach that allows evo-devo researchers to infer the presence of nonpreserved developmental traits in fossil species and to detect discordant evolutionary patterns and processes across levels of biological organization. © 2015 Wiley Periodicals, Inc.

German National Proficiency Scales in Biology: Internal Structure, Relations to General Cognitive Abilities and Verbal Skills

PubMed Central

KÖLLER, OLAF

2016-01-01

ABSTRACT National and international large‐scale assessments (LSA) have a major impact on educational systems, which raises fundamental questions about the validity of the measures regarding their internal structure and their relations to relevant covariates. Given its importance, research on the validity of instruments specifically developed for LSA is still sparse, especially in science and its subdomains biology, chemistry, and physics. However, policy decisions for the improvement of educational quality based on LSA can only be helpful if valid information on students’ achievement levels is provided. In the present study, the nature of the measurement instruments based on the German Educational Standards in Biology is examined. On the basis of data from 3,165 students in Grade 10, we present dimensional analyses and report the relationship between different subdimensions of biology literacy and cognitive covariates such as general cognitive abilities and verbal skills. A theory‐driven two‐dimensional model fitted the data best. Content knowledge and scientific inquiry, two subdimensions of biology literacy, are highly correlated and show differential correlational patterns to the covariates. We argue that the underlying structure of biology should be incorporated into curricula, teacher training and future assessments. PMID:27818532

German National Proficiency Scales in Biology: Internal Structure, Relations to General Cognitive Abilities and Verbal Skills.

PubMed

Kampa, Nele; Köller, Olaf

2016-09-01

National and international large-scale assessments (LSA) have a major impact on educational systems, which raises fundamental questions about the validity of the measures regarding their internal structure and their relations to relevant covariates. Given its importance, research on the validity of instruments specifically developed for LSA is still sparse, especially in science and its subdomains biology, chemistry, and physics. However, policy decisions for the improvement of educational quality based on LSA can only be helpful if valid information on students' achievement levels is provided. In the present study, the nature of the measurement instruments based on the German Educational Standards in Biology is examined. On the basis of data from 3,165 students in Grade 10, we present dimensional analyses and report the relationship between different subdimensions of biology literacy and cognitive covariates such as general cognitive abilities and verbal skills. A theory-driven two-dimensional model fitted the data best. Content knowledge and scientific inquiry, two subdimensions of biology literacy, are highly correlated and show differential correlational patterns to the covariates. We argue that the underlying structure of biology should be incorporated into curricula, teacher training and future assessments.

Multiple Use One-Sided Hypotheses Testing in Univariate Linear Calibration

NASA Technical Reports Server (NTRS)

Krishnamoorthy, K.; Kulkarni, Pandurang M.; Mathew, Thomas

1996-01-01

Consider a normally distributed response variable, related to an explanatory variable through the simple linear regression model. Data obtained on the response variable, corresponding to known values of the explanatory variable (i.e., calibration data), are to be used for testing hypotheses concerning unknown values of the explanatory variable. We consider the problem of testing an unlimited sequence of one sided hypotheses concerning the explanatory variable, using the corresponding sequence of values of the response variable and the same set of calibration data. This is the situation of multiple use of the calibration data. The tests derived in this context are characterized by two types of uncertainties: one uncertainty associated with the sequence of values of the response variable, and a second uncertainty associated with the calibration data. We derive tests based on a condition that incorporates both of these uncertainties. The solution has practical applications in the decision limit problem. We illustrate our results using an example dealing with the estimation of blood alcohol concentration based on breath estimates of the alcohol concentration. In the example, the problem is to test if the unknown blood alcohol concentration of an individual exceeds a threshold that is safe for driving.

Citizen science networks in natural history and the collective validation of biodiversity data.

PubMed

Turnhout, Esther; Lawrence, Anna; Turnhout, Sander

2016-06-01

Biodiversity data are in increasing demand to inform policy and management. A substantial portion of these data is generated in citizen science networks. To ensure the quality of biodiversity data, standards and criteria for validation have been put in place. We used interviews and document analysis from the United Kingdom and The Netherlands to examine how data validation serves as a point of connection between the diverse people and practices in natural history citizen science networks. We found that rather than a unidirectional imposition of standards, validation was performed collectively. Specifically, it was enacted in ongoing circulations of biodiversity records between recorders and validators as they jointly negotiated the biodiversity that was observed and the validity of the records. These collective validation practices contributed to the citizen science character or natural history networks and tied these networks together. However, when biodiversity records were included in biodiversity-information initiatives on different policy levels and scales, the circulation of records diminished. These initiatives took on a more extractive mode of data use. Validation ceased to be collective with important consequences for the natural history networks involved and citizen science more generally. © 2016 The Authors. Conservation Biology published by Wiley Periodicals, Inc. on behalf of Society for Conservation Biology.

Construct validity of the Moral Development Scale for Professionals (MDSP)

PubMed Central

Söderhamn, Olle; Bjørnestad, John Olav; Skisland, Anne; Cliffordson, Christina

2011-01-01

The aim of this study was to investigate the construct validity of the Moral Development Scale for Professionals (MDSP) using structural equation modeling. The instrument is a 12-item self-report instrument, developed in the Scandinavian cultural context and based on Kohlberg’s theory. A hypothesized simplex structure model underlying the MDSP was tested through structural equation modeling. Validity was also tested as the proportion of respondents older than 20 years that reached the highest moral level, which according to the theory should be small. A convenience sample of 339 nursing students with a mean age of 25.3 years participated. Results confirmed the simplex model structure, indicating that MDSP reflects a moral construct empirically organized from low to high. A minority of respondents >20 years of age (13.5%) scored more than 80% on the highest moral level. The findings support the construct validity of the MDSP and the stages and levels in Kohlberg’s theory. PMID:21655343

Construct validity of the Moral Development Scale for Professionals (MDSP).

PubMed

Söderhamn, Olle; Bjørnestad, John Olav; Skisland, Anne; Cliffordson, Christina

2011-01-01

The aim of this study was to investigate the construct validity of the Moral Development Scale for Professionals (MDSP) using structural equation modeling. The instrument is a 12-item self-report instrument, developed in the Scandinavian cultural context and based on Kohlberg's theory. A hypothesized simplex structure model underlying the MDSP was tested through structural equation modeling. Validity was also tested as the proportion of respondents older than 20 years that reached the highest moral level, which according to the theory should be small. A convenience sample of 339 nursing students with a mean age of 25.3 years participated. Results confirmed the simplex model structure, indicating that MDSP reflects a moral construct empirically organized from low to high. A minority of respondents >20 years of age (13.5%) scored more than 80% on the highest moral level. The findings support the construct validity of the MDSP and the stages and levels in Kohlberg's theory.

Integrating evolutionary and functional tests of adaptive hypotheses: a case study of altitudinal differentiation in hemoglobin function in an Andean Sparrow, Zonotrichia capensis.

PubMed

Cheviron, Zachary A; Natarajan, Chandrasekhar; Projecto-Garcia, Joana; Eddy, Douglas K; Jones, Jennifer; Carling, Matthew D; Witt, Christopher C; Moriyama, Hideaki; Weber, Roy E; Fago, Angela; Storz, Jay F

2014-11-01

In air-breathing vertebrates, the physiologically optimal blood-O2 affinity is jointly determined by the prevailing partial pressure of atmospheric O2, the efficacy of pulmonary O2 transfer, and internal metabolic demands. Consequently, genetic variation in the oxygenation properties of hemoglobin (Hb) may be subject to spatially varying selection in species with broad elevational distributions. Here we report the results of a combined functional and evolutionary analysis of Hb polymorphism in the rufous-collared sparrow (Zonotrichia capensis), a species that is continuously distributed across a steep elevational gradient on the Pacific slope of the Peruvian Andes. We integrated a population genomic analysis that included all postnatally expressed Hb genes with functional studies of naturally occurring Hb variants, as well as recombinant Hb (rHb) mutants that were engineered through site-directed mutagenesis. We identified three clinally varying amino acid polymorphisms: Two in the α(A)-globin gene, which encodes the α-chain subunits of the major HbA isoform, and one in the α(D)-globin gene, which encodes the α-chain subunits of the minor HbD isoform. We then constructed and experimentally tested single- and double-mutant rHbs representing each of the alternative α(A)-globin genotypes that predominate at different elevations. Although the locus-specific patterns of altitudinal differentiation suggested a history of spatially varying selection acting on Hb polymorphism, the experimental tests demonstrated that the observed amino acid mutations have no discernible effect on respiratory properties of the HbA or HbD isoforms. These results highlight the importance of experimentally validating the hypothesized effects of genetic changes in protein function to avoid the pitfalls of adaptive storytelling. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please

Examining Preservice Science Teachers' Skills of Formulating Hypotheses and Identifying Variables

ERIC Educational Resources Information Center

Aydogdu, Bülent

2015-01-01

The aim of this study is to examine preservice science teachers' skills of formulating hypotheses and identifying variables. The research has a phenomenological research design. The data was gathered qualitatively. In this study, preservice science teachers were first given two scenarios (Scenario-1 & Scenario-2) containing two different…

ENFIN--A European network for integrative systems biology.

PubMed

Kahlem, Pascal; Clegg, Andrew; Reisinger, Florian; Xenarios, Ioannis; Hermjakob, Henning; Orengo, Christine; Birney, Ewan

2009-11-01

Integration of biological data of various types and the development of adapted bioinformatics tools represent critical objectives to enable research at the systems level. The European Network of Excellence ENFIN is engaged in developing an adapted infrastructure to connect databases, and platforms to enable both the generation of new bioinformatics tools and the experimental validation of computational predictions. With the aim of bridging the gap existing between standard wet laboratories and bioinformatics, the ENFIN Network runs integrative research projects to bring the latest computational techniques to bear directly on questions dedicated to systems biology in the wet laboratory environment. The Network maintains internally close collaboration between experimental and computational research, enabling a permanent cycling of experimental validation and improvement of computational prediction methods. The computational work includes the development of a database infrastructure (EnCORE), bioinformatics analysis methods and a novel platform for protein function analysis FuncNet.

Evaluating alternative stem cell hypotheses for adult corneal epithelial maintenance

PubMed Central

West, John D; Dorà, Natalie J; Collinson, J Martin

2015-01-01

In this review we evaluate evidence for three different hypotheses that explain how the corneal epithelium is maintained. The limbal epithelial stem cell (LESC) hypothesis is most widely accepted. This proposes that stem cells in the basal layer of the limbal epithelium, at the periphery of the cornea, maintain themselves and also produce transient (or transit) amplifying cells (TACs). TACs then move centripetally to the centre of the cornea in the basal layer of the corneal epithelium and also replenish cells in the overlying suprabasal layers. The LESCs maintain the corneal epithelium during normal homeostasis and become more active to repair significant wounds. Second, the corneal epithelial stem cell (CESC) hypothesis postulates that, during normal homeostasis, stem cells distributed throughout the basal corneal epithelium, maintain the tissue. According to this hypothesis, LESCs are present in the limbus but are only active during wound healing. We also consider a third possibility, that the corneal epithelium is maintained during normal homeostasis by proliferation of basal corneal epithelial cells without any input from stem cells. After reviewing the published evidence, we conclude that the LESC and CESC hypotheses are consistent with more of the evidence than the third hypothesis, so we do not consider this further. The LESC and CESC hypotheses each have difficulty accounting for one main type of evidence so we evaluate the two key lines of evidence that discriminate between them. Finally, we discuss how lineage-tracing experiments have begun to resolve the debate in favour of the LESC hypothesis. Nevertheless, it also seems likely that some basal corneal epithelial cells can act as long-term progenitors if limbal stem cell function is compromised. Thus, this aspect of the CESC hypothesis may have a lasting impact on our understanding of corneal epithelial maintenance, even if it is eventually shown that stem cells are restricted to the limbus as proposed

Ant Abundance along a Productivity Gradient: Addressing Two Conflicting Hypotheses

PubMed Central

Segev, Udi; Kigel, Jaime; Lubin, Yael; Tielbörger, Katja

2015-01-01

The number of individuals within a population or community and their body size can be associated with changes in resource supply. While these relationships may provide a key to better understand the role of abiotic vs. biotic constraints in animal communities, little is known about the way size and abundance of organisms change along resource gradients. Here, we studied this interplay in ants, addressing two hypotheses with opposite predictions regarding variation in population densities along resource gradients- the ‘productivity hypothesis’ and the ‘productivity-based thinning hypothesis’. The hypotheses were tested in two functional groups of ground-dwelling ants that are directly primary consumers feeding on seeds: specialized seed-eaters and generalist species. We examined variations in colony density and foraging activity (a size measurement of the forager caste) in six ant assemblages along a steep productivity gradient in a semi-arid region, where precipitation and plant biomass vary 6-fold over a distance of 250km. An increase in the density or foraging activity of ant colonies along productivity gradients is also likely to affect competitive interactions among colonies, and consequently clinal changes in competition intensity were also examined. Ant foraging activity increased with productivity for both functional groups. However, colony density revealed opposing patterns: it increased with productivity for the specialized seed-eaters, but decreased for the generalist species. Competition intensity, evaluated by spatial partitioning of species at food baits and distribution of colonies, was uncorrelated with productivity in the specialized seed-eaters, but decreased with increasing productivity in the generalists. Our results provide support for two contrasting hypotheses regarding the effect of resource availability on the abundance of colonial organisms- the ‘productivity hypothesis’ for specialized seed-eaters and the �

Examining subtypes of behavior problems among 3-year-old children, Part I: investigating validity of subtypes and biological risk-factors.

PubMed

Harvey, Elizabeth A; Friedman-Weieneth, Julie L; Goldstein, Lauren H; Sherman, Alison H

2007-02-01

This study examined 3-year-old children who were classified as hyperactive (HYP), oppositional-defiant (OD), hyperactive and oppositional defiant (HYP/OD), and non-problem based on mothers' reports of behavior. Using fathers,' teachers,' and observers' ratings of children's behavior, concurrent validity was excellent for the HYP/OD group, moderate for the HYP group, and poor for the OD group. As predicted, both the HYP/OD and HYP groups reported more prenatal/perinatal birth complications and a greater family history of hyperactivity than did non-problem children. Furthermore, the HYP/OD group showed a greater family history of conduct disorder and oppositional defiant disorder (ODD) symptoms than did non-problem children; however, the HYP group also showed a greater family history of ODD than did non-problem children. Results suggest that as early as age 3, these behavior subtypes appear to be linked to biologically-based risk-factors in ways that are consistent with theories of the development of ADHD.

An engineer's view on genetic information and biological evolution.

PubMed

Battail, Gérard

2004-01-01

We develop ideas on genome replication introduced in Battail [Europhys. Lett. 40 (1997) 343]. Starting with the hypothesis that the genome replication process uses error-correcting means, and the auxiliary one that nested codes are used to this end, we first review the concepts of redundancy and error-correcting codes. Then we show that these hypotheses imply that: distinct species exist with a hierarchical taxonomy, there is a trend of evolution towards complexity, and evolution proceeds by discrete jumps. At least the first two features above may be considered as biological facts so, in the absence of direct evidence, they provide an indirect proof in favour of the hypothesized error-correction system. The very high redundancy of genomes makes it possible. In order to explain how it is implemented, we suggest that soft codes and replication decoding, to be briefly described, are plausible candidates. Experimentally proven properties of long-range correlation of the DNA message substantiate this claim.

Epidemiology of childhood leukemia in New Zealand: studies of infectious hypotheses.

PubMed

Dockerty, John D

2009-01-01

The etiology of childhood leukemia remains an enigma despite decades of research. Hypotheses of an infectious etiology have been around for a long time, and in the last 20 years there have been two main theoretical contenders. One of these involves the possibility of a specific infectious agent having a causative role, and animal leukemia viruses would be analogous to this. Another theory relates to the possible involvement of unusual patterns of infections in infancy and how they might relate to aberrant immune responses. The first of these is easier to test. In New Zealand, since the early 1990s we have embarked on a program of research on the epidemiology of childhood leukemia. One of the goals has been to test hypotheses about the role of infection in causation. A variety of study designs have been employed, including descriptive, clustering, case-control and contributions to pooled international analyses. Some of the more interesting findings include: there has been a marked increase in the incidence of acute lymphoblastic leukemia among young children in New Zealand since the mid 1960s, poorer families are at greater risk, and there is no clear support for hypotheses of an infectious cause from the New Zealand data. However because of our small total population (4 million people) we cannot produce clear results on our own. Hence our current international collaborations, for example in CLIC (the Childhood Leukemia International Consortium) represent an important step forward. As countries work together across international boundaries we have a renewed hope that the causes of the childhood leukemias will be unlocked in the foreseeable future.

Bayes factors for testing inequality constrained hypotheses: Issues with prior specification.

PubMed

Mulder, Joris

2014-02-01

Several issues are discussed when testing inequality constrained hypotheses using a Bayesian approach. First, the complexity (or size) of the inequality constrained parameter spaces can be ignored. This is the case when using the posterior probability that the inequality constraints of a hypothesis hold, Bayes factors based on non-informative improper priors, and partial Bayes factors based on posterior priors. Second, the Bayes factor may not be invariant for linear one-to-one transformations of the data. This can be observed when using balanced priors which are centred on the boundary of the constrained parameter space with a diagonal covariance structure. Third, the information paradox can be observed. When testing inequality constrained hypotheses, the information paradox occurs when the Bayes factor of an inequality constrained hypothesis against its complement converges to a constant as the evidence for the first hypothesis accumulates while keeping the sample size fixed. This paradox occurs when using Zellner's g prior as a result of too much prior shrinkage. Therefore, two new methods are proposed that avoid these issues. First, partial Bayes factors are proposed based on transformed minimal training samples. These training samples result in posterior priors that are centred on the boundary of the constrained parameter space with the same covariance structure as in the sample. Second, a g prior approach is proposed by letting g go to infinity. This is possible because the Jeffreys-Lindley paradox is not an issue when testing inequality constrained hypotheses. A simulation study indicated that the Bayes factor based on this g prior approach converges fastest to the true inequality constrained hypothesis. © 2013 The British Psychological Society.

Individual differences in processing styles: validity of the Rational-Experiential Inventory.

PubMed

Björklund, Fredrik; Bäckström, Martin

2008-10-01

In Study 1 (N= 203) the factor structure of a Swedish translation of Pacini and Epstein's Rational-Experiential Inventory (REI-40) was investigated using confirmatory factor analysis. The hypothesized model with rationality and experientiality as orthogonal factors had satisfactory fit to the data, significantly better than alternative models (with two correlated factors or a single factor). Inclusion of "ability" and "favorability" subscales for rationality and experientiality increased fit further. It was concluded that the structural validity of the REI is adequate. In Study 2 (N= 72) the REI-factors were shown to have theoretically meaningful correlations to other personality traits, indicating convergent and discriminant validity. Finally, scores on the rationality scale were negatively related to risky choice framing effects in Kahneman and Tversky's Asian disease task, indicating concurrent validity. On the basis of these findings it was concluded that the test has satisfactory psychometric properties.

Structural biology data archiving - where we are and what lies ahead.

PubMed

Kleywegt, Gerard J; Velankar, Sameer; Patwardhan, Ardan

2018-05-10

For almost 50 years, structural biology has endeavoured to conserve and share its experimental data and their interpretations (usually, atomistic models) through global public archives such as the Protein Data Bank, Electron Microscopy Data Bank and Biological Magnetic Resonance Data Bank (BMRB). These archives are treasure troves of freely accessible data that document our quest for molecular or atomic understanding of biological function and processes in health and disease. They have prepared the field to tackle new archiving challenges as more and more (combinations of) techniques are being utilized to elucidate structure at ever increasing length scales. Furthermore, the field has made substantial efforts to develop validation methods that help users to assess the reliability of structures and to identify the most appropriate data for their needs. In this Review, we present an overview of public data archives in structural biology and discuss the importance of validation for users and producers of structural data. Finally, we sketch our efforts to integrate structural data with bioimaging data and with other sources of biological data. This will make relevant structural information available and more easily discoverable for a wide range of scientists. © 2018 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Validation of Structures in the Protein Data Bank.

PubMed

Gore, Swanand; Sanz García, Eduardo; Hendrickx, Pieter M S; Gutmanas, Aleksandras; Westbrook, John D; Yang, Huanwang; Feng, Zukang; Baskaran, Kumaran; Berrisford, John M; Hudson, Brian P; Ikegawa, Yasuyo; Kobayashi, Naohiro; Lawson, Catherine L; Mading, Steve; Mak, Lora; Mukhopadhyay, Abhik; Oldfield, Thomas J; Patwardhan, Ardan; Peisach, Ezra; Sahni, Gaurav; Sekharan, Monica R; Sen, Sanchayita; Shao, Chenghua; Smart, Oliver S; Ulrich, Eldon L; Yamashita, Reiko; Quesada, Martha; Young, Jasmine Y; Nakamura, Haruki; Markley, John L; Berman, Helen M; Burley, Stephen K; Velankar, Sameer; Kleywegt, Gerard J

2017-12-05

The Worldwide PDB recently launched a deposition, biocuration, and validation tool: OneDep. At various stages of OneDep data processing, validation reports for three-dimensional structures of biological macromolecules are produced. These reports are based on recommendations of expert task forces representing crystallography, nuclear magnetic resonance, and cryoelectron microscopy communities. The reports provide useful metrics with which depositors can evaluate the quality of the experimental data, the structural model, and the fit between them. The validation module is also available as a stand-alone web server and as a programmatically accessible web service. A growing number of journals require the official wwPDB validation reports (produced at biocuration) to accompany manuscripts describing macromolecular structures. Upon public release of the structure, the validation report becomes part of the public PDB archive. Geometric quality scores for proteins in the PDB archive have improved over the past decade. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Biological age as a useful index to predict seventeen-year survival and mortality in Koreans.

PubMed

Yoo, Jinho; Kim, Yangseok; Cho, Eo Rin; Jee, Sun Ha

2017-01-05

Many studies have been conducted to quantitatively estimate biological age using measurable biomarkers. Biological age should function as a valid proxy for aging, which is closely related with future work ability, frailty, physical fitness, and/or mortality. A validation study using cohort data found biological age to be a superior index for disease-related mortality than chronological age. The purpose of this study is to demonstrate the validity of biological age as a useful index to predict a person's risk of death in the future. The data consists of 13,106 cases of death from 557,940 Koreans at 20-93 years old, surveyed from 1994 to 2011. Biological ages were computed using 15 biomarkers measured in general health check-ups using an algorithm based on principal component analysis. The influence of biological age on future mortality was analyzed using Cox proportional hazards regression considering gender, chronological age, and event type. In the living subjects, the average biological age was almost the same as the average chronological age. In the deceased, the biological age was larger than the chronological age: largest increment of biological age over chronological age was observed when their baseline chronological age was within 50-59 years. The death rate significantly increased as biological age became larger than chronological age (linear trend test, p value < 0.0001). The largest hazard ratio was observed in subjects whose baseline chronological age was within 50-59 years when the cause was death from non-cancerous diseases (HR = 1.30, 95% confidence intervals = 1.26 - 1.34). The survival probability, over the 17 year term of the study, was significantly decreased in the people whose biological age was larger than chronological age (log rank test, p value < 0.001). Biological age could be used to predict future risk of death, and its effect size varied according to gender, chronological age, and cause of death.

Estimating effectiveness and cost of biologics for rheumatoid arthritis: application of a validated algorithm to commercial insurance claims.

PubMed

Curtis, Jeffrey R; Schabert, Vernon F; Harrison, David J; Yeaw, Jason; Korn, Jonathan R; Quach, Caroleen; Yun, Huifeng; Joseph, George J; Collier, David H

2014-07-01

The aim of this analysis was to implement a claims-based algorithm to estimate biologic cost per effectively treated patient for biologics approved for moderate to severe rheumatoid arthritis (RA). This retrospective analysis included commercially insured adults (aged 18-63 years) with RA in a commercial database, who initiated biologic treatment with abatacept, adalimumab, etanercept, golimumab, or infliximab between 2007 and 2010. The algorithm defined effectiveness as having all of the following: high adherence, no biologic dose increase, no biologic switching, no new nonbiologic disease-modifying antirheumatic drug, no increased or new oral glucocorticoid use, and no more than 1 glucocorticoid injection. For each biologic, cost per effectively treated patient was defined as total drug and administration costs (from allowed amounts on claims), divided by the number of patients categorized as effectively treated. Of 15,351 patients, 12,018 (78.3%) were women, and the mean (SD) age was 49.7 (9.6) years. The algorithm categorized treatment as effective in the first year for 30% (1899/6374) of etanercept, 30% (1396/4661) of adalimumab, 20% (560/2765) of infliximab, 27% (361/1338) of abatacept, and 29% (62/213) of golimumab treated patients. The 1-year biologic cost per effectively treated patient, as defined by the algorithm, was nominally lower for subcutaneously injected biologics than for infused biologics. The 1-year biologic cost per effectively treated patient, as defined by the algorithm, was lowest for etanercept ($49,952), followed by golimumab ($50,189), adalimumab ($52,858), abatacept ($71,866), and infliximab ($104,333). Algorithm-defined effectiveness was similar for biologics other than infliximab. The 1-year biologic cost per effectively treated patient, as defined by the algorithm, was nominally lower for subcutaneously injected biologics than for infused biologics. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

Criteria of validity for animal models of psychiatric disorders: focus on anxiety disorders and depression

PubMed Central

2011-01-01

Animal models of psychiatric disorders are usually discussed with regard to three criteria first elaborated by Willner; face, predictive and construct validity. Here, we draw the history of these concepts and then try to redraw and refine these criteria, using the framework of the diathesis model of depression that has been proposed by several authors. We thus propose a set of five major criteria (with sub-categories for some of them); homological validity (including species validity and strain validity), pathogenic validity (including ontopathogenic validity and triggering validity), mechanistic validity, face validity (including ethological and biomarker validity) and predictive validity (including induction and remission validity). Homological validity requires that an adequate species and strain be chosen: considering species validity, primates will be considered to have a higher score than drosophila, and considering strains, a high stress reactivity in a strain scores higher than a low stress reactivity in another strain. Pathological validity corresponds to the fact that, in order to shape pathological characteristics, the organism has been manipulated both during the developmental period (for example, maternal separation: ontopathogenic validity) and during adulthood (for example, stress: triggering validity). Mechanistic validity corresponds to the fact that the cognitive (for example, cognitive bias) or biological mechanisms (such as dysfunction of the hormonal stress axis regulation) underlying the disorder are identical in both humans and animals. Face validity corresponds to the observable behavioral (ethological validity) or biological (biomarker validity) outcomes: for example anhedonic behavior (ethological validity) or elevated corticosterone (biomarker validity). Finally, predictive validity corresponds to the identity of the relationship between the triggering factor and the outcome (induction validity) and between the effects of the treatments

The Online Social Support Scale: Measure development and validation.

PubMed

Nick, Elizabeth A; Cole, David A; Cho, Sun-Joo; Smith, Darcy K; Carter, T Grace; Zelkowitz, Rachel L

2018-05-21

A new measure, the Online Social Support Scale, was developed based on previous theory, research, and measurement of in-person social support. It includes four subscales: Esteem/Emotional Support, Social Companionship, Informational Support, and Instrumental Support. In college and community samples, factor analytic and item response theory results suggest that subtypes of in-person social support also pertain in the online world. Evidence of reliability, convergent validity, and discriminant validity provide excellent psychometric support for the measure. Construct validity accrues to the measure vis-à-vis support for three hypotheses: (a) Various broad types of Internet platforms for social interactions are differentially associated with online social support and online victimization; (b) similar to in-person social support, online social support offsets the adverse effect of negative life events on self-esteem and depression-related outcome; and (c) online social support counteracts the effects of online victimization in much the same way that in-person friends in one social niche counterbalance rejection in other social niches. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Modest validity and fair reproducibility of dietary patterns derived by cluster analysis.

PubMed

Funtikova, Anna N; Benítez-Arciniega, Alejandra A; Fitó, Montserrat; Schröder, Helmut

2015-03-01

Cluster analysis is widely used to analyze dietary patterns. We aimed to analyze the validity and reproducibility of the dietary patterns defined by cluster analysis derived from a food frequency questionnaire (FFQ). We hypothesized that the dietary patterns derived by cluster analysis have fair to modest reproducibility and validity. Dietary data were collected from 107 individuals from population-based survey, by an FFQ at baseline (FFQ1) and after 1 year (FFQ2), and by twelve 24-hour dietary recalls (24-HDR). Repeatability and validity were measured by comparing clusters obtained by the FFQ1 and FFQ2 and by the FFQ2 and 24-HDR (reference method), respectively. Cluster analysis identified a "fruits & vegetables" and a "meat" pattern in each dietary data source. Cluster membership was concordant for 66.7% of participants in FFQ1 and FFQ2 (reproducibility), and for 67.0% in FFQ2 and 24-HDR (validity). Spearman correlation analysis showed reasonable reproducibility, especially in the "fruits & vegetables" pattern, and lower validity also especially in the "fruits & vegetables" pattern. κ statistic revealed a fair validity and reproducibility of clusters. Our findings indicate a reasonable reproducibility and fair to modest validity of dietary patterns derived by cluster analysis. Copyright © 2015 Elsevier Inc. All rights reserved.

Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses

PubMed Central

2017-01-01

Introduction Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. Aim The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia. Methods A search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia. Results The literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR. Conclusion Innovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor

Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses.

PubMed

Sultana, Janet; Calabró, Marco; Garcia-Serna, Ricard; Ferrajolo, Carmen; Crisafulli, Concetta; Mestres, Jordi; Trifirò', Gianluca

2017-01-01

Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia. A search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia. The literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR. Innovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor pharmacological therapies to patient risk

Dreaming and waking experiences in schizophrenia: how should the (dis)continuity hypotheses be approached empirically?

PubMed

Noreika, Valdas

2011-06-01

A number of differences between the dreams of schizophrenia patients and those of healthy participants have been linked to changes in waking life that schizophrenia may cause. This way, the "continuity hypothesis" has become a standard way to relate dreaming and waking experiences in schizophrenia. Nevertheless, some of the findings in dream literature are not compatible with the continuity hypothesis and suggest some other ways how dream content and waking experiences could interact. Conceptually, the continuity hypothesis could be sharpened into the "waking-to-dreaming" and the "dreaming-to-waking" hypotheses, whereas a less explored type of "discontinuity" could embrace the "compensated waking" and the "compensated dreaming" hypotheses. A careful consideration and empirical testing of each of those hypotheses may reveal a multiplicity of the ways how dreaming and waking life interact in schizophrenia. Copyright © 2010 Elsevier Inc. All rights reserved.

Measurement Properties of the Persian Translated Version of Graves Orbitopathy Quality of Life Questionnaire: A Validation Study.

PubMed

Kashkouli, Mohsen Bahmani; Karimi, Nasser; Aghamirsalim, Mohamadreza; Abtahi, Mohammad Bagher; Nojomi, Marzieh; Shahrad-Bejestani, Hadi; Salehi, Masoud

2017-02-01

To determine the measurement properties of the Persian language version of the Graves orbitopathy quality of life questionnaire (GO-QOL). Following a systematic translation and cultural adaptation process, 141 consecutive unselected thyroid eye disease (TED) patients answered the Persian GO-QOL and underwent complete ophthalmic examination. The questionnaire was again completed by 60 patients on the second visit, 2-4 weeks later. Construct validity (cross-cultural validity, structural validity and hypotheses testing), reliability (internal consistency and test-retest reliability), and floor and ceiling effects of the Persian version of the GO-QOL were evaluated. Furthermore, Rasch analysis was used to assess its psychometric properties. Cross-cultural validity was established by back-translation techniques, committee review and pretesting techniques. Bi-dimensionality of the questionnaire was confirmed by factor analysis. Construct validity was also supported through confirmation of 6 out of 8 predefined hypotheses. Cronbach's α and intraclass correlation coefficient (ICC) were 0.650 and 0.859 for visual functioning and 0.875 and 0.896 for appearance subscale, respectively. Mean quality of life (QOL) scores for visual functioning and appearance were 78.18 (standard deviation, SD, 21.57) and 56.25 (SD 26.87), respectively. Person reliabilities from the Rasch rating scale model for both visual functioning and appearance revealed an acceptable internal consistency for the Persian GO-QOL. The Persian GO-QOL questionnaire is a valid and reliable tool with good psychometric properties in evaluation of Persian-speaking patients with TED. Applying Rasch analysis to future versions of the GO-QOL is recommended in order to perform tests for linearity between the estimated item measures in different versions.

Hypothesized eye movements of neurolinguistic programming: a statistical artifact.

PubMed

Farmer, A; Rooney, R; Cunningham, J R

1985-12-01

Neurolinguistic programming's hypothesized eye-movements were measured independently from videotapes of 30 subjects, aged 15 to 76 yr., who were asked to recall visual pictures, recorded audio sounds, and textural objects. chi 2 indicated that subjects' responses were significantly different from those predicted. When chi 2 comparisons were weighted by number of eye positions assigned to each modality (3 visual, 3 auditory, 1 kinesthetic), subjects' responses did not differ significantly from the expected pattern. These data indicate that the eye-movement hypothesis may represent randomly occurring rather than sensory-modality-related positions.

Translational systems biology using an agent-based approach for dynamic knowledge representation: An evolutionary paradigm for biomedical research.

PubMed

An, Gary C

2010-01-01

The greatest challenge facing the biomedical research community is the effective translation of basic mechanistic knowledge into clinically effective therapeutics. This challenge is most evident in attempts to understand and modulate "systems" processes/disorders, such as sepsis, cancer, and wound healing. Formulating an investigatory strategy for these issues requires the recognition that these are dynamic processes. Representation of the dynamic behavior of biological systems can aid in the investigation of complex pathophysiological processes by augmenting existing discovery procedures by integrating disparate information sources and knowledge. This approach is termed Translational Systems Biology. Focusing on the development of computational models capturing the behavior of mechanistic hypotheses provides a tool that bridges gaps in the understanding of a disease process by visualizing "thought experiments" to fill those gaps. Agent-based modeling is a computational method particularly well suited to the translation of mechanistic knowledge into a computational framework. Utilizing agent-based models as a means of dynamic hypothesis representation will be a vital means of describing, communicating, and integrating community-wide knowledge. The transparent representation of hypotheses in this dynamic fashion can form the basis of "knowledge ecologies," where selection between competing hypotheses will apply an evolutionary paradigm to the development of community knowledge.

Improving data analysis in herpetology: Using Akaike's information criterion (AIC) to assess the strength of biological hypotheses

USGS Publications Warehouse

Mazerolle, M.J.

2006-01-01

In ecology, researchers frequently use observational studies to explain a given pattern, such as the number of individuals in a habitat patch, with a large number of explanatory (i.e., independent) variables. To elucidate such relationships, ecologists have long relied on hypothesis testing to include or exclude variables in regression models, although the conclusions often depend on the approach used (e.g., forward, backward, stepwise selection). Though better tools have surfaced in the mid 1970's, they are still underutilized in certain fields, particularly in herpetology. This is the case of the Akaike information criterion (AIC) which is remarkably superior in model selection (i.e., variable selection) than hypothesis-based approaches. It is simple to compute and easy to understand, but more importantly, for a given data set, it provides a measure of the strength of evidence for each model that represents a plausible biological hypothesis relative to the entire set of models considered. Using this approach, one can then compute a weighted average of the estimate and standard error for any given variable of interest across all the models considered. This procedure, termed model-averaging or multimodel inference, yields precise and robust estimates. In this paper, I illustrate the use of the AIC in model selection and inference, as well as the interpretation of results analysed in this framework with two real herpetological data sets. The AIC and measures derived from it is should be routinely adopted by herpetologists. ?? Koninklijke Brill NV 2006.

Hypotheses to explain the origin of species in Amazonia.

PubMed

Haffer, J

2008-11-01

The main hypotheses proposed to explain barrier formation separating populations and causing the differentiation of species in Amazonia during the course of geological history are based on different factors, as follow: (1) Changes in the distribution of land and sea or in the landscape due to tectonic movements or sea level fluctuations (Paleogeography hypothesis), (2) the barrier effect of Amazonian rivers (River hypothesis), (3) a combination of the barrier effect of broad rivers and vegetational changes in northern and southern Amazonia (River-refuge hypothesis), (4) the isolation of humid rainforest blocks near areas of surface relief in the periphery of Amazonia separated by dry forests, savannas and other intermediate vegetation types during dry climatic periods of the Tertiary and Quaternary (Refuge hypothesis), (5) changes in canopy-density due to climatic reversals (Canopy-density hypothesis) (6) the isolation and speciation of animal populations in small montane habitat pockets around Amazonia due to climatic fluctuations without major vegetational changes (Museum hypothesis), (7) competitive species interactions and local species isolations in peripheral regions of Amazonia due to invasion and counterinvasion during cold/warm periods of the Pleistocene (Disturbance-vicariance hypothesis) and (8) parapatric speciation across steep environmental gradients without separation of the respective populations (Gradient hypothesis). Several of these hypotheses probably are relevant to a different degree for the speciation processes in different faunal groups or during different geological periods. The basic paleogeography model refers mainly to faunal differentiation during the Tertiary and in combination with the Refuge hypothesis. Milankovitch cycles leading to global main hypotheses proposed to explain barrier formation separating populations and causing the differentiation of species in Amazonia during the course of geological history are based on different

Payment for Environmental Services: Hypotheses and Evidence

PubMed Central

Alston, Lee J.; Andersson, Krister; Smith, Steven M.

2014-01-01

The use of payment for environmental services (PES) is not a new type of contract, but PES programs have become more in vogue because of the potential for sequestering carbon by paying to prevent deforestation and degradation of forestlands. We provide a framework utilizing transaction costs to hypothesize which services are more likely to be provided effectively. We then interpret the literature on PES programs to see the extent to which transaction costs vary as predicted across the type of service and to assess the performance of PES programs. As predicted, we find that transaction costs are the least for club goods like water and greatest for pure public goods like carbon reduction. Actual performance is difficult to measure and varies across the examples. More work and experimentation are needed to gain a better outlook on what elements support effective delivery of environmental services. PMID:25143798

Synthetic biology: evolution or revolution? A co-founder's perspective.

PubMed

Gardner, Timothy S; Hawkins, Kristy

2013-12-01

In this article, we relate the story of Synthetic Biology's birth, from the perspective of a co-founder, and consider its original premise--that standardization and abstraction of biological components will unlock the full potential of biological engineering. The standardization ideas of Synthetic Biology emerged in the late 1990s from a convergence of research on cellular computing, and were motivated by an array of applications from tissue regeneration to bio-sensing to mathematical programming. As the definition of Synthetic Biology has grown to be synonymous with Biological Engineering and Biotechnology, the field has lost sight of the fact that its founding premise has not yet been validated. While the value of standardization has been proven in many other engineering disciplines, none of them involve self-replicating systems. The engineering of self-replicating systems will likely benefit from standardization, and also by embracing the forces of evolution that inexorably shape such systems. Copyright © 2013 Elsevier Ltd. All rights reserved.

Biological validation of self-reported condom use among sex workers in Guinea.

PubMed

Aho, Joséphine; Koushik, Anita; Diakité, Soumaïla Laye; Loua, Kovana Marcel; Nguyen, Vinh-Kim; Rashed, Sélim

2010-12-01

Self-reported condom use may be prone to social desirability bias. Our aim was to assess the validity of self-reported condom use in a population of female sex workers using prostate specific antigen (PSA) as a gold standard biomarker of recent unprotected vaginal intercourse. We collected data on 223 sex-workers in Conakry, Guinea in order to assess the sensitivity and specificity of self-reported condom use as well as to examine the predictors of discordance between self-report and PSA presence. PSA was detected in 38.4% of samples. Sensitivity of self-reported condom use was 14.6% and its specificity was 94.7%. Self-perceived high risk of HIV infection was the only significant independent predictor of misreported condom use. PSA could be useful to validate self-reported condom use in surveys and to allow a better understanding of factors associated with social desirability in sexual behaviour reporting.

Invasion Biology on Your Campus: Investigating the Red Imported Fire Ant in the Southeastern United States.

ERIC Educational Resources Information Center

Forys, Elizabeth A.; Kelly, William B.; Ward, David T.

2003-01-01

Describes a laboratory activity on invasion biology to improve students' cognitive skills as well as manual skills. Requires students to develop hypotheses in which a common invasive species will succeed. Focuses on the red imported fire ant in the Southeastern United States, which is a non-native invasive species. (Contains 17 references.) (YDS)

Onanism and child sexual abuse: a comparative study of two hypotheses.

PubMed

Malón, Agustín

2010-06-01

For some decades now in the West, there has been a growing social anxiety with regard to a phenomenon which has become known as child sexual abuse (CSA). This anxiety is fed by scientific theories whose cornerstone is the assessment of these experiences as necessarily harmful, due to their presumed serious consequences for the present and future lives of the minors involved in them. This principle, widely held by experts and laypersons alike, was also part and parcel of the danger presumably posed by Onanism, a phenomenon which occupied a similar position in society and medical science in the West during the eighteenth through twentieth centuries. The present work is a comparative review of these two hypotheses and the central objective was to compare the evolution and fundamental elements of the two hypotheses in light of what history tells us about Onanism theory. This comparative analysis will allow a critical look at the assumptions of the CSA hypothesis in order to make evident the similarities to the conceptual model that enabled the Onanism hypothesis in the past.

No evidence for bilingual cognitive advantages: A test of four hypotheses.

PubMed

von Bastian, Claudia C; Souza, Alessandra S; Gade, Miriam

2016-02-01

The question whether being bilingual yields cognitive benefits is highly controversial with prior studies providing inconsistent results. Failures to replicate the bilingual advantage have been attributed to methodological factors such as comparing dichotomous groups and measuring cognitive abilities separately with single tasks. Therefore, the authors evaluated the 4 most prominent hypotheses of bilingual advantages for inhibitory control, conflict monitoring, shifting, and general cognitive performance by assessing bilingualism on 3 continuous dimensions (age of acquisition, proficiency, and usage) in a sample of 118 young adults and relating it to 9 cognitive abilities each measured by multiple tasks. Linear mixed-effects models accounting for multiple sources of variance simultaneously and controlling for parents' education as an index of socioeconomic status revealed no evidence for any of the 4 hypotheses. Hence, the authors' results suggest that bilingual benefits are not as broad and as robust as has been previously claimed. Instead, earlier effects were possibly due to task-specific effects in selective and often small samples. PsycINFO Database Record (c) 2016 APA, all rights reserved.

[Numerical simulation and operation optimization of biological filter].

PubMed

Zou, Zong-Sen; Shi, Han-Chang; Chen, Xiang-Qiang; Xie, Xiao-Qing

2014-12-01

BioWin software and two sensitivity analysis methods were used to simulate the Denitrification Biological Filter (DNBF) + Biological Aerated Filter (BAF) process in Yuandang Wastewater Treatment Plant. Based on the BioWin model of DNBF + BAF process, the operation data of September 2013 were used for sensitivity analysis and model calibration, and the operation data of October 2013 were used for model validation. The results indicated that the calibrated model could accurately simulate practical DNBF + BAF processes, and the most sensitive parameters were the parameters related to biofilm, OHOs and aeration. After the validation and calibration of model, it was used for process optimization with simulating operation results under different conditions. The results showed that, the best operation condition for discharge standard B was: reflux ratio = 50%, ceasing methanol addition, influent C/N = 4.43; while the best operation condition for discharge standard A was: reflux ratio = 50%, influent COD = 155 mg x L(-1) after methanol addition, influent C/N = 5.10.

The Screening Test for Emotional Problems--Teacher-Report Version (Step-T): Studies of Reliability and Validity

ERIC Educational Resources Information Center

Erford, Bradley T.; Butler, Caitlin; Peacock, Elizabeth

2015-01-01

The Screening Test for Emotional Problems-Teacher Version (STEP-T) was designed to identify students aged 7-17 years with wide-ranging emotional disturbances. Coefficients alpha and test-retest reliability were adequate for all subscales except Anxiety. The hypothesized five-factor model fit the data very well and external aspects of validity were…

Multilevel Assessment of the Predictive Validity of Teacher Made Tests in the Zimbabwean Primary Education Sector

ERIC Educational Resources Information Center

Machingambi, Zadzisai

2017-01-01

The principal focus of this study was to undertake a multilevel assessment of the predictive validity of teacher made tests in the Zimbabwean primary education sector. A correlational research design was adopted for the study, mainly to allow for statistical treatment of data and subsequent classical hypotheses testing using the spearman's rho.…

The archiving and dissemination of biological structure data.

PubMed

Berman, Helen M; Burley, Stephen K; Kleywegt, Gerard J; Markley, John L; Nakamura, Haruki; Velankar, Sameer

2016-10-01

The global Protein Data Bank (PDB) was the first open-access digital archive in biology. The history and evolution of the PDB are described, together with the ways in which molecular structural biology data and information are collected, curated, validated, archived, and disseminated by the members of the Worldwide Protein Data Bank organization (wwPDB; http://wwpdb.org). Particular emphasis is placed on the role of community in establishing the standards and policies by which the PDB archive is managed day-to-day. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

A comparative test of adaptive hypotheses for sexual size dimorphism in lizards.

PubMed

Cox, Robert M; Skelly, Stephanie L; John-Alder, Henry B

2003-07-01

It is commonly argued that sexual size dimorphism (SSD) in lizards has evolved in response to two primary, nonexclusive processes: (1) sexual selection for large male size, which confers an advantage in intrasexual mate competition (intrasexual selection hypothesis), and (2) natural selection for large female size, which confers a fecundity advantage (fecundity advantage hypothesis). However, outside of several well-studied lizard genera, the empirical support for these hypotheses has not been examined with appropriate phylogenetic control. We conducted a comparative phylogenetic analysis to test these hypotheses using literature data from 497 lizard populations representing 302 species and 18 families. As predicted by the intrasexual selection hypothesis, male aggression and territoriality are correlated with SSD, but evolutionary shifts in these categorical variables each explain less than 2% of the inferred evolutionary change in SSD. We found stronger correlations between SSD and continuous estimates of intrasexual selection such as male to female home range ratio and female home range size. These results are consistent with the criticism that categorical variables may obscure much of the actual variation in intrasexual selection intensity needed to explain patterns in SSD. In accordance with the fecundity advantage hypothesis, SSD is correlated with clutch size, reproductive frequency, and reproductive mode (but not fecundity slope, reduced major axis estimator of fecundity slope, length of reproductive season, or latitude). However, evolutionary shifts in clutch size explain less than 8% of the associated change in SSD, which also varies significantly in the absence of evolutionary shifts in reproductive frequency and mode. A multiple regression model retained territoriality and clutch size as significant predictors of SSD, but only 16% of the variation in SSD is explained using these variables. Intrasexual selection for large male size and fecundity

Validity of EQ-5D in general population of Taiwan: results of the 2009 National Health Interview and Drug Abuse Survey of Taiwan.

PubMed

Yu, Sheng-Tsung; Chang, Hsing-Yi; Yao, Kai-Ping; Lin, Yu-Hsuan; Hurng, Baai-Shyun

2015-10-01

The aim of this study was to examine the validity of the EuroQOL five dimensions questionnaire (EQ-5D) using a nationally representative data from the National Health Interview Survey (NHIS) through comparison with short-form 36 (SF-36). Data for this study came from the 2009 NHIS in Taiwan. The study sample was the 4007 participants aged 20-64 years who completed the survey. We used SUDAAN 10.0 (SAS-Callable) to carry out weighed estimation and statistical inference. The EQ index was estimated using norm values from a Taiwanese study as well as from Japan and the United Kingdom (UK). The SF-36 score was standardized using American norm values. In terms of concurrent validity, the EQ-5D met the five hypotheses. The results did not fulfill hypothesis that women would have lower visual analogue scale (EQ-VAS) scores. In terms of discriminant validity, the EQ-5D fulfilled two hypotheses. Our results approached but did not fulfill hypothesis that there would be a weak association between the physical and psychological dimensions of the EQ-5D and the mental component summary score of the SF-36. Results were comparable regardless of whether the Japanese or UK norm value sets were used. We were able to fulfill many, not all of our validity hypotheses regardless of whether the established Japanese or UK norm value sets or the Taiwanese norm values were used. The EQ-5D is an effective and simple instrument for assessing health-related quality of life of general population in Taiwan.

Dogs Evaluate Threatening Facial Expressions by Their Biological Validity – Evidence from Gazing Patterns

PubMed Central

Somppi, Sanni; Törnqvist, Heini; Kujala, Miiamaaria V.; Hänninen, Laura; Krause, Christina M.; Vainio, Outi

2016-01-01

Appropriate response to companions’ emotional signals is important for all social creatures. The emotional expressions of humans and non-human animals have analogies in their form and function, suggesting shared evolutionary roots, but very little is known about how animals other than primates view and process facial expressions. In primates, threat-related facial expressions evoke exceptional viewing patterns compared with neutral or positive stimuli. Here, we explore if domestic dogs (Canis familiaris) have such an attentional bias toward threatening social stimuli and whether observed emotional expressions affect dogs’ gaze fixation distribution among the facial features (eyes, midface and mouth). We recorded the voluntary eye gaze of 31 domestic dogs during viewing of facial photographs of humans and dogs with three emotional expressions (threatening, pleasant and neutral). We found that dogs’ gaze fixations spread systematically among facial features. The distribution of fixations was altered by the seen expression, but eyes were the most probable targets of the first fixations and gathered longer looking durations than mouth regardless of the viewed expression. The examination of the inner facial features as a whole revealed more pronounced scanning differences among expressions. This suggests that dogs do not base their perception of facial expressions on the viewing of single structures, but the interpretation of the composition formed by eyes, midface and mouth. Dogs evaluated social threat rapidly and this evaluation led to attentional bias, which was dependent on the depicted species: threatening conspecifics’ faces evoked heightened attention but threatening human faces instead an avoidance response. We propose that threatening signals carrying differential biological validity are processed via distinctive neurocognitive pathways. Both of these mechanisms may have an adaptive significance for domestic dogs. The findings provide a novel

The lexeme hypotheses: Their use to generate highly grammatical and completely computerized medical records.

PubMed

Macfarlane, Donald

2016-07-01

Medical records often contain free text created by harried clinicians. Free text often contains errors which make it an unsuitable target for computerized data extraction. The cost of healthcare can be reduced by creating medical records that are fully computerized at their inception. We examine hypotheses that enable us to construct such records. We regard the text of the medical record as being an ordered collection of meaningful fragments. The intellectual content (or "lexeme") of each text fragment in the record is considered separately from the language that used to express it. We further consider that each lexeme exists as a combination of a lexeme query (defining the issue being addressed) and a lexeme response to that query. The medical record can then be perceived as a stream of these responses. The responses can be expressed in any style or language, including computer code. Examining medical records in this light gives rise to a number of observations and hypotheses. The physical location and nature of the medical episode (which we term "context") determines the general layout of the record. The order that lexeme-queries are addressed in within the record is highly consistent ("coherence"). Issues are only addressed if they are logically called-for by the context or by a previously-selected lexeme response ("predicance"), and only to a needed depth of detail ("level"). We hypothesize that all of the lexeme queries required to write any clinical notes can be stored in a large database ("lexicon") in coherence order, wherein each lexeme query is associated with its own collection of lexeme responses. We hypothesize that the issue a note-writer will need to address next is identifiable purely by using the rules of coherence, level and predicance. We have tested these hypotheses with a computer program which repeatedly offers the user a menu of lexeme responses with associated text. On selection, the program issues the text fragment, and its corresponding

Probabilistic biological network alignment.

PubMed

Todor, Andrei; Dobra, Alin; Kahveci, Tamer

2013-01-01

Interactions between molecules are probabilistic events. An interaction may or may not happen with some probability, depending on a variety of factors such as the size, abundance, or proximity of the interacting molecules. In this paper, we consider the problem of aligning two biological networks. Unlike existing methods, we allow one of the two networks to contain probabilistic interactions. Allowing interaction probabilities makes the alignment more biologically relevant at the expense of explosive growth in the number of alternative topologies that may arise from different subsets of interactions that take place. We develop a novel method that efficiently and precisely characterizes this massive search space. We represent the topological similarity between pairs of aligned molecules (i.e., proteins) with the help of random variables and compute their expected values. We validate our method showing that, without sacrificing the running time performance, it can produce novel alignments. Our results also demonstrate that our method identifies biologically meaningful mappings under a comprehensive set of criteria used in the literature as well as the statistical coherence measure that we developed to analyze the statistical significance of the similarity of the functions of the aligned protein pairs.

Thinking and working relationally: interviewing and constructing hypotheses to create compassionate understanding.

PubMed

Sheinberg, Marcia; Brewster, Mary Kim

2014-12-01

In the initial interviews of family therapy sessions, the therapist faces the challenge of obtaining and organizing the information that is most relevant toward understanding the essential concerns that families and couples bring to therapy. This article describes the process of clinical interviewing and case conceptualization used in training family therapists at the Ackerman Institute for the Family. This approach helps the therapist bring forward, and organize, specific information into relational hypotheses, or systemic-relational conceptualizations, that allow both family members and the therapist to understand presenting problems within their relational contexts. While always provisional, relational hypotheses help anchor the therapist in a systemic-relational frame and provide a conceptual through-line to guide the ongoing work of the therapy. The process of interviewing and the construction of clear and complex conceptualizations of presenting problems are illustrated through case examples. © 2014 Family Process Institute.

Hypotheses for Near-Surface Exchange of Methane on Mars

NASA Astrophysics Data System (ADS)

Hu, Renyu; Bloom, A. Anthony; Gao, Peter; Miller, Charles E.; Yung, Yuk L.

2016-07-01

The Curiosity rover recently detected a background of 0.7 ppb and spikes of 7 ppb of methane on Mars. This in situ measurement reorients our understanding of the martian environment and its potential for life, as the current theories do not entail any geological source or sink of methane that varies sub-annually. In particular, the 10-fold elevation during the southern winter indicates episodic sources of methane that are yet to be discovered. Here we suggest a near-surface reservoir could explain this variability. Using the temperature and humidity measurements from the rover, we find that perchlorate salts in the regolith deliquesce to form liquid solutions, and deliquescence progresses to deeper subsurface in the season of the methane spikes. We therefore formulate the following three testable hypotheses. The first scenario is that the regolith in Gale Crater adsorbs methane when dry and releases this methane to the atmosphere upon deliquescence. The adsorption energy needs to be 36 kJ mol-1 to explain the magnitude of the methane spikes, higher than existing laboratory measurements. The second scenario is that microorganisms convert organic matter in the soil to methane when they are in liquid solutions. This scenario does not require regolith adsorption but entails extant life on Mars. The third scenario is that deep subsurface aquifers produce the bursts of methane. Continued in situ measurements of methane and water, as well as laboratory studies of adsorption and deliquescence, will test these hypotheses and inform the existence of the near-surface reservoir and its exchange with the atmosphere.

A Test of Biological and Behavioral Explanations for Gender Differences in Telomere Length: The Multi-Ethnic Study of Atherosclerosis

PubMed Central

NEEDHAM, BELINDA L.; DIEZ ROUX, ANA V.; BIRD, CHLOE E.; BRADLEY, RYAN; FITZPATRICK, ANNETTE L.; JACOBS, DAVID R.; OUYANG, PAMELA; SEEMAN, TERESA E.; THURSTON, REBECCA C.; VAIDYA, DHANANJAY; WANG, STEVEN

2015-01-01

The purpose of this study was to examine biological and behavioral explanations for gender differences in leukocyte telomere length (LTL), a biomarker of cell aging that has been hypothesized to contribute to women’s greater longevity. Data are from a subsample (n = 851) of the Multi-Ethnic Study of Atherosclerosis, a population-based study of women and men aged 45 to 84. Mediation models were used to examine study hypotheses. We found that women had longer LTL than men, but the gender difference was smaller at older ages. Gender differences in smoking and processed meat consumption partially mediated gender differences in telomere length, whereas gender differences in estradiol, total testosterone, oxidative stress, and body mass index did not. Neither behavioral nor biological factors explained why the gender difference in LTL was smaller at older ages. Longitudinal studies are needed to assess gender differences in the rate of change in LTL over time; to identify the biological, behavioral, and psychosocial factors that contribute to these differences throughout the life course; and to determine whether gender differences in LTL explain the gender gap in longevity. PMID:25343364

Systems Biology and Biomechanical Model of Heart Failure

PubMed Central

Louridas, George E; Lourida, Katerina G

2012-01-01

Heart failure is seen as a complex disease caused by a combination of a mechanical disorder, cardiac remodeling and neurohormonal activation. To define heart failure the systems biology approach integrates genes and molecules, interprets the relationship of the molecular networks with modular functional units, and explains the interaction between mechanical dysfunction and cardiac remodeling. The biomechanical model of heart failure explains satisfactorily the progression of myocardial dysfunction and the development of clinical phenotypes. The earliest mechanical changes and stresses applied in myocardial cells and/or myocardial loss or dysfunction activate left ventricular cavity remodeling and other neurohormonal regulatory mechanisms such as early release of natriuretic peptides followed by SAS and RAAS mobilization. Eventually the neurohormonal activation and the left ventricular remodeling process are leading to clinical deterioration of heart failure towards a multi-organic damage. It is hypothesized that approaching heart failure with the methodology of systems biology we promote the elucidation of its complex pathophysiology and most probably we can invent new therapeutic strategies. PMID:22935019

Validation of the Simple Shoulder Test in a Portuguese-Brazilian population. Is the latent variable structure and validation of the Simple Shoulder Test Stable across cultures?

PubMed

Neto, Jose Osni Bruggemann; Gesser, Rafael Lehmkuhl; Steglich, Valdir; Bonilauri Ferreira, Ana Paula; Gandhi, Mihir; Vissoci, João Ricardo Nickenig; Pietrobon, Ricardo

2013-01-01

The validation of widely used scales facilitates the comparison across international patient samples. The objective of this study was to translate, culturally adapt and validate the Simple Shoulder Test into Brazilian Portuguese. Also we test the stability of factor analysis across different cultures. The objective of this study was to translate, culturally adapt and validate the Simple Shoulder Test into Brazilian Portuguese. Also we test the stability of factor analysis across different cultures. The Simple Shoulder Test was translated from English into Brazilian Portuguese, translated back into English, and evaluated for accuracy by an expert committee. It was then administered to 100 patients with shoulder conditions. Psychometric properties were analyzed including factor analysis, internal reliability, test-retest reliability at seven days, and construct validity in relation to the Short Form 36 health survey (SF-36). Factor analysis demonstrated a three factor solution. Cronbach's alpha was 0.82. Test-retest reliability index as measured by intra-class correlation coefficient (ICC) was 0.84. Associations were observed in the hypothesized direction with all subscales of SF-36 questionnaire. The Simple Shoulder Test translation and cultural adaptation to Brazilian-Portuguese demonstrated adequate factor structure, internal reliability, and validity, ultimately allowing for its use in the comparison with international patient samples.

Validation of the Simple Shoulder Test in a Portuguese-Brazilian Population. Is the Latent Variable Structure and Validation of the Simple Shoulder Test Stable across Cultures?

PubMed Central

Neto, Jose Osni Bruggemann; Gesser, Rafael Lehmkuhl; Steglich, Valdir; Bonilauri Ferreira, Ana Paula; Gandhi, Mihir; Vissoci, João Ricardo Nickenig; Pietrobon, Ricardo

2013-01-01

Background The validation of widely used scales facilitates the comparison across international patient samples. The objective of this study was to translate, culturally adapt and validate the Simple Shoulder Test into Brazilian Portuguese. Also we test the stability of factor analysis across different cultures. Objective The objective of this study was to translate, culturally adapt and validate the Simple Shoulder Test into Brazilian Portuguese. Also we test the stability of factor analysis across different cultures. Methods The Simple Shoulder Test was translated from English into Brazilian Portuguese, translated back into English, and evaluated for accuracy by an expert committee. It was then administered to 100 patients with shoulder conditions. Psychometric properties were analyzed including factor analysis, internal reliability, test-retest reliability at seven days, and construct validity in relation to the Short Form 36 health survey (SF-36). Results Factor analysis demonstrated a three factor solution. Cronbach’s alpha was 0.82. Test-retest reliability index as measured by intra-class correlation coefficient (ICC) was 0.84. Associations were observed in the hypothesized direction with all subscales of SF-36 questionnaire. Conclusion The Simple Shoulder Test translation and cultural adaptation to Brazilian-Portuguese demonstrated adequate factor structure, internal reliability, and validity, ultimately allowing for its use in the comparison with international patient samples. PMID:23675436

Validity and reliability of the Short Form 36 Health Surveys (SF-36) among patients with spondyloarthritis in Singapore.

PubMed

Kwan, Yu Heng; Fong, Warren Weng Seng; Lui, Nai Lee; Yong, Si Ting; Cheung, Yin Bun; Malhotra, Rahul; Østbye, Truls; Thumboo, Julian

2016-12-01

The Short Form 36 Health Survey (SF-36) is a popular health-related quality of life (HrQoL) tool. However, few studies have assessed its psychometric properties in patients with spondyloarthritis (SpA). We therefore aimed to assess the reliability and validity of the SF-36 in patients with SpA in Singapore. Cross-sectional data from a registry of 196 SpA patients recruited from a dedicated tertiary referral clinic in Singapore from 2011 to 2014 was used. Analyses were guided by the COnsensus-based Standards for the selection of health Measurement INstruments framework. Internal consistency reliability was assessed using Cronbach's alpha. Construct validity was assessed through 33 a priori hypotheses by correlations of the eight subscales and two summary scores of SF-36 with other health outcomes. Known-group construct validity was assessed by comparison of the means of the subscales and summary scores of the SF-36 of SpA patients and the general population of Singapore using student's t tests. Among 196 patients (155 males (79.0 %), median (range) age: 36 (17-70), 166 Chinese (84.6 %)), SF-36 scales showed high internal consistency ranging from 0.88 to 0.90. Convergent construct validity was supported as shown by fulfillment of all hypotheses. Divergent construct validity was supported, as SF-36 MCS was not associated with PGA, pain and HAQ. Known-group construct validity showed SpA patients had lower scores of 3.8-12.5 when compared to the general population at p < 0.001. This study supports the SF-36 as a valid and reliable measure of HrQoL for use in patients with SpA at a single time point.

Measuring Educators' Attitudes and Beliefs about Evaluation: Construct Validity and Reliability of the Teacher Evaluation Experience Scale

ERIC Educational Resources Information Center

Reddy, Linda A.; Dudek, Christopher M.; Kettler, Ryan J.; Kurz, Alexander; Peters, Stephanie

2016-01-01

This study presents the reliability and validity of the Teacher Evaluation Experience Scale--Teacher Form (TEES-T), a multidimensional measure of educators' attitudes and beliefs about teacher evaluation. Confirmatory factor analyses of data from 583 teachers were conducted on the TEES-T hypothesized five-factor model, as well as on alternative…

Acne and nutrition: hypotheses, myths and facts.

PubMed

Claudel, J P; Auffret, N; Leccia, M T; Poli, F; Dréno, B

2018-04-06

Acne is an inflammatory and multifactorial skin disease. Different external and internal factors, including air pollution, aggressive skincare products, medication, mechanical, hormonal and familial factors and, more recently, lifestyle and stress, have been suggested as having an impact on acne. Moreover, for many years nutrition was believed to cause or worsen acne. Over the last decades, however, it has become a dermatological doctrine that there is no direct association between diet and acne. Even if recent research has allowed to identify certain nutritional elements and behaviour that may impact on acne, including the excessive intake of dairy products and hyperglycaemic food, modern lifestyle nutrition, obesity and eating disorders, knowledge about the role of nutrition in the physiopathology of acne still remains sparse and hypotheses and myths continue to dominate the debate. Thus, further clinical and translational research is necessary to investigate and confirm the association between nutrition and acne. © 2018 European Academy of Dermatology and Venereology.

Economic and evolutionary hypotheses for cross-population variation in parochialism.

PubMed

Hruschka, Daniel J; Henrich, Joseph

2013-09-11

Human populations differ reliably in the degree to which people favor family, friends, and community members over strangers and outsiders. In the last decade, researchers have begun to propose several economic and evolutionary hypotheses for these cross-population differences in parochialism. In this paper, we outline major current theories and review recent attempts to test them. We also discuss the key methodological challenges in assessing these diverse economic and evolutionary theories for cross-population differences in parochialism.

Economic and evolutionary hypotheses for cross-population variation in parochialism

PubMed Central

Hruschka, Daniel J.; Henrich, Joseph

2013-01-01

Human populations differ reliably in the degree to which people favor family, friends, and community members over strangers and outsiders. In the last decade, researchers have begun to propose several economic and evolutionary hypotheses for these cross-population differences in parochialism. In this paper, we outline major current theories and review recent attempts to test them. We also discuss the key methodological challenges in assessing these diverse economic and evolutionary theories for cross-population differences in parochialism. PMID:24062662

Validation and Application of the Survey of Teaching Beliefs and Practices for Undergraduates (STEP-U): Identifying Factors Associated with Valuing Important Workplace Skills among Biology Students.

PubMed

Marbach-Ad, Gili; Rietschel, Carly; Thompson, Katerina V

2016-01-01

We present a novel assessment tool for measuring biology students' values and experiences across their undergraduate degree program. Our Survey of Teaching Beliefs and Practices for Undergraduates (STEP-U) assesses the extent to which students value skills needed for the workplace (e.g., ability to work in groups) and their experiences with teaching practices purported to promote such skills (e.g., group work). The survey was validated through factor analyses in a large sample of biology seniors (n = 1389) and through response process analyses (five interviewees). The STEP-U skills items were characterized by two underlying factors: retention (e.g., memorization) and transfer (e.g., knowledge application). Multiple linear regression models were used to examine relationships between classroom experiences, values, and student characteristics (e.g., gender, cumulative grade point average [GPA], and research experience). Student demographic and experiential factors predicted the extent to which students valued particular skills. Students with lower GPAs valued retention skills more than those with higher GPAs. Students with research experience placed greater value on scientific writing and interdisciplinary understanding. Greater experience with specific teaching practices was associated with valuing the corresponding skills more highly. The STEP-U can provide feedback vital for designing curricula that better prepare students for their intended postgraduate careers. © 2016 G. Marbach-Ad et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Use of Bayesian Networks to Probabilistically Model and Improve the Likelihood of Validation of Microarray Findings by RT-PCR

PubMed Central

English, Sangeeta B.; Shih, Shou-Ching; Ramoni, Marco F.; Smith, Lois E.; Butte, Atul J.

2014-01-01

Though genome-wide technologies, such as microarrays, are widely used, data from these methods are considered noisy; there is still varied success in downstream biological validation. We report a method that increases the likelihood of successfully validating microarray findings using real time RT-PCR, including genes at low expression levels and with small differences. We use a Bayesian network to identify the most relevant sources of noise based on the successes and failures in validation for an initial set of selected genes, and then improve our subsequent selection of genes for validation based on eliminating these sources of noise. The network displays the significant sources of noise in an experiment, and scores the likelihood of validation for every gene. We show how the method can significantly increase validation success rates. In conclusion, in this study, we have successfully added a new automated step to determine the contributory sources of noise that determine successful or unsuccessful downstream biological validation. PMID:18790084

Properties of hypothesis testing techniques and (Bayesian) model selection for exploration-based and theory-based (order-restricted) hypotheses.

PubMed

Kuiper, Rebecca M; Nederhoff, Tim; Klugkist, Irene

2015-05-01

In this paper, the performance of six types of techniques for comparisons of means is examined. These six emerge from the distinction between the method employed (hypothesis testing, model selection using information criteria, or Bayesian model selection) and the set of hypotheses that is investigated (a classical, exploration-based set of hypotheses containing equality constraints on the means, or a theory-based limited set of hypotheses with equality and/or order restrictions). A simulation study is conducted to examine the performance of these techniques. We demonstrate that, if one has specific, a priori specified hypotheses, confirmation (i.e., investigating theory-based hypotheses) has advantages over exploration (i.e., examining all possible equality-constrained hypotheses). Furthermore, examining reasonable order-restricted hypotheses has more power to detect the true effect/non-null hypothesis than evaluating only equality restrictions. Additionally, when investigating more than one theory-based hypothesis, model selection is preferred over hypothesis testing. Because of the first two results, we further examine the techniques that are able to evaluate order restrictions in a confirmatory fashion by examining their performance when the homogeneity of variance assumption is violated. Results show that the techniques are robust to heterogeneity when the sample sizes are equal. When the sample sizes are unequal, the performance is affected by heterogeneity. The size and direction of the deviations from the baseline, where there is no heterogeneity, depend on the effect size (of the means) and on the trend in the group variances with respect to the ordering of the group sizes. Importantly, the deviations are less pronounced when the group variances and sizes exhibit the same trend (e.g., are both increasing with group number). © 2014 The British Psychological Society.

The impact of an introductory college-level biology class on biology self-efficacy and attitude towards science

NASA Astrophysics Data System (ADS)

Thomas, Megan Elizabeth

Self-efficacy theory was first introduced in a seminal article by Albert Bandura in 1977 entitled "Self-efficacy: Toward a unifying theory of behavioral change". Since its original introduction, self-efficacy has been a major focus of academic performance, anxiety, career development, and teacher retention research. Self-efficacy can be defined as the belief an individual possesses about their ability to perform a given task. Bandura proposed that self-efficacy should be measured at the highest level of specificity due to the fact that different people are efficacious in different areas. Interested in students' efficacy toward biology, Ebert-May, Baldwin, & Allred (1997) created and validated a survey to measure students' biology self-efficacy. Their survey was modeled after the guidelines for science literacy, and loaded to three sub-factors; methods of biology, generalization to other science courses, and application of the concepts. As self-efficacy theory has been related to effort expenditure and persistence (Bandura, 1977; 1997), one might think it would have some effect on students' attitudes toward the topic at hand. The current research investigated what changes in biology self-efficacy occurred after an introductory biology course with an inquiry based laboratory learning environment. In addition, changes in students' attitudes towards science were explored and how self-efficacy might affect them.

Independence of long-term contextual memory and short-term perceptual hypotheses: Evidence from contextual cueing of interrupted search.

PubMed

Schlagbauer, Bernhard; Mink, Maurice; Müller, Hermann J; Geyer, Thomas

2017-02-01

Observers are able to resume an interrupted search trial faster relative to responding to a new, unseen display. This finding of rapid resumption is attributed to short-term perceptual hypotheses generated on the current look and confirmed upon subsequent looks at the same display. It has been suggested that the contents of perceptual hypotheses are similar to those of other forms of memory acquired long-term through repeated exposure to the same search displays over the course of several trials, that is, the memory supporting "contextual cueing." In three experiments, we investigated the relationship between short-term perceptual hypotheses and long-term contextual memory. The results indicated that long-term, contextual memory of repeated displays neither affected the generation nor the confirmation of short-term perceptual hypotheses for these displays. Furthermore, the analysis of eye movements suggests that long-term memory provides an initial benefit in guiding attention to the target, whereas in subsequent looks guidance is entirely based on short-term perceptual hypotheses. Overall, the results reveal a picture of both long- and short-term memory contributing to reliable performance gains in interrupted search, while exerting their effects in an independent manner.

The Ranschburg Effect: Tests of the Guessing-Bias and Proactive Interference Hypotheses

ERIC Educational Resources Information Center

Walsh, Michael F.; Schwartz, Marian

1977-01-01

The guessing-bias and proactive interference hypotheses of the Ranschburg Effect were investigated by giving three groups different instructions as to guessing during recall. Results failed to support the prediction that the effect should be reduced or eliminated on shift trials. Neither hypothesis received significant support. (CHK)

Generalized Beer-Lambert model for near-infrared light propagation in thick biological tissues

NASA Astrophysics Data System (ADS)

Bhatt, Manish; Ayyalasomayajula, Kalyan R.; Yalavarthy, Phaneendra K.

2016-07-01

The attenuation of near-infrared (NIR) light intensity as it propagates in a turbid medium like biological tissue is described by modified the Beer-Lambert law (MBLL). The MBLL is generally used to quantify the changes in tissue chromophore concentrations for NIR spectroscopic data analysis. Even though MBLL is effective in terms of providing qualitative comparison, it suffers from its applicability across tissue types and tissue dimensions. In this work, we introduce Lambert-W function-based modeling for light propagation in biological tissues, which is a generalized version of the Beer-Lambert model. The proposed modeling provides parametrization of tissue properties, which includes two attenuation coefficients μ0 and η. We validated our model against the Monte Carlo simulation, which is the gold standard for modeling NIR light propagation in biological tissue. We included numerous human and animal tissues to validate the proposed empirical model, including an inhomogeneous adult human head model. The proposed model, which has a closed form (analytical), is first of its kind in providing accurate modeling of NIR light propagation in biological tissues.

Multi-scale modeling in cell biology

PubMed Central

Meier-Schellersheim, Martin; Fraser, Iain D. C.; Klauschen, Frederick

2009-01-01

Biomedical research frequently involves performing experiments and developing hypotheses that link different scales of biological systems such as, for instance, the scales of intracellular molecular interactions to the scale of cellular behavior and beyond to the behavior of cell populations. Computational modeling efforts that aim at exploring such multi-scale systems quantitatively with the help of simulations have to incorporate several different simulation techniques due to the different time and space scales involved. Here, we provide a non-technical overview of how different scales of experimental research can be combined with the appropriate computational modeling techniques. We also show that current modeling software permits building and simulating multi-scale models without having to become involved with the underlying technical details of computational modeling. PMID:20448808

Modeling biological gradient formation: combining partial differential equations and Petri nets.

PubMed

Bertens, Laura M F; Kleijn, Jetty; Hille, Sander C; Heiner, Monika; Koutny, Maciej; Verbeek, Fons J

2016-01-01

Both Petri nets and differential equations are important modeling tools for biological processes. In this paper we demonstrate how these two modeling techniques can be combined to describe biological gradient formation. Parameters derived from partial differential equation describing the process of gradient formation are incorporated in an abstract Petri net model. The quantitative aspects of the resulting model are validated through a case study of gradient formation in the fruit fly.

Biased and unbiased strategies to identify biologically active small molecules.

PubMed

Abet, Valentina; Mariani, Angelica; Truscott, Fiona R; Britton, Sébastien; Rodriguez, Raphaël

2014-08-15

Small molecules are central players in chemical biology studies. They promote the perturbation of cellular processes underlying diseases and enable the identification of biological targets that can be validated for therapeutic intervention. Small molecules have been shown to accurately tune a single function of pluripotent proteins in a reversible manner with exceptional temporal resolution. The identification of molecular probes and drugs remains a worthy challenge that can be addressed by the use of biased and unbiased strategies. Hypothesis-driven methodologies employs a known biological target to synthesize complementary hits while discovery-driven strategies offer the additional means of identifying previously unanticipated biological targets. This review article provides a general overview of recent synthetic frameworks that gave rise to an impressive arsenal of biologically active small molecules with unprecedented cellular mechanisms. Copyright © 2014. Published by Elsevier Ltd.

Testing and Validation of Computational Methods for Mass Spectrometry.

PubMed

Gatto, Laurent; Hansen, Kasper D; Hoopmann, Michael R; Hermjakob, Henning; Kohlbacher, Oliver; Beyer, Andreas

2016-03-04

High-throughput methods based on mass spectrometry (proteomics, metabolomics, lipidomics, etc.) produce a wealth of data that cannot be analyzed without computational methods. The impact of the choice of method on the overall result of a biological study is often underappreciated, but different methods can result in very different biological findings. It is thus essential to evaluate and compare the correctness and relative performance of computational methods. The volume of the data as well as the complexity of the algorithms render unbiased comparisons challenging. This paper discusses some problems and challenges in testing and validation of computational methods. We discuss the different types of data (simulated and experimental validation data) as well as different metrics to compare methods. We also introduce a new public repository for mass spectrometric reference data sets ( http://compms.org/RefData ) that contains a collection of publicly available data sets for performance evaluation for a wide range of different methods.

The Quality and Validation of Structures from Structural Genomics

PubMed Central

Domagalski, Marcin J.; Zheng, Heping; Zimmerman, Matthew D.; Dauter, Zbigniew; Wlodawer, Alexander; Minor, Wladek

2014-01-01

Quality control of three-dimensional structures of macromolecules is a critical step to ensure the integrity of structural biology data, especially those produced by structural genomics centers. Whereas the Protein Data Bank (PDB) has proven to be a remarkable success overall, the inconsistent quality of structures reveals a lack of universal standards for structure/deposit validation. Here, we review the state-of-the-art methods used in macromolecular structure validation, focusing on validation of structures determined by X-ray crystallography. We describe some general protocols used in the rebuilding and re-refinement of problematic structural models. We also briefly discuss some frontier areas of structure validation, including refinement of protein–ligand complexes, automation of structure redetermination, and the use of NMR structures and computational models to solve X-ray crystal structures by molecular replacement. PMID:24203341

Human female orgasm as evolved signal: a test of two hypotheses.

PubMed

Ellsworth, Ryan M; Bailey, Drew H

2013-11-01

We present the results of a study designed to empirically test predictions derived from two hypotheses regarding human female orgasm behavior as an evolved communicative trait or signal. One hypothesis tested was the female fidelity hypothesis, which posits that human female orgasm signals a woman's sexual satisfaction and therefore her likelihood of future fidelity to a partner. The other was sire choice hypothesis, which posits that women's orgasm behavior signals increased chances of fertilization. To test the two hypotheses of human female orgasm, we administered a questionnaire to 138 females and 121 males who reported that they were currently in a romantic relationship. Key predictions of the female fidelity hypothesis were not supported. In particular, orgasm was not associated with female sexual fidelity nor was orgasm associated with male perceptions of partner sexual fidelity. However, faked orgasm was associated with female sexual infidelity and lower male relationship satisfaction. Overall, results were in greater support of the sire choice signaling hypothesis than the female fidelity hypothesis. Results also suggest that male satisfaction with, investment in, and sexual fidelity to a mate are benefits that favored the selection of orgasmic signaling in ancestral females.

NDEx: A Community Resource for Sharing and Publishing of Biological Networks.

PubMed

Pillich, Rudolf T; Chen, Jing; Rynkov, Vladimir; Welker, David; Pratt, Dexter

2017-01-01

Networks are a powerful and flexible paradigm that facilitate communication and computation about interactions of any type, whether social, economic, or biological. NDEx, the Network Data Exchange, is an online commons to enable new modes of collaboration and publication using biological networks. NDEx creates an access point and interface to a broad range of networks, whether they express molecular interactions, curated relationships from literature, or the outputs of systematic analysis of big data. Research organizations can use NDEx as a distribution channel for networks they generate or curate. Developers of bioinformatic applications can store and query NDEx networks via a common programmatic interface. NDEx can also facilitate the integration of networks as data in electronic publications, thus making a step toward an ecosystem in which networks bearing data, hypotheses, and findings flow seamlessly between scientists.

The RNA-world and co-evolution hypotheses and the origin of life: Implications, research strategies and perspectives

NASA Astrophysics Data System (ADS)

Lahav, Noam

1993-12-01

The applicability of the RNA-world and co-evolution hypotheses to the study of the very first stages of the origin of life is discussed. The discussion focuses on the basic differences between the two hypotheses and their implications, with regard to the reconstruction methodology, ribosome emergence, balance between ribozymes and protein enzymes, and their major difficulties. Additional complexities of the two hypotheses, such as membranes and the energy source of the first reactions, are not treated in the present work. A central element in the proposed experimental strategies is the study of the catalytic activities of very small peptides and RNA-like oligomers, according to existing, as well as to yet-to-be-invented scenarios of the two hypotheses under consideration. It is suggested that the noveldirected molecular evolution technology, andmolecular computational modeling, can be applied to this research. This strategy is assumed to be essential for the suggested goal of future studies of the origin of life, namely, the establishment of a ‘Primordial Darwinian entity’.

Sequence-related amplified polymorphism (SRAP) markers: A potential resource for studies in plant molecular biology(1.).

PubMed

Robarts, Daniel W H; Wolfe, Andrea D

2014-07-01

In the past few decades, many investigations in the field of plant biology have employed selectively neutral, multilocus, dominant markers such as inter-simple sequence repeat (ISSR), random-amplified polymorphic DNA (RAPD), and amplified fragment length polymorphism (AFLP) to address hypotheses at lower taxonomic levels. More recently, sequence-related amplified polymorphism (SRAP) markers have been developed, which are used to amplify coding regions of DNA with primers targeting open reading frames. These markers have proven to be robust and highly variable, on par with AFLP, and are attained through a significantly less technically demanding process. SRAP markers have been used primarily for agronomic and horticultural purposes, developing quantitative trait loci in advanced hybrids and assessing genetic diversity of large germplasm collections. Here, we suggest that SRAP markers should be employed for research addressing hypotheses in plant systematics, biogeography, conservation, ecology, and beyond. We provide an overview of the SRAP literature to date, review descriptive statistics of SRAP markers in a subset of 171 publications, and present relevant case studies to demonstrate the applicability of SRAP markers to the diverse field of plant biology. Results of these selected works indicate that SRAP markers have the potential to enhance the current suite of molecular tools in a diversity of fields by providing an easy-to-use, highly variable marker with inherent biological significance.

Sequence-related amplified polymorphism (SRAP) markers: A potential resource for studies in plant molecular biology1

PubMed Central

Robarts, Daniel W. H.; Wolfe, Andrea D.

2014-01-01

In the past few decades, many investigations in the field of plant biology have employed selectively neutral, multilocus, dominant markers such as inter-simple sequence repeat (ISSR), random-amplified polymorphic DNA (RAPD), and amplified fragment length polymorphism (AFLP) to address hypotheses at lower taxonomic levels. More recently, sequence-related amplified polymorphism (SRAP) markers have been developed, which are used to amplify coding regions of DNA with primers targeting open reading frames. These markers have proven to be robust and highly variable, on par with AFLP, and are attained through a significantly less technically demanding process. SRAP markers have been used primarily for agronomic and horticultural purposes, developing quantitative trait loci in advanced hybrids and assessing genetic diversity of large germplasm collections. Here, we suggest that SRAP markers should be employed for research addressing hypotheses in plant systematics, biogeography, conservation, ecology, and beyond. We provide an overview of the SRAP literature to date, review descriptive statistics of SRAP markers in a subset of 171 publications, and present relevant case studies to demonstrate the applicability of SRAP markers to the diverse field of plant biology. Results of these selected works indicate that SRAP markers have the potential to enhance the current suite of molecular tools in a diversity of fields by providing an easy-to-use, highly variable marker with inherent biological significance. PMID:25202637

Validation of systems biology derived molecular markers of renal donor organ status associated with long term allograft function.

PubMed

Perco, Paul; Heinzel, Andreas; Leierer, Johannes; Schneeberger, Stefan; Bösmüller, Claudia; Oberhuber, Rupert; Wagner, Silvia; Engler, Franziska; Mayer, Gert

2018-05-03

Donor organ quality affects long term outcome after renal transplantation. A variety of prognostic molecular markers is available, yet their validity often remains undetermined. A network-based molecular model reflecting donor kidney status based on transcriptomics data and molecular features reported in scientific literature to be associated with chronic allograft nephropathy was created. Significantly enriched biological processes were identified and representative markers were selected. An independent kidney pre-implantation transcriptomics dataset of 76 organs was used to predict estimated glomerular filtration rate (eGFR) values twelve months after transplantation using available clinical data and marker expression values. The best-performing regression model solely based on the clinical parameters donor age, donor gender, and recipient gender explained 17% of variance in post-transplant eGFR values. The five molecular markers EGF, CD2BP2, RALBP1, SF3B1, and DDX19B representing key molecular processes of the constructed renal donor organ status molecular model in addition to the clinical parameters significantly improved model performance (p-value = 0.0007) explaining around 33% of the variability of eGFR values twelve months after transplantation. Collectively, molecular markers reflecting donor organ status significantly add to prediction of post-transplant renal function when added to the clinical parameters donor age and gender.

Hypotheses for Near-Surface Exchange of Methane on Mars.

PubMed

Hu, Renyu; Bloom, A Anthony; Gao, Peter; Miller, Charles E; Yung, Yuk L

2016-07-01

The Curiosity rover recently detected a background of 0.7 ppb and spikes of 7 ppb of methane on Mars. This in situ measurement reorients our understanding of the martian environment and its potential for life, as the current theories do not entail any geological source or sink of methane that varies sub-annually. In particular, the 10-fold elevation during the southern winter indicates episodic sources of methane that are yet to be discovered. Here we suggest a near-surface reservoir could explain this variability. Using the temperature and humidity measurements from the rover, we find that perchlorate salts in the regolith deliquesce to form liquid solutions, and deliquescence progresses to deeper subsurface in the season of the methane spikes. We therefore formulate the following three testable hypotheses. The first scenario is that the regolith in Gale Crater adsorbs methane when dry and releases this methane to the atmosphere upon deliquescence. The adsorption energy needs to be 36 kJ mol(-1) to explain the magnitude of the methane spikes, higher than existing laboratory measurements. The second scenario is that microorganisms convert organic matter in the soil to methane when they are in liquid solutions. This scenario does not require regolith adsorption but entails extant life on Mars. The third scenario is that deep subsurface aquifers produce the bursts of methane. Continued in situ measurements of methane and water, as well as laboratory studies of adsorption and deliquescence, will test these hypotheses and inform the existence of the near-surface reservoir and its exchange with the atmosphere. Mars-Methane-Astrobiology-Regolith. Astrobiology 16, 539-550.

Interest in STEM is contagious for students in biology, chemistry, and physics classes

PubMed Central

Hazari, Zahra; Potvin, Geoff; Cribbs, Jennifer D.; Godwin, Allison; Scott, Tyler D.; Klotz, Leidy

2017-01-01

We report on a study of the effect of peers’ interest in high school biology, chemistry, and physics classes on students’ STEM (science, technology, engineering, and mathematics)–related career intentions and course achievement. We define an interest quorum as a science class where students perceive a high level of interest for the subject matter from their classmates. We hypothesized that students who experience such an interest quorum are more likely to choose STEM careers. Using data from a national survey study of students‘ experiences in high school science, we compared the effect of five levels of peer interest reported in biology, chemistry, and physics courses on students‘ STEM career intentions. The results support our hypothesis, showing a strong, positive effect of an interest quorum even after controlling for differences between students that pose competing hypotheses such as previous STEM career interest, academic achievement, family support for mathematics and science, and gender. Smaller positive effects of interest quorums were observed for course performance in some cases, with no detrimental effects observed across the study. Last, significant effects persisted even after controlling for differences in teaching quality. This work emphasizes the likely importance of interest quorums for creating classroom environments that increase students’ intentions toward STEM careers while enhancing or maintaining course performance. PMID:28808678

Interest in STEM is contagious for students in biology, chemistry, and physics classes.

PubMed

Hazari, Zahra; Potvin, Geoff; Cribbs, Jennifer D; Godwin, Allison; Scott, Tyler D; Klotz, Leidy

2017-08-01

We report on a study of the effect of peers' interest in high school biology, chemistry, and physics classes on students' STEM (science, technology, engineering, and mathematics)-related career intentions and course achievement. We define an interest quorum as a science class where students perceive a high level of interest for the subject matter from their classmates. We hypothesized that students who experience such an interest quorum are more likely to choose STEM careers. Using data from a national survey study of students' experiences in high school science, we compared the effect of five levels of peer interest reported in biology, chemistry, and physics courses on students' STEM career intentions. The results support our hypothesis, showing a strong, positive effect of an interest quorum even after controlling for differences between students that pose competing hypotheses such as previous STEM career interest, academic achievement, family support for mathematics and science, and gender. Smaller positive effects of interest quorums were observed for course performance in some cases, with no detrimental effects observed across the study. Last, significant effects persisted even after controlling for differences in teaching quality. This work emphasizes the likely importance of interest quorums for creating classroom environments that increase students' intentions toward STEM careers while enhancing or maintaining course performance.

A conceptual review on systems biology in health and diseases: from biological networks to modern therapeutics.

PubMed

Somvanshi, Pramod Rajaram; Venkatesh, K V

2014-03-01

Human physiology is an ensemble of various biological processes spanning from intracellular molecular interactions to the whole body phenotypic response. Systems biology endures to decipher these multi-scale biological networks and bridge the link between genotype to phenotype. The structure and dynamic properties of these networks are responsible for controlling and deciding the phenotypic state of a cell. Several cells and various tissues coordinate together to generate an organ level response which further regulates the ultimate physiological state. The overall network embeds a hierarchical regulatory structure, which when unusually perturbed can lead to undesirable physiological state termed as disease. Here, we treat a disease diagnosis problem analogous to a fault diagnosis problem in engineering systems. Accordingly we review the application of engineering methodologies to address human diseases from systems biological perspective. The review highlights potential networks and modeling approaches used for analyzing human diseases. The application of such analysis is illustrated in the case of cancer and diabetes. We put forth a concept of cell-to-human framework comprising of five modules (data mining, networking, modeling, experimental and validation) for addressing human physiology and diseases based on a paradigm of system level analysis. The review overtly emphasizes on the importance of multi-scale biological networks and subsequent modeling and analysis for drug target identification and designing efficient therapies.

Development and validation of a measure of workplace climate for healthy weight maintenance.

PubMed

Sliter, Katherine A

2013-07-01

Due to the obesity epidemic, an increasing amount of research is being conducted to better understand the antecedents and consequences of excess employee weight. One construct often of interest to researchers in this area is organizational climate. Unfortunately, a viable measure of climate, as related to employee weight, does not exist. The purpose of this study was to remedy this by developing and validating a concise, psychometrically sound measure of climate for healthy weight. An item pool was developed based on surveys of full-time employees, and a sorting task was used to eliminate ambiguous items. Items were pilot tested by a sample of 338 full-time employees, and the item pool was reduced through item response theory (IRT) and reliability analyses. Finally, the retained 14 items, comprising 3 subscales, were completed by a sample of 360 full-time employees, representing 26 different organizations from across the United States. Multilevel modeling indicated that sufficient variance was explained by group membership to support aggregation, and confirmatory factor analysis (CFA) supported the hypothesized model of 3 subscale factors and an overall climate factor. Nine hypotheses specific to construct validation were tested. Scores on the new scale correlated significantly with individual-level reports of psychological constructs (e.g., health motivation, general leadership support for health) and physiological phenomena (e.g., body mass index [BMI], physical health problems) to which they should theoretically relate, supporting construct validity. Implications for the use of this scale in both applied and research settings are discussed. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Surface Biology of DNA by Atomic Force Microscopy

NASA Astrophysics Data System (ADS)

Hansma, Helen G.

2001-10-01

The atomic force microscope operates on surfaces. Since surfaces occupy much of the space in living organisms, surface biology is a valid and valuable form of biology that has been difficult to investigate in the past owing to a lack of good technology. Atomic force microscopy (AFM) of DNA has been used to investigate DNA condensation for gene therapy, DNA mapping and sizing, and a few applications to cancer research and to nanotechnology. Some of the most exciting new applications for atomic force microscopy of DNA involve pulling on single DNA molecules to obtain measurements of single-molecule mechanics and thermodynamics.

A High-Resolution Tile-Based Approach for Classifying Biological Regions in Whole-Slide Histopathological Images

PubMed Central

Hoffman, R.A.; Kothari, S.; Phan, J.H.; Wang, M.D.

2016-01-01

Computational analysis of histopathological whole slide images (WSIs) has emerged as a potential means for improving cancer diagnosis and prognosis. However, an open issue relating to the automated processing of WSIs is the identification of biological regions such as tumor, stroma, and necrotic tissue on the slide. We develop a method for classifying WSI portions (512x512-pixel tiles) into biological regions by (1) extracting a set of 461 image features from each WSI tile, (2) optimizing tile-level prediction models using nested cross-validation on a small (600 tile) manually annotated tile-level training set, and (3) validating the models against a much larger (1.7x106 tile) data set for which ground truth was available on the whole-slide level. We calculated the predicted prevalence of each tissue region and compared this prevalence to the ground truth prevalence for each image in an independent validation set. Results show significant correlation between the predicted (using automated system) and reported biological region prevalences with p < 0.001 for eight of nine cases considered. PMID:27532012

A High-Resolution Tile-Based Approach for Classifying Biological Regions in Whole-Slide Histopathological Images.

PubMed

Hoffman, R A; Kothari, S; Phan, J H; Wang, M D

Computational analysis of histopathological whole slide images (WSIs) has emerged as a potential means for improving cancer diagnosis and prognosis. However, an open issue relating to the automated processing of WSIs is the identification of biological regions such as tumor, stroma, and necrotic tissue on the slide. We develop a method for classifying WSI portions (512x512-pixel tiles) into biological regions by (1) extracting a set of 461 image features from each WSI tile, (2) optimizing tile-level prediction models using nested cross-validation on a small (600 tile) manually annotated tile-level training set, and (3) validating the models against a much larger (1.7x10 6 tile) data set for which ground truth was available on the whole-slide level. We calculated the predicted prevalence of each tissue region and compared this prevalence to the ground truth prevalence for each image in an independent validation set. Results show significant correlation between the predicted (using automated system) and reported biological region prevalences with p < 0.001 for eight of nine cases considered.

Synthetic Biology Open Language (SBOL) Version 2.2.0.

PubMed

Cox, Robert Sidney; Madsen, Curtis; McLaughlin, James Alastair; Nguyen, Tramy; Roehner, Nicholas; Bartley, Bryan; Beal, Jacob; Bissell, Michael; Choi, Kiri; Clancy, Kevin; Grünberg, Raik; Macklin, Chris; Misirli, Goksel; Oberortner, Ernst; Pocock, Matthew; Samineni, Meher; Zhang, Michael; Zhang, Zhen; Zundel, Zach; Gennari, John H; Myers, Chris; Sauro, Herbert; Wipat, Anil

2018-04-02

Synthetic biology builds upon the techniques and successes of genetics, molecular biology, and metabolic engineering by applying engineering principles to the design of biological systems. The field still faces substantial challenges, including long development times, high rates of failure, and poor reproducibility. One method to ameliorate these problems would be to improve the exchange of information about designed systems between laboratories. The synthetic biology open language (SBOL) has been developed as a standard to support the specification and exchange of biological design information in synthetic biology, filling a need not satisfied by other pre-existing standards. This document details version 2.2.0 of SBOL that builds upon version 2.1.0 published in last year's JIB special issue. In particular, SBOL 2.2.0 includes improved description and validation rules for genetic design provenance, an extension to support combinatorial genetic designs, a new class to add non-SBOL data as attachments, a new class for genetic design implementations, and a description of a methodology to describe the entire design-build-test-learn cycle within the SBOL data model.

Synthetic Biology Open Language (SBOL) Version 2.1.0.

PubMed

Beal, Jacob; Cox, Robert Sidney; Grünberg, Raik; McLaughlin, James; Nguyen, Tramy; Bartley, Bryan; Bissell, Michael; Choi, Kiri; Clancy, Kevin; Macklin, Chris; Madsen, Curtis; Misirli, Goksel; Oberortner, Ernst; Pocock, Matthew; Roehner, Nicholas; Samineni, Meher; Zhang, Michael; Zhang, Zhen; Zundel, Zach; Gennari, John H; Myers, Chris; Sauro, Herbert; Wipat, Anil

2016-09-01

Synthetic biology builds upon the techniques and successes of genetics, molecular biology, and metabolic engineering by applying engineering principles to the design of biological systems. The field still faces substantial challenges, including long development times, high rates of failure, and poor reproducibility. One method to ameliorate these problems would be to improve the exchange of information about designed systems between laboratories. The Synthetic Biology Open Language (SBOL) has been developed as a standard to support the specification and exchange of biological design information in synthetic biology, filling a need not satisfied by other pre-existing standards. This document details version 2.1 of SBOL that builds upon version 2.0 published in last year's JIB special issue. In particular, SBOL 2.1 includes improved rules for what constitutes a valid SBOL document, new role fields to simplify the expression of sequence features and how components are used in context, and new best practices descriptions to improve the exchange of basic sequence topology information and the description of genetic design provenance, as well as miscellaneous other minor improvements.

Synthetic Biology Open Language (SBOL) Version 2.1.0.

PubMed

Beal, Jacob; Cox, Robert Sidney; Grünberg, Raik; McLaughlin, James; Nguyen, Tramy; Bartley, Bryan; Bissell, Michael; Choi, Kiri; Clancy, Kevin; Macklin, Chris; Madsen, Curtis; Misirli, Goksel; Oberortner, Ernst; Pocock, Matthew; Roehner, Nicholas; Samineni, Meher; Zhang, Michael; Zhang, Zhen; Zundel, Zach; Gennari, John; Myers, Chris; Sauro, Herbert; Wipat, Anil

2016-12-18

Synthetic biology builds upon the techniques and successes of genetics, molecular biology, and metabolic engineering by applying engineering principles to the design of biological systems. The field still faces substantial challenges, including long development times, high rates of failure, and poor reproducibility. One method to ameliorate these problems would be to improve the exchange of information about designed systems between laboratories. The Synthetic Biology Open Language (SBOL) has been developed as a standard to support the specification and exchange of biological design information in synthetic biology, filling a need not satisfied by other pre-existing standards. This document details version 2.1 of SBOL that builds upon version 2.0 published in last year’s JIB special issue. In particular, SBOL 2.1 includes improved rules for what constitutes a valid SBOL document, new role fields to simplify the expression of sequence features and how components are used in context, and new best practices descriptions to improve the exchange of basic sequence topology information and the description of genetic design provenance, as well as miscellaneous other minor improvements.

The Center for Computational Biology: resources, achievements, and challenges

PubMed Central

Dinov, Ivo D; Thompson, Paul M; Woods, Roger P; Van Horn, John D; Shattuck, David W; Parker, D Stott

2011-01-01

The Center for Computational Biology (CCB) is a multidisciplinary program where biomedical scientists, engineers, and clinicians work jointly to combine modern mathematical and computational techniques, to perform phenotypic and genotypic studies of biological structure, function, and physiology in health and disease. CCB has developed a computational framework built around the Manifold Atlas, an integrated biomedical computing environment that enables statistical inference on biological manifolds. These manifolds model biological structures, features, shapes, and flows, and support sophisticated morphometric and statistical analyses. The Manifold Atlas includes tools, workflows, and services for multimodal population-based modeling and analysis of biological manifolds. The broad spectrum of biomedical topics explored by CCB investigators include the study of normal and pathological brain development, maturation and aging, discovery of associations between neuroimaging and genetic biomarkers, and the modeling, analysis, and visualization of biological shape, form, and size. CCB supports a wide range of short-term and long-term collaborations with outside investigators, which drive the center's computational developments and focus the validation and dissemination of CCB resources to new areas and scientific domains. PMID:22081221

The Center for Computational Biology: resources, achievements, and challenges.

PubMed

Toga, Arthur W; Dinov, Ivo D; Thompson, Paul M; Woods, Roger P; Van Horn, John D; Shattuck, David W; Parker, D Stott

2012-01-01

The Center for Computational Biology (CCB) is a multidisciplinary program where biomedical scientists, engineers, and clinicians work jointly to combine modern mathematical and computational techniques, to perform phenotypic and genotypic studies of biological structure, function, and physiology in health and disease. CCB has developed a computational framework built around the Manifold Atlas, an integrated biomedical computing environment that enables statistical inference on biological manifolds. These manifolds model biological structures, features, shapes, and flows, and support sophisticated morphometric and statistical analyses. The Manifold Atlas includes tools, workflows, and services for multimodal population-based modeling and analysis of biological manifolds. The broad spectrum of biomedical topics explored by CCB investigators include the study of normal and pathological brain development, maturation and aging, discovery of associations between neuroimaging and genetic biomarkers, and the modeling, analysis, and visualization of biological shape, form, and size. CCB supports a wide range of short-term and long-term collaborations with outside investigators, which drive the center's computational developments and focus the validation and dissemination of CCB resources to new areas and scientific domains.

A Decentralized Approach to the Formulation of Hypotheses: A Hierarchical Structural Model for a Prion Self-Assembled System

NASA Astrophysics Data System (ADS)

Wang, Mingyang; Zhang, Feifei; Song, Chao; Shi, Pengfei; Zhu, Jin

2016-07-01

Innovation in hypotheses is a key transformative driver for scientific development. The conventional centralized hypothesis formulation approach, where a dominant hypothesis is typically derived from a primary phenomenon, can, inevitably, impose restriction on the range of conceivable experiments and legitimate hypotheses, and ultimately impede understanding of the system of interest. We report herein the proposal of a decentralized approach for the formulation of hypotheses, through initial preconception-free phenomenon accumulation and subsequent reticular logical reasoning processes. The two-step approach can provide an unbiased, panoramic view of the system and as such should enable the generation of a set of more coherent and therefore plausible hypotheses. As a proof-of-concept demonstration of the utility of this open-ended approach, a hierarchical model has been developed for a prion self-assembled system, allowing insight into hitherto elusive static and dynamic features associated with this intriguing structure.

Validation of a motor activity system by a robotically controlled vehicle and using standard reference compounds.

PubMed

Patterson, John P; Markgraf, Carrie G; Cirino, Maria; Bass, Alan S

2005-01-01

A series of experiments were undertaken to evaluate the accuracy, precision, specificity, and sensitivity of an automated, infrared photo beam-based open field motor activity system, the MotorMonitor v. 4.01, Hamilton-Kinder, LLC, for use in a good laboratory practices (GLP) Safety Pharmacology laboratory. This evaluation consisted of two phases: (1) system validation, employing known inputs using the EM-100 Controller Photo Beam Validation System, a robotically controlled vehicle representing a rodent and (2) biologic validation, employing groups of rats treated with the standard pharmacologic agents diazepam or D-amphetamine. The MotorMonitor's parameters that described the open-field activity of a subject were: basic movements, total distance, fine movements, x/y horizontal ambulations, rearing, and total rest time. These measurements were evaluated over a number of zones within each enclosure. System validation with the EM-100 Controller Photo Beam Validation System showed that all the parameters accurately and precisely measured what they were intended to measure, with the exception of fine movements and x/y ambulations. Biologic validation using the central nervous system depressant diazepam at 1, 2, or 5 mg/kg, i.p. produced the expected dose-dependent reduction in rat motor activity. In contrast, the central nervous system stimulant D-amphetamine produced the expected increases in rat motor activity at 0.1 and 1 mg/kg, i.p, demonstrating the specificity and sensitivity of the system. Taken together, these studies of the accuracy, precision, specificity, and sensitivity show the importance of both system and biologic validation in the evaluation of an automated open field motor activity system for use in a GLP compliant laboratory.

Angiosperm phylogeny inferred from multiple genes as a tool for comparative biology.

PubMed

Soltis, P S; Soltis, D E; Chase, M W

1999-11-25

Comparative biology requires a firm phylogenetic foundation to uncover and understand patterns of diversification and evaluate hypotheses of the processes responsible for these patterns. In the angiosperms, studies of diversification in floral form, stamen organization, reproductive biology, photosynthetic pathway, nitrogen-fixing symbioses and life histories have relied on either explicit or implied phylogenetic trees. Furthermore, to understand the evolution of specific genes and gene families, evaluate the extent of conservation of plant genomes and make proper sense of the huge volume of molecular genetic data available for model organisms such as Arabidopsis, Antirrhinum, maize, rice and wheat, a phylogenetic perspective is necessary. Here we report the results of parsimony analyses of DNA sequences of the plastid genes rbcL and atpB and the nuclear 18S rDNA for 560 species of angiosperms and seven non-flowering seed plants and show a well-resolved and well-supported phylogenetic tree for the angiosperms for use in comparative biology.

Chaos Versus Noisy Periodicity: Alternative Hypotheses for Childhood Epidemics

NASA Astrophysics Data System (ADS)

Olsen, L. F.; Schaffer, W. M.

1990-08-01

Whereas case rates for some childhood diseases (chickenpox) often vary according to an almost regular annual cycle, the incidence of more efficiently transmitted infections such as measles is more variable. Three hypotheses have been proposed to account for such fluctuations. (i) Irregular dynamics result from random shocks to systems with stable equilibria. (ii) The intrinsic dynamics correspond to biennial cycles that are subject to stochastic forcing. (iii) Aperiodic fluctuations are intrinsic to the epidemiology. Comparison of real world data and epidemiological models suggests that measles epidemics are inherently chaotic. Conversely, the extent to which chickenpox outbreaks approximate a yearly cycle depends inversely on the population size.

Drug Use Disorder (DUD) Questionnaire: Scale Development and Validation

ERIC Educational Resources Information Center

Scherer, Michael; Furr-Holden, C. Debra; Voas, Robert B.

2013-01-01

Background: Despite the ample interest in the measurement of substance abuse and dependence, obtaining biological samples from participants as a means to validate a scale is considered time and cost intensive and is, subsequently, largely overlooked. Objectives: To report the psychometric properties of the drug use disorder (DUD) questionnaire…

The Importance of Intertrophic Interactions in Biological Weed Control

USDA-ARS?s Scientific Manuscript database

The earliest research leading to successful weed biocontrol included observations and some analysis that the strict “gate-keeping” by peer reviewers, editors and publishers does not often allow today. Within these pioneering studies was a valid picture of the biology of weed biocontrol that is appli...

The Internalized Homophobia Scale for Vietnamese Sexual Minority Women (IHVN-W): Conceptualization, factor structure, reliability, and associations with hypothesized correlates

PubMed Central

Nguyen, Trang Quynh; Poteat, Tonia; Bandeen-Roche, Karen; German, Danielle; Nguyen, Yen Hai; Vu, Loan Kieu-Chau; Nguyen, Nam Thi-Thu; Knowlton, Amy R.

2016-01-01

We developed the first Vietnamese internalized homophobia (IH) scale, for use with Vietnamese sexual minority women (SMW). Drawing from existing IH scales in the international literature and based on prior qualitative research about SMW in the Viet Nam context, the scale covers two domains: self-stigma (negative attitudes toward oneself as a sexual minority person) and sexual prejudice (negative attitudes toward homosexuality/same-sex relations in general). Scale items, including items borrowed from existing scales and items based on local expressions, were reviewed and confirmed by members of the target population. Quantitative evaluation used data from an anonymous web-based survey of Vietnamese SMW, including those who identified as lesbian (n=1187), or as bisexual (n=641) and those who were unsure about their sexual identity (n=353). The scale was found to consist of two highly correlated factors reflecting self-stigma (not normal/wholesome and self-reproach and wishing away same-sex sexuality) and one factor reflecting sexual prejudice, and to have excellent internal consistency. Construct validity was evidenced by subscales’ associations with a wide range of hypothesized correlates including perceived sexual stigma, outness, social support, connection to other SMW, relationship quality, psychological well-being, anticipation of heterosexual marriage and endorsement of same-sex marriage legalization. Self-stigma was more strongly associated with psychosocial correlates and sexual prejudice was more associated with endorsement of legal same-sex marriage. The variations in these associations across the hypothesized correlates and across sexual identity groups were consistent with the Minority Stress Model and the IH literature, and exhibited context-specific features, which are discussed. PMID:27007469

Bullying Victimization and Adolescent Self-Harm: Testing Hypotheses from General Strain Theory

ERIC Educational Resources Information Center

Hay, Carter; Meldrum, Ryan

2010-01-01

Self-harm is widely recognized as a significant adolescent social problem, and recent research has begun to explore its etiology. Drawing from Agnew's (1992) social psychological strain theory of deviance, this study considers this issue by testing three hypotheses about the effects of traditional and cyber bullying victimization on deliberate…

The Origins of Children's Career Aspirations: IV. Testing Hypotheses from Four Theories.

ERIC Educational Resources Information Center

Trice, Ashton D.; And Others

1995-01-01

A study of elementary students (n=949) revealed some support for each of the hypotheses of Ginzberg, Roe, and Havinghurst. Results indicate that interests play the major role in both the selection and rejection of careers throughout childhood, that family configuration influenced occupational choice/no choice, and that identification with a…

Towards human-computer synergetic analysis of large-scale biological data.

PubMed

Singh, Rahul; Yang, Hui; Dalziel, Ben; Asarnow, Daniel; Murad, William; Foote, David; Gormley, Matthew; Stillman, Jonathan; Fisher, Susan

2013-01-01

Advances in technology have led to the generation of massive amounts of complex and multifarious biological data in areas ranging from genomics to structural biology. The volume and complexity of such data leads to significant challenges in terms of its analysis, especially when one seeks to generate hypotheses or explore the underlying biological processes. At the state-of-the-art, the application of automated algorithms followed by perusal and analysis of the results by an expert continues to be the predominant paradigm for analyzing biological data. This paradigm works well in many problem domains. However, it also is limiting, since domain experts are forced to apply their instincts and expertise such as contextual reasoning, hypothesis formulation, and exploratory analysis after the algorithm has produced its results. In many areas where the organization and interaction of the biological processes is poorly understood and exploratory analysis is crucial, what is needed is to integrate domain expertise during the data analysis process and use it to drive the analysis itself. In context of the aforementioned background, the results presented in this paper describe advancements along two methodological directions. First, given the context of biological data, we utilize and extend a design approach called experiential computing from multimedia information system design. This paradigm combines information visualization and human-computer interaction with algorithms for exploratory analysis of large-scale and complex data. In the proposed approach, emphasis is laid on: (1) allowing users to directly visualize, interact, experience, and explore the data through interoperable visualization-based and algorithmic components, (2) supporting unified query and presentation spaces to facilitate experimentation and exploration, (3) providing external contextual information by assimilating relevant supplementary data, and (4) encouraging user-directed information

Towards human-computer synergetic analysis of large-scale biological data

PubMed Central

2013-01-01

Background Advances in technology have led to the generation of massive amounts of complex and multifarious biological data in areas ranging from genomics to structural biology. The volume and complexity of such data leads to significant challenges in terms of its analysis, especially when one seeks to generate hypotheses or explore the underlying biological processes. At the state-of-the-art, the application of automated algorithms followed by perusal and analysis of the results by an expert continues to be the predominant paradigm for analyzing biological data. This paradigm works well in many problem domains. However, it also is limiting, since domain experts are forced to apply their instincts and expertise such as contextual reasoning, hypothesis formulation, and exploratory analysis after the algorithm has produced its results. In many areas where the organization and interaction of the biological processes is poorly understood and exploratory analysis is crucial, what is needed is to integrate domain expertise during the data analysis process and use it to drive the analysis itself. Results In context of the aforementioned background, the results presented in this paper describe advancements along two methodological directions. First, given the context of biological data, we utilize and extend a design approach called experiential computing from multimedia information system design. This paradigm combines information visualization and human-computer interaction with algorithms for exploratory analysis of large-scale and complex data. In the proposed approach, emphasis is laid on: (1) allowing users to directly visualize, interact, experience, and explore the data through interoperable visualization-based and algorithmic components, (2) supporting unified query and presentation spaces to facilitate experimentation and exploration, (3) providing external contextual information by assimilating relevant supplementary data, and (4) encouraging user

CAM Modalities Can Stimulate Advances in Theoretical Biology

PubMed Central

2005-01-01

Most complementary medicine is distinguished by not being supported by underlying theory accepted by Western science. However, for those who accept their validity, complementary and alternative medicine (CAM) modalities offer clues to understanding physiology and medicine more deeply. Ayurveda and vibrational medicine are stimulating new approaches to biological regulation. The new biophysics can be integrated to yield a single consistent theory, which may well underly much of CAM—a true ‘physics of physick’. The resulting theory seems to be a new, fundamental theory of health and etiology. It suggests that many CAM approaches to health care are scientifically in advance of those based on current Western biology. Such theories may well constitute the next steps in our scientific understanding of biology itself. If successfully developed, these ideas could result in a major paradigm shift in both biology and medicine, which will benefit all interested parties—consumers, health professionals, scientists, institutions and governments. PMID:15841271

The bogus taste test: Validity as a measure of laboratory food intake.

PubMed

Robinson, Eric; Haynes, Ashleigh; Hardman, Charlotte A; Kemps, Eva; Higgs, Suzanne; Jones, Andrew

2017-09-01

Because overconsumption of food contributes to ill health, understanding what affects how much people eat is of importance. The 'bogus' taste test is a measure widely used in eating behaviour research to identify factors that may have a causal effect on food intake. However, there has been no examination of the validity of the bogus taste test as a measure of food intake. We conducted a participant level analysis of 31 published laboratory studies that used the taste test to measure food intake. We assessed whether the taste test was sensitive to experimental manipulations hypothesized to increase or decrease food intake. We examined construct validity by testing whether participant sex, hunger and liking of taste test food were associated with the amount of food consumed in the taste test. In addition, we also examined whether BMI (body mass index), trait measures of dietary restraint and over-eating in response to palatable food cues were associated with food consumption. Results indicated that the taste test was sensitive to experimental manipulations hypothesized to increase or decrease food intake. Factors that were reliably associated with increased consumption during the taste test were being male, have a higher baseline hunger, liking of the taste test food and a greater tendency to overeat in response to palatable food cues, whereas trait dietary restraint and BMI were not. These results indicate that the bogus taste test is likely to be a valid measure of food intake and can be used to identify factors that have a causal effect on food intake. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Using computational fluid dynamics to test functional and ecological hypotheses in fossil taxa

NASA Astrophysics Data System (ADS)

Rahman, Imran

2016-04-01

Reconstructing how ancient organisms moved and fed is a major focus of study in palaeontology. Traditionally, this has been hampered by a lack of objective data on the functional morphology of extinct species, especially those without a clear modern analogue. However, cutting-edge techniques for characterizing specimens digitally and in three dimensions, coupled with state-of-the-art computer models, now provide a robust framework for testing functional and ecological hypotheses even in problematic fossil taxa. One such approach is computational fluid dynamics (CFD), a method for simulating fluid flows around objects that has primarily been applied to complex engineering-design problems. Here, I will present three case studies of CFD applied to fossil taxa, spanning a range of specimen sizes, taxonomic groups and geological ages. First, I will show how CFD enabled a rigorous test of hypothesized feeding modes in an enigmatic Ediacaran organism with three-fold symmetry, revealing previously unappreciated complexity of pre-Cambrian ecosystems. Second, I will show how CFD was used to evaluate hydrodynamic performance and feeding in Cambrian stem-group echinoderms, shedding light on the probable feeding strategy of the latest common ancestor of all deuterostomes. Third, I will show how CFD allowed us to explore the link between form and function in Mesozoic ichthyosaurs. These case studies serve to demonstrate the enormous potential of CFD for addressing long-standing hypotheses for a variety of fossil taxa, opening up an exciting new avenue in palaeontological studies of functional morphology.

Analysis procedures and subjective flight results of a simulator validation and cue fidelity experiment

NASA Technical Reports Server (NTRS)

Carr, Peter C.; Mckissick, Burnell T.

1988-01-01

A joint experiment to investigate simulator validation and cue fidelity was conducted by the Dryden Flight Research Facility of NASA Ames Research Center (Ames-Dryden) and NASA Langley Research Center. The primary objective was to validate the use of a closed-loop pilot-vehicle mathematical model as an analytical tool for optimizing the tradeoff between simulator fidelity requirements and simulator cost. The validation process includes comparing model predictions with simulation and flight test results to evaluate various hypotheses for differences in motion and visual cues and information transfer. A group of five pilots flew air-to-air tracking maneuvers in the Langley differential maneuvering simulator and visual motion simulator and in an F-14 aircraft at Ames-Dryden. The simulators used motion and visual cueing devices including a g-seat, a helmet loader, wide field-of-view horizon, and a motion base platform.

Ein Klassiker der Padagogik in Evolutionarer Perspektive: Eduard Sprangers "Lebensformen" im Lichte der Modernen Biologie (A Classic of Pedagogics from an Evolutionary Perspective: Edward Spranger's "Forms of Life" in the Light of Modern Biology).

ERIC Educational Resources Information Center

Neumann, Dieter

2002-01-01

Interprets Edward Spranger's "Forms of Life" against the background of the findings of modern biology. Shows how far Spranger's diagnosis of different human types, which are not affected by external influences on characteristics, conform with research hypotheses of modern biological sciences. (CAJ)

Validation of the Implementation Leadership Scale (ILS) in Substance Use Disorder Treatment Organizations

PubMed Central

Ehrhart, Mark G.; Torres, Elisa M.; Finn, Natalie K.; Roesch, Scott C.

2016-01-01

There have been recent calls for pragmatic measures to assess factors that influence evidence-based practice (EBP) implementation processes and outcomes. The Implementation Leadership Scale (ILS) is a brief and efficient measure that can be used for research or organizational development purposes to assess leader behaviors and actions that actively support effective EBP implementation. The ILS was developed and validated in mental health settings. This study validates the ILS factor structure with providers in alcohol and other drug (AOD) use treatment agencies. Participants were 323 service providers working in 72 workgroups from three AOD use treatment agencies. Confirmatory factor analyses and reliability analyses were conducted to examine the psychometric properties of the ILS. Convergent and discriminant validity were also assessed. Confirmatory factor analyses demonstrated good fit to the hypothesized first and second order factor structure. Internal consistency reliability was excellent. Convergent and discriminant validity was supported. The ILS psychometric characteristics, reliability, and validity were supported in AOD use treatment agencies. The ILS is a brief and pragmatic measure that can be used for research and practice to assess leadership for EBP implementation in AOD use treatment agencies. PMID:27431044

[Validity and reliability of the Culture of Quality Health Services questionnaire in Mexico].

PubMed

Herrera-Kiengelher, L; Zepeda-Zaragoza, J; Austria-Corrales, F; Vázquez-Zarate, V M

2013-01-01

Patient Safety is a major public health problem worldwide and is responsibility of all those involved in health care. Establishing a Safety Culture has proved to be a factor that favors the integration of work teams, communication and construction of clear procedures in various organizations. Promote a culture of safety depends on several factors, such as organization, work unit and staff. Objective assessment of these factors will help to identify areas for improvement and establish strategic lines of action. [corrected] To adapt, validate and calibrate the questionnaire Culture of Quality in Health Services (CQHS) in Mexican population. A cross with a stratified representative sample of 522 health workers. The questionnaire was translated and adapted from Singer's. Content was validated by experts, internal consistency, confirmatory factorial validity and item calibration with Samejima's Graded Response Model. Convergent and divergent construct validity was confirmed from the CQHS, item calibration showed that the questionnaire is able to discriminate between patients and represent different levels of the hypothesized dimensions with greater accuracy and lower standard error. The CQHS is a valid and reliable instrument to assess patient safety culture in hospitals in Mexico. Copyright © 2013 SECA. Published by Elsevier Espana. All rights reserved.

Validation of the Implementation Leadership Scale (ILS) in Substance use Disorder Treatment Organizations.

PubMed

Aarons, Gregory A; Ehrhart, Mark G; Torres, Elisa M; Finn, Natalie K; Roesch, Scott C

2016-09-01

There have been recent calls for pragmatic measures to assess factors that influence evidence-based practice (EBP) implementation processes and outcomes. The Implementation Leadership Scale (ILS) is a brief and efficient measure that can be used for research or organizational development purposes to assess leader behaviors and actions that actively support effective EBP implementation. The ILS was developed and validated in mental health settings. This study validates the ILS factor structure with providers in alcohol and other drug (AOD) use treatment agencies. Participants were 323 service providers working in 72 workgroups from three AOD use treatment agencies. Confirmatory factor analyses and reliability analyses were conducted to examine the psychometric properties of the ILS. Convergent and discriminant validity were also assessed. Confirmatory factor analyses demonstrated good fit to the hypothesized first and second order factor structure. Internal consistency reliability was excellent. Convergent and discriminant validity was supported. The ILS psychometric characteristics, reliability, and validity were supported in AOD use treatment agencies. The ILS is a brief and pragmatic measure that can be used for research and practice to assess leadership for EBP implementation in AOD use treatment agencies. Copyright © 2016 Elsevier Inc. All rights reserved.

Descriptive analysis of the verbal behavior of a therapist: a known-group validity analysis of the putative behavioral functions involved in clinical interaction.

PubMed

Virues-Ortega, Javier; Montaño-Fidalgo, Montserrat; Froján-Parga, María Xesús; Calero-Elvira, Ana

2011-12-01

This study analyzes the interobserver agreement and hypothesis-based known-group validity of the Therapist's Verbal Behavior Category System (SISC-INTER). The SISC-INTER is a behavioral observation protocol comprised of a set of verbal categories representing putative behavioral functions of the in-session verbal behavior of a therapist (e.g., discriminative, reinforcing, punishing, and motivational operations). The complete therapeutic process of a clinical case of an individual with marital problems was recorded (10 sessions, 8 hours), and data were arranged in a temporal sequence using 10-min periods. Hypotheses based on the expected performance of the putative behavioral functions portrayed by the SISC-INTER codes across prevalent clinical activities (i.e., assessing, explaining, Socratic method, providing clinical guidance) were tested using autoregressive integrated moving average (ARIMA) models. Known-group validity analyses provided support to all hypotheses. The SISC-INTER may be a useful tool to describe therapist-client interaction in operant terms. The utility of reliable and valid protocols for the descriptive analysis of clinical practice in terms of verbal behavior is discussed. Copyright © 2011. Published by Elsevier Ltd.

Prototype Biology-Based Radiation Risk Module Project

NASA Technical Reports Server (NTRS)

Terrier, Douglas; Clayton, Ronald G.; Patel, Zarana; Hu, Shaowen; Huff, Janice

2015-01-01

Biological effects of space radiation and risk mitigation are strategic knowledge gaps for the Evolvable Mars Campaign. The current epidemiology-based NASA Space Cancer Risk (NSCR) model contains large uncertainties (HAT #6.5a) due to lack of information on the radiobiology of galactic cosmic rays (GCR) and lack of human data. The use of experimental models that most accurately replicate the response of human tissues is critical for precision in risk projections. Our proposed study will compare DNA damage, histological, and cell kinetic parameters after irradiation in normal 2D human cells versus 3D tissue models, and it will use a multi-scale computational model (CHASTE) to investigate various biological processes that may contribute to carcinogenesis, including radiation-induced cellular signaling pathways. This cross-disciplinary work, with biological validation of an evolvable mathematical computational model, will help reduce uncertainties within NSCR and aid risk mitigation for radiation-induced carcinogenesis.

The planetary biology of cytochrome P450 aromatases.

PubMed

Gaucher, Eric A; Graddy, Logan G; Li, Tang; Simmen, Rosalia C M; Simmen, Frank A; Schreiber, David R; Liberles, David A; Janis, Christine M; Benner, Steven A

2004-08-17

Joining a model for the molecular evolution of a protein family to the paleontological and geological records (geobiology), and then to the chemical structures of substrates, products, and protein folds, is emerging as a broad strategy for generating hypotheses concerning function in a post-genomic world. This strategy expands systems biology to a planetary context, necessary for a notion of fitness to underlie (as it must) any discussion of function within a biomolecular system. Here, we report an example of such an expansion, where tools from planetary biology were used to analyze three genes from the pig Sus scrofa that encode cytochrome P450 aromatases-enzymes that convert androgens into estrogens. The evolutionary history of the vertebrate aromatase gene family was reconstructed. Transition redundant exchange silent substitution metrics were used to interpolate dates for the divergence of family members, the paleontological record was consulted to identify changes in physiology that correlated in time with the change in molecular behavior, and new aromatase sequences from peccary were obtained. Metrics that detect changing function in proteins were then applied, including KA/KS values and those that exploit structural biology. These identified specific amino acid replacements that were associated with changing substrate and product specificity during the time of presumed adaptive change. The combined analysis suggests that aromatase paralogs arose in pigs as a result of selection for Suoidea with larger litters than their ancestors, and permitted the Suoidea to survive the global climatic trauma that began in the Eocene. This combination of bioinformatics analysis, molecular evolution, paleontology, cladistics, global climatology, structural biology, and organic chemistry serves as a paradigm in planetary biology. As the geological, paleontological, and genomic records improve, this approach should become widely useful to make systems biology statements about

The planetary biology of cytochrome P450 aromatases

PubMed Central

Gaucher, Eric A; Graddy, Logan G; Li, Tang; Simmen, Rosalia CM; Simmen, Frank A; Schreiber, David R; Liberles, David A; Janis, Christine M; Benner, Steven A

2004-01-01

Background Joining a model for the molecular evolution of a protein family to the paleontological and geological records (geobiology), and then to the chemical structures of substrates, products, and protein folds, is emerging as a broad strategy for generating hypotheses concerning function in a post-genomic world. This strategy expands systems biology to a planetary context, necessary for a notion of fitness to underlie (as it must) any discussion of function within a biomolecular system. Results Here, we report an example of such an expansion, where tools from planetary biology were used to analyze three genes from the pig Sus scrofa that encode cytochrome P450 aromatases–enzymes that convert androgens into estrogens. The evolutionary history of the vertebrate aromatase gene family was reconstructed. Transition redundant exchange silent substitution metrics were used to interpolate dates for the divergence of family members, the paleontological record was consulted to identify changes in physiology that correlated in time with the change in molecular behavior, and new aromatase sequences from peccary were obtained. Metrics that detect changing function in proteins were then applied, including KA/KS values and those that exploit structural biology. These identified specific amino acid replacements that were associated with changing substrate and product specificity during the time of presumed adaptive change. The combined analysis suggests that aromatase paralogs arose in pigs as a result of selection for Suoidea with larger litters than their ancestors, and permitted the Suoidea to survive the global climatic trauma that began in the Eocene. Conclusions This combination of bioinformatics analysis, molecular evolution, paleontology, cladistics, global climatology, structural biology, and organic chemistry serves as a paradigm in planetary biology. As the geological, paleontological, and genomic records improve, this approach should become widely useful to make

Educational Transitions in Israel: A Test of the Industrialization and Credentialism Hypotheses.

ERIC Educational Resources Information Center

Shavit, Yossi; Kraus, Vered

1990-01-01

Explores the industrialization and credentialism hypotheses and predictions of educational attainment levels. Finds the effects of the father's education and occupation were stable for those attending school in the 1940s, 1950s, and 1960s. Notes that the effects of ethnicity declined in the transition from primary to secondary school. (NL)

Biological Control Outcomes Using the Generalist Aphid Predator Aphidoletes aphidimyza under Multi-Prey Conditions.

PubMed

Jandricic, Sarah E; Wraight, Stephen P; Gillespie, Dave R; Sanderson, John P

2016-12-14

The aphidophagous midge Aphidoletes aphidimyza (Diptera: Cecidomyiidae) is used in biological control programs against aphids in many crops. Short-term trials with this natural enemy demonstrated that that females prefer to oviposit among aphids colonizing the new growth of plants, leading to differential attack rates for aphid species that differ in their within-plant distributions. Thus, we hypothesized that biological control efficacy could be compromised when more than one aphid species is present. We further hypothesized that control outcomes may be different at different crop stages if aphid species shift their preferred feeding locations. Here, we used greenhouse trials to determine biological control outcomes using A. aphidimyza under multi-prey conditions and at different crop stages. At all plant stages, aphid species had a significant effect on the number of predator eggs laid. More eggs were found on M. persicae versus A. solani -infested plants, since M. persicae consistently colonized plant meristems across plant growth stages. This translated to higher numbers of predatory larvae on M. periscae -infested plants in two out of our three experiments, and more consistent control of this pest (78%-95% control across all stages of plant growth). In contrast, control of A. solani was inconsistent in the presence of M. persicae , with 36%-80% control achieved. An additional experiment demonstrated control of A. solani by A. aphidimyza was significantly greater in the absence of M. persicae than in its presence. Our study illustrates that suitability of a natural enemy for pest control may change over a crop cycle as the position of prey on the plant changes, and that prey preference based on within-plant prey location can negatively influence biological control programs in systems with pest complexes. Careful monitoring of the less-preferred pest and its relative position on the plant is suggested.

EDITORIAL: MEMS in biology and medicine MEMS in biology and medicine

NASA Astrophysics Data System (ADS)

Pruitt, Beth L.; Herr, Amy E.

2011-05-01

this generation of MEMS researchers encapsulate the mission of JMM to 'cover all aspects of microelectromechanical systems, devices and structures as well as micromechanics, microengineering and microfabrication' as the physics and chemical processes under study match the scales of the MEMS technologies now possible. As evidenced by the articles assembled in this issue, the combined maturation of both our biological model systems and our tools is driving a new paradigm in the formulation of biological hypotheses. The intersection of MEMS with cell biology is evidenced in reviews of both methods for applying microscale forces in biological environments by Zheng and Zhang [9] as well as the manipulation of biology through mechanical interactions by Rajagopalan and Saif [10]. Additionally, the potential for microfluidic platforms to miniaturize and improve for a diverse set of biological measurements and assays for medical diagnostics is further reviewed by Tentori and Herr [11]. We hope that you find, as we do, this special issue to be 'essential reading for all MEMS researchers' and perhaps even of technical interest to your life sciences colleagues. References [1] Yetisen A K et al 2011 J. Micromech. Microeng. 21 054018 [2] Morimoto Y et al 2011 J. Micromech. Microeng. 21 054031 [3] Inglis D W et al 2011 J. Micromech. Microeng. 21 054024 [4] Meyer M T et al 2011 J. Micromech. Microeng. 21 054023 [5] Cheung L S-L et al 2011 J. Micromech. Microeng. 21 054033 [6] Lee S A et al 2011 J. Micromech. Microeng. 21 054006 [7] Hess A E et al 2011 J. Micromech. Microeng. 21 054009 [8] Chu J et al 2011 J. Micromech. Microeng. 21 054030 [9] Zheng X R and Zhang X 2011 J. Micromech. Microeng. 21 054003 [10] Rajagopalan J and Saif M T A 2011 J. Micromech. Microeng. 21 054002 [11] Tentori A M and Herr A E 2011 J. Micromech. Microeng. 21 054001

Construct and Predictive Validity of the Core Phonics Survey: A Diagnostic Assessment for Students with Specific Learning Disabilities

ERIC Educational Resources Information Center

Park, Yujeong; Benedict, Amber E.; Brownell, Mary T.

2014-01-01

The factor structure of the CORE Phonics Survey was analyzed using a sample of 165 students in upper elementary school with specific learning disabilities. Confirmatory factor analysis was used to identify the hypothesized constructs of the CORE Phonics Survey and predictive validity of the CORE Phonics Survey to predict students' success in word…

Energy utilization in fluctuating biological energy converters

PubMed Central

Szőke, Abraham; Hajdu, Janos

2016-01-01

We have argued previously [Szoke et al., FEBS Lett. 553, 18–20 (2003); Curr. Chem. Biol. 1, 53–57 (2007)] that energy utilization and evolution are emergent properties based on a small number of established laws of physics and chemistry. The relevant laws constitute a framework for biology on a level intermediate between quantum chemistry and cell biology. There are legitimate questions whether these concepts are valid at the mesoscopic level. Such systems fluctuate appreciably, so it is not clear what their efficiency is. Advances in fluctuation theorems allow the description of such systems on a molecular level. We attempt to clarify this topic and bridge the biochemical and physical descriptions of mesoscopic systems. PMID:27191009

Involvement of MicroRNAs in Lung Cancer Biology and Therapy

PubMed Central

Liu, Xi; Sempere, Lorenzo F.; Guo, Yongli; Korc, Murray; Kauppinen, Sakari; Freemantle, Sarah J.; Dmitrovsky, Ethan

2011-01-01

MicroRNAs (miRNAs) are a class of small RNAs that regulate gene expression. Expression profiles of specific miRNAs have improved cancer diagnosis and classification and even provided prognostic information in many human cancers, including lung cancer. Tumor suppressive and oncogenic miRNAs were uncovered in lung carcinogenesis. The biological functions of these miRNAs in lung cancer were recently validated in well characterized cellular, murine transgenic as well as transplantable lung cancer models and in human paired normal-malignant lung tissue banks and tissue arrays. Tumor suppressive and oncogenic miRNAs that were identified in lung cancer will be reviewed here. Emphasis is placed on highlighting those functionally validated miRNAs that are not only biomarkers of lung carcinogenesis, but also candidate pharmacologic targets. How these miRNA findings advance an understanding of lung cancer biology and could improve lung cancer therapy are discussed in this article. PMID:21420030

Biology: Discipline Analysis. Women in the Curriculum Series.

ERIC Educational Resources Information Center

Spanier, Bonnie

This essay examines the ways in which biology, as a discipline, has been influenced by feminist scholarship and research into the areas of gender and sexuality, focusing on the validity, limits, and gender bias of scientific objectivity. It explains that gender bias exists not only in who traditionally has been expected to do science (namely white…

The Dutch language anterior cruciate ligament return to sport after injury scale (ACL-RSI) - validity and reliability.

PubMed

Slagers, Anton J; Reininga, Inge H F; van den Akker-Scheek, Inge

2017-02-01

The ACL-Return to Sport after Injury scale (ACL-RSI) measures athletes' emotions, confidence in performance, and risk appraisal in relation to return to sport after ACL reconstruction. Aim of this study was to study the validity and reliability of the Dutch version of the ACL-RSI (ACL-RSI (NL)). Total 150 patients, who were 3-16 months postoperative, completed the ACL-RSI(NL) and 5 other questionnaires regarding psychological readiness to return to sports, knee-specific physical functioning, kinesiophobia, and health-specific locus of control. Construct validity of the ACL-RSI(NL) was determined with factor analysis and by exploring 10 hypotheses regarding correlations between ACL-RSI(NL) and the other questionnaires. For test-retest reliability, 107 patients (5-16 months postoperative) completed the ACL-RSI(NL) again 2 weeks after the first administration. Cronbach's alpha, Intraclass Correlation Coefficient (ICC), SEM, and SDC, were calculated. Bland-Altman analysis was conducted to assess bias between test and retest. Nine hypotheses (90%) were confirmed, indicating good construct validity. The ACL-RSI(NL) showed good internal consistency (Cronbach's alpha 0.94) and test-retest reliability (ICC 0.93). SEM was 5.5 and SDC was 15. A significant bias of 3.2 points between test and retest was found. Therefore, the ACL-RSI(NL) can be used to investigate psychological factors relevant to returning to sport after ACL reconstruction.

Reference Proteome Extracts for Mass Spec Instrument Performance Validation and Method Development

PubMed Central

Rosenblatt, Mike; Urh, Marjeta; Saveliev, Sergei

2014-01-01

Biological samples of high complexity are required to test protein mass spec sample preparation procedures and validate mass spec instrument performance. Total cell protein extracts provide the needed sample complexity. However, to be compatible with mass spec applications, such extracts should meet a number of design requirements: compatibility with LC/MS (free of detergents, etc.)high protein integrity (minimal level of protein degradation and non-biological PTMs)compatibility with common sample preparation methods such as proteolysis, PTM enrichment and mass-tag labelingLot-to-lot reproducibility Here we describe total protein extracts from yeast and human cells that meet the above criteria. Two extract formats have been developed: Intact protein extracts with primary use for sample preparation method development and optimizationPre-digested extracts (peptides) with primary use for instrument validation and performance monitoring

The EvoDevoCI: A Concept Inventory for Gauging Students’ Understanding of Evolutionary Developmental Biology

PubMed Central

Perez, Kathryn E.; Hiatt, Anna; Davis, Gregory K.; Trujillo, Caleb; French, Donald P.; Terry, Mark; Price, Rebecca M.

2013-01-01

The American Association for the Advancement of Science 2011 report Vision and Change in Undergraduate Biology Education encourages the teaching of developmental biology as an important part of teaching evolution. Recently, however, we found that biology majors often lack the developmental knowledge needed to understand evolutionary developmental biology, or “evo-devo.” To assist in efforts to improve evo-devo instruction among undergraduate biology majors, we designed a concept inventory (CI) for evolutionary developmental biology, the EvoDevoCI. The CI measures student understanding of six core evo-devo concepts using four scenarios and 11 multiple-choice items, all inspired by authentic scientific examples. Distracters were designed to represent the common conceptual difficulties students have with each evo-devo concept. The tool was validated by experts and administered at four institutions to 1191 students during preliminary (n = 652) and final (n = 539) field trials. We used student responses to evaluate the readability, difficulty, discriminability, validity, and reliability of the EvoDevoCI, which included items ranging in difficulty from 0.22–0.55 and in discriminability from 0.19–0.38. Such measures suggest the EvoDevoCI is an effective tool for assessing student understanding of evo-devo concepts and the prevalence of associated common conceptual difficulties among both novice and advanced undergraduate biology majors. PMID:24297293

Development and validation of the simulation-based learning evaluation scale.

PubMed

Hung, Chang-Chiao; Liu, Hsiu-Chen; Lin, Chun-Chih; Lee, Bih-O

2016-05-01

The instruments that evaluate a student's perception of receiving simulated training are English versions and have not been tested for reliability or validity. The aim of this study was to develop and validate a Chinese version Simulation-Based Learning Evaluation Scale (SBLES). Four stages were conducted to develop and validate the SBLES. First, specific desired competencies were identified according to the National League for Nursing and Taiwan Nursing Accreditation Council core competencies. Next, the initial item pool was comprised of 50 items related to simulation that were drawn from the literature of core competencies. Content validity was established by use of an expert panel. Finally, exploratory factor analysis and confirmatory factor analysis were conducted for construct validity, and Cronbach's coefficient alpha determined the scale's internal consistency reliability. Two hundred and fifty students who had experienced simulation-based learning were invited to participate in this study. Two hundred and twenty-five students completed and returned questionnaires (response rate=90%). Six items were deleted from the initial item pool and one was added after an expert panel review. Exploratory factor analysis with varimax rotation revealed 37 items remaining in five factors which accounted for 67% of the variance. The construct validity of SBLES was substantiated in a confirmatory factor analysis that revealed a good fit of the hypothesized factor structure. The findings tally with the criterion of convergent and discriminant validity. The range of internal consistency for five subscales was .90 to .93. Items were rated on a 5-point scale from 1 (strongly disagree) to 5 (strongly agree). The results of this study indicate that the SBLES is valid and reliable. The authors recommend that the scale could be applied in the nursing school to evaluate the effectiveness of simulation-based learning curricula. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cross-cultural adaptation and validation of the Korean version of the EQ-5D in patients with rheumatic diseases.

PubMed

Kim, Myoung-Hee; Cho, Young-Shin; Uhm, Wan-Sik; Kim, Sehyun; Bae, Sang-Cheol

2005-06-01

This study aimed to determine the cross-cultural adaptation and validation of the Korean version of the EQ-5D in rheumatic conditions. Translation, back-translation and cognitive debriefing were performed according to the EuroQol group's guidelines. For validity, 508 patients were recruited and administered the EQ-5D, Short-Form 36 and condition-specific measures. Construct validity and sensitivity were evaluated by testing a-priori hypotheses. For reliability, another 57 patients repeated the EQ-5D at 1-week interval, and intra-class correlations (ICC) and kappa statistics were estimated. For responsiveness, another 60 patients repeated it at 12-week interval within the context of clinical trial, and standardized response mean(SRM) were calculated. The cross-cultural adaptation produced no major modifications in the scale. The associations of the EQ-5D with the generic- and condition-specific measures were observed as expected in hypotheses: the higher EQ-5Dindex and EQ-5D(VAS) scores, the better health status by generic- or condition-specific measures, and the better functional class. The ICCs were 0.751 and 0.767, respectively, and kappa ranged from 0.455 to 0.772. The SRM were 0.649 and 0.410, respectively. The Korean EQ-5D exhibits good validity and sensitivity in various rheumatic conditions. Although its reliability and responsiveness were not excellent, it seems acceptable if condition-specific measures are applied together.

Chemical Biology Probes from Advanced DNA-encoded Libraries.

PubMed

Salamon, Hazem; Klika Škopić, Mateja; Jung, Kathrin; Bugain, Olivia; Brunschweiger, Andreas

2016-02-19

The identification of bioactive compounds is a crucial step toward development of probes for chemical biology studies. Screening of DNA-encoded small molecule libraries (DELs) has emerged as a validated technology to interrogate vast chemical space. DELs consist of chimeric molecules composed of a low-molecular weight compound that is conjugated to a DNA identifier tag. They are screened as pooled libraries using selection to identify "hits." Screening of DELs has identified numerous bioactive compounds. Some of these molecules were instrumental in gaining a deeper understanding of biological systems. One of the main challenges in the field is the development of synthesis methodology for DELs.

Unified Deep Learning Architecture for Modeling Biology Sequence.

PubMed

Wu, Hongjie; Cao, Chengyuan; Xia, Xiaoyan; Lu, Qiang

2017-10-09

Prediction of the spatial structure or function of biological macromolecules based on their sequence remains an important challenge in bioinformatics. When modeling biological sequences using traditional sequencing models, characteristics, such as long-range interactions between basic units, the complicated and variable output of labeled structures, and the variable length of biological sequences, usually lead to different solutions on a case-by-case basis. This study proposed the use of bidirectional recurrent neural networks based on long short-term memory or a gated recurrent unit to capture long-range interactions by designing the optional reshape operator to adapt to the diversity of the output labels and implementing a training algorithm to support the training of sequence models capable of processing variable-length sequences. Additionally, the merge and pooling operators enhanced the ability to capture short-range interactions between basic units of biological sequences. The proposed deep-learning model and its training algorithm might be capable of solving currently known biological sequence-modeling problems through the use of a unified framework. We validated our model on one of the most difficult biological sequence-modeling problems currently known, with our results indicating the ability of the model to obtain predictions of protein residue interactions that exceeded the accuracy of current popular approaches by 10% based on multiple benchmarks.

A standardised protocol for the validation of banking methodologies for arterial allografts.

PubMed

Lomas, R J; Dodd, P D F; Rooney, P; Pegg, D E; Hogg, P A; Eagle, M E; Bennett, K E; Clarkson, A; Kearney, J N

2013-09-01

The objective of this study was to design and test a protocol for the validation of banking methodologies for arterial allografts. A series of in vitro biomechanical and biological assessments were derived, and applied to paired fresh and banked femoral arteries. The ultimate tensile stress and strain, suture pullout stress and strain, expansion/rupture under hydrostatic pressure, histological structure and biocompatibility properties of disinfected and cryopreserved femoral arteries were compared to those of fresh controls. No significant differences were detected in any of the test criteria. This validation protocol provides an effective means of testing and validating banking protocols for arterial allografts.

Williams Syndrome Hypersociability: A Neuropsychological Study of the Amygdala and Prefrontal Cortex Hypotheses

ERIC Educational Resources Information Center

Capitao, Liliana; Sampaio, Adriana; Fernandez, Montse; Sousa, Nuno; Pinheiro, Ana; Goncalves, Oscar F.

2011-01-01

Individuals with Williams syndrome display indiscriminate approach towards strangers. Neuroimaging studies conducted so far have linked this social profile to structural and/or functional abnormalities in WS amygdala and prefrontal cortex. In this study, the neuropsychological hypotheses of amygdala and prefrontal cortex involvement in WS…

Why Consumers Choose Managed Mutual Funds over Index Funds: Hypotheses from Consumer Behavior.

ERIC Educational Resources Information Center

Lichtenstein, Donald R.; Kaufmann, Patrick J.; Bhagat, Sanjai

1999-01-01

Using the literature of psychology, consumer behavior, and behavioral finance, a series of hypotheses is presented that account for consumer choices of managed over index mutual funds. Results indicate a need for consumer education to increase awareness of the benefits of index investing. (SK)

A critical review of biologic mesh use in ventral hernia repairs under contaminated conditions.

PubMed

Primus, F E; Harris, H W

2013-02-01

We used an evidence-based approach to determine whether the promotions and claims of superiority of biologic mesh over synthetic mesh use in ventral hernia repairs (VHRs) under contaminated conditions were sound and valid. We searched the Medline database to specifically identify review articles relating to biologic mesh and VHR and critically reviewed these studies using an evidence-based approach. For the past 45 years, four clinical reviews and one systematic review have included biologic meshes as part of a larger discussion on available prosthetics for VHR. All reviews supported biologic mesh use, especially in the setting of contaminated fields. Yet, the primary literature included in these reviews and served as the basis for these conclusions consisted entirely of case series and case reports, which have the lowest level of evidence in determining scientific validity. Furthermore, the FDA has neither cleared nor approved this particular use. The cumulative data regarding biologic mesh use in VHRs under contaminated conditions does not support the claim that it is better than synthetic mesh used under the same conditions. The highly promoted and at least moderately utilized practice of placing biologic mesh in contamination is being done outside of the original intended use, and a re-evaluation of or possible moratorium on biologic mesh use in hernia surgery is seriously warranted. Alternatively, an industry-sponsored national registry of patients in whom ventral hernia repairs involved biologic mesh would substantively add to our understanding regarding how these intriguing biomaterials are being used and their overall clinical efficacy.

Using climate, energy, and spatial-based hypotheses to interpret macroecological patterns of North America chelonians

USGS Publications Warehouse

Ennen, Joshua R.; Agha, Mickey; Matamoros, Wilfredo A.; Hazzard, Sarah C.; Lovich, Jeffrey E.

2016-01-01

Our study investigates how factors, such as latitude, productivity, and several environmental variables, influence contemporary patterns of the species richness in North American turtles. In particular, we test several hypotheses explaining broad-scale species richness patterns on several species richness data sets: (i) total turtles, (ii) freshwater turtles only, (iii) aquatic turtles, (iv) terrestrial turtles only, (v) Emydidae, and (vi) Kinosternidae. In addition to spatial data, we used a combination of 25 abiotic variables in spatial regression models to predict species richness patterns. Our results provide support for multiple hypotheses related to broad-scale patterns of species richness, and in particular, hypotheses related to climate, productivity, water availability, topography, and latitude. In general, species richness patterns were positively associated with temperature, precipitation, diversity of streams, coefficient of variation of elevation, and net primary productivity. We also found that North America turtles follow the general latitudinal diversity gradient pattern (i.e., increasing species richness towards equator) by exhibiting a negative association with latitude. Because of the incongruent results among our six data sets, our study highlights the importance of considering phylogenetic constraints and guilds when interpreting species richness patterns, especially for taxonomic groups that occupy a myriad of habitats.

Cultural group selection is plausible, but the predictions of its hypotheses should be tested with real-world data.

PubMed

Turchin, Peter; Currie, Thomas E

2016-01-01

The evidence compiled in the target article demonstrates that the assumptions of cultural group selection (CGS) theory are often met, and it is therefore a useful framework for generating plausible hypotheses. However, more can be said about how we can test the predictions of CGS hypotheses against competing explanations using historical, archaeological, and anthropological data.

Biodegradation of phytosanitary products in biological wastewater treatment.

PubMed

Massot, A; Estève, K; Noilet, P; Méoule, C; Poupot, C; Mietton-Peuchot, M

2012-04-15

Agricultural activity generates two types of waste: firstly, biodegradable organic effluents generally treated by biological processes and, secondly, phytosanitary effluents which contain residues of plant protection products. The latter are collected and treated. Current technological solutions are essentially based on concentration or physical-chemical processes. However, recent improvements in the biodegradability of pesticides open the way to the consideration of alternative, biological, treatment using mixed liquor from wastewater plant activated sludge. The feasibility of the biological treatment of viticultural effluents has been evaluated by the application of pesticides to activated sludge. The necessity for selection of a pesticide-resistant biomass has been highlighted. The elimination of the phytosanitary products shows the potential of a resistant biomass in the treatment of pesticides. The aerated biological storage ponds at three wineries, followed by a sand or reed-bed filter, were used for the treatment of the total annual volume of the viticulture effluents and validate the laboratory experiments. The results show that the biological purification of pesticides by activated sludge is possible by allowing approximately 8 days for biomass adaptation. Stability of purification occurs between 20 and 30 days. Copyright © 2012 Elsevier Ltd. All rights reserved.

Node fingerprinting: an efficient heuristic for aligning biological networks.

PubMed

Radu, Alex; Charleston, Michael

2014-10-01

With the continuing increase in availability of biological data and improvements to biological models, biological network analysis has become a promising area of research. An emerging technique for the analysis of biological networks is through network alignment. Network alignment has been used to calculate genetic distance, similarities between regulatory structures, and the effect of external forces on gene expression, and to depict conditional activity of expression modules in cancer. Network alignment is algorithmically complex, and therefore we must rely on heuristics, ideally as efficient and accurate as possible. The majority of current techniques for network alignment rely on precomputed information, such as with protein sequence alignment, or on tunable network alignment parameters, which may introduce an increased computational overhead. Our presented algorithm, which we call Node Fingerprinting (NF), is appropriate for performing global pairwise network alignment without precomputation or tuning, can be fully parallelized, and is able to quickly compute an accurate alignment between two biological networks. It has performed as well as or better than existing algorithms on biological and simulated data, and with fewer computational resources. The algorithmic validation performed demonstrates the low computational resource requirements of NF.

Development of the Biological Experimental Design Concept Inventory (BEDCI)

ERIC Educational Resources Information Center

Deane, Thomas; Nomme, Kathy; Jeffery, Erica; Pollock, Carol; Birol, Gulnur

2014-01-01

Interest in student conception of experimentation inspired the development of a fully validated 14-question inventory on experimental design in biology (BEDCI) by following established best practices in concept inventory (CI) design. This CI can be used to diagnose specific examples of non-expert-like thinking in students and to evaluate the…

Hypotheses generation as supervised link discovery with automated class labeling on large-scale biomedical concept networks

PubMed Central

2012-01-01

Computational approaches to generate hypotheses from biomedical literature have been studied intensively in recent years. Nevertheless, it still remains a challenge to automatically discover novel, cross-silo biomedical hypotheses from large-scale literature repositories. In order to address this challenge, we first model a biomedical literature repository as a comprehensive network of biomedical concepts and formulate hypotheses generation as a process of link discovery on the concept network. We extract the relevant information from the biomedical literature corpus and generate a concept network and concept-author map on a cluster using Map-Reduce frame-work. We extract a set of heterogeneous features such as random walk based features, neighborhood features and common author features. The potential number of links to consider for the possibility of link discovery is large in our concept network and to address the scalability problem, the features from a concept network are extracted using a cluster with Map-Reduce framework. We further model link discovery as a classification problem carried out on a training data set automatically extracted from two network snapshots taken in two consecutive time duration. A set of heterogeneous features, which cover both topological and semantic features derived from the concept network, have been studied with respect to their impacts on the accuracy of the proposed supervised link discovery process. A case study of hypotheses generation based on the proposed method has been presented in the paper. PMID:22759614

The use of biological grafts for reconstruction of the inferior vena cava is a safe and valid alternative: results in 32 patients in a single institution

PubMed Central

Pulitanó, Carlo; Crawford, Michael; Ho, Phong; Gallagher, James; Joseph, David; Stephen, Michael; Sandroussi, Charbel

2013-01-01

Background Resection and reconstruction of the inferior vena cava (IVC) is occasionally required in the surgical treatment of intra-abdominal tumours. IVC reconstruction can be performed with biological or synthetic graft material, with most centres preferring synthetic grafts. In spite of the potential advantages of biological grafts in terms of handling characteristics, and safety, very limited data are available about their use in patients requiring an IVC resection. Methods Medical records of 32 patients who underwent an IVC resection and reconstruction from 1990 and 2011 with autogenous peritoneo-fascial (N = 22) and bovine pericardial (N = 10) grafts were reviewed. Results A tangential resection with patch repair was performed in 10 patients, whereas in the remaining 22 it was necessary to resect and replace a segment or all of the retrohepatic IVC. A concomitant liver resection was performed in 14 patients, nephrectomy in 10 and pancreaticoduodenectomy in 2 patients. There were no acute or late complications related to graft thrombosis or infection. Three patients died as a consequence of multi-organ failure. Overall survival at 1 and 5 years was 78% and 48%, respectively. Conclusions The preferential use of synthetic grafts in IVC replacement is not evidence based. Selection of an appropriate prosthetic graft for IVC reconstruction should be based on the safety and its handling features. The use of biological grafts for IVC repair is a valid alternative to current synthetic materials and may in fact be superior in terms of biocompatability, ease of handling, reduced rate of infection and improved long-term patency without permanent anticoagulation. PMID:23458108

The use of biological grafts for reconstruction of the inferior vena cava is a safe and valid alternative: results in 32 patients in a single institution.

PubMed

Pulitanó, Carlo; Crawford, Michael; Ho, Phong; Gallagher, James; Joseph, David; Stephen, Michael; Sandroussi, Charbel

2013-08-01

Resection and reconstruction of the inferior vena cava (IVC) is occasionally required in the surgical treatment of intra-abdominal tumours. IVC reconstruction can be performed with biological or synthetic graft material, with most centres preferring synthetic grafts. In spite of the potential advantages of biological grafts in terms of handling characteristics, and safety, very limited data are available about their use in patients requiring an IVC resection. Medical records of 32 patients who underwent an IVC resection and reconstruction from 1990 and 2011 with autogenous peritoneo-fascial (N = 22) and bovine pericardial (N = 10) grafts were reviewed. A tangential resection with patch repair was performed in 10 patients, whereas in the remaining 22 it was necessary to resect and replace a segment or all of the retrohepatic IVC. A concomitant liver resection was performed in 14 patients, nephrectomy in 10 and pancreaticoduodenectomy in 2 patients. There were no acute or late complications related to graft thrombosis or infection. Three patients died as a consequence of multi-organ failure. Overall survival at 1 and 5 years was 78% and 48%, respectively. The preferential use of synthetic grafts in IVC replacement is not evidence based. Selection of an appropriate prosthetic graft for IVC reconstruction should be based on the safety and its handling features. The use of biological grafts for IVC repair is a valid alternative to current synthetic materials and may in fact be superior in terms of biocompatability, ease of handling, reduced rate of infection and improved long-term patency without permanent anticoagulation. © 2013 International Hepato-Pancreato-Biliary Association.

Cancer Systems Biology: a peak into the future of patient care?

PubMed Central

Werner, Henrica M. J.; Mills, Gordon B.; Ram, Prahlad T.

2015-01-01

Traditionally, scientific research has focused on studying individual events, such as single mutations, gene function or the effect of the manipulation of one protein on a biological phenotype. A range of technologies, combined with the ability to develop robust and predictive mathematical models, is beginning to provide information that will enable a holistic view of how the genomic and epigenetic aberrations in cancer cells can alter the homeostasis of signalling networks within these cells, between cancer cells and the local microenvironment, at the organ and organism level. This systems biology process needs to be integrated with an iterative approach wherein hypotheses and predictions that arise from modelling are refined and constrained by experimental evaluation. Systems biology approaches will be vital for developing and implementing effective strategies to deliver personalized cancer therapy. Specifically, these approaches will be important to select those patients most likely to benefit from targeted therapies as well as for the development and implementation of rational combinatorial therapies. Systems biology can help to increase therapy efficacy or bypass the emergence of resistance, thus converting the current (often short term) effects of targeted therapies into durable responses, ultimately to improve quality of life and provide a cure. PMID:24492837

Biomedical Research Experiences for Biology Majors at a Small College

ERIC Educational Resources Information Center

Stover, Shawn K.; Mabry, Michelle L.

2010-01-01

A program-level assessment of the biology curriculum at a small liberal arts college validates a previous study demonstrating success in achieving learning outcomes related to content knowledge and communication skills. Furthermore, research opportunities have been provided to complement pedagogical strategies and give students a more complete…

Teaching Trajectories and Students' Understanding of Difficult Concepts in Biology in Obio/Akpor Local Government Area in Rivers State

ERIC Educational Resources Information Center

Mumuni, Abosede Anthonia Olufemi; Dike, John Worlu; Uzoma-Nwogu, Azibaolanari

2017-01-01

This study investigated the effects of teaching trajectories on students' understanding of difficult concepts in Biology. Two research questions and two null hypotheses guided the study which was carried out in Obio/Akpor Local Government Area of Rivers State. Two public coeducational schools out of thirteen drawn through purposive sampling…

Phylogenetic Reconstruction as a Broadly Applicable Teaching Tool in the Biology Classroom: The Value of Data in Estimating Likely Answers

ERIC Educational Resources Information Center

Julius, Matthew L.; Schoenfuss, Heiko L.

2006-01-01

This laboratory exercise introduces students to a fundamental tool in evolutionary biology--phylogenetic inference. Students are required to create a data set via observation and through mining preexisting data sets. These student data sets are then used to develop and compare competing hypotheses of vertebrate phylogeny. The exercise uses readily…

Coping with the Stigma of Mental Illness: Empirically-Grounded Hypotheses from Computer Simulations

ERIC Educational Resources Information Center

Kroska, Amy; Har, Sarah K.

2011-01-01

This research demonstrates how affect control theory and its computer program, "Interact", can be used to develop empirically-grounded hypotheses regarding the connection between cultural labels and behaviors. Our demonstration focuses on propositions in the modified labeling theory of mental illness. According to the MLT, negative societal…

Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers

PubMed Central

Tang, Fei; Hartz, Anika M. S.; Bauer, Björn

2017-01-01

Epilepsy is a common neurological disorder that affects over 70 million people worldwide. Despite the recent introduction of new antiseizure drugs (ASDs), about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early identification of patients who will become refractory to ASDs could help direct such patients to appropriate non-pharmacological treatment, but the complexity in the temporal patterns of epilepsy could make such identification difficult. The target hypothesis and transporter hypothesis are the most cited theories trying to explain refractory epilepsy, but neither theory alone fully explains the neurobiological basis of pharmacoresistance. This review summarizes evidence for and against several major theories, including the pharmacokinetic hypothesis, neural network hypothesis, intrinsic severity hypothesis, gene variant hypothesis, target hypothesis, and transporter hypothesis. The discussion is mainly focused on the transporter hypothesis, where clinical and experimental data are discussed on multidrug transporter overexpression, substrate profiles of ASDs, mechanism of transporter upregulation, polymorphisms of transporters, and the use of transporter inhibitors. Finally, future perspectives are presented for the improvement of current hypotheses and the development of treatment strategies as guided by the current understanding of refractory epilepsy. PMID:28729850

Parental self-efficacy in childhood overweight: validation of the Lifestyle Behavior Checklist in the Netherlands.

PubMed

Gerards, Sanne M P L; Hummel, Karin; Dagnelie, Pieter C; de Vries, Nanne K; Kremers, Stef P J

2013-01-18

Evaluating whether parental challenges and self-efficacy toward managing children's lifestyle behaviors are successfully addressed by interventions requires valid instruments. The Lifestyle Behavior Checklist (LBC) has recently been developed in the Australian context. It consists of two subscales: the Problem scale, which measures parental perceptions of children's behavioral problems related to overweight and obesity, and the Confidence scale, measuring parental self-efficacy in dealing with these problems. The aim of the current study was to systematically translate the questionnaire into Dutch and to evaluate its internal consistency, construct validity and test-retest reliability. The LBC was systematically translated by four experts at Maastricht University. In total, 392 parents of 3-to13-year-old children were invited to fill out two successive online questionnaires with a two-week interval. Of these, 273 parents responded to the first questionnaire (test, response rate = 69.6%), and of the 202 who could be invited for the second questionnaire (retest), 100 responded (response rate = 49.5%). We assessed the questionnaire's internal consistency (Cronbach's α), construct validity (Spearman's Rho correlation tests, using the criterion measures: restrictiveness, nurturance, and psychological control), and test-retest reliability (Spearman's Rho correlation tests). Both scales had high internal consistency (Cronbach's α ≥ 0.90). Spearman correlation coefficients indicated acceptable test-retest reliability for both the Problem scale (rs = 0.74) and the Confidence scale (rs = 0.70). The LBC Problem scale was significantly correlated to all criterion scales (nurturance, restrictiveness, psychological control) in the hypothesized direction, and the LBC Confidence scale was significantly correlated with nurturance and psychological control in the hypothesized direction, but not with restrictiveness. The Dutch translation of the LBC was found to be a reliable and

From themes to hypotheses: following up with quantitative methods.

PubMed

Morgan, David L

2015-06-01

One important category of mixed-methods research designs consists of quantitative studies that follow up on qualitative research. In this case, the themes that serve as the results from the qualitative methods generate hypotheses for testing through the quantitative methods. That process requires operationalization to translate the concepts from the qualitative themes into quantitative variables. This article illustrates these procedures with examples that range from simple operationalization to the evaluation of complex models. It concludes with an argument for not only following up qualitative work with quantitative studies but also the reverse, and doing so by going beyond integrating methods within single projects to include broader mutual attention from qualitative and quantitative researchers who work in the same field. © The Author(s) 2015.

Subtyping attention-deficit/hyperactivity disorder using temperament dimensions: toward biologically based nosologic criteria.

PubMed

Karalunas, Sarah L; Fair, Damien; Musser, Erica D; Aykes, Kamari; Iyer, Swathi P; Nigg, Joel T

2014-09-01

Psychiatric nosology is limited by behavioral and biological heterogeneity within existing disorder categories. The imprecise nature of current nosologic distinctions limits both mechanistic understanding and clinical prediction. We demonstrate an approach consistent with the National Institute of Mental Health Research Domain Criteria initiative to identify superior, neurobiologically valid subgroups with better predictive capacity than existing psychiatric categories for childhood attention-deficit/hyperactivity disorder (ADHD). To refine subtyping of childhood ADHD by using biologically based behavioral dimensions (i.e., temperament), novel classification algorithms, and multiple external validators. A total of 437 clinically well-characterized, community-recruited children, with and without ADHD, participated in an ongoing longitudinal study. Baseline data were used to classify children into subgroups based on temperament dimensions and examine external validators including physiological and magnetic resonance imaging measures. One-year longitudinal follow-up data are reported for a subgroup of the ADHD sample to address stability and clinical prediction. Parent/guardian ratings of children on a measure of temperament were used as input features in novel community detection analyses to identify subgroups within the sample. Groups were validated using 3 widely accepted external validators: peripheral physiological characteristics (cardiac measures of respiratory sinus arrhythmia and pre-ejection period), central nervous system functioning (via resting-state functional connectivity magnetic resonance imaging), and clinical outcomes (at 1-year longitudinal follow-up). The community detection algorithm suggested 3 novel types of ADHD, labeled as mild (normative emotion regulation), surgent (extreme levels of positive approach-motivation), and irritable (extreme levels of negative emotionality, anger, and poor soothability). Types were independent of existing

Detecting biological responses to flow management: Missed opportunities; future directions

USGS Publications Warehouse

Souchon, Y.; Sabaton, C.; Deibel, R.; Reiser, D.; Kershner, J.; Gard, M.; Katopodis, C.; Leonard, P.; Poff, N.L.; Miller, W.J.; Lamb, B.L.

2008-01-01

The conclusions of numerous stream restoration assessments all around the world are extremely clear and convergent: there has been insufficient appropriate monitoring to improve general knowledge and expertise. In the specialized field of instream flow alterations, we consider that there are several opportunities comparable to full-size experiments. Hundreds of water management decisions related to instream flow releases have been made by government agencies, native peoples, and non-governmental organizations around the world. These decisions are based on different methods and assumptions and many flow regimes have been adopted by formal or informal rules and regulations. Although, there have been significant advances in analytical capabilities, there has been very little validation monitoring of actual outcomes or research related to the response of aquatic dependent species to new flow regimes. In order to be able to detect these kinds of responses and to better guide decision, a general design template is proposed. The main steps of this template are described and discussed, in terms of objectives, hypotheses, variables, time scale, data management, and information, in the spirit of adaptive management. The adoption of such a framework is not always easy, due to differing interests of actors for the results, regarding the duration of monitoring, nature of funding and differential timetables between facilities managers and technicians. Nevertheless, implementation of such a framework could help researchers and practitioners to coordinate and federate their efforts to improve the general knowledge of the links between the habitat dynamics and biological aquatic responses. Copyright ?? 2008 John Wiley & Sons, Ltd.

Systems biology by the rules: hybrid intelligent systems for pathway modeling and discovery.

PubMed

Bosl, William J

2007-02-15

Expert knowledge in journal articles is an important source of data for reconstructing biological pathways and creating new hypotheses. An important need for medical research is to integrate this data with high throughput sources to build useful models that span several scales. Researchers traditionally use mental models of pathways to integrate information and development new hypotheses. Unfortunately, the amount of information is often overwhelming and these are inadequate for predicting the dynamic response of complex pathways. Hierarchical computational models that allow exploration of semi-quantitative dynamics are useful systems biology tools for theoreticians, experimentalists and clinicians and may provide a means for cross-communication. A novel approach for biological pathway modeling based on hybrid intelligent systems or soft computing technologies is presented here. Intelligent hybrid systems, which refers to several related computing methods such as fuzzy logic, neural nets, genetic algorithms, and statistical analysis, has become ubiquitous in engineering applications for complex control system modeling and design. Biological pathways may be considered to be complex control systems, which medicine tries to manipulate to achieve desired results. Thus, hybrid intelligent systems may provide a useful tool for modeling biological system dynamics and computational exploration of new drug targets. A new modeling approach based on these methods is presented in the context of hedgehog regulation of the cell cycle in granule cells. Code and input files can be found at the Bionet website: www.chip.ord/~wbosl/Software/Bionet. This paper presents the algorithmic methods needed for modeling complicated biochemical dynamics using rule-based models to represent expert knowledge in the context of cell cycle regulation and tumor growth. A notable feature of this modeling approach is that it allows biologists to build complex models from their knowledge base without

Delinquency and Peer Acceptance in Adolescence: A Within-Person Test of Moffitt's Hypotheses

ERIC Educational Resources Information Center

Rulison, Kelly L.; Kreager, Derek A.; Osgood, D. Wayne

2014-01-01

We tested 2 hypotheses derived from Moffitt's (1993) taxonomic theory of antisocial behavior, both of which are central to her explanation for the rise in delinquency during adolescence. We tested whether persistently delinquent individuals become more accepted by their peers during adolescence and whether individuals who abstain from delinquent…

[Physical activity patterns of school adolescents: Validity, reliability and percentiles proposal for their evaluation].

PubMed

Cossío Bolaños, Marco; Méndez Cornejo, Jorge; Luarte Rocha, Cristian; Vargas Vitoria, Rodrigo; Canqui Flores, Bernabé; Gomez Campos, Rossana

2017-02-01

Regular physical activity (PA) during childhood and adolescence is important for the prevention of non-communicable diseases and their risk factors. To validate a questionnaire for measuring patterns of PA, verify the reliability, comparing the levels of PA aligned with chronological and biological age, and to develop percentile curves to assess PA levels depending on biological maturation. Descriptive cross-sectional study was performed on a sample non-probabilistic quota of 3,176 Chilean adolescents (1685 males and 1491 females), with a mean age range from 10.0 to 18.9 years. An analysis was performed on, weight, standing and sitting height. The biological age through the years of peak growth rate and chronological age in years was determined. Body Mass Index was calculated and a survey of PA was applied. The LMS method was used to develop percentiles. The values for the confirmatory analysis showed saturations between 0.517 and 0.653. The value of adequacy of Kaiser-Meyer-Olkin (KMO) was 0.879 and with 70.8% of the variance explained. The Cronbach alpha values ranged from 0.81 to 0.86. There were differences between the genders when aligned chronological age. There were no differences when aligned by biological age. Percentiles are proposed to classify the PA of adolescents of both genders according to biological age and sex. The questionnaire used was valid and reliable, plus the PA should be evaluated by biological age. These findings led to the development of percentiles to assess PA according to biological age and gender.

Disrupting the brain to validate hypotheses on the neurobiology of language

PubMed Central

Papeo, Liuba; Pascual-Leone, Alvaro; Caramazza, Alfonso

2013-01-01

Comprehension of words is an important part of the language faculty, involving the joint activity of frontal and temporo-parietal brain regions. Transcranial Magnetic Stimulation (TMS) enables the controlled perturbation of brain activity, and thus offers a unique tool to test specific predictions about the causal relationship between brain regions and language understanding. This potential has been exploited to better define the role of regions that are classically accepted as part of the language-semantic network. For instance, TMS has contributed to establish the semantic relevance of the left anterior temporal lobe, or to solve the ambiguity between the semantic vs. phonological function assigned to the left inferior frontal gyrus (LIFG). We consider, more closely, the results from studies where the same technique, similar paradigms (lexical-semantic tasks) and materials (words) have been used to assess the relevance of regions outside the classically-defined language-semantic network—i.e., precentral motor regions—for the semantic analysis of words. This research shows that different aspects of the left precentral gyrus (primary motor and premotor sites) are sensitive to the action-non action distinction of words' meanings. However, the behavioral changes due to TMS over these sites are incongruent with what is expected after perturbation of a task-relevant brain region. Thus, the relationship between motor activity and language-semantic behavior remains far from clear. A better understanding of this issue could be guaranteed by investigating functional interactions between motor sites and semantically-relevant regions. PMID:23630480

All biology is computational biology.

PubMed

Markowetz, Florian

2017-03-01

Here, I argue that computational thinking and techniques are so central to the quest of understanding life that today all biology is computational biology. Computational biology brings order into our understanding of life, it makes biological concepts rigorous and testable, and it provides a reference map that holds together individual insights. The next modern synthesis in biology will be driven by mathematical, statistical, and computational methods being absorbed into mainstream biological training, turning biology into a quantitative science.

Pharmacological tests of hypotheses for acquired pendular nystagmus.

PubMed

Shaikh, Aasef G; Thurtell, Matthew J; Optican, Lance M; Leigh, R John

2011-09-01

Acquired pendular nystagmus (APN) occurs with multiple sclerosis (MS) and oculopalatal tremor (OPT); distinct features of the nystagmus have led to the development of separate models for their pathogenesis. APN in MS has been attributed to instability in the neural integrator, which normally ensures steady gaze. APN in OPT may result from electrotonic coupling between neurons in the hypertrophied inferior olivary nucleus, which induces maladaptive learning in cerebellar cortex. We tested these two hypotheses by analyzing the effects of gabapentin, memantine, and baclofen on both forms of nystagmus. No drug changed the dominant frequency of either form of APN, but the variability of frequency was affected with gabapentin and memantine in patients with OPT. The amplitude of APN in both MS and OPT was reduced with gabapentin and memantine, but not baclofen. Analyzing the effects of drug therapies on ocular oscillations provides a novel approach to test models of nystagmus. © 2011 New York Academy of Sciences.

Pharmacological tests of hypotheses for acquired pendular nystagmus

PubMed Central

Shaikh, Aasef G.; Thurtell, Matthew J.; Optican, Lance M.; Leigh, R. John

2011-01-01

Acquired pendular nystagmus (APN) occurs with multiple sclerosis (MS) and oculopalatal tremor (OPT); distinct features of the nystagmus have led to the development of separate models for the pathogenesis. APN in MS has been attributed to instability in the neural integrator, which normally ensures steady gaze. APN in OPT may result from electrotonic coupling between neurons in the hypertrophied inferior olivary nucleus, which induces maladaptive learning in cerebellar cortex. We tested these two hypotheses by analyzing the effects of gabapentin, memantine, and baclofen on both forms of nystagmus. No drug changed the dominant frequency of either form of APN, but the variability of frequency was affected with gabapentin and memantine in patients with OPT. The amplitude of APN in both MS and OPT was reduced with gabapentin and memantine, but not baclofen. Analyzing the effects of drug therapies on ocular oscillations provides a novel approach to test models of nystagmus. PMID:21951011

The Biological Activities of Oleocanthal from a Molecular Perspective

PubMed Central

Pang, Kok-Lun; Chin, Kok-Yong

2018-01-01

Oleocanthal is a minor constituent of olive oil with strong anti-inflammatory activities. Since the pathogenesis of many chronic diseases involves inflammatory and oxidative components, oleocanthal is a promising agent to prevent these conditions. This review aimed to summarise the current beneficial health effects of oleocanthal and the molecular basis of its biological actions. The anti-inflammatory, antioxidative, antimicrobial, anticancer and neuroprotective activities of oleocanthal have been examined by previous studies. Of these, studies on the anticancer effects have been the most extensive. Oleocanthal was reported to suppress melanoma, breast, liver, and colon cancer cells. Neurological studies focused on the effects of oleocanthal against Alzheimer’s disease. Oleocanthal improved clearance of the amyloid beta protein from neurons and reduced the inflammation of astrocytes. Despite the positive results, validation of the biological effects of oleocanthal in animal disease models is limited and should be emphasized in the future. As a conclusion, oleocanthal may act together with other bioactive compounds in olive oil to achieve its therapeutic potential. The use of oleocanthal alone as a single therapeutic measure awaits validation from future studies. PMID:29734791

The Biological Activities of Oleocanthal from a Molecular Perspective.

PubMed

Pang, Kok-Lun; Chin, Kok-Yong

2018-05-06

Oleocanthal is a minor constituent of olive oil with strong anti-inflammatory activities. Since the pathogenesis of many chronic diseases involves inflammatory and oxidative components, oleocanthal is a promising agent to prevent these conditions. This review aimed to summarise the current beneficial health effects of oleocanthal and the molecular basis of its biological actions. The anti-inflammatory, antioxidative, antimicrobial, anticancer and neuroprotective activities of oleocanthal have been examined by previous studies. Of these, studies on the anticancer effects have been the most extensive. Oleocanthal was reported to suppress melanoma, breast, liver, and colon cancer cells. Neurological studies focused on the effects of oleocanthal against Alzheimer’s disease. Oleocanthal improved clearance of the amyloid beta protein from neurons and reduced the inflammation of astrocytes. Despite the positive results, validation of the biological effects of oleocanthal in animal disease models is limited and should be emphasized in the future. As a conclusion, oleocanthal may act together with other bioactive compounds in olive oil to achieve its therapeutic potential. The use of oleocanthal alone as a single therapeutic measure awaits validation from future studies.

Do US Black Women Experience Stress-Related Accelerated Biological Aging?

PubMed Central

Hicken, Margaret T.; Pearson, Jay A.; Seashols, Sarah J.; Brown, Kelly L.; Cruz, Tracey Dawson

2010-01-01

We hypothesize that black women experience accelerated biological aging in response to repeated or prolonged adaptation to subjective and objective stressors. Drawing on stress physiology and ethnographic, social science, and public health literature, we lay out the rationale for this hypothesis. We also perform a first population-based test of its plausibility, focusing on telomere length, a biomeasure of aging that may be shortened by stressors. Analyzing data from the Study of Women's Health Across the Nation (SWAN), we estimate that at ages 49–55, black women are 7.5 years biologically “older” than white women. Indicators of perceived stress and poverty account for 27% of this difference. Data limitations preclude assessing objective stressors and also result in imprecise estimates, limiting our ability to draw firm inferences. Further investigation of black-white differences in telomere length using large-population-based samples of broad age range and with detailed measures of environmental stressors is merited. PMID:20436780

Impact of Non-Suicidal Self-Injury Scale: Initial Psychometric Validation

PubMed Central

Burke, Taylor A.; Ammerman, Brooke A.; Hamilton, Jessica L.; Alloy, Lauren B.

2017-01-01

The current study examined the psychometric properties of the Impact of Non-Suicidal Self-Injury Scale (INS), a scale developed to assess the social, behavioral, and emotional consequences of engaging in non-suicidal self-injury (NSSI). University students (N=128) who endorsed a history of NSSI were administered the INS, as well as measures of hypothesized convergent and divergent validity. Results suggested that the INS is best conceptualized as a one-factor scale, and internal consistency analyses indicated excellent reliability. The INS was significantly correlated with well-known measures of NSSI severity (i.e., NSSI frequency, NSSI recency), and measures of suicide attempt history and emotional reactivity. Logistic regression analyses indicated that the INS contributed unique variance to the prediction of physical disfigurement (i.e., NSSI scarring) and clinically significant social anxiety, even after taking into account NSSI frequency. Furthermore, the INS demonstrated divergent validity. Implications for research on NSSI disorder and clinical practice are discussed. PMID:28824214

How Does Biological Belief in Race Relate to Our Feelings towards In-Group and Out-Groups?: A Cognitive Dissonance Framework

ERIC Educational Resources Information Center

Tawa, John; Kim, Grace S.

2011-01-01

This study considered the effect of belief in race as a biological construct (RACEBIO) and inter-group anxiety (IGA) on in-group racial salience (IGRS) and out-group discomfort (OGD). Participants included 66 racially and ethnically diverse high school boarding students. As hypothesized, RACEBIO was positively related to both IGRS and OGD. In…

Adapting Social Neuroscience Measures for Schizophrenia Clinical Trials, Part 3: Fathoming External Validity

PubMed Central

Olbert, Charles M.

2013-01-01

It is unknown whether measures adapted from social neuroscience linked to specific neural systems will demonstrate relationships to external variables. Four paradigms adapted from social neuroscience were administered to 173 clinically stable outpatients with schizophrenia to determine their relationships to functionally meaningful variables and to investigate their incremental validity beyond standard measures of social and nonsocial cognition. The 4 paradigms included 2 that assess perception of nonverbal social and action cues (basic biological motion and emotion in biological motion) and 2 that involve higher level inferences about self and others’ mental states (self- referential memory and empathic accuracy). Overall, social neuroscience paradigms showed significant relationships to functional capacity but weak relationships to community functioning; the paradigms also showed weak correlations to clinical symptoms. Evidence for incremental validity beyond standard measures of social and nonsocial cognition was mixed with additional predictive power shown for functional capacity but not community functioning. Of the newly adapted paradigms, the empathic accuracy task had the broadest external validity. These results underscore the difficulty of translating developments from neuroscience into clinically useful tasks with functional significance. PMID:24072806

Adapting social neuroscience measures for schizophrenia clinical trials, part 3: fathoming external validity.

PubMed

Olbert, Charles M; Penn, David L; Kern, Robert S; Lee, Junghee; Horan, William P; Reise, Steven P; Ochsner, Kevin N; Marder, Stephen R; Green, Michael F

2013-11-01

It is unknown whether measures adapted from social neuroscience linked to specific neural systems will demonstrate relationships to external variables. Four paradigms adapted from social neuroscience were administered to 173 clinically stable outpatients with schizophrenia to determine their relationships to functionally meaningful variables and to investigate their incremental validity beyond standard measures of social and nonsocial cognition. The 4 paradigms included 2 that assess perception of nonverbal social and action cues (basic biological motion and emotion in biological motion) and 2 that involve higher level inferences about self and others' mental states (self-referential memory and empathic accuracy). Overall, social neuroscience paradigms showed significant relationships to functional capacity but weak relationships to community functioning; the paradigms also showed weak correlations to clinical symptoms. Evidence for incremental validity beyond standard measures of social and nonsocial cognition was mixed with additional predictive power shown for functional capacity but not community functioning. Of the newly adapted paradigms, the empathic accuracy task had the broadest external validity. These results underscore the difficulty of translating developments from neuroscience into clinically useful tasks with functional significance.

Worldwide Protein Data Bank biocuration supporting open access to high-quality 3D structural biology data

PubMed Central

Westbrook, John D; Feng, Zukang; Persikova, Irina; Sala, Raul; Sen, Sanchayita; Berrisford, John M; Swaminathan, G Jawahar; Oldfield, Thomas J; Gutmanas, Aleksandras; Igarashi, Reiko; Armstrong, David R; Baskaran, Kumaran; Chen, Li; Chen, Minyu; Clark, Alice R; Di Costanzo, Luigi; Dimitropoulos, Dimitris; Gao, Guanghua; Ghosh, Sutapa; Gore, Swanand; Guranovic, Vladimir; Hendrickx, Pieter M S; Hudson, Brian P; Ikegawa, Yasuyo; Kengaku, Yumiko; Lawson, Catherine L; Liang, Yuhe; Mak, Lora; Mukhopadhyay, Abhik; Narayanan, Buvaneswari; Nishiyama, Kayoko; Patwardhan, Ardan; Sahni, Gaurav; Sanz-García, Eduardo; Sato, Junko; Sekharan, Monica R; Shao, Chenghua; Smart, Oliver S; Tan, Lihua; van Ginkel, Glen; Yang, Huanwang; Zhuravleva, Marina A; Markley, John L; Nakamura, Haruki; Kurisu, Genji; Kleywegt, Gerard J; Velankar, Sameer; Berman, Helen M; Burley, Stephen K

2018-01-01

Abstract The Protein Data Bank (PDB) is the single global repository for experimentally determined 3D structures of biological macromolecules and their complexes with ligands. The worldwide PDB (wwPDB) is the international collaboration that manages the PDB archive according to the FAIR principles: Findability, Accessibility, Interoperability and Reusability. The wwPDB recently developed OneDep, a unified tool for deposition, validation and biocuration of structures of biological macromolecules. All data deposited to the PDB undergo critical review by wwPDB Biocurators. This article outlines the importance of biocuration for structural biology data deposited to the PDB and describes wwPDB biocuration processes and the role of expert Biocurators in sustaining a high-quality archive. Structural data submitted to the PDB are examined for self-consistency, standardized using controlled vocabularies, cross-referenced with other biological data resources and validated for scientific/technical accuracy. We illustrate how biocuration is integral to PDB data archiving, as it facilitates accurate, consistent and comprehensive representation of biological structure data, allowing efficient and effective usage by research scientists, educators, students and the curious public worldwide. Database URL: https://www.wwpdb.org/ PMID:29688351

Orchid biology: from Linnaeus via Darwin to the 21st century

PubMed Central

Fay, Michael F.; Chase, Mark W.

2009-01-01

Orchidaceae are the largest family of flowering plants, with at least 24 000 species, and perhaps better than any other family of flowering plants, orchids represent the extreme specializations that are possible. As a result, they have long fascinated luminaries of the botanical world including Linnaeus and Darwin, but the size of the family has historically been an impediment to their study. Specifically, the lack of detailed information about relationships within the family made it difficult to formulate explicit evolutionary hypotheses for such a large group, but the advent of molecular systematics has revolutionized our understanding of the orchids. Their complex life histories make orchids particularly vulnerable to environmental change, and as result many are now threatened with extinction. In this Special Issue we present a series of 20 papers on orchid biology ranging from phylogenetics, floral evolutionary development, taxonomy, mycorrhizal associations, pollination biology, population genetics and conservation. PMID:19654223

Reactions of copper macrocycles with antioxidants and HOCl: potential for biological redox sensing.

PubMed

Sowden, Rebecca J; Trotter, Katherine D; Dunbar, Lynsey; Craig, Gemma; Erdemli, Omer; Spickett, Corinne M; Reglinski, John

2013-02-01

A series of simple copper N(2)S(2) macrocycles were examined for their potential as biological redox sensors, following previous characterization of their redox potentials and crystal structures. The divalent species were reduced by glutathione or ascorbate at a biologically relevant pH in aqueous buffer. A less efficient reduction was also achieved by vitamin E in DMSO. Oxidation of the corresponding univalent copper species by sodium hypochlorite resulted in only partial (~65 %) recovery of the divalent form. This was concluded to be due to competition between metal oxidation and ligand oxidation, which is believed to contribute to macrocycle demetallation. Electrospray mass spectrometry confirmed that ligand oxidation had occurred. Moreover, the macrocyclic complexes could be demetallated by incubation with EDTA and bovine serum albumin, demonstrating that they would be inappropriate for use in biological systems. The susceptibility to oxidation and demetallation was hypothesized to be due to oxidation of the secondary amines. Consequently these were modified to incorporate additional oxygen donor atoms. This modification led to greater resistance to demetallation and ligand oxidation, providing a better platform for further development of copper macrocycles as redox sensors for use in biological systems.

Integrative biological analysis for neuropsychopharmacology.

PubMed

Emmett, Mark R; Kroes, Roger A; Moskal, Joseph R; Conrad, Charles A; Priebe, Waldemar; Laezza, Fernanda; Meyer-Baese, Anke; Nilsson, Carol L

2014-01-01

Although advances in psychotherapy have been made in recent years, drug discovery for brain diseases such as schizophrenia and mood disorders has stagnated. The need for new biomarkers and validated therapeutic targets in the field of neuropsychopharmacology is widely unmet. The brain is the most complex part of human anatomy from the standpoint of number and types of cells, their interconnections, and circuitry. To better meet patient needs, improved methods to approach brain studies by understanding functional networks that interact with the genome are being developed. The integrated biological approaches--proteomics, transcriptomics, metabolomics, and glycomics--have a strong record in several areas of biomedicine, including neurochemistry and neuro-oncology. Published applications of an integrated approach to projects of neurological, psychiatric, and pharmacological natures are still few but show promise to provide deep biological knowledge derived from cells, animal models, and clinical materials. Future studies that yield insights based on integrated analyses promise to deliver new therapeutic targets and biomarkers for personalized medicine.

Integrative Biological Analysis For Neuropsychopharmacology

PubMed Central

Emmett, Mark R; Kroes, Roger A; Moskal, Joseph R; Conrad, Charles A; Priebe, Waldemar; Laezza, Fernanda; Meyer-Baese, Anke; Nilsson, Carol L

2014-01-01

Although advances in psychotherapy have been made in recent years, drug discovery for brain diseases such as schizophrenia and mood disorders has stagnated. The need for new biomarkers and validated therapeutic targets in the field of neuropsychopharmacology is widely unmet. The brain is the most complex part of human anatomy from the standpoint of number and types of cells, their interconnections, and circuitry. To better meet patient needs, improved methods to approach brain studies by understanding functional networks that interact with the genome are being developed. The integrated biological approaches—proteomics, transcriptomics, metabolomics, and glycomics—have a strong record in several areas of biomedicine, including neurochemistry and neuro-oncology. Published applications of an integrated approach to projects of neurological, psychiatric, and pharmacological natures are still few but show promise to provide deep biological knowledge derived from cells, animal models, and clinical materials. Future studes that yield insights based on integrated analyses promise to deliver new therapeutic targets and biomarkers for personalized medicine. PMID:23800968

Validation and Application of the Survey of Teaching Beliefs and Practices for Undergraduates (STEP-U): Identifying Factors Associated with Valuing Important Workplace Skills among Biology Students

PubMed Central

Marbach-Ad, Gili; Rietschel, Carly; Thompson, Katerina V.

2016-01-01

We present a novel assessment tool for measuring biology students’ values and experiences across their undergraduate degree program. Our Survey of Teaching Beliefs and Practices for Undergraduates (STEP-U) assesses the extent to which students value skills needed for the workplace (e.g., ability to work in groups) and their experiences with teaching practices purported to promote such skills (e.g., group work). The survey was validated through factor analyses in a large sample of biology seniors (n = 1389) and through response process analyses (five interviewees). The STEP-U skills items were characterized by two underlying factors: retention (e.g., memorization) and transfer (e.g., knowledge application). Multiple linear regression models were used to examine relationships between classroom experiences, values, and student characteristics (e.g., gender, cumulative grade point average [GPA], and research experience). Student demographic and experiential factors predicted the extent to which students valued particular skills. Students with lower GPAs valued retention skills more than those with higher GPAs. Students with research experience placed greater value on scientific writing and interdisciplinary understanding. Greater experience with specific teaching practices was associated with valuing the corresponding skills more highly. The STEP-U can provide feedback vital for designing curricula that better prepare students for their intended postgraduate careers. PMID:27856547

Development and validation of the Family Motivational Climate Questionnaire (FMC-Q).

PubMed

Alonso Tapia, Jesús; Simón Rueda, Cecilia; Asensio Fuentes, César

2013-01-01

The goal of this study was to develop and validate the Family Motivational Climate Questionnaire (FMCQ). Parental involvement (PI) affects children's academic orientations. However, PI questionnaires had not considered parenting behaviours from the perspective of motivational theories. It was therefore decided to develop the FMCQ. 570 Secondary-School students formed the sample. To validate the FMCQ, confirmatory factor analyses, reliability analysis and correlation and regression analyses were conducted. Children's attribution to parents of perceived change in motivational variables affecting achievement, were used as external criteria. Results support most of the hypotheses either related to the FMCQ structure or to its moderating role as predictor of school achievement and of attribution to parents of changes in different motivational variables --interest, effort, perceived ability, success expectancies, resilience, and satisfaction. The results underline the importance of acting on FMC-components in order to improve Children's motivation and achievement.

Skin stem cell hypotheses and long term clone survival--explored using agent-based modelling.

PubMed

Li, X; Upadhyay, A K; Bullock, A J; Dicolandrea, T; Xu, J; Binder, R L; Robinson, M K; Finlay, D R; Mills, K J; Bascom, C C; Kelling, C K; Isfort, R J; Haycock, J W; MacNeil, S; Smallwood, R H

2013-01-01

Epithelial renewal in skin is achieved by the constant turnover and differentiation of keratinocytes. Three popular hypotheses have been proposed to explain basal keratinocyte regeneration and epidermal homeostasis: 1) asymmetric division (stem-transit amplifying cell); 2) populational asymmetry (progenitor cell with stochastic fate); and 3) populational asymmetry with stem cells. In this study, we investigated lineage dynamics using these hypotheses with a 3D agent-based model of the epidermis. The model simulated the growth and maintenance of the epidermis over three years. The offspring of each proliferative cell was traced. While all lineages were preserved in asymmetric division, the vast majority were lost when assuming populational asymmetry. The third hypothesis provided the most reliable mechanism for self-renewal by preserving genetic heterogeneity in quiescent stem cells, and also inherent mechanisms for skin ageing and the accumulation of genetic mutation.