Can temporal fine structure represent the fundamental frequency of unresolved harmonics?

PubMed

Oxenham, Andrew J; Micheyl, Christophe; Keebler, Michael V

2009-04-01

At least two modes of pitch perception exist: in one, the fundamental frequency (F0) of harmonic complex tones is estimated using the temporal fine structure (TFS) of individual low-order resolved harmonics; in the other, F0 is derived from the temporal envelope of high-order unresolved harmonics that interact in the auditory periphery. Pitch is typically more accurate in the former than in the latter mode. Another possibility is that pitch can sometimes be coded via the TFS from unresolved harmonics. A recent study supporting this third possibility [Moore et al. (2006a). J. Acoust. Soc. Am. 119, 480-490] based its conclusion on a condition where phase interaction effects (implying unresolved harmonics) accompanied accurate F0 discrimination (implying TFS processing). The present study tests whether these results were influenced by audible distortion products. Experiment 1 replicated the original results, obtained using a low-level background noise. However, experiments 2-4 found no evidence for the use of TFS cues with unresolved harmonics when the background noise level was raised, or the stimulus level was lowered, to render distortion inaudible. Experiment 5 measured the presence and phase dependence of audible distortion products. The results provide no evidence that TFS cues are used to code the F0 of unresolved harmonics.

A Structural Approach to Unresolved Mourning in Single Parent Family Systems.

ERIC Educational Resources Information Center

Fulmer, Richard H.

1983-01-01

Considers the mother's depression as a special problem in therapy of single-parent families, resulting from unresolved mourning maintained by the family system. Offers reasons why the single-parent family's structure seems inherently vulnerable to unresolved mourning. Suggests techniques of Structural Family Therapy to facilitate mourning in such…

Unresolved trauma in mothers: intergenerational effects and the role of reorganization

PubMed Central

Iyengar, Udita; Kim, Sohye; Martinez, Sheila; Fonagy, Peter; Strathearn, Lane

2014-01-01

A mother's unresolved trauma may interfere with her ability to sensitively respond to her infant, thus affecting the development of attachment in her own child, and potentially contributing to the intergenerational transmission of trauma. One novel construct within the Dynamic Maturational Model of Attachment and Adaptation (DMM) coding of the Adult Attachment Interview (AAI) is “reorganization,” a process whereby speakers are actively changing their understanding of past and present experiences and moving toward attachment security. We conducted a study of mothers with unresolved trauma, exploring their own attachment classification, attachment outcomes of their children, and the potential effects of reorganization on child attachment. Forty-seven first-time mothers participated in the AAI during pregnancy, and returned with their child at 11 months to assess child attachment using the Strange Situation Procedure. Mothers with and without unresolved trauma were compared. We found that mothers with unresolved trauma had insecure attachment themselves and were more likely to have infants with insecure attachment. However, the one exception was that all of the mothers with unresolved trauma who were reorganizing toward secure attachment had infants with secure attachment. These preliminary findings suggest that mothers who are reorganizing may be able to more sensitively respond to their child's cues, contributing to the development of secure attachment. While our results need to be replicated in a larger cohort, this study is the first to explore the construct of reorganization and its potential relationship with child attachment. If confirmed in future studies, it may provide clinical insight into the intergenerational transmission of insecure attachment within the context of unresolved trauma. PMID:25225490

Attachment stability and the emergence of unresolved representations during adolescence.

PubMed

Aikins, Julie Wargo; Howes, Carollee; Hamilton, Claire

2009-09-01

This 15-year longitudinal study examined the stability of attachment representations from infancy to adolescence and investigated the emergence of unresolved representations during adolescence in a sample of 47 16-year-olds. Attachment was assessed at 12 months using the Strange Situation Procedure, at 4 years using the modified Strange Situation Procedure, and again at 16 years with the Adult Attachment Projective (AAP). The emergence of unresolved classifications in adolescence (AAP) was associated with higher rates of negative life events, low levels of early mother-child relationship security (an aggregate measure of the 12-month and 4-year measures), negative teacher-child relationship experiences in middle childhood, and low early adolescent friendship quality. The results support the growing body of evidence suggesting that changes in attachment are lawful, while adding to the growing understanding of the emergence of unresolved attachment representations.

Error due to unresolved scales in estimation problems for atmospheric data assimilation

NASA Astrophysics Data System (ADS)

Janjic, Tijana

The error arising due to unresolved scales in data assimilation procedures is examined. The problem of estimating the projection of the state of a passive scalar undergoing advection at a sequence of times is considered. The projection belongs to a finite- dimensional function space and is defined on the continuum. Using the continuum projection of the state of a passive scalar, a mathematical definition is obtained for the error arising due to the presence, in the continuum system, of scales unresolved by the discrete dynamical model. This error affects the estimation procedure through point observations that include the unresolved scales. In this work, two approximate methods for taking into account the error due to unresolved scales and the resulting correlations are developed and employed in the estimation procedure. The resulting formulas resemble the Schmidt-Kalman filter and the usual discrete Kalman filter, respectively. For this reason, the newly developed filters are called the Schmidt-Kalman filter and the traditional filter. In order to test the assimilation methods, a two- dimensional advection model with nonstationary spectrum was developed for passive scalar transport in the atmosphere. An analytical solution on the sphere was found depicting the model dynamics evolution. Using this analytical solution the model error is avoided, and the error due to unresolved scales is the only error left in the estimation problem. It is demonstrated that the traditional and the Schmidt- Kalman filter work well provided the exact covariance function of the unresolved scales is known. However, this requirement is not satisfied in practice, and the covariance function must be modeled. The Schmidt-Kalman filter cannot be computed in practice without further approximations. Therefore, the traditional filter is better suited for practical use. Also, the traditional filter does not require modeling of the full covariance function of the unresolved scales, but only

Global-scale Ionospheric Outflow: Major Processes and Unresolved Problems

NASA Astrophysics Data System (ADS)

Liemohn, M. W.; Welling, D. T.; Ilie, R.; Khazanov, G. V.; Jahn, J. M.; Zou, S.; Ganushkina, N. Y.; Valek, P. W.; Elliott, H. A.; Gilchrist, B. E.; Hoegy, W. R.; Glocer, A.

2016-12-01

Outflow from the ionosphere is a major source of plasma to the magnetosphere. Its presence, especially that of ions heavier than He+, mass loads the magnetosphere and changes reconnection rates, current system configurations, plasma wave excitation and wave-particle interactions. It even impacts the propagation of information. We present a brief overview of the major processes and scientific history of this field. There are still major gaps, however, in our understanding of the global-scale nature of ionospheric outflow. We discuss these unresolved problems highlighting the leading questions still outstanding on this topic. First and foremost, since the measurements of ionospheric outflow have largely come from individual satellites and sounding rockets, the processes are best known on the local level, while the spatial distribution of outflow has never been simultaneously measured on more global scales. The spatial coherence and correlation of outflow across time and space have not been quantified. Furthermore, the composition of the outflow is often only measured at a coarse level of H+, He+, and O+, neglecting other species such as N+ or moleculars. However, resolving O+ from N+, as is customary in planetary research, aids in revealing the physics and altitude dependence of the energization processes in the ionosphere. Similarly, fine-resolution velocity space measurements of ionospheric outflow have been limited, yet such observations can also reveal energization processes driving the outflow. A final unresolved issue to mention is magnetically conjugate outflow and the full extent of hemispherically asymmetric outflow fluxes or fluence. Each of these open questions have substantial ramifications for magnetospheric physics; their resolution could yield sweeping changes in our understanding of nonlinear feedback and cross-scale physical interactions, magnetosphere-ionosphere coupling, and geospace system-level science.

Cognitive science as an interface between rational and mechanistic explanation.

PubMed

Chater, Nick

2014-04-01

Cognitive science views thought as computation; and computation, by its very nature, can be understood in both rational and mechanistic terms. In rational terms, a computation solves some information processing problem (e.g., mapping sensory information into a description of the external world; parsing a sentence; selecting among a set of possible actions). In mechanistic terms, a computation corresponds to causal chain of events in a physical device (in engineering context, a silicon chip; in biological context, the nervous system). The discipline is thus at the interface between two very different styles of explanation--as the papers in the current special issue well illustrate, it explores the interplay of rational and mechanistic forces. Copyright © 2014 Cognitive Science Society, Inc.

Evidence for Unresolved Exoplanet-hosting Binaries in Gaia DR2

NASA Astrophysics Data System (ADS)

Evans, Daniel F.

2018-05-01

This note describes an effort to detect additional stellar sources in known transiting exoplanet (TEP) systems, which are unresolved or barely resolved in the Gaia Data Release 2 (DR2) catalogue. The presence of multiple unresolved stars in photometric and spectroscopic observations of a transiting planetary system biases measurements of the planet's radius, mass, and atmospheric conditions. In addition to the effect on individual planetary systems, the presence of unresolved stars across the sample of known exoplanets biases our overall understanding of planetary systems, due to the systematic underestimation of both masses and radii. This work uses the Astrometric Goodness of Fit in the Along-Scan direction (GOF_AL) and the Astrometric Excess Noise as indicators of poorly-resolved binaries. Many known close binaries in the exoplanet host star sample have highly significant GOF_AL and Astrometric Excess Noise values, such as WASP-20AB with Astrometric Excess Noise significant at $4720\\sigma$ and GOF_AL=124.

University Management Education and Research in Canada: Some Unresolved Issues.

ERIC Educational Resources Information Center

von Zur-Muehlen, Max

An historical overview of university management education and research in Canada is presented and issues relevant to the present status of management education and research opportunities are discussed. Management and administrative studies schools in Canada receive, on the average, about four percent of the operating budget of the university…

Characterization of Sound Radiation by Unresolved Scales of Motion in Computational Aeroacoustics

NASA Technical Reports Server (NTRS)

Rubinstein, Robert; Zhou, Ye

1999-01-01

Evaluation of the sound sources in a high Reynolds number turbulent flow requires time-accurate resolution of an extremely large number of scales of motion. Direct numerical simulations will therefore remain infeasible for the forseeable future: although current large eddy simulation methods can resolve the largest scales of motion accurately the, they must leave some scales of motion unresolved. A priori studies show that acoustic power can be underestimated significantly if the contribution of these unresolved scales is simply neglected. In this paper, the problem of evaluating the sound radiation properties of the unresolved, subgrid-scale motions is approached in the spirit of the simplest subgrid stress models: the unresolved velocity field is treated as isotropic turbulence with statistical descriptors, evaluated from the resolved field. The theory of isotropic turbulence is applied to derive formulas for the total power and the power spectral density of the sound radiated by a filtered velocity field. These quantities are compared with the corresponding quantities for the unfiltered field for a range of filter widths and Reynolds numbers.

The Nature of the Unresolved Extragalactic Cosmic Soft X-Ray Background

NASA Technical Reports Server (NTRS)

Cappelluti, N.; Ranalli, P.; Roncarelli, M.; Arevalo, P.; Zamorani, G.; Comastri, A.; Gilli, R.; Rovilos, E.; Vignali, C.; Allevato, V.;

Perception of the pitch of unresolved harmonics by 3- and 7-month-old human infants.

PubMed

Lau, Bonnie K; Werner, Lynne A

2014-08-01

Three-month-olds discriminate resolved harmonic complexes on the basis of missing fundamental (MF) pitch. In view of reported difficulty in discriminating unresolved complexes at 7 months and striking changes in the organization of the auditory system during early infancy, infants' ability to discriminate unresolved complexes is of some interest. This study investigated the ability of 3-month-olds, 7-month-olds, and adults to discriminate the pitch of unresolved harmonic complexes using an observer-based method. Stimuli were MF complexes bandpass filtered with a -12 dB/octave slope, combined in random phase, presented at 70 dB sound pressure level (SPL) for 650 ms with a 50 ms rise/fall with a pink noise at 65 dB SPL. The conditions were (1) "LOW" unresolved harmonics (2500-4500 Hz) based on MFs of 160 and 200 Hz and (2) "HIGH" unresolved harmonics (4000-6000 Hz) based on MFs of 190 and 200 Hz. To demonstrate MF discrimination, participants had to ignore spectral changes in complexes with the same fundamental and respond only when the fundamental changed. Nearly all infants tested categorized complexes by MF pitch suggesting discrimination of pitch extracted from unresolved harmonics by 3 months. Adults also categorized the complexes by MF pitch, although musically trained adults were more successful than musically untrained adults.

The American Indian Holocaust: Healing Historical Unresolved Grief.

ERIC Educational Resources Information Center

Brave Heart, Maria Yellow Horse; DeBruyn, Lemyra M.

1998-01-01

Argues for the existence of historical unresolved grief among American Indians. Outlines the historical legacy of war, genocide, and boarding schools resulting in intergenerational trauma and a host of associated social problems. Suggests healing strategies that integrate modern and traditional approaches to healing at the individual, family, and…

Problems and Issues of Diversity in the United States.

ERIC Educational Resources Information Center

Naylor, Larry L., Ed.

A number of social problems created by cultural diversity in the United States seem to defy resolution. The essays in this collection address some of these issues and are designed to initiate serious discussions on some of the most serious questions. The chapters are: (1) "Introduction to American Cultural Diversity: Unresolved Questions, Issues,…

28 CFR 42.610 - Agency enforcement of unresolved complaints.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Agency enforcement of unresolved complaints. 42.610 Section 42.610 Judicial Administration DEPARTMENT OF JUSTICE NONDISCRIMINATION; EQUAL EMPLOYMENT OPPORTUNITY; POLICIES AND PROCEDURES Procedures for Complaints of Employment Discrimination Filed...

Observation of Unresolved Features in the Microwave Sky

NASA Astrophysics Data System (ADS)

Kowitt, M. S.; Cheng, E. S.; Cottingham, D. A.; Fixsen, D. J.; Silverberg, R. F.; Inman, C. A.; Meyer, S. S.; Puchalla, J. L.; Ruhl, J. E.; Page, L. A.

1994-12-01

We report on the detection of unresolved features in broadband observations from 5.6 to 22.5 cm(-1) with a 0\\fdg5 beam by the Medium Scale Anisotropy Measurement (Cheng et al. 1994, ApJ, 422, L37). Spectra for the features will be presented, along with a discussion of their possible origin.

29 CFR 1691.10 - Agency enforcement of unresolved complaints.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Section 1691.10 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION... ASSISTANCE § 1691.10 Agency enforcement of unresolved complaints. (a) Upon EEOC's transmittal of a reasonable cause determination and notice of failure of conciliation under § 1691.9(b)(2) of this regulation, the...

29 CFR 1691.10 - Agency enforcement of unresolved complaints.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Section 1691.10 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION... ASSISTANCE § 1691.10 Agency enforcement of unresolved complaints. (a) Upon EEOC's transmittal of a reasonable cause determination and notice of failure of conciliation under § 1691.9(b)(2) of this regulation, the...

29 CFR 1691.10 - Agency enforcement of unresolved complaints.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Section 1691.10 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION... ASSISTANCE § 1691.10 Agency enforcement of unresolved complaints. (a) Upon EEOC's transmittal of a reasonable cause determination and notice of failure of conciliation under § 1691.9(b)(2) of this regulation, the...

29 CFR 1691.10 - Agency enforcement of unresolved complaints.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Section 1691.10 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION... ASSISTANCE § 1691.10 Agency enforcement of unresolved complaints. (a) Upon EEOC's transmittal of a reasonable cause determination and notice of failure of conciliation under § 1691.9(b)(2) of this regulation, the...

29 CFR 1691.10 - Agency enforcement of unresolved complaints.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Section 1691.10 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION... ASSISTANCE § 1691.10 Agency enforcement of unresolved complaints. (a) Upon EEOC's transmittal of a reasonable cause determination and notice of failure of conciliation under § 1691.9(b)(2) of this regulation, the...

Neuroprotective properties of citicoline: facts, doubts and unresolved issues.

PubMed

Grieb, Pawel

2014-03-01

Citicoline is the generic name of the pharmaceutical substance that chemically is cytidine-5'-diphosphocholine (CDP-choline), which is identical to the natural intracellular precursor of phospholipid phosphatidylcholine. Following injection or ingestion, citicoline is believed to undergo quick hydrolysis and dephosphorylation to yield cytidine and choline, which then enter the brain separately and are used to resynthesize CDP-choline inside brain cells. Neuroprotective activity of citicoline has been repeatedly shown in preclinical models of brain ischaemia and trauma, but two recent, large, pivotal clinical trials have revealed no benefits in ischaemic stroke and traumatic brain injury. However, the substance seems to be beneficial in some slowly advancing neurodegenerative disorders such as glaucoma and mild vascular cognitive impairment. This paper critically discusses issues related to the clinical pharmacology of citicoline, including its pharmacokinetics/biotransformation and pharmacodynamics/mode of action. It is concluded that at present, there is no adequate description of the mechanism(s) of the pharmacological actions of this substance. The possibility should be considered and tested that, in spite of apparently fast catabolism, the intact citicoline molecule or the phosphorylated intermediate products of its hydrolysis, cytidine monophosphate and phosphocholine, are pharmacologically active.

From the exposome to mechanistic understanding of chemical ...

EPA Pesticide Factsheets

BACKGROUND: Current definitions of the exposome expand beyond the initial idea to consider the totality of exposure and aim to relate to biological effects. While the exposome has been established for human health, its principles can be extended to include broader ecological issues. The assessment of exposure is tightly interlinked with hazard assessment. OBJECTIVES: We explore if mechanistic understanding of the causal links between exposure and adverse effects on human health and the environment can be improved by integrating the exposome approach with the adverse outcome pathway (AOP) concept - a framework to structure and organize the sequence of toxicological events from an initial molecular interaction of a chemical to an adverse outcome.METHODS: This review was informed by a Workshop organized by the Integrated Project EXPOSOME at the UFZ Helmholtz Centre for Environmental Research in Leipzig, Germany. DISCUSSION: The exposome encompasses all chemicals, including exogenous chemicals and endogenous compounds that are produced in response to external factors. By complementing the exposome research with the AOP concept, we can achieve a better mechanistic understanding, weigh the importance of various components of the exposome, and determine primary risk drivers. The ability to interpret multiple exposures and mixture effects at the mechanistic level requires a more holistic approach facilitated by the exposome concept.CONCLUSION: Incorporating the AOP conc

Spatially unresolved SED fitting can underestimate galaxy masses: a solution to the missing mass problem

NASA Astrophysics Data System (ADS)

Sorba, Robert; Sawicki, Marcin

2018-05-01

We perform spatially resolved, pixel-by-pixel Spectral Energy Distribution (SED) fitting on galaxies up to z ˜ 2.5 in the Hubble eXtreme Deep Field (XDF). Comparing stellar mass estimates from spatially resolved and spatially unresolved photometry we find that unresolved masses can be systematically underestimated by factors of up to 5. The ratio of the unresolved to resolved mass measurement depends on the galaxy's specific star formation rate (sSFR): at low sSFRs the bias is small, but above sSFR ˜ 10-9.5 yr-1 the discrepancy increases rapidly such that galaxies with sSFRs ˜ 10-8 yr-1 have unresolved mass estimates of only one-half to one-fifth of the resolved value. This result indicates that stellar masses estimated from spatially unresolved data sets need to be systematically corrected, in some cases by large amounts, and we provide an analytic prescription for applying this correction. We show that correcting stellar mass measurements for this bias changes the normalization and slope of the star-forming main sequence and reduces its intrinsic width; most dramatically, correcting for the mass bias increases the stellar mass density of the Universe at high redshift and can resolve the long-standing discrepancy between the directly measured cosmic SFR density at z ≳ 1 and that inferred from stellar mass densities (`the missing mass problem').

Unresolved issues in mammalian fertilization.

PubMed

Olds-Clarke, Patricia

2003-01-01

This review considers the role of the sperm in fertilization, addressing areas of misunderstanding and unfounded assumptions and taking particular advantage of the large body of data resulting from work with rodent species in vitro. Considerable attention is given to the appropriate use and interpretation of assays for capacitation, acrosomal exocytosis, hyperactivation, and sperm protein phosphorylation, as well as tests for sperm-zona and sperm-oocyte membrane interactions. The lack of general agreement on the means of sperm adhesion to and penetration of the zona pellucida is addressed, and the need for new approaches to this problem is pointed out. Some molecular advances in our understanding of specific steps in the process of fertilization are discussed in the context of intact cell-matrix and cell-cell interaction. This review should provide practical information for researchers just beginning the study of fertilization and interesting but not widely known observations to stimulate new ideas in experienced scientists.

Bigeye Bomb: Unresolved Development Issues

DTIC Science & Technology

1989-08-11

the lethal agent formed inside the Bigeye bomb) at the purity or equivalent- biotoxicity level required by the Test and Eval- uation Master Plan (TEMP...during the 5 through 30-second period after mixing starts, with- out specifying either wheit the required purity or equivalent biotoxicity level should...revision of the purity or equivalent biotoxicity requirement. However, we believe that a bomb that produces lethal agent at the required purity level for 1

Cost Issues Unresolved in Chicago

ERIC Educational Resources Information Center

Sawchuk, Stephen

2012-01-01

Chicago teachers voted last week to suspend a 7-day-old strike, sending some 350,000 students back to the classroom and paving the way for the teaching force to vote on a tentative contract. But for many in the Windy City, the contract has raised another potentially tall hurdle: how the cash-strapped district will manage to pay for it. District…

Congenital Adrenal Hyperplasia: Unresolved Issues.

PubMed

Yau, Mabel; Khattab, Ahmed; Poppas, Dix; Ghizzoni, Lucia; New, Maria

2016-01-01

Congenital adrenal hyperplasia (CAH) describes a family of disorders that comes from enzymatic deficiencies in cortisol production, with 21-hydroxylase deficiency causing ∼90% of cases. Distinction is made between the severe classical form and milder nonclassical form of CAH. Molecular genetic analysis is used to confirm the hormonal diagnosis. A high rate of genotype-phenotype disconcordance has been found in 21-hydroxylase deficiency. The goal of treatment is to replace with synthetic glucocorticoids and mineralocorticoids and suppress adrenal androgen production. The treatment of patients affected with nonclassical CAH, particularly males, remains controversial. Variable synthetic glucocorticoids are used and new modes of glucocorticoid delivery are under investigation. To improve height, growth hormone and other adjuvant therapies are employed. Long-term outcomes of genital surgery using modern techniques in females affected with classical CAH continue to be investigated. Prenatal treatment with dexamethasone is available to avoid ambiguous genitalia in these females. Although studies have shown its safety to mother and fetus, prenatal treatment is still regarded as experimental. Currently, prenatal diagnosis of CAH can only be obtained through invasive methods. Recently, the detection of cell-free fetal DNA in maternal plasma has made it possible to make this diagnosis earlier and noninvasively. © 2016 S. Karger AG, Basel.

Crunch Seen on Ed. Issues after Election

ERIC Educational Resources Information Center

Klein, Alyson

2012-01-01

From the White House to Capitol Hill, the winners in this week's elections won't have much time to savor their victories. Even as federal policymakers sort out the political landscape, the remainder of 2012 and the early months of 2013 are likely to be dominated by divisive, unresolved issues with broad consequences for K-12 and higher…

Sickle red cell adhesion: many issues and some answers.

PubMed

Kaul, D K

2008-01-01

Among multiple pathologies associated with sickle cell disease, sickle red cell-endothelial interaction has been implicated as a potential initiating mechanism in vaso-occlusive events that characterize this disease. Vast literature exists on various aspects of sickle red cell adhesion, but many issues remain unresolved, especially pertaining to the role of sickle red cell heterogeneity, the relative role of multiple adhesion mechanisms and targets of antiadhesive therapy. This review briefly analyzes these issues.

Space station human productivity study. Volume 4: Issues

NASA Technical Reports Server (NTRS)

1985-01-01

The 305 Issues contained represent topics recommended for study in order to develop requirements in support of space station crew performance/productivity. The overall subject matter, space station elements affecting crew productivity, was organized into a coded subelement listing, which is included for the reader's reference. Each issue is numbered according to the 5-digit topical coding scheme. The requirements column on each Issue page shows a cross-reference to the unresolved requirement statement(s). Because topical overlaps were frequently encountered, many initial Issues were consolidated. Apparent gaps, therefore, may be accounted for by an Issue described within a related subelement. A glossary of abbreviations used throughout the study documentation is also included.

Unresolved Galaxy Classifier for ESA/Gaia mission: Support Vector Machines approach

NASA Astrophysics Data System (ADS)

Bellas-Velidis, Ioannis; Kontizas, Mary; Dapergolas, Anastasios; Livanou, Evdokia; Kontizas, Evangelos; Karampelas, Antonios

A software package Unresolved Galaxy Classifier (UGC) is being developed for the ground-based pipeline of ESA's Gaia mission. It aims to provide an automated taxonomic classification and specific parameters estimation analyzing Gaia BP/RP instrument low-dispersion spectra of unresolved galaxies. The UGC algorithm is based on a supervised learning technique, the Support Vector Machines (SVM). The software is implemented in Java as two separate modules. An offline learning module provides functions for SVM-models training. Once trained, the set of models can be repeatedly applied to unknown galaxy spectra by the pipeline's application module. A library of galaxy models synthetic spectra, simulated for the BP/RP instrument, is used to train and test the modules. Science tests show a very good classification performance of UGC and relatively good regression performance, except for some of the parameters. Possible approaches to improve the performance are discussed.

Thyrotropin receptor mutations and thyroid hyperfunctioning adenomas ten years after their first discovery: unresolved questions.

PubMed

Arturi, F; Scarpelli, D; Coco, A; Sacco, R; Bruno, R; Filetti, S; Russo, D

2003-04-01

Ten years after the first description of activating mutations in the thyroid stimulating hormone receptor (TSHR) gene in sporadic autonomous hyperfunctioning thyroid adenomas, there is general agreement in assigning a major pathogenic role of this genetic abnormality, acting via the constitutive activation of the cAMP pathway, in both the growth and functional characteristic of these tumours. From the beginning, however, the pathophysiological and clinical relevance of somatic TSHR mutations has been debated and some arguments still exist against a fully causative role of these mutations and the practical value of detecting these mutations for the diagnosis, treatment and prognosis of thyroid hot nodules. Some major issues will be examined herein, including (a) the frequency of TSHR alterations in various reports showing that the genetic abnormality underlying the pathogenesis of a substantial subset of thyroid tumours has yet to be identified; (b) the limitations of the present experimental models, which suggest greater caution in the interpretation of in vitro results; (c) the still unresolved question of absence of genotype-phenotype correlation. Clarification of these issues may hopefully provide new and useful tools for improving the clinical management of this disease.

Results of arthroscopic treatment in unresolved Osgood-Schlatter disease in athletes.

PubMed

Circi, Esra; Beyzadeoglu, Tahsin

2017-02-01

In this study we aimed to determine outcomes following arthroscopic ossicle excision in athletes with unresolved Osgood-Schlatter disease (OSD). Arthroscopy was performed on 11 patients (11 knees) with OSD between September 2008 and November 2014. Surgical treatment inclusion criteria were determined as: failure of conservative treatment; isolated pain over the tibial tubercle and distal patellar tendon; pain limiting sporting performance at a competitive level. All patients had a documented history of OSD; the mean duration of persistent pain over the tibial tubercle was 15.5 months. The mean age was 23 years. The mean follow-up period was 66.1 months. The mean latency in returning to sports related training activities after the surgery was 6.7 weeks. The mean Kujala patello-femoral score improved from 82.9 points pre-operatively, to 98.5 points at the final follow-up (p < 0.01). The mean Lysholm knee scale score was 87.5 points in the pre-operative period, increasing to a score of 96.9 points at final follow-up (p < 0.01). The mean Tegner activity level score was 7.5 in the pre-operative period, increasing to 8.5 post-operatively (p < 0.01). We investigated the functional outcomes after arthroscopic treatment of unresolved OSD in athletes. All athletes with OSD showed satisfactory functional recovery following arthroscopic treatment. All patients were able to return to the same level of athletic activity. Arthroscopic surgery for unresolved OSD has the major advantage of faster recovery and avoiding damage to the patellar tendon.

Emotion theory and research: highlights, unanswered questions, and emerging issues.

PubMed

Izard, Carroll E

2009-01-01

Emotion feeling is a phase of neurobiological activity, the key component of emotions and emotion-cognition interactions. Emotion schemas, the most frequently occurring emotion experiences, are dynamic emotion-cognition interactions that may consist of momentary/situational responding or enduring traits of personality that emerge over developmental time. Emotions play a critical role in the evolution of consciousness and the operations of all mental processes. Types of emotion relate differentially to types or levels of consciousness. Unbridled imagination and the ability for sympathetic regulation of empathy may represent both potential gains and losses from the evolution and ontogeny of emotion processes and consciousness. Unresolved issues include psychology's neglect of levels of consciousness that are distinct from access or reflective consciousness and use of the term "unconscious mind" as a dumpster for all mental processes that are considered unreportable. The relation of memes and the mirror neuron system to empathy, sympathy, and cultural influences on the development of socioemotional skills are unresolved issues destined to attract future research.

Supporting Mechanistic Reasoning in Domain-Specific Contexts

ERIC Educational Resources Information Center

Weinberg, Paul J.

2017-01-01

Mechanistic reasoning is an epistemic practice central within science, technology, engineering, and mathematics disciplines. Although there has been some work on mechanistic reasoning in the research literature and standards documents, much of this work targets domain-general characterizations of mechanistic reasoning; this study provides…

Unresolved Attachment, PTSD, and Dissociation in Women with Childhood Abuse Histories

ERIC Educational Resources Information Center

Stovall-McClough, K. Chase; Cloitre, Marylene

2006-01-01

The primary objective of this study was to examine unresolved trauma as assessed by the Adult Attachment Interview and current psychiatric symptoms, focusing on posttraumatic stress disorder (PTSD) and dissociation, in a group of adult female childhood abuse survivors. The authors examined psychiatric symptoms and attachment representations in a…

Mechanistic-empirical Pavement Design Guide Implementation

DOT National Transportation Integrated Search

2010-06-01

The recently introduced Mechanistic-Empirical Pavement Design Guide (MEPDG) and associated computer software provides a state-of-practice mechanistic-empirical highway pavement design methodology. The MEPDG methodology is based on pavement responses ...

Unresolved Subclinical Hypothyroidism is Independently Associated with Progression of Chronic Kidney Disease

PubMed Central

Kim, Eun Oh; Lee, Ihn Suk; Choi, Yoo A; Lee, Sang Ju; Chang, Yoon Kyung; Yoon, Hye Eun; Jang, Yi Sun; Lee, Jong Min; Kim, Hye Soo; Yang, Chul Woo; Kim, Suk Young; Hwang, Hyeon Seok

2014-01-01

Background and Aim: Patients with chronic kidney disease (CKD) often have subclinical hypothyroidism. However, few reports have investigated changes in the status of subclinical hypothyroidism in CKD patients and its clinical significance in CKD progression. Methods: We included 168 patients with nondialysis-dependent CKD stages 2-4. The normalization of subclinical hypothyroidism during follow-up was assessed, and the association between transitions in subclinical hypothyroid status and the rate of decline of the estimated glomerular filtration rate (eGFR) was investigated. Results: At baseline, 127 patients were euthyroid and 41 (24.4%) patients were diagnosed with subclinical hypothyroidism. Of these 41 patients, 21 (51.2%) spontaneously resolved to euthyroid during follow-up. The rate of eGFR decline of patients with resolved subclinical hypothyroidism was similar to that of euthyroid patients. The patients with unresolved subclinical hypothyroidism showed a steeper renal function decline than patients with euthyroidism or resolved subclinical hypothyroidism (all p < 0.05). The progression to end-stage renal disease was more frequent in those with unresolved subclinical hypothyroidism than in those who were euthyroid (p = 0.006). In multivariate linear regression for rate of eGFR decrease, unresolved subclinical hypothyroidism (β = -5.77, p = 0.001), baseline renal function (β = -0.12, p < 0.001) and level of proteinuria (β = -2.36, p = 0.015) were independently associated with the rate of renal function decline. Conclusions: Half of the CKD patients with subclinical hypothyroidism did not resolve to euthyroidism, and this lack of resolution was independently associated with rapid renal function decline. PMID:24396286

Unresolved subclinical hypothyroidism is independently associated with progression of chronic kidney disease.

PubMed

Kim, Eun Oh; Lee, Ihn Suk; Choi, Yoo A; Lee, Sang Ju; Chang, Yoon Kyung; Yoon, Hye Eun; Jang, Yi Sun; Lee, Jong Min; Kim, Hye Soo; Yang, Chul Woo; Kim, Suk Young; Hwang, Hyeon Seok

2014-01-01

Patients with chronic kidney disease (CKD) often have subclinical hypothyroidism. However, few reports have investigated changes in the status of subclinical hypothyroidism in CKD patients and its clinical significance in CKD progression. We included 168 patients with nondialysis-dependent CKD stages 2-4. The normalization of subclinical hypothyroidism during follow-up was assessed, and the association between transitions in subclinical hypothyroid status and the rate of decline of the estimated glomerular filtration rate (eGFR) was investigated. At baseline, 127 patients were euthyroid and 41 (24.4%) patients were diagnosed with subclinical hypothyroidism. Of these 41 patients, 21 (51.2%) spontaneously resolved to euthyroid during follow-up. The rate of eGFR decline of patients with resolved subclinical hypothyroidism was similar to that of euthyroid patients. The patients with unresolved subclinical hypothyroidism showed a steeper renal function decline than patients with euthyroidism or resolved subclinical hypothyroidism (all p < 0.05). The progression to end-stage renal disease was more frequent in those with unresolved subclinical hypothyroidism than in those who were euthyroid (p = 0.006). In multivariate linear regression for rate of eGFR decrease, unresolved subclinical hypothyroidism (β = -5.77, p = 0.001), baseline renal function (β = -0.12, p < 0.001) and level of proteinuria (β = -2.36, p = 0.015) were independently associated with the rate of renal function decline. Half of the CKD patients with subclinical hypothyroidism did not resolve to euthyroidism, and this lack of resolution was independently associated with rapid renal function decline.

Assessing uncertainty in mechanistic models

Treesearch

Edwin J. Green; David W. MacFarlane; Harry T. Valentine

2000-01-01

Concern over potential global change has led to increased interest in the use of mechanistic models for predicting forest growth. The rationale for this interest is that empirical models may be of limited usefulness if environmental conditions change. Intuitively, we expect that mechanistic models, grounded as far as possible in an understanding of the biology of tree...

Emotion Theory and Research: Highlights, Unanswered Questions, and Emerging Issues

PubMed Central

Izard, Carroll E.

2009-01-01

Emotion feeling is a phase of neurobiological activity, the key component of emotions and emotion-cognition interactions. Emotion schemas, the most frequently occurring emotion experiences, are dynamic emotion-cognition interactions that may consist of momentary/ situational responding or enduring traits of personality that emerge over developmental time. Emotions play a critical role in the evolution of consciousness and the operations of all mental processes. Types of emotion relate differentially to types or levels of consciousness. Unbridled imagination and the ability for sympathetic regulation of empathy may represent both potential gains and losses from the evolution and ontogeny of emotion processes and consciousness. Unresolved issues include psychology’s neglect of levels of consciousness that are distinct from access or reflective consciousness and use of the term “unconscious mind” as a dumpster for all mental processes that are considered unreportable. The relation of memes and the mirror neuron system to empathy, sympathy, and cultural influences on the development of socioemotional skills are unresolved issues destined to attract future research. PMID:18729725

Simulated cosmic microwave background maps at 0.5 deg resolution: Unresolved features

NASA Technical Reports Server (NTRS)

Kogut, A.; Hinshaw, G.; Bennett, C. L.

1995-01-01

High-contrast peaks in the cosmic microwave background (CMB) anisotropy can appear as unresolved sources to observers. We fit simluated CMB maps generated with a cold dark matter model to a set of unresolved features at instrumental resolution 0.5 deg-1.5 deg to derive the integral number density per steradian n (greater than absolute value of T) of features brighter than threshold temperature absolute value of T and compare the results to recent experiments. A typical medium-scale experiment observing 0.001 sr at 0.5 deg resolution would expect to observe one feature brighter than 85 micro-K after convolution with the beam profile, with less than 5% probability to observe a source brighter than 150 micro-K. Increasing the power-law index of primordial density perturbations n from 1 to 1.5 raises these temperature limits absolute value of T by a factor of 2. The MSAM features are in agreement with standard cold dark matter models and are not necessarily evidence for processes beyond the standard model.

A computer program for analyzing unresolved Mossbauer hyperfine spectra

NASA Technical Reports Server (NTRS)

Schiess, J. R.; Singh, J. J.

1978-01-01

The program for analyzing unresolved Mossbauer hyperfine spectra was written in FORTRAN 4 language for the Control Data CYBER 170 series digital computer system with network operating system 1.1. With the present dimensions, the program requires approximately 36,000 octal locations of core storage. A typical case involving two innermost coordination shells in which the amplitudes and the peak positions of all three components were estimated in 25 iterations requires 30 seconds on CYBER 173. The program was applied to determine the effects of various near neighbor impurity shells on hyperfine fields in dilute FeAl alloys.

Mechanistic kinetic models of enzymatic cellulose hydrolysis-A review.

PubMed

Jeoh, Tina; Cardona, Maria J; Karuna, Nardrapee; Mudinoor, Akshata R; Nill, Jennifer

2017-07-01

Bioconversion of lignocellulose forms the basis for renewable, advanced biofuels, and bioproducts. Mechanisms of hydrolysis of cellulose by cellulases have been actively studied for nearly 70 years with significant gains in understanding of the cellulolytic enzymes. Yet, a full mechanistic understanding of the hydrolysis reaction has been elusive. We present a review to highlight new insights gained since the most recent comprehensive review of cellulose hydrolysis kinetic models by Bansal et al. (2009) Biotechnol Adv 27:833-848. Recent models have taken a two-pronged approach to tackle the challenge of modeling the complex heterogeneous reaction-an enzyme-centric modeling approach centered on the molecularity of the cellulase-cellulose interactions to examine rate limiting elementary steps and a substrate-centric modeling approach aimed at capturing the limiting property of the insoluble cellulose substrate. Collectively, modeling results suggest that at the molecular-scale, how rapidly cellulases can bind productively (complexation) and release from cellulose (decomplexation) is limiting, while the overall hydrolysis rate is largely insensitive to the catalytic rate constant. The surface area of the insoluble substrate and the degrees of polymerization of the cellulose molecules in the reaction both limit initial hydrolysis rates only. Neither enzyme-centric models nor substrate-centric models can consistently capture hydrolysis time course at extended reaction times. Thus, questions of the true reaction limiting factors at extended reaction times and the role of complexation and decomplexation in rate limitation remain unresolved. Biotechnol. Bioeng. 2017;114: 1369-1385. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Parameterizing unresolved obstacles with source terms in wave modeling: A real-world application

NASA Astrophysics Data System (ADS)

Mentaschi, Lorenzo; Kakoulaki, Georgia; Vousdoukas, Michalis; Voukouvalas, Evangelos; Feyen, Luc; Besio, Giovanni

2018-06-01

Parameterizing the dissipative effects of small, unresolved coastal features, is fundamental to improve the skills of wave models. The established technique to deal with this problem consists in reducing the amount of energy advected within the propagation scheme, and is currently available only for regular grids. To find a more general approach, Mentaschi et al., 2015b formulated a technique based on source terms, and validated it on synthetic case studies. This technique separates the parameterization of the unresolved features from the energy advection, and can therefore be applied to any numerical scheme and to any type of mesh. Here we developed an open-source library for the estimation of the transparency coefficients needed by this approach, from bathymetric data and for any type of mesh. The spectral wave model WAVEWATCH III was used to show that in a real-world domain, such as the Caribbean Sea, the proposed approach has skills comparable and sometimes better than the established propagation-based technique.

Comparison of mechanistic transport cycle models of ABC exporters.

PubMed

Szöllősi, Dániel; Rose-Sperling, Dania; Hellmich, Ute A; Stockner, Thomas

2018-04-01

ABC (ATP binding cassette) transporters, ubiquitous in all kingdoms of life, carry out essential substrate transport reactions across cell membranes. Their transmembrane domains bind and translocate substrates and are connected to a pair of nucleotide binding domains, which bind and hydrolyze ATP to energize import or export of substrates. Over four decades of investigations into ABC transporters have revealed numerous details from atomic-level structural insights to their functional and physiological roles. Despite all these advances, a comprehensive understanding of the mechanistic principles of ABC transporter function remains elusive. The human multidrug resistance transporter ABCB1, also referred to as P-glycoprotein (P-gp), is one of the most intensively studied ABC exporters. Using ABCB1 as the reference point, we aim to compare the dominating mechanistic models of substrate transport and ATP hydrolysis for ABC exporters and to highlight the experimental and computational evidence in their support. In particular, we point out in silico studies that enhance and complement available biochemical data. "This article is part of a Special Issue entitled: Beyond the Structure-Function Horizon of Membrane Proteins edited by Ute Hellmich, Rupak Doshi and Benjamin McIlwain." Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Regulating the chromatin landscape: structural and mechanistic perspectives.

PubMed

Bartholomew, Blaine

2014-01-01

A large family of chromatin remodelers that noncovalently modify chromatin is crucial in cell development and differentiation. They are often the targets of cancer, neurological disorders, and other human diseases. These complexes alter nucleosome positioning, higher-order chromatin structure, and nuclear organization. They also assemble chromatin, exchange out histone variants, and disassemble chromatin at defined locations. We review aspects of the structural organization of these complexes, the functional properties of their protein domains, and variation between complexes. We also address the mechanistic details of these complexes in mobilizing nucleosomes and altering chromatin structure. A better understanding of these issues will be vital for further analyses of subunits of these chromatin remodelers, which are being identified as targets in human diseases by NGS (next-generation sequencing).

On-the-fly Doppler broadening of unresolved resonance region cross sections

DOE PAGES

Walsh, Jonathan A.; Forget, Benoit; Smith, Kord S.; ...

2017-07-29

In this paper, two methods for computing temperature-dependent unresolved resonance region cross sections on-the-fly within continuous-energy Monte Carlo neutron transport simulations are presented. The first method calculates Doppler broadened cross sections directly from zero-temperature average resonance parameters. In a simulation, at each event that requires cross section values, a realization of unresolved resonance parameters is generated about the desired energy and temperature-dependent single-level Breit-Wigner resonance cross sections are computed directly via the analytical Ψ-x Doppler integrals. The second method relies on the generation of equiprobable cross section magnitude bands on an energy-temperature mesh. Within a simulation, the bands are sampledmore » and interpolated in energy and temperature to obtain cross section values on-the-fly. Both of the methods, as well as their underlying calculation procedures, are verified numerically in extensive code-to-code comparisons. Energy-dependent pointwise cross sections calculated with the newly-implemented procedures are shown to be in excellent agreement with those calculated by a widely-used nuclear data processing code. Relative differences at or below 0.1% are observed. Integral criticality benchmark results computed with the proposed methods are shown to reproduce those computed with a state-of-the-art processed nuclear data library very well. In simulations of fast spectrum systems which are highly-sensitive to the representation of cross section data in the unresolved region, k-eigenvalue and neutron flux spectra differences of <10 pcm and <1.0% are observed, respectively. The direct method is demonstrated to be well-suited to the calculation of reference solutions — against which results obtained with a discretized representation may be assessed — as a result of its treatment of the energy, temperature, and cross section magnitude variables as continuous. Also, because there is no pre

Unresolved versus resolved: testing the validity of young simple stellar population models with VLT/MUSE observations of NGC 3603

NASA Astrophysics Data System (ADS)

Kuncarayakti, H.; Galbany, L.; Anderson, J. P.; Krühler, T.; Hamuy, M.

2016-09-01

Context. Stellar populations are the building blocks of galaxies, including the Milky Way. The majority, if not all, extragalactic studies are entangled with the use of stellar population models given the unresolved nature of their observation. Extragalactic systems contain multiple stellar populations with complex star formation histories. However, studies of these systems are mainly based upon the principles of simple stellar populations (SSP). Hence, it is critical to examine the validity of SSP models. Aims: This work aims to empirically test the validity of SSP models. This is done by comparing SSP models against observations of spatially resolved young stellar population in the determination of its physical properties, that is, age and metallicity. Methods: Integral field spectroscopy of a young stellar cluster in the Milky Way, NGC 3603, was used to study the properties of the cluster as both a resolved and unresolved stellar population. The unresolved stellar population was analysed using the Hα equivalent width as an age indicator and the ratio of strong emission lines to infer metallicity. In addition, spectral energy distribution (SED) fitting using STARLIGHT was used to infer these properties from the integrated spectrum. Independently, the resolved stellar population was analysed using the colour-magnitude diagram (CMD) to determine age and metallicity. As the SSP model represents the unresolved stellar population, the derived age and metallicity were tested to determine whether they agree with those derived from resolved stars. Results: The age and metallicity estimate of NGC 3603 derived from integrated spectroscopy are confirmed to be within the range of those derived from the CMD of the resolved stellar population, including other estimates found in the literature. The result from this pilot study supports the reliability of SSP models for studying unresolved young stellar populations. Based on observations collected at the European Organisation

Intriguing mechanistic labyrinths in gold(i) catalysis

PubMed Central

Obradors, Carla

2014-01-01

Many mechanistically intriguing reactions have been developed in the last decade using gold(i) as catalyst. Here we review the main mechanistic proposals in gold-catalysed activation of alkynes and allenes, in which this metal plays a central role by stabilising a variety of complex cationic intermediates. PMID:24176910

The use of mechanistic evidence in drug approval.

PubMed

Aronson, Jeffrey K; La Caze, Adam; Kelly, Michael P; Parkkinen, Veli-Pekka; Williamson, Jon

2018-06-11

The role of mechanistic evidence tends to be under-appreciated in current evidence-based medicine (EBM), which focusses on clinical studies, tending to restrict attention to randomized controlled studies (RCTs) when they are available. The EBM+ programme seeks to redress this imbalance, by suggesting methods for evaluating mechanistic studies alongside clinical studies. Drug approval is a problematic case for the view that mechanistic evidence should be taken into account, because RCTs are almost always available. Nevertheless, we argue that mechanistic evidence is central to all the key tasks in the drug approval process: in drug discovery and development; assessing pharmaceutical quality; devising dosage regimens; assessing efficacy, harms, external validity, and cost-effectiveness; evaluating adherence; and extending product licences. We recommend that, when preparing for meetings in which any aspect of drug approval is to be discussed, mechanistic evidence should be systematically analysed and presented to the committee members alongside analyses of clinical studies. © 2018 The Authors Journal of Evaluation in Clinical Practice Published by John Wiley & Sons Ltd.

Transitioning from AOP to IATA - Exploiting mechanistic ...

EPA Pesticide Factsheets

Slide presentation at satellite meeting of the QSAR2016 Meeting on How to Transition from AOP to IATA-Exploiting mechanistic insight for practical decision making. . Slide presentation at satellite meeting of the QSAR2016 Meeting on How to Transition from AOP to IATA-Exploiting mechanistic insight for practical decision making. .

Distinguishing dark matter from unresolved point sources in the Inner Galaxy with photon statistics

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

Lee, Samuel K.; Lisanti, Mariangela; Safdi, Benjamin R., E-mail: samuelkl@princeton.edu, E-mail: mlisanti@princeton.edu, E-mail: bsafdi@princeton.edu

2015-05-01

Data from the Fermi Large Area Telescope suggests that there is an extended excess of GeV gamma-ray photons in the Inner Galaxy. Identifying potential astrophysical sources that contribute to this excess is an important step in verifying whether the signal originates from annihilating dark matter. In this paper, we focus on the potential contribution of unresolved point sources, such as millisecond pulsars (MSPs). We propose that the statistics of the photons—in particular, the flux probability density function (PDF) of the photon counts below the point-source detection threshold—can potentially distinguish between the dark-matter and point-source interpretations. We calculate the flux PDFmore » via the method of generating functions for these two models of the excess. Working in the framework of Bayesian model comparison, we then demonstrate that the flux PDF can potentially provide evidence for an unresolved MSP-like point-source population.« less

Qualitative and quantitative assessment of Unresolved Complex Mixture in PM2.5 of Bakersfield, CA.

EPA Science Inventory

The 2010 CalNex (California Nexus) field experiment offered an opportunity for detailed characterization of atmospheric particulate carbon composition and sources in Bakersfield, CA. In the current study, the authors describe and employ a new protocol for reporting unresolved com...

Cutaneous electrical stimulation treatment in unresolved facial nerve paralysis: an exploratory study.

PubMed

Hyvärinen, Antti; Tarkka, Ina M; Mervaala, Esa; Pääkkönen, Ari; Valtonen, Hannu; Nuutinen, Juhani

2008-12-01

The purpose of this study was to assess clinical and neurophysiological changes after 6 mos of transcutaneous electrical stimulation in patients with unresolved facial nerve paralysis. A pilot case series of 10 consecutive patients with chronic facial nerve paralysis either of idiopathic origin or because of herpes zoster oticus participated in this open study. All patients received below sensory threshold transcutaneous electrical stimulation for 6 mos for their facial nerve paralysis. The intervention consisted of gradually increasing the duration of electrical stimulation of three sites on the affected area for up to 6 hrs/day. Assessments of the facial nerve function were performed using the House-Brackmann clinical scale and neurophysiological measurements of compound motor action potential distal latencies on the affected and nonaffected sides. Patients were tested before and after the intervention. A significant improvement was observed in the facial nerve upper branch compound motor action potential distal latency on the affected side in all patients. An improvement of one grade in House-Brackmann scale was observed and some patients also reported subjective improvement. Transcutaneous electrical stimulation treatment may have a positive effect on unresolved facial nerve paralysis. This study illustrates a possibly effective treatment option for patients with the chronic facial paresis with no other expectations of recovery.

Unresolved pain in children: a relational ethics perspective.

PubMed

Olmstead, Deborah L; Scott, Shannon D; Austin, Wendy J

2010-11-01

It is considered the right of children to have their pain managed effectively. Yet, despite extensive research findings, policy guidelines and practice standard recommendations for the optimal management of paediatric pain, clinical practices remain inadequate. Empirical evidence definitively shows that unrelieved pain in children has only harmful consequences, with no benefits. Contributing factors identified in this undermanaged pain include the significant role of nurses. Nursing attitudes and beliefs about children's pain experiences, the relationships nurses share with children who are suffering, and knowledge deficits in pain management practices are all shown to impact unresolved pain in children. In this article, a relational ethics perspective is used to explore the need for nurses to engage in authentic relationships with children who are experiencing pain, and to use evidence-based practices to manage that pain in order for this indefensible suffering of children to end.

Brainstem auditory responses to resolved and unresolved harmonics of a synthetic vowel in quiet and noise.

PubMed

Laroche, Marilyn; Dajani, Hilmi R; Prévost, François; Marcoux, André M

2013-01-01

This study investigated speech auditory brainstem responses (speech ABR) with variants of a synthetic vowel in quiet and in background noise. Its objectives were to study the noise robustness of the brainstem response at the fundamental frequency F0 and at the first formant F1, evaluate how the resolved/unresolved harmonics regions in speech contribute to the response at F0, and investigate the origin of the response at F0 to resolved and unresolved harmonics in speech. In total, 18 normal-hearing subjects (11 women, aged 18-33 years) participated in this study. Speech ABRs were recorded using variants of a 300 msec formant-synthesized /a/ vowel in quiet and in white noise. The first experiment employed three variants containing the first three formants F1 to F3, F1 only, and F2 and F3 only with relative formant levels following those reported in the literature. The second experiment employed three variants containing F1 only, F2 only, and F3 only, with the formants equalized to the same level and the signal-to-noise ratio (SNR) maintained at -5 dB. Overall response latency was estimated, and the amplitude and local SNR of the envelope following response at F0 and of the frequency following response at F1 were compared for the different stimulus variants in quiet and in noise. The response at F0 was more robust to noise than that at F1. There were no statistically significant differences in the response at F0 caused by the three stimulus variants in both experiments in quiet. However, the response at F0 with the variant dominated by resolved harmonics was more robust to noise than the response at F0 with the stimulus variants dominated by unresolved harmonics. The latencies of the responses in all cases were very similar in quiet, but the responses at F0 due to resolved and unresolved harmonics combined nonlinearly when both were present in the stimulus. Speech ABR has been suggested as a marker of central auditory processing. The results of this study support

Family and medical leave act: unresolved issues.

PubMed

Pyle, Jean L; Pelletier, Marianne S

2003-01-01

The United States' Family and Medical Leave Act (FMLA) of 1993 was an effort to provide national support for families attempting to balance the demands of the workplace and the need to care for a new child, one's own health, or an ill child, spouse, or parent. It is seriously limited, however, in terms of its accessibility for many workers. We briefly compare the FMLA to the substantially broader policies of Western European countries. We highlight its reported benefits to workers but document disparities in employees' use of the FMLA by gender, race, and income level. We evaluate whether employers' fears of higher costs were justified. We point out current challenges that may limit the FMLA further. We close by examining the range of alternative policies in effect at the state level and proposals that would address the current limitations of the FMLA and broaden its coverage.

Unresolved Issues With Inner Magnetosphere-Ionosphere Coupling

NASA Technical Reports Server (NTRS)

Gallagher, D. L.; Khazanov, G.

2004-01-01

Dipolarization and the release of stored magnetic energy is strongly evident in the energized plasma sheet electrons and ions injected earthward from the magnetotail. While some of these plasma are presumed lost into the dayside magnetosheath, much of the energy is dissipated into the ionosphere through electric currents, through collisions into low energy plasma, and into plasma waves, which then go on to heat and energize plasma of the inner magnetosphere. Many mechanisms for the transfer of energy and the consequences to inner magnetospheric plasma populations have been proposed. The sophistication of theoretical models to represent the interdependencies between plasma populations is rapidly increasing. However without the restraint and reality imposed on theory by relevant measurements, the degree to which specific mechanisms participate in the exchange of energy as a function of location and time cannot be known. ORBITALS offers this capability. Some of the outstanding problems in inner magnetospheric physics and the opportunities presented by the ORBITAL concept to solve problems will be discussed.

Collins Center Update. Volume 15, Issue 3. April-June 2013

DTIC Science & Technology

2013-06-01

and unresolved boundary issues with Mali, Niger , and Benin . Within this security environment the Burkinabe Armed Forces are working with the U.S...Analytical Exchanges at Collins Hall • Burkina Faso Military Strategy Review Phase II • Joint Land, Air and Sea Strategic Exercise (JLASS-EX) 2013...Prescribed by ANSI Std Z39-18 2 C S L D Burkina Faso Military Strategy Review Phase II Prof. B.F. Griffard and Prof. Bert B. Tussing Center for Strategic

Integration of collinear-type doubly unresolved counterterms in NNLO jet cross sections

NASA Astrophysics Data System (ADS)

Del Duca, Vittorio; Somogyi, Gábor; Trócsányi, Zoltán

2013-06-01

In the context of a subtraction method for jet cross sections at NNLO accuracy in the strong coupling, we perform the integration over the two-particle factorised phase space of the collinear-type contributions to the doubly unresolved counterterms. We present the final result as a convolution in colour space of the Born cross section and of an insertion operator, which is written in terms of master integrals that we expand in the dimensional regularisation parameter.

The autism puzzle: challenging a mechanistic model on conceptual and historical grounds

PubMed Central

2013-01-01

Although clinicians and researchers working in the field of autism are generally not concerned with philosophical categories of kinds, a model for understanding the nature of autism is important for guiding research and clinical practice. Contemporary research in the field of autism is guided by the depiction of autism as a scientific object that can be identified with systematic neuroscientific investigation. This image of autism is compatible with a permissive account of natural kinds: the mechanistic property cluster (MPC) account of natural kinds, recently proposed as the model for understanding psychiatric disorders. Despite the heterogeneity, multicausality and fuzzy boundaries that complicate autism research, a permissive account of natural kinds (MPC kinds) provides prescriptive guidance for the investigation of objective causal mechanisms that should inform nosologists in their attempt to carve autism’s boundaries at its natural joints. However, this essay will argue that a mechanistic model of autism is limited since it disregards the way in which autism relates to ideas about what kind of behavior is abnormal. As historical studies and definitions of autism show, normative issues concerning disability, impairment and societal needs have been and still are inextricably linked to how we recognize and understand autism. The current search for autism’s unity in neurobiological mechanisms ignores the values, social norms and various perspectives on mental pathology that play a significant role in 'the thing called autism’. Autism research needs to engage with these issues in order to achieve more success in the effort to become clinically valuable. PMID:24207065

Mechanistic Explanations for Restricted Evolutionary Paths That Emerge from Gene Regulatory Networks

PubMed Central

Cotterell, James; Sharpe, James

2013-01-01

The extent and the nature of the constraints to evolutionary trajectories are central issues in biology. Constraints can be the result of systems dynamics causing a non-linear mapping between genotype and phenotype. How prevalent are these developmental constraints and what is their mechanistic basis? Although this has been extensively explored at the level of epistatic interactions between nucleotides within a gene, or amino acids within a protein, selection acts at the level of the whole organism, and therefore epistasis between disparate genes in the genome is expected due to their functional interactions within gene regulatory networks (GRNs) which are responsible for many aspects of organismal phenotype. Here we explore epistasis within GRNs capable of performing a common developmental function – converting a continuous morphogen input into discrete spatial domains. By exploring the full complement of GRN wiring designs that are able to perform this function, we analyzed all possible mutational routes between functional GRNs. Through this study we demonstrate that mechanistic constraints are common for GRNs that perform even a simple function. We demonstrate a common mechanistic cause for such a constraint involving complementation between counter-balanced gene-gene interactions. Furthermore we show how such constraints can be bypassed by means of “permissive” mutations that buffer changes in a direct route between two GRN topologies that would normally be unviable. We show that such bypasses are common and thus we suggest that unlike what was observed in protein sequence-function relationships, the “tape of life” is less reproducible when one considers higher levels of biological organization. PMID:23613807

Mechanistic models versus machine learning, a fight worth fighting for the biological community?

PubMed

Baker, Ruth E; Peña, Jose-Maria; Jayamohan, Jayaratnam; Jérusalem, Antoine

2018-05-01

Ninety per cent of the world's data have been generated in the last 5 years ( Machine learning: the power and promise of computers that learn by example Report no. DES4702. Issued April 2017. Royal Society). A small fraction of these data is collected with the aim of validating specific hypotheses. These studies are led by the development of mechanistic models focused on the causality of input-output relationships. However, the vast majority is aimed at supporting statistical or correlation studies that bypass the need for causality and focus exclusively on prediction. Along these lines, there has been a vast increase in the use of machine learning models, in particular in the biomedical and clinical sciences, to try and keep pace with the rate of data generation. Recent successes now beg the question of whether mechanistic models are still relevant in this area. Said otherwise, why should we try to understand the mechanisms of disease progression when we can use machine learning tools to directly predict disease outcome? © 2018 The Author(s).

Human Health Effects of Trichloroethylene: Key Findings and Scientific Issues

PubMed Central

Jinot, Jennifer; Scott, Cheryl Siegel; Makris, Susan L.; Cooper, Glinda S.; Dzubow, Rebecca C.; Bale, Ambuja S.; Evans, Marina V.; Guyton, Kathryn Z.; Keshava, Nagalakshmi; Lipscomb, John C.; Barone, Stanley; Fox, John F.; Gwinn, Maureen R.; Schaum, John; Caldwell, Jane C.

2012-01-01

Background: In support of the Integrated Risk Information System (IRIS), the U.S. Environmental Protection Agency (EPA) completed a toxicological review of trichloroethylene (TCE) in September 2011, which was the result of an effort spanning > 20 years. Objectives: We summarized the key findings and scientific issues regarding the human health effects of TCE in the U.S. EPA’s toxicological review. Methods: In this assessment we synthesized and characterized thousands of epidemiologic, experimental animal, and mechanistic studies, and addressed several key scientific issues through modeling of TCE toxicokinetics, meta-analyses of epidemiologic studies, and analyses of mechanistic data. Discussion: Toxicokinetic modeling aided in characterizing the toxicological role of the complex metabolism and multiple metabolites of TCE. Meta-analyses of the epidemiologic data strongly supported the conclusions that TCE causes kidney cancer in humans and that TCE may also cause liver cancer and non-Hodgkin lymphoma. Mechanistic analyses support a key role for mutagenicity in TCE-induced kidney carcinogenicity. Recent evidence from studies in both humans and experimental animals point to the involvement of TCE exposure in autoimmune disease and hypersensitivity. Recent avian and in vitro mechanistic studies provided biological plausibility that TCE plays a role in developmental cardiac toxicity, the subject of substantial debate due to mixed results from epidemiologic and rodent studies. Conclusions: TCE is carcinogenic to humans by all routes of exposure and poses a potential human health hazard for noncancer toxicity to the central nervous system, kidney, liver, immune system, male reproductive system, and the developing embryo/fetus. PMID:23249866

Testing mechanistic models of growth in insects.

PubMed

Maino, James L; Kearney, Michael R

2015-11-22

Insects are typified by their small size, large numbers, impressive reproductive output and rapid growth. However, insect growth is not simply rapid; rather, insects follow a qualitatively distinct trajectory to many other animals. Here we present a mechanistic growth model for insects and show that increasing specific assimilation during the growth phase can explain the near-exponential growth trajectory of insects. The presented model is tested against growth data on 50 insects, and compared against other mechanistic growth models. Unlike the other mechanistic models, our growth model predicts energy reserves per biomass to increase with age, which implies a higher production efficiency and energy density of biomass in later instars. These predictions are tested against data compiled from the literature whereby it is confirmed that insects increase their production efficiency (by 24 percentage points) and energy density (by 4 J mg(-1)) between hatching and the attainment of full size. The model suggests that insects achieve greater production efficiencies and enhanced growth rates by increasing specific assimilation and increasing energy reserves per biomass, which are less costly to maintain than structural biomass. Our findings illustrate how the explanatory and predictive power of mechanistic growth models comes from their grounding in underlying biological processes. © 2015 The Author(s).

A Comparison of Unresolved Versus Resolved Status and Its Relationship to Behaviour in Maltreated Adolescents

ERIC Educational Resources Information Center

Webster, Linda; Hackett, Rachelle Kisst

2007-01-01

This exploratory investigation sought both to gain a better understanding of the mental representations of attachment in high-risk, maltreated adolescents and to explain how, if at all, unresolved attachment representations are related to behavioural maladjustment. Parent ratings, self-report ratings and attachment state of mind were obtained from…

A subtraction scheme for computing QCD jet cross sections at NNLO: integrating the iterated singly-unresolved subtraction terms

NASA Astrophysics Data System (ADS)

Bolzoni, Paolo; Somogyi, Gábor; Trócsányi, Zoltán

2011-01-01

We perform the integration of all iterated singly-unresolved subtraction terms, as defined in ref. [1], over the two-particle factorized phase space. We also sum over the unresolved parton flavours. The final result can be written as a convolution (in colour space) of the Born cross section and an insertion operator. We spell out the insertion operator in terms of 24 basic integrals that are defined explicitly. We compute the coefficients of the Laurent expansion of these integrals in two different ways, with the method of Mellin-Barnes representations and sector decomposition. Finally, we present the Laurent-expansion of the full insertion operator for the specific examples of electron-positron annihilation into two and three jets.

Treating Unresolved Grief and Posttraumatic Stress Symptoms in Orphaned Children in Tanzania: Group-based Trauma-focused Cognitive Behavioral Therapy

PubMed Central

O’Donnell, Karen; Dorsey, Shannon; Gong, Wenfeng; Ostermann, Jan; Whetten, Rachel; Cohen, Judith A.; Itemba, Dafrosa; Manongi, Rachel; Whetten, Kathryn

2015-01-01

The study was designed to test the feasibility and child clinical outcomes for a group-based application of Trauma-focused Cognitive Behavior Therapy (TF-CBT) for orphaned children with unresolved grief in Moshi, Tanzania. Sixty-four orphaned children with at least mild symptoms of unresolved grief and/or traumatic stress and their guardians participated in the open trial. The evidence-based TF-CBT protocol was adapted for group delivery, resulting in 12 weekly sessions for child and guardians separately with conjoint activities and three individual visits. Using a task-sharing approach, the intervention was delivered by lay counselors with no prior mental health experience. Primary outcomes assessed were symptoms of unresolved grief and posttraumatic stress (PTS); secondary outcomes included symptoms of depression and overall behavioral adjustment. All assessments were conducted pre-treatment, post-treatment, and 3- and 12-months after the end of treatment. Results showed improved scores on all outcomes post-treatment, sustained at 3 and 12 months. Effect sizes (Cohen’s d) for baseline to post-treatment were 1.36 for child reported grief symptoms; 1.87 for child-reported PTS, and 1.15 for caregiver report of child PTS. PMID:25418514

Bridging paradigms: hybrid mechanistic-discriminative predictive models.

PubMed

Doyle, Orla M; Tsaneva-Atansaova, Krasimira; Harte, James; Tiffin, Paul A; Tino, Peter; Díaz-Zuccarini, Vanessa

2013-03-01

Many disease processes are extremely complex and characterized by multiple stochastic processes interacting simultaneously. Current analytical approaches have included mechanistic models and machine learning (ML), which are often treated as orthogonal viewpoints. However, to facilitate truly personalized medicine, new perspectives may be required. This paper reviews the use of both mechanistic models and ML in healthcare as well as emerging hybrid methods, which are an exciting and promising approach for biologically based, yet data-driven advanced intelligent systems.

A method for selecting M dwarfs with an increased likelihood of unresolved ultracool companionship

NASA Astrophysics Data System (ADS)

Cook, N. J.; Pinfield, D. J.; Marocco, F.; Burningham, B.; Jones, H. R. A.; Frith, J.; Zhong, J.; Luo, A. L.; Qi, Z. X.; Lucas, P. W.; Gromadzki, M.; Day-Jones, A. C.; Kurtev, R. G.; Guo, Y. X.; Wang, Y. F.; Bai, Y.; Yi, Z. P.; Smart, R. L.

2016-04-01

Locating ultracool companions to M dwarfs is important for constraining low-mass formation models, the measurement of substellar dynamical masses and radii, and for testing ultracool evolutionary models. We present an optimized method for identifying M dwarfs which may have unresolved ultracool companions. We construct a catalogue of 440 694 M dwarf candidates, from Wide-Field Infrared Survey Explorer, Two Micron All-Sky Survey and Sloan Digital Sky Survey, based on optical- and near-infrared colours and reduced proper motion. With strict reddening, photometric and quality constraints we isolate a subsample of 36 898 M dwarfs and search for possible mid-infrared M dwarf + ultracool dwarf candidates by comparing M dwarfs which have similar optical/near-infrared colours (chosen for their sensitivity to effective temperature and metallicity). We present 1082 M dwarf + ultracool dwarf candidates for follow-up. Using simulated ultracool dwarf companions to M dwarfs, we estimate that the occurrence of unresolved ultracool companions amongst our M dwarf + ultracool dwarf candidates should be at least four times the average for our full M dwarf catalogue. We discuss possible contamination and bias and predict yields of candidates based on our simulations.

CO activation pathways and the mechanism of Fischer–Tropsch synthesis

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

Ojeda, Manuel; Nabar, Rahul P.; Nilekar, Anand U.

2010-06-15

Unresolved mechanistic details of monomer formation in Fischer–Tropsch synthesis (FTS) and of its oxygen rejection routes are addressed here by combining kinetic and theoretical analyses of elementary steps on representative Fe and Co surfaces saturated with chemisorbed CO. These studies provide experimental and theoretical evidence for hydrogen-assisted CO activation as the predominant kinetically-relevant step on Fe and Co catalysts at conditions typical of FTS practice. H2 and CO kinetic effects on FTS rates and oxygen rejection selectivity (as H2O or CO2) and density functional theory estimates of activation barriers and binding energies are consistent with H-assisted CO dissociation, but notmore » with the previously accepted kinetic relevance of direct CO dissociation and chemisorbed carbon hydrogenation elementary steps. H-assisted CO dissociation removes O-atoms as H2O, while direct dissociation forms chemisorbed oxygen atoms that desorb as CO2. Direct CO dissociation routes are minor contributors to monomer formation on Fe and may become favored at high temperatures on alkali-promoted catalysts, but not on Co catalysts, which remove oxygen predominantly as H2O because of the preponderance of Hassisted CO dissociation routes. The merging of experiment and theory led to the clarification of persistent mechanistic issues previously unresolved by separate experimental and theoretical inquiries.« less

Unresolved Loss, a Risk Factor for Offspring, Predicts Event-Related Potential Responses to Death-Related Imagery

ERIC Educational Resources Information Center

Bahm, Naomi I. Gribneau; Simon-Thomas, Emiliana R.; Main, Mary; Hesse, Erik

2017-01-01

This study investigates whether individual differences in attachment status can be detected by electrophysiological responses to loss-themed pictures. The Adult Attachment Interview (AAI) was used to identify discourse/reasoning lapses during the discussion of loss experiences via death that place speakers in the Unresolved/disorganized AAI…

Development of an Art Psychotherapy Model for the Prevention and Treatment of Unresolved Grief during Midlife.

ERIC Educational Resources Information Center

Turetsky, Cheryl J.; Hays, Ronald E.

2003-01-01

Presents an integrated model as an appropriate intervention to enable mourning and creativity and thus help in the prevention and treatment of unresolved grief in midlife. Two examples of this model in art-psychotherapy group treatment are provided. (Contains 53 references, 1 table, and 2 figures.) (GCP)

Auxiliary-cavity-assisted ground-state cooling of an optically levitated nanosphere in the unresolved-sideband regime

NASA Astrophysics Data System (ADS)

Feng, Jin-Shan; Tan, Lei; Gu, Huai-Qiang; Liu, Wu-Ming

2017-12-01

We theoretically analyze the ground-state cooling of an optically levitated nanosphere in the unresolved-sideband regime by introducing a coupled high-quality-factor cavity. On account of the quantum interference stemming from the presence of the coupled cavity, the spectral density of the optical force exerting on the nanosphere gets changed and then the symmetry between the heating and the cooling processes is broken. Through adjusting the detuning of a strong-dissipative cavity mode, one obtains an enhanced net cooling rate for the nanosphere. It is illustrated that the ground-state cooling can be realized in the unresolved sideband regime even if the effective optomechanical coupling is weaker than the frequency of the nanosphere, which can be understood by the picture that the effective interplay of the nanosphere and the auxiliary cavity mode brings the system back to an effective resolved regime. Besides, the coupled cavity refines the dynamical stability of the system.

Patterns of Drug Distribution: Implications and Issues#

PubMed Central

Johnson, Bruce D.

2007-01-01

This article delineates various patterns of illicit sales of drugs, especially at the retail (and near-retail) level, addressing a variety of central issues about drug sales and distribution documented during the past 30 years, including: a) the links between drug consumption and drug distribution activities; b) the various distribution roles; c) various levels of the distribution hierarchy; d) types of retail and wholesale markets; e) the association of drug distribution with nondrug associated criminality and violence. The article also will address the implications of drug distribution: whether various public policies such as supply reduction and source interdiction affect illicit drug markets, and how policing strategies and various law enforcement strategies can influence the involvement of individual participation in drug distribution activities. The overlooked contribution of treatment for “drug abuse” to reducing drug sales and distribution activities also will be considered as will other critical unresolved issues. PMID:14582578

Patterns of drug distribution: implications and issues.

PubMed

Johnson, Bruce D

2003-01-01

This article delineates various patterns of illicit sales of drugs, especially at the retail (and near-retail) level, addressing a variety of central issues about drug sales and distribution documented during the past 30 years. including: a) the links between drug consumption and drug distribution activities; b) the various distribution roles; c) various levels of the distribution hierarchy; d) types of retail and wholesale markets; e) the association of drug distribution with nondrug associated criminality and violence. The article also will address the implications of drug distribution: whether various public policies such as supply reduction and source interdiction affect illicit drug markets, and how policing strategies and various law enforcement strategies can influence the involvement of individual participation in drug distribution activities. The overlooked contribution of treatment for "drug abuse" to reducing drug sales and distribution activities also will be considered as will other critical unresolved issues.

Putting the psychology back into psychological models: mechanistic versus rational approaches.

PubMed

Sakamoto, Yasuaki; Jones, Mattr; Love, Bradley C

2008-09-01

Two basic approaches to explaining the nature of the mind are the rational and the mechanistic approaches. Rational analyses attempt to characterize the environment and the behavioral outcomes that humans seek to optimize, whereas mechanistic models attempt to simulate human behavior using processes and representations analogous to those used by humans. We compared these approaches with regard to their accounts of how humans learn the variability of categories. The mechanistic model departs in subtle ways from rational principles. In particular, the mechanistic model incrementally updates its estimates of category means and variances through error-driven learning, based on discrepancies between new category members and the current representation of each category. The model yields a prediction, which we verify, regarding the effects of order manipulations that the rational approach does not anticipate. Although both rational and mechanistic models can successfully postdict known findings, we suggest that psychological advances are driven primarily by consideration of process and representation and that rational accounts trail these breakthroughs.

Mechanistic species distribution modelling as a link between physiology and conservation.

PubMed

Evans, Tyler G; Diamond, Sarah E; Kelly, Morgan W

2015-01-01

Climate change conservation planning relies heavily on correlative species distribution models that estimate future areas of occupancy based on environmental conditions encountered in present-day ranges. The approach benefits from rapid assessment of vulnerability over a large number of organisms, but can have poor predictive power when transposed to novel environments and reveals little in the way of causal mechanisms that define changes in species distribution or abundance. Having conservation planning rely largely on this single approach also increases the risk of policy failure. Mechanistic models that are parameterized with physiological information are expected to be more robust when extrapolating distributions to future environmental conditions and can identify physiological processes that set range boundaries. Implementation of mechanistic species distribution models requires knowledge of how environmental change influences physiological performance, and because this information is currently restricted to a comparatively small number of well-studied organisms, use of mechanistic modelling in the context of climate change conservation is limited. In this review, we propose that the need to develop mechanistic models that incorporate physiological data presents an opportunity for physiologists to contribute more directly to climate change conservation and advance the field of conservation physiology. We begin by describing the prevalence of species distribution modelling in climate change conservation, highlighting the benefits and drawbacks of both mechanistic and correlative approaches. Next, we emphasize the need to expand mechanistic models and discuss potential metrics of physiological performance suitable for integration into mechanistic models. We conclude by summarizing other factors, such as the need to consider demography, limiting broader application of mechanistic models in climate change conservation. Ideally, modellers, physiologists and

Identification of geostationary satellites using polarization data from unresolved images

NASA Astrophysics Data System (ADS)

Speicher, Andy

In order to protect critical military and commercial space assets, the United States Space Surveillance Network must have the ability to positively identify and characterize all space objects. Unfortunately, positive identification and characterization of space objects is a manual and labor intensive process today since even large telescopes cannot provide resolved images of most space objects. Since resolved images of geosynchronous satellites are not technically feasible with current technology, another method of distinguishing space objects was explored that exploits the polarization signature from unresolved images. The objective of this study was to collect and analyze visible-spectrum polarization data from unresolved images of geosynchronous satellites taken over various solar phase angles. Different collection geometries were used to evaluate the polarization contribution of solar arrays, thermal control materials, antennas, and the satellite bus as the solar phase angle changed. Since materials on space objects age due to the space environment, it was postulated that their polarization signature may change enough to allow discrimination of identical satellites launched at different times. The instrumentation used in this experiment was a United States Air Force Academy (USAFA) Department of Physics system that consists of a 20-inch Ritchey-Chretien telescope and a dual focal plane optical train fed with a polarizing beam splitter. A rigorous calibration of the system was performed that included corrections for pixel bias, dark current, and response. Additionally, the two channel polarimeter was calibrated by experimentally determining the Mueller matrix for the system and relating image intensity at the two cameras to Stokes parameters S0 and S1. After the system calibration, polarization data was collected during three nights on eight geosynchronous satellites built by various manufacturers and launched several years apart. Three pairs of the eight

Astrophysical interpretation of the anisotropies in the unresolved gamma-ray background

NASA Astrophysics Data System (ADS)

Ando, Shin'ichiro; Fornasa, Mattia; Fornengo, Nicolao; Regis, Marco; Zechlin, Hannes-S.

2017-06-01

Recently, a new measurement of the auto- and cross-correlation angular power spectrum (APS) of the isotropic gamma-ray background was performed, based on 81 months of data of the Fermi Large-Area Telescope (LAT). Here, we fit, for the first time, the new APS data with a model describing the emission of unresolved blazars. These sources are expected to dominate the anisotropy signal. The model we employ in our analysis reproduces well the blazars resolved by Fermi LAT. When considering the APS obtained by masking the sources listed in the 3FGL catalog, we find that unresolved blazars underproduce the measured APS below ˜1 GeV . Contrary to past results, this suggests the presence of a new contribution to the low-energy APS, with a significance of, at least, 5 σ . The excess can be ascribed to a new class of faint gamma-ray emitters. If we consider the APS obtained by masking the sources in the 2FGL catalog, there is no underproduction of the APS below 1 GeV, but the new source class is still preferred over the blazars-only scenario (with a significance larger than 10 σ ). The properties of the new source class and the level of anisotropies induced in the isotropic gamma-ray background are the same, independent of the APS data used. In particular, the new gamma-ray emitters must have a soft energy spectrum, with a spectral index ranging, approximately, from 2.7 to 3.2. This complicates their interpretation in terms of known sources, since, normally, star-forming and radio galaxies are observed with a harder spectrum. The new source class identified here is also expected to contribute significantly to the intensity of the isotropic gamma-ray background.

Multimode four-wave mixing in an unresolved sideband optomechanical system

NASA Astrophysics Data System (ADS)

Li, Zongyang; You, Xiang; Li, Yongmin; Liu, Yong-Chun; Peng, Kunchi

2018-03-01

We have studied multimode four-wave mixing (FWM) in an unresolved sideband cavity optomechanical system. The radiation pressure coupling between the cavity fields and multiple mechanical modes results in the formation of a series of tripod-type energy-level systems, which induce the multimode FWM phenomenon. The FWM mechanism enables remarkable amplification of a weak signal field accompanied by the generation of an FWM field when only a microwatt-level pump field is applied. For proper system parameters, the amplified signal and FWM fields have equal intensity with opposite phases. The gain and frequency response bandwidth of the signal field can be dynamically tuned by varying the pump intensity, optomechanical coupling strength, and additional feedback control. Under certain conditions, the frequency response bandwidth can be very narrow and reaches the level of hertz.

Fundamental issues in the geology and geophysics of venus.

PubMed

Solomon, S C; Head, J W

1991-04-12

A number of important and currently unresolved issues in the global geology and geophysics of Venus will be addressable with the radar imaging, altimetry, and gravity measurements now forthcoming from the Magellan mission. Among these are the global volcanic flux and the rate of formation of new crust; the global heat flux and its regional variations; the relative importance of localized hot spots and linear centers of crustal spreading to crustal formation and tectonics; and the planform of mantle convection on Venus and the nature of the interactions among interior convective flow, near-surface deformation and magmatism.

A high-significance measurement of correlation between unresolved IRAS sources and optically-selected galaxy clusters

NASA Astrophysics Data System (ADS)

Hincks, Adam D.; Hajian, Amir; Addison, Graeme E.

2013-05-01

We cross-correlate the 100 μm Improved Reprocessing of the IRAS Survey (IRIS) map and galaxy clusters at 0.1 < z < 0.3 in the maxBCG catalogue taken from the Sloan Digital Sky Survey, measuring an angular cross-power spectrum over multipole moments 150 < l < 3000 at a total significance of over 40σ. The cross-spectrum, which arises from the spatial correlation between unresolved dusty galaxies that make up the cosmic infrared background (CIB) in the IRIS map and the galaxy clusters, is well-fit by a single power law with an index of -1.28±0.12, similar to the clustering of unresolved galaxies from cross-correlating far-infrared and submillimetre maps at longer wavelengths. Using a recent, phenomenological model for the spectral and clustering properties of the IRIS galaxies, we constrain the large-scale bias of the maxBCG clusters to be 2.6±1.4, consistent with existing analyses of the real-space cluster correlation function. The success of our method suggests that future CIB-optical cross-correlations using Planck and Herschel data will significantly improve our understanding of the clustering and redshift distribution of the faint CIB sources.

Ethics, policy, and educational issues in genetic testing.

PubMed

Williams, Janet K; Skirton, Heather; Masny, Agnes

2006-01-01

Analyze ethics, public policy, and education issues that arise in the United States (US) and the United Kingdom (UK) when genomic information acquired as a result of genetic testing is introduced into healthcare services. Priorities in the Ethical, Legal, and Social Issues Research Program include privacy, integration of genetic services into clinical health care, and educational preparation of the nursing workforce. These constructs are used to examine health policies in the US and UK, and professional interactions of individuals and families with healthcare providers. Individual, family, and societal goals may conflict with current healthcare practices and policies when genetic testing is done. Current health policies do not fully address these concerns. Unresolved issues include protection of privacy of individuals while considering genetic information needs of family members, determination of appropriate monitoring of genetic tests, addressing genetic healthcare discrepancies, and assuring appropriate nursing workforce preparation. Introduction of genetic testing into health care requires that providers are knowledgeable regarding ethical, policy, and practice issues in order to minimize risk for harm, protect the rights of individuals and families, and consider societal context in the management of genetic test results. Understanding of these issues is a component of genetic nursing competency that must be addressed at all levels of nursing education.

Generative mechanistic explanation building in undergraduate molecular and cellular biology

NASA Astrophysics Data System (ADS)

Southard, Katelyn M.; Espindola, Melissa R.; Zaepfel, Samantha D.; Bolger, Molly S.

2017-09-01

When conducting scientific research, experts in molecular and cellular biology (MCB) use specific reasoning strategies to construct mechanistic explanations for the underlying causal features of molecular phenomena. We explored how undergraduate students applied this scientific practice in MCB. Drawing from studies of explanation building among scientists, we created and applied a theoretical framework to explore the strategies students use to construct explanations for 'novel' biological phenomena. Specifically, we explored how students navigated the multi-level nature of complex biological systems using generative mechanistic reasoning. Interviews were conducted with introductory and upper-division biology students at a large public university in the United States. Results of qualitative coding revealed key features of students' explanation building. Students used modular thinking to consider the functional subdivisions of the system, which they 'filled in' to varying degrees with mechanistic elements. They also hypothesised the involvement of mechanistic entities and instantiated abstract schema to adapt their explanations to unfamiliar biological contexts. Finally, we explored the flexible thinking that students used to hypothesise the impact of mutations on multi-leveled biological systems. Results revealed a number of ways that students drew mechanistic connections between molecules, functional modules (sets of molecules with an emergent function), cells, tissues, organisms and populations.

The Impact of Unresolved Turbulence on the Escape Fraction of Lyman Continuum Photons

NASA Astrophysics Data System (ADS)

Safarzadeh, M.; Scannapieco, E.

2016-11-01

We investigate the relation between the turbulent Mach number ({ M }) and the escape fraction of Lyman continuum photons ({f}{esc}) in high-redshift galaxies. Approximating the turbulence as isothermal and isotropic, we show that the increase in the variance in column densities from { M }=1 to { M }=10 causes {f}{esc} to increase by ≈ 25%, and the increase from { M }=1 to { M }=20 causes {f}{esc} to increases by ≈ 50% for a medium with opacity τ ≈ 1. At a fixed Mach number, the correction factor for escape fraction relative to a constant column density case scales exponentially with the opacity in the cell, which has a large impact for simulated star-forming regions. Furthermore, in simulations of isotropic turbulence with full atomic/ionic cooling and chemistry, the fraction of HI drops by a factor of ≈ 2.5 at { M }≈ 10 even when the mean temperature is ≈ 5× {10}3 {{K}}. If turbulence is unresolved, these effects together enhance {f}{esc} by a factor \\gt 3 at Mach numbers above 10. Such Mach numbers are common at high redshifts where vigorous turbulence is driven by supernovae, gravitational instabilities, and merger activity, as shown both by numerical simulations and observations. These results, if implemented in the current hydrodynamical cosmological simulations to account for unresolved turbulence, can boost the theoretical predictions of the Lyman Continuum photon escape fraction and further constrain the sources of reionization.

Ebola epidemic of 2014-2015: unresolved ethical issues.

PubMed

Garbuglia, Anna Rosa

2016-01-01

Some ethical aspects of the management of the Ebola epidemic in Guinea, Liberia and Sierra Leone which started in January 2014, have been questionable. First, as regards the prevention of the spread of the virus, the necessary epidemiological investigations on the origin of the infection were not carried out adequately and this did not help to curb the spread of the disease. A disparity has been observed between the western and African countries' access to the treatment of patients; this infringes on the principle of equality. This paper also focuses on how the Global Public Goods for Health principle was not fully respected in the management of the epidemic.

Androgyny as Trait and as Role: Unresolved Issues.

ERIC Educational Resources Information Center

Spence, Janet T.

In the late 1970's androgyny as a concept gained respectability, accompanied, however, by a backlash. Debate centered primarily on scientific grounds and both sides failed to define the concepts of masculinity, femininity and androgyny, including possible cultural relativity. Most empirical research on androgyny uses either the BSRI or the PAQ…

NATO and Hybrid Conflict: Unresolved Issues from the Past or Unresolvable Threats of the Present?

DTIC Science & Technology

2012-09-01

order to strengthen the relationship between the UK and France, the Treaty of Dunkirk was signed in March 1947 expressing the Western European... Dunkirk Treaty was mainly a projection of European concerns about the reemergence of German aggression. The Rio Pact was more a representation of

The Contribution of z < or Approx. 6 Sources to the Spatial Coherence in the Unresolved Cosmic Near-Infrared and X-Ray Backgrounds

NASA Technical Reports Server (NTRS)

Helgason, K.; Cappelluti, N.; Hasinger, G.; Kashlinsky, A.; Ricotti, M.

2014-01-01

A spatial clustering signal has been established in Spitzer/IRAC measurements of the unresolved cosmic near-infrared background (CIB) out to large angular scales, approx. 1deg. This CIB signal, while significantly exceeding the contribution from the remaining known galaxies, was further found to be coherent at a highly statistically significant level with the unresolved soft cosmic X-ray background (CXB). This measurement probes the unresolved CXB to very faint source levels using deep near-IR source subtraction.We study contributions from extragalactic populations at low to intermediate redshifts to the measured positive cross-power signal of the CIB fluctuations with the CXB. We model the X-ray emission from active galactic nuclei (AGNs), normal galaxies, and hot gas residing in virialized structures, calculating their CXB contribution including their spatial coherence with all infrared emitting counterparts. We use a halo model framework to calculate the auto and cross-power spectra of the unresolved fluctuations based on the latest constraints of the halo occupation distribution and the biasing of AGNs, galaxies, and diffuse emission. At small angular scales (1), the 4.5microns versus 0.5-2 keV coherence can be explained by shot noise from galaxies and AGNs. However, at large angular scales (approx.10), we find that the net contribution from the modeled populations is only able to account for approx. 3% of the measured CIB×CXB cross-power. The discrepancy suggests that the CIB×CXB signal originates from the same unknown source population producing the CIB clustering signal out to approx. 1deg.

A climate-driven mechanistic population model of Aedes albopictus with diapause.

PubMed

Jia, Pengfei; Lu, Liang; Chen, Xiang; Chen, Jin; Guo, Li; Yu, Xiao; Liu, Qiyong

2016-03-24

The mosquito Aedes albopitus is a competent vector for the transmission of many blood-borne pathogens. An important factor that affects the mosquitoes' development and spreading is climate, such as temperature, precipitation and photoperiod. Existing climate-driven mechanistic models overlook the seasonal pattern of diapause, referred to as the survival strategy of mosquito eggs being dormant and unable to hatch under extreme weather. With respect to diapause, several issues remain unaddressed, including identifying the time when diapause eggs are laid and hatched under different climatic conditions, demarcating the thresholds of diapause and non-diapause periods, and considering the mortality rate of diapause eggs. Here we propose a generic climate-driven mechanistic population model of Ae. albopitus applicable to most Ae. albopictus-colonized areas. The new model is an improvement over the previous work by incorporating the diapause behaviors with many modifications to the stage-specific mechanism of the mosquitoes' life-cycle. monthly Container Index (CI) of Ae. albopitus collected in two Chinese cities, Guangzhou and Shanghai is used for model validation. The simulation results by the proposed model is validated with entomological field data by the Pearson correlation coefficient r (2) in Guangzhou (r (2) = 0.84) and in Shanghai (r (2) = 0.90). In addition, by consolidating the effect of diapause-related adjustments and temperature-related parameters in the model, the improvement is significant over the basic model. The model highlights the importance of considering diapause in simulating Ae. albopitus population. It also corroborates that temperature and photoperiod are significant in affecting the population dynamics of the mosquito. By refining the relationship between Ae. albopitus population and climatic factors, the model serves to establish a mechanistic relation to the growth and decline of the species. Understanding this relationship in a better way

Evolutionary and mechanistic theories of aging.

PubMed

Hughes, Kimberly A; Reynolds, Rose M

2005-01-01

Senescence (aging) is defined as a decline in performance and fitness with advancing age. Senescence is a nearly universal feature of multicellular organisms, and understanding why it occurs is a long-standing problem in biology. Here we present a concise review of both evolutionary and mechanistic theories of aging. We describe the development of the general evolutionary theory, along with the mutation accumulation, antagonistic pleiotropy, and disposable soma versions of the evolutionary model. The review of the mechanistic theories focuses on the oxidative stress resistance, cellular signaling, and dietary control mechanisms of life span extension. We close with a discussion of how an approach that makes use of both evolutionary and molecular analyses can address a critical question: Which of the mechanisms that can cause variation in aging actually do cause variation in natural populations?

Eating disorders in adolescence: attachment issues from a developmental perspective

PubMed Central

Gander, Manuela; Sevecke, Kathrin; Buchheim, Anna

2015-01-01

In the present article we review findings from an emerging body of research on attachment issues in adolescents with eating disorders from a developmental perspective. Articles for inclusion in this review were identified from PsychINFO (1966–2013), Sciencedirect (1970–2013), Psychindex (1980–2013), and Pubmed (1980–2013). First, we will outline the crucial developmental changes in the attachment system and discuss how they might be related to the early onset of the disease. Then we will report on the major results from attachment studies using self-report and narrative instruments in that age group. Studies with a developmental approach on attachment will be analyzed in more detail. The high incidence of the unresolved attachment pattern in eating disorder samples is striking, especially for patients with anorexia nervosa. Interestingly, this predominance of the unresolved category was also found in their mothers. To date, these transgenerational aspects are still poorly understood and therefore represent an exciting research frontier. Future studies that include larger adolescent samples and provide a more detailed description including symptom severity and comorbidity would contribute to a better understanding of this complex and painful condition. PMID:26321974

"Ratio via Machina": Three Standards of Mechanistic Explanation in Sociology

ERIC Educational Resources Information Center

Aviles, Natalie B.; Reed, Isaac Ariail

2017-01-01

Recently, sociologists have expended much effort in attempts to define social mechanisms. We intervene in these debates by proposing that sociologists in fact have a choice to make between three standards of what constitutes a good mechanistic explanation: substantial, formal, and metaphorical mechanistic explanation. All three standards are…

THE EFFECT OF UNRESOLVED BINARIES ON GLOBULAR CLUSTER PROPER-MOTION DISPERSION PROFILES

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

Bianchini, P.; Norris, M. A.; Ven, G. van de

2016-03-20

High-precision kinematic studies of globular clusters (GCs) require an accurate knowledge of all possible sources of contamination. Among other sources, binary stars can introduce systematic biases in the kinematics. Using a set of Monte Carlo cluster simulations with different concentrations and binary fractions, we investigate the effect of unresolved binaries on proper-motion dispersion profiles, treating the simulations like Hubble Space Telescope proper-motion samples. Since GCs evolve toward a state of partial energy equipartition, more-massive stars lose energy and decrease their velocity dispersion. As a consequence, on average, binaries have a lower velocity dispersion, since they are more-massive kinematic tracers. Wemore » show that, in the case of clusters with high binary fractions (initial binary fractions of 50%) and high concentrations (i.e., closer to energy equipartition), unresolved binaries introduce a color-dependent bias in the velocity dispersion of main-sequence stars of the order of 0.1–0.3 km s{sup −1} (corresponding to 1%−6% of the velocity dispersion), with the reddest stars having a lower velocity dispersion, due to the higher fraction of contaminating binaries. This bias depends on the ability to distinguish binaries from single stars, on the details of the color–magnitude diagram and the photometric errors. We apply our analysis to the HSTPROMO data set of NGC 7078 (M15) and show that no effect ascribable to binaries is observed, consistent with the low binary fraction of the cluster. Our work indicates that binaries do not significantly bias proper-motion velocity-dispersion profiles, but should be taken into account in the error budget of kinematic analyses.« less

CXB surface brightness fluctuations: A new frontier of ICM structure and outskirts studies of (un)resolved galaxy clusters?

NASA Astrophysics Data System (ADS)

Kolodzig, A.; Gilfanov, M.; Hutsi, G.; Sunyaev, R.

2017-10-01

Surface brightness fluctuations of the cosmic X-ray background (CXB) carry unique information about the intracluster-medium (ICM) structure of galaxy clusters and groups up to the virial radius, which is inaccessible by conventional observations of selected nearby resolved clusters. We present results of our CXB fluctuation analysis of the ˜5ks-deep, ˜9deg^2-large Chandra survey XBOOTES. We find that our fluctuation signal of resolved clusters is dominated by nearby, high-luminosity sources. The shape of its power spectrum suggests that for the brightest cluster we are sensitive to the ICM structure up to ˜2× R_{500};(˜2 Mpc/h). The energy spectrum of the fluctuation signal from resolved and unresolved clusters follows a typical ICM spectrum, where redshifts and temperatures are consistent with expectations. It also demonstrates that fluctuations of our unresolved CXB are dominated by unresolved clusters with an average z˜0.4 and T˜1.3keV, suggesting an average L_{0.5-2keV}˜3×10^{42} erg/s and M_{500}˜4×10^{13} M_{Sun}/h. Comparison with modeling suggests, that our fluctuation signal can be described with the one-halo-term of clusters and that it might be sensitive to the presence of substructures. Discrepancies between model and measurement could be utilized to improve our understanding of the ICM structure in a statistical manner. We briefly discuss the potential of larger surveys (e.g. Stripe82, XXL, SRG/eRosita).

Explanation and inference: mechanistic and functional explanations guide property generalization.

PubMed

Lombrozo, Tania; Gwynne, Nicholas Z

2014-01-01

The ability to generalize from the known to the unknown is central to learning and inference. Two experiments explore the relationship between how a property is explained and how that property is generalized to novel species and artifacts. The experiments contrast the consequences of explaining a property mechanistically, by appeal to parts and processes, with the consequences of explaining the property functionally, by appeal to functions and goals. The findings suggest that properties that are explained functionally are more likely to be generalized on the basis of shared functions, with a weaker relationship between mechanistic explanations and generalization on the basis of shared parts and processes. The influence of explanation type on generalization holds even though all participants are provided with the same mechanistic and functional information, and whether an explanation type is freely generated (Experiment 1), experimentally provided (Experiment 2), or experimentally induced (Experiment 2). The experiments also demonstrate that explanations and generalizations of a particular type (mechanistic or functional) can be experimentally induced by providing sample explanations of that type, with a comparable effect when the sample explanations come from the same domain or from a different domains. These results suggest that explanations serve as a guide to generalization, and contribute to a growing body of work supporting the value of distinguishing mechanistic and functional explanations.

Unresolved tensions in consumer engagement in CER: a US research perspective.

PubMed

Workman, Thomas; Maurer, Maureen; Carman, Kristin

2013-03-01

Efforts to engage patients and consumers in comparative effectiveness research (CER) in the USA are still in the early stages, and the outcomes of these partnerships have yet to be fully understood or realized. Our work assisting federal agencies and national organizations who engage patients and consumers in CER reveal three unresolved tensions around the representation of the patient experience in the research process, the culture of research and capacity to partner with patients and consumers, and the conflict between the methodological approaches to CER and the outcomes of interest to patients and caregivers. Several approaches to address these tensions have emerged, yet resolving these tensions will require addressing many system-level challenges and building an evidence base for consumer engagement in CER.

Mechanistic analysis of challenge-response experiments.

PubMed

Shotwell, M S; Drake, K J; Sidorov, V Y; Wikswo, J P

2013-09-01

We present an application of mechanistic modeling and nonlinear longitudinal regression in the context of biomedical response-to-challenge experiments, a field where these methods are underutilized. In this type of experiment, a system is studied by imposing an experimental challenge, and then observing its response. The combination of mechanistic modeling and nonlinear longitudinal regression has brought new insight, and revealed an unexpected opportunity for optimal design. Specifically, the mechanistic aspect of our approach enables the optimal design of experimental challenge characteristics (e.g., intensity, duration). This article lays some groundwork for this approach. We consider a series of experiments wherein an isolated rabbit heart is challenged with intermittent anoxia. The heart responds to the challenge onset, and recovers when the challenge ends. The mean response is modeled by a system of differential equations that describe a candidate mechanism for cardiac response to anoxia challenge. The cardiac system behaves more variably when challenged than when at rest. Hence, observations arising from this experiment exhibit complex heteroscedasticity and sharp changes in central tendency. We present evidence that an asymptotic statistical inference strategy may fail to adequately account for statistical uncertainty. Two alternative methods are critiqued qualitatively (i.e., for utility in the current context), and quantitatively using an innovative Monte-Carlo method. We conclude with a discussion of the exciting opportunities in optimal design of response-to-challenge experiments. © 2013, The International Biometric Society.

MECHANISTIC INDICATORS OF CHILDHOOD ASTHMA (MICA)

EPA Science Inventory

The US Environmental Protection Agency (EPA) is interested in the interplay of environmental and genetic factors on the development and exacerbation of asthma. The Mechanistic Indicators of Childhood Asthma (MICA) study will use exposure measurements and markers of environmental ...

Current issues relating to psychosocial job strain and cardiovascular disease research.

PubMed

Theorell, T; Karasek, R A

1996-01-01

The authors comment on recent reviews of cardiovascular job strain research by P. L. Schnall and P. A. Landsbergis (1994), and by T. S. Kristensen (1995), which conclude that job strain as defined by the demand-control model (the combination of contributions of low job decision latitudes and high psychological job demands) is confirmed as a risk factor for cardiovascular mortality in a large majority of studies. Lack of social support at work appears to further increase risk. Several still-unresolved research questions are examined in light of recent studies: (a) methodological issues related to use of occupational aggregate estimations and occupational career aggregate assessments, use of standard scales for job analysis and recall bias issues in self-reporting; (b) confounding factors and differential strengths of association by subgroups in job strain-cardiovascular disease analyses with respect to social class, gender, and working hours; and (c) review of results of monitoring job strain-blood pressure associations and associated methodological issues.

Managing mechanistic and organic structure in health care organizations.

PubMed

Olden, Peter C

2012-01-01

Managers at all levels in a health care organization must organize work to achieve the organization's mission and goals. This requires managers to decide the organization structure, which involves dividing the work among jobs and departments and then coordinating them all toward the common purpose. Organization structure, which is reflected in an organization chart, may range on a continuum from very mechanistic to very organic. Managers must decide how mechanistic versus how organic to make the entire organization and each of its departments. To do this, managers should carefully consider 5 factors for the organization and for each individual department: external environment, goals, work production, size, and culture. Some factors may push toward more mechanistic structure, whereas others may push in the opposite direction toward more organic structure. Practical advice can help managers at all levels design appropriate structure for their departments and organization.

Assessing 1D Atmospheric Solar Radiative Transfer Models: Interpretation and Handling of Unresolved Clouds.

NASA Astrophysics Data System (ADS)

Barker, H. W.; Stephens, G. L.; Partain, P. T.; Bergman, J. W.; Bonnel, B.; Campana, K.; Clothiaux, E. E.; Clough, S.; Cusack, S.; Delamere, J.; Edwards, J.; Evans, K. F.; Fouquart, Y.; Freidenreich, S.; Galin, V.; Hou, Y.; Kato, S.; Li, J.;  Mlawer, E.;  Morcrette, J.-J.;  O'Hirok, W.;  Räisänen, P.;  Ramaswamy, V.;  Ritter, B.;  Rozanov, E.;  Schlesinger, M.;  Shibata, K.;  Sporyshev, P.;  Sun, Z.;  Wendisch, M.;  Wood, N.;  Yang, F.

2003-08-01

The primary purpose of this study is to assess the performance of 1D solar radiative transfer codes that are used currently both for research and in weather and climate models. Emphasis is on interpretation and handling of unresolved clouds. Answers are sought to the following questions: (i) How well do 1D solar codes interpret and handle columns of information pertaining to partly cloudy atmospheres? (ii) Regardless of the adequacy of their assumptions about unresolved clouds, do 1D solar codes perform as intended?One clear-sky and two plane-parallel, homogeneous (PPH) overcast cloud cases serve to elucidate 1D model differences due to varying treatments of gaseous transmittances, cloud optical properties, and basic radiative transfer. The remaining four cases involve 3D distributions of cloud water and water vapor as simulated by cloud-resolving models. Results for 25 1D codes, which included two line-by-line (LBL) models (clear and overcast only) and four 3D Monte Carlo (MC) photon transport algorithms, were submitted by 22 groups. Benchmark, domain-averaged irradiance profiles were computed by the MC codes. For the clear and overcast cases, all MC estimates of top-of-atmosphere albedo, atmospheric absorptance, and surface absorptance agree with one of the LBL codes to within ±2%. Most 1D codes underestimate atmospheric absorptance by typically 15-25 W m-2 at overhead sun for the standard tropical atmosphere regardless of clouds.Depending on assumptions about unresolved clouds, the 1D codes were partitioned into four genres: (i) horizontal variability, (ii) exact overlap of PPH clouds, (iii) maximum/random overlap of PPH clouds, and (iv) random overlap of PPH clouds. A single MC code was used to establish conditional benchmarks applicable to each genre, and all MC codes were used to establish the full 3D benchmarks. There is a tendency for 1D codes to cluster near their respective conditional benchmarks, though intragenre variances typically exceed those for

Dependence of NOAA-AVHRR recorded radiance on scan angle, atmospheric turbidity and unresolved cloud

NASA Technical Reports Server (NTRS)

Piwinski, D. J.; Schoch, L. B.; Duggin, M. J.; Whitehead, V.; Ryland, E.

1984-01-01

Experimental evidence on the scan angle and sun angle dependence of radiance recorded by the Advanced Very High Resolution Radiometer (AVHRR) devices on the NOAA-6 and NOAA-7 satellites is presented. The effects of atmospheric turbidity at various scan angles is shown, and simulations of angular anisotropy and recorded radiance are compared with the recorded digital data from the AVHRR obtained over the Great Plains area of the US. Evidence is presented on the effects of unresolved cloud on the recorded radiance and vegetative indices from uniform, vegetative targets.

Delivery Issues in the Day Care Debate. Occasional Papers in Education: Paper No. 2 - Policy Studies of the Early Childhood Planning Project.

ERIC Educational Resources Information Center

McGee, Maureen

The question of who should provide day care services is an unresolved issue in the current day care debate and a topic now on the national agenda because it is the common concern of a constellation of diverse, highly motivated interest groups. Motivation for extending day care in the United States stems from several factors: among these are the…

Development of Alabama traffic factors for use in mechanistic-empirical pavement design.

DOT National Transportation Integrated Search

2015-02-01

The pavement engineering community is moving toward design practices that use mechanistic-empirical (M-E) approaches to the design and analysis of pavement structures. This effort is : embodied in the Mechanistic-Empirical Pavement Design Guide (MEPD...

Mechanistic materials modeling for nuclear fuel performance

DOE PAGES

Tonks, Michael R.; Andersson, David; Phillpot, Simon R.; ...

2017-03-15

Fuel performance codes are critical tools for the design, certification, and safety analysis of nuclear reactors. However, their ability to predict fuel behavior under abnormal conditions is severely limited by their considerable reliance on empirical materials models correlated to burn-up (a measure of the number of fission events that have occurred, but not a unique measure of the history of the material). In this paper, we propose a different paradigm for fuel performance codes to employ mechanistic materials models that are based on the current state of the evolving microstructure rather than burn-up. In this approach, a series of statemore » variables are stored at material points and define the current state of the microstructure. The evolution of these state variables is defined by mechanistic models that are functions of fuel conditions and other state variables. The material properties of the fuel and cladding are determined from microstructure/property relationships that are functions of the state variables and the current fuel conditions. Multiscale modeling and simulation is being used in conjunction with experimental data to inform the development of these models. Finally, this mechanistic, microstructure-based approach has the potential to provide a more predictive fuel performance capability, but will require a team of researchers to complete the required development and to validate the approach.« less

Kinetic Profiling of Catalytic Organic Reactions as a Mechanistic Tool.

PubMed

Blackmond, Donna G

2015-09-02

The use of modern kinetic tools to obtain virtually continuous reaction progress data over the course of a catalytic reaction opens up a vista that provides mechanistic insights into both simple and complex catalytic networks. Reaction profiles offer a rate/concentration scan that tells the story of a batch reaction time course in a qualitative "fingerprinting" manner as well as in quantitative detail. Reaction progress experiments may be mathematically designed to elucidate catalytic rate laws from only a fraction of the number of experiments required in classical kinetic measurements. The information gained from kinetic profiles provides clues to direct further mechanistic analysis by other approaches. Examples from a variety of catalytic reactions spanning two decades of the author's work help to delineate nuances on a central mechanistic theme.

Improving Interpretation of New and Old Serum Biomarkers of Drug-Induced Liver Injury Through Mechanistic Modeling.

PubMed

Watkins, Paul B

2018-04-26

The study by Mason et al. in this issue used mechanistic modeling and simulation to address how both the dose of acetaminophen consumed and the time since ingestion can be estimated from biomarkers measured in a single serum sample in mice. Translation into the clinic would potentially be an advance in the treatment of acetaminophen poisoning. Importantly, this approach could transform the evaluation of liver safety in clinical trials of new drug candidates. © 2018 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Identifying ethical issues of the Department of the Army civilian and Army Nurse Corps certified registered nurse anesthetists.

PubMed

Jenkins, Constance L; Elliott, Aaron R; Harris, Janet R

2006-08-01

The purposes of this study were to identify the ethical issues Department of the Army civilian and Army Nurse Corps certified registered nurse anesthetists (CRNAs) encountered in their anesthesia practice and how disturbed they were by these issues. This descriptive study used a secondary data analysis of a cross-sectional survey of Army Nurse Corps officers and Department of the Army civilian registered nurses (N = 5,293). The CRNA subset (n = 97) was obtained from questionnaires that indicated a primary practice setting as anesthesia. The most frequently occurring ethical issue identified was conflict in the nurse-physician relationship, whereas the most disturbing issue was working with incompetent/impaired colleagues. Unresolved ethical conflicts can negatively influence the nurses' morale, leading to avoidance of the issue and contributing to burnout. Identifying the ethical issues and disturbance level experienced by CRNAs should contribute to the development of an ethics education program that addresses issues encountered in CRNA practice.

Mechanistic Links Between PARP, NAD, and Brain Inflammation After TBI

DTIC Science & Technology

2015-10-01

1 AWARD NUMBER: W81XWH-13-2-0091 TITLE: Mechanistic Links Between PARP, NAD , and Brain Inflammation After TBI PRINCIPAL INVESTIGATOR...COVERED 25 Sep 2014 - 24 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Mechanistic Links Between PARP, NAD , and Brain Inflammation After TBI 5b. GRANT...efficacy of veliparib and NAD as agents for suppressing inflammation and improving outcomes after traumatic brain injury. The animal models include

Fast charging technique for high power LiFePO4 batteries: A mechanistic analysis of aging

NASA Astrophysics Data System (ADS)

Anseán, D.; Dubarry, M.; Devie, A.; Liaw, B. Y.; García, V. M.; Viera, J. C.; González, M.

2016-07-01

One of the major issues hampering the acceptance of electric vehicles (EVs) is the anxiety associated with long charging time. Hence, the ability to fast charging lithium-ion battery (LIB) systems is gaining notable interest. However, fast charging is not tolerated by all LIB chemistries because it affects battery functionality and accelerates its aging processes. Here, we investigate the long-term effects of multistage fast charging on a commercial high power LiFePO4-based cell and compare it to another cell tested under standard charging. Coupling incremental capacity (IC) and IC peak area analysis together with mechanistic model simulations ('Alawa' toolbox with harvested half-cell data), we quantify the degradation modes that cause aging of the tested cells. The results show that the proposed fast charging technique caused similar aging effects as standard charging. The degradation is caused by a linear loss of lithium inventory, coupled with a less degree of linear loss of active material on the negative electrode. This study validates fast charging as a feasible mean of operation for this particular LIB chemistry and cell architecture. It also illustrates the benefits of a mechanistic approach to understand cell degradation on commercial cells.

New Theoretical Estimates of the Contribution of Unresolved Star-Forming Galaxies to the Extragalactic Gamma-Ray Background (EGB) as Measured by EGRET and the Fermi-LAT

NASA Technical Reports Server (NTRS)

Venters, Tonia M.

2011-01-01

We present new theoretical estimates of the contribution of unresolved star-forming galaxies to the extragalactic gamma-ray background (EGB) as measured by EGRET and the Fermi-LAT. We employ several methods for determining the star-forming galaxy contribution the the EGB, including a method positing a correlation between the gamma-ray luminosity of a galaxy and its rate of star formation as calculated from the total infrared luminosity, and a method that makes use of a model of the evolution of the galaxy gas mass with cosmic time. We find that depending on the model, unresolved star-forming galaxies could contribute significantly to the EGB as measured by the Fermi-LAT at energies between approx. 300 MeV and approx. few GeV. However, the overall spectrum of unresolved star-forming galaxies can explain neither the EGRET EGB spectrum at energies between 50 and 200 MeV nor the Fermi-LAT EGB spectrum at energies above approx. few GeV.

Fine particulate matter air pollution and atherosclerosis: Mechanistic insights.

PubMed

Bai, Yuntao; Sun, Qinghua

2016-12-01

Atherosclerosis is a progressive disease characterized by the accumulation of lipids and fibrous plaque in the arteries. Its etiology is very complicated and its risk factors primarily include genetic defects, smoking, hyperlipidemia, hypertension, lack of exercise, and infection. Recent studies suggest that fine particulate matter (PM2.5) air pollution may also contribute to the development of atherosclerosis. The present review integrates current experimental evidence with mechanistic pathways whereby PM2.5 exposure can promote the development of atherosclerosis. PM2.5-mediated enhancement of atherosclerosis is likely due to its pro-oxidant and pro-inflammatory effects, involving multiple organs, different cell types, and various molecular mediators. Studies about the effects of PM2.5inhalation on atherosclerosis may yield a better understanding of the link between air pollution and major cardiovascular diseases, and provide useful information for policy makers to determine acceptable levels of PM2.5 air quality. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu. Copyright © 2016 Elsevier B.V. All rights reserved.

Status of thermalhydraulic modelling and assessment: Open issues

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

Bestion, D.; Barre, F.

1997-07-01

This paper presents the status of the physical modelling in present codes used for Nuclear Reactor Thermalhydraulics (TRAC, RELAP 5, CATHARE, ATHLET,...) and attempts to list the unresolved or partially resolved issues. First, the capabilities and limitations of present codes are presented. They are mainly known from a synthesis of the assessment calculations performed for both separate effect tests and integral effect tests. It is also interesting to list all the assumptions and simplifications which were made in the establishment of the system of equations and of the constitutive relations. Many of the present limitations are associated to physical situationsmore » where these assumptions are not valid. Then, recommendations are proposed to extend the capabilities of these codes.« less

The Newtonian Mechanistic Paradigm, Special Education, and Contours of Alternatives: An Overview.

ERIC Educational Resources Information Center

Heshusius, Lous

1989-01-01

The article examines theoretical reorientations in special education away from the Newtonian mechanistic paradigm toward an emerging holistic paradigm. Recent literature is critiqued for renaming theories as paradigms, thereby providing an illusion of change while leaving fundamental mechanistic assumptions in place. (Author/DB)

Progress Towards an LES Wall Model Including Unresolved Roughness

NASA Astrophysics Data System (ADS)

Craft, Kyle; Redman, Andrew; Aikens, Kurt

2015-11-01

Wall models used in large eddy simulations (LES) are often based on theories for hydraulically smooth walls. While this is reasonable for many applications, there are also many where the impact of surface roughness is important. A previously developed wall model has been used primarily for jet engine aeroacoustics. However, jet simulations have not accurately captured thick initial shear layers found in some experimental data. This may partly be due to nozzle wall roughness used in the experiments to promote turbulent boundary layers. As a result, the wall model is extended to include the effects of unresolved wall roughness through appropriate alterations to the log-law. The methodology is tested for incompressible flat plate boundary layers with different surface roughness. Correct trends are noted for the impact of surface roughness on the velocity profile. However, velocity deficit profiles and the Reynolds stresses do not collapse as well as expected. Possible reasons for the discrepancies as well as future work will be presented. This work used the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by National Science Foundation grant number ACI-1053575. Computational resources on TACC Stampede were provided under XSEDE allocation ENG150001.

Mechanistic model for catalytic recombination during aerobraking maneuvers

NASA Technical Reports Server (NTRS)

Willey, Ronald J.

1989-01-01

Several mechanistic models are developed to predict recombination coefficients for use in heat shield design for reusable surface insulation (RSI) on aerobraking vehicles such as space shuttles. The models are applied over a temperature range of 300 to 1800 K and a stagnation pressure range of 0 to 3,000 Pa. A four parameter model in temperature was found to work best; however, several models (including those with atom concentrations at the surface) were also investigated. Mechanistic models developed with atom concentration terms may be applicable when sufficient data becomes available. The requirement is shown for recombination experiments in the 300 to 1000 K and 1500 to 1850 K temperature range, with deliberate concentration variations.

Mechanistic Biomarkers in Acetaminophen-induced Hepatotoxicity and Acute Liver Failure: From Preclinical Models to Patients

PubMed Central

McGill, Mitchell R.; Jaeschke, Hartmut

2015-01-01

SUMMARY Introduction Drug hepatotoxicity is a major clinical issue. Acetaminophen (APAP) overdose is especially common. Serum biomarkers used to follow patient progress reflect either liver injury or function, but focus on biomarkers that can provide insight into the basic mechanisms of hepatotoxicity is increasing and enabling us to translate mechanisms of toxicity from animal models to humans. Areas covered We review recent advances in mechanistic serum biomarker research in drug hepatotoxicity. Specifically, biomarkers for reactive drug intermdiates, mitochondrial dysfunction, nuclear DNA damage, mode of cell death and inflammation are discussed, as well as microRNAs. Emphasis is placed on APAP-induced liver injury. Expert Opinion Several serum biomarkers of reactive drug intermediates, mitochondrial damage, nuclear DNA damage, apoptosis and necrosis, and inflammation have been described. These studies have provided evidence that mitochondrial damage is critical in APAP hepatotoxicity in humans, while apoptosis has only a minor role, and inflammation is important for recovery and regeneration after APAP overdose. Additionally, mechanistic serum biomarkers have been shown to predict outcome as well as, or better than, some clinical scores. In the future, such biomarkers will help determine the need for liver transplantation and, with improved understanding of the human pathophysiology, identify novel therapeutic targets. PMID:24836926

Specialists without spirit: limitations of the mechanistic biomedical model.

PubMed

Hewa, S; Hetherington, R W

1995-06-01

This paper examines the origin and the development of the mechanistic model of the human body and health in terms of Max Weber's theory of rationalization. It is argued that the development of Western scientific medicine is a part of the broad process of rationalization that began in sixteenth century Europe as a result of the Reformation. The development of the mechanistic view of the human body in Western medicine is consistent with the ideas of calculability, predictability, and control-the major tenets of the process of rationalization as described by Weber. In recent years, however, the limitations of the mechanistic model have been the topic of many discussions. George Engel, a leading advocate of general systems theory, is one of the leading proponents of a new medical model which includes the general quality of life, clean environment, and psychological, or spiritual stability of life. The paper concludes with consideration of the potential of Engel's proposed new model in the context of the current state of rationalization in modern industrialized society.

X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes.

PubMed

Hu, H; Haas, S A; Chelly, J; Van Esch, H; Raynaud, M; de Brouwer, A P M; Weinert, S; Froyen, G; Frints, S G M; Laumonnier, F; Zemojtel, T; Love, M I; Richard, H; Emde, A-K; Bienek, M; Jensen, C; Hambrock, M; Fischer, U; Langnick, C; Feldkamp, M; Wissink-Lindhout, W; Lebrun, N; Castelnau, L; Rucci, J; Montjean, R; Dorseuil, O; Billuart, P; Stuhlmann, T; Shaw, M; Corbett, M A; Gardner, A; Willis-Owen, S; Tan, C; Friend, K L; Belet, S; van Roozendaal, K E P; Jimenez-Pocquet, M; Moizard, M-P; Ronce, N; Sun, R; O'Keeffe, S; Chenna, R; van Bömmel, A; Göke, J; Hackett, A; Field, M; Christie, L; Boyle, J; Haan, E; Nelson, J; Turner, G; Baynam, G; Gillessen-Kaesbach, G; Müller, U; Steinberger, D; Budny, B; Badura-Stronka, M; Latos-Bieleńska, A; Ousager, L B; Wieacker, P; Rodríguez Criado, G; Bondeson, M-L; Annerén, G; Dufke, A; Cohen, M; Van Maldergem, L; Vincent-Delorme, C; Echenne, B; Simon-Bouy, B; Kleefstra, T; Willemsen, M; Fryns, J-P; Devriendt, K; Ullmann, R; Vingron, M; Wrogemann, K; Wienker, T F; Tzschach, A; van Bokhoven, H; Gecz, J; Jentsch, T J; Chen, W; Ropers, H-H; Kalscheuer, V M

2016-01-01

X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4(-/-) mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases.

X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes

PubMed Central

Hu, H; Haas, S A; Chelly, J; Van Esch, H; Raynaud, M; de Brouwer, A P M; Weinert, S; Froyen, G; Frints, S G M; Laumonnier, F; Zemojtel, T; Love, M I; Richard, H; Emde, A-K; Bienek, M; Jensen, C; Hambrock, M; Fischer, U; Langnick, C; Feldkamp, M; Wissink-Lindhout, W; Lebrun, N; Castelnau, L; Rucci, J; Montjean, R; Dorseuil, O; Billuart, P; Stuhlmann, T; Shaw, M; Corbett, M A; Gardner, A; Willis-Owen, S; Tan, C; Friend, K L; Belet, S; van Roozendaal, K E P; Jimenez-Pocquet, M; Moizard, M-P; Ronce, N; Sun, R; O'Keeffe, S; Chenna, R; van Bömmel, A; Göke, J; Hackett, A; Field, M; Christie, L; Boyle, J; Haan, E; Nelson, J; Turner, G; Baynam, G; Gillessen-Kaesbach, G; Müller, U; Steinberger, D; Budny, B; Badura-Stronka, M; Latos-Bieleńska, A; Ousager, L B; Wieacker, P; Rodríguez Criado, G; Bondeson, M-L; Annerén, G; Dufke, A; Cohen, M; Van Maldergem, L; Vincent-Delorme, C; Echenne, B; Simon-Bouy, B; Kleefstra, T; Willemsen, M; Fryns, J-P; Devriendt, K; Ullmann, R; Vingron, M; Wrogemann, K; Wienker, T F; Tzschach, A; van Bokhoven, H; Gecz, J; Jentsch, T J; Chen, W; Ropers, H-H; Kalscheuer, V M

2016-01-01

X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4−/− mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases. PMID:25644381

Gas kinematics in FIRE simulated galaxies compared to spatially unresolved H I observations

NASA Astrophysics Data System (ADS)

El-Badry, Kareem; Bradford, Jeremy; Quataert, Eliot; Geha, Marla; Boylan-Kolchin, Michael; Weisz, Daniel R.; Wetzel, Andrew; Hopkins, Philip F.; Chan, T. K.; Fitts, Alex; Kereš, Dušan; Faucher-Giguère, Claude-André

2018-06-01

The shape of a galaxy's spatially unresolved, globally integrated 21-cm emission line depends on its internal gas kinematics: galaxies with rotationally supported gas discs produce double-horned profiles with steep wings, while galaxies with dispersion-supported gas produce Gaussian-like profiles with sloped wings. Using mock observations of simulated galaxies from the FIRE project, we show that one can therefore constrain a galaxy's gas kinematics from its unresolved 21-cm line profile. In particular, we find that the kurtosis of the 21-cm line increases with decreasing V/σ and that this trend is robust across a wide range of masses, signal-to-noise ratios, and inclinations. We then quantify the shapes of 21-cm line profiles from a morphologically unbiased sample of ˜2000 low-redshift, H I-detected galaxies with Mstar = 107-11 M⊙ and compare to the simulated galaxies. At Mstar ≳ 1010 M⊙, both the observed and simulated galaxies produce double-horned profiles with low kurtosis and steep wings, consistent with rotationally supported discs. Both the observed and simulated line profiles become more Gaussian like (higher kurtosis and less-steep wings) at lower masses, indicating increased dispersion support. However, the simulated galaxies transition from rotational to dispersion support more strongly: at Mstar = 108-10 M⊙, most of the simulations produce more Gaussian-like profiles than typical observed galaxies with similar mass, indicating that gas in the low-mass simulated galaxies is, on average, overly dispersion supported. Most of the lower-mass-simulated galaxies also have somewhat lower gas fractions than the median of the observed population. The simulations nevertheless reproduce the observed line-width baryonic Tully-Fisher relation, which is insensitive to rotational versus dispersion support.

Why did Jacques Monod make the choice of mechanistic determinism?

PubMed

Loison, Laurent

2015-06-01

The development of molecular biology placed in the foreground a mechanistic and deterministic conception of the functioning of macromolecules. In this article, I show that this conception was neither obvious, nor necessary. Taking Jacques Monod as a case study, I detail the way he gradually came loose from a statistical understanding of determinism to finally support a mechanistic understanding. The reasons of the choice made by Monod at the beginning of the 1950s can be understood only in the light of the general theoretical schema supported by the concept of mechanistic determinism. This schema articulates three fundamental notions for Monod, namely that of the rigidity of the sequence of the genetic program, that of the intrinsic stability of macromolecules (DNA and proteins), and that of the specificity of molecular interactions. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Polychromatic wave-optics models for image-plane speckle. 2. Unresolved objects.

PubMed

Van Zandt, Noah R; Spencer, Mark F; Steinbock, Michael J; Anderson, Brian M; Hyde, Milo W; Fiorino, Steven T

2018-05-20

Polychromatic laser light can reduce speckle noise in many wavefront-sensing and imaging applications. To help quantify the achievable reduction in speckle noise, this study investigates the accuracy of three polychromatic wave-optics models under the specific conditions of an unresolved object. Because existing theory assumes a well-resolved object, laboratory experiments are used to evaluate model accuracy. The three models use Monte-Carlo averaging, depth slicing, and spectral slicing, respectively, to simulate the laser-object interaction. The experiments involve spoiling the temporal coherence of laser light via a fiber-based, electro-optic modulator. After the light scatters off of the rough object, speckle statistics are measured. The Monte-Carlo method is found to be highly inaccurate, while depth-slicing error peaks at 7.8% but is generally much lower in comparison. The spectral-slicing method is the most accurate, always producing results within the error bounds of the experiment.

MECHANISTIC-BASED DISINFECTION AND DISINFECTION BYPRODUCT MODELS

EPA Science Inventory

We propose developing a mechanistic-based numerical model for chlorine decay and regulated DBP (THM and HAA) formation derived from (free) chlorination; the model framework will allow future modifications for other DBPs and chloramination. Predicted chlorine residual and DBP r...

Mechanistic Indicators of Childhood Asthma (MICA) Study

EPA Science Inventory

The Mechanistic Indicators of Childhood Asthma (MICA) Study has been designed to incorporate state-of-the-art technologies to examine the physiological and environmental factors that interact to increase the risk of asthmatic responses. MICA is primarily a clinically-bases obser...

Simulation analysis of photometric data for attitude estimation of unresolved space objects

NASA Astrophysics Data System (ADS)

Du, Xiaoping; Gou, Ruixin; Liu, Hao; Hu, Heng; Wang, Yang

2017-10-01

The attitude information acquisition of unresolved space objects, such as micro-nano satellites and GEO objects under the way of ground-based optical observations, is a challenge to space surveillance. In this paper, a useful method is proposed to estimate the SO attitude state according to the simulation analysis of photometric data in different attitude states. The object shape model was established and the parameters of the BRDF model were determined, then the space object photometric model was established. Furthermore, the photometric data of space objects in different states are analyzed by simulation and the regular characteristics of the photometric curves are summarized. The simulation results show that the photometric characteristics are useful for attitude inversion in a unique way. Thus, a new idea is provided for space object identification in this paper.

Chronic hyperkalemia in non-dialysis CKD: controversial issues in nephrology practice.

PubMed

De Nicola, Luca; Di Lullo, Luca; Paoletti, Ernesto; Cupisti, Adamasco; Bianchi, Stefano

2018-06-07

Chronic hyperkalemia is a major complication of chronic kidney disease (CKD) that occurs frequently, heralds poor prognosis, and necessitates careful management by the nephrologist. Current strategies aimed at prevention and treatment of hyperkalemia are still suboptimal, as evidenced by the relatively high prevalence of hyperkalemia in patients under stable nephrology care, and even in the ideal setting of randomized trials where best treatment and monitoring are mandatory. The aim of this review was to identify and discuss a range of unresolved issues related to the management of chronic hyperkalemia in non-dialysis CKD. The following topics of clinical interest were addressed: diagnosis, relationship with main comorbidities of CKD, therapy with inhibitors of the renin-angiotensin-aldosterone system, efficacy of current dietary and pharmacological treatment, and the potential role of the new generation of potassium binders. Opinion-based answers are provided for each of these controversial issues.

Chromospheric counterparts of solar transition region unresolved fine structure loops

NASA Astrophysics Data System (ADS)

Pereira, Tiago M. D.; Rouppe van der Voort, Luc; Hansteen, Viggo H.; De Pontieu, Bart

2018-04-01

Low-lying loops have been discovered at the solar limb in transition region temperatures by the Interface Region Imaging Spectrograph (IRIS). They do not appear to reach coronal temperatures, and it has been suggested that they are the long-predicted unresolved fine structures (UFS). These loops are dynamic and believed to be visible during both heating and cooling phases. Making use of coordinated observations between IRIS and the Swedish 1-m Solar Telescope, we study how these loops impact the solar chromosphere. We show for the first time that there is indeed a chromospheric signal of these loops, seen mostly in the form of strong Doppler shifts and a conspicuous lack of chromospheric heating. In addition, we find that several instances have a inverse Y-shaped jet just above the loop, suggesting that magnetic reconnection is driving these events. Our observations add several puzzling details to the current knowledge of these newly discovered structures; this new information must be considered in theoretical models. Two movies associated to Fig. 1 are available at http://https://www.aanda.org

Causal Indicator Models: Unresolved Issues of Construction and Evaluation

ERIC Educational Resources Information Center

West, Stephen G.; Grimm, Kevin J.

2014-01-01

These authors agree with Bainter and Bollen that causal effects represents a useful measurement structure in some applications. The structure of the science of the measurement problem should determine the model; the measurement model should not determine the science. They also applaud Bainter and Bollen's important reminder that the full…

Unresolved issues in the management of chronic stable angina.

PubMed

Camm, A John; Manolis, Athanasios; Ambrosio, Giuseppe; Daly, Caroline; Komajda, Michel; Lopez de Sa, Esteban; Lopez-Sendon, Jose Luis; Mugelli, Alessandro; Muggli, Franco; Tamargo, Juan

2015-12-15

Chronic stable angina is a common and progressive disease which has a major impact on patient quality of life and imposes a high financial and medical burden on society. Given the range of agents now available, optimal medical therapy - which according to guidelines is the preferred option in the majority of patients with low-risk disease - offers the opportunity for effective control. However, recent studies suggest that management remains suboptimal in up to a third of patients and that physicians often underestimate the extent to which angina continues to limit patients' lives. A higher frequency of angina also relates directly to increased healthcare costs. These factors suggest the need for the development and implementation of appropriate guidelines, for tools to encourage the regular, systematic assessment of the management of chronic stable angina patients, and for improved means of communication between doctors and patients. Neither physicians nor their patients need to accept that a certain level of angina symptoms is unavoidable. Copyright © 2015. Published by Elsevier Ireland Ltd.

Unresolved antiretroviral treatment management issues in HIV-infected children.

PubMed

Heidari, Shirin; Mofenson, Lynne M; Hobbs, Charlotte V; Cotton, Mark F; Marlink, Richard; Katabira, Elly

2012-02-01

Antiretroviral therapy in children has expanded dramatically in low-income and middle-income countries. The World Health Organization revised its pediatric HIV guidelines to recommend initiation of antiretroviral therapy in all HIV-infected children younger than 2 years, regardless of CD4 count or clinical stage. The number of children starting life-long antiretroviral therapy should therefore expand dramatically over time. The early initiation of antiretroviral therapy has indisputable benefits for children, but there is a paucity of definitive information on the potential adverse effects. In this review, a comprehensive literature search was conducted to provide an overview of our knowledge about the complications of treating pediatric HIV. Antiretroviral therapy in children, as in adults, is associated with enhanced survival, reduction in opportunistic infections, improved growth and neurocognitive function, and better quality of life. Despite antiretroviral therapy, HIV-infected children may continue to lag behind their uninfected peers in growth and development. In addition, epidemic concurrent conditions, such as tuberculosis, malaria, and malnutrition, can combine with HIV to yield more rapid disease progression and poor treatment outcomes. Additional studies are required to evaluate the long-term effects of antiretroviral therapy in HIV-infected infants, children, and adolescents, particularly in resource-limited countries where concomitant infections and conditions may enhance the risk of adverse effects. There is an urgent need to evaluate drug-drug interactions in children to determine optimal treatment regimens for both HIV and coinfections.

Attachment-based family therapy and emotion-focused therapy for unresolved anger: The role of productive emotional processing.

PubMed

Diamond, Gary M; Shahar, Ben; Sabo, Daphna; Tsvieli, Noa

2016-03-01

A growing body of research suggests that emotional processing is a central and common change mechanism across various types of therapies (Diener & Hilsenroth, 2009; Foa, Huppert, & Cahill, 2006; Greenberg, 2011). This study examined whether 10 weeks of attachment-based family therapy (ABFT), characterized by the use of in-session young adult-parent dialogues, were more effective than 10 weeks of individual emotion-focused therapy (EFT), characterized by the use of imaginal dialogues, in terms of facilitating productive emotional processing among a sample of 32 young adults presenting with unresolved anger toward a parent. This study also examined whether greater amounts of productive emotional processing predicted more favorable treatment outcomes. In contrast to our expectations, we found significantly more productive emotional processing in individual EFT than in conjoint ABFT. Results also showed that while both treatments led to significant and equivalent decreases in unresolved anger, state anger, attachment anxiety, and psychological symptoms, only ABFT was associated with decreases in attachment avoidance. Although amount of emotional processing did not explain the unique decrease in attachment avoidance in ABFT, greater amounts of productive emotional processing predicted greater decreases in psychological symptoms (but not other outcome measures) across both treatments. (c) 2016 APA, all rights reserved).

Exploring Organic Mechanistic Puzzles with Molecular Modeling

ERIC Educational Resources Information Center

Horowitz, Gail; Schwartz, Gary

2004-01-01

The molecular modeling was used to reinforce more general skills such as deducing and drawing reaction mechanisms, analyzing reaction kinetics and thermodynamics and drawing reaction coordinate energy diagrams. This modeling was done through the design of mechanistic puzzles, involving reactions not familiar to the students.

A subtraction scheme for computing QCD jet cross sections at NNLO: integrating the doubly unresolved subtraction terms

NASA Astrophysics Data System (ADS)

Somogyi, Gábor

2013-04-01

We finish the definition of a subtraction scheme for computing NNLO corrections to QCD jet cross sections. In particular, we perform the integration of the soft-type contributions to the doubly unresolved counterterms via the method of Mellin-Barnes representations. With these final ingredients in place, the definition of the scheme is complete and the computation of fully differential rates for electron-positron annihilation into two and three jets at NNLO accuracy becomes feasible.

Human Health Effects of Biphenyl: Key Findings and Scientific Issues.

PubMed

Li, Zheng; Hogan, Karen A; Cai, Christine; Rieth, Susan

2016-06-01

In support of the Integrated Risk Information System (IRIS), the U.S. Environmental Protection Agency (EPA) has evaluated the human health hazards of biphenyl exposure. We review key findings and scientific issues regarding expected human health effects of biphenyl. Scientific literature from 1926 through September 2012 was critically evaluated to identify potential human health hazards associated with biphenyl exposure. Key issues related to the carcinogenicity and noncancer health hazards of biphenyl were examined based on evidence from experimental animal bioassays and mechanistic studies. Systematic consideration of experimental animal studies of oral biphenyl exposure took into account the variety of study designs (e.g., study sizes, exposure levels, and exposure durations) to reconcile differing reported results. The available mechanistic and toxicokinetic evidence supports the hypothesis that male rat urinary bladder tumors arise through urinary bladder calculi formation but is insufficient to hypothesize a mode of action for liver tumors in female mice. Biphenyl and its metabolites may induce genetic damage, but a role for genotoxicity in biphenyl-induced carcinogenicity has not been established. The available health effects data for biphenyl provides suggestive evidence for carcinogenicity in humans, based on increased incidences of male rat urinary bladder tumors at high exposure levels and on female mouse liver tumors. Kidney toxicity is also a potential human health hazard of biphenyl exposure. Li Z, Hogan KA, Cai C, Rieth S. 2016. Human health effects of biphenyl: key findings and scientific issues. Environ Health Perspect 124:703-712; http://dx.doi.org/10.1289/ehp.1509730.

Human Health Effects of Biphenyl: Key Findings and Scientific Issues

PubMed Central

Li, Zheng; Hogan, Karen A.; Cai, Christine; Rieth, Susan

2015-01-01

Background: In support of the Integrated Risk Information System (IRIS), the U.S. Environmental Protection Agency (EPA) has evaluated the human health hazards of biphenyl exposure. Objectives: We review key findings and scientific issues regarding expected human health effects of biphenyl. Methods: Scientific literature from 1926 through September 2012 was critically evaluated to identify potential human health hazards associated with biphenyl exposure. Key issues related to the carcinogenicity and noncancer health hazards of biphenyl were examined based on evidence from experimental animal bioassays and mechanistic studies. Discussion: Systematic consideration of experimental animal studies of oral biphenyl exposure took into account the variety of study designs (e.g., study sizes, exposure levels, and exposure durations) to reconcile differing reported results. The available mechanistic and toxicokinetic evidence supports the hypothesis that male rat urinary bladder tumors arise through urinary bladder calculi formation but is insufficient to hypothesize a mode of action for liver tumors in female mice. Biphenyl and its metabolites may induce genetic damage, but a role for genotoxicity in biphenyl-induced carcinogenicity has not been established. Conclusions: The available health effects data for biphenyl provides suggestive evidence for carcinogenicity in humans, based on increased incidences of male rat urinary bladder tumors at high exposure levels and on female mouse liver tumors. Kidney toxicity is also a potential human health hazard of biphenyl exposure. Citation: Li Z, Hogan KA, Cai C, Rieth S. 2016. Human health effects of biphenyl: key findings and scientific issues. Environ Health Perspect 124:703–712; http://dx.doi.org/10.1289/ehp.1509730 PMID:26529796

Food for Thought ... Mechanistic Validation

PubMed Central

Hartung, Thomas; Hoffmann, Sebastian; Stephens, Martin

2013-01-01

Summary Validation of new approaches in regulatory toxicology is commonly defined as the independent assessment of the reproducibility and relevance (the scientific basis and predictive capacity) of a test for a particular purpose. In large ring trials, the emphasis to date has been mainly on reproducibility and predictive capacity (comparison to the traditional test) with less attention given to the scientific or mechanistic basis. Assessing predictive capacity is difficult for novel approaches (which are based on mechanism), such as pathways of toxicity or the complex networks within the organism (systems toxicology). This is highly relevant for implementing Toxicology for the 21st Century, either by high-throughput testing in the ToxCast/ Tox21 project or omics-based testing in the Human Toxome Project. This article explores the mostly neglected assessment of a test's scientific basis, which moves mechanism and causality to the foreground when validating/qualifying tests. Such mechanistic validation faces the problem of establishing causality in complex systems. However, pragmatic adaptations of the Bradford Hill criteria, as well as bioinformatic tools, are emerging. As critical infrastructures of the organism are perturbed by a toxic mechanism we argue that by focusing on the target of toxicity and its vulnerability, in addition to the way it is perturbed, we can anchor the identification of the mechanism and its verification. PMID:23665802

A preliminary study of mechanistic approach in pavement design to accommodate climate change effects

NASA Astrophysics Data System (ADS)

Harnaeni, S. R.; Pramesti, F. P.; Budiarto, A.; Setyawan, A.

2018-03-01

Road damage is caused by some factors, including climate changes, overload, and inappropriate procedure for material and development process. Meanwhile, climate change is a phenomenon which cannot be avoided. The effects observed include air temperature rise, sea level rise, rainfall changes, and the intensity of extreme weather phenomena. Previous studies had shown the impacts of climate changes on road damage. Therefore, several measures to anticipate the damage should be considered during the planning and construction in order to reduce the cost of road maintenance. There are three approaches generally applied in the design of flexible pavement thickness, namely mechanistic approach, mechanistic-empirical (ME) approach and empirical approach. The advantages of applying mechanistic approach or mechanistic-empirical (ME) approaches are its efficiency and reliability in the design of flexible pavement thickness as well as its capacity to accommodate climate changes in compared to empirical approach. However, generally, the design of flexible pavement thickness in Indonesia still applies empirical approach. This preliminary study aimed to emphasize the importance of the shifting towards a mechanistic approach in the design of flexible pavement thickness.

Fluorescence Cross-Correlation Spectroscopy Reveals Mechanistic Insights into the Effect of 2′-O-Methyl Modified siRNAs in Living Cells

PubMed Central

Ohrt, Thomas; Staroske, Wolfgang; Mütze, Jörg; Crell, Karin; Landthaler, Markus; Schwille, Petra

2011-01-01

RNA interference (RNAi) offers a powerful tool to specifically direct the degradation of complementary RNAs, and thus has great therapeutic potential for targeting diseases. Despite the reported preferences of RNAi, there is still a need for new techniques that will allow for a detailed mechanistic characterization of RNA-induced silencing complex (RISC) assembly and activity to further improve the biocompatibility of modified siRNAs. In contrast to previous reports, we investigated the effects of 2′-O-methyl (2′OMe) modifications introduced at specific positions within the siRNA at the early and late stages of RISC assembly, as well as their influence on target recognition and cleavage directly in living cells. We found that six to 10 2′OMe nucleotides on the 3′-end inhibit passenger-strand release as well as target-RNA cleavage without changing the affinity, strand asymmetry, or target recognition. 2′OMe modifications introduced at the 5′-end reduced activated RISC stability, whereas incorporations at the cleavage site showed only minor effects on passenger-strand release when present on the passenger strand. Our new fluorescence cross-correlation spectroscopy assays resolve different steps and stages of RISC assembly and target recognition with heretofore unresolved detail in living cells, which is needed to develop therapeutic siRNAs with optimized in vivo properties. PMID:21689532

AASHTO mechanistic-empirical pavement design guide parametric study.

DOT National Transportation Integrated Search

2012-03-01

This study focuses on assessing the robustness of the AASHTO Mechanistic-Empirical Pavement Design Guide (MEPDG v 1.1) for rigid pavement : design projects in Wisconsin. The primary tasks conducted in this study included performing sensitivity analys...

Atopic Dermatitis According to GARP: New Mechanistic Insights in Disease Pathogenesis.

PubMed

Nousbeck, Janna; Irvine, Alan D

2016-12-01

In complex disease such as atopic dermatitis, the journey from identification of strong risk loci to profound functional and mechanistic insights can take several years. Here, Manz et al. have elegantly deciphered the mechanistic pathways in the well-established 11q13.5 atopic dermatitis risk locus. Their genetic and functional insights emphasize a role for T regulatory cells in atopic dermatitis pathogenesis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Physician Perspectives on Unresolved Issues in the Management of Ulcerative Colitis: The UC Horizons Project.

PubMed

Gisbert, Javier P; Barreiro-de Acosta, Manuel; Esteve, María; García-Sánchez, Valle; Gomollón, Fernando; Guardiola, Jordi; Hinojosa, Joaquin; Martín Arranz, Maria-Dolores; Minguez, Miguel; Taxonera, Carlos; Vera, Isabel

2016-03-01

There is still uncertainty about what constitutes the best therapeutic practice in ulcerative colitis (UC). The purpose of the "UC Horizons Project" was to raise a series of questions regarding the management of UC to provide responses based on the best scientific evidence available. The 11 members of the scientific committee prepared draft answers to the 10 questions from available evidence after a literature search. A total of 48 Spanish gastroenterology specialists nationwide participated in the project. The national meeting discussed the 10 issues in working groups and reached consensus regarding the recommendations by anonymous, interactive vote following the Delphi methodology. Final answers were developed, based on evidence and clinical experience of the participants. All the recommendations achieved a high level of agreement in the plenary vote, although the quality of the evidence was markedly heterogeneous. The lowest percentage of agreement corresponded to the questions with the weakest level of evidence, highlighting the necessity of conducting further studies in these areas. The recommendations focused on (1) aminosalicylates therapy (regarding dose and appropriateness of coadministration with thiopurines), (2) corticosteroid therapy (regarding dose and route of administration), (3) thiopurine treatment (regarding indications and possibility of withdrawal), (4) anti-tumor necrosis factor therapy (regarding appropriateness of combination with thiopurines, intensification, or discontinuation of treatment), and (5) colorectal cancer (regarding risk and time trends). The UC Horizons Project raised a series of eminently practical questions about the management of UC and provided responses based on the best scientific evidence available.

"Unresolved Complex Mixture" (UCM): A brief history of the term and moving beyond it.

PubMed

Farrington, John W; Quinn, James G

2015-07-15

The term "Unresolved Complex Mixture" (UCM) has been used extensively for decades to describe a gas chromatographic characteristic indicative of the presence of fossil fuel hydrocarbons (mainly petroleum hydrocarbons) in hydrocarbons isolated from aquatic samples. We chronicle the origin of the term. While it is still a useful characteristic for screening samples, more modern higher resolution two dimensional gas chromatography and gas chromatography coupled with advanced mass spectrometry techniques (Time-of-Flight or Fourier Transform-Ion Cyclotron Resonance) should be employed for analyses of petroleum contaminated samples. This will facilitate advances in understanding of the origins, fates and effects of petroleum compounds in aquatic environments. Copyright © 2015 Elsevier Ltd. All rights reserved.

NATURE OF UNRESOLVED COMPLEX MIXTURE IN SIZE-DISTRIBUTED EMISSIONS FROM RESIDENTIAL WOOD COMBUSTION AS MEASURED BY THERMAL DESORPTION-GAS CHROMATOGRAPHY-MASS SPECTROMETRY

EPA Science Inventory

In this study, the unresolved complex mixture (UCM) in size resolved fine aerosol emissions from residential wood combustion (RWC) is examined. The aerosols are sorted by size in an electrical low-pressure impactor (ELPI) and subsequently analyzed by thermal desorbtion/gas chroma...

Combining correlative and mechanistic habitat suitability models to improve ecological compensation.

PubMed

Meineri, Eric; Deville, Anne-Sophie; Grémillet, David; Gauthier-Clerc, Michel; Béchet, Arnaud

2015-02-01

Only a few studies have shown positive impacts of ecological compensation on species dynamics affected by human activities. We argue that this is due to inappropriate methods used to forecast required compensation in environmental impact assessments. These assessments are mostly descriptive and only valid at limited spatial and temporal scales. However, habitat suitability models developed to predict the impacts of environmental changes on potential species' distributions should provide rigorous science-based tools for compensation planning. Here we describe the two main classes of predictive models: correlative models and individual-based mechanistic models. We show how these models can be used alone or synoptically to improve compensation planning. While correlative models are easier to implement, they tend to ignore underlying ecological processes and lack accuracy. On the contrary, individual-based mechanistic models can integrate biological interactions, dispersal ability and adaptation. Moreover, among mechanistic models, those considering animal energy balance are particularly efficient at predicting the impact of foraging habitat loss. However, mechanistic models require more field data compared to correlative models. Hence we present two approaches which combine both methods for compensation planning, especially in relation to the spatial scale considered. We show how the availability of biological databases and software enabling fast and accurate population projections could be advantageously used to assess ecological compensation requirement efficiently in environmental impact assessments. © 2014 The Authors. Biological Reviews © 2014 Cambridge Philosophical Society.

A case of woman abuse: gender ideologies, power paradoxes, and unresolved conflict.

PubMed

Rosen, K H; Bird, K

1996-09-01

This paper describes some of the complex individual and relationship processes that occurred in an intimate relationship where love and violence coexisted. It presents a longitudinal, qualitative study of a premarital relationship in which the man had been repeatedly violent towards his female partner. It describes how gender role ideologies, the distribution of power between partners, and unresolved conflict are related to each other and to the emergence of violence and maintenance of couple bonds. A grounded theory approach was used to collect and analyze data for this single case and qualitative study in which both partners were interviewed several times each over the course of 1.5 years. Overall, it was found that intimate relationships that become contexts for expressions of love and violence are indeed complex, and the flexibility to consider the complexities that are involved provide a context for developing creative solutions.

MECHANISTIC AND SOURCE UNDERSTANDING OF PCDD/F FORMATION

EPA Science Inventory

The paper discusses mechanistic and source understanding of polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/F) formation. (NOTE: Considerable research effort has been expended over the last 15-plus years to understand how combustion sources result in formation of PCDDs/F...

Interpreting The Unresolved Intensity Of Cosmologically Redshifted Line Radiation

NASA Technical Reports Server (NTRS)

Switzer, E. R.; Chang, T.-C.; Masui, K. W.; Pen, U.-L.; Voytek, T. C.

2016-01-01

Intensity mapping experiments survey the spectrum of diffuse line radiation rather than detect individual objects at high signal-to-noise ratio. Spectral maps of unresolved atomic and molecular line radiation contain three-dimensional information about the density and environments of emitting gas and efficiently probe cosmological volumes out to high redshift. Intensity mapping survey volumes also contain all other sources of radiation at the frequencies of interest. Continuum foregrounds are typically approximately 10(sup 2)-10(Sup 3) times brighter than the cosmological signal. The instrumental response to bright foregrounds will produce new spectral degrees of freedom that are not known in advance, nor necessarily spectrally smooth. The intrinsic spectra of fore-grounds may also not be well known in advance. We describe a general class of quadratic estimators to analyze data from single-dish intensity mapping experiments and determine contaminated spectral modes from the data themselves. The key attribute of foregrounds is not that they are spectrally smooth, but instead that they have fewer bright spectral degrees of freedom than the cosmological signal. Spurious correlations between the signal and foregrounds produce additional bias. Compensation for signal attenuation must estimate and correct this bias. A successful intensity mapping experiment will control instrumental systematics that spread variance into new modes, and it must observe a large enough volume that contaminant modes can be determined independently from the signal on scales of interest.

Position statement--altitude training for improving team-sport players' performance: current knowledge and unresolved issues.

PubMed

Girard, Olivier; Amann, Markus; Aughey, Robert; Billaut, François; Bishop, David J; Bourdon, Pitre; Buchheit, Martin; Chapman, Robert; D'Hooghe, Michel; Garvican-Lewis, Laura A; Gore, Christopher J; Millet, Grégoire P; Roach, Gregory D; Sargent, Charli; Saunders, Philo U; Schmidt, Walter; Schumacher, Yorck O

2013-12-01

Despite the limited research on the effects of altitude (or hypoxic) training interventions on team-sport performance, players from all around the world engaged in these sports are now using altitude training more than ever before. In March 2013, an Altitude Training and Team Sports conference was held in Doha, Qatar, to establish a forum of research and practical insights into this rapidly growing field. A round-table meeting in which the panellists engaged in focused discussions concluded this conference. This has resulted in the present position statement, designed to highlight some key issues raised during the debates and to integrate the ideas into a shared conceptual framework. The present signposting document has been developed for use by support teams (coaches, performance scientists, physicians, strength and conditioning staff) and other professionals who have an interest in the practical application of altitude training for team sports. After more than four decades of research, there is still no consensus on the optimal strategies to elicit the best results from altitude training in a team-sport population. However, there are some recommended strategies discussed in this position statement to adopt for improving the acclimatisation process when training/competing at altitude and for potentially enhancing sea-level performance. It is our hope that this information will be intriguing, balanced and, more importantly, stimulating to the point that it promotes constructive discussion and serves as a guide for future research aimed at advancing the bourgeoning body of knowledge in the area of altitude training for team sports.

Position statement—altitude training for improving team-sport players’ performance: current knowledge and unresolved issues

PubMed Central

Girard, Olivier; Amann, Markus; Aughey, Robert; Billaut, François; Bishop, David J; Bourdon, Pitre; Buchheit, Martin; Chapman, Robert; D'Hooghe, Michel; Garvican-Lewis, Laura A; Gore, Christopher J; Millet, Grégoire P; Roach, Gregory D; Sargent, Charli; Saunders, Philo U; Schmidt, Walter; Schumacher, Yorck O

2013-01-01

Despite the limited research on the effects of altitude (or hypoxic) training interventions on team-sport performance, players from all around the world engaged in these sports are now using altitude training more than ever before. In March 2013, an Altitude Training and Team Sports conference was held in Doha, Qatar, to establish a forum of research and practical insights into this rapidly growing field. A round-table meeting in which the panellists engaged in focused discussions concluded this conference. This has resulted in the present position statement, designed to highlight some key issues raised during the debates and to integrate the ideas into a shared conceptual framework. The present signposting document has been developed for use by support teams (coaches, performance scientists, physicians, strength and conditioning staff) and other professionals who have an interest in the practical application of altitude training for team sports. After more than four decades of research, there is still no consensus on the optimal strategies to elicit the best results from altitude training in a team-sport population. However, there are some recommended strategies discussed in this position statement to adopt for improving the acclimatisation process when training/competing at altitude and for potentially enhancing sea-level performance. It is our hope that this information will be intriguing, balanced and, more importantly, stimulating to the point that it promotes constructive discussion and serves as a guide for future research aimed at advancing the bourgeoning body of knowledge in the area of altitude training for team sports. PMID:24282213

Unresolved issues in the understanding of the pathogenesis of local tissue damage induced by snake venoms.

PubMed

Gutiérrez, José María; Rucavado, Alexandra; Escalante, Teresa; Herrera, Cristina; Fernández, Julián; Lomonte, Bruno; Fox, Jay W

2018-06-15

Snakebite envenoming by viperid species, and by some elapids, is characterized by a complex pattern of tissue damage at the anatomical site of venom injection. In severe cases, tissue destruction may be so extensive as to lead to permanent sequelae, with serious pathophysiological, social and psychological consequences. Significant advances have been performed in the study of venom-induced tissue damage, including identification and characterization of the toxins involved, insights into the mechanisms of action of venoms and toxins, and study of tissue responses to venom-induced injury. Nevertheless, much remains to be known and understood on the pathogenesis of these alterations. This review focuses on some of the pending issues in the topic of snake venom-induced local tissue damage. The traditional 'reductionist' approach, which has predominated in the study of snake venoms and their actions, needs to be complemented by more integrative and holistic perspectives aimed at capturing the complexity of these pathological alterations. Future advances in the study of these topics will certainly pave the way for innovative therapeutic interventions, with the goal of reducing the impact of this aspect of snakebite envenoming. Copyright © 2018 Elsevier Ltd. All rights reserved.

Biomarker Discovery and Mechanistic Studies of Prostate Cancer Using Targeted Proteomic Approaches

DTIC Science & Technology

2010-07-01

1-0431 TITLE: Biomarker Discovery and Mechanistic Studies of Prostate Cancer Using Targeted Proteomic Approaches PRINCIPAL INVESTIGATOR...June 2010 4. TITLE AND SUBTITLE Biomarker Discovery and Mechanistic Studies of Prostate Cancer Using Targeted Proteomic 5a. CONTRACT NUMBER...1-0430; W81XWH-08-1-0431; Grant sponsor: NIH/NCRR COBRE Grant; Grant number: 1P20RR020171; Grant sponsor: NIH/NIDDK Grant; Grant number: R01DK053525

Mechanistic and Technical Challenges in Studying the Human Microbiome and Cancer Epidemiology.

PubMed

Verma, Mukesh

2017-04-01

This article reviews the significance of the microbiome in cancer epidemiology, mechanistic and technical challenges in the field, and characterization of the microbiome in different tumor types to identify biomarkers of risk, progression, and prognosis. Publications on the microbiome and cancer epidemiology were reviewed to analyze sample collection and processing, microbiome taxa characterization by 16S ribosomal RNA sequencing, and microbiome metabolite characterization (metabotyping) by nuclear magnetic resonance and mass spectrometry. The analysis identified methodology types, research design, sample types, and issues in integrating data from different platforms. Aerodigestive cancer epidemiology studies conducted by different groups demonstrated the significance of microbiome information in developing approaches to improve health. Challenges exist in sample preparation and processing (eg, standardization of methods for collection and analysis). These challenges relate to technology, data integration from "omics" studies, inherent bias in primer selection during 16S ribosomal RNA sequencing, the need for large consortia with well-characterized biospecimens, cause and effect issues, resilience of microbiota to exposure events (requires longitudinal studies), and expanding studies for fungal and viral diversity (most studies used bacterial 16S ribosomal RNA sequencing for microbiota characterization). Despite these challenges, microbiome and cancer epidemiology studies are significant and may facilitate cancer risk assessment, diagnosis, and prognosis. In the future, clinical trials likely will use microbiota modifications to improve the efficacy of existing treatments.

Mechanistic and Technical Challenges in Studying the Human Microbiome and Cancer Epidemiology

PubMed Central

2016-01-01

This article reviews the significance of the microbiome in cancer epidemiology, mechanistic and technical challenges in the field, and characterization of the microbiome in different tumor types to identify biomarkers of risk, progression, and prognosis. Publications on the microbiome and cancer epidemiology were reviewed to analyze sample collection and processing, microbiome taxa characterization by 16S ribosomal RNA sequencing, and microbiome metabolite characterization (metabotyping) by nuclear magnetic resonance and mass spectrometry. The analysis identified methodology types, research design, sample types, and issues in integrating data from different platforms. Aerodigestive cancer epidemiology studies conducted by different groups demonstrated the significance of microbiome information in developing approaches to improve health. Challenges exist in sample preparation and processing (eg, standardization of methods for collection and analysis). These challenges relate to technology, data integration from “omics” studies, inherent bias in primer selection during 16S ribosomal RNA sequencing, the need for large consortia with well-characterized biospecimens, cause and effect issues, resilience of microbiota to exposure events (requires longitudinal studies), and expanding studies for fungal and viral diversity (most studies used bacterial 16S ribosomal RNA sequencing for microbiota characterization). Despite these challenges, microbiome and cancer epidemiology studies are significant and may facilitate cancer risk assessment, diagnosis, and prognosis. In the future, clinical trials likely will use microbiota modifications to improve the efficacy of existing treatments. PMID:27121074

Calibrating the mechanistic-empirical pavement design guide for Kansas.

DOT National Transportation Integrated Search

2015-04-01

The Kansas Department of Transportation (KDOT) is moving toward the implementation of the new American : Association of State Highway and Transportation Officials (AASHTO) Mechanistic-Empirical Pavement Design Guide (MEPDG) : for pavement design. The...

Mechanistic explanation, cognitive systems demarcation, and extended cognition.

PubMed

van Eck, Dingmar; Looren de Jong, Huib

2016-10-01

Approaches to the Internalism-Externalism controversy in the philosophy of mind often involve both (broadly) metaphysical and explanatory considerations. Whereas originally most emphasis seems to have been placed on metaphysical concerns, recently the explanation angle is getting more attention. Explanatory considerations promise to offer more neutral grounds for cognitive systems demarcation than (broadly) metaphysical ones. However, it has been argued that explanation-based approaches are incapable of determining the plausibility of internalist-based conceptions of cognition vis-à-vis externalist ones. On this perspective, improved metaphysics is the route along which to solve the Internalist-Externalist stalemate. In this paper we challenge this claim. Although we agree that explanation-orientated approaches have indeed so far failed to deliver solid means for cognitive system demarcation, we elaborate a more promising explanation-oriented framework to address this issue. We argue that the mutual manipulability account of constitutive relevance in mechanisms, extended with the criterion of 'fat-handedness', is capable of plausibly addressing the cognitive systems demarcation problem, and thus able to decide on the explanatory traction of Internalist vs. Externalist conceptions, on a case-by-case basis. Our analysis also highlights why some other recent mechanistic takes on the problem of cognitive systems demarcation have been unsuccessful. We illustrate our claims with a case on gestures and learning. Copyright © 2016 Elsevier Ltd. All rights reserved.

Characterizing Students' Mechanistic Reasoning about London Dispersion Forces

ERIC Educational Resources Information Center

Becker, Nicole; Noyes, Keenan; Cooper, Melanie

2016-01-01

Characterizing how students construct causal mechanistic explanations for chemical phenomena can provide us with important insights into the ways that students develop understanding of chemistry concepts. Here, we present two qualitative studies of undergraduate general chemistry students' reasoning about the causes of London dispersion forces in…

Warming will affect phytoplankton differently: evidence through a mechanistic approach

PubMed Central

Huertas, I. Emma; Rouco, Mónica; López-Rodas, Victoria; Costas, Eduardo

2011-01-01

Although the consequences of global warming in aquatic ecosystems are only beginning to be revealed, a key to forecasting the impact on aquatic communities is an understanding of individual species' vulnerability to increased temperature. Despite their microscopic size, phytoplankton support about half of the global primary production, drive essential biogeochemical cycles and represent the basis of the aquatic food web. At present, it is known that phytoplankton are important targets and, consequently, harbingers of climate change in aquatic systems. Therefore, investigating the capacity of phytoplankton to adapt to the predicted warming has become a relevant issue. However, considering the polyphyletic complexity of the phytoplankton community, different responses to increased temperature are expected. We experimentally tested the effects of warming on 12 species of phytoplankton isolated from a variety of environments by using a mechanistic approach able to assess evolutionary adaptation (the so-called ratchet technique). We found different degrees of tolerance to temperature rises and an interspecific capacity for genetic adaptation. The thermal resistance level reached by each species is discussed in relation to their respective original habitats. Our study additionally provides evidence on the most resistant phytoplankton groups in a future warming scenario. PMID:21508031

Warming will affect phytoplankton differently: evidence through a mechanistic approach.

PubMed

Huertas, I Emma; Rouco, Mónica; López-Rodas, Victoria; Costas, Eduardo

2011-12-07

Although the consequences of global warming in aquatic ecosystems are only beginning to be revealed, a key to forecasting the impact on aquatic communities is an understanding of individual species' vulnerability to increased temperature. Despite their microscopic size, phytoplankton support about half of the global primary production, drive essential biogeochemical cycles and represent the basis of the aquatic food web. At present, it is known that phytoplankton are important targets and, consequently, harbingers of climate change in aquatic systems. Therefore, investigating the capacity of phytoplankton to adapt to the predicted warming has become a relevant issue. However, considering the polyphyletic complexity of the phytoplankton community, different responses to increased temperature are expected. We experimentally tested the effects of warming on 12 species of phytoplankton isolated from a variety of environments by using a mechanistic approach able to assess evolutionary adaptation (the so-called ratchet technique). We found different degrees of tolerance to temperature rises and an interspecific capacity for genetic adaptation. The thermal resistance level reached by each species is discussed in relation to their respective original habitats. Our study additionally provides evidence on the most resistant phytoplankton groups in a future warming scenario.

Mechanistic-empirical pavement design guide calibration for pavement rehabilitation.

DOT National Transportation Integrated Search

2013-01-01

The Oregon Department of Transportation (ODOT) is in the process of implementing the recently introduced AASHTO : Mechanistic-Empirical Pavement Design Guide (MEPDG) for new pavement sections. The majority of pavement work : conducted by ODOT involve...

Draft user's guide for UDOT mechanistic-empirical pavement design.

DOT National Transportation Integrated Search

2009-10-01

Validation of the new AASHTO Mechanistic-Empirical Pavement Design Guides (MEPDG) nationally calibrated pavement distress and smoothness prediction models when applied under Utah conditions, and local calibration of the new hot-mix asphalt (HMA) p...

Cueing an unresolved personal goal causes persistent ruminative self-focus: an experimental evaluation of control theories of rumination.

PubMed

Roberts, Henrietta; Watkins, Edward R; Wills, Andy J

2013-12-01

Control theory predicts that the detection of goal discrepancies initiates ruminative self-focus (Martin & Tesser, 1996). Despite the breadth of applications and interest in control theory, there is a lack of experimental evidence evaluating this prediction. The present study provided the first experimental test of this prediction. We examined uninstructed state rumination in response to the cueing of resolved and unresolved goals in a non-clinical population using a novel measure of online rumination. Consistent with control theory, cueing an unresolved goal resulted in significantly greater recurrent intrusive ruminative thoughts than cueing a resolved goal. Individual differences in trait rumination moderated the impact of the goal cueing task on the extent of state rumination: individuals who had a stronger tendency to habitually ruminate were more susceptible to the effects of cueing goal discrepancies. The findings await replication in a clinically depressed sample where there is greater variability and higher levels of trait rumination. These results indicate that control theories of goal pursuit provide a valuable framework for understanding the circumstances that trigger state rumination. Additionally, our measure of uninstructed online state rumination was found to be a valid and sensitive index of the extent and temporal course of state rumination, indicating its value for further investigating the proximal causes of state rumination. Copyright © 2013 Elsevier Ltd. All rights reserved.

Regulatory Technology Development Plan - Sodium Fast Reactor: Mechanistic Source Term – Trial Calculation

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

Grabaskas, David; Bucknor, Matthew; Jerden, James

2016-10-01

The potential release of radioactive material during a plant incident, referred to as the source term, is a vital design metric and will be a major focus of advanced reactor licensing. The U.S. Nuclear Regulatory Commission has stated an expectation for advanced reactor vendors to present a mechanistic assessment of the potential source term in their license applications. The mechanistic source term presents an opportunity for vendors to realistically assess the radiological consequences of an incident, and may allow reduced emergency planning zones and smaller plant sites. However, the development of a mechanistic source term for advanced reactors is notmore » without challenges, as there are often numerous phenomena impacting the transportation and retention of radionuclides. This project sought to evaluate U.S. capabilities regarding the mechanistic assessment of radionuclide release from core damage incidents at metal fueled, pool-type sodium fast reactors (SFRs). The purpose of the analysis was to identify, and prioritize, any gaps regarding computational tools or data necessary for the modeling of radionuclide transport and retention phenomena. To accomplish this task, a parallel-path analysis approach was utilized. One path, led by Argonne and Sandia National Laboratories, sought to perform a mechanistic source term assessment using available codes, data, and models, with the goal to identify gaps in the current knowledge base. The second path, performed by an independent contractor, performed sensitivity analyses to determine the importance of particular radionuclides and transport phenomena in regards to offsite consequences. The results of the two pathways were combined to prioritize gaps in current capabilities.« less

Pelvic fracture urethral injuries: the unresolved controversy.

PubMed

Koraitim, M M

1999-05-01

The unresolved controversies about pelvic fracture urethral injuries and whether any conclusions can be reached to develop a treatment plan for this lesion are determined. All data on pelvic fracture urethral injuries in the English literature for the last 50 years were critically analyzed. Studies were eligible only if data were complete and conclusive. The risk of urethral injury is influenced by the number of broken pubic rami as well as involvement of the sacroiliac joint. Depending on the magnitude of trauma, the membranous urethra is first stretched and then partially or completely ruptured at the bulbomembranous junction. Injuries to the prostatic urethra and bladder neck occur only in children. Injury to the female urethra usually is a partial tear of the anterior wall and rarely complete disruption of the proximal or distal urethra. Diagnosis depends on urethrography in men and on a high index of suspicion and urethroscopy in women. Of the 3 conventional treatment methods primary suturing of the disrupted urethral ends has the greatest complication rates of incontinence and impotence (21 and 56%, respectively). Primary realignment has double the incidence of impotence and half that of stricture compared to suprapubic cystostomy and delayed repair (36 versus 19 and 53 versus 97%, respectively, p <0.0001). In men surgical and endoscopic procedures do not compete but rather complement each other for treatment of different injuries under different circumstances, including indwelling catheter for urethral stretch injury, endoscopic stenting or suprapubic cystostomy for partial rupture, endoscopic realignment or suprapubic cystostomy for complete rupture with a minimal distraction defect and surgical realignment if the distraction defect is wide. Associated injury to the bladder, bladder neck or rectum dictates immediate exploration for repair but does not necessarily indicate exploration of the urethral injury site. In women treatment modalities are dictated by

Issues impacting therapeutic outcomes in pediatric patients: an overview.

PubMed

Kalra, Atin; Goindi, Shishu

2014-01-01

The quest for achieving optimal therapeutic outcomes in pediatric patients has evaded the healthcare professionals for long and often lack of child specific dosage forms and the associated events that follow with it have been considered to be major contributor towards suboptimal outcomes. Consequently, there have been sustained efforts over the years to address this issue with the enactment of legislations like Best Pharmaceutical for Children Act (BPCA), Pediatric Research Equity Act (PREA) and Pediatric Regulation by European Union (EU) to incentivise the participation of pharmaceutical industry towards development of child friendly dosage forms. Initiatives taken in past by organisations like World Health Organisation (WHO) and Drugs for Neglected Diseases Initiative (DNDi) to spur the development of child friendly dosage forms has helped to address issues pertaining to management of Human Immunodeficiency Virus (HIV) and malaria in pediatric patients. Present efforts aimed at developing child friendly dosage forms include oro-dispersible platforms including thin films and mini-tablets. Despite these leaps and advancements in developing better dosage forms for children, lower therapeutic outcomes in pediatric patients continue to remain an unresolved issue because of detrimental effects of additional factors such as parents understanding of label instructions and complexities involved in executing pediatric clinical studies thus requiring a concerted effort from pharmaceutical companies, academic researchers, parents and healthcare providers to work for better treatment outcomes in children.

Biomarker Discovery and Mechanistic Studies of Prostate Cancer Using Targeted Proteomic Approaches

DTIC Science & Technology

2012-07-01

1-0431 TITLE: Biomarker Discovery and Mechanistic Studies of Prostate Cancer Using Targeted Proteomic Approaches PRINCIPAL INVESTIGATOR...July 2012 2. REPORT TYPE Final 3. DATES COVERED (From - To) 1 July 2008 – 30 June 2012 4. TITLE AND SUBTITLE Biomarker Discovery and Mechanistic...Department of Defense Synergistic Idea Development Award W81XWH-08-1-0430 (to H.Z) and W81XWH-08-1-0431 (to N.K.), an NIH/NCRR COBRE grant 1P20RR020171 (to

Application of Mechanistic Toxicology Data to Ecological Risk Assessments

EPA Science Inventory

The ongoing evolution of knowledge and tools in the areas of molecular biology, bioinformatics, and systems biology holds significant promise for reducing uncertainties associated with ecological risk assessment. As our understanding of the mechanistic basis of responses of organ...

Implementation of mechanistic pavement design : field and laboratory implementation.

DOT National Transportation Integrated Search

2006-12-01

One of the most important parameters needed for 2002 Mechanistic Pavement Design Guide is the dynamic modulus (E*). : The dynamic modulus (E*) describes the relationship between stress and strain for a linear viscoelastic material. The E* is the : pr...

Mechanistic movement models to understand epidemic spread.

PubMed

Fofana, Abdou Moutalab; Hurford, Amy

2017-05-05

An overlooked aspect of disease ecology is considering how and why animals come into contact with one and other resulting in disease transmission. Mathematical models of disease spread frequently assume mass-action transmission, justified by stating that susceptible and infectious hosts mix readily, and foregoing any detailed description of host movement. Numerous recent studies have recorded, analysed and modelled animal movement. These movement models describe how animals move with respect to resources, conspecifics and previous movement directions and have been used to understand the conditions for the occurrence and the spread of infectious diseases when hosts perform a type of movement. Here, we summarize the effect of the different types of movement on the threshold conditions for disease spread. We identify gaps in the literature and suggest several promising directions for future research. The mechanistic inclusion of movement in epidemic models may be beneficial for the following two reasons. Firstly, the estimation of the transmission coefficient in an epidemic model is possible because animal movement data can be used to estimate the rate of contacts between conspecifics. Secondly, unsuccessful transmission events, where a susceptible host contacts an infectious host but does not become infected can be quantified. Following an outbreak, this enables disease ecologists to identify 'near misses' and to explore possible alternative epidemic outcomes given shifts in ecological or immunological parameters.This article is part of the themed issue 'Opening the black box: re-examining the ecology and evolution of parasite transmission'. © 2017 The Author(s).

[Bioethics in end-of-life decisions in neonatology: Unresolved issues].

PubMed

Arnaez, Juan; Tejedor, Juan Carlos; Caserío, Sonia; Montes, María Teresa; Moral, María Teresa; González de Dios, Javier; García-Alix, Alfredo

2017-12-01

This document is the result of previous work carried out by different expert groups and submitted to multidisciplinary debate at a Conference about controversial, deficient, or new aspects in the field of neonatal palliative care, such as: 1) the deliberative decision-making process, 2) hospital and domiciliary palliative care, 3) donation after controlled cardiac death, and 4) moral stress in professionals. The most relevant conclusions were: the need to instruct professionals in bioethics and in the deliberative method to facilitate thorough and reasonable decision-making; the lack of development in the field of perinatal palliative care and domiciliary palliative care in hospitals that attend newborns; the need to provide neonatal units with resources that help train professionals in communication skills and in the management of moral distress, as well as delineate operational procedure and guidelines for neonatal organ donation. Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Determination of Passing Scores on Certification Examinations: An Unresolved Issue.

ERIC Educational Resources Information Center

Karni, Karen R.; Lofsness, Karen G.

1985-01-01

This study examined the results obtained from certification applicants and practitioners on a national certification examination for clinical laboratory scientists (medical technologists), using a modified Angoff procedure to establish the cut-off score. The major question of the investigation concerned whether the cut-off score was appropriate.…

Student Personnel Administration and the Adult Learner: An Unresolved Issue.

ERIC Educational Resources Information Center

Watson, Rollin J.

The role of college student personnel administration in serving adult learners is considered. Historical trends in the student personnel function and the philosophy that student personnel workers are educators who create programs that contribute to the student's overall educational growth are examined. Changes for the student development personnel…

A review on the current issues and barriers of Industrialised Building System (IBS) adoption in Malaysia’s construction industry

NASA Astrophysics Data System (ADS)

Amin, M. A. Mohd; Abas, N. H.; Shahidan, S.; Rahmat, M. H.; Suhaini, N. A.; Nagapan, S.; Rahim, R. Abdul

2017-11-01

Malaysia considers the construction industry as one of the main contributors to its Gross Domestic Product (GDP). However, there are some unresolved issues arising from the ongoing and widespread adoption of the conventional method of construction such as the resultant fragmentation of the industry itself; delays in production and delivery time of unnecessary wastages and lack of sustainability practice. Malaysian Government has been continuously encouraging the industry to use, partly or if not wholly, the Industrialized Building System (IBS), which is considered to be an important part of sustainable construction initiative. IBS was introduced to Malaysia as the solution to issues related to dependencies of foreign workers, raising demand for affordable accommodations and improving image, quality and productivity of construction industry. However, the IBS adoption in Malaysia remains low. This paper presents the review of the current issues and barriers of IBS adoption in Malaysian construction industry.

Mechanistic modeling of pesticide exposure: The missing keystone of honey bee toxicology.

PubMed

Sponsler, Douglas B; Johnson, Reed M

2017-04-01

The role of pesticides in recent honey bee losses is controversial, partly because field studies often fail to detect effects predicted by laboratory studies. This dissonance highlights a critical gap in the field of honey bee toxicology: there exists little mechanistic understanding of the patterns and processes of exposure that link honey bees to pesticides in their environment. The authors submit that 2 key processes underlie honey bee pesticide exposure: 1) the acquisition of pesticide by foraging bees, and 2) the in-hive distribution of pesticide returned by foragers. The acquisition of pesticide by foraging bees must be understood as the spatiotemporal intersection between environmental contamination and honey bee foraging activity. This implies that exposure is distributional, not discrete, and that a subset of foragers may acquire harmful doses of pesticide while the mean colony exposure would appear safe. The in-hive distribution of pesticide is a complex process driven principally by food transfer interactions between colony members, and this process differs importantly between pollen and nectar. High priority should be placed on applying the extensive literature on honey bee biology to the development of more rigorously mechanistic models of honey bee pesticide exposure. In combination with mechanistic effects modeling, mechanistic exposure modeling has the potential to integrate the field of honey bee toxicology, advancing both risk assessment and basic research. Environ Toxicol Chem 2017;36:871-881. © 2016 SETAC. © 2016 SETAC.

DEVELOPMENT AND VALIDATION OF A MECHANISTIC GROUND SPRAYER MODEL

EPA Science Inventory

In the last ten years the Spray Drift Task Force (SDTF), U.S. Environmental Protection Agency (EPA), USDA Agricultural Research Service, and USDA Forest Service cooperated in the refinement and evaluation of a mechanistically-based aerial spray model (contained within AGDISP and ...

A Decade of e-Cigarettes: Limited Research & Unresolved Safety Concerns

PubMed Central

Kaisar, Mohammad Abul; Prasad, Shikha; Liles, Tylor; Cucullo, Luca

2016-01-01

It is well known that tobacco consumption is a leading cause of preventable deaths worldwide and has been linked to major diseases ranging from cancer to chronic obstructive pulmonary disease, atherosclerosis, stroke and a host of neurological/neurodegenerative disorders. In the past decade a number of alternative vaping products have hit the market, rapidly gaining consumers especially among the younger population. Electronic nicotine delivery systems or e-cigarettes have become the sought-after product due to the belief that they are much safer than traditional cigarettes. However, inadequate research and lack of regulatory guidelines for both the manufacturing process and the content of the vaping solution of the e-cigarette has become a major concern. Highly debated and unresolved questions such as whether e-cigarettes may help smokers quit and whether e-cigarettes will promote the use of nicotine among non-smokers add to the confusion of the safety of e-cigarettes. In this review article, we summarize the current understanding (and lack thereof) of the potential health impacts of e-cigarettes. We will also highlight the most recent studies (in vivo/in vitro) which seem to conflict with the broad safety claims put forward by the manufacturers. Finally, we provide potential solutions to overcome the research gap of the short and long-term health impact of e-cigarettes. PMID:27477296

A decade of e-cigarettes: Limited research & unresolved safety concerns.

PubMed

Kaisar, Mohammad Abul; Prasad, Shikha; Liles, Tylor; Cucullo, Luca

2016-07-15

It is well known that tobacco consumption is a leading cause of preventable deaths worldwide and has been linked to major diseases ranging from cancer to chronic obstructive pulmonary disease, atherosclerosis, stroke and a host of neurological/neurodegenerative disorders. In the past decade a number of alternative vaping products have hit the market, rapidly gaining consumers especially among the younger population. Electronic nicotine delivery systems or e-cigarettes have become the sought-after product due to the belief that they are much safer than traditional cigarettes. However, inadequate research and lack of regulatory guidelines for both the manufacturing process and the content of the vaping solution of the e-cigarette has become a major concern. Highly debated and unresolved questions such as whether e-cigarettes may help smokers quit and whether e-cigarettes will promote the use of nicotine among non-smokers add to the confusion of the safety of e-cigarettes. In this review article, we summarize the current understanding (and lack thereof) of the potential health impacts of e-cigarettes. We will also highlight the most recent studies (in vivo/in vitro) which seem to conflict with the broad safety claims put forward by the manufacturers. Finally, we provide potential solutions to overcome the research gap of the short and long-term health impact of e-cigarettes. Published by Elsevier Ireland Ltd.

Special issue: Volcanic geology of the Azores Islands

USGS Publications Warehouse

Nunes, João Carlos; Tilling, Robert I.; Sigvaldason, Gudmundur E.

2006-01-01

The volcanic islands making up the Azores Archipelago rise above sea from a prominent submarine topographic high (the “Azores Plateau”), marked by the 2000-m bathymetric contour. Specifically, the Azores Islands lie at the so-called “Azores Triple Junction” (ATJ), where the Eurasian, North American, and African (or Nubian) tectonic plates meet. In general terms, the ATJ is defined by the Mid-Atlantic Ridge (MAR) separating the North American plate from the other two, and the Azores–Gibraltar fault zone separating the Eurasian and African plates. In addition, the existence of a mantle plume (“hotspot) beneath Azores Plateau has been inferred in many previous investigations. Not surprisingly, because of its distinctive plate-tectonics setting and attributes, the Azores Archipelago has been the site of intense research, serving as an ideal natural laboratory for scientific studies involving diverse disciplines, including geology, seismotectonics, climatology, ecology, and oceanography. Of course, a special field of interest and research is volcanology, with particular emphasis not only on the eruptive processes and products of the individual island volcanoes, but also of the volcanic and structural evolution of the ATJ and the “Azores Plateau” as a whole.There has been, and remains, considerable scientific debate about the dynamics of the ATJ, including the characterization of the nature and location of the involved plate boundaries, the determination of the sense and amount of plate motions, and the influence of the Azores hotspot on the involved three plates. At present, the basic nature of the ATJ is still not fully understood and the main unresolved issues are: where is the westernmost extent of Azores–Gibraltar fault zone? What is the nature of that extent? Is this fault zone a single, narrowly constricted linear boundary, or does it behave as a much larger, complex tectonic block (i.e., a “miniplate“ or “microplate”)? What is the size

How to bridge the gap between "unresolved" model and "resolved" model in CFD-DEM coupled method for sediment transport?

NASA Astrophysics Data System (ADS)

Liu, D.; Fu, X.; Liu, X.

2016-12-01

In nature, granular materials exist widely in water bodies. Understanding the fundamentals of solid-liquid two-phase flow, such as turbulent sediment-laden flow, is of importance for a wide range of applications. A coupling method combining computational fluid dynamics (CFD) and discrete element method (DEM) is now widely used for modeling such flows. In this method, when particles are significantly larger than the CFD cells, the fluid field around each particle should be fully resolved. On the other hand, the "unresolved" model is designed for the situation where particles are significantly smaller than the mesh cells. Using "unresolved" model, large amount of particles can be simulated simultaneously. However, there is a gap between these two situations when the size of DEM particles and CFD cell is in the same order of magnitude. In this work, the most commonly used void fraction models are tested with numerical sedimentation experiments. The range of applicability for each model is presented. Based on this, a new void fraction model, i.e., a modified version of "tri-linear" model, is proposed. Particular attention is paid to the smooth function of void fraction in order to avoid numerical instability. The results show good agreement with the experimental data and analytical solution for both single-particle motion and also group-particle motion, indicating great potential of the new void fraction model.

Tear gas: an epidemiological and mechanistic reassessment

PubMed Central

Rothenberg, Craig; Achanta, Satyanarayana; Svendsen, Erik R.

2016-01-01

Deployments of tear gas and pepper spray have rapidly increased worldwide. Large amounts of tear gas have been used in densely populated cities, including Cairo, Istanbul, Rio de Janeiro, Manama (Bahrain), and Hong Kong. In the United States, tear gas was used extensively during recent riots in Ferguson, Missouri. Whereas tear gas deployment systems have rapidly improved—with aerial drone systems tested and requested by law enforcement—epidemiological and mechanistic research have lagged behind and have received little attention. Case studies and recent epidemiological studies revealed that tear gas agents can cause lung, cutaneous, and ocular injuries, with individuals affected by chronic morbidities at high risk for complications. Mechanistic studies identified the ion channels TRPV1 and TRPA1 as targets of capsaicin in pepper spray, and of the tear gas agents chloroacetophenone, CS, and CR. TRPV1 and TRPA1 localize to pain‐sensing peripheral sensory neurons and have been linked to acute and chronic pain, cough, asthma, lung injury, dermatitis, itch, and neurodegeneration. In animal models, transient receptor potential inhibitors show promising effects as potential countermeasures against tear gas injuries. On the basis of the available data, a reassessment of the health risks of tear gas exposures in the civilian population is advised, and development of new countermeasures is proposed. PMID:27391380

Specific issues in living donor kidney transplantation: ABO - incompatibility.

PubMed

Thaiss, Friedrich

2009-12-29

Pre-emptive living kidney transplantation is the best choice of therapy to treat patients with advanced renal insufficiency. Unfortunately in up to one third of all cases kidney donation was refused due to blood group incompatibility. Limitations in donor availability for kidney transplantation therefore require that ABO-incompatible transplantation is safely established. This has changed when a new protocol was introduced in Stockholm, Sweden, in 2001. Almost 400 ABO-incompatible transplantations have since been performed in more than 20 centers with this protocol in Europe. ABO-incompatible living kidney transplantation can now be offered to our patients with advanced kidney disease as a safe procedure. To get more insight into the role ABO-incompatible organ transplantation might play in the near future transplantation centers currently involved in these processes should share their data to answer the unresolved issues we are concerned. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Modeling systems-level dynamics: Understanding without mechanistic explanation in integrative systems biology.

PubMed

MacLeod, Miles; Nersessian, Nancy J

2015-02-01

In this paper we draw upon rich ethnographic data of two systems biology labs to explore the roles of explanation and understanding in large-scale systems modeling. We illustrate practices that depart from the goal of dynamic mechanistic explanation for the sake of more limited modeling goals. These processes use abstract mathematical formulations of bio-molecular interactions and data fitting techniques which we call top-down abstraction to trade away accurate mechanistic accounts of large-scale systems for specific information about aspects of those systems. We characterize these practices as pragmatic responses to the constraints many modelers of large-scale systems face, which in turn generate more limited pragmatic non-mechanistic forms of understanding of systems. These forms aim at knowledge of how to predict system responses in order to manipulate and control some aspects of them. We propose that this analysis of understanding provides a way to interpret what many systems biologists are aiming for in practice when they talk about the objective of a "systems-level understanding." Copyright © 2014 Elsevier Ltd. All rights reserved.

Air pollution, inflammation and preterm birth: a potential mechanistic link.

PubMed

Vadillo-Ortega, Felipe; Osornio-Vargas, Alvaro; Buxton, Miatta A; Sánchez, Brisa N; Rojas-Bracho, Leonora; Viveros-Alcaráz, Martin; Castillo-Castrejón, Marisol; Beltrán-Montoya, Jorge; Brown, Daniel G; O'Neill, Marie S

2014-02-01

Preterm birth is a public health issue of global significance, which may result in mortality during the perinatal period or may lead to major health and financial consequences due to lifelong impacts. Even though several risk factors for preterm birth have been identified, prevention efforts have failed to halt the increasing rates of preterm birth. Epidemiological studies have identified air pollution as an emerging potential risk factor for preterm birth. However, many studies were limited by study design and inadequate exposure assessment. Due to the ubiquitous nature of ambient air pollution and the potential public health significance of any role in causing preterm birth, a novel focus investigating possible causal mechanisms influenced by air pollution is therefore a global health priority. We hypothesize that air pollution may act together with other biological factors to induce systemic inflammation and influence the duration of pregnancy. Evaluation and testing of this hypothesis is currently being conducted in a prospective cohort study in Mexico City and will provide an understanding of the pathways that mediate the effects of air pollution on preterm birth. The important public health implication is that crucial steps in this mechanistic pathway can potentially be acted on early in pregnancy to reduce the risk of preterm birth. Copyright © 2013 Elsevier Ltd. All rights reserved.

AIR POLLUTION, INFLAMMATION AND PRETERM BIRTH: A POTENTIAL MECHANISTIC LINK

PubMed Central

Vadillo-Ortega, Felipe; Osornio-Vargas, Alvaro; Buxton, Miatta A.; Sánchez, Brisa N.; Rojas-Bracho, Leonora; Viveros-Alcaráz, Martin; Castillo-Castrejón, Marisol; Beltrán-Montoya, Jorge; Brown, Daniel G.; O´Neill, Marie S.

2014-01-01

Preterm birth is a public health issue of global significance, which may result in mortality during the perinatal period or may lead to major health and financial consequences due to lifelong impacts. Even though several risk factors for preterm birth have been identified, prevention efforts have failed to halt the increasing rates of preterm birth. Epidemiological studies have identified air pollution as an emerging potential risk factor for preterm birth. However, many studies were limited by study design and inadequate exposure assessment. Due to the ubiquitous nature of ambient air pollution and the potential public health significance of any role in causing preterm birth, a novel focus investigating possible causal mechanisms influenced by air pollution is therefore a global health priority. We hypothesize that air pollution may act together with other biological factors to induce systemic inflammation and influence the duration of pregnancy. Evaluation and testing of this hypothesis is currently being conducted in a prospective cohort study in Mexico City and will provide an understanding of the pathways that mediate the effects of air pollution on preterm birth. The important public health implication is that crucial steps in this mechanistic pathway can potentially be acted on early in pregnancy to reduce the risk of preterm birth. PMID:24382337

Investigation of mechanistic deterioration modeling for bridge design and management.

DOT National Transportation Integrated Search

2017-04-01

The ongoing deterioration of highway bridges in Colorado dictates that an effective method for allocating limited management resources be developed. In order to predict bridge deterioration in advance, mechanistic models that analyze the physical pro...

Some critical issues and concerns related to research advances on toxicology of chemical mixtures.

PubMed Central

Yang, R S

1998-01-01

This paper addresses some of the issues and concerns on research advances on the toxicology of chemical mixtures. Emphases will be selectively given to the following questions and answers: Can mechanistic studies be conducted on chemical mixtures? The fact that any studies, including mechanistic studies, of single chemicals are really the study of the parent chemical plus its metabolites underscores the relevance of mechanistic studies on chemical mixtures. Can predictions be made on the health effects of chemical mixtures? Some successes are already evident in the literature on simpler chemical mixtures. For more complex mixtures, it is possible and we propose an approach here. What can we learn from other disciplines (the importance of interdisciplinary collaboration)? Two aspects, the knowledge and methodologies available in clinical pharmacology and the latest advances in structure-oriented lumping in chemical engineering, are discussed in detail. Unrepeatable results: The possibility of magnification of biologic variability because of low-level exposures to chemical mixtures is suggested with special reference to some known examples, including the controversial study on synergistic interactions of endocrine disruptors. Is the driving force for scientific investigations on chemical mixtures the legislative and regulatory atmosphere? Two laws with chemical mixtures specifically in the language are quoted and discussed. Their implications regarding research funding and activities are described. What are the pitfalls of applying for research funding on investigating chemical mixtures? The dilemma at least one investigator faces in pursuing research funding is elaborated. The questions and issues listed above are not all inclusive, but they represent some of the aspects that need to be brought into the open in the scientific community for discussion and/or debate. Thus, the primary objective of this paper is to provide some momentum for the beginning of a fruitful

A comprehensive mechanistic model for upward two-phase flow in wellbores

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

Sylvester, N.D.; Sarica, C.; Shoham, O.

1994-05-01

A comprehensive model is formulated to predict the flow behavior for upward two-phase flow. This model is composed of a model for flow-pattern prediction and a set of independent mechanistic models for predicting such flow characteristics as holdup and pressure drop in bubble, slug, and annular flow. The comprehensive model is evaluated by using a well data bank made up of 1,712 well cases covering a wide variety of field data. Model performance is also compared with six commonly used empirical correlations and the Hasan-Kabir mechanistic model. Overall model performance is in good agreement with the data. In comparison withmore » other methods, the comprehensive model performed the best.« less

MECHANISTIC DOSIMETRY MODELS OF NANOMATERIAL DEPOSITION IN THE RESPIRATORY TRACT

EPA Science Inventory

Accurate health risk assessments of inhalation exposure to nanomaterials will require dosimetry models that account for interspecies differences in dose delivered to the respiratory tract. Mechanistic models offer the advantage to interspecies extrapolation that physicochemica...

Reflecting on ethical and legal issues in wildlife disease.

PubMed

McCallum, Hamish; Hocking, Barbara Ann

2005-08-01

Disease in wildlife raises a number of issues that have not been widely considered in the bioethical literature. However, wildlife disease has major implications for human welfare. The majority of emerging human infectious diseases are zoonotic: this is, they occur in humans by cross-species transmissions from animal hosts. Managing these diseases often involves balancing concerns with human health against animal welfare and conservation concerns. Many infectious diseases of domestic animals are shared with wild animals, although it is often unclear whether the infection spills over from wild animals to domestic animals or vice versa. Culling is the standard means of managing such diseases, bringing economic considerations, animal welfare and conservation into conflict. Infectious diseases are also major threatening processes in conservation biology and their appropriate management by culling, vaccination or treatment raises substantial animal ethics issues. One particular issue of great significance in Australia is an ongoing research program to develop genetically modified pathogens to control vertebrate pests including rabbits, foxes and house mice. Release of any self-replicating GMO vertebrate pathogen gives rise to a whole series of ethical questions. We briefly review current Australian legal responses to these problems. Finally, we present two unresolved problems of general importance that are exemplified by wildlife disease. First, to what extent can or should 'bioethics' be broadened beyond direct concerns with human welfare to animal welfare and environmental welfare? Second, how should the irreducible uncertainty of ecological systems be accounted for in ethical decision making?

A Physics-Inspired Mechanistic Model of Migratory Movement Patterns in Birds.

PubMed

Revell, Christopher; Somveille, Marius

2017-08-29

In this paper, we introduce a mechanistic model of migratory movement patterns in birds, inspired by ideas and methods from physics. Previous studies have shed light on the factors influencing bird migration but have mainly relied on statistical correlative analysis of tracking data. Our novel method offers a bottom up explanation of population-level migratory movement patterns. It differs from previous mechanistic models of animal migration and enables predictions of pathways and destinations from a given starting location. We define an environmental potential landscape from environmental data and simulate bird movement within this landscape based on simple decision rules drawn from statistical mechanics. We explore the capacity of the model by qualitatively comparing simulation results to the non-breeding migration patterns of a seabird species, the Black-browed Albatross (Thalassarche melanophris). This minimal, two-parameter model was able to capture remarkably well the previously documented migration patterns of the Black-browed Albatross, with the best combination of parameter values conserved across multiple geographically separate populations. Our physics-inspired mechanistic model could be applied to other bird and highly-mobile species, improving our understanding of the relative importance of various factors driving migration and making predictions that could be useful for conservation.

Electrochemical processes and mechanistic aspects of field-effect sensors for biomolecules

PubMed Central

Huang, Weiguo; Diallo, Abdou Karim; Dailey, Jennifer L.; Besar, Kalpana

2017-01-01

Electronic biosensing is a leading technology for determining concentrations of biomolecules. In some cases, the presence of an analyte molecule induces a measured change in current flow, while in other cases, a new potential difference is established. In the particular case of a field effect biosensor, the potential difference is monitored as a change in conductance elsewhere in the device, such as across a film of an underlying semiconductor. Often, the mechanisms that lead to these responses are not specifically determined. Because improved understanding of these mechanisms will lead to improved performance, it is important to highlight those studies where various mechanistic possibilities are investigated. This review explores a range of possible mechanistic contributions to field-effect biosensor signals. First, we define the field-effect biosensor and the chemical interactions that lead to the field effect, followed by a section on theoretical and mechanistic background. We then discuss materials used in field-effect biosensors and approaches to improving signals from field-effect biosensors. We specifically cover the biomolecule interactions that produce local electric fields, structures and processes at interfaces between bioanalyte solutions and electronic materials, semiconductors used in biochemical sensors, dielectric layers used in top-gated sensors, and mechanisms for converting the surface voltage change to higher signal/noise outputs in circuits. PMID:29238595

Identification of key characteristics of male reproductive toxicants as an approach for screening and sorting mechanistic evidence.

EPA Science Inventory

The application of systematic review practices in human health assessment includes integration of multi-disciplinary evidence from epidemiological, experimental, and mechanistic studies. Although mode of action analysis relies on the evaluation of mechanistic and toxicological ou...

Mechanistic applicability domain classification of a local lymph node assay dataset for skin sensitization.

PubMed

Roberts, David W; Patlewicz, Grace; Kern, Petra S; Gerberick, Frank; Kimber, Ian; Dearman, Rebecca J; Ryan, Cindy A; Basketter, David A; Aptula, Aynur O

2007-07-01

The goal of eliminating animal testing in the predictive identification of chemicals with the intrinsic ability to cause skin sensitization is an important target, the attainment of which has recently been brought into even sharper relief by the EU Cosmetics Directive and the requirements of the REACH legislation. Development of alternative methods requires that the chemicals used to evaluate and validate novel approaches comprise not only confirmed skin sensitizers and non-sensitizers but also substances that span the full chemical mechanistic spectrum associated with skin sensitization. To this end, a recently published database of more than 200 chemicals tested in the mouse local lymph node assay (LLNA) has been examined in relation to various chemical reaction mechanistic domains known to be associated with sensitization. It is demonstrated here that the dataset does cover the main reaction mechanistic domains. In addition, it is shown that assignment to a reaction mechanistic domain is a critical first step in a strategic approach to understanding, ultimately on a quantitative basis, how chemical properties influence the potency of skin sensitizing chemicals. This understanding is necessary if reliable non-animal approaches, including (quantitative) structure-activity relationships (Q)SARs, read-across, and experimental chemistry based models, are to be developed.

Results from an experiment that collected visible-light polarization data using unresolved imagery for classification of geosynchronous satellites

NASA Astrophysics Data System (ADS)

Speicher, Andy; Matin, Mohammad; Tippets, Roger; Chun, Francis; Strong, David

2015-05-01

In order to protect critical military and commercial space assets, the United States Space Surveillance Network must have the ability to positively identify and characterize all space objects. Unfortunately, positive identification and characterization of space objects is a manual and labor intensive process today since even large telescopes cannot provide resolved images of most space objects. The objective of this study was to collect and analyze visible-spectrum polarization data from unresolved images of geosynchronous satellites taken over various solar phase angles. Different collection geometries were used to evaluate the polarization contribution of solar arrays, thermal control materials, antennas, and the satellite bus as the solar phase angle changed. Since materials on space objects age due to the space environment, their polarization signature may change enough to allow discrimination of identical satellites launched at different times. Preliminary data suggests this optical signature may lead to positive identification or classification of each satellite by an automated process on a shorter timeline. The instrumentation used in this experiment was a United States Air Force Academy (USAFA) Department of Physics system that consists of a 20-inch Ritchey-Chrétien telescope and a dual focal plane optical train fed with a polarizing beam splitter. Following a rigorous calibration, polarization data was collected during two nights on eight geosynchronous satellites built by various manufacturers and launched several years apart. When Stokes parameters were plotted against time and solar phase angle, the data indicates that a polarization signature from unresolved images may have promise in classifying specific satellites.

Composite Nanomechanics: A Mechanistic Properties Prediction

NASA Technical Reports Server (NTRS)

Chamis, Christos C.; Handler, Louis M.; Manderscheid, Jane M.

2007-01-01

A unique mechanistic theory is described to predict the properties of nanocomposites. The theory is based on composite micromechanics with progressive substructuring down to a nanoscale slice of a nanofiber where all the governing equations are formulated. These equations hav e been programmed in a computer code. That computer code is used to predict 25 properties of a mononanofiber laminate. The results are pr esented graphically and discussed with respect to their practical sig nificance. Most of the results show smooth distributions. Results for matrix-dependent properties show bimodal through-the-thickness distr ibution with discontinuous changes from mode to mode.

Unresolved fine-scale structure in solar coronal loop-tops

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

Scullion, E.; Van der Voort, L. Rouppe; Wedemeyer, S.

2014-12-10

New and advanced space-based observing facilities continue to lower the resolution limit and detect solar coronal loops in greater detail. We continue to discover even finer substructures within coronal loop cross-sections, in order to understand the nature of the solar corona. Here, we push this lower limit further to search for the finest coronal loop substructures, through taking advantage of the resolving power of the Swedish 1 m Solar Telescope/CRisp Imaging Spectro-Polarimeter (CRISP), together with co-observations from the Solar Dynamics Observatory/Atmospheric Image Assembly (AIA). High-resolution imaging of the chromospheric Hα 656.28 nm spectral line core and wings can, under certainmore » circumstances, allow one to deduce the topology of the local magnetic environment of the solar atmosphere where its observed. Here, we study post-flare coronal loops, which become filled with evaporated chromosphere that rapidly condenses into chromospheric clumps of plasma (detectable in Hα) known as a coronal rain, to investigate their fine-scale structure. We identify, through analysis of three data sets, large-scale catastrophic cooling in coronal loop-tops and the existence of multi-thermal, multi-stranded substructures. Many cool strands even extend fully intact from loop-top to footpoint. We discover that coronal loop fine-scale strands can appear bunched with as many as eight parallel strands within an AIA coronal loop cross-section. The strand number density versus cross-sectional width distribution, as detected by CRISP within AIA-defined coronal loops, most likely peaks at well below 100 km, and currently, 69% of the substructure strands are statistically unresolved in AIA coronal loops.« less

Rearrangements of Allylic Sulfinates to Sulfones: A Mechanistic Study

ERIC Educational Resources Information Center

Ball, David B.; Mollard, Paul; Voigtritter, Karl R.; Ball, Jenelle L.

2010-01-01

Most current organic chemistry textbooks are organized by functional groups and those of us who teach organic chemistry use functional-group organization in our courses but ask students to learn organic chemistry from a mechanistic approach. To enrich and extend the chemical understanding and knowledge of pericyclic-type reactions for chemistry…

Brain Networks for Working Memory and Factors of Intelligence Assessed in Males and Females with fMRI and DTI

ERIC Educational Resources Information Center

Tang, C. Y.; Eaves, E. L.; Ng, J. C.; Carpenter, D. M.; Mai, X.; Schroeder, D. H.; Condon, C. A.; Colom, R.; Haier, R. J.

2010-01-01

Neuro-imaging studies of intelligence implicate the importance of a parietal-frontal network. One unresolved issue is whether this network underlies a general factor of intelligence ("g") or other specific cognitive factors. A second unresolved issue is whether males and females use different parts of this network. Here we obtained intelligence…

M Dwarfs From The SDSS, 2MASS and WISE Surveys: Identification, Characterisation and Unresolved Ultracool Companionship

NASA Astrophysics Data System (ADS)

Cook, Neil James

2016-08-01

The aim of this thesis is to use a cross-match between WISE, 2MASS and SDSS to identify a large sample of M dwarfs. Through the careful characterisation and quality control of these M dwarfs I aim to identify rare systems (i.e. unresolved UCD companions, young M dwarfs, late M dwarfs and M dwarfs with common proper motion companions). Locating ultracool companions to M dwarfs is important for constraining low-mass formation models, the measurement of substellar dynamical masses and radii, and for testing ultracool evolutionary models. This is done by using an optimised method for identifying M dwarfs which may have unresolved ultracool companions. To do this I construct a catalogue of 440 694 M dwarf candidates, from WISE, 2MASS and SDSS, based on optical- and near-infrared colours and reduced proper motion. With strict reddening, photometric and quality constraints I isolate a sub-sample of 36 898 M dwarfs and search for possible mid-infrared M dwarf + ultracool dwarf candidates by comparing M dwarfs which have similar optical/near-infrared colours (chosen for their sensitivity to effective temperature and metallicity). I present 1 082 M dwarf + ultracool dwarf candidates for follow-up. Using simulated ultracool dwarf companions to M dwarfs, I estimate that the occurrence of unresolved ultracool companions amongst my M dwarf + ultracool dwarf candidates should be at least four times the average for my full M dwarf catalogue. I discuss yields of candidates based on my simulations. The possible contamination and bias from misidentified M dwarfs is then discussed, from chance alignments with other M dwarfs and UCDs, from chance alignments with giant stars, from chance alignments with galaxies, and from blended systems (via visual inspection). I then use optical spectra from LAMOST to spectral type a subset of my M dwarf + ultracool dwarf candidates. These candidates need confirming as true M dwarf + ultracool dwarf systems thus I present a new method I developed to

Mechanistic modelling of the inhibitory effect of pH on microbial growth.

PubMed

Akkermans, Simen; Van Impe, Jan F

2018-06-01

Modelling and simulation of microbial dynamics as a function of processing, transportation and storage conditions is a useful tool to improve microbial food safety and quality. The goal of this research is to improve an existing methodology for building mechanistic predictive models based on the environmental conditions. The effect of environmental conditions on microbial dynamics is often described by combining the separate effects in a multiplicative way (gamma concept). This idea was extended further in this work by including the effects of the lag and stationary growth phases on microbial growth rate as independent gamma factors. A mechanistic description of the stationary phase as a function of pH was included, based on a novel class of models that consider product inhibition. Experimental results on Escherichia coli growth dynamics indicated that also the parameters of the product inhibition equations can be modelled with the gamma approach. This work has extended a modelling methodology, resulting in predictive models that are (i) mechanistically inspired, (ii) easily identifiable with a limited work load and (iii) easily extended to additional environmental conditions. Copyright © 2017. Published by Elsevier Ltd.

Does Mechanistic Thinking Improve Student Success in Organic Chemistry?

ERIC Educational Resources Information Center

Grove, Nathaniel P.; Cooper, Melanie M.; Cox, Elizabeth L.

2012-01-01

The use of the curved-arrow notation to depict electron flow during mechanistic processes is one of the most important representational conventions in the organic chemistry curriculum. Our previous research documented a disturbing trend: when asked to predict the products of a series of reactions, many students do not spontaneously engage in…

Survey on Security Issues in Cloud Computing and Associated Mitigation Techniques

NASA Astrophysics Data System (ADS)

Bhadauria, Rohit; Sanyal, Sugata

2012-06-01

Cloud Computing holds the potential to eliminate the requirements for setting up of high-cost computing infrastructure for IT-based solutions and services that the industry uses. It promises to provide a flexible IT architecture, accessible through internet for lightweight portable devices. This would allow multi-fold increase in the capacity or capabilities of the existing and new software. In a cloud computing environment, the entire data reside over a set of networked resources, enabling the data to be accessed through virtual machines. Since these data-centers may lie in any corner of the world beyond the reach and control of users, there are multifarious security and privacy challenges that need to be understood and taken care of. Also, one can never deny the possibility of a server breakdown that has been witnessed, rather quite often in the recent times. There are various issues that need to be dealt with respect to security and privacy in a cloud computing scenario. This extensive survey paper aims to elaborate and analyze the numerous unresolved issues threatening the cloud computing adoption and diffusion affecting the various stake-holders linked to it.

Ionizing radiation induced cataracts: Recent biological and mechanistic developments and perspectives for future research.

PubMed

Ainsbury, Elizabeth A; Barnard, Stephen; Bright, Scott; Dalke, Claudia; Jarrin, Miguel; Kunze, Sarah; Tanner, Rick; Dynlacht, Joseph R; Quinlan, Roy A; Graw, Jochen; Kadhim, Munira; Hamada, Nobuyuki

The lens of the eye has long been considered as a radiosensitive tissue, but recent research has suggested that the radiosensitivity is even greater than previously thought. The 2012 recommendation of the International Commission on Radiological Protection (ICRP) to substantially reduce the annual occupational equivalent dose limit for the ocular lens has now been adopted in the European Union and is under consideration around the rest of the world. However, ICRP clearly states that the recommendations are chiefly based on epidemiological evidence because there are a very small number of studies that provide explicit biological, mechanistic evidence at doses <2Gy. This paper aims to present a review of recently published information on the biological and mechanistic aspects of cataracts induced by exposure to ionizing radiation (IR). The data were compiled by assessing the pertinent literature in several distinct areas which contribute to the understanding of IR induced cataracts, information regarding lens biology and general processes of cataractogenesis. Results from cellular and tissue level studies and animal models, and relevant human studies, were examined. The main focus was the biological effects of low linear energy transfer IR, but dosimetry issues and a number of other confounding factors were also considered. The results of this review clearly highlight a number of gaps in current knowledge. Overall, while there have been a number of recent advances in understanding, it remains unknown exactly how IR exposure contributes to opacification. A fuller understanding of how exposure to relatively low doses of IR promotes induction and/or progression of IR-induced cataracts will have important implications for prevention and treatment of this disease, as well as for the field of radiation protection. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

REDUCING UNCERTAINTY IN RISK ASSESSMENT USING MECHANISTIC DATA: ENHANCING THE U.S. EPA DEVELOPMENTAL NEUROTOXICITY TESTING GUIDELINES

EPA Science Inventory

SUMMARY: Mechanistic data should provide the Agency with a more accurate basis to estimate risk than do the Agency’s default assumptions (10x uncertainty factors, etc.), thereby improving risk assessment decisions. NTD is providing mechanistic data for toxicant effects on two maj...

Evaluation of neutron total and capture cross sections on 99Tc in the unresolved resonance region

NASA Astrophysics Data System (ADS)

Iwamoto, Nobuyuki; Katabuchi, Tatsuya

2017-09-01

Long-lived fission product Technetium-99 is one of the most important radioisotopes for nuclear transmutation. The reliable nuclear data are indispensable for a wide energy range up to a few MeV, in order to develop environmental load reducing technology. The statistical analyses of resolved resonances were performed by using the truncated Porter-Thomas distribution, coupled-channels optical model, nuclear level density model and Bayes' theorem on conditional probability. The total and capture cross sections were calculated by a nuclear reaction model code CCONE. The resulting cross sections have statistical consistency between the resolved and unresolved resonance regions. The evaluated capture data reproduce those recently measured at ANNRI of J-PARC/MLF above resolved resonance region up to 800 keV.

Mechanistic-empirical design concepts for continuously reinforced concrete pavements in Illinois.

DOT National Transportation Integrated Search

2009-04-01

The Illinois Department of Transportation (IDOT) currently has an existing jointed plain concrete pavement : (JPCP) design based on mechanistic-empirical (M-E) principles. However, their continuously reinforced concrete : pavement (CRCP) design proce...

The evolution of honey bee dance communication: a mechanistic perspective.

PubMed

Barron, Andrew B; Plath, Jenny Aino

2017-12-01

Honey bee dance has been intensively studied as a communication system, and yet we still know very little about the neurobiological mechanisms supporting how dances are produced and interpreted. Here, we discuss how new information on the functions of the central complex (CX) of the insect brain might shed some light on possible neural mechanisms of dance behaviour. We summarise the features of dance communication across the species of the genus Apis We then propose that neural mechanisms of orientation and spatial processing found to be supported by the CX may function in dance communication also, and that this mechanistic link could explain some specific features of the dance form. This is purely a hypothesis, but in proposing this hypothesis, and how it might be investigated, we hope to stimulate new mechanistic analyses of dance communication. © 2017. Published by The Company of Biologists Ltd.

Existing pavement input information for the mechanistic-empirical pavement design guide.

DOT National Transportation Integrated Search

2009-02-01

The objective of this study is to systematically evaluate the Iowa Department of Transportations (DOTs) existing Pavement Management Information System (PMIS) with respect to the input information required for Mechanistic-Empirical Pavement Des...

Calibrating the mechanistic-empirical pavement design guide for Kansas : [technical summary].

DOT National Transportation Integrated Search

2015-04-01

The Kansas Department of Transportation (KDOT) is moving toward the implementation : of the new American Association of State Highway and Transportation Officials : (AASHTO) Mechanistic-Empirical Pavement Design Guide (MEPDG) for pavement : design. T...

Mechanistic studies of the radical SAM enzyme spore photoproduct lyase (SPL).

PubMed

Li, Lei

2012-11-01

Spore photoproduct lyase (SPL) repairs a special thymine dimer 5-thyminyl-5,6-dihydrothymine, which is commonly called spore photoproduct or SP at the bacterial early germination phase. SP is the exclusive DNA photo-damage product in bacterial endospores; its generation and swift repair by SPL are responsible for the spores' extremely high UV resistance. The early in vivo studies suggested that SPL utilizes a direct reversal strategy to repair the SP in the absence of light. The research in the past decade further established SPL as a radical SAM enzyme, which utilizes a tri-cysteine CXXXCXXC motif to harbor a [4Fe-4S] cluster. At the 1+ oxidation state, the cluster provides an electron to the S-adenosylmethionine (SAM), which binds to the cluster in a bidentate manner as the fourth and fifth ligands, to reductively cleave the CS bond associated with the sulfonium ion in SAM, generating a reactive 5'-deoxyadenosyl (5'-dA) radical. This 5'-dA radical abstracts the proR hydrogen atom from the C6 carbon of SP to initiate the repair process; the resulting SP radical subsequently fragments to generate a putative thymine methyl radical, which accepts a back-donated H atom to yield the repaired TpT. SAM is suggested to be regenerated at the end of each catalytic cycle; and only a catalytic amount of SAM is needed in the SPL reaction. The H atom source for the back donation step is suggested to be a cysteine residue (C141 in Bacillus subtilis SPL), and the H-atom transfer reaction leaves a thiyl radical behind on the protein. This thiyl radical thus must participate in the SAM regeneration process; however how the thiyl radical abstracts an H atom from the 5'-dA to regenerate SAM is unknown. This paper reviews and discusses the history and the latest progress in the mechanistic elucidation of SPL. Despite some recent breakthroughs, more questions are raised in the mechanistic understanding of this intriguing DNA repair enzyme. This article is part of a Special Issue

Mechanistic modeling of reactive soil nitrogen emissions across agricultural management practices

NASA Astrophysics Data System (ADS)

Rasool, Q. Z.; Miller, D. J.; Bash, J. O.; Venterea, R. T.; Cooter, E. J.; Hastings, M. G.; Cohan, D. S.

2017-12-01

The global reactive nitrogen (N) budget has increased by a factor of 2-3 from pre-industrial levels. This increase is especially pronounced in highly N fertilized agricultural regions in summer. The reactive N emissions from soil to atmosphere can be in reduced (NH3) or oxidized (NO, HONO, N2O) forms, depending on complex biogeochemical transformations of soil N reservoirs. Air quality models like CMAQ typically neglect soil emissions of HONO and N2O. Previously, soil NO emissions estimated by models like CMAQ remained parametric and inconsistent with soil NH3 emissions. Thus, there is a need to more mechanistically and consistently represent the soil N processes that lead to reactive N emissions to the atmosphere. Our updated approach estimates soil NO, HONO and N2O emissions by incorporating detailed agricultural fertilizer inputs from EPIC, and CMAQ-modeled N deposition, into the soil N pool. EPIC addresses the nitrification, denitrification and volatilization rates along with soil N pools for agricultural soils. Suitable updates to account for factors like nitrite (NO2-) accumulation not addressed in EPIC, will also be made. The NO and N2O emissions from nitrification and denitrification are computed mechanistically using the N sub-model of DAYCENT. These mechanistic definitions use soil water content, temperature, NH4+ and NO3- concentrations, gas diffusivity and labile C availability as dependent parameters at various soil layers. Soil HONO emissions found to be most probable under high NO2- availability will be based on observed ratios of HONO to NO emissions under different soil moistures, pH and soil types. The updated scheme will utilize field-specific soil properties and N inputs across differing manure management practices such as tillage. Comparison of the modeled soil NO emission rates from the new mechanistic and existing schemes against field measurements will be discussed. Our updated framework will help to predict the diurnal and daily variability

`Inverse Crime' and Model Integrity in Lightcurve Inversion applied to unresolved Space Object Identification

NASA Astrophysics Data System (ADS)

Henderson, Laura S.; Subbarao, Kamesh

2017-12-01

This work presents a case wherein the selection of models when producing synthetic light curves affects the estimation of the size of unresolved space objects. Through this case, "inverse crime" (using the same model for the generation of synthetic data and data inversion), is illustrated. This is done by using two models to produce the synthetic light curve and later invert it. It is shown here that the choice of model indeed affects the estimation of the shape/size parameters. When a higher fidelity model (henceforth the one that results in the smallest error residuals after the crime is committed) is used to both create, and invert the light curve model the estimates of the shape/size parameters are significantly better than those obtained when a lower fidelity model (in comparison) is implemented for the estimation. It is therefore of utmost importance to consider the choice of models when producing synthetic data, which later will be inverted, as the results might be misleadingly optimistic.

Generative Mechanistic Explanation Building in Undergraduate Molecular and Cellular Biology

ERIC Educational Resources Information Center

Southard, Katelyn M.; Espindola, Melissa R.; Zaepfel, Samantha D.; Bolger, Molly S.

2017-01-01

When conducting scientific research, experts in molecular and cellular biology (MCB) use specific reasoning strategies to construct mechanistic explanations for the underlying causal features of molecular phenomena. We explored how undergraduate students applied this scientific practice in MCB. Drawing from studies of explanation building among…

Expanding Horizons and Unresolved Conundrums: Language Testing and Assessment

ERIC Educational Resources Information Center

Leung, Constant; Lewkowicz, Jo

2006-01-01

Since the last "TESOL Quarterly" commemorative issue 15 years ago, there have been too many important developments in language testing and assessment for all of them to be discussed in a single article. Therefore, this article focuses on issues that we believe are integrally linked to pedagogic and curriculum concerns of English language teaching.…

Key Scientific Issues in the Health Risk Assessment of Trichloroethylene

PubMed Central

Chiu, Weihsueh A.; Caldwell, Jane C.; Keshava, Nagalakshmi; Scott, Cheryl Siegel

2006-01-01

Trichloroethylene (TCE) is a common environmental contaminant at hazardous waste sites and in ambient and indoor air. Assessing the human health risks of TCE is challenging because of its inherently complex metabolism and toxicity and the widely varying perspectives on a number of critical scientific issues. Because of this complexity, the U.S. Environmental Protection Agency (EPA) drew upon scientific input and expertise from a wide range of groups and individuals in developing its 2001 draft health risk assessment of TCE. This scientific outreach, which was aimed at engaging a diversity of perspectives rather than developing consensus, culminated in 2000 with 16 state-of-the-science articles published together as an Environmental Health Perspectives supplement. Since that time, a substantial amount of new scientific research has been published that is relevant to assessing TCE health risks. Moreover, a number of difficult or controversial scientific issues remain unresolved and are the subject of a scientific consultation with the National Academy of Sciences coordinated by the White House Office of Science and Technology Policy and co-sponsored by a number of federal agencies, including the U.S. EPA. The articles included in this mini-monograph provide a scientific update on the most prominent of these issues: the pharmacokinetics of TCE and its metabolites, mode(s) of action and effects of TCE metabolites, the role of peroxisome proliferator–activated receptor in TCE toxicity, and TCE cancer epidemiology. PMID:16966103

Improvements In AF Ablation Outcome Will Be Based More On Technological Advancement Versus Mechanistic Understanding.

PubMed

Jiang Md, Chen-Yang; Jiang Ms, Ru-Hong

2014-01-01

Atrial fibrillation (AF) is one of the most common cardiac arrhythmias. Catheter ablation has proven more effective than antiarrhythmic drugs in preventing clinical recurrence of AF, however long-term outcome remains unsatisfactory. Ablation strategies have evolved based on progress in mechanistic understanding, and technologies have advanced continuously. This article reviews current mechanistic concepts and technological advancements in AF treatment, and summarizes their impact on improvement of AF ablation outcome.

USE OF MECHANISTIC DATA TO HELP DEFINE DOSE-RESPONSE CURVES

EPA Science Inventory

Use of Mechanistic Data to Help Define Dose-Response Curves

The cancer risk assessment process described by the U.S. EPA necessitates a description of the dose-response curve for tumors in humans at low (environmental) exposures. This description can either be a default l...

Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation: Report of an FDA Public Workshop

PubMed Central

Duan, J; Kesisoglou, F; Novakovic, J; Amidon, GL; Jamei, M; Lukacova, V; Eissing, T; Tsakalozou, E; Zhao, L; Lionberger, R

2017-01-01

On May 19, 2016, the US Food and Drug Administration (FDA) hosted a public workshop, entitled “Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation.”1 The topic of mechanistic oral absorption modeling, which is one of the major applications of physiologically based pharmacokinetic (PBPK) modeling and simulation, focuses on predicting oral absorption by mechanistically integrating gastrointestinal transit, dissolution, and permeation processes, incorporating systems, active pharmaceutical ingredient (API), and the drug product information, into a systemic mathematical whole‐body framework.2 PMID:28571121

Base course resilient modulus for the mechanistic-empirical pavement design guide.

DOT National Transportation Integrated Search

2011-11-01

The Mechanistic-Empirical Pavement Design Guidelines (MEPDG) recommend use of modulus in lieu of structural number for base layer thickness design. Modulus is nonlinear with respect to effective confinement stress, loading strain, and moisture. For d...

Dose-response relationships and extrapolation in toxicology - Mechanistic and statistical considerations

EPA Science Inventory

Controversy on toxicological dose-response relationships and low-dose extrapolation of respective risks is often the consequence of misleading data presentation, lack of differentiation between types of response variables, and diverging mechanistic interpretation. In this chapter...

Implementation of the AASHTO mechanistic-empirical pavement design guide for Colorado.

DOT National Transportation Integrated Search

2000-01-01

The objective of this project was to integrate the American Association of State Highway and Transportation Officials (AASHTO) Mechanistic-Empirical Pavement Design Guide, Interim Edition: A Manual of Practice and its accompanying software into the d...

A precision medicine approach to a patient with unresolved pain following orthopedic surgery: a case report.

PubMed

Gazzaniga, David; Brenton, Ashley; Meshkin, Brian

2017-02-24

Precision medicine is a promising technology in patient care that combines genetic analysis with clinical data, such as health, behavioral, functional, environment, and lifestyle information. Here we present the case of a 54-year old woman who, following an accident, had uncontrolled chronic pain and was subsequently labeled a drug seeker. A 54-year-old white woman who was experiencing severe calf pain was referred for treatment. Her pain was insufficiently controlled immediately following knee arthroplasty with multiple opioid medications, as well as non-opioids. Precision medicine testing was ordered for her so that we could assess her pain sensitivity objectively to determine if the pill seeker designation was correct and to determine the best medications for her. Based on the Proove profiles, we determined that she had moderately low pain sensitivity, which means that clinically she may underreport pain and may have decreased medication needs. This result suggested that her continued reporting of unresolved pain was probably due to a condition unresolved by her right knee arthroplasty. In addition, she was found to be at low risk of opioid addiction, based on the Proove Opioid Risk Profile. Taken together, along with the high levels of pain she described, we determined that her pain was not properly controlled and that the designation of pill seeker was incorrect. The next step was to determine which medications and which doses would result in the most favorable outcomes for our patient. To determine this, we used the results of the Proove Opioid Response, Proove Drug Metabolism, and Proove Non-Opioid Profiles to guide her treatment. We reduced her pain medications to a single opioid, Vicodin (acetaminophen and hydrocodone), which also eliminated the adverse side effects she experienced. Precision medicine offers an important health care decision tool which can reduce emotional and physical costs to patients and may reduce the economic health care burden of

Mechanistic equivalent circuit modelling of a commercial polymer electrolyte membrane fuel cell

NASA Astrophysics Data System (ADS)

Giner-Sanz, J. J.; Ortega, E. M.; Pérez-Herranz, V.

2018-03-01

Electrochemical impedance spectroscopy (EIS) has been widely used in the fuel cell field since it allows deconvolving the different physic-chemical processes that affect the fuel cell performance. Typically, EIS spectra are modelled using electric equivalent circuits. In this work, EIS spectra of an individual cell of a commercial PEM fuel cell stack were obtained experimentally. The goal was to obtain a mechanistic electric equivalent circuit in order to model the experimental EIS spectra. A mechanistic electric equivalent circuit is a semiempirical modelling technique which is based on obtaining an equivalent circuit that does not only correctly fit the experimental spectra, but which elements have a mechanistic physical meaning. In order to obtain the aforementioned electric equivalent circuit, 12 different models with defined physical meanings were proposed. These equivalent circuits were fitted to the obtained EIS spectra. A 2 step selection process was performed. In the first step, a group of 4 circuits were preselected out of the initial list of 12, based on general fitting indicators as the determination coefficient and the fitted parameter uncertainty. In the second step, one of the 4 preselected circuits was selected on account of the consistency of the fitted parameter values with the physical meaning of each parameter.

Mathematical Description and Mechanistic Reasoning: A Pathway toward STEM Integration

ERIC Educational Resources Information Center

Weinberg, Paul J.

2017-01-01

Because reasoning about mechanism is critical to disciplined inquiry in science, technology, engineering, and mathematics (STEM) domains, this study focuses on ways to support the development of this form of reasoning. This study attends to how mechanistic reasoning is constituted through mathematical description. This study draws upon Smith's…

Temporal behavior of unresolved transition array emission in water window soft x-ray spectral region from multiply charged ions

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

Dinh, Thanh-Hung, E-mail: dinh@cc.utsunomiya-u.ac.jp; Suzuki, Yuhei; Arai, Goki

2015-09-21

We have characterized the spectral structure and the temporal history of the laser-produced high-Z multi-charged ion plasmas for the efficient water window soft x-ray sources. Strong unresolved transition array emission was observed due to 4d–4f and 4f–5g transitions from Au, Pb, and Bi plasmas in the 280–700 eV photon energy region. The temporal behavior of the emission was essentially similar of that of the laser pulse with a slight delay between different transitions. These results provide feedback for accurate modeling of the atomic processes with the radiative hydrodynamic simulations.

Explicit Global Simulation of Gravity Waves up to the Lower Thermosphere

NASA Astrophysics Data System (ADS)

Becker, E.

2016-12-01

At least for short-term simulations, middle atmosphere general circulation models (GCMs) can be run with sufficiently high resolution in order to describe a good part of the gravity wave spectrum explicitly. Nevertheless, the parameterization of unresolved dynamical scales remains an issue, especially when the scales of parameterized gravity waves (GWs) and resolved GWs become comparable. In addition, turbulent diffusion must always be parameterized along with other subgrid-scale dynamics. A practical solution to the combined closure problem for GWs and turbulent diffusion is to dispense with a parameterization of GWs, apply a high spatial resolution, and to represent the unresolved scales by a macro-turbulent diffusion scheme that gives rise to wave damping in a self-consistent fashion. This is the approach of a few GCMs that extend from the surface to the lower thermosphere and simulate a realistic GW drag and summer-to-winter-pole residual circulation in the upper mesosphere. In this study we describe a new version of the Kuehlungsborn Mechanistic general Circulation Model (KMCM), which includes explicit (though idealized) computations of radiative transfer and the tropospheric moisture cycle. Particular emphasis is spent on 1) the turbulent diffusion scheme, 2) the attenuation of resolved GWs at critical levels, 3) the generation of GWs in the middle atmosphere from body forces, and 4) GW-tidal interactions (including the energy deposition of GWs and tides).

Widening Access to Scottish Higher Education: Unresolved Issues and Future Challenges

ERIC Educational Resources Information Center

Riddell, Sheila

2016-01-01

Despite the Scottish Government's frequent affirmation of its commitment to social justice principles, there has of late been a recognition of the need for firmer action to tackle the social class gap in higher education participation, reflecting wider social inequalities in Scotland. In a recent policy statement, Angela Constance, Cabinet…

Global scale analysis and evaluation of an improved mechanistic representation of plant nitrogen and carbon dynamics in the Community Land Model (CLM)

NASA Astrophysics Data System (ADS)

Ghimire, B.; Riley, W. J.; Koven, C. D.; Randerson, J. T.; Mu, M.; Kattge, J.; Rogers, A.; Reich, P. B.

2014-12-01

In many ecosystems, nitrogen is the most limiting nutrient for plant growth and productivity. However mechanistic representation of nitrogen uptake linked to root traits, and functional nitrogen allocation among different leaf enzymes involved in respiration and photosynthesis is currently lacking in Earth System models. The linkage between nitrogen availability and plant productivity is simplistically represented by potential photosynthesis rates, and is subsequently downregulated depending on nitrogen supply and other nitrogen consumers in the model (e.g., nitrification). This type of potential photosynthesis rate calculation is problematic for several reasons. Firstly, plants do not photosynthesize at potential rates and then downregulate. Secondly, there is considerable subjectivity on the meaning of potential photosynthesis rates. Thirdly, there exists lack of understanding on modeling these potential photosynthesis rates in a changing climate. In addition to model structural issues in representing photosynthesis rates, the role of plant roots in nutrient acquisition have been largely ignored in Earth System models. For example, in CLM4.5, nitrogen uptake is linked to leaf level processes (e.g., primarily productivity) rather than root scale process involved in nitrogen uptake. We present a new plant model for CLM with an improved mechanistic presentation of plant nitrogen uptake based on root scale Michaelis Menten kinetics, and stronger linkages between leaf nitrogen and plant productivity by inferring relationships observed in global databases of plant traits (including the TRY database and several individual studies). We also incorporate improved representation of plant nitrogen leaf allocation, especially in tropical regions where significant over-prediction of plant growth and productivity in CLM4.5 simulations exist. We evaluate our improved global model simulations using the International Land Model Benchmarking (ILAMB) framework. We conclude that

The lens of the eye: exposures in the UK medical sector and mechanistic studies of radiation effects.

PubMed

Bouffler, S D; Peters, S; Gilvin, P; Slack, K; Markiewicz, E; Quinlan, R A; Gillan, J; Coster, M; Barnard, S; Rothkamm, K; Ainsbury, E

2015-06-01

The recommendation from the International Commission on Radiological Protection that the occupational equivalent dose limit for the lens of the eye should be reduced to 20 mSv year(-1), averaged over 5 years with no year exceeding 50 mSv, has stimulated a discussion on the practicalities of implementation of this revised dose limit, and the most appropriate risk and protection framework to adopt. This brief paper provides an overview of some of the drivers behind the move to a lower recommended dose limit. The issue of implementation in the medical sector in the UK has been addressed through a small-scale survey of doses to the lens of the eye amongst interventional cardiologists and radiologists. In addition, a mechanistic study of early and late post-irradiation changes in the lens of the eye in in-vivo-exposed mice is outlined. Surveys and studies such as those described can contribute to a deeper understanding of fundamental and practical issues, and therefore contribute to a robust evidence base for ensuring adequate protection of the eye while avoiding undesirable restrictions to working practices. © The International Society for Prosthetics and Orthotics Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Wynoochee Hydropower/Fish Hatchery: Feasibility Report and Environmental Impact Statement.

DTIC Science & Technology

1982-09-30

Unresolved Issues. There are no unresolved issues associated with the Wynoochee hydropower/fish hatchery plan. 4. Relationship to Environmental...Requirements.l/ The relationship of the Wynoochee hydropower/fish hatchery plan to environmental requirements is summarized in the following table...Implementation of the plan would I/The relationship of the satellite fish station to the environmental requirements is not included in this discussion. Compliance

Identification of unresolved complex mixtures (UCMs) of hydrocarbons in commercial fish oil supplements.

PubMed

Reid, Anna-Jean M; Budge, Suzanne M

2015-01-01

Heightened awareness of the health benefits of fish oil consumption has led to a great increase in the number of fish oil supplements available to the consumer. Therefore manufacturers are continually looking for ways to distinguish their products from those of competitors. Minimally refined or virgin fish oils provide a unique feature; however, petroleum hydrocarbon contamination from oil spills is a reality in the world's oceans. The question arises whether oil produced from fish species caught in these polluted areas is free of petroleum hydrocarbons, with particular interest in unresolved complex mixtures (UCMs). This study investigates the presence of UCMs in commercially available fish oil supplements advertised as being virgin, as well as refined. Weathered petroleum hydrocarbons in the form of a UCM were found at 523 µg g(-1) in a virgin Alaskan salmon oil supplement. Supplements that were refined were free of this contamination. Fish used in the production of fish oil supplements appear to have accumulated petrogenic hydrocarbons in their tissues which were not removed by minimal oil refining. Further study is required to determine if there are any health implications associated with long-term consumption of these contaminated supplements. © 2014 Society of Chemical Industry.

CHEMICAL MUTAGENESIS AND CARCINOGENESIS: INCORPORATION OF MECHANISTIC DATA INTO RISK ASSESSMENT

EPA Science Inventory

CHEMICAL MUTAGENESIS AND CARCINOGENESIS: INCORPORATION OF MECHANISTIC DATA INTO RISK ASSESSMENT

The current understanding of cancer as a genetic disease, requiring a specific set of genomic alterations for a normal cell to form a metastatic tumor, has provided the oppor...

INCORPORATION OF MECHANISTIC INFORMATION IN THE ARSENIC PBPK MODEL DEVELOPMENT PROCESS

EPA Science Inventory

INCORPORATING MECHANISTIC INSIGHTS IN A PBPK MODEL FOR ARSENIC

Elaina M. Kenyon, Michael F. Hughes, Marina V. Evans, David J. Thomas, U.S. EPA; Miroslav Styblo, University of North Carolina; Michael Easterling, Analytical Sciences, Inc.

A physiologically based phar...

Integration of QSAR and SAR methods for the mechanistic interpretation of predictive models for carcinogenicity

PubMed Central

Fjodorova, Natalja; Novič, Marjana

2012-01-01

The knowledge-based Toxtree expert system (SAR approach) was integrated with the statistically based counter propagation artificial neural network (CP ANN) model (QSAR approach) to contribute to a better mechanistic understanding of a carcinogenicity model for non-congeneric chemicals using Dragon descriptors and carcinogenic potency for rats as a response. The transparency of the CP ANN algorithm was demonstrated using intrinsic mapping technique specifically Kohonen maps. Chemical structures were represented by Dragon descriptors that express the structural and electronic features of molecules such as their shape and electronic surrounding related to reactivity of molecules. It was illustrated how the descriptors are correlated with particular structural alerts (SAs) for carcinogenicity with recognized mechanistic link to carcinogenic activity. Moreover, the Kohonen mapping technique enables one to examine the separation of carcinogens and non-carcinogens (for rats) within a family of chemicals with a particular SA for carcinogenicity. The mechanistic interpretation of models is important for the evaluation of safety of chemicals. PMID:24688639

Engineering properties of resin modified pavement (RMP) for mechanistic design

NASA Astrophysics Data System (ADS)

Anderton, Gary Lee

1997-11-01

The research study described in this report focuses on determining the engineering properties of the resin modified pavement (RMP) material relating to pavement performance, and then developing a rational mechanistic design procedure to replace the current empirical design procedure. A detailed description of RMP is provided, including a review of the available literature on this relatively new pavement technology. Field evaluations of four existing and two new RMP project sites were made to assess critical failure modes and to obtain pavement samples for subsequent laboratory testing. Various engineering properties of laboratory-produced and field-recovered samples of RMP were measured and analyzed. The engineering properties evaluated included those relating to the material's stiffness, strength, thermal properties, and traffic-related properties. Comparisons of these data to typical values for asphalt concrete and portland cement concrete were made to relate the physical nature of RMP to more common pavement surfacing materials. A mechanistic design procedure was developed to determine appropriate thickness profiles of RMP, using stiffness and fatigue properties determined by this study. The design procedure is based on the U.S. Army Corps of Engineers layered elastic method for airfield flexible pavements. The WESPAVE computer program was used to demonstrate the new design procedure for a hypothetical airfield apron design. The results of the study indicated that RMP is a relatively stiff, viscoelastic pavement surfacing material with many of its strength and stiffness properties falling between those of typical asphalt concrete and portland cement concrete. The RMP's thermal and traffic-related properties indicated favorable field performance. The layered elastic design approach appeared to be a reasonable and practical method for RMP mechanistic pavement design, and this design procedure was recommended for future use and development.

Mechanistic species distribution modeling reveals a niche shift during invasion.

PubMed

Chapman, Daniel S; Scalone, Romain; Štefanić, Edita; Bullock, James M

2017-06-01

Niche shifts of nonnative plants can occur when they colonize novel climatic conditions. However, the mechanistic basis for niche shifts during invasion is poorly understood and has rarely been captured within species distribution models. We quantified the consequence of between-population variation in phenology for invasion of common ragweed (Ambrosia artemisiifolia L.) across Europe. Ragweed is of serious concern because of its harmful effects as a crop weed and because of its impact on public health as a major aeroallergen. We developed a forward mechanistic species distribution model based on responses of ragweed development rates to temperature and photoperiod. The model was parameterized and validated from the literature and by reanalyzing data from a reciprocal common garden experiment in which native and invasive populations were grown within and beyond the current invaded range. It could therefore accommodate between-population variation in the physiological requirements for flowering, and predict the potentially invaded ranges of individual populations. Northern-origin populations that were established outside the generally accepted climate envelope of the species had lower thermal requirements for bud development, suggesting local adaptation of phenology had occurred during the invasion. The model predicts that this will extend the potentially invaded range northward and increase the average suitability across Europe by 90% in the current climate and 20% in the future climate. Therefore, trait variation observed at the population scale can trigger a climatic niche shift at the biogeographic scale. For ragweed, earlier flowering phenology in established northern populations could allow the species to spread beyond its current invasive range, substantially increasing its risk to agriculture and public health. Mechanistic species distribution models offer the possibility to represent niche shifts by varying the traits and niche responses of individual

Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation: Report of an FDA Public Workshop.

PubMed

Zhang, X; Duan, J; Kesisoglou, F; Novakovic, J; Amidon, G L; Jamei, M; Lukacova, V; Eissing, T; Tsakalozou, E; Zhao, L; Lionberger, R

2017-08-01

On May 19, 2016, the US Food and Drug Administration (FDA) hosted a public workshop, entitled "Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation." The topic of mechanistic oral absorption modeling, which is one of the major applications of physiologically based pharmacokinetic (PBPK) modeling and simulation, focuses on predicting oral absorption by mechanistically integrating gastrointestinal transit, dissolution, and permeation processes, incorporating systems, active pharmaceutical ingredient (API), and the drug product information, into a systemic mathematical whole-body framework. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Base course resilient modulus for the mechanistic-empirical pavement design guide : [summary].

DOT National Transportation Integrated Search

2011-01-01

Elastic modulus determination is often used in designing pavements and evaluating pavement performance. The Mechanistic-Empirical Pavement Design Guide (MEPDG) has become an important source of guidance for pavement design and rehabilitation. MEPDG r...

Proceedings of the Hydrokinetic and Wave Energy Technologies Technical and Environmental Issues Workshop

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

None

2006-03-01

Renewable energy technologies offer the promise of non-polluting alternatives to fossil and nuclear-fueled power plants to meet growing demand for electrical energy. Two emerging categories of renewable energy technologies, hydrokinetic and wave energy conversion devices, offer ways to tap the energy of moving water without impoundment (dams) or diversion required by many conventional hydroelectric facilities. These technologies include devices designed for deployment in natural streams, tidal estuaries, ocean currents, and constructed waterways, as well as devices designed to capture the energy of ocean waves. On October 26-28, 2005, 54 representatives from government, non-governmental organizations, and private business met to (1)more » identify the varieties of hydrokinetic energy and wave technology devices, their stages of development, and the projected cost to bring each to market; (2) identify where these technologies can best operate; (3) identify the potential environmental issues associated with these technologies and possible mitigation measures; (4) develop a list of research needs and/or practical solutions to address unresolved environmental issues. These workshop proceedings include detailed summaries of the 24 presentations made and the discussions that followed.« less

VICTORIA: A mechanistic model for radionuclide behavior in the reactor coolant system

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

Schaperow, J.H.; Bixler, N.E.

1996-12-31

VICTORIA is the U.S. Nuclear Regulatory Commission`s (NRC`s) mechanistic, best-estimate code for analysis of fission product release from the core and subsequent transport in the reactor vessel and reactor coolant system. VICTORIA requires thermal-hydraulic data (i.e., temperatures, pressures, and velocities) as input. In the past, these data have been taken from the results of calculations from thermal-hydraulic codes such as SCDAP/RELAP5, MELCOR, and MAAP. Validation and assessment of VICTORIA 1.0 have been completed. An independent peer review of VICTORIA, directed by Brookhaven National Laboratory and supported by experts in the areas of fuel release, fission product chemistry, and aerosol physics,more » has been undertaken. This peer review, which will independently assess the code`s capabilities, is nearing completion with the peer review committee`s final report expected in Dec 1996. A limited amount of additional development is expected as a result of the peer review. Following this additional development, the NRC plans to release VICTORIA 1.1 and an updated and improved code manual. Future plans mainly involve use of the code for plant calculations to investigate specific safety issues as they arise. Also, the code will continue to be used in support of the Phebus experiments.« less

Deaf murderers: clinical and forensic issues.

PubMed

Vernon, M; Steinberg, A G; Montoya, L A

1999-01-01

Data are reported on 28 deaf individuals who were convicted, pled guilty, or have been charged and awaiting trial for murder. The unique forensic issues raised by these cases are discussed, and their clinical picture presented. A significant percentage of these deaf murderers and defendants had such severely limited communication skills in both English and American Sign Language that they lacked the linguistic ability to understand the charges against them and/or to participate in their own defense. As such, they were incompetent to stand trial, due not to mental illness or mental retardation, but to linguistic deficits. This form of incompetence poses a dilemma to the courts that remains unresolved. This same linguistic disability makes it impossible for some deaf suspects to be administered Miranda Warnings in a way comprehensible to them. This paper identifies the reasons for the communication problems many deaf persons face in court and offers remedial steps to help assure fair trials and police interrogations for deaf defendants. The roles and responsibilities of psychiatric and psychological experts in these cases are discussed. Data are provided on the etiology of the 28 individuals' hearing losses, psychiatric/psychological histories, IQs, communication characteristics, educational levels, and victim characteristics. Copyright 1999 John Wiley & Sons, Ltd.

Mechanistic and "natural" body metaphors and their effects on attitudes to hormonal contraception.

PubMed

Walker, Susan

2012-01-01

A small, self-selected convenience sample of male and female contraceptive users in the United Kingdom (n = 34) were interviewed between 2006 and 2008 concerning their feelings about the body and their contraceptive attitudes and experiences. The interviewees were a sub-sample of respondents (n = 188) who completed a paper-based questionnaire on similar topics, who were recruited through a poster placed in a family planning clinic, web-based advertisements on workplace and university websites, and through direct approaches to social groups. The bodily metaphors used when discussing contraception were analyzed using an interpretative phenomenological analytical approach facilitated by Atlas.ti software. The dominant bodily metaphor was mechanistic (i.e.,"body as machine"). A subordinate but influential bodily metaphor was the "natural" body, which had connotations of connection to nature and a quasi-sacred bodily order. Interviewees drew upon this "natural" metaphorical image in the context of discussing their anxieties about hormonal contraception. Drawing upon a "natural," non-mechanistic body image in the context of contraceptive decision-making contributed to reluctance to use a hormonal form of contraception. This research suggests that clinicians could improve communication and advice about contraception by recognizing that some users may draw upon non-mechanistic body imagery.

Toxicity of organic compounds from unresolved complex mixtures (UCMs) to primary fish hepatocytes.

PubMed

Petersen, Karina; Hultman, Maria T; Rowland, Steven J; Tollefsen, Knut Erik

2017-09-01

Many environmental matrices contaminated with organic pollutants derived from crude oil or degraded petroleum contain mixtures so complex that they are typically unresolved by conventional analytical techniques such as gas chromatography. The resulting chromatographic features have become known as 'humps' or unresolved complex mixtures (UCMs). These UCMs often dominate the organic contaminants of polluted environmental samples: for example, in oil sands produced water up to 150mgL -1 of 'naphthenic acids' appear as UCMs when examined by gas chromatography as the esters. In oil-contaminated mussels, aromatic hydrocarbon UCMs may comprise almost all of the total toxic hydrocarbons, with over 7000μgg -1 dry weight reported in some samples. Over the last 25 years, efforts to resolve and thus identify, or at least to produce average structures, for some UCM components, have proved fruitful. Numerous non-polar UCM hydrocarbons and more polar UCM acids have been identified, then synthesised or purchased from commercial suppliers. As UCMs have been proposed to represent a risk to aquatic organisms, the need for assessment of the ecotoxicological effects and characterisation of the mode of action (MoA) of these environmental pollutants has arisen. In the present study, several chemicals with structures typical of those found in some UCMs, were assessed for their potential to disrupt membrane integrity, inhibit metabolic activity, activate the aryl hydrocarbon receptor (AhR), and activate the estrogen receptor (ER) in primary rainbow trout hepatocytes (Oncorhynchus mykiss). These endpoints were determined in order to screen for common toxic modes of action (MoA) in this diverse group of chemicals. The results from the in vitro screening indicated that of the endpoints tested, the predominant toxic MoA was cytotoxicity. EC 50 values for cytotoxicity were obtained for 16 compounds and ranged from 77μM-24mM, whereof aliphatic monocyclic acids, monoaromatic acids, polycyclic

Validation of pavement performance curves for the mechanistic-empirical pavement design guide.

DOT National Transportation Integrated Search

2009-02-01

The objective of this research is to determine whether the nationally calibrated performance models used in the Mechanistic-Empirical : Pavement Design Guide (MEPDG) provide a reasonable prediction of actual field performance, and if the desired accu...

Mechanistic-empirical evaluation of the Mn/ROAD low volume road test sections.

DOT National Transportation Integrated Search

1998-05-01

The purpose of this study was to use Mn/ROAD mainline flexible pavement data to verify, refine, and modify the Illinois Department of Transportation (IDOT) Mechanistic-Empirical (M-E) based flexible pavement design procedures and concepts.

Characterization of unbound materials (soils/aggregates) for mechanistic-empirical pavement design guide.

DOT National Transportation Integrated Search

2009-02-01

The resilient modulus (MR) input parameters in the Mechanistic-Empirical Pavement Design Guide (MEPDG) program have a significant effect on the projected pavement performance. The MEPDG program uses three different levels of inputs depending on the d...

Mechanistic-empirical design, implementation, and monitoring for flexible pavements : a project summary.

DOT National Transportation Integrated Search

2014-05-01

This document is a summary of tasks performed for Project ICT-R27-060. : Mechanistic-empirical (M-E)based flexible pavement design concepts and procedures were : developed in previous Illinois Cooperative Highway Research Program projects (IHR-510...

Issues in energy finance

NASA Astrophysics Data System (ADS)

Khokher, Zeigham Islam

As opposed to the well developed and understood equity markets, the energy markets are still in their infancy. The explosion of contracts, of both the primary and derivative types, are testament both to the existing size and the untapped growth potential of this exciting industry. However, because of its relative youth many basic issues in the energy markets remain unresolved. This thesis introduces some interesting questions and provides insights into these issues. Thematically, the chapters of this thesis are linked by an emphasis on valuation and risk management decisions. A contribution of this thesis is to show that subtle differences between the endogenous price process in our general equilibrium setting and the exogenous processes considered in earlier papers can generate significant differences in both financial and real option values. In addition to these valuation concerns there has been much debate about the corporate risk management function. Finance theory suggests that a value maximizing corporation should either be indifferent to hedging or, in the presence of certain imperfections, it should completely hedge all exposures. Both these extremes contradict empirical evidence. We show that existing corporate hedging behaviour is best explained in light of both physical market imperfections and directional predictions on future prices. While these speculative motives may arise from corporate hubris or genuine informational advantages, we argue that it would be difficult to implement private information in the absence of noise traders. Related to the risk management decision is the existence of futures risk premia. These premia have been thought to be cause by covariance with priced factors or due to the hedging demands of consumers and producers. This thesis argues that inventories serve as a signal of available quantity, which coupled with consumers fears regarding stockouts can induce a positive relationship between premia and inventories. In

The Combined Use of Correlative and Mechanistic Species Distribution Models Benefits Low Conservation Status Species.

PubMed

Rougier, Thibaud; Lassalle, Géraldine; Drouineau, Hilaire; Dumoulin, Nicolas; Faure, Thierry; Deffuant, Guillaume; Rochard, Eric; Lambert, Patrick

2015-01-01

Species can respond to climate change by tracking appropriate environmental conditions in space, resulting in a range shift. Species Distribution Models (SDMs) can help forecast such range shift responses. For few species, both correlative and mechanistic SDMs were built, but allis shad (Alosa alosa), an endangered anadromous fish species, is one of them. The main purpose of this study was to provide a framework for joint analyses of correlative and mechanistic SDMs projections in order to strengthen conservation measures for species of conservation concern. Guidelines for joint representation and subsequent interpretation of models outputs were defined and applied. The present joint analysis was based on the novel mechanistic model GR3D (Global Repositioning Dynamics of Diadromous fish Distribution) which was parameterized on allis shad and then used to predict its future distribution along the European Atlantic coast under different climate change scenarios (RCP 4.5 and RCP 8.5). We then used a correlative SDM for this species to forecast its distribution across the same geographic area and under the same climate change scenarios. First, projections from correlative and mechanistic models provided congruent trends in probability of habitat suitability and population dynamics. This agreement was preferentially interpreted as referring to the species vulnerability to climate change. Climate change could not be accordingly listed as a major threat for allis shad. The congruence in predicted range limits between SDMs projections was the next point of interest. The difference, when noticed, required to deepen our understanding of the niche modelled by each approach. In this respect, the relative position of the northern range limit between the two methods strongly suggested here that a key biological process related to intraspecific variability was potentially lacking in the mechanistic SDM. Based on our knowledge, we hypothesized that local adaptations to cold

The Combined Use of Correlative and Mechanistic Species Distribution Models Benefits Low Conservation Status Species

PubMed Central

Rougier, Thibaud; Lassalle, Géraldine; Drouineau, Hilaire; Dumoulin, Nicolas; Faure, Thierry; Deffuant, Guillaume; Rochard, Eric; Lambert, Patrick

2015-01-01

Species can respond to climate change by tracking appropriate environmental conditions in space, resulting in a range shift. Species Distribution Models (SDMs) can help forecast such range shift responses. For few species, both correlative and mechanistic SDMs were built, but allis shad (Alosa alosa), an endangered anadromous fish species, is one of them. The main purpose of this study was to provide a framework for joint analyses of correlative and mechanistic SDMs projections in order to strengthen conservation measures for species of conservation concern. Guidelines for joint representation and subsequent interpretation of models outputs were defined and applied. The present joint analysis was based on the novel mechanistic model GR3D (Global Repositioning Dynamics of Diadromous fish Distribution) which was parameterized on allis shad and then used to predict its future distribution along the European Atlantic coast under different climate change scenarios (RCP 4.5 and RCP 8.5). We then used a correlative SDM for this species to forecast its distribution across the same geographic area and under the same climate change scenarios. First, projections from correlative and mechanistic models provided congruent trends in probability of habitat suitability and population dynamics. This agreement was preferentially interpreted as referring to the species vulnerability to climate change. Climate change could not be accordingly listed as a major threat for allis shad. The congruence in predicted range limits between SDMs projections was the next point of interest. The difference, when noticed, required to deepen our understanding of the niche modelled by each approach. In this respect, the relative position of the northern range limit between the two methods strongly suggested here that a key biological process related to intraspecific variability was potentially lacking in the mechanistic SDM. Based on our knowledge, we hypothesized that local adaptations to cold

Proposed key characteristics of male reproductive toxicants as a method for organizing and screening mechanistic evidence for non-cancer outcomes.

EPA Science Inventory

The adoption of systematic review practices for risk assessment includes integration of evidence obtained from experimental, epidemiological, and mechanistic studies. Although mechanistic evidence plays an important role in mode of action analysis, the process of sorting and anal...

MECHANISTIC DATA & CANCER RISK ASSESSMENT: THE NEED FOR QUANTITATIVE MOLECULAR ENDPOINTS

EPA Science Inventory

The cancer risk assessment process as currently proposed by the U.S. Environmental Protection Agency allows for the use of mechanistic data to inform the low dose tumor response in humans and in laboratory animals. The aim is to reduce the reliance on defaults that introduce a re...

Mechanistic elucidation of the antitumor properties of withaferin A in breast cancer

PubMed Central

Nagalingam, Arumugam; Kuppusamy, Panjamurthy; Singh, Shivendra V.; Sharma, Dipali; Saxena, Neeraj K.

2014-01-01

Withaferin A (WFA) is a steroidal lactone with antitumor effects manifested at multiple levels which are mechanistically obscure. Using a phospho-kinase screening array, we discovered that WFA activated phosphorylation of the S6 kinase RSK in breast cancer cells. Pursuing this observation, we defined activation of ERK-RSK and Elk1-CHOP kinase pathways in upregulating transcription of the death receptor DR5. Through this route, WFA acted as an effective DR5 activator capable of potentiating the biological effects of celecoxib, etoposide and TRAIL. Accordingly, WFA treatment inhibited breast tumor formation in xenograft and MMTV-neu mouse models in a manner associated with activation of the ERK/RSK axis, DR5 upregulation and elevated nuclear accumulation of Elk1 and CHOP. Together, our results offer mechanistic insight into how WFA inhibits breast tumor growth. PMID:24732433

Millifluidics for Chemical Synthesis and Time-resolved Mechanistic Studies

PubMed Central

Krishna, Katla Sai; Biswas, Sanchita; Navin, Chelliah V.; Yamane, Dawit G.; Miller, Jeffrey T.; Kumar, Challa S.S.R.

2013-01-01

Procedures utilizing millifluidic devices for chemical synthesis and time-resolved mechanistic studies are described by taking three examples. In the first, synthesis of ultra-small copper nanoclusters is described. The second example provides their utility for investigating time resolved kinetics of chemical reactions by analyzing gold nanoparticle formation using in situ X-ray absorption spectroscopy. The final example demonstrates continuous flow catalysis of reactions inside millifluidic channel coated with nanostructured catalyst. PMID:24327099

A mechanistic assessment of nutrient flushing at the catchment scale

Treesearch

Willem J. van Verseveld; Jeffrey J. McDonnell; Kate Lajtha

2008-01-01

This paper mechanistically assesses the flushing mechanism of DOC, DON, and DIN at the hillslope and catchment scales during two storm events, in a small catchment (WS10), H.J. Andrews Experimental Forest in the western Cascade Mountains of Oregon. Using a combination of natural tracer and hydrometric data, and end-member mixing analysis, we were able to describe the...

Predictive and mechanistic multivariate linear regression models for reaction development

PubMed Central

Santiago, Celine B.; Guo, Jing-Yao

2018-01-01

Multivariate Linear Regression (MLR) models utilizing computationally-derived and empirically-derived physical organic molecular descriptors are described in this review. Several reports demonstrating the effectiveness of this methodological approach towards reaction optimization and mechanistic interrogation are discussed. A detailed protocol to access quantitative and predictive MLR models is provided as a guide for model development and parameter analysis. PMID:29719711

Biases in Planet Occurrence Caused by Unresolved Binaries in Transit Surveys

NASA Astrophysics Data System (ADS)

Bouma, L. G.; Masuda, Kento; Winn, Joshua N.

2018-06-01

Wide-field surveys for transiting planets, such as the NASA Kepler and TESS missions, are usually conducted without knowing which stars have binary companions. Unresolved and unrecognized binaries give rise to systematic errors in planet occurrence rates, including misclassified planets and mistakes in completeness corrections. The individual errors can have different signs, making it difficult to anticipate the net effect on inferred occurrence rates. Here, we use simplified models of signal-to-noise limited transit surveys to try and clarify the situation. We derive a formula for the apparent occurrence rate density measured by an observer who falsely assumes all stars are single. The formula depends on the binary fraction, the mass function of the secondary stars, and the true occurrence of planets around primaries, secondaries, and single stars. It also takes into account the Malmquist bias by which binaries are over-represented in flux-limited samples. Application of the formula to an idealized Kepler-like survey shows that for planets larger than 2 R ⊕, the net systematic error is of order 5%. In particular, unrecognized binaries are unlikely to be the reason for the apparent discrepancies between hot-Jupiter occurrence rates measured in different surveys. For smaller planets the errors are potentially larger: the occurrence of Earth-sized planets could be overestimated by as much as 50%. We also show that whenever high-resolution imaging reveals a transit host star to be a binary, the planet is usually more likely to orbit the primary star than the secondary star.

Interactive effects of body-size structure and adaptive foraging on food-web stability.

PubMed

Heckmann, Lotta; Drossel, Barbara; Brose, Ulrich; Guill, Christian

2012-03-01

Body-size structure of food webs and adaptive foraging of consumers are two of the dominant concepts of our understanding how natural ecosystems maintain their stability and diversity. The interplay of these two processes, however, is a critically important yet unresolved issue. To fill this gap in our knowledge of ecosystem stability, we investigate dynamic random and niche model food webs to evaluate the proportion of persistent species. We show that stronger body-size structures and faster adaptation stabilise these food webs. Body-size structures yield stabilising configurations of interaction strength distributions across food webs, and adaptive foraging emphasises links to resources closer to the base. Moreover, both mechanisms combined have a cumulative effect. Most importantly, unstructured random webs evolve via adaptive foraging into stable size-structured food webs. This offers a mechanistic explanation of how size structure adaptively emerges in complex food webs, thus building a novel bridge between these two important stabilising mechanisms. © 2012 Blackwell Publishing Ltd/CNRS.

The use of mechanistic descriptions of algal growth and zooplankton grazing in an estuarine eutrophication model

NASA Astrophysics Data System (ADS)

Baird, M. E.; Walker, S. J.; Wallace, B. B.; Webster, I. T.; Parslow, J. S.

2003-03-01

A simple model of estuarine eutrophication is built on biomechanical (or mechanistic) descriptions of a number of the key ecological processes in estuaries. Mechanistically described processes include the nutrient uptake and light capture of planktonic and benthic autotrophs, and the encounter rates of planktonic predators and prey. Other more complex processes, such as sediment biogeochemistry, detrital processes and phosphate dynamics, are modelled using empirical descriptions from the Port Phillip Bay Environmental Study (PPBES) ecological model. A comparison is made between the mechanistically determined rates of ecological processes and the analogous empirically determined rates in the PPBES ecological model. The rates generally agree, with a few significant exceptions. Model simulations were run at a range of estuarine depths and nutrient loads, with outputs presented as the annually averaged biomass of autotrophs. The simulations followed a simple conceptual model of eutrophication, suggesting a simple biomechanical understanding of estuarine processes can provide a predictive tool for ecological processes in a wide range of estuarine ecosystems.

Mechanistic investigation of the formation of H2 from HCOOH with a dinuclear Ru model complex for formate hydrogen lyase.

PubMed

Tokunaga, Taisuke; Yatabe, Takeshi; Matsumoto, Takahiro; Ando, Tatsuya; Yoon, Ki-Seok; Ogo, Seiji

2017-01-01

We report the mechanistic investigation of catalytic H 2 evolution from formic acid in water using a formate-bridged dinuclear Ru complex as a formate hydrogen lyase model. The mechanistic study is based on isotope-labeling experiments involving hydrogen isotope exchange reaction.

The coefficient of restitution of pressurized balls: a mechanistic model

NASA Astrophysics Data System (ADS)

Georgallas, Alex; Landry, Gaëtan

2016-01-01

Pressurized, inflated balls used in professional sports are regulated so that their behaviour upon impact can be anticipated and allow the game to have its distinctive character. However, the dynamics governing the impacts of such balls, even on stationary hard surfaces, can be extremely complex. The energy transformations, which arise from the compression of the gas within the ball and from the shear forces associated with the deformation of the wall, are examined in this paper. We develop a simple mechanistic model of the dependence of the coefficient of restitution, e, upon both the gauge pressure, P_G, of the gas and the shear modulus, G, of the wall. The model is validated using the results from a simple series of experiments using three different sports balls. The fits to the data are extremely good for P_G > 25 kPa and consistent values are obtained for the value of G for the wall material. As far as the authors can tell, this simple, mechanistic model of the pressure dependence of the coefficient of restitution is the first in the literature. *%K Coefficient of Restitution, Dynamics, Inflated Balls, Pressure, Impact Model

Development of an unresolved CFD-DEM model for the flow of viscous suspensions and its application to solid-liquid mixing

NASA Astrophysics Data System (ADS)

Blais, Bruno; Lassaigne, Manon; Goniva, Christoph; Fradette, Louis; Bertrand, François

2016-08-01

Although viscous solid-liquid mixing plays a key role in the industry, the vast majority of the literature on the mixing of suspensions is centered around the turbulent regime of operation. However, the laminar and transitional regimes face considerable challenges. In particular, it is important to know the minimum impeller speed (Njs) that guarantees the suspension of all particles. In addition, local information on the flow patterns is necessary to evaluate the quality of mixing and identify the presence of dead zones. Multiphase computational fluid dynamics (CFD) is a powerful tool that can be used to gain insight into local and macroscopic properties of mixing processes. Among the variety of numerical models available in the literature, which are reviewed in this work, unresolved CFD-DEM, which combines CFD for the fluid phase with the discrete element method (DEM) for the solid particles, is an interesting approach due to its accurate prediction of the granular dynamics and its capability to simulate large amounts of particles. In this work, the unresolved CFD-DEM method is extended to viscous solid-liquid flows. Different solid-liquid momentum coupling strategies, along with their stability criteria, are investigated and their accuracies are compared. Furthermore, it is shown that an additional sub-grid viscosity model is necessary to ensure the correct rheology of the suspensions. The proposed model is used to study solid-liquid mixing in a stirred tank equipped with a pitched blade turbine. It is validated qualitatively by comparing the particle distribution against experimental observations, and quantitatively by compairing the fraction of suspended solids with results obtained via the pressure gauge technique.

Students' Interpretations of Mechanistic Language in Organic Chemistry before Learning Reactions

ERIC Educational Resources Information Center

Galloway, Kelli R.; Stoyanovich, Carlee; Flynn, Alison B.

2017-01-01

Research on mechanistic thinking in organic chemistry has shown that students attribute little meaning to the electron-pushing (i.e., curved arrow) formalism. At the University of Ottawa, a new curriculum has been developed in which students are taught the electron-pushing formalism prior to instruction on specific reactions--this formalism is…

Perspectives on the Application of Mechanistic Information in Chemical Hazard and Dose-Response Assessments

EPA Science Inventory

This overview summarizes several EPA Assessment publications reviewing approaches for applying mechanistic information in human health risk assessment and exploring opportunities for progress in this area.

Characterization of material properties for mechanistic-empirical pavement design in Wyoming : final report.

DOT National Transportation Integrated Search

2016-12-01

The Wyoming Department of Transportation (WYDOT) recently transitioned from the empirical AASHTO Design for Design of Pavement Structures to the Mechanistic Empirical Pavement Design Guide (MEPDG) as their standard pavement design procedure. A compre...

A mechanistic physicochemical model of carbon dioxide transport in blood.

PubMed

O'Neill, David P; Robbins, Peter A

2017-02-01

A number of mathematical models have been produced that, given the Pco 2 and Po 2 of blood, will calculate the total concentrations for CO 2 and O 2 in blood. However, all these models contain at least some empirical features, and thus do not represent all of the underlying physicochemical processes in an entirely mechanistic manner. The aim of this study was to develop a physicochemical model of CO 2 carriage by the blood to determine whether our understanding of the physical chemistry of the major chemical components of blood together with their interactions is sufficiently strong to predict the physiological properties of CO 2 carriage by whole blood. Standard values are used for the ionic composition of the blood, the plasma albumin concentration, and the hemoglobin concentration. All K m values required for the model are taken from the literature. The distribution of bicarbonate, chloride, and H + ions across the red blood cell membrane follows that of a Gibbs-Donnan equilibrium. The system of equations that results is solved numerically using constraints for mass balance and electroneutrality. The model reproduces the phenomena associated with CO 2 carriage, including the magnitude of the Haldane effect, very well. The structural nature of the model allows various hypothetical scenarios to be explored. Here we examine the effects of 1) removing the ability of hemoglobin to form carbamino compounds; 2) allowing a degree of Cl - binding to deoxygenated hemoglobin; and 3) removing the chloride (Hamburger) shift. The insights gained could not have been obtained from empirical models. This study is the first to incorporate a mechanistic model of chloride-bicarbonate exchange between the erythrocyte and plasma into a full physicochemical model of the carriage of carbon dioxide in blood. The mechanistic nature of the model allowed a theoretical study of the quantitative significance for carbon dioxide transport of carbamino compound formation; the putative binding

A mechanistic physicochemical model of carbon dioxide transport in blood

PubMed Central

O’Neill, David P.

2017-01-01

A number of mathematical models have been produced that, given the Pco2 and Po2 of blood, will calculate the total concentrations for CO2 and O2 in blood. However, all these models contain at least some empirical features, and thus do not represent all of the underlying physicochemical processes in an entirely mechanistic manner. The aim of this study was to develop a physicochemical model of CO2 carriage by the blood to determine whether our understanding of the physical chemistry of the major chemical components of blood together with their interactions is sufficiently strong to predict the physiological properties of CO2 carriage by whole blood. Standard values are used for the ionic composition of the blood, the plasma albumin concentration, and the hemoglobin concentration. All Km values required for the model are taken from the literature. The distribution of bicarbonate, chloride, and H+ ions across the red blood cell membrane follows that of a Gibbs-Donnan equilibrium. The system of equations that results is solved numerically using constraints for mass balance and electroneutrality. The model reproduces the phenomena associated with CO2 carriage, including the magnitude of the Haldane effect, very well. The structural nature of the model allows various hypothetical scenarios to be explored. Here we examine the effects of 1) removing the ability of hemoglobin to form carbamino compounds; 2) allowing a degree of Cl− binding to deoxygenated hemoglobin; and 3) removing the chloride (Hamburger) shift. The insights gained could not have been obtained from empirical models. NEW & NOTEWORTHY This study is the first to incorporate a mechanistic model of chloride-bicarbonate exchange between the erythrocyte and plasma into a full physicochemical model of the carriage of carbon dioxide in blood. The mechanistic nature of the model allowed a theoretical study of the quantitative significance for carbon dioxide transport of carbamino compound formation; the putative

Unresolved issues in hematopoietic stem cell transplantation for severe combined immunodeficiency: Need for safer conditioning and reduced late effects

PubMed Central

Horn, Biljana; Cowan, Morton J.

2017-01-01

In this review we discuss recent outcomes of hematopoietic cell transplantation (HCT) for patients with severe combined immunodeficiency (SCID), including survival, T- and B-cell reconstitution, and late effects, particularly those related to genotype, use of conditioning regimen, and use of alternative donors. We identify the following issues that require additional data, which can be obtained through cooperative studies: outcomes of patients with SCID who did not receive conditioning before alternative donor HCT; outcomes of patients with SCID who did not receive graft-versus-host disease prophylaxis after T cell–replete HCT; late effects of HCT for patients with SCID, including neurocognitive outcomes, growth, and development; and their relationship to genotype and use of alkylating agents for conditioning. Careful follow-up of outcomes of all newborns receiving diagnoses based on newborn screening programs for SCID is essential because data are scarce on the effects of conditioning regimens in very young patients. A consensus on the definition of T- and B-cell recovery, criteria for additional “boosts,” pharmacokinetic data of chemotherapy agents used in young children, and uniformity of the use of various chemotherapy agents are needed to compare results among institutions. Finally, development of new nontoxic conditioning regimens for HCT that can be safely used in very young children is required. PMID:23622119

Mechanistic ecohydrological modeling with Tethys-Chloris: an attempt to unravel complexity

NASA Astrophysics Data System (ADS)

Fatichi, S.; Ivanov, V. Y.; Caporali, E.

2010-12-01

The role of vegetation in controlling and mediating hydrological states and fluxes at the level of individual processes has been largely explored, which has lead to the improvement of our understanding of mechanisms and patterns in ecohydrological systems. Nonetheless, relatively few efforts have been directed toward the development of continuous, complex, mechanistic ecohydrological models operating at the watershed-scale. This study presents a novel ecohydrological model Tethys-Chloris (T&C) and aims to discuss current limitations and perspectives of the mechanistic approach in ecohydrology. The model attempts to synthesize the state-of-the-art knowledge on individual processes and mechanisms drawn from various disciplines such as hydrology, plant physiology, ecology, and biogeochemistry. The model reproduces all essential components of hydrological cycle resolving the mass and energy budgets at the hourly scale; it includes energy and mass exchanges in the atmospheric boundary layer; a module of saturated and unsaturated soil water dynamics; two layers of vegetation, and a module of snowpack evolution. The vegetation component parsimoniously parameterizes essential plant life-cycle processes, including photosynthesis, phenology, carbon allocation, tissues turnover, and soil biogeochemistry. Quantitative metrics of model performance are discussed and highlight the capabilities of T&C in reproducing ecohydrological dynamics. The simulated patterns mimic the outcome of hydrological dynamics with high realism, given the uncertainty of imposed boundary conditions and limited data availability. Furthermore, highly satisfactory results are obtained without significant (e.g., automated) calibration efforts despite the large phase-space dimensionality of the model. A significant investment into model design and development leads to such desirable behavior. This suggests that while using the presented tool for high-precision predictions can be still problematic, the

A traffic data plan for mechanistic-empirical pavement designs (2002 pavement design guide).

DOT National Transportation Integrated Search

2003-01-01

The Virginia Department of Transportation (VDOT) is preparing to implement the mechanistic-empirical pavement design methodology being developed under the National Cooperative Research Program's Project 1-37A, commonly referred to as the 2002 Pavemen...

From Source to Sink: Mechanistic Reasoning Using the Electron-Pushing Formalism

ERIC Educational Resources Information Center

Bhattacharyya, Gautam

2013-01-01

Since the introduction of Morrison and Boyd's textbook in organic chemistry over 50 years ago, reaction mechanisms and mechanistic reasoning using the electron-pushing formalism (EPF) have become a mainstay of organic chemistry courses. In recent years there have even been several papers in this Journal and others detailing research on how…

Magnetophoresis for enhancing transdermal drug delivery: Mechanistic studies and patch design

PubMed Central

Murthy, S. Narasimha; Sammeta, Srinivasa M.; Bower, C.

2017-01-01

Magnetophoresis is a method of enhancement of drug permeation across the biological barriers by application of magnetic field. The present study investigated the mechanistic aspects of magnetophoretic transdermal drug delivery and also assessed the feasibility of designing a magnetophoretic transdermal patch system for the delivery of lidocaine. In vitro drug permeation studies were carried out across the porcine epidermis at different magnetic field strengths. The magnetophoretic drug permeation “flux enhancement factor” was found to increase with the applied magnetic field strength. The mechanistic studies revealed that the magnetic field applied in this study did not modulate permeability of the stratum corneum barrier. The predominant mechanism responsible for magnetically mediated drug permeation enhancement was found to be “magnetokinesis”. The octanol/water partition coefficient of drugs was also found to increase when exposed to the magnetic field. A reservoir type transdermal patch system with a magnetic backing was designed for in vivo studies. The dermal bioavailability (AUC0–6 h) from the magnetophoretic patch system in vivo, in rats was significantly higher than the similarly designed nonmagnetic control patch. PMID:20728484

A New Method for Generating Probability Tables in the Unresolved Resonance Region

DOE PAGES

Holcomb, Andrew M.; Leal, Luiz C.; Rahnema, Farzad; ...

2017-04-18

One new method for constructing probability tables in the unresolved resonance region (URR) has been developed. This new methodology is an extensive modification of the single-level Breit-Wigner (SLBW) pseudo-resonance pair sequence method commonly used to generate probability tables in the URR. The new method uses a Monte Carlo process to generate many pseudo-resonance sequences by first sampling the average resonance parameter data in the URR and then converting the sampled resonance parameters to the more robust R-matrix limited (RML) format. Furthermore, for each sampled set of pseudo-resonance sequences, the temperature-dependent cross sections are reconstructed on a small grid around themore » energy of reference using the Reich-Moore formalism and the Leal-Hwang Doppler broadening methodology. We then use the effective cross sections calculated at the energies of reference to construct probability tables in the URR. The RML cross-section reconstruction algorithm has been rigorously tested for a variety of isotopes, including 16O, 19F, 35Cl, 56Fe, 63Cu, and 65Cu. The new URR method also produced normalized cross-section factor probability tables for 238U that were found to be in agreement with current standards. The modified 238U probability tables were shown to produce results in excellent agreement with several standard benchmarks, including the IEU-MET-FAST-007 (BIG TEN), IEU-MET-FAST-003, and IEU-COMP-FAST-004 benchmarks.« less

Could a change in diet revitalize children who suffer from unresolved fatigue?

PubMed

Steenbruggen, Tessa Gerjanne; Hoekstra, Sietske Johanna; van der Gaag, Ellen José

2015-03-13

Many children deal with fatigue for which no proper treatment can be given. A possible explanation for their fatigue is a micro deficiency of minerals and vitamins. In this non-randomized controlled trial, we clinically evaluated symptoms of fatigue in children for whom a nutrient-rich diet was advised. A group of 98 children (2-18 years old) with unexplained symptoms of fatigue was examined. The dietary modifications consisted of green vegetables, beef, whole milk and full-fat butter. Children in the intervention group were asked to follow the diet for three months, whereas the control-group followed their normal diet. The primary outcome was symptoms of fatigue, as determined by a PedsQL Multidimensional Fatigue Scale, and secondary outcomes were compliance with the diet and BMI. Children, who followed the diet showed a significant decrease in the need to sleep (CI 0.83; 14.86, p = 0.03). They slept better through the night and took fewer naps. When analyzing components of the advised diet separately, a significant larger decrease in cognitive fatigue symptoms was seen for eating green vegetables according to the diet guidelines (CI 2.27; 30.63, p = 0.024). Furthermore, a lower need to sleep was seen when whole milk was consumed almost daily (CI 0.02; 14.62, p = 0.049). Our study showed that nutritional advice is an elegant, and effective method for decreasing some symptoms of medically unresolved fatigue in children.

Could a Change in Diet Revitalize Children Who Suffer from Unresolved Fatigue?

PubMed Central

Steenbruggen, Tessa Gerjanne; Hoekstra, Sietske Johanna; van der Gaag, Ellen José

2015-01-01

Many children deal with fatigue for which no proper treatment can be given. A possible explanation for their fatigue is a micro deficiency of minerals and vitamins. In this non-randomized controlled trial, we clinically evaluated symptoms of fatigue in children for whom a nutrient-rich diet was advised. A group of 98 children (2–18 years old) with unexplained symptoms of fatigue was examined. The dietary modifications consisted of green vegetables, beef, whole milk and full-fat butter. Children in the intervention group were asked to follow the diet for three months, whereas the control-group followed their normal diet. The primary outcome was symptoms of fatigue, as determined by a PedsQL Multidimensional Fatigue Scale, and secondary outcomes were compliance with the diet and BMI. Children, who followed the diet showed a significant decrease in the need to sleep (CI 0.83; 14.86, p = 0.03). They slept better through the night and took fewer naps. When analyzing components of the advised diet separately, a significant larger decrease in cognitive fatigue symptoms was seen for eating green vegetables according to the diet guidelines (CI 2.27; 30.63, p = 0.024). Furthermore, a lower need to sleep was seen when whole milk was consumed almost daily (CI 0.02; 14.62, p = 0.049). Our study showed that nutritional advice is an elegant, and effective method for decreasing some symptoms of medically unresolved fatigue in children. PMID:25781221

Contributions of clinical disconnections and unresolved conflict to failures in intrapartum safety

PubMed Central

Lyndon, Audrey; Zlatnik, Marya G.; Maxfield, David G.; Lewis, Annie; McMillan, Chase; Kennedy, Holly Powell

2014-01-01

Objective To explore clinician perspectives on whether they experience difficulty resolving patient-related concerns or observe problems with the performance or behavior of colleagues involved in intrapartum care. Design Qualitative descriptive study of physician, nursing, and midwifery professional association members. Participants and Setting Participants (N=1932) were drawn from the membership lists of the Association of Women’s Health, Obstetric, and Neonatal Nurses (AWHONN), American College of Obstetricians and Gynecologists (ACOG), American College of Nurse Midwives (ACNM), and Society for Maternal-Fetal Medicine (SMFM). Methods Email survey with multiple choice and free text responses. Descriptive statistics and inductive thematic analysis were used to characterize the data. Results Forty-seven percent of participants reported experiencing situations in which patients were put at risk due to failure of team members to listen or respond to a concern. Thirty-seven percent reported unresolved concerns regarding another clinician’s performance. The overarching theme was clinical disconnection, which included disconnections between clinicians about patient needs and plans of care and disconnections between clinicians and administration about the support required to provide safe and appropriate clinical care. Lack of responsiveness to concerns by colleagues and administration contributed to resignation and defeatism among participants who had experienced such situations. Conclusion Despite encouraging progress in developing cultures of safety in individual centers and systems, significant work is needed to improve collaboration and reverse historic normalization of both systemic disrespect and overt disruptive behaviors in intrapartum care. PMID:24354506

Dynamic and accurate assessment of acetaminophen-induced hepatotoxicity by integrated photoacoustic imaging and mechanistic biomarkers in vivo.

PubMed

Brillant, Nathalie; Elmasry, Mohamed; Burton, Neal C; Rodriguez, Josep Monne; Sharkey, Jack W; Fenwick, Stephen; Poptani, Harish; Kitteringham, Neil R; Goldring, Christopher E; Kipar, Anja; Park, B Kevin; Antoine, Daniel J

2017-10-01

The prediction and understanding of acetaminophen (APAP)-induced liver injury (APAP-ILI) and the response to therapeutic interventions is complex. This is due in part to sensitivity and specificity limitations of currently used assessment techniques. Here we sought to determine the utility of integrating translational non-invasive photoacoustic imaging of liver function with mechanistic circulating biomarkers of hepatotoxicity with histological assessment to facilitate the more accurate and precise characterization of APAP-ILI and the efficacy of therapeutic intervention. Perturbation of liver function and cellular viability was assessed in C57BL/6J male mice by Indocyanine green (ICG) clearance (Multispectral Optoacoustic Tomography (MSOT)) and by measurement of mechanistic (miR-122, HMGB1) and established (ALT, bilirubin) circulating biomarkers in response to the acetaminophen and its treatment with acetylcysteine (NAC) in vivo. We utilised a 60% partial hepatectomy model as a situation of defined hepatic functional mass loss to compared acetaminophen-induced changes to. Integration of these mechanistic markers correlated with histological features of APAP hepatotoxicity in a time-dependent manner. They accurately reflected the onset and recovery from hepatotoxicity compared to traditional biomarkers and also reported the efficacy of NAC with high sensitivity. ICG clearance kinetics correlated with histological scores for acute liver damage for APAP (i.e. 3h timepoint; r=0.90, P<0.0001) and elevations in both of the mechanistic biomarkers, miR-122 (e.g. 6h timepoint; r=0.70, P=0.005) and HMGB1 (e.g. 6h timepoint; r=0.56, P=0.04). For the first time we report the utility of this non-invasive longitudinal imaging approach to provide direct visualisation of the liver function coupled with mechanistic biomarkers, in the same animal, allowing the investigation of the toxicological and pharmacological aspects of APAP-ILI and hepatic regeneration. Copyright © 2017

Development of traffic data input resources for the mechanistic empirical pavement design process.

DOT National Transportation Integrated Search

2011-12-12

The Mechanistic-Empirical Pavement Design Guide (MEPDG) for New and Rehabilitated Pavement Structures uses : nationally based data traffic inputs and recommends that state DOTs develop their own site-specific and regional : values. To support the MEP...

Mechanistic-Empirical (M-E) Design Implementation & Monitoring for Flexible Pavements : 2018 PROJECT SUMMARY

DOT National Transportation Integrated Search

2018-06-01

This document is a summary of the tasks performed for Project ICT-R27-149-1. Mechanistic-empirical (M-E)based flexible pavement design concepts and procedures were previously developed in Illinois Cooperative Highway Research Program projects IHR-...

Bird Migration Under Climate Change - A Mechanistic Approach Using Remote Sensing

NASA Technical Reports Server (NTRS)

Smith, James A.; Blattner, Tim; Messmer, Peter

2010-01-01

The broad-scale reductions and shifts that may be expected under climate change in the availability and quality of stopover habitat for long-distance migrants is an area of increasing concern for conservation biologists. Researchers generally have taken two broad approaches to the modeling of migration behaviour to understand the impact of these changes on migratory bird populations. These include models based on causal processes and their response to environmental stimulation, "mechanistic models", or models that primarily are based on observed animal distribution patterns and the correlation of these patterns with environmental variables, i.e. "data driven" models. Investigators have applied the latter technique to forecast changes in migration patterns with changes in the environment, for example, as might be expected under climate change, by forecasting how the underlying environmental data layers upon which the relationships are built will change over time. The learned geostatstical correlations are then applied to the modified data layers.. However, this is problematic. Even if the projections of how the underlying data layers will change are correct, it is not evident that the statistical relationships will remain the same, i.e. that the animal organism may not adapt its' behaviour to the changing conditions. Mechanistic models that explicitly take into account the physical, biological, and behaviour responses of an organism as well as the underlying changes in the landscape offer an alternative to address these shortcomings. The availability of satellite remote sensing observations at multiple spatial and temporal scales, coupled with advances in climate modeling and information technologies enable the application of the mechanistic models to predict how continental bird migration patterns may change in response to environmental change. In earlier work, we simulated the impact of effects of wetland loss and inter-annual variability on the fitness of

Mechanistic modelling of cancer: some reflections from software engineering and philosophy of science.

PubMed

Cañete-Valdeón, José M; Wieringa, Roel; Smallbone, Kieran

2012-12-01

There is a growing interest in mathematical mechanistic modelling as a promising strategy for understanding tumour progression. This approach is accompanied by a methodological change of making research, in which models help to actively generate hypotheses instead of waiting for general principles to become apparent once sufficient data are accumulated. This paper applies recent research from philosophy of science to uncover three important problems of mechanistic modelling which may compromise its mainstream application, namely: the dilemma of formal and informal descriptions, the need to express degrees of confidence and the need of an argumentation framework. We report experience and research on similar problems from software engineering and provide evidence that the solutions adopted there can be transferred to the biological domain. We hope this paper can provoke new opportunities for further and profitable interdisciplinary research in the field.

Unresolved issues in theories of autoimmune disease using myocarditis as a framework

PubMed Central

Root-Bernstein, Robert; Fairweather, DeLisa

2014-01-01

Many theories of autoimmune disease have been proposed since the discovery that the immune system can attack the body. These theories include the hidden or cryptic antigen theory, modified antigen theory, T cell bypass, T cell-B cell mismatch, epitope spread or drift, the bystander effect, molecular mimicry, anti-idiotype theory, antigenic complementarity, and dual-affinity T cell receptors. We critically review these theories and relevant mathematical models as they apply to autoimmune myocarditis. All theories share the common assumption that autoimmune diseases are triggered by environmental factors such as infections or chemical exposure. Most, but not all, theories and mathematical models are unifactorial assuming single-agent causation of disease. Experimental and clinical evidence and mathematical models exist to support some aspects of most theories, but evidence/models that support one theory almost invariably supports other theories as well. More importantly, every theory (and every model) lacks the ability to account for some key autoimmune disease phenomena such as the fundamental roles of innate immunity, sex differences in disease susceptibility, the necessity for adjuvants in experimental animal models, and the often paradoxical effect of exposure timing and dose on disease induction. We argue that a more comprehensive and integrated theory of autoimmunity associated with new mathematical models is needed and suggest specific experimental and clinical tests for each major theory that might help to clarify how they relate to clinical disease and reveal how theories are related. PMID:25484004

Unresolved issues in theories of autoimmune disease using myocarditis as a framework.

PubMed

Root-Bernstein, Robert; Fairweather, DeLisa

2015-06-21

Many theories of autoimmune disease have been proposed since the discovery that the immune system can attack the body. These theories include the hidden or cryptic antigen theory, modified antigen theory, T cell bypass, T cell-B cell mismatch, epitope spread or drift, the bystander effect, molecular mimicry, anti-idiotype theory, antigenic complementarity, and dual-affinity T cell receptors. We critically review these theories and relevant mathematical models as they apply to autoimmune myocarditis. All theories share the common assumption that autoimmune diseases are triggered by environmental factors such as infections or chemical exposure. Most, but not all, theories and mathematical models are unifactorial assuming single-agent causation of disease. Experimental and clinical evidence and mathematical models exist to support some aspects of most theories, but evidence/models that support one theory almost invariably supports other theories as well. More importantly, every theory (and every model) lacks the ability to account for some key autoimmune disease phenomena such as the fundamental roles of innate immunity, sex differences in disease susceptibility, the necessity for adjuvants in experimental animal models, and the often paradoxical effect of exposure timing and dose on disease induction. We argue that a more comprehensive and integrated theory of autoimmunity associated with new mathematical models is needed and suggest specific experimental and clinical tests for each major theory that might help to clarify how they relate to clinical disease and reveal how theories are related. Copyright © 2014 Elsevier Ltd. All rights reserved.

Genomic medicine: health care issues and the unresolved ethical and social dilemmas.

PubMed

Idemyor, Vincent

2014-01-01

Our perception of the mechanism by which single genes can cause disease is evolving. This has led to the understanding of the pathophysiological basis of common diseases. Genomic Medicine continues to contribute to the understanding of the molecular basis of disease. Medicine has strived to achieve the goal of tailoring interventions to individual variations in risk and treatment response and advances in medical genomics will facilitate this process. Relevant to present-day practice is the use of genomic information to classify individuals according to disease susceptibility or expected responsiveness to a pharmacologic treatment and to provide targeted interventions. By investigating the genetic profile of individuals, medical professionals are able to select patients and use the information obtained to plan out a course of treatment that is much more in step with the way their body works. However, society is concerned about the effect genetic knowledge will have on ethnic or racial groups. Currently, the Health Insurance Portability and Accountability Act prohibits discrimination based on genetics. There is a need to increase the understanding of the social and ethical challenges that genomics information may pose to clinicians and scientists. This review is not meant to be exhaustive; rather, clinically relevant examples are used to illustrate how genomic medicine can facilitate the provision of molecular diagnostic methods that improve drug therapy. Finally, the rapid pace of change in genomics may likely make my conclusions today obsolete tomorrow.

Modeling of batch sorber system: kinetic, mechanistic, and thermodynamic modeling

NASA Astrophysics Data System (ADS)

Mishra, Vishal

2017-10-01

The present investigation has dealt with the biosorption of copper and zinc ions on the surface of egg-shell particles in the liquid phase. Various rate models were evaluated to elucidate the kinetics of copper and zinc biosorptions, and the results indicated that the pseudo-second-order model was more appropriate than the pseudo-first-order model. The curve of the initial sorption rate versus the initial concentration of copper and zinc ions also complemented the results of the pseudo-second-order model. Models used for the mechanistic modeling were the intra-particle model of pore diffusion and Bangham's model of film diffusion. The results of the mechanistic modeling together with the values of pore and film diffusivities indicated that the preferential mode of the biosorption of copper and zinc ions on the surface of egg-shell particles in the liquid phase was film diffusion. The results of the intra-particle model showed that the biosorption of the copper and zinc ions was not dominated by the pore diffusion, which was due to macro-pores with open-void spaces present on the surface of egg-shell particles. The thermodynamic modeling reproduced the fact that the sorption of copper and zinc was spontaneous, exothermic with the increased order of the randomness at the solid-liquid interface.

Modeling of Mn/Road test sections with the CRREL mechanistic pavement design procedure

DOT National Transportation Integrated Search

1996-09-01

The U.S. Army Cold Regions Research and Engineering Laboratory is developing a mechanistic pavement design procedure for use in seasonal frost areas. The procedure was used to predict pavement performance of some test sections under construction at t...

Generalized Radiative Transfer as an Efficient Computational Tool for Spatial and/or Spectral Integration over Unresolved Variability in Multi-Angle Observations

NASA Astrophysics Data System (ADS)

Davis, A. B.; Xu, F.; Diner, D. J.

2017-12-01

Two perennial problems in applied theoretical and computational radiative transfer (RT) are: (1) the impact of unresolved spatial variability on large-scale fluxes (in climate models) or radiances (in remote sensing); and (2) efficient-yet-accurate estimation of broadband spectral integrals in radiant energy budget estimation as well as in remote sensing, in particular, of trace gases.Generalized RT (GRT) is a modification of classic RT in an optical medium with uniform extinction where Beer's exponential law for direct transmission is replaced by a monotonically decreasing function with a slower power-law decay. In a convenient parameterized version of GRT, mean extinction replaces the uniform value and just one new property is introduced. As a non-dimensional metric for the unresolved variability, we use the square of the mean extinction coefficient divided by its variance. This parameter is also the exponent of the power-law tail of the modified transmission law.This specific form of sub-exponential transmission has explored for almost two decades in application to spatial variability in the presence of long-range correlations, much like in turbulent media such as clouds, with a focus on multiple scattering. It has also been proposed by Conley and Collins (JQSRT, 112, 1525-, 2011) to improve on the standard (weak-line) implementation of the correlated-k technique for efficient spectral integration.We have merged these two applications within a rigorous formulation of the combined problem, and solve the new integral RT equations in the single-scattering limit. The result is illustrated by addressing practical problems in multi-angle remote sensing of aerosols using the O2 A-band, an emerging methodology for passive profiling of coarse aerosols and clouds.

A rat model system to study complex disease risks, fitness, aging, and longevity.

PubMed

Koch, Lauren Gerard; Britton, Steven L; Wisløff, Ulrik

2012-02-01

The association between low exercise capacity and all-cause morbidity and mortality is statistically strong yet mechanistically unresolved. By connecting clinical observation with a theoretical base, we developed a working hypothesis that variation in capacity for oxygen metabolism is the central mechanistic determinant between disease and health (aerobic hypothesis). As an unbiased test, we show that two-way artificial selective breeding of rats for low and high intrinsic endurance exercise capacity also produces rats that differ for numerous disease risks, including the metabolic syndrome, cardiovascular complications, premature aging, and reduced longevity. This contrasting animal model system may prove to be translationally superior relative to more widely used simplistic models for understanding geriatric biology and medicine. Copyright © 2012 Elsevier Inc. All rights reserved.

Mechanistic Drifting Forecast Model for A Small Semi-Submersible Drifter Under Tide-Wind-Wave Conditions

NASA Astrophysics Data System (ADS)

Zhang, Wei-Na; Huang, Hui-ming; Wang, Yi-gang; Chen, Da-ke; Zhang, lin

2018-03-01

Understanding the drifting motion of a small semi-submersible drifter is of vital importance regarding monitoring surface currents and the floating pollutants in coastal regions. This work addresses this issue by establishing a mechanistic drifting forecast model based on kinetic analysis. Taking tide-wind-wave into consideration, the forecast model is validated against in situ drifting experiment in the Radial Sand Ridges. Model results show good performance with respect to the measured drifting features, characterized by migrating back and forth twice a day with daily downwind displacements. Trajectory models are used to evaluate the influence of the individual hydrodynamic forcing. The tidal current is the fundamental dynamic condition in the Radial Sand Ridges and has the greatest impact on the drifting distance. However, it loses its leading position in the field of the daily displacement of the used drifter. The simulations reveal that different hydrodynamic forces dominate the daily displacement of the used drifter at different wind scales. The wave-induced mass transport has the greatest influence on the daily displacement at Beaufort wind scale 5-6; while wind drag contributes mostly at wind scale 2-4.

Mechanistic Studies at the Interface Between Organometallic Chemistry and Homogeneous Catalysis

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

Casey, Charles P

Mechanistic Studies at the Interface Between Organometallic Chemistry and Homogeneous Catalysis Charles P. Casey, Principal Investigator Department of Chemistry, University of Wisconsin - Madison, Madison, Wisconsin 53706 Phone 608-262-0584 FAX: 608-262-7144 Email: casey@chem.wisc.edu http://www.chem.wisc.edu/main/people/faculty/casey.html Executive Summary. Our goal was to learn the intimate mechanistic details of reactions involved in homogeneous catalysis and to use the insight we gain to develop new and improved catalysts. Our work centered on the hydrogenation of polar functional groups such as aldehydes and ketones and on hydroformylation. Specifically, we concentrated on catalysts capable of simultaneously transferring hydride from a metal center and a proton frommore » an acidic oxygen or nitrogen center to an aldehyde or ketone. An economical iron based catalyst was developed and patented. Better understanding of fundamental organometallic reactions and catalytic processes enabled design of energy and material efficient chemical processes. Our work contributed to the development of catalysts for the selective and mild hydrogenation of ketones and aldehydes; this will provide a modern green alternative to reductions by LiAlH4 and NaBH4, which require extensive work-up procedures and produce waste streams. (C5R4OH)Ru(CO)2H Hydrogenation Catalysts. Youval Shvo described a remarkable catalytic system in which the key intermediate (C5R4OH)Ru(CO)2H (1) has an electronically coupled acidic OH unit and a hydridic RuH unit. Our efforts centered on understanding and improving upon this important catalyst for reduction of aldehydes and ketones. Our mechanistic studies established that the reduction of aldehydes by 1 to produce alcohols and a diruthenium bridging hydride species occurs much more rapidly than regeneration of the ruthenium hydride from the diruthenium bridging hydride species. Our mechanistic studies require simultaneous transfer of hydride from

The Relationship between Psychological Well-Being and Perceived Wellness in Graduate-Level Counseling Students

ERIC Educational Resources Information Center

Harris, Michel; Martin, Magy; Martin, Don

2013-01-01

Research has established that individuals who provide personal therapy to others should have stable personal and professional lives, and possess a keen and accurate perception of wellness. Unfortunately, sometimes students pursuing careers in counseling and psychotherapy have unresolved psychological issues that, if unresolved, could later affect…

Emergent Global Patterns of Ecosystem Structure and Function from a Mechanistic General Ecosystem Model

PubMed Central

Emmott, Stephen; Hutton, Jon; Lyutsarev, Vassily; Smith, Matthew J.; Scharlemann, Jörn P. W.; Purves, Drew W.

2014-01-01

Anthropogenic activities are causing widespread degradation of ecosystems worldwide, threatening the ecosystem services upon which all human life depends. Improved understanding of this degradation is urgently needed to improve avoidance and mitigation measures. One tool to assist these efforts is predictive models of ecosystem structure and function that are mechanistic: based on fundamental ecological principles. Here we present the first mechanistic General Ecosystem Model (GEM) of ecosystem structure and function that is both global and applies in all terrestrial and marine environments. Functional forms and parameter values were derived from the theoretical and empirical literature where possible. Simulations of the fate of all organisms with body masses between 10 µg and 150,000 kg (a range of 14 orders of magnitude) across the globe led to emergent properties at individual (e.g., growth rate), community (e.g., biomass turnover rates), ecosystem (e.g., trophic pyramids), and macroecological scales (e.g., global patterns of trophic structure) that are in general agreement with current data and theory. These properties emerged from our encoding of the biology of, and interactions among, individual organisms without any direct constraints on the properties themselves. Our results indicate that ecologists have gathered sufficient information to begin to build realistic, global, and mechanistic models of ecosystems, capable of predicting a diverse range of ecosystem properties and their response to human pressures. PMID:24756001

Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model.

PubMed

Harfoot, Michael B J; Newbold, Tim; Tittensor, Derek P; Emmott, Stephen; Hutton, Jon; Lyutsarev, Vassily; Smith, Matthew J; Scharlemann, Jörn P W; Purves, Drew W

2014-04-01

Anthropogenic activities are causing widespread degradation of ecosystems worldwide, threatening the ecosystem services upon which all human life depends. Improved understanding of this degradation is urgently needed to improve avoidance and mitigation measures. One tool to assist these efforts is predictive models of ecosystem structure and function that are mechanistic: based on fundamental ecological principles. Here we present the first mechanistic General Ecosystem Model (GEM) of ecosystem structure and function that is both global and applies in all terrestrial and marine environments. Functional forms and parameter values were derived from the theoretical and empirical literature where possible. Simulations of the fate of all organisms with body masses between 10 µg and 150,000 kg (a range of 14 orders of magnitude) across the globe led to emergent properties at individual (e.g., growth rate), community (e.g., biomass turnover rates), ecosystem (e.g., trophic pyramids), and macroecological scales (e.g., global patterns of trophic structure) that are in general agreement with current data and theory. These properties emerged from our encoding of the biology of, and interactions among, individual organisms without any direct constraints on the properties themselves. Our results indicate that ecologists have gathered sufficient information to begin to build realistic, global, and mechanistic models of ecosystems, capable of predicting a diverse range of ecosystem properties and their response to human pressures.

Development of local calibration factors and design criteria values for mechanistic-empirical pavement design.

DOT National Transportation Integrated Search

2015-08-01

A mechanistic-empirical (ME) pavement design procedure allows for analyzing and selecting pavement structures based : on predicted distress progression resulting from stresses and strains within the pavement over its design life. The Virginia : Depar...

A precision oncology approach to the pharmacological targeting of mechanistic dependencies in neuroendocrine tumors. | Office of Cancer Genomics

Cancer.gov

We introduce and validate a new precision oncology framework for the systematic prioritization of drugs targeting mechanistic tumor dependencies in individual patients. Compounds are prioritized on the basis of their ability to invert the concerted activity of master regulator proteins that mechanistically regulate tumor cell state, as assessed from systematic drug perturbation assays. We validated the approach on a cohort of 212 gastroenteropancreatic neuroendocrine tumors (GEP-NETs), a rare malignancy originating in the pancreas and gastrointestinal tract.

Ultrasound and Microbubble Guided Drug Delivery: Mechanistic Understanding and Clinical Implications

PubMed Central

Wang, Tzu-Yin; Wilson, Katheryne E.; Machtaler, Steven; Willmann, Jürgen K.

2014-01-01

Ultrasound mediated drug delivery using microbubbles is a safe and noninvasive approach for spatially localized drug administration. This approach can create temporary and reversible openings on cellular membranes and vessel walls (a process called “sonoporation”), allowing for enhanced transport of therapeutic agents across these natural barriers. It is generally believed that the sonoporation process is highly associated with the energetic cavitation activities (volumetric expansion, contraction, fragmentation, and collapse) of the microbubble. However, a thorough understanding of the process was unavailable until recently. Important progress on the mechanistic understanding of sonoporation and the corresponding physiological responses in vitro and in vivo has been made. Specifically, recent research shed light on the cavitation process of microbubbles and fluid motion during insonation of ultrasound, on the spatio-temporal interactions between microbubbles and cells or vessel walls, as well as on the temporal course of the subsequent biological effects. These findings have significant clinical implications on the development of optimal treatment strategies for effective drug delivery. In this article, current progress in the mechanistic understanding of ultrasound and microbubble mediated drug delivery and its implications for clinical translation is discussed. PMID:24372231

Physician-Assisted Suicide and Euthanasia in the Intensive Care Unit: A Dialogue on Core Ethical Issues

PubMed Central

Goligher, Ewan C.; Ely, E. Wesley; Sulmasy, Daniel P.; Bakker, Jan; Raphael, John; Volandes, Angelo E.; Patel, Bhavesh M.; Payne, Kate; Hosie, Annmarie; Churchill, Larry; White, Douglas B.; Downar, James

2016-01-01

Objective Many patients are admitted to the intensive care unit at or near the end of their lives. Consequently, the increasingly common debate regarding physician-assisted suicide and euthanasia (PAS/E) holds implications for the practice of critical care medicine. The objective of this manuscript is to explore core ethical issues related to PAS/E from the perspective of healthcare professionals and ethicists on both sides of the debate. Synthesis We identified four issues highlighting the key areas of ethical tension central to evaluating PAS/E in medical practice: (1) the benefit or harm of death itself, (2) the relationship between PAS/E and withholding or withdrawing life support, (3) the morality of a physician deliberately causing death, and (4) the management of conscientious objection related to PAS/E in the critical care setting. We present areas of common ground as well as important unresolved differences. Conclusions We reached differing positions on the first three core ethical questions and achieved significant agreement on how critical care clinicians should manage conscientious objections related to PAS/E. The alternative positions presented in this paper may serve to promote open and informed dialogue within the critical care community. PMID:28098622

Mechanistic exploration of a bi-directional PDT-based combination in pancreatic cancer (Conference Presentation)

NASA Astrophysics Data System (ADS)

Huang, Huang-Chiao; Mallidi, Srivalleesha; Liu, Joyce; Chiang, Chun-Te; Mai, Zhiming; Goldschmidt, Ruth; Rizvi, Imran; Ebrahim-Zadeh, Neema; Hasan, Tayyaba

2016-03-01

It is increasingly evident that the most effective cancer treatments will involve interactive regimens that target multiple non-overlapping pathways, preferably such that each component enhances the others to improve outcomes while minimizing systemic toxicities. Toward this goal, we developed a combination of photodynamic therapy and irinotecan, which mechanistically cooperate with each other, beyond their individual tumor destruction pathways, to cause synergistic reduction in orthotopic pancreatic tumor burden. A three-way mechanistic basis of the observed the synergism will be discussed: (i) PDT downregulates drug efflux transporters to increase intracellular irinotecan levels. (ii) Irinotecan reduces the expression of hypoxia-induced marker, which is upregulated by PDT. (iii) PDT downregulates irinotecan-induced survivin expression to amplify the apoptotic and anti-proliferative effects. The clinical translation potential of the combination will also be highlighted.

LASSIM-A network inference toolbox for genome-wide mechanistic modeling.

PubMed

Magnusson, Rasmus; Mariotti, Guido Pio; Köpsén, Mattias; Lövfors, William; Gawel, Danuta R; Jörnsten, Rebecka; Linde, Jörg; Nordling, Torbjörn E M; Nyman, Elin; Schulze, Sylvie; Nestor, Colm E; Zhang, Huan; Cedersund, Gunnar; Benson, Mikael; Tjärnberg, Andreas; Gustafsson, Mika

2017-06-01

Recent technological advancements have made time-resolved, quantitative, multi-omics data available for many model systems, which could be integrated for systems pharmacokinetic use. Here, we present large-scale simulation modeling (LASSIM), which is a novel mathematical tool for performing large-scale inference using mechanistically defined ordinary differential equations (ODE) for gene regulatory networks (GRNs). LASSIM integrates structural knowledge about regulatory interactions and non-linear equations with multiple steady state and dynamic response expression datasets. The rationale behind LASSIM is that biological GRNs can be simplified using a limited subset of core genes that are assumed to regulate all other gene transcription events in the network. The LASSIM method is implemented as a general-purpose toolbox using the PyGMO Python package to make the most of multicore computers and high performance clusters, and is available at https://gitlab.com/Gustafsson-lab/lassim. As a method, LASSIM works in two steps, where it first infers a non-linear ODE system of the pre-specified core gene expression. Second, LASSIM in parallel optimizes the parameters that model the regulation of peripheral genes by core system genes. We showed the usefulness of this method by applying LASSIM to infer a large-scale non-linear model of naïve Th2 cell differentiation, made possible by integrating Th2 specific bindings, time-series together with six public and six novel siRNA-mediated knock-down experiments. ChIP-seq showed significant overlap for all tested transcription factors. Next, we performed novel time-series measurements of total T-cells during differentiation towards Th2 and verified that our LASSIM model could monitor those data significantly better than comparable models that used the same Th2 bindings. In summary, the LASSIM toolbox opens the door to a new type of model-based data analysis that combines the strengths of reliable mechanistic models with truly

Physician-Assisted Suicide and Euthanasia in the ICU: A Dialogue on Core Ethical Issues.

PubMed

Goligher, Ewan C; Ely, E Wesley; Sulmasy, Daniel P; Bakker, Jan; Raphael, John; Volandes, Angelo E; Patel, Bhavesh M; Payne, Kate; Hosie, Annmarie; Churchill, Larry; White, Douglas B; Downar, James

2017-02-01

Many patients are admitted to the ICU at or near the end of their lives. Consequently, the increasingly common debate regarding physician-assisted suicide and euthanasia holds implications for the practice of critical care medicine. The objective of this article is to explore core ethical issues related to physician-assisted suicide and euthanasia from the perspective of healthcare professionals and ethicists on both sides of the debate. We identified four issues highlighting the key areas of ethical tension central to evaluating physician-assisted suicide and euthanasia in medical practice: 1) the benefit or harm of death itself, 2) the relationship between physician-assisted suicide and euthanasia and withholding or withdrawing life support, 3) the morality of a physician deliberately causing death, and 4) the management of conscientious objection related to physician-assisted suicide and euthanasia in the critical care setting. We present areas of common ground and important unresolved differences. We reached differing positions on the first three core ethical questions and achieved unanimity on how critical care clinicians should manage conscientious objections related to physician-assisted suicide and euthanasia. The alternative positions presented in this article may serve to promote open and informed dialogue within the critical care community.

Corrigendum: Free Will and Punishment: A Mechanistic View of Human Nature Reduces Retribution.

PubMed

2018-02-01

Original article: Shariff, A. F., Greene, J. D., Karremans, J. C., Luguri, J. B., Clark, C. J., Schooler, J. W., . . . Vohs, K. D. (2014). Free will and punishment: A mechanistic view of human nature reduces retribution. Psychological Science, 25, 1563-1570. doi:10.1177/0956797614534693.

Qualitative and quantitative assessment of unresolved complex mixture in PM2.5 of Bakersfield, CA

NASA Astrophysics Data System (ADS)

Nallathamby, Punith Dev; Lewandowski, Michael; Jaoui, Mohammed; Offenberg, John H.; Kleindienst, Tadeusz E.; Rubitschun, Caitlin; Surratt, Jason D.; Usenko, Sascha; Sheesley, Rebecca J.

2014-12-01

The 2010 CalNex (California Nexus) field experiment offered an opportunity for detailed characterization of atmospheric particulate carbon composition and sources in Bakersfield, CA. In the current study, the authors describe and employ a new protocol for reporting unresolved complex mixture (UCM) in over 30 daily samples. The Bakersfield, CA site has significant contribution from UCM, 2.9 ± 2.2% of the daily OC, which makes it an ideal first application. The new protocol reports two UCM peaks for Bakersfield with unique mean vapor pressure, retention time, mass spectra and daily ambient concentration trends. The first UCM peak, UCM-A, was comprised of semi-volatile compounds including alkanes, alkenes, and alkynes, with a mean vapor pressure of 2E-04 Torr and medium to heavy-duty diesel exhaust as a likely source. The second UCM peak, UCM-B, was comprised of linear, branched, and cyclic alkanes, with a mean vapor pressure of 1E-08 Torr. UCM-B had strong similarities to UCM in the NIST Standard Reference Material 1649b (urban dust) and to previously reported, detailed UCM for a representative Bakersfield sample, with possible sources including: motor vehicle exhaust, agricultural activities, and construction activities.

Molecular Signaling Network Motifs Provide a Mechanistic Basis for Cellular Threshold Responses

PubMed Central

Bhattacharya, Sudin; Conolly, Rory B.; Clewell, Harvey J.; Kaminski, Norbert E.; Andersen, Melvin E.

2014-01-01

Background: Increasingly, there is a move toward using in vitro toxicity testing to assess human health risk due to chemical exposure. As with in vivo toxicity testing, an important question for in vitro results is whether there are thresholds for adverse cellular responses. Empirical evaluations may show consistency with thresholds, but the main evidence has to come from mechanistic considerations. Objectives: Cellular response behaviors depend on the molecular pathway and circuitry in the cell and the manner in which chemicals perturb these circuits. Understanding circuit structures that are inherently capable of resisting small perturbations and producing threshold responses is an important step towards mechanistically interpreting in vitro testing data. Methods: Here we have examined dose–response characteristics for several biochemical network motifs. These network motifs are basic building blocks of molecular circuits underpinning a variety of cellular functions, including adaptation, homeostasis, proliferation, differentiation, and apoptosis. For each motif, we present biological examples and models to illustrate how thresholds arise from specific network structures. Discussion and Conclusion: Integral feedback, feedforward, and transcritical bifurcation motifs can generate thresholds. Other motifs (e.g., proportional feedback and ultrasensitivity)produce responses where the slope in the low-dose region is small and stays close to the baseline. Feedforward control may lead to nonmonotonic or hormetic responses. We conclude that network motifs provide a basis for understanding thresholds for cellular responses. Computational pathway modeling of these motifs and their combinations occurring in molecular signaling networks will be a key element in new risk assessment approaches based on in vitro cellular assays. Citation: Zhang Q, Bhattacharya S, Conolly RB, Clewell HJ III, Kaminski NE, Andersen ME. 2014. Molecular signaling network motifs provide a

Improved characterization of truck traffic volumes and axle loads for mechanistic-empirical pavement design.

DOT National Transportation Integrated Search

2012-12-01

The recently developed mechanistic-empirical pavement design guide (MEPDG) requires a multitude of traffic : inputs to be defined for the design of pavement structures, including the initial two-way annual average daily truck : traffic (AADTT), direc...

Layer moduli of Nebraska pavements for the new Mechanistic-Empirical Pavement Design Guide (MEPDG).

DOT National Transportation Integrated Search

2010-12-01

As a step-wise implementation effort of the Mechanistic-Empirical Pavement Design Guide (MEPDG) for the design : and analysis of Nebraska flexible pavement systems, this research developed a database of layer moduli dynamic : modulus, creep compl...

Using a bias aware EnKF to account for unresolved structure in an unsaturated zone model

NASA Astrophysics Data System (ADS)

Erdal, D.; Neuweiler, I.; Wollschläger, U.

2014-01-01

When predicting flow in the unsaturated zone, any method for modeling the flow will have to define how, and to what level, the subsurface structure is resolved. In this paper, we use the Ensemble Kalman Filter to assimilate local soil water content observations from both a synthetic layered lysimeter and a real field experiment in layered soil in an unsaturated water flow model. We investigate the use of colored noise bias corrections to account for unresolved subsurface layering in a homogeneous model and compare this approach with a fully resolved model. In both models, we use a simplified model parameterization in the Ensemble Kalman Filter. The results show that the use of bias corrections can increase the predictive capability of a simplified homogeneous flow model if the bias corrections are applied to the model states. If correct knowledge of the layering structure is available, the fully resolved model performs best. However, if no, or erroneous, layering is used in the model, the use of a homogeneous model with bias corrections can be the better choice for modeling the behavior of the system.

Comparative evaluation of statistical and mechanistic models of Escherichia coli at beaches in southern Lake Michigan

USGS Publications Warehouse

Safaie, Ammar; Wendzel, Aaron; Ge, Zhongfu; Nevers, Meredith; Whitman, Richard L.; Corsi, Steven R.; Phanikumar, Mantha S.

2016-01-01

Statistical and mechanistic models are popular tools for predicting the levels of indicator bacteria at recreational beaches. Researchers tend to use one class of model or the other, and it is difficult to generalize statements about their relative performance due to differences in how the models are developed, tested, and used. We describe a cooperative modeling approach for freshwater beaches impacted by point sources in which insights derived from mechanistic modeling were used to further improve the statistical models and vice versa. The statistical models provided a basis for assessing the mechanistic models which were further improved using probability distributions to generate high-resolution time series data at the source, long-term “tracer” transport modeling based on observed electrical conductivity, better assimilation of meteorological data, and the use of unstructured-grids to better resolve nearshore features. This approach resulted in improved models of comparable performance for both classes including a parsimonious statistical model suitable for real-time predictions based on an easily measurable environmental variable (turbidity). The modeling approach outlined here can be used at other sites impacted by point sources and has the potential to improve water quality predictions resulting in more accurate estimates of beach closures.

Radiation Safety Issues in High Altitude Commercial Aircraft

NASA Technical Reports Server (NTRS)

Wilson, John W.; Cucinotta, Francis A.; Shinn, Judy L.

1995-01-01

The development of a global economy makes the outlook for high speed commercial intercontinental flight feasible, and the development of various configurations operating from 20 to 30 km have been proposed. In addition to the still unresolved issues relating to current commercial operations (12-16 km), the higher dose rates associated with the higher operating altitudes makes il imperative that the uncertainties in the atmospheric radiation environment and the associated health risks be re-examined. Atmospheric radiation associated with the galactic cosmic rays forms a background level which may, under some circumstances, exceed newly recommended allowable exposure limits proposed on the basis of recent evaluations of the A -bomb survivor data (due to increased risk coefficients). These larger risk coefficients, within the context of the methodology for estimating exposure limits, are resulting in exceedingly low estimated allowable exposure limits which may impact even present day flight operations and was the reason for the CEC workshop in Luxembourg (1990). At higher operating altitudes, solar particles events can produce exposures many orders of magnitude above background levels and pose significant health risks to the most sensitive individuals (such as during pregnancy). In this case the appropriate quality factors are undefined, and some evidence exists which indicates that the quality factor for stochastic effects is a substantial underestimate.

Physiologically induced color-pattern changes in butterfly wings: mechanistic and evolutionary implications.

PubMed

Otaki, Joji M

2008-07-01

A mechanistic understanding of the butterfly wing color-pattern determination can be facilitated by experimental pattern changes. Here I review physiologically induced color-pattern changes in nymphalid butterflies and their mechanistic and evolutionary implications. A type of color-pattern change can be elicited by elemental changes in size and position throughout the wing, as suggested by the nymphalid groundplan. These changes of pattern elements are bi-directional and bi-sided dislocation toward or away from eyespot foci and in both proximal and distal sides of the foci. The peripheral elements are dislocated even in the eyespot-less compartments. Anterior spots are more severely modified, suggesting the existence of an anterior-posterior gradient. In one species, eyespots are transformed into white spots with remnant-like orange scales, and such patterns emerge even at the eyespot-less "imaginary" foci. A series of these color-pattern modifications probably reveal "snap-shots" of a dynamic morphogenic signal due to heterochronic uncoupling between the signaling and reception steps. The conventional gradient model can be revised to account for these observed color-pattern changes.

Nonspecific immunomodulators for recurrent respiratory tract infections, wheezing and asthma in children: a systematic review of mechanistic and clinical evidence.

PubMed

Esposito, Susanna; Soto-Martinez, Manuel E; Feleszko, Wojciech; Jones, Marcus H; Shen, Kun-Ling; Schaad, Urs B

2018-06-01

To provide an overview of the mechanistic and clinical evidence for the use of nonspecific immunomodulators in paediatric respiratory tract infection (RTI) and wheezing/asthma prophylaxis. Nonspecific immunomodulators have a long history of empirical use for the prevention of RTIs in vulnerable populations, such as children. The past decade has seen an increase in both the number and quality of studies providing mechanistic and clinical evidence for the prophylactic potential of nonspecific immunomodulators against both respiratory infections and wheezing/asthma in the paediatric population. Orally administered immunomodulators result in the mounting of innate and adaptive immune responses to infection in the respiratory mucosa and anti-inflammatory effects in proinflammatory environments. Clinical data reflect these mechanistic effects in reductions in the recurrence of respiratory infections and wheezing events in high-risk paediatric populations. A new generation of clinical studies is currently underway with the power to position the nonspecific bacterial lysate immunomodulator OM-85 as a potential antiasthma prophylactic. An established mechanistic and clinical role for prophylaxis against paediatric respiratory infections by nonspecific immunomodulators exists. Clinical trials underway promise to provide high-quality data to establish whether a similar role exists in wheezing/asthma prevention.

Characterization of truck traffic in Michigan for the new mechanistic empirical pavement design guide.

DOT National Transportation Integrated Search

2009-12-01

The purpose of this study is to characterize traffic inputs in support of the new Mechanistic- : Empirical Pavement Design Guide (M-E PDG) for the state of Michigan. These traffic : characteristics include monthly distribution factors (MDF), hourly d...

Deriving physical parameters of unresolved star clusters. V. M 31 PHAT star clusters

NASA Astrophysics Data System (ADS)

de Meulenaer, P.; Stonkutė, R.; Vansevičius, V.

2017-06-01

Context. This study is the fifth of a series that investigates the degeneracy and stochasticity problems present in the determination of physical parameters such as age, mass, extinction, and metallicity of partially resolved or unresolved star cluster populations in external galaxies when using HST broad-band photometry. Aims: In this work we aim to derive parameters of star clusters using models with fixed and free metallicity based on the HST WFC3+ACS photometric system. The method is applied to derive parameters of a subsample of 1363 star clusters in the Andromeda galaxy observed with the HST. Methods: Following Paper III, we derive the star cluster parameters using a large grid of stochastic models that are compared to the six observed integrated broad-band WFC3+ACS magnitudes of star clusters. Results: We show that the age, mass, and extinction of the M 31 star clusters, derived assuming fixed solar metallicity, are in agreement with previous studies. We also demonstrate the ability of the WFC3+ACS photometric system to derive metallicity of star clusters older than 1 Gyr. We show that the metallicity derived using broad-band photometry of 36 massive M 31 star clusters is in good agreement with the metallicity derived using spectroscopy. Table 1 is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/602/A112

Mechanistic and clinical insights at the scleroderma-cancer interface

PubMed Central

Shah, Ami A.; Casciola-Rosen, Livia

2017-01-01

Emerging data suggest tantalizing links between cancer and systemic inflammatory rheumatic syndromes. In scleroderma, patients may have an increased risk of cancer secondary to chronic inflammation and damage from the disease, malignant transformation promoted by immunosuppressive therapies, a shared susceptibility to both cancer and autoimmunity, or a common inciting exposure. However, it is increasingly recognized that a subset of patients develop cancer around the time that scleroderma clinically manifests, raising the question of cancer-induced autoimmunity. In this review, we discuss data suggesting a mechanistic link between cancer and the development of scleroderma, and the clinical implications of these findings. PMID:29264402

A Mechanistic Study of Arsenic (III) Rejection by Reverse Osmosis and Nanofiltration Membranes

ERIC Educational Resources Information Center

Suzuki, Tasuma

2009-01-01

Reverse osmosis/nanofiltration (RO/NF) membranes are capable to provide an effective barrier for a wide range of contaminants (including disinfection by-products precursors) in a single treatment step. However, solute rejection mechanisms by RO/NF membranes are not well understood. The lack of mechanistic information arises from experimental…

Ecological Forecasting in Chesapeake Bay: Using a Mechanistic-Empirical Modelling Approach

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

Brown, C. W.; Hood, Raleigh R.; Long, Wen

The Chesapeake Bay Ecological Prediction System (CBEPS) automatically generates daily nowcasts and three-day forecasts of several environmental variables, such as sea-surface temperature and salinity, the concentrations of chlorophyll, nitrate, and dissolved oxygen, and the likelihood of encountering several noxious species, including harmful algal blooms and water-borne pathogens, for the purpose of monitoring the Bay's ecosystem. While the physical and biogeochemical variables are forecast mechanistically using the Regional Ocean Modeling System configured for the Chesapeake Bay, the species predictions are generated using a novel mechanistic empirical approach, whereby real-time output from the coupled physical biogeochemical model drives multivariate empirical habitat modelsmore » of the target species. The predictions, in the form of digital images, are available via the World Wide Web to interested groups to guide recreational, management, and research activities. Though full validation of the integrated forecasts for all species is still a work in progress, we argue that the mechanistic–empirical approach can be used to generate a wide variety of short-term ecological forecasts, and that it can be applied in any marine system where sufficient data exist to develop empirical habitat models. This paper provides an overview of this system, its predictions, and the approach taken.« less

Evolutionary and mechanistic drivers of laterality: A review and new synthesis.

PubMed

Wiper, Mallory L

2017-11-01

Laterality, best understood as asymmetries of bilateral structures or biases in behaviour, has been demonstrated in species from all major vertebrate classes, and in many invertebrates, showing a large degree of evolutionary conservation across vertebrate groups. Despite the establishment of this phenomenon in so many species, however, the evolutionary and mechanistic study of laterality is uneven with numerous areas in this field requiring greater attention. Here, I present a partial review of how far the study of laterality has come, outlining previous pioneering work, I discuss the hypothesized costs and benefits of a lateralized brain and the suggested path of the evolution of laterality for populations and individuals. I propose an expansion of laterality research into areas that have been touched upon in the past but require stronger evidence from which the field will greatly benefit. Namely, I suggest a continuation of the phylogenetic approach to investigating laterality to better understand its evolutionary path; and a further focus on mechanistic drivers, with special attention to genetic and environmental effects. Putting together the puzzle of laterality using as many pieces as possible will provide a stronger understanding of this field, allowing us to continue to expand the field in novel ways.

Mechanistic investigations of the hydrolysis of amides, oxoesters and thioesters via kinetic isotope effects and positional isotope exchange.

PubMed

Robins, Lori I; Fogle, Emily J; Marlier, John F

2015-11-01

The hydrolysis of amides, oxoesters and thioesters is an important reaction in both organic chemistry and biochemistry. Kinetic isotope effects (KIEs) are one of the most important physical organic methods for determining the most likely transition state structure and rate-determining step of these reaction mechanisms. This method induces a very small change in reaction rates, which, in turn, results in a minimum disturbance of the natural mechanism. KIE studies were carried out on both the non-enzymatic and the enzyme-catalyzed reactions in an effort to compare both types of mechanisms. In these studies the amides and esters of formic acid were chosen because this molecular structure allowed development of methodology to determine heavy-atom solvent (nucleophile) KIEs. This type of isotope effect is difficult to measure, but is rich in mechanistic information. Results of these investigations point to transition states with varying degrees of tetrahedral character that fit a classical stepwise mechanism. This article is part of a special issue entitled: Enzyme Transition States from Theory and Experiment. Copyright © 2014 Elsevier B.V. All rights reserved.

Asphalt materials characterization in support of implementation of the proposed mechanistic-empirical pavement design guide.

DOT National Transportation Integrated Search

2007-01-01

The proposed Mechanistic-Empirical Pavement Design Guide (MEPDG) procedure is an improved methodology for pavement design and evaluation of paving materials. Since this new procedure depends heavily on the characterization of the fundamental engineer...

Assessing Metal Levels in Children from the Mechanistic Indicators of Childhood Asthma(MICA) study

EPA Science Inventory

Toxic and essential metals levels can be used as health indicators. Here, we quantitatively compare and contrast toxic and essential metals levels in vacuum dust, urine, and fingernail samples of 109 children in Detroit, Michigan as part of The Mechanistic Indicators of Childhood...

Mechanistic variables can enhance predictive models of endotherm distributions: the American pika under current, past, and future climates.

PubMed

Mathewson, Paul D; Moyer-Horner, Lucas; Beever, Erik A; Briscoe, Natalie J; Kearney, Michael; Yahn, Jeremiah M; Porter, Warren P

2017-03-01

How climate constrains species' distributions through time and space is an important question in the context of conservation planning for climate change. Despite increasing awareness of the need to incorporate mechanism into species distribution models (SDMs), mechanistic modeling of endotherm distributions remains limited in this literature. Using the American pika (Ochotona princeps) as an example, we present a framework whereby mechanism can be incorporated into endotherm SDMs. Pika distribution has repeatedly been found to be constrained by warm temperatures, so we used Niche Mapper, a mechanistic heat-balance model, to convert macroclimate data to pika-specific surface activity time in summer across the western United States. We then explored the difference between using a macroclimate predictor (summer temperature) and using a mechanistic predictor (predicted surface activity time) in SDMs. Both approaches accurately predicted pika presences in current and past climate regimes. However, the activity models predicted 8-19% less habitat loss in response to annual temperature increases of ~3-5 °C predicted in the region by 2070, suggesting that pikas may be able to buffer some climate change effects through behavioral thermoregulation that can be captured by mechanistic modeling. Incorporating mechanism added value to the modeling by providing increased confidence in areas where different modeling approaches agreed and providing a range of outcomes in areas of disagreement. It also provided a more proximate variable relating animal distribution to climate, allowing investigations into how unique habitat characteristics and intraspecific phenotypic variation may allow pikas to exist in areas outside those predicted by generic SDMs. Only a small number of easily obtainable data are required to parameterize this mechanistic model for any endotherm, and its use can improve SDM predictions by explicitly modeling a widely applicable direct physiological effect

Mechanistic variables can enhance predictive models of endotherm distributions: The American pika under current, past, and future climates

USGS Publications Warehouse

Mathewson, Paul; Moyer-Horner, Lucas; Beever, Erik; Briscoe, Natalie; Kearney, Michael T.; Yahn, Jeremiah; Porter, Warren P.

2017-01-01

How climate constrains species’ distributions through time and space is an important question in the context of conservation planning for climate change. Despite increasing awareness of the need to incorporate mechanism into species distribution models (SDMs), mechanistic modeling of endotherm distributions remains limited in this literature. Using the American pika (Ochotona princeps) as an example, we present a framework whereby mechanism can be incorporated into endotherm SDMs. Pika distribution has repeatedly been found to be constrained by warm temperatures, so we used Niche Mapper, a mechanistic heat-balance model, to convert macroclimate data to pika-specific surface activity time in summer across the western United States. We then explored the difference between using a macroclimate predictor (summer temperature) and using a mechanistic predictor (predicted surface activity time) in SDMs. Both approaches accurately predicted pika presences in current and past climate regimes. However, the activity models predicted 8–19% less habitat loss in response to annual temperature increases of ~3–5 °C predicted in the region by 2070, suggesting that pikas may be able to buffer some climate change effects through behavioral thermoregulation that can be captured by mechanistic modeling. Incorporating mechanism added value to the modeling by providing increased confidence in areas where different modeling approaches agreed and providing a range of outcomes in areas of disagreement. It also provided a more proximate variable relating animal distribution to climate, allowing investigations into how unique habitat characteristics and intraspecific phenotypic variation may allow pikas to exist in areas outside those predicted by generic SDMs. Only a small number of easily obtainable data are required to parameterize this mechanistic model for any endotherm, and its use can improve SDM predictions by explicitly modeling a widely applicable direct physiological effect

Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard.

PubMed

Rusyn, Ivan; Chiu, Weihsueh A; Lash, Lawrence H; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z

2014-01-01

The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. The strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE. © 2013.

Trichloroethylene: Mechanistic, Epidemiologic and Other Supporting Evidence of Carcinogenic Hazard

PubMed Central

Rusyn, Ivan; Chiu, Weihsueh A.; Lash, Lawrence H.; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z.

2013-01-01

The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including from hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. Strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin's lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE. PMID:23973663

A semi-mechanistic model of dead fine fuel moisture for Temperate and Mediterranean ecosystems

NASA Astrophysics Data System (ADS)

Resco de Dios, Víctor; Fellows, Aaron; Boer, Matthias; Bradstock, Ross; Nolan, Rachel; Goulden, Michel

2014-05-01

Fire is a major disturbance in terrestrial ecosystems globally. It has an enormous economic and social cost, and leads to fatalities in the worst cases. The moisture content of the vegetation (fuel moisture) is one of the main determinants of fire risk. Predicting the moisture content of dead and fine fuel (< 2.5 cm in diameter) is particularly important, as this is often the most important component of the fuel complex for fire propagation. A variety of drought indices, empirical and mechanistic models have been proposed to model fuel moisture. A commonality across these different approaches is that they have been neither validated across large temporal datasets nor validated across broadly different vegetation types. Here, we present the results of a study performed at 6 locations in California, USA (5 sites) and New South Wales, Australia (1 site), where 10-hours fuel moisture content was continuously measured every 30 minutes during one full year at each site. We observed that drought indices did not accurately predict fuel moisture, and that empirical and mechanistic models both needed site-specific calibrations, which hinders their global application as indices of fuel moisture. We developed a novel, single equation and semi-mechanistic model, based on atmospheric vapor-pressure deficit. Across sites and years, mean absolute error (MAE) of predicted fuel moisture was 4.7%. MAE dropped <1% in the critical range of fuel moisture <10%. The high simplicity, accuracy and precision of our model makes it suitable for a wide range of applications: from operational purposes, to global vegetation models.

A Cycloaromatization Protocol for Synthesis of Polysubstituted Phenol Derivatives: Method Development and Mechanistic Studies

PubMed Central

Spencer, William T.

2012-01-01

The scope of the cycloaromatization of propargylic ethers was explored using operationally simple air- and moisture-insensitive conditions. Highly substituted phenol derivatives were obtained in high yields. Mechanistic experiments indicate that the reaction occurs by an electrocyclization followed by 1,3-proton transfer. PMID:22891882

Mechanistic studies of high-density lipoproteins.

PubMed

Kashyap, M L

1998-12-17

There is increasing evidence that high-density lipoprotein (HDL) and its subfractions are protective against atherosclerotic cardiovascular disease. Physical exercise, weight reduction, smoking cessation, diabetes mellitus control, and specific drugs, including niacin, fibrates, and estrogens, are effective methods to increase HDL levels. Niacin is the oldest and most powerful clinical agent for raising HDL levels. Niaspan, an extended-release niacin formulation, is as potent as immediate-release niacin in increasing levels of HDL cholesterol; subfractions HDL2 and HDL3; apolipoprotein A-I, the major protein of HDL, and its cardioprotective subfraction lipoprotein A-I. Recent research from our laboratory suggests a novel mechanism by which niacin inhibits hepatic removal of HDL-apoprotein A-I without interfering with the removal of cholesterol carried by HDL, thus augmenting reverse cholesterol transport. Other mechanistic studies indicate that fibrates and estrogens stimulate the synthesis and production of HDL-apoprotein A-I. Because niacin decreases HDL-apoprotein A-I removal, and fibrates and estrogens increase HDL-apoprotein A-I production, combinations of niacin with these agents may raise HDL levels more than fibrates or estrogens alone.

Unresolved grief and its consequences. A nationwide follow-up of teenage loss of a parent to cancer 6-9 years earlier.

PubMed

Bylund-Grenklo, T; Fürst, C J; Nyberg, T; Steineck, G; Kreicbergs, U

2016-07-01

The early loss of a parent is a tragedy and a serious life event. This study investigated grief resolution and morbidity in cancer-bereaved teenagers 6 to 9 years after the loss of a parent to cancer. In a nationwide population-based study of 622 of 851 (73 %) youths who as teenagers 6 to 9 years earlier had lost a parent to cancer, we explored the magnitude of unresolved grief and its association with psychological and physiological morbidity. Participants answered a study-specific anonymous questionnaire including questions about if they had worked through their grief and about their current health. Six to nine years post-loss 49 % reported unresolved grief (8 % no and 41 % a little grief resolution). They had, in comparison with youths reporting resolved grief, statistically significantly elevated risks, e.g. for insomnia (sons' relative risk (RR) 2.3, 95 % CI 1.3-4.0; daughters' RR 1.7, 95 % CI 1.1-2.7), fatigue (sons' RR 1.8, 95 % CI 1.3-2.5; daughters' RR 1.4, 95 % CI 1.1-1.7) and moderate to severe depression, i.e. score >9, PHQ-9 (sons' RR 3.6, 95 % CI 1.4-8.8; daughters' RR 1.8, 95 % CI 1.1-3.1). Associations remained for insomnia in sons, exhaustion in daughters and fatigue in both sons and daughters when depression, negative intrusive thoughts and avoiding reminders of the parents' disease or death were included in a model. Approximately half of cancer-bereaved youth report no or little grief resolution 6 to 9 years post-loss, which is associated with fatigue, sleeping problems and depressive symptoms.

Actin and Endocytosis in Budding Yeast

PubMed Central

Goode, Bruce L.; Eskin, Julian A.; Wendland, Beverly

2015-01-01

Endocytosis, the process whereby the plasma membrane invaginates to form vesicles, is essential for bringing many substances into the cell and for membrane turnover. The mechanism driving clathrin-mediated endocytosis (CME) involves > 50 different protein components assembling at a single location on the plasma membrane in a temporally ordered and hierarchal pathway. These proteins perform precisely choreographed steps that promote receptor recognition and clustering, membrane remodeling, and force-generating actin-filament assembly and turnover to drive membrane invagination and vesicle scission. Many critical aspects of the CME mechanism are conserved from yeast to mammals and were first elucidated in yeast, demonstrating that it is a powerful system for studying endocytosis. In this review, we describe our current mechanistic understanding of each step in the process of yeast CME, and the essential roles played by actin polymerization at these sites, while providing a historical perspective of how the landscape has changed since the preceding version of the YeastBook was published 17 years ago (1997). Finally, we discuss the key unresolved issues and where future studies might be headed. PMID:25657349

Mechanistic systems modeling to guide drug discovery and development

PubMed Central

Schmidt, Brian J.; Papin, Jason A.; Musante, Cynthia J.

2013-01-01

A crucial question that must be addressed in the drug development process is whether the proposed therapeutic target will yield the desired effect in the clinical population. Pharmaceutical and biotechnology companies place a large investment on research and development, long before confirmatory data are available from human trials. Basic science has greatly expanded the computable knowledge of disease processes, both through the generation of large omics data sets and a compendium of studies assessing cellular and systemic responses to physiologic and pathophysiologic stimuli. Given inherent uncertainties in drug development, mechanistic systems models can better inform target selection and the decision process for advancing compounds through preclinical and clinical research. PMID:22999913

Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease

PubMed Central

Allison, Beth J.; Kaandorp, Joepe J.; Kane, Andrew D.; Camm, Emily J.; Lusby, Ciara; Cross, Christine M.; Nevin-Dolan, Rhianon; Thakor, Avnesh S.; Derks, Jan B.; Tarry-Adkins, Jane L.; Ozanne, Susan E.; Giussani, Dino A.

2016-01-01

Aging and developmental programming are both associated with oxidative stress and endothelial dysfunction, suggesting common mechanistic origins. However, their interrelationship has been little explored. In a rodent model of programmed cardiovascular dysfunction we determined endothelial function and vascular telomere length in young (4 mo) and aged (15 mo) adult offspring of normoxic or hypoxic pregnancy with or without maternal antioxidant treatment. We show loss of endothelial function [maximal arterial relaxation to acetylcholine (71 ± 3 vs. 55 ± 3%) and increased vascular short telomere abundance (4.2–1.3 kb) 43.0 ± 1.5 vs. 55.1 ± 3.8%) in aged vs. young offspring of normoxic pregnancy (P < 0.05). Hypoxic pregnancy in young offspring accelerated endothelial dysfunction (maximal arterial relaxation to acetylcholine: 42 ± 1%, P < 0.05) but this was dissociated from increased vascular short telomere length abundance. Maternal allopurinol rescued maximal arterial relaxation to acetylcholine in aged offspring of normoxic or hypoxic pregnancy but not in young offspring of hypoxic pregnancy. Aged offspring of hypoxic allopurinol pregnancy compared with aged offspring of untreated hypoxic pregnancy had lower levels of short telomeres (vascular short telomere length abundance 35.1 ± 2.5 vs. 48.2 ± 2.6%) and of plasma proinflammatory chemokine (24.6 ± 2.8 vs. 36.8 ± 5.5 pg/ml, P < 0.05). These data provide evidence for divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease, and aging being decelerated by antioxidants even prior to birth.—Allison, B. J., Kaandorp, J. J., Kane, A. D., Camm, E. J., Lusby, C., Cross, C. M., Nevin-Dolan, R., Thakor, A. S., Derks, J. B., Tarry-Adkins, J. L., Ozanne, S. E., Giussani, D. A. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease. PMID:26932929

Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease.

PubMed

Allison, Beth J; Kaandorp, Joepe J; Kane, Andrew D; Camm, Emily J; Lusby, Ciara; Cross, Christine M; Nevin-Dolan, Rhianon; Thakor, Avnesh S; Derks, Jan B; Tarry-Adkins, Jane L; Ozanne, Susan E; Giussani, Dino A

2016-05-01

Aging and developmental programming are both associated with oxidative stress and endothelial dysfunction, suggesting common mechanistic origins. However, their interrelationship has been little explored. In a rodent model of programmed cardiovascular dysfunction we determined endothelial function and vascular telomere length in young (4 mo) and aged (15 mo) adult offspring of normoxic or hypoxic pregnancy with or without maternal antioxidant treatment. We show loss of endothelial function [maximal arterial relaxation to acetylcholine (71 ± 3 vs. 55 ± 3%) and increased vascular short telomere abundance (4.2-1.3 kb) 43.0 ± 1.5 vs. 55.1 ± 3.8%) in aged vs. young offspring of normoxic pregnancy (P < 0.05). Hypoxic pregnancy in young offspring accelerated endothelial dysfunction (maximal arterial relaxation to acetylcholine: 42 ± 1%, P < 0.05) but this was dissociated from increased vascular short telomere length abundance. Maternal allopurinol rescued maximal arterial relaxation to acetylcholine in aged offspring of normoxic or hypoxic pregnancy but not in young offspring of hypoxic pregnancy. Aged offspring of hypoxic allopurinol pregnancy compared with aged offspring of untreated hypoxic pregnancy had lower levels of short telomeres (vascular short telomere length abundance 35.1 ± 2.5 vs. 48.2 ± 2.6%) and of plasma proinflammatory chemokine (24.6 ± 2.8 vs. 36.8 ± 5.5 pg/ml, P < 0.05). These data provide evidence for divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease, and aging being decelerated by antioxidants even prior to birth.-Allison, B. J., Kaandorp, J. J., Kane, A. D., Camm, E. J., Lusby, C., Cross, C. M., Nevin-Dolan, R., Thakor, A. S., Derks, J. B., Tarry-Adkins, J. L., Ozanne, S. E., Giussani, D. A. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease. © FASEB.

Traffic load spectra for implementing and using the mechanistic-empirical pavement design guide in Georgia.

DOT National Transportation Integrated Search

2014-02-01

The GDOT is preparing for implementation of the Mechanistic-Empirical Pavement Design : Guide (MEPDG). As part of this preparation, a statewide traffic load spectra program is being : developed for gathering truck axle loading data. This final report...

PROPERTIES AND MODELING OF UNRESOLVED FINE STRUCTURE LOOPS OBSERVED IN THE SOLAR TRANSITION REGION BY IRIS

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

Brooks, David H.; Reep, Jeffrey W.; Warren, Harry P.

Recent observations from the Interface Region Imaging Spectrograph ( IRIS ) have discovered a new class of numerous low-lying dynamic loop structures, and it has been argued that they are the long-postulated unresolved fine structures (UFSs) that dominate the emission of the solar transition region. In this letter, we combine IRIS measurements of the properties of a sample of 108 UFSs (intensities, lengths, widths, lifetimes) with one-dimensional non-equilibrium ionization simulations, using the HYDRAD hydrodynamic model to examine whether the UFSs are now truly spatially resolved in the sense of being individual structures rather than being composed of multiple magnetic threads.more » We find that a simulation of an impulsively heated single strand can reproduce most of the observed properties, suggesting that the UFSs may be resolved, and the distribution of UFS widths implies that they are structured on a spatial scale of 133 km on average. Spatial scales of a few hundred kilometers appear to be typical for a range of chromospheric and coronal structures, and we conjecture that this could be an important clue for understanding the coronal heating process.« less

Comparison of Two-Phase Pipe Flow in OpenFOAM with a Mechanistic Model

NASA Astrophysics Data System (ADS)

Shuard, Adrian M.; Mahmud, Hisham B.; King, Andrew J.

2016-03-01

Two-phase pipe flow is a common occurrence in many industrial applications such as power generation and oil and gas transportation. Accurate prediction of liquid holdup and pressure drop is of vast importance to ensure effective design and operation of fluid transport systems. In this paper, a Computational Fluid Dynamics (CFD) study of a two-phase flow of air and water is performed using OpenFOAM. The two-phase solver, interFoam is used to identify flow patterns and generate values of liquid holdup and pressure drop, which are compared to results obtained from a two-phase mechanistic model developed by Petalas and Aziz (2002). A total of 60 simulations have been performed at three separate pipe inclinations of 0°, +10° and -10° respectively. A three dimensional, 0.052m diameter pipe of 4m length is used with the Shear Stress Transport (SST) k - ɷ turbulence model to solve the turbulent mixtures of air and water. Results show that the flow pattern behaviour and numerical values of liquid holdup and pressure drop compare reasonably well to the mechanistic model.

Application of Pulse Radiolysis to Mechanistic Investigations of Catalysis Relevant to Artificial Photosynthesis

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

Fujita, Etsuko; Grills, David C.; Polyansky, Dmitry E.

Taking inspiration from natural photosystems, the goal of artificial photosynthesis is to harness solar energy to convert abundant materials, such as CO 2 and H 2O, into solar fuels. Catalysts are required to ensure that the necessary redox half-reactions proceed in the most energy-efficient manner. It is thus critical to gain a detailed mechanistic understanding of these catalytic reactions in order to develop new and improved catalysts. Many of the key catalytic intermediates are short-lived transient species, requiring time-resolved spectroscopic techniques for their observation. The two main methods for rapidly generating such species on the sub-microsecond timescale are laser flashmore » photolysis and pulse radiolysis. These methods complement one another, and both can provide important spectroscopic and kinetic information. However, pulse radiolysis proves to be superior in systems with significant spectroscopic overlap between photosensitizer and other species present during the reaction. In this paper, we review the pulse radiolysis technique and how it has been applied to mechanistic investigations of half-reactions relevant to artificial photosynthesis.« less

Application of Pulse Radiolysis to Mechanistic Investigations of Catalysis Relevant to Artificial Photosynthesis

DOE PAGES

Fujita, Etsuko; Grills, David C.; Polyansky, Dmitry E.

2017-09-12

Taking inspiration from natural photosystems, the goal of artificial photosynthesis is to harness solar energy to convert abundant materials, such as CO 2 and H 2O, into solar fuels. Catalysts are required to ensure that the necessary redox half-reactions proceed in the most energy-efficient manner. It is thus critical to gain a detailed mechanistic understanding of these catalytic reactions in order to develop new and improved catalysts. Many of the key catalytic intermediates are short-lived transient species, requiring time-resolved spectroscopic techniques for their observation. The two main methods for rapidly generating such species on the sub-microsecond timescale are laser flashmore » photolysis and pulse radiolysis. These methods complement one another, and both can provide important spectroscopic and kinetic information. However, pulse radiolysis proves to be superior in systems with significant spectroscopic overlap between photosensitizer and other species present during the reaction. In this paper, we review the pulse radiolysis technique and how it has been applied to mechanistic investigations of half-reactions relevant to artificial photosynthesis.« less

Toward a Mechanistic Understanding of Environmentally Forced Zoonotic Disease Emergence: Sin Nombre Hantavirus

PubMed Central

Carver, Scott; Mills, James N.; Parmenter, Cheryl A.; Parmenter, Robert R.; Richardson, Kyle S.; Harris, Rachel L.; Douglass, Richard J.; Kuenzi, Amy J.; Luis, Angela D.

2015-01-01

Understanding the environmental drivers of zoonotic reservoir and human interactions is crucial to understanding disease risk, but these drivers are poorly predicted. We propose a mechanistic understanding of human–reservoir interactions, using hantavirus pulmonary syndrome as a case study. Crucial processes underpinning the disease's incidence remain poorly studied, including the connectivity among natural and peridomestic deer mouse host activity, virus transmission, and human exposure. We found that disease cases were greatest in arid states and declined exponentially with increasing precipitation. Within arid environments, relatively rare climatic conditions (e.g., El Niño) are associated with increased rainfall and reservoir abundance, producing more frequent virus transmission and host dispersal. We suggest that deer mice increase their occupancy of peridomestic structures during spring–summer, amplifying intraspecific transmission and human infection risk. Disease incidence in arid states may increase with predicted climatic changes. Mechanistic approaches incorporating reservoir behavior, reservoir–human interactions, and pathogen spillover could enhance our understanding of global hantavirus ecology, with applications to other directly transmitted zoonoses. PMID:26955081

Assessing causal mechanistic interactions: a peril ratio index of synergy based on multiplicativity.

PubMed

Lee, Wen-Chung

2013-01-01

The assessments of interactions in epidemiology have traditionally been based on risk-ratio, odds-ratio or rate-ratio multiplicativity. However, many epidemiologists fail to recognize that this is mainly for statistical conveniences and often will misinterpret a statistically significant interaction as a genuine mechanistic interaction. The author adopts an alternative metric system for risk, the 'peril'. A peril is an exponentiated cumulative rate, or simply, the inverse of a survival (risk complement) or one plus an odds. The author proposes a new index based on multiplicativity of peril ratios, the 'peril ratio index of synergy based on multiplicativity' (PRISM). Under the assumption of no redundancy, PRISM can be used to assess synergisms in sufficient cause sense, i.e., causal co-actions or causal mechanistic interactions. It has a less stringent threshold to detect a synergy as compared to a previous index of 'relative excess risk due to interaction'. Using the new PRISM criterion, many situations in which there is not evidence of interaction judged by the traditional indices are in fact corresponding to bona fide positive or negative synergisms.

ASSESSING POPULATION EXPOSURES TO MULTIPLE AIR POLLUTANTS USING A MECHANISTIC SOURCE-TO-DOSE MODELING FRAMEWORK

EPA Science Inventory

The Modeling Environment for Total Risks studies (MENTOR) system, combined with an extension of the SHEDS (Stochastic Human Exposure and Dose Simulation) methodology, provide a mechanistically consistent framework for conducting source-to-dose exposure assessments of multiple pol...

Attractor learning in synchronized chaotic systems in the presence of unresolved scales

NASA Astrophysics Data System (ADS)

Wiegerinck, W.; Selten, F. M.

2017-12-01

Recently, supermodels consisting of an ensemble of interacting models, synchronizing on a common solution, have been proposed as an alternative to the common non-interactive multi-model ensembles in order to improve climate predictions. The connection terms in the interacting ensemble are to be optimized based on the data. The supermodel approach has been successfully demonstrated in a number of simulation experiments with an assumed ground truth and a set of good, but imperfect models. The supermodels were optimized with respect to their short-term prediction error. Nevertheless, they produced long-term climatological behavior that was close to the long-term behavior of the assumed ground truth, even in cases where the long-term behavior of the imperfect models was very different. In these supermodel experiments, however, a perfect model class scenario was assumed, in which the ground truth and imperfect models belong to the same model class and only differ in parameter setting. In this paper, we consider the imperfect model class scenario, in which the ground truth model class is more complex than the model class of imperfect models due to unresolved scales. We perform two supermodel experiments in two toy problems. The first one consists of a chaotically driven Lorenz 63 oscillator ground truth and two Lorenz 63 oscillators with constant forcings as imperfect models. The second one is more realistic and consists of a global atmosphere model as ground truth and imperfect models that have perturbed parameters and reduced spatial resolution. In both problems, we find that supermodel optimization with respect to short-term prediction error can lead to a long-term climatological behavior that is worse than that of the imperfect models. However, we also show that attractor learning can remedy this problem, leading to supermodels with long-term behavior superior to the imperfect models.

Wear-dependent specific coefficients in a mechanistic model for turning of nickel-based superalloy with ceramic tools

NASA Astrophysics Data System (ADS)

López de Lacalle, Luis Norberto; Urbicain Pelayo, Gorka; Fernández-Valdivielso, Asier; Alvarez, Alvaro; González, Haizea

2017-09-01

Difficult to cut materials such as nickel and titanium alloys are used in the aeronautical industry, the former alloys due to its heat-resistant behavior and the latter for the low weight - high strength ratio. Ceramic tools made out alumina with reinforce SiC whiskers are a choice in turning for roughing and semifinishing workpiece stages. Wear rate is high in the machining of these alloys, and consequently cutting forces tends to increase along one operation. This paper establishes the cutting force relation between work-piece and tool in the turning of such difficult-to-cut alloys by means of a mechanistic cutting force model that considers the tool wear effect. The cutting force model demonstrates the force sensitivity to the cutting engagement parameters (ap, f) when using ceramic inserts and wear is considered. Wear is introduced through a cutting time factor, being useful in real conditions taking into account that wear quickly appears in alloys machining. A good accuracy in the cutting force model coefficients is the key issue for an accurate prediction of turning forces, which could be used as criteria for tool replacement or as input for chatter or other models.

Characterizing seasonal variations in pavement material properties for use in a mechanistic-empirical design procedure

DOT National Transportation Integrated Search

2000-12-01

Recent advances in flexible pavement design have prompted agencies to move toward the development and use of mechanistic-empirical (M-E) design procedures. This report analyzed seasonal trends in flexible pavement layer moduli to calibrate a M-E desi...

Mechanistic models of biofilm growth in porous media

NASA Astrophysics Data System (ADS)

Jaiswal, Priyank; Al-Hadrami, Fathiya; Atekwana, Estella A.; Atekwana, Eliot A.

2014-07-01

Nondestructive acoustics methods can be used to monitor in situ biofilm growth in porous media. In practice, however, acoustic methods remain underutilized due to the lack of models that can translate acoustic data into rock properties in the context of biofilm. In this paper we present mechanistic models of biofilm growth in porous media. The models are used to quantitatively interpret arrival times and amplitudes recorded in the 29 day long Davis et al. (2010) physical scale biostimulation experiment in terms of biofilm morphologies and saturation. The model pivots on addressing the sediment elastic behavior using the lower Hashin-Shtrikman bounds for grain mixing and Gassmann substitution for fluid saturation. The time-lapse P wave velocity (VP; a function of arrival times) is explained by a combination of two rock models (morphologies); "load bearing" which assumes the biofilm as an additional mineral in the rock matrix and "pore filling" which assumes the biofilm as an additional fluid phase in the pores. The time-lapse attenuation (QP-1; a function of amplitudes), on the other hand, can be explained adequately in two ways; first, through squirt flow where energy is lost from relative motion between rock matrix and pore fluid, and second, through an empirical function of porosity (φ), permeability (κ), and grain size. The squirt flow model-fitting results in higher internal φ (7% versus 5%) and more oblate pores (0.33 versus 0.67 aspect ratio) for the load-bearing morphology versus the pore-filling morphology. The empirical model-fitting results in up to 10% increase in κ at the initial stages of the load-bearing morphology. The two morphologies which exhibit distinct mechanical and hydraulic behavior could be a function of pore throat size. The biofilm mechanistic models developed in this study can be used for the interpretation of seismic data critical for the evaluation of biobarriers in bioremediation, microbial enhanced oil recovery, and CO2

Use of Gene Expression Changes in Blood to Elucidate Mechanistic Indicators of Childhood Asthma (MICA)

EPA Science Inventory

Risk assessment increasingly relies more heavily on mode of action, thus the identification of human bioindicators of disease becomes all the more important. Genomic methods represent a tool for both mode of action determination and bioindicator identification. The Mechanistic In...

The Most Critical Unresolved Issues Associated with Race, Ethnicity, Culture, and Substance Use

PubMed Central

Unger, Jennifer B.

2015-01-01

This paper discusses the limitations of previous research on race, ethnicity, culture, and substance use. The study offers the following recommendations for future research in this area: (1) move beyond simple comparisons of mutually exclusive groups, (2) focus on the meaning of an ethnic label to the individual, (3) consider the complex interactions between an individual’s cultural identity and the cultural context, (4) understand and acknowledge the researcher’s inherent biases, and (5) translate research findings into practice and policy change. PMID:22217334

A dynamic and mechanistic model of PCB bioaccumulation in the European hake ( Merluccius merluccius)

NASA Astrophysics Data System (ADS)

Bodiguel, Xavier; Maury, Olivier; Mellon-Duval, Capucine; Roupsard, François; Le Guellec, Anne-Marie; Loizeau, Véronique

2009-08-01

Bioaccumulation is difficult to document because responses differ among chemical compounds, with environmental conditions, and physiological processes characteristic of each species. We use a mechanistic model, based on the Dynamic Energy Budget (DEB) theory, to take into account this complexity and study factors impacting accumulation of organic pollutants in fish through ontogeny. The bioaccumulation model proposed is a comprehensive approach that relates evolution of hake PCB contamination to physiological information about the fish, such as diet, metabolism, reserve and reproduction status. The species studied is the European hake ( Merluccius merluccius, L. 1758). The model is applied to study the total concentration and the lipid normalised concentration of 4 PCB congeners in male and female hakes from the Gulf of Lions (NW Mediterranean sea) and the Bay of Biscay (NE Atlantic ocean). Outputs of the model compare consistently to measurements over the life span of fish. Simulation results clearly demonstrate the relative effects of food contamination, growth and reproduction on the PCB bioaccumulation in hake. The same species living in different habitats and exposed to different PCB prey concentrations exhibit marked difference in the body accumulation of PCBs. At the adult stage, female hakes have a lower PCB concentration compared to males for a given length. We successfully simulated these sex-specific PCB concentrations by considering two mechanisms: a higher energy allocation to growth for females and a transfer of PCBs from the female to its eggs when allocating lipids from reserve to eggs. Finally, by its mechanistic description of physiological processes, the model is relevant for other species and sets the stage for a mechanistic understanding of toxicity and ecological effects of organic contaminants in marine organisms.

Antimony photoresists for EUV lithography: mechanistic studies

NASA Astrophysics Data System (ADS)

Murphy, Michael; Narasimhan, Amrit; Grzeskowiak, Steven; Sitterly, Jacob; Schuler, Philip; Richards, Jeff; Denbeaux, Greg; Brainard, Robert L.

2017-03-01

We have developed a method to study the photomechanism of our antimony carboxylate platform R3Sb(COOR')2. A series of mechanistic studies followed the production of reaction byproducts by mass spectrometer, as they left the film during exposure to EUV photons and 80 eV electrons. We identified several prominent outgassing fragments and their rates of production as a function of ligand structure. The degree of outgassing appears to be well-correlated with the bond dissociation energy of the carboxylate ligand R' group. Furthermore, a deuterium labeling study was conducted to determine from which ligand hydrogen is abstracted to form benzene and phenol during exposure. Benzene and phenol were found to abstract hydrogen from opposing sites within the film, and with greater than 95% isotopic purity. Using the results of the outgassing studies alongside established mechanisms for electron-induced reactions; a series of reaction pathways were proposed to generate the aforementioned outgassing species and a possible nonvolatile negative-tone photoproduct.

Unfinished Business in Bereavement

PubMed Central

Klingspon, Kara L.; Holland, Jason M.; Neimeyer, Robert A.; Lichtenthal, Wendy G.

2016-01-01

Unfinished business (incomplete, unexpressed or unresolved relationship issues with the deceased) is frequently discussed as a risk factor for chronic and severe grief reactions. However, few empirical studies have examined this construct. The present study aimed to address this gap in the literature by examining the presence and severity of unfinished business as well as common themes of unfinished business reported in open-ended qualitative narratives among a sample of 224 bereaved individuals. In bivariate analyses, self-reported presence of unfinished business and the severity of distress due to unfinished business were both found to be associated with poorer bereavement outcomes. However, after controlling for potential confounds, distress related to unresolved issues with the deceased emerged as a more robust correlate of these outcomes. Qualitative responses were categorized, and the type of reported unfinished business was not significantly related to the degree of unfinished business distress or other bereavement outcomes. These findings provide preliminary justification for bereavement interventions that aim to ameliorate distress related to unresolved relational issues with the deceased. PMID:26057117

Unfinished Business in Bereavement.

PubMed

Klingspon, Kara L; Holland, Jason M; Neimeyer, Robert A; Lichtenthal, Wendy G

2015-01-01

Unfinished business (incomplete, unexpressed or unresolved relationship issues with the deceased) is frequently discussed as a risk factor for chronic and severe grief reactions. However, few empirical studies have examined this construct. The present study aimed to address this gap in the literature by examining the presence and severity of unfinished business as well as common themes of unfinished business reported in open-ended qualitative narratives among a sample of 224 bereaved individuals. In bivariate analyses, self-reported presence of unfinished business and the severity of distress due to unfinished business were both found to be associated with poorer bereavement outcomes. However, after controlling for potential confounds, distress related to unresolved issues with the deceased emerged as a more robust correlate of these outcomes. Qualitative responses were categorized, and the type of reported unfinished business was not significantly related to the degree of unfinished business distress or other bereavement outcomes. These findings provide preliminary justification for bereavement interventions that aim to ameliorate distress related to unresolved relational issues with the deceased.

Mechanistic systems modeling to guide drug discovery and development.

PubMed

Schmidt, Brian J; Papin, Jason A; Musante, Cynthia J

2013-02-01

A crucial question that must be addressed in the drug development process is whether the proposed therapeutic target will yield the desired effect in the clinical population. Pharmaceutical and biotechnology companies place a large investment on research and development, long before confirmatory data are available from human trials. Basic science has greatly expanded the computable knowledge of disease processes, both through the generation of large omics data sets and a compendium of studies assessing cellular and systemic responses to physiologic and pathophysiologic stimuli. Given inherent uncertainties in drug development, mechanistic systems models can better inform target selection and the decision process for advancing compounds through preclinical and clinical research. Copyright © 2012 Elsevier Ltd. All rights reserved.

From patterns to emerging processes in mechanistic urban ecology.

PubMed

Shochat, Eyal; Warren, Paige S; Faeth, Stanley H; McIntyre, Nancy E; Hope, Diane

2006-04-01

Rapid urbanization has become an area of crucial concern in conservation owing to the radical changes in habitat structure and loss of species engendered by urban and suburban development. Here, we draw on recent mechanistic ecological studies to argue that, in addition to altered habitat structure, three major processes contribute to the patterns of reduced species diversity and elevated abundance of many species in urban environments. These activities, in turn, lead to changes in animal behavior, morphology and genetics, as well as in selection pressures on animals and plants. Thus, the key to understanding urban patterns is to balance studying processes at the individual level with an integrated examination of environmental forces at the ecosystem scale.

An Emphasis on Perception: Teaching Image Formation Using a Mechanistic Model of Vision.

ERIC Educational Resources Information Center

Allen, Sue; And Others

An effective way to teach the concept of image is to give students a model of human vision which incorporates a simple mechanism of depth perception. In this study two almost identical versions of a curriculum in geometrical optics were created. One used a mechanistic, interpretive eye model, and in the other the eye was modeled as a passive,…

Application of empirical and mechanistic-empirical pavement design procedures to Mn/ROAD concrete pavement test sections

DOT National Transportation Integrated Search

1997-05-01

Current pavement design procedures are based principally on empirical approaches. The current trend toward developing more mechanistic-empirical type pavement design methods led Minnesota to develop the Minnesota Road Research Project (Mn/ROAD), a lo...

A new mechanistic framework to predict OCS fluxes in soils

NASA Astrophysics Data System (ADS)

Sauze, Joana; Ogee, Jérôme; Launois, Thomas; Kesselmeier, Jürgen; Van Diest, Heidi; Wingate, Lisa

2015-04-01

A better description of the amplitude of photosynthetic and respiratory gross CO2 fluxes at large scales is needed to improve our predictions of the current and future global CO2 cycle. Carbonyl sulfide (COS) is the most abundant sulphur gas in the atmosphere and has been proposed as a new tracer of gross photosynthesis, as the uptake of COS from the atmosphere is dominated by the activity of carbonic anhydrase (CA), an enzyme abundant in leaves that also catalyses CO2 hydration during photosynthesis. However, soils also exchange COS with the atmosphere and there is growing evidence that this flux must also be accounted for in atmospheric budgets. In this context a new mechanistic description of soil-atmosphere COS exchange is clearly needed. Soils can take up COS from the atmosphere as the soil biota also contain CA, and COS emissions from soils have also been reported in agricultural fields or anoxic soils. Previous studies have also shown that soil COS fluxes present an optimum soil water content and soil temperature. Here we propose a new mechanistic framework to predict the fluxes of COS between the soils and the atmosphere. We describe the COS soil budget by a first-order reaction-diffusion-production equation, assuming that the hydrolysis of COS by CA is total and irreversible. To describe COS diffusion through the soil matrix, we use different formulations of soil air-filled pore space and temperature, depending on the turbulence level above the soil surface. Using this model we are able to explain the observed presence of an optimum temperature for soil COS uptake and show how this optimum can shift to cooler temperatures in the presence of soil COS emissions. Our model can also explain the observed optimum with soil moisture content previously described in the literature (e.g. Van Diest & Kesselmeier, 2008) as a result of diffusional constraints on COS hydrolysis. These diffusional constraints are also responsible for the response of COS uptake to soil

Combining Solvent Isotope Effects with Substrate Isotope Effects in Mechanistic Studies of Alcohol and Amine Oxidation by Enzymes*

PubMed Central

Fitzpatrick, Paul F.

2014-01-01

Oxidation of alcohols and amines is catalyzed by multiple families of flavin-and pyridine nucleotide-dependent enzymes. Measurement of solvent isotope effects provides a unique mechanistic probe of the timing of the cleavage of the OH and NH bonds, necessary information for a complete description of the catalytic mechanism. The inherent ambiguities in interpretation of solvent isotope effects can be significantly decreased if isotope effects arising from isotopically labeled substrates are measured in combination with solvent isotope effects. The application of combined solvent and substrate (mainly deuterium) isotope effects to multiple enzymes is described here to illustrate the range of mechanistic insights that such an approach can provide. PMID:25448013

ISSUES IN DEVELOPING A TWO-GENERATION AVIAN TOXICITY TEST WITH JAPANESE QUAIL

EPA Science Inventory

As a subgroup of the OECD Expert Group on Assessment of Endocrine Disrupting Effects in Birds, we reviewed unresolved methodological issures important for the development of a two-generation toxicity test, discussed advantages and disadvantages of alternative approaches, and prop...

Analysis of Virginia-specific traffic data inputs for use with the mechanistic-empirical pavement design guide.

DOT National Transportation Integrated Search

2010-02-01

This study developed traffic inputs for use with the Guide for the Mechanistic-Empirical Design of New & Rehabilitated Pavement Structures (MEPDG) in Virginia and sought to determine if the predicted distresses showed differences between site-specifi...

Risks and issues in fire safety on the Space Station

NASA Technical Reports Server (NTRS)

Friedman, Robert

1993-01-01

A fire in the inhabited portion of a spacecraft is a greatly feared hazard, but fire protection in space operations is complicated by two factors. First, the spacecraft cabin is an enclosed volume, which limits the resources for fire fighting and the options for crew escape. Second, an orbiting spacecraft experiences a balance of forces, creating a near-zero-gravity (microgravity) environment that profoundly affects the characteristics of fire initiation, spread, and suppression. The current Shuttle Orbiter is protected by a fire-detection and suppression system whose requirements are derived of necessity from accepted terrestrial and aircraft standards. While experience has shown that Shuttle fire safety is adequate, designers recognize that improved systems to respond specifically to microgravity fire characteristics are highly desirable. Innovative technology is particularly advisable for the Space Station, a forthcoming space community with a complex configuration and long-duration orbital missions, in which the effectiveness of current fire-protection systems is unpredictable. The development of risk assessments to evaluate the probabilities and consequences of fire incidents in spacecraft are briefly reviewed. It further discusses the important unresolved issues and needs for improved fire safety in the Space Station, including those of material selection, spacecraft atmospheres, fire detection, fire suppression, and post-fire restoration.

Assessing Causal Mechanistic Interactions: A Peril Ratio Index of Synergy Based on Multiplicativity

PubMed Central

Lee, Wen-Chung

2013-01-01

The assessments of interactions in epidemiology have traditionally been based on risk-ratio, odds-ratio or rate-ratio multiplicativity. However, many epidemiologists fail to recognize that this is mainly for statistical conveniences and often will misinterpret a statistically significant interaction as a genuine mechanistic interaction. The author adopts an alternative metric system for risk, the ‘peril’. A peril is an exponentiated cumulative rate, or simply, the inverse of a survival (risk complement) or one plus an odds. The author proposes a new index based on multiplicativity of peril ratios, the ‘peril ratio index of synergy based on multiplicativity’ (PRISM). Under the assumption of no redundancy, PRISM can be used to assess synergisms in sufficient cause sense, i.e., causal co-actions or causal mechanistic interactions. It has a less stringent threshold to detect a synergy as compared to a previous index of ‘relative excess risk due to interaction’. Using the new PRISM criterion, many situations in which there is not evidence of interaction judged by the traditional indices are in fact corresponding to bona fide positive or negative synergisms. PMID:23826299

Mechanistic insights on the cycloisomerization of polyunsaturated precursors catalyzed by platinum and gold complexes.

PubMed

Soriano, Elena; Marco-Contelles, José

2009-08-18

Organometallic chemistry provides powerful tools for the stereocontrolled synthesis of heterocycles and carbocycles. The electrophilic transition metals Pt(II) and Au(I, III) are efficient catalysts in these transitions and promote a variety of organic transformations of unsaturated precursors. These reactions produce functionalized cyclic and acyclic scaffolds for the synthesis of natural and non-natural products efficiently, under mild conditions, and with excellent chemoselectivity. Because these transformations are strongly substrate-dependent, they are versatile and may yield diverse molecular scaffolds. Therefore, synthetic chemists need a mechanistic interpretation to optimize this reaction process and design a new generation of catalysts. However, so far, no intermediate species has been isolated or characterized, so the formulated mechanistic hypotheses have been primarily based on labeling studies or trapping reactions. Recently, theoretical DFT studies have become a useful tool in our research, giving us insights into the key intermediates and into a variety of plausible reaction pathways. In this Account, we present a comprehensive mechanistic overview of transformations promoted by Pt and Au in a non-nucleophilic medium based on quantum-mechanical studies. The calculations are consistent with the experimental observations and provide fundamental insights into the versatility of these reaction processes. The reactivity of these metals results from their peculiar Lewis acid properties: the alkynophilic character of these soft metals and the pi-acid activation of unsaturated groups promotes the intra- or intermolecular attack of a nucleophile. 1,n-Enynes (n = 3-8) are particularly important precursors, and their transformation may yield a variety of cycloadducts depending on the molecular structure. However, the calculations suggest that these different cyclizations would have closely related reaction mechanisms, and we propose a unified mechanistic

Meditative Movement, Energetic, and Physical Analyses of Three Qigong Exercises: Unification of Eastern and Western Mechanistic Exercise Theory.

PubMed

Klein, Penelope; Picard, George; Baumgarden, Joseph; Schneider, Roger

2017-09-23

Abstract : Qigong is the meditative movement and therapeutic exercise of Eastern medicine. A growing body of evidence is validating its health benefits leading to mechanistic questions of how it works. The purpose of this article is to explore mechanisms of action related to Qigong, with the intent of unifying Eastern and Western exercise theory and to present a model for Qigong exercise analysis. Three exercises from a standardized Qigong form: 'Plucking the Stars', 'Lotus Leaves Rustle in the Wind', and 'Pacing Forwards and Backwards' were selected for meditative, energetic, and physical analyses. Meditative aspects include relaxation response, interoception and exteroception. Energetic aspects include stimulation of meridians through mental intent, acupressure, and self-massage. Physical aspects include flexibility, strength, articular stimulation, neuro-integration, respiratory effect, fascial stretch, visceral massage, balance challenge CranioSacral pump, lymphatic and venous return and glandular stimulation, and physiologic response to relaxation. Knowledge of mechanisms of action for specific Qigong exercises can guide operational definition of Qigong, selection of outcomes assessment in future research, inform prescriptive practice addressing clinical health issues, and advance adoption of Qigong practice within integrative health care. The model of analysis demonstrated in this discussion may assist in these endeavors.

Task 4 : testing Iowa Portland cement concrete mixtures for the AASHTO mechanistic-empirical pavement design procedure.

DOT National Transportation Integrated Search

2008-05-01

The present research project was designed to identify the typical Iowa material input values that are required by the Mechanistic- : Empirical Pavement Design Guide (MEPDG) for the Level 3 concrete pavement design. It was also designed to investigate...

Mechanistic determinants of the directionality and energetics of active export by a heterodimeric ABC transporter

DOE PAGES

Grossmann, Nina; Vakkasoglu, Ahmet S.; Hulpke, Sabine; ...

2014-11-07

The ATP-binding cassette (ABC) transporter associated with antigen processing (TAP) participates in immune surveillance by moving proteasomal products into the endoplasmic reticulum (ER) lumen for major histocompatibility complex class I loading and cell surface presentation to cytotoxic T cells. Here we delineate the mechanistic basis for antigen translocation. Notably, TAP works as a molecular diode, translocating peptide substrates against the gradient in a strict unidirectional way. We reveal the importance of the D-loop at the dimer interface of the two nucleotide-binding domains (NBDs) in coupling substrate translocation with ATP hydrolysis and defining transport vectoriality. Substitution of the converved aspartate, whichmore » coordinates the ATP-binding site, decreases NBD dimerization affinity and turns the unidirectional primary active pump into a passive bidirectional nucleotide-gated facilitator. Thus, ATP hydrolysis is not required for translocation per se, but is essential for both active and unidirectional transport. As a result, our data provide detailed mechanistic insight into how heterodimeric ABC exporters operate.« less

Parameter and uncertainty estimation for mechanistic, spatially explicit epidemiological models

NASA Astrophysics Data System (ADS)

Finger, Flavio; Schaefli, Bettina; Bertuzzo, Enrico; Mari, Lorenzo; Rinaldo, Andrea

2014-05-01

Epidemiological models can be a crucially important tool for decision-making during disease outbreaks. The range of possible applications spans from real-time forecasting and allocation of health-care resources to testing alternative intervention mechanisms such as vaccines, antibiotics or the improvement of sanitary conditions. Our spatially explicit, mechanistic models for cholera epidemics have been successfully applied to several epidemics including, the one that struck Haiti in late 2010 and is still ongoing. Calibration and parameter estimation of such models represents a major challenge because of properties unusual in traditional geoscientific domains such as hydrology. Firstly, the epidemiological data available might be subject to high uncertainties due to error-prone diagnosis as well as manual (and possibly incomplete) data collection. Secondly, long-term time-series of epidemiological data are often unavailable. Finally, the spatially explicit character of the models requires the comparison of several time-series of model outputs with their real-world counterparts, which calls for an appropriate weighting scheme. It follows that the usual assumption of a homoscedastic Gaussian error distribution, used in combination with classical calibration techniques based on Markov chain Monte Carlo algorithms, is likely to be violated, whereas the construction of an appropriate formal likelihood function seems close to impossible. Alternative calibration methods, which allow for accurate estimation of total model uncertainty, particularly regarding the envisaged use of the models for decision-making, are thus needed. Here we present the most recent developments regarding methods for parameter and uncertainty estimation to be used with our mechanistic, spatially explicit models for cholera epidemics, based on informal measures of goodness of fit.

Laboratory study of concrete properties to support implementation of the new AASHTO mechanistic-empirical pavement design guide.

DOT National Transportation Integrated Search

2012-09-01

Properties of concrete embodying materials typically used in Wisconsin paving projects were evaluated in support of future : implementation of the AASHTO Mechanistic-Empirical Pavement Design Guide (MEPDG). The primary concrete : properties studied w...

Laboratory study of concrete properties to support implementation of the new AASHTO mechanistic empirical pavement design guide.

DOT National Transportation Integrated Search

2012-09-01

Properties of concrete embodying materials typically used in Wisconsin paving projects were evaluated in support of future : implementation of the AASHTO Mechanistic-Empirical Pavement Design Guide (MEPDG). The primary concrete : properties studied w...

DEVELOPING MECHANISTIC DATA FOR INCORPORATION INTO CANCER AND GENETIC RISK ASSESSMENTS: OLD PROBLEMS AND NEW APPROACHES

EPA Science Inventory

26th Lauriston S. Taylor Lecture
DEVELOPING MECHANISTIC DATA FOR INCORPORATION INTO CANCER AND
GENETIC RISK ASSESSMENTS: OLD PROBLEMS AND NEW APPROACHES
R. Julian Preston, Environmental Carcinogenesis Division, U.S. Environmental Protection
Agency, NHEERL, Research Tr...

The effect of environmental factors on the implementation of the Mechanistic-empirical pavement design guide (MEPDG).

DOT National Transportation Integrated Search

2011-07-01

Current pavement design based on the AASHTO Design Guide uses an empirical approach from the results of the AASHO Road Test conducted in 1958. To address some of the limitations of the original design guide, AASHTO developed a new guide: Mechanistic ...

'Long-Cell Action' Corrosion: A Basic Mechanism Hidden Behind Components Degradation Issues in Nuclear Power Plants

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

Genn Saji

2006-07-01

In spite of industries' effort over the last 40 years, corrosion-related issues continue to be one of the largest unresolved problems for nuclear power plants worldwide. There are several types of strange corrosion phenomena from the point of view of our current understanding of corrosion science established in other fields. Some of these are IGSCC, PWSCC, AOA, and FAC (Erosion-Corrosion). Through studying and coping with diverse corrosion phenomena, the author believes that they share a common basis with respect to the assumed corrosion mechanism (e.g., 'local cell action' hypothesis). In general, local cell action is rarely severe since it producesmore » a fairly uniform corrosion. The 'long cell action' that transports electrons through structures far beyond the region of local cell corrosion activities has been identified as a basic mechanism in soil corrosion. If this mechanism is assumed in nuclear power plants, the structure becomes anodic in the area where the potential is less positive and cathodic where this potential is more positive. Metallic ions generated at anodic corrosion sites are transported to remote cathodic sites through the circulation of water and deposits as corrosion products. The SCC, FAC (E-C) and PWSCC occur in the anodic sites as the structure itself acts as a short-circuiting conductor between the two sites, the action is similar to a galvanic cell but in a very large scale. This situation is the same as a battery that has been short-circuited at the terminals. No apparent external potential difference exists between the two electrodes, but an electrochemical reaction is still taking place inside the battery cell with a large internal short current. In this example what is important is the potential difference between the local coolant and the surface of the structural material. Long cell action corrosion is likely enhancing the local cell action's anodic corrosion activities, such as SCC, FAC/E-C, and PWSCC. It tends to be more

Mechanistic Prediction of the Effect of Microstructural Coarsening on Creep Response of SnAgCu Solder Joints

NASA Astrophysics Data System (ADS)

Mukherjee, S.; Chauhan, P.; Osterman, M.; Dasgupta, A.; Pecht, M.

2016-07-01

Mechanistic microstructural models have been developed to capture the effect of isothermal aging on time dependent viscoplastic response of Sn3.0Ag0.5Cu (SAC305) solders. SnAgCu (SAC) solders undergo continuous microstructural coarsening during both storage and service because of their high homologous temperature. The microstructures of these low melting point alloys continuously evolve during service. This results in evolution of creep properties of the joint over time, thereby influencing the long term reliability of microelectronic packages. It is well documented that isothermal aging degrades the creep resistance of SAC solder. SAC305 alloy is aged for (24-1000) h at (25-100)°C (~0.6-0.8 × T melt). Cross-sectioning and image processing techniques were used to periodically quantify the effect of isothermal aging on phase coarsening and evolution. The parameters monitored during isothermal aging include size, area fraction, and inter-particle spacing of nanoscale Ag3Sn intermetallic compounds (IMCs) and the volume fraction of micronscale Cu6Sn5 IMCs, as well as the area fraction of pure tin dendrites. Effects of microstructural evolution on secondary creep constitutive response of SAC305 solder joints were then modeled using a mechanistic multiscale creep model. The mechanistic phenomena modeled include: (1) dispersion strengthening by coarsened nanoscale Ag3Sn IMCs in the eutectic phase; and (2) load sharing between pro-eutectic Sn dendrites and the surrounding coarsened eutectic Sn-Ag phase and microscale Cu6Sn5 IMCs. The coarse-grained polycrystalline Sn microstructure in SAC305 solder was not captured in the above model because isothermal aging does not cause any significant change in the initial grain size and orientation of SAC305 solder joints. The above mechanistic model can successfully capture the drop in creep resistance due to the influence of isothermal aging on SAC305 single crystals. Contribution of grain boundary sliding to the creep strain of

Incorporation of lysosomal sequestration in the mechanistic model for prediction of tissue distribution of basic drugs.

PubMed

Assmus, Frauke; Houston, J Brian; Galetin, Aleksandra

2017-11-15

The prediction of tissue-to-plasma water partition coefficients (Kpu) from in vitro and in silico data using the tissue-composition based model (Rodgers & Rowland, J Pharm Sci. 2005, 94(6):1237-48.) is well established. However, distribution of basic drugs, in particular into lysosome-rich lung tissue, tends to be under-predicted by this approach. The aim of this study was to develop an extended mechanistic model for the prediction of Kpu which accounts for lysosomal sequestration and the contribution of different cell types in the tissue of interest. The extended model is based on compound-specific physicochemical properties and tissue composition data to describe drug ionization, distribution into tissue water and drug binding to neutral lipids, neutral phospholipids and acidic phospholipids in tissues, including lysosomes. Physiological data on the types of cells contributing to lung, kidney and liver, their lysosomal content and lysosomal pH were collated from the literature. The predictive power of the extended mechanistic model was evaluated using a dataset of 28 basic drugs (pK a ≥7.8, 17 β-blockers, 11 structurally diverse drugs) for which experimentally determined Kpu data in rat tissue have been reported. Accounting for the lysosomal sequestration in the extended mechanistic model improved the accuracy of Kpu predictions in lung compared to the original Rodgers model (56% drugs within 2-fold or 88% within 3-fold of observed values). Reduction in the extent of Kpu under-prediction was also evident in liver and kidney. However, consideration of lysosomal sequestration increased the occurrence of over-predictions, yielding overall comparable model performances for kidney and liver, with 68% and 54% of Kpu values within 2-fold error, respectively. High lysosomal concentration ratios relative to cytosol (>1000-fold) were predicted for the drugs investigated; the extent differed depending on the lysosomal pH and concentration of acidic phospholipids among

Mechanistic Investigations of Water Oxidation by a Molecular Cobalt Oxide Analogue: Evidence for a Highly Oxidized Intermediate and Exclusive Terminal Oxo Participation.

PubMed

Nguyen, Andy I; Ziegler, Micah S; Oña-Burgos, Pascual; Sturzbecher-Hohne, Manuel; Kim, Wooyul; Bellone, Donatela E; Tilley, T Don

2015-10-14

Artificial photosynthesis (AP) promises to replace society's dependence on fossil energy resources via conversion of sunlight into sustainable, carbon-neutral fuels. However, large-scale AP implementation remains impeded by a dearth of cheap, efficient catalysts for the oxygen evolution reaction (OER). Cobalt oxide materials can catalyze the OER and are potentially scalable due to the abundance of cobalt in the Earth's crust; unfortunately, the activity of these materials is insufficient for practical AP implementation. Attempts to improve cobalt oxide's activity have been stymied by limited mechanistic understanding that stems from the inherent difficulty of characterizing structure and reactivity at surfaces of heterogeneous materials. While previous studies on cobalt oxide revealed the intermediacy of the unusual Co(IV) oxidation state, much remains unknown, including whether bridging or terminal oxo ligands form O2 and what the relevant oxidation states are. We have addressed these issues by employing a homogeneous model for cobalt oxide, the [Co(III)4] cubane (Co4O4(OAc)4py4, py = pyridine, OAc = acetate), that can be oxidized to the [Co(IV)Co(III)3] state. Upon addition of 1 equiv of sodium hydroxide, the [Co(III)4] cubane is regenerated with stoichiometric formation of O2. Oxygen isotopic labeling experiments demonstrate that the cubane core remains intact during this stoichiometric OER, implying that terminal oxo ligands are responsible for forming O2. The OER is also examined with stopped-flow UV-visible spectroscopy, and its kinetic behavior is modeled, to surprisingly reveal that O2 formation requires disproportionation of the [Co(IV)Co(III)3] state to generate an even higher oxidation state, formally [Co(V)Co(III)3] or [Co(IV)2Co(III)2]. The mechanistic understanding provided by these results should accelerate the development of OER catalysts leading to increasingly efficient AP systems.

Mechanistic Studies of Oligonucleotide Aptamers With Potent Antiproliferative and Pro-Apoptotic Activity Against Prostate Cancer Cells

DTIC Science & Technology

2007-05-01

AD_________________ Award Number: W81XWH-04-1-0183 TITLE: Mechanistic Studies of Oligonucleotide...Ph.D. CONTRACTING ORGANIZATION: University of Louisville...Louisville, KY 40292-0001 REPORT DATE: May 2007 TYPE OF REPORT: Final PREPARED FOR: U.S. Army Medical Research and Materiel Command

Effects of mixing on resolved and unresolved scales on stratospheric age of air

NASA Astrophysics Data System (ADS)

Dietmüller, Simone; Garny, Hella; Plöger, Felix; Jöckel, Patrick; Cai, Duy

2017-06-01

Mean age of air (AoA) is a widely used metric to describe the transport along the Brewer-Dobson circulation. We seek to untangle the effects of different processes on the simulation of AoA, using the chemistry-climate model EMAC (ECHAM/MESSy Atmospheric Chemistry) and the Chemical Lagrangian Model of the Stratosphere (CLaMS). Here, the effects of residual transport and two-way mixing on AoA are calculated. To do so, we calculate the residual circulation transit time (RCTT). The difference of AoA and RCTT is defined as aging by mixing. However, as diffusion is also included in this difference, we further use a method to directly calculate aging by mixing on resolved scales. Comparing these two methods of calculating aging by mixing allows for separating the effect of unresolved aging by mixing (which we term aging by diffusion in the following) in EMAC and CLaMS. We find that diffusion impacts AoA by making air older, but its contribution plays a minor role (order of 10 %) in all simulations. However, due to the different advection schemes of the two models, aging by diffusion has a larger effect on AoA and mixing efficiency in EMAC, compared to CLaMS. Regarding the trends in AoA, in CLaMS the AoA trend is negative throughout the stratosphere except in the Northern Hemisphere middle stratosphere, consistent with observations. This slight positive trend is neither reproduced in a free-running nor in a nudged simulation with EMAC - in both simulations the AoA trend is negative throughout the stratosphere. Trends in AoA are mainly driven by the contributions of RCTT and aging by mixing, whereas the contribution of aging by diffusion plays a minor role.

A mechanistic model for the evolution of multicellularity

NASA Astrophysics Data System (ADS)

Amado, André; Batista, Carlos; Campos, Paulo R. A.

2018-02-01

Through a mechanistic approach we investigate the formation of aggregates of variable sizes, accounting mechanisms of aggregation, dissociation, death and reproduction. In our model, cells can produce two metabolites, but the simultaneous production of both metabolites is costly in terms of fitness. Thus, the formation of larger groups can favor the aggregates to evolve to a configuration where division of labor arises. It is assumed that the states of the cells in a group are those that maximize organismal fitness. In the model it is considered that the groups can grow linearly, forming a chain, or compactly keeping a roughly spherical shape. Starting from a population consisting of single-celled organisms, we observe the formation of groups with variable sizes and usually much larger than two-cell aggregates. Natural selection can favor the formation of large groups, which allows the system to achieve new and larger fitness maxima.

Mechanistic assessment of hillslope transpiration controls of diel subsurface flow: a steady-state irrigation approach

Treesearch

H.R. Barnard; C.B. Graham; W.J. van Verseveld; J.R. Brooks; B.J. Bond; J.J. McDonnell

2010-01-01

Mechanistic assessment of how transpiration influences subsurface flow is necessary to advance understanding of catchment hydrology. We conducted a 24-day, steady-state irrigation experiment to quantify the relationships among soil moisture, transpiration and hillslope subsurface flow. Our objectives were to: (1) examine the time lag between maximum transpiration and...

Studying Diversity in Teacher Education

ERIC Educational Resources Information Center

Ball, Arnetha, Ed.; Tyson, Cynthia A., Ed.

2011-01-01

"Studying Diversity in Teacher Education" is a collaborative effort by experts seeking to elucidate one of the most important issues facing education today. First, the volume examines historically persistent, yet unresolved issues in teacher education and presents research that is currently being done to address these issues. Second, it…

Establishing appropriate inputs when using the mechanistic-empirical pavement design guide to design rigid pavements in Pennsylvania.

DOT National Transportation Integrated Search

2011-03-01

Each design input in the Mechanistic-Empirical Design Guide (MEPDG) required for the design of Jointed Plain Concrete : Pavements (JPCPs) is introduced and discussed in this report. Best values for Pennsylvania conditions were established and : recom...

Establishing Appropriate Inputs When Using the Mechanistic-Empirical Pavement Design Guide To Design Rigid Pavements in Pennsylvania

DOT National Transportation Integrated Search

2011-03-01

Each design input in the Mechanistic-Empirical Design Guide (MEPDG) required for the design of Jointed Plain Concrete Pavements (JPCPs) is introduced and discussed in this report. Best values for Pennsylvania conditions were established and recommend...

Somatodendritic dopamine release: recent mechanistic insights

PubMed Central

Rice, Margaret E.; Patel, Jyoti C.

2015-01-01

Dopamine (DA) is a key transmitter in motor, reward and cogitative pathways, with DA dysfunction implicated in disorders including Parkinson's disease and addiction. Located in midbrain, DA neurons of the substantia nigra pars compacta project via the medial forebrain bundle to the dorsal striatum (caudate putamen), and DA neurons in the adjacent ventral tegmental area project to the ventral striatum (nucleus accumbens) and prefrontal cortex. In addition to classical vesicular release from axons, midbrain DA neurons exhibit DA release from their cell bodies and dendrites. Somatodendritic DA release leads to activation of D2 DA autoreceptors on DA neurons that inhibit their firing via G-protein-coupled inwardly rectifying K+ channels. This helps determine patterns of DA signalling at distant axonal release sites. Somatodendritically released DA also acts via volume transmission to extrasynaptic receptors that modulate local transmitter release and neuronal activity in the midbrain. Thus, somatodendritic release is a pivotal intrinsic feature of DA neurons that must be well defined in order to fully understand the physiology and pathophysiology of DA pathways. Here, we review recent mechanistic aspects of somatodendritic DA release, with particular emphasis on the Ca2+ dependence of release and the potential role of exocytotic proteins. PMID:26009764

Mechanistic Insights into the Efficacy of Sodium Bicarbonate Supplementation to Improve Athletic Performance.

PubMed

Siegler, Jason C; Marshall, Paul W M; Bishop, David; Shaw, Greg; Green, Simon

2016-12-01

A large proportion of empirical research and reviews investigating the ergogenic potential of sodium bicarbonate (NaHCO 3 ) supplementation have focused predominately on performance outcomes and only speculate about underlying mechanisms responsible for any benefit. The aim of this review was to critically evaluate the influence of NaHCO 3 supplementation on mechanisms associated with skeletal muscle fatigue as it translates directly to exercise performance. Mechanistic links between skeletal muscle fatigue, proton accumulation (or metabolic acidosis) and NaHCO 3 supplementation have been identified to provide a more targeted, evidence-based approach to direct future research, as well as provide practitioners with a contemporary perspective on the potential applications and limitations of this supplement. The mechanisms identified have been broadly categorised under the sections 'Whole-body Metabolism', 'Muscle Physiology' and 'Motor Pathways', and when possible, the performance outcomes of these studies contextualized within an integrative framework of whole-body exercise where other factors such as task demand (e.g. large vs. small muscle groups), cardio-pulmonary and neural control mechanisms may outweigh any localised influence of NaHCO 3 . Finally, the 'Performance Applications' section provides further interpretation for the practitioner founded on the mechanistic evidence provided in this review and other relevant, applied NaHCO 3 performance-related studies.

Secondary dispersal driven by overland flow in drylands: Review and mechanistic model development.

PubMed

Thompson, Sally E; Assouline, Shmuel; Chen, Li; Trahktenbrot, Ana; Svoray, Tal; Katul, Gabriel G

2014-01-01

Seed dispersal alters gene flow, reproduction, migration and ultimately spatial organization of dryland ecosystems. Because many seeds in drylands lack adaptations for long-distance dispersal, seed transport by secondary processes such as tumbling in the wind or mobilization in overland flow plays a dominant role in determining where seeds ultimately germinate. Here, recent developments in modeling runoff generation in spatially complex dryland ecosystems are reviewed with the aim of proposing improvements to mechanistic modeling of seed dispersal processes. The objective is to develop a physically-based yet operational framework for determining seed dispersal due to surface runoff, a process that has gained recent experimental attention. A Buoyant OBject Coupled Eulerian - Lagrangian Closure model (BOB-CELC) is proposed to represent seed movement in shallow surface flows. The BOB-CELC is then employed to investigate the sensitivity of seed transport to landscape and storm properties and to the spatial configuration of vegetation patches interspersed within bare earth. The potential to simplify seed transport outcomes by considering the limiting behavior of multiple runoff events is briefly considered, as is the potential for developing highly mechanistic, spatially explicit models that link seed transport, vegetation structure and water movement across multiple generations of dryland plants.

Simulating the Risk of Liver Fluke Infection using a Mechanistic Hydro-epidemiological Model

NASA Astrophysics Data System (ADS)

Beltrame, Ludovica; Dunne, Toby; Rose, Hannah; Walker, Josephine; Morgan, Eric; Vickerman, Peter; Wagener, Thorsten

2016-04-01

Liver Fluke (Fasciola hepatica) is a common parasite found in livestock and responsible for considerable economic losses throughout the world. Risk of infection is strongly influenced by climatic and hydrological conditions, which characterise the host environment for parasite development and transmission. Despite on-going control efforts, increases in fluke outbreaks have been reported in recent years in the UK, and have been often attributed to climate change. Currently used fluke risk models are based on empirical relationships derived between historical climate and incidence data. However, hydro-climate conditions are becoming increasingly non-stationary due to climate change and direct anthropogenic impacts such as land use change, making empirical models unsuitable for simulating future risk. In this study we introduce a mechanistic hydro-epidemiological model for Liver Fluke, which explicitly simulates habitat suitability for disease development in space and time, representing the parasite life cycle in connection with key environmental conditions. The model is used to assess patterns of Liver Fluke risk for two catchments in the UK under current and potential future climate conditions. Comparisons are made with a widely used empirical model employing different datasets, including data from regional veterinary laboratories. Results suggest that mechanistic models can achieve adequate predictive ability and support adaptive fluke control strategies under climate change scenarios.

Mechanistic study of manganese-substituted glycerol dehydrogenase using a kinetic and thermodynamic analysis.

PubMed

Fang, Baishan; Niu, Jin; Ren, Hong; Guo, Yingxia; Wang, Shizhen

2014-01-01

Mechanistic insights regarding the activity enhancement of dehydrogenase by metal ion substitution were investigated by a simple method using a kinetic and thermodynamic analysis. By profiling the binding energy of both the substrate and product, the metal ion's role in catalysis enhancement was revealed. Glycerol dehydrogenase (GDH) from Klebsiella pneumoniae sp., which demonstrated an improvement in activity by the substitution of a zinc ion with a manganese ion, was used as a model for the mechanistic study of metal ion substitution. A kinetic model based on an ordered Bi-Bi mechanism was proposed considering the noncompetitive product inhibition of dihydroxyacetone (DHA) and the competitive product inhibition of NADH. By obtaining preliminary kinetic parameters of substrate and product inhibition, the number of estimated parameters was reduced from 10 to 4 for a nonlinear regression-based kinetic parameter estimation. The simulated values of time-concentration curves fit the experimental values well, with an average relative error of 11.5% and 12.7% for Mn-GDH and GDH, respectively. A comparison of the binding energy of enzyme ternary complex for Mn-GDH and GDH derived from kinetic parameters indicated that metal ion substitution accelerated the release of dioxyacetone. The metal ion's role in catalysis enhancement was explicated.

A MECHANISTIC MODEL FOR MERCURY CAPTURE WITH IN-SITU GENERATED TITANIA PARTICLES: ROLE OF WATER VAPOR

EPA Science Inventory

A mechanistic model to predict the capture of gas phase mercury species using in-situ generated titania nanosize particles activated by UV irradiation is developed. The model is an extension of a recently reported model1 for photochemical reactions that accounts for the rates of...

Insect Phylogenomics: Exploring the Source of Incongruence Using New Transcriptomic Data

PubMed Central

Simon, Sabrina; Narechania, Apurva; DeSalle, Rob; Hadrys, Heike

2012-01-01

The evolution of the diverse insect lineages is one of the most fascinating issues in evolutionary biology. Despite extensive research in this area, the resolution of insect phylogeny especially of interordinal relationships has turned out to be still a great challenge. One of the challenges for insect systematics is the radiation of the polyneopteran lineages with several contradictory and/or unresolved relationships. Here, we provide the first transcriptomic data for three enigmatic polyneopteran orders (Dermaptera, Plecoptera, and Zoraptera) to clarify one of the most debated issues among higher insect systematics. We applied different approaches to generate 3 data sets comprising 78 species and 1,579 clusters of orthologous genes. Using these three matrices, we explored several key mechanistic problems of phylogenetic reconstruction including missing data, matrix selection, gene and taxa number/choice, and the biological function of the genes. Based on the first phylogenomic approach including these three ambiguous polyneopteran orders, we provide here conclusive support for monophyletic Polyneoptera, contesting the hypothesis of Zoraptera + Paraneoptera and Plecoptera + remaining Neoptera. In addition, we employ various approaches to evaluate data quality and highlight problematic nodes within the Insect Tree that still exist despite our phylogenomic approach. We further show how the support for these nodes or alternative hypotheses might depend on the taxon- and/or gene-sampling. PMID:23175716

International issues in transplantation. Setting the scene and flagging the most urgent and controversial issues.

PubMed

Miranda, B; Matesanz, R

1998-12-30

Organ transplantation is the primary technique for treatment of end-stage organ failure and has benefited more than one million persons world wide. A number of patients have survived for well over 25 years and survival rates at 5 years can be 70% or higher for many organ transplant programs. However, currently more than 40,000 patients are waiting for a kidney, and in western Europe mortality rates for patients waiting for a heart, liver, or lung range from 15 to 30%. The potential need for transplants is even greater and this imbalance between supply and demand creates technical and ethical problems including the risk of organ trafficking. Consequently the number of available organs must be increased. In some cases the organ shortage reflects a true lack of donors, but more often it results from the failure to turn potential into actual donors. The transplant commission of the Council of Europe has just approved a document recommending that member states ensure that all potential donors are identified and as many as possible converted to actual donors. Even with the highest organ donation rate, the indications for organ and tissue transplantation will continue to increase, perpetuating the gap between supply and demand. Organ transplantation, whether living or cadaveric, might be supplemented or replaced by the use of artificial organs, although problems such as power supply, thrombosis, infection, and biocompatibility pose obstacles to long-term function. The use of animals as an alternative source is considered, but so many problems still remain unresolved that xenotransplantation cannot be put forth as a solution at this time. This paper reviews these issues and, citing the Spanish experience, offers strategies to improve the organ donation rate.

Genetic and mechanistic diversity of piRNA 3' end formation

PubMed Central

Handler, Dominik; Mohn, Fabio; Ameres, Stefan L.; Brennecke, Julius

2016-01-01

Small regulatory RNAs guide Argonaute (Ago) proteins in a sequence-specific manner to their targets and thereby play important roles in eukaryotic gene silencing1. Of the three small RNA classes, microRNAs and siRNAs are processed from double-stranded precursors into defined 21- to 23-mers by Dicer, an endoribonuclease with intrinsic ruler function. piRNAs—the 22-30 nt long guides for PIWI-clade Ago proteins that silence transposons in animal gonads—are generated Dicer-independently from single-stranded precursors2,3. piRNA 5' ends are defined either by Zucchini, a mitochondria-anchored endonuclease4,5, or by piRNA-guided target cleavage6,7. Formation of piRNA 3' ends is poorly understood. Here, we find that two genetically and mechanistically distinct pathways generate piRNA 3' ends in Drosophila. The initiating nucleases are either Zucchini or the PIWI-clade proteins Aubergine (Aub)/Ago3. While Zucchini-mediated cleavages directly define mature piRNA 3' ends8,9, Aub/Ago3-mediated cleavages liberate pre-piRNAs that require extensive resection by the 3'-to-5' exoribonuclease Nibbler/Mut-710–13. The relative activity of these two pathways dictates the extent to which piRNAs are fueled into cytoplasmic or nuclear PIWI-clade proteins and thereby sets the balance between post-transcriptional and transcriptional silencing. Strikingly, loss of both Zucchini and Nibbler reveals a minimal, Argonaute-driven small RNA biogenesis pathway where piRNA 5' and 3' ends are directly produced by closely spaced Aub/Ago3-mediated cleavage events. Our data establish a coherent blueprint for piRNA biogenesis, and set the stage for the mechanistic dissection of the processes that govern piRNA 3' end formation. PMID:27851737

Problems in mechanistic theoretical models for cell transformation by ionizing radiation

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

Chatterjee, A.; Holley, W.R.

1991-10-01

A mechanistic model based on yields of double strand breaks has been developed to determine the dose response curves for cell transformation frequencies. At its present stage the model is applicable to immortal cell lines and to various qualities (X-rays, Neon and Iron) of ionizing radiation. Presently, we have considered four types of processes which can lead to activation phenomena: (1) point mutation events on a regulatory segment of selected oncogenes, (2) inactivation of suppressor genes, through point mutation, (3) deletion of a suppressor gene by a single track, and (4) deletion of a suppressor gene by two tracks.

Evaluation of current Louisiana flexible pavement structures using PMS data and new mechanistic-empirical pavement design guide.

DOT National Transportation Integrated Search

2012-04-01

The new Mechanistic-Empirical Pavement Design Guide (MEPDG) developed under the National Cooperative Highway Research Program (NCHRP) Project 1-37A represents a major change as compared to the 1993 AASHTO Pavement Design Guide. The MEPDG provides a r...

Productivity of "collisions generate heat" for reconciling an energy model with mechanistic reasoning: A case study

NASA Astrophysics Data System (ADS)

Scherr, Rachel E.; Robertson, Amy D.

2015-06-01

We observe teachers in professional development courses about energy constructing mechanistic accounts of energy transformations. We analyze a case in which teachers investigating adiabatic compression develop a model of the transformation of kinetic energy to thermal energy. Among their ideas is the idea that thermal energy is generated as a byproduct of individual particle collisions, which is represented in science education research literature as an obstacle to learning. We demonstrate that in this instructional context, the idea that individual particle collisions generate thermal energy is not an obstacle to learning, but instead is productive: it initiates intellectual progress. Specifically, this idea initiates the reconciliation of the teachers' energy model with mechanistic reasoning about adiabatic compression, and leads to a canonically correct model of the transformation of kinetic energy into thermal energy. We claim that the idea's productivity is influenced by features of our particular instructional context, including the instructional goals of the course, the culture of collaborative sense making, and the use of certain representations of energy.

Functional and mechanistic diversity of distal transcription enhancers

PubMed Central

Bulger, Michael; Groudine, Mark

2013-01-01

Biological differences among metazoans, and between cell types in a given organism, arise in large part due to differences in gene expression patterns. The sequencing of multiple metazoan genomes, coupled with recent advances in genome-wide analysis of histone modifications and transcription factor binding, has revealed that among regulatory DNA sequences, gene-distal enhancers appear to exhibit the greatest diversity and cell-type specificity. Moreover, such elements are emerging as important targets for mutations that can give rise to disease and to genetic variability that underlies evolutionary change. Studies of long-range interactions between distal genomic sequences in the nucleus indicate that enhancers are often important determinants of nuclear organization, contributing to a general model for enhancer function that involves direct enhancer-promoter contact. In a number of systems, however, mechanisms for enhancer function are emerging that do not fit solely within such a model, suggesting that enhancers as a class of DNA regulatory element may be functionally and mechanistically diverse. PMID:21295696

Mechanistic Role of Thioredoxin 2 in Heart Failure.

PubMed

Chen, Chaofei; Chen, Haixuan; Zhou, Huanjiao Jenny; Ji, Weidong; Min, Wang

2017-01-01

Thioredoxin 2 (Trx2) is a pivotal mitochondrial protein that regulates redox signaling. The mitochondrial Trx2 is expressed ubiquitously, but it is found at the highest levels in metabolically active tissues like the heart. Global gene knockout of Trx2 results in embryonic lethality, likely due to the increased cellular oxidative stress. Moreover, mice with cardiac-specific Trx2 deletion develop spontaneous dilated cardiomyopathy (DCM), correlating with increased apoptosis stress kinase-1 (ASK1) signaling and increased cardiomyocyte apoptosis. Cardiomyocyte apoptosis is a common mechanism in the pathogenesis of heart failure. Our results show that Trx2 is essential for maintaining cardiac function. In this chapter, we summarize the key mechanistic role of Trx2 in preserving cardiac function by suppressing mitochondrial reactive oxygen species (ROS) generation and by inhibiting ASK1-dependent apoptosis in heart failure. Trx2 and ASK1 represent promising targets to develop therapeutic strategies for the treatment of DCM and heart failure.

2MASS J20261584-2943124: an Unresolved L0.5 + T6 Spectral Binary

NASA Astrophysics Data System (ADS)

Gelino, Christopher R.; Burgasser, Adam J.

2010-07-01

We identify the L dwarf 2MASS J20261584-2943124 as an unresolved spectral binary, based on low-resolution, near-infrared spectroscopy from IRTF/SpeX. The data reveal a peculiar absorption feature at 1.6 μm, previously noted in the spectra of other very low-mass spectral binaries, which likely arises from overlapping FeH and CH4 absorption bands in the blended light of an L dwarf/T dwarf pair. Spectral template matching analysis indicates component types of L0.5 and T6, with relative brightness ΔH = 4.2 ± 0.6. Laser guide star adaptive optics imaging observations with Keck/NIRC2 fail to resolve the source, indicating a maximum separation at the observing epoch of 0farcs25, or a projected separation of 9 AU assuming a distance of 36 ± 5 pc. With an age that is likely to be relatively older (gsim5 Gyr) based on the system's large V tan and mass ratio arguments, the relative motion of the potentially "massive" (0.06-0.08 M sun) components of 2MASS J2026-2943 may be detectable through radial velocity variations, like its earlier-type counterpart 2MASS J03202839-0446358 (M8+T5), providing dynamical mass measurements that span the hydrogen burning limit. Some of the data presented herein were obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation.

Unmasking the hidden NGTS-3Ab: a hot Jupiter in an unresolved binary system

NASA Astrophysics Data System (ADS)

Günther, Maximilian N.; Queloz, Didier; Gillen, Edward; Delrez, Laetitia; Bouchy, François; McCormac, James; Smalley, Barry; Almleaky, Yaseen; Armstrong, David J.; Bayliss, Daniel; Burdanov, Artem; Burleigh, Matthew; Cabrera, Juan; Casewell, Sarah L.; Cooke, Benjamin F.; Csizmadia, Szilárd; Ducrot, Elsa; Eigmüller, Philipp; Erikson, Anders; Gänsicke, Boris T.; Gibson, Neale P.; Gillon, Michaël; Goad, Michael R.; Jehin, Emmanuël; Jenkins, James S.; Louden, Tom; Moyano, Maximiliano; Murray, Catriona; Pollacco, Don; Poppenhaeger, Katja; Rauer, Heike; Raynard, Liam; Smith, Alexis M. S.; Sohy, Sandrine; Thompson, Samantha J.; Udry, Stéphane; Watson, Christopher A.; West, Richard G.; Wheatley, Peter J.

2018-05-01

We present the discovery of NGTS-3Ab, a hot Jupiter found transiting the primary star of an unresolved binary system. We develop a joint analysis of multi-colour photometry, centroids, radial velocity (RV) cross-correlation function (CCF) profiles and their bisector inverse slopes (BIS) to disentangle this three-body system. Data from the Next Generation Transit Survey (NGTS), SPECULOOS and HARPS are analysed and modelled with our new BLENDFITTER software. We find that the binary consists of NGTS-3A (G6V-dwarf) and NGTS-3B (K1V-dwarf) at <1" separation. NGTS-3Ab orbits every 1.675 days. The planet radius and mass are Rplanet=1.48 ± 0.37 RJand Mplanet=2.38 ± 0.26 MJ, suggesting it is potentially inflated. We emphasise that only combining all the information from multi-colour photometry, centroids and RV CCF profiles can resolve systems like NGTS-3. Such systems cannot be disentangled from single-colour photometry and RV measurements alone. Importantly, the presence of a BIS correlation indicates a blend scenario, but is not sufficient to determine which star is orbited by the third body. Moreover, even if no BIS correlation is detected, a blend scenario cannot be ruled out without further information. The choice of methodology for calculating the BIS can influence the measured significance of its correlation. The presented findings are crucial to consider for wide-field transit surveys, which require wide CCD pixels (>5") and are prone to contamination by blended objects. With TESS on the horizon, it is pivotal for the candidate vetting to incorporate all available follow-up information from multi-colour photometry and RV CCF profiles.

The physicochemical process of bacterial attachment to abiotic surfaces: Challenges for mechanistic studies, predictability and the development of control strategies.

PubMed

Wang, Yi; Lee, Sui Mae; Dykes, Gary

2015-01-01

Bacterial attachment to abiotic surfaces can be explained as a physicochemical process. Mechanisms of the process have been widely studied but are not yet well understood due to their complexity. Physicochemical processes can be influenced by various interactions and factors in attachment systems, including, but not limited to, hydrophobic interactions, electrostatic interactions and substratum surface roughness. Mechanistic models and control strategies for bacterial attachment to abiotic surfaces have been established based on the current understanding of the attachment process and the interactions involved. Due to a lack of process control and standardization in the methodologies used to study the mechanisms of bacterial attachment, however, various challenges are apparent in the development of models and control strategies. In this review, the physicochemical mechanisms, interactions and factors affecting the process of bacterial attachment to abiotic surfaces are described. Mechanistic models established based on these parameters are discussed in terms of their limitations. Currently employed methods to study these parameters and bacterial attachment are critically compared. The roles of these parameters in the development of control strategies for bacterial attachment are reviewed, and the challenges that arise in developing mechanistic models and control strategies are assessed.

Preparation for implementation of the mechanistic-empirical pavement design guide in Michigan : part 1 - HMA mixture characterization.

DOT National Transportation Integrated Search

2013-03-01

This is the final report of the Part 1 (HMA Mixture Characterization) of the Preparation for Implementation of the Mechanistic-Empirical Pavement Design Guide in Michigan project. The main objectives of the Part 1 were (i) to conduct a literatu...

Linking spring phenology with mechanistic models of host movement to predict disease transmission risk

USGS Publications Warehouse

Merkle, Jerod A.; Cross, Paul C.; Scurlock, Brandon M.; Cole, Eric K.; Courtemanch, Alyson B.; Dewey, Sarah R.; Kauffman, Matthew J.

2018-01-01

Disease models typically focus on temporal dynamics of infection, while often neglecting environmental processes that determine host movement. In many systems, however, temporal disease dynamics may be slow compared to the scale at which environmental conditions alter host space-use and accelerate disease transmission.Using a mechanistic movement modelling approach, we made space-use predictions of a mobile host (elk [Cervus Canadensis] carrying the bacterial disease brucellosis) under environmental conditions that change daily and annually (e.g., plant phenology, snow depth), and we used these predictions to infer how spring phenology influences the risk of brucellosis transmission from elk (through aborted foetuses) to livestock in the Greater Yellowstone Ecosystem.Using data from 288 female elk monitored with GPS collars, we fit step selection functions (SSFs) during the spring abortion season and then implemented a master equation approach to translate SSFs into predictions of daily elk distribution for five plausible winter weather scenarios (from a heavy snow, to an extreme winter drought year). We predicted abortion events by combining elk distributions with empirical estimates of daily abortion rates, spatially varying elk seroprevelance and elk population counts.Our results reveal strong spatial variation in disease transmission risk at daily and annual scales that is strongly governed by variation in host movement in response to spring phenology. For example, in comparison with an average snow year, years with early snowmelt are predicted to have 64% of the abortions occurring on feedgrounds shift to occurring on mainly public lands, and to a lesser extent on private lands.Synthesis and applications. Linking mechanistic models of host movement with disease dynamics leads to a novel bridge between movement and disease ecology. Our analysis framework offers new avenues for predicting disease spread, while providing managers tools to proactively mitigate

ReactionPredictor: prediction of complex chemical reactions at the mechanistic level using machine learning.

PubMed

Kayala, Matthew A; Baldi, Pierre

2012-10-22

Proposing reasonable mechanisms and predicting the course of chemical reactions is important to the practice of organic chemistry. Approaches to reaction prediction have historically used obfuscating representations and manually encoded patterns or rules. Here we present ReactionPredictor, a machine learning approach to reaction prediction that models elementary, mechanistic reactions as interactions between approximate molecular orbitals (MOs). A training data set of productive reactions known to occur at reasonable rates and yields and verified by inclusion in the literature or textbooks is derived from an existing rule-based system and expanded upon with manual curation from graduate level textbooks. Using this training data set of complex polar, hypervalent, radical, and pericyclic reactions, a two-stage machine learning prediction framework is trained and validated. In the first stage, filtering models trained at the level of individual MOs are used to reduce the space of possible reactions to consider. In the second stage, ranking models over the filtered space of possible reactions are used to order the reactions such that the productive reactions are the top ranked. The resulting model, ReactionPredictor, perfectly ranks polar reactions 78.1% of the time and recovers all productive reactions 95.7% of the time when allowing for small numbers of errors. Pericyclic and radical reactions are perfectly ranked 85.8% and 77.0% of the time, respectively, rising to >93% recovery for both reaction types with a small number of allowed errors. Decisions about which of the polar, pericyclic, or radical reaction type ranking models to use can be made with >99% accuracy. Finally, for multistep reaction pathways, we implement the first mechanistic pathway predictor using constrained tree-search to discover a set of reasonable mechanistic steps from given reactants to given products. Webserver implementations of both the single step and pathway versions of Reaction

Development of a Mechanistically Based, Basin-Scale Stream Temperature Model: Applications to Cumulative Effects Modeling

Treesearch

Douglas Allen; William Dietrich; Peter Baker; Frank Ligon; Bruce Orr

2007-01-01

We describe a mechanistically-based stream model, BasinTemp, which assumes that direct shortwave radiation moderated by riparian and topographic shading, controls stream temperatures during the hottest part of the year. The model was developed to support a temperature TMDL for the South Fork Eel basin in Northern California and couples a GIS and a 1-D energy balance...

Progress toward an explicit mechanistic model for the light-driven pump, bacteriorhodopsin

NASA Technical Reports Server (NTRS)

Lanyi, J. K.

1999-01-01

Recent crystallographic information about the structure of bacteriorhodopsin and some of its photointermediates, together with a large amount of spectroscopic and mutational data, suggest a mechanistic model for how this protein couples light energy to the translocation of protons across the membrane. Now nearing completion, this detailed molecular model will describe the nature of the steric and electrostatic conflicts at the photoisomerized retinal, as well as the means by which it induces proton transfers in the two half-channels leading to the two membrane surfaces, thereby causing unidirectional, uphill transport.

Determination of the in-place hot-mix asphalt layer modulus for rehabilitation projects using a mechanistic-empirical procedure.

DOT National Transportation Integrated Search

2006-01-01

This project evaluated the procedures proposed by the Mechanistic-Empirical Pavement Design Guide (MEPDG) to characterize existing hot-mix asphalt (HMA) layers for rehabilitation purposes. Thirty-three cores were extracted from nine sites in Virginia...

Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions

PubMed Central

Clemente, Maria Grazia; Mandato, Claudia; Poeta, Marco; Vajro, Pietro

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A “multiple-hit” pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data (BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR (acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy (the “imperfect” gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention. Effective pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended lifestyle changes. When morbid obesity prevails, bariatric surgery should be considered. PMID:27688650

Reducing low-value care in endometriosis between limited evidence and unresolved issues: a proposal.

PubMed

Vercellini, Paolo; Giudice, Linda C; Evers, Johannes L H; Abrao, Mauricio S

2015-09-01

Quantification of benefits and harms of medical interventions should be based on high-quality evidence, which is not always the case in the endometriosis field. In many clinical circumstances, healthcare decisions in women with endometriosis are taken based on suboptimal evidence or on evidence of coexistence of benefits and harms that must be balanced. In these conditions, it is important to avoid or reduce the use of low-value care, i.e. interventions with defined harms and uncertain benefits, or whose effectiveness is comparable with less expensive alternatives. In particular, we suggest that: (i) non-surgical diagnosis based on symptoms, physical findings and transvaginal ultrasonography is possible in most women with symptomatic endometriosis. Thus, except in doubtful cases, laparoscopy should be intended for surgical treatment, not for diagnostic purposes: early diagnosis and diagnostic laparoscopy are not synonymous; (ii) future trials on new drugs for endometriosis should address those outcomes that are most important to patients, should be designed as superiority trials and should include a progestin or an estrogen-progestin as a comparator. Moreover, limitation of repetitive surgery for recurrent endometriosis is among the objectives of long-term medical treatment; (iii) indications for surgery should be the result of a balance between demonstrated benefits in terms of fertility enhancement and pain relief, specific risks associated with excision of different types of endometriotic lesions, cost-effectiveness and patient preference after detailed information; (iv) physicians, health professionals and policy makers should discriminate between screening for and diagnosis of endometriosis. Limited peritoneal foci, which are frequently observed also in asymptomatic women, regress or remain stable in about two thirds of cases. Therefore, the theoretical premises for a screening campaign are currently unclear; (v) physicians should develop the ability to effectively communicate quantitative information based on international guidelines and systematic literature reviews. This will assist a woman's understanding of the interaction between the evidence and her priorities, facilitating the transition towards value-based medicine. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

New French Coverage with Evidence Development for Innovative Medical Devices: Improvements and Unresolved Issues.

PubMed

Martelli, Nicolas; van den Brink, Hélène; Borget, Isabelle

2016-01-01

We describe here recent modifications to the French Coverage with Evidence Development (CED) scheme for innovative medical devices. CED can be defined as temporary coverage for a novel health product during collection of the additional evidence required to determine whether definitive coverage is possible. The principle refinements to the scheme include a more precise definition of what may be considered an innovative product, the possibility for device manufacturers to request CED either independently or in partnership with hospitals, and the establishment of processing deadlines for health authorities. In the long term, these modifications may increase the number of applications to the CED scheme, which could lead to unsustainable funding for future projects. It will also be necessary to ensure that the study conditions required by national health authorities are suitable for medical devices and that processing deadlines are met for the scheme to be fully operational. Overall, the modifications recently applied to the French CED scheme for innovative medical devices should increase the transparency of the process, and therefore be more appealing to medical device manufacturers. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Family Interaction in the Newborn Period: Some Findings, Some Observations, and Some Unresolved Issues.

ERIC Educational Resources Information Center

Parke, Ross D.

This paper presents two studies which explored the manner in which the father interacts with his newborn infant and compared paternal and maternal interaction patterns. In contrast to earlier studies, a direct observational approach was employed that permitted a detailed specification of father behaviors in the presence of the newborn. In the…

Productivity of "Collisions Generate Heat" for Reconciling an Energy Model with Mechanistic Reasoning: A Case Study

ERIC Educational Resources Information Center

Scherr, Rachel E.; Robertson, Amy D.

2015-01-01

We observe teachers in professional development courses about energy constructing mechanistic accounts of energy transformations. We analyze a case in which teachers investigating adiabatic compression develop a model of the transformation of kinetic energy to thermal energy. Among their ideas is the idea that thermal energy is generated as a…

Mechanistic Basis of Cocrystal Dissolution Advantage.

PubMed

Cao, Fengjuan; Amidon, Gordon L; Rodríguez-Hornedo, Naír; Amidon, Gregory E

2018-01-01

Current interest in cocrystal development resides in the advantages that the cocrystal may have in solubility and dissolution compared with the parent drug. This work provides a mechanistic analysis and comparison of the dissolution behavior of carbamazepine (CBZ) and its 2 cocrystals, carbamazepine-saccharin (CBZ-SAC) and carbamazepine-salicylic acid (CBZ-SLC) under the influence of pH and micellar solubilization. A simple mathematical equation is derived based on the mass transport analyses to describe the dissolution advantage of cocrystals. The dissolution advantage is the ratio of the cocrystal flux to drug flux and is defined as the solubility advantage (cocrystal to drug solubility ratio) times the diffusivity advantage (cocrystal to drug diffusivity ratio). In this work, the effective diffusivity of CBZ in the presence of surfactant was determined to be different and less than those of the cocrystals. The higher effective diffusivity of drug from the dissolved cocrystals, the diffusivity advantage, can impart a dissolution advantage to cocrystals with lower solubility than the parent drug while still maintaining thermodynamic stability. Dissolution conditions where cocrystals can display both thermodynamic stability and a dissolution advantage can be obtained from the mass transport models, and this information is useful for both cocrystal selection and formulation development. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Behavioural and physiological limits to vision in mammals

PubMed Central

Field, Greg D.

2017-01-01

Human vision is exquisitely sensitive—a dark-adapted observer is capable of reliably detecting the absorption of a few quanta of light. Such sensitivity requires that the sensory receptors of the retina, rod photoreceptors, generate a reliable signal when single photons are absorbed. In addition, the retina must be able to extract this information and relay it to higher visual centres under conditions where very few rods signal single-photon responses while the majority generate only noise. Critical to signal transmission are mechanistic optimizations within rods and their dedicated retinal circuits that enhance the discriminability of single-photon responses by mitigating photoreceptor and synaptic noise. We describe behavioural experiments over the past century that have led to the appreciation of high sensitivity near absolute visual threshold. We further consider mechanisms within rod photoreceptors and dedicated rod circuits that act to extract single-photon responses from cellular noise. We highlight how these studies have shaped our understanding of brain function and point out several unresolved questions in the processing of light near the visual threshold. This article is part of the themed issue ‘Vision in dim light’. PMID:28193817

Impulse control disorders in Parkinson's disease: crossroads between neurology, psychiatry and neuroscience.

PubMed

Bugalho, Paulo; Oliveira-Maia, Albino J

2013-01-01

Non-motor symptoms contribute significantly to Parkinson's disease (PD) related disability. Impulse control disorders (ICDs) have been recently added to the behavioural spectrum of PD-related non-motor symptoms. Such behaviours are characterized by an inappropriate drive to conduct repetitive behaviours that are usually socially inadequate or result in harmful consequences. Parkinson disease impulse control disorders (PD-ICDs) have raised significant interest in the scientific and medical community, not only because of their incapacitating nature, but also because they may represent a valid model of ICDs beyond PD and a means to study the physiology of drive, impulse control and compulsive actions in the normal brain. In this review, we discuss some unresolved issues regarding PD-ICDs, including the association with psychiatric co-morbidities such as obsessive-compulsive disorder and with dopamine related side effects, such as hallucinations and dyskinesias; the relationship with executive cognitive dysfunction; and the neural underpinnings of ICDs in PD. We also discuss the contribution of neuroscience studies based on animal-models towards a mechanistic explanation of the development of PD-ICDs, specifically regarding corticostriatal control of goal directed and habitual actions.

An example problem illustrating the application of the national lime association mixture design and testing protocol (MDTP) to ascertain engineering properties of lime-treated subgrades for mechanistic pavement design/analysis.

DOT National Transportation Integrated Search

2001-09-01

This document presents an example of mechanistic design and analysis using a mix design and : testing protocol. More specifically, it addresses the structural properties of lime-treated subgrade, : subbase, and base layers through mechanistic design ...

Mechanistic Studies on the Copper-Catalyzed N-Arylation of Amides

PubMed Central

Strieter, Eric R.; Bhayana, Brijesh; Buchwald, Stephen L.

2009-01-01

The copper-catalyzed N-arylation of amides, i.e., the Goldberg reaction, is an efficient method for the construction of products relevant to both industry and academic settings. Herein, we present mechanistic details concerning the catalytic and stoichiometric N-arylation of amides. In the context of the catalytic reaction, our findings reveal the importance of chelating diamine ligands in controlling the concentration of the active catalytic species. The consistency between the catalytic and stoichiometric results suggest that the activation of aryl halides occurs through a 1,2-diamine-ligated copper(I) amidate complex. Kinetic studies on the stoichiometric N-arylation of aryl iodides using 1,2-diamine ligated Cu(I) amidates also provide insights into the mechanism of aryl halide activation. PMID:19072233

New Simulation Methods to Facilitate Achieving a Mechanistic Understanding of Basic Pharmacology Principles in the Classroom

ERIC Educational Resources Information Center

Grover, Anita; Lam, Tai Ning; Hunt, C. Anthony

2008-01-01

We present a simulation tool to aid the study of basic pharmacology principles. By taking advantage of the properties of agent-based modeling, the tool facilitates taking a mechanistic approach to learning basic concepts, in contrast to the traditional empirical methods. Pharmacodynamics is a particular aspect of pharmacology that can benefit from…

Unconscious Inhibition and Facilitation at the Objective Detection Threshold: Replicable and Qualitatively Different Unconscious Perceptual Effects

ERIC Educational Resources Information Center

Snodgrass, Michael; Shevrin, Howard

2006-01-01

Although the veridicality of unconscious perception is increasingly accepted, core issues remain unresolved [Jack, A., & Shallice, T. (2001). Introspective physicalism as an approach to the science of consciousness. "Cognition, 79," 161-196], and sharp disagreement persists regarding fundamental methodological and theoretical issues. The most…

Ionizing Radiation: The issue of radiation quality

NASA Astrophysics Data System (ADS)

Prise, Kevin; Schettino, Giuseppe

Types of Ionising radiations are differentiated from each other by fundamental characteristics of their energy deposition patterns when they interact with biological materials. At the level of the DNA these non-random patterns drive differences in the yields and distributions of DNA damage patterns and specifically the production of clustered damage or complex lesions. The complex radiation fields found in space bring significant challenges for developing a mechanistic understanding of radiation effects from the perspective of radiation quality as these consist of a diverse range of particle and energy types unique to the space environment. Linear energy transfer, energy deposited per unit track length in units of keV per micron, has long been used as a comparator for different types of radiation but has limitations in that it is an average value. Difference in primary core ionizations relative to secondary delta ray ranges vary significantly with particle mass and energy leading to complex interrelationships with damage production at the cellular level. At the cellular level a greater mechanistic understanding is necessary, linking energy deposition patterns to DNA damage patterns and cellular response, to build appropriate biophysical models that are predictive for different radiation qualities and mixed field exposures. Defined studies using monoenergetic beams delivered under controlled conditions are building quantitative data sets of both initial and long term changes in cells as a basis for a great mechanistic understanding of radiation quality effects of relevance to not only space exposures but clinical application of ion-beams.

Dynamic mechanistic explanation: computational modeling of circadian rhythms as an exemplar for cognitive science.

PubMed

Bechtel, William; Abrahamsen, Adele

2010-09-01

We consider computational modeling in two fields: chronobiology and cognitive science. In circadian rhythm models, variables generally correspond to properties of parts and operations of the responsible mechanism. A computational model of this complex mechanism is grounded in empirical discoveries and contributes a more refined understanding of the dynamics of its behavior. In cognitive science, on the other hand, computational modelers typically advance de novo proposals for mechanisms to account for behavior. They offer indirect evidence that a proposed mechanism is adequate to produce particular behavioral data, but typically there is no direct empirical evidence for the hypothesized parts and operations. Models in these two fields differ in the extent of their empirical grounding, but they share the goal of achieving dynamic mechanistic explanation. That is, they augment a proposed mechanistic explanation with a computational model that enables exploration of the mechanism's dynamics. Using exemplars from circadian rhythm research, we extract six specific contributions provided by computational models. We then examine cognitive science models to determine how well they make the same types of contributions. We suggest that the modeling approach used in circadian research may prove useful in cognitive science as researchers develop procedures for experimentally decomposing cognitive mechanisms into parts and operations and begin to understand their nonlinear interactions.

Mechanistic, Mathematical Model to Predict the Dynamics of Tissue Genesis in Bone Defects via Mechanical Feedback and Mediation of Biochemical Factors

PubMed Central

Moore, Shannon R.; Saidel, Gerald M.; Knothe, Ulf; Knothe Tate, Melissa L.

2014-01-01

The link between mechanics and biology in the generation and the adaptation of bone has been well studied in context of skeletal development and fracture healing. Yet, the prediction of tissue genesis within - and the spatiotemporal healing of - postnatal defects, necessitates a quantitative evaluation of mechano-biological interactions using experimental and clinical parameters. To address this current gap in knowledge, this study aims to develop a mechanistic mathematical model of tissue genesis using bone morphogenetic protein (BMP) to represent of a class of factors that may coordinate bone healing. Specifically, we developed a mechanistic, mathematical model to predict the dynamics of tissue genesis by periosteal progenitor cells within a long bone defect surrounded by periosteum and stabilized via an intramedullary nail. The emergent material properties and mechanical environment associated with nascent tissue genesis influence the strain stimulus sensed by progenitor cells within the periosteum. Using a mechanical finite element model, periosteal surface strains are predicted as a function of emergent, nascent tissue properties. Strains are then input to a mechanistic mathematical model, where mechanical regulation of BMP-2 production mediates rates of cellular proliferation, differentiation and tissue production, to predict healing outcomes. A parametric approach enables the spatial and temporal prediction of endochondral tissue regeneration, assessed as areas of cartilage and mineralized bone, as functions of radial distance from the periosteum and time. Comparing model results to histological outcomes from two previous studies of periosteum-mediated bone regeneration in a common ovine model, it was shown that mechanistic models incorporating mechanical feedback successfully predict patterns (spatial) and trends (temporal) of bone tissue regeneration. The novel model framework presented here integrates a mechanistic feedback system based on the

Modeling Bird Migration under Climate Change: A Mechanistic Approach

NASA Technical Reports Server (NTRS)

Smith, James A.

2009-01-01

How will migrating birds respond to changes in the environment under climate change? What are the implications for migratory success under the various accelerated climate change scenarios as forecast by the Intergovernmental Panel on Climate Change? How will reductions or increased variability in the number or quality of wetland stop-over sites affect migratory bird species? The answers to these questions have important ramifications for conservation biology and wildlife management. Here, we describe the use of continental scale simulation modeling to explore how spatio-temporal changes along migratory flyways affect en-route migration success. We use an individually based, biophysical, mechanistic, bird migration model to simulate the movement of shorebirds in North America as a tool to study how such factors as drought and wetland loss may impact migratory success and modify migration patterns. Our model is driven by remote sensing and climate data and incorporates important landscape variables. The energy budget components of the model include resting, foraging, and flight, but presently predation is ignored. Results/Conclusions We illustrate our model by studying the spring migration of sandpipers through the Great Plains to their Arctic breeding grounds. Why many species of shorebirds have shown significant declines remains a puzzle. Shorebirds are sensitive to stop-over quality and spacing because of their need for frequent refueling stops and their opportunistic feeding patterns. We predict bird "hydrographs that is, stop-over frequency with latitude, that are in agreement with the literature. Mean stop-over durations predicted from our model for nominal cases also are consistent with the limited, but available data. For the shorebird species simulated, our model predicts that shorebirds exhibit significant plasticity and are able to shift their migration patterns in response to changing drought conditions. However, the question remains as to whether this

Recognizing Mechanistic Reasoning in Student Scientific Inquiry: A Framework for Discourse Analysis Developed from Philosophy of Science

ERIC Educational Resources Information Center

Russ, Rosemary S.; Scherr, Rachel E.; Hammer, David; Mikeska, Jamie

2008-01-01

Science education reform has long focused on assessing student inquiry, and there has been progress in developing tools specifically with respect to experimentation and argumentation. We suggest the need for attention to another aspect of inquiry, namely "mechanistic reasoning." Scientific inquiry focuses largely on understanding causal…

This Mechanistic Step Is ''Productive'': Organic Chemistry Students' Backward-Oriented Reasoning

ERIC Educational Resources Information Center

Caspari, I.; Weinrich, M. L.; Sevian, H.; Graulich, N.

2018-01-01

If an organic chemistry student explains that she represents a mechanistic step because ''it's a productive part of the mechanism,'' what meaning could the professor teaching the class attribute to this statement, what is actually communicated, and what does it mean for the student? The professor might think that the explanation is based on…

A mechanistic investigation of the algae growth "Droop" model.

PubMed

Lemesle, V; Mailleret, L

2008-06-01

In this work a mechanistic explanation of the classical algae growth model built by M. R. Droop in the late sixties is proposed. We first recall the history of the construction of the "predictive" variable yield Droop model as well as the meaning of the introduced cell quota. We then introduce some theoretical hypotheses on the biological phenomena involved in nutrient storage by the algae that lead us to a "conceptual" model. Though more complex than Droop's one, our model remains accessible to a complete mathematical study: its confrontation to the Droop model shows both have the same asymptotic behavior. However, while Droop's cell quota comes from experimental bio-chemical measurements not related to intra-cellular biological phenomena, its analogous in our model directly follows our theoretical hypotheses. This new model should then be looked at as a re-interpretation of Droop's work from a theoretical biologist's point of view.

BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling.

PubMed

He, Xi C; Zhang, Jiwang; Tong, Wei-Gang; Tawfik, Ossama; Ross, Jason; Scoville, David H; Tian, Qiang; Zeng, Xin; He, Xi; Wiedemann, Leanne M; Mishina, Yuji; Li, Linheng

2004-10-01

In humans, mutations in BMPR1A, SMAD4 and PTEN are responsible for juvenile polyposis syndrome, juvenile intestinal polyposis and Cowden disease, respectively. The development of polyposis is a common feature of these diseases, suggesting that there is an association between BMP and PTEN pathways. The mechanistic link between BMP and PTEN pathways and the related etiology of juvenile polyposis is unresolved. Here we show that conditional inactivation of Bmpr1a in mice disturbs homeostasis of intestinal epithelial regeneration with an expansion of the stem and progenitor cell populations, eventually leading to intestinal polyposis resembling human juvenile polyposis syndrome. We show that BMP signaling suppresses Wnt signaling to ensure a balanced control of stem cell self-renewal. Mechanistically, PTEN, through phosphatidylinosital-3 kinase-Akt, mediates the convergence of the BMP and Wnt pathways on control of beta-catenin. Thus, BMP signaling may control the duplication of intestinal stem cells, thereby preventing crypt fission and the subsequent increase in crypt number.

Kohlberg and Gilligan: Duet or Duel?

ERIC Educational Resources Information Center

Jorgensen, Gunnar

2006-01-01

Most moral psychologists have come to accept two types of moral reasoning: Kohlberg's "justice" and Gilligan's "care", but there still seem to be some unresolved issues. By analysing and comparing Kohlberg's statement on some theoretical issues with some of Gilligan's statements in an interview in April 2003, I will look at some key issues in the…

Liquid lithium loop system to solve challenging technology issues for fusion power plant

NASA Astrophysics Data System (ADS)

Ono, M.; Majeski, R.; Jaworski, M. A.; Hirooka, Y.; Kaita, R.; Gray, T. K.; Maingi, R.; Skinner, C. H.; Christenson, M.; Ruzic, D. N.

2017-11-01

Steady-state fusion power plant designs present major divertor technology challenges, including high divertor heat flux both in steady-state and during transients. In addition to these concerns, there are the unresolved technology issues of long term dust accumulation and associated tritium inventory and safety issues. It has been suggested that radiation-based liquid lithium (LL) divertor concepts with a modest lithium-loop could provide a possible solution for these outstanding fusion reactor technology issues, while potentially improving reactor plasma performance. The application of lithium (Li) in NSTX resulted in improved H-mode confinement, H-mode power threshold reduction, and reduction in the divertor peak heat flux while maintaining essentially Li-free core plasma operation even during H-modes. These promising results in NSTX and related modeling calculations motivated the radiative liquid lithium divertor concept and its variant, the active liquid lithium divertor concept, taking advantage of the enhanced or non-coronal Li radiation in relatively poorly confined divertor plasmas. To maintain the LL purity in a 1 GW-electric class fusion power plant, a closed LL loop system with a modest circulating capacity of ~1 l s-1 is envisioned. We examined two key technology issues: (1) dust or solid particle removal and (2) real time recovery of tritium from LL while keeping the tritium inventory level to an acceptable level. By running the LL-loop continuously, it can carry the dust particles and impurities generated in the vacuum vessel to the outside where the dust/impurities can be removed by relatively simple dust filter, cold trap and/or centrifugal separation systems. With ~1 l s-1 LL flow, even a small 0.1% dust content by weight (or 0.5 g s-1) suggests that the LL-loop could carry away nearly 16 tons of dust per year. In a 1 GW-electric (or ~3 GW fusion power) fusion power plant, about 0.5 g s-1 of tritium is needed to maintain the fusion fuel cycle

New mechanistic insights in the NH 3-SCR reactions at low temperature

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

Ruggeri, Maria Pia; Selleri, Tomasso; Nova, Isabella

2016-05-06

The present study is focused on the investigation of the low temperature Standard SCR reaction mechanism over Fe- and Cu-promoted zeolites. Different techniques are employed, including in situ DRIFTS, transient reaction analysis and chemical trapping techniques. The results present strong evidence of nitrite formation in the oxidative activation of NO and of their role in SCR reactions. These elements lead to a deeper understanding of the standard SCR chemistry at low temperature and can potentially improve the consistency of mechanistic mathematical models. Furthermore, comprehension of the mechanism on a fundamental level can contribute to the development of improved SCR catalysts.

Predicting subsurface uranium transport: Mechanistic modeling constrained by experimental data

NASA Astrophysics Data System (ADS)

Ottman, Michael; Schenkeveld, Walter D. C.; Kraemer, Stephan

2017-04-01

Depleted uranium (DU) munitions and their widespread use throughout conflict zones around the world pose a persistent health threat to the inhabitants of those areas long after the conclusion of active combat. However, little emphasis has been put on developing a comprehensive, quantitative tool for use in remediation and hazard avoidance planning in a wide range of environments. In this context, we report experimental data on U interaction with soils and sediments. Here, we strive to improve existing risk assessment modeling paradigms by incorporating a variety of experimental data into a mechanistic U transport model for subsurface environments. 20 different soils and sediments from a variety of environments were chosen to represent a range of geochemical parameters that are relevant to U transport. The parameters included pH, organic matter content, CaCO3, Fe content and speciation, and clay content. pH ranged from 3 to 10, organic matter content from 6 to 120 g kg-1, CaCO3 from 0 to 700 g kg-1, amorphous Fe content from 0.3 to 6 g kg-1 and clay content from 4 to 580 g kg-1. Sorption experiments were then performed, and linear isotherms were constructed. Sorption experiment results show that among separate sets of sediments and soils, there is an inverse correlation between both soil pH and CaCO¬3 concentration relative to U sorptive affinity. The geological materials with the highest and lowest sorptive affinities for U differed in CaCO3 and organic matter concentrations, as well as clay content and pH. In a further step, we are testing if transport behavior in saturated porous media can be predicted based on adsorption isotherms and generic geochemical parameters, and comparing these modeling predictions with the results from column experiments. The comparison of these two data sets will examine if U transport can be effectively predicted from reactive transport modeling that incorporates the generic geochemical parameters. This work will serve to show

Mechanistic understanding of monosaccharide-air flow battery electrochemistry

NASA Astrophysics Data System (ADS)

Scott, Daniel M.; Tsang, Tsz Ho; Chetty, Leticia; Aloi, Sekotilani; Liaw, Bor Yann

Recently, an inexpensive monosaccharide-air flow battery configuration has been demonstrated to utilize a strong base and a mediator redox dye to harness electrical power from the partial oxidation of glucose. Here the mechanistic understanding of glucose oxidation in this unique glucose-air power source is further explored by acid-base titration experiments, 13C NMR, and comparison of results from chemically different redox mediators (indigo carmine vs. methyl viologen) and sugars (fructose vs. glucose) via studies using electrochemical techniques. Titration results indicate that gluconic acid is the main product of the cell reaction, as supported by evidence in the 13C NMR spectra. Using indigo carmine as the mediator dye and fructose as the energy source, an abiotic cell configuration generates a power density of 1.66 mW cm -2, which is greater than that produced from glucose under similar conditions (ca. 1.28 mW cm -2). A faster transition from fructose into the ene-diol intermediate than from glucose likely contributed to this difference in power density.

Mechanistic, kinetic, and processing aspects of tungsten chemical mechanical polishing

NASA Astrophysics Data System (ADS)

Stein, David

This dissertation presents an investigation into tungsten chemical mechanical polishing (CMP). CMP is the industrially predominant unit operation that removes excess tungsten after non-selective chemical vapor deposition (CVD) during sub-micron integrated circuit (IC) manufacture. This work explores the CMP process from process engineering and fundamental mechanistic perspectives. The process engineering study optimized an existing CMP process to address issues of polish pad and wafer carrier life. Polish rates, post-CMP metrology of patterned wafers, electrical test data, and synergy with a thermal endpoint technique were used to determine the optimal process. The oxidation rate of tungsten during CMP is significantly lower than the removal rate under identical conditions. Tungsten polished without inhibition during cathodic potentiostatic control. Hertzian indenter model calculations preclude colloids of the size used in tungsten CMP slurries from indenting the tungsten surface. AFM surface topography maps and TEM images of post-CMP tungsten do not show evidence of plow marks or intergranular fracture. Polish rate is dependent on potassium iodate concentration; process temperature is not. The colloid species significantly affects the polish rate and process temperature. Process temperature is not a predictor of polish rate. A process energy balance indicates that the process temperature is predominantly due to shaft work, and that any heat of reaction evolved during the CMP process is negligible. Friction and adhesion between alumina and tungsten were studied using modified AFM techniques. Friction was constant with potassium iodate concentration, but varied with applied pressure. This corroborates the results from the energy balance. Adhesion between the alumina and the tungsten was proportional to the potassium iodate concentration. A heuristic mechanism, which captures the relationship between polish rate, pressure, velocity, and slurry chemistry, is presented

Mindfulness & Self-Compassion Meditation for Combat Posttraumatic Stress Disorder: Randomized Controlled Trial and Mechanistic Study

DTIC Science & Technology

2013-10-01

VA Ann Arbor PTSD clinic; and c.) conducting a translational neuroimaging mechanistic study with pre- and post fMRI and neurocognitive testing . 15...might be helpful – both in terms of the psychological characteristics of change, and in terms of neural mechanisms in the brain. Mindfulness...neurocognitive testing . Our novel 16 week Mindfulness and Self-compassion group intervention, “Mindfulness-based Exposure therapy” (MBET), was developed

Non-directed aromatic C–H amination: catalytic and mechanistic studies enabled by Pd catalyst and reagent design†

PubMed Central

Bandara, H. M. D.; Jin, D.; Mantell, M. A.; Field, K. D.; Wang, A.; Narayanan, R. P.; Deskins, N. A.; Emmert, M. H.

2016-01-01

This manuscript describes the systematic development of pyridine-type ligands, which promote the Pd catalyzed, non-directed amination of benzene in combination with novel, hydroxylamine-based electrophilic amination reagents. DFT calculations and mechanistic experiments provide insights into the factors influencing the arene C–H amination protocol. PMID:28066540

Analysis of unresolved transition arrays in XUV spectral region from highly charged lead ions produced by subnanosecond laser pulse

NASA Astrophysics Data System (ADS)

Wu, Tao; Higashiguchi, Takeshi; Li, Bowen; Arai, Goki; Hara, Hiroyuki; Kondo, Yoshiki; Miyazaki, Takanori; Dinh, Thanh-Hung; O'Reilly, Fergal; Sokell, Emma; O'Sullivan, Gerry

2017-02-01

Soft x-ray and extreme ultraviolet (XUV) spectra from lead (Pb, Z=82) laser-produced plasmas (LPPs) were measured in the 1.0-7.0 nm wavelength region employing a 150-ps, 1064-nm Nd:YAG laser with focused power densities in the range from 3.1×1013 W/cm2 to 1.4×1014 W/cm2. The flexible atomic code (FAC) and the Cowan's suite of atomic structure codes were applied to compute and explain the radiation properties of the lead spectra observed. The most prominent structure in the spectra is a broad double peak, which is produced by Δn=0, n=4-4 and Δn=1, n=4-5 transition arrays emitted from highly charged lead ions. The emission characteristics of Δn=1, n=4-5 transitions were investigated by the use of the unresolved transition arrays (UTAs) model. Numerous new spectral features generated by Δn=1, n=4-5 transitions in ions from Pb21+ to Pb45+ are discerned with the aid of the results from present computations as well as consideration of previous theoretical predictions and experimental data.

Toxic effects of unresolved complex mixtures of aromatic hydrocarbons accumulated by mussels, Mytilus edulis, from contaminated field sites.

PubMed

Donkin, Peter; Smith, Emma L; Rowland, Steven J

2003-11-01

Exposure of marine mussels (Mytilus edulis) to an unresolved complex mixture (UCM) of aromatic hydrocarbons isolated from a crude oil has been shown to reduce their feeding rate by 40%. The present study was undertaken to determine whether UCMs bioaccumulated by mussels in the field are also toxic. The feeding rate of mussels derived from polluted sites increased when they were placed in clean water, pointing to a loss of toxic agents from the tissues. At the end of the depuration period, water in which mussels from an oil-polluted site had been held contained a UCM. Steam-distillation extracts of the tissues of mussels taken from several polluted sites were shown to be highly toxic to the feeding activity of juvenile mussels. The tissues of mussels from these sites contained UCMs. Nontoxic steam distillates from clean mussels did not. Steam-distillation extracts of mussels from an oil-polluted site were fractionated by normal-phase high-performance liquid chromatography. A fraction, largely comprising a "monoaromatic" UCM, reduced the feeding rate of juvenile mussels by 70%. Two later-eluting fractions containing aromatic UCMs also produced smaller depressions in feeding rate. These results support our contention that some aromatic UCM hydrocarbons constitute a forgotten pollutant burden in the marine environment.

Mechanistic failure mode investigation and resolution of parvovirus retentive filters.

PubMed

LaCasse, Daniel; Lute, Scott; Fiadeiro, Marcus; Basha, Jonida; Stork, Matthew; Brorson, Kurt; Godavarti, Ranga; Gallo, Chris

2016-07-08

Virus retentive filters are a key product safety measure for biopharmaceuticals. A simplistic perception is that they function solely based on a size-based particle removal mechanism of mechanical sieving and retention of particles based on their hydrodynamic size. Recent observations have revealed a more nuanced picture, indicating that changes in viral particle retention can result from process pressure and/or flow interruptions. In this study, a mechanistic investigation was performed to help identify a potential mechanism leading to the reported reduced particle retention in small virus filters. Permeate flow rate or permeate driving force were varied and analyzed for their impact on particle retention in three commercially available small virus retentive filters. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:959-970, 2016. © 2016 American Institute of Chemical Engineers.

Evaluation of LTPP Climatic Data for Use in Mechanistic-Empirical Pavement Design Guide (MEPDG) Calibration and Other Pavement Analysis

DOT National Transportation Integrated Search

2015-02-01

This TechBrief describes evaluating the use of the Modern-Era Retrospective Analysis for Research and Applications (MERRA) product as an alternative climatic data source for the Mechanistic-Empirical Pavement Design Guide (MEPDG) and other transporta...

Flow-mediated dilation: can new approaches provide greater mechanistic insight into vascular dysfunction in preeclampsia and other diseases?

PubMed

Weissgerber, Tracey L

2014-11-01

Endothelial dysfunction is a key feature of preeclampsia and may contribute to increased cardiovascular disease risk years after pregnancy. Flow-mediated dilation (FMD) is a non-invasive endothelial function test that predicts cardiovascular event risk. New protocols allow researchers to measure three components of the FMD response: FMD, low flow-mediated constriction, and shear stimulus. This review encourages researchers to think beyond "low FMD" by examining how these three components may provide additional insights into the mechanisms and location of vascular dysfunction. The review then examines what FMD studies reveal about vascular dysfunction in preeclampsia while highlighting opportunities to gain greater mechanistic insight from new protocols. Studies using traditional protocols show that FMD is low in mid-pregnancy prior to preeclampsia, at diagnosis, and for 3 years post-partum. However, FMD returns to normal by 10 years post-partum. Studies using new protocols are needed to gain more mechanistic insight.

Mechanistic Indicators of Childhood Asthma (MICA): piloting ...

EPA Pesticide Factsheets

Background: Modem methods in molecular biology and advanced computational tools show promise in elucidating complex interactions that occur between genes and environmental factors in diseases such as asthma; however appropriately designed studies are critical for these methods to reach their full potential. Objective: We used a case-control study to investigate whether genomic data (blood gene expression), viewed together with a spectrum of exposure effects and susceptibility markers (blood, urine and nail), can provide a mechanistic explanation for the increased susceptibility of asthmatics to ambient air pollutants. Methods: We studied 205 non-asthmatic and asthmatic children, (9-12 years of age) who participated in a clinical study in Detroit, Michigan. The study combines a traditional epidemiological design with an integrative approach to investigate the environmental exposure of children to indoor-outdoor air. The study includes measurements of internal dose (metals, allergen specific IgE, PAH and VOC metabolites) and clinical measures of health outcome (immunological, cardiovascular and respiratory). Results: Expected immunological indications of asthma have been obtained. In addition, initial results from our analyses point to the complex nature of childhood health and risk factors linked to metabolic syndrome (obesity, blood pressure and dyslipidemia). For example, 31% and 34% of the asthmatic MICA subjects were either overweight (BMI > 25) o

Liquid lithium applications for solving challenging fusion reactor issues and NSTX-U contributions

DOE PAGES

Ono, M.; Jaworski, M. A.; Kaita, R.; ...

2016-08-05

Steady-state fusion reactor operation presents major divertor technology challenges, including high divertor heat flux both steady-state and transients. In addition to those issues, there are unresolved issues of long term dust accumulation and associated tritium inventory and safety issues. It has been suggested that radiative liquid lithium divertor concepts with a modest lithium-loop could provide a possible solution for these outstanding fusion reactor technology issues while potentially improving the reactor plasma performance. The application of lithium (Li) in NSTX resulted in improved H-mode confinement, H-mode power threshold reduction, and reduction in the divertor peak heat flux while maintaining essentially Li-freemore » core plasma operation even during H-modes. These promising results in NSTX and related modeling calculations motivated the radiative liquid lithium divertor (RLLD) concept and its variant, the active liquid lithium divertor concept (ARLLD), taking advantage of the enhanced Li radiation in relatively poorly confined divertor plasmas. It was estimated that only a few moles/sec of lithium injection would be needed to significantly reduce the divertor heat flux in a tokamak fusion power plant. By operating at lower temperatures ≤ 500°C than the first wall ~ 600 – 700°C, the LL-covered divertor chamber wall surfaces can serve as an effective particle pump, as impurities generally migrate toward lower temperature LL divertor surfaces. To maintain the LL purity, a closed LL loop system with a modest circulating capacity of ~ 1 liter/second (l/sec) is envisioned to sustain the steady-state operation of a 1 GW-electric class fusion power plant. By running the Li loop continuously, it can carry the dust particles and impurities generated in the vacuum vessel to outside where the dust / impurities are removed by relatively simple filter and cold/hot trap systems. Using a cold trap system, it can recover in tritium (T) in real time from LL

High Performance Distributed Computing in a Supercomputer Environment: Computational Services and Applications Issues

NASA Technical Reports Server (NTRS)

Kramer, Williams T. C.; Simon, Horst D.

1994-01-01

This tutorial proposes to be a practical guide for the uninitiated to the main topics and themes of high-performance computing (HPC), with particular emphasis to distributed computing. The intent is first to provide some guidance and directions in the rapidly increasing field of scientific computing using both massively parallel and traditional supercomputers. Because of their considerable potential computational power, loosely or tightly coupled clusters of workstations are increasingly considered as a third alternative to both the more conventional supercomputers based on a small number of powerful vector processors, as well as high massively parallel processors. Even though many research issues concerning the effective use of workstation clusters and their integration into a large scale production facility are still unresolved, such clusters are already used for production computing. In this tutorial we will utilize the unique experience made at the NAS facility at NASA Ames Research Center. Over the last five years at NAS massively parallel supercomputers such as the Connection Machines CM-2 and CM-5 from Thinking Machines Corporation and the iPSC/860 (Touchstone Gamma Machine) and Paragon Machines from Intel were used in a production supercomputer center alongside with traditional vector supercomputers such as the Cray Y-MP and C90.

The Challenges of Intersectionality: Researching Difference in Physical Education

ERIC Educational Resources Information Center

Flintoff, A.; Fitzgerald, H.; Scraton, S.

2008-01-01

Researching the intersection of class, race, gender, sexuality and disability raises many issues for educational research. Indeed, Maynard (2002, 33) has recently argued that "difference is one of the most significant, yet unresolved, issues for feminist and social thinking at the beginning of the twentieth century". This paper reviews…

Toward a Rational and Mechanistic Account of Mental Effort.

PubMed

Shenhav, Amitai; Musslick, Sebastian; Lieder, Falk; Kool, Wouter; Griffiths, Thomas L; Cohen, Jonathan D; Botvinick, Matthew M

2017-07-25

In spite of its familiar phenomenology, the mechanistic basis for mental effort remains poorly understood. Although most researchers agree that mental effort is aversive and stems from limitations in our capacity to exercise cognitive control, it is unclear what gives rise to those limitations and why they result in an experience of control as costly. The presence of these control costs also raises further questions regarding how best to allocate mental effort to minimize those costs and maximize the attendant benefits. This review explores recent advances in computational modeling and empirical research aimed at addressing these questions at the level of psychological process and neural mechanism, examining both the limitations to mental effort exertion and how we manage those limited cognitive resources. We conclude by identifying remaining challenges for theoretical accounts of mental effort as well as possible applications of the available findings to understanding the causes of and potential solutions for apparent failures to exert the mental effort required of us.

Mechanistic characterization of chloride interferences in electrothermal atomization systems

USGS Publications Warehouse

Shekiro, J.M.; Skogerboe, R.K.; Taylor, Howard E.

1988-01-01

A computer-controlled spectrometer with a photodiode array detector has been used for wavelength and temperature resolved characterization of the vapor produced by an electrothermal atomizer. The system has been used to study the chloride matrix interference on the atomic absorption spectrometric determination of manganese and copper. The suppression of manganese and copper atom populations by matrix chlorides such as those of calcium and magnesium is due to the gas-phase formation of an analyte chloride species followed by the diffusion of significant fractions of these species from the atom cell prior to completion of the atomization process. The analyte chloride species cannot be formed when matrix chlorides with metal-chloride bond dissociation energies above those of the analyte chlorides are the principal entitles present. The results indicate that multiple wavelength spectrometry used to obtain temperature-resolved spectra is a viable tool in the mechanistic characterization of interference effects observed with electrothermal atomization systems. ?? 1988 American Chemical Society.

Evaluation of current Louisiana flexible pavement structures using PMS data and new mechanistic-empirical pavement design guide : tech summary.

DOT National Transportation Integrated Search

2012-04-01

The new Mechanistic-Empirical Pavement Design Guide (MEPDG) developed under the National Cooperative Highway : Research Program (NCHRP) Project 1-37A represents a major change as compared to the 1993 AASHTO Pavement : Design Guide. MEPDG provides a r...

Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p‐Synephrine

PubMed Central

2017-01-01

Citrus aurantium L. (bitter orange) extracts that contain p‐synephrine as the primary protoalkaloid are widely used for weight loss/weight management, sports performance, appetite control, energy, and mental focus and cognition. Questions have been raised about the safety of p‐synephrine because it has some structural similarity to ephedrine. This review focuses on current human, animal, in vitro, and mechanistic studies that address the safety, efficacy, and mechanisms of action of bitter orange extracts and p‐synephrine. Numerous studies have been conducted with respect to p‐synephrine and bitter orange extract because ephedra and ephedrine were banned from use in dietary supplements in 2004. Approximately 30 human studies indicate that p‐synephrine and bitter orange extracts do not result in cardiovascular effects and do not act as stimulants at commonly used doses. Mechanistic studies suggest that p‐synephrine exerts its effects through multiple actions, which are discussed. Because p‐synephrine exhibits greater adrenergic receptor binding in rodents than humans, data from animals cannot be directly extrapolated to humans. This review, as well as several other assessments published in recent years, has concluded that bitter orange extract and p‐synephrine are safe for use in dietary supplements and foods at the commonly used doses. Copyright © 2017 The Authors Phytotherapy Research Published by John Wiley & Sons Ltd. PMID:28752649

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

PubMed Central

2013-01-01

Summary The copper-catalyzed azide–alkyne cycloaddition (CuAAC) is one of the most broadly applicable and easy-to-handle reactions in the arsenal of organic chemistry. However, the mechanistic understanding of this reaction has lagged behind the plethora of its applications for a long time. As reagent mixtures of copper salts and additives are commonly used in CuAAC reactions, the structure of the catalytically active species itself has remained subject to speculation, which can be attributed to the multifaceted aggregation chemistry of copper(I) alkyne and acetylide complexes. Following an introductory section on common catalyst systems in CuAAC reactions, this review will highlight experimental and computational studies from early proposals to very recent and more sophisticated investigations, which deliver more detailed insights into the CuAAC’s catalytic cycle and the species involved. As diverging mechanistic views are presented in articles, books and online resources, we intend to present the research efforts in this field during the past decade and finally give an up-to-date picture of the currently accepted dinuclear mechanism of CuAAC. Additionally, we hope to inspire research efforts on the development of molecularly defined copper(I) catalysts with defined structural characteristics, whose main advantage in contrast to the regularly used precatalyst reagent mixtures is twofold: on the one hand, the characteristics of molecularly defined, well soluble catalysts can be tuned according to the particular requirements of the experiment; on the other hand, the understanding of the CuAAC reaction mechanism can be further advanced by kinetic studies and the isolation and characterization of key intermediates. PMID:24367437

Mechanistic insights into EgGST1, a Mu class glutathione S-transferase from the cestode parasite Echinococcus granulosus.

PubMed

Arbildi, Paula; Turell, Lucía; López, Verónica; Alvarez, Beatriz; Fernández, Verónica

2017-11-01

Glutathione transferases (GSTs) comprise a major detoxification system in helminth parasites, displaying both catalytic and non-catalytic activities. The kinetic mechanism of these enzymes is complex and depends on the isoenzyme which is being analyzed. Here, we characterized the kinetic mechanism of rEgGST1, a recombinant form of a cytosolic GST from Echinococcus granulosus (EgGST1), which is related to the Mu-class of mammalian enzymes, using the canonical substrates glutathione (GSH) and 1-chloro-2,4-dinitrobenzene (CDNB). Initial rate and product inhibition studies were consistent with a steady-state random sequential mechanism, where both substrates are bound to the enzyme before the products are released. Kinetic constants were also determined (pH 6.5 and 30 °C). Moreover, rEgGST1 lowered the pK a of GSH from 8.71 ± 0.07 to 6.77 ± 0.08, and enzyme-bound GSH reacted with CDNB 1 × 10 5 times faster than free GSH at pH 7.4. Finally, the dissociation of the enzyme-GSH complex was studied by means of intrinsic fluorescence, as well as that of the complex with the anthelminth drug mebendazole. This is the first report on mechanistic issues related to a helminth parasitic GST. Copyright © 2017 Elsevier Inc. All rights reserved.

14 CFR 431.37 - Mission readiness.

Code of Federal Regulations, 2014 CFR

2014-01-01

... contingency abort plans and procedures, if any, as required under § 431.39; (vi) Unresolved safety issues.... (2) Procedures that ensure mission constraints, rules, contingency abort and emergency abort...

14 CFR 431.37 - Mission readiness.

Code of Federal Regulations, 2012 CFR

2012-01-01

... contingency abort plans and procedures, if any, as required under § 431.39; (vi) Unresolved safety issues.... (2) Procedures that ensure mission constraints, rules, contingency abort and emergency abort...

14 CFR 431.37 - Mission readiness.

Code of Federal Regulations, 2013 CFR

2013-01-01

... contingency abort plans and procedures, if any, as required under § 431.39; (vi) Unresolved safety issues.... (2) Procedures that ensure mission constraints, rules, contingency abort and emergency abort...

14 CFR 431.37 - Mission readiness.

Code of Federal Regulations, 2011 CFR

2011-01-01

... contingency abort plans and procedures, if any, as required under § 431.39; (vi) Unresolved safety issues.... (2) Procedures that ensure mission constraints, rules, contingency abort and emergency abort...

14 CFR 431.37 - Mission readiness.

Code of Federal Regulations, 2010 CFR

2010-01-01

... contingency abort plans and procedures, if any, as required under § 431.39; (vi) Unresolved safety issues.... (2) Procedures that ensure mission constraints, rules, contingency abort and emergency abort...

Utilizing Mechanistic Cross-Linking Technology to Study Protein-Protein Interactions: An Experiment Designed for an Undergraduate Biochemistry Lab

ERIC Educational Resources Information Center

Finzel, Kara; Beld, Joris; Burkart, Michael D.; Charkoudian, Louise K.

2017-01-01

Over the past decade, mechanistic cross-linking probes have been used to study protein-protein interactions in natural product biosynthetic pathways. This approach is highly interdisciplinary, combining elements of protein biochemistry, organic chemistry, and computational docking. Herein, we described the development of an experiment to engage…

Channel microband electrode arrays for mechanistic electrochemistry. Two-dimensional voltammetry:  transport-limited currents.

PubMed

Alden, J A; Feldman, M A; Hill, E; Prieto, F; Oyama, M; Coles, B A; Compton, R G; Dobson, P J; Leigh, P A

1998-05-01

A channel electrode array, with electrodes ranging in size from the millimeter to the submicrometer scale, is used for the amperometric interrogation of mechanistically complex electrode processes. In this way, the transport-limited current, measured as a function of both electrode size and electrolyte flow rate (convection), is shown to provide a highly sensitive probe of mechanism and kinetics. The application of "two-dimensional voltammetry" to diverse electrode processes, including E, ECE, ECEE, EC', and DISP2 reactions, is reported.

Mechanistic and kinetic insights into the thermally induced rearrangement of alpha-pinene.

PubMed

Stolle, Achim; Ondruschka, Bernd; Findeisen, Matthias

2008-11-07

The thermal rearrangement of alpha-pinene (1) is interesting from mechanistic as well as kinetic point of view. Carrier gas pyrolyses with 1 and its acyclic isomers ocimene (2) and alloocimene (3) were performed to investigate the thermal network of these hydrocarbons. Kinetic analysis of the major reaction steps allows for a deeper insight in the reaction mechanism. Thus it was possible to explain the racemization of 1, the formation of racemic limonene (4), and the absence of the primary pyrolysis product 2 in the reaction mixture resulting from thermal rearrangement of 1. Results supported the conclusion that the reactions starting with 1 involve biradical transition states.

A Biologically Informed, Mechanistic Model of Desert Shrub Population Dynamics Bearing on Arid Landscape Evolution

NASA Astrophysics Data System (ADS)

Worman, Stacey; Furbish, David; Fathel, Siobhan

2014-05-01

In arid landscapes, desert shrubs individually and collectively modify how sediment is transported (e.g by wind, overland-flow, and rain-splash). Addressing how desert shrubs modify landscapes on geomorphic timescales therefore necessitates spanning multiple shrub lifetimes and accounting for how processes affecting shrub dynamics on these longer timescales (e.g. fire, grazing, drought, and climate change) may in turn impact sediment transport. To fulfill this need, we present a mechanistic model of the spatiotemporal dynamics of a desert-shrub population that uses a simple accounting framework and tracks individual shrubs as they enter, age, and exit the population (via recruitment, growth, and mortality). Our model is novel insomuch as it (1) features a strong biophysical foundation, (2) mimics well-documented aspects of how shrub populations respond to changes in precipitation, and (3) possesses the process granularity appropriate for use in geomorphic simulations. In a complimentary abstract (Fathel et al. 2014), we demonstrate the potential of this biological model by coupling it to a physical model of rain-splash sediment transport: We mechanistically reproduce the empirical observation that the erosion rate of a hillslope decreases as its vegetation coverage increases and we predict erosion rates under different climate-change scenarios.

A brief exegesis of End Triassic Extinction issues

NASA Astrophysics Data System (ADS)

Whiteside, J. H.; Grice, K.; Fox, C.; Kent, D. V.; Olsen, P. E.; Irmis, R. B.

2017-12-01

Recent reports of environmental proxy records through the end-Triassic extinction (ETE), in some cases coupled with high-resolution geochronologic data, provide new insights into cause and effect. For example, the emplacement of vast volumes of basalt in the Central Atlantic Magmatic Province (CAMP) are temporally associated with carbon isotopic excursions (CIEs), indications of widespread oceanic euxinia, distinct regional and perhaps very abrupt global sea level change, massive changes in atmospheric CO2, and the proliferation of "disaster" species, both on land and ocean. In the least, these indicate major disruptions in how the Earth works. However some striking and critical issues remain unresolved at a very basic level. Most important are the uncertainties in the stratigraphic relationships of marine extinctions to the various environmental proxy sections, particularly the GSSP for the base Hettangian in Austria, and the UK sections (notably St. Audrie's Bay). Here, the sequence of sporomorph and marine "invertebrate" turnover occurs in different order relative to the proxy record and lithostratigraphy. Thus the sequence of environmental events are, at present, of uncertain relationship to the extinction. Second, it is unclear what processes the various CIEs reflect in different environments; the canonical initial isotopic excursion in the UK, demonstrably correlatable over a huge area, was recorded in a lake in a restricted basin, unlike the isotopic data from surrounding marine strata. Could some CIEs in non-marine basins be diagenetic in nature, caused by the contact effects of overlying basalts? Finally, how does the clear and dramatic tropical non-marine record of the ETE, precisely located relative to the CAMP, relate to the marine record of the ETE, particularly at higher latitudes, where continental biotic turnover is not nearly as dramatic? Do these records correlate in a sufficiently tight temporal interval such that causation can be inferred? These

Flow-mediated Dilation: Can New Approaches Provide Greater Mechanistic Insight into Vascular Dysfunction in Preeclampsia and Other Diseases?

PubMed Central

Weissgerber, Tracey L.

2015-01-01

Endothelial dysfunction is a key feature of preeclampsia, and may contribute to increased cardiovascular disease risk years after pregnancy. Flow-mediated dilation (FMD) is a non-invasive endothelial function test that predicts cardiovascular event risk. New protocols allow researchers to measure three components of the FMD response: FMD, low flow-mediated constriction and the shear stimulus. This review encourages researchers to think beyond “low FMD” by examining how these three components may provide additional insights into the mechanisms and location of vascular dysfunction. The review then examines what FMD studies reveal about vascular dysfunction in preeclampsia, while highlighting opportunities to gain greater mechanistic insight from new protocols. Studies using traditional protocols show that FMD is low in mid-pregnancy prior to preeclampsia, at diagnosis, and for three years post-partum. However, FMD returns to normal by ten years post-partum. Studies using new protocols are needed to gain more mechanistic insight. PMID:25182159

Mechanistic Investigations into the Application of Sulfoxides in Carbohydrate Synthesis

PubMed Central

Brabham, Robin

2016-01-01

Abstract The utility of sulfoxides in a diverse range of transformations in the field of carbohydrate chemistry has seen rapid growth since the first introduction of a sulfoxide as a glycosyl donor in 1989. Sulfoxides have since developed into more than just anomeric leaving groups, and today have multiple roles in glycosylation reactions. These include as activators for thioglycosides, hemiacetals, and glycals, and as precursors to glycosyl triflates, which are essential for stereoselective β‐mannoside synthesis, and bicyclic sulfonium ions that facilitate the stereoselective synthesis of α‐glycosides. In this review we highlight the mechanistic investigations undertaken in this area, often outlining strategies employed to differentiate between multiple proposed reaction pathways, and how the conclusions of these investigations have and continue to inform upon the development of more efficient transformations in sulfoxide‐based carbohydrate synthesis. PMID:26744250

Continually emerging mechanistic complexity of the multi-enzyme cellulosome complex.

PubMed

Smith, Steven P; Bayer, Edward A; Czjzek, Mirjam

2017-06-01

The robust plant cell wall polysaccharide-degrading properties of anaerobic bacteria are harnessed within elegant, marcomolecular assemblages called cellulosomes, in which proteins of complementary activities amass on scaffold protein networks. Research efforts have focused and continue to focus on providing detailed mechanistic insights into cellulosomal complex assembly, topology, and function. The accumulated information is expanding our fundamental understanding of the lignocellulosic biomass decomposition process and enhancing the potential of engineered cellulosomal systems for biotechnological purposes. Ongoing biochemical studies continue to reveal unexpected functional diversity within traditional cellulase families. Genomic, proteomic, and functional analyses have uncovered unanticipated cellulosomal proteins that augment the function of the native and designer cellulosomes. In addition, complementary structural and computational methods are continuing to provide much needed insights on the influence of cellulosomal interdomain linker regions on cellulosomal assembly and activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bridging the boundaries between scientists and clinicians-mechanistic hypotheses and patient stories in risk assessment of drugs.

PubMed

Rocca, Elena

2017-02-01

The cultural divide between scientists and clinicians has been described as undermining the advance of medical science, by hindering the production of practice-relevant research and of research-informed clinical decisions. Here, I consider the field of post-marketing risk assessment of drugs as an example of strict interdependence between basic biomedical research, clinical research, and clinical evaluation and show how it would benefit from a closer collaboration between scientists and clinicians. The risk assessment of drugs after their marketing relies on spontaneous adverse effect reports to drug agencies and on peer-reviewed case reports. I emphasize the importance of qualitative analysis of such reports for the improvement of mechanistic understanding of harmful effects of drugs. I argue that mechanistic explanations of drug effects are at least as important as determination of their frequency, in order to establish causation. An ideal risk assessment, then, verifies not only the frequency of undesired effects but also why and how the harm happens. For this purpose, the frequency or novelty of the unintended outcome, although contextually indicative, should not determine the epistemic value of a report. Details about the context that generated an unexpected outcome, instead, can offer the chance of improving causal understanding about how the intervention works. This is illustrated through examples from medical research. Mechanistic understanding is a domain of joint collaboration among (1) clinicians, in charge of detailed, qualitative reporting of patient stories about side effects, (2) qualitative clinical researchers, in charge of analyzing clinical contexts or harmful effects and formulating explanatory hypotheses, and (3) basic biomedical researchers, in charge of verifying such hypotheses. In addition, direct information flow can on one side focus clinicians' attention on knowledge gaps about drugs/effects where more research is needed, while on the

Bacterial Diterpene Synthases: New Opportunities for Mechanistic Enzymology and Engineered Biosynthesis

PubMed Central

Smanski, Michael J.; Peterson, Ryan M.; Huang, Sheng-Xiong; Shen, Ben

2012-01-01

Diterpenoid biosynthesis has been extensively studied in plants and fungi, yet cloning and engineering diterpenoid pathways in these organisms remain challenging. Bacteria are emerging as prolific producers of diterpenoid natural products, and bacterial diterpene synthases are poised to make significant contributions to our understanding of terpenoid biosynthesis. Here we will first survey diterpenoid natural products of bacterial origin and briefly review their biosynthesis with emphasis on diterpene synthases (DTSs) that channel geranylgeranyl diphosphate to various diterpenoid scaffolds. We will then highlight differences of DTSs of bacterial and higher organism origins and discuss the challenges in discovering novel bacterial DTSs. We will conclude by discussing new opportunities for DTS mechanistic enzymology and applications of bacterial DTS in biocatalysis and metabolic pathway engineering. PMID:22445175

Use of mechanistic simulations as a quantitative risk-ranking tool within the quality by design framework.

PubMed

Stocker, Elena; Toschkoff, Gregor; Sacher, Stephan; Khinast, Johannes G

2014-11-20

The purpose of this study is to evaluate the use of computer simulations for generating quantitative knowledge as a basis for risk ranking and mechanistic process understanding, as required by ICH Q9 on quality risk management systems. In this specific publication, the main focus is the demonstration of a risk assessment workflow, including a computer simulation for the generation of mechanistic understanding of active tablet coating in a pan coater. Process parameter screening studies are statistically planned under consideration of impacts on a potentially critical quality attribute, i.e., coating mass uniformity. Based on computer simulation data the process failure mode and effects analysis of the risk factors is performed. This results in a quantitative criticality assessment of process parameters and the risk priority evaluation of failure modes. The factor for a quantitative reassessment of the criticality and risk priority is the coefficient of variation, which represents the coating mass uniformity. The major conclusion drawn from this work is a successful demonstration of the integration of computer simulation in the risk management workflow leading to an objective and quantitative risk assessment. Copyright © 2014. Published by Elsevier B.V.

Mathematical and Numerical Studies of Nonstandard Difference Equation Models of Differential Equations

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

Mickens, Ronald E.

2008-12-22

This research examined the following items/issues: the NSFD methodology, technical achievements and applications, dissemination efforts and research related professional activities. Also a list of unresolved issues were identified that could form the basis for future research in the area of constructing and analyzing NSFD schemes for both ODE's and PDE's.

Mechanistic Distinctions between CHK1 and WEE1 Inhibition Guide the Scheduling of Triple Therapy with Gemcitabine.

PubMed

Koh, Siang-Boon; Wallez, Yann; Dunlop, Charles R; Bernaldo de Quirós Fernández, Sandra; Bapiro, Tashinga E; Richards, Frances M; Jodrell, Duncan I

2018-06-01

Combination of cytotoxic therapy with emerging DNA damage response inhibitors (DDRi) has been limited by tolerability issues. However, the goal of most combination trials has been to administer DDRi with standard-of-care doses of chemotherapy. We hypothesized that mechanism-guided treatment scheduling could reduce the incidence of dose-limiting toxicities and enable tolerable multitherapeutic regimens. Integrative analyses of mathematical modeling and single-cell assays distinguished the synergy kinetics of WEE1 inhibitor (WEE1i) from CHEK1 inhibitor (CHK1i) by potency, spatiotemporal perturbation, and mitotic effects when combined with gemcitabine. These divergent properties collectively supported a triple-agent strategy, whereby a pulse of gemcitabine and CHK1i followed by WEE1i durably suppressed tumor cell growth. In xenografts, CHK1i exaggerated replication stress without mitotic CDK hyperactivation, enriching a geminin-positive subpopulation and intratumoral gemcitabine metabolite. Without overt toxicity, addition of WEE1i to low-dose gemcitabine and CHK1i was most effective in tumor control compared with single and double agents. Overall, our work provides quantitative insights into the mechanisms of DDRi chemosensitization, leading to the rational development of a tolerable multitherapeutic regimen. Significance: Multiple lines of mechanistic insight regarding DNA damage response inhibitors rationally guide the preclinical development of a tolerable multitherapeutic regimen. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/11/3054/F1.large.jpg Cancer Res; 78(11); 3054-66. ©2018 AACR . ©2018 American Association for Cancer Research.

Sexuality and the Curriculum: The Politics and Practices of Sexuality Education. Critical Issues in the Curriculum.

ERIC Educational Resources Information Center

Sears, James T., Ed.

This book of essays explores the explicit and hidden curriculum of sexuality from kindergarten through college. The 15 interrelated essays challenge conventional assumptions regarding sexuality and the curriculum by applying non-traditional perspectives to traditionally unresolved problems while proposing specific curricular strategies and…

Dronabinol and chronic pain: importance of mechanistic considerations.

PubMed

de Vries, Marjan; van Rijckevorsel, Dagmar C M; Wilder-Smith, Oliver H G; van Goor, Harry

2014-08-01

Although medicinal cannabis has been used for many centuries, the therapeutic potential of delta-9-tetrahydrocannabinol (Δ9-THC; international non-proprietary name = dronabinol) in current pain management remains unclear. Several pharmaceutical products with defined natural or synthesized Δ9-THC content have been developed, resulting in increasing numbers of clinical trials investigating the analgesic efficacy of dronabinol in various pain conditions. Different underlying pain mechanisms, including sensitization of nociceptive sensory pathways and alterations in cognitive and autonomic processing, might explain the varying analgesic effects of dronabinol in chronic pain states. The pharmacokinetics, pharmacodynamics and mechanisms of action of products with a defined dronabinol content are summarized. Additionally, randomized clinical trials investigating the analgesic efficacy of pharmaceutical cannabis based products are reviewed for the treatment of chronic nonmalignant pain. We suggest a mechanism-based approach beyond measurement of subjective pain relief to evaluate the therapeutic potential of dronabinol in chronic pain management. Development of objective mechanistic diagnostic biomarkers reflecting altered sensory and cognitive processing in the brain is essential to evaluate dronabinol induced analgesia, and to permit identification of responders and/or non-responders to dronabinol treatment.

How long bones grow children: Mechanistic paths to variation in human height growth.

PubMed

Lampl, Michelle; Schoen, Meriah

2017-03-01

Eveleth and Tanner's descriptive documentation of worldwide variability in human growth provided evidence of the interaction between genetics and environment during development that has been foundational to the science of human growth. There remains a need, however, to describe the mechanistic foundations of variability in human height growth patterns. A review of research documenting cellular activities at the endochondral growth plate aims to show how the unique microenvironment and cell functions during the sequential phases of the chondrocyte lifecycle affect long bone elongation, a fundamental source of height growth. There are critical junctures within the chondrocytic differentiation cascade at which environmental influences are integrated and have the ability to influence progression to the hypertrophic chondrocyte phase, the primary driver of long bone elongation. Phenotypic differences in height growth patterns reflect variability in amplitude and frequency of discretely timed hypertrophic cellular expansion events, the cellular basis of saltation and stasis growth biology. Final height is a summary of the dynamic processes carried out by the growth plate cellular machinery. As these cell-level mechanisms unfold in an individual, time-specific manner, there are many critical points at which a genetic growth program can be enhanced or perturbed. Recognizing both the complexity and fluidity of this adaptive system questions the likelihood of a single, optimal growth pattern and instead identifies a larger bandwidth of saltatory frequencies for "normal" growth. Further inquiry into mechanistic sources of variability acting at critical organizational points of chondrogenesis can provide new opportunities for growth interventions. © 2017 Wiley Periodicals, Inc.

Exploring the pros and cons of mechanistic case diagrams for problem-based learning

PubMed Central

2017-01-01

Purpose Mechanistic case diagram (MCD) was recommended for increasing the depth of understanding of disease, but with few articles on its specific methods. We address the experience of making MCD in the fullest depth to identify the pros and cons of using MCDs in such ways. Methods During problem-based learning, we gave guidelines of MCD for its mechanistic exploration from subcellular processes to clinical features, being laid out in as much detail as possible. To understand the students’ attitudes and depth of study using MCDs, we analyzed the results of a questionnaire in an open format about experiencing MCDs and examined the resulting products. Results Through the responses to questionnaire, we found several favorable outcomes, major of which was deeper insight and comprehensive understanding of disease facilitated by the process of making well-organized diagram. The main disadvantages of these guidelines were the feeling of too much workload and difficulty of finding mechanisms. Students gave suggestions to overcome these problems: cautious reading of comprehensive texts, additional guidance from staff about depth and focus of mechanisms, and cooperative group work. From the analysis of maps, we recognized there should be allowance of diversities in the appearance of maps and many hypothetical connections, which could be related to an insufficient understanding of mechanisms in nature. Conclusion The more detailed an MCD task is, the better students can become acquainted with deep knowledges. However, this advantage should be balanced by the results that there are many ensuing difficulties for the work and deliberate help plans should be prepared. PMID:28870018

Mutual Dependence Between Sedimentary Organic Carbon and Infaunal Macrobenthos Resolved by Mechanistic Modeling

NASA Astrophysics Data System (ADS)

Zhang, Wenyan; Wirtz, Kai

2017-10-01

The mutual dependence between sedimentary total organic carbon (TOC) and infaunal macrobenthos is here quantified by a mechanistic model. The model describes (i) the vertical distribution of infaunal macrobenthic biomass resulting from a trade-off between nutritional benefit (quantity and quality of TOC) and the costs of burial (respiration) and mortality, and (ii) the variable vertical distribution of TOC being in turn shaped by bioturbation of local macrobenthos. In contrast to conventional approaches, our model emphasizes variations of bioturbation both spatially and temporally depending on local food resources and macrobenthic biomass. Our implementation of the dynamic interaction between TOC and infaunal macrobenthos is able to capture a temporal benthic response to both depositional and erosional environments and provides improved estimates of the material exchange flux at the sediment-water interface. Applications to literature data for the North Sea demonstrate the robustness and accuracy of the model and its potential as an analysis tool for the status of TOC and macrobenthos in marine sediments. Results indicate that the vertical distribution of infaunal biomass is shaped by both the quantity and the quality of OC, while the community structure is determined only by the quality of OC. Bioturbation intensity may differ by 1 order of magnitude over different seasons owing to variations in the OC input, resulting in a significant modulation on the distribution of OC. Our relatively simple implementation may further improve models of early diagenesis and marine food web dynamics by mechanistically connecting the vertical distribution of both TOC and macrobenthic biomass.

Descriptive vs. mechanistic network models in plant development in the post-genomic era.

PubMed

Davila-Velderrain, J; Martinez-Garcia, J C; Alvarez-Buylla, E R

2015-01-01

Network modeling is now a widespread practice in systems biology, as well as in integrative genomics, and it constitutes a rich and diverse scientific research field. A conceptually clear understanding of the reasoning behind the main existing modeling approaches, and their associated technical terminologies, is required to avoid confusions and accelerate the transition towards an undeniable necessary more quantitative, multidisciplinary approach to biology. Herein, we focus on two main network-based modeling approaches that are commonly used depending on the information available and the intended goals: inference-based methods and system dynamics approaches. As far as data-based network inference methods are concerned, they enable the discovery of potential functional influences among molecular components. On the other hand, experimentally grounded network dynamical models have been shown to be perfectly suited for the mechanistic study of developmental processes. How do these two perspectives relate to each other? In this chapter, we describe and compare both approaches and then apply them to a given specific developmental module. Along with the step-by-step practical implementation of each approach, we also focus on discussing their respective goals, utility, assumptions, and associated limitations. We use the gene regulatory network (GRN) involved in Arabidopsis thaliana Root Stem Cell Niche patterning as our illustrative example. We show that descriptive models based on functional genomics data can provide important background information consistent with experimentally supported functional relationships integrated in mechanistic GRN models. The rationale of analysis and modeling can be applied to any other well-characterized functional developmental module in multicellular organisms, like plants and animals.

Semi-mechanistic autoinduction model of midazolam in critically ill patients: population pharmacokinetic analysis.

PubMed

Aoyama, T; Hirata, K; Yamamoto, Y; Yokota, H; Hayashi, H; Aoyama, Y; Matsumoto, Y

2016-08-01

Midazolam (MDZ) is commonly used for sedating critically ill patients. The daily dose required for adequate sedation increases in increments over 100 h after administration. The objectives of this study were to characterize the MDZ pharmacokinetics in critically ill patients and to describe the phenomenon of increasing daily dose by means of population pharmacokinetic analysis. Data were obtained from 30 patients treated in an intensive care unit. The patients received MDZ intravenously as a combination of bolus and continuous infusion. Serum MDZ concentration was assayed by high-performance liquid chromatography. Population pharmacokinetic analysis was performed using the NONMEM software package. The alteration of clearance unexplained by demographic factors and clinical laboratory data was described as an autoinduction of MDZ clearance using a semi-mechanistic pharmacokinetic-enzyme turnover model. The final population pharmacokinetic model was a one-compartment model estimated by incorporating a semi-mechanistic pharmacokinetic-enzyme turnover model for clearance, taking autoinduction into account. A significant covariate for MDZ clearance was total bilirubin. An increase in total bilirubin indicated a reduction in MDZ clearance. From simulation using the population pharmacokinetic parameters obtained in this study, MDZ clearance increased 2·3 times compared with pre-induced clearance 100 h after the start of 12·5 mg/h continuous infusion. Autoinduction and total bilirubin were significant predictors of the clearance of MDZ in this population. Step-by-step dosage adjustment using this population pharmacokinetic model may be useful for establishing a MDZ dosage regimen in critically ill patients. © 2016 John Wiley & Sons Ltd.

Mechanistic models as a transferable framework for projecting effects of habitat change on production and delivery of ecosystem services

EPA Science Inventory

Drawing a link between habitat change and the production and delivery of ecosystem services is a priority in coastal estuarine ecosystems. Mechanistic modeling tools are highly functional for exploring this link because they allow for the synthesis of multiple ecological and beh...

GENE ARRAYS FOR ELUCIDATING MECHANISTIC DATA FROM MODELS OF MALE INFERTILITY AND CHEMICAL EXPOSURE IN MICE, RATS AND HUMANS

EPA Science Inventory

Gene arrays for elucidating mechanistic data from models of male infertility and chemical exposure in mice, rats and humans
John C. Rockett and David J. Dix
Gamete and Early Embryo Biology Branch, Reproductive Toxicology Division, National Health and Environmental Effects ...

Kinetic and mechanistic reactivity. Isoprene impact on ozone levels in an urban area near Tijuca Forest, Rio de Janeiro.

PubMed

da Silva, Cleyton Martins; da Silva, Luane Lima; Corrêa, Sergio Machado; Arbilla, Graciela

2016-12-01

Volatile organic compounds (VOCs) play a central role in atmospheric chemistry. In this work, the kinetic and mechanistic reactivities of VOCs are analyzed, and the contribution of the organic compounds emitted by anthropogenic and natural sources is estimated. VOCs react with hydroxyl radicals and other photochemical oxidants, such as ozone and nitrate radicals, which cause the conversion of NO to NO 2 in various potential reaction paths, including photolysis, to form oxygen atoms, which generate ozone. The kinetic reactivity was evaluated based on the reaction coefficients for hydroxyl radicals with VOCs. The mechanistic reactivity was estimated using a detailed mechanism and the incremental reactivity scale that Carter proposed. Different scenarios were proposed and discussed, and a minimum set of compounds, which may describe the tropospheric reactivity in the studied area, was determined. The role of isoprene was analyzed in terms of its contribution to ozone formation.

Regioselective, borinic acid-catalyzed monoacylation, sulfonylation and alkylation of diols and carbohydrates: expansion of substrate scope and mechanistic studies.

PubMed

Lee, Doris; Williamson, Caitlin L; Chan, Lina; Taylor, Mark S

2012-05-16

Synthetic and mechanistic aspects of the diarylborinic acid-catalyzed regioselective monofunctionalization of 1,2- and 1,3-diols are presented. Diarylborinic acid catalysis is shown to be an efficient and general method for monotosylation of pyranoside derivatives bearing three secondary hydroxyl groups (7 examples, 88% average yield). In addition, the scope of the selective acylation, sulfonylation, and alkylation is extended to 1,2- and 1,3-diols not derived from carbohydrates (28 examples); the efficiency, generality, and operational simplicity of this method are competitive with those of state-of-the-art protocols including the broadly applied organotin-catalyzed or -mediated reactions. Mechanistic details of the organoboron-catalyzed processes are explored using competition experiments, kinetics, and catalyst structure-activity relationships. These experiments are consistent with a mechanism in which a tetracoordinate borinate complex reacts with the electrophilic species in the turnover-limiting step of the catalytic cycle.

Physiologic, demographic and mechanistic factors predicting New Injury Severity Score (NISS) in motor vehicle accident victims.

PubMed

Staff, T; Eken, T; Wik, L; Røislien, J; Søvik, S

2014-01-01

Current literature on motor vehicle accidents (MVAs) has few reports regarding field factors that predict the degree of injury. Also, studies of mechanistic factors rarely consider concurrent predictive effects of on-scene patient physiology. The New Injury Severity Score (NISS) has previously been found to correlate with mortality, need for ICU admission, length of hospital stay, and functional recovery after trauma. To potentially increase future precision of trauma triage, we assessed how the NISS is associated with physiologic, demographic and mechanistic variables from the accident site. Using mixed-model linear regression analyses, we explored the association between NISS and pre-hospital Glasgow Coma Scale (GCS) score, Revised Trauma Score (RTS) categories of respiratory rate (RR) and systolic blood pressure (SBP), gender, age, subject position in the vehicle, seatbelt use, airbag deployment, and the estimated squared change in vehicle velocity on impact ((Δv)(2)). Missing values were handled with multiple imputation. We included 190 accidents with 353 dead or injured subjects (mean NISS 17, median NISS 8, IQR 1-27). For the 307 subjects in front-impact MVAs, the mean increase in NISS was -2.58 per GCS point, -2.52 per RR category level, -2.77 per SBP category level, -1.08 for male gender, 0.18 per year of age, 4.98 for driver vs. rear passengers, 4.83 for no seatbelt use, 13.52 for indeterminable seatbelt use, 5.07 for no airbag deployment, and 0.0003 per (km/h)(2) velocity change (all p<0.002). This study in victims of MVAs demonstrated that injury severity (NISS) was concurrently and independently predicted by poor pre-hospital physiologic status, increasing age and female gender, and several mechanistic measures of localised and generalised trauma energy. Our findings underscore the need for precise information from the site of trauma, to reduce undertriage, target diagnostic efforts, and anticipate need for high-level care and rehabilitative resources

Nationwide genetic analysis for molecularly unresolved cystic fibrosis patients in a multiethnic society: implications for preconception carrier screening.

PubMed

Behar, Doron M; Inbar, Ori; Shteinberg, Michal; Gur, Michal; Mussaffi, Huda; Shoseyov, David; Ashkenazi, Moshe; Alkrinawi, Soliman; Bormans, Concetta; Hakim, Fahed; Mei-Zahav, Meir; Cohen-Cymberknoh, Malena; Dagan, Adi; Prais, Dario; Sarouk, Ifat; Stafler, Patrick; Bar Aluma, Bat El; Akler, Gidon; Picard, Elie; Aviram, Micha; Efrati, Ori; Livnat, Galit; Rivlin, Joseph; Bentur, Lea; Blau, Hannah; Kerem, Eitan; Singer, Amihood

2017-05-01

Preconception carrier screening for cystic fibrosis (CF) is usually performed using ethnically targeted panels of selected mutations. This has been recently challenged by the use of expanded, ethnically indifferent, pan-population panels. Israel is characterized by genetically heterogeneous populations carrying a wide range of CFTR mutations. To assess the potential of expanding the current Israeli preconception screening program, we sought the subset of molecularly unresolved CF patients listed in the Israeli CF data registry comprising ~650 patients. An Israeli nationwide genotyping of 152 CF cases, representing 176 patients lacking molecular diagnosis, was conducted. Molecular analysis included Sanger sequencing for all exons and splice sites, multiplex ligation probe amplification (MLPA), and next-generation sequencing of the poly-T/TG tracts. We identified 54 different mutations, of which only 16 overlapped the 22 mutations included in the Israeli preconception screening program. A total of 29/54 (53.7%) mutations were already listed as CF causing by the CFTR2 database, and only 4/54 (7.4%) were novel. Molecular diagnosis was reached in 78/152 (51.3%) cases. Prenatal diagnosis of 24/78 (30.8%) cases could have been achieved by including all CFTR2-causing mutations in the Israeli panel. Our data reveal an overwhelming hidden abundance of CFTR gene mutations suggesting that expanded preconception carrier screening might achieve higher preconception detection rates.